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1

Neuronal Glucose Transporter Isoform 3 Deficient Mice Demonstrate Features of Autism Spectrum Disorders  

PubMed Central

Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristics of autism spectrum disorders. This clinical presentation occurred despite metabolic adaptations consisting of an increase in microvascular/glial GLUT1, neuronal GLUT8 and monocarboxylate transporter (MCT) isoform 2 concentrations, with minimal to no change in brain glucose uptake but an increase in lactate uptake. Neuron-specific glucose deficiency has a negative impact on neurodevelopment interfering with functional competence. This is the first description of GLUT3 deficiency that forms a possible novel genetic mechanism for pervasive developmental disorders, such as the neuropsychiatric autism spectrum disorders, requiring further investigation in humans. PMID:19506559

Zhao, Yuanzi; Fung, Camille; Shin, Don; Shin, Bo-Chul; Thamotharan, Shanthie; Sankar, Raman; Ehninger, Dan; Silva, Alcino; Devaskar, Sherin U.

2014-01-01

2

Mast cells can promote the development of multiple features of chronic asthma in mice  

PubMed Central

Bronchial asthma, the most prevalent cause of significant respiratory morbidity in the developed world, typically is a chronic disorder associated with long-term changes in the airways. We developed a mouse model of chronic asthma that results in markedly increased numbers of airway mast cells, enhanced airway responses to methacholine or antigen, chronic inflammation including infiltration with eosinophils and lymphocytes, airway epithelial goblet cell hyperplasia, enhanced expression of the mucin genes Muc5ac and Muc5b, and increased levels of lung collagen. Using mast cell–deficient (KitW-sh/W-sh and/or KitW/W-v) mice engrafted with FcR?+/+ or FcR?–/– mast cells, we found that mast cells were required for the full development of each of these features of the model. However, some features also were expressed, although usually at less than wild-type levels, in mice whose mast cells lacked FcR? and therefore could not be activated by either antigen- and IgE-dependent aggregation of Fc?RI or the binding of antigen-IgG1 immune complexes to Fc?RIII. These findings demonstrate that mast cells can contribute to the development of multiple features of chronic asthma in mice and identify both FcR?-dependent and FcR?-independent pathways of mast cell activation as important for the expression of key features of this asthma model. PMID:16710480

Yu, Mang; Tsai, Mindy; Tam, See-Ying; Jones, Carol; Zehnder, James; Galli, Stephen J.

2006-01-01

3

Oxytocin knockout mice demonstrate enhanced intake of sweet and nonsweet carbohydrate solutions.  

PubMed

Oxytocin knockout (OT KO) mice display enhanced intake of nutritive and nonnutritive sweet solutions (i.e., sucrose and saccharin) compared with wild-type (WT) mice of the same C57BL/6 background strain. The present study further investigated the differential behavioral response of OT KO and WT mice to sucrose solutions and also examined intake preferences of OT KO and WT mice for palatable but nonsweet isocaloric solutions of carbohydrate and fat. A progressive ratio operant licking procedure demonstrated that OT KO and WT mice display a similar motivational drive to consume 10% sucrose. A series of two-bottle intake tests revealed that OT KO mice consume significantly larger amounts of both sweet and nonsweet carbohydrate solutions (i.e., sucrose, Polycose, and cornstarch) compared with WT cohorts. Intake pattern analyses revealed that OT KO mice overconsume carbohydrate solutions by initiating more drinking bouts compared with WT mice; bout sizes did not differ between the genotypes. In contrast, OT KO and WT mice did not differ in their intake of Intralipid, a palatable soybean oil emulsion. These findings indicate that the absence of OT in mice does not affect their appetitive drive to consume palatable sucrose solutions. Instead, the absence of OT may increase daily intake of palatable sweet and nonsweet solutions of carbohydrate (but not fat) by selectively blunting or masking processes that contribute to postingestive satiety. PMID:17272659

Sclafani, Anthony; Rinaman, Linda; Vollmer, Regis R; Amico, Janet A

2007-05-01

4

Spontaneous Colitis in Muc2-Deficient Mice Reflects Clinical and Cellular Features of Active Ulcerative Colitis  

PubMed Central

Background The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows bacterial contact with the intestinal epithelium and results in spontaneous colitis. A defective mucus barrier is also a key feature of active ulcerative colitis (UC). Alterations in the immune compartment due to intestinal bacterial breach in mice lacking the colon mucus barrier have not been characterized and correlated to active UC. Aims To characterize alterations in the immune compartment due to intestinal bacterial breach in Muc2?/? mice, which lack the colon mucus barrier, and correlate the findings to active UC. Methods Bacterial contact with colon epithelium and penetration into colon tissue was examined in Muc2?/? mice and colon biopsies from patients with active UC using fluorescence microscopy and qPCR. Neutrophils, lymphocytes, CD103+ dendritic cell subsets and macrophages in colon from Muc2?/? mice and biopsies from UC patients were quantitated by flow cytometry. Results Inflamed UC patients and Muc2?/? mice had bacteria in contact with the colon epithelium. Bacterial rRNA was present in colonic mucosa in humans and Muc2?/? mice and in the draining lymph nodes of mice. Inflamed Muc2?/? mice and UC patients had elevated colon neutrophils, T cells and macrophages while a reduced frequency of CD103+ DCs was present in the inflamed colon of both mice and humans. Conclusions The parallel features of the colon immune cell compartment in Muc2?/? mice and UC patients supports the usefulness of this model to understand the early phase of spontaneous colitis and will provide insight into novel strategies to treat UC. PMID:24945909

Wenzel, Ulf A.; Magnusson, Maria K.; Rydström, Anna; Jonstrand, Caroline; Hengst, Julia; Johansson, Malin EV.; Velcich, Anna; Öhman, Lena; Strid, Hans; Sjövall, Henrik; Hansson, Gunnar C.; Wick, Mary Jo

2014-01-01

5

Leptin deficiency recapitulates the histological features of pulmonary arterial hypertension in mice  

PubMed Central

Leptin is a neuroendocrine peptide released by adipose tissue that enhances metabolism and acts on the hypothalamus to suppress appetite. Leptin also regulates aspects of cardiovascular function and low serum leptin has been associated with increased mortality in humans. We hypothesized that leptin deficiency alters the structure and function of the pulmonary vasculature. Methods: We examined two groups of C57BL/6 male mice aged 12 weeks: five ob/ob (B6.VLepob/ob) leptin-deficient and five wild type (WT) (C57BL/6) control mice. As expected, weight was significantly greater in ob/ob mice relative to WT mice [weight (g), Mean ± SD): ob/ob 52 ± 2.5 g, wild type 30 ± 2.5 g; p < 0.001]. The pulmonary vasculature of ob/ob mice and WT control animals was examined by histology, immunohistochemistry and immunofluorescence staining. Results: Pulmonary arterial wall thickness was significantly increased in ob/ob mice relative to WT littermates [median (interquartile range) distance in pixels: ob/ob 0.13 (0.05-0.18), wild type 0.03 (0.02-0.04); p = 0.001]. The ob/ob mice also exhibited significant right ventricular hypertrophy in comparison to control animals [RV thickness (Mean ± SD): ob/ob 0.75 ± 0.19, wild type; 0.58 ± 0.13 p < 0.001]. We observed substantial macrophage infiltration and abundant proliferation of myofibroblasts and fibroblasts in histological sections of pulmonary arterioles of ob/ob mice. In addition, we noted increased hyaluronan deposition, colocalizing with SMC-actin in the pulmonary vasculature of ob/ob mice relative to WT controls. Conclusions: The pulmonary pathology of leptin deficiency in ob/ob mice recapitulates many of the histological features of pulmonary vascular diseases, including pulmonary hypertension, suggesting that leptin deficiency is associated to the pathogenesis of pulmonary vascular disease. PMID:24966903

Aytekin, Metin; Tonelli, Adriano R; Farver, Carol F; Feldstein, Ariel E; Dweik, Raed A

2014-01-01

6

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 July 20, 2009) The hypothesis that amyloid- (A ) peptides are the primary cause of Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disorder that begins with deficits in short-term memory

7

Premature Skin Aging Features Rescued by Inhibition of NADPH Oxidase Activity in XPC-Deficient Mice.  

PubMed

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 (ROS), 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 NADPH oxidase 1 (NOX1) activity by using a novel NOX1 peptide inhibitor, suggesting that the continuous oxidative stress due to overactivation of NOX1 plays a causative role in the underlying pathophysiology.Journal of Investigative Dermatology accepted article preview online, 01 December 2014. doi:10.1038/jid.2014.511. PMID:25437426

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

2014-12-01

8

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

PubMed Central

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

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

2014-01-01

9

Fabry Disease: Preclinical Studies Demonstrate the Effectiveness of ?-Galactosidase A Replacement in Enzyme-Deficient Mice  

PubMed Central

Preclinical studies of enzyme-replacement therapy for Fabry disease (deficient ?-galactosidase A [?-Gal A] activity) were performed in ?-Gal A–deficient mice. The pharmacokinetics and biodistributions were determined for four recombinant human ?-Gal A glycoforms, which differed in sialic acid and mannose-6-phosphate content. The plasma half-lives of the glycoforms were ?2–5 min, with the more sialylated glycoforms circulating longer. After intravenous doses of 1 or 10 mg/kg body weight were administered, each glycoform was primarily recovered in the liver, with detectable activity in other tissues but not in the brain. Normal or greater activity levels were reconstituted in various tissues after repeated doses (10 mg/kg every other day for eight doses) of the highly sialylated AGA-1 glycoform; 4 d later, enzyme activity was retained in the liver and spleen at levels that were, respectively, 30% and 10% of that recovered 1 h postinjection. Importantly, the globotriaosylceramide (GL-3) substrate was depleted in various tissues and plasma in a dose-dependent manner. A single or repeated doses (every 48 h for eight doses) of AGA-1 at 0.3–10.0 mg/kg cleared hepatic GL-3, whereas higher doses were required for depletion of GL-3 in other tissues. After a single dose of 3 mg/kg, hepatic GL-3 was cleared for ?4 wk, whereas cardiac and splenic GL-3 reaccumulated at 3 wk to ?30% and ?10% of pretreatment levels, respectively. Ultrastructural studies demonstrated reduced GL-3 storage posttreatment. These preclinical animal studies demonstrate the dose-dependent clearance of tissue and plasma GL-3 by administered ?-Gal A, thereby providing the in vivo rationale—and the critical pharmacokinetic and pharmacodynamic data—for the design of enzyme-replacement trials in patients with Fabry disease. PMID:11115376

Ioannou, Yiannis A.; Zeidner, Ken M.; Gordon, Ronald E.; Desnick, Robert J.

2001-01-01

10

Behavioral Phenotyping of Parkin-Deficient Mice: Looking for Early Preclinical Features of Parkinson's Disease  

PubMed Central

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

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

2014-01-01

11

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

PubMed Central

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

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

12

The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.  

PubMed

Diabetic nephropathy is the leading cause of end-stage renal disease in humans in the Western world. The recent development of Na+-glucose cotransporter 2 (SGLT2) inhibitors offers a new antidiabetic therapy via enhanced glucose excretion. Whether this strategy exerts beneficial effects on the development of type 2 diabetic nephropathy is still largely unclear. We investigated the effects of the specific SGLT2 inhibitor empagliflozin in BTBR.Cg-Lep/WiscJ (BTBR ob/ob) mice, which spontaneously develop type 2 diabetic nephropathy. In the first experiment, BTBR ob/ob mice received either a diet containing 300 ppm empagliflozin or equicaloric placebo chow for 12 wk. In the second experiment, BTBR ob/ob mice received 1 ?g·kg body wt(-1)·day(-1) ANG II to induce arterial hypertension and were separated into the same two diet groups for 6 wk. In both experiments, empagliflozin treatment enhanced glucosuria, thereby lowering blood glucose. Independently of hypertension, empagliflozin reduced albuminuria in diabetic mice. However, empagliflozin treatment affected diabetes-related glomerular hypertrophy, markers of renal inflammation, and mesangial matrix expansion only in BTBR ob/ob mice without hypertension. In summary, empagliflozin demonstrated significant antihyperglycemic effects, differentially ameliorating early features of diabetic nephropathy in BTBR ob/ob mice with and without hypertension. PMID:24944269

Gembardt, Florian; Bartaun, Christoph; Jarzebska, Natalia; Mayoux, Eric; Todorov, Vladimir T; Hohenstein, Bernd; Hugo, Christian

2014-08-01

13

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

PubMed

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 p16(INK4a) or/and p21(WAF1) 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 (Recql4(HD)). Tail fibroblasts from Recql4(HD) showed increased SA-?-gal staining and increased DNA damage foci. We also identified sparser tail hair and fewer blood cells in Recql4(HD) 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

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

2014-01-01

14

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

PubMed Central

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

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

2014-01-01

15

Cushing's Syndrome and Fetal Features Resurgence in Adrenal Cortex–Specific Prkar1a Knockout Mice  

PubMed Central

Carney complex (CNC) is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD), a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 ?-regulatory subunit (R1?) of the cAMP–dependent protein kinase (PKA) have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1? loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO). AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1? loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1? is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD. PMID:20548949

Sahut-Barnola, Isabelle; de Joussineau, Cyrille; Val, Pierre; Lambert-Langlais, Sarah; Damon, Christelle; Lefrançois-Martinez, Anne-Marie; Pointud, Jean-Christophe; Marceau, Geoffroy; Sapin, Vincent; Tissier, Frédérique; Ragazzon, Bruno; Bertherat, Jérôme; Kirschner, Lawrence S.; Stratakis, Constantine A.; Martinez, Antoine

2010-01-01

16

Nonallele-specific Silencing of Mutant and Wild-type Huntingtin Demonstrates Therapeutic Efficacy in Huntington's Disease Mice  

PubMed Central

Huntington's disease (HD) is a fatal neurodegenerative disease caused by mutant huntingtin (htt) protein, and there are currently no effective treatments. Recently, we and others demonstrated that silencing mutant htt via RNA interference (RNAi) provides therapeutic benefit in HD mice. We have since found that silencing wild-type htt in adult mouse striatum is tolerated for at least 4 months. However, given the role of htt in various cellular processes, it remains unknown whether nonallele-specific silencing of both wild-type and mutant htt is a viable therapeutic strategy for HD. Here, we tested whether cosilencing wild-type and mutant htt provides therapeutic benefit and is tolerable in HD mice. After treatment, HD mice showed significant reductions in wild-type and mutant htt, and demonstrated improved motor coordination and survival. We performed transcriptional profiling to evaluate the effects of reducing wild-type htt in adult mouse striatum. We identified gene expression changes that are concordant with previously described roles for htt in various cellular processes. Also, several abnormally expressed transcripts associated with early-stage HD were differentially expressed in our studies, but intriguingly, those involved in neuronal function changed in opposing directions. Together, these encouraging and surprising findings support further testing of nonallele-specific RNAi therapeutics for HD. PMID:19240687

Boudreau, Ryan L; McBride, Jodi L; Martins, Inęs; Shen, Shihao; Xing, Yi; Carter, Barrie J; Davidson, Beverly L

2009-01-01

17

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

PubMed

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

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

2014-07-01

18

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

PubMed Central

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

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

2014-01-01

19

Citric acid and quinine share perceived chemosensory features making oral discrimination difficult in C57BL/6J mice.  

PubMed

Evidence in the literature shows that in rodents, some taste-responsive neurons respond to both quinine and acid stimuli. Also, under certain circumstances, rodents display some degree of difficulty in discriminating quinine and acid stimuli. Here, C57BL/6J mice were trained and tested in a 2-response operant discrimination task. Mice had severe difficulty discriminating citric acid from quinine and 6-n-propylthiouracil (PROP) with performance slightly, but significantly, above chance. In contrast, mice were able to competently discriminate sucrose from citric acid, NaCl, quinine, and PROP. In another experiment, mice that were conditioned to avoid quinine by pairings with LiCl injections subsequently suppressed licking responses to quinine and citric acid but not to NaCl or sucrose in a brief-access test, relative to NaCl-injected control animals. However, mice that were conditioned to avoid citric acid did not display cross-generalization to quinine. These mice significantly suppressed licking only to citric acid, and to a much lesser extent NaCl, compared with controls. Collectively, the findings from these experiments suggest that in mice, citric acid and quinine share chemosensory features making discrimination difficult but are not perceptually identical. PMID:21421543

Treesukosol, Yada; Mathes, Clare M; Spector, Alan C

2011-06-01

20

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

PubMed Central

SUMMARY 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 (NETP/P) was nearly abolished. NET+/P and NETP/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

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.

2013-01-01

21

Software defined networking (SDN) over space division multiplexing (SDM) optical networks: features, benefits and experimental demonstration.  

PubMed

We present results from the first demonstration of a fully integrated SDN-controlled bandwidth-flexible and programmable SDM optical network utilizing sliceable self-homodyne spatial superchannels to support dynamic bandwidth and QoT provisioning, infrastructure slicing and isolation. Results show that SDN is a suitable control plane solution for the high-capacity flexible SDM network. It is able to provision end-to-end bandwidth and QoT requests according to user requirements, considering the unique characteristics of the underlying SDM infrastructure. PMID:24663655

Amaya, N; Yan, S; Channegowda, M; Rofoee, B R; Shu, Y; Rashidi, M; Ou, Y; Hugues-Salas, E; Zervas, G; Nejabati, R; Simeonidou, D; Puttnam, B J; Klaus, W; Sakaguchi, J; Miyazawa, T; Awaji, Y; Harai, H; Wada, N

2014-02-10

22

Leukocyte rolling: a prominent feature of venules in intact skin of anesthetized hairless mice.  

PubMed

Leukocyte (white blood cell; WBC) rolling in postcapillary venules is a frequently reported phenomenon in the microvasculature of experimental preparations. In most reports where this phenomenon has been systematically studied the confounding effects of various procedures associated with tissue preparation have been present. Thus there is sparse information on the extent of WBC rolling under fairly normal conditions. Here observations and features of this phenomenon in venules in the intact skin microvasculature of the homozygous hairless mouse ear are described. One venule in each of 10 mice was observed and continuously video recorded for 90 min. The parameters determined (mean +/- SD) were diameter, 15.9 +/- 3.1 microns; red blood cell velocity, 359 +/- 227 micron/s; flux of rolling WBCs, 3.2 +/- 2.6/min; velocity of rolling WBCs, 9.6 +/- 1.1 micron/s; systemic WBC count (CWBC), 3,220 +/- 1,072/microliters; and total WBC flux, estimated as the product of CWBC and calculated venule blood flow, 8.5 +/- 3.0/min. Overall, 44.8 +/- 13.8% of the total WBC flux exhibited rolling with a velocity that was 3.6 +/- 2.9% of the red blood cell velocity. During the total 15-h combined observation time, no WBCs were seen to be adherent. These findings establish that in small venules of normal skin, WBC rolling is common, since on the average nearly one of two WBCs delivered to the venule exhibits rolling. Furthermore, because the translational rolling speed is very low, they contribute to the marginated pool, which, according to the present data, might be better termed the "rolling" pool. PMID:1733306

Mayrovitz, H N

1992-01-01

23

[The features of defensive behavior of early postnatal C57BL/6 mice in response to the predator odor].  

PubMed

The ontogeny of defensive behavior of laboratory rodents underlying many experimental models has been still poorly understood. In this study, we investigated the age-related features of behavior of 8- and 12-day-old laboratory mice in response to presentation of the predator odor using olfactory discrimination method and determination of sleep and wakefulness states. Transcription factor c-Fos was used as a molecular marker to map the activity of the reticular formation. Neither preference nor avoidance of the predator odor was detected, as assessed by the proportion of time spent in the compartment with this odor. However, a reduction of locomotor activity and an increase in the proportion of sleep were found in 8-day-old mice, which corresponded to the c-Fos expression in the oral pontine reticular nucleus. The increase in the proportion of passive wakefulness was found in 12-day-old mice, it could be regarded as an early form of freezing. Thus, we identified age-specific features of the defensive behavior of early postnatal mice as well as the dynamics of its formation. PMID:22690551

Burenkova, O V; Aleksandrova, E A; Zara?skaia, I Iu

2012-01-01

24

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

PubMed Central

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

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

2013-01-01

25

Treatment with CB2 agonist JWH-133 reduces histological features associated with erectile dysfunction in hypercholesterolemic mice.  

PubMed

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

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

2013-01-01

26

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

PubMed Central

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

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

2012-01-01

27

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

PubMed

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

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

2015-03-01

28

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

E-print Network

. The enzymatic degradation of brain 5-HT is mainly mediated by monoamine oxidase (MAO)A and, in the absence of this enzyme, by its cognate isoenzyme MAOB. MAOA and A/B knockout (KO) mice display high 5-HT levels, particularly during early developmental stages...

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

29

Inherited glaucoma in DBA/2J mice: pertinent disease features for studying the neurodegeneration.  

PubMed

The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8-9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy. PMID:16332275

Libby, Richard T; Anderson, Michael G; Pang, Iok-Hou; Robinson, Zachary H; Savinova, Olga V; Cosma, I Mihai; Snow, Amy; Wilson, Lawriston A; Smith, Richard S; Clark, Abbot F; John, Simon W M

2005-01-01

30

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

SciTech Connect

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.

Klebig, M.L.; Woychik, R.P. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Wilkinson, J.E. [Univ. of Tennessee, Knoxville, TN (United States); Geisler, J.G. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)]|[Univ. of Tennessee, Knoxville, TN (United States)

1995-05-23

31

Fabry disease: preclinical studies demonstrate the effectiveness of alpha-galactosidase A replacement in enzyme-deficient mice.  

PubMed

Preclinical studies of enzyme-replacement therapy for Fabry disease (deficient alpha-galactosidase A [alpha-Gal A] activity) were performed in alpha-Gal A-deficient mice. The pharmacokinetics and biodistributions were determined for four recombinant human alpha-Gal A glycoforms, which differed in sialic acid and mannose-6-phosphate content. The plasma half-lives of the glycoforms were approximately 2-5 min, with the more sialylated glycoforms circulating longer. After intravenous doses of 1 or 10 mg/kg body weight were administered, each glycoform was primarily recovered in the liver, with detectable activity in other tissues but not in the brain. Normal or greater activity levels were reconstituted in various tissues after repeated doses (10 mg/kg every other day for eight doses) of the highly sialylated AGA-1 glycoform; 4 d later, enzyme activity was retained in the liver and spleen at levels that were, respectively, 30% and 10% of that recovered 1 h postinjection. Importantly, the globotriaosylceramide (GL-3) substrate was depleted in various tissues and plasma in a dose-dependent manner. A single or repeated doses (every 48 h for eight doses) of AGA-1 at 0.3-10.0 mg/kg cleared hepatic GL-3, whereas higher doses were required for depletion of GL-3 in other tissues. After a single dose of 3 mg/kg, hepatic GL-3 was cleared for > or =4 wk, whereas cardiac and splenic GL-3 reaccumulated at 3 wk to approximately 30% and approximately 10% of pretreatment levels, respectively. Ultrastructural studies demonstrated reduced GL-3 storage posttreatment. These preclinical animal studies demonstrate the dose-dependent clearance of tissue and plasma GL-3 by administered alpha-Gal A, thereby providing the in vivo rationale-and the critical pharmacokinetic and pharmacodynamic data-for the design of enzyme-replacement trials in patients with Fabry disease. PMID:11115376

Ioannou, Y A; Zeidner, K M; Gordon, R E; Desnick, R J

2001-01-01

32

Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy  

PubMed Central

The fatty acid transport protein family is a group of evolutionarily conserved proteins that are involved in the cellular uptake and metabolism of long and very long chain fatty acids. However, little is known about their respective physiological roles. To analyze the functional significance of fatty acid transport protein 4 (Fatp4, Slc27a4), we generated mice with a targeted disruption of the Fatp4 gene. Fatp4-null mice displayed features of a neonatally lethal restrictive dermopathy. Their skin was characterized by hyperproliferative hyperkeratosis with a disturbed epidermal barrier, a flat dermal–epidermal junction, a reduced number of pilo-sebaceous structures, and a compact dermis. The rigid skin consistency resulted in an altered body shape with facial dysmorphia, generalized joint flexion contractures, and impaired movement including suckling and breathing deficiencies. Lipid analysis demonstrated a disturbed fatty acid composition of epidermal ceramides, in particular a decrease in the C26:0 and C26:0-OH fatty acid substitutes. These findings reveal a previously unknown, essential function of Fatp4 in the formation of the epidermal barrier. PMID:12821645

Herrmann, Thomas; van der Hoeven, Frank; Gröne, Hermann-Josef; Stewart, Adrian Francis; Langbein, Lutz; Kaiser, Iris; Liebisch, Gerhard; Gosch, Isabella; Buchkremer, Florian; Drobnik, Wolfgang; Schmitz, Gerd; Stremmel, Wolfgang

2003-01-01

33

Chemically induced mammary gland adenomyoepitheliomas and myoepithelial carcinomas of mice. Immunohistochemical and ultrastructural features.  

PubMed

Myoepithelial cell tumors of the mammary gland have been observed in several mammalian species and are composed of a single cell type (myoepithelium) or, more often, present as a biphasic process including neoplastic ductal epithelial cells. In dogs, these are common tumors, but in humans they are rare neoplasms of the breast, and little is yet known of their pathogenesis, particularly with respect to myoepithelial origin. The present report describes bicellular mammary gland tumors arising from the duct epithelium that were induced in (C57BL/6NCr X DBA/2NCr)F1 (B6D2F1) mice by four weekly oral applications of 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) starting at 8 weeks of age. Mammary tumors developed 7 to 8 months later in 14 of 57 mice, and most showed great morphologic resemblance to human adenomyoepitheliomas and myoepithelial carcinomas. Ultrastructurally, the induced tumors were composed of cuboidal epithelium with a microvillous border originating from the lining duct epithelium and plump oval or highly elongated cells that were identified as myoepithelial in origin. These spindle cells contained abundant microfilaments in parallel orientation, some with focal densities and intermediate filaments that frequently formed loose bundles or compact tonofibrils. The myoepithelial cells possessed well-developed desmosomes and plasma membrane caveolae and were regularly bordered by single or reduplicated basement membranes. By immunohistochemistry, strong immunoreactivity was observed for actin in the myoepithelial tumor component only, whereas cytokeratin was variably present in both duct epithelium and myoepithelium. Neoplastic myoepithelial cells stained purple with phosphotungstic acid hematoxylin (PTAH) and brilliant red with Masson's trichrome. It is suggested that DMBA-induced mouse mammary gland adenomyoepitheliomas and myoepithelial carcinomas may serve as very useful animal models to study myoepithelial tumorigenesis. PMID:1690510

Rehm, S

1990-03-01

34

Chemically induced mammary gland adenomyoepitheliomas and myoepithelial carcinomas of mice. Immunohistochemical and ultrastructural features.  

PubMed Central

Myoepithelial cell tumors of the mammary gland have been observed in several mammalian species and are composed of a single cell type (myoepithelium) or, more often, present as a biphasic process including neoplastic ductal epithelial cells. In dogs, these are common tumors, but in humans they are rare neoplasms of the breast, and little is yet known of their pathogenesis, particularly with respect to myoepithelial origin. The present report describes bicellular mammary gland tumors arising from the duct epithelium that were induced in (C57BL/6NCr X DBA/2NCr)F1 (B6D2F1) mice by four weekly oral applications of 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) starting at 8 weeks of age. Mammary tumors developed 7 to 8 months later in 14 of 57 mice, and most showed great morphologic resemblance to human adenomyoepitheliomas and myoepithelial carcinomas. Ultrastructurally, the induced tumors were composed of cuboidal epithelium with a microvillous border originating from the lining duct epithelium and plump oval or highly elongated cells that were identified as myoepithelial in origin. These spindle cells contained abundant microfilaments in parallel orientation, some with focal densities and intermediate filaments that frequently formed loose bundles or compact tonofibrils. The myoepithelial cells possessed well-developed desmosomes and plasma membrane caveolae and were regularly bordered by single or reduplicated basement membranes. By immunohistochemistry, strong immunoreactivity was observed for actin in the myoepithelial tumor component only, whereas cytokeratin was variably present in both duct epithelium and myoepithelium. Neoplastic myoepithelial cells stained purple with phosphotungstic acid hematoxylin (PTAH) and brilliant red with Masson's trichrome. It is suggested that DMBA-induced mouse mammary gland adenomyoepitheliomas and myoepithelial carcinomas may serve as very useful animal models to study myoepithelial tumorigenesis. Images Figure 1 to 4 Figure 5 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:1690510

Rehm, S.

1990-01-01

35

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

PubMed Central

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

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

36

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

PubMed

The application of boron neutron capture therapy (BNCT) following liposomal delivery of a (10)B-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 × 10(12) neutrons per cm(2) (±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

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

2013-04-16

37

Keratin 16 null mice develop palmoplantar keratoderma, a hallmark feature of pachyonychia congenita and related disorders  

PubMed Central

Keratin 16 (KRT16 in human, Krt16 in mouse), a type I intermediate filament protein, is constitutively expressed in epithelial appendages and is induced in the epidermis upon wounding and other stressors. Mutations altering the coding sequence of KRT16 cause Pachyonychia Congenita (PC), a rare autosomal dominant disorder characterized by hypertrophic nail dystrophy, oral leukokeratosis, and palmoplantar keratoderma (PPK). PPK associated with PC are extremely painful and compromise patient mobility, making them the most debilitating PC symptom. In this study, we show that, although inherited in a recessive fashion, the inactivation of Krt16 in mice consistently causes oral lesions as well as PPK-like hyperkeratotic calluses on Krt16?/? front and hind paws, which severely compromise the animals’ ability to walk. Our findings call into question the view that PC-related PPK arise exclusively as a gain-of-function on the account of dominantly acting mutated keratins, and highlight the key role of modifiers in the clinical heterogeneity of PC symptoms. PMID:22336941

Lessard, Juliane C.; Coulombe, Pierre A.

2011-01-01

38

Motor Neuron Rescue in Spinal Muscular Atrophy Mice Demonstrates That Sensory-Motor Defects Are a Consequence, Not a Cause, of Motor Neuron Dysfunction  

PubMed Central

The loss of motor neurons (MNs) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however, it is unclear whether this phenotype autonomously originates within the MN. To address this question, we developed an inducible mouse model of severe SMA that has perinatal lethality, decreased motor function, motor unit pathology, and hyperexcitable MNs. Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs and demonstrate that MN rescue significantly improves all phenotypes and pathologies commonly described in SMA mice. MN rescue also corrects hyperexcitability in SMA motor neurons and prevents sensory-motor synaptic stripping. Survival in MN-rescued SMA mice is extended by only 5 d, due in part to failed autonomic innervation of the heart. Collectively, this work demonstrates that the SMA phenotype autonomously originates in MNs and that sensory-motor synapse loss is a consequence, not a cause, of MN dysfunction. PMID:22423102

Gogliotti, Rocky G.; Quinlan, Katharina A.; Barlow, Courtenay B.; Heier, Christopher R.; Heckman, C. J.

2012-01-01

39

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

PubMed Central

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

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

2012-01-01

40

A Structural Feature of the Non-Peptide Ligand Interactions with Mice Mu-Opioid Receptors.  

PubMed

By binding to and activating the G-protein coupled ?-, ?- and ?-opioid receptors in the central nervous system, opiates are known to induce analgesic and sedative effects. In particular, non-peptide opioid ligands are often used in clinical applications to induce these therapeutically beneficial effects, due to their superior pharmacokinetics and bioavailability in comparison to endogenous neuropeptides. However, since opioid alkaloids are highly addictive substances, it is necessary to understand the exact mechanisms of their actions, specifically the ligand-binding properties of the target receptors, in order to safely apply opiates for therapeutic purposes. Using an in silico molecular docking approach (AutoDock Vina) combined with two-step cluster analysis, we have computationally obtained the docking scores and the ligand-binding pockets of twelve representative non-peptide non-endogenous agonists and antagonists at the crystallographically identified ?-opioid receptor. Our study predicts the existence of two main binding sites that are congruently present in all opioid receptor types. Interestingly, in terms of the agonist or antagonist properties of the substances on the receptors, the clustering analysis suggests a relationship with the position of the ligand-binding pockets, particularly its depth within the receptor structure. Furthermore, the binding affinity of the substances is directly correlated to the proximity of the binding pockets to the extracellular space. In conclusion, the results provide further insights into the structural features of the functional pharmacology of opioid receptors, suggesting the importance of the binding position of non-peptide agonists and antagonists- specifically the distance and the level of exposure to the extracellular space- to their dissociation kinetics and subsequent potency. PMID:25360566

Noori, Hamid R; Mücksch, Christian; Urbassek, Herbert M

2014-10-30

41

The development of autoimmune features in aging mice is closely associated with alterations of the peripheral CD4? T-cell compartment.  

PubMed

Some signs of potential autoimmunity, such as the appearance of antinuclear antibodies (ANAs) become prevalent with age. In most cases, elderly people with ANAs remain healthy. Here, we investigated whether the same holds true for inbred strains of mice. Indeed, we show that most mice of the C57BL/6 (B6) strain spontaneously produced IgG ANA at 8-12 months of age, showed IgM deposition in kidneys and lymphocyte infiltrates in submandibular salivary glands. Despite all of this, the mice remained healthy. ANA production is likely CD4(+) T-cell dependent, since old (40-50 weeks of age) B6 mice deficient for MHC class II do not produce IgG ANAs. BM chimeras showed that ANA production was not determined by age-related changes in radiosensitive, hematopoietic progenitor cells, and that the CD4(+) T cells that promote ANA production were radioresistant. Thymectomy of B6 mice at 5 weeks of age led to premature alterations in T-cell homeostasis and ANA production, by 15 weeks of age, similar to that in old mice. Our findings suggest that a disturbed T-cell homeostasis may drive the onset of some autoimmune features. PMID:25044476

Nusser, Anja; Nuber, Natko; Wirz, Oliver F; Rolink, Hannie; Andersson, Jan; Rolink, Antonius

2014-10-01

42

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

SciTech Connect

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.

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

2013-12-15

43

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

PubMed Central

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

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

44

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

PubMed Central

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

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

2014-01-01

45

Temporal evolution of neurophysiological and behavioral features of synapsin I/II/III triple knock-out mice  

PubMed Central

Summary Deletion of one or more synapsin genes in mice results in a spontaneous epilepsy. In these animals, seizures can be evoked by opening or moving the cage. Aim of the present study was to characterize the evolution of the epileptic phenotype by neurophysiological examination and behavioral observation in synapsin triple knock-out (Syn-TKO) mice. Syn-TKO mice were studied from 20 postnatal days (PND) up to 6 months of age by video-EEG recording and behavioral observation. Background EEG spectral analysis was performed and data were compared to WT animals. Syn-TKO revealed rare spontaneous seizures and increased susceptibility to evoked seizures in mice from 60 to 100 PND. Spontaneous and evoked seizures presented similar duration and morphology. At times, seizures were followed by a post-ictal phase characterized by a 4 Hz rhythmic activity and immobility of the animal. Spectral analysis of background EEG evidenced a slowing of the theta-alpha peak in Syn-TKO mice compared to WT mice within the period from PND 40 to 100. These data indicate that Syn-TKO mice do not exhibit a linear progression of the epileptic phenotype, with the period corresponding to a higher susceptibility to evoked seizures characterized by background EEG slowing. This aspect might be connected to brain dysfunction often associated to epilepsy in the interictal period. PMID:22846639

Cambiaghi, Marco; Cursi, Marco; Monzani, Elena; Benfenati, Fabio; Comi, Giancarlo; Minicucci, Fabio; Valtorta, Flavia; Leocani, Letizia

2013-01-01

46

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

SciTech Connect

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.

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

47

Demonstration of 22nm SRAM features with patternable hafnium oxide-based resist material using electron-beam lithography  

NASA Astrophysics Data System (ADS)

To fulfill the requirements of future technology nodes new resists with high resolution, high sensitivity and low LWR and LER respectively are needed. A new inorganic non-chemically amplified resist (XE15IB, an experimental resist provided by Inpria Corp.) was investigated. The resist is spin-cast from aqueous solution and is based on hafnium oxide. Metal oxide based resist as XE15IB supersede other resist materials due to its high etch resistance.1, 2 This new material can be considered as a direct patternable spin on hard mask. XE15IB was processed in a 300mm complementary metal oxide semiconductor (CMOS) manufacturing environment and exposed on a 50 kV VISTEC SB3050DW variable shaped electron beam direct writer at Fraunhofer Center Nanoelectronic Technologies (CNT). The resist was evaluated in terms of contrast, sensitivity and resolution. The process characteristics required for CMOS manufacturing such as delay stability were also examined. Furthermore, by printing a large static random access Memory (SRAM) pattern (design CD of 22 nm), the exposure of a real application pattern was demonstrated.

Thrun, Xaver; Choi, Kang-Hoon; Freitag, Martin; Grenville, Andrew; Gutsch, Manuela; Hohle, Christoph; Stowers, Jason K.; Bartha, Johann W.

2012-03-01

48

FVB/NJ mice demonstrate a youthful sensitivity to noise-induced hearing loss and provide a useful genetic model for the study of neural hearing loss  

PubMed Central

The hybrid mouse diversity panel (HMDP), a panel of 100 strains, has been employed in genome wide association studies (GWAS) to study complex traits in mice. Hearing is a complex trait and the CBA/CaJ mouse strain is a widely used model for age-related hearing loss (ARHI) and noise induced hearing loss (NIHL). The CBA/CaJ strain's youthful sensitivity to noise and limited age-related loss led us to attempt to identify additional strains segregating a similar phenotype for our panel. FVB/NJ is part of the HMDP and has been previously described as having a similar ARHI phenotype to CBA/CaJ. For these reasons, we have studied the FVB/NJ mouse for ARHI and NIHL phenotypes in hopes of incorporating its phenotype into HMDP studies. We demonstrate that FVB/NJ exhibits ARHI at an earlier age than CBA/CaJ and young FVB/NJ mice are vulnerable to NIHL up until 10 to 12 weeks. This suggests that FVB/NJ may be used as an additional genetic model for neural forms of progressive hearing loss and for the study of youthful sensitivity to noise. PMID:24707282

Ho, Maria K.; Li, Xin; Wang, Juemei; Ohmen, Jeffrey D.; Friedman, Rick A.

2014-01-01

49

Smallpox vaccine with integrated IL-15 demonstrates enhanced in vivo viral clearance in immunodeficient mice and confers long term protection against a lethal monkeypox challenge in cynomolgus monkeys  

PubMed Central

Despite the eradication of smallpox, there is heightened concern that it could be reintroduced as a result of intentional release of Variola major virus through an act of bioterrorism. The live vaccine that was pivotal in the eradication of smallpox though considered a gold standard for its efficacy still retains sufficient residual virulence that can cause life-threatening sequelae especially in immune deficient individuals. Therefore, a safer smallpox vaccine that can match the efficacy of first generation vaccines is urgently needed. We previously reported that the integration of human IL-15 cytokine into the genome of Wyeth strain of vaccinia (Wyeth/IL-15), the same strain as the licensed vaccine, generates a vaccine with superior immunogenicity and efficacy in a mouse model. We now demonstrate that Wyeth/IL-15 is non-lethal to athymic nude mice when administered intravenously at a dose of 107 plaque forming units and it undergoes enhanced in vivo clearance in these immune deficient mice. Furthermore, a majority of cynomolgus monkeys vaccinated with vaccinia viruses with integrated IL-15, when challenged 3 years later with a lethal dose of monkeypox virus displayed milder clinical manifestations with complete recovery supporting the utility of Wyeth/IL-15 for contemporary populations as a safer and efficacious smallpox vaccine. PMID:20728526

Zielinski, Rafal J.; Smedley, Jeremy V.; Perera, Pin-Yu; Silvera, Peter M.; Waldmann, Thomas A.; Capala, Jacek; Perera, Liyanage P.

2010-01-01

50

Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration  

PubMed Central

Mechanisms of brain and retinal iron homeostasis have become subjects of increased interest after the discovery of elevated iron levels in brains of patients with Alzheimer's disease and retinas of patients with age-related macular degeneration. To determine whether the ferroxidase ceruloplasmin (Cp) and its homolog hephaestin (Heph) are important for retinal iron homeostasis, we studied retinas from mice deficient in Cp and/or Heph. In normal mice, Cp and Heph localize to Müller glia and retinal pigment epithelium, a blood–brain barrier. Mice deficient in both Cp and Heph, but not each individually, had a striking, age-dependent increase in retinal pigment epithelium and retinal iron. The iron storage protein ferritin was also increased in Cp–/–Heph–/Y retinas. After retinal iron levels had increased, Cp–/–Heph–/Y mice had age-dependent retinal pigment epithelium hypertrophy, hyperplasia and death, photoreceptor degeneration, and subretinal neovascularization, providing a model of some features of the human retinal diseases aceruloplasminemia and age-related macular degeneration. This pathology indicates that Cp and Heph are critical for CNS iron homeostasis and that loss of Cp and Heph in the mouse leads to age-dependent retinal neurodegeneration, providing a model that can be used to test the therapeutic efficacy of iron chelators and antiangiogenic agents. PMID:15365174

Hahn, Paul; Qian, Ying; Dentchev, Tzvete; Chen, Lin; Beard, John; Harris, Zena Leah; Dunaief, Joshua L.

2004-01-01

51

Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apolipoprotein E-deficient mice. Demonstration of epitopes of oxidized low density lipoprotein in human plasma.  

PubMed Central

Many reactive products may be formed when LDL undergoes lipid peroxidation, which in turn can react with lipids, apoproteins, and proteins, generating immunogenic neoepitopes. Autoantibodies recognizing model epitopes of oxidized low density lipoprotein, such as malondialdehydelysine, occur in plasma and in atherosclerotic lesions of humans and animals. Because apo E-deficient mice develop particularly high titers of such autoantibodies, we used their spleens to clone 13 monoclonal antibodies to various epitopes of oxidized LDL ("E0 antibodies"). Binding and competitive RIAs demonstrated significant differences in fine specificity even between E0 antibodies initially selected for binding to the same screening antigen. For example, some E0 antibodies selected for binding to malondialdehyde-LDL also recognized copper oxidized LDL, acrolein-LDL, or LDL modified by arachidonic or linoleic acid oxidation products. Circulating IgG and IgM autoantibodies binding to copper-oxidized LDL, 4-hydroxynonenal-LDL, acrolein-LDL, and LDL modified with arachidonic or linoleic acid oxidation products were found in apo E-deficient mice, suggesting that the respective antigens are formed in vivo. Epitopes recognized by some of the E0 monoclonal antibodies were also found on human circulating LDL. Each of the E0 monoclonal antibodies immunostained rabbit and human atherosclerotic lesions, and some of them yielded distinct staining patterns in advanced lesions. Together, this suggests that the natural monoclonal antibodies recognize different epitopes of complex structures formed during oxidation of lipoproteins, or epitopes formed independently at different lesion sites. Our data demonstrate that a profound immunological response to a large number of different epitopes of oxidized lipoproteins occurs in vivo. The availability of "natural" monoclonal autoantibodies should facilitate the identification of specific epitopes inducing this response. PMID:8698873

Palinski, W; Hörkkö, S; Miller, E; Steinbrecher, U P; Powell, H C; Curtiss, L K; Witztum, J L

1996-01-01

52

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L.

1982-01-01

53

Loss of Magel2, a Candidate Gene for Features of Prader-Willi Syndrome, Impairs Reproductive Function in Mice  

PubMed Central

Background MAGEL2 is one of several genes typically inactivated in the developmental obesity disorder Prader-Willi syndrome (PWS). The physiological consequences of loss of MAGEL2, but without the concurrent loss of other PWS genes, are not well understood. Gene-targeted mutation of Magel2 in mice disrupts circadian rhythm and metabolism causing reduced total activity, reduced weight gain before weaning, and increased adiposity after weaning. Principal Findings We now show that loss of Magel2 in mice causes reduced fertility in both males and females through extended breeding intervals and early reproductive decline and termination. Female Magel2-null mice display extended and irregular estrous cycles, while males show decreased testosterone levels, and reduced olfactory preference for female odors. Conclusions Our results suggest that loss of MAGEL2 contributes to the reproductive deficits seen in people with PWS, and further highlights the role of normal circadian rhythm in the maintenance of fertility. PMID:19172181

Mercer, Rebecca E.; Wevrick, Rachel

2009-01-01

54

Fibrotic response as a distinguishing feature of resistance and susceptibility to pulmonary infection with Mycobacterium tuberculosis in mice.  

PubMed

The differential susceptibility of inbred mouse strains DBA/2J (susceptible) and C57BL/6J (resistant) to pulmonary tuberculosis following aerosol infection is under complex genetic control. In this report, transcriptional profiling with RNAs from Mycobacterium tuberculosis-infected lungs was used to investigate the physiological response, cell type, and biochemical pathways underlying differential susceptibility to infection. Statistical analysis of cDNA-based microarrays revealed that 1,097 transcripts showed statistically significant changes in abundance (changes of > or = 1.5-fold) in at least one of four experimental group comparisons (C57BL/6J [day 0] versus DBA/2J [day 0] mice, C57BL/6J [day 90] versus DBA/2J [day 90] mice, C57BL/6J [day 90] versus C57BL/6J [day 0] mice, or DBA/2J [day 90] versus DBA/2J [day 0] mice). A group of genes showing very high degrees of significance (changes of > or = 2.0-fold) displayed enrichment for transcripts associated with tissue remodeling and the fibrotic response. The differential expression of fibrotic response genes (Sparc, Col1a1, Col1a2, Col4a1, and Col4a2) in the infected lungs of the two mouse strains was validated by another microarray platform (Affymetrix oligonucleotide chips) and by reverse transcription-PCR. Furthermore, the differential expression of additional genes known to be associated with fibrosis (Mmp2, Timp1, and Arg1) was also validated by these approaches. Overall, these results identify the differential fibrotic response as a pathological basis for the high susceptibility of DBA/2J mice to pulmonary tuberculosis. PMID:17938213

Marquis, Jean-François; Nantel, André; LaCourse, Ronald; Ryan, Lynn; North, Robert J; Gros, Philippe

2008-01-01

55

Fibrotic Response as a Distinguishing Feature of Resistance and Susceptibility to Pulmonary Infection with Mycobacterium tuberculosis in Mice? †  

PubMed Central

The differential susceptibility of inbred mouse strains DBA/2J (susceptible) and C57BL/6J (resistant) to pulmonary tuberculosis following aerosol infection is under complex genetic control. In this report, transcriptional profiling with RNAs from Mycobacterium tuberculosis-infected lungs was used to investigate the physiological response, cell type, and biochemical pathways underlying differential susceptibility to infection. Statistical analysis of cDNA-based microarrays revealed that 1,097 transcripts showed statistically significant changes in abundance (changes of ?1.5-fold) in at least one of four experimental group comparisons (C57BL/6J [day 0] versus DBA/2J [day 0] mice, C57BL/6J [day 90] versus DBA/2J [day 90] mice, C57BL/6J [day 90] versus C57BL/6J [day 0] mice, or DBA/2J [day 90] versus DBA/2J [day 0] mice). A group of genes showing very high degrees of significance (changes of ?2.0-fold) displayed enrichment for transcripts associated with tissue remodeling and the fibrotic response. The differential expression of fibrotic response genes (Sparc, Col1a1, Col1a2, Col4a1, and Col4a2) in the infected lungs of the two mouse strains was validated by another microarray platform (Affymetrix oligonucleotide chips) and by reverse transcription-PCR. Furthermore, the differential expression of additional genes known to be associated with fibrosis (Mmp2, Timp1, and Arg1) was also validated by these approaches. Overall, these results identify the differential fibrotic response as a pathological basis for the high susceptibility of DBA/2J mice to pulmonary tuberculosis. PMID:17938213

Marquis, Jean-François; Nantel, André; LaCourse, Ronald; Ryan, Lynn; North, Robert J.; Gros, Philippe

2008-01-01

56

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

PubMed Central

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

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

2014-01-01

57

Biological features of core networks that result from a high-fat diet in hepatic and pulmonary tissues in mammary tumour-bearing, obesity-resistant mice.  

PubMed

We previously demonstrated that the chronic consumption of a high-fat diet (HFD) promotes lung and liver metastases of 4T1 mammary carcinoma cells in obesity-resistant BALB/c mice. To examine early transcriptional responses to tumour progression in the liver and lungs of HFD-fed mice, 4-week-old female BALB/c mice were divided into four groups: sham-injected, control diet (CD)-fed; sham-injected, HFD-fed (SH); 4T1 cell-injected, CD-fed (TC); 4T1 cell-injected, HFD-fed (TH). Following 16 weeks of either a CD or HFD, 4T1 cells were injected into the mammary fat pads of mice in the TC and TH groups and all mice were continuously fed identical diets. At 14 d post-injection, RNA was isolated from hepatic and pulmonary tissues for microarray analysis of mRNA expression. Functional annotation and core network analyses were conducted for the TH/SH Unique gene set. Inflammation in hepatic tissues and cell mitosis in pulmonary tissues were the most significant biological functions in the TH/SH Unique gene set. The biological core networks of the hepatic TH/SH Unique gene set were characterised as those genes involved in the activation of acute inflammatory responses (Orm1, Lbp, Hp and Cfb), disordered lipid metabolism and deregulated cell cycle progression. Networks of the pulmonary Unique gene set displayed the deregulation of cell cycle progression (Cdc20, Cdk1 and Bub1b). These HFD-influenced alterations may have led to favourable conditions for the formation of both pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as the infiltration and proliferation of metastatic tumour cells. PMID:23234678

Kim, Eun Ji; Oh, Hea Young; Heo, Hyoung-Sam; Hong, Ji Eun; Jung, Sung-Jae; Lee, Ki Won; Park, Jong Hoon; Hur, Cheol-Goo; Park, Jung Han Yoon

2013-07-28

58

Induction of oxazolone-mediated features of atopic dermatitis in NOD-scid IL2R?null mice engrafted with human peripheral blood mononuclear cells  

PubMed Central

SUMMARY Animal models mimicking human diseases have been used extensively to study the pathogenesis of autoimmune diseases and the efficacy of potential therapeutics. They are, however, limited with regard to their similarity to the human disease and cannot be used if the antagonist and its cognate receptor require high similarity in structure or binding. Here, we examine the induction of oxazolone-mediated features of atopic dermatitis (AD) in NOD-scid IL2R?null mice engrafted with human peripheral blood mononuclear cells (PBMC). The mice developed the same symptoms as immunocompetent BALB/c mice. Histological alterations induced by oxazolone were characterized by keratosis, epithelial hyperplasia and influx of inflammatory cells into the dermis and epidermis. The cellular infiltrate was identified as human leukocytes, with T cells being the major constituent. In addition, oxazolone increased human serum IgE levels. The response, however, required the engraftment of PBMC derived from patients suffering from AD, which suggests that this model reflects the immunological status of the donor. Taken together, the model described here has the potential to evaluate the efficacy of therapeutics targeting human lymphocytes in vivo and, in addition, might be developed further to elucidate molecular mechanisms inducing and sustaining flares of the disease. PMID:22822046

Nolte, Thomas; Zadeh-Khorasani, Maryam; Safarov, Orkhan; Rueff, Franziska; Varga, Rita; Herbach, Nadja; Wanke, Rüdiger; Wollenberg, Andreas; Mueller, Thomas; Gropp, Roswitha; Wolf, Eckhard; Siebeck, Matthias

2013-01-01

59

Mineralizing Enthesopathy Is a Common Feature of Renal Phosphate-Wasting Disorders Attributed to FGF23 and Is Exacerbated by Standard Therapy in Hyp Mice  

PubMed Central

We have previously confirmed a paradoxical mineralizing enthesopathy as a hallmark of X-linked hypophosphatemia. X-linked hypophosphatemia is the most common of the phosphate-wasting disorders mediated by elevated fibroblast growth factor 23 (FGF23) and occurs as a consequence of inactivating mutations of the PHEX gene product. Despite childhood management of the disease, these complications of tendon and ligament insertion sites account for a great deal of the disease's morbidity into adulthood. It is unclear whether the enthesopathy occurs in other forms of renal phosphate-wasting disorders attributable to high FGF23 levels. Here we describe two patients with autosomal recessive hypophosphatemic rickets due to the Met1Val mutation in dentin matrix acidic phosphoprotein 1 (DMP1). In addition to the biochemical and skeletal features of long-standing rickets with elevated FGF23 levels, these individuals exhibited severe, debilitating, generalized mineralized enthesopathy. These data suggest that enthesophytes are a feature common to FGF23-mediated phosphate-wasting disorders. To address this possibility, we examined a murine model of FGF23 overexpression using a transgene encoding the secreted form of human FGF23 (R176Q) cDNA (FGF23-TG mice). We report that FGF23-TG mice display a similar mineralizing enthesopathy of the Achilles and plantar facial insertions. In addition, we examined the impact of standard therapy for phosphate-wasting disorders on enthesophyte progression. We report that fibrochondrocyte hyperplasia persisted in Hyp mice treated with oral phosphate and calcitriol. In addition, treatment had the untoward effect of further exacerbating the mineralization of fibrochondrocytes that define the bone spur of the Achilles insertion. These studies support the need for newer interventions targeted at limiting the actions of FGF23 and minimizing both the toxicities and potential morbidities associated with standard therapy. PMID:23038738

Karaplis, Andrew C.; Bai, Xiuying; Falet, Jean-Pierre

2012-01-01

60

Dr. Cui's group at Wake Forest has been investigating a newly discovered innate anticancer immunity in a colony of cancer resistant mice, and already demonstrated that the anticancer activity in the mice stems from  

E-print Network

Dr. Cui's group at Wake Forest has been investigating a newly discovered innate anticancer immunity from the innate immune system, specifically from the granulocytes and macrophages. In 2007 immunity in spontaneous regression/complete resistance mice. Proceedings of the National Academy

Wang, Ge

61

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

PubMed

Fibrous dysplasia of bone (FD) is a crippling skeletal disease associated with postzygotic 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 were 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

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

2014-11-01

62

A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models  

PubMed Central

Frequent infusions of intravenous factor VIII (FVIII) are required to prevent bleeding associated with hemophilia A. To reduce the treatment burden, recombinant FVIII with a longer half-life was developed without changing the protein structure. FVIII–polyethylene glycol (PEG) conjugates were prepared using an enzymatic process coupling PEG (ranging from 10 to 80 kDa) selectively to a unique O-linked glycan in the FVIII B-domain. Binding to von Willebrand factor (VWF) was maintained for all conjugates. Upon cleavage by thrombin, the B-domain and the associated PEG were released, generating activated FVIII (FVIIIa) with the same primary structure and specific activity as native FVIIIa. In both FVIII- and VWF-deficient mice, the half-life was found to increase with the size of PEG. In vivo potency and efficacy of FVIII conjugated with a 40-kDa PEG (N8-GP) and unmodified FVIII were not different. N8-GP had a longer duration of effect in FVIII-deficient mouse models, approximately a twofold prolonged half-life in mice, rabbits, and cynomolgus monkeys; however, the prolongation was less pronounced in rats. Binding capacity of N8-GP on human monocyte-derived dendritic cells was reduced compared with unmodified FVIII, resulting in several-fold reduced cellular uptake. In conclusion, N8-GP has the potential to offer efficacious prevention and treatment of bleeds in hemophilia A at reduced dosing frequency. PMID:23335368

Kjalke, Marianne; Karpf, Ditte M.; Balling, Kristoffer W.; Johansen, Peter B.; Elm, Torben; Řvlisen, Kristine; Möller, Flemming; Holmberg, Heidi L.; Gudme, Charlotte N.; Persson, Egon; Hilden, Ida; Pelzer, Hermann; Rahbek-Nielsen, Henrik; Jespersgaard, Christina; Bogsnes, Are; Pedersen, Anette A.; Kristensen, Anne K.; Peschke, Bernd; Kappers, Wendy; Rode, Frederik; Thim, Lars; Tranholm, Mikael; Ezban, Mirella; Olsen, Eva H. N.; Bjřrn, Sřren E.

2013-01-01

63

Genetic engineering of carbohydrate biosynthetic pathways in transgenic mice demonstrates cell cycle-associated regulation of glycoconjugate production in small intestinal epithelial cells.  

PubMed

Proliferation, migration-associated differentiation, and cell death occur continuously and in a spatially well-organized fashion along the crypt-villus axis of the mouse small intestine, making it an attractive system for studying how these processes are regulated and interrelated. A pathway for producing glycoconjugates was engineered in adult FVB/N transgenic mice by expressing a human alpha 1,3/4-fucosyltransferase (alpha 1,3/4-FT; EC 2.4.1.65) along the length of this crypt-villus axis. The alpha 1,3/4-FT can use lacto-N-tetraose or lacto-neo-N-tetraose core chains to generate Lewis (Le) blood group antigens Le(a) or Le(x), respectively, and H type 1 or H type 2 core chains to produce Leb and Le(y). Single- and multilabel immunohistochemical studies revealed that expression of the alpha 1,3/4-FT results in production of Le(a) and Leb antigens in both undifferentiated proliferated crypt cells and in differentiated postmitotic villus-associated epithelial cells. In contrast, Le(x) antigens were restricted to crypt cells. Villus enterocytes can be induced to reenter the cell cycle by expression of simian virus 40 tumor antigen under the control of a promoter that only functions in differentiated members of this lineage. Bitransgenic animals, generated from a cross of FVB/N alpha 1,3/4-FT with FVB/N simian virus 40 tumor antigen mice, expand the range of Le(x) expression to include villus-associated enterocytes that have reentered the cell cycle. Thus, the fucosylations unveil a proliferation-dependent switch in oligosaccharide production, as defined by a monoclonal antibody specific for the Le(x) epitope. These findings show that genetic engineering of oligosaccharide biosynthetic pathways can be used to define markers for entry into, or progression through, the cell cycle and to identify changes in endogenous carbohydrate metabolism that occur when proliferative status is altered in a manner that is not deleterious to the system under study. PMID:8577733

Bry, L; Falk, P G; Gordon, J L

1996-02-01

64

Genetic engineering of carbohydrate biosynthetic pathways in transgenic mice demonstrates cell cycle-associated regulation of glycoconjugate production in small intestinal epithelial cells.  

PubMed Central

Proliferation, migration-associated differentiation, and cell death occur continuously and in a spatially well-organized fashion along the crypt-villus axis of the mouse small intestine, making it an attractive system for studying how these processes are regulated and interrelated. A pathway for producing glycoconjugates was engineered in adult FVB/N transgenic mice by expressing a human alpha 1,3/4-fucosyltransferase (alpha 1,3/4-FT; EC 2.4.1.65) along the length of this crypt-villus axis. The alpha 1,3/4-FT can use lacto-N-tetraose or lacto-neo-N-tetraose core chains to generate Lewis (Le) blood group antigens Le(a) or Le(x), respectively, and H type 1 or H type 2 core chains to produce Leb and Le(y). Single- and multilabel immunohistochemical studies revealed that expression of the alpha 1,3/4-FT results in production of Le(a) and Leb antigens in both undifferentiated proliferated crypt cells and in differentiated postmitotic villus-associated epithelial cells. In contrast, Le(x) antigens were restricted to crypt cells. Villus enterocytes can be induced to reenter the cell cycle by expression of simian virus 40 tumor antigen under the control of a promoter that only functions in differentiated members of this lineage. Bitransgenic animals, generated from a cross of FVB/N alpha 1,3/4-FT with FVB/N simian virus 40 tumor antigen mice, expand the range of Le(x) expression to include villus-associated enterocytes that have reentered the cell cycle. Thus, the fucosylations unveil a proliferation-dependent switch in oligosaccharide production, as defined by a monoclonal antibody specific for the Le(x) epitope. These findings show that genetic engineering of oligosaccharide biosynthetic pathways can be used to define markers for entry into, or progression through, the cell cycle and to identify changes in endogenous carbohydrate metabolism that occur when proliferative status is altered in a manner that is not deleterious to the system under study. Images Fig. 2 Fig. 3 PMID:8577733

Bry, L; Falk, P G; Gordon, J L

1996-01-01

65

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

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

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

66

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 Central

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

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

67

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1984-01-01

68

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1988-01-01

69

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

PubMed

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

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

2015-02-01

70

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

PubMed Central

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

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

71

Tested Demonstrations.  

ERIC Educational Resources Information Center

Describes three flame test demonstrations including "Student-Presented Demonstrations on the Colors of Transition Metal Complexes,""A Flame Test Demonstration Device," and "Vivid Flame Tests." Preparation and procedures are discussed. Included in the first demonstration is an evaluation scheme for grading student demonstrations. (CW)

Gilbert, George L., Ed.

1988-01-01

72

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1987-01-01

73

Tested Demonstrations.  

ERIC Educational Resources Information Center

Background information (including chemical reactions) and procedures used are provided for (1) three buffer demonstrations and (2) a demonstration of phase transfer catalysis and carbanion formation. (JN)

Gilbert, George L., Ed.

1985-01-01

74

Tested Demonstrations.  

ERIC Educational Resources Information Center

This article details two demonstrations involving color changes. Included are "Manganese Color Reactions" and "Flame Colors Demonstration." Include a list of materials needed, procedures, cautions, and results. (CW)

Gilbert, George L., Ed.

1988-01-01

75

Tested Demonstrations  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1977-01-01

76

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1987-01-01

77

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1981-01-01

78

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1985-01-01

79

Mice with heterozygous deficiency of manganese superoxide dismutase (SOD2) have a skin immune system with features of "inflamm-aging".  

PubMed

Dendritic cells (DC) are central in regulating skin immunity. Immunosenescence is associated with a chronic inflammatory state. Little is known about the contribution of DC to "inflamm-aging". When determining langerhans cell (LC) numbers, we found a 60 % reduction of LC in aged epidermis. Reactive oxygen species(ROS) are linked with aging. The mitochondrial manganese superoxide dismutase (SOD2) is in the first line of antioxidant defense. We investigated the function of DC from SOD2 heterozygous mice (SOD2+/-) and found that at 4 months of age LC numbers are not altered, but activated LC have impaired expression of MHC-II and CD44. Immature SOD2+/- DC produced increased proinflammatory IL-6 and chemokines CXCL1 and CXCL2. Upon challenge SOD2+/- DC accumulated ROS. When activating SOD2+/- DC by LPS they less efficiently upregulated MHC-II, CD86 and CD44. Surprisingly, in vivo contact hypersensitivity (CHS) was enhanced in SOD2+/- mice although SOD2+/- DC were less potent in stimulating wt T cells. However, SOD2+/- T cells showed increased proliferation, even when stimulated with SOD2+/- DC, possibly explaining the increased CHS. Our findings suggest that SOD2 is a molecular candidate in the regulation of "inflamm-aging" conveying both immunosuppressive and proinflammatory signals through alteration of DC and T cell functions. PMID:23856836

Scheurmann, J; Treiber, N; Weber, C; Renkl, A C; Frenzel, D; Trenz-Buback, F; Ruess, A; Schulz, G; Scharffetter-Kochanek, K; Weiss, J M

2014-03-01

80

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

PubMed

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

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

2014-10-01

81

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1987-01-01

82

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1979-01-01

83

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1990-01-01

84

Tested Demonstrations.  

ERIC Educational Resources Information Center

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.…

Gilbert, George L., Ed.

1982-01-01

85

Tested Demonstrations.  

ERIC Educational Resources Information Center

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…

Gilbert, George L., Ed.

1983-01-01

86

Tested Demonstrations.  

ERIC Educational Resources Information Center

Free radical chlorination of methane is used in organic chemistry to introduce free radical/chain reactions. In spite of its common occurrence, demonstrations of the reaction are uncommon. Therefore, such a demonstration is provided, including background information, preparation of reactants/reaction vessel, introduction of reactants, irradiation,…

Gilbert, George L., Ed.

1983-01-01

87

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1984-01-01

88

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1989-01-01

89

Microgravity Demonstrator  

NSDL National Science Digital Library

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

90

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1986-01-01

91

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1983-01-01

92

Physics Demonstrations  

NSDL National Science Digital Library

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

93

Tested Demonstrations.  

ERIC Educational Resources Information Center

Two demonstrations are described. The first (useful as an introduction to kinetics) shows how the rate of a reaction is fast at first and then gradually decreases to zero when one reactant has been used up. The second is a gas density demonstration using 1,1,2-trichloro-1,2,2-trifluoro ethane. (JN)

Gilbert, George L., Ed.

1985-01-01

94

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1983-01-01

95

Tested Demonstrations.  

ERIC Educational Resources Information Center

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…

Gilbert, George L., Ed.

1986-01-01

96

Tested Demonstrations.  

ERIC Educational Resources Information Center

Describes two demonstrations suitable for chemistry instruction. One involves fractal structures obtained by electrodeposition of silver at an air-water interface and the other deals with molecular weights and music. (TW)

Gilbert, George L., Ed.

1987-01-01

97

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1980-01-01

98

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1988-01-01

99

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Roffia, Sergio; And Others

1988-01-01

100

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1986-01-01

101

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Rehfeld, D. W.; And Others

1988-01-01

102

Physics Demonstrations  

NSDL National Science Digital Library

The teaching of physics is clearly enhanced by the use of demonstrations. Visual examples of abstract concepts aid immeasurably in their mastery. They also provide an opportunity to illustrate the scientific method and to teach the student to relate experimental observation to scientific theory. Experiments represent the means by which scientific knowledge has advanced so rapidly in modern times. Finally, not to be underestimated, the use of demonstrations makes the learning of physics much more enjoyable! This book is a compilation of many of the demonstrations that have been used at the University of Wisconsin - Madison in the teaching of elementary physics over the years as well as a number of demonstrations that I have developed for use in a series of popular lectures, "The Wonders of Physics," aimed at the general public and children in particular. Included also are a number of demonstrations that have been suggested and used by friends or colleagues. All of the demonstrations have been thoroughly tested in a classroom setting or before an audience of the general public.

Sprott, Julien

2009-05-20

103

Inflammatory Dilated Cardiomyopathy in Abcg5 Deficient Mice  

PubMed Central

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

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

2014-01-01

104

Demonstration Explosion  

NASA Astrophysics Data System (ADS)

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

Lee, Charles "Skip"

1998-05-01

105

Demonstrating Microgravity  

NASA Technical Reports Server (NTRS)

Dr. Richard DeLombard of NASA's Glenn Research Center, hands the relase line for the Microgravity Demonstrator to a visitor for her to start a short experiment showing the effects of microgravity on candle flames. Combustion physics will be a major line of investigation for NASA aboard the International Space Station (ISS). The Microgravity Demonstrator is frequently used at shows and schools to illustrate how phenomena change in microgravity. The exhibit was part of the NASA outreach activity at AirVenture 2000 sponsored by the Experimental Aircraft Association in Oshkosh, WI

2000-01-01

106

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1984-01-01

107

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1987-01-01

108

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1981-01-01

109

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1985-01-01

110

Tested Demonstrations.  

ERIC Educational Resources Information Center

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)

Gilbert, George L., Ed.

1987-01-01

111

Tested Demonstrations.  

ERIC Educational Resources Information Center

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.…

Gilbert, George L.

1983-01-01

112

Passive transfer of antibodies to the linear epitope 60 kD Ro 273-289 induces features of Sjögren's syndrome in naďve mice.  

PubMed

Sjögren's syndrome (SS) is an autoimmune inflammatory disease that primarily affects the lacrimal and salivary glands causing dry eyes and mouth. Antibodies to Ro60 are frequently observed in patients with SS; however, the role of these antibodies in SS initiation and progression remains unclear. The sequence Ro60 273-289 (Ro274) is a known B cell epitope of Ro60and antibodies to this epitope have been observed in a subset of SS patients and in animals immunized with Ro60 protein. Animals immunized with Ro274 linear peptide develop a Sjögren's-like illness. We hypothesized that passive transfer of anti-Ro274-specific IgG would induce a Sjögren's-like phenotype. To evaluate this hypothesis, we adoptively transferred affinity-purified Ro274 antibodies into naďve BALB/c animals then evaluated salivary gland histology, function and IgG localization four days post-transfer. At this timepoint, there was no demonstrable mononuclear cell infiltration and salivary glands were histologically normal, but we observed a functional deficit in stimulated salivary flow of animals receiving Ro274 antibodies compared to animals receiving control IgG. Cellular fractionation and ELISA revealed Ro274-specific antibodies in the nucleus and cytoplasmic fractions of isolated parotid salivary gland cells that was confirmed by immunohistochemistry. These data support the hypothesis that antibodies to Ro274 deposit in salivary glands, can enter intact salivary gland cells and are involved in the dysregulation of salivary flow in SS. PMID:25370295

Maier-Moore, Jacen S; Kurien, Biji T; D'Souza, Anil; Bockus, Lee; Asfa, Sima; Dorri, Yaser; Hubbell, Sherry; Yeliosof, Olga; Obeso, David; Schoeb, Trenton R; Jonsson, Roland; Scofield, R Hal

2014-11-01

113

Partial Return Yoke for MICE  

SciTech Connect

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.

Witte H.; Plate, S; ,

2013-05-03

114

Feature extraction of multispectral data  

NASA Technical Reports Server (NTRS)

A method is presented for feature extraction of multispectral scanner data. Non-training data is used to demonstrate the reduction in processing time that can be obtained by using feature extraction rather than feature selection.

Crane, R. B.; Crimmins, T.; Reyer, J. F.

1973-01-01

115

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

Microsoft Academic Search

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

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

1997-01-01

116

Genetic and Phenotypic Properties of Vero Cell-Adapted Japanese Encephalitis Virus SA14-14-2 Vaccine Strain Variants and a Recombinant Clone, Which Demonstrates Attenuation and Immunogenicity in Mice.  

PubMed

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

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

2015-01-01

117

Volcanic Features  

NSDL National Science Digital Library

This interactive resource adapted from the National Park Service illustrates the variety of landforms and features created by volcanoes. Featured are calderas, craters, fumaroles and other geothermal features, igneous rocks, lava flows, lava tubes, and maars.

2005-12-17

118

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

PubMed Central

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

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

119

Mice Rule! (or Not)  

NSDL National Science Digital Library

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

Engineering K-PhD Program,

120

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

PubMed Central

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

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

2013-01-01

121

Development of Social Vocalizations in Mice  

PubMed Central

Adult mice are highly vocal animals, with both males and females vocalizing in same sex and cross sex social encounters. Mouse pups are also highly vocal, producing isolation vocalizations when they are cold or removed from the nest. This study examined patterns in the development of pup isolation vocalizations, and compared these to adult vocalizations. In three litters of CBA/CaJ mice, we recorded isolation vocalizations at ages postnatal day 5 (p5), p7, p9, p11, and p13. Adult vocalizations were obtained in a variety of social situations. Altogether, 28,384 discrete vocal signals were recorded using high-frequency-sensitive equipment and analyzed for syllable type, spectral and temporal features, and the temporal sequencing within bouts. We found that pups produced all but one of the 11 syllable types recorded from adults. The proportions of syllable types changed developmentally, but even the youngest pups produced complex syllables with frequency-time variations. When all syllable types were pooled together for analysis, changes in the peak frequency or the duration of syllables were small, although significant, from p5 through p13. However, individual syllable types showed different, large patterns of change over development, requiring analysis of each syllable type separately. Most adult syllables were substantially lower in frequency and shorter in duration. As pups aged, the complexity of vocal bouts increased, with a greater tendency to switch between syllable types. Vocal bouts from older animals, p13 and adult, had significantly more sequential structure than those from younger mice. Overall, these results demonstrate substantial changes in social vocalizations with age. Future studies are required to identify whether these changes result from developmental processes affecting the vocal tract or control of vocalization, or from vocal learning. To provide a tool for further research, we developed a MATLAB program that generates bouts of vocalizations that correspond to mice of different ages. PMID:21408007

Grimsley, Jasmine M. S.; Monaghan, Jessica J. M.; Wenstrup, Jeffrey J.

2011-01-01

122

The MICE Muon Beam Line  

SciTech Connect

In the Muon Ionization Cooling Experiment (MICE) at RAL, muons are produced and transported in a dedicated beam line connecting the production point (target) to the cooling channel. We discuss the main features of the beamline, meant to provide muons with momenta between 140 MeV/c and 240 MeV/c and emittances up to 10 mm rad, which is accomplished by means of a diffuser. Matching procedures to the MICE cooling channel are also described. In summer 2010 we performed an intense data taking campaign to finalize the calibration of the MICE Particle Identification (PID) detectors and the understanding of the beam line, which completes the STEPI phase of MICE. We highlight the main results from these data.

Apollonio, Marco [High Energy Physics Group, Department of Physics, Imperial College London SW7 2AZ (United Kingdom)

2011-10-06

123

A lymphatic defect causes ocular hypertension and glaucoma in mice  

PubMed Central

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

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

2014-01-01

124

Status of MICE  

SciTech Connect

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.

Soler, F. J. P. [University of Glasgow, Glasgow G12 8QQ (United Kingdom)

2010-03-30

125

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

PubMed

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. Am. J. Hematol. 90:8-14, 2015. © 2014 Wiley Periodicals, Inc. PMID:25236856

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

2015-01-01

126

Growth characteristics of human Wilms' tumor in nude mice.  

PubMed

Ten Wilms' tumors (WT) were heterotransplated into athymic (nude) mice. Eight of the tumors (80%) grew and were serially passaged as many as 20 times. The histology of the primary heterotransplants resembled that of the surgically excised tumors (seven classical and one anaplastic). Histological examination of serial passages of the classical WT demonstrated the tendency of the stromal and tubular components to disappear. The anaplastic tumor, however, maintained histological features identical to the primary tumor through all passages examined. One WT cell line that exhibited a prominent skeletal muscle component failed to grow beyond the third passage. Spontaneous glomerular differentiation was noted in several heterotransplants. The site of transplantation (subcutaneous, peritoneal, or renal capsule) had no effect on the differentiation of the tumors, and attempts to produce intravenous metastases were unsuccessful. Unilateral nephrectomy of WT-bearing mice gave a transient increase in pulse labeling of the tumors with bromodeoxyuridine, a thymidine analogue, compared with sham-operated controls or mice bearing Ewings' sarcoma heterotransplants. The increased labeling of tumor nuclei reached a maximum at 48 h. Similar increased labeling was observed in the remaining kidney following unilateral nephrectomy. These data show that although WT is a malignant neoplasm, its cells retain the capacity to respond to physiological signals resulting from nephrectomy and that differentiation cannot be modulated by the site of heterotransplantation or serial passage in athymic mice. PMID:2854254

Garvin, A J; Congleton, L; Inabnett, T; Gansler, T; Sens, D A

1988-01-01

127

Characterization of carbon disulfide neurotoxicity in C57BL6 mice: behavioral, morphologic, and molecular effects.  

PubMed

Female C57BL6 mice were exposed to 0 or 800 ppm carbon disulfide (CS2), 6 h/d, 5 d/wk for 20 weeks. The neurologic function of all mice was assessed once at the end of exposures using a functional observational battery. General health effects included a decrease in body weight gain, piloerection, hunched body posture, and ptosis. Treatment-related effects included altered gait (uncoordinated placement of hind limbs and ataxia) and impaired function on an inverted screen test. In addition, rearing and locomotor movement were decreased in treated mice. Focal to multifocal axonal swelling was seen predominantly in the muscular branch of the posterior tibial nerve, and occasionally giant axonal swelling was detected in the lumbar segment of the spinal cord. Electron microscopic examination revealed swollen axons with massive accumulation of neurofilament proteins within the axoplasm. Covalent cross-linking of erythrocyte spectrin (surrogate protein to neurofilament protein) was demonstrated in mice exposed to CS2 but not in mice receiving filtered air. These data provide supportive evidence that covalent cross-linking of neurofilament proteins is a significant feature of the axonal swellings in mice produced by inhalation exposure to CS2. PMID:10669001

Sills, R C; Valentine, W M; Moser, V; Graham, D G; Morgan, D L

2000-01-01

128

Favorite Demonstration: An Illuminating Catalysis Demonstration  

NSDL National Science Digital Library

The catalase demonstration presented here is a variation of a traditional experiment that is normally run to demonstrate enzyme activity in basic undergraduate biology classes. It is one of the easiest laboratory activities to demonstrate organic catalysis. The setup involves minimum preparation and inexpensive materials (Mader 1995).

Hoots, Rita

2004-02-01

129

Features | Poster  

Cancer.gov

Skip to main content About Us Services Science For Our Staff Phonebook Poster Search form Search Main menu Home Science Publications Platinum Highlight Platinum Publications Technology Transfer Awards Health and Safety Outreach Students Features Poster

130

FEATURE ARTICLE Terahertz Spectroscopy  

E-print Network

about 13 years ago with the demonstration that nearly single-cycle pulses of far-infrared radiation covers the spectral range from about 3 cm-1 to about 600 cm-1, also known as the far-infrared (far- IR#12;FEATURE ARTICLE Terahertz Spectroscopy Matthew C. Beard, Gordon M. Turner, and Charles A

131

Demonstrational Features of the Tuskegee Institute Retraining Project, Volume I.  

ERIC Educational Resources Information Center

This 52-week Tuskegee Institute project, undertaken in 1964 to train a sample of culturally deprived male heads of households in Alabama, included vocational skills (brickmasonry, carpentry, farm machinery, and meat processing), academic skills (mathematics, English, and remedial reading), group, individual, and family counseling, medical care,…

Tuskegee Inst., AL.

132

Web Features  

NSDL National Science Digital Library

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

133

Favorite Demonstration: Demonstrating a Thermodynamics Fountain  

NSDL National Science Digital Library

Cryogenic materials, mainly liquefied and solidified gases, are probably the most fascinating materials to use for demonstrating chemical reactions to introductory college students. A popular series of articles (Blachley 1997; Coppola et al. 1994; Haub 20

Miodrag Micic

2002-05-01

134

Favorite Demonstration: A Fruity Biochemistry Demonstration  

NSDL National Science Digital Library

Inquiry, high-order thinking, reasoning skills, and critical thinking are buzzwords for the outcomes for which college science instructors strive. They can all be succinctly summarized as "get students thinking about what they are learning." Classroom demonstrations are a great vechicle for getting students to apply information they have heard in a lecture. A good example of this type of application is a demonstration that uses simple fruit and vegetable spoilage biochemistry principles to teach scientific reasoning skills.

Brian R. Shmaefsky

2005-05-01

135

Mice Offer Lessons on Aging  

NSDL National Science Digital Library

The Lawrence Berkeley Laboratory's Science Beat offers interesting feature articles about research from Berkeley lab and partner organizations. This article offers a fascinating look at aging research utilizing transgenic mice -- an inquiry into "the genetic roots of aging in everyone." The article includes Web links to related material from the institutions participating in these research projects, as well as links to academic articles from the journal Science (not available without paid subscription).

Krotz, Dan.

2003-01-01

136

NOD-Rag2null IL-2R?null Mice: An Alternative to NOG Mice for Generation of Humanized Mice  

PubMed Central

We have developed NOD-Rag2null IL-2R?null (NR2G) mice similar to NOD-scidIL-2R?null (NOG) mice that are known as an excellent host to generate humanized mice. To evaluate the usefulness of NR2G mice as a host for humanized mice, the engraftment rates and differentiation of human cells after human hematopoietic stem cell (HSC) transplantation were compared among NR2G, NOG, and NOD-scid mice. For this purpose, the appropriate irradiation doses to expand the niche for human stem cells in the bone marrow were first determined. As a result, 8 and 2.5 Gy in adult, and 4 and 1 Gy in newborn NR2G and NOG mice, respectively, were found to be appropriate. Next, 5 × 104 human umbilical cord blood CD34+ cells were intravenously inoculated into irradiated adult or newborn of the immunodeficient mice. These HSC transplantation experiments demonstrated that both NR2G and NOG mice showed high engraftment rates compared with NOD-scid mice, although NOG mice showed a slightly higher engraftment rate than that for NR2G mice. However, no difference was found in the human cell populations differentiated from HSCs between NR2G and NOG mice. The HSC transplantation experiments to adults and newborns of two immunodeficient mice also revealed that the HSC transplantation into newborn mice resulted in higher engraftment rate than those into adults. These results showed that NR2G mice could be used as an alternative host to NOG mice to generate humanized mice. PMID:25077762

Katano, Ikumi; Ito, Ryoji; Kamisako, Tsutomu; Eto, Tomoo; Ogura, Tomoyuki; Kawai, Kenji; Suemizu, Hiroshi; Takahashi, Takeshi; Kawakami, Yutaka; Ito, Mamoru

2014-01-01

137

Desert Features  

NSDL National Science Digital Library

Sand covers only about 20 percent of the Earth's deserts. Nearly 50 percent of desert surfaces are gravel plains where removal of fine-grained material by the wind has exposed loose gravel and occasional cobbles. This web page, produced by the U.S. Geological Survey, features text and photographs that describe desert landforms, soils, plants, and the role of water in the formation of desert landscapes.

138

Characterization of Sleeping Beauty transposition and its application to genetic screening in mice.  

PubMed

The use of mutant mice plays a pivotal role in determining the function of genes, and the recently reported germ line transposition of the Sleeping Beauty (SB) transposon would provide a novel system to facilitate this approach. In this study, we characterized SB transposition in the mouse germ line and assessed its potential for generating mutant mice. Transposition sites not only were clustered within 3 Mb near the donor site but also were widely distributed outside this cluster, indicating that the SB transposon can be utilized for both region-specific and genome-wide mutagenesis. The complexity of transposition sites in the germ line was high enough for large-scale generation of mutant mice. Based on these initial results, we conducted germ line mutagenesis by using a gene trap scheme, and the use of a green fluorescent protein reporter made it possible to select for mutant mice rapidly and noninvasively. Interestingly, mice with mutations in the same gene, each with a different insertion site, were obtained by local transposition events, demonstrating the feasibility of the SB transposon system for region-specific mutagenesis. Our results indicate that the SB transposon system has unique features that complement other mutagenesis approaches. PMID:14645530

Horie, Kyoji; Yusa, Kosuke; Yae, Kojiro; Odajima, Junko; Fischer, Sylvia E J; Keng, Vincent W; Hayakawa, Tomoko; Mizuno, Sumi; Kondoh, Gen; Ijiri, Takashi; Matsuda, Yoichi; Plasterk, Ronald H A; Takeda, Junji

2003-12-01

139

Third-generation FLIR demonstrator  

NASA Astrophysics Data System (ADS)

One of the benefits of 3 rd Generation FLIR technology is the potential to maintain range performance but with a much smaller optical system. A 3 rd Gen Demonstrator (3GD) has been assembled and tested to demonstrate this capability. The 3GD features a four field of view optical system incorporating dual f/number optics with an all-reflective folded three mirror anastigmat (TMA) afocal, axial zoom dual band imager, internal thermal reference, and a beam splitter port for integrating other sensors such as a visible camera. This paper discusses the results of the fabrication of this 3 rd Gen demonstration system with an emphasis on lessons learned from the challenges of 3 rd Gen optics.

Vizgaitis, Jay; Miller, Jason; Hall, John; Berube, Dan

2008-04-01

140

Laithwaite's Heavy Spinning Disk Demonstration  

NASA Astrophysics Data System (ADS)

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.

Cross, Rod

2014-09-01

141

Favorite Demonstration: An Inexpensive Resonance Demonstration  

NSDL National Science Digital Library

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

Dukes, Phillip

2005-01-01

142

General features  

SciTech Connect

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.

Wallace, R.E.

1990-01-01

143

HIF2? cooperates with RAS to promote lung tumorigenesis in mice  

PubMed Central

Members of the hypoxia-inducible factor (HIF) family of transcription factors regulate the cellular response to hypoxia. In non–small cell lung cancer (NSCLC), high HIF2? levels correlate with decreased overall survival, and inhibition of either the protein encoded by the canonical HIF target gene VEGF or VEGFR2 improves clinical outcomes. However, whether HIF2? is causal in imparting this poor prognosis is unknown. Here, we generated mice that conditionally express both a nondegradable variant of HIF2? and a mutant form of Kras (KrasG12D) that induces lung tumors. Mice expressing both Hif2a and KrasG12D in the lungs developed larger tumors and had an increased tumor burden and decreased survival compared with mice expressing only KrasG12D. Additionally, tumors expressing both KrasG12D and Hif2a were more invasive, demonstrated features of epithelial-mesenchymal transition (EMT), and exhibited increased angiogenesis associated with mobilization of circulating endothelial progenitor cells. These results implicate HIF2? causally in the pathogenesis of lung cancer in mice, demonstrate in vivo that HIF2? can promote expression of markers of EMT, and define HIF2? as a promoter of tumor growth and progression in a solid tumor other than renal cell carcinoma. They further suggest a possible causal relationship between HIF2? and prognosis in patients with NSCLC. PMID:19662677

Kim, William Y.; Perera, Samanthi; Zhou, Bing; Carretero, Julian; Yeh, Jen Jen; Heathcote, Samuel A.; Jackson, Autumn L.; Nikolinakos, Petros; Ospina, Beatriz; Naumov, George; Brandstetter, Kathleyn A.; Weigman, Victor J.; Zaghlul, Sara; Hayes, D. Neil; Padera, Robert F.; Heymach, John V.; Kung, Andrew L.; Sharpless, Norman E.; Kaelin, William G.; Wong, Kwok-Kin

2009-01-01

144

Special Feature: Quantum Measurement Standards  

Microsoft Academic Search

This special feature is intended to present a comprehensive review of the present state and novel trends in the field of quantum measurement standards. Most of the present metrological research is concentrated on establishing and strengthening the links between the units and fundamental constants. This will be demonstrated in the nine articles in this feature.The first four articles are devoted

Erich Braun

2003-01-01

145

Preventing formation of reticulon 3 immunoreactive dystrophic neurites improves cognitive function in mice.  

PubMed

Neuritic dystrophy is one of the important pathological features associated with amyloid plaques in Alzheimer's disease (AD) and age-dependent neuronal dysfunctions. We reported previously that reticulon-3 (RTN3) immunoreactive dystrophic neurites (RIDNs) are abundantly present in the hippocampus of AD patients, in AD mouse models, and in aged wild-type mice. Transgenic mice overexpressing the human RTN3 transgene spontaneously develop RIDNs in their hippocampi, and the formation of RIDNs correlates with the appearance of RTN3 aggregation. To further elucidate whether the formation of RIDNs is reversible, we generated transgenic mice expressing wild-type human RTN3 under the control of a tetracycline-responsive promoter. Treatment with doxycycline for 2 months effectively turned off expression of the human RTN3 transgene, confirming the inducible nature of the system. However, the formation of hippocampal RIDNs was dependent on whether the transgene was turned off before or after the formation of RTN3 aggregates. When transgenic human RTN3 expression was turned off at young age, formation of RIDNs was essentially eliminated compared with the vehicle-treated transgenic mice. More importantly, a fear conditioning study demonstrated that contextual associative learning and memory in inducible transgenic mice was improved if the density of RIDNs was lowered. Additional mechanistic study suggested that a reduction in BDNF levels in transgenic mice might contribute to the reduced learning and memory in transgenic mice overexpressing RTN3. Hence, we conclude that age-dependent RIDNs cannot be effectively cleared once they have formed, and we postulate that successful prevention of RIDN formation should be initiated before RTN3 aggregation. PMID:23407961

Shi, Qi; Prior, Marguerite; Zhou, Xiangdong; Tang, Xiaoying; He, Wanxia; Hu, Xiangyou; Yan, Riqiang

2013-02-13

146

Metallothionein deletion exacerbates intermittent hypoxia-induced renal injury in mice.  

PubMed

As a main clinical feature of obstructive sleep apnea (OSA), intermittent hypoxia (IH) induces oxidative stress, leading to damage to a variety of organs, including kidney. Metallothionein (MT) is a potent antioxidant that protects kidney against oxidative damage. Our previous studies demonstrated that MT prevented IH-induced cardiomyopathy in mice. However, the role of MT in protecting against IH-induced renal injury is unknown. Therefore, MT knockout (MT KO) mice and wild type (WT) control mice (129S) were culled for exposure to intermittent air as control or IH for a time course of 3 days, 1 week, 3 weeks and 8 weeks. MT KO mice developed higher urinary albumin to creatinine ratio (UACR) after exposure to IH for 8 weeks. Compared with either MT KO control or WT IH mice, MT deletion significantly aggravated IH-induced renal oxidative damage and inflammation at all four time points, along with significant acceleration of renal fibrosis after exposure to IH for 3 weeks and 8 weeks. Antioxidants including MT, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1) and NAD (P) H dehydrogenase [quinone] 1 (NQO1) were increased in response to short-term IH (3 days, 1 week and 3 weeks) but decreased after long-term IH (8 weeks) in WT mice. Interestingly, Nrf2, HO1 and NQO1 were significantly attenuated under IH conditions in the absence of MT, which were in parallel with the inactivation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK). These findings demonstrated that MT played a key role in preventing IH-induced renal injury possibly via preserving Nrf2 signaling pathway. PMID:25448280

Wu, Hao; Zhou, Shanshan; Kong, Lili; Chen, Jing; Feng, Wenke; Cai, Jun; Miao, Lining; Tan, Yi

2015-01-22

147

LIMB Demonstration Project Extension and Coolside Demonstration  

SciTech Connect

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.

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

1992-11-10

148

Cardio Lab Powerpoint Demonstration  

NSDL National Science Digital Library

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

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

2010-05-24

149

Polarized Light Corridor Demonstrations.  

ERIC Educational Resources Information Center

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)

Davies, G. R.

1990-01-01

150

Traveling Wave Demonstration.  

ERIC Educational Resources Information Center

Describes a traveling-wave demonstration that uses inexpensive materials (crepe-paper streamers) and is simple to assemble and perform. Explains how the properties of light waves are illustrated using the demonstration apparatus. (LZ)

Kluger-Bell, Barry

1995-01-01

151

Experimental Demonstrations in Teaching Chemical Reactions.  

ERIC Educational Resources Information Center

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…

Hugerat, Muhamad; Basheer, Sobhi

2001-01-01

152

METCAN demonstration manual, version 1.0  

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

153

Data surety demonstrations  

SciTech Connect

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

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

1998-08-01

154

Strategy Guideline: Demonstration Home  

SciTech Connect

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.

Savage, C.; Hunt, A.

2012-12-01

155

New Technology Demonstration Program  

E-print Network

the basic functions covered by BCS's. These new energy information systems (EIS) include utility EIS, demand for this report, some features of this new wave of EIS products are supported. These vendors were chosen because

156

Increased Adiposity in Annexin A1-Deficient Mice  

PubMed Central

Production of Annexin A1 (ANXA1), a protein that mediates the anti-inflammatory action of glucocorticoids, is altered in obesity, but its role in modulation of adiposity has not yet been investigated. The objective of this study was to investigate modulation of ANXA1 in adipose tissue in murine models of obesity and to study the involvement of ANXA1 in diet-induced obesity in mice. Significant induction of ANXA1 mRNA was observed in adipose tissue of both C57BL6 and Balb/c mice with high fat diet (HFD)-induced obesity versus mice on chow diet. Upregulation of ANXA1 mRNA was independent of leptin or IL-6, as demonstrated by use of leptin-deficient ob/ob mice and IL-6 KO mice. Compared to WT mice, female Balb/c ANXA1 KO mice on HFD had increased adiposity, as indicated by significantly elevated body weight, fat mass, leptin levels, and adipocyte size. Whereas Balb/c WT mice upregulated expression of enzymes involved in the lipolytic pathway in response to HFD, this response was absent in ANXA1 KO mice. A significant increase in fasting glucose and insulin levels as well as development of insulin resistance was observed in ANXA1 KO mice on HFD compared to WT mice. Elevated plasma corticosterone levels and blunted downregulation of 11-beta hydroxysteroid dehydrogenase type 1 in adipose tissue was observed in ANXA1 KO mice compared to diet-matched WT mice. However, no differences between WT and KO mice on either chow or HFD were observed in expression of markers of adipose tissue inflammation. These data indicate that ANXA1 is an important modulator of adiposity in mice, with female ANXA1 KO mice on Balb/c background being more susceptible to weight gain and diet-induced insulin resistance compared to WT mice, without significant changes in inflammation. PMID:24312665

Akasheh, Rand T.; Pini, Maria; Pang, Jingbo; Fantuzzi, Giamila

2013-01-01

157

Cilia, tubby mice, and obesity  

PubMed Central

Primary cilia have been previously linked to the central regulation of satiety. The tubby mouse is characterized by maturity-onset obesity and blindness. A recent paper demonstrates molecular defects in trafficking of ciliary GPCRs in the central neurons of tubby mice, underscoring the role of ciliary signaling in the pathogenesis of this monogenic obesity syndrome. Please see related Research article by Li et al., http://www.ciliajournal.com/content/1/1/21 PMID:23351214

2013-01-01

158

Demonstrating Newton's Second Law.  

ERIC Educational Resources Information Center

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)

Fricker, H. S.

1994-01-01

159

Kinetics and Catalysis Demonstrations.  

ERIC Educational Resources Information Center

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…

Falconer, John L.; Britten, Jerald A.

1984-01-01

160

Thermohaline Circulation Demonstration  

NSDL National Science Digital Library

This activity helps the students to visualize the effects of temperature and salinity on water density, and the resulting thermohaline circulation. Important processes visualized in this demonstration are upwelling, downwelling, and the formation of haloclines, thermoclines and pycnoclines. In addition, mixing by advection is clearly demonstrated.

Venn, Cynthia

161

The Microgravity Demonstrator.  

ERIC Educational Resources Information Center

The Microgravity Demonstrator is a tool used to create microgravity conditions in the classroom. A series of demonstrations is used to provide a dramatically visual, physical connection between free-fall and microgravity conditions in order to understand why various types of experiments are performed under microgravity conditions. The manual is…

Rogers, Melissa J. B.; Wargo, Michael J.

162

ISU Demonstration Road Show  

NSDL National Science Digital Library

The Idaho State University Department of Physics conducts science demonstration shows at SE Idaho schools. Four different presentations are currently available; "Forces and Motion", "States of Matter", "Electricity and Magnetism", and "Sound and Waves". Student activities and descriptions of the demonstrated material are also provided.

Shropshire, Steven

2004-04-06

163

Angular momentum conservation demonstration  

NSDL National Science Digital Library

A short article describing the fabrication and operation of a simple angular momentum conservation demonstration. The demonstration is based on a Lazy Susan, and cylindrical brass weights tied with a nylon string. The string can be pulled or released changing the radius or rotation of the weights.

Berg, Richard E.; Anders, Robert E.

2010-12-23

164

Token Ring Demonstration  

NSDL National Science Digital Library

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

165

Chemical Domino Demonstration  

Microsoft Academic Search

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

M. Dale Alexander

1998-01-01

166

FDDI Ring Demonstration  

NSDL National Science Digital Library

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

2007-01-23

167

Pilots's Associate Demonstration One  

Microsoft Academic Search

A brief overview is given of the DARPA- and AFWAL-sponsored Pilot's Associate Demonstration One project. The project developed prototypes for four avionics expert systems, with an emphasis on a crew station information manager (CSIM) system. CSIM operated on information from three supporting subsystems: a situation assessor, a mission planner, and an integration controller. These expert system (ES) prototypes were demonstrated

Lawrence D. Pohlmann; J. R. Payne

1988-01-01

168

A Stellar Demonstrator  

ERIC Educational Resources Information Center

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…

Ros, Rosa M.

2009-01-01

169

USFWS demonstration fees  

USGS Publications Warehouse

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.

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

2002-01-01

170

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

PubMed Central

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

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

2014-01-01

171

Tested Demonstrations: Spectroscopy Illustrated.  

ERIC Educational Resources Information Center

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

Gilbert, George L., Ed.

1983-01-01

172

Microgravity Plant Growth Demonstration  

NASA Technical Reports Server (NTRS)

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.

2000-01-01

173

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

PubMed Central

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

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

2012-01-01

174

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

PubMed

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

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

2014-06-01

175

Favorite Demonstration: Biological Membranes  

NSDL National Science Digital Library

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

Gilbert Ellis

2009-01-01

176

A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice  

PubMed Central

Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community–host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to ‘fingerprint' microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography–mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota's metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest ‘personalized' aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host. PMID:23739052

Marcobal, A; Kashyap, P C; Nelson, T A; Aronov, P A; Donia, M S; Spormann, A; Fischbach, M A; Sonnenburg, J L

2013-01-01

177

A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice.  

PubMed

Defining the functional status of host-associated microbial ecosystems has proven challenging owing to the vast number of predicted genes within the microbiome and relatively poor understanding of community dynamics and community-host interaction. Metabolomic approaches, in which a large number of small molecule metabolites can be defined in a biological sample, offer a promising avenue to 'fingerprint' microbiota functional status. Here, we examined the effects of the human gut microbiota on the fecal and urinary metabolome of a humanized (HUM) mouse using an optimized ultra performance liquid chromatography-mass spectrometry-based method. Differences between HUM and conventional mouse urine and fecal metabolomic profiles support host-specific aspects of the microbiota's metabolomic contribution, consistent with distinct microbial compositions. Comparison of microbiota composition and metabolome of mice humanized with different human donors revealed that the vast majority of metabolomic features observed in donor samples are produced in the corresponding HUM mice, and individual-specific features suggest 'personalized' aspects of functionality can be reconstituted in mice. Feeding the mice a defined, custom diet resulted in modification of the metabolite signatures, illustrating that host diet provides an avenue for altering gut microbiota functionality, which in turn can be monitored via metabolomics. Using a defined model microbiota consisting of one or two species, we show that simplified communities can drive major changes in the host metabolomic profile. Our results demonstrate that metabolomics constitutes a powerful avenue for functional characterization of the intestinal microbiota and its interaction with the host. PMID:23739052

Marcobal, A; Kashyap, P C; Nelson, T A; Aronov, P A; Donia, M S; Spormann, A; Fischbach, M A; Sonnenburg, J L

2013-10-01

178

Humanized Mice, a New Model To Study the Influence of Drug Treatment on Neonatal Sepsis  

PubMed Central

Bacterial infection with group B Streptococcus (GBS) represents a prominent threat to neonates and fetuses in the Western world, causing severe organ damage and even death. To improve current therapeutic strategies and to investigate new approaches, an appropriate in vivo model to study the immune response of a human immune system is needed. Therefore, we introduced humanized mice as a new model for GBS-induced sepsis. Humanized mice feature deficiencies similar to those found in neonates, such as lower immunoglobulin levels and myeloid cell dysfunction. Due to the husbandry in specific-pathogen-free (SPF) facilities, the human immune cells in these mice also exhibit a naive phenotype which mimics the conditions in fetuses/neonates. Following infection, cytokine release and leukocyte trafficking from the bone marrow to the lymphoid organ (spleen) and into the peritoneum (site of infection) as well as bacterial spreading and clearance were traceable in the humanized mice. Furthermore, we investigated the effects of betamethasone and indomethacin treatment using this novel sepsis model. Although both drugs are commonly used in perinatal care, little is known about their effects on the neonatal immune system. Treatment of infected humanized mice not only induced the reduction of human leukocytes in the spleen but also increased the bacterial load in all analyzed organs, including the brain, which did not show infiltration of live GBS in untreated controls. These studies demonstrate the utility of the humanized mice as a new model to study an immature human immune response during bacterial infection and allow the investigation of side effects induced by various treatments. PMID:23439310

Ernst, Wolfgang; Zimara, Nicole; Hanses, Frank; Männel, Daniela N.; Seelbach-Göbel, Birgit

2013-01-01

179

Diaphragm muscle sarcopenia in aging mice.  

PubMed

Sarcopenia, defined as muscle weakness and fiber atrophy, of respiratory muscles such as the diaphragm (DIAm) has not been well characterized. The DIAm is the main inspiratory muscle and knowledge of DIAm sarcopenia is important for establishing the effects of aging on respiratory function. We hypothesized that aging is associated with a loss of DIAm force and reduced fiber cross-sectional area (CSA), and that these changes vary across fiber types. DIAm sarcopenia was assessed in young (5 month; n = 11) and old (23 month; n = 12) wild-type mice reflecting ~100 and 75% survival, respectively. In addition, DIAm sarcopenia was evaluated in BubR1(H/H) mice (n = 4) that display accelerated aging (~60% survival at 5 months) as a result of expression of a hypomorphic allele (H) of the mitotic checkpoint protein BubR1. Maximum specific force (normalized for CSA) of the DIAm was 34% less in old mice and 57% lower in BubR1(H/H) mice compared to young mice. Mean CSA of type IIx and/or IIb DIAm fibers was 27% smaller in old wild-type mice and 47% smaller in BubR1(H/H) mice compared to young mice. Mean CSA of type I or IIa fibers was not different between groups. Collectively these results demonstrate sarcopenia of the DIAm in aging wild-type mice and in BubR1(H/H) mice displaying accelerated aging. Sarcopenia may limit the ability of the DIAm to accomplish expulsive, non-ventilatory behaviors essential for airway clearance. As a result, these changes in the DIAm may contribute to respiratory complications with aging. PMID:23792145

Greising, Sarah M; Mantilla, Carlos B; Gorman, Britney A; Ermilov, Leonid G; Sieck, Gary C

2013-09-01

180

Diaphragm Muscle Sarcopenia in Aging Mice  

PubMed Central

Sarcopenia, defined as muscle weakness and fiber atrophy, of respiratory muscles such as the diaphragm (DIAm) has not been well characterized. The DIAm is the main inspiratory muscle and knowledge of DIAm sarcopenia is important for establishing the effects of aging on respiratory function. We hypothesized that aging is associated with a loss of DIAm force and reduced fiber cross-sectional area (CSA), and that these changes vary across fiber types. DIAm sarcopenia was assessed in young (5 month; n=11) and old (23 month; n=12) wild-type mice reflecting ~100 and 75% survival, respectively. In addition, DIAm sarcopenia was evaluated in BubR1H/H mice (n=4) that display accelerated aging (~60% survival at 5 months) as a result of expression of a hypomorphic allele (H) of the mitotic checkpoint protein BubR1. Maximum specific force (normalized for CSA) of the DIAm was 34% less in old mice and 57% lower in BubR1H/H mice compared to young mice. Mean CSA of type IIx and/or IIb DIAm fibers was 27% smaller in old wild-type mice and 47% smaller in BubR1H/H mice compared to young mice. Mean CSA of type I or IIa fibers was not different between groups. Collectively these results demonstrate sarcopenia of the DIAm in aging wild-type mice and in BubR1H/H mice displaying accelerated aging. Sarcopenia may limit the ability of the DIAm to accomplish expulsive, non-ventilatory behaviors essential for airway clearance. As a result, these changes in the DIAm may contribute to respiratory complications with aging. PMID:23792145

Greising, Sarah M.; Mantilla, Carlos B.; Gorman, Britney A.; Ermilov, Leonid G.; Sieck, Gary C.

2013-01-01

181

Demonstration of Surface Tension.  

ERIC Educational Resources Information Center

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)

Rosenthal, Andrew J.

2001-01-01

182

Remote Agent Demonstration  

NASA Technical Reports Server (NTRS)

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.

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

1999-01-01

183

Time Lapse Season Demonstrator  

NSDL National Science Digital Library

This animation demonstrates the changing declination of the sun with a time-lapse animation. It shows how the shadow of a building changes over the course of a year as the declination of the sun changes.

Lincoln, University O.

184

Favorite Demonstration: Differential Weathering  

NSDL National Science Digital Library

In this inquiry-based demonstration, the consumption of a Baby Ruth candy bar is used to nurture students' interest in chemical and physical weathering. In addition, two other concepts can be illustrated: the difference between weathering and erosion and

Francek, Mark

2002-10-01

185

Classroom Demonstration of Sunspots.  

ERIC Educational Resources Information Center

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)

Callaway, Thomas O.; And Others

1982-01-01

186

Methanol Cannon Demonstrations Revisited.  

ERIC Educational Resources Information Center

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)

Dolson, David A.; And Others

1995-01-01

187

Overhead Projector Demonstrations.  

ERIC Educational Resources Information Center

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

Kolb, Doris, Ed.

1989-01-01

188

Innovative technology demonstration  

SciTech Connect

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.

Anderson, D.B.; Luttrell, S.P. (Pacific Northwest Lab., Richland, WA (United States)); Hartley, J.N. (Battelle Environmental Management Operations, Richland, WA (United States)); Hinchee, R. (Battelle, Columbus, OH (United States))

1992-04-01

189

Innovative technology demonstration  

SciTech Connect

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.

Anderson, D.B.; Luttrell, S.P. [Pacific Northwest Lab., Richland, WA (United States); Hartley, J.N. [Battelle Environmental Management Operations, Richland, WA (United States); Hinchee, R. [Battelle, Columbus, OH (United States)

1992-04-01

190

Spacecraft servicing demonstration plan  

NASA Technical Reports Server (NTRS)

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.

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

1984-01-01

191

Water Contamination Demonstration  

NSDL National Science Digital Library

Summary: Misplaced Matter and Water Pollution The drinking water pollution demonstration provides a very simple but dramatic way to get students to think about water contamination and drinking water standards, ...

192

Thermal Conductivity Demonstrations  

NSDL National Science Digital Library

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

193

Behavioral and neural correlates of acute and scheduled hunger in C57BL/6 mice.  

PubMed

In rodents, daily feeding schedules induce food anticipatory activity (FAA) rhythms with formal properties suggesting mediation by food-entrained circadian oscillators (FEOs). The search for the neuronal substrate of FEOs responsible for FAA is an active area of research, but studies spanning several decades have yet to identify unequivocally a brain region required for FAA. Variability of results across studies leads to questions about underlying biology versus methodology. Here we describe in C57BL/6 male mice the effects of varying the 'dose' of caloric restriction (0%, 60%, 80%, 110%) on the expression of FAA as measured by a video-based analysis system, and on the induction of c-Fos in brain regions that have been implicated in FAA. We determined that more severe caloric restriction (60%) leads to a faster onset of FAA with increased magnitude. Using the 60% caloric restriction, we found little evidence for unique signatures of neuronal activation in the brains of mice anticipating a daily mealtime compared to mice that were fasted acutely or fed ad-libitum-even in regions such as the dorsomedial and ventrolateral hypothalamus, nucleus accumbens, and cerebellum that have previously been implicated in FAA. These results underscore the importance of feeding schedule parameters in determining quantitative features of FAA in mice, and demonstrate dissociations between behavioral FAA and neural activity in brain areas thought to harbor FEOs or participate in their entrainment or output. PMID:24806659

Gallardo, Christian M; Hsu, Cynthia T; Gunapala, Keith M; Parfyonov, Maksim; Chang, Chris H; Mistlberger, Ralph E; Steele, Andrew D

2014-01-01

194

Behavioral and Neural Correlates of Acute and Scheduled Hunger in C57BL/6 Mice  

PubMed Central

In rodents, daily feeding schedules induce food anticipatory activity (FAA) rhythms with formal properties suggesting mediation by food-entrained circadian oscillators (FEOs). The search for the neuronal substrate of FEOs responsible for FAA is an active area of research, but studies spanning several decades have yet to identify unequivocally a brain region required for FAA. Variability of results across studies leads to questions about underlying biology versus methodology. Here we describe in C57BL/6 male mice the effects of varying the ‘dose’ of caloric restriction (0%, 60%, 80%, 110%) on the expression of FAA as measured by a video-based analysis system, and on the induction of c-Fos in brain regions that have been implicated in FAA. We determined that more severe caloric restriction (60%) leads to a faster onset of FAA with increased magnitude. Using the 60% caloric restriction, we found little evidence for unique signatures of neuronal activation in the brains of mice anticipating a daily mealtime compared to mice that were fasted acutely or fed ad-libitum–even in regions such as the dorsomedial and ventrolateral hypothalamus, nucleus accumbens, and cerebellum that have previously been implicated in FAA. These results underscore the importance of feeding schedule parameters in determining quantitative features of FAA in mice, and demonstrate dissociations between behavioral FAA and neural activity in brain areas thought to harbor FEOs or participate in their entrainment or output. PMID:24806659

Gunapala, Keith M.; Parfyonov, Maksim; Chang, Chris H.; Mistlberger, Ralph E.; Steele, Andrew D.

2014-01-01

195

Chimeric TK-NOG Mice: A Predictive Model for Cholestatic Human Liver Toxicity.  

PubMed

Due to the substantial interspecies differences in drug metabolism and disposition, drug-induced liver injury (DILI) in humans is often not predicted by studies performed in animal species. For example, a drug (bosentan) used to treat pulmonary artery hypertension caused unexpected cholestatic liver toxicity in humans, which was not predicted by preclinical toxicology studies in multiple animal species. In this study, we demonstrate that NOG mice expressing a thymidine kinase transgene (TK-NOG) with humanized livers have a humanized profile of biliary excretion of a test (cefmetazole) drug, which was shown by an in situ perfusion study to result from interspecies differences in the rate of biliary transport and in liver retention of this drug. We also found that readily detectable cholestatic liver injury develops in TK-NOG mice with humanized livers after 1 week of treatment with bosentan (160, 32, or 6 mg/kg per day by mouth), whereas liver toxicity did not develop in control mice after 1 month of treatment. The laboratory and histologic features of bosentan-induced liver toxicity in humanized mice mirrored that of human subjects. Because DILI has become a significant public health problem, drug safety could be improved if preclinical toxicology studies were performed using humanized TK-NOG. PMID:25424997

Xu, Dan; Wu, Manhong; Nishimura, Sachiko; Nishimura, Toshihiko; Michie, Sara A; Zheng, Ming; Yang, Zicheng; Yates, Alexander John; Day, Jeffrey S; Hillgren, Kathleen M; Takeda, Saori Takedai; Guan, Yuan; Guo, Yingying; Peltz, Gary

2015-02-01

196

Functional consequences of EpCam mutation in mice and men.  

PubMed

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

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

2014-02-15

197

Witches' Potion Demonstration  

NSDL National Science Digital Library

In this chemistry demonstration, learners will discover that phenolphthalein is an acid/base indicator. One learner will read a poem about four witches making a potion. Four learners will act out the parts, adding chemicals and water to different beakers (with adult supervision). Learners will enjoy the poem as the indicators react with the substances and change color. This is a fun chemistry demonstration to use during Halloween.

The Science House

2014-01-28

198

Growth Hormone (GH) Hypersecretion and GH Receptor Resistance in Streptozotocin Diabetic Mice in Response to a GH Secretagogue  

PubMed Central

The growth hormone (GH) and insulin-like growth factor I (IGF-I) axis were studied in streptozotocin (STZ) diabetic and nondiabetic female mice following intravenous (IV) injection of the GH secretagogue (GHS) ipamorelin or saline. On day 14, blood samples were obtained before and 10 minutes after the injection. Livers were removed and frozen for determination of the mRNA expressions of the GH receptor, GH-binding protein, and IGF-I, and hepatic IGF-I peptide. Serum samples were analyzed for GH and IGF-I. Following ipamorelin injection, the GH levels were found to be 150 ± 35 ?g/L and 62 ± 11 ?g/L in the diabetic compared to the nondiabetic mice (P < .05). Serum IGF-I levels were lower in diabetic than in nondiabetic animals, and rose after stimulation only in the nondiabetic animals. Furthermore, hepatic GH resistance and IGF-I mRNA levels and IGF-I peptide were increased in nondiabetic animals in response to GH stimulation, whereas the low levels per se of all these parameters in diabetic mice were unaffected. The study shows that STZ diabetic mice demonstrate a substantial part of the clinical features of type 1 diabetes in humans, including GH hypersecretion and GH resistance. Accordingly, it is proposed that STZ diabetic mice may be a better model of the perturbations of the GH/IGF-I axis in diabetes than STZ diabetic rats. PMID:14630569

Segev, Yael; Landau, Daniel; Phillip, Moshe; Flyvbjerg, Allan

2003-01-01

199

Evaluation of the Medicaid Competition Demonstrations  

PubMed Central

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

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

1989-01-01

200

MICE: a mouse imaging collaboration environment  

NASA Astrophysics Data System (ADS)

With the ever-increasing complexity of science and engineering, many important research problems are being addressed by collaborative, multidisciplinary teams. We present a web-based collaborative environment for small animal imaging research, called the Mouse Imaging Collaboration Environment (MICE). MICE provides an effective and user-friendly tool for managing and sharing of the terabytes of high-resolution and high-dimension image data generated at small animal imaging core facilities. We describe the design of MICE and our experience in the implementation and deployment of a beta-version baseline-MICE. The baseline-MICE provides an integrated solution from image data acquisition to end-user access and long-term data storage at our UH/Case Small Animal Imaging Resource Center. As image data is acquired from scanners, it is pushed to the MICE server which automatically stores it in a directory structure according to its DICOM metadata. The directory structure reflects imaging modality, principle investigators, animal models, scanning dates and study details. Registered end-users access this imaging data through an authenticated web-interface. Thumbnail images are created by custom scripts running on the MICE server while data down-loading is achieved through standard web-browser ftp. MICE provides a security infrastructure that manages user roles, their access privileges such as read/write, and the right to modify the access privileges. Additional data security measures include a two server paradigm with the Web access server residing outside a network firewall to provide access through the Internet, and the imaging data server - a large RAID storage system supporting flexible backup policies - residing behind the protected firewall with a dedicated link to the Web access server. Direct network link to the RAID storage system outside the firewall other than this dedicated link is not permitted. Establishing the initial image directory structure and letting the project leader manage data access through a web-interface represent Phase I implementation. In Phase II, features for uploading image analysis scripts and results back to the MICE server will be implemented, as well as mechanisms facilitating asynchronous and synchronous discussion, annotation, and analysis. Most of MICE features are being implemented in the Plone 5 object-oriented database environment which greatly shortens developmental time and effort by the reuse of a variety of Plone's open-source modules for Content Management Systems. 7, 8 The open-source modules are well suited as an implementation basis of MICE and provide data integration as a built-in primitive.

Szymanski, Jacek; Flask, Chris; Wilson, David; Johnson, David; Muzic, Raymond F., Jr.; Zhang, Guo-Qiang

2006-03-01

201

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

PubMed Central

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

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

2014-01-01

202

Listeria Infection Demonstration  

NSDL National Science Digital Library

Dr. Finlay and a student volunteer show how Listeria infects a cell, using a marble and some yellow gelatin. Also featured on the DVD 2000 and Beyond: Confronting the Microbe Menace, available free from HHMI. This video is one minute and 4 seconds in length, and available in MOV (7 MB) and WMV (10 MB). All Infectious Disease videos are located at: http://www.hhmi.org/biointeractive/disease/video.html.

Dr. Brett Finlay (Howard Hughes Medical Institute;)

2007-03-27

203

Feature Subset Selection Using a Genetic Algorithm  

Microsoft Academic Search

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

Jihoon Yang; Vasant Honavar

1998-01-01

204

TRUEX hot demonstration  

SciTech Connect

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.

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

1990-04-01

205

Autonomous docking ground demonstration  

NASA Technical Reports Server (NTRS)

The Autonomous Docking Ground Demonstration is an evaluation of the laser sensor system to support the docking phase (12 ft to contact) when operated in conjunction with the guidance, navigation, and control (GN&C) software. The docking mechanism being used was developed for the Apollo/Soyuz Test Program. This demonstration will be conducted using the 6-DOF Dynamic Test System (DTS). The DTS simulates the Space Station Freedom as the stationary or target vehicle and the Orbiter as the active or chase vehicle. For this demonstration, the laser sensor will be mounted on the target vehicle and the retroflectors will be on the chase vehicle. This arrangement was chosen to prevent potential damage to the laser. The laser sensor system, GN&C, and 6-DOF DTS will be operated closed-loop. Initial conditions to simulate vehicle misalignments, translational and rotational, will be introduced within the constraints of the systems involved.

Lamkin, Steve L.; Le, Thomas Quan; Othon, L. T.; Prather, Joseph L.; Eick, Richard E.; Baxter, Jim M.; Boyd, M. G.; Clark, Fred D.; Spehar, Peter T.; Teters, Rebecca T.

1991-01-01

206

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

PubMed Central

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

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

2014-01-01

207

Video Demonstration: Proportions  

NSDL National Science Digital Library

This video demonstration from Watch Know Learn will help students learning about proportions. The video will help students with some knowledge of proportions by showing examples of how to solve them. The definition of a proportion is included as well as examples of how to cross-multiply to solve proportion problems. The demonstration shows what a non-proportion problem looks like and how to solve it as well as a few examples of using the lowest common denominator to solve proportions. Flash player is required to view the video, and the running time for the video is 8:09.

2012-08-28

208

Standing Wave Demonstration  

NSDL National Science Digital Library

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

209

Hardware demonstration of flexible beam control  

NASA Technical Reports Server (NTRS)

An experiment employing a pinned-free flexible beam has been constructed to demonstrate and verify several facets of the control of flexible structures. The desired features of the experiment are to demonstrate active shape control, active dynamic control, adaptive control, various control law design approaches, and associated hardware requirements and mechanization difficulties. This paper contains the analytical work performed in support of the facility development, the final design specifications, control law synthesis, and some preliminary results.

Schaechter, D. B.

1980-01-01

210

A Biofeedback Demonstration.  

ERIC Educational Resources Information Center

Describes a demonstration for measurement of biophysical signals produced by the human body. The signals, after amplification, could provide acoustical feedback through a voltage-controlled oscillator (VCO), or they could be seen either with an oscilloscope or a high speed chart recorder. (GA)

Garrity, Michael K.

1978-01-01

211

Overhead Projector Demonstrations.  

ERIC Educational Resources Information Center

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)

Kolb, Doris, Ed.

1988-01-01

212

Overhead Projector Demonstrations.  

ERIC Educational Resources Information Center

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)

Kolb, Doris, Ed.

1989-01-01

213

Astronomy LITE Demonstrations  

NASA Astrophysics Data System (ADS)

Project LITE (Light Inquiry Through Experiments) is a materials, software, and curriculum development project. It focuses on light, optics, color and visual perception. According to two recent surveys of college astronomy faculty members, these are among the topics most often included in the large introductory astronomy courses. The project has aimed largely at the design and implementation of hands-on experiences for students. However, it has also included the development of lecture demonstrations that employ novel light sources and materials. In this presentation, we will show some of our new lecture demonstrations concerning geometrical and physical optics, fluorescence, phosphorescence and polarization. We have developed over 200 Flash and Java applets that can be used either by teachers in lecture settings or by students at home. They are all posted on the web at http://lite.bu.edu. For either purpose they can be downloaded directly to the user's computer or run off line. In lecture demonstrations, some of these applets can be used to control the light emitted by video projectors to produce physical effects in materials (e.g. fluorescence). Other applets can be used, for example, to demonstrate that the human percept of color does not have a simple relationship with the physical frequency of the stimulating source of light. Project LITE is supported by Grant #DUE-0125992 from the NSF Division of Undergraduate Education.

Brecher, Kenneth

2006-12-01

214

A Fruity Biochemistry Demonstration  

ERIC Educational Resources Information Center

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…

Shmaefsky, Brian R.

2005-01-01

215

New Technology Demonstration Program  

E-print Network

New Technology Demonstration Program FEMPFederal Energy Management Program Trends in Energy Management Technology ­ Part 4 Review of Advanced Applications in Energy Management, Control, and Information to emerging trends in EMCIS and potential benefits to the Federal sector. The first article [1] covered

216

Demonstration Road Show  

NSDL National Science Digital Library

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

2009-04-06

217

Why Demonstrations Matter  

ERIC Educational Resources Information Center

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

Black, Richard

2005-01-01

218

Participatory Lecture Demonstrations.  

ERIC Educational Resources Information Center

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…

Battino, Rubin

1979-01-01

219

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...

220

Musical acoustics demonstrations  

NASA Astrophysics Data System (ADS)

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

Hoekje, P. L.

2003-10-01

221

Space fabrication demonstration system  

NASA Technical Reports Server (NTRS)

The lower right aluminum beam cap roll forming mill was delivered and installed in the beam builder. The beam was brought to full operational status and beams of one to six bay lengths were produced to demonstrate full system capability. Although the cap flange waviness problem persists, work is progressing within cost and schedule.

1978-01-01

222

Calculus Demonstrations Using MATLAB  

ERIC Educational Resources Information Center

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…

Dunn, Peter K.; Harman, Chris

2002-01-01

223

Structural Vibrations Laboratory Demonstrator  

Microsoft Academic Search

The primary objective of this project was to develop a laboratory demonstrator of structural vibrations. When the ground moves under a structure the effect on that structure is dependent upon the relationship between the frequency of the ground motion and the natural frequency of the structure. As this relationship, the frequency ratio, approaches one (1) the effect is at its

Reen E Foley

2006-01-01

224

Electromagnetic Induction Demonstration  

NSDL National Science Digital Library

This simple demonstration shows the interaction between electricity and magnetism. Two coils of wire are held close to each other, but not touching. One is attached to a music source, such as a small radio or iPod, and the other is attached to an external speaker. Students can hear the music through the speaker even though there is no direct connection.

Hobbs, Marsha

225

Astronomy Demonstrations and Models.  

ERIC Educational Resources Information Center

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,…

Eckroth, Charles A.

226

AP Biology Demonstrations  

NSDL National Science Digital Library

A collection of experiments and demonstrations presented by biology teachers addressing some of the most difficult-to-understand topics in the AP biology curriculum which include evolutionary traits, genetics, bacterial transformation, antibody diversity, comparative anatomy, photosynthesis, human genetics, protein synthesis, recombinant DNA and RNA polymerase.

The College Board The College Board (The College Board;)

2003-06-03

227

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...

228

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...

229

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

PubMed

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

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

2012-03-27

230

Hepcidin as a therapeutic tool to limit iron overload and improve anemia in ?-thalassemic mice  

PubMed Central

Excessive iron absorption is one of the main features of ?-thalassemia and can lead to severe morbidity and mortality. Serial analyses of ?-thalassemic mice indicate that while hemoglobin levels decrease over time, the concentration of iron in the liver, spleen, and kidneys markedly increases. Iron overload is associated with low levels of hepcidin, a peptide that regulates iron metabolism by triggering degradation of ferroportin, an iron-transport protein localized on absorptive enterocytes as well as hepatocytes and macrophages. Patients with ?-thalassemia also have low hepcidin levels. These observations led us to hypothesize that more iron is absorbed in ?-thalassemia than is required for erythropoiesis and that increasing the concentration of hepcidin in the body of such patients might be therapeutic, limiting iron overload. Here we demonstrate that a moderate increase in expression of hepcidin in ?-thalassemic mice limits iron overload, decreases formation of insoluble membrane-bound globins and reactive oxygen species, and improves anemia. Mice with increased hepcidin expression also demonstrated an increase in the lifespan of their red cells, reversal of ineffective erythropoiesis and splenomegaly, and an increase in total hemoglobin levels. These data led us to suggest that therapeutics that could increase hepcidin levels or act as hepcidin agonists might help treat the abnormal iron absorption in individuals with ?-thalassemia and related disorders. PMID:21099112

Gardenghi, Sara; Ramos, Pedro; Marongiu, Maria Franca; Melchiori, Luca; Breda, Laura; Guy, Ella; Muirhead, Kristen; Rao, Niva; Roy, Cindy N.; Andrews, Nancy C.; Nemeth, Elizabeta; Follenzi, Antonia; An, Xiuli; Mohandas, Narla; Ginzburg, Yelena; Rachmilewitz, Eliezer A.; Giardina, Patricia J.; Grady, Robert W.; Rivella, Stefano

2010-01-01

231

Experimental aspergillosis in mice: aspects of resistance  

PubMed Central

Intravenous inoculation of Aspergillus fumigatus spores was used to study experimentally induced and natural resistance. Slight resistance resulted in increased survival time and higher resistance produced in addition a decreased infection rate. Sublethal doses of living spores gave significant protection against challenge 3 weeks later, but large doses of heat-killed spores had no demonstrable effect. Mice from one source showed a single, dramatic decrease in dose response to a deep-frozen strain of the organism over a period of 34 months. The dose response initially resembled that described by Scholer (1959) in which one million spores killed the majority of mice. The change was almost certainly due to an increase in resistance of the mice due to environmental factors, and the resistance was probably also effective against other strains of the organism. Although not proved, it seemed likely that the resistance was due to increased natural contact with A. fumigatus or related fungi. Possibly for a similar reason, mice of the same stock bred on different premises differed in their susceptibility to infection. The results indicated that environmental resistance-producing factors may have been operating simultaneously on a number of premises housing laboratory animals in south-east England. These findings may have significance in relation to the occurrence of natural aspergillosis of mammals and birds. Of five A. fumigatus strains, four were of closely similar virulence; the fifth strain grew more slowly in vitro and was somewhat less virulent. Isolates from mice which died sporadically after small doses of spores were of no greater virulence than the inoculated strain. Although the susceptibility of mice aged 3 weeks was not uniform under all conditions, such animals were less resistant than young adult mice. Mice from six different sources showed only slight differences in susceptibility between each other, or from mice known to have developed a natural resistance. PMID:4567315

Smith, G. R.

1972-01-01

232

Measuring the strength of mice.  

PubMed

Kondziela devised the inverted screen test and published it in 1964. It is a test of muscle strength using all four limbs. Most normal mice easily score maximum on this task; it is a quick but insensitive gross screen, and the weights test described in this article will provide a finer measure of muscular strength. There are also several strain gauge-based pieces of apparatus available commercially that will provide more graded data than the inverted screen test, but their cost may put them beyond the reach of many laboratories which do not specialize in strength testing. Hence in 2000 a cheap and simple apparatus was devised by the author. It consists of a series of chain links of increasing length, attached to a "fur collector" a ball of fine wire mesh sold for preventing limescale build up in hard water areas. An accidental observation revealed that mice could grip these very tightly, so they proved ideal as a grip point for a weight-lifting apparatus. A common fault with commercial strength meters is that the bar or other grip feature is not thin enough for mice to exert a maximum grip. As a general rule, the thinner the wire or bar, the better a mouse can grip with its small claws. This is a pure test of strength, although as for any test motivational factors could potentially play a role. The use of scale collectors, however, seems to minimize motivational problems as the motivation appears to be very high for most normal young adult mice. PMID:23770643

Deacon, Robert M J

2013-01-01

233

Fabrication, Testing and Modeling of the MICE Superconducting Spectrometer Solenoids  

SciTech Connect

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.

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

2010-05-16

234

Technology Tips: Building Interactive Demonstrations with Sage  

ERIC Educational Resources Information Center

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…

Murray, Maura

2013-01-01

235

Automatic lighting controls demonstration  

SciTech Connect

The purpose of this work was to demonstrate, in a real building situation, the energy and peak demand reduction capabilities of an electronically ballasted lighting control system that can utilize all types of control strategies to efficiently manage lighting. The project has demonstrated that a state-of-the-art electronically ballasted dimmable lighting system can reduce energy and lighting demand by as least 50% using various combinations of control strategies. By reducing light levels over circulation areas (tuning) and reducing after hours light levels to accommodate the less stringent lighting demands of the cleaning crew (scheduling), lighting energy consumption on weekdays was reduced an average of 54% relative to the initial condition. 10 refs., 14 figs., 3 tabs.

Rubinstein, F.; Verderber, R.

1990-03-01

236

AVNG system demonstration  

SciTech Connect

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.

Thron, Jonathan Louis [Los Alamos National Laboratory; Mac Arthur, Duncan W [Los Alamos National Laboratory; Kondratov, Sergey [VNIIEF; Livke, Alexander [VNIIEF; Razinkov, Sergey [VNIIEF

2010-01-01

237

Nucla CFB Demonstration Project  

SciTech Connect

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)

Not Available

1990-12-01

238

Molecular Dynamics Demonstration Model  

NSDL National Science Digital Library

The EJS Molecular Dynamics Demonstration model is constructed using the Lennard-Jones potential truncated at a distance of 3 molecular diameters. The motion of the molecules is governed by Newton's laws, approximated using the Verlet algorithm with the indicated Time step. For sufficiently small time steps dt, the system's total energy should be approximately conserved. Users can select various initial configurations using the drop down menu. Ejs Molecular Dynamics Demonstration model was created using the Easy Java Simulations (Ejs) modeling tool. It is distributed as a ready-to-run (compiled) Java archive. Double clicking the js_stp_md_MolecularDynamicsDemo.jar file will run the program if Java is installed. Ejs is a part of the Open Source Physics Project and is designed to make it easier to access, modify, and generate computer models. Additional Ejs models for statistical mechanics are available. They can be found by searching ComPADRE for Open Source Physics, OSP, or Ejs.

Christian, Wolfgang

2008-11-15

239

Chemical Domino Demonstration  

NASA Astrophysics Data System (ADS)

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.

Alexander, M. Dale

1998-04-01

240

Mars Umbilical Technology Demonstrator  

NASA Technical Reports Server (NTRS)

The objective of this project is to develop a autonomous umbilical mating for the mars umbilical technology demonstrator. The Mars Umbilical Technology Demonstrator (MUTD) shall provide electrical power and fiber optic data cable connections between two simulated mars vehicles. The Omnibot is used to provide the mobile base for the system. The mate to umbilical plate is mounted on a three axis Cartesian table, which is installed on the Omnibot mobile base. The Omnibot is controlled in a teleoperated mode. The operator using the vision system will guide the Omnibot to get close to the mate to plate. The information received from four ultrasonic sensors is used to identify the position of mate to plate and mate the umbilical plates autonomously. A successful experimentation verifies the approach.

Houshangi, Nasser

2000-01-01

241

Invisible Ink Demonstration  

NSDL National Science Digital Library

In this chemistry demonstration, learners will discover that phenolphthalein is a chemical that displays different colors depending on the acidity or basicity of the environment. Learners will be surprised to see a "secret message" appear in bright pink ink when it is sprayed with Windex containing ammonia (a base). They compare this to what happens when the message is sprayed with Windex containing acetic acid (nothing!).

House, The S.

2014-01-28

242

Joined Beryllium Mirror Demonstrator  

NASA Technical Reports Server (NTRS)

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.

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

2001-01-01

243

Decaborane ion source demonstration  

Microsoft Academic Search

This project demonstrated concept and feasibility of a proprietary high current decaborane ion source suitable for ultra shallow doping. This was motivated by the attractive scaling of decaborane ions for space charge dominated extraction and transport. A highly modified Bernas source was mounted on an NV-10\\/80 implanter. Using standard extraction and beamline components, 2.3 mA of boron nucleon current was

M. C. Vella; R. Tysinger; M. Reilly; B. Brown

2000-01-01

244

Foveated imaging demonstration  

NASA Astrophysics Data System (ADS)

A wide field-of-view (FOV), theoretically diffraction-limited imaging system is demonstrated using a single positive lens (a singlet), a reflective liquid crystal spatial light modulator (SLM), a turning mirror and a CCD camera. The SLM is used to correct the off-axis aberrations that would otherwise limit the useful FOV of our system. Foveated imaging refers to the variation in spatial resolution across the image caused by using the SLM in this manner.

Wick, David V.; Martinez, Ty; Restaino, Sergio R.; Stone, B. R.

2002-01-01

245

Foveated imaging demonstration.  

PubMed

A wide field-of-view (FOV), theoretically diffraction-limited imaging system is demonstrated using a single positive lens (a singlet), a reflective liquid crystal spatial light modulator (SLM), a turning mirror and a CCD camera. The SLM is used to correct the off-axis aberrations that would otherwise limit the useful FOV of our system. Foveated imaging refers to the variation in spatial resolution across the image caused by using the SLM in this manner. PMID:19424331

Wick, David; Martinez, Ty; Restaino, Sergio; Stone, B

2002-01-14

246

Overhead Projector Demonstrations.  

ERIC Educational Resources Information Center

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

Kolb, Doris

1988-01-01

247

Chronic Cigarette Smoke Causes Oxidative Damage and Apoptosis to Retinal Pigmented Epithelial Cells in Mice  

PubMed Central

The purpose of this study was to determine whether mice exposed to chronic cigarette smoke develop features of early age-related macular degeneration (AMD). Two month old C57Bl6 mice were exposed to either filtered air or cigarette smoke in a smoking chamber for 5 h/day, 5 days/week for 6 months. Eyes were fixed in 2.5% glutaraldehyde/2% paraformaldehyde and examined for ultrastructural changes by transmission electron microscopy. The contralateral eye was fixed in 2% paraformaldehyde and examined for oxidative injury to the retinal pigmented epithelium (RPE) by 8-oxo-7,8-dihydro-2?-deoxyguanosine (8-OHdG) immunolabeling and apoptosis by TUNEL labeling. Mice exposed to cigarette smoke had immunolabeling for 8-OHdG in 85±3.7% of RPE cells counted compared to 9.5±3.9% in controls (p<0.00001). Bruch membrane was thicker in mice exposed to smoke (1086±332 nm) than those raised in air (543±132 nm; p?=?0.0069). The two most pronounced ultrastructural changes (severity grading scale from 0–3) seen were a loss of basal infoldings (mean difference in grade?=?1.98; p<0.0001), and an increase in intracellular vacuoles (mean difference in grade?=?1.7; p<0.0001). Ultrastructural changes to Bruch membrane in cigarette-smoke exposed mice were smaller in magnitude but consistently demonstrated significantly higher grade injury in cigarette-exposed mice, including basal laminar deposits (mean difference in grade?=?0.54; p<0.0001), increased outer collagenous layer deposits (mean difference in grade?=?0.59; p?=?0.002), and increased basal laminar deposit continuity (mean difference in grade?=?0.4; p<0.0001). TUNEL assay showed a higher percentage of apoptotic RPE from mice exposed to cigarette smoke (average 8.0±1.1%) than room air (average 0±0%; p?=?0.043). Mice exposed to chronic cigarette smoke develop evidence of oxidative damage with ultrastructural degeneration to the RPE and Bruch membrane, and RPE cell apoptosis. This model could be useful for studying the mechanism of smoke induced changes during early AMD. PMID:18769672

Fujihara, Masashi; Nagai, Norihiro; Sussan, Thomas E.; Biswal, Shyam; Handa, James T.

2008-01-01

248

Unsupervised Feature Selection Using Feature Similarity  

Microsoft Academic Search

In this article, we describe an unsupervised feature selection algorithm suitable for data sets, large in both dimension and size. The method is based on measuring similarity between features whereby redundancy therein is removed. This does not need any search and, therefore, is fast. A new feature similarity measure, called maximum information compression index, is introduced. The algorithm is generic

Pabitra Mitra; C. A. Murthy; Sankar K. Pal

2002-01-01

249

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 ...

250

NAVAJO ELECTRIFICATION DEMONSTRATION PROJECT  

SciTech Connect

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.

Terry W. Battiest

2008-06-11

251

Space Research Benefits Demonstrated  

NASA Technical Reports Server (NTRS)

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.

2000-01-01

252

Demonstration of optical microfluidics  

NASA Astrophysics Data System (ADS)

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.

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

2004-06-01

253

Exploration Medical System Demonstration  

NASA Technical Reports Server (NTRS)

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.

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

2014-01-01

254

Slime: Classroom Demonstration  

NSDL National Science Digital Library

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

Goodwin, Debbie; Nydam, Andrew

2010-08-06

255

Sirt1-deficient mice exhibit an altered cartilage phenotype  

PubMed Central

Objective We previously demonstrated that Sirt1 regulates apoptosis in cartilage in vitro. Here we attempt to examine in vivo cartilage homeostasis, using Sirt1 total body knockout (KO) mice. Method Articular cartilage was harvested from hind paws of 1-week and 3-week-old mice carrying wild type (WT) or null Sirt1 gene. Knees of Sirt1 haploinsufficient mice also were examined, at 6 months. Joint cartilage was processed for histologic examination or biochemical analyses of chondrocyte cultures. Results We found that articular cartilage tissue sections from Sirt1 KO mice up to 3 weeks of age exhibited low levels of type 2 collagen, aggrecan, and glycosaminoglycan content. In contrast, protein levels of MMP-13 were elevated in the Sirt1 KO mice, leading to a potential increase of cartilage breakdown, already shown in the heterozygous mice. Additional results showed elevated chondrocyte apoptosis in Sirt1 KO mice, as compared to WT controls. In addition to these observations, PTP1b (protein tyrosine phosphatase b) was elevated in the Sirt1 KO mice, in line with previous reports. Conclusion The findings from this animal model demonstrated that Sirt1 KO mice presented an altered cartilage phenotype, with an elevated apoptotic process and a potential degradative cartilage process. PMID:23587642

Gabaya, Odile; Zaal, Kristien J.; Sanchez, Christelle; Dvir-Ginzberg, Mona; Gagarina, Viktoria; Song, Yingjie; He, Xiao Hong; McBurney, Michael W.

2014-01-01

256

Resistance of Fc receptor- deficient mice to fatal glomerulonephritis.  

PubMed Central

Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We examined the contribution of Fc receptors in the induction of nephrotoxic GN by establishing and analyzing mice deficient in the Fc receptor gamma chain (FcRgamma). Whereas all wild-type mice died from severe glomerulonephritis with hypernitremia by administration of anti-glomerular basement membrane (GBM) antibodies, all FcRgamma-deficient mice survived. Histologically, wild-type mice showed glomerular hypercellularity and thrombotic changes, whereas the renal tissue in FcRgamma-deficient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GBM were equally observed in both wild-type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR+ cells. PMID:9739057

Park, S Y; Ueda, S; Ohno, H; Hamano, Y; Tanaka, M; Shiratori, T; Yamazaki, T; Arase, H; Arase, N; Karasawa, A; Sato, S; Ledermann, B; Kondo, Y; Okumura, K; Ra, C; Saito, T

1998-01-01

257

Solar Thermal Demonstration Project  

SciTech Connect

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.

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

2012-01-30

258

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

PubMed Central

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

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

2013-01-01

259

The Stimulus Properties of LSD in C57BL/6 Mice1  

PubMed Central

Rationale Drug-induced stimulus control has proven to be a powerful tool for the assessment of a wide range of psychoactive drugs. Though a variety of species have been employed, the majority of studies have been in the rat. However, with the development of techniques which permit the genetic modification of mice, the latter species has taken on new importance. Lysergic acid diethylamide [LSD], the prototypic indoleamine hallucinogen, has not previously been trained as a discriminative stimulus in mice. Objective To demonstrate the feasibility of LSD-induced stimulus control in the mouse and to provide a preliminary characterization of the stimulus properties of LSD in that species. Methods Male C57BL/6 mice were trained using a left or right nose-poke operant on a fixed-ratio 10, water reinforced task following the injection of lysergic acid diethylamide [LSD, 0.17 or 0.30 mg/kg, SC; 15 min pretreatment] or vehicle. Results Stimulus control was established in 6 of 16 mice at a dose of LSD of 0.17 mg/kg after 39 sessions. An increase in dose to 0.30 mg/kg for the remaining mice resulted in stimulus control in an additional 5 subjects. In the low dose group, subsequent experiments demonstrated an orderly dose-effect relationship for LSD and a rapid offset of drug action with an absence of LSD effects 60 min after injection. When LSD [0.17 mg/kg] was administered in combination with the selective 5-HT2A antagonist, M100907, LSD-appropriate responding was significantly but incompletely reduced to approximately 50%; concurrently, response rates declined significantly. In mice trained with a dose of LSD of 0.30 mg/kg, full generalization to the phenethylamine hallucinogen, [-]-2,5-dimethoxy-4-methylamphetamine [DOM] was observed. Conclusions The present data demonstrate the feasibility of LSD-induced stimulus control in the mouse. The general features of stimulus control by LSD in the mouse closely resemble those observed in the rat but the present data suggest that there may be significant differences as well. PMID:16005500

Winter, J. C.; Kiers, A. K.; Zimmerman, M. D.; Reissig, C. J; Eckler, J.R.; Ullrich, T.; Rice, K. C.; Rabin, R. A.; Richards, J. B.

2005-01-01

260

Electrodynamic Dust Shield Demonstrator  

NASA Technical Reports Server (NTRS)

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

Stankie, Charles G.

2013-01-01

261

Fuel Cell Demonstration Program  

SciTech Connect

In an effort to promote clean energy projects and aid in the commercialization of new fuel cell technologies the Long Island Power Authority (LIPA) initiated a Fuel Cell Demonstration Program in 1999 with six month deployments of Proton Exchange Membrane (PEM) non-commercial Beta model systems at partnering sites throughout Long Island. These projects facilitated significant developments in the technology, providing operating experience that allowed the manufacturer to produce fuel cells that were half the size of the Beta units and suitable for outdoor installations. In 2001, LIPA embarked on a large-scale effort to identify and develop measures that could improve the reliability and performance of future fuel cell technologies for electric utility applications and the concept to establish a fuel cell farm (Farm) of 75 units was developed. By the end of October of 2001, 75 Lorax 2.0 fuel cells had been installed at the West Babylon substation on Long Island, making it the first fuel cell demonstration of its kind and size anywhere in the world at the time. Designed to help LIPA study the feasibility of using fuel cells to operate in parallel with LIPA's electric grid system, the Farm operated 120 fuel cells over its lifetime of over 3 years including 3 generations of Plug Power fuel cells (Lorax 2.0, Lorax 3.0, Lorax 4.5). Of these 120 fuel cells, 20 Lorax 3.0 units operated under this Award from June 2002 to September 2004. In parallel with the operation of the Farm, LIPA recruited government and commercial/industrial customers to demonstrate fuel cells as on-site distributed generation. From December 2002 to February 2005, 17 fuel cells were tested and monitored at various customer sites throughout Long Island. The 37 fuel cells operated under this Award produced a total of 712,635 kWh. As fuel cell technology became more mature, performance improvements included a 1% increase in system efficiency. Including equipment, design, fuel, maintenance, installation, and decommissioning the total project budget was approximately $3.7 million.

Gerald Brun

2006-09-15

262

Fusion Power Demonstration III  

SciTech Connect

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.

Lee, J.D. (ed.)

1985-07-01

263

Jennings Demonstration PLant  

SciTech Connect

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.

Russ Heissner

2010-08-31

264

Demonstrating An Epidemic  

NSDL National Science Digital Library

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

Powel, M. B.

2009-01-01

265

Space Research Benefits Demonstrated  

NASA Technical Reports Server (NTRS)

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.

2000-01-01

266

Demonstration of microfiltration technology  

SciTech Connect

The U.S. Environmental Protection Agency, under the Superfund Innovative Technology Evaluation (SITE) program in cooperation with E.I. DuPont de Nemours and Company, Inc. (DuPont) and the Oberlin Filter Company (Oberlin), undertook a field demonstration project to evaluate microfiltration technology for removal of zinc and suspended solids from wastewater. The microfiltration system utilized DuPont's Tyvek T-980 membrane filter media in conjunction with the Oberlin automatic pressure filter. The project was undertaken at the Palmerton Zinc Superfund site in April, 1990. Analysis of the treated filtrate indicated that the system removed precipitated zinc and other suspended solids at an efficiency greater than 99.9 percent. (Copyright (c) 1991--Air and Waste Management Association.)

Martin, J.F.; Topudurti, K.; Labunski, S.

1991-01-01

267

Selective pattern of motor system damage in gamma-synuclein transgenic mice mirrors the respective pathology in amyotrophic lateral sclerosis  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is characterised by substantial loss of both upper and lower motor neuron function, with sensory and cognitive systems less affected. Though heritable forms of the disease have been described, the vast majority of cases are sporadic with poorly defined underlying pathogenic mechanisms. Here we demonstrate that the neurological pathology induced in transgenic mice by overexpression of ?-synuclein, a protein not previously associated with ALS, recapitulates key features of the disease, namely selective damage and loss of discrete populations of upper and lower motor neurons and their axons, contrasted by limited effects upon the sensory system. PMID:22750530

Peters, Owen M.; Millership, Steven; Shelkovnikova, Tatyana A.; Soto, Ileana; Keeling, Lora; Hann, Anthony; Marsh-Armstrong, Nicholas; Buchman, Vladimir L.; Ninkina, Natalia

2012-01-01

268

Metabolomics reveals significant impairments in the immune system of the APP/PS1 transgenic mice of Alzheimer's disease.  

PubMed

Inflammatory processes and other failures related to the immune system are common features associated with Alzheimer's disease (AD), in both brain and the peripheral system. Thus, the study of the main organs of the immune system may have a great potential for the elucidation of pathological mechanisms underlying these abnormalities. This is the first metabolomic investigation performed in spleen and thymus from transgenic mice of AD. Tissues were fingerprinted using a metabolomic platform comprising GC-MS and ultra-HPLC-MS. Multivariate statistics demonstrated significant differences in numerous metabolites between the APP/PS1 mice and wild-type controls, and it was proven that multiple biochemical pathways are disturbed in these organs including abnormal metabolism of phospholipids, energy deficiencies, altered homeostasis of amino acids, oxidative stress, and others. Therefore, these findings highlight the importance of the proper metabolic functioning of peripheral immune system in the development of neurodegenerative disorders such as AD. PMID:25393935

González-Domínguez, Raúl; García-Barrera, Tamara; Vitorica, Javier; Gómez-Ariza, José Luis

2015-02-01

269

Plug cluster module demonstration  

NASA Technical Reports Server (NTRS)

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

Rousar, D. C.

1978-01-01

270

NASA Bioreactor Demonstration System  

NASA Technical Reports Server (NTRS)

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.

2002-01-01

271

Altered Tnnt3 characterizes selective weakness of fast fibers in mice overexpressing FSHD region gene 1 (FRG1)  

PubMed Central

Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is characterized by atrophy and weakness of selective muscle groups. FSHD is considered an autosomal dominant disease with incomplete penetrance and unpredictable variability of clinical expression within families. Mice overexpressing FRG1 (FSHD region gene 1), a candidate gene for this disease, develop a progressive myopathy with features of the human disorder. Here, we show that in FRG1-overexpressing mice, fast muscles, which are the most affected by the dystrophic process, display anomalous fast skeletal troponin T (fTnT) isoform, resulting from the aberrant splicing of the Tnnt3 mRNA that precedes the appearance of dystrophic signs. We determine that muscles of FRG1 mice develop less strength due to impaired contractile properties of fast-twitch fibers associated with an anomalous MyHC-actin ratio and a reduced sensitivity to Ca2+. We demonstrate that the decrease of Ca2+ sensitivity of fast-twitch fibers depends on the anomalous troponin complex and can be rescued by the substitution with the wild-type proteins. Finally, we find that the presence of aberrant splicing isoforms of TNNT3 characterizes dystrophic muscles in FSHD patients. Collectively, our results suggest that anomalous TNNT3 profile correlates with the muscle impairment in both humans and mice. On the basis of these results, we propose that aberrant fTnT represents a biological marker of muscle phenotype severity and disease progression. PMID:24305066

Sancisi, Valentina; Germinario, Elena; Esposito, Alessandra; Morini, Elisabetta; Peron, Samantha; Moggio, Maurizio; Tomelleri, Giuliano; Danieli-Betto, Daniela

2013-01-01

272

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

PubMed

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

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

2014-08-01

273

Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2  

PubMed Central

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant familial Parkinson's disease (PD) and also contribute to idiopathic PD. LRRK2 mutations represent the most common cause of PD with clinical and neurochemical features that are largely indistinguishable from idiopathic disease. Currently, transgenic mice expressing wild-type or disease-causing mutants of LRRK2 have failed to produce overt neurodegeneration, although abnormalities in nigrostriatal dopaminergic neurotransmission have been observed. Here, we describe the development and characterization of transgenic mice expressing human LRRK2 bearing the familial PD mutations, R1441C and G2019S. Our study demonstrates that expression of G2019S mutant LRRK2 induces the degeneration of nigrostriatal pathway dopaminergic neurons in an age-dependent manner. In addition, we observe autophagic and mitochondrial abnormalities in the brains of aged G2019S LRRK2 mice and markedly reduced neurite complexity of cultured dopaminergic neurons. These new LRRK2 transgenic mice will provide important tools for understanding the mechanism(s) through which familial mutations precipitate neuronal degeneration and PD. PMID:21494637

Lin, Brian M.; Stafa, Klodjan; Kim, Jaekwang; Banerjee, Rebecca; Westerlund, Marie; Pletnikova, Olga; Glauser, Liliane; Yang, Lichuan; Liu, Ying; Swing, Deborah A.; Beal, M. Flint; Troncoso, Juan C.; McCaffery, J. Michael; Jenkins, Nancy A.; Copeland, Neal G.; Galter, Dagmar; Thomas, Bobby; Lee, Michael K.; Dawson, Ted M.; Dawson, Valina L.; Moore, Darren J.

2011-01-01

274

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

PubMed

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

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

2014-11-01

275

Apollo 14 composite casting demonstration  

NASA Technical Reports Server (NTRS)

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.

1971-01-01

276

VPAC2 (vasoactive intestinal peptide receptor type 2) receptor deficient mice develop exacerbated experimental autoimmune encephalomyelitis with increased Th1/Th17 and reduced Th2/Treg responses.  

PubMed

Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating polypeptide (PACAP) are two structurally-related neuropeptides with widespread expression in the central and peripheral nervous systems. Although these peptides have been repeatedly shown to exert potent anti-inflammatory actions when administered in animal models of inflammatory disease, mice deficient in VIP and PACAP were recently shown to exhibit different phenotypes (ameliorated and exacerbated, respectively) in response to experimental autoimmune encephalomyelitis (EAE). Therefore, elucidating what are the specific immunoregulatory roles played by each of their receptor subtypes (VPAC1, VPAC2, and PAC1) is critical. In this study, we found that mice with a genetic deletion of VIPR2, encoding the VPAC2 receptor, exhibited exacerbated (MOG35-55)-induced EAE compared to wild type mice, characterized by enhanced clinical and histopathological features, increased proinflammatory cytokines (TNF-?, IL-6, IFN-? (Th1), and IL-17 (Th17)) and reduced anti-inflammatory cytokines (IL-10, TGF?, and IL-4 (Th2)) in the CNS and lymph nodes. Moreover, the abundance and proliferative index of lymph node, thymus and CNS CD4(+)CD25(+)FoxP3(+) Tregs were strikingly reduced in VPAC2-deficient mice with EAE. Finally, the in vitro suppressive activity of lymph node and splenic Tregs from VPAC2-deficient mice was impaired. Overall, our results demonstrate critical protective roles for PACAP and the VPAC2 receptor against autoimmunity, promoting the expansion and maintenance of the Treg pool. PMID:25305591

Tan, Yossan-Var; Abad, Catalina; Wang, Yuqi; Lopez, Robert; Waschek, James A

2015-02-01

277

The evolution of hod mice The evolution of hod mice  

E-print Network

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

Koellner, Peter

278

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

PubMed

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

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

2014-03-20

279

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

ERIC Educational Resources Information Center

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)

Kauffman, George B.; Ebner, Ronald D.

1985-01-01

280

VLBI2010 Demonstrator Project  

NASA Astrophysics Data System (ADS)

The next generation geodetic VLBI instrument is being developed with a goal of 1 mm position uncertainty in twenty-four hours. Knowing that spatial and temporal fluctuations in the atmosphere delay are a major component of the error in position determination, the VLBI2010 committee has carried out a large number of simulations to arrive at design goals for the antenna system. These goals are fast slewing antennas and high delay precision per observation. With existing and anticipated data recording capabilities, these translate to an antenna diameter of 12 m or larger and a per-observation delay precision of approximately 4 psec. The major innovation for the VLBI2010 concept that allows the use of relatively small antennas to achieve these goals is the proposal to observe in four frequency bands, instead of the two currently used, in order to gain the higher precision of phase delays compared to the group delay. The other advance that enables the use of small antennas is the significant increase in data acquisition rates that has been made possible by the development of disk-based recorders and digital back ends. To evaluate this concept, a prototype of the feed-to-recorder system has been implemented by the Broadband Development Team* on two antennas, the 5 m MV-3 antenna at Goddard Space Flight Center near Washington, D.C., and the 18 m Westford antenna at Haystack Observatory near Boston. The system includes a broadband feed and low noise amplifiers covering the range approximately 2 GHz to 13 GHz, all cooled to 20K; a newly developed phase calibration generator; a flexible local oscillator (LO) that allows selection of any band in the range of the feed/LNAs; Digital Back End; and a disk-based recorder capable of a sustained rate of 2 gigabits per second (gbps). Four sets of the LO/DBE/recorder chain are used at each antenna to give a total record rate of 8 gbps. The systems have been successfully used in the band 8.5 to 9 GHz with one set of the recorder chain. Observations demonstrating the full four-band configuration are planned for October. In this talk the results of these tests, the improvements that are anticipated for the operational VLBI2010 network, and the status of other developments in the next generation of geodetic VLBI systems will be presented. * Bruce Whittier, Mike Titus, Jason SooHoo, Dan Smythe, Alan Rogers, Jay Redmond, Mike Poirier, Chuck Kodak, Alan Hinton, Ed Himwich, Skip Gordon, Mark Evangelista, Irv Diegel, Brian Corey, Tom Clark, Chris Beaudoin (in reverse alphabetical order)

Niell, A.

2008-12-01

281

Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration  

PubMed Central

The molecular mechanism underlying the selective vulnerability of certain neuronal populations associated with neurodegenerative diseases remains poorly understood. Basal autophagy is important for maintaining axonal homeostasis and preventing neurodegeneration. In this paper, we demonstrate that mice deficient in the metazoan-specific autophagy gene Epg5/epg-5 exhibit selective damage of cortical layer 5 pyramidal neurons and spinal cord motor neurons. Pathologically, Epg5 knockout mice suffered muscle denervation, myofiber atrophy, late-onset progressive hindquarter paralysis, and dramatically reduced survival, recapitulating key features of amyotrophic lateral sclerosis (ALS). Epg5 deficiency impaired autophagic flux by blocking the maturation of autophagosomes into degradative autolysosomes, leading to accumulation of p62 aggregates and ubiquitin-positive inclusions in neurons and glial cells. Epg5 knockdown also impaired endocytic trafficking. Our study establishes Epg5-deficient mice as a model for investigating the pathogenesis of ALS and indicates that dysfunction of the autophagic–endolysosomal system causes selective damage of neurons associated with neurodegenerative diseases. PMID:23479740

Zhao, Hongyu; Wang, Xingwei; Xu, Lanjun; Miao, Lin; Feng, Du; Chen, Quan; Kovács, Attila L.; Fan, Dongsheng

2013-01-01

282

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

PubMed

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

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

2012-04-01

283

Good features to track  

Microsoft Academic Search

No feature-based vision system can work until good features can be identified and tracked from frame to frame. Although tracking itself is by and large a solved problem, selecting features that can be tracked well and correspond to physical points in the world is still an open problem. We propose a feature selection criterion that is optimal by construction because

Jianbo Shi; C. Toamsi

1994-01-01

284

Statistics Department Feature SelectionFeature Selection  

E-print Network

;Wharton Statistics Department TCNJ January, 2005 5 DataData''s getting obese!s getting obese! NumberWharton Statistics Department Feature SelectionFeature Selection in Models For Data Miningin Models For Data Mining Robert Stine Statistics Department The Wharton School, Univ of Pennsylvania January, 2005

Stine, Robert A.

285

Feature Clustering for Accelerating Parallel Coordinate Descent  

SciTech Connect

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.

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

2012-12-06

286

Decreased Proteasomal Activity Causes Photoreceptor Degeneration in Mice  

PubMed Central

Purpose. To study the retinal degeneration caused by decreased proteasomal activity in ?5t transgenic (?5t-Tg) mice, an animal model of senescence acceleration. Methods. ?5t-Tg mice and age-matched littermate control (WT) mice were used. Proteasomal activities and protein level of poly-ubiquitinated protein in retinal extracts were quantified. Fundus images of ?5t-Tg mice were taken and their features were assessed. For histologic evaluation, the thicknesses of inner nuclear layer (INL), outer nuclear layer (ONL), and photoreceptor outer segment (OS) were measured. For functional analysis, ERG was recorded under scotopic and photopic illumination conditions. Immunofluorescence (IF) staining and TUNEL were performed to investigate the mechanism of photoreceptor degeneration. Results. Chymotrypsin-like activity was partially suppressed in retinal tissues of ?5t-Tg mice. Retinal degenerative changes with arterial attenuation were present in ?5t-Tg, but not in WT mice. Inner nuclear layer thickness showed no significant change between ?5t-Tg and WT mice at 1, 3, 6, and 9 months of age. By contrast, thicknesses of ONL and OS in ?5t-Tg mice were significantly decreased at 3, 6, and 9 months compared with those in WT mice. Electroretinograms showed decrease of scotopic a-wave amplitude in ?5t-Tg mice. The number of TUNEL-positive cells in ONL were significantly increased in ?5t-Tg mice and colocalized with apoptosis-inducing factor, but not with cleaved caspase-3 and -9, indicating that the photoreceptor cell death was induced via a caspase-independent pathway. Conclusions. The current data showed that impaired proteasomal function causes photoreceptor degeneration. PMID:24994871

Ando, Ryo; Noda, Kousuke; Tomaru, Utano; Kamoshita, Mamoru; Ozawa, Yoko; Notomi, Shoji; Hisatomi, Toshio; Noda, Mika; Kanda, Atsuhiro; Ishibashi, Tatsuro; Kasahara, Masanori; Ishida, Susumu

2014-01-01

287

Cat face detection with two heterogeneous features  

Microsoft Academic Search

In this paper, we propose a generic and efficient object detection framework based on two heterogeneous features and demonstrate effectiveness of our method for a cat face detection problem. Simple Haar-like features with AdaBoost are fast to compute but they are not discriminative enough to deal with complicated shape and texture. Therefore, we cascade joint Haar-like features with AdaBoost and

Tatsuo Kozakaya; Satoshi Ito; Susumu Kubota; Osamu Yamaguchi

2009-01-01

288

Macromegakaryocytosis after hydroxyurea. [Mice  

SciTech Connect

A single injection of hydroxyurea (OHU) produced transient megakaryocytopenia in mice. An increase in the average mean size of mature, stage III megakaryocytes coincided with their depopulation. This was due to a selective reduction in numbers of smaller cells. In contrast, the macromegakaryocytosis of immunothrombocytopenia showed substantial increases in numbers of larger cells and reductions in smaller. Further reduction in numbers of smaller cells occurred when OHU was given to mice with immunothrombocytopenia, and the megakaryocytopenia was somewhat more severe than that produced by OHU in normal mice. OHU produced mild thrombocytopenia in normal mice and compromised recovery of the platelet count from immunothrombocytopenia. The most likely explanation for the increase in mean megakaryocyte size in the hypomegakaryocytic state produced by OHU is that the temporary imbalance between a low rate of influx and a normal rate of maturation produced a shift of the age distribution of the cells due to a deficiency of immature cells.

Ebbe, S. (Univ. of California, Berkeley); Phalen, E.

1982-11-01

289

Fast webpage classification using URL features  

Microsoft Academic Search

We demonstrate the usefulness of the uniform resource locator (URL) alone in performing web page classification. This approach is faster than typical web page classification, as the pages do not have to be fetched and analyzed. Our approach segments the URL into meaningful chunks and adds component, sequential and orthographic features to model salient patterns. The resulting features are used

Min-Yen Kan; Hoang Oanh Nguyen Thi

2005-01-01

290

Pharmacokinetics of Pentoxifylline and Its Metabolites in Healthy Mice and in Mice Infected with Candida albicans  

PubMed Central

Pentoxifylline has immunomodulatory properties and has been shown to decrease organ damage and improve survival in animals with gram-negative sepsis or endotoxemia. This effect is mediated by a reduction in endotoxin-induced production of tumor necrosis factor alpha (TNF-?) by the host. In earlier studies, we observed an unexpected increase in mortality in mice infected with Candida albicans that were given pentoxifylline even though concentrations of TNF-? in serum were not affected. The current study was designed to determine whether the pharmacokinetics of pentoxifylline and its metabolites were altered in C. albicans-infected mice and, if so, whether these changes could have contributed to the increased mortality. Noninfected mice and mice infected with C. albicans were treated with pentoxifylline (60 mg/kg of body weight) intraperitoneally every 8 h. Serum was collected from animals after one (day 0), four (day 1), or seven (day 2) injections of pentoxifylline or saline (controls). The first dose was administered 6 h after C. albicans infection. Serum was pooled. Concentrations of pentoxifylline and metabolites I, IV, and V were determined by capillary gas chromatography. Renal function and hepatic profiles were assessed. Pharmacokinetic parameters (maximum concentration of pentoxifylline in serum, half-life, and area under the concentration-time curve from 0 h to infinity [AUC0–?]) for all noninfected mice were similar and did not differ from those for day 0-infected mice. For day 1-infected mice, values of these three pharmacokinetic parameters for pentoxifylline and metabolite I were increased two- to fourfold over values for noninfected and day 0-infected mice. For metabolites IV and V, the AUC0–? was increased approximately eightfold over control values. In addition, day 1-infected mice demonstrated evidence of renal and hepatic dysfunction. In summary, C. albicans infection produced marked changes in the pharmacokinetics of pentoxifylline and its metabolites in the mice. The high concentrations of pentoxifylline and its metabolites in serum attained in infected mice may have contributed to the increased mortality of mice with systemic candidiasis. PMID:9736571

Miller, Kenneth; Louie, Arnold; Baltch, Aldona L.; Smith, Raymond P.; Davis, Patrick J.; Gordon, Morris A.

1998-01-01

291

Mapping pathological phenotypes in reelin mutant mice.  

PubMed

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

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

2014-01-01

292

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

Microsoft Academic Search

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

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

2010-01-01

293

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

PubMed

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

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

294

Neuroprotective effects of enriched environment in MPTP-treated SAMP8 mice.  

PubMed

Neuroprotective effects of enriched environment (EE) have been well established. Recent study suggests that exposure to EE can protect dopaminergic neurons against MPTP-induced Parkinsonism. After 64 female SAMP8 mice were reared in EE and standard environment (SE) for 3 months, the effects of EE and SE were compared on behavioural change, tyrosine hydroxylase (TH) immunoreaction positive neuron and dopaminetransporter (DAT) expression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated SAMP8. EE mice showed decreased spontaneous activity compared with SE mice. But EE+MPTP mice showed less decreased spontaneous activity compared with SE+MPTP mice. Otherwise, EE mice showed increased percentage of entries into the open arms and percentage of time spent in the open arms. Furthermore, EE mice demonstrated reduced neurotoxicity, with less decreased TH mRNA and protein expression in Substantia Nigra (SN) after MPTP administration compared with SE mice. SE mice showed a 53.77% loss of TH-positive neurons, whereas EE mice only showed a 42.28% loss. Moreover, EE mice showed decreased DAT mRNA and protein expression compared with SE mice. These data demonstrate that EE can protect dopaminergic neurons against MPTP-induced neuronal damage, which suggest that the probability of developing Parkinson's disease (PD) may be related to life environment. PMID:19429044

Yuan, Zhen-Yun; Gu, Ping; Liu, Li; Wang, Yan-Yong; Liu, Jing; Cui, Dong-Sheng; Geng, Yuan; Zhang, Zhong-Xia; Zhu, Ai-Ping; Ma, Lin; Wang, Ming-Wei

2009-04-17

295

Youth/Leader Demonstration/Illustrated Talk Guide  

E-print Network

, machine, clothing, musical instrument or model, is used in the presentation. Example: A demonstration on "How to Sew on a Button", would feature someone actually sewing on a button. An ILLUSTRATED TALK

New Hampshire, University of

296

Transgenic knockout mice with exclusively human sickle hemoglobinand sickle cell disease  

SciTech Connect

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.

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

1997-06-13

297

32 wk Old C3H/HeJ Mice Actively Respond to Mechanical Loading  

PubMed Central

Numerous studies indicate that C3H/HeJ (C3H) mice are mildly responsive to mechanical loading compared to C57BL/6J (C57) mice. Guided by data indicating high baseline periosteal osteoblast activity in 16 wk C3H mice, we speculated that simply allowing the C3H mice to age until basal periosteal bone formation was equivalent to that of 16 wk C57 mice would restore mechanoresponsiveness in C3H mice. We tested this hypothesis by subjecting the right tibiae of 32 wk old C3H mice and 16 wk old C57 mice to low magnitude rest-inserted loading (peak strain: 1235??) and then exposing the right tibiae of 32 wk C3H mice to low (1085??) or moderate (1875 ??) magnitude cyclic loading. The osteoblastic response to loading on the endocortical and periosteal surfaces was evaluated via dynamic histomorphometry. At 32 wk of age, C3H mice responded to low magnitude rest-inserted loading with significantly elevated periosteal mineralizing surface, mineral apposition rate and bone formation compared to unloaded contralateral bones. Surprisingly, the periosteal bone formation induced by low magnitude rest-inserted loading in C3H mice exceeded that induced in 16 wk C57 mice. At 32 wk of age, C3H mice also demonstrated an elevated response to increased magnitudes of cyclic loading. We conclude that a high level of basal osteoblast function in 16 wk C3H mice appears to overwhelm the ability of the tissue to respond to an otherwise anabolic mechanical loading stimulus. However, when basal surface osteoblast activity is equivalent to that of 16 wk C57 mice, C3H mice demonstrate a clear ability to respond to either rest-inserted or cyclic loading. PMID:18280231

Poliachik, Sandra L.; Threet, DeWayne; Srinivasan, Sundar; Gross, Ted S.

2008-01-01

298

A Toxicogenomic Approach for the Prediction of Murine Hepatocarcinogenesis Using Ensemble Feature Selection  

PubMed Central

The current strategy for identifying the carcinogenicity of drugs involves the 2-year bioassay in male and female rats and mice. As this assay is cost-intensive and time-consuming there is a high interest in developing approaches for the screening and prioritization of drug candidates in preclinical safety evaluations. Predictive models based on toxicogenomics investigations after short-term exposure have shown their potential for assessing the carcinogenic risk. In this study, we investigated a novel method for the evaluation of toxicogenomics data based on ensemble feature selection in conjunction with bootstrapping for the purpose to derive reproducible and characteristic multi-gene signatures. This method was evaluated on a microarray dataset containing global gene expression data from liver samples of both male and female mice. The dataset was generated by the IMI MARCAR consortium and included gene expression profiles of genotoxic and nongenotoxic hepatocarcinogens obtained after treatment of CD-1 mice for 3 or 14 days. We developed predictive models based on gene expression data of both sexes and the models were employed for predicting the carcinogenic class of diverse compounds. Comparing the predictivity of our multi-gene signatures against signatures from literature, we demonstrated that by incorporating our gene sets as features slightly higher accuracy is on average achieved by a representative set of state-of-the art supervised learning methods. The constructed models were also used for the classification of Cyproterone acetate (CPA), Wy-14643 (WY) and Thioacetamid (TAA), whose primary mechanism of carcinogenicity is controversially discussed. Based on the extracted mouse liver gene expression patterns, CPA would be predicted as a nongenotoxic compound. In contrast, both WY and TAA would be classified as genotoxic mouse hepatocarcinogens. PMID:24040119

Eichner, Johannes; Kossler, Nadine; Wrzodek, Clemens; Kalkuhl, Arno; Bach Toft, Dorthe; Ostenfeldt, Nina; Richard, Virgile; Zell, Andreas

2013-01-01

299

Buried Waste Integrated Demonstration lessons learned: 1993 technology demonstrations  

SciTech Connect

An integrated technology demonstration was conducted by the Buried Waste Integrated Demonstration (BWID) at the Idaho National Engineering Laboratory Cold Test Pit in the summer of 1993. This program and demonstration was sponsored by the US Department of Energy Office of Technology Development. The demonstration included six technologies representing a synergistic system for the characterization and retrieval of a buried hazardous waste site. The integrated technology demonstration proved very successful and a summary of the technical accomplishments is presented. Upon completion of the integrated technology demonstration, cognizant program personnel participated in a lessons learned exercise. This exercise was conducted at the Simplot Decision Support Center at Idaho State University and lessons learned activity captured additional information relative to the integration of technologies for demonstration purposes. This information will be used by BWID to enhance program planning and strengthen future technology demonstrations.

Kostelnik, K.M.; Owens, K.J.

1994-12-31

300

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

PubMed

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

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

2014-02-14

301

Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice  

PubMed Central

Background A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV) followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG) and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH) wide dynamic range neurons in oxaliplatin-treated mice Results We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. Conclusions Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds. PMID:21521528

2011-01-01

302

Myeloperoxidase deficiency ameliorates progression of chronic kidney disease in mice.  

PubMed

Myeloperoxidase (MPO) is an enzyme expressed in neutrophils and monocytes/macrophages. Beside its well-defined role in innate immune defence, it may also be responsible for tissue damage. To identify the role of MPO in the progression of chronic kidney disease (CKD), we investigated CKD in a model of renal ablation in MPO knockout and wild-type mice. CKD was induced by 5/6 nephrectomy. Mice were followed for 10 wk to evaluate the impact of MPO deficiency on renal morbidity. Renal ablation induced CKD in wild-type mice with increased plasma levels of MPO compared with controls. No difference was found between MPO-deficient and wild-type mice regarding albuminuria 1 wk after renal ablation, indicating similar acute responses to renal ablation. Over the next 10 wk, however, MPO-deficient mice developed significantly less albuminuria and glomerular injury than wild-type mice. This was accompanied by a significantly lower renal mRNA expression of the fibrosis marker genes plasminogen activator inhibitor-I, collagen type III, and collagen type IV as well as matrix metalloproteinase-2 and matrix metalloproteinase-9. MPO-deficient mice also developed less renal inflammation after renal ablation, as indicated by a lower infiltration of CD3-positive T cells and F4/80-positive monocytes/macrophages compared with wild-type mice. In vitro chemotaxis of monocyte/macrophages isolated from MPO-deficient mice was impaired compared with wild-type mice. No significant differences were observed for mortality and blood pressure after renal ablation. In conclusion, these results demonstrate that MPO deficiency ameliorates renal injury in the renal ablation model of CKD in mice. PMID:24990898

Lehners, Alexander; Lange, Sascha; Niemann, Gianina; Rosendahl, Alva; Meyer-Schwesinger, Catherine; Oh, Jun; Stahl, Rolf; Ehmke, Heimo; Benndorf, Ralf; Klinke, Anna; Baldus, Stephan; Wenzel, Ulrich Otto

2014-08-15

303

Collaborative Writing Features  

ERIC Educational Resources Information Center

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,…

Yong Mei Fung

2010-01-01

304

Favorite Demonstration: Forensic Analysis Demonstration via Hawaii Five-O  

NSDL National Science Digital Library

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

Shmaefsky, Brian R.

2006-09-01

305

Biotherapeutic effects of probiotic bacteria on candidiasis in immunodeficient mice.  

PubMed Central

Four species of probiotic bacteria were assessed for their capacities to protect athymic bg/bg-nu/nu and euthymic bg/bg-nu/+ mice from mucosal and systemic candidiasis. Each bacterial species and Candida albicans colonized the gastrointestinal tracts of both strains of mice. The presence of probiotic bacteria (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei GG, or Bifidobacterium animalis) in the gastrointestinal tracts prolonged the survival of adult and neonatal bg/bg-nu/nu mice compared to that of isogenic mice colonized with C. albicans alone. The incidence of systemic candidiasis in bg/bg-nu/nu mice was significantly reduced by each of the four probiotic bacterial species. The numbers of C. albicans present in the alimentary tracts of euthymic bg/bg-nu/+ mice were significantly reduced by L. casei GG and B. animalis. None of the probiotic bacteria species completely prevented mucosal candidiasis, but B. animalis reduced its incidence and severity. Probiotic bacteria also modulated antibody- and cell-mediated immune responses to C. albicans. The prolonged survival of mice, decreased severity of mucosal and systemic candidiasis, modulation of immune responses, decreased number of C. albicans in the alimentary tract, and reduced numbers of orogastric infections demonstrated not only that probiotic bacteria have biotherapeutic potential for prophylaxis against and therapy of this fungal disease but also that probiotic bacteria protect mice from candidiasis by a variety of immunologic (thymic and extrathymic) and nonimmunologic mechanisms in this model. PMID:9317023

Wagner, R D; Pierson, C; Warner, T; Dohnalek, M; Farmer, J; Roberts, L; Hilty, M; Balish, E

1997-01-01

306

Crybb2 deficiency impairs fertility in female mice.  

PubMed

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

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

307

Gene expression: RNA interference in adult mice  

NASA Astrophysics Data System (ADS)

RNA interference is an evolutionarily conserved surveillance mechanism that responds to double-stranded RNA by sequence-specific silencing of homologous genes. Here we show that transgene expression can be suppressed in adult mice by synthetic small interfering RNAs and by small-hairpin RNAs transcribed in vivo from DNA templates. We also show the therapeutic potential of this technique by demonstrating effective targeting of a sequence from hepatitis C virus by RNA interference in vivo.

McCaffrey, Anton P.; Meuse, Leonard; Pham, Thu-Thao T.; Conklin, Douglas S.; Hannon, Gregory J.; Kay, Mark A.

2002-07-01

308

Morphology of the external genitalia of the adult male and female mice as an endpoint of sex differentiation  

PubMed Central

Adult external genitalia (ExG) are the endpoints of normal sex differentiation. Detailed morphometric analysis and comparison of adult mouse ExG has revealed 10 homologous features distinguishing the penis and clitoris that define masculine vs. feminine sex differentiation. These features have enabled the construction of a simple metric to evaluate various intersex conditions in mutant or hormonally manipulated mice. This review focuses on the morphology of the adult mouse penis and clitoris through detailed analysis of histologic sections, scanning electron microscopy, and three-dimensional reconstruction. We also present previous results from evaluation of “non-traditional” mammals, such as the spotted hyena and wallaby to demonstrate the complex process of sex differentiation that involves not only androgen-dependent processes, but also estrogen-dependent and hormone-independent mechanisms. PMID:21893161

Weiss, Dana A.; Rodriguez, Esequiel; Cunha, Tristan; Menshenina, Julia; Barcellos, Dale; Chan, Lok Yun; Risbridger, Gail; Baskin, Laurence; Cunha, Gerald

2013-01-01

309

Impaired Vibration of Auditory Ossicles in Osteopetrotic Mice  

PubMed Central

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

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

2011-01-01

310

A Dramatic Flame Test Demonstration.  

ERIC Educational Resources Information Center

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)

Johnson, Kristin A.; Schreiner, Rodney

2001-01-01

311

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

PubMed Central

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

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

312

Development of a Computational High-Throughput Tool for the Quantitative Examination of Dose-Dependent Histological Features.  

PubMed

High-resolution digitalizing of histology slides facilitates the development of computational alternatives to manual quantitation of features of interest. We developed a MATLAB-based quantitative histological analysis tool (QuHAnT) for the high-throughput assessment of distinguishable histological features. QuHAnT validation was demonstrated by comparison with manual quantitation using liver sections from mice orally gavaged with sesame oil vehicle or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0.001-30 ?g/kg) every 4 days for 28 days, which elicits hepatic steatosis with mild fibrosis. A quality control module of QuHAnT reduced the number of quantifiable Oil Red O (ORO)-stained images from 3,123 to 2,756. Increased ORO staining was measured at 10 and 30 ?g/kg TCDD with a high correlation between manual and computational volume densities (Vv ), although the dynamic range of QuHAnT was 10-fold greater. Additionally, QuHAnT determined the size of each ORO vacuole, which could not be accurately quantitated by visual examination or manual point counting. PicroSirius Red quantitation demonstrated superior collagen deposition detection due to the ability to consider all images within each section. QuHAnT dramatically reduced analysis time and facilitated the comprehensive assessment of features improving accuracy and sensitivity and represents a complementary tool for tissue/cellular features that are difficult and tedious to assess via subjective or semiquantitative methods. PMID:25274660

Nault, Rance; Colbry, Dirk; Brandenberger, Christina; Harkema, Jack R; Zacharewski, Timothy R

2014-10-01

313

Mice over-expressing BDNF in forebrain neurons develop an altered behavioral phenotype with age.  

PubMed

Evidence from clinical studies suggests that abnormal activity of brain derived neurotrophic factor (BDNF) contributes to the pathogenesis of autism spectrum disorders (ASDs). A genetically modified line of mice over-expressing a BDNF transgene in forebrain neurons was used to investigate if this mutation leads to changes in behavior consistent with ASD. The mice used in these experiments were behaviorally tested past 5 months of age when spontaneous seizures were evident. These seizures were not observed in age-matched wildtype (WT) mice or younger mice from this transgenic line. The BDNF mice in these experiments weighed less than their WT littermates. The BDNF transgenic (BDNF-tg) mice demonstrated similar levels of sociability in the social approach test. Conversely, the BDNF-tg mice demonstrated less obsessive compulsive-like behavior in the marble burying test, less anxiety-like behavior in the elevated plus maze test, and less depressive-like behavior in the forced swim test. Changes in behavior were found in these older mice that have not been observed in younger mice from this transgenic line, which may be due to the development of seizures as the mice age. These mice do not have an ASD phenotype but may be useful to study adult onset epilepsy. PMID:24768643

Weidner, Kate L; Buenaventura, Diego F; Chadman, Kathryn K

2014-07-15

314

Favorite Demonstrations for College Science  

ERIC Educational Resources Information Center

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 …

Shmaefsky, Brian

2004-01-01

315

FGF21 analogs of sustained action enabled by orthogonal biosynthesis demonstrate enhanced antidiabetic pharmacology in rodents.  

PubMed

Fibroblast growth factor 21 (FGF21) mitigates many of the pathogenic features of type 2 diabetes, despite a short circulating half-life. PEGylation is a proven approach to prolonging the duration of action while enhancing biophysical solubility and stability. However, in the absence of a specific protein PEGylation site, chemical conjugation is inherently heterogeneous and commonly leads to dramatic loss in bioactivity. This work illustrates a novel means of specific PEGylation, producing FGF21 analogs with high specific activity and salutary biological activities. Using homology modeling and structure-based design, specific sites were chosen in human FGF21 for site-specific PEGylation to ensure that receptor binding regions were preserved. The in vitro activity of the PEGylated FGF21 ana-logs corresponded with the site of PEG placement within the binding model. Site-specific PEGylated analogs demonstrated dramatically increased circulating half-life and enhanced efficacy in db/db mice. Twice-weekly dosing of an optimal FGF21 analog reduced blood glucose, plasma lipids, liver triglycerides, and plasma glucagon and enhanced pancreatic insulin content, islet number, and glucose-dependent insulin secretion. Restoration of insulin sensitivity was demonstrated by the enhanced ability of insulin to induce Akt/protein kinase B phosphorylation in liver, muscle, and adipose tissues. PEGylation of human FGF21 at a specific and preferred site confers superior metabolic pharmacology. PMID:22210323

Mu, James; Pinkstaff, Jason; Li, Zhihua; Skidmore, Lillian; Li, Nina; Myler, Heather; Dallas-Yang, Qing; Putnam, Anna-Maria; Yao, Jun; Bussell, Stuart; Wu, Margaret; Norman, Thea C; Rodriguez, Carlos G; Kimmel, Bruce; Metzger, Joseph M; Manibusan, Anthony; Lee, Darin; Zaller, Dennis M; Zhang, Bei B; DiMarchi, Richard D; Berger, Joel P; Axelrod, Douglas W

2012-02-01

316

Bovine ephemeral fever virus in cell culture and mice  

Microsoft Academic Search

Summary Light, immunofluorescent and electron microscopic observations were carried out sequentially on mice and VERO cell cultures infected with bovine ephemeral fever (BEF) virus. In early harvests from cell culture, 185×73 nm cone-shaped particles with nearly parallel sides predominated; these particles had all other features typical of the Rhabdoviruses (surface projections, envelope, axial channel, precisely coiled helical nucleocapsid with 35

Frederick A. Murphy; William P. Taylor; Cedric A. Mims; Sylvia G. Whitfield

1972-01-01

317

Improved engraftment of human spleen cells in NOD\\/LtSz-scid\\/scid mice as compared with C.B17-scid\\/scid mice  

Microsoft Academic Search

T and B lymphocyte-deficient mice homozygous for the severe combined immunodeficiency (SCID) mutation can be immunologically engrafted with human lymphocytes. However, low levels of human peripheral blood mononuclear cell engraftment are commonly observed, impeding full use of this model. We now demonstrate that strain background in mice homozygous for the scid mutation is a strong determinant of levels of human

D L Greiner; L D Shultz; J Yates; M C Appel; G Perdrizet; R M Hesselton; I Schweitzer; W G Beamer; K L Shultz; S C Pelsue; Jean H Leif; Thiruchandurai V Rajan

1995-01-01

318

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

PubMed

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

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

2014-01-01

319

Surgery-Related Thrombosis Critically Affects the Brain Infarct Volume in Mice Following Transient Middle Cerebral Artery Occlusion  

PubMed Central

Transient middle cerebral artery occlusion (tMCAO) model is widely used to mimic human focal ischemic stroke in order to study ischemia/reperfusion brain injury in rodents. In tMCAO model, intraluminal suture technique is widely used to achieve ischemia and reperfusion. However, variation of infarct volume in this model often requires large sample size, which hinders the progress of preclinical research. Our previous study demonstrated that infarct volume was related to the success of reperfusion although the reason remained unclear. The aim of present study is to explore the relationship between focal thrombus formation and model reproducibility with respect to infarct volume. We hypothesize that suture-induced thrombosis causes infarct volume variability due to insufficient reperfusion after suture withdrawal. Seventy-two adult male CD-1 mice underwent 90 minutes of tMCAO with or without intraperitoneal administration of heparin. Dynamic synchrotron radiation microangiography (SRA) and laser speckle contrast imaging (LSCI) were performed before and after tMCAO to observe the cerebral vascular morphology and to measure the cerebral blood flow in vivo. Infarct volume and neurological score were examined to evaluate severity of ischemic brain injury. We found that the rate of successful reperfusion was much higher in heparin-treated mice compared to that in heparin-free mice according to the result of SRA and LSCI at 1 and 3 hours after suture withdrawal (p<0.05). Pathological features and SRA revealed that thrombus formed in the internal carotid artery, middle cerebral artery or anterior cerebral artery, which blocked reperfusion following tMCAO. LSCI showed that cortical collateral circulation could be disturbed by thrombi. Our results demonstrated that suture-induced thrombosis was a critical element, which affects the success of reperfusion. Appropriate heparin management provides a useful approach for improving reproducibility of reperfusion model in mice. PMID:24086572

Lin, Xiaojie; Miao, Peng; Wang, Jixian; Yuan, Falei; Guan, Yongjing; Tang, Yaohui; He, Xiaosong; Wang, Yongting; Yang, Guo-Yuan

2013-01-01

320

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

PubMed Central

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

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

321

Effect of melittin on mice stomach  

PubMed Central

Melittin, the main bee venom component, has many positive biological effects and a relatively low toxicity in various cell types. However, there is no evidence of the effect of melittin on gastrointestinal cells. In the present study, we investigated the histological and immuonohistochemical effects of melittin on mice stomach. Adult male mice (Albino Swiss) were randomly divided into two groups (7 mice for each group): control group and melittin only treated group (10 and 40 ?g/kg). These mice were sacrificed, then samples from the stomach were collected and prepared for histopathological studies by using alcian blue stain and immuonohistochemical studies by using smooth muscle actin (SMA) antibody. Treatment with melittin alone do not cause any harmful effect on the stomach tissue where the microscopic examination of Alcian blue stained section showed the normal distribution of the mucous secreting cells of the stomach tissues. On other hand, no changes were observed on smooth muscle cells. This study demonstrated the safety of using melittin on gastrointestinal tissues if used in definite dose and for suitable duration, which offers an opportunity for its use as a treatment for many diseases of the gastrointestinal tract. PMID:24596505

Abu-Zinadah, Osama; Rahmy, Tarek; Alahmari, Abeer; Abdu, Faiza

2013-01-01

322

Progress with the MICE scintillating fiber trackers  

NASA Astrophysics Data System (ADS)

The International Muon Ionization Cooling Experiment (MICE) is a proof of principle demonstration of ionization cooling, for application in a future neutrino factory or muon collider. MICE is under construction at the Rutherford Appleton Laboratory (UK), where a dedicated beam line has been commissioned to transport particles produced inside the ISIS accelerator facility. The beam emittance will be measured using two scintillating fiber trackers on each side of the cooling channel, which will be mounted inside a 4 T solenoid. As particles pass through the tracker, their position will be measured at 5 stations, each of which provides a position resolution of less than 0.5 mm. The fiber trackers have been validated using cosmic ray tests, which have allowed the light yield to be found. In addition, a spare tracking station was exposed to the MICE beam, which has enabled the tracker readout to be integrated with the MICE DAQ for the first time. This test required the integration gate on the D0 AFE-IIt readout boards to be synchronized with particle arrival by using diagnostic signals from the ISIS accelerator.

Overton, Edward

2013-12-01

323

Effect of melittin on mice stomach.  

PubMed

Melittin, the main bee venom component, has many positive biological effects and a relatively low toxicity in various cell types. However, there is no evidence of the effect of melittin on gastrointestinal cells. In the present study, we investigated the histological and immuonohistochemical effects of melittin on mice stomach. Adult male mice (Albino Swiss) were randomly divided into two groups (7 mice for each group): control group and melittin only treated group (10 and 40 ?g/kg). These mice were sacrificed, then samples from the stomach were collected and prepared for histopathological studies by using alcian blue stain and immuonohistochemical studies by using smooth muscle actin (SMA) antibody. Treatment with melittin alone do not cause any harmful effect on the stomach tissue where the microscopic examination of Alcian blue stained section showed the normal distribution of the mucous secreting cells of the stomach tissues. On other hand, no changes were observed on smooth muscle cells. This study demonstrated the safety of using melittin on gastrointestinal tissues if used in definite dose and for suitable duration, which offers an opportunity for its use as a treatment for many diseases of the gastrointestinal tract. PMID:24596505

Abu-Zinadah, Osama; Rahmy, Tarek; Alahmari, Abeer; Abdu, Faiza

2014-01-01

324

Gnathostoma spinigerum: immunodepression in experimental infected mice.  

PubMed

Mice were infected with 8- or 25-infective worms of advanced third stage Gnathostoma spinigerum larvae (L3) which were obtained from natural infected eels. On day 14, 60 and 200 post infections (PI), spleen cells of infected mice were tested for lymphoproliferative responses in vitro against the mitogen and specific L3 somatic antigen in order to clarify the cellular immune status of the host upon this nematode infection. Reduced responsiveness to Con A was observed in infected mice. These depressed responses were more pronounced in chronically infected mice (day 200, PI) than in day 14 and day 60, PI. There was no significant difference of lymphoproliferative response between groups of high (25 L3) and low (8 L3)-infective dose in the chronic readily stage. Regarding to the L3 somatic Ag stimulation, the depressed response was obviously detected in high dose and chronic infection. Our results demonstrated that in this G. spinigerum-mouse system T-cell response is defective. The depression could be reversible and was associated with active infection because it was abolished by anthelmintic (ivermectin) treatment. This study shows the involvement of Th-2 response to this nematode in regulating T cell proliferation. PMID:22947220

Saksirisampant, Wilai; Thaisom, Sunida; Ratanavararak, Mai; Thanomsub, Benjamas Wongsatayanon

2012-11-01

325

Macromegakaryocytosis after hydroxyurea. [Mice  

Microsoft Academic Search

A single injection of hydroxyurea (OHU) produced transient megakaryocytopenia in mice. An increase in the average mean size of mature, stage III megakaryocytes coincided with their depopulation. This was due to a selective reduction in numbers of smaller cells. In contrast, the macromegakaryocytosis of immunothrombocytopenia showed substantial increases in numbers of larger cells and reductions in smaller. Further reduction in

S. Ebbe; E. Phalen

1982-01-01

326

Exacerbated susceptibility to infection-stimulated immunopathology in CD1d-deficient mice1  

PubMed Central

Mice lacking functional CD1d genes were used to study mechanisms of resistance to the protozoan parasite Toxoplasma gondii. Wild type BALB/c mice, CD1-deficient BALB/c mice, and wild type C57BL/6 mice all survived an acute oral infection with a low dose of mildly virulent strain ME49 T. gondii cysts. In contrast, most CD1d-deficient C57BL/6 mice died within two weeks of infection. Despite having parasite burdens that were only slightly higher than wild type mice, CD1d-deficient C57BL/6 mice displayed greater weight loss and intestinal pathology. In C57BL/6 mice, CD4+ cells can cause intestinal pathology during T. gondii infection. Compared with wild type mice, infected CD1d-deficient C57BL/6 mice had higher frequencies and numbers of activated (CD44hi) CD4+ cells in mesenteric lymph nodes. Depletion of CD4+ cells from CD1d-deficient mice reduced weight loss and prolonged survival, demonstrating a functional role for CD4+ cells in their increased susceptibility to T. gondii infection. CD1d-deficient mice are deficient in V?14+ T cells, a major population of NKT cells. Involvement of these cells in resistance to T. gondii was investigated using gene-targeted J?18-deficient C57BL/6 mice, which are deficient in V?14+ T cells. These mice did not succumb to acute infection, but experienced greater weight loss and more deaths than B6 mice during chronic infection, indicating that V?14+ cells contribute to resistance to T. gondii. The data identify CD4+ cells as a significant component of the marked susceptibility to T. gondii infection observed in CD1d-deficient C57BL/6mice, and establish T. gondii as a valuable tool for deciphering CD1d-dependent protective mechanisms. PMID:15944296

Smiley, Stephen T.; Lanthier, Paula A.; Couper, Kevin N.; Szaba, Frank M.; Boyson, Jonathan E.; Chen, Wangxue; Johnson, Lawrence L.

2010-01-01

327

Nuclear Localization of Human Superoxide Dismutase 1 (SOD1) and Mutant SOD1-Specific Disruption of Survival Motor Neuron Protein Complex in Transgenic Amyotrophic Lateral Sclerosis Mice  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease that causes degeneration of motor neurons and paralysis. Approximately 20% of familial ALS cases have been linked to mutations in the copper/zinc superoxide dismutase (SOD1) gene but it is unclear how mutations in the protein result in motor neuron degeneration. Transgenic (tg) mice expressing mutated forms of human SOD1 (hSOD1) develop clinical and pathological features similar to those of ALS. We used tg mice expressing hSOD1-G93A, hSOD1-G37R, and hSOD1-wild type to investigate a new subcellular pathology involving mutant hSOD1 protein prominently localizing to the nuclear compartment and disruption of the architecture of nuclear gems. We developed methods for extracting relatively pure cell nucleus fractions from mouse CNS tissues and demonstrate low nuclear presence of endogenous SOD1 in mouse brain and spinal cord, but prominent nuclear accumulation of hSOD1-G93A, -G37R and -wild type in tg mice. hSOD1 concentrated in nuclei of spinal cord cells, particularly motor neurons, at a young age. The survival motor neuron protein (SMN) complex is disrupted in motor neuron nuclei prior to disease onset in hSOD1-G93A and -G37R mice; age-matched hSOD1-wild type mice did not show SMN disruption despite a nuclear presence. Our data suggest new mechanisms involving hSOD1 accumulation in the cell nucleus and mutant hSOD1-specific perturbations in SMN localization with disruption of the nuclear SMN complex in the ALS model mice and suggest overlap of pathogenic mechanisms with spinal muscular atrophy. PMID:22249462

Gertz, Barry; Wong, Margaret; Martin, Lee J.

2012-01-01

328

Reduction of ?-amyloid accumulation by reticulon 3 in transgenic mice.  

PubMed

Inhibition of the ?-secretase, BACE1, which cleaves amyloid precursor protein (APP) to produce ?-amyloid protein (A?), is thought to be a feasible therapeutic strategy for Alzheimer's disease. Reticulon (RTN) proteins such as RTN3 have been identified as membrane proteins that interact with BACE1 and inhibit its A?-generating activity. In this study, we investigated whether RTN3 can regulate A? production in vivo, using transgenic (Tg) mice expressing APP with Swedish and London mutations (APP Tg mice) and those expressing RTN3; the latter mice showed ~1.4-fold higher expression levels of RTN3 protein in the cerebral cortex than non-Tg controls. We analyzed the brains of single APP Tg and double APP/RTN3 Tg mice at the age of approximately 15 months. The levels of secreted APP-?, a direct BACE1 cleavage product of APP, in Tris-soluble fraction were considerably reduced in the hippocampus and cerebral cortex of APP/RTN3 Tg mice relative to those in APP Tg mice. Immunohistochemical analyses demonstrated that A? burden and plaques were significantly (by approximately 50%) decreased in both the hippocampus and cerebral cortex of double Tg mice compared to APP Tg mice. Furthermore, the levels of guanidine-soluble A?40 and A?42 in these brain regions of APP/RTN3 Tg mice were relatively lower than those in APP Tg mice. These findings indicate that even a small increase in RTN3 expression exerts suppressive effects on amyloidogenic processing of APP and A? accumulation through modulation of BACE1 activity in vivo, and suggest that induction of RTN3 might be an effective therapeutic strategy against Alzheimer's disease. PMID:22742855

Araki, Wataru; Oda, Akiko; Motoki, Kazumi; Hattori, Kotaro; Itoh, Masayuki; Yuasa, Shigeki; Konishi, Yoshihiro; Shin, Ryong-Woon; Tamaoka, Akira; Ogino, Koichi

2013-02-01

329

Reduced Choroidal Neovascular Membrane Formation in Cyclooxygenase-2 Null Mice  

PubMed Central

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

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

2011-01-01

330

Salty taste deficits in CALHM1 knockout mice.  

PubMed

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

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

2014-07-01

331

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

PubMed Central

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

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

332

Mast cell-deficient Kit(W-sh) "Sash" mutant mice display aberrant myelopoiesis leading to the accumulation of splenocytes that act as myeloid-derived suppressor cells.  

PubMed

Mast cell-deficient Kit(W-sh) "sash" mice are widely used to investigate mast cell functions. However, mutations of c-Kit also affect additional cells of hematopoietic and nonimmune origin. In this study, we demonstrate that Kit(W-sh) causes aberrant extramedullary myelopoiesis characterized by the expansion of immature lineage-negative cells, common myeloid progenitors, and granulocyte/macrophage progenitors in the spleen. A consistent feature shared by these cell types is the reduced expression of c-Kit. Populations expressing intermediate and high levels of Ly6G, a component of the myeloid differentiation Ag Gr-1, are also highly expanded in the spleen of sash mice. These cells are able to suppress T cell responses in vitro and phenotypically and functionally resemble myeloid-derived suppressor cells (MDSC). MDSC typically accumulate in tumor-bearing hosts and are able to dampen immune responses. Consequently, transfer of MDSC from naive sash mice into line 1 alveolar cell carcinoma tumor-bearing wild-type littermates leads to enhanced tumor progression. However, although it can also be observed in sash mice, accelerated growth of transplanted line 1 alveolar cell carcinoma tumors is a mast cell-independent phenomenon. Thus, the Kit(W-sh) mutation broadly affects key steps in myelopoiesis that may have an impact on mast cell research. PMID:23636054

Michel, Anastasija; Schüler, Andrea; Friedrich, Pamela; Döner, Fatma; Bopp, Tobias; Radsak, Markus; Hoffmann, Markus; Relle, Manfred; Distler, Ute; Kuharev, Jörg; Tenzer, Stefan; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Schild, Hansjörg; Schmitt, Edgar; Becker, Marc; Stassen, Michael

2013-06-01

333

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

ERIC Educational Resources Information Center

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…

McCandless, B. R.

334

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....

335

Height of Moon's Features  

NSDL National Science Digital Library

This is an activity about utilizing proportional mathematics to determine the height of lunar features. Learners will use the length of shadows to calculate the height of some of the lunar features. This activity is Astronomy Activity 6 in a larger resource entitled Space Update.

336

Feature Selection for Classification  

Microsoft Academic Search

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

Manoranjan Dash; Huan Liu

1997-01-01

337

Formation of Oceanic Features  

NSDL National Science Digital Library

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

Katlyn Wicks

2012-07-16

338

The syntax of features.  

PubMed

The syntax of features is a complicated and densely researched domain, from a variety of theoretical perspectives. The present paper takes one influential syntactic framework [the minimalist program of Chomsky, 1995] as its vantage point, and discusses the major issues that arise within this framework in the domain of the syntax of features, with particular emphasis on Case and agreement. PMID:10723707

den Dikken, M

2000-01-01

339

Phenotype of cloned mice: development, behavior, and physiology.  

PubMed

Cloning technology has potential to be a valuable tool in basic research, clinical medicine, and agriculture. However, it is critical to determine the consequences of this technique in resulting offspring before widespread use of the technology. Mammalian cloning using somatic cells was first demonstrated in sheep in 1997 and since then has been extended to a number of other species. We examined development, behavior, physiology, and longevity in B6C3F1 female mice cloned from adult cumulus cells. Control mice were naturally fertilized embryos subjected to the same in vitro manipulation and culture conditions as clone embryos. Clones attained developmental milestones similar to controls. Activity level, motor ability and coordination, and learning and memory skills of cloned mice were comparable with controls. Interestingly, clones gained more body weight than controls during adulthood. Increased body weight was attributable to higher body fat and was associated with hyperleptinemia and hyperinsulinemia indicating that cloned mice are obese. Cloned mice were not hyperphagic as adults and had hypersensitive leptin and melanocortin signaling systems. Longevity of cloned mice was comparable with that reported by the National Institute on Aging and the causes of death were typical for this strain of mouse. These studies represent the first comprehensive set of data to characterize cloned mice and provide critical information about the long-term effects of somatic cell cloning. PMID:14610260

Tamashiro, Kellie L K; Wakayama, Teruhiko; Yamazaki, Yukiko; Akutsu, Hidenori; Woods, Stephen C; Kondo, Sylvia; Yanagimachi, Ryuzo; Sakai, Randall R

2003-11-01

340

Thermal latency studies in opiate-treated mice  

PubMed Central

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

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

2014-01-01

341

CORYNEBACTERIAL PSEUDOTUBERCULOSIS IN MICE  

PubMed Central

Latent corynebactenai infection occurs naturally in many strains of mice. It can be evoked into the active disease, pseudotuberculosis, by a single injection of 10 mg of cortisone. The cortisone effect was tested in 21 colonies, representing 11 genetically different strains of mice. Animals of the C57B1/6, DBA/2, and RIII strains were shown to be latently infected with Corynebacterium kutscheri by the fact that they developed fatal pseudotuberculosis following cortisone treatment. Virulent C. kutscheri could not be isolated from homogenates of organs obtained from latently infected animals before cortisone administration; however, these homogenates yielded small translucent colonies of avirulent organisms. Recovery of these atypical colonies was facilitated by preincubating the organ homogenates before plating. The organisms constituting such colonies differed morphologically and immunologically from C. kutscheri, but had similar biochemical properties with the exception that they lacked urease and catalase activity. Mice treated with cortisone yielded both the avirulent bacteria and virulent C. kutscheri. The latter was the predominant organism present in the organs at the height of infection. Injection of avirulent organisms into Swiss Lynch mice, which are normally free of latent corynebacteria, occasionally established a latent infection which could be converted into corynebacterial pseudotuberculosis by cortisone. Cultures of fully virulent C. kutscheri were then obtained from the lesions. Latency was produced experimentally with a streptomycin-resistant strain of virulent C. kutscheri (CKsr) derived from the stock culture. When sublethal doses of CKsr were injected into NCS mice (Institut Pasteur colony), they induced a latent infection characterized by the presence of avirulent organisms possessing the streptomycin resistance marker. These were isolated in the form of small translucent colonies from the livers of the infected animals. Administration of cortisone to these animals subsequently evoked active infection from which virulent CKsr could be obtained. Injection of the avirulent streptomycin-resistant organisms into normal NCS mice established a latent infection which could be uniformly converted into corynebacterial pseudotuberculosis by cortisone. The virulent C. kutscheri obtained from the lesions bore the genetic marker of streptomycin resistance, thus being identical with CKsr. Except for streptomycin resistance, the avirulent organisms isolated from the experimentally induced latent infections were identical with those found in the naturally occurring latent infections. These results suggest that C. kutscheri can persist in vitro in an avirulent form which is resistant to the defense mechanisms of the host, and can thus establish a latent infection. Treatment of the animal with cortisone results in the conversion of the avirulent form into virulent C. kutscheri, and of the latent infection into active corynebacterial pseudotuberculosis. The findings are discussed with regard to their relevance to infection immunity, and to the conversion of latent infection into overt disease. PMID:14208250

Fauve, Robert M.; Pierce-Chase, Cynthia H.; Dubos, Rene

1964-01-01

342

Mice Drawer System  

NASA Technical Reports Server (NTRS)

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.

Cancedda, Ranieri

2008-01-01

343

Prenatal androgen exposure programs metabolic dysfunction in female mice  

PubMed Central

Polycystic ovary syndrome (PCOS) is a common fertility disorder with metabolic sequelae. Our lab previously characterized reproductive phenotypes in a prenatally androgenized (PNA) mouse model for PCOS. PNA mice exhibited elevated testosterone and luteinising hormone (LH) levels, irregular oestrous cycles, and neuroendocrine abnormalities suggesting increased central drive to the reproductive system. In this study we examined metabolic characteristics of female PNA mice. PNA mice exhibited increased fasting glucose and impaired glucose tolerance (IGT) that were independent of age and were not associated with changes in body composition or peripheral insulin sensitivity. IGT was associated with defects in pancreatic islet function leading to an impaired response to high glucose, consistent with impaired insulin secretion. Exposure of isolated pancreatic islets to androgen in vitro demonstrated an impaired response to glucose stimulation similar to that in PNA mice, suggesting androgens may have activational in addition to organizational effects on pancreatic islet function. PNA mice also exhibited increased size of visceral adipocytes, suggesting androgens programmed differences in adipocyte differentiation and/or function. These studies demonstrate that in addition to causing reproductive axis abnormalities, in utero androgen exposure can induce long-term metabolic alterations in female mice. PMID:20713501

Roland, Alison V.; Nunemaker, Craig S.; Keller, Susanna R.; Moenter, Suzanne M.

2013-01-01

344

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 ...

345

Computer Demonstrations for Your Benefit.  

ERIC Educational Resources Information Center

Summarizes procedures of the Houston Independent School District's Technology Hardware Selection Committee for demonstrations of microcomputer products being considered for purchase, including identification of user needs, turning needs into specifications, and seeing the computer demonstrate that it can meet those needs. Committee…

Smith, Richard Alan

1984-01-01

346

A Demonstration of Sample Segregation  

ERIC Educational Resources Information Center

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.

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

2005-01-01

347

Demonstrating Allotropic Modifications of Sulfur.  

ERIC Educational Resources Information Center

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)

McCarty, Jillian L.; Dragojlovic, Veljko

2002-01-01

348

The "Mushroom Cloud" Demonstration Revisited  

ERIC Educational Resources Information Center

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…

Panzarasa, Guido; Sparnacci, Katia

2013-01-01

349

Understanding Statistics Using Computer Demonstrations  

ERIC Educational Resources Information Center

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…

Dunn, Peter K.

2004-01-01

350

Offsite demonstrations for MWLID technologies  

Microsoft Academic Search

The goal of the Offsite Demonstration Project for Mixed Waste Landfill Integrated Demonstration (MWLID)-developed environmental site characterization and remediation technologies is to facilitate the transfer, use, and commercialization of these technologies to the public and private sector. The meet this goal, the project identified environmental restoration needs of mixed waste and\\/or hazardous waste landfill owners (Native American, municipal, DOE, and

C. Williams; R. Gruebel

1995-01-01

351

A Demonstration on Every Exam.  

ERIC Educational Resources Information Center

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,…

Julian, Glenn M.

1995-01-01

352

A Classroom Demonstration of Psychrometrics.  

ERIC Educational Resources Information Center

Presented is a bench-top demonstration of heating/humidification designed to provide visual confirmation of psychrometric principles outlined in thermodynamics texts. Includes a schematic sketch of the heater/humidifier apparatus, discussion of the six steps involved during the demonstration, and a table of experimental results. (JN)

Clark, Jim A.; Nikolajczyk, David R.

1983-01-01

353

FGF23 Deficiency Leads to Mixed Hearing Loss and Middle Ear Malformation in Mice  

PubMed Central

Fibroblast growth factor 23 (FGF23) is a circulating hormone important in phosphate homeostasis. Abnormal serum levels of FGF23 result in systemic pathologies in humans and mice, including renal phosphate wasting diseases and hyperphosphatemia. We sought to uncover the role FGF23 plays in the auditory system due to shared molecular mechanisms and genetic pathways between ear and kidney development, the critical roles multiple FGFs play in auditory development and the known hearing phenotype in mice deficient in klotho (KL), a critical co-factor for FGF23 signaling. Using functional assessments of hearing, we demonstrate that Fgf mice are profoundly deaf. Fgf mice have moderate hearing loss above 20 kHz, consistent with mixed conductive and sensorineural pathology of both middle and inner ear origin. Histology and high-voltage X-ray computed tomography of Fgf mice demonstrate dysplastic bulla and ossicles; Fgf mice have near-normal morphology. The cochleae of mutant mice appear nearly normal on gross and microscopic inspection. In wild type mice, FGF23 is ubiquitously expressed throughout the cochlea. Measurements from Fgf mice do not match the auditory phenotype of Kl?/? mice, suggesting that loss of FGF23 activity impacts the auditory system via mechanisms at least partially independent of KL. Given the extensive middle ear malformations and the overlap of initiation of FGF23 activity and Eustachian tube development, this work suggests a possible role for FGF23 in otitis media. PMID:25243481

Lysaght, Andrew C.; Yuan, Quan; Fan, Yi; Kalwani, Neil; Caruso, Paul; Cunnane, MaryBeth; Lanske, Beate; Stankovi?, Konstantina M.

2014-01-01

354

Evaluation of Common Anesthetic and Analgesic Techniques for Tail Biopsy in Mice  

PubMed Central

Tail biopsy in mice is a common procedure in genetically modified mouse colonies. We evaluated the anesthetic and analgesic effects of various agents commonly used to mitigate pain after tail biopsy. We used a hot-water immersion assay to evaluate the analgesic effects of isoflurane, ice-cold ethanol, ethyl chloride, buprenorphine, and 2-point local nerve blocks before studying their effects on mice receiving tail biopsies. Mice treated with ethyl chloride spray, isoflurane and buprenorphine, and 2-point local nerve blocks demonstrated increased tail-flick latency compared with that of untreated mice. When we evaluated the behavior of adult and preweanling mice after tail biopsy, untreated mice demonstrated behavioral changes immediately after tail biopsy that lasted 30 to 60 min before returning to normal. The use of isoflurane, isoflurane and buprenorphine, buprenorphine, 2-point nerve block, or ethyl chloride spray in adult mice did not significantly improve their behavioral response to tail biopsy. Similarly, the use of buprenorphine and ethyl chloride spray in preweanling mice did not improve their behavioral response to tail biopsy compared with that of the untreated group. However, immersion in bupivacaine for 30 s after tail biopsy decreased tail grooming behavior during the first 30 min after tail biopsy. The anesthetic and analgesic regimens tested provide little benefit in adult and preweanling mice. Given that tail biopsy results in pain that lasts 30 to 60 min, investigators should carefully consider the appropriate anesthetic or analgesic regimen to incorporate into tail-biopsy procedures for mice. PMID:23294888

Jones, Carissa P; Carver, Scott; Kendall, Lon V

2012-01-01

355

Buried Waste Integrated Demonstration: Selection of potential demonstration locations  

SciTech Connect

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

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

1991-11-01

356

Tested Demonstrations. A Chemiluminescence Demonstration - Oxalyl Chloride Oxidation.  

ERIC Educational Resources Information Center

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)

Gilber, George L., Ed.

1979-01-01

357

Time Varying Feature Data  

NASA Astrophysics Data System (ADS)

The infrastructure to gather, store and access information about our environment is improving and growing rapidly. The increasing amount of information allows us to get a better understanding of the current state of our environment, historical processes and to simulate and predict the future state of the environment. Finer grained spatial and temporal data and more reliable communications make it easier to model dynamic states and ephemeral features. The exchange of information within and across geospatial domains is facilitated through the use of harmonized information models. The Observations & Measurements (O&M) developed through OGC and standardised by ISO is an example of such a cross-domain information model. It is used in many domains, including meteorology, hydrology as well as the emergency management. O&M enables harmonized representation of common metadata that belong to the act of determining the state of a feature property, whether by sensors, simulations or humans. In addition to the resulting feature property value, information such as the result quality but especially the time that the result applies to the feature property can be represented. Temporal metadata is critical to modelling past and future states of a feature. The features, and the semantics of each property, are defined in domain specific Application Schema using the General Feature Model (GFM) from ISO 19109 and usually encoded following ISO 19136. However, at the moment these standards provide only limited support for the representation and handling of time varying feature data. Features like rivers, wildfires or gas plumes have a defined state - for example geographic extent - at any given point in time. To keep track of changes, a more complex model for example using time-series coverages is required. Furthermore, the representation and management of feature property value changes via the service interfaces defined by OGC and ISO - namely: WFS and WCS - would be rather complex. Keeping track of feature property value corrections or even feature (state change) cancellations for auditing purposes is also not easy to achieve. The aviation domain has strong requirements to represent and manage the state of aeronautical features through time. Being able to efficiently encode and manage feature state changes, keeping track of all changes for auditing purposes and being able to determine the future state of an aeronautical feature as currently known to the system are vital for aeronautical applications. In order to support these requirements, the Aeronautical Information Exchange Model (AIXM) which has been developed by the aviation domain is based on the so called AIXM Temporality Model (AIXM-TM). The AIXM-TM defines various rules for modeling, representing and handling the state of aeronautical features through time. This is a promising approach that can be incorporated into the GFM so that ultimately the modeling and management of time varying feature data is supported in an interoperable and harmonized way in all geospatial domains. This presentation gives an introduction to the main concepts of the AIXM-TM. It also shows how the GFM can be extended to support time varying feature data. Finally, the relationship of O&M and time varying features is discussed.

Echterhoff, J.; Simonis, I.; Atkinson, R.

2012-04-01

358

Dengue Virus Tropism in Humanized Mice Recapitulates Human Dengue Fever  

PubMed Central

Animal models of dengue virus disease have been very difficult to develop because of the virus' specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem cells from umbilical cord blood. These mice show measurable signs of dengue disease as in humans (fever, viremia, erythema and thrombocytopenia), and after infection with the most virulent strain of dengue serotype 2, humanized mice showed infection in human cells in bone marrow, spleen and blood. Cytokines and chemokines were secreted by these human cells into the mouse bloodstream. We demonstrated that the pathology of dengue virus infection in these mice follows that reported in human patients, making this the first valid and relevant model for studying dengue fever pathogenesis in humans. PMID:21695193

Mota, Javier; Rico-Hesse, Rebeca

2011-01-01

359

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

PubMed Central

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

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

360

Transthoracic echocardiography in mice.  

PubMed

In recent years, murine models have become the primary avenue for studying the molecular mechanisms of cardiac dysfunction resulting from changes in gene expression. Transgenic and gene targeting methods can be used to generate mice with altered cardiac size and function, and as a result, in vivo techniques are needed to evaluate their cardiac phenotype. Transthoracic echocardiography, pulse wave Doppler (PWD), and tissue Doppler imaging (TDI) can be used to provide dimensional measurements of the mouse heart and to quantify the degree of cardiac systolic and diastolic performance. Two-dimensional imaging is used to detect abnormal anatomy or movements of the left ventricle, whereas M-mode echo is used for quantification of cardiac dimensions and contractility. In addition, PWD is used to quantify localized velocity of turbulent flow, whereas TDI is used to measure the velocity of myocardial motion. Thus, transthoracic echocardiography offers a comprehensive method for the noninvasive evaluation of cardiac function in mice. PMID:20517201

Respress, Jonathan L; Wehrens, Xander H T

2010-01-01

361

Decreased albumin mRNA in immunodeficient wasted' mice  

SciTech Connect

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.

Libertin, C.R.; Buczek, N.; Weaver, P.; Mobarhan, S.; Woloschak, G.E. (Loyola Univ. of Chicago, Maywood, IL (United States) Argonne National Lab., IL (United States))

1991-03-15

362

Deletion of ELOVL5 leads to fatty liver through activation of SREBP-1c in mice*s?  

PubMed Central

Elongation of very long chain fatty acids (ELOVL)5 is one of seven mammalian fatty acid condensing enzymes involved in microsomal fatty acid elongation. To determine the in vivo substrates and function of ELOVL5, we generated Elovl5?/? mice. Studies using liver microsomal protein from wild-type and knockout mice demonstrated that the elongation of ?-linolenic (C18:3, n-6) to dihomo-?-linolenic (C20:3, n-6) and stearidonic (C18:4, n-3) to ?3-arachidonic acid (C20:4, n-3) required ELOVL5 activity. Tissues of Elovl5?/? mice accumulated the C18 substrates of ELOVL5 and the levels of the downstream products, arachidonic acid (C20:4, n-6) and docosahexaenoic acid (DHA, C22:6, n-3), were decreased. A consequence of decreased cellular arachidonic acid and DHA concentrations was the activation of sterol regulatory element-binding protein (SREBP)-1c and its target genes involved in fatty acid and triglyceride synthesis, which culminated in the development of hepatic steatosis in Elovl5?/? mice. The molecular and metabolic changes in fatty acid metabolism in Elovl5?/? mice were reversed by dietary supplementation with arachidonic acid and DHA. These studies demonstrate that reduced ELOVL5 activity leads to hepatic steatosis, and endogenously synthesized PUFAs are key regulators of SREBP-1c activation and fatty acid synthesis in livers of mice. PMID:18838740

Moon, Young-Ah; Hammer, Robert E.; Horton, Jay D.

2009-01-01

363

FeaturePlugin: feature modeling plug-in for Eclipse  

Microsoft Academic Search

Feature modeling is a key technique used in product-line development to model commonalities and variabilities of product-line members. In this paper, we present FeaturePlugin, a feature modeling plug-in for Eclipse. The tool supports cardinality-based feature modeling, specialization of feature diagrams, and configuration based on feature diagrams.

Michal Antkiewicz; Krzysztof Czarnecki

2004-01-01

364

Offsite demonstrations for MWLID technologies  

SciTech Connect

The goal of the Offsite Demonstration Project for Mixed Waste Landfill Integrated Demonstration (MWLID)-developed environmental site characterization and remediation technologies is to facilitate the transfer, use, and commercialization of these technologies to the public and private sector. The meet this goal, the project identified environmental restoration needs of mixed waste and/or hazardous waste landfill owners (Native American, municipal, DOE, and DoD); documenting potential demonstration sites and the contaminants present at each site; assessing the environmental regulations that would effect demonstration activities; and evaluating site suitability for demonstrating MWLID technologies at the tribal and municipal sites identified. Eighteen landfill sites within a 40.2-km radius of Sandia National Laboratories are listed on the CERCLIS Site/Event Listing for the state of New Mexico. Seventeen are not located within DOE or DoD facilities and are potential offsite MWLID technology demonstration sites. Two of the seventeen CERCLIS sites, one on Native American land and one on municipal land, were evaluated and identified as potential candidates for off-site demonstrations of MWLID-developed technologies. Contaminants potentially present on site include chromium waste, household/commercial hazardous waste, volatile organic compounds, and petroleum products. MWLID characterization technologies applicable to these sites include Magnetometer Towed Array, Cross-borehole Electromagnetic Imaging, SitePlanner {trademark}/PLUME, Hybrid Directional Drilling, Seamist{trademark}/Vadose Zone Monitoring, Stripping Analyses, and x-ray Fluorescence Spectroscopy for Heavy Metals.

Williams, C. [Sandia National Labs., Albuquerque, NM (United States); Gruebel, R. [Tech. Reps., Inc., Albuquerque, NM (United States)

1995-04-01

365

Thyroid Cancer - Featured Clinical Trials  

Cancer.gov

Thyroid Cancer - Featured Clinical Trials The following list shows Featured Clinical Trials for a specific type of cancer. You may also want to view: Multiple Cancer Types - Featured Clinical Trials Supportive Care - Featured Clinical Trials

366

Esophageal Cancer - Featured Clinical Trials  

Cancer.gov

Esophageal Cancer - Featured Clinical Trials The following list shows Featured Clinical Trials for a specific type of cancer. You may also want to view: Multiple Cancer Types - Featured Clinical Trials Supportive Care - Featured Clinical Trials

367

Notional Airspace Operations Demonstration Plan  

NASA Technical Reports Server (NTRS)

The airspace operations demonstration (AOD) is intended to show that the Access 5 Step 1 functional requirements can be met. The demonstration will occur in two phases. The initial on-range phase will be carried out in restricted airspace to demonstrate the cooperative collision avoidance (CCA) functional requirements and to provide risk-reduction for the AOD by allowing the test team to rehearse some elements of the demonstration mission. The CCA system to be used in these flights is based on Automatic Dependent Surveillance-Broadcast (ADS-B) which is a commercially-available system by which airplanes constantly broadcast their current position and altitude to other aircraft and ground resources over a dedicated radio datalink. The final phase will occur in the national airspace (NAS) and will be the formal demonstration of the remainder of the proposed functional requirements. The general objectives of the AOD are as follows: (1) Demonstrate that the UAS can aviate in the NAS (2) Demonstrate that the UAS can navigate in the NAS (3) Demonstrate that the UAS can communicate with the NAS (4) Demonstrate that the UAS can perform selected collision avoidance functions in the NAS (5) Demonstrate that the UAS can evaluate and avoid weather conflicts in the NAS (6) Demonstrate that the UAS can provide adequate command and control in the NAS In addition to the stated objectives, there are a number of goals for the flight demonstration. The demo can be accomplished successfully without achieving these goals, but these goals are to be used as a guideline for preparing for the mission. The goals are: (1) Mission duration of at least 24 hours (2) Loiter over heavy traffic to evaluate the data block issue identified during the Access 5 Airspace Operations Simulations (3) Document the contingency management process and lessons learned (4) Document the coordination process for Ground Control Stations (GCS) handoff (5) Document lessons learned regarding the process of flying in the NAS Preliminary planning for a notional mission to achieve the objectives and goals has been prepared. The planning is intended to serve as a guide for detailed planning of the AOD.

Trongale, Nicholas A.

2006-01-01

368

Constitutive Notch2 signaling in neural stem cells promotes tumorigenic features and astroglial lineage entry  

PubMed Central

Recent studies identified a highly tumorigenic subpopulation of glioma stem cells (GSCs) within malignant gliomas. GSCs are proposed to originate from transformed neural stem cells (NSCs). Several pathways active in NSCs, including the Notch pathway, were shown to promote proliferation and tumorigenesis in GSCs. Notch2 is highly expressed in glioblastoma multiforme (GBM), a highly malignant astrocytoma. It is therefore conceivable that increased Notch2 signaling in NSCs contributes to the formation of GBM. Here, we demonstrate that mice constitutively expressing the activated intracellular domain of Notch2 in NSCs display a hyperplasia of the neurogenic niche and reduced neuronal lineage entry. Neurospheres derived from these mice show increased proliferation, survival and resistance to apoptosis. Moreover, they preferentially differentiate into astrocytes, which are the characteristic cellular population of astrocytoma. Likewise, we show that Notch2 signaling increases proliferation and resistance to apoptosis in human GBM cell lines. Gene expression profiling of GBM patient tumor samples reveals a positive correlation of Notch2 transcripts with gene transcripts controlling anti-apoptotic processes, stemness and astrocyte fate, and a negative correlation with gene transcripts controlling proapoptotic processes and oligodendrocyte fate. Our data show that Notch2 signaling in NSCs produces features of GSCs and induces astrocytic lineage entry, consistent with a possible role in astrocytoma formation. PMID:22717580

Tchorz, J S; Tome, M; Cloëtta, D; Sivasankaran, B; Grzmil, M; Huber, R M; Rutz-Schatzmann, F; Kirchhoff, F; Schaeren-Wiemers, N; Gassmann, M; Hemmings, B A; Merlo, A; Bettler, B

2012-01-01

369

Reduced platelet-derived growth factor receptor expression is a primary feature of human bronchopulmonary dysplasia.  

PubMed

Animal studies have shown that platelet-derived growth factor (PDGF) signaling is required for normal alveolarization. Changes in PDGF receptor (PDGFR) expression in infants with bronchopulmonary dysplasia (BPD), a disease of hypoalveolarization, have not been examined. We hypothesized that PDGFR expression is reduced in neonatal lung mesenchymal stromal cells (MSCs) from infants who develop BPD. MSCs from tracheal aspirates of premature infants requiring mechanical ventilation in the first week of life were studied. MSC migration was assessed in a Boyden chamber. Human lung tissue was obtained from the University of Rochester Neonatal Lung Biorepository. Neonatal mice were exposed to air or 75% oxygen for 14 days. PDGFR expression was quantified by qPCR, immunoblotting, and stereology. MSCs were isolated from 25 neonates (mean gestational age 27.7 wk); 13 developed BPD and 12 did not. MSCs from infants who develop BPD showed lower PDGFR-? and PDGFR-? mRNA and protein expression and decreased migration to PDGF isoforms. Lungs from infants dying with BPD show thickened alveolar walls and paucity of PDGFR-?-positive cells in the dysmorphic alveolar septa. Similarly, lungs from hyperoxia-exposed neonatal mice showed lower expression of PDGFR-? and PDGFR-?, with significant reductions in the volume of PDGFR-?-positive alveolar tips. In conclusion, MSCs from infants who develop BPD hold stable alterations in PDGFR gene expression that favor hypoalveolarization. These data demonstrate that defective PDGFR signaling is a primary feature of human BPD. PMID:24907056

Popova, Antonia P; Bentley, J Kelley; Cui, Tracy X; Richardson, Michelle N; Linn, Marisa J; Lei, Jing; Chen, Qiang; Goldsmith, Adam M; Pryhuber, Gloria S; Hershenson, Marc B

2014-08-01

370

Absence of a Major Role for the Snai1 and Snai3 Genes in Regulating Skeletal Muscle Regeneration in Mice  

PubMed Central

The Snail gene family encodes DNA-binding zinc finger proteins that function as transcriptional repressors. While the Snai1 and Snai2 genes are required for normal development in mice, Snai3 mutant mice exhibit no obvious abnormalities. The Snai3 gene is expressed at high levels in skeletal muscle. However, we demonstrate by histological analysis that Snai3 null mutant mice exhibit normal skeletal muscle. During hindlimb muscle regeneration after cardiotoxin-mediated injury, the Snai3 null mice exhibited efficient regeneration. To determine whether the Snai3 gene functions redundantly with the Snai1 gene during skeletal muscle regeneration, we performed hindlimb muscle regeneration in mice with skeletal muscle-specific deletion of the Snai1 gene on a Snai3 null genetic background. These mice also exhibited efficient regeneration, demonstrating that there is no major role for the Snai1 and Snai3 genes in regulating skeletal muscle regeneration in mice. PMID:24270643

Norton, Christine R.; Chen, Ying; Han, Xiang Hua; Bradley, Cara K.; Krebs, Luke T.; Yoon, Jeong Kyo; Gridley, Thomas

2013-01-01

371

State Machine Operation of the MICE Cooling Channel  

NASA Astrophysics Data System (ADS)

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.

Hanlet, Pierrick; Mice Collaboration

2014-06-01

372

Taste sensitivities to PROP and PTC vary independently in mice.  

PubMed

Mammals use common mechanisms to detect, transduce and process taste stimulus information. For example, they share families of receptors that respond to amino acids, and sweet- and bitter-tasting stimuli. Nonetheless, it also clear that different species exhibit unique taste sensitivities that may reflect specific genetic variations. In humans, sensitivities to the chemically similar, bitter-tasting compounds 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC) are heritable and strongly correlated, suggesting a common genetic basis. However, it is unknown whether PROP and PTC taste sensitivities are similarly correlated in mice. Here we report that PROP and PTC taste sensitivities vary independently between two inbred strains of mice. In brief-access taste tests C3HeB/FeJ (C3) and SWR/J (SW) mice possess similar taste sensitivity to PTC, while SW mice are significantly more sensitive to PROP than are C3 mice. In two-bottle preference tests, however, SW mice display greater aversion to both compounds. This discrepancy may be explained by the observation that SW mice consumed taste solutions at a greater rate during the intake test than did C3 mice. Therefore, PTC avoidance is correlated with the amount of PTC consumed in the intake tests rather than the concentration of PTC tested. These findings suggest that post-ingestive factors play a significant role in PTC avoidance during intake tests and highlight an important advantage of brief-access tests over intake tests in resolving the gustatory and post-ingestive contributions to taste-related behaviors. Most strikingly, these results demonstrate that in mice, unlike in humans, PTC and PROP taste sensitivities vary independently, thereby suggesting a subtle functional diversity of bitter-taste mechanisms across mammalian species. PMID:14627538

Nelson, Theodore M; Munger, Steven D; Boughter, John D

2003-10-01

373

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

PubMed Central

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

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

2008-01-01

374

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

PubMed

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

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

2008-01-01

375

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. ...

376

Significance Of Apoptosis And Its Relationship To Antioxidants After Ochratoxin A Administration In Mice  

Microsoft Academic Search

A study of the appearance of liver apoptosis after ochratoxin A (OTA) administration was performed in male mice. Administration of OTA twice a week for one or two weeks period results in the occurrence of apoptosis in mice's liver. The presence of intracellular apoptosis bod- ies was detected at two weeks after toxin treatment. Light microscopic examination demonstrated the presence

Faik Atroshi; Isa Biese; Hannu Saloniemi; Terhi Ali-Vehmas; Seppo Saari; Aldo Rizzo; Pirjo Veijalainen

2000-01-01

377

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

378

Cholesterol and Bile Acid Metabolism Are Impaired in Mice Lacking the Nuclear Oxysterol Receptor LXR?  

Microsoft Academic Search

We demonstrate that mice lacking the oxysterol receptor, LXR?, lose their ability to respond normally to dietary cholesterol and are unable to tolerate any amount of cholesterol in excess of that which they synthesize de novo. When fed diets containing cholesterol, LXR? (?\\/?) mice fail to induce transcription of the gene encoding cholesterol 7?-hydroxylase (Cyp7a), the rate-limiting enzyme in bile

Daniel J Peet; Stephen D Turley; Wenzhen Ma; Bethany A Janowski; Jean-Marc A Lobaccaro; Robert E Hammer; David J Mangelsdorf

1998-01-01

379

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

E-print Network

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

Mecham, Robert

380

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...

381

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...

382

Energy Research, Development and Demonstration  

E-print Network

, and demonstration. The Technology Development Section carries out these functions by maintaining contact with recognized technical experts; monitoring state, federal, and other energy-related technology development; providing staff support to Council advisory...

Ray, R. R., Jr.

1980-01-01

383

Status of the MAJORANA Demonstrator  

E-print Network

The MAJORANA Collaboration is constructing the MAJORANA Demonstrator, an ultra-low background, 40-kg modular high purity Ge detector array to search for neutrinoless double-beta decay in Ge. In view of the next generation of tonne-scale Ge-based neutrinoless double-beta decay searches that will probe the neutrino mass scale in the inverted-hierarchy region, a major goal of the Demonstrator is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. The current status of the Demonstrator is discussed, as are plans for its completion.

C. Cuesta; N. Abgrall; I. J. Arnquist; F. T. Avignone III; A. S. Barabash; F. E. Bertrand; V. Brudanin; M. Busch; M. Buuck; D. Byram; A. S. Caldwell; Y-D. Chan; C. D. Christofferson; J. A. Detwiler; Yu. Efremenko; H. Ejiri; S. R. Elliott; A. Galindo-Uribarri; G. K. Giovanetti; J. Goett; M. P. Greenn; J. Gruszko; I. S. Guinn; V. E. Guiseppe; R. Henning; E. W. Hoppe; S. Howard; M. A. Howe; B. R. Jasinski; K. J. Keeter; M. F. Kidd; S. I. Konovalov; R. T. Kouzes; B. D. LaFerriere; J. Leon; J. MacMullin; R. D. Martin; S. J. Meijer; S. Mertens; J. L. Orrell; C. O'Shaughnessy; N. R. Overman; A. W. P. Poon; D. C. Radford; J. Rager; K. Rielage; R. G. H. Robertson; E. Romero-Romero; C. Schmitt; B. Shanks; M. Shirchenko; N. Snyder; A. M. Suriano; D. Tedeschi; V. Timkin; J. E. Trimble; R. L. Varner; S. Vasilyev; K. Vetter; K. Vorren; B. R. White; J. F. Wilkerson; C. Wiseman; W. Xu; E. Yakushev; C. -H. Yu; V. Yumatov

2015-01-07

384

Rubens Flame-Tube Demonstration.  

ERIC Educational Resources Information Center

Investigates and explains the phenomenon associated with Rubens flame-tube demonstration, specifically the persistance of flames at regular intervals along the tube for few minutes after the gas is turned off. (GA)

Ficken, George W.; Stephenson, Francis C.

1979-01-01

385

Novel Third-Law Demonstration.  

ERIC Educational Resources Information Center

Presents an easy method to demonstrate Third-Law interactions using identical button magnets sliding along a smooth (nonmagnetic) knitting needle. Explains the gravitational and magnetic interactions in the case of horizontal and vertical positions of the needle. (JRH)

Lonc, William

1995-01-01

386

Classroom Demonstrations of Auditory Perception.  

ERIC Educational Resources Information Center

Presents activities to help students gain understanding about auditory perception. Describes demonstrations that cover topics, such as sound localization, wave cancellation, frequency/pitch variation, and the influence of media on sound propagation. (CMK)

Haws, LaDawn; Oppy, Brian J.

2002-01-01

387

Classroom Demonstrations of Polymer Principles.  

ERIC Educational Resources Information Center

Classroom demonstrations of selected mechanical properties of polymers are described that can be used to make quantitative measurements. Stiffness, strength, and extensibility are mechanical properties used to distinguish one polymer from another. (KR)

Rodriguez, F.

1990-01-01

388

Demonstrating and Calculating Electrostatic Forces  

NSDL National Science Digital Library

This lesson plan from the Beacon Learning Center educates students on the topic of demonstrating and calculating electrostatic forces. The lesson focuses on how electrostatic forces exist between charged objects. Florida state educational standards which the experiment exemplifies are included.

Rosen, Robert

2011-07-15

389

Rotating Cylinder Treatment System Demonstration  

EPA Science Inventory

In August 2008, a rotating cylinder treatment system (RCTSTM) demonstration was conducted near Gladstone, CO. The RCTSTM is a novel technology developed to replace the aeration/oxidation and mixing components of a conventional lime precipitation treatment s...

390

The Physics Video Demonstration Database  

NSDL National Science Digital Library

This web site contains a database of a wide range of short videos demonstrating physics concepts. The videos can be used during lecture by instructors, by students for coursework outside lecture, and for students to review demonstrations after class. The database can be browsed by topic or searched by keyword. Those with videos they may wish to contribute can contact the creator of the web site.

Liepe, Mattias

2008-09-17

391

Slant Borehole Demonstration Summary Report  

SciTech Connect

This report provides a summary of the demonstration project for development of a slant borehole to retrieve soil samples from beneath the SX-108 single-shell tank. It provides a summary of the findings from the demonstration activities and recommendations for tool selection and methods to deploy into the SX Tank Farm. Daily work activities were recorded on Drilling and Sampling Daily Work Record Reports. The work described in this document was performed during March and April 2000.

GARDNER, M.G.

2000-07-19

392

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

393

Wave rotor demonstrator engine assessment  

NASA Technical Reports Server (NTRS)

The objective of the program was to determine a wave rotor demonstrator engine concept using the Allison 250 series engine. The results of the NASA LERC wave rotor effort were used as a basis for the wave rotor design. A wave rotor topped gas turbine engine was identified which incorporates five basic requirements of a successful demonstrator engine. Predicted performance maps of the wave rotor cycle were used along with maps of existing gas turbine hardware in a design point study. The effects of wave rotor topping on the engine cycle and the subsequent need to rematch compressor and turbine sections in the topped engine were addressed. Comparison of performance of the resulting engine is made on the basis of wave rotor topped engine versus an appropriate baseline engine using common shaft compressor hardware. The topped engine design clearly demonstrates an impressive improvement in shaft horsepower (+11.4%) and SFC (-22%). Off design part power engine performance for the wave rotor topped engine was similarly improved including that at engine idle conditions. Operation of the engine at off design was closely examined with wave rotor operation at less than design burner outlet temperatures and rotor speeds. Challenges identified in the development of a demonstrator engine are discussed. A preliminary design was made of the demonstrator engine including wave rotor to engine transition ducts. Program cost and schedule for a wave rotor demonstrator engine fabrication and test program were developed.

Snyder, Philip H.

1996-01-01

394

Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice  

PubMed Central

Background The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss. Results We report that in addition to decreased mRNA expression, there was decreased overall Na+/K+ ATPase enzyme activity in the amyloid-containing hippocampi of the APP+PS1 mice (although not in the amyloid-free cerebellum). In addition, dual immunolabeling revealed an absence of Na+/K+ ATPase staining in a zone surrounding congophilic plaques that was occupied by dystrophic neurites. We also demonstrate that cerebral Na+/K+ ATPase activity can be directly inhibited by high concentrations of soluble A?. Conclusions The data suggest that the reductions in Na+/K+ ATPase activity in Alzheimer tissue may not be purely secondary to neuronal loss, but may results from direct effects of amyloid on this enzyme. This disruption of ion homeostasis and osmotic balance may interfere with normal electrotonic properties of dendrites, blocking intraneuronal signal processing, and contribute to neuritic dystrophia. These results suggest that therapies aimed at enhancing Na+/K+ ATPase activity in AD may improve symptoms and/or delay disease progression. PMID:15689237

Dickey, Chad A; Gordon, Marcia N; Wilcock, Donna M; Herber, Donna L; Freeman, Melissa J; Morgan, Dave

2005-01-01

395

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

PubMed

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

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

2015-01-01

396

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

PubMed Central

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

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

2010-01-01

397

Progress on the Fabrication and Testing of the MICE Spectrometer Solenoids  

SciTech Connect

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.

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

2009-05-19

398

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

PubMed

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

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

2014-12-01

399

Near-infrared-labeled tetracycline derivative is an effective marker of bone deposition in mice.  

PubMed

Bone-specific compounds have been used effectively for the detection of bone mineralization, growth, and morphological changes. These agents typically contain iminodiacetic acid groups that can form complexes with apatite and fluoresce in the visible spectrum. We exploited a subset of these chemical chelators to produce a near-infrared (NIR) optical bone marker for preclinical animal imaging. By conjugating target compounds to IRDye 800CW, we extended the effective fluorescence signal detection to the NIR region without affecting the compound's ability to function as a marker of the mineralization process. Calcein and a tetracycline derivative (BoneTag agent [BT]) bound specifically to differentiated mineralized osteoblast cultures, with the latter exhibiting 6-fold higher signal intensities. Subsequent in vivo testing demonstrated effective skeletal labeling with IRDye 800CW BT. We were able to identify a changing mineralization front in bone sections from (i) normal growing mice injected with IRDye 800CW BT 6weeks prior to the administration of IRDye 680 BT and (ii) an osteoporosis mouse model comparing cortical bone in sham-treated and ovariectomized mice. These results provide evidence that the NIR-labeled BT is effective as a general marker of skeletal features and an indicator of the bone mineralization and remodeling processes. PMID:21645491

Kovar, Joy L; Xu, Xinshe; Draney, Dan; Cupp, Andrea; Simpson, Melanie A; Olive, D Michael

2011-09-15

400

Fusion of Multiple Facial Features for Age Estimation  

NASA Astrophysics Data System (ADS)

A novel age estimation method is presented which improves performance by fusing complementary information acquired from global and local features of the face. Two-directional two-dimensional principal component analysis ((2D)2PCA) is used for dimensionality reduction and construction of individual feature spaces. Each feature space contributes a confidence value which is calculated by Support vector machines (SVMs). The confidence values of all the facial features are then fused for final age estimation. Experimental results demonstrate that fusing multiple facial features can achieve significant accuracy gains over any single feature. Finally, we propose a fusion method that further improves accuracy.

Lu, Li; Shi, Pengfei

401

PKC? regulates hepatic triglyceride accumulation and insulin signaling in Lepr(db/db) mice.  

PubMed

PKC? has been linked to key pathophysiological features of non-alcoholic fatty liver disease (NAFLD). Yet, our knowledge of PKC?'s role in NAFLD development and progression in obese models is limited. PKC?(-/-)/Lepr(db)(/)(db) mice were generated to evaluate key pathophysiological features of NAFLD in mice. Hepatic histology, oxidative stress, apoptosis, gene expression, insulin signaling, and serum parameters were analyzed in Lepr(db)(/)(db) and PKC?(-/-)/Lepr(db)(/)(db) mice. The absence of PKC? did not abrogate the development of obesity in Lepr(db)(/)(db) mice. In contrast, serum triglyceride levels and epididymal white adipose tissue weight normalized to body weight were reduced in PKC?(-/-)/Lepr(db)(/)(db) mice compared Lepr(db)(/)(db) mice. Analysis of insulin signaling in mice revealed that hepatic Akt and GSK3? phosphorylation were strongly stimulated by insulin in PKC?(-/-)/Lepr(db)(/)(db) compared Lepr(db)(/)(db) mice. PKC? may be involved in the development of obesity-associated NAFLD by regulating hepatic lipid metabolism and insulin signaling. PMID:25035929

Zhang, Jian; Burrington, Christine M; Davenport, Samantha K; Johnson, Andrew K; Horsman, Melissa J; Chowdhry, Saleem; Greene, Michael W

2014-08-01

402

Tested Demonstrations. Brownian Motion: A Classroom Demonstration and Student Experiment.  

ERIC Educational Resources Information Center

Shows how video recordings of the Brownian motion of tiny particles may be made. Describes a classroom demonstration and cites a reported experiment designed to show the random nature of Brownian motion. Suggests a student experiment to discover the distance a tiny particle travels as a function of time. (MVL)

Kirksey, H. Graden; Jones, Richard F.

1988-01-01

403

Demonstration Extension: Copper-to-Silver-to-Gold Penny Demonstration  

ERIC Educational Resources Information Center

This demonstration, if done in the original way, can lead to fires in waste containers (sometimes in the middle of the night after the experiment has been conducted), because pyrophoric zinc is generated by suspending powdered zinc in hot sodium hydroxide. This is avoided by using hot ZnSO[subscript 4].

Vitz, Ed

2008-01-01

404

Demonstration of Active Combustion Control  

NASA Technical Reports Server (NTRS)

The primary objective of this effort was to demonstrate active control of combustion instabilities in a direct-injection gas turbine combustor that accurately simulates engine operating conditions and reproduces an engine-type instability. This report documents the second phase of a two-phase effort. The first phase involved the analysis of an instability observed in a developmental aeroengine and the design of a single-nozzle test rig to replicate that phenomenon. This was successfully completed in 2001 and is documented in the Phase I report. This second phase was directed toward demonstration of active control strategies to mitigate this instability and thereby demonstrate the viability of active control for aircraft engine combustors. This involved development of high-speed actuator technology, testing and analysis of how the actuation system was integrated with the combustion system, control algorithm development, and demonstration testing in the single-nozzle test rig. A 30 percent reduction in the amplitude of the high-frequency (570 Hz) instability was achieved using actuation systems and control algorithms developed within this effort. Even larger reductions were shown with a low-frequency (270 Hz) instability. This represents a unique achievement in the development and practical demonstration of active combustion control systems for gas turbine applications.

Lovett, Jeffrey A.; Teerlinck, Karen A.; Cohen, Jeffrey M.

2008-01-01

405

Buried Waste Integrated Demonstration Plan  

SciTech Connect

This document presents the plan of activities for the Buried Waste Integrated Demonstration (BWID) program which supports the environmental restoration (ER) objectives of the Department of Energy (DOE) Complex. Discussed in this plan are the objectives, organization, roles and responsibilities, and the process for implementing and managing BWID. BWID is hosted at the Idaho National Engineering Laboratory (INEL), but involves participants from throughout the DOE Complex, private industry, universities, and the international community. These participants will support, demonstrate, and evaluate a suite of advanced technologies representing a comprehensive remediation system for the effective and efficient remediation of buried waste. The processes for identifying technological needs, screening candidate technologies for applicability and maturity, selecting appropriate technologies for demonstration, field demonstrating, evaluation of results and transferring technologies to environmental restoration programs are also presented. This document further describes the elements of project planning and control that apply to BWID. It addresses the management processes, operating procedures, programmatic and technical objectives, and schedules. Key functions in support of each demonstration such as regulatory coordination, safety analyses, risk evaluations, facility requirements, and data management are presented.

Kostelnik, K.M.

1991-12-01

406

Auditory demonstrations simulating Mayan architecture  

NASA Astrophysics Data System (ADS)

Fascination with the ancient temples and ball court at Chichen Itza provide rich opportunities for science education. Children of all ages are delighted to learn that the sound of handclaps scattered from long temple staircases are transformed into bird chirps. Their engagement in such seemingly magical phenomena provides magic moments for teaching acoustical principals, including the picket-fence effect (PFE). PFE transforms impulsive sounds scattered from spatially periodic structures into tonal sounds. PFE is demonstrated with a computer possessing a sound card and a simple sound editing program. The inverse relationship between tonal frequency and the time interval between periodic impulses is easily demonstrated. The number of impulses needed to produce an audible tone is easily demonstrated and compared with the number of steps on the staircase. Transformation of audible tones into downward-gliding chirps is simulated by monotonically increasing the time between impulses. The Great Ball Court also provides opportunities for acoustical demonstration. Observers clapping their hands while standing between the long, tall, and parallel walls of the playing field marvel at the profound flutter echo heard for about 1.5 s. The flutter echo sonogram demonstrates the speed of sound and frequency-selective atmospheric attenuation.

Lubman, David

2005-09-01

407

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

NASA Astrophysics Data System (ADS)

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.

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

2013-05-01

408

Traumatic Brain Injury Precipitates Cognitive Impairment and Extracellular A? Aggregation in Alzheimer's Disease Transgenic Mice  

PubMed Central

Traumatic brain injury (TBI) has become a signature wound of the wars in Iraq and Afghanistan. Many American soldiers, even those undiagnosed but likely suffering from mild TBI, display Alzheimer's disease (AD)-like cognitive impairments, suggesting a pathological overlap between TBI and AD. This study examined the cognitive and neurohistological effects of TBI in presymptomatic APP/PS1 AD-transgenic mice. AD mice and non-transgenic (NT) mice received an experimental TBI on the right parietal cortex using the controlled cortical impact model. Animals were trained in a water maze task for spatial memory before TBI, and then reevaluated in the same task at two and six weeks post-TBI. The results showed that AD mice with TBI made significantly more errors in the task than AD mice without TBI and NT mice regardless of TBI. A separate group of AD mice and NT mice were evaluated neurohistologically at six weeks after TBI. The number of extracellular beta-amyloid (A?)-deposits significantly increased by at least one fold in the cortex of AD mice that received TBI compared to the NT mice that received TBI or the AD and NT mice that underwent sham surgery. A significant decrease in MAP2 positive cells, indicating neuronal loss, was observed in the cortex of both the AD and NT mice that received TBI compared to the AD and NT mice subjected to sham surgery. Similar changes in extracellular A? deposits and MAP2 positive cells were also seen in the hippocampus. These results demonstrate for the first time that TBI precipitates cognitive impairment in presymptomatic AD mice, while also confirming extracellular A? deposits following TBI. The recognition of this pathological link between TBI and AD should aid in developing novel treatments directed at abrogating cellular injury and extracellular A? deposition in the brain. PMID:24223856

Shimizu, Toru; Arendash, Gary W.; Borlongan, Cesar V.

2013-01-01

409

Cardiomyocyte-specific expression of lamin a improves cardiac function in Lmna-/- mice.  

PubMed

Lmna(-/-) mice display multiple tissue defects and die by 6-8 weeks of age reportedly from dilated cardiomyopathy with associated conduction defects. We sought to determine whether restoration of lamin A in cardiomyocytes improves cardiac function and extends the survival of Lmna(-/-) mice. We observed increased total desmin protein levels and disorganization of the cytoplasmic desmin network in ~20% of Lmna(-/-) ventricular myocytes, rescued in a cell-autonomous manner in Lmna(-/-) mice expressing a cardiac-specific lamin A transgene (Lmna(-/-); Tg). Lmna(-/-); Tg mice displayed significantly increased contractility and preservation of myocardial performance compared to Lmna(-/-) mice. Lmna(-/-); Tg mice attenuated ERK1/2 phosphorylation relative to Lmna(-/-) mice, potentially underlying the improved localization of connexin43 to the intercalated disc. Electrocardiographic recordings from Lmna(-/-) mice revealed arrhythmic events and increased frequency of PR interval prolongation, which is partially rescued in Lmna(-/-); Tg mice. These findings support our observation that Lmna(-/-); Tg mice have a 12% median extension in lifespan compared to Lmna(-/-) mice. While significant, Lmna(-/-); Tg mice only have modest improvement in cardiac function and survival likely stemming from the observation that only 40% of Lmna(-/-); Tg cardiomyocytes have detectable lamin A expression. Cardiomyocyte-specific restoration of lamin A in Lmna(-/-) mice improves heart-specific pathology and extends lifespan, demonstrating that the cardiac pathology of Lmna(-/-) mice limits survival. The expression of lamin A is sufficient to rescue certain cellular defects associated with loss of A-type lamins in cardiomyocytes in a cell-autonomous fashion. PMID:22905185

Frock, Richard L; Chen, Steven C; Da, Dao-Fu; Frett, Ellie; Lau, Carmen; Brown, Christina; Pak, Diana N; Wang, Yuexia; Muchir, Antoine; Worman, Howard J; Santana, Luis F; Ladiges, Warren C; Rabinovitch, Peter S; Kennedy, Brian K

2012-01-01

410

Iterative feature removal yields highly discriminative pathways  

PubMed Central

Background We introduce Iterative Feature Removal (IFR) as an unbiased approach for selecting features with diagnostic capacity from large data sets. The algorithm is based on recently developed tools in machine learning that are driven by sparse feature selection goals. When applied to genomic data, our method is designed to identify genes that can provide deeper insight into complex interactions while remaining directly connected to diagnostic utility. We contrast this approach with the search for a minimal best set of discriminative genes, which can provide only an incomplete picture of the biological complexity. Results Microarray data sets typically contain far more features (genes) than samples. For this type of data, we demonstrate that there are many equivalently-predictive subsets of genes. We iteratively train a classifier using features identified via a sparse support vector machine. At each iteration, we remove all the features that were previously selected. We found that we could iterate many times before a sustained drop in accuracy occurs, with each iteration removing approximately 30 genes from consideration. The classification accuracy on test data remains essentially flat even as hundreds of top-genes are removed. Our method identifies sets of genes that are highly predictive, even when comprised of genes that individually are not. Through automated and manual analysis of the selected genes, we demonstrate that the selected features expose relevant pathways that other approaches would have missed. Conclusions Our results challenge the paradigm of using feature selection techniques to design parsimonious classifiers from microarray and similar high-dimensional, small-sample-size data sets. The fact that there are many subsets of genes that work equally well to classify the data provides a strong counter-result to the notion that there is a small number of “top genes” that should be used to build classifiers. In our results, the best classifiers were formed using genes with limited univariate power, thus illustrating that deeper mining of features using multivariate techniques is important. PMID:24274115

2013-01-01

411

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. ...

412

SECURES: Austin, Texas demonstration results  

NASA Astrophysics Data System (ADS)

The Law Enforcement technology development community has a growing interest in the technologies associated with gunshot detection and localization. These interests revolve around community-oriented policing. Technologies of interest include those associated with muzzle blast and bullet shockwave detection and the inter-netting of these acoustic sensors with electro-optic sensors. To date, no one sensor technology has proven totally effective for a complete solution. PSI has a muzzle blast detection and localization product which is wireless, highly mobile and reconfigurable, with a user-friendly laptop processor and display unit, which completed a one-year demonstration in Austin, Texas on July 6, 2002. This demonstration was conducted under a Cooperative Agreement with the National Institute of Justice and in cooperation with the Austin Police Department. This paper will discuss the details of the demonstrations, provide a summarized evaluation, elucidate the lessons learned, make recommendations for future deployments and discuss the developmental directions indicated for the future.

Lewis, Glynn; Shaw, Scott; Scharf, Peter; Stellingworth, Bob

2003-09-01

413

Experiment to demonstrate diffusion doping  

NASA Astrophysics Data System (ADS)

Single crystals of CdS possess a translucent yellow color but when indium is diffused into the crystal from the vapor in an evacuated silica capsule it becomes opaque. This type of diffusion is linearly dependent on the indium concentration and produces a sharp interface between the diffused and undiffused regions of the crystal. The process of diffusion doping can be demonstrated by studying the variation of the depth of the interface with anneal time and temperature, using an optical microscope. In addition, as CdS possesses a hexagonal crystal structure of the ``wurtzite'' type, this is a sensitive method for studying diffusion anisotropy along the two principal crystal directions, and the sharpness of the interface can be demonstrated by the dispersion produced by a narrow beam of white light. This article describes how these properties can be incorporated into an undergraduate student experiment, or an open ended project for demonstrating Fick's laws and the process of diffusion doping.

Jones, E. D.

1995-01-01

414

Apollo 14 composite casting demonstration  

NASA Technical Reports Server (NTRS)

The purpose of the demonstration was to show that mixtures of materials of different specific gravities would remain stable in the liquid state and during freezing in low g and not segregate as they do on earth. An inflight demonstration was performed on the Apollo 14 mission during the translunar and and transearth coast periods. The apparatus consisted of an electrical heater, a heat sink device for cooling, and sealed metal capsules containing matrix materials having a low-melting point and dispersants. The evaluation of the demonstration samples was accomplished by comparing space processed (flight) samples with (control) samples processed on the ground under otherwise similar conditions. In the low q environment of space flight the dispersions of particles, fibers, and gases in a liquid metal matrix were maintained during solidification. Dispersions of normally immiscible liquids were also maintained during solidification.

Yates, I. C., Jr.

1971-01-01

415

Yo-yo Pull Demonstration  

NASA Astrophysics Data System (ADS)

A popular demonstration involves placing a yo-yo on a level table and gently pulling the string horizontally when it is wrapped to come out below the center of the yo-yo's axis. Students are then asked to predict which way the yo-yo will move. A similar demonstration is performed with a tricycle by pulling forward on a pedal with the pedal down in its lowest position.2,3 As well as pulling the yo-yo horizontally, often the string is lifted until the angle it makes with the table causes no motion. This occurs when the line extended from the string intersects the point of contact of the yo-yo with the table.4 This paper describes an apparatus that extends these demonstrations to the situation where the force pulling the yo-yo is still horizontal yet is below the level of the table.

Layton, William

2013-03-01

416

TRUEX hot demonstration. Final report  

SciTech Connect

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.

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

1990-04-01

417

Loudspeaker line array educational demonstration.  

PubMed

This paper presents a physical demonstration of an audio-range line array used to teach interference of multiple sources in a classroom or laboratory exercise setting. Software has been developed that permits real-time control and steering of the array. The graphical interface permits a user to vary the frequency, the angular response by phase shading, and reduce sidelobes through amplitude shading. An inexpensive, eight-element loudspeaker array has been constructed to test the control program. Directivity measurements of this array in an anechoic chamber and in a large classroom are presented. These measurements have good agreement with theoretical directivity predictions, thereby allowing its use as a quantitative learning tool for advanced students as well as a qualitative demonstration of arrays in other settings. Portions of this paper are directed toward educators who may wish to implement a similar demonstration for their advanced undergraduate or graduate level course in acoustics. PMID:22423785

Anderson, Brian E; Moser, Brad; Gee, Kent L

2012-03-01

418

Transfer of gut microbiota from lean and obese mice to antibiotic-treated mice.  

PubMed

Transferring gut microbiota from one individual to another may enable researchers to "humanize" the gut of animal models and transfer phenotypes between species. To date, most studies of gut microbiota transfer are performed in germ-free mice. In the studies presented, it was tested whether an antibiotic treatment approach could be used instead. C57BL/6 mice were treated with ampicillin prior to inoculation at weaning or eight weeks of age with gut microbiota from lean or obese donors. The gut microbiota and clinical parameters of the recipients was characterized one and six weeks after inoculation. The results demonstrate, that the donor gut microbiota was introduced, established, and changed the gut microbiota of the recipients. Six weeks after inoculation, the differences persisted, however alteration of the gut microbiota occurred with time within the groups. The clinical parameters of the donor phenotype were partly transmissible from obese to lean mice, in particularly ? cell hyperactivity in the obese recipients. Thus, a successful inoculation of gut microbiota was not age dependent in order for the microbes to colonize, and transferring different microbial compositions to conventional antibiotic-treated mice was possible at least for a time period during which the microbiota may permanently modulate important host functions. PMID:25082483

Ellekilde, Merete; Selfjord, Ellika; Larsen, Christian S; Jakesevic, Maja; Rune, Ida; Tranberg, Britt; Vogensen, Finn K; Nielsen, Dennis S; Bahl, Martin I; Licht, Tine R; Hansen, Axel K; Hansen, Camilla H F

2014-01-01

419

EUVE Satellite Data Flow Demonstration  

NSDL National Science Digital Library

This is a hands-on demonstration of the communication path between the Extreme Ultraviolet Explorer (EUVE) satellite and a scientist on Earth, where students play the parts of various satellites, ground stations, and science centers. The module includes a Java applet animation of the Satellite data flow and background information on the various communication links. The purpose of this lesson plan is to show students how the data are sent and received by making them active participants in the chain of events. This demonstration also allows students to get a feel for the dynamic of satellite communications and orbital motion around the Earth.

1996-07-01

420

Stromal activation associated with development of prostate cancer in prostate-targeted fibroblast growth factor 8b transgenic mice.  

PubMed

Expression of fibroblast growth factor 8 (FGF-8) is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG) mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelial morphology progressing from atypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN) lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation. PMID:21076617

Elo, Teresa D; Valve, Eeva M; Seppänen, Jani A; Vuorikoski, Heikki J; Mäkelä, Sari I; Poutanen, Matti; Kujala, Paula M; Härkönen, Pirkko L

2010-11-01

421

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

PubMed Central

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

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

2014-01-01

422

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 ...

423

Hepatotoxic effects of mycotoxin combinations in mice.  

PubMed

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

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

2014-10-22

424

Heart regeneration in adult MRL mice  

NASA Astrophysics Data System (ADS)

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.

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

2001-08-01

425

Histochemical response of mice to mistletoe lectin I (ML I)  

Microsoft Academic Search

The acute toxicity of lectin ML I from the toxic drug, mistletoe, was demonstrated in previous experiments. Because the reason for this extremely high toxicity is not yet clear, mice were studied histochemically at different times after treatment with various doses of ML I, ML I A or ML I B chain separately, or recombinations of ML I A and

R. Gossrau; H. Franz

1990-01-01

426

A Flight Demonstration of Plasma Rocket Propulsion  

NASA Technical Reports Server (NTRS)

The Advanced Space Propulsion Laboratory at the Johnson Space Center has been engaged in the development of a magneto-plasma rocket for several years. This type of rocket could be used in the future to propel interplanetary spacecraft. One advantageous feature of this rocket concept is the ability to vary its specific impulse so that it can be operated in a mode which maximizes propellant efficiency or a mode which maximizes thrust. This presentation will describe a proposed flight experiment in which a simple version of the rocket will be tested in space. In addition to the plasma rocket, the flight experiment will also demonstrate the use of a superconducting electromagnet, extensive use of heat pipes, and possibly the transfer of cryogenic propellant in space.

Petro, Andrew

1999-01-01

427

Feature selection using sparse Bayesian inference  

NASA Astrophysics Data System (ADS)

A process for selecting a sparse subset of features that maximize discrimination between target classes is described in a Bayesian framework. Demonstrated on high range resolution radar (HRR) signature data, this has the effect of selecting the most informative range bins for a classification task. The sparse Bayesian classifier (SBC) model is directly compared against Fisher's linear discriminant analysis (LDA), showing a clear performance gain with the Bayesian framework using HRRs from the publicly available MSTAR data set. The discriminative power of the selected features from the SBC is shown to be particularly dominant over LDA when only a few features are selected or when there is a shift in training and testing data sets, as demonstrated by training on a specific target type and testing on a slightly different target type.

Brandes, T. Scott; Baxter, James R.; Woodworth, Jonathan

2014-06-01

428

Norepinephrine Transporter Heterozygous Knockout Mice Exhibit Altered Transport and Behavior  

PubMed Central

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

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

2013-01-01

429

Norepinephrine transporter heterozygous knockout mice exhibit altered transport and behavior.  

PubMed

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

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

430

Enhanced Malignant Tumorigenesis in Cdk4-Transgenic Mice  

PubMed Central

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

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

2010-01-01

431

TASK channel deletion in mice causes primary hyperaldosteronism.  

PubMed

When inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (ZG) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown. Here, we show that genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels removes an important background K current that results in a marked depolarization of ZG cell membrane potential. Although TASK channel deletion mice (TASK-/-) adjust urinary Na excretion and aldosterone production to match Na intake, they produce more aldosterone than control mice across the range of Na intake. Overproduction of aldosterone is not the result of enhanced activity of the renin-angiotensin system because circulating renin concentrations remain either unchanged or lower than those of control mice at each level of Na intake. In addition, TASK-/- mice fail to suppress aldosterone production in response to dietary Na loading. Autonomous aldosterone production is also demonstrated by the failure of an angiotensin type 1 receptor blocker, candesartan, to normalize aldosterone production to control levels in TASK-/- mice. Thus, TASK-/- channel knockout mice exhibit the hallmarks of primary hyperaldosteronism. Our studies establish an animal model of nontumorigenic primary hyperaldosteronism and identify TASK channels as a possible therapeutic target for primary hyperaldosteronism. PMID:18250325

Davies, Lucinda A; Hu, Changlong; Guagliardo, Nick A; Sen, Neil; Chen, Xiangdong; Talley, Edmund M; Carey, Robert M; Bayliss, Douglas A; Barrett, Paula Q

2008-02-12

432

Favorite Demonstration: Demonstrating Translation With a Student-Centered Activity  

NSDL National Science Digital Library

The process of protein synthesis translation is difficult for many students to understand. The reasons for this include the fact that it is difficult to visualize the process since the components involved in the process are not observable. Also, there are many details, often dependent on each other and difficult to grasp independently that are necessary to know in order to understand the process. With that in mind, an interactive group demonstration was developed to help students vizualize the process of translation.

Poole, Therese M.

2006-03-01

433

NASA: Interactive Features  

NSDL National Science Digital Library

Amidst many strong and detailed government websites, the National Aeronautics and Space Administration (NASA) site always presents a rich variety of material for the space-curious public. Their "Interactive Features" area is embedded in their larger "Multimedia" site, and it's a fantastic kaleidoscope of sweeping views of Saturn, fun with the X-15 spacecraft, and more than a few (several dozen, actually) interactive timelines. First-time users can browse through the archive of features at their leisure, or they can also use the search engine to look for specific items. Some of the more noteworthy features here include a timeline which explores the history of "planet hunting" ("PlanetQuest Historic Timeline") and the trip through space in the "Virtual Lunar Outpost". It's easy to while away a few hours on the site and it is one that budding space scientists will want to bookmark.

434

Feature of the Month  

NSDL National Science Digital Library

The Northern Prairie Wildlife Research Center (NPWRC) maintains a special section entitled "Feature of the Month," which provides detailed information on a timely subject. Previous features, accessible through the site archive, include 'Spring Migration Guide' (March), 'The Conservation Reserve Program' (June), and 'How Old Is My Deer?' (November). In response to scientific and public attention to amphibian malformations in the US and Canada, this month's feature highlights the North American Reporting Center for Amphibian Malformations (NARCAM), "a centralized database of confirmed malformation sightings and related information." The database includes background information, an online amphibian identification guide, a map of historical and recent reports, examples of malformations, a bibliography, forms for submitting reports, and technical information for researchers.

435

Three featured plenary sessions  

NASA Astrophysics Data System (ADS)

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.

2012-07-01

436

LIMB Demonstration Project Extension and Coolside Demonstration. [Final report  

SciTech Connect

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.

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

1992-11-10

437

Phenolphthalein-Pink Tornado Demonstration  

ERIC Educational Resources Information Center

The titration of HCl with NaOH has traditionally been used to introduce beginning chemistry students to the concepts of acid-base chemistry and stoichiometry. The demonstration described in this article utilizes this reaction as a means of providing students an opportunity to observe the dynamic motion associated with a swirling vortex and its…

Prall, Bruce R.

2008-01-01