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  1. Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

    Science.gov (United States)

    Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

    2016-10-01

    Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model. © 2016 Society for Endocrinology.

  2. Maporal Hantavirus Causes Mild Pathology in Deer Mice (Peromyscus maniculatus

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    Amanda McGuire

    2016-10-01

    Full Text Available Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4 containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the deer mouse (Peromyscus maniculatus, the natural reservoir host of Sin Nombre virus (SNV, and a virus that is pathogenic in another animal model to examine immune response of a reservoir host species. Deer mice were inoculated with MAPV, and viral RNA was detected in several organs of all deer mice during the 56 day experiment. Infected animals generated both nucleocapsid-specific and neutralizing antibodies. Histopathological lesions were minimal to mild with the peak of the lesions detected at 7–14 days postinfection, mainly in the lungs, heart, and liver. Low to modest levels of cytokine gene expression were detected in spleens and lungs of infected deer mice, and deer mouse primary pulmonary cells generated with endothelial cell growth factors were susceptible to MAPV with viral RNA accumulating in the cellular fraction compared to infected Vero cells. Most features resembled that of SNV infection of deer mice, suggesting this model may be an ABSL-3 surrogate for studying the host response of a New World hantavirus reservoir.

  3. Male aromatase-knockout mice exhibit normal levels of activity, anxiety and "depressive-like" symptomatology.

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    Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

    2005-09-08

    It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital behavior and are sexually less motivated. We wondered whether these behavioral deficits of ArKO males could be related to changes in activity, exploration, anxiety and "depressive-like" symptomatology. ArKO and wild type (WT) males were subjected to open field (OF), elevated plus maze (EPM), and forced swim tests (FST), after being exposed or not to chronic mild stress (CMS). CMS was used to evaluate the impact of chronic stressful procedures and to unveil possible differences between genotypes. There was no effect of genotype on OF, EPM and FST behavioral parameters. WT and ArKO mice exposed to CMS or not exhibited the same behavioral profile during these three types of tests. However, all CMS-exposed mice (ArKO and WT) spent less time in the center of the EPM. Additionally, floating duration measured in the FST increased between two tests in both WT and ArKO mice, though that increase was less prominent in mice previously subjected to CMS than in controls. Therefore, both ArKO and WT males displayed the same behavior and had the same response to CMS however CMS exposure slightly modified the behavior displayed by mice of both genotypes in the FST and EPM paradigms. These results show that ArKO males display normal levels of activity, exploration, anxiety and "depressive-like" symptomatology and thus their deficits in sexual behavior are specific in nature and do not result indirectly from other behavioral changes.

  4. Effects of diet quality on vulnerability to mild subchronic social defeat stress in mice.

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    Goto, Tatsuhiko; Kubota, Yoshifumi; Toyoda, Atsushi

    2016-09-01

    The chronic social defeat stress (CSDS) mouse model is a potentially useful system for understanding stress responses to social environments. We previously developed a mouse model of subchronic and mild social defeat stress (sCSDS) that exhibits increased body weight gain and food intake following polydipsia-like features. sCSDS mice also show avoidance behavior in a social interaction test. In this study, we examined the effects of diet quality on susceptibility to sCSDS by feeding these mice semi- and non-purified diets. Male C57BL/6J (B6; n = 82) mice were exposed to sCSDS using male ICR mice. The B6 mice were divided into four test groups: semi-purified pellet diet + sCSDS, non-purified pellet diet + sCSDS, semi-purified diet + control (no sCSDS), and non-purified diet + control. Although increased body weight, and food and water intake following sCSDS exposure were consistently observed in the groups that were fed semi- and non-purified diets, social avoidance behavior was influenced by food type (i.e., sCSDS mice fed semi-purified diet showed the greatest social avoidance behavior). In addition, the rates of stress susceptibility were estimated at 73.9 and 34.8% in sCSDS mice fed semi-purified and non-purified diets, respectively (P healthy control mice fed semi-purified and non-purified diets, respectively. These results suggest that diet quality affects the vulnerability of mice to social defeat stress.

  5. Exhibition

    CERN Document Server

    Staff Association

    2017-01-01

    A Look of Hope Islam Mahmoud Sweity From 19 to 30 June 2017 CERN Meyrin, Main Building Islam Mahmoud Sweity Islam Mahmoud Sweity was born in 1997 at Beit Awwa, Palestine. She is currently following a course to get an Art diploma of Painting at the college of Fine Arts at An-Najah National University under the supervision of Esmat Al As'aad. Her portraits, landscapes and still life paintings are full of life and shining colours. Charged of emotional empathy they catch the attention of the viewer and are reminding us that life is beautiful and worth living in spite of all difficulties we have to go through. She participated in many exhibitions and has exposed her drawings in 2015 at CERN and in France in the framework of the exhibition "The Origin“, and in 2017 in the Former Yugoslav Republic of Macedonia, Palestina and Jordan. In this exhibition the oil paintings made in the past year will be presented. For more information : staff.association@cern.ch | T&eacu...

  6. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    Encounters Hanne Blitz From February 1st to 12th 2016 CERN Meyrin, Main Building What is our reaction to a first encounter with a tourist attraction? Contemporary Dutch painter Hanne Blitz captures visitors' responses to art and architecture, sweeping vistas and symbolic memorials. Encounters, a series of oil paintings curated specially for this CERN exhibition, depicts tourists visiting cultural highlights around the world. A thought-provoking journey not to be missed, and a tip of the hat to CERN's large Hadron Collider.

  7. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Sintropie Flavio Pellegrini From 13 to 24 March 2017 CERN Meyrin, Main Building Energia imprigionata - Flavio Pellegrini. The exhibition is composed by eleven wood artworks with the expression of movement as theme. The artworks are the result of harmonics math applied to sculpture. The powerful black colour is dominated by the light source, generating reflexes and modulations. The result is a continuous variation of perspective visions. The works generate, at a first approach, an emotion of mystery and incomprehension, only a deeper contemplation lets one discover entangling and mutative details, evidencing the elegance of the lines and letting the meaning emerge. For more information : staff.association@cern.ch | Tél: 022 766 37 38

  8. Mice lacking Brinp2 or Brinp3, or both, exhibit behaviours consistent with neurodevelopmental disorders

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    Susie Ruth Berkowicz

    2016-10-01

    Full Text Available Background: Brinps 1 – 3, and Astrotactins (Astn 1 and 2, are members of the Membrane Attack Complex / Perforin (MACPF superfamily that are predominantly expressed in the mammalian brain during development. Genetic variation at the human BRINP2/ASTN1 and BRINP1/ASTN2 loci has been implicated in neurodevelopmental disorders. We, and others, have previously shown that Brinp1-/- mice exhibit behaviour reminiscent of autism spectrum disorder (ASD and attention deficit hyperactivity disorder (ADHD.Method: We created Brinp2-/- mice and Brinp3-/- mice via the Cre-mediated LoxP system to investigate the effect of gene deletion on anatomy and behaviour. Additionally, Brinp2-/-Brinp3-/- double knock-out mice were generated by interbreeding Brinp2-/- and Brinp3-/- mice. Genomic validation was carried out for each knock-out line, followed by histological, weight and behavioural examination. Brinp1-/-Brinp2-/-Brinp3-/- triple knock-out mice were also generated by crossing Brinp2/3 double knock-out mice with previously generated Brinp1-/- mice, and examined by weight and histological analysis.Results: Brinp2-/- and Brinp3-/- mice differ in their behaviour: Brinp2-/- mice are hyperactive, whereas Brinp3-/- mice exhibit marked changes in anxiety-response on the elevated plus maze. Brinp3-/- mice also show evidence of altered sociability. Both Brinp2-/- and Brinp3-/- mice have normal short-term memory, olfactory responses, pre-pulse inhibition and motor learning. The double knock-out mice show behaviours of Brinp2-/- and Brinp3-/- mice, without evidence of new or exacerbated phenotypes. Conclusion: Brinp3 is important in moderation of anxiety, with potential relevance to anxiety disorders. Brinp2 dysfunction resulting in hyperactivity may be relevant to the association of ADHD with chromosome locus 1q25.2. Brinp2-/- and Brinp3-/- genes do not compensate in the mammalian brain and likely have distinct molecular or cell-type specific functions.

  9. Dopamine D3 receptor knockout mice exhibit abnormal nociception in a sex-different manner.

    Science.gov (United States)

    Liu, Peng; Xing, Bo; Chu, Zheng; Liu, Fei; Lei, Gang; Zhu, Li; Gao, Ya; Chen, Teng; Dang, Yong-Hui

    2017-07-01

    Pain is a complex and subjective experience. Previous studies have shown that mice lacking the dopamine D3 receptor (D3RKO) exhibit hypoalgesia, indicating a role of the D3 receptor in modulation of nociception. Given that there are sex differences in pain perception, there may be differences in responses to nociceptive stimuli between male and female D3RKO mice. In the current study, we examined the role of the D3 receptor in modulating nociception in male and female D3RKO mice. Acute thermal pain was modeled by hot-plate test. This test was performed at different temperatures including 52°C, 55°C, and 58°C. The von Frey hair test was applied to evaluate mechanical pain. And persistent pain produced by peripheral tissue injury and inflammation was modeled by formalin test. In the hot-plate test, compared with wild-type (WT) mice, D3RKO mice generally exhibited longer latencies at each of the three temperatures. Specially, male D3RKO mice showed hypoalgesia compared with male WT mice when the temperature was 55°C, while for the female mice, there was a statistical difference between genotypes when the test condition was 52°C. In the von Frey hair test, both male and female D3RKO mice exhibited hypoalgesia. In the formalin test, the male D3RKO mice displayed a similar nociceptive behavior as their sex-matched WT littermates, whereas significantly depressed late-phase formalin-induced nociceptive behaviors were observed in the female mutants. These findings indicated that the D3 receptor affects nociceptive behaviors in a sex-specific manner and that its absence induces more analgesic behavior in the female knockout mice. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2013-01-01

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

  11. Tau reduction diminishes spatial learning and memory deficits after mild repetitive traumatic brain injury in mice.

    Directory of Open Access Journals (Sweden)

    Jason S Cheng

    Full Text Available OBJECTIVE: Because reduction of the microtubule-associated protein Tau has beneficial effects in mouse models of Alzheimer's disease and epilepsy, we wanted to determine whether this strategy can also improve the outcome of mild traumatic brain injury (TBI. METHODS: We adapted a mild frontal impact model of TBI for wildtype C57Bl/6J mice and characterized the behavioral deficits it causes in these animals. The Barnes maze, Y maze, contextual and cued fear conditioning, elevated plus maze, open field, balance beam, and forced swim test were used to assess different behavioral functions. Magnetic resonance imaging (MRI, 7 Tesla and histological analysis of brain sections were used to look for neuropathological alterations. We also compared the functional effects of this TBI model and of controlled cortical impact in mice with two, one or no Tau alleles. RESULTS: Repeated (2-hit, but not single (1-hit, mild frontal impact impaired spatial learning and memory in wildtype mice as determined by testing of mice in the Barnes maze one month after the injury. Locomotor activity, anxiety, depression and fear related behaviors did not differ between injured and sham-injured mice. MRI imaging did not reveal focal injury or mass lesions shortly after the injury. Complete ablation or partial reduction of tau prevented deficits in spatial learning and memory after repeated mild frontal impact. Complete tau ablation also showed a trend towards protection after a single controlled cortical impact. Complete or partial reduction of tau also reduced the level of axonopathy in the corpus callosum after repeated mild frontal impact. INTERPRETATION: Tau promotes or enables the development of learning and memory deficits and of axonopathy after mild TBI, and tau reduction counteracts these adverse effects.

  12. An ethanolic extract of Desmodium adscendens exhibits antipsychotic-like activity in mice.

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    Amoateng, Patrick; Adjei, Samuel; Osei-Safo, Dorcas; Kukuia, Kennedy K E; Karikari, Thomas K; Nyarko, Alexander K

    2017-09-26

    Desmodium adscendens extract (DAE) is used traditionally in Ghana for the management of psychosis. The present study aimed at providing pharmacological evidence for its ethnomedical use by testing the hypothesis that an ethanolic extract of Desmodium adscendens may possess antipsychotic properties. The primary behavioral effects of DAE on the central nervous system of mice were investigated using Irwin's test paradigm. Novelty-induced and apomorphine-induced locomotor and rearing behaviors in mice were explored in an open-field observational test system. Apomorphine-induced cage climbing test in mice was used as the antipsychotic animal model. The ability of DAE to induce catalepsy and enhance haloperidol-induced catalepsy was also investigated in mice. The DAE produced sedation, cholinergic-, and serotonergic-like effects in mice when evaluated using the Irwin's test. No lethality was observed after 24 h post-treatment. The LD50 in mice was estimated to be greater than 3000 mg/kg. The DAE significantly decreased the frequency of novelty- and apomorphine-induced rearing and locomotor activities in mice. It also significantly lowered the frequency and duration of apomorphine-induced climbing activities in mice. It did not induce any cataleptic event in naïve mice but only significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg. The ethanolic extract of Desmodium adscendens exhibited antipsychotic-like activities in mice. Motor side effects are only likely to develop at higher doses of the extract.

  13. Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide

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    Catherine B. Lawrence

    2012-09-01

    Obesity is associated with an increase in the prevalence and severity of infections. Genetic animal models of obesity (ob/ob and db/db mice display altered centrally-mediated sickness behaviour in response to acute inflammatory stimuli such as lipopolysaccharide (LPS. However, the effect of diet-induced obesity (DIO on the anorectic and febrile response to LPS in mice is unknown. This study therefore determined how DIO and ob/ob mice respond to a systemic inflammatory challenge. C57BL/6 DIO and ob/ob mice, and their respective controls, were given an intraperitoneal (i.p. injection of LPS. Compared with controls, DIO and ob/ob mice exhibited an altered febrile response to LPS (100 μg/kg over 8 hours. LPS caused a greater and more prolonged anorexic effect in DIO compared with control mice and, in ob/ob mice, LPS induced a reduction in food intake and body weight earlier than it did in controls. These effects of LPS in obese mice were also seen after a fixed dose of LPS (5 μg. LPS (100 μg/kg induced Fos protein expression in several brain nuclei of control mice, with fewer Fos-positive cells observed in the brains of obese mice. An altered inflammatory response to LPS was also observed in obese mice compared with controls: changes in cytokine expression and release were detected in the plasma, spleen, liver and peritoneal macrophages in obese mice. In summary, DIO and ob/ob mice displayed an altered behavioural response and cytokine release to systemic inflammatory challenge. These findings could help explain why obese humans show increased sensitivity to infections.

  14. Stressful Presentations: Mild Chronic Cold Stress in Mice Influences Baseline Properties of Dendritic Cells

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    Kathleen Marie Kokolus

    2014-02-01

    Full Text Available The ability of dendritic cells to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to study immune responses. Physiological stress is well recognized to impair several arms of immune protection. The goals of this report are to briefly summarize previous work revealing how DCs respond to various forms of physiologically relevant stress and to present new data highlighting the potential for chronic mild cold stress inherent in mice housed at standard ambient temperatures required for laboratory mice to influence baseline DCs properties. Since recent data from our group shows that CD8+ T cell function is altered by mild chronic cold stress and since DC function is crucial for CD8+ T cell activation, we wondered whether mild cold stress may also be influencing DC properties. We found increased numbers of splenic DCs (CD11c+ in cold stressed mice compared to mice housed at a thermoneutral temperature, which significantly reduces cold stress. However, many of the DCs which are expanded in cold stressed mice express an immature phenotype. We also found that antigen presentation and ability of splenocytes to activate T cells were impaired compared to that seen in DCs isolated from mice at thermoneutrality. The new data presented here strongly suggest that the housing temperature of mice can affect fundamental properties of DC function which in turn could be influencing the response of DCs to added experimental stressors or other treatments.

  15. Specificity in Sociality: Mice and Prairie Voles Exhibit Different Patterns of Peer Affiliation

    Science.gov (United States)

    Beery, Annaliese K.; Christensen, Jennifer D; Lee, Nicole S.; Blandino, Katrina L.

    2018-01-01

    Social behavior is often described as a unified concept, but highly social (group-living) species exhibit distinct social structures and may make different social decisions. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that often reside in extended family groups, and exhibit robust preferences for familiar social partners (same- and opposite-sex) during extended choice tests, although short-term preferences are not known. Mice (Mus musculus) are gregarious and colonial, but in brief laboratory tests of social preference they typically prefer social novelty. This preference for novel vs. familiar peers may represent a species-specific difference in social decision-making between mice and prairie voles. However, the tests used to measure preferences in each species differ markedly in duration and degree of contact, such that the behaviors cannot be directly compared. We assessed whether social preferences for novelty or familiarity differed between mice and prairie voles of both sexes when assessed with matching protocols: the sociability/social preference test (SPT) typically used in mice (short, no direct contact), and the partner preference test (PPT) used in voles (long, direct contact). A subset of voles also underwent a PPT using barriers (long, no direct contact). In the short SPT, behavior did not differ between species. In the longer test, pronounced partner preferences emerged in prairie voles, but mice exhibited no social preferences and rarely huddled. No sex differences were evident in either test. Direct physical contact was required for partner preferences in huddling time in voles, but preference for the partner chamber was evident with or without contact. Both prairie voles and mice are social, but they exhibit important differences in the specificity and extent of their social behavior. While mice are often used to study social approach and other behaviors, voles are a more suitable species for the study of selective social

  16. Specificity in Sociality: Mice and Prairie Voles Exhibit Different Patterns of Peer Affiliation

    Directory of Open Access Journals (Sweden)

    Annaliese K. Beery

    2018-03-01

    Full Text Available Social behavior is often described as a unified concept, but highly social (group-living species exhibit distinct social structures and may make different social decisions. Prairie voles (Microtus ochrogaster are socially monogamous rodents that often reside in extended family groups, and exhibit robust preferences for familiar social partners (same- and opposite-sex during extended choice tests, although short-term preferences are not known. Mice (Mus musculus are gregarious and colonial, but in brief laboratory tests of social preference they typically prefer social novelty. This preference for novel vs. familiar peers may represent a species-specific difference in social decision-making between mice and prairie voles. However, the tests used to measure preferences in each species differ markedly in duration and degree of contact, such that the behaviors cannot be directly compared. We assessed whether social preferences for novelty or familiarity differed between mice and prairie voles of both sexes when assessed with matching protocols: the sociability/social preference test (SPT typically used in mice (short, no direct contact, and the partner preference test (PPT used in voles (long, direct contact. A subset of voles also underwent a PPT using barriers (long, no direct contact. In the short SPT, behavior did not differ between species. In the longer test, pronounced partner preferences emerged in prairie voles, but mice exhibited no social preferences and rarely huddled. No sex differences were evident in either test. Direct physical contact was required for partner preferences in huddling time in voles, but preference for the partner chamber was evident with or without contact. Both prairie voles and mice are social, but they exhibit important differences in the specificity and extent of their social behavior. While mice are often used to study social approach and other behaviors, voles are a more suitable species for the study of

  17. Tissue inhibitor of metalloproteinase-3 knockout mice exhibit enhanced energy expenditure through thermogenesis.

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    Yohsuke Hanaoka

    Full Text Available Tissue inhibitors of metalloproteinases (TIMPs regulate matrix metalloproteinase activity and maintain extracellular matrix homeostasis. Although TIMP-3 has multiple functions (e.g., apoptosis, inhibition of VEGF binding to VEGF receptor, and inhibition of TNFα converting enzyme, its roles in thermogenesis and metabolism, which influence energy expenditure and can lead to the development of metabolic disorders when dysregulated, are poorly understood. This study aimed to determine whether TIMP-3 is implicated in metabolism by analyzing TIMP-3 knockout (KO mice. TIMP-3 KO mice had higher body temperature, oxygen consumption, and carbon dioxide production than wild-type (WT mice, although there were no differences in food intake and locomotor activity. These results suggest that metabolism is enhanced in TIMP-3 KO mice. Real-time PCR analysis showed that the expression of PPAR-δ, UCP-2, NRF-1 and NRF-2 in soleus muscle, and PGC-1α and UCP-2 in gastrocnemius muscle, was higher in TIMP-3 KO mice than in WT mice, suggesting that TIMP-3 deficiency may increase mitochondrial activity. When exposed to cold for 8 hours to induce thermogenesis, TIMP-3 KO mice had a higher body temperature than WT mice. In the treadmill test, oxygen consumption and carbon dioxide production were higher in TIMP-3 KO mice both before and after starting exercise, and the difference was more pronounced after starting exercise. Our findings suggest that TIMP-3 KO mice exhibit enhanced metabolism, as reflected by a higher body temperature than WT mice, possibly due to increased mitochondrial activity. Given that TIMP-3 deficiency increases energy expenditure, TIMP-3 may present a novel therapeutic target for preventing metabolic disorders.

  18. Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye.

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    Takaaki Inaba

    Full Text Available Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the pathways, the Ca2+ channel, which is responsible for the Ca2+ elevation in the sympathetic pathway, has not been sufficiently analyzed. In this study, we examined tear secretion in mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R types 2 and 3 (Itpr2-/-;Itpr3-/-double-knockout mice. We found that tear secretion in both the parasympathetic and sympathetic pathways was abolished in Itpr2-/-;Itpr3-/- mice. Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and epinephrine stimulation was abolished in Itpr2-/-;Itpr3-/- mice. Consequently, Itpr2-/-;Itpr3-/- mice exhibited keratoconjunctival alteration and corneal epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal glands and elevation of serum autoantibodies, a representative marker for Sjögren's syndrome (SS in humans, were also detected in older Itpr2-/-;Itpr3-/- mice. These results suggested that IP3Rs are essential for tear secretion in both parasympathetic and sympathetic pathways and that Itpr2-/-;Itpr3-/- mice could be a new dry eye mouse model with symptoms that mimic those of SS.

  19. A Novel Closed-head Model of Mild Traumatic Brain Injury Caused by Primary Overpressure Blast to the Cranium Produces Sustained Emotional Deficits in Mice

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    Scott A Heldt

    2014-01-01

    Full Text Available Emotional disorders are a common outcome from mild traumatic brain injury (TBI in humans, but their pathophysiological basis is poorly understood. We have developed a mouse model of closed-head blast injury using an air pressure wave delivered to a small area on one side of the cranium, which we have used to create mild TBI. We found that 20-psi blasts in 3-month old C57BL/6 male mice yielded no obvious behavioral or histological evidence of brain injury, while 25-40 psi blasts produced transient anxiety in an open field arena but little histological evidence of brain damage. By contrast, 50-60 psi blasts resulted in anxiety-like behavior in an open field arena that became more evident with time after blast. In additional behavioral tests conducted 2-8 weeks after blast, 50-60 psi mice also demonstrated increased acoustic startle, perseverance of learned fear, and enhanced contextual fear, as well as depression-like behavior and diminished prepulse inhibition. We found no evident cerebral pathology, however, and only scattered axonal degeneration in brain sections from 50-60 psi mice 3-8 weeks after blast. Thus, the TBI caused by single 50-60 psi blasts in mice exhibits the minimal neuronal loss coupled to diffuse axonal injury characteristic of human mild TBI. A reduction in the abundance of a subpopulation of excitatory projection neurons in basolateral amygdala enriched in Thy1 was, however, observed. The reported link of this neuronal population to fear suppression suggests their damage by mild TBI may contribute to the heightened anxiety and fearfulness observed after blast in our mice. Our overpressure air blast model of concussion in mice will enable further studies of the mechanisms underlying the diverse emotional deficits seen after mild TBI.

  20. Selenoprotein-deficient transgenic mice exhibit enhanced exercise-induced muscle growth.

    Science.gov (United States)

    Hornberger, Troy A; McLoughlin, Thomas J; Leszczynski, Jori K; Armstrong, Dustin D; Jameson, Ruth R; Bowen, Phyllis E; Hwang, Eun-Sun; Hou, Honglin; Moustafa, Mohamed E; Carlson, Bradley A; Hatfield, Dolph L; Diamond, Alan M; Esser, Karyn A

    2003-10-01

    Dietary intake of selenium has been implicated in a wide range of health issues, including aging, heart disease and cancer. Selenium deficiency, which can reduce selenoprotein levels, has been associated with several striated muscle pathologies. To investigate the role of selenoproteins in skeletal muscle biology, we used a transgenic mouse (referred to as i6A-) that has reduced levels of selenoproteins due to the introduction and expression of a dominantly acting mutant form of selenocysteine transfer RNA (tRNA[Ser]Sec). As a consequence, each organ contains reduced levels of most selenoproteins, yet these mice are normal with regard to fertility, overall health, behavior and blood chemistries. In the present study, although skeletal muscles from i6A- mice were phenotypically indistinguishable from those of wild-type mice, plantaris muscles were approximately 50% heavier after synergist ablation, a model of exercise overload. Like muscle in wild-type mice, the enhanced growth in the i6A- mice was completely blocked by inhibition of the mammalian target of rapamycin (mTOR) pathway. Muscles of transgenic mice exhibited increased site-specific phosphorylation on both Akt and p70 ribosomal S6 kinase (p70S6k) (P accounting for the enhanced response to synergist ablation. Thus, a single genetic alteration resulted in enhanced skeletal muscle adaptation after exercise, and this is likely through subtle changes in the resting phosphorylation state of growth-related kinases.

  1. Mice with a targeted deletion of the tetranectin gene exhibit a spinal deformity

    DEFF Research Database (Denmark)

    Iba, K; Durkin, M E; Johnsen, L

    2001-01-01

    and muscle. To test the functional role of tetranectin directly, we have generated mice with a targeted disruption of the gene. We report that the tetranectin-deficient mice exhibit kyphosis, a type of spinal deformity characterized by an increased curvature of the thoracic spine. The kyphotic angles were...... in the morphology of the vertebrae. Histological analysis of the spines of these mice revealed an apparently asymmetric development of the growth plate and of the intervertebral disks of the vertebrae. In the most advanced cases, the growth plates appeared disorganized and irregular, with the disk material...... in tissue growth and remodeling. The tetranectin-deficient mouse is the first mouse model that resembles common human kyphotic disorders, which affect up to 8% of the population....

  2. Strategi Pengembangan Kota Surakarta Menjadi Kota Mice (Meeting, Incentive, Convention, Exhibition)

    OpenAIRE

    Mahadi, Khairul; Hidayat, Teguh

    2013-01-01

    Seiring dengan berkembangnnya sistem transportasi yang ada di dunia baik transportasi laut, darat, dan udara dimana dapat memudahkan seseorang atau sebuah kelompok berpergian dari satu wilayah ke wilayah lain, dari sinilah MICE (meeting, incentive, convention, exhibition) dilihat sebagai peluang bisnis dimana seseorang atau kelompok melakukan sebuah pertemuan atau konferensi conference). Indonesia sudah berkembang menjadi salah satu negara tujuan bisnis dan wisata. Hal itu dibuktikan dengan p...

  3. Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

    Science.gov (United States)

    Hasen, Nina S; Gammie, Stephen C

    2011-03-01

    The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Decreased hepatic contents of coenzyme A molecular species in mice after subchronic mild social defeat stress.

    Science.gov (United States)

    Kubota, Yoshifumi; Goto, Tatsuhiko; Hagiya, Yuki; Chohnan, Shigeru; Toyoda, Atsushi

    2016-01-01

    Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down-regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down-regulation of liver CoA pools in sCSDS mice.

  5. Mild overexpression of Mecp2 in mice causes a higher susceptibility toward seizures.

    Science.gov (United States)

    Bodda, Chiranjeevi; Tantra, Martesa; Mollajew, Rustam; Arunachalam, Jayamuruga P; Laccone, Franco A; Can, Karolina; Rosenberger, Albert; Mironov, Sergej L; Ehrenreich, Hannelore; Mannan, Ashraf U

    2013-07-01

    An intriguing finding about the gene encoding methyl-CpG binding protein 2 (MeCP2) is that the loss-of-function mutations cause Rett syndrome and duplication (gain-of-function) of MECP2 leads to another neurological disorder termed MECP2 duplication syndrome. To ensure proper neurodevelopment, a precise regulation of MeCP2 expression is critical, and any gain or loss of MeCP2 over a narrow threshold level may lead to postnatal neurological impairment. To evaluate MeCP2 dosage effects, we generated Mecp2(WT_EGFP) transgenic (TG) mouse in which MeCP2 (endogenous plus TG) is mildly overexpressed (approximately 1.5×). The TG MeCP2(WT_EGFP) fusion protein is functionally active, as cross breeding of these mice with Mecp2 knockout mice led to alleviation of major phenotypes in the null mutant mice, including premature lethality. To characterize the Mecp2(WT_EGFP) mouse model, we performed an extensive battery of behavioral tests, which revealed that these mice manifest increased aggressiveness and higher pentylenetetrazole (PTZ)-induced seizure propensity. Evaluation of neuronal parameters revealed a reduction in the number of tertiary branching sites and increased spine density in Mecp2(WT_EGFP) transgenic (TG) neurons. Treatment of TG neurons with epileptogenic compound-PTZ led to a marked increase in amplitude and frequency of calcium spikes. Based on our ex vivo and in vivo data, we conclude that epileptic seizures are manifested as the first symptom when MeCP2 is mildly overexpressed in mice. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

    Science.gov (United States)

    Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

    2013-11-15

    Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

  7. The meetings, incentives, conferences, and exhibitions (MICE industry: Determinants of Thai organizational effectiveness

    Directory of Open Access Journals (Sweden)

    Songsiri Bandhuseve

    2018-01-01

    Full Text Available Studies have shown that there is more money in business tourism than leisure travel, and on average, business travellers spend more money. To understand this phenomenon, this study aimed to investigate the effect of relationships between capacity management, customer relationship management, information computer technology (ICT, service quality, supplier relationship management, and supply chain management on Thailand’s meetings, incentives, conferences, and exhibitions (MICE industry organizational effectiveness. The researchers embraced a descriptive survey methodology designed to assess how the 500 managers surveyed viewed their organization’s effectiveness. The design employed the self-administration of questionnaires to a sample of individuals which was aimed at finding each individual’s attitudes and opinion about how the 21 observed variables impacted their operations. Of the 10 hypotheses and 21 observed variables, nine hypotheses were proven, with the findings confirming that service quality and information computer technology having a significant effect on MICE organizational effectiveness.

  8. Mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior

    Directory of Open Access Journals (Sweden)

    Atsushi Tsujimura

    2008-09-01

    Full Text Available KF-1 was originally identified as a protein encoded by human gene with increased expression in the cerebral cortex of a patient with Alzheimer’s disease. In mouse brain, kf-1 mRNA is detected predominantly in the hippocampus and cerebellum, and kf-1 gene expression is elevated also in the frontal cortex of rats after chronic antidepressant treatments. KF-1 mediates E2-dependent ubiquitination and may modulate cellular protein levels as an E3 ubiquitin ligase, though its target proteins are not yet identified. To elucidate the role of kf-1 in the central nervous system, we generated kf-1 knockout mice by gene targeting, using Cre-lox recombination. The resulting kf-1−/− mice were normal and healthy in appearance. Behavioral analyses revealed that kf-1−/− mice showed significantly increased anxiety-like behavior compared with kf-1+/+ littermates in the light/dark transition and elevated plus maze tests; however, no significant differences were observed in exploratory locomotion using the open field test or in behavioral despair using the forced swim and tail suspension tests. These observations suggest that KF-1 suppresses selectively anxiety under physiological conditions probably through modulating protein levels of its unknown target(s. Interestingly, kf-1−/− mice exhibited significantly increased prepulse inhibition, which is usually reduced in human schizophrenic patients. Thus, the kf-1−/− mice provide a novel animal model for elucidating molecular mechanisms of psychiatric diseases such as anxiety/depression, and may be useful for screening novel anxiolytic/antidepressant compounds.

  9. Chronic mild stress increases alcohol intake in mice with low dopamine D2 receptor levels.

    Science.gov (United States)

    Delis, Foteini; Thanos, Panayotis K; Rombola, Christina; Rosko, Lauren; Grandy, David; Wang, Gene-Jack; Volkow, Nora D

    2013-02-01

    Alcohol use disorders emerge from a complex interaction between environmental and genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to play a central role in alcoholism. To better understand the interactions between DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at the end of the experiment, the animals were tested in the forced swim and open field tests. We measured ethanol intake and preference, immobility in the force swim test, and activity in the open field. We show that under no CMS, Drd2+/- and Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+. Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had significantly lower activity in the open field than Drd2+/+, whereas no genotype differences were observed in the forced swim test. Exposure to CMS increased immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed in open field test measures. These findings suggest that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  10. Mild Staphylococcus aureus Skin Infection Improves the Course of Subsequent Endogenous S. aureus Bacteremia in Mice.

    Directory of Open Access Journals (Sweden)

    Sanne van den Berg

    Full Text Available Staphylococcus aureus carriers with S. aureus bacteremia may have a reduced mortality risk compared to non-carriers. A role for the immune system is suggested. Here, we study in mice the effect of mild S. aureus skin infection prior to endogenous or exogenous S. aureus bacteremia, and evaluate protection in relation to anti-staphylococcal antibody levels. Skin infections once or twice by a clinical S. aureus isolate (isolate P or S. aureus strain 8325-4 were induced in mice free of S. aureus and anti-staphylococcal antibodies. Five weeks later, immunoglobulin G (IgG levels in blood against 25 S. aureus antigens were determined, and LD50 or LD100 bacteremia caused by S. aureus isolate P was induced. S. aureus skin infections led to elevated levels of anti-staphylococcal IgG in blood. One skin infection improved the course of subsequent severe endogenous bacteremia only. A second skin infection further improved animal survival rate, which was associated with increased pre-bacteremia IgG levels against Efb, IsaA, LukD, LukE, Nuc, PrsA and WTA. In conclusion, S. aureus isolate P skin infection in mice reduces the severity of subsequent endogenous S. aureus bacteremia only. Although cellular immune effects cannot be rules out, anti-staphylococcal IgG against specified antigens may contribute to this effect.

  11. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice

    Directory of Open Access Journals (Sweden)

    Yeshwant Kurhe

    2016-06-01

    Full Text Available Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o./escitalopram (10 mg/kg p.o./vehicle (10 ml/kg p.o. daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST, tail suspension test (TST and elevated plus maze (EPM were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  12. Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.

    Directory of Open Access Journals (Sweden)

    Nicole Purrier

    Full Text Available Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods. Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light.

  13. Neuroinflammation, myelin and behavior: Temporal patterns following mild traumatic brain injury in mice.

    Directory of Open Access Journals (Sweden)

    Toufik Taib

    Full Text Available Traumatic brain injury (TBI results in white matter injury (WMI that is associated with neurological deficits. Neuroinflammation originating from microglial activation may participate in WMI and associated disorders. To date, there is little information on the time courses of these events after mild TBI. Therefore we investigated (i neuroinflammation, (ii WMI and (iii behavioral disorders between 6 hours and 3 months after mild TBI. For that purpose, we used experimental mild TBI in mice induced by a controlled cortical impact. (i For neuroinflammation, IL-1b protein as well as microglial phenotypes, by gene expression for 12 microglial activation markers on isolated CD11b+ cells from brains, were studied after TBI. IL-1b protein was increased at 6 hours and 1 day. TBI induced a mixed population of microglial phenotypes with both pro-inflammatory, anti-inflammatory and immunomodulatory markers from 6 hours to 3 days post-injury. At 7 days, microglial activation was completely resolved. (ii Three myelin proteins were assessed after TBI on ipsi- and contralateral corpus callosum, as this structure is enriched in white matter. TBI led to an increase in 2',3'-cyclic-nucleotide 3'-phosphodiesterase, a marker of immature and mature oligodendrocyte, at 2 days post-injury; a bilateral demyelination, evaluated by myelin basic protein, from 7 days to 3 months post-injury; and an increase in myelin oligodendrocyte glycoprotein at 6 hours and 3 days post-injury. Transmission electron microscopy study revealed various myelin sheath abnormalities within the corpus callosum at 3 months post-TBI. (iii TBI led to sensorimotor deficits at 3 days post-TBI, and late cognitive flexibility disorder evidenced by the reversal learning task of the Barnes maze 3 months after injury. These data give an overall invaluable overview of time course of neuroinflammation that could be involved in demyelination and late cognitive disorder over a time-scale of 3 months in a model

  14. Mild Social Stress in Mice Produces Opioid-Mediated Analgesia in Visceral but Not Somatic Pain States.

    Science.gov (United States)

    Pitcher, Mark H; Gonzalez-Cano, Rafael; Vincent, Kathleen; Lehmann, Michael; Cobos, Enrique J; Coderre, Terence J; Baeyens, José M; Cervero, Fernando

    2017-06-01

    Visceral pain has a greater emotional component than somatic pain. To determine if the stress-induced analgesic response is differentially expressed in visceral versus somatic pain states, we studied the effects of a mild social stressor in either acute visceral or somatic pain states in mice. We show that the presence of an unfamiliar conspecific mouse (stranger) in an adjacent cubicle of a standard transparent observation box produced elevated plasma corticosterone levels compared with mice tested alone, suggesting that the mere presence of a stranger is stressful. We then observed noxious visceral or somatic stimulation-induced nociceptive behavior in mice tested alone or in mildly stressful conditions (ie, beside an unfamiliar stranger). Compared with mice tested alone, the presence of a stranger produced a dramatic opioid-dependent reduction in pain behavior associated with visceral but not somatic pain. This social stress-induced reduction of visceral pain behavior relied on visual but not auditory/olfactory cues. These findings suggest that visceral pain states may provoke heightened responsiveness to mild stressors, an effect that could interfere with testing outcomes during simultaneous behavioral testing of multiple rodents. In mice, mild social stress due to the presence of an unfamiliar conspecific mouse reduces pain behavior associated with noxious visceral but not somatic stimulation, suggesting that stress responsiveness may be enhanced in visceral pain versus somatic pain states. Published by Elsevier Inc.

  15. In Utero and Postnatal Propylthiouracil-Induced Mild Hypothyroidism Impairs Maternal Behavior in Mice

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    Miski Aghnia Khairinisa

    2018-05-01

    Full Text Available Thyroid hormones (THs play crucial roles in general and brain development. Even if the hypothyroidism is mild, it may alter brain function, resulting in irreversible behavioral alterations. Although various behavioral analyses have been conducted, the effects of propylthiouracil (PTU treatment during in utero and postnatal periods on maternal behavior have not yet been studied. The present study examined in mice whether THs insufficiency during development induce behavioral changes. Pregnant C57BL/6j mice were divided into three groups, and each group was administered different dosages of PTU (0, 5, or 50 ppm in drinking water during in utero and postnatal periods (from gestational day 14 to postnatal day 21. First, locomotor activity and cognitive function were assessed in the offspring at 10 weeks. Next, female offspring were mated with normal mice and they and their offspring were used to assess several aspects of maternal behavior (identifying first pup, returning all pups to nest, time spent nursing, and licking pups. As expected, locomotor and cognitive functions in these mice were disrupted in a PTU dose-dependent manner. On postpartum day 2, dams who had been exposed 50 ppm PTU during in utero and postnatal periods displayed a significantly longer time identifying the first pup and returning all three pups back to the nest, less time nursing, and decreased licking behavior. The decrease in maternal behavior was significantly correlated with a decrease in cognition. These results indicate that insufficiency of THs during in utero and postnatal periods impairs maternal behavior, which may be partly induced by impaired cognitive function.

  16. Combat Veterans with PTSD after Mild TBI Exhibit Greater ERPs from Posterior-medial Cortical Areas While Appraising Facial Features

    Science.gov (United States)

    2014-01-01

    E.W., Karl , A., 2013. Meta-analytic review of P3 components in posttraumatic stress disorder and their clinical utility. Clin. EEG Neurosci.. Jorge...Weiner, J., Marx , C.E., Cernak, I., McCarthy, G., Group, M.W., 2012. Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and

  17. Antidepressant-Like Effects of Cordycepin in a Mice Model of Chronic Unpredictable Mild Stress

    Directory of Open Access Journals (Sweden)

    Zhang Tianzhu

    2014-01-01

    Full Text Available Cordycepin (3′-deoxyadenosine, a major bioactive component isolated from Cordyceps militaris, has multiple pharmacological activities. This study is attempted to investigate whether cordycepin (COR possesses beneficial effects on chronic unpredictable mild stress- (CUMS- induced behavioral deficits (depression-like behaviors and explore the possible mechanisms. ICR mice were subjected to chronic unpredictable mild stress for 42 consecutive days. Then, COR and fluoxetine (FLU, positive control drug were administered for 21 consecutive days at the last three weeks of CUMS procedure. The classical behavioral tests, open field test (OFT, sucrose preference test (SPT, tail suspension test (TST, and forced swimming test (FST, were applied to evaluate the antidepressant effects of COR. Then the serotonin (5-HT and noradrenaline (NE concentrations in hippocampal were evaluated by HPLC; tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 in hippocampal were evaluated, and the proteins of TNF-α, IL-6, NF-κBP65 5-HT receptor (5-HTR, and brain-derived neurotrophic factor (BDNF in hippocampal were evaluated by Western blot. Our results indicated that 6 weeks of CUMS exposure induced significant depression-like behavior, with low 5-HT and NE levels, high TNF-α and IL-6 in brain and high hippocampal TNF-α, IL-6, P-NF-κBP65, and 5-HTR levels, and low BDNF expression levels. Whereas, chronic COR (20, 40 mg/kg treatments reversed the behavioral deficiency induced by CUMS exposure, treatment with COR normalized the change of TNF-α, IL-6, 5-HT, and NE levels, which demonstrated that COR could partially restore CUMS-induced 5-HT receptor impairments and inflammation. Besides, hippocampal BDNF expressions were also upregulated after COR treatments. In conclusion, COR remarkably improved depression-like behavior in CUMS mice and its antidepressant activity is mediated, at least in part, by the upregulating BDNF and downregulating 5-HTR levels and

  18. Telomerase-Deficient Mice Exhibit Bone Loss Owing to Defects in Osteoblasts and Increased Osteoclastogenesis by Inflammatory Microenvironment

    DEFF Research Database (Denmark)

    Saeed, H.; Abdallah, B. M.; Ditzel, N.

    2011-01-01

    Telomere shortening owing to telomerase deficiency leads to accelerated senescence of human skeletal (mesenchymal) stem cells (MSCs) in vitro, whereas overexpression leads to telomere elongation, extended life span, and enhanced bone formation. To study the role of telomere shortening in vivo, we...... studied the phenotype of telomerase-deficient mice (Terc(-/-)).Terc(-/-) mice exhibited accelerated age-related bone loss starting at 3 months of age and during 12 months of follow-up revealed by dual-energy X-ray absorptiometric (DXA) scanning and by micro-computed tomography (mu CT). Bone...... histomorphometry revealed decreased mineralized surface and bone-formation rate as well as increased osteoclast number and size in Terc(-/-) mice. Also, serum total deoxypyridinoline (tDPD) was increased in Terc(-/-) mice. MSCs and osteoprogenitors isolated from Terc(-l-) mice exhibited intrinsic defects...

  19. Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

    Science.gov (United States)

    Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

    2005-03-01

    Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure.

  20. Behavioral testing of mice exposed to intermediate frequency magnetic fields indicates mild memory impairment.

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    Kajal Kumari

    Full Text Available Human exposure to intermediate frequency magnetic fields (MF is increasing due to applications like electronic article surveillance systems and induction heating cooking hobs. However, limited data is available on their possible health effects. The present study assessed behavioral and histopathological consequences of exposing mice to 7.5 kHz MF at 12 or 120 μT for 5 weeks. No effects were observed on body weight, spontaneous activity, motor coordination, level of anxiety or aggression. In the Morris swim task, mice in the 120 μT group showed less steep learning curve than the other groups, but did not differ from controls in their search bias in the probe test. The passive avoidance task indicated a clear impairment of memory over 48 h in the 120 μT group. No effects on astroglial activation or neurogenesis were observed in the hippocampus. The mRNA expression of brain-derived neurotrophic factor did not change but expression of the proinflammatory cytokine tumor necrosis factor alpha mRNA was significantly increased in the 120 μT group. These findings suggest that 7.5 kHz MF exposure may lead to mild learning and memory impairment, possibly through an inflammatory reaction in the hippocampus.

  1. Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function.

    Science.gov (United States)

    Toque, Haroldo A; Nunes, Kenia P; Yao, Lin; Xu, Zhimin; Kondrikov, Dmitry; Su, Yunchao; Webb, R Clinton; Caldwell, Ruth B; Caldwell, R William

    2013-01-01

    Elevated arginase (Arg) activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO) synthase (NOS) and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. We determined the role of Arg in a time-course of diabetes-associated endothelial dysfunction in aorta and corpora cavernosa (CC) from Akita mice. Endothelium-dependent relaxation, Arg and NOS activity, and protein expression levels of Arg and constitutive NOS were assessed in aortas and CC from Akita and non-diabetic wild type (WT) mice at 4, 12 and 24 wks of age. Systolic blood pressure (SBP) was assessed by tail cuff. In aorta and CC, Akita mice exhibited a progressive impairment of vascular endothelial and nitrergic function increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in CC) compared with that of age-matched WT mice. Treatment of aorta and CC from Akita mice with an Arg inhibitor (BEC or ABH) reduced diabetes-induced elevation of Arg activity and restored endothelial and nitrergic function. Reduced levels of phospho-eNOS at Ser(1177) (in aorta and CC) and nNOS expression (in CC) were observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment. Further, Akita mice exhibited moderately increased SBP at 24 wks and increased sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation in CC at 12 and 24 wks. Over 24 wks of diabetes in Akita mice, both aortic and cavernosal tissues exhibited increased Arg activity/expression, contributing to impaired endothelial and nitrergic function and reduced NO production. Our findings demonstrate involvement of Arg activity in diabetes-induced impairment of vascular function in Akita mouse.

  2. Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function.

    Directory of Open Access Journals (Sweden)

    Haroldo A Toque

    Full Text Available Elevated arginase (Arg activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO synthase (NOS and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. We determined the role of Arg in a time-course of diabetes-associated endothelial dysfunction in aorta and corpora cavernosa (CC from Akita mice.Endothelium-dependent relaxation, Arg and NOS activity, and protein expression levels of Arg and constitutive NOS were assessed in aortas and CC from Akita and non-diabetic wild type (WT mice at 4, 12 and 24 wks of age. Systolic blood pressure (SBP was assessed by tail cuff. In aorta and CC, Akita mice exhibited a progressive impairment of vascular endothelial and nitrergic function increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in CC compared with that of age-matched WT mice. Treatment of aorta and CC from Akita mice with an Arg inhibitor (BEC or ABH reduced diabetes-induced elevation of Arg activity and restored endothelial and nitrergic function. Reduced levels of phospho-eNOS at Ser(1177 (in aorta and CC and nNOS expression (in CC were observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment. Further, Akita mice exhibited moderately increased SBP at 24 wks and increased sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation in CC at 12 and 24 wks.Over 24 wks of diabetes in Akita mice, both aortic and cavernosal tissues exhibited increased Arg activity/expression, contributing to impaired endothelial and nitrergic function and reduced NO production. Our findings demonstrate involvement of Arg activity in diabetes-induced impairment of vascular function in Akita mouse.

  3. Pulmonary oxidative stress is increased in cyclooxygenase-2 knockdown mice with mild pulmonary hypertension induced by monocrotaline.

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    Francesca Seta

    Full Text Available The aim of this study was to examine the role of cyclooxygenase-2 (COX-2 and downstream signaling of prostanoids in the pathogenesis of pulmonary hypertension (PH using mice with genetically manipulated COX-2 expression. COX-2 knockdown (KD mice, characterized by 80-90% suppression of COX-2, and wild-type (WT control mice were treated weekly with monocrotaline (MCT over 10 weeks. Mice were examined for cardiac hypertrophy/function and right ventricular pressure. Lung histopathological analysis was performed and various assays were carried out to examine oxidative stress, as well as gene, protein, cytokine and prostanoid expression. We found that MCT increased right ventricular systolic and pulmonary arterial pressures in comparison to saline-treated mice, with no evidence of cardiac remodeling. Gene expression of endothelin receptor A and thromboxane synthesis, regulators of vasoconstriction, were increased in MCT-treated lungs. Bronchoalveolar lavage fluid and lung sections demonstrated mild inflammation and perivascular edema but activation of inflammatory cells was not predominant under the experimental conditions. Heme oxygenase-1 (HO-1 expression and indicators of oxidative stress in lungs were significantly increased, especially in COX-2 KD MCT-treated mice. Gene expression of NOX-4, but not NOX-2, two NADPH oxidase subunits crucial for superoxide generation, was induced by ∼4-fold in both groups of mice by MCT. Vasodilatory and anti-aggregatory prostacyclin was reduced by ∼85% only in MCT-treated COX-2 KD mice. This study suggests that increased oxidative stress-derived endothelial dysfunction, vasoconstriction and mild inflammation, exacerbated by the lack of COX-2, contribute to the pathogenesis of early stages of PH when mild hemodynamic changes are evident and not yet accompanied by vascular and cardiac remodeling.

  4. Can Ocimum basilicum relieve chronic unpredictable mild stress-induced depression in mice?

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    Ayuob, Nasra Naeim; Firgany, Alaa El-Din L; El-Mansy, Ahmed A; Ali, Soad

    2017-10-01

    Depression is one of the important world-wide health problems. This study aimed to assess the ameliorative effect of Ocimum basilicum (OB) essential oil on the behavioral, biochemical and histopathological changes resulted from exposure to chronic unpredictable mild stress (CUMS). It also aimed to investigate the underlying mechanism in an animal model of depression. Forty male Swiss albino mice were divided into four groups (n=10): control, CUMS (exposed to CUMS for 4weeks), CUMS plus fluoxetine, and CUMS plus OB. At the end of the experiment, behavioral changes, serum corticosterone level, protein and gene expressions of brain derived neurotropic factor (BDNF) and glucocorticoid receptors (GR) in the hippocampus was all assessed. Immunoexpression of surface makers of glial fibrillary acidic protein (GFAP), Ki67, Caspase-3, BDNF and GR in the hippocampus were estimated. Data were analyzed by using the statistical package for the social sciences (SPSS). OB alleviated both behavioral and biochemical changes recorded in mice after exposure to CUMS. It also reduced neuronal atrophy observed in the hippocampal region III cornu ammonis (CA3) and dentate gyrus and restored back astrocyte number. OB decreased apoptosis in both neurons and glial cells and increased neurogenesis in the dentate gyrus in a pattern comparable to that of fluoxetine. Increased BDNF and GR gene and protein expressions seems to be behind the antidepressant-like effect of OB. Ocimum basilicum ameliorates the changes induced after exposure to the chronic stress. Assessing Ocimum basilicum efficacy on human as antidepressant is recommended in further studies. Copyright © 2017. Published by Elsevier Inc.

  5. Pelaksanaan Manajemen Mice (Meeting Incentive Convention Exhibition) di Hotel Pangeran Pekanbaru

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    Achmnes, Syofia; Siregar, Damara Saputra

    2014-01-01

    Implementation of MICE management operationalize theoretical concepts inthe book P.Hasibuan Terry GR (2005) that state that the management process consistsof: planning, organizing, actuating, and controlling.Growing MICE industry in Indonesia, including the city of Pekanbaru. CityGoverment continues to initiate Pekanbaru city as MICE city in Sumatera. One of theleading institutions that have a major role in the realization of this idea is thePangeran hotel Pekanbaru. which is a four-star hote...

  6. Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology.

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    Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

    2004-07-01

    We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or 'depressive-like' symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild-type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the 'depressive-like' profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.

  7. STRATEGI PENINGKATAN PENDAPATAN ASLI DAERAH, INVESTASI DAN PERTUMBUHAN EKONOMI KOTA SEMARANG MELALUI MICE (MEETING, INCENTIVE, CONVENTION DAN EXHIBITION)

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    Tika Putri Pratiwi

    2015-01-01

    Abstrak ___________________________________________________________________ Semarang sebagai ibukota Provinsi Jawa Tengah memiliki potensi yang besar dalam mengembangkan sektor industri dan pariwisata. Langkah awal pemerintah yang serius dalam mengolah kedua industri ini yaitu dengan menjadikan Kota Semarang sebagai salah satu destinasi MICE (Meeting, Incentive, Convention, Exhibition). Penelitian ini bertujuan untuk memilih strategi apa yang dapat dilakukan dalam pembangunan Kota...

  8. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

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    Aunis Dominique

    2010-12-01

    Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

  9. Both brown adipose tissue and skeletal muscle thermogenesis processes are activated during mild to severe cold adaptation in mice.

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    Bal, Naresh C; Singh, Sushant; Reis, Felipe C G; Maurya, Santosh K; Pani, Sunil; Rowland, Leslie A; Periasamy, Muthu

    2017-10-06

    Thermogenesis is an important homeostatic mechanism essential for survival and normal physiological functions in mammals. Both brown adipose tissue (BAT) ( i.e. uncoupling protein 1 (UCP1)-based) and skeletal muscle ( i.e. sarcolipin (SLN)-based) thermogenesis processes play important roles in temperature homeostasis, but their relative contributions differ from small to large mammals. In this study, we investigated the functional interplay between skeletal muscle- and BAT-based thermogenesis under mild versus severe cold adaptation by employing UCP1 -/- and SLN -/- mice. Interestingly, adaptation of SLN -/- mice to mild cold conditions (16 °C) significantly increased UCP1 expression, suggesting increased reliance on BAT-based thermogenesis. This was also evident from structural alterations in BAT morphology, including mitochondrial architecture, increased expression of electron transport chain proteins, and depletion of fat droplets. Similarly, UCP1 -/- mice adapted to mild cold up-regulated muscle-based thermogenesis, indicated by increases in muscle succinate dehydrogenase activity, SLN expression, mitochondrial content, and neovascularization, compared with WT mice. These results further confirm that SLN-based thermogenesis is a key player in muscle non-shivering thermogenesis (NST) and can compensate for loss of BAT activity. We also present evidence that the increased reliance on BAT-based NST depends on increased autonomic input, as indicated by abundant levels of tyrosine hydroxylase and neuropeptide Y. Our findings demonstrate that both BAT and muscle-based NST are equally recruited during mild and severe cold adaptation and that loss of heat production from one thermogenic pathway leads to increased recruitment of the other, indicating a functional interplay between these two thermogenic processes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior

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    Fuka Aizawa

    2016-12-01

    Full Text Available The free fatty acid receptor 1 (GPR40/FFAR1 is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO mice. The emotional behavior in wild and KO male mice was evaluated at 9–10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC–MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.

  11. GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

    Science.gov (United States)

    Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

    2016-12-01

    The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  12. Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

    Science.gov (United States)

    Hwang, M; Go, Y; Park, J-H; Shin, S-K; Song, S E; Oh, B-C; Im, S-S; Hwang, I; Jeon, Y H; Lee, I-K; Seino, S; Song, D-K

    2017-02-01

    The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic

  13. BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.

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    Chen, Mei-Rong; Dai, Ping; Wang, Shu-Fen; Song, Shu-Hua; Wang, Hang-Ping; Zhao, Ya; Wang, Ting-Hua; Liu, Jia

    2016-10-01

    Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

  14. Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion*

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    Dong, Ke; Yan, Qingshang; Lu, Ming; Wan, Laxiang; Hu, Haiyan; Guo, Junhua; Boulpaep, Emile; Wang, WenHui; Giebisch, Gerhard; Hebert, Steven C.; Wang, Tong

    2016-01-01

    Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. Unlike Romk−/− mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1−/− mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1+/+ and Romk1−/− mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1+/+, but such regulation by high K intake was diminished with significant hyperkalemia in Romk1−/− mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K+ secretion in the collecting tubule. PMID:26728465

  15. Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion.

    Science.gov (United States)

    Dong, Ke; Yan, Qingshang; Lu, Ming; Wan, Laxiang; Hu, Haiyan; Guo, Junhua; Boulpaep, Emile; Wang, WenHui; Giebisch, Gerhard; Hebert, Steven C; Wang, Tong

    2016-03-04

    Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. Unlike Romk(-/-) mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1(-/-) mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1(+/+) and Romk1(-/-) mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1(+/+), but such regulation by high K intake was diminished with significant hyperkalemia in Romk1(-/-) mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K(+) secretion in the collecting tubule. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy.

    Science.gov (United States)

    Osaki, Yoshinori; Nakagawa, Yoshimi; Miyahara, Shoko; Iwasaki, Hitoshi; Ishii, Akiko; Matsuzaka, Takashi; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Sone, Hirohito; Ohashi, Ken; Ishibashi, Shun; Yamada, Nobuhiro; Shimano, Hitoshi

    2015-10-23

    HMG-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonic acid (MVA); this is the rate-limiting enzyme of the mevalonate pathway that synthesizes cholesterol. Statins, HMGCR inhibitors, are widely used as cholesterol-reducing drugs. However, statin-induced myopathy is the most adverse side effect of statins. To eludicate the mechanisms underlying statin the myotoxicity and HMGCR function in the skeletal muscle, we developed the skeletal muscle-specific HMGCR knockout mice. Knockout mice exhibited postnatal myopathy with elevated serum creatine kinase levels and necrosis. Myopathy in knockout mice was completely rescued by the oral administration of MVA. These results suggest that skeletal muscle toxicity caused by statins is dependent on the deficiencies of HMGCR enzyme activity and downstream metabolites of the mevalonate pathway in skeletal muscles rather than the liver or other organs. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Yam storage protein dioscorins from Dioscorea alata and Dioscorea japonica exhibit distinct immunomodulatory activities in mice.

    Science.gov (United States)

    Lin, Pei-Lan; Lin, Kuo-Wei; Weng, Ching-Feng; Lin, Kuo-Chih

    2009-06-10

    The aim of this study was to elucidate the effect of the major storage protein dioscorin isolated from two different yam species, Tainong No. 1 (TN1-dioscorins) and Japanese yam (Dj-dioscorins), on the immune activities of mice. Dj-dioscorins, like TN1-dioscorins, could induce expression of the pro-inflammatory cytokines and stimulate phagocytosis of RAW 264.7. Intraperitoneal injection of the TN1-dioscorins into mice stimulated phagocytosis of bone marrow, spleen, and thymic cells. In contrast, the T and B cells in bone marrow, spleen, and thymus isolated from mice injected with Dj-dioscorins had higher proliferative responses to mitogens. Furthermore, Dj-dioscorins enhanced proliferation of CD4(+), CD8(+), and Tim3(+) (Th1) cells in spleen and CD19(+) cells in both spleen and thymus. Supplement of Dj-dioscorins in the lymphoid cells isolated from Dj-dioscorins primed mice induced cell proliferation of both spleen and thymic cells. These findings indicated that TN1-dioscorins have a higher ability to stimulate the phagocytic activity of the lymphoid cells than Dj-dioscorins, whereas Dj-dioscorins possess more abilities than TN1-dioscorins to enhance the proliferation of the lymphoid cells.

  18. Quantitative immunofluorescence microscopy of renal glomeruli from mice exhibiting murien lupus erythematosus

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    Jensen, R H [Lawrence Livermore Lab., CA; Greenspan, J S; Moore, D II; Talal, N; Roubinian, J R

    1981-01-01

    Pathologic changes in renal glomeruli of mice with systemic murine lupus erythematosus were quantified using microfluorophotometry. Cryostat sections were taken from kidneys of affected mice, stained with fluorescein-conjugated anti-mouse immunoglobulin, and the extent of immune complex glomerulonephritis was determined. A subjective microscopic examination procedure, which has been used previously, was compared with quantitative microfluorophotometry and a close correlation between the results using each of the two methods was found. Since the microfluorometric procedure measures the total fluorescence per glomerulus, subjective microscopy must estimate that same quantity in a linear fashion. The present advance in measuring capability indicates good potential for rapid, quantitive measurements for further studies on systemic lupus erythematosus, and on other tissue sections stained with fluorescent antibodies.

  19. Mild Concussion, but Not Moderate Traumatic Brain Injury, Is Associated with Long-Term Depression-Like Phenotype in Mice.

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    Nikita M Bajwa

    Full Text Available Mild traumatic brain injuries can lead to long-lasting cognitive and motor deficits, increasing the risk of future behavioral, neurological, and affective disorders. Our study focused on long-term behavioral deficits after repeated injury in which mice received either a single mild CHI (mCHI, a repeated mild CHI (rmCHI consisting of one impact to each hemisphere separated by 3 days, or a moderate controlled cortical impact injury (CCI. Shams received only anesthesia. Behavioral tests were administered at 1, 3, 5, 7, and 90 days post-injury (dpi. CCI animals showed significant motor and sensory deficits in the early (1-7 dpi and long-term (90 dpi stages of testing. Interestingly, sensory and subtle motor deficits in rmCHI animals were found at 90 dpi. Most importantly, depression-like behaviors and social passiveness were observed in rmCHI animals at 90 dpi. These data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate TBI.

  20. Abnormal brain iron metabolism in Irp2 deficient mice is associated with mild neurological and behavioral impairments.

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    Kimberly B Zumbrennen-Bullough

    Full Text Available Iron Regulatory Protein 2 (Irp2, Ireb2 is a central regulator of cellular iron homeostasis in vertebrates. Two global knockout mouse models have been generated to explore the role of Irp2 in regulating iron metabolism. While both mouse models show that loss of Irp2 results in microcytic anemia and altered body iron distribution, discrepant results have drawn into question the role of Irp2 in regulating brain iron metabolism. One model shows that aged Irp2 deficient mice develop adult-onset progressive neurodegeneration that is associated with axonal degeneration and loss of Purkinje cells in the central nervous system. These mice show iron deposition in white matter tracts and oligodendrocyte soma throughout the brain. A contrasting model of global Irp2 deficiency shows no overt or pathological signs of neurodegeneration or brain iron accumulation, and display only mild motor coordination and balance deficits when challenged by specific tests. Explanations for conflicting findings in the severity of the clinical phenotype, brain iron accumulation and neuronal degeneration remain unclear. Here, we describe an additional mouse model of global Irp2 deficiency. Our aged Irp2-/- mice show marked iron deposition in white matter and in oligodendrocytes while iron content is significantly reduced in neurons. Ferritin and transferrin receptor 1 (TfR1, Tfrc, expression are increased and decreased, respectively, in the brain from Irp2-/- mice. These mice show impairments in locomotion, exploration, motor coordination/balance and nociception when assessed by neurological and behavioral tests, but lack overt signs of neurodegenerative disease. Ultrastructural studies of specific brain regions show no evidence of neurodegeneration. Our data suggest that Irp2 deficiency dysregulates brain iron metabolism causing cellular dysfunction that ultimately leads to mild neurological, behavioral and nociceptive impairments.

  1. Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

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    Yu Ri Kim

    2017-02-01

    Full Text Available The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ augmentation for cilostazol (CLS-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS. Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus. Greater proliferation of neuronal progenitor cells was also observed in the ipsilateral striatum of the mice receiving combined treatment compared to mice receiving either drug alone. Phosphorylation of the cyclic adenosine monophosphate response element binding protein (CREB was increased in the striatum, hippocampus, and midbrain of mice receiving combined treatment compared to treatment with either drug alone, particularly in the neurons of the striatum and hippocampus, and dopaminergic neurons of the midbrain. Our results suggest that APZ may augment the antidepressant effects of CLS via co-regulation of the CREB signaling pathway, resulting in the synergistic enhancement of their neuroprotective effects.

  2. Stressful presentations: mild cold stress in laboratory mice influences phenotype of dendritic cells in naïve and tumor-bearing mice.

    Science.gov (United States)

    Kokolus, Kathleen M; Spangler, Haley M; Povinelli, Benjamin J; Farren, Matthew R; Lee, Kelvin P; Repasky, Elizabeth A

    2014-01-01

    The ability of dendritic cells (DCs) to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to model immune responses. The goals of this report are to 1) briefly summarize previous work revealing how DCs respond to various forms of physiological stress and 2) to present new data highlighting the potential for chronic mild cold stress inherent to mice housed at the required standard ambient temperatures to influence baseline DCs properties in naïve and tumor-bearing mice. As recent data from our group shows that CD8(+) T cell function is significantly altered by chronic mild cold stress and since DC function is crucial for CD8(+) T cell activation, we wondered whether housing temperature may also be influencing DC function. Here we report that there are several significant phenotypical and functional differences among DC subsets in naïve and tumor-bearing mice housed at either standard housing temperature or at a thermoneutral ambient temperature, which significantly reduces the extent of cold stress. The new data presented here strongly suggests that, by itself, the housing temperature of mice can affect fundamental properties and functions of DCs. Therefore differences in basal levels of stress due to housing should be taken into consideration when interpreting experiments designed to evaluate the impact of additional variables, including other stressors on DC function.

  3. Alzheimer’s Disease Mutant Mice Exhibit Reduced Brain Tissue Stiffness Compared to Wild-type Mice in both Normoxia and following Intermittent Hypoxia Mimicking Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Maria José Menal

    2018-01-01

    Full Text Available BackgroundEvidence from patients and animal models suggests that obstructive sleep apnea (OSA may increase the risk of Alzheimer’s disease (AD and that AD is associated with reduced brain tissue stiffness.AimTo investigate whether intermittent hypoxia (IH alters brain cortex tissue stiffness in AD mutant mice exposed to IH mimicking OSA.MethodsSix-eight month old (B6C3-Tg(APPswe,PSEN1dE985Dbo/J AD mutant mice and wild-type (WT littermates were subjected to IH (21% O2 40 s to 5% O2 20 s; 6 h/day or normoxia for 8 weeks. After euthanasia, the stiffness (E of 200-μm brain cortex slices was measured by atomic force microscopy.ResultsTwo-way ANOVA indicated significant cortical softening and weight increase in AD mice compared to WT littermates, but no significant effects of IH on cortical stiffness and weight were detected. In addition, reduced myelin was apparent in AD (vs. WT, but no significant differences emerged in the cortex extracellular matrix components laminin and glycosaminoglycans when comparing baseline AD and WT mice.ConclusionAD mutant mice exhibit reduced brain tissue stiffness following both normoxia and IH mimicking sleep apnea, and such differences are commensurate with increased edema and demyelination in AD.

  4. ApoB100/LDLR-/- hypercholesterolaemic mice as a model for mild cognitive impairment and neuronal damage.

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    Carlos Ramírez

    Full Text Available Recent clinical findings support the notion that the progressive deterioration of cholesterol homeostasis is a central player in Alzheimer's disease (AD. Epidemiological studies suggest that high midlife plasma total cholesterol levels are associated with an increased risk of AD. This paper reports the plasma cholesterol concentrations, cognitive performance, locomotor activity and neuropathological signs in a murine model (transgenic mice expressing apoB100 but knockout for the LDL receptor [LDLR] of human familial hypercholesterolaemia (FH. From birth, these animals have markedly elevated LDL-cholesterol and apolipoprotein B100 (apoB100 levels. These transgenic mice were confirmed to have higher plasma cholesterol concentrations than wild-type mice, an effect potentiated by aging. Further, 3-month-old transgenic mice showed cholesterol (total and fractions concentrations considerably higher than those of 18-month-old wild-type mice. The hypercholesterolaemia of the transgenic mice was associated with a clear locomotor deficit (as determined by rotarod, grip strength and open field testing and impairment of the episodic-like memory (determined by the integrated memory test. This decline in locomotor activity and cognitive status was associated with neuritic dystrophy and/or the disorganization of the neuronal microtubule network, plus an increase in astrogliosis and lipid peroxidation in the brain regions associated with AD, such as the motor and lateral entorhinal cortex, the amygdaloid basal nucleus, and the hippocampus. Aortic atherosclerotic lesions were positively correlated with age, although potentiated by the transgenic genotype, while cerebral β-amyloidosis was positively correlated with genetic background rather than with age. These findings confirm hypercholesterolaemia as a key biomarker for monitoring mild cognitive impairment, and shows these transgenic mice can be used as a model for cognitive and psycho-motor decline.

  5. Tight Skin 2 Mice Exhibit Delayed Wound Healing Caused by Increased Elastic Fibers in Fibrotic Skin.

    Science.gov (United States)

    Long, Kristen B; Burgwin, Chelsea M; Huneke, Richard; Artlett, Carol M; Blankenhorn, Elizabeth P

    2014-09-01

    Rationale: The Tight Skin 2 (Tsk2) mouse model of systemic sclerosis (SSc) has many features of human disease, including tight skin, excessive collagen deposition, alterations in the extracellular matrix (ECM), increased elastic fibers, and occurrence of antinuclear antibodies with age. A tight skin phenotype is observed by 2 weeks of age, but measurable skin fibrosis is only apparent at 10 weeks. We completed a series of wound healing experiments to determine how fibrosis affects wound healing in Tsk2/+ mice compared with their wild-type (WT) littermates. Method: We performed these experiments by introducing four 4 mm biopsy punched wounds on the back of each mouse, ventral of the midline, and observed wound healing over 10 days. Tsk2/+ mice showed significantly delayed wound healing and increased wound size compared with the WT littermates at both 5 and 10 weeks of age. We explored the potential sources of this response by wounding Tsk2/+ mice that were genetically deficient either for the NLRP3 inflammasome (a known fibrosis mediator), or for elastic fibers in the skin, using a fibulin-5 knockout. Conclusion: We found that the loss of elastic fibers restores normal wound healing in the Tsk2/+ mouse and that the loss of the NLRP3 inflammasome had no effect. We conclude that elastic fiber dysregulation is the primary cause of delayed wound healing in the Tsk2/+ mouse and therapies that promote collagen deposition in the tissue matrix in the absence of elastin deposition might be beneficial in promoting wound healing in SSc and other diseases.

  6. Growth hormone secretagogue receptor (GHS-R1a) knockout mice exhibit improved spatial memory and deficits in contextual memory.

    Science.gov (United States)

    Albarran-Zeckler, Rosie G; Brantley, Alicia Faruzzi; Smith, Roy G

    2012-06-15

    Although the hormone ghrelin is best known for its stimulatory effect on appetite and regulation of growth hormone release, it is also reported to have beneficial effects on learning and memory formation in mice. Nevertheless, controversy exists about whether endogenous ghrelin acts on its receptors in extra-hypothalamic areas of the brain. The ghrelin receptor (GHS-R1a) is co-expressed in neurons that express dopamine receptor type-1 (DRD1a) and type-2 (DRD2), and we have shown that a subset of GHS-R1a, which are not occupied by the agonist (apo-GHSR1a), heterodimerize with these two receptors to regulate dopamine signaling in vitro and in vivo. To determine the consequences of ghsr ablation on brain function, congenic ghsr -/- mice on the C57BL6/J background were subjected to a battery of behavioral tests. We show that the ghsr -/- mice exhibit normal balance, movement, coordination, and pain sensation, outperform ghsr +/+ mice in the Morris water maze, but show deficits in contextual fear conditioning. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. β2-Adrenergic Receptor Knockout Mice Exhibit A Diabetic Retinopathy Phenotype

    Science.gov (United States)

    Jiang, Youde; Zhang, Qiuhua; Liu, Li; Tang, Jie; Kern, Timothy S.; Steinle, Jena J.

    2013-01-01

    There is considerable evidence from our lab and others for a functional link between β-adrenergic receptor and insulin receptor signaling pathways in retina. Furthermore, we hypothesize that this link may contribute to lesions similar to diabetic retinopathy in that the loss of adrenergic input observed in diabetic retinopathy may disrupt normal anti-apoptotic insulin signaling, leading to retinal cell death. Our studies included assessment of neural retina function (ERG), vascular degeneration, and Müller glial cells (which express only β1 and β2-adrenergic receptor subtypes). In the current study, we produced β2-adrenergic receptor knockout mice to examine this deletion on retinal neurons and vasculature, and to identify specific pathways through which β2-adrenergic receptor modulates insulin signaling. As predicted from our hypothesis, β2-adrenergic receptor knockout mice display certain features similar to diabetic retinopathy. In addition, loss of β2-adrenergic input resulted in an increase in TNFα, a key inhibitor of insulin receptor signaling. Increased TNFα may be associated with insulin-dependent production of the anti-apoptotic factor, Akt. Since the effects occurred in vivo under normal glucose conditions, we postulate that aspects of the diabetic retinopathy phenotype might be triggered by loss of β2-adrenergic receptor signaling. PMID:23894672

  8. Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

    Science.gov (United States)

    Liu, Bo; Gulati, Ajay S; Cantillana, Viviana; Henry, Stanley C; Schmidt, Elyse A; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A; Sartor, R Balfour; Taylor, Gregory A

    2013-10-15

    Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

  9. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation

    Science.gov (United States)

    Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa; Weston, Rory M.; Guide, Jolene R.; Arjomand, Jamshid; Kwak, Seung; Clish, Clary B.; MacDonald, Marcy E.

    2015-01-01

    The HTT CAG expansion mutation causes Huntington’s Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident

  10. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Carroll

    Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

  11. Fucoidan Supplementation Improves Exercise Performance and Exhibits Anti-Fatigue Action in Mice

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    Yi-Ming Chen

    2014-12-01

    Full Text Available Fucoidan (FCD is a well-known bioactive constituent of seaweed extract that possess a wide spectrum of activities in biological systems, including anti-cancer, anti-inflammation and modulation of immune systems. However, evidence on the effects of FCD on exercise performance and physical fatigue is limited. Therefore, we investigated the potential beneficial effects of FCD on ergogenic and anti-fatigue functions following physiological challenge. Male ICR mice from three groups (n = 8 per group were orally administered FCD for 21 days at 0, 310 and 620 mg/kg/day, which were, respectively, designated the vehicle, FCD-1X and FCD-2X groups. The results indicated that the FCD supplementations increased the grip strength (p = 0.0002 and endurance swimming time (p = 0.0195 in a dose-depend manner. FCD treatments also produced dose-dependent decreases in serum levels of lactate (p < 0.0001 and ammonia (p = 0.0025, and also an increase in glucose level (p < 0.0001 after the 15-min swimming test. In addition, FCD supplementation had few subchronic toxic effects. Therefore, we suggest that long-term supplementation with FCD can have a wide spectrum of bioactivities on health promotion, performance improvement and anti-fatigue.

  12. Transgenic Mice Expressing Yeast CUP1 Exhibit Increased Copper Utilization from Feeds

    Science.gov (United States)

    Chen, Zhenliang; Liao, Rongrong; Zhang, Xiangzhe; Wang, Qishan; Pan, Yuchun

    2014-01-01

    Copper is required for structural and catalytic properties of a variety of enzymes participating in many vital biological processes for growth and development. Feeds provide most of the copper as an essential micronutrient consumed by animals, but inorganic copper could not be utilized effectively. In the present study, we aimed to develop transgenic mouse models to test if copper utilization will be increased by providing the animals with an exogenous gene for generation of copper chelatin in saliva. Considering that the S. cerevisiae CUP1 gene encodes a Cys-rich protein that can bind copper as specifically as copper chelatin in yeast, we therefore constructed a transgene plasmid containing the CUP1 gene regulated for specific expression in the salivary glands by a promoter of gene coding pig parotid secretory protein. Transgenic CUP1 was highly expressed in the parotid and submandibular salivary glands and secreted in saliva as a 9-kDa copper-chelating protein. Expression of salivary copper-chelating proteins reduced fecal copper contents by 21.61% and increased body-weight by 12.97%, suggesting that chelating proteins improve the utilization and absorbed efficacy of copper. No negative effects on the health of the transgenic mice were found by blood biochemistry and histology analysis. These results demonstrate that the introduction of the salivary CUP1 transgene into animals offers a possible approach to increase the utilization efficiency of copper and decrease the fecal copper contents. PMID:25265503

  13. Voluntary exercise and increased food intake after mild chronic stress improve social avoidance behavior in mice.

    Science.gov (United States)

    Otsuka, Airi; Shiuchi, Tetsuya; Chikahisa, Sachiko; Shimizu, Noriyuki; Séi, Hiroyoshi

    2015-11-01

    It is well-established that exercise can influence psychological conditions, cognitive function, and energy metabolism in peripheral tissues including the skeletal muscle. However, it is not clear whether exercise can influence social interaction with others and alleviate defeat stress. This study investigated the effect of voluntary wheel running on impaired social interaction induced by chronic social defeat stress (SDS) using the resident-intruder social defeat model. Mice were divided into three groups: control, stress alone, and stress+exercise. SDS was performed by exposing C57BL/6 mice to retired ICR mice for 2.5 min. The C57BL/6 mice were continuously defeated by these resident (aggressor) mice and, following 5 days of SDS, experienced 2 days of rest with no SDS. Mice in the stress+exercise group were allowed to voluntarily run on a wheel for 2h after every SDS exposure. Two weeks later, compared to the control group, the stress group showed a higher ratio of time spent in the corner zone of a social interaction paradigm even though SDS did not elicit depressive- and anxiety-like behaviors. We also observed that voluntary exercise, which did not affect muscle weight and gene expression, decreased social avoidance behavior of stressed mice without clear changes in brain monoamine levels. Interestingly, food intake in the stress+exercise group was the greatest among the three groups. To test the effect of the exercise-induced increase in food intake on social behavior, we set up a pair-fed group where food intake was restricted. We then compared these mice to mice in the stress alone group. We found that the ratio of time spent in the corner zone of the social interaction test was not different between ad libitum- and pair-fed groups, although pair-fed mice spent more time in the corner zone when an aggressor mouse was present than when it was absent. In addition, pair-feeding did not show exercise-induced reductions of adrenal gland weight and enhanced the

  14. STRATEGI PENINGKATAN PENDAPATAN ASLI DAERAH, INVESTASI DAN PERTUMBUHAN EKONOMI KOTA SEMARANG MELALUI MICE (MEETING, INCENTIVE, CONVENTION DAN EXHIBITION

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    Tika Putri Pratiwi

    2015-05-01

    Full Text Available Abstrak ___________________________________________________________________ Semarang sebagai ibukota Provinsi Jawa Tengah memiliki potensi yang besar dalam mengembangkan sektor industri dan pariwisata. Langkah awal pemerintah yang serius dalam mengolah kedua industri ini yaitu dengan menjadikan Kota Semarang sebagai salah satu destinasi MICE (Meeting, Incentive, Convention, Exhibition. Penelitian ini bertujuan untuk memilih strategi apa yang dapat dilakukan dalam pembangunan Kota Semarang Melalui MICE. Data yang digunakan dalam penelitian ini adalah data primer dan data sekunder. Data primer bersumber dari hasil pengisian kuesioner oleh pihak dinas dan Swasta. Data sekunder dalam penelitian ini berupa data-data yang diperoleh dari dinas terkait serta Badan Pusat Statistik (BPS Provinsi Jawa Tengah dan Kota Semarang dan jurnal serta literatur yang berkaitan dengan penelitian. Metode analisis yang digunakan yaituAnalitical Hierarki Process (AHP dan diolah menggunakan expert choice versi 9.0. Hasil penelitian ini menunjukkan bahwa strategi pembangunan Kota Semarang melalui MICE dapat mengutamakan pada kriteria (1 peningkatan sektor investasi dengan bobot tertinggi yaitu sebesar 0,614 dan dilanjutkan dengan (2 memperbaiki pertumbuhan ekonomi kota dengan bobot 0,260, sehingga akan membantu dalam (3 peningkatan Pendapatan Asli Daerah Kota Semarang melalui MICE dengan bobot 0,126. Berdasarkan temuan tersebut, saran yang dapat disampaikan yaitu Memperkenalkan Kota Semarang melalui jalur promosi dengan menggunakan media-media sosal dan media elektronik. Hal tersebut merupakan salah satu alternatif membuka investasi yang lebih luas di Kota Semarang, sehingga tidak hanya masyarakat dalam negeri namun masyarakat internasional juga dapat lebih mengenal Kota Semarang. Memperbanyak even berskala nasional maupun internasional yang diselenggarakan di Kota Semarang dan lebih memperkenalkan Kota Semarang baik di dalam maupun di luar negeri. Memberikan pelatihan

  15. Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

    International Nuclear Information System (INIS)

    Wu, Hsu-Pin; Hsu, Shu-Yuan; Wu, Wen-Ai; Hu, Ji-Wei; Ouyang, Pin

    2014-01-01

    Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB +/− mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity

  16. Transgenic mice expressing mutant Pinin exhibit muscular dystrophy, nebulin deficiency and elevated expression of slow-type muscle fiber genes

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hsu-Pin; Hsu, Shu-Yuan [Department of Anatomy, Chang Gung University Medical College, Taiwan (China); Wu, Wen-Ai; Hu, Ji-Wei [Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan (China); Ouyang, Pin, E-mail: ouyang@mail.cgu.edu.tw [Department of Anatomy, Chang Gung University Medical College, Taiwan (China); Transgenic Mouse Core Laboratory, Chang Gung University, Taiwan (China); Molecular Medicine Research Center, Chang Gung University, Taiwan (China)

    2014-01-03

    Highlights: •Pnn CCD domain functions as a dominant negative mutant regulating Pnn expression and function. •Pnn CCD mutant Tg mice have a muscle wasting phenotype during development and show dystrophic histological features. •Pnn mutant muscles are susceptible to slow fiber type gene transition and NEB reduction. •The Tg mouse generated by overexpression of the Pnn CCD domain displays many characteristics resembling NEB{sup +/−} mice. -- Abstract: Pinin (Pnn) is a nuclear speckle-associated SR-like protein. The N-terminal region of the Pnn protein sequence is highly conserved from mammals to insects, but the C-terminal RS domain-containing region is absent in lower species. The N-terminal coiled-coil domain (CCD) is, therefore, of interest not only from a functional point of view, but also from an evolutionarily standpoint. To explore the biological role of the Pnn CCD in a physiological context, we generated transgenic mice overexpressing Pnn mutant in skeletal muscle. We found that overexpression of the CCD reduces endogenous Pnn expression in cultured cell lines as well as in transgenic skeletal muscle fibers. Pnn mutant mice exhibited reduced body mass and impaired muscle function during development. Mutant skeletal muscles show dystrophic histological features with muscle fibers heavily loaded with centrally located myonuclei. Expression profiling and pathway analysis identified over-representation of genes in gene categories associated with muscle contraction, specifically those related to slow type fiber. In addition nebulin (NEB) expression level is repressed in Pnn mutant skeletal muscle. We conclude that Pnn downregulation in skeletal muscle causes a muscular dystrophic phenotype associated with NEB deficiency and the CCD domain is incapable of replacing full length Pnn in terms of functional capacity.

  17. The Antidepressant Agomelatine Improves Memory Deterioration and Upregulates CREB and BDNF Gene Expression Levels in Unpredictable Chronic Mild Stress (UCMS-Exposed Mice

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    Esen Gumuslu

    2014-01-01

    Full Text Available Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT 1 and MT 2 receptors and as an antagonist of 5-HT 2C receptors. The present study was undertaken to investigate whether chronic treatment with agomelatine would block unpredictable chronic mild stress (UCMS-induced cognitive deterioration in mice in passive avoidance (PA, modified elevated plus maze (mEPM, novel object recognition (NOR, and Morris water maze (MWM tests. Moreover, the effects of stress and agomelatine on brain-derived neurotrophic factor (BDNF and cyclic adenosine monophosphate (cAMP response element binding protein (CREB messenger ribonucleic acid (mRNA levels in the hippocampus was also determined using quantitative real-time polymerase chain reaction (RT-PCR. Male inbred BALB/c mice were treated with agomelatine (10 mg/kg, i.p., melatonin (10 mg/kg, or vehicle daily for five weeks. The results of this study revealed that UCMS-exposed animals exhibited memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic administration of melatonin had a positive effect in the PA and +mEPM tests, whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked stress-induced impairment in visual memory in the NOR test and reversed spatial learning and memory impairment in the stressed group in the MWM test. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in UCMS-exposed mice, and these alterations were reversed by chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important role in blocking stress-induced hippocampal memory deterioration and activates molecular mechanisms of memory storage in response to a learning experience.

  18. Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis

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    Yoshitaka Kondo

    2014-01-01

    Full Text Available Superoxide dismutase 1 (SOD1 is an antioxidant enzyme that converts superoxide anion radicals into hydrogen peroxide and molecular oxygen. The senescence marker protein-30 (SMP30 is a gluconolactonase that functions as an antioxidant protein in mammals due to its involvement in ascorbic acid (AA biosynthesis. SMP30 also participates in Ca2+ efflux by activating the calmodulin-dependent Ca2+-pump. To reveal the role of oxidative stress in lipid metabolism defects occurring in non-alcoholic fatty liver disease pathogenesis, we generated SMP30/SOD1-double knockout (SMP30/SOD1-DKO mice and investigated their survival curves, plasma and hepatic lipid profiles, amounts of hepatic oxidative stress, and hepatic protein levels expressed by genes related to lipid metabolism. While SMP30/SOD1-DKO pups had no growth retardation by 14 days of age, they did have low plasma and hepatic AA levels. Thereafter, 39% and 53% of male and female pups died by 15–24 and 89 days of age, respectively. Compared to wild type, SMP30-KO and SOD1-KO mice, by 14 days SMP30/SOD1-DKO mice exhibited: (1 higher plasma levels of triglyceride and aspartate aminotransferase; (2 severe accumulation of hepatic triglyceride and total cholesterol; (3 higher levels of superoxide anion radicals and thiobarbituric acid reactive substances in livers; and (4 decreased mRNA and protein levels of Apolipoprotein B (ApoB in livers – ApoB is an essential component of VLDL secretion. These results suggest that high levels of oxidative stress due to concomitant deficiency of SMP30 and/or AA, and SOD1 cause abnormal plasma lipid metabolism, hepatic lipid accumulation and premature death resulting from impaired VLDL secretion.

  19. Motor, visual and emotional deficits in mice after closed-head mild traumatic brain injury are alleviated by the novel CB2 inverse agonist SMM-189.

    Science.gov (United States)

    Reiner, Anton; Heldt, Scott A; Presley, Chaela S; Guley, Natalie H; Elberger, Andrea J; Deng, Yunping; D'Surney, Lauren; Rogers, Joshua T; Ferrell, Jessica; Bu, Wei; Del Mar, Nobel; Honig, Marcia G; Gurley, Steven N; Moore, Bob M

    2014-12-31

    We have developed a focal blast model of closed-head mild traumatic brain injury (TBI) in mice. As true for individuals that have experienced mild TBI, mice subjected to 50-60 psi blast show motor, visual and emotional deficits, diffuse axonal injury and microglial activation, but no overt neuron loss. Because microglial activation can worsen brain damage after a concussive event and because microglia can be modulated by their cannabinoid type 2 receptors (CB2), we evaluated the effectiveness of the novel CB2 receptor inverse agonist SMM-189 in altering microglial activation and mitigating deficits after mild TBI. In vitro analysis indicated that SMM-189 converted human microglia from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype. Studies in mice showed that daily administration of SMM-189 for two weeks beginning shortly after blast greatly reduced the motor, visual, and emotional deficits otherwise evident after 50-60 psi blasts, and prevented brain injury that may contribute to these deficits. Our results suggest that treatment with the CB2 inverse agonist SMM-189 after a mild TBI event can reduce its adverse consequences by beneficially modulating microglial activation. These findings recommend further evaluation of CB2 inverse agonists as a novel therapeutic approach for treating mild TBI.

  20. Motor, Visual and Emotional Deficits in Mice after Closed-Head Mild Traumatic Brain Injury Are Alleviated by the Novel CB2 Inverse Agonist SMM-189

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    Anton Reiner

    2014-12-01

    Full Text Available We have developed a focal blast model of closed-head mild traumatic brain injury (TBI in mice. As true for individuals that have experienced mild TBI, mice subjected to 50–60 psi blast show motor, visual and emotional deficits, diffuse axonal injury and microglial activation, but no overt neuron loss. Because microglial activation can worsen brain damage after a concussive event and because microglia can be modulated by their cannabinoid type 2 receptors (CB2, we evaluated the effectiveness of the novel CB2 receptor inverse agonist SMM-189 in altering microglial activation and mitigating deficits after mild TBI. In vitro analysis indicated that SMM-189 converted human microglia from the pro-inflammatory M1 phenotype to the pro-healing M2 phenotype. Studies in mice showed that daily administration of SMM-189 for two weeks beginning shortly after blast greatly reduced the motor, visual, and emotional deficits otherwise evident after 50–60 psi blasts, and prevented brain injury that may contribute to these deficits. Our results suggest that treatment with the CB2 inverse agonist SMM-189 after a mild TBI event can reduce its adverse consequences by beneficially modulating microglial activation. These findings recommend further evaluation of CB2 inverse agonists as a novel therapeutic approach for treating mild TBI.

  1. Antidepressant-like effect of Butea superba in mice exposed to chronic mild stress and its possible mechanism of action.

    Science.gov (United States)

    Mizuki, Daishu; Matsumoto, Kinzo; Tanaka, Ken; Thi Le, Xoan; Fujiwara, Hironori; Ishikawa, Tsutomu; Higuchi, Yoshihiro

    2014-10-28

    Butea superba (BS) is a Thai medicinal plant that has been used as a folk medicine to improve physical and mental conditions and to prevent impaired sexual performance in middle-aged or elderly males. We have previously reported that this plant extract could improve cognitive deficits and depression-like behavior in olfactory bulbectomized mice, an animal model of dementia and depression. In this study we examined the effect of BS on depression-like behavior in mice subjected to unpredictable chronic mild stress (UCMS) to clarify the antidepressant-like activity of BS and the molecular mechanism underlying this effect. UCMS mice were administered BS daily (300 mg of dried herb weight/kg, p.o.) or a reference drug, imipramine (IMP, 10 mg/kg, i.p.), 1 week after starting the UCMS procedure. We employed the sucrose preference test and the tail suspension test to analyze anhedonia and depression-like behavior of mice, respectively. Serum and brain tissues of mice were used for neurochemical and immunohistochemical studies. The UCMS procedure induced anhedonia and depression-like behavior, and BS treatment, as well as IMP treatment, attenuated these symptoms. UCMS caused an elevation of serum corticosterone level, an index of hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis, in a manner attenuated by BS and IMP treatment. BS treatment also attenuated UCMS-induced decrease in the expression levels of brain-derived neurotrophic factor (BDNF) mRNA, cyclic AMP-responsive element binding protein (CREB) and a phosphorylated form of N-methyl-d-aspartate receptor subunit NR1, synaptic plasticity-related signaling proteins. Moreover, the UCMS procedure reduced doublecortin-positive cells in the dentate gyrus region of the hippocampus. BS administration reversed these UCMS-induced neurochemical and histological abnormalities. These results suggest that BS can ameliorate chronic stress-induced depression-like symptoms and that the effects of BS are mediated by

  2. Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress.

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    Xian-cang Ma

    Full Text Available Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS, an animal model of depression.C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST and forced swimming test (FST, the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice.These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS.

  3. PSAPP mice exhibit regionally selective reductions in gliosis and plaque deposition in response to S100B ablation

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    Young Keith A

    2010-11-01

    Full Text Available Abstract Background Numerous studies have reported that increased expression of S100B, an intracellular Ca2+ receptor protein and secreted neuropeptide, exacerbates Alzheimer's disease (AD pathology. However, the ability of S100B inhibitors to prevent/reverse AD histopathology remains controversial. This study examines the effect of S100B ablation on in vivo plaque load, gliosis and dystrophic neurons. Methods Because S100B-specific inhibitors are not available, genetic ablation was used to inhibit S100B function in the PSAPP AD mouse model. The PSAPP/S100B-/- line was generated by crossing PSAPP double transgenic males with S100B-/- females and maintained as PSAPP/S100B+/- crosses. Congo red staining was used to quantify plaque load, plaque number and plaque size in 6 month old PSAPP and PSAPP/S100B-/- littermates. The microglial marker Iba1 and astrocytic marker glial fibrillary acidic protein (GFAP were used to quantify gliosis. Dystrophic neurons were detected with the phospho-tau antibody AT8. S100B immunohistochemistry was used to assess the spatial distribution of S100B in the PSAPP line. Results PSAPP/S100B-/- mice exhibited a regionally selective decrease in cortical but not hippocampal plaque load when compared to PSAPP littermates. This regionally selective reduction in plaque load was accompanied by decreases in plaque number, GFAP-positive astrocytes, Iba1-positive microglia and phospho-tau positive dystrophic neurons. These effects were not attributable to regional variability in the distribution of S100B. Hippocampal and cortical S100B immunoreactivity in PSAPP mice was associated with plaques and co-localized with astrocytes and microglia. Conclusions Collectively, these data support S100B inhibition as a novel strategy for reducing cortical plaque load, gliosis and neuronal dysfunction in AD and suggest that both extracellular as well as intracellular S100B contribute to AD histopathology.

  4. Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature.

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    Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

    2012-09-01

    Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K(+) channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here, we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during

  5. OCT imaging of acute vascular changes following mild traumatic brain injury in mice (Conference Presentation)

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    Chico-Calero, Isabel; Shishkov, Milen; Welt, Jonathan; Blatter, Cedric; Vakoc, Benjamin J.

    2016-03-01

    While most people recover completely from mild traumatic brain injuries (mTBIs) and concussions, a subset develop lasting neurological disorders. Understanding the complex pathophysiology of these injuries is critical to developing improved prognostic and therapeutic approaches. Multiple studies have shown that the structure and perfusion of brain vessels are altered after mTBI. It is possible that these vascular injuries contribute to or trigger neurodegeneration. Intravital microscopy and mouse models of TBI offer a powerful platform to study the vascular component of mTBI. Because optical coherence tomography based angiography is based on perfusion contrast and is not significantly degraded by vessel leakage or blood brain barrier disruption, it is uniquely suited to studies of brain perfusion in the setting of trauma. However, existing TBI imaging models require surgical exposure of the brain at the time of injury which conflates TBI-related vascular changes with those caused by surgery. In this work, we describe a modified cranial window preparation based on a flexible, transparent polyurethane membrane. Impact injuries were delivered directly through this membrane, and imaging was performed immediately after injury without the need for additional surgical procedures. Using this model, we demonstrate that mTBI induces a transient cessation of flow in the capillaries and smaller vessels near the injury point. Reperfusion is observed in all animals within 3 hours of injury. This work describes new insight into the transient vascular changes induced by mTBI, and demonstrates more broadly the utility of the OCT/polyurethane window model platform in preclinical studies of mTBI.

  6. Effects of Mild and Severe Vitamin B Deficiencies on the Meiotic Maturation of Mice Oocytes

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    Ai Tsuji

    2017-03-01

    Full Text Available We investigated the effects of vitamin B 1 deficiency on the meiosis maturation of oocytes. Female Crl:CD1 (ICR mice were fed a 20% casein diet (control group or a vitamin B 1 –free diet (test group. The vitamin B 1 concentration in ovary was approximately 30% lower in the test group than in the control group. Oocyte meiosis was not affected by vitamin B 1 deficiency when the deficiency was not accompanied by body weight loss. On the contrary, frequency of abnormal oocyte was increased by vitamin B 1 deficiency when deficiency was accompanied by body weight loss (referred to as severe vitamin B 1 deficiency; frequency of abnormal oocyte, 13.8% vs 43.7%, P  = .0071. The frequency of abnormal oocytes was decreased by refeeding of a vitamin B 1 –containing diet (13.9% vs 22.9%, P  = .503. These results suggest that severe vitamin B 1 deficiency inhibited meiotic maturation of oocytes but did not damage immature oocytes.

  7. The decidua of preeclamptic-like BPH/5 mice exhibits an exaggerated inflammatory response during early pregnancy.

    Science.gov (United States)

    Heyward, C Y; Sones, J L; Lob, H E; Yuen, L C; Abbott, K E; Huang, W; Begun, Z R; Butler, S D; August, A; Leifer, C A; Davisson, R L

    2017-04-01

    Preeclampsia is a devastating complication of pregnancy characterized by late-gestation hypertension and proteinuria. Because the only definitive treatment is delivery of the fetus and placenta, preeclampsia contributes to increased morbidity and mortality of both mother and fetus. The BPH/5 mouse model, which spontaneously develops a syndrome strikingly similar to preeclampsia, displays excessive inflammation and suppression of inflammation improves pregnancy outcomes. During early pregnancy, decidual macrophages play an important role in promoting maternal tolerance to fetal antigens and regulating tissue remodeling, two functions that are critical for normal placental development. BPH/5 pregnancies are characterized by abnormal placentation; therefore, we hypothesized that macrophage localization and/or function is altered during early pregnancy at the site of placental formation (the decidua) compared to C57BL/6 controls. At early gestation time points, before the onset of maternal hypertension or proteinuria, there was a reduction in the number of macrophages in BPH/5 decidua and a concomitant increase in activated T cells compared with C57BL/6. BPH/5 decidua also exhibited decreased expression of the immunosuppressive cytokine, IL-10, and increased expression of pro-inflammatory, inducible nitric oxide synthase. Together, these data suggest that a reduction in decidual macrophages during pregnancy is associated with immune activation in BPH/5 mice, inadequate placental development and may contribute to adverse pregnancy outcomes in this model. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Kharon1 null mutants of Leishmania mexicana are avirulent in mice and exhibit a cytokinesis defect within macrophages.

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    Khoa D Tran

    Full Text Available In a variety of eukaryotes, flagella play important roles both in motility and as sensory organelles that monitor the extracellular environment. In the parasitic protozoan Leishmania mexicana, one glucose transporter isoform, LmxGT1, is targeted selectively to the flagellar membrane where it appears to play a role in glucose sensing. Trafficking of LmxGT1 to the flagellar membrane is dependent upon interaction with the KHARON1 protein that is located at the base of the flagellar axoneme. Remarkably, while Δkharon1 null mutants are viable as insect stage promastigotes, they are unable to survive as amastigotes inside host macrophages. Although Δkharon1 promastigotes enter macrophages and transform into amastigotes, these intracellular parasites are unable to execute cytokinesis and form multinucleate cells before dying. Notably, extracellular axenic amastigotes of Δkharon1 mutants replicate and divide normally, indicating a defect in the mutants that is only exhibited in the intra-macrophage environment. Although the flagella of Δkharon1 amastigotes adhere to the phagolysomal membrane of host macrophages, the morphology of the mutant flagella is often distorted. Additionally, these null mutants are completely avirulent following injection into BALB/c mice, underscoring the critical role of the KHARON1 protein for viability of intracellular amastigotes and disease in the animal model of leishmaniasis.

  9. Antidepressant-like effect of essential oil of Perilla frutescens in a chronic, unpredictable, mild stress-induced depression model mice.

    Science.gov (United States)

    Ji, Wei-Wei; Li, Rui-Peng; Li, Meng; Wang, Shu-Yuan; Zhang, Xian; Niu, Xing-Xing; Li, Wei; Yan, Lu; Wang, Yang; Fu, Qiang; Ma, Shi-Ping

    2014-10-01

    Perilla frutescens (Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens (EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress (CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF (3, 6, and 9 mg·kg(-1)) and a positive control drug fluoxetine (20 mg·kg(-1)) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3(rd) week. Open-field test, sucrose consumption test, tail suspension test (TST), and forced swimming test (FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in mouse hippocampus were determined by HPLC-ECD. Serum interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between

  10. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    International Nuclear Information System (INIS)

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C.

    2013-01-01

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level

  11. Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

    2013-08-15

    Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

  12. A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

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    Douglas S. Kernodle

    2013-01-01

    Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

  13. Analysis of the intestinal microbiota of oligo-saccharide fed mice exhibiting reduced resistance to Salmonella infection

    DEFF Research Database (Denmark)

    Petersen, Anne; Bergström, Anders; Andersen, Jens Bo

    2010-01-01

    recently demonstrated a reduced resistance to Salmonella infection in mice fed diets containing fructo-oligosaccharides (FOS) or xylo-oligosaccharides (XOS). In the present study, faecal and caecal samples from the same mice were analysed in order to study microbial changes potentially explaining...... the observed effects on the pathogenesis of Salmonella. Denaturing gradient gel electrophoresis revealed that the microbiota in faecal samples from mice fed FOS or XOS were different from faecal samples collected before the feeding trial as well as from faecal profiles generated from control animals...... of short-chain fatty acids was recorded. In conclusion, diets supplemented with FOS or XOS induced a number of microbial changes in the faecal microbiota of mice. The observed effects of XOS were qualitatively similar to those of FOS, but the most prominent bifidogenic effect was seen for XOS. An increased...

  14. Diacylglycerol kinase β knockout mice exhibit attention-deficit behavior and an abnormal response on methylphenidate-induced hyperactivity.

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    Mitsue Ishisaka

    Full Text Available BACKGROUND: Diacylglycerol kinase (DGK is an enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. DGKβ is one of the subtypes of the DGK family and regulates many intracellular signaling pathways in the central nervous system. Previously, we demonstrated that DGKβ knockout (KO mice showed various dysfunctions of higher brain function, such as cognitive impairment (with lower spine density, hyperactivity, reduced anxiety, and careless behavior. In the present study, we conducted further tests on DGKβ KO mice in order to investigate the function of DGKβ in the central nervous system, especially in the pathophysiology of attention deficit hyperactivity disorder (ADHD. METHODOLOGY/PRINCIPAL FINDINGS: DGKβ KO mice showed attention-deficit behavior in the object-based attention test and it was ameliorated by methylphenidate (MPH, 30 mg/kg, i.p.. In the open field test, DGKβ KO mice displayed a decreased response to the locomotor stimulating effects of MPH (30 mg/kg, i.p., but showed a similar response to an N-methyl-d-aspartate (NMDA receptor antagonist, MK-801 (0.3 mg/kg, i.p., when compared to WT mice. Examination of the phosphorylation of extracellular signal-regulated kinase (ERK, which is involved in regulation of locomotor activity, indicated that ERK1/2 activation induced by MPH treatment was defective in the striatum of DGKβ KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKβ KO mice showed attention-deficit and hyperactive phenotype, similar to ADHD. Furthermore, the hyporesponsiveness of DGKβ KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGKβ has a pivotal involvement in ERK regulation in the striatum.

  15. MICE Tourism (Meetings, Incentives, Conferecing and Exhibitions como gerador de Turismo Interno: Analisando a cidade de Pelotas, RS

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    Adriana Fumi Chim-Miki

    2016-06-01

    Full Text Available Este artigo objetiva apresentar as oportunidades do Turismo MICE Interno para as cidades consideradas regionais. Esta modalidade de turismo urbano, em termos mundiais e nacionais tem apresentado expressivo crescimento. Além disso, está sendo indicada como um produto complementar ou substituto ao clássico turismo de Sol e Praia, especialmente para destinos que estão apresentando sintomas da maturidade deste modelo, ou áreas em que não há condições naturais favoráveis a um completo desenvolvimento baseado em Sol e Praia. Objetivando contribuir com a literatura acadêmica, se apresenta uma revisão conceitual e tipológica do turismo MICE, seguido de uma revisão de determinantes ou atributos para destinos MICE. Desta revisão se extrai os principais determinantes da competitividade do turismo MICE regional, aplicando-os em uma análise empírica da cidade de Pelotas como candidata a Destino MICE Regional. A metodologia é qualitativa, sendo um estudo de caso que utiliza dados primários através de informação coletada nos sites de promoção turística oficiais do município. Conclui-se que a cidade de Pelotas, situada no sul do Estado do Rio Grande do Sul, possui condições de tornar-se um Destino MICE Regional, porém se recomenda uma melhoria no planejamento turístico, em términos de focalizar no desenvolvimento dos atributos de competitividade MICE, e especialmente uma melhoria na qualidade e quantidade das informações sobre suas capacidades como Destino MICE.

  16. IL-23 p19 knockout mice exhibit minimal defects in responses to primary and secondary infection with Francisella tularensis LVS.

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    Sherry L Kurtz

    Full Text Available Our laboratory's investigations into mechanisms of protective immunity against Francisella tularensis Live Vaccine Strain (LVS have uncovered mediators important in host defense against primary infection, as well as those correlated with successful vaccination. One such potential correlate was IL-12p40, a pleiotropic cytokine that promotes Th1 T cell function as part of IL-12p70. LVS-infected IL-12p40 deficient knockout (KO mice maintain a chronic infection, but IL-12p35 KO mice clear LVS infection; thus the role that IL-12p40 plays in immunity to LVS is independent of the IL-12p70 heterodimer. IL-12p40 can also partner with IL-23p19 to create the heterodimeric cytokine IL-23. Here, we directly tested the role of IL-23 in LVS resistance, and found IL-23 to be largely dispensable for immunity to LVS following intradermal or intranasal infection. IL-23p19 KO splenocytes were fully competent in controlling intramacrophage LVS replication in an in vitro overlay assay. Further, antibody responses in IL-23p19 KO mice were similar to those of normal wild type mice after LVS infection. IL-23p19 KO mice or normal wild type mice that survived primary LVS infection survived maximal doses of LVS secondary challenge. Thus p40 has a novel role in clearance of LVS infection that is unrelated to either IL-12 or IL-23.

  17. Chronic mild stress impairs latent inhibition and induces region-specific neural activation in CHL1-deficient mice, a mouse model of schizophrenia.

    Science.gov (United States)

    Buhusi, Mona; Obray, Daniel; Guercio, Bret; Bartlett, Mitchell J; Buhusi, Catalin V

    2017-08-30

    Schizophrenia is a neurodevelopmental disorder characterized by abnormal processing of information and attentional deficits. Schizophrenia has a high genetic component but is precipitated by environmental factors, as proposed by the 'two-hit' theory of schizophrenia. Here we compared latent inhibition as a measure of learning and attention, in CHL1-deficient mice, an animal model of schizophrenia, and their wild-type littermates, under no-stress and chronic mild stress conditions. All unstressed mice as well as the stressed wild-type mice showed latent inhibition. In contrast, CHL1-deficient mice did not show latent inhibition after exposure to chronic stress. Differences in neuronal activation (c-Fos-positive cell counts) were noted in brain regions associated with latent inhibition: Neuronal activation in the prelimbic/infralimbic cortices and the nucleus accumbens shell was affected solely by stress. Neuronal activation in basolateral amygdala and ventral hippocampus was affected independently by stress and genotype. Most importantly, neural activation in nucleus accumbens core was affected by the interaction between stress and genotype. These results provide strong support for a 'two-hit' (genes x environment) effect on latent inhibition in CHL1-deficient mice, and identify CHL1-deficient mice as a model of schizophrenia-like learning and attention impairments. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy

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    Gabriel Nasri Marzuca-Nassr

    2017-10-01

    Full Text Available The consequences of two-week hindlimb suspension (HS on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA, and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2 and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1 were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively, muscle isotonic and tetanic force (by 29% and 18%, respectively, CSA of the soleus muscle (by 36%, and soleus muscle fibers (by 45%. Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs ratio as compared with C57BL/6 wild-type mice (56%, p < 0.001. Fat-1 mice had lower soleus muscle dry mass loss (by 10% and preserved absolute isotonic force (by 17% and CSA of the soleus muscle (by 28% after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70% and MuRF-1 content decreased (by 50% in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.

  19. Mice from lines selectively bred for high voluntary wheel running exhibit lower blood pressure during withdrawal from wheel access.

    Science.gov (United States)

    Kolb, Erik M; Kelly, Scott A; Garland, Theodore

    2013-03-15

    Exercise is known to be rewarding and have positive effects on mental and physical health. Excessive exercise, however, can be the result of an underlying behavioral/physiological addiction. Both humans who exercise regularly and rodent models of exercise addiction sometimes display behavioral withdrawal symptoms, including depression and anxiety, when exercise is denied. However, few studies have examined the physiological state that occurs during this withdrawal period. Alterations in blood pressure (BP) are common physiological indicators of withdrawal in a variety of addictions. In this study, we examined exercise withdrawal in four replicate lines of mice selectively bred for high voluntary wheel running (HR lines). Mice from the HR lines run almost 3-fold greater distances on wheels than those from non-selected control lines, and have altered brain activity as well as increased behavioral despair when wheel access is removed. We tested the hypothesis that male HR mice have an altered cardiovascular response (heart rate, systolic, diastolic, and mean arterial pressure [MAP]) during exercise withdrawal. Measurements using an occlusion tail-cuff system were taken during 8 days of baseline, 6 days of wheel access, and 2 days of withdrawal (wheel access blocked). During withdrawal, HR mice had significantly lower systolic BP, diastolic BP, and MAP than controls, potentially indicating a differential dependence on voluntary wheel running in HR mice. This is the first characterization of a cardiovascular withdrawal response in an animal model of high voluntary exercise. Copyright © 2013. Published by Elsevier Inc.

  20. Healthy Active Duty Military with Lifetime Experience of Mild Traumatic Brain Injury Exhibits Subtle Deficits in Sensory Reactivity and Sensory Integration During Static Balance.

    Science.gov (United States)

    Wright, W Geoffrey; Handy, Justin D; Avcu, Pelin; Ortiz, Alejandro; Haran, F Jay; Doria, Michael; Servatius, Richard J

    2018-03-01

    Postural control and stress reactivity were investigated in active duty coast guard personnel to determine whether they are sensitive to lifetime effects of mild traumatic brain injury (mTBI). A custom-designed and validated virtual reality-based computerized posturography device was used to assess postural stability, whereas emotional reactivity was assessed using the acoustic startle response (ASR), and neurocognitive performance was assessed using the defense-automated neurobehavioral assessment (DANA). It was hypothesized that residual and subtle postural control imbalance and deficits in cognitive and sensory reactivity would be evident in those reporting multiple lifetime mTBI. Active duty military personnel (N = 36; 7 females and 29 males) with no Deployment Limiting Medical Condition were recruited and tested on all assessments. Medical history information provided a history of head injury. Thirty-nine percent of participants reported having a previous mTBI (nine reporting one and five reporting more than one incident). No participant had experienced a head injury within the past year and all were symptom free. A significant effect of number of mTBI was found in the postural assessment (p = 0.002). Lifetime mTBI was associated with suppressed ASR magnitude (p = 0.03) but did not affect neurocognitive performance. The current findings provide new insight into ongoing controversies concerning sensitivity to functional deficits following mTBI and when the window for treatment or restoration ends.

  1. Older Adults with Mild Cognitive Impairments Show Less Driving Errors after a Multiple Sessions Simulator Training Program but Do Not Exhibit Long Term Retention.

    Science.gov (United States)

    Teasdale, Normand; Simoneau, Martin; Hudon, Lisa; Germain Robitaille, Mathieu; Moszkowicz, Thierry; Laurendeau, Denis; Bherer, Louis; Duchesne, Simon; Hudon, Carol

    2016-01-01

    The driving performance of individuals with mild cognitive impairment (MCI) is suboptimal when compared to healthy older adults. It is expected that the driving will worsen with the progression of the cognitive decline and thus, whether or not these individuals should continue to drive is a matter of debate. The aim of the study was to provide support to the claim that individuals with MCI can benefit from a training program and improve their overall driving performance in a driving simulator. Fifteen older drivers with MCI participated in five training sessions in a simulator (over a 21-day period) and in a 6-month recall session. During training, they received automated auditory feedback on their performance when an error was noted about various maneuvers known to be suboptimal in MCI individuals (for instance, weaving, omitting to indicate a lane change, to verify a blind spot, or to engage in a visual search before crossing an intersection). The number of errors was compiled for eight different maneuvers for all sessions. For the initial five sessions, a gradual and significant decrease in the number of errors was observed, indicating learning and safer driving. The level of performance, however, was not maintained at the 6-month recall session. Nevertheless, the initial learning observed opens up possibilities to undertake more regular interventions to maintain driving skills and safe driving in MCI individuals.

  2. The Internationalization of the Meetings - Incentives - Conventions - and Exhibitions - (MICE industry: Its Influences on the Actors in the Tourism Business Activity

    Directory of Open Access Journals (Sweden)

    Natalia Smagina

    2017-02-01

    Full Text Available This article is aimed to analyze the link between internationalization and Meetings-, Incentives-, Conventions- and Exhibitions (MICE industry which is refer to the destination development. A comprehensive review of the totality of the processes associated with the regional market of business tourism, allowed to develop a number of actual tools that make it possible to obtain important practical results. One of these tools is a so called public-private partnership (PPP, to strengthen the trust between government and business representatives on regional level. This article reveals the cooperation process between foreign private companies and the local government in organizing the development of the industry connected to MICE. This vision may help all parties connected to the MICE industry to achieve a new level of understanding of the business tourism destination as a result of internationalization processes.

  3. ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

    Science.gov (United States)

    2013-01-01

    Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious

  4. Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization

    Directory of Open Access Journals (Sweden)

    Amanda Clause

    2017-06-01

    Full Text Available Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits. In α9KO mice, the developmental refinement of inhibitory afferents to the lateral superior olive is disturbed, resulting in decreased tonotopic organization of this sound localization nucleus. In this study, we used behavioral tests to investigate whether the circuit anomalies in α9KO mice correlate with sound localization or sound frequency processing. Using a conditioned lick suppression task to measure sound localization, we found that three out of four α9KO mice showed impaired minimum audible angles. Using a prepulse inhibition of the acoustic startle response paradigm, we found that the ability of α9KO mice to detect sound frequency changes was impaired, whereas their ability to detect sound intensity changes was not. These results demonstrate that cholinergic, nicotinic α9 subunit mediated transmission in the developing cochlear plays an important role in the maturation of hearing.

  5. Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice

    NARCIS (Netherlands)

    Espinosa, J.C.; Andreoletti, O.; Castilla, J.; Herva, M.E.; Morales, M.; Alamillo, E.; San-Segundo, F.D.; Lacroux, C.; Lugan, S.; Salguero, F.J.; Langeveld, J.P.M.; Torres, J.M.

    2007-01-01

    Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions

  6. Prion protein-deficient mice exhibit decreased CD4 T and LTi cell numbers and impaired spleen structure.

    Science.gov (United States)

    Kim, Soochan; Han, Sinsuk; Lee, Ye Eun; Jung, Woong-Jae; Lee, Hyung Soo; Kim, Yong-Sun; Choi, Eun-Kyoung; Kim, Mi-Yeon

    2016-01-01

    The cellular prion protein is expressed in almost all tissues, including the central nervous system and lymphoid tissues. To investigate the effects of the prion protein in lymphoid cells and spleen structure formation, we used prion protein-deficient (Prnp(0/0)) Zürich I mice generated by inactivation of the Prnp gene. Prnp(0/0) mice had decreased lymphocytes, in particular, CD4 T cells and lymphoid tissue inducer (LTi) cells. Decreased CD4 T cells resulted from impaired expression of CCL19 and CCL21 in the spleen rather than altered chemokine receptor CCR7 expression. Importantly, some of the white pulp regions in spleens from Prnp(0/0) mice displayed impaired T zone structure as a result of decreased LTi cell numbers and altered expression of the lymphoid tissue-organizing genes lymphotoxin-α and CXCR5, although expression of the lymphatic marker podoplanin and CXCL13 by stromal cells was not affected. In addition, CD3(-)CD4(+)IL-7Rα(+) LTi cells were rarely detected in impaired white pulp in spleens of these mice. These data suggest that the prion protein is required to form the splenic white pulp structure and for development of normal levels of CD4 T and LTi cells. Copyright © 2015. Published by Elsevier GmbH.

  7. Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy.

    Science.gov (United States)

    Marzuca-Nassr, Gabriel Nasri; Murata, Gilson Masahiro; Martins, Amanda Roque; Vitzel, Kaio Fernando; Crisma, Amanda Rabello; Torres, Rosângela Pavan; Mancini-Filho, Jorge; Kang, Jing Xuan; Curi, Rui

    2017-10-06

    The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively), muscle isotonic and tetanic force (by 29% and 18%, respectively), CSA of the soleus muscle (by 36%), and soleus muscle fibers (by 45%). Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs) ratio as compared with C57BL/6 wild-type mice (56%, p Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.

  8. D-penicillamine exhibits a higher radioprotective effect in suckling mice than in grown-up animals

    International Nuclear Information System (INIS)

    Oroszlan, Gy.; Lakatos, L.; Dezsi, Z.; Hatvani, I.; Pintye, E.; Karmazsin, L.; Orvostudomanyi Egyetem, Debrecen; Orvostudomanyi Egyetem, Debrecen

    1982-01-01

    Grown-up and suckling mice were exposed to whole-body 60 Co-irradiation of 6-10 Gy. The survival time was significantly increased in suckling animals by 3000 mg per kg body weight D-penicillamine applied intraperitoneally 60 min before irradiation, whereas the same treatment had no significant effect in grown-up animals. (L.E.)

  9. Female mucopolysaccharidosis IIIA mice exhibit hyperactivity and a reduced sense of danger in the open field test.

    Directory of Open Access Journals (Sweden)

    Alex Langford-Smith

    Full Text Available Reliable behavioural tests in animal models of neurodegenerative diseases allow us to study the natural history of disease and evaluate the efficacy of novel therapies. Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A, is a severe, neurodegenerative lysosomal storage disorder caused by a deficiency in the heparan sulphate catabolising enzyme, sulfamidase. Undegraded heparan sulphate accumulates, resulting in lysosomal enlargement and cellular dysfunction. Patients suffer a progressive loss of motor and cognitive function with severe behavioural manifestations and premature death. There is currently no treatment. A spontaneously occurring mouse model of the disease has been described, that has approximately 3% of normal enzyme activity levels. Behavioural phenotyping of the MPS IIIA mouse has been previously reported, but the results are conflicting and variable, even after full backcrossing to the C57BL/6 background. Therefore we have independently backcrossed the MPS IIIA model onto the C57BL/6J background and evaluated the behaviour of male and female MPS IIIA mice at 4, 6 and 8 months of age using the open field test, elevated plus maze, inverted screen and horizontal bar crossing at the same circadian time point. Using a 60 minute open field, we have demonstrated that female MPS IIIA mice are hyperactive, have a longer path length, display rapid exploratory behaviour and spend less time immobile than WT mice. Female MPS IIIA mice also display a reduced sense of danger and spend more time in the centre of the open field. There were no significant differences found between male WT and MPS IIIA mice and no differences in neuromuscular strength were seen with either sex. The altered natural history of behaviour that we observe in the MPS IIIA mouse will allow more accurate evaluation of novel therapeutics for MPS IIIA and potentially other neurodegenerative disorders.

  10. Female mucopolysaccharidosis IIIA mice exhibit hyperactivity and a reduced sense of danger in the open field test.

    Science.gov (United States)

    Langford-Smith, Alex; Langford-Smith, Kia J; Jones, Simon A; Wynn, Robert F; Wraith, J E; Wilkinson, Fiona L; Bigger, Brian W

    2011-01-01

    Reliable behavioural tests in animal models of neurodegenerative diseases allow us to study the natural history of disease and evaluate the efficacy of novel therapies. Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A), is a severe, neurodegenerative lysosomal storage disorder caused by a deficiency in the heparan sulphate catabolising enzyme, sulfamidase. Undegraded heparan sulphate accumulates, resulting in lysosomal enlargement and cellular dysfunction. Patients suffer a progressive loss of motor and cognitive function with severe behavioural manifestations and premature death. There is currently no treatment. A spontaneously occurring mouse model of the disease has been described, that has approximately 3% of normal enzyme activity levels. Behavioural phenotyping of the MPS IIIA mouse has been previously reported, but the results are conflicting and variable, even after full backcrossing to the C57BL/6 background. Therefore we have independently backcrossed the MPS IIIA model onto the C57BL/6J background and evaluated the behaviour of male and female MPS IIIA mice at 4, 6 and 8 months of age using the open field test, elevated plus maze, inverted screen and horizontal bar crossing at the same circadian time point. Using a 60 minute open field, we have demonstrated that female MPS IIIA mice are hyperactive, have a longer path length, display rapid exploratory behaviour and spend less time immobile than WT mice. Female MPS IIIA mice also display a reduced sense of danger and spend more time in the centre of the open field. There were no significant differences found between male WT and MPS IIIA mice and no differences in neuromuscular strength were seen with either sex. The altered natural history of behaviour that we observe in the MPS IIIA mouse will allow more accurate evaluation of novel therapeutics for MPS IIIA and potentially other neurodegenerative disorders.

  11. Absence of Wdr13 Gene Predisposes Mice to Mild Social Isolation – Chronic Stress, Leading to Depression-Like Phenotype Associated With Differential Expression of Synaptic Proteins

    Science.gov (United States)

    Mitra, Shiladitya; Sameer Kumar, Ghantasala S.; Jyothi Lakshmi, B.; Thakur, Suman; Kumar, Satish

    2018-01-01

    We earlier reported that the male mice lacking the Wdr13 gene (Wdr13-/0) showed mild anxiety, better memory retention, and up-regulation of synaptic proteins in the hippocampus. With increasing evidences from parallel studies in our laboratory about the possible role of Wdr13 in stress response, we investigated its role in brain. We observed that Wdr13 transcript gets up-regulated in the hippocampus of the wild-type mice exposed to stress. To further dissect its function, we analyzed the behavioral and molecular phenotypes of Wdr13-/0 mice when subjected to mild chronic psychological stress, namely; mild (attenuated) social isolation. We employed iTRAQ based quantitative proteomics, real time PCR and western blotting to investigate molecular changes. Three weeks of social isolation predisposed Wdr13-/0 mice to anhedonia, heightened anxiety-measured by Open field test (OFT), increased behavior despair- measured by Forced swim test (FST) and reduced dendritic branching along with decreased spine density of hippocampal CA1 neurons as compared to wild-type counterparts. This depression-like-phenotype was however ameliorated when treated with anti-depressant imipramine. Molecular analysis revealed that out of 1002 quantified proteins [1% False discovery rate (FDR), at-least two unique peptides], strikingly, a significant proportion of synaptic proteins including, SYN1, CAMK2A, and RAB3A were down-regulated in the socially isolated Wdr13-/0 mice as compared to its wild-type counterparts. This was in contrast to the elevated levels of these proteins in non-stressed mutants as compared to the controls. We hypothesized that a de-regulated transcription factor upstream of the synaptic genes might be responsible for the observed phenotype. Indeed, in the socially isolated Wdr13-/0 mice, there was an up-regulation of GATA1 – a transcription factor that negatively regulates synaptic genes and has been associated with Major Depression (MD) in humans. The present study

  12. Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

    DEFF Research Database (Denmark)

    Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

    2003-01-01

    of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

  13. Mice deficient in cryptochrome 1 (Cry1-/- exhibit resistance to obesity induced by a high fat diet

    Directory of Open Access Journals (Sweden)

    Guy eGriebel

    2014-04-01

    Full Text Available Disruption of circadian clock enhances the risk of metabolic syndrome, obesity, and type 2 diabetes. Circadian clocks rely on a highly regulated network of transcriptional and translational loops that drive clock-controlled gene expression. Among these transcribed clock genes are cryptochrome (CRY family members, which comprise Cry1 and Cry2. While the metabolic effects of deletion of several core components of the clock gene machinery have been well characterized, those of selective inactivation of Cry1 or Cry2 genes have not been described. In this study we demonstrate that ablation of Cry1, but not Cry2, prevents high-fat diet (HFD-induced obesity in mice. Despite similar caloric intake, Cry1-/- mice on HFD gained markedly less weight (-18 % at the end of the 16-week experiment and displayed reduced fat accumulation compared to wild-type (WT littermates (-61 %, suggesting increased energy expenditure. Analysis of serum lipid and glucose profiles showed no difference between Cry1-/- and WT mice. Both Cry1-/- and Cry2-/- mice are indistinguishable from WT controls in body weight, fat and protein contents, and food consumption when they are allowed unlimited access to a standard rodent diet. We conclude that although CRY signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, Cry1 may play a role in readjusting energy balance under changing nutritional circumstances. These studies reinforce the important role of circadian clock genes in energy homeostasis and suggest that Cry1 is a plausible target for antiobesity therapy.

  14. Mice deficient in cryptochrome 1 (cry1 (-/-)) exhibit resistance to obesity induced by a high-fat diet.

    Science.gov (United States)

    Griebel, Guy; Ravinet-Trillou, Christine; Beeské, Sandra; Avenet, Patrick; Pichat, Philippe

    2014-01-01

    Disruption of circadian clock enhances the risk of metabolic syndrome, obesity, and type 2 diabetes. Circadian clocks rely on a highly regulated network of transcriptional and translational loops that drive clock-controlled gene expression. Among these transcribed clock genes are cryptochrome (CRY) family members, which comprise Cry1 and Cry2. While the metabolic effects of deletion of several core components of the clock gene machinery have been well characterized, those of selective inactivation of Cry1 or Cry2 genes have not been described. In this study, we demonstrate that ablation of Cry1, but not Cry2, prevents high-fat diet (HFD)-induced obesity in mice. Despite similar caloric intake, Cry1 (-/-) mice on HFD gained markedly less weight (-18%) at the end of the 16-week experiment and displayed reduced fat accumulation compared to wild-type (WT) littermates (-61%), suggesting increased energy expenditure. Analysis of serum lipid and glucose profiles showed no difference between Cry1 (-/-) and WT mice. Both Cry1 (-/-) and Cry2 (-/-) mice are indistinguishable from WT controls in body weight, fat and protein contents, and food consumption when they are allowed unlimited access to a standard rodent diet. We conclude that although CRY signaling may not be essential for the maintenance of energy homeostasis under steady-state nutritional conditions, Cry1 may play a role in readjusting energy balance under changing nutritional circumstances. These studies reinforce the important role of circadian clock genes in energy homeostasis and suggest that Cry1 is a plausible target for anti-obesity therapy.

  15. Sirt3 deficiency does not affect venous thrombosis or NETosis despite mild elevation of intracellular ROS in platelets and neutrophils in mice.

    Directory of Open Access Journals (Sweden)

    Hideki Hayashi

    Full Text Available Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets. Using Sirt3-/- mice as a model of accelerated aging, we investigated the effects of Sirt3 deficiency on NETosis and platelet function, aiming to detect enhancement of thrombosis. More mitochondrial reactive oxygen species (ROS were generated in neutrophils and platelets of Sirt3-/- mice compared to WT, when stimulated with a low concentration of phorbol 12-myristate 13-acetate (PMA and a high concentration of thrombin, respectively. There were no differences in in vitro NETosis, with or without stimulation. Platelet aggregation was mildly augmented in Sirt3-/- mice compared to WT mice, when stimulated with a low concentration of collagen. The effect of Sirt3 deficiency on platelet and neutrophil activation in vivo was examined by the venous thrombosis model of inferior vena cava stenosis. Elevation of plasma DNA concentration was observed after stenosis in both genotypes, but no difference was shown between the two genotypes. The systemic response to thrombosis was enhanced in Sirt3-/- mice with significantly elevated neutrophil count and reduced platelet count. However, no differences were observed in incidence of thrombus formation, thrombus weight and thrombin-antithrombin complex generation between WT and Sirt3-/- mice. We conclude that Sirt3 does not considerably impact NET formation, platelet function, or venous

  16. Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Survive in Kupffer Cells and Exhibit High Virulence in Mice

    Directory of Open Access Journals (Sweden)

    Takuto Oyama

    2016-06-01

    Full Text Available Although Staphylococcus aureus is part of the normal body flora, heavy usage of antibiotics has resulted in the emergence of methicillin-resistant strains (MRSA. MRSA can form biofilms and cause indwelling foreign body infections, bacteremia, soft tissue infections, endocarditis, and osteomyelitis. Using an in vitro assay, we screened 173 clinical blood isolates of MRSA and selected 20 high-biofilm formers (H-BF and low-biofilm formers (L-BF. These were intravenously administered to mice and the general condition of mice, the distribution of bacteria, and biofilm in the liver, lung, spleen, and kidney were investigated. MRSA count was the highest in the liver, especially within Kupffer cells, which were positive for acid polysaccharides that are associated with intracellular biofilm. After 24 h, the general condition of the mice worsened significantly in the H-BF group. In the liver, bacterial deposition and aggregation and the biofilm-forming spot number were all significantly greater for H-BF group than for L-BF. CFU analysis revealed that bacteria in the H-BF group survived for long periods in the liver. These results indicate that the biofilm-forming ability of MRSA is a crucial factor for intracellular persistence, which could lead to chronic infections.

  17. Antidepressant-like Effect of Bacopaside I in Mice Exposed to Chronic Unpredictable Mild Stress by Modulating the Hypothalamic-Pituitary-Adrenal Axis Function and Activating BDNF Signaling Pathway.

    Science.gov (United States)

    Zu, Xianpeng; Zhang, Mingjian; Li, Wencai; Xie, Haisheng; Lin, Zhang; Yang, Niao; Liu, Xinru; Zhang, Weidong

    2017-11-01

    Preliminary studies conducted in our laboratory have confirmed that Bacopaside I (BS-I), a saponin compound isolated from Bacopa monnieri, displayed antidepressant-like activity in the mouse behavioral despair model. The present investigation aimed to verify the antidepressant-like action of BS-I using a mouse model of behavioral deficits induced by chronic unpredictable mild stress (CUMS) and further probe its underlying mechanism of action. Mice were exposed to CUMS for a period of 5 consecutive weeks to induce depression-like behavior. Then, oral gavage administrations with vehicle (model group), fluoxetine (12 mg/kg, positive group) or BS-I (5, 15, 45 mg/kg, treated group) once daily were started during the last two weeks of CUMS procedure. The results showed that BS-I significantly ameliorated CUMS-induced depression-like behaviors in mice, as characterized by an elevated sucrose consumption in the sucrose preference test and reduced immobility time without affecting spontaneous locomotor activity in the forced swimming test, tail suspension test and open field test. It was also found that BS-I treatment reversed the increased level of plasma corticosterone and decreased mRNA and protein expressions of glucocorticoid receptor induced by CUMS exposure, indicating that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity of CUMS-exposed mice was restored by BS-I treatment. Furthermore, chronic administration of BS-I elevated expression levels of brain-derived neurotrophic factor (BDNF) (mRNA and protein) and activated the phosphorylation of extracellular signal-regulated kinase and cAMP response element-binding protein in the hippocampus and prefrontal cortex in mice subjected to CUMS procedure. Taken together, these results indicated that BS-I exhibited an obvious antidepressant-like effect in mouse model of CUMS-induced depression that was mediated, at least in part, by modulating HPA hyperactivity and activating BDNF signaling pathway.

  18. HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice.

    Science.gov (United States)

    Kruse, Robert L; Shum, Thomas; Tashiro, Haruko; Barzi, Mercedes; Yi, Zhongzhen; Whitten-Bauer, Christina; Legras, Xavier; Bissig-Choisat, Beatrice; Garaigorta, Urtzi; Gottschalk, Stephen; Bissig, Karl-Dimiter

    2018-04-06

    Chronic hepatitis B virus (HBV) infection remains incurable. Although HBsAg-specific chimeric antigen receptor (HBsAg-CAR) T cells have been generated, they have not been tested in animal models with authentic HBV infection. We generated a novel CAR targeting HBsAg and evaluated its ability to recognize HBV+ cell lines and HBsAg particles in vitro. In vivo, we tested whether human HBsAg-CAR T cells would have efficacy against HBV-infected hepatocytes in human liver chimeric mice. HBsAg-CAR T cells recognized HBV-positive cell lines and HBsAg particles in vitro as judged by cytokine production. However, HBsAg-CAR T cells did not kill HBV-positive cell lines in cytotoxicity assays. Adoptive transfer of HBsAg-CAR T cells into HBV-infected humanized mice resulted in accumulation within the liver and a significant decrease in plasma HBsAg and HBV-DNA levels compared with control mice. Notably, the fraction of HBV core-positive hepatocytes among total human hepatocytes was greatly reduced after HBsAg-CAR T cell treatment, pointing to noncytopathic viral clearance. In agreement, changes in surrogate human plasma albumin levels were not significantly different between treatment and control groups. HBsAg-CAR T cells have anti-HBV activity in an authentic preclinical HBV infection model. Our results warrant further preclinical exploration of HBsAg-CAR T cells as immunotherapy for HBV. Copyright © 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  19. Mice with an Oncogenic HRAS Mutation are Resistant to High-Fat Diet-Induced Obesity and Exhibit Impaired Hepatic Energy Homeostasis

    Directory of Open Access Journals (Sweden)

    Daiju Oba

    2018-01-01

    Full Text Available Costello syndrome is a “RASopathy” that is characterized by growth retardation, dysmorphic facial appearance, hypertrophic cardiomyopathy and tumor predisposition. >80% of patients with Costello syndrome harbor a heterozygous germline G12S mutation in HRAS. Altered metabolic regulation has been suspected because patients with Costello syndrome exhibit hypoketotic hypoglycemia and increased resting energy expenditure, and their growth is severely retarded. To examine the mechanisms of energy reprogramming by HRAS activation in vivo, we generated knock-in mice expressing a heterozygous Hras G12S mutation (HrasG12S/+ mice as a mouse model of Costello syndrome. On a high-fat diet, HrasG12S/+ mice developed a lean phenotype with microvesicular hepatic steatosis, resulting in early death compared with wild-type mice. Under starvation conditions, hypoketosis and elevated blood levels of long-chain fatty acylcarnitines were observed, suggesting impaired mitochondrial fatty acid oxidation. Our findings suggest that the oncogenic Hras mutation modulates energy homeostasis in vivo.

  20. Virulent variants emerging in mice infected with the apathogenic prototype strain of the parvovirus minute virus of mice exhibit a capsid with low avidity for a primary receptor.

    Science.gov (United States)

    Rubio, Mari-Paz; López-Bueno, Alberto; Almendral, José M

    2005-09-01

    The mechanisms involved in the emergence of virulent mammalian viruses were investigated in the adult immunodeficient SCID mouse infected by the attenuated prototype strain of the parvovirus Minute Virus of Mice (MVMp). Cloned MVMp intravenously inoculated in mice consistently evolved during weeks of subclinical infection to variants showing altered plaque phenotypes. All the isolated large-plaque variants spread systemically from the oronasal cavity and replicated in major organs (brain, kidney, liver), in sharp contrast to the absolute inability of the MVMp and small-plaque variants to productively invade SCID organs by this natural route of infection. The virulent variants retained the MVMp capacity to infect mouse fibroblasts, consistent with the lack of genetic changes across the 220-to-335 amino acid sequence of VP2, a capsid domain containing main determinants of MVM tropism. However, the capsid of the virulent variants shared a lower affinity than the wild type for a primary receptor used in the cytotoxic infection. The capsid gene of a virulent variant engineered in the MVMp background endowed the recombinant virus with a large-plaque phenotype, lower affinity for the receptor, and productive invasiveness by the oronasal route in SCID mice, eventually leading to 100% mortality. In the analysis of virulence in mice, both MVMp and the recombinant virus similarly gained the bloodstream 1 to 2 days postoronasal inoculation and remained infectious when adsorbed to blood cells in vitro. However, the wild-type MVMp was cleared from circulation a few days afterwards, in contrast to the viremia of the recombinant virus, which was sustained for life. Significantly, attachment to an abundant receptor of primary mouse kidney epithelial cells by both viruses could be quantitatively competed by wild-type MVMp capsids, indicating that virulence is not due to an extended receptor usage in target tissues. We conclude that the selection of capsid-receptor interactions of

  1. Dietary broccoli mildly improves neuroinflammation in aged mice but does not reduce lipopolysaccharide-induced sickness behavior.

    Science.gov (United States)

    Townsend, Brigitte E; Chen, Yung-Ju; Jeffery, Elizabeth H; Johnson, Rodney W

    2014-11-01

    Aging is associated with oxidative stress and heightened inflammatory response to infection. Dietary interventions to reduce these changes are therefore desirable. Broccoli contains glucoraphanin, which is converted to sulforaphane (SFN) by plant myrosinase during cooking preparation or digestion. Sulforaphane increases antioxidant enzymes including NAD(P)H quinone oxidoreductase and heme oxygenase I and inhibits inflammatory cytokines. We hypothesized that dietary broccoli would support an antioxidant response in brain and periphery of aged mice and inhibit lipopolysaccharide (LPS)-induced inflammation and sickness. Young adult and aged mice were fed control or 10% broccoli diet for 28 days before an intraperitoneal LPS injection. Social interactions were assessed 2, 4, 8, and 24 hours after LPS, and mRNA was quantified in liver and brain at 24 hours. Dietary broccoli did not ameliorate LPS-induced decrease in social interactions in young or aged mice. Interleukin-1β (IL-1β) expression was unaffected by broccoli consumption but was induced by LPS in brain and liver of adult and aged mice. In addition, IL-1β was elevated in brain of aged mice without LPS. Broccoli consumption decreased age-elevated cytochrome b-245 β, an oxidative stress marker, and reduced glial activation markers in aged mice. Collectively, these data suggest that 10% broccoli diet provides a modest reduction in age-related oxidative stress and glial reactivity, but is insufficient to inhibit LPS-induced inflammation. Thus, it is likely that SFN would need to be provided in supplement form to control the inflammatory response to LPS. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Emodin opposes chronic unpredictable mild stress induced depressive-like behavior in mice by upregulating the levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor.

    Science.gov (United States)

    Li, Meng; Fu, Qiang; Li, Ying; Li, Shanshan; Xue, Jinsong; Ma, Shiping

    2014-10-01

    Emodin, the major active component of Rhubarb, has shown neuroprotective activity. This study is attempted to investigate whether emodin possesses beneficial effects on chronic unpredictable mild stress (CUMS)-induced behavioral deficits (depression-like behaviors) and explore the possible mechanisms. ICR mice were subjected to chronic unpredictable mild stress for 42 consecutive days. Then, emodin and fluoxetine (positive control drug) were administered for 21 consecutive days at the last three weeks of CUMS procedure. The classical behavioral tests: open field test (OFT), sucrose preference test (SPT), tail suspension test (TST) and forced swimming test (FST) were applied to evaluate the antidepressant effects of emodin. Then plasma corticosterone concentration, hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) levels were tested to probe the mechanisms. Our results indicated that 6 weeks of CUMS exposure induced significant depression-like behavior, with high, plasma corticosterone concentration and low hippocampal GR and BDNF expression levels. Whereas, chronic emodin (20, 40 and 80 mg/kg) treatments reversed the behavioral deficiency induced by CUMS exposure. Treatment with emodin normalized the change of plasma corticosterone level, which demonstrated that emodin could partially restore CUMS-induced HPA axis impairments. Besides, hippocampal GR (mRNA and protein) and BDNF (mRNA) expressions were also up-regulated after emodin treatments. In conclusion, emodin remarkably improved depression-like behavior in CUMS mice and its antidepressant activity is mediated, at least in part, by the up-regulating GR and BDNF levels in hippocampus. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. cGMP-dependent protein kinase type II knockout mice exhibit working memory impairments, decreased repetitive behavior, and increased anxiety-like traits.

    Science.gov (United States)

    Wincott, Charlotte M; Abera, Sinedu; Vunck, Sarah A; Tirko, Natasha; Choi, Yoon; Titcombe, Roseann F; Antoine, Shannon O; Tukey, David S; DeVito, Loren M; Hofmann, Franz; Hoeffer, Charles A; Ziff, Edward B

    2014-10-01

    Neuronal activity regulates AMPA receptor trafficking, a process that mediates changes in synaptic strength, a key component of learning and memory. This form of plasticity may be induced by stimulation of the NMDA receptor which, among its activities, increases cyclic guanosine monophosphate (cGMP) through the nitric oxide synthase pathway. cGMP-dependent protein kinase type II (cGKII) is ultimately activated via this mechanism and AMPA receptor subunit GluA1 is phosphorylated at serine 845. This phosphorylation contributes to the delivery of GluA1 to the synapse, a step that increases synaptic strength. Previous studies have shown that cGKII-deficient mice display striking spatial learning deficits in the Morris Water Maze compared to wild-type littermates as well as lowered GluA1 phosphorylation in the postsynaptic density of the prefrontal cortex (Serulle et al., 2007; Wincott et al., 2013). In the current study, we show that cGKII knockout mice exhibit impaired working memory as determined using the prefrontal cortex-dependent Radial Arm Maze (RAM). Additionally, we report reduced repetitive behavior in the Marble Burying task (MB), and heightened anxiety-like traits in the Novelty Suppressed Feeding Test (NSFT). These data suggest that cGKII may play a role in the integration of information that conveys both anxiety-provoking stimuli as well as the spatial and environmental cues that facilitate functional memory processes and appropriate behavioral response. Published by Elsevier Inc.

  4. Effect of chronic mild stress on hippocampal transcriptome in mice selected for high and low stress-induced analgesia and displaying different emotional behaviors.

    Science.gov (United States)

    Lisowski, Pawel; Juszczak, Grzegorz R; Goscik, Joanna; Wieczorek, Marek; Zwierzchowski, Lech; Swiergiel, Artur H

    2011-01-01

    There is increasing evidence that mood disorders may derive from the impact of environmental pressure on genetically susceptible individuals. Stress-induced hippocampal plasticity has been implicated in depression. We studied hippocampal transcriptomes in strains of mice that display high (HA) and low (LA) swim stress-induced analgesia and that differ in emotional behaviors and responses to different classes of antidepressants. Chronic mild stress (CMS) affected expression of a number of genes common for both strains. CMS also produced strain specific changes in expression suggesting that hippocampal responses to stress depend on genotype. Considerably larger number of genes, biological processes, molecular functions, biochemical pathways, and gene networks were affected by CMS in LA than in HA mice. The results suggest that potential drug targets against detrimental effects of stress include glutamate transporters, and cholinergic, cholecystokinin (CCK), glucocorticoids, and thyroid hormones receptors. Furthermore, some biological processes evoked by stress and different between the strains, such as apoptosis, neurogenesis and chromatin modifications, may be responsible for the long-term, irreversible effects of stress and suggest a role for epigenetic regulation of mood related stress responses. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

  5. Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and "depressed" mice exposed to chronic mild stress.

    Science.gov (United States)

    Franceschelli, A; Sens, J; Herchick, S; Thelen, C; Pitychoutis, P M

    2015-04-02

    During the past decade, one of the most striking discoveries in the treatment of major depression was the clinical finding that a single infusion of a sub-anesthetic dose of the N-methyl-d-aspartate receptor antagonist ketamine produces a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks) antidepressant effect in both treatment-resistant depressed patients and in animal models of depression. Notably, converging clinical and preclinical evidence support that responsiveness to antidepressant drugs is sex-differentiated. Strikingly, research regarding the antidepressant-like effects of ketamine has focused almost exclusively on the male sex. Herein we report that female C57BL/6J stress-naïve mice are more sensitive to the rapid and the sustained antidepressant-like effects of ketamine in the forced swim test (FST). In particular, female mice responded to lower doses of ketamine (i.e. 3mg/kg at 30 min and 5mg/kg at 24h post-injection), doses that were not effective in their male counterparts. Moreover, tissue levels of the excitatory amino acids glutamate and aspartate, as well as serotonergic activity, were affected in a sex-dependent manner in the prefrontal cortex and the hippocampus, at the same time-points. Most importantly, a single injection of ketamine (10mg/kg) induced sex-dependent behavioral effects in mice subjected to the chronic mild stress (CMS) model of depression. Intriguingly, female mice were more reactive to the earlier effects of ketamine, as assessed in the open field and the FST (at 30 min and 24h post-treatment, respectively) but the antidepressant potential of the drug proved to be longer lasting in males, as assessed in the splash test and the FST (days 5 and 7 post-treatment, respectively). Taken together, present data revealed that ketamine treatment induces sex-dependent rapid and sustained neurochemical and behavioral antidepressant-like effects in stress-naïve and CMS-exposed C57BL/6J mice. Copyright © 2015 IBRO

  6. Reduced coupling of oxidative phosphorylation in vivo precedes electron transport chain defects due to mild oxidative stress in mice.

    Directory of Open Access Journals (Sweden)

    Michael P Siegel

    Full Text Available Oxidative stress and mitochondrial function are at the core of many degenerative conditions. However, the interaction between oxidative stress and in vivo mitochondrial function is unclear. We used both pharmacological (2 week paraquat (PQ treatment of wild type mice and transgenic (mice lacking Cu, Zn-superoxide dismutase (SOD1(-/- models to test the effect of oxidative stress on in vivo mitochondrial function in skeletal muscle. Magnetic resonance and optical spectroscopy were used to measure mitochondrial ATP and oxygen fluxes and cell energetic state. In both models of oxidative stress, coupling of oxidative phosphorylation was significantly lower (lower P/O at rest in vivo in skeletal muscle and was dose-dependent in the PQ model. Despite this reduction in efficiency, in vivo mitochondrial phosphorylation capacity (ATPmax was maintained in both models, and ex vivo mitochondrial respiration in permeabilized muscle fibers was unchanged following PQ treatment. In association with the reduced P/O, PQ treatment led to a dose-dependent reduction in PCr/ATP ratio and increased phosphorylation of AMPK. These results indicate that oxidative stress uncouples oxidative phosphorylation in vivo and results in energetic stress in the absence of defects in the mitochondrial electron transport chain.

  7. Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress.

    Science.gov (United States)

    Culig, Luka; Surget, Alexandre; Bourdey, Marlene; Khemissi, Wahid; Le Guisquet, Anne-Marie; Vogel, Elise; Sahay, Amar; Hen, René; Belzung, Catherine

    2017-11-01

    Major depression is hypothesized to be associated with dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and impairments in adult hippocampal neurogenesis. Adult-born hippocampal neurons are required for several effects of antidepressants and increasing the rate of adult hippocampal neurogenesis (AHN) before exposure to chronic corticosterone is sufficient to protect against its harmful effects on behavior. However, it is an open question if increasing AHN after the onset of chronic stress exposure would be able to rescue behavioral deficits and which mechanisms might be involved in recovery. We investigated this question by using a 10-week unpredictable chronic mild stress (UCMS) model on a transgenic mouse line (iBax mice), in which the pro-apoptotic gene Bax can be inducibly ablated in neural stem cells following Tamoxifen injection, therefore enhancing the survival of newborn neurons in the adult brain. We did not observe any effect of our treatment in non-stress conditions, but we did find that increasing AHN after 2 weeks of UCMS is sufficient to counteract the effects of UCMS on certain behaviors (splash test and changes in coat state) and endocrine levels and thus to display some antidepressant-like effects. We observed that increasing AHN lowered the elevated basal corticosterone levels in mice exposed to UCMS. This was accompanied by a tamoxifen-induced reversal of the lack of stress-induced decrease in neuronal activation in the anteromedial division of the bed nucleus of the stria terminalis (BSTMA) after intrahippocampal dexamethasone infusion, pointing to a possible mechanism through which adult-born neurons might have exerted their effects. Our results contribute to the neurogenesis hypothesis of depression by suggesting that increasing AHN may be beneficial not just before, but also after exposure to stress by counteracting several of its effects, in part through regulating the HPA axis. Copyright © 2017 Elsevier Ltd. All rights

  8. Technology Exhibition

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1979-09-15

    Linked to the 25th Anniversary celebrations, an exhibition of some of CERN's technological achievements was opened on 22 June. Set up in a new 600 m{sup 2} Exhibition Hall on the CERN site, the exhibition is divided into eight technology areas — magnets, vacuum, computers and data handling, survey and alignment, radiation protection, beam monitoring and handling, detectors, and workshop techniques.

  9. Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang; Jin, Wenwen

    2014-05-01

    Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain.

  10. Ondansetron attenuates depression co-morbid with obesity in obese mice subjected to chronic unpredictable mild stress; an approach using behavioral battery tests.

    Science.gov (United States)

    Kurhe, Yeshwant; Radhakrishnan, Mahesh; Gupta, Deepali

    2014-09-01

    The aim of the present work was to investigate the role of ondansetron on the high fat diet (HFD) induced obese mice for behavioral and biochemical alterations using chronic unpredictable mild stress (CUMS) model of depression. Animals were fed with high fat diet for 14 weeks and subjected to different stress procedures for 4 weeks. Treatment with ondansetron was started on day 15. After day 28 behavioral assays and biochemical estimations were performed. Behavioral paradigms viz. sucrose preference test, locomotor score, forced swim test (FST) and elevated plus maze (EPM), whereas biochemical parameters like plasma glucose, total cholesterol, triglycerides and total proteins were estimated. Results examines that in behavioral assays, ondansetron significantly (P glucose, total cholesterol, triglycerides and total proteins were significantly (P glucose level indicates that, it could be "altered glucose level" playing an important role in depression co-morbid with obesity. Ondansetron through allosteric modulation of serotonergic system elevates the serotonin level and thereby regulates the insulin secretion and hence, reversing the "altered glucose level", could be the possible antidepressive-like mechanism against depression co-morbid with obesity.

  11. Immersive Exhibitions

    DEFF Research Database (Denmark)

    Achiam, Marianne

    2015-01-01

    The immersive exhibition is a specialized exhibition genre in museums, which creates the illusion of time and place by representing key characteristics of a reference world and by integrating the visitor in this three-dimensionally reconstructed world (Mortensen 2010). A successful representation...... of the reference world depends on three criteria: whether the exhibition is staged as a coherent whole with all the displayed objects supporting the representation, whether the visitor is integrated as a component of the exhibition, and whether the content and message of the exhibition become dramatized...

  12. Exhibit Engineering

    DEFF Research Database (Denmark)

    Mortensen, Marianne Foss

    Science museums define the objectives of their exhibitions in terms of visitor learning outcomes. Yet, exhibit designers lack theoretical and empirical research findings on which to base the creation of such educational environments. Here, this shortcoming is addressed through the development...... of tools and processes to guide the design of educational science exhibits. The guiding paradigm for this development is design-based research, which is characterised by an iterative cycle of design, enactment, and analysis. In the design phase, an educational intervention is planned and carried out based...... on the generation of theoretical ideas for exhibit design is offered in a fourth and parallel research undertaking, namely the application of the notion of cultural border-crossing to a hypothetical case of exhibit design....

  13. Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway.

    Science.gov (United States)

    Tao, Weiwei; Dong, Yu; Su, Qiang; Wang, Hanqing; Chen, Yanyan; Xue, Wenda; Chen, Chang; Xia, Baomei; Duan, Jinao; Chen, Gang

    2016-07-15

    Major depression is a common long-lasting or recurrent psychiatric disease with high lifetime prevalence and high incidence of suicide. The main purpose of the current study was to verify whether liquiritigenin conferred an antidepressant-like effect on the depressive mouse model established by unpredictable chronic mild stress (UCMS) and explore its possible mechanism. The results of depression-related behaviors including sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) indicated that both liquiritigenin (7.5mg/kg, 15mg/kg) and fluoxetine (20mg/kg) dramatically improved the depression symptoms. Enzyme-linked immunosorbent assay (ELISA) revealed that treatment with liquiritigenin significantly reduced the concentrations of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α in serum and hippocampus. Compared with the UCMS group, the administrations of liquiritigenin, increased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and decreased Malondialdehyde (MDA) content. Meanwhile, glucocorticoids (GC) content was reduced in the liquiritigenin group, which suggested that liquiritigenin exhibiting the ameliorative effect on activated hypothalamic-pituitary-adrenal (HPA) axis stimulated with UCMS. Mice treated with liquiritigenin showed restored levels of neurotransmitter norepinephrine (NE) and serotonin (5-HT). Western blot analysis displayed up-regulated expressions of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p- mammalian target of rapamycin (mTOR), p-tropomyosin-related kinase B (TrkB), brain-derived neurotrophic factor (BDNF). Thus, it was supposed that liquiritigenin might be useful for the treatment of chronic depression possibly through PI3K/Akt/mTOR mediated BDNF/TrkB pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. CD1d knockout mice exhibit aggravated contact hypersensitivity responses due to reduced interleukin-10 production predominantly by regulatory B cells

    DEFF Research Database (Denmark)

    Fjelbye, Jonas; Antvorskov, Julie C; Buschard, Karsten

    2015-01-01

    .05) and peritoneal cavity (80.8% decrease; P challenge, which suggests an important regulatory and protective role of CD1d-dependent NKT cells in CHS in our model, at least in part via regulation of IL-10 producing B(regs) ....... knockout (CD1d KO) and wild-type (Wt) mice after contact allergen exposure. For induction of CHS, C57BL/6 CD1d KO mice (n = 6) and C57BL/6 Wt mice (n = 6) were sensitised with 1% (w/v) dinitrochlorobenzene (DNCB) or vehicle for three consecutive days and subsequently challenged with a single dose of 0...

  15. Cystathionine-gamma-lyase deficient mice are protected against the development of multiorgan failure and exhibit reduced inflammatory response during burn.

    Science.gov (United States)

    Ahmad, Akbar; Druzhyna, Nadiya; Szabo, Csaba

    2017-08-01

    Considering the role of H 2 S in critical illness, the aim of this study was to compare the outcome of burn in wild-type mice and in mice deficient in CSE, one of the principal mammalian H 2 S-generating enzymes. Animals were subjected to scald burn. Outcome variables included indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. Plasma levels of H 2 S significantly increased in response to burn in wild-type mice, but remained unchanged in CSE -/- mice. Expression of the three H 2 S-producing enzymes (CSE, CBS and 3-MST) in the lung and liver, and the capacity of tissue homogenates to produce H 2 S, however, was not affected by burn. In CSE deficient mice there was a significant amelioration of burn-induced accumulation of myeloperoxidase levels in heart, lung, liver and kidney and significantly lower degree of malon dialdehyde accumulation in the heart, lung and kidney than in wild-type mice. CSE deficient mice, compared to wild-type mice, showed a significant attenuation of the burn-induced elevation in circulating alkaline aminotransferase and blood urea nitrogen and creatinine levels, indicative of protective effects of CSE deficiency against burn-induced hepatic, and renal functional impairment. Multiple burn-induced inflammatory mediators (TNF-α, IL-1β, IL-4, IL-6, IL-10 and IL-12) were significantly lower in the plasma of CSE -/- animals after burn than in the plasma of wild-type controls subjected to burns. In conclusion, CSE deficiency improves organ function and attenuates the inflammatory response in a murine model of burn. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  16. Measurement of airway function using invasive and non-invasive methods in mild and severe models for allergic airway inflammation in mice

    NARCIS (Netherlands)

    Verheijden, Kim A T; Henricks, Paul A J; Redegeld, Frank A.; Garssen, Johan; Folkerts, Gert

    2014-01-01

    In this study a direct comparison was made between non-invasive and non-ventilated unrestrained whole body plethysmography (Penh) (conscious animals) and the invasive ventilated lung resistance (RL) method (anesthetized animals) in both mild and severe allergic airway inflammation models. Mild

  17. Differential replication of foot-and-mouth disease viruses in mice determine lethality

    Science.gov (United States)

    Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...

  18. GPR39 (zinc receptor) knockout mice exhibit depression-like behavior and CREB/BDNF down-regulation in the hippocampus.

    Science.gov (United States)

    Młyniec, Katarzyna; Budziszewska, Bogusława; Holst, Birgitte; Ostachowicz, Beata; Nowak, Gabriel

    2014-10-31

    Zinc may act as a neurotransmitter in the central nervous system by activation of the GPR39 metabotropic receptors. In the present study, we investigated whether GPR39 knockout would cause depressive-like and/or anxiety-like behavior, as measured by the forced swim test, tail suspension test, and light/dark test. We also investigated whether lack of GPR39 would change levels of cAMP response element-binding protein (CREB),brain-derived neurotrophic factor (BDNF) and tropomyosin related kinase B (TrkB) protein in the hippocampus and frontal cortex of GPR39 knockout mice subjected to the forced swim test, as measured by Western-blot analysis. In this study, GPR39 knockout mice showed an increased immobility time in both the forced swim test and tail suspension test, indicating depressive-like behavior and displayed anxiety-like phenotype. GPR39 knockout mice had lower CREB and BDNF levels in the hippocampus, but not in the frontal cortex, which indicates region specificity for the impaired CREB/BDNF pathway (which is important in antidepressant response) in the absence of GPR39. There were no changes in TrkB protein in either structure. In the present study, we also investigated activity in the hypothalamus-pituitary-adrenal axis under both zinc- and GPR39-deficient conditions. Zinc-deficient mice had higher serum corticosterone levels and lower glucocorticoid receptor levels in the hippocampus and frontal cortex. There were no changes in the GPR39 knockout mice in comparison with the wild-type control mice, which does not support a role of GPR39 in hypothalamus-pituitary-adrenal axis regulation. The results of this study indicate the involvement of the GPR39 Zn(2+)-sensing receptor in the pathophysiology of depression with component of anxiety. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  19. Human Exhibitions

    DEFF Research Database (Denmark)

    Andreassen, Rikke

    light on the staging of exhibitions, the daily life of the exhibitees, the wider connections between shows across Europe and the thinking of the time on matters of race, science, gender and sexuality. A window onto contemporary racial understandings, the book presents interviews with the descendants...... of displayed people, connecting the attitudes and science of the past with both our (continued) modern fascination with ‘the exotic’, and contemporary language and popular culture. As such, it will be of interest to scholars of sociology, anthropology and history working in the areas of gender and sexuality...

  20. Young APOE[subscript 4] Targeted Replacement Mice Exhibit Poor Spatial Learning and Memory, with Reduced Dendritic Spine Density in the Medial Entorhinal Cortex

    Science.gov (United States)

    Rodriguez, Gustavo A.; Burns, Mark P.; Weeber, Edwin J.; Rebeck, G. William

    2013-01-01

    The apolipoprotein E4 ("APOE-[epsilon]4") allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, and may predispose individuals to Alzheimer's-related cognitive decline by affecting normal brain function early in life. To investigate the impact of human APOE alleles on cognitive performance in mice, we trained…

  1. Dietary feeding of flavokawain A, a Kava chalcone, exhibits a satisfactory safety profile and its association with enhancement of phase II enzymes in mice

    Directory of Open Access Journals (Sweden)

    Xuesen Li

    2014-01-01

    Full Text Available Flavokawain A (FKA, a major chalcone in the Kava plant, has recently demonstrated promising anti-cancer activities. A systematic evaluation of FKA's safety profile has not been reported before. In this study, male FVB/N mice were fed with an AIN-76A diet or AIN-76A diet supplemented with 0.6% (6 g/kg food FKA or 0.6% commercial kava root extract (KRE for three weeks. Dietary feeding of FKA did not affect food consumption and body weight. Histopathological examination of liver, kidney, colon, lung, heart, spleen, and thymus revealed no signs of FKA-induced toxicity. Biochemical serum analysis and histological examination confirmed normal organ function in FKA-treated mice. The cytotoxicity profile showed FKA had minimal side effects on bone marrow and small intestinal epithelial cells compared with Adriamycin. In addition, oral feeding of FKA increased activities of both glutathione S-transferase and quinone reductase in the liver, lung, prostate and bladder tissues of mice. In comparison, dietary feeding of 0.6% KRE increased liver/body weight ratio and decreased spleen, thymus, and testis/body weight ratios, as well as induced nodular proliferation in liver tissues. Therefore, dietary feeding FKA showed no adverse effects on major organ function and homeostasis in mice, suggesting the potential of FKA for chemoprevention study of human cancers.

  2. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    Science.gov (United States)

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models.

  3. Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oral administration of the transgenic plants.

    Science.gov (United States)

    Kalbina, Irina; Lagerqvist, Nina; Moiane, Bélisario; Ahlm, Clas; Andersson, Sören; Strid, Åke; Falk, Kerstin I

    2016-11-01

    The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula. The economic impact of this pathogen due to livestock losses, as well as its relevance to public health, underscores the importance of developing effective and easily distributed vaccines. Vaccines that can be delivered orally are of particular interest. Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virus antigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein. Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Western blotting, respectively. Furthermore, the plant-expressed antigens were evaluated for their immunogenicity in mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportion of the mice elicited specific IgG antibody responses, as compared to the control animals that were fed wild-type plants and of which none sero-converted. Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virus proteins, and that the plants are immunogenic when given orally to mice. These are promising findings and provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. GPR39 (zinc receptor) knockout mice exhibit depression-like behavior and CREB/BDNF down-regulation in the hippocampus

    DEFF Research Database (Denmark)

    Młyniec, Katarzyna; Budziszewska, Bogusława; Holst, Birgitte

    2015-01-01

    Background: Zinc may act as a neurotransmitter in the central nervous system by activation of the GPR39 metabotropic receptors. Methods: In the present study, we investigated whether GPR39 knockout would cause depressive-like and/or anxiety-like behavior, as measured by the forced swim test, tail...... investigated activity in the hypothalamus-pituitary-adrenal axis under both zinc- and GPR39-deficient conditions. Zinc-deficient mice had higher serum corticosterone levels and lower glucocorticoid receptor levels in the hippocampus and frontal cortex. Conclusions: There were no changes in the GPR39 knockout...

  5. Dietary incorporation of whey proteins and galactooligosaccharides exhibits improvement in glucose homeostasis and insulin resistance in high fat diet fed mice

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Kavadi

    2017-09-01

    Full Text Available Background: The present study was planned to investigate the effectiveness of whey protein isolate (WPI of high purity and a galactooligosaccharides (GOS preparation on glucose homeostasis and insulin resistance under high fat diet (45.47% energy from fat fed conditions in C57BL/6 mice. The mRNA expression of genes related to gluconeogenesis was also examined. Methods: Fasting blood glucose level, serum insulin & GLP-1 (ELISA were measured; HOMA-IR determined in different treatment groups. mRNA expression of gluconeogenesis genes in liver and small intestine tissues analysed by qRT-PCR. Results: Dietary incorporation of WPI/GOS alone or in combination was observed to significantly resist (p [J Complement Med Res 2017; 6(3.000: 326-332

  6. Topical application of zinc oxide nanoparticles reduces bacterial skin infection in mice and exhibits antibacterial activity by inducing oxidative stress response and cell membrane disintegration in macrophages.

    Science.gov (United States)

    Pati, Rashmirekha; Mehta, Ranjit Kumar; Mohanty, Soumitra; Padhi, Avinash; Sengupta, Mitali; Vaseeharan, Baskarlingam; Goswami, Chandan; Sonawane, Avinash

    2014-08-01

    Here we studied immunological and antibacterial mechanisms of zinc oxide nanoparticles (ZnO-NPs) against human pathogens. ZnO-NPs showed more activity against Staphylococcus aureus and least against Mycobacterium bovis-BCG. However, BCG killing was significantly increased in synergy with antituberculous-drug rifampicin. Antibacterial mechanistic studies showed that ZnO-NPs disrupt bacterial cell membrane integrity, reduce cell surface hydrophobicity and down-regulate the transcription of oxidative stress-resistance genes in bacteria. ZnO-NP treatment also augmented the intracellular bacterial killing by inducing reactive oxygen species production and co-localization with Mycobacterium smegmatis-GFP in macrophages. Moreover, ZnO-NPs disrupted biofilm formation and inhibited hemolysis by hemolysin toxin producing S. aureus. Intradermal administration of ZnO-NPs significantly reduced the skin infection, bacterial load and inflammation in mice, and also improved infected skin architecture. We envision that this study offers novel insights into antimicrobial actions of ZnO-NPs and also demonstrates ZnO-NPs as a novel class of topical anti-infective agent for the treatment of skin infections. This in-depth study demonstrates properties of ZnO nanoparticles in infection prevention and treatment in several skin infection models, dissecting the potential mechanisms of action of these nanoparticles and paving the way to human applications. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Hao Hong

    Full Text Available New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM were then genetically modified to express an anti-L1-CAM CAR (CE7R, which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p. administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.

  8. Cysteine-stabilised peptide extract of Morinda lucida (Benth) leaf exhibits antimalarial activity and augments antioxidant defense system in P. berghei-infected mice.

    Science.gov (United States)

    Adebayo, Joseph O; Adewole, Kayode E; Krettli, Antoniana U

    2017-07-31

    Cysteine-stabilised peptides (CSP) are majorly explored for their bioactivities with applications in medicine and agriculture. Morinda lucida leaf is used indigenously for the treatment of malaria; it also contains CSP but the role of CSP in the antimalarial activity of the leaf has not been evaluated. This study was therefore performed to evaluate the antimalarial activity of partially purified cysteine-stabilised peptide extract (PPCPE) of Morinda lucida leaf and its possible augmentation of the antioxidant systems of liver and erythrocytes in murine malaria. PPCPE was prepared from Morinda lucida leaf. The activity of PPCPE was evaluated in vitro against Plasmodium falciparum W2 and its cytotoxicity against a BGM kidney cell line. PPCPE was also evaluated for its antimalarial activity and its effects on selected liver and erythrocyte antioxidant parameters in P. berghei NK65-infected mice. PPCPE was not active against P. falciparum W2 (IC 50 : >50µg/ml) neither was it cytotoxic (MLD 50 : >1000µg/ml). However, PPCPE was active against P. berghei NK65 in vivo, causing 51.52% reduction in parasitaemia at 31.25mg/Kg body weight on day 4 post-inoculation. PPCPE significantly reduced (P activities of glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase in a dose-dependent manner, which was significant (P antimalarial effect and that PPCPE may augment the antioxidant defense system to alleviate the reactive oxygen species-mediated complications of malaria. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  9. Autoreactive effector/memory CD4+ and CD8+ T cells infiltrating grafted and endogenous islets in diabetic NOD mice exhibit similar T cell receptor usage.

    Directory of Open Access Journals (Sweden)

    Ramiro Diz

    Full Text Available Islet transplantation provides a "cure" for type 1 diabetes but is limited in part by recurrent autoimmunity mediated by β cell-specific CD4(+ and CD8(+ T cells. Insight into the T cell receptor (TCR repertoire of effector T cells driving recurrent autoimmunity would aid the development of immunotherapies to prevent islet graft rejection. Accordingly, we used a multi-parameter flow cytometry strategy to assess the TCR variable β (Vβ chain repertoires of T cell subsets involved in autoimmune-mediated rejection of islet grafts in diabetic NOD mouse recipients. Naïve CD4(+ and CD8(+ T cells exhibited a diverse TCR repertoire, which was similar in all tissues examined in NOD recipients including the pancreas and islet grafts. On the other hand, the effector/memory CD8(+ T cell repertoire in the islet graft was dominated by one to four TCR Vβ chains, and specific TCR Vβ chain usage varied from recipient to recipient. Similarly, islet graft- infiltrating effector/memory CD4(+ T cells expressed a limited number of prevalent TCR Vβ chains, although generally TCR repertoire diversity was increased compared to effector/memory CD8(+ T cells. Strikingly, the majority of NOD recipients showed an increase in TCR Vβ12-bearing effector/memory CD4(+ T cells in the islet graft, most of which were proliferating, indicating clonal expansion. Importantly, TCR Vβ usage by effector/memory CD4(+ and CD8(+ T cells infiltrating the islet graft exhibited greater similarity to the repertoire found in the pancreas as opposed to the draining renal lymph node, pancreatic lymph node, or spleen. Together these results demonstrate that effector/memory CD4(+ and CD8(+ T cells mediating autoimmune rejection of islet grafts are characterized by restricted TCR Vβ chain usage, and are similar to T cells that drive destruction of the endogenous islets.

  10. Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

    International Nuclear Information System (INIS)

    Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.; Longo, D.L.

    1984-01-01

    The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for education of I region-restricted T cells

  11. A flavonoid component from Docynia delavayi (Franch.) Schneid represses transplanted H22 hepatoma growth and exhibits low toxic effect on tumor-bearing mice.

    Science.gov (United States)

    Zhao, Xiangpei; Shu, Guangwen; Chen, Lvyi; Mi, Xue; Mei, Zhinan; Deng, Xukun

    2012-09-01

    The fruit of Docynia delavayi (Franch.) Schneid is a kind of popular food in southwestern areas of China. Additionally, its rhizome has been long used as a folk medicine in the treatment of liver cancer by local people. Chrysin is a kind of flavonoid which induces cancer cell death in vitro. However, its anti-tumor activity in vivo and toxicological effects on the tumor-bearing animals still remain poorly understood. In this study, we obtained four flavonoids from this herb. Among them, chrysin showed the strongest cytotoxic effect on an array of cultured tumor cells. Further investigations revealed that it significantly repressed transplanted H22 ascitic hepatic tumor cell growth in vivo. Moreover, this compound displayed little toxic effects. Additionally, we demonstrated that in transplanted tumor tissues, chrysin not only activated caspase-3 and induced apoptosis, but also inhibited the production of vascular endothelial growth factor (VEGF) and suppressed angiogenesis. These data showed that chrysin exhibited prominent anti-tumor activities and low toxic effects in vivo. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. A high fat diet-induced decrease in hippocampal newly-born neurons of male mice is exacerbated by mild psychological stress using a Communication Box.

    Science.gov (United States)

    Murata, Yusuke; Narisawa, Yukiyasu; Shimono, Rima; Ohmori, Hiraku; Mori, Masayoshi; Ohe, Kenji; Mine, Kazunori; Enjoji, Munechika

    2017-02-01

    Obese persons have a higher incidence of depression than healthy-weight persons. Several studies indicated that the exposure to a high fat diet (HFD) results in a decrease in hippocampal neurogenesis, which leads to higher stress response and stress-induced depression. Although stress is a risk factor for obesity and depression, no studies to date have investigated the effect of stress on the hippocampal neurogenesis of HFD-induced obese animals. The aim of this study was to elucidate whether or not obese HFD-fed mice are vulnerable to stress-induced depression by investigating hippocampal neurogenesis. Sixty-four male ICR mice (four weeks of age) were fed a control (N=24) or 45%HFD (N=40) for seven weeks. Of the HFD-fed group, twenty-four mice met the criteria for "diet-induced obesity". The animals were then exposed to three consecutive days of psychological stress using a Communication Box. Half were sacrificed to evaluate the physiological changes, and the other half were perfused to quantify hippocampal neuroblasts/immature neurons by the estimation of doublecortin-immunopositive cells. In the HFD-fed mice, psychological stress resulted in increases in caloric intake and visceral adipose tissue and a significant decrease in doublecortin-positive cells in the dentate gyrus; however, no such differences were found in the control diet-fed group. Limitations Further study using other neurogenic markers to assess the stage-specific changes in hippocampal neurogenesis will be required CONCLUSIONS: Our findings suggest that an HFD-induced decrease in hippocampal newly-born neurons leads to stress vulnerability, which may contribute to a high risk of stress-induced depression for obese persons. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Immunologic and metabolic effects of high-refined carbohydrate-containing diet in food allergic mice.

    Science.gov (United States)

    Yamada, Letícia Tamie Paiva; de Oliveira, Marina Chaves; Batista, Nathália Vieira; Fonseca, Roberta Cristelli; Pereira, Rafaela Vaz Sousa; Perez, Denise Alves; Teixeira, Mauro Martins; Cara, Denise Carmona; Ferreira, Adaliene Versiani Matos

    2016-02-01

    Allergic mice show a reduction in body weight and adiposity with a higher inflammatory response in the adipose tissue similar to obese fat tissue. This study aimed to evaluate whether the low-grade inflammatory milieu of mice with diet-induced mild obesity interferes with the allergic response induced by ovalbumin (OVA). BALB/c mice were divided into four groups: 1) non-allergic (OVA-) mice fed chow diet, 2) allergic (OVA+) mice fed chow diet, 3) OVA- mice fed high-refined carbohydrate-containing (HC) diet, and 4) OVA+ mice fed HC diet. After 5 wk, allergic groups were sensitized with OVA and received a booster 14 d later. All groups received an oral OVA challenge 7 d after the booster. Allergic groups showed increased serum levels of total IgE, anti-OVA IgE, and IgG1; a high disease activity index score; aversion to OVA; and increased intestinal eosinophil infiltration. Non-allergic mild-obese mice also showed aversion to OVA and an increased number of eosinophils in the proximal jejunum. After the allergic challenge, OVA+ mice fed chow diet showed weight loss and lower adiposity in several adipose tissue depots. OVA+ mice fed HC diet showed a loss of fat mass only in the mesenteric adipose tissue. Furthermore, increased levels of TNF, IL-6, and IL-10 were observed in this tissue. Our data show that mild-obese allergic mice do not present severe pathologic features of food allergy similar to those exhibited by lean allergic mice. Mild obesity promoted by HC diet ingestion causes important intestinal disorders that appear to modulate the inflammatory response during the antigen challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

    Directory of Open Access Journals (Sweden)

    Antonini James M

    2010-06-01

    Full Text Available Abstract Background Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6 mice and a trend for increased tumor incidence after stainless steel (SS fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant or non-carcinogenic (iron abundant metal-containing welding fumes at the transcriptome level. Methods Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS, Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done. Results Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as S100A8, S100A9 and

  15. Britain exhibition at CERN

    CERN Multimedia

    Bertin; CERN PhotoLab

    1969-01-01

    The United Kingdom inaugurated the Industrial Exhibitions in 1968, and it wasn't till 1971 that other countries staged exhibitions at CERN. This photo was taken in 1969, at the second British exhibition, where 16 companies were present.

  16. Mild Cognitive Impairment (MCI)

    Science.gov (United States)

    Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It ...

  17. Digital collections and exhibits

    CERN Document Server

    Denzer, Juan

    2015-01-01

    Today's libraries are taking advantage of cutting-edge technologies such as flat panel displays using touch, sound, and hands-free motions to design amazing exhibits using everything from simple computer hardware to advanced technologies such as the Microsoft Kinect. Libraries of all types are striving to add new interactive experiences for their patrons through exciting digital exhibits, both online and off. Digital Collections and Exhibits takes away the mystery of designing stunning digital exhibits to spotlight library trea

  18. Exhibiting Epistemic Objects

    DEFF Research Database (Denmark)

    Tybjerg, Karin

    2017-01-01

    of exhibiting epistemic objects that utilize their knowledge-generating potential and allow them to continue to stimulate curiosity and generate knowledge in the exhibition. The epistemic potential of the objects can then be made to work together with the function of the exhibition as a knowledge-generating set...

  19. Discrimination? - Exhibition of posters

    OpenAIRE

    Jakimovska, Jana

    2017-01-01

    Participation in the exhibition with the students form the Art Academy. The exhibition consisted of 15 posters tackling the subjects of hate speech and discrimination. The exhibition happened thanks to the invitation of the Faculty of Law at UGD, and it was a part of a larger event of launching books on the aforementioned subjects.

  20. Mild Traumatic Brain Injury

    Science.gov (United States)

    ... mild Traumatic Brain Injury Resilience Families with Kids Depression Families & Friendships Tobacco Life Stress Spirituality Anger Physical Injury Stigma Health & Wellness Work Adjustment Community Peer-2-Peer Forum ...

  1. Medan Convention & Exhibition Center (Arsitektur Ekspresionisme)

    OpenAIRE

    Iskandar, Nurul Auni

    2015-01-01

    Medan is one of the third largest city in Indonesia, which is currently being developed, and a city with lots of activities. In the city of Medan has a high investment opportunities for a convention, because of its strategic position in Southeast Asia and also supported by the facility and the potential for tourism in North Sumatra, Medan city has the potential for industrial MICE (Meeting, Incentive, Conference, Exhibition). The construction of Medan Convention & Exhibition Cente...

  2. Exhibition; Image display agency

    International Nuclear Information System (INIS)

    Normazlin Ismail

    2008-01-01

    This article touches on the role of Malaysian Nuclear Agency as nuclear research institutions to promote, develop and encourage the peaceful uses of nuclear technology in its agricultural, medical, manufacturing, industrial, health and environment for the development of the country running successfully. Maturity of Malaysian Nuclear Agency in dealing with nuclear technology that are very competitive and globalization cannot be denied. On this basis Malaysian Nuclear Agency was given the responsibility to strengthen the nuclear technology in Malaysia. One way is through an exhibition featuring the research, discoveries and new technology products of the nuclear technology. Through this exhibition is to promote the nuclear technology and introduce the image of the agency in the public eye. This article also states a number of exhibits entered by the Malaysian Nuclear Agency and achievements during the last exhibition. Authors hope that the exhibition can be intensified further in the future.

  3. Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone.

    Science.gov (United States)

    Gould, Elizabeth A; Busquet, Nicolas; Shepherd, Douglas; Dietz, Robert M; Herson, Paco S; Simoes de Souza, Fabio M; Li, Anan; George, Nicholas M; Restrepo, Diego; Macklin, Wendy B

    2018-02-13

    Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/maintenance is disrupted. Axon disruption occurs in Plp1 -null mice as early as 2 months in cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase in oligodendrocyte density in the olfactory bulb and rostral corpus callosum that increased during adulthood. A distinct proliferative response of progenitor cells was observed in the subventricular zone (SVZ), while the number and proliferation of parenchymal oligodendrocyte progenitor cells was unchanged. This SVZ proliferative response occurred prior to evidence of axonal disruption. Thus, a novel SVZ response contributes to the region-specific increase in oligodendrocytes in Plp1 -null mice. Young adult Plp1- null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption. © 2018, Gould et al.

  4. The association between asymptomatic and mild neurocognitive ...

    African Journals Online (AJOL)

    2018-04-12

    Apr 12, 2018 ... antiretroviral therapy among people living with human .... larger than 0.05.26 This is as shown below: = +. −. 1. 1 ..... HAND in general, and did not focus on the mild forms of .... Poster exhibition: Sydney – IAS 2007: Abstract no.

  5. Reducing Truancy in Students with Mild Handicaps.

    Science.gov (United States)

    Hess, Albert M.; And Others

    1990-01-01

    Contingency contracting and group counseling were provided to 26 mildly to moderately handicapped middle school students with high rates of truancy. Subjects exhibited attendance gains after treatment; gains were not maintained at followup but attendance rates were still higher than the rates of control students. Measures of academic performance…

  6. Hearts from mice fed a non-obesogenic high-fat diet exhibit changes in their oxidative state, calcium and mitochondria in parallel with increased susceptibility to reperfusion injury.

    Science.gov (United States)

    Littlejohns, Ben; Pasdois, Philippe; Duggan, Simon; Bond, Andrew R; Heesom, Kate; Jackson, Christopher L; Angelini, Gianni D; Halestrap, Andrew P; Suleiman, M-Saadeh

    2014-01-01

    High-fat diet with obesity-associated co-morbidities triggers cardiac remodeling and renders the heart more vulnerable to ischemia/reperfusion injury. However, the effect of high-fat diet without obesity and associated co-morbidities is presently unknown. To characterize a non-obese mouse model of high-fat diet, assess the vulnerability of hearts to reperfusion injury and to investigate cardiac cellular remodeling in relation to the mechanism(s) underlying reperfusion injury. Feeding C57BL/6J male mice high-fat diet for 20 weeks did not induce obesity, diabetes, cardiac hypertrophy, cardiac dysfunction, atherosclerosis or cardiac apoptosis. However, isolated perfused hearts from mice fed high-fat diet were more vulnerable to reperfusion injury than those from mice fed normal diet. In isolated cardiomyocytes, high-fat diet was associated with higher diastolic intracellular Ca2+ concentration and greater damage to isolated cardiomyocytes following simulated ischemia/reperfusion. High-fat diet was also associated with changes in mitochondrial morphology and expression of some related proteins but not mitochondrial respiration or reactive oxygen species turnover rates. Proteomics, western blot and high-performance liquid chromatography techniques revealed that high-fat diet led to less cardiac oxidative stress, higher catalase expression and significant changes in expression of putative components of the mitochondrial permeability transition pore (mPTP). Inhibition of the mPTP conferred relatively more cardio-protection in the high-fat fed mice compared to normal diet. This study shows for the first time that high-fat diet, independent of obesity-induced co-morbidities, triggers changes in cardiac oxidative state, calcium handling and mitochondria which are likely to be responsible for increased vulnerability to cardiac insults.

  7. Prolonged desipramine treatment increases the production of interleukin-10, an anti-inflammatory cytokine, in C57BL/6 mice subjected to the chronic mild stress model of depression

    Czech Academy of Sciences Publication Activity Database

    Kubera, M.; Maes, M.; Holáň, Vladimír; Basta-Kaim, A.; Roman, A.; Shani, J.

    2001-01-01

    Roč. 63, 1-3 (2001), s. 171-178 ISSN 0165-0327 R&D Projects: GA ČR GA310/99/0360 Institutional research plan: CEZ:AV0Z5052915 Keywords : mild stress model * desipramine * cytokines Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.868, year: 2001

  8. Council Chamber exhibition

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    To complete the revamp of CERN’s Council Chamber, a new exhibition is being installed just in time for the June Council meetings.   Panels will showcase highlights of CERN’s history, using some of the content prepared for the exhibitions marking 50 years of the PS, which were displayed in the main building last November. The previous photo exhibition in the Council Chamber stopped at the 1970s. To avoid the new panels becoming quickly out of date, photos are grouped together around specific infrastructures, rather than following a classic time-line. “We have put the focus on the accelerators – the world-class facilities that CERN has been offering researchers over the years, from the well-known large colliders to the lesser-known smaller facilities,” says Emma Sanders, who worked on the content. The new exhibition will be featured in a future issue of the Bulletin with photos and an interview with Fabienne Marcastel, designer of the exhibit...

  9. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's 50th anniversary celebrations. Fifty candles for CERN, an international laboratory renowned for fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting exhibitions of plastic arts and performances entitled: Accelerated Particles. Several works will be exhibited and performed in two 'salons'. Salon des matières: An exhibition of plastic arts From Tues 12 October to Wed 3 November 2004 Tuesdays to Fridays: 16:00 to 19:00 Saturdays: 14:00 to 18:00 Exhibition open late on performance nights, entrance free Salon des particules: Musical and visual performances Tues 12 and Mon 25 October from 20:00 to 23:00 Preview evening for both events: Tues 12 October from 18:...

  10. The reduced serum free triiodothyronine and increased dorsal hippocampal SNAP-25 and Munc18-1 had existed in middle-aged CD-1 mice with mild spatial cognitive impairment.

    Science.gov (United States)

    Cao, Lei; Jiang, Wei; Wang, Fang; Yang, Qi-Gang; Wang, Chao; Chen, Yong-Ping; Chen, Gui-Hai

    2013-12-02

    Changes of synaptic proteins in highlighted brain regions and decreased serum thyroid hormones (THs) have been implied in age-related learning and memory decline. Previously, we showed significant pairwise correlations among markedly impaired spatial learning and memory ability, decreased serum free triiodothyronine (FT3) and increased hippocampal SNAP-25 and Munc18-1 in old Kunming mice. However, whether these changes and the correlations occur in middle-age mice remains unclear. Since this age is one of the best stages to study age-related cognitive decline, we explored the spatial learning and memory ability, serum THs, cerebral SNAP-25 and Munc18-1 levels and their relationships of middle-aged mice in this study. The learning and memory abilities of 35 CD-1 mice (19 mice aged 6 months and 16 mice aged 12 months) were measured with a radial six-arm water maze (RAWM). The SNAP-25 and Munc18-1 levels were semi-quantified by Western blotting and the serum THs were detected by radioimmunoassay. The results showed the middle-aged mice had decreased serum FT3, increased dorsal hippocampal (DH) SNAP-25 and Munc18-1, and many or long number of errors and latency in both learning and memory phases of the RAWM. The Pearson's correlation test showed that the DH SANP-25 and Munc18-1 levels were positively correlated with the number of errors and latency in learning phases of the RAWM. Meanwhile, the DH SANP-25 and Munc18-1 levels negatively correlated with the serum FT3 level. These results suggested that reduced FT3 with increased DH SNAP-25 and Munc18-1 levels might be involved in the spatial learning ability decline in the middle-aged mice. © 2013 Elsevier B.V. All rights reserved.

  11. Steel fiber replacement of mild steel in prestressed concrete beams

    Science.gov (United States)

    2010-10-01

    In traditional prestressed concrete beams, longitudinal prestressed tendons serve to resist bending moment and : transverse mild steel bars (or stirrups) are used to carry shear forces. However, traditional prestressed concrete I-beams : exhibit earl...

  12. Steel fiber replacement of mild steel in prestressed concrete beams.

    Science.gov (United States)

    2011-01-01

    In traditional prestressed concrete beams, longitudinal prestressed tendons serve to resist bending moment and transverse mild : steel bars (or stirrups) are used to carry shear forces. However, traditional prestressed concrete I-beams exhibit early-...

  13. EXHIBITION: Accelerated Particles

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ An exhibition of plastic arts and two evenings of performances by sound and visual artists as part of CERN's fiftieth anniversary celebrations. The fiftieth anniversary of a world famous organization like CERN, an international laboratory specializing in fundamental research, is a cause for celebration. Since March this year, Geneva and neighbouring parts of France have been the venues for a wealth of small and large-scale events, which will continue until November. Given CERN's location in the commune of Meyrin, the ForuMeyrin is hosting two "salons" consisting of an exhibition of plastic arts and evenings of music and visual arts performances with the collective title of "Accelerated Particles". Several works will be exhibited and performed. Salon des matières: An exhibition of plastic arts Until Wednesday 3 November 2004. Tuesdays to Fridays: 4.00 p.m. to 7.00 p.m. Saturdays: 2.00 p.m. to 6.00 p.m. Doors open late on the evening of the performances. Salon des ...

  14. The n-hexane and chloroform fractions of Piper betle L. trigger different arms of immune responses in BALB/c mice and exhibit antifilarial activity against human lymphatic filarid Brugia malayi.

    Science.gov (United States)

    Singh, Meghna; Shakya, Shilpy; Soni, Vishal Kumar; Dangi, Anil; Kumar, Nikhil; Bhattacharya, Shailja-Misra

    2009-06-01

    Modulation of immune functions by using herbal plants and their products has become fundamental regime of therapeutic approach. Piper betle Linn. (Piperaceae) is a widely distributed plant in the tropical and subtropical regions of the world and has been attributed as traditional herbal remedy for many diseases. We have recently reported the antifilarial and antileishmanial efficacy in the leaf extract of Bangla Mahoba landrace of P. betle which is a female plant. The present report describes the in vivo immunomodulatory efficacy of the crude methanolic extract and its n-hexane, chloroform, n-butanol fractions of the female plant at various dose levels ranging between 0.3 and 500 mg/kg in BALB/c. Attempts were also made to observe antifilarial activity of the active extracts and correlate it with the antigen specific immune responses in another rodent Mastomys coucha infected with human lymphatic filarial parasite Brugia malayi. The crude methanol extract and n-hexane fraction were found to potentiate significant (p<0.001) enhancement of both humoral (plaque forming cells, hemagglutination titre) as well as cell-mediated (lymphoproliferation, macrophage activation, delayed type hypersensitivity) immune responses in mice. The flow cytometric analysis of splenocytes of treated mice indicated enhanced population of T-cells (CD4(+), CD8(+)) and B-cells (CD19(+)). The n-hexane fraction (3 mg/kg) was found to induce biased type 2 cytokine response as revealed by increased IL-4(+) and decreased IFN-gamma(+) T-cell population while the chloroform fraction (10 mg/kg) produced a predominant type 1 cytokines. Crude methanolic extract (100 mg/kg) demonstrated a mixed type 1 and type 2 cytokine responses thus suggesting a remarkable immunomodulatory property in this plant. The induction of differential T-helper cell immune response appears ideal to overcome immunosuppression as observed in case of lymphatic, filarial Brugia malayi infection which may also be extended to other

  15. International Space Station exhibit

    Science.gov (United States)

    2000-01-01

    The International Space Station (ISS) exhibit in StenniSphere at John C. Stennis Space Center in Hancock County, Miss., gives visitors an up-close look at the largest international peacetime project in history. Step inside a module of the ISS and glimpse how astronauts will live and work in space. Currently, 16 countries contribute resources and hardware to the ISS. When complete, the orbiting research facility will be larger than a football field.

  16. Upcycling CERN Exhibitions

    CERN Multimedia

    Katarina Anthony

    2015-01-01

    Summer is coming - and with it, a new Microcosm exhibition showcasing CERN (see here). But while the new exhibit is preparing to enchant visitors, many have been asking about the site's former content. Will it simply be out with the old and in with the new? Not as such!   The plasma ball from Microcosm is now on display at the LHCb site. As Microcosm's new content is moving in, its old content is moving up. From LHCb to IdeaSquare, former Microcosm displays and objects are being installed across the CERN site. "Microcosm featured many elements that were well suited to life outside of the exhibition," says Emma Sanders, Microcosm project leader in the EDU group. "We didn't want this popular content to go to waste, and so set out to find them new homes across CERN." The LHCb experiment has received a number of Microcosm favourites, including the Rutherford experiment, the cosmic ray display and the Thomson experiment. "We&...

  17. Online Exhibits & Concept Maps

    Science.gov (United States)

    Douma, M.

    2009-12-01

    Presenting the complexity of geosciences to the public via the Internet poses a number of challenges. For example, utilizing various - and sometimes redundant - Web 2.0 tools can quickly devour limited time. Do you tweet? Do you write press releases? Do you create an exhibit or concept map? The presentation will provide participants with a context for utilizing Web 2.0 tools by briefly highlighting methods of online scientific communication across several dimensions. It will address issues of: * breadth and depth (e.g. from narrow topics to well-rounded views), * presentation methods (e.g. from text to multimedia, from momentary to enduring), * sources and audiences (e.g. for experts or for the public, content developed by producers to that developed by users), * content display (e.g. from linear to non-linear, from instructive to entertaining), * barriers to entry (e.g. from an incumbent advantage to neophyte accessible, from amateur to professional), * cost and reach (e.g. from cheap to expensive), and * impact (e.g. the amount learned, from anonymity to brand awareness). Against this backdrop, the presentation will provide an overview of two methods of online information dissemination, exhibits and concept maps, using the WebExhibits online museum (www.webexhibits.org) and SpicyNodes information visualization tool (www.spicynodes.org) as examples, with tips on how geoscientists can use either to communicate their science. Richly interactive online exhibits can serve to engage a large audience, appeal to visitors with multiple learning styles, prompt exploration and discovery, and present a topic’s breadth and depth. WebExhibits, which was among the first online museums, delivers interactive information, virtual experiments, and hands-on activities to the public. While large, multidisciplinary exhibits on topics like “Color Vision and Art” or “Calendars Through the Ages” require teams of scholars, user interface experts, professional writers and editors

  18. A mild mutator phenotype arises in a mouse model for malignancies associated with neurofibromatosis type 1

    International Nuclear Information System (INIS)

    Garza, Rene; Hudson, Robert A.; McMahan, C. Alex; Walter, Christi A.; Vogel, Kristine S.

    2007-01-01

    Defects in genes that control DNA repair, proliferation, and apoptosis can increase genomic instability, and thus promote malignant progression. Although most tumors that arise in humans with neurofibromatosis type 1 (NF1) are benign, these individuals are at increased risk for malignant peripheral nerve sheath tumors (MPNST). To characterize additional mutations required for the development of MPNST from benign plexiform neurofibromas, we generated a mouse model for these tumors by combining targeted null mutations in Nf1 and p53, in cis. CisNf1+/-; p53+/- mice spontaneously develop PNST, and these tumors exhibit loss-of-heterozygosity at both the Nf1 and p53 loci. Because p53 has well-characterized roles in the DNA damage response, DNA repair, and apoptosis, and because DNA repair genes have been proposed to act as modifiers in NF1, we used the cisNf1+/-; p53+/- mice to determine whether a mutator phenotype arises in NF1-associated malignancies. To quantitate spontaneous mutant frequencies (MF), we crossed the Big Blue mouse, which harbors a lacI transgene, to the cisNf1+/-; p53+/- mice, and isolated genomic DNA from both tumor and normal tissues in compound heterozygotes and wild-type siblings. Many of the PNST exhibited increased mutant frequencies (MF = 4.70) when compared to normal peripheral nerve and brain (MF = 2.09); mutations occurred throughout the entire lacI gene, and included base substitutions, insertions, and deletions. Moreover, the brains, spleens, and livers of these cisNf1+/-; p53+/- animals exhibited increased mutant frequencies when compared to tissues from wild-type littermates. We conclude that a mild mutator phenotype arises in the tumors and tissues of cisNf1+/-; p53+/- mice, and propose that genomic instability influences NF1 tumor progression and disease severity

  19. Mild Cognitive Impairment

    Science.gov (United States)

    ... more: Key Types of Dementia , What Is Alzheimer's? , Alzheimer's Risk Factors Symptoms back to top Experts classify Mild cognitive ... in Chronic Traumatic Encephalopathy 2014 Thor Stein Genetic Risk Factors Underlying Chronic Trauma and Alzheimer's Disease Pathology 2014 Kun Ping Lu Validation of ...

  20. Mobile exhibition in Mexico

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1960-04-15

    Since January this year, a mobile atomic energy exhibition has been touring the principal cities of Mexico. In organizing this exhibition, the National Nuclear Energy Commission of Mexico was assisted by the International Atomic Energy Agency which has placed its second mobile radioisotope laboratory at the disposal of the Mexican authorities. In many States of the Republic, the visit of the mobile laboratory has given a powerful impetus to atomic training and research. Universities have made use of the laboratory for the training of young scientists in the basic isotope techniques. As a sequel to the work initiated with its aid, some universities are planning to start regular training courses in this field. The laboratory, which is a gift to the Agency from the United States, has been put to its first assignment in Mexico. It will shortly be sent to Argentina for a period of six months for use in training courses. IAEA's first mobile radioisotope unit, also donated by the United States, has been used for training purposes in Austria, the Federal Republic of Germany, Greece and Yugoslavia, and has now been sent to the Far East

  1. Mobile exhibition in Mexico

    International Nuclear Information System (INIS)

    1960-01-01

    Since January this year, a mobile atomic energy exhibition has been touring the principal cities of Mexico. In organizing this exhibition, the National Nuclear Energy Commission of Mexico was assisted by the International Atomic Energy Agency which has placed its second mobile radioisotope laboratory at the disposal of the Mexican authorities. In many States of the Republic, the visit of the mobile laboratory has given a powerful impetus to atomic training and research. Universities have made use of the laboratory for the training of young scientists in the basic isotope techniques. As a sequel to the work initiated with its aid, some universities are planning to start regular training courses in this field. The laboratory, which is a gift to the Agency from the United States, has been put to its first assignment in Mexico. It will shortly be sent to Argentina for a period of six months for use in training courses. IAEA's first mobile radioisotope unit, also donated by the United States, has been used for training purposes in Austria, the Federal Republic of Germany, Greece and Yugoslavia, and has now been sent to the Far East

  2. Enhancement of immunological activity after mild hyperthermia

    International Nuclear Information System (INIS)

    Noguchi, Kenichi; Hasegawa, Takeo; Takahashi, Tohru

    2002-01-01

    At present, hyperthermia is clinically very important as interdisciplinary therapeutic method, and studies are being performed on combined effects with surgical treatment, radiotherapy, chemotherapy and gene therapy for the treatment of malignant tumors. We evaluated the effects of hyperthermia under temperature of 42.5C and demonstrated that the activation of immunological response is increased and anti-tumor effect cabn be obtained in this studies. We used animals were C3H mice (male,7W) bearing SCC-VII tumor on femur skin. Then, the mice were divided to 10 mice in each group, and only femur region was immersed in warm water for thermal treatment. Also we measured the tumor growth, changes of blood cell fraction and NK cell activity. The results of the present study confirmed: (1) Anti-tumor effect can be given by thermal treatment at relatively mild temperature (mild temperature at 39C-42C); (2) The increase of neutrophils is dependent on the quantity of heat added; (3) Immunological response of monocytes and lymphocytes is associated with it; (4) Activity of the immunological potency as a whole such as activation of NK cells was also confirmed

  3. Anniversary Exhibition. Nechvolodov.

    Directory of Open Access Journals (Sweden)

    - -

    2006-03-01

    Full Text Available On the 10th of August, 2005 in Tartu (the second biggest educational and cultural city in Estonia Stanislav Nechvolodov's exhibition was opened to show the 5-year cycle of his work, traditional for the author and his admirers. At the opening ceremony Nechvolodov said that the exhibition was the last one and appointed on his 70th anniversary.The architectural and building society in Irkutsk remembers Stanislav Nechvolodov as an architect working on dwelling and civil buildings in 1960-70s. Below are some extracts from the Estonian press.«Postimees» newspaper, December 1993. The interview «Expressionistic naturalist, conservative Nechvolodov» by journalist Eric Linnumyagi. He asks about all the details and describes the troubles experienced by Nechvolodov during the perestroika period in Estonia, for example: the Tartu University refused to install the sculpture of Socrat, the art school refused to engage him as an instructor, the sculpture of Socrat moved to Vrotzlav, Poland, and Nechvolodov moved to Poland to read lectures there.«Tartu» newspaper, November 2000. Mats Oun, artist, says in the article «Nechvolodov: a man of Renaissance»: «Nechvolodov works in Estonia, his works are placed in many local and foreign museums. Regardless some insignificant faults, he deserves a high estimation, and his manysided open exhibition can be an example for other artists. He is a man of Renaissance».

  4. Specific-locus experiments show that female mice exposed near the time of birth to low-LET ionizing radiation exhibit both a low mutational response and a dose-rate effect

    International Nuclear Information System (INIS)

    Selby, P.B.; Lee, S.S.; Kelly, E.M.; Bangham, J.W.; Raymer, G.D.; Hunsicker, P.R.

    1991-01-01

    Female mice were exposed to 300 R of 73-93 R/min X-radiation either as fetuses at 18.5d post conception (p.c.) or within 9h after birth. Combining the similar results from these 2 groups yielded a specific-locus mutation frequency of 9.4x10 -8 mutation/locus/R, which is statistically significantly higher than the historical-control mutation frequency, but much lower than the rate obtained by irradiating mature and maturing oocytes in adults. Other females, exposed at 18.5 days p.c. to 300 R of 0.79 R/min γ-radiation, yielded a mutation frequency that was statistically significantly lower than the frequency at high dose rates. The low-dose-rate group also had markedly higher fertility. It appears that the doe-rate effect for mutations induced near the time of birth may be more pronounced than that reported for mature and maturing oocytes of adults. A hypothesis sometimes advanced to explain low mutation frequencies recovered from cell populations that experience considerable radiation-induced cell killing is that there is selection against mutant cells. The reason for the relatively low mutational response following acute irradiation in the experiments is unknown; however, the finding of a dose-rate effect in these oocytes in the presence of only minor radiation-induced cell killing (as judged from fertility) makes it seem unlikely that selection was responsible for the low mutational response following acute exposure. Had selection been an important factor, the mutation frequency should have increased when oocyte killing was markedly reduced. (author). 32 refs.; 5 figs.; 5 tabs

  5. Mild induced hypothermia

    DEFF Research Database (Denmark)

    Johansen, Maria E; Jensen, Jens-Ulrik; Bestle, Morten H

    2014-01-01

    INTRODUCTION: Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. MATERIALS AND METHODS: Interim analysis data from an ongoing randomized controlled...... trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature). TRIAL REGISTRATION: NCT01455116. Thrombelastography (TEG) is performed three....... At enrollment, 3%, 38%, and 59% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (MA), respectively. In the hypothermia group, functional coagulopathy improved during the hypothermia phase, measured by R and MA, in patients with hypercoagulation as well as in patients...

  6. Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Juteau Jean-Marc

    2009-12-01

    Full Text Available Abstract Background Phosphorothioated oligonucleotides (PS-ONs have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV infections in vitro and in vivo was therefore investigated. Results In vitro, a 40 mer degenerate AP (REP 9 inhibited both murine CMV (MCMV and guinea pig CMV (GPCMV with an IC50 of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C inhibited MCMV with an IC50 of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism in vivo. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers. Conclusion These studies indicate that APs exhibit potent, well tolerated

  7. Comprehensive behavioral analysis of pituitary adenylate cyclase-activating polypeptide (PACAP knockout mice

    Directory of Open Access Journals (Sweden)

    Satoko eHattori

    2012-10-01

    Full Text Available Pituitary adenylate cyclase-activating polypeptide (PACAP is a neuropeptide acting as a neurotransmitter, neuromodulator, or neurotrophic factor. PACAP is widely expressed throughout the brain and exerts its functions through the PACAP-specific receptor (PAC1. Recent studies reveal that genetic variants of the PACAP and PAC1 genes are associated with mental disorders, and several behavioral abnormalities of PACAP knockout (KO mice are reported. However, an insufficient number of backcrosses was made using PACAP KO mice on the C57BL/6J background due to their postnatal mortality. To elucidate the effects of PACAP on neuropsychiatric function, the PACAP gene was knocked out in F1 hybrid mice (C57BL/6J x 129SvEv for appropriate control of the genetic background. The PACAP KO mice were then subjected to a behavioral test battery. PACAP deficiency had no significant effects on neurological screen. As shown previously, the mice exhibited significantly increased locomotor activity in a novel environment and abnormal anxiety-like behavior, while no obvious differences between genotypes were shown in home cage activity. In contrast to previous reports, the PACAP KO mice showed normal prepulse inhibition and slightly decreased depression-like behavior. Previous study demonstrates that the social interaction in a resident-intruder test was decreased in PACAP KO mice. On the other hand, we showed that PACAP KO mice exhibited increased social interaction in Crawley’s three-chamber social approach test, although PACAP KO had no significant impact on social interaction in a home cage. PACAP KO mice also exhibited mild performance deficit in working memory in an eight-arm radial maze and the T-maze, while they did not show any significant abnormalities in the left-right discrimination task in the T-maze. These results suggest that PACAP has an important role in the regulation of locomotor activity, social behavior, anxiety-like behavior and, potentially

  8. Corrosion inhibition of mild steel by Capsicum annuum fruit paste

    Directory of Open Access Journals (Sweden)

    Chandan M. Reddy

    2016-09-01

    Full Text Available The anti-corrosive property of Capsicum annuum fruit paste (CFP on mild steel was investigated. Weight loss and SEM analysis showed that the aqueous and ethanolic solutions of CFP exhibits excellent corrosion inhibition in 2 M HCl. Contact angle, surface atomic composition and FTIR studies verified the presence of an organic film on the mild steel surface. The FTIR spectra also indicated the formation of active compound-Fe complex. CFP thus shows potential as an inexpensive environment friendly corrosion inhibitor for mild steel.

  9. Pharmacotherapy for mild hypertension

    Directory of Open Access Journals (Sweden)

    Diana Diao

    2012-01-01

    Full Text Available BACKGROUND: People with no previous cardiovascular events or cardiovascular disease represent a primary prevention population. The benefits and harms of treating mild hypertension in primary prevention patients are not known at present. This review examines the existing randomized controlled trial (RCT evidence. OBJECTIVE: Primary objective: To quantify the effects of antihypertensive drug therapy on mortality and morbidity in adults with mild hypertension (systolic blood pressure (BP 140-159 mmHg and/or diastolic BP 90-99 mmHg and without cardiovascular disease. METHODS: Search: We searched CENTRAL (2011, Issue 1, MEDLINE (1948 to May 2011, EMBASE (1980 to May 2011 and reference lists of articles. The Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effectiveness (DARE were searched for previous reviews and meta-analyses of anti-hypertensive drug treatment compared to placebo or no treatment trials up until the end of 2011. Selection criteria: RCTs of at least 1 year duration. Data collection and analysis: The outcomes assessed were mortality, stroke, coronary heart disease (CHD, total cardiovascular events (CVS, and withdrawals due to adverse effects. MAIN RESULTS: Of 11 RCTs identified 4 were included in this review, with 8,912 participants. Treatment for 4 to 5 years with antihypertensive drugs as compared to placebo did not reduce total mortality (RR 0.85, 95% CI 0.63, 1.15. In 7,080 participants treatment with antihypertensive drugs as compared to placebo did not reduce coronary heart disease (RR 1.12, 95% CI 0.80, 1.57, stroke (RR 0.51, 95% CI 0.24, 1.08, or total cardiovascular events (RR 0.97, 95% CI 0.72, 1.32. Withdrawals due to adverse effects were increased by drug therapy (RR 4.80, 95% CI 4.14, 5.57, ARR 9%. AUTHORS' CONCLUSIONS: Antihypertensive drugs used in the treatment of adults (primary prevention with mild hypertension (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg have not been

  10. Curating a Mild Apocalypse

    DEFF Research Database (Denmark)

    Brichet, Nathalia Sofie; Hastrup, Frida

    2018-01-01

    that often go unnoticed? We argue that exhibition work when practiced as a form of research provides an opportunity for turning “trivial” environmental disaster into sensational experience by deliberately playing with objects to make what we think of as analytical figures. That is, exhibition artefacts...... created and displayed neither as representational ethnographic objects nor as free-floating art work, but as unsettled think pieces that are at once familiar and strange. We suggest that a feature of the Anthropocene is that ecologies have been messed up so as to become unrecognizable – and that research...

  11. Exhibition

    CERN Multimedia

    Staff Association

    2014-01-01

    Energie sombre, matière noire J.-J. Dalmais - J. Maréchal Du 11 au 27 novembre 2014, CERN Meyrin, Bâtiment principal A l’image des particules atomiques qui ont tissé des liens pour créer la matière, deux artistes haut bugistes croisent leurs regards et conjuguent leurs expressions singulières pour faire naître une vision commune de l’univers, produit des forces primordiales. Les sculptures de Jean-Jacques Dalmais et les peintures de Jacki Maréchal se rencontrent pour la première fois et se racontent par un enrichissement mutuel la belle histoire de la Vie. Dialogue magique des œuvres en mouvement qui questionnent en écho l’énergie sombre et la matière noire. Cette harmonieuse confluence de jeux de miroir et de résonnance illumine de poésie et de sobriété l’espace expos&...

  12. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Gaïa Manuella Cany Du 10 au 28 avril 2017 CERN Meyrin, Bâtiment principal Oiseau - Manuella Cany. Tableaux abstraits inspirés de vues satellites ou photos prises du ciel. Certains sont à la frontière du figuratif alors que d'autres permettent de laisser libre cours à son imagination. Aux détails infinis, ces tableaux sont faits pour être vus de loin et de près grâce à une attention toute particulière apportée aux effets de matières et aux couleurs le long de volutes tantôt nuancées tantôt contrastées.   Pour plus d’informations : staff.association@cern.ch | Tél: 022 766 37 38

  13. Exhibition

    CERN Document Server

    Staff Association

    2018-01-01

    En dehors des frontières Maxence Piquet Du 2 au 11 mai 2018 | CERN Meyrin, Bâtiment principal Exposition de peinture d'un artiste autodidacte Maxence Piquet (signature artiste M-P), avec différentes techniques (acrylique, huile, fusain, collage...) et sur différents supports. Un art souvent brut et parfois provoquant, avec des touches expressionnistes et cubistes principale origine de son art. Des œuvres souvent vivent et colorées... Cette exposition est la première en dehors d ses frontières Lorraine et a pour but de faire voyager son art au regard du plus grand nombre . Pour plus d’informations et demandes d’accès : staff.association@cern.ch | Tél: 022 766 37 38

  14. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    The Elementary Particles of Painting Alfonso Fratteggiani Bianchi and Ermanno Imbergamo From September 26 to October 7, 2016 CERN Meyrin, Main Building With intentions similar to those of CERN physicists, the artist Alfonso Fratteggiani Bianchi investigates the color pigment, studying its interaction with light and with the support on which it is deposited. He creates monochrome paintings by spreading the color pigment in the pure state on stones, without using glue or any other type of adhesive. With intentions similar to artists, the physicist Ermanno Imbergamo investigates the use of luminescent wavelength shifters, materials commonly used in Particle Physics, for art. He creates other monochrome artworks, which disclose further aspects of interaction among light, color pigments and support. For more information: staff.association@cern.ch | Tel: 022 767 28 19

  15. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    COLORATION Sandra Duchêne From September 5 to 16, 2016 CERN Meyrin, Main Building La recherche de l’Universel. Après tout ! C’est de l’Amour ! What else to say ? …La couleur, l’ENERGIE de la vie…

  16. Exhibition

    CERN Multimedia

    Staff Association

    2014-01-01

      Parallels vision Astronomical subjects which evoke extrasensory kinetic visions Alberto Di Fabio From 8 to 10 October, CERN Meyrin, Main Building In the framework of Italy@cern, the Staff Association presents Alberto Di Fabio. Di Fabio’s work is inspired by the fundamental laws of the physical world, as well as organic elements and their interrelation. His paintings and works on paper merge the worlds of art and science, depicting natural forms and biological structures in vivid colour and imaginative detail. For all additional information: staff.association@cern.ch | Tel: 022 767 28 19

  17. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Le Point Isabelle Gailland Du 20 février au 3 mars 2017 CERN Meyrin, Bâtiment principal La Diagonale - Isabelle Gailland. Au départ, un toujours même point minuscule posé au centre de ce que la toile est un espace. Une réplique d'autres points, condensés, alignés, isolés, disséminés construiront dans leur extension, la ligne. Ces lignes, croisées, courbées, déviées, prolongées, seront la structure contenant et séparant la matière des couleurs. La rotation de chaque toile en cours d'exécution va offrir un accès illimité à la non-forme et à la forme. Le point final sera l'ouverture sur différents points de vue de ce que le point et la ligne sont devenus une représentation pour l'œil et l'im...

  18. Exhibition

    CERN Multimedia

    Staff Association

    2018-01-01

    La danse mécanique Daria Grigoryeva Du 22 mai au 1er juin 2018 | CERN Meyrin, Bâtiment principal La danse mécanique est une métaphore large. La mécanique établit les règles et les limites, les frontières dans lesquelles la vie et la créativité peuvent se développer. La musique est « mathématique », une poupée mécanique se tourne toujours dans la même direction, selon les règles prescrites par la nature les fleurs fleurissent au printemps. Même s'ils ne le voulaient pas. La participation à la "danse mécanique" est prédéterminée et inévitable. Il ne reste plus qu'à comprendre comment le faire "magnifiquement". En tout, il y a une signification cachée et un...

  19. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Still Life Jérémy Bajulaz Du 25 septembre au 6 octobre 2017 CERN Meyrin, Main Building (Aubergine - Jérémy Bajulaz) Né en 1991 en Haute-Savoie, France. Diplômé de l'Ecole Emile Cohl à Lyon, Jérémy Bajulaz intègre en 2014 le programme d'artiste en résidence au Centre Genevois de Gravure Contemporaine. C'est là que son travail prendra corps, autour de la lumière et de ses vibrations aux travers de sujets comme le portrait et la nature morte, dans le souci de l'observation; le regard prenant une place importante dans le processus créatif. Lauréat 2017 du VII Premio AAAC, son travail a été présenté dans de nombreuses expositions collectives, en 2015 au Bâtiment d’Art Contemporain de Genève, en 2016 au 89e Salon de Lyon et du ...

  20. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Œuvres recentes Fabienne Wyler Du 6 au 17 février 2017 CERN Meyrin, Bâtiment principal L'escalier du diable B - aquarelle, encre de Chine XLV - Fabienne Wyler. En relation avec certains procédés d’écriture contemporaine (par ex. Webern ou certaines musiques conçues par ordinateur), les compositions picturales de Fabienne Wyler s’élaborent à partir de « modules » (groupes de quadrangles) qu’elle reproduit en leur faisant subir toutes sortes de transformations et de déplacements : étirements, renversements, rotations, effet miroir, transpositions, déphasages, superpositions, etc., et ceci à toutes les échelles. Au fil des œuvres sont apparues des séries intitulées, Bifurcations, Intermittences, Attracteurs étranges, Polyrythmies. Ces titres ont un lien &e...

  1. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Les vibrantes Patrick Robbe-Grillet Du 30 octobre au 10 novembre 2017 CERN Meyrin, Main Building Patrick Robbe-Grillet - Feux d'artifices Qui est Patrick Robbe-Grillet ? Artiste Franco-Suisse, né en 1968 à Genève. En recherche du sentiment de paix, autodidacte, après un séjour en Chine en 2000, puis au Japon en 2002, suivi d’un long questionnement, il trouve sa voie dans la peinture, élément libérateur de sa créativité et expression de sa sensibilité à fleur de peau. « La Chine m’a enseigné les courbes, les nuances. Le Japon, la ligne droite, la rigueur. » Vous avez su rendre visible l'invisible ! - commentaire de Monsieur Fawaz Gruosi Pour plus d’informations et demandes d’accès : staff.association@cern.ch | Tél : 022 766 37 38

  2. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    La couleur des jours oriSio Du 2 au 12 mai 2017 CERN Meyrin, Bâtiment principal oriSio - Motus Suite à un fort intérêt pour la Chine et une curiosité pour un médium très ancien, la laque ! Je réinterprète cet art à travers un style abstrait. Je présente ici des laques sur aluminium, travaillés au plasma et ensuite colorés à l’aide de pigments pour l’essentiel. Mes œuvres je les veux brutes, déchirées, évanescentes, gondolées, voire trouées mais avec une belle approche de profondeur de la couleur.   Pour plus d’informations : staff.association@cern.ch | Tél: 022 766 37 38

  3. Exhibition

    CERN Multimedia

    Staff Association

    2011-01-01

    Jan Hladky, physicien de l'Institut de Physique de l'Académie des Sciences de la République tchèque, et membre de la collaboration Alice, expose ses œuvres au Bâtiment principal du 20 avril au 6 mai. Son exposition est dédiée aux victimes du séisme de Sendai. Des copies de ses œuvres seront mises en vente et les sommes récoltées seront versées au profit des victimes.

  4. Exhibition

    CERN Multimedia

    Staff Association

    2016-01-01

    La mosaïque ou quand détruire permet de construire Lauren Decamps Du 28 novembre au 9 décembre 2016 CERN Meyrin, Bâtiment principal Paysage d'Amsterdam - Lauren Decamps On ne doit jamais rien détruire qu'on ne soit sûr de pouvoir remplacer aussi avantageusement " écrivait Plutarque dans ses Œuvres morales du 1er siècle après JC. L'artiste mosaïste Lauren Decamps adhère à cette idée et tente à sa manière de donner une nouvelle vie à ses matériaux en les taillant puis les réassemblant, créant ainsi des œuvres abstraites et figuratives.

  5. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Firmament des toiles Joëlle Lalagüe Du 6 au 16 juin 2017 CERN Meyrin, Bâtiment principal Phylaë Voyage - Joëlle Lalagüe. Each picture is an invitation for a cosmic trip. This is a whispering of soul, which comes from origins. A symphony of the world, some notes of love, a harmony for us to fly to infinity. Pour plus d’informations et demandes d'accès : staff.association@cern.ch | Tél: 022 766 37 38

  6. Exhibition

    CERN Multimedia

    Staff Association

    2018-01-01

    Univers Du 9 au 20 avril 2018 | CERN Meyrin, Bâtiment principal Stéphanie Cousin Obsédée par les rêves, les mondes surréalistes et insolites, je m’empare de formes provenant des mes propres travaux photographiques ou d’images que je modifie et mixe. Je fais évoluer mes univers oniriques de femmes-animaux ainsi que mes espaces et natures imaginaires. Avec ma démarche artistique, je cherche à mettre en images nos rêves et nos cauchemars, l’irréel et le surréel, le mystique et les affres de notre inconscient. Je cherche à représenter tout ce qui sommeille au plus profond de nous-même à l’aide de symboles, parfois en utilisant des images de cultures ancestrales. Photographie-collage, je cherche à ajouter quelques notes à la définition de la photographie du 21iè...

  7. Exhibition

    CERN Multimedia

    Staff Association

    2017-01-01

    Harmonie Nathalie Lenoir Du 4 au 15 septembre 2017 CERN Meyrin, Bâtiment principal Peindre est un langage. Le tracé du pinceau sur le lin en est l'expression. A qui appartient un tableau en définitive ? A celui qui l'a peint ? A celui qui le regarde ? A celui qui l'emporte ? La peinture est une émotion partagée... Laissez-vous projeter de l'autre côté de la toile, prenez un moment pour rêver, en harmonie avec les éléments, parce-que la peinture parle à votre âme… Pour plus d’informations et demandes d’accès : staff.association@cern.ch | Tél : 022 766 37 38

  8. Exhibition

    CERN Multimedia

    Staff Association

    2018-01-01

    Cosmos KOLI Du 15 au 26 janvier 2018 CERN Meyrin, Main Building (Nébuleuse d'Orion- KOLI) KOLI, Artiste confirmé, diplômé de l’Académie de Beaux Arts de Tirana, depuis 26 ans en Suisse, où il a participé à maintes expositions collectives et organisé 10 expositions privées avec  beaucoup de succès, s’exprime actuellement dans un bonheur de couleur et de matières qui côtoient des hautes sphères… le cosmos ! Gagnant d’un premier prix lors d’une exposition collective organisée par le consulat Italien, il s’est installé au bord du lac dans le canton de Vaud où il vit depuis maintenant déjà 13 ans. www.kolicreation.com Pour plus d’informations et demandes d’accès : staff.association@cern.ch | T&eacut...

  9. Exhibition at the AAA library

    DEFF Research Database (Denmark)

    2013-01-01

    Sonnesgade 11 The exhibition at the AAA library presents selected work produced by students prior to the exhibition of installations in project and praxis constructing an archive at Sonnesgade 11. The exhibition at Sonnesgade 11 was the culmination of collaboration with SLETH architects and studio...

  10. Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice.

    Science.gov (United States)

    Gainetdinov, R R; Bohn, L M; Walker, J K; Laporte, S A; Macrae, A D; Caron, M G; Lefkowitz, R J; Premont, R T

    1999-12-01

    G protein-coupled receptor kinase 5 (GRK5) is a member of a family of enzymes that phosphorylate activated G protein-coupled receptors (GPCR). To address the physiological importance of GRK5-mediated regulation of GPCRs, mice bearing targeted deletion of the GRK5 gene (GRK5-KO) were generated. GRK5-KO mice exhibited mild spontaneous hypothermia as well as pronounced behavioral supersensitivity upon challenge with the nonselective muscarinic agonist oxotremorine. Classical cholinergic responses such as hypothermia, hypoactivity, tremor, and salivation were enhanced in GRK5-KO animals. The antinociceptive effect of oxotremorine was also potentiated and prolonged. Muscarinic receptors in brains from GRK5-KO mice resisted oxotremorine-induced desensitization, as assessed by oxotremorine-stimulated [5S]GTPgammaS binding. These data demonstrate that elimination of GRK5 results in cholinergic supersensitivity and impaired muscarinic receptor desensitization and suggest that a deficit of GPCR desensitization may be an underlying cause of behavioral supersensitivity.

  11. The World of Virtual Exhibitions

    Directory of Open Access Journals (Sweden)

    Irena Eiselt

    2013-09-01

    Full Text Available EXTENDED ABSTRACTSpecial collections of the National and University Library (NUK hide a lot of items of precious value. The Slovenian cultural heritage is stored on paper or on other media as a part of the library’s Manuscripts, Incunabula and Rare Books Collection, Old Prints Collection, Maps and Pictorial Collection, Music Collection, Ephemera Collection, Serials Collection, and Slovenian Diaspora Publications Collection. Only a small part of the treasures is temporary revealed to the public on special exhibitions. The idea of virtual exhibitions of library treasures was born in 2005. The library aimed to exhibit precious items of special collections of high historical or artistic value. In 2008 the first two virtual exhibitions were created in-house offering access to the rich collections of old postcards of Ljubljana at the beginning of 20th century kept in the Maps and Pictorial Collection of NUK. They were soon followed by other virtual exhibitions. At the beginning they were organised in the same way as physical exhibitions, afterwards different programs were used for creation of special effects (for ex. 3D wall. About two years ago it was decided that the creation of virtual exhibitions will be simplified. Files of digitised and borndigital library materials in jpg format are imported to MS PowerPoint 2010. Each jpg file is now formatted by adding a frame, a description … to the slides which are saved as jpg files. The last step is the import of jpg files into Cooliris application used for NUK web exhibitions. In the paper the virtual exhibition design and creation, the technical point of view and criteria for the selection of exhibition content are explained following the example of the virtual exhibitions the Old Postcards of Ljubljana, Photo Ateliers in Slovenia, a collection of photographs Four Seasons by Fran Krašovec and photos of Post-Earthquake Ljubljana in 1895.

  12. Gait disorder as a predictor of spatial learning and memory impairment in aged mice

    Directory of Open Access Journals (Sweden)

    Xin Wang

    2017-01-01

    Full Text Available Objective To investigate whether gait dysfunction is a predictor of severe spatial learning and memory impairment in aged mice. Methods A total of 100 12-month-old male mice that had no obvious abnormal motor ability and whose Morris water maze performances were not significantly different from those of two-month-old male mice were selected for the study. The selected aged mice were then divided into abnormal or normal gait groups according to the results from the quantitative gait assessment. Gaits of aged mice were defined as abnormal when the values of quantitative gait parameters were two standard deviations (SD lower or higher than those of 2-month-old male mice. Gait parameters included stride length, variability of stride length, base of support, cadence, and average speed. After nine months, mice exhibiting severe spatial learning and memory impairment were separated from mice with mild or no cognitive dysfunction. The rate of severe spatial learning and memory impairment in the abnormal and normal gait groups was tested by a chi-square test and the correlation between gait dysfunction and decline in cognitive function was tested using a diagnostic test. Results The 12-month-old aged mice were divided into a normal gait group (n = 75 and an abnormal gait group (n = 25. Nine months later, three mice in the normal gait group and two mice in the abnormal gait group had died. The remaining mice were subjected to the Morris water maze again, and 17 out of 23 mice in the abnormal gait group had developed severe spatial learning and memory impairment, including six with stride length deficits, 15 with coefficient of variation (CV in stride length, two with base of support (BOS deficits, five with cadence dysfunction, and six with average speed deficits. In contrast, only 15 out of 72 mice in the normal gait group developed severe spatial learning and memory impairment. The rate of severe spatial learning and memory impairment was

  13. Ultrapathological evaluation of the anticancer effect of blackseed (Nigella sativa and garlic (Allium sativum in mice

    Directory of Open Access Journals (Sweden)

    Wael Gamal Nouh

    2013-07-01

    Full Text Available In this experimental work, 120 virgin female mice (body weight 40±10 gm were divided into 6 equal groups. Mice in Group 1 served as a control. Mice in Groups 2 and 3 were fed on a basal diet provided with 100 mg/kg b.wt from each of blackseed (Nigella sativa and garlic (Allium sativum, respectively, for one month. Mice in Group 4 were inoculated subcutanously (S/C with Ehrlich tumor cells after one month from the start of the experiment. Mice in Groups 5 and 6 were treated similarly to those in Groups 3 and 4, respectively, for one month and then immediately inoculated S/C with Ehrlich tumor cells (ETC, 0.1 mL/mouse. Blood samples were taken from mice of Groups 1, 2 and 3 at one month of experiment and tissue specimens were collected from mice in all groups two weeks after inoculation of Ehrlich tumor cells. Histopathologically, Groups 2 and 3 showed proliferation of mononuclear phagocytic system and mild degeneration of internal organs. In Group 4, histopathology revealed neoplastic mass with signs of malignancy, ultrastructurely exhibited pleomorphism, degenerated organelles with activated euo- and heterochromatin and cavitations of the cytoplasm. Groups 5 and 6 revealed much smaller neoplastic growth with necrosis and hemorrhage. The necrotic neoplastic cells replaced by empty cavities with congested blood vessels, the others showed pyknotic or karryolytic nuclei. In Groups 5 and 6, the electron microsopic appearance of the neoplastic growth exhibited degenerated and swollen cells with multiple cavitations. Most of the cytoplasmic organelles were degenerated with activation of lysozymes. It could be concluded that, both garlic and black seed minimize the histopathological and electron microscopic alterations of ETC in mice.

  14. Photowalk Exhibition opens at Microcosm

    CERN Document Server

    Katarina Anthony

    2011-01-01

    The winning photographs from the 2010 Global Particle Physics Photowalk competition will go on display at Microcosm from 11 February to 2 April. The exhibition is part of a global photography event taking place over three continents, with Photowalk exhibitions opening simultaneously at Fermilab in the US, KEK in Japan and here at CERN.   DESY wire chamber - First place people's choice; second place global jury competition. Photographer: Hans-Peter Hildebrandt  If you were one of the 1,300 photography lovers who voted in last year’s Photowalk competition, this exhibition is your chance to see the winning entries in print. The exhibition will take place in the downstairs gallery of Microcosm, overlooking the garden. 15 photographs will be on display, with each of the laboratories that participated in Photowalk represented by their 3 winning entries. Among them will be the “people’s choice” sunburst photo of a particle detector at DESY (Photo 1), and...

  15. Globe exhibit wins international acclaim

    CERN Multimedia

    Katarina Anthony

    2011-01-01

    The Globe’s “Universe of Particles” exhibition has recently received four prestigious awards for its avant-garde design. This external praise is great encouragement for the CERN exhibitions currently on the drawing board.   The Universe of Particles exhibition has won 4 awards for its avant-garde design. Back in 2008, the design company Atelier Brückner was presented with a challenge: to design the layout of a new permanent exhibition for CERN, one that would epitomize both the Organization and its research. The brief was concise but complex: the exhibit had to be symbolic of the Organization, use modern technology, engage and immerse visitors, and, preferably, use touch-screen technology. With the help of IArt, an interactive technology firm, and based on the content provided by CERN’s Education Group, Atelier Brückner developed the “Universe of Particles” exhibit as it is today. Its principal concept centred on the s...

  16. Greenhouse Earth: A Traveling Exhibition

    International Nuclear Information System (INIS)

    Booth, W.H.; Caesar, S.

    1992-09-01

    The Franklin Institute Science Museum provided an exhibit entitled the Greenhouse Earth: A Traveling Exhibition. This 3500 square-foot exhibit on global climate change was developed in collaboration with the Association of Science-Technology Centers. The exhibit opened at The Franklin Institute on February 14, 1992, welcoming 291,000 visitors over its three-month stay. During its three-year tour, Greenhouse Earth will travel to ten US cities, reaching two million visitors. Greenhouse Earth aims to deepen public understanding of the scientific issues of global warming and the conservation measures that can be taken to slow its effects. The exhibit features hands-on exhibitry, interactive computer programs and videos, a theater production, a ''demonstration cart,'' guided tours, and lectures. supplemental educational programs at the Institute included a teachers preview, a symposium on climate change, and a ''satellite field trip.'' The development of Greenhouse Earth included front-end and formative evaluation procedures. Evaluation includes interviews with visitors, prototypes, and summative surveys for participating museums. During its stay in Philadelphia, Greenhouse Earth was covered by the local and national press, with reviews in print and broadcast media. Greenhouse Earth is the first large-scale museum exhibit to address global climate change

  17. Bias-corrected estimation in potentially mildly explosive autoregressive models

    DEFF Research Database (Denmark)

    Haufmann, Hendrik; Kruse, Robinson

    This paper provides a comprehensive Monte Carlo comparison of different finite-sample bias-correction methods for autoregressive processes. We consider classic situations where the process is either stationary or exhibits a unit root. Importantly, the case of mildly explosive behaviour is studied...... that the indirect inference approach oers a valuable alternative to other existing techniques. Its performance (measured by its bias and root mean squared error) is balanced and highly competitive across many different settings. A clear advantage is its applicability for mildly explosive processes. In an empirical...

  18. Exhibition - Mathematics, A Beautiful Elsewhere

    CERN Multimedia

    2011-01-01

    From 21 October 2011 to 18 March 2012, the Fondation Cartier pour l’art contemporain will present the exhibition Mathematics: A Beautiful Elsewhere, an exhibition developed in association with the Institut des Hautes Études Scientifiques (IHÉS) and under the patronage of UNESCO. For this unprecedented event, the foundation invited mathematicians to work with artists with whom it has previously worked to create an exhibition that allows visitors to see, hear, do, interpret and think about mathematics. By bringing mathematics into its premises, the Fondation Cartier is itself undergoing the “sudden change of scenery” described by mathematician Alexandre Grothendieck. More information is available here. Fondation Cartier pour l’art contemporain 261, boulevard Raspail 75014 Paris http://fondation.cartier.com Private Visit For professors, researchers and all the staff of Mathematics departments...

  19. Learning from Exhibitions: Chuck Close.

    Science.gov (United States)

    Johnson, Mark M.

    1998-01-01

    Discusses the artwork of Chuck Close, who is well known for his over-sized portraits of fellow artists and anonymous sitters, and the exhibition of his work that premiered at New York's Museum of Modern Art before traveling to other cities in the United States. (CMK)

  20. Inhaled nitric oxide improves short term memory and reduces the inflammatory reaction in a mouse model of mild traumatic brain injury.

    Science.gov (United States)

    Liu, Ping; Li, Yong-Sheng; Quartermain, David; Boutajangout, Allal; Ji, Yong

    2013-07-19

    Although the mechanisms underlying mild traumatic brain injury (mTBI) are becoming well understood, treatment options are still limited. In the present study, mTBI was induced by a weight drop model to produce a closed head injury to mice and the effect of inhaled nitric oxide (INO) was evaluated by a short term memory task (object recognition task) and immunohistochemical staining of glial fibrillary acidic protein (GFAP) and CD45 for the detection of reactive astrocytes and microglia. Results showed that mTBI model did not produce brain edema, skull fracture or sensorimotor coordination dysfunctions. Mice did however exhibit a significant deficit in short term memory (STM) and strong inflammatory reaction in the ipsilateral cortex and hippocampus compared to sham-injured controls 24h after mTBI. Additional groups of untreated mice tested 3 and 7 days later, demonstrated that recognition memory had recovered to normal levels by Day 3. Mice treated with 10ppm INO for 4 or 8h, beginning immediately after TBI demonstrated significantly improved STM at 24h when compared with room air controls (pshort durations of INO prevents this memory loss and also attenuates the inflammatory response. These findings may have relevance for the treatment of patients diagnosed with concussion. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Serum Metabonomics of Mild Acute Pancreatitis.

    Science.gov (United States)

    Xu, Hongmin; Zhang, Lei; Kang, Huan; Zhang, Jiandong; Liu, Jie; Liu, Shuye

    2016-11-01

    Mild acute pancreatitis (MAP) is a common acute abdominal disease, and exhibits rising incidence in recent decades. As an important component of systemic biology, metabonomics is a new discipline developed following genomics and proteomics. In this study, the objective was to analyze the serum metabonomics of patients with MAP, aiming to screen metabolic markers with potential diagnostic values. An analysis platform with ultra performance liquid chromatography-high-resolution mass spectrometry was used to screen the difference metabolites related to MAP diagnosis and disease course monitoring. A total of 432 endogenous metabolites were screened out from 122 serum samples, and 49 difference metabolites were verified, among which 12 difference metabolites were identified by nonparametric test. After material identification, eight metabolites exhibited reliable results, and their levels in MAP serum were higher than those in healthy serum. Four metabolites exhibited gradual downward trend with treatment process going on, and the differences were statistically significant (P Metabonomic analysis has revealed eight metabolites with potential diagnostic values toward MAP, among which four metabolites can be used to monitor the disease course. © 2016 Wiley Periodicals, Inc.

  2. [Unpredictable chronic mild stress effects on antidepressants activities in forced swim test].

    Science.gov (United States)

    Kudryashov, N V; Kalinina, T S; Voronina, T A

    2015-02-01

    The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test.

  3. Mobile Technologies in Museum Exhibitions

    OpenAIRE

    Sandra Medić; Nataša Pavlović

    2014-01-01

    In order to be up–to–date and give visitors a memorable and unique experience, museums are including usage of digital technologies in their exhibitions. Even though museums in Serbia are very important part of tourism offer, they still have traditional settings that are poorly interpreted. The majority of them have a scientific and historical review which is unattractive for various target groups of visitors and for museums it’s important to continually try out new ways in interpretation of t...

  4. A New Exhibition in Microcosm

    CERN Document Server

    2000-01-01

    Sebastien Pelletier explains states of matter to an enthusiastic group of youngsters during the opening of a new exhibition in Microcosm last week. The Fun with Physics workshop will be offered to all 13-14 year olds in school groups visiting CERN this year. The new Microcosm contents have been developed in collaboration with the local teaching community, and cover particles and the forces that act between them.

  5. "Big Science" exhibition at Balexert

    CERN Multimedia

    2008-01-01

    CERN is going out to meet those members of the general public who were unable to attend the recent Open Day. The Laboratory will be taking its "Big Science" exhibition from the Globe of Science and Innovation to the Balexert shopping centre from 19 to 31 May 2008. The exhibition, which shows the LHC and its experiments through the eyes of a photographer, features around thirty spectacular photographs measuring 4.5 metres high and 2.5 metres wide. Welcomed and guided around the exhibition by CERN volunteers, shoppers at Balexert will also have the opportunity to discover LHC components on display and watch films. "Fun with Physics" workshops will be held at certain times of the day. Main hall of the Balexert shopping centre, ground floor, from 9.00 a.m. to 7.00 p.m. Monday to Friday and from 10 a.m. to 6 p.m. on the two Saturdays. Call for volunteers All members of the CERN personnel are invited to enrol as volunteers to help welcom...

  6. Mobile Technologies in Museum Exhibitions

    Directory of Open Access Journals (Sweden)

    Sandra Medić

    2014-10-01

    Full Text Available In order to be up–to–date and give visitors a memorable and unique experience, museums are including usage of digital technologies in their exhibitions. Even though museums in Serbia are very important part of tourism offer, they still have traditional settings that are poorly interpreted. The majority of them have a scientific and historical review which is unattractive for various target groups of visitors and for museums it’s important to continually try out new ways in interpretation of their settings. Because technology continues to rapidly change the way we communicate, cultural institutions should adapt to new ways of communication with their visitors. This paper examines mobile technologies that can be used in museums to give visitors a different experience and transfer the knowledge innovatively. In that way it will be presented the modern concept of presentation of museum exhibitions, focusing on usage of mobile devices through mobile applications and QR codes. The paper provides the broad understanding of usage mobile technologies in museum exhibitions with its advantages and limitations. The research results can help the museums management to improve interpretation and communication with visitors and enrich the visitor experience.

  7. Contemporary Developments in Cinema Exhibition

    OpenAIRE

    Hanson, Stuart

    2014-01-01

    he work offered for this PhD by Published Works charts the history of cinema exhibition in Britain from the late 1950s to the present. At the start of this period, cinemagoing as a form of public entertainment entered a long period of decline that was only arrested with the development and growth of multiplex cinemas in the 1980s and 1990s. Despite these changes, the feature film itself remained a culturally and commercially valuable artefact, though increasingly this meant the Hollywood fil...

  8. Collaborative virtual environments art exhibition

    Science.gov (United States)

    Dolinsky, Margaret; Anstey, Josephine; Pape, Dave E.; Aguilera, Julieta C.; Kostis, Helen-Nicole; Tsoupikova, Daria

    2005-03-01

    This panel presentation will exhibit artwork developed in CAVEs and discuss how art methodologies enhance the science of VR through collaboration, interaction and aesthetics. Artists and scientists work alongside one another to expand scientific research and artistic expression and are motivated by exhibiting collaborative virtual environments. Looking towards the arts, such as painting and sculpture, computer graphics captures a visual tradition. Virtual reality expands this tradition to not only what we face, but to what surrounds us and even what responds to our body and its gestures. Art making that once was isolated to the static frame and an optimal point of view is now out and about, in fully immersive mode within CAVEs. Art knowledge is a guide to how the aesthetics of 2D and 3D worlds affect, transform, and influence the social, intellectual and physical condition of the human body through attention to psychology, spiritual thinking, education, and cognition. The psychological interacts with the physical in the virtual in such a way that each facilitates, enhances and extends the other, culminating in a "go together" world. Attention to sharing art experience across high-speed networks introduces a dimension of liveliness and aliveness when we "become virtual" in real time with others.

  9. Enrico Fermi exhibition at CERN

    CERN Multimedia

    2002-01-01

    A touring exhibition celebrating the centenary of Enrico Fermi's birth in 1901 will be on display at CERN (Main Building, Mezzanine) from 12-27 September. You are cordially invited to the opening celebration on Thursday 12 September at 16:00 (Main Building, Council Chamber), which will include speechs from: Luciano Maiani Welcome and Introduction Arnaldo Stefanini Celebrating Fermi's Centenary in Documents and Pictures Antonino Zichichi The New 'Centro Enrico Fermi' at Via Panisperna Ugo Amaldi Fermi at Via Panisperna and the birth of Nuclear Medicine Jack Steinberger Fermi in Chicago Valentin Telegdi A Close-up of Fermi and the screening of a documentary video about Fermi: Scienziati a Pisa: Enrico Fermi (Scientists at Pisa: Enrico Fermi) created by Francesco Andreotti for La Limonaia from early film, photographs and sound recordings (In Italian, with English subtitles - c. 30 mins). This will be followed by an aperitif on the Mezz...

  10. Crows spontaneously exhibit analogical reasoning.

    Science.gov (United States)

    Smirnova, Anna; Zorina, Zoya; Obozova, Tanya; Wasserman, Edward

    2015-01-19

    Analogical reasoning is vital to advanced cognition and behavioral adaptation. Many theorists deem analogical thinking to be uniquely human and to be foundational to categorization, creative problem solving, and scientific discovery. Comparative psychologists have long been interested in the species generality of analogical reasoning, but they initially found it difficult to obtain empirical support for such thinking in nonhuman animals (for pioneering efforts, see [2, 3]). Researchers have since mustered considerable evidence and argument that relational matching-to-sample (RMTS) effectively captures the essence of analogy, in which the relevant logical arguments are presented visually. In RMTS, choice of test pair BB would be correct if the sample pair were AA, whereas choice of test pair EF would be correct if the sample pair were CD. Critically, no items in the correct test pair physically match items in the sample pair, thus demanding that only relational sameness or differentness is available to support accurate choice responding. Initial evidence suggested that only humans and apes can successfully learn RMTS with pairs of sample and test items; however, monkeys have subsequently done so. Here, we report that crows too exhibit relational matching behavior. Even more importantly, crows spontaneously display relational responding without ever having been trained on RMTS; they had only been trained on identity matching-to-sample (IMTS). Such robust and uninstructed relational matching behavior represents the most convincing evidence yet of analogical reasoning in a nonprimate species, as apes alone have spontaneously exhibited RMTS behavior after only IMTS training. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.

    Science.gov (United States)

    Iwaniec, U T; Philbrick, K A; Wong, C P; Gordon, J L; Kahler-Quesada, A M; Olson, D A; Branscum, A J; Sargent, J L; DeMambro, V E; Rosen, C J; Turner, R T

    2016-10-01

    Room temperature housing (22 °C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 °C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies. Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18-23 °C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 °C for up to 18 weeks. C57BL/6J mice housed at 22 °C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 °C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. Housing female mice at 22 °C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies

  12. EU Climate Change Exhibition Held

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>On April 25, the CPAFFC, the China-EU Association (CEUA) and the Delegation of the European Commission to China jointly held the opening ceremony for the EU Exhibition on Climate Change in the CPAFFC. He Luli, former vice chairperson of the NPC Standing Committee and honorary president of the CEUA, Jose Manuel Barroso, president of the European Commission, and Li Jianping, vice president of the CPAFFC, attended the opening ceremony and made speeches. Honorary President He Luli highly praised the achievements made by China and the EU in their longtime cooperation of mutual benefits in various fields including environmental protection. She said, for many years China and EU have both committed to the development of all-round strategic partnership and establishment of a multi-level mechanism of political dialogue. She expressed, with increasing enthusiasm the CEUA would continue to actively carry out nongovernmental exchanges between China and the EU, and promote cooperation between the two sides in the fields of economy, society, environmental protection, science and technology, culture, etc.

  13. The pathways by which mild hypothermia inhibits neuronal apoptosis following ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Chun Luo

    2015-01-01

    Full Text Available Several studies have demonstrated that mild hypothermia exhibits a neuroprotective role and it can inhibit endothelial cell apoptosis following ischemia/reperfusion injury by decreasing casp-ase-3 expression. It is hypothesized that mild hypothermia exhibits neuroprotective effects on neurons exposed to ischemia/reperfusion condition produced by oxygen-glucose deprivation. Mild hypothermia significantly reduced the number of apoptotic neurons, decreased the expression of pro-apoptotic protein Bax and increased mitochondrial membrane potential, with the peak of anti-apoptotic effect appearing between 6 and 12 hours after the injury. These findings indicate that mild hypothermia inhibits neuronal apoptosis following ischemia/reperfusion injury by protecting the mitochondria and that the effective time window is 6-12 hours after ischemia/reperfusion injury

  14. Comparison of the serial position effect in very mild Alzheimer's disease, mild Alzheimer's disease, and amnesia associated with electroconvulsive therapy.

    Science.gov (United States)

    Bayley, P J; Salmon, D P; Bondi, M W; Bui, B K; Olichney, J; Delis, D C; Thomas, R G; Thal, L J

    2000-03-01

    Individuals given a series of words to memorize normally show better immediate recall for items from the beginning and end of the list than for mid-list items. This phenomenon, known as the serial position effect, is thought to reflect the concurrent contributions of secondary and primary memory, respectively, to recall performance. The present study compared the serial position effects produced on Trial 1 of the California Verbal Learning Test (CVLT) in mildly demented (N = 25; M MMSE = 20.0) and very mildly demented (N = 25; M MMSE = 25.5) patients with Alzheimer's disease (AD), and age- and education-matched normal control (NC) participants (N = 50). In addition, the serial position effects of the very mildly demented AD patients were compared to those of patients with a transient, circumscribed amnesia arising from a prescribed series of electroconvulsive therapy (ECT) treatments for the relief of depressive illness (N = 11). While the NC group exhibited the typical serial position effect, AD patients recalled significantly fewer words than NC participants overall, and exhibited a significantly reduced primacy effect (i.e., recall of the first 2 list items) with a normal recency effect (i.e., recall of the last 2 list items). Patients with circumscribed amnesia due to ECT were as impaired as the very mildly demented AD patients on most standard CVLT measures of learning and memory, but exhibited primacy and recency effects, which were within normal limits. These results suggest that a reduction in the primacy effect, but not the recency effect, is an early and ubiquitous feature of the memory impairment of AD. It is not, however, a necessary feature of all causes of memory impairment.

  15. L-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters.

    Science.gov (United States)

    Xue, Jinsong; Li, Hongyan; Deng, Xueyang; Ma, Zhanqiang; Fu, Qiang; Ma, Shiping

    2015-07-01

    L-Menthone (MTN) is a Chinese old remedy extracted from the genus Mentha. It has been widely used as a cooling agent and a counterirritant for pain relief, although its antidepressant-like effects have not yet been reported. The present study was designed to investigate whether MTN confers an antidepressant-like effect in mice exposed to unpredictable chronic mild stress (UCMS) and to explore its potential mechanisms. The effects of MTN on mouse behavioral changes were investigated in our study. We determined the levels of the nucleotide binding, oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, inflammatory cytokines and neurotransmitters in the hippocampus of mice. Behavioral tests, including the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) revealed that MTN (15 and 30mg/kg) treatments for 3weeks alleviated the depression symptoms of UCMS in mice. Mice receiving MTN treatments exhibited reduced levels of NLRP3 and caspase-1. Moreover, MTN treatments reversed the UCMS-induced alterations in the concentrations of neurotransmitter norepinephrine (NE) and serotonin (5-HT) and inhibited the expression of pro-inflammatory cytokines (PIC) interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus of mice. Taken together, our findings suggested that MTN may play a potential antidepressant-like role in the UCMS mouse model by regulating the NLRP3 inflammasome and mediating inflammatory cytokines and central neurotransmitters, which together provide insight towards the development of novel therapeutic treatments for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Mild expression differences of MECP2 influencing aggressive social behavior.

    Science.gov (United States)

    Tantra, Martesa; Hammer, Christian; Kästner, Anne; Dahm, Liane; Begemann, Martin; Bodda, Chiranjeevi; Hammerschmidt, Kurt; Giegling, Ina; Stepniak, Beata; Castillo Venzor, Aracely; Konte, Bettina; Erbaba, Begun; Hartmann, Annette; Tarami, Asieh; Schulz-Schaeffer, Walter; Rujescu, Dan; Mannan, Ashraf U; Ehrenreich, Hannelore

    2014-05-01

    The X-chromosomal MECP2/Mecp2 gene encodes methyl-CpG-binding protein 2, a transcriptional activator and repressor regulating many other genes. We discovered in male FVB/N mice that mild (~50%) transgenic overexpression of Mecp2 enhances aggression. Surprisingly, when the same transgene was expressed in C57BL/6N mice, transgenics showed reduced aggression and social interaction. This suggests that Mecp2 modulates aggressive social behavior. To test this hypothesis in humans, we performed a phenotype-based genetic association study (PGAS) in >1000 schizophrenic individuals. We found MECP2 SNPs rs2239464 (G/A) and rs2734647 (C/T; 3'UTR) associated with aggression, with the G and C carriers, respectively, being more aggressive. This finding was replicated in an independent schizophrenia cohort. Allele-specific MECP2 mRNA expression differs in peripheral blood mononuclear cells by ~50% (rs2734647: C > T). Notably, the brain-expressed, species-conserved miR-511 binds to MECP2 3'UTR only in T carriers, thereby suppressing gene expression. To conclude, subtle MECP2/Mecp2 expression alterations impact aggression. While the mouse data provides evidence of an interaction between genetic background and mild Mecp2 overexpression, the human data convey means by which genetic variation affects MECP2 expression and behavior.

  17. Increased susceptibility of dystrophin-deficient brain to mild hypoxia

    International Nuclear Information System (INIS)

    Wallis, T.; Rae, C.; Bubb, W.A.; Head, S.I.

    2002-01-01

    Full text: Duchenne muscular dystrophy is an X-linked disorder resulting from total absence of the 427 kDa protein dystrophin. Dystrophin is normally expressed in the brain mainly in a neuronal subpopulation: cortical pyramidal cells, hippocampal CA1 neurons and cerebellar Purkinje cells. One suggested role for dystrophin is in colocalising mitochondrial creatine kinase with ADP translocase and ATP synthase in mitochondria. Brain tissue slices in the murine model of Duchenne dystrophy, the mdx mouse, have been shown to be more sensitive to hypoxia than control. In this work, we used 13 C NMR to monitor the metabolic response of mdx cortical brain tissue slices to normoxia (95%O 2 /5% CO 2 ) and mild hypoxia (95%air/5% CO 2 ). Under normoxic conditions, mdx cortical slices displayed increased net flux through the Krebs cycle and glutamate/glutamine cycle, consistent with the proposed GABA A lesion which results in decreased inhibitory input. By contrast, mild hypoxia resulted in a significant increase in the total pool size of lactate and decreased net flux of 13 C from [3- 13 C]pyruvate into glutamate C4, GABA C2 and Ala C2, as well as decreased anaplerotic activity as measured by the ratio of Asp C2: Asp C3 label. Mild hypoxia has a significantly greater effect on brain oxidative metabolism in mdx mice, than in control

  18. Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system.

    Science.gov (United States)

    Ni, Yu-Fei; Wang, Hao; Gu, Qiu-Yan; Wang, Fei-Ying; Wang, Ying-Jie; Wang, Jin-Liang; Jiang, Bo

    2018-04-01

    Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.

  19. Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.

    Science.gov (United States)

    Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han

    2015-02-01

    The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (PPiper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.

  20. Muscle-directed gene therapy for phenylketonuria (PKU): Development of transgenic mice with muscle-specific phenylalanine hydroxylase expression

    Energy Technology Data Exchange (ETDEWEB)

    Harding, C.O.; Messing, A.; Wolff, J.A. [Univ. of Wisconsin, Madison, WI (United States)

    1994-09-01

    Phenylketonuria (PKU) is an attractive target for gene therapy because of shortcomings in current therapy including lifelong commitment to a difficult and expensive diet, persistent mild cognitive deficits in some children despite adequate dietary therapy, and maternal PKU syndrome. Phenylalanine hydroxylase (PAH) is normally expressed only in liver, but we propose to treat PKU by introducing the gene for PAH into muscle. In order to evaluate both the safety and efficacy of this approach, we have a developed a trangenic mouse which expresses PAH in both cardiac and skeletal muscle. The transgene includes promoter and enhancer sequences from the mouse muscle creatine kinase (MCK) gene fused to the mouse liver PAH cDNA. Mice which have inherited the transgene are healthy, active, and do not exhibit any signs of muscle weakness or wasting. Ectopic PAH expression in muscle is not detrimental to the health, neurologic function, or reproduction of the mice. Pah{sup enu2} hyperphenylalaninemic mice, a model of human PAH deficiency, bred to carry the transgene have substantial PAH expression in cardiac and skeletal muscle but none in liver. Muscle PAH expression alone does not complement the hyperphenylalaninemic phenotype of Pah{sup enu2} mice. However, administration of reduced tetrahydrobiopterin to transgenic Pah{sup enu2} mice is associated with a 25% mean decrease in serum phenylalanine levels. We predict that ectopic expression of PAH in muscle along with adequate muscle supplies of reduced biopterin cofactor will decrease hyperphenylalaninemia in PKU.

  1. Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Yubin Wang

    2016-06-01

    Full Text Available A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1, which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

  2. Consumer preferences for mild cheddar cheese flavors.

    Science.gov (United States)

    Drake, S L; Gerard, P D; Drake, M A

    2008-11-01

    Flavor is an important factor in consumer selection of cheeses. Mild Cheddar cheese is the classification used to describe Cheddar cheese that is not aged extensively and has a "mild" flavor. However, there is no legal definition or age limit for Cheddar cheese to be labeled mild, medium, or sharp, nor are the flavor profiles or flavor expectations of these cheeses specifically defined. The objectives of this study were to document the distinct flavor profiles among commercially labeled mild Cheddar cheeses, and to characterize if consumer preferences existed for specific mild Cheddar cheese flavors or flavor profiles. Flavor descriptive sensory profiles of a representative array of commercial Cheddar cheeses labeled as mild (n= 22) were determined using a trained sensory panel and an established cheese flavor sensory language. Nine representative Cheddar cheeses were selected for consumer testing. Consumers (n= 215) assessed the cheeses for overall liking and other consumer liking attributes. Internal preference mapping, cluster analysis, and discriminant analysis were conducted. Mild Cheddar cheeses were diverse in flavor with many displaying flavors typically associated with more age. Four distinct consumer clusters were identified. The key drivers of liking for mild Cheddar cheese were: color, cooked/milky, whey and brothy flavors, and sour taste. Consumers have distinct flavor and color preferences for mild Cheddar cheese. These results can help manufacturers understand consumer preferences for mild Cheddar cheese.

  3. Mild mental stress in diabetes

    DEFF Research Database (Denmark)

    Hildebrandt, P; Mehlsen, J; Sestoft, L

    1985-01-01

    A TV-game of tennis of 20 min duration was used to study the influence of mild mental stress on subcutaneous blood-flow (SBF), blood-pressure and heart rate in nine insulin-dependent diabetics and nine healthy subjects. SBF was measured on the thigh by local clearance of xenon-133. Measurements...... were made before, during and after the period of stress. During stress, SBF increased significantly by 26% in the healthy subjects, while SBF remained unchanged in the diabetics. The difference between the two groups was significant (P less than 0.05). Following stress, SBF returned to pre-stress level...... in the healthy subjects, while a significant decrease of 33% was observed in the diabetics. The pre-stress heart rate level was higher and the stress-induced increase in heart rate was less in the diabetics compared with the healthy subjects (P less than 0.05). During the stress a slight--but insignificant...

  4. Understanding mild persistent asthma in children

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Szefler, Stanley J

    2005-01-01

    Limitations in asthma prevalence studies and difficulties in diagnosing pediatric asthma lead to uncertainty over the full extent of mild persistent asthma in children and adolescents. Although recent surveys have reported that the majority of pediatric patients with asthma in the United States...... and Europe have symptoms consistent with mild disease, these surveys have limitations in design. Thus, the true prevalence of mild asthma remains unknown. It is unclear whether children with mild persistent asthma progress to more severe asthma, but the risk of severe asthma exacerbations seems...... to be unrelated to the symptom severity. Clinical studies restricted to pediatric patients with mild asthma are limited, but available data do suggest substantial morbidity of mild persistent asthma in this population and support inhaled corticosteroid intervention. There is a need for further investigation...

  5. Opening of the blood-brain barrier before cerebral pathology in mild hyperhomocysteinemia.

    Directory of Open Access Journals (Sweden)

    Bryce C Rhodehouse

    Full Text Available Hyperhomocysteinemia (HHcy is a risk factor for cognitive impairment. The purpose of this study was to determine the temporal pattern of cerebral pathology in a mouse model of mild HHcy, because understanding this time course provides the basis for understanding the mechanisms involved. C57Bl/6 mice with heterozygous deletion cystathionine β-synthase (cbs (+/-; Het were used as a model of mild HHcy along with their wild-type littermates (cbs (+/+; WT. Mice were 'young' (5.3±0.2 months of age and 'old' (16.6±0.9 months of age. Blood-brain barrier (BBB permeability was quantified from Evans blue and sodium fluorescein extravasation. Microvascular architecture was assessed by z-stack confocal microscopy. Leukoaraiosis was measured from Luxol fast blue stained slides of paraffin brain sections. Inflammation was quantified using standard antibody-based immunohistochemical techniques. Cognitive function was assessed using the Morris water maze. BBB permeability was significantly greater in Het vs. WT mice at all ages (p<0.05. There were no differences in microvascular architecture among the groups. Compared with all other groups, old Het mice had significantly greater leukoaraiosis, inflammation in the fornix, and cognitive impairment (p<0.05. In mild HHcy, increased permeability of the BBB precedes the onset of cerebral pathology. This new paradigm may play a role in the progression of disease in HHcy.

  6. Incoordination among Subcellular Compartments Is Associated with Depression-Like Behavior Induced by Chronic Mild Stress

    Science.gov (United States)

    Xu, Aiping; Cui, Shan

    2016-01-01

    Background: Major depressive disorder is characterized as persistent low mood. A chronically stressful life in genetically susceptible individuals is presumably the major etiology that leads to dysfunctions of monoamine and hypothalamus-pituitary-adrenal axis. These pathogenic factors cause neuron atrophy in the limbic system for major depressive disorder. Cell-specific pathophysiology is unclear, so we investigated prelimbic cortical GABAergic neurons and their interaction with glutamatergic neurons in depression-like mice. Methods: Mice were treated with chronic unpredictable mild stress for 3 weeks until they expressed depression-like behaviors confirmed by sucrose preference, Y-maze, and forced swimming tests. The structures and functions of GABAergic and glutamatergic units in prelimbic cortices were studied by cell imaging and electrophysiology in chronic unpredictable mild stress-induced depression mice vs controls. Results: In depression-like mice, prelimbic cortical GABAergic neurons show incoordination among the subcellular compartments, such as decreased excitability and synaptic outputs as well as increased reception from excitatory inputs. GABAergic synapses on glutamatergic cells demonstrate decreased presynaptic innervation and increased postsynaptic responsiveness. Conclusions: Chronic unpredictable mild stress-induced incoordination in prelimbic cortical GABAergic and glutamatergic neurons dysregulates their target neurons, which may be the pathological basis for depressive mood. The rebalance of compatibility among subcellular compartments would be an ideal strategy to treat neural disorders. PMID:26506857

  7. Establishment of HSV1 latency in immunodeficient mice facilitates efficient in vivo reactivation.

    Directory of Open Access Journals (Sweden)

    Chandran Ramakrishna

    2015-03-01

    Full Text Available The establishment of latent infections in sensory neurons is a remarkably effective immune evasion strategy that accounts for the widespread dissemination of life long Herpes Simplex Virus type 1 (HSV1 infections in humans. Periodic reactivation of latent virus results in asymptomatic shedding and transmission of HSV1 or recurrent disease that is usually mild but can be severe. An in-depth understanding of the mechanisms regulating the maintenance of latency and reactivation are essential for developing new approaches to block reactivation. However, the lack of a reliable mouse model that supports efficient in vivo reactivation (IVR resulting in production of infectious HSV1 and/or disease has hampered progress. Since HSV1 reactivation is enhanced in immunosuppressed hosts, we exploited the antiviral and immunomodulatory activities of IVIG (intravenous immunoglobulins to promote survival of latently infected immunodeficient Rag mice. Latently infected Rag mice derived by high dose (HD, but not low dose (LD, HSV1 inoculation exhibited spontaneous reactivation. Following hyperthermia stress (HS, the majority of HD inoculated mice developed HSV1 encephalitis (HSE rapidly and synchronously, whereas for LD inoculated mice reactivated HSV1 persisted only transiently in trigeminal ganglia (Tg. T cells, but not B cells, were required to suppress spontaneous reactivation in HD inoculated latently infected mice. Transfer of HSV1 memory but not OVA specific or naïve T cells prior to HS blocked IVR, revealing the utility of this powerful Rag latency model for studying immune mechanisms involved in control of reactivation. Crossing Rag mice to various knockout strains and infecting them with wild type or mutant HSV1 strains is expected to provide novel insights into the role of specific cellular and viral genes in reactivation, thereby facilitating identification of new targets with the potential to block reactivation.

  8. Meal parameters and vagal gastrointestinal afferents in mice that experienced early postnatal overnutrition.

    Science.gov (United States)

    Biddinger, Jessica E; Fox, Edward A

    2010-08-04

    Early postnatal overnutrition results in a predisposition to develop obesity due in part to hypothalamic and sympathetic dysfunction. Potential involvement of another major regulatory system component--the vagus nerve--has not been examined. Moreover, feeding disturbances have rarely been investigated prior to development of obesity when confounds due to obesity are minimized. To examine these issues, litters were culled on the day of birth to create small litters (SL; overnutrition), or normal size litters (NL; normal nutrition). Body weight, fat pad weight, meal patterns, and vagal sensory duodenal innervation were compared between SL and NL adult mice prior to development of obesity. Meal patterns were studied 18 h/day for 3 weeks using a balanced diet. Then vagal mechanoreceptors were labeled using anterograde transport of wheatgerm agglutinin-horseradish peroxidase injected into the nodose ganglion and their density and morphology were examined. Between postnatal day 1 and weaning, body weight of SL mice was greater than for NL mice. By young adulthood it was similar in both groups, whereas SL fat pad weight was greater in males, suggesting postnatal overnutrition produced a predisposition to obesity. SL mice exhibited increased food intake, decreased satiety ratio, and increased first meal rate (following mild food deprivation) compared to NL mice, suggesting postnatal overnutrition disrupted satiety. The density and structure of intestinal IGLEs appeared similar in SL and NL mice. Thus, although a vagal role cannot be excluded, our meal parameter and anatomical findings provided no evidence for significant postnatal overnutrition effects on vagal gastrointestinal afferents. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM.

    Directory of Open Access Journals (Sweden)

    Patrícia Kellen Martins Oliveira Brito

    Full Text Available Toll-like receptors (TLR contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c. ArtinM (0.5 μg in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval with ArtinM (0.5, 1.0, 2.5, or 5.0 μg, LPS (positive control, or PBS (negative control and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg. Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice.

  10. Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

    Science.gov (United States)

    Oliveira Brito, Patrícia Kellen Martins; Gonçalves, Thiago Eleutério; Fernandes, Fabrício Freitas; Miguel, Camila Botelho; Rodrigues, Wellington Francisco; Lazo Chica, Javier Emílio; Roque-Barreira, Maria Cristina

    2017-01-01

    Toll-like receptors (TLR) contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from Artocarpus heterophyllus interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c.) ArtinM (0.5 μg) in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in naïve BALB/c mice. The mice were s.c. injected twice (7 days interval) with ArtinM (0.5, 1.0, 2.5, or 5.0 μg), LPS (positive control), or PBS (negative control) and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg). Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB) and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected naïve mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in naïve mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to naïve mice. PMID:29084277

  11. Artefacts and the performance of an exhibition

    DEFF Research Database (Denmark)

    Svabo, Connie

    2008-01-01

    The article explores the role of mediating artefacts in children's encounters with a museum of natural history. Using actor network theory it explores how a specific artefact shapes the way users relate to exhibited objects and how the artefact guides users' movements in the exhibition....... The mediated performance of an exhibition is explored through an empirical case....

  12. Affordances and distributed cognition in museum exhibitions

    DEFF Research Database (Denmark)

    Achiam, Marianne; May, Michael; Marandino, Martha

    2014-01-01

    consistent framework. Here, we invoke the notions of affordance and distributed cognition to explain in a coherent way how visitors interact with exhibits and exhibit spaces and make meaning from those interactions, and we exemplify our points using observations of twelve visitors to exhibits at a natural...... history museum. We show how differences in exhibit characteristics give rise to differences in the interpretive strategies used by visitors in their meaning-making process, and conclude by discussing how the notions of affordance and distributed cognition can be used in an exhibit design perspective....

  13. Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.

    Directory of Open Access Journals (Sweden)

    Guangyu Zhao

    Full Text Available The Middle East Respiratory Syndrome Coronavirus (MERS-CoV causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4, the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.

  14. Knockout of Vasohibin-1 Gene in Mice Results in Healthy Longevity with Reduced Expression of Insulin Receptor, Insulin Receptor Substrate 1, and Insulin Receptor Substrate 2 in Their White Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Eichi Takeda

    2017-01-01

    Full Text Available Vasohibin-1 (Vash1, originally isolated as an endothelium-derived angiogenesis inhibitor, has a characteristic of promoting stress tolerance in endothelial cells (ECs. We therefore speculated that the lack of the vash1 gene would result in a short lifespan. However, to our surprise, vash1−/− mice lived significantly longer with a milder senescence phenotype than wild-type (WT mice. We sought the cause of this healthy longevity and found that vash1−/− mice exhibited mild insulin resistance along with reduced expression of the insulin receptor (insr, insulin receptor substrate 1 (irs-1, and insulin receptor substrate 2 (irs-2 in their white adipose tissue (WAT but not in their liver or skeletal muscle. The expression of vash1 dominated in the WAT among those 3 organs. Importantly, vash1−/− mice did not develop diabetes even when fed a high-fat diet. These results indicate that the expression of vash1 was required for the normal insulin sensitivity of the WAT and that the target molecules for this activity were insr, irs1, and irs2. The lack of vash1 caused mild insulin resistance without the outbreak of overt diabetes and might contribute to healthy longevity.

  15. Evaluation of the Anti-schistosomal Effects of Turmeric (Curcuma longa) Versus Praziquantel in Schistosoma mansoni Infected Mice.

    Science.gov (United States)

    Hussein, Atef; Rashed, Samia; El Hayawan, Ibrahim; El-Sayed, Rabab; Ali, Hemat

    2017-01-01

    Curcumin is the major active ingredient of Curcuma longa L. , traditionally known as turmeric and has been shown to exhibit a wide range of pharmacological activities including anti-parasitic effect. However, it is found to be water-insoluble and has low bioavailability. The aim of this study was to explore the potential role of turmeric solved in olive oil either alone or in combination with praziquantel (PZQ) in treatment of schistosomiasis mansoni . The whole turmeric powder suspended in olive oil (as a solvent) is indicated to S. mansoni -infected mice aiming to study its potential therapeutic role, either alone or in combination with PZQ. Turmeric significantly reduced S. mansoni worm burden and complete absence of adult worms achieved in mice treated with combination of turmeric and PZQ. Turmeric has slight non-significant effect on the oogram pattern in all examined S. mansoni infected mice. Turmeric and PZQ found to exert a significant reduction of granuloma size in comparison with control. However, turmeric has a non-significant effect on granuloma number. On the other hand, turmeric or/and PZQ treated mice showed obvious improvement of pathology with mild cloudy swelling and less hydropic degeneration. Turmeric significantly reduced parasite worm burden, granuloma size and consequently the pathology of affected liver, it still far less effective than PZQ.

  16. Evaluation of the Anti-schistosomal Effects of Turmeric (Curcuma longa Versus Praziquantel in Schistosoma mansoni Infected Mice

    Directory of Open Access Journals (Sweden)

    Atef HUSSEIN

    2017-12-01

    Full Text Available AbstractBackground: Curcumin is the major active ingredient of Curcuma longa L., traditionally known as turmeric and has been shown to exhibit a wide range of pharmacological activities including anti-parasitic effect. However, it is found to be water-insoluble and has low bioavailability. The aim of this study was to explore the potential role of turmeric solved in olive oil either alone or in combination with praziquantel (PZQ in treatment of schistosomiasis mansoni.Methods: The whole turmeric powder suspended in olive oil (as a solvent is indicated to S. mansoni-infected mice aiming to study its potential therapeutic role, either alone or in combination with PZQ.Results: Turmeric significantly reduced S. mansoni worm burden and complete absence of adult worms achieved in mice treated with combination of turmeric and PZQ. Turmeric has slight non-significant effect on the oogram pattern in all examined S. mansoni infected mice. Turmeric and PZQ found to exert a significant reduction of granuloma size in comparison with control. However, turmeric has a non-significant effect on granuloma number. On the other hand, turmeric or/and PZQ treated mice showed obvious improvement of pathology with mild cloudy swelling and less hydropic degeneration.Conclusion: Turmeric significantly reduced parasite worm burden, granuloma size and consequently the pathology of affected liver, it still far less effective than PZQ.

  17. Pharmacokinetics, Tissue Distribution and Therapeutic Effect of Cationic Thermosensitive Liposomal Doxorubicin Upon Mild Hyperthermia

    OpenAIRE

    Dicheva, Bilyana M.; Seynhaeve, Ann L. B.; Soulie, Thomas; Eggermont, Alexander M. M.; ten Hagen, Timo L. M.; Koning, Gerben A.

    2015-01-01

    textabstractPurpose: To evaluate pharmacokinetic profile, biodistribution and therapeutic effect of cationic thermosensitive liposomes (CTSL) encapsulating doxorubicin (Dox) upon mild hyperthermia (HT). Methods: Non-targeted thermosensitive liposomes (TSL) and CTSL were developed, loaded with Dox and characterized. Blood kinetics and biodistribution of Dox-TSL and Dox-CTSL were followed in B16BL6 tumor bearing mice upon normothermia (NT) or initial hyperthermia conditions. Efficacy study in B...

  18. Inhibition of the corrosion of mild steel in hydrochloric acid by isatin ...

    African Journals Online (AJOL)

    The inhibition of corrosion of mild steel in hydrochloric acid by isatin glycine (ING) and isatin (IN) at 30-60 oC and concentrations of 0.0001 M to 0.0005 M was studied via weight loss method. At the highest inhibitor concentration studied ING exhibited inhibition efficiency of 87% while IN exhibited 84% at 60 oC. A chemical ...

  19. Investigating Design Research Landscapes through Exhibition

    DEFF Research Database (Denmark)

    Jönsson, Li; Hansen, Flemming Tvede; Mäkelä, Maarit

    2013-01-01

    What characterizes a design research exhibition compared to a traditional design and art exhibition? How do you show the very materialities of the design experiments as a means for communicating knowledge of research and of practice? How do you present, review and utilize such an exhibition......? With those questions in mind, the intention and challenge for the Nordes 2013 Design Research Exhibition was to expand on current notions of staging research enquires in design research conference contexts. Artefacts, installations, performances, and other materialities that relate to the theme...... of the conference - Experiments in Design Research – were displayed as tools to express and communicate different design research enquires. Through this paper we will describe the Nordes exhibition as a specific case that renders questions visible in relation to how to utilize a design research exhibition...

  20. [Definition and clinical characteristics of mild hypertension].

    Science.gov (United States)

    Saruta, Takao

    2008-08-01

    Mild hypertension is defined as blood pressure level of 140-159 mmHg systolic and/or 90-99 mmHg diastolic. The patients with blood pressure level of mild hypertension occupy about 60% of total hypertensive patients in Japan, and most of them are free of subjective symptoms except elevated blood pressure. However, some of the patients with mild hypertension develop cardiovascular events, since thay have occasionally cardiovascular damages on this level of blood pressure and several risk factors of cardiovascular diseases such as diabetes mellitus and hyperlipidemia.

  1. Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

    Science.gov (United States)

    Cacciabue, Marco; García-Núñez, María Soledad; Delgado, Fernando; Currá, Anabella; Marrero, Rubén; Molinari, Paula; Rieder, Elizabeth; Carrillo, Elisa; Gismondi, María Inés

    2017-09-01

    Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Mutant Mice Lacking the p53 C-Terminal Domain Model Telomere Syndromes

    Directory of Open Access Journals (Sweden)

    Iva Simeonova

    2013-06-01

    Full Text Available Mutations in p53, although frequent in human cancers, have not been implicated in telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53Δ31, a p53 lacking the C-terminal domain, exhibit increased p53 activity and suffer from aplastic anemia and pulmonary fibrosis, hallmarks of syndromes caused by short telomeres. Indeed, p53Δ31/Δ31 mice had short telomeres and other phenotypic traits associated with the telomere disease dyskeratosis congenita and its severe variant the Hoyeraal-Hreidarsson syndrome. Heterozygous p53+/Δ31 mice were only mildly affected, but decreased levels of Mdm4, a negative regulator of p53, led to a dramatic aggravation of their symptoms. Importantly, several genes involved in telomere metabolism were downregulated in p53Δ31/Δ31 cells, including Dyskerin, Rtel1, and Tinf2, which are mutated in dyskeratosis congenita, and Terf1, which is implicated in aplastic anemia. Together, these data reveal that a truncating mutation can activate p53 and that p53 plays a major role in the regulation of telomere metabolism.

  3. Superconductive microstrip exhibiting negative differential resistivity

    International Nuclear Information System (INIS)

    Huebener, R.P.; Gallus, D.E.

    1975-01-01

    A device capable of exhibiting negative differential electrical resistivity over a range of values of current and voltage is formed by vapor-depositing a thin layer of a material capable of exhibiting superconductivity on an insulating substrate, establishing electrical connections at opposite ends of the deposited strip, and cooling the alloy into its superconducting range. The device will exhibit negative differential resistivity when biased in the current-induced resistive state

  4. Probable mild Opitz trigonocephaly C syndrome

    African Journals Online (AJOL)

    Rabah M. Shawky

    2011-12-11

    Dec 11, 2011 ... brachycephaly shape to the skull, hypoplastic scrotum and bilateral undescended testes, and mild generalised ... It may occur isolated or syndromic involving other abnor- ..... [12] Sargent C, Burn J, Baraitser M, Pembrey ME.

  5. Postpartum Depression After Mild and Severe Preeclampsia

    NARCIS (Netherlands)

    Hoedjes, Meeke; Berks, Durk; Vogel, Ineke; Franx, Arie; Bangma, Meike; Darlington, Anne-Sophie E.; Visser, Willy; Duvekot, Johannes J.; Habbema, J. Dik F.; Steegers, Eric A. P.; Raat, Hein

    2011-01-01

    Objective: To describe the prevalence of postpartum depressive symptoms after preeclampsia, to assess the extent to which the prevalence of postpartum depressive symptoms differs after mild and severe preeclampsia, and to investigate which factors contribute to such differences. Methods: Women

  6. Thermophysiological adaptations to passive mild heat acclimation

    NARCIS (Netherlands)

    Pallubinsky, H; Schellen, L; Kingma, B R M; Dautzenberg, B; van Baak, M A; van Marken Lichtenbelt, W D

    Passive mild heat acclimation (PMHA) reflects realistic temperature challenges encountered in everyday life. Active heat acclimation, combining heat exposure and exercise, influences several important thermophysiological parameters; for example, it decreases core temperature and enhances heat

  7. Mild TBI Diagnosis and Management Strategies

    Data.gov (United States)

    Department of Veterans Affairs — The Mild Traumatic Brain Injury (TBI) Diagnosis and Management Strategies will assist in the study of TBI issues, such as the Influence of Concussion on Persistent...

  8. Visualizing Hyperactivation in Neurodegeneration Based on Prefrontal Oxygenation: A Comparative Study of Mild Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls

    Directory of Open Access Journals (Sweden)

    Kah Hui Yap

    2017-09-01

    Full Text Available Background: Cognitive performance is relatively well preserved during early cognitive impairment owing to compensatory mechanisms.Methods: We explored functional near-infrared spectroscopy (fNIRS alongside a semantic verbal fluency task (SVFT to investigate any compensation exhibited by the prefrontal cortex (PFC in Mild Cognitive Impairment (MCI and mild Alzheimer's disease (AD. In addition, a group of healthy controls (HC was studied. A total of 61 volunteers (31 HC, 12 patients with MCI and 18 patients with mild AD took part in the present study.Results: Although not statistically significant, MCI exhibited a greater mean activation of both the right and left PFC, followed by HC and mild AD. Analysis showed that in the left PFC, the time taken for HC to achieve the activation level was shorter than MCI and mild AD (p = 0.0047 and 0.0498, respectively; in the right PFC, mild AD took a longer time to achieve the activation level than HC and MCI (p = 0.0469 and 0.0335, respectively; in the right PFC, HC, and MCI demonstrated a steeper slope compared to mild AD (p = 0.0432 and 0. 0107, respectively. The results were, however, not significant when corrected by the Bonferroni-Holm method. There was also found to be a moderately positive correlation (R = 0.5886 between the oxygenation levels in the left PFC and a clinical measure [Mini-Mental State Examination (MMSE score] in MCI subjects uniquely.Discussion: The hyperactivation in MCI coupled with a better SVFT performance may suggest neural compensation, although it is not known to what degree hyperactivation manifests as a potential indicator of compensatory mechanisms. However, hypoactivation plus a poorer SVFT performance in mild AD might indicate an inability to compensate due to the degree of structural impairment.Conclusion: Consistent with the scaffolding theory of aging and cognition, the task-elicited hyperactivation in MCI might reflect the presence of compensatory mechanisms and

  9. A Heuristic for Improving Transmedia Exhibition Experience

    DEFF Research Database (Denmark)

    Selvadurai, Vashanth; Rosenstand, Claus Andreas Foss

    2017-01-01

    in the scientific field of designing transmedia experience in an exhibition context that links the pre- and post-activities to the actual visit (during-activities). The result of this study is a preliminary heuristic for establishing a relation between the platform and content complexity in transmedia exhibitions....

  10. Memory and Mourning: An Exhibit History

    Science.gov (United States)

    Eberle, Scott G.

    2005-01-01

    Mounted by the Strong Museum in Rochester, New York, in 1993, and traveling nationally thereafter, the exhibit Memory and Mourning provided historical and contemporary perspectives to help museum guests explore their own reactions to loss and grief. In the process the exhibit's development team encountered a range of philosophical, historical,…

  11. Let's play game exhibitions : A curator's perspective

    NARCIS (Netherlands)

    de Vos, Jesse; Glas, M.A.J.|info:eu-repo/dai/nl/330981447; van Vught, J.F.|info:eu-repo/dai/nl/413532682

    2017-01-01

    The Netherlands Institute for Sound and Vision is home to The Experience, a museum exhibiting the history of media in the Netherlands. For ten months in 2016 and 2017, The Experience hosted a temporary exhibition entitled Let’s YouTube . During the Let’s YouTube game month, we programmed a ten-day

  12. Science Fiction Exhibits as STEM Gateways

    Science.gov (United States)

    Robie, Samantha

    Women continue to hold less than a quarter of all STEM jobs in the United States, prompting many museums to develop programs and exhibits with the express goal of interesting young girls in scientific fields. At the same time, a number of recent museum exhibits have harnessed the popularity of pop culture and science fiction in order to interest general audiences in STEM subject matter, as well as using the exhibits as springboards to expand or shift mission goals and focus. Because science fiction appears to be successful at raising interest in STEM fields, it may be an effective way to garner the interest of young girls in STEM in particular. This research seeks to describe the ways in which museums are currently using science fiction exhibits to interest young girls in STEM fields and careers. Research focused on four institutions across the country hosting three separate exhibits, and included staff interviews and content analysis of exhibit descriptions, promotional materials, a summative evaluation and supplementary exhibit productions. In some ways, science fiction exhibits do serve young girls, primarily through the inclusion of female role models, staff awareness, and prototype testing to ensure interactives are attractive to girls as well as to boys. However, STEM appears to be underutilized, which may be partly due to a concern within the field that the outcome of targeting a specific gender could be construed as "stereotyping".

  13. The Culture of Exhibitions and Conservation

    Directory of Open Access Journals (Sweden)

    Dimitrios Doumas

    2013-11-01

    Full Text Available The article reflects on temporary exhibitions from a theoretical as well as practical perspective. Regarded as a particularly effective mass-communication medium, exhibitions have a dual nature: they are scholarly undertakings, bringing off a curator’s vision and, simultaneously, they are projects with economic implications that need to be well managed and administered. The role of conservation in the making of temporary exhibitions, either in-house or touring, is here discussed in relation to how work is planned and prioritized as well as how time is managed and staff is allocated. Reference to weaknesses that lessen the crucial input of conservation in the decision-making process is also made. Much of the debate, which focuses on art exhibitions, concerns practicalities encountered in a private museum that extend from the very early stages of selecting objects for display to the mounting of an exhibition.

  14. Holland at CERN – Industrial exhibition

    CERN Multimedia

    GS Department

    2010-01-01

    Sponsored by EVD, an agency of the Dutch Ministry of the Economy From 8 to 11 November 2010 Industrial Exhibition Administration Building Bldg. 61 9-00 - 17-30 Twenty seven companies will present their latest technology at the industrial exhibition "Holland at CERN". Dutch industry will exhibit products and technologies which are related to the field of particle physics. Individual interviews will take place directly at the stands in the Main Building. The firms will contact relevant users/technicians but any user wishing to make contact with a particular firm is welcome to use the contact details which are available from each departmental secretariat or at the following URL: http://gs-dep.web.cern.ch/gs-dep/groups/sem/ls/Industrial_Exhibitions.htm#Industrial_exhibitions You will find the list of exhibitors below. LIST OF EXHIBITORS: Schelde Exotech Vernooy BV Triumph Group INCAA Computers DeMaCo Holland bv TNO Science & Industry Janssen Precision Engi...

  15. Investigating Ongoing Strategic Behaviour of Students with Mild Mental Retardation: Implementation and Relations to Performance in a Problem-Solving Situation

    Science.gov (United States)

    Dermitzaki, Irini; Stavroussi, Panayiota; Bandi, Maria; Nisiotou, Ioulia

    2008-01-01

    The aim of this study was to investigate to what extent students with mild mental retardation exhibit strategic behaviour during problem solving and to investigate the relationships between the ongoing behaviours examined and the students' respective performance. Eleven students with non-organic mild mental retardation participated in the study.…

  16. A mini-exhibition with maximum content

    CERN Multimedia

    Laëtitia Pedroso

    2011-01-01

    The University of Budapest has been hosting a CERN mini-exhibition since 8 May. While smaller than the main travelling exhibition it has a number of major advantages: its compact design alleviates transport difficulties and makes it easier to find suitable venues in the Member States. Its content can be updated almost instantaneously and it will become even more interactive and high-tech as time goes by.   The exhibition on display in Budapest. The purpose of CERN's new mini-exhibition is to be more interactive and easier to install. Due to its size, the main travelling exhibition cannot be moved around quickly, which is why it stays in the same country for 4 to 6 months. But this means a long waiting list for the other Member States. To solve this problem, the Education Group has designed a new exhibition, which is smaller and thus easier to install. Smaller maybe, but no less rich in content, as the new exhibition conveys exactly the same messages as its larger counterpart. However, in the slimm...

  17. Combat Veterans with Comorbid PTSD and Mild TBI Exhibit a Greater Inhibitory Processing ERP from the Dorsal Anterior Cingulate Cortex

    Science.gov (United States)

    2014-08-08

    emotion processing biases in depressed undergraduates. Biological Psychology 81, 153–163. Krompinger, J.W., Simons, R.F., 2011. Cognitive inefficiency...in depressive under- graduates: stroop processing and ERPs. Biological Psychology 86, 239–246. Lanius, R.A., Vermetten, E., Loewenstein, R.J., Brand...prefrontal cortex and anterior cingulate during error processing. Psychosomatic Medicine 74, 471–475. I.-W. Shu et al. / Psychiatry Research: Neuroimaging 224

  18. Environmental Enrichment Mitigates Deficits after Repetitive Mild Traumatic Brain Injury.

    Science.gov (United States)

    Liu, Xixia; Qiu, Jianhua; Alcon, Sasha; Hashim, Jumana; Meehan, William P; Mannix, Rebekah

    2017-08-15

    Although environmental enrichment has been shown to improve functional and histologic outcomes in pre-clinical moderate-to-severe traumatic brain injury (TBI), there are a paucity of pre-clinical data regarding enrichment strategies in the setting of repetitive mild traumatic brain injury (rmTBI). Given the vast numbers of athletes and those in the military who sustain rmTBI, the mounting evidence of the long-term and progressive sequelae of rmTBI, and the lack of targeted therapies to mitigate these sequelae, successful enrichment interventions in rmTBI could have large public health significance. Here, we evaluated enrichment strategies in an established pre-clinical rmTBI model. Seventy-one male C57BL/6 mice were randomized to two different housing conditions, environmental enrichment (EE) or normal condition (NC), then subjected to rmTBI injury (seven injuries in 9 days) or sham injury (anesthesia only). Functional outcomes in all four groups (NC-TBI, EE-TBI, NC-sham, and EE-sham) were assessed by motor, exploratory/anxiety, and mnemonic behavioral tests. At the synaptic level, N-methyl d-aspartate receptor (NMDAR) subunit expression of phosphorylated glutamate receptor 1 (GluR1), phosphorylated Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), and calpain were evaluated by western blot. Compared to injured NC-TBI mice, EE-TBI mice had improved memory and decreased anxiety and exploratory activity post-injury. Treatment with enrichment also corresponded to normal NMDAR subunit expression, decreased GluR1 phosphorylation, decreased phosphorylated CaMKII, and normal calpain expression post-rmTBI. These data suggest that enrichment strategies may improve functional outcomes and mitigate synaptic changes post-rmTBI. Given that enrichment strategies are feasible in the clinical setting, particularly for athletes and soldiers for whom the risk of repetitive injury is greatest, these data suggest that clinical trials may be warranted.

  19. France at CERN – Industrial exhibition

    CERN Multimedia

    FP Department

    2012-01-01

    Industrial Exhibition Administration Building Bldg 61 – 1st Floor Tuesday 27 March: 9 a.m. – 5.30 p.m. Wednesday 28 March: 9 a.m. – 2 p.m.   About thirty French companies are presenting their latest technological advances during the industrial exhibition "France at CERN", featuring products and technologies specifically related to CERN activities. Individual B2B meetings can be organized with the sales and technical representatives of participating firms and will take place at either the companies’ exhibition stands or in conference rooms in the Main Building. Individuals wishing to make contact with one or more companies must use the contact details available from each secretariat of department or by using this link. B2B meetings will be coordinated by UBIFRANCE. You will also find the list of exhibiting and participating companies online here. This event is sponsored by the French subsidiary of RS Components, the most important distri...

  20. High Quality Virtual Reality for Architectural Exhibitions

    DEFF Research Database (Denmark)

    Kreutzberg, Anette

    2016-01-01

    This paper will summarise the findings from creating and implementing a visually high quality Virtual Reality (VR) experiment as part of an international architecture exhibition. It was the aim to represent the architectural spatial qualities as well as the atmosphere created from combining natural...... and artificial lighting in a prominent not yet built project. The outcome is twofold: Findings concerning the integration of VR in an exhibition space and findings concerning the experience of the virtual space itself. In the exhibition, an important aspect was the unmanned exhibition space, requiring the VR...... experience to be self-explanatory. Observations of different visitor reactions to the unmanned VR experience compared with visitor reactions at guided tours with personal instructions are evaluated. Data on perception of realism, spatial quality and light in the VR model were collected with qualitative...

  1. Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis

    Science.gov (United States)

    Loos, Julia A.; Dávila, Valeria A.; Rodrígues, Christian R.; Petrigh, Romina; Zoppi, Jorge A.; Crocenzi, Fernando A.; Cumino, Andrea C.

    2017-01-01

    Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy. PMID:28182659

  2. Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.

    Directory of Open Access Journals (Sweden)

    Julia A Loos

    2017-02-01

    Full Text Available Metformin (Met is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy.

  3. The presentation of energy topics at exhibitions

    International Nuclear Information System (INIS)

    Moergeli, H.P.

    1984-01-01

    The author examines the problems confronting an electricity supply company when trying to communicate its energy policy to the general public at exhibitions and fairs. The company has to convey a message of reliable power supplies, increasing demand, the advantages of nuclear energy, the safe storage of radioactive waste and the need for new generating plants. The author describes some of the displays being used to attract the public to the Bern Power Stations stand at the Bern Exhibition 1984. (R.S.)

  4. An Astrobiology Microbes Exhibit and Education Module

    Science.gov (United States)

    Lindstrom, Marilyn M.; Allen, Jaclyn S.; Stocco, Karen; Tobola, Kay; Olendzenski, Lorraine

    2001-01-01

    Telling the story of NASA-sponsored scientific research to the public in exhibits is best done by partnerships of scientists and museum professionals. Likewise, preparing classroom activities and training teachers to use them should be done by teams of teachers and scientists. Here we describe how we used such partnerships to develop a new astrobiology augmentation to the Microbes! traveling exhibit and a companion education module. "Additional information is contained in the original extended abstract."

  5. Adipose gene expression response of lean and obese mice to short-term dietary restriction.

    NARCIS (Netherlands)

    Schothorst, Evert M van; Keijer, Jaap; Pennings, Jeroen L A; Opperhuizen, Antoon; Brom, Charissa E van den; Kohl, Thomas; Franssen-van Hal, Nicole L W; Hoebee, Barbara

    2006-01-01

    Overweight and obesity lead to higher morbidity risks, which are alleviated even by mild weight loss. To gain insight in the molecular effects of weight loss in adipose tissue, we analyzed the effects of short-term dietary restriction (DR) on mice fed a low-fat diet (lean mice) or a high-fat diet

  6. Mild Primary Hyperparathyroidism: A Literature Review

    Science.gov (United States)

    Applewhite, Megan K.

    2014-01-01

    The biochemical profile of classic primary hyperparathyroidism (pHPT) consists of both elevated calcium and parathyroid hormone levels. The standard of care is parathyroidectomy unless prohibited by medical comorbidities. Because more patients are undergoing routine bone density evaluation and neck imaging studies for other purposes, there is a subset of people identified with a biochemically mild form of the pHPT that expresses itself as either elevated calcium or parathyroid hormone levels. These patients often do not fall into the criteria for operation based on the National Institutes of Health consensus guidelines, and they can present a challenge of diagnosis and management. The purpose of this paper is to review the available literature on mild pHPT in an effort to better characterize this patient population and to determine whether patients benefit from parathyroidectomy. Evidence suggests that there are patients with mild pHPT who have overt symptoms that are found to improve after parathyroidectomy. There is also a group of patients with biochemically mild pHPT who are found to progress to classic pHPT over time; however, it is not predictable which group of patients this will be. Early intervention for this group with mild pHPT may prevent progression of bone, psychiatric, and renal complications, and parathyroidectomy has proven safe in appropriately selected patients at high volume centers. PMID:25063228

  7. Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras/Rap-associating domain.

    Science.gov (United States)

    Maeta, Kazuhiro; Hattori, Satoko; Ikutomo, Junji; Edamatsu, Hironori; Bilasy, Shymaa E; Miyakawa, Tsuyoshi; Kataoka, Tohru

    2018-05-10

    Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap small GTPases, characterized by the possession of the Ras/Rap-associating domain. Previous genomic analyses suggested their possible involvement in the etiology of schizophrenia. We recently demonstrated the development of an ectopic cortical mass (ECM), which resembles the human subcortical band heterotopia, in the dorsal telencephalon-specific Rapgef2 conditional knockout (Rapgef2-cKO) brains. Additional knockout of Rapgef6 in Rapgef2-cKO mice resulted in gross enlargement of the ECM whereas knockout of Rapgef6 alone (Rapgef6-KO) had no discernible effect on the brain morphology. Here, we performed a battery of behavioral tests to examine the effects of Rapgef2 or Rapgef6 deficiency on higher brain functions. Rapgef2-cKO mice exhibited hyperlocomotion phenotypes. They showed decreased anxiety-like behavior in the elevated plus maze and the open-field tests as well as increased depression-like behavior in the Porsolt forced swim and tail suspension tests. They also exhibited increased sociability especially in novel environments. They showed defects in cognitive function as evidenced by reduced learning ability in the Barnes circular maze test and by impaired working memory in the T maze tests. In contrast, although Rapgef6 and Rapgef2 share similarities in biochemical roles, Rapgef6-KO mice exhibited mild behavioral abnormalities detected with a number of behavioral tests, such as hyperlocomotion phenotype in the open-field test and the social interaction test with a novel environment and working-memory defects in the T-maze test. In conclusion, although there were differences in their brain morphology and the magnitude of the behavioral abnormalities, Rapgef2-cKO mice and Rapgef6-KO mice exhibited hyperlocomotion phenotype and working-memory defect, both of which could be recognized as schizophrenia-like behavior.

  8. Radiation carcinogenesis in scid mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Hiroko; Nishimura, Mayumi; Kobayashi, Shigeru; Tsuji, Hideo; Shimada, Yoshiya; Ogiu, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan); Suzuki, Fumio; Sado, Toshihiko

    1999-06-01

    Scid mice which have the defect of DNA-dependent protein kinase catalitic subunit, exhibit the limited activities of repair from DNA double strand breaks, and are sensitive to ionizing radiation. In order to study the relationship between repair capacity for DNA double strand breaks and carcinogenesis, the effects of ionizing radiation were studied using scid homozygotes (scid/scid), scid heterozygotes (scid/+) and CB-17 (+/+) mice. Both the Scid bone marrow cells and fibroblast cell lines from Scid embryos were highly sensitivity to acute effects of ionizing radiation. Carcinogenesis experiments showed the high incidence of thymic lymphomas (80 to 90%) in 1 to 3 Gy {sup 137}Cs-{gamma}-ray-irradiated Scid mice. (author)

  9. Skeletal muscle weakness in osteogenesis imperfecta mice.

    Science.gov (United States)

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

    2010-09-01

    Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the proα1(I) or proα2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (P(o), P(o)/mg and P(o)/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased P(o) and an inability to sustain P(o) for the 300-ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Turning energy around: an interactive exhibition experience

    Directory of Open Access Journals (Sweden)

    Sarah Kellberg

    2018-05-01

    Full Text Available A transition from the fossil-fuel driven to a sustainable energy system is an enormous global challenge: climate change and finite resources require countries all over the world to change their way of producing, transporting and using energy. The Energiewende (energy transition will require major changes in the current energy supply system in Germany – but also worldwide. These changes will not only affect the technical sector but will also include ecological questions, social issues and political matters. Whether any transition is going to favour large scale solutions or decentralised technologies depends on local situations and global interconnections, and above all on a democratic process. Hence energy transition succeeds or fails with the acceptance and participation of society. To deal with this overwhelmingly complex topic and its multi-layered dependencies, the Deutsches Museum has designed an exhibition providing visitors with background knowledge about the necessities and challenges of energy transition, unpicking the links between the different technical, economic and social challenges. The exhibition accomplishes the task with an engaging and facilitating approach while taking into account the highly emotive aspects of energy transition as a societal issue. This paper presents the concept of the travelling exhibition energie.wenden, relating it to the Deutsches Museum´s tradition of exhibitions as well as to the challenge of how to deal with socio-scientific topics in scientific exhibitions.

  11. CERN exhibition a big hit in Bulgaria

    CERN Multimedia

    2005-01-01

    The first CERN exhibition in Bulgaria attracted many visitors. In the first ever CERN exhibition to be held in Bulgaria, over 1,400 visitors, many of them students and young physicists, visited the 10-day event in Sofia. The CERN mini-exhibition took place at the National Earth and Mankind Museum between 8 and 17 November. Permanently staffed by young physicists from Sofia University, there were exhibits on display about research activities at CERN, as well as four additional posters describing Bulgaria's participation. The inauguration took place on the morning of 8 November in the presence of the Vice-Minister for Science and Education, Mrs. Vanya Dobreva, and some 200 guests. A series of short speeches were followed by a visit to the exhibition. CERN's representative at the event, Ray Lewis, was then asked by Professor Matey Mateev, President of the Union of Physicists in Bulgaria, to say a few words on behalf of the Organization. Numerous journalists were also present at the inauguration. A painting enti...

  12. Education or business? - exhibition of human corpses

    Directory of Open Access Journals (Sweden)

    Grzegorz Wróbel

    2017-09-01

    Full Text Available Exhibition "BODY WORLDS" which are presented exhibits of human remains are presented all over the world and are a major problem for the modern man, as presented on the preparations of the human not only serve scientific research, are not transferred to the medical schools to educate future doctors, but they were made available to the general public in the form of commercial and ambiguous. The aim of this study was to assess the ethical commercialization of human corpses "BODY WORLDS" exhibitions. Individual approach to the problems presented the dignity and value of human remains after death, of course, strongly related to the professed worldview. In the exhibits can be seen in both the scientific interest anatomical structures, as well as desecrated human remains or beautiful by its functional perfection of the body, understood also in terms of art. The question of ethics determines the right to decide for themselves, on the other hand, allows you to protect bodily integrity even after death. "BODY WORLDS" exhibition goes for the moral and ethical boundaries. In terms of people Gunther von Hagens for plastination of human remains which became a very profitable business, and its current activities defined as "plastination business" should be firmly said about the lack of moral principles.

  13. Neuropsychological function following mild exposure to pentaborane

    International Nuclear Information System (INIS)

    Hart, R.P.; Silverman, J.J.; Garrettson, L.K.; Schulz, C.; Hamer, R.M.

    1984-01-01

    Neuropsychological tests and self-report personality inventories were administered to 14 workers and rescue squad personnel approximately 2 months following mild exposure to pentaborane, a highly toxic volatile liquid boron hydride. Performance decrements were evident on 5 of 11 neuropsychological tests, including Block Design and measures of sustained attention and recent memory. Neuropsychological deficits were not related to emotional changes reported on the Hopkins Symptom Checklist nor to the presence of CT scan abnormality. These results indicate mild residual brain dysfunction following pentaborane intoxication, including possible dysfunction in subcortical regions mediating memory processes and in cortical areas mediating visuo-spatial abilities

  14. The exploration of the exhibition informatization

    Science.gov (United States)

    Zhang, Jiankang

    2017-06-01

    The construction and management of exhibition informatization is the main task and choke point during the process of Chinese exhibition industry’s transformation and promotion. There are three key points expected to realize a breakthrough during the construction of Chinese exhibition informatization, and the three aspects respectively are adopting service outsourcing to construct and maintain the database, adopting advanced chest card technology to collect various kinds of information, developing statistics analysis to maintain good cutomer relations. The success of Chinese exhibition informatization mainly calls for mature suppliers who can provide construction and maintenance of database, the proven technology, a sense of data security, advanced chest card technology, the ability of data mining and analysis and the ability to improve the exhibition service basing on the commercial information got from the data analysis. Several data security measures are expected to apply during the process of system developing, including the measures of the terminal data security, the internet data security, the media data security, the storage data security and the application data security. The informatization of this process is based on the chest card designing. At present, there are several types of chest card technology: bar code chest card; two-dimension code card; magnetic stripe chest card; smart-chip chest card. The information got from the exhibition data will help the organizers to make relevant service strategies, quantify the accumulated indexes of the customers, and improve the level of the customer’s satisfaction and loyalty, what’s more, the information can also provide more additional services like the commercial trips, VIP ceremonial reception.

  15. Inhibiting Effect of Nicotinic Acid Hydrazide on Corrosion of Aluminum and Mild Steel in Acidic Medium

    Energy Technology Data Exchange (ETDEWEB)

    Bhat, J. Ishwara [Mangalore Univ., Karnataka (India); Alva, Vijaya D. P. [Shree Devi Institute of Technology, Karnataka (India)

    2014-02-15

    The corrosion behavior of aluminum and mild steel in hydrochloric acid medium was studied using a nicotinic acid hydrazide as inhibitor by potentiodynamic polarization, electrochemical impedance spectroscopy technique and gravimetric methods. The effects of inhibitor concentration and temperature were investigated. The experimental results suggested, nicotinic acid hydrazide is a good corrosion inhibitor for both aluminum and mild steel in hydrochloric acid medium and the inhibition efficiency increased with increase in the inhibitor concentration. The polarization studies revealed that nicotinic acid hydrazide exhibits mixed type of inhibition. The inhibition was assumed to occur via adsorption of the inhibitor molecules on the aluminum and mild steel surface and inhibits corrosion by blocking the reaction sites on the surface of aluminum.

  16. Inhibiting Effect of Nicotinic Acid Hydrazide on Corrosion of Aluminum and Mild Steel in Acidic Medium

    International Nuclear Information System (INIS)

    Bhat, J. Ishwara; Alva, Vijaya D. P.

    2014-01-01

    The corrosion behavior of aluminum and mild steel in hydrochloric acid medium was studied using a nicotinic acid hydrazide as inhibitor by potentiodynamic polarization, electrochemical impedance spectroscopy technique and gravimetric methods. The effects of inhibitor concentration and temperature were investigated. The experimental results suggested, nicotinic acid hydrazide is a good corrosion inhibitor for both aluminum and mild steel in hydrochloric acid medium and the inhibition efficiency increased with increase in the inhibitor concentration. The polarization studies revealed that nicotinic acid hydrazide exhibits mixed type of inhibition. The inhibition was assumed to occur via adsorption of the inhibitor molecules on the aluminum and mild steel surface and inhibits corrosion by blocking the reaction sites on the surface of aluminum

  17. Exhibits in libraries a practical guide

    CERN Document Server

    Brown, Mary E

    2005-01-01

    "Ccomprehensive...detailed"--Booklist; "thoroughly reseached...highly recommended"--Journal of Access Services. Library exhibits are more than entertainment for patrons. They can inspire and educate, stimulate an interest that can be explored in a book, or attract visitors who otherwise wouldn't stop by. Displays are also an opportunity for a library to put its creative foot forward or help patrons navigate the facility itself. This comprehensive "how-to" includes everything a librarian or staff member needs to know to put on an exhibit, from hatching ideas to evaluating the end result. Illustrations and photographs show practical methods of planning, labeling and displaying.

  18. Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis Due to Dysfunction of the Hypothalamic Glucocorticoid Receptor in Sigma-1 Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    Tingting Di

    2017-09-01

    Full Text Available Sigma-1 receptor knockout (σ1R-KO mice exhibit a depressive-like phenotype. Because σ1R is highly expressed in the neuronal cells of hypothalamic paraventricular nuclei (PVN, this study investigated the influence of σ1R deficiency on the regulation of the hypothalamic-pituitary-adrenocortical (HPA axis. Here, we show that the levels of basal serum corticosterone (CORT, adrenocorticotropic hormone (ACTH and corticotrophin releasing factor (CRF as well as the level of CRF mRNA in PVN did not significantly differ between adult male σ1R-KO mice and wild-type (WT mice. Acute mild restraint stress (AMRS induced a higher and more sustainable increase in activity of HPA axis and CRF expression in σ1R-KO mice. Percentage of dexamethasone (Dex-induced reduction in level of CORT was markedly attenuated in σ1R−/− mice. The levels of glucocorticoid receptor (GR and protein kinase C (PKC phosphorylation were reduced in the PVN of σ1R-KO mice and σ1R antagonist NE100-treated WT mice. The exposure to AMRS in σ1R-KO mice induced a stronger phosphorylation of cAMP-response element binding protein (CREB in PVN than that in WT mice. Intracerebroventricular (i.c.v. injection of PKC activator PMA for 3 days in σ1R-KO mice not only recovered the GR phosphorylation and the percentage of Dex-reduced CORT but also corrected the AMRS-induced hyperactivity of HPA axis and enhancement of CRF mRNA and CREB phosphorylation. Furthermore, the injection (i.c.v. of PMA in σ1R-KO mice corrected the prolongation of immobility time in forced swim test (FST and tail suspension test (TST. These results indicate that σ1R deficiency causes down-regulation of GR by reducing PKC phosphorylation, which attenuates GR-mediated feedback inhibition of HPA axis and facilitates the stress response of HPA axis leading to the production of depressive-like behaviors.

  19. Cloning Mice.

    Science.gov (United States)

    Ogura, Atsuo

    2017-08-01

    Viable and fertile mice can be generated by somatic nuclear transfer into enucleated oocytes, presumably because the transplanted somatic cell genome becomes reprogrammed by factors in the oocyte. The first somatic cloned offspring of mice were obtained by directly injecting donor nuclei into recipient enucleated oocytes. When this method is used (the so-called Honolulu method of somatic cell nuclear transfer [SCNT]), the donor nuclei readily and completely condense within the enucleated metaphase II-arrested oocytes, which contain high levels of M-phase-promoting factor (MPF). It is believed that the condensation of the donor chromosomes promotes complete reprogramming of the donor genome within the mouse oocytes. Another key to the success of mouse cloning is the use of blunt micropipettes attached to a piezo impact-driving micromanipulation device. This system saves a significant amount of time during the micromanipulation of oocytes and thus minimizes the loss of oocyte viability in vitro. For example, a group of 20 oocytes can be enucleated within 10 min by an experienced operator. This protocol is composed of seven parts: (1) preparing micropipettes, (2) setting up the enucleation and injection micropipettes, (3) collecting and enucleating oocytes, (4) preparing nucleus donor cells, (5) injecting donor nuclei, (6) activating embryos and culturing, and (7) transferring cloned embryos. © 2017 Cold Spring Harbor Laboratory Press.

  20. How do exhibition visitors describe aesthetic qualities?

    DEFF Research Database (Denmark)

    Thomsen, Bente Dahl; Ravn, Anders Peter

    2007-01-01

    In this investigation, visitors to an art and design exhibition have used an interactive computer program to express the qualities they consider important for an art or design object (artefact). They have then used the program with their individually selected qualities to assess the artefacts. In...

  1. CERN exhibition wins yet another design prize

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    The “Universe of Particles” exhibition in CERN’s Globe wins the silver design prize from the German direct business communications association FAMAB.   Not only do tens of thousands of people visit the “Universe of Particles” exhibition each year, but juries for design prizes are crossing its threshold more and more frequently too. In 2011 alone it claimed 8 awards, including winning outright the 2011 Annual Multimedia award, the iF Communication Design for Corporate Architecture award and the Modern Decoration Media award (the Bulletin already reported on some of these in July 2011). The FAMAB award is the latest to join the prestigious list. The jury of FAMAB’s “ADAM 2011” award was particularly impressed by the hands-on nature of the exhibition, which encourages visitors to get interested in science. They also appreciated the way that the space in the Globe is not just a container for the exhibits, but itself ...

  2. 49 CFR 250.2 - Required exhibits.

    Science.gov (United States)

    2010-10-01

    ... carried; and identification of the ten most important industries served. (6) As Exhibit 6, statement as to... application for the financing has been made, evidencing that they have declined the financing unless guaranteed by the Secretary or specifying the terms upon which they will undertake the financing without such...

  3. CCPIT Machinery Exhibition Succeeded in Kuala Lumpur

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ From August 18 to 20, 2005, China Council for the Promotion of International Trade(CCPIT) held China Machinery and Electronics Trade Exhibition, CME 2005 in Kuala Lumpur, the capital of Malaysia on behalf of China, a good job has been done.

  4. CCPIT Machinery Exhibition Succeeded in Kuala Lumpur

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

      From August 18 to 20, 2005, China Council for the Promotion of International Trade(CCPIT) held China Machinery and Electronics Trade Exhibition, CME 2005 in Kuala Lumpur, the capital of Malaysia on behalf of China, a good job has been done.……

  5. Comic Strips to Accompany Science Museum Exhibits

    Science.gov (United States)

    Chung, Beom Sun; Park, Eun-mi; Kim, Sang-Hee; Cho, Sook-kyoung; Chung, Min Suk

    2016-01-01

    Science museums make the effort to create exhibits with amusing explanations. However, existing explanation signs with lengthy text are not appealing, and as such, visitors do not pay attention to them. In contrast, conspicuous comic strips composed of simple drawings and humors can attract science museum visitors. This study attempted to reveal…

  6. 18 CFR 50.7 - Applications: exhibits.

    Science.gov (United States)

    2010-04-01

    ... systems, including the special protective systems' automatic switching or load shedding system; and (ii... transfer capability (NITC); system protection; and system stability. (3) A stability analysis including... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Applications: exhibits...

  7. Do we over treat mild hypertension?

    Science.gov (United States)

    Zanchetti, Alberto

    2015-06-01

    The important question whether 'mild' hypertension should or should not be treated by drugs is difficult to answer, because the only randomized controlled trials (RCTs) investigating this question were conducted when the definition of 'mild' hypertension was based on diastolic blood pressure only, whereas the present definition of grade 1 hypertension includes both systolic and diastolic values (SBP/DBP), and the concept of 'mild' hypertension also includes that of low-moderate cardiovascular risk (hypertension only on the basis of expert opinion. However, recent meta-analyses have provided some support to drug treatment intervention in low-moderate risk grade 1 hypertensives and have shown that, when treatment is deferred until organ damage or cardiovascular disease occur, absolute residual risk (events occurring despite treatment) markedly increases. Although evidence favoring therapeutic intervention in mild hypertension is nowadays stronger than expert opinion, meta-analyses are not substitutes for specific RCTs, and the wide BP spans defining grade 1 hypertension as well as the span defining low-moderate risk leave a wide space for individualized or personalized decisions.

  8. Mission Connect Mild TBI Translational Research Consortium

    Science.gov (United States)

    2013-08-01

    and covered with dental acrylic . Isoflurane was discontinued; rats were connected to the trauma device and subjected to a mild 1.0-atm fluid-percussion...thought to play roles in the regulation of extracellular concentrations of water, potassium and other ions, and glutamate and other transmitters and

  9. Learning Strategies for Adolescents with Mild Disabilities

    Science.gov (United States)

    Conderman, Greg; Koman, Kara; Schibelka, Mary; Higgin, Karen; Cooper, Cody; Butler, Jordyn

    2013-01-01

    Learning strategy instruction is an evidence-based practice for teaching adolescents with mild disabilities. However, researchers have not developed strategies for every content area or skill. Therefore, teachers need to be able develop strategies based on the needs of their students. This article reviews the process for developing and teaching…

  10. Mild disintegration of green microalgae and macroalgae

    NARCIS (Netherlands)

    Postma, Richard

    2016-01-01

    An increased worldwide protein demand for food and feed and the necessity to release the water soluble proteins in the first stage of the cascade biorefinery require the development of mild protein extraction technologies. Cell disintegration is the first hurdle and is considered as one of the

  11. SHORT COMMUNICATION CONVENIENT AND MILD SYNTHESIS ...

    African Journals Online (AJOL)

    Preferred Customer

    *Corresponding author. E-mail: naeimi@kashanu.ac.ir. SHORT COMMUNICATION. CONVENIENT AND MILD SYNTHESIS AND CHARACTERISATION OF. SOME NEW SCHIFF BASES. Hossein Naeimi* and Zahra Sadat Nazifi. Department of Organic Chemistry, Faculty of Chemistry, University of Kashan,. Kashan, 87317 ...

  12. Travelling CERN Exhibition ''When Energy Becomes Matter''

    International Nuclear Information System (INIS)

    2001-01-01

    Full text: The European Laboratory for Nuclear Research (CERN) and the H. Niewodniczanski Institute of Nuclear Physics together with the Institute of Physics of the Jagiellonian University and the University of Mining and Metallurgy, and under the auspices of the Polish National Atomic Energy Agency organized in the Museum of Nature in Cracow from October 16 till December 16, 2000 the exhibition ''When Energy Becomes Matter''. The Office of the ''Festival Cracow 2000'' was the main sponsor of that event. The exhibition was a part of the F estival Cracow 2000'' called ''Festival of Youngsters Cracow 2000''. Invitations, posters and information leaflets were sent to more than 3000 schools in southern Poland. The exhibition was divided into four specially designed quadrants. In the first the visitor was informed what kind of scales are in use to describe the Universe and the atom. The second introduced elementary particles via the cosmic ray demonstrations. Particle acceleration was demonstrated with the help of a TV set. The third segment was devoted to the Large Hadron Collider and its experiments: CMS, ATLAS, ALICE and LHCb. The last segment was an attempt to explain what are quarks, leptons and intermediate bosons. In addition it was also explained what is antimatter and why symmetry is broken in Nature. In one of the rooms we arranged the cinema where five movies was continuously presented. Thanks to the Cracow TV it was possible to prepare Polish translations of the films: B ack to creation , P owers of ten , L HC - time machine , S tars underground , and G eneva event . Another attraction of the exhibition was the Internet room equipped with the help of Polish Telecommunication. The exhibition was open seven days per week from 10 to 17 h. During the working days every 20 minutes a new group of about 25-30 people was visiting the exhibition. Each group was guided by students and PhD students from our Institute, Jagiellonian University and University of Mining

  13. Adaptation and possible attenuation of Theileria parva-infected cells grown in irradiated mice

    International Nuclear Information System (INIS)

    Irvin, A.D.; Brown, C.G.D.; Stagg, D.A.; Kanhai, G.K.; Kimber, C.D.; Radley, D.E.

    1976-01-01

    Theileria parva-infected bovine lymphoid cells were taken from 8 cattle immediately after death from East Coast fever (ECF). Cells were inoculated into groups of irradiated Swiss and athymic nude mice. The irradiated mice were exposed to 800 rad doses from a 60 Co source. Cells became established in one group of Swiss mice and 2 groups of athymic mice. Development of cells in mice only occurred if cells concurrently established in culture; when establishment in culture was delayed, cells failed to develop in mice. Cells from one of the isolates in athymic mice were passaged 6 times through further mice. On inoculation of these mouse-passaged cells into cattle, the animals underwent mild reactions and subsequently resisted a lethal ECF challenge. The possibility of vaccinating cattle aginst ECF by means of mouse passaged cells merits further study. (author)

  14. inhibition performance of mild ste thiophene ac rmance of mild steel

    African Journals Online (AJOL)

    userpc

    d Industrial Chemistry, Faculty of Physical Science, Bayero University, Kan. P. M. B. 3011 ..... chemical studies on the inhibition potentials of some ... Efficiency of Thiophene Derivatives on. Mild Steel : A QSAR Model. International. Journal.

  15. LHC INAUGURATION, LHC Fest highlights: exhibition time!

    CERN Multimedia

    2008-01-01

    David Gross, one of the twenty-one Nobel Laureates who have participated in the project.Tuesday 21 October 2008 Accelerating Nobels Colliding Charm, Atomic Cuisine, The Good Anomaly, A Quark Somewhere on the White Paper, Wire Proliferation, A Tale of Two Liquids … these are just some of the titles given to artworks by Physics Nobel Laureates who agreed to make drawings of their prize-winning discoveries (more or less reluctantly) during a special photo session. Science photographer Volker Steger made portraits of Physics Nobel Laureates and before the photo sessions he asked them to make a drawing of their most important discovery. The result is "Accelerating Nobels", an exhibition that combines unusual portraits of and original drawings by twenty-one Nobel laureates in physics whose work is closely related to CERN and the LHC. This exhibition will be one of the highlights of the LHC celebrations on 21 October in the SM18 hall b...

  16. Exhibition: Women and Sciences by Fiami

    CERN Multimedia

    Globe Info

    2011-01-01

    The 19-panel exhibition is on display at CERN's Microcosm from Monday to Saturday from 10.00 a.m. to 5.00 p.m.   Marie Curie won the Nobel Prize for Chemistry one hundred years ago. She is the only woman ever to win two Nobel Prizes, which is a testament to her remarkable work. But throughout history, women have played a role in science either in their own right or alongside other scientists. In this special exhibition, the comic-strip artist Fiami takes a look back at the relationship between women and science through his portraits of Mileva Einstein, Marie-Anne Lavoisier and, of course, Marie Curie. Fiami has recently published an entire album devoted to Marie Curie. Texts in French All ages - Entrance free Femmes et Sciences is on display at Microcosm: From Wednesday 21 September 2011 to Tuesday 20 December 2011.

  17. Kuala Namu Convention And Exhibition Centre

    OpenAIRE

    Gustriana, Trisna

    2017-01-01

    Aerotropolis area development that is expected to accommodate the development of business and commercial appeal and this is the chance for the designer to be able to take advantage of the situation and condition of land as well as possible. So that the revolutionary changes but is able to embrace all stakeholders is the solution needed to development Aerotropolis. Kuala Namu's Convention and Exhibition Center is expected to be a solution for regional development of Kuala Namu a...

  18. 22nd Annual Logistics Conference and Exhibition

    Science.gov (United States)

    2006-04-20

    Bill” Kenwell, Vice President, Sales and Marketing, Maersk 5:30pm-7:30pm Reception in Exhibit Hall Wednesday, April 19, 2006 7:00am-5:30pm...some commercial sales of our products, services and platforms. We provide surface, air, and undersea applications on more than 460 programs for US...diagnostic system & process • Seamless B2B integration with maintenance systems Enabled By… EOATM Overview Sensor Data Maintenance Logs Repair Data Expert

  19. The Factory of the Future, Group Exhibition

    OpenAIRE

    Dean, Lionel T.

    2016-01-01

    3D Printing, The factory of the future, Lieu du Design (centre for Design), Paris This exhibition dedicated entirely to 3D printing technology was billed as “the first in France wholly devoted to exploring the interdisciplinary and multifaceted topic of 3D printing technology and its undeniable influence on everything from industry, to economics, to creative and social issues, demonstrated to the public through achievements in the fields of 3D design, 3D printed architecture, 3D printed fa...

  20. Brazilian air traffic controllers exhibit excessive sleepiness.

    Science.gov (United States)

    Ribas, Valdenilson Ribeiro; de Almeida, Cláudia Ângela Vilela; Martins, Hugo André de Lima; Alves, Carlos Frederico de Oliveira; Alves, Marcos José Pinheiro Cândido; Carneiro, Severino Marcos de Oliveira; Ribas, Valéria Ribeiro; de Vasconcelos, Carlos Augusto Carvalho; Sougey, Everton Botelho; de Castro, Raul Manhães

    2011-01-01

    Excessive sleepiness (ES) is an increased tendency to initiate involuntary sleep for naps at inappropriate times. The objective of this study was to assess ES in air traffic controllers (ATCo). 45 flight protection professionals were evaluated, comprising 30 ATCo, subdivided into ATCo with ten or more years in the profession (ATCo≥10, n=15) and ATCo with less than ten years in the profession (ATCoair traffic controllers exhibit excessive sleepiness.

  1. Naval Meteorology and Oceanography Command exhibit entrance

    Science.gov (United States)

    2000-01-01

    StenniSphere at NASA's John C. Stennis Space Center in Hancock County, Miss., invites visitors to discover why America comes to Stennis Space Center before going into space. Designed to entertain while educating, StenniSphere includes informative displays and exhibits from NASA and other agencies located at Stennis, such as this one from the Naval Meteorology and Oceanography Command. Visitors can 'travel' three-dimensionally under the sea and check on the weather back home in the Weather Center.

  2. Naval Meteorology and Oceanography Command exhibit

    Science.gov (United States)

    2000-01-01

    Designed to entertain while educating, StenniSphere at the John C. Stennis Space Center in Hancock County, Miss., includes informative displays and exhibits from NASA and other agencies located at Stennis, such as this one from the Naval Meteorology and Oceanography Command. Visitors can 'travel' three-dimensionally under the sea and check on the weather back home in the Weather Center. StenniSphere is open free of charge from 9 a.m. to 5 p.m. daily.

  3. Exhibition: Linus Pauling and the Twentieth Century

    CERN Document Server

    2003-01-01

    On April 28 the exhibit Linus Pauling and the Twentieth Century organised by UNIDIR (United Nations Institute for Disarmament Research) and SGI (Soka Gakkai International) as well as with the contributions of CERN and the University of Geneva, opened at the United Nations Office of Geneva. Linus Pauling is the only person to date to have won two unshared Nobel Prizes: Chemistry in 1954 and Peace in 1962. The first was awarded for his landmark research on the nature of the chemical bond and its application in understanding the structure of complex substances. The second one acknowledged his courageous protest against atmospheric nuclear testing and his championship of international peace. The exhibit, for audience of all ages, traces seven decades of Linus Pauling's life and influence on the 20th century. Before starting its European tour at the UNESCO headquarters in Paris, the exhibit opened in 1998 in San Francisco and then travelled within the United-States and to Japan with an attendance of more than one...

  4. Exhibition: Linus Pauling and the Twentieth Century

    CERN Document Server

    2003-01-01

    On April 28 the exhibit Linus Pauling and the Twentieth Century organised by UNIDIR (United Nations Institute for Disarmament Research) and SGI (Soka Gakkai International) as well as with the contributions of CERN and the University of Geneva, opens at the United Nations Office of Geneva. Linus Pauling is the only person to date to have won two unshared Nobel Prizes: Chemistry in 1954 and Peace in 1962. The first was awarded for his landmark research on the nature of the chemical bond and its application in understanding the structure of complex substances. The second one acknowledged his courageous protest against atmospheric nuclear testing and his championship of international peace. The exhibit, for all ages' audiences, traces seven decades of Linus Pauling's life and influence on the 20th century. Before starting its European tour at the UNESCO headquarters in Paris, the exhibit opened in 1998 in San Francisco and then travelled within the United-States and to Japan with an attendance of more than one m...

  5. Bumblebees exhibit the memory spacing effect

    Science.gov (United States)

    Toda, Nicholas R. T.; Song, Jeremy; Nieh, James C.

    2009-10-01

    Associative learning is key to how bees recognize and return to rewarding floral resources. It thus plays a major role in pollinator floral constancy and plant gene flow. Honeybees are the primary model for pollinator associative learning, but bumblebees play an important ecological role in a wider range of habitats, and their associative learning abilities are less well understood. We assayed learning with the proboscis extension reflex (PER), using a novel method for restraining bees (capsules) designed to improve bumblebee learning. We present the first results demonstrating that bumblebees exhibit the memory spacing effect. They improve their associative learning of odor and nectar reward by exhibiting increased memory acquisition, a component of long-term memory formation, when the time interval between rewarding trials is increased. Bombus impatiens forager memory acquisition (average discrimination index values) improved by 129% and 65% at inter-trial intervals (ITI) of 5 and 3 min, respectively, as compared to an ITI of 1 min. Memory acquisition rate also increased with increasing ITI. Encapsulation significantly increases olfactory memory acquisition. Ten times more foragers exhibited at least one PER response during training in capsules as compared to traditional PER harnesses. Thus, a novel conditioning assay, encapsulation, enabled us to improve bumblebee-learning acquisition and demonstrate that spaced learning results in better memory consolidation. Such spaced learning likely plays a role in forming long-term memories of rewarding floral resources.

  6. Exhibition: Dialogue between Science and religion

    CERN Multimedia

    2001-01-01

    Can the theory of the Big Bang reached by physicists and the concept of creation beloved of religion ever be reconciled? The two approaches have at least one point in common: they do not provide a final answer to the mysteries of the birth of the Universe. And this means that dialogue is alays possible between the two. It is to show the potential of such an exchange that Geneva's Société Evangélique organization is opening an exhibition under the title 'Big Bang and Creation', at the Planète Charmilles shopping centre, to run from 19 to 30 March. View of the 'Big Bang and Creation' exhibition. The exhibition is divided into three sections, showing the views of the scientist and those of the believer without setting them up in opposition to one another. In the first section, under a representation of the vault of heaven, the visitor will discover the different ideas explaining the birth of the Universe: Genesis and the Big Bang, and the different dominant theories ...

  7. Art exhibit focuses on African astronomy

    Science.gov (United States)

    Showstack, Randy

    2012-07-01

    Connections between Africans and astronomy are the focus of a new exhibition in the National Museum of African Art in Washington, D. C. "African Cosmos: Stellar Arts," which includes artwork, cultural items, and scientific displays from ancient to contemporary times, is the first major exhibit "that brings together arts and science focused on Africa's contribution to keen observations of the heavens over time," curator Christine Mullen Kreamer said at a 20 June news briefing. Among the exhibit's nearly 100 objects are an ancient Egyptian mummy board that includes a representation of the sky goddess Nut, sculptures by the Dogon people of Mali depicting figures in relation to the cosmos, a video that uses data from two square degrees of the Hubble Space Telescope Cosmic Evolution Survey, and a nearly floor-to-ceiling "Rainbow Serpent" constructed of plastic containers by Benin artist Hazoume. An untitled acrylic painting (Figure 1) by South African Gavin Jantjes evokes a myth of the Khoi San people of southern Africa, as it portrays a girl throwing evening fire embers into the night sky, where they remained as the Milky Way.

  8. Metabolic characteristics of long-lived mice

    Directory of Open Access Journals (Sweden)

    Andrzej eBartke

    2012-12-01

    Full Text Available Genetic suppression of insulin/insulin-like growth factor signaling (IIS can extend longevity in worms, insects, and mammals. In laboratory mice, mutations with the greatest, most consistent, and best documented positive impact on lifespan are those that disrupt growth hormone (GH release or actions. These mutations lead to major alterations in IIS but also have a variety of effects that are not directly related to the actions of insulin or insulin-like growth factor (IGF-1. Long-lived GH-resistant GHRKO mice with targeted disruption of the GH receptor gene, as well as Ames dwarf (Prop1df and Snell dwarf (Pit1dw mice lacking GH (along with prolactin and TSH, are diminutive in size and have major alterations in body composition and metabolic parameters including increased subcutaneous adiposity, increased relative brain weight, small liver, hypoinsulinemia, mild hypoglycemia, increased adiponectin levels and insulin sensitivity, and reduced serum lipids. Body temperature is reduced in Ames, Snell, and female GHRKO mice. Indirect calorimetry revealed that both Ames dwarf and GHRKO mice utilize more oxygen per gram (g of body weight than sex- and age-matched normal animals from the same strain. They also have reduced respiratory quotient (RQ, implying greater reliance on fats, as opposed to carbohydrates, as an energy source. Differences in oxygen consumption (VO2 were seen in animals fed or fasted during the measurements as well as in animals that had been exposed to 30% calorie restriction or every-other-day feeding. However, at the thermoneutral temperature of 30°C, VO2 did not differ between GHRKO and normal mice. Thus, the increased metabolic rate of the GHRKO mice, at a standard animal room temperature of 23°C, is apparently related to increased energy demands for thermoregulation in these diminutive animals. We suspect that increased oxidative metabolism combined with enhanced fatty acid oxidation contribute to the extended longevity of

  9. Measurement and analysis of polarization curves of mild steel in sodium carbonate/bicarbonate solution under erosion-corrosion conditions

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Q. [Taiyuan University of Technology, Taiyuan (China). Research Institute of Surface Engineering

    2002-06-01

    The polarization curves of mild steel in de-aerated 0.5 and mol NaHCO{sub 3} + 0.5 mol Na{sub 2}CO{sub 3} solution with and without erodent particles of 300 g/L of 100 {mu}m alumina have been measured using a rotating cylinder electrode (RCE) apparatus over the range of rotation speeds fro 0 to 4,000 r/min. The results show that the mild steel in the de-aerated slurry exhibits classical active/passive polarization behavior. The speed of cylinder rotation has a great effect in the presence of particles on the active dissolution current density. The erosion-corrosion process is severely erosion-dominated for the mild steel. However, the poor corrosion resistance of the mild steel in such turbulent slurries is also significant, especially at lower than 4 m/s. 19 refs., 5 figs.

  10. Establishment of a Radiation-Induced Fibrosis Model in BALB/c Mice

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Seung Hee; Lee, Sang Wook; Moon, Soo Young; Oh, Jeong Yoon; Yang, Youn Joo; Park, Jin Hong [Dept. of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2010-11-15

    Although radiation-induced fibrosis is one of the common sequelae occurring after irradiation of skin and soft tissues, the treatment methods are not well standardized. This study aimed to establish the skin fibrosis mouse model by fractionated radiation for the further mechanism studies or testing the efficacy of therapeutic candidates. The right hind limbs of BALB/c mice received two fractions of 20 Gy using a therapeutic linear accelerator. Early skin damages were scored and tissue fibrosis was assessed by the measurement of a leg extension. Morphological changes were assessed by H and E staining and by Masson's Trichrome staining. TGF-{beta}1 expression from soft tissues was also detected by immunohistochemistry and PCR. Two fractions of 20 Gy irradiation were demonstrated as being enough to induce early skin damage effects such as erythema, mild skin dryness, dry and wet desquamation within several weeks of radiation. After 13 weeks of irradiation, the average radiation-induced leg contraction was 11.1 {+-} 6.2 mm. Morphologic changes in irradiated skin biopsies exhibited disorganized collagen and extracellular matrix fibers, as well as the accumulation of myofibroblasts compared to the non-irradiated skin. Moreover, TGF-{beta}1 expression in tissue was increased by radiation. These results show that two fractions of 20 Gy irradiation can induce skin fibrosis in BALB/c mice accompanied by other common characteristics of skin damages. This animal model can be a useful tool for studying skin fibrosis induced by radiation.

  11. Thyroid disorders in mild iodine deficiency

    DEFF Research Database (Denmark)

    Laurberg, P; Nøhr, S B; Pedersen, K M

    2000-01-01

    Comparative epidemiologic studies in areas with low and high iodine intake and controlled studies of iodine supplementation have demonstrated that the major consequence of mild-to-moderate iodine deficiency for the health of the population is an extraordinarily high occurrence of hyperthyroidism...... endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine...... deficiency should be corrected. However, there is evidence that a high iodine intake may be associated with more autoimmune hypothyroidism, and that Graves' disease may manifest at a younger age and be more difficult to treat. Hence, the iodine intake should be brought to a level at which iodine deficiency...

  12. Mild Hydrothermal Synthesis of Ni–Cu Nanoparticles

    Directory of Open Access Journals (Sweden)

    G. H. Mohamed Saeed

    2010-01-01

    Full Text Available Magnetic Ni-rich Ni–Cu nanoparticles with Ni : Cu mass ratio (S of 2.0 and 2.6 were prepared using a mixture of polyoxyethylene (10 isooctylphenyl ether (Triton X-100 and sodium dodecyl sulfate (SDS in a mild hydrothermal condition at 95ºC. X-ray diffractometry (XRD showed that the nanoparticles prepared at S=2.0 possessed Ni–Cu alloy characteristic whereas the characteristic was absent at S=2.6. The XRD data was enhanced by Fourier transform infrared spectroscopy (FTIR which exhibited metal-metal (Ni–Cu band at 455 cm−1. Based on transmission electron microscopy (TEM, the average particle sizes for the nanoparticles prepared at S=2.0 and 2.6 were in the range of 19–23 nm. The as-prepared nanoparticles exhibited paramagnetic behaviour measured using a vibrating sample magnetometer (VSM and the specific saturation magnetization decreased at the higher concentration of Ni.

  13. Ventilatory response of the newborn infant to mild hypoxia.

    Science.gov (United States)

    Cohen, G; Malcolm, G; Henderson-Smart, D

    1997-09-01

    The transition from an immature (biphasic) to a mature (sustained hyperpneic) response to a brief period of sustained hypoxia is believed to be well advanced by postnatal day 10 for newborn infants. However, a review of the supporting evidence convinced us that this issue warranted further, more systematic investigation. Seven healthy term infants aged 2 days to 8 weeks were studied. The ventilatory response (VR) elicited by 5 min breathing of 15% O2 was measured during quiet sleep. Arterial SaO2 (pulse oximeter) and minute ventilation (expressed as a change from control, delta V'i) were measured continuously. Infants were wrapped in their usual bedding and slept in open cots at room temperature (23 degrees-25 degrees). Infants aged 2-3 days exhibited predominantely a sustained hypopnea during the period of hypoxia (delta V'i = -2% at 1 min, -13% at 5 min). At 8 weeks of age, the mean response was typically biphasic (delta V'i = +9% at 1 min, -4% at 5 min). This age-related difference between responses was statistically significant (two-way ANOVA by time and age-group; interaction P < 0.05). These data reveal that term infants studied under ambient conditions during defined quiet sleep may exhibit an immature VR to mild, sustained hypoxia for at least 2 months after birth. This suggests that postnatal development of the O2 chemoreflex is slower than previously thought.

  14. A mild form of Proteus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hauer, M.P.; Allmann, K.H.; Langer, M. [Abteilung Roentgendiagnostik, Radiologische Universitaetsklinik, Albert-Ludwigs-Universitaet Freiburg (Germany); Uhl, M. [Sektion Kinderradiologie, Albert-Ludwigs-Universitaet (Germany); Darge, K. [Radiologische Universitaetsklinik, Abteilung Kinderradiologie, Universitaet Heidelberg (Germany)

    1998-05-01

    Proteus syndrome is a rare congenital hamartomatous syndrome. We report on the clinical and radiological appearances of a boy in order to illustrate the typical signs which include subcutaneous masses, in mild forms partial gigantism of hands and feet, hemihypertrophy, and bony abnormalities. We discuss how to make the definitive diagnosis on the basis of using a known rating scale, important aspects of differential diagnosis and clinical features, and diagnostic management. (orig.) With 3 figs., 1 tab., 14 refs.

  15. Developmental Exposure to Mild Variable Stress: Adult ...

    Science.gov (United States)

    In utero exposure to mild variable stress has been reported to influence learning and memory formation in offspring. Our research aims to examine whether nonchemical environmental stressors will exacerbate effects to chemical exposure. This study utilized a varying stress paradigm to simulate human psychosocial stress incurred during and after pregnancy to identify phenotypic learning changes in adult offspring that are potential stress markers. We additionally wanted to compare these behavioral outcomes to rat performance induced by perinatal exposure to manganese (Mn), a neurotoxic environmental element, at 2 or 5 g/l in drinking water throughout gestation and lactation. Pregnant Long Evans rats were exposed to an unpredictable series of mild stressful events which had previously been shown to increase maternal corticosterone levels. Nonchemical stressors were presented from GD 13 through GD 21 and included varying noise, light, housing, and confinement during both sleep and wake cycles. A subgroup of offspring was also exposed to periods of maternal separation. Starting at PND 97 offspring were trained with a trace fear conditioning protocol whereby rats were exposed to a compound cue (light and tone) followed by 30 seconds (trace period) and a mild foot shock (1mA, 0.5 seconds). Five paired training sessions occurred on the first day. The following day, context and cue learning were assessed by measuring motor activity. Preliminary data suggests adu

  16. Library exhibits and programs boost science education

    Science.gov (United States)

    Dusenbery, Paul B.; Curtis, Lisa

    2012-05-01

    Science museums let visitors explore and discover, but for many families there are barriers—such as cost or distance—that prevent them from visiting museums and experiencing hands-on science, technology, engineering, and mathematics (STEM) learning. Now educators are reaching underserved audiences by developing STEM exhibits and programs for public libraries. With more than 16,000 outlets in the United States, public libraries serve almost every community in the country. Nationwide, they receive about 1.5 billion visits per year, and they offer their services for free.

  17. Mild obstructive sleep apnoea: clinical relevance and approaches to management.

    Science.gov (United States)

    McNicholas, Walter T; Bonsignore, Maria R; Lévy, Patrick; Ryan, Silke

    2016-10-01

    Obstructive sleep apnoea is highly prevalent in the general population worldwide, especially in its mild form. Clinical manifestations correlate poorly with disease severity measured by the apnoea-hypopnoea index (AHI), which complicates diagnosis. Full polysomnography might be more appropriate to assess suspected mild cases because limited ambulatory diagnostic systems are least accurate in mild disease. Treatment options in mild obstructive sleep apnoea include continuous positive airway pressure (CPAP) and oral appliance therapy, in addition to positional therapy and weight reduction when appropriate. The superior efficacy of CPAP in reducing AHI is offset by greater tolerance of oral appliances, especially in mild disease. Although severe obstructive sleep apnoea is associated with adverse health consequences, including cardiometabolic comorbidities, the association with mild disease is unclear, and reports differ regarding the clinical relevance of mild obstructive sleep apnoea. Improved diagnostic techniques and evidence-based approaches to management in mild obstructive sleep apnoea require further research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Mild Cognitive Impairment and Progession to Dementia: New Findings

    Science.gov (United States)

    ... David C. Spencer, MD Steven Karceski, MD Mild cognitive impairment and progression to dementia New findings John C.S. ... exami- nations showed that 534 persons had mild cognitive impairment, or MCI (see About MCI, following sec- tion). ...

  19. Impact of Mild versus Moderate Intensity Aerobic Walking Exercise ...

    African Journals Online (AJOL)

    2014-03-01

    Mar 1, 2014 ... Objective: To compare the effects of mild and moderate intensity treadmill walking exercises on markers of bone ... second group (B) received mild intensity aerobic exercise training. ..... Using functional loading to influence.

  20. Transgenic Mice Expressing an Inhibitory Truncated Form of p300 Exhibit Long-Term Memory Deficits

    Science.gov (United States)

    Oliveira, Ana M. M.; Wood, Marcelo A.; McDonough, Conor B.; Abel, Ted

    2007-01-01

    The formation of many forms of long-term memory requires several molecular mechanisms including regulation of gene expression. The mechanisms directing transcription require not only activation of individual transcription factors but also recruitment of transcriptional coactivators. CBP and p300 are transcriptional coactivators that interact with…

  1. "Gadd45b" Knockout Mice Exhibit Selective Deficits in Hippocampus-Dependent Long-Term Memory

    Science.gov (United States)

    Leach, Prescott T.; Poplawski, Shane G.; Kenney, Justin W.; Hoffman, Barbara; Liebermann, Dan A.; Abel, Ted; Gould, Thomas J.

    2012-01-01

    Growth arrest and DNA damage-inducible [beta] ("Gadd45b") has been shown to be involved in DNA demethylation and may be important for cognitive processes. "Gadd45b" is abnormally expressed in subjects with autism and psychosis, two disorders associated with cognitive deficits. Furthermore, several high-throughput screens have identified "Gadd45b"…

  2. Subregion-Specific p300 Conditional Knock-Out Mice Exhibit Long-Term Memory Impairments

    Science.gov (United States)

    Oliveira, Ana M. M.; Estevez, Marcel A.; Hawk, Joshua D.; Grimes, Shannon; Brindle, Paul K.; Abel, Ted

    2011-01-01

    Histone acetylation plays a critical role during long-term memory formation. Several studies have demonstrated that the histone acetyltransferase (HAT) CBP is required during long-term memory formation, but the involvement of other HAT proteins has not been extensively investigated. The HATs CBP and p300 have at least 400 described interacting…

  3. Perancangan Supply Chain Management Pada Sistem Pengelolaan Mice (Meetings Incentives Conferences Exhibitions) Di STMIK STIKOM Bali

    OpenAIRE

    Agustino, Dedy Panji

    2015-01-01

    Sebuah perguruan tinggi saat ini memiliki peran yang sangat penting bagi dunia pendidikan dalam mencetak lulusan-lulusan yang terampil dan siap kerja. Demikian juga dengan STIKOM Bali yang merupakan perguruan tinggi ICT di Bali yang sudah berdiri sejak 2002 dan saat ini memiliki 6000 mahasiswa dan telah meluluskan lebih dari 2000 lulusan. Sebagai perguruan tinggi yang sedang berkembang, tentu nya STIKOM Bali tidak hanya menjalankan aktifitas belajar mengajar saja, namun juga kegiatan akademis...

  4. Steroid sulfatase-deficient mice exhibit endophenotypes relevant to Attention Deficit Hyperactivity Disorder

    OpenAIRE

    Trent, Simon; Dennehy, Alison; Richardson, Heather; Ojarikre, Obah A.; Burgoyne, Paul S.; Humby, Trevor; Davies, William

    2012-01-01

    Summary Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition characterised by inattention, impulsivity and hyperactivity; it is frequently co-morbid with anxiety and conduct disorders, sleep perturbation and abnormal consummatory behaviours. Recent studies have implicated the neurosteroid-modulating enzyme steroid sulfatase (STS) as a modulator of ADHD-related endophenotypes. The effects of steroid sulfatase deficiency on homecage activity, feeding/drinking...

  5. Radiation-related information at science exhibitions

    Energy Technology Data Exchange (ETDEWEB)

    Bannai, Tadaaki [Inst. for Environmental Sciences, Rokkasho, Aomori (Japan)

    1999-09-01

    The aim of the present report was to promote an efficient utilization of science museums providing with educational information concerning radiations. Investigations were made on radiation-related materials exhibited at 38 museums including PR event sites between April 1996 and July 1998 mainly located on Kanto and Tohoku area in Japan. The investigation concerned as to whether the displays on radiation-related material (cosmic rays, X-rays, etc) existed or not, and as to the background of the display as well. As the result, 14 locations had no relevant displays, 10 of them not having things about atomic energy at all. The locations belonging to electricity company mostly had displays related to radiations and atomic energy power generation. A spark chamber was exhibited at 9 locations and a cloud chamber at 3 locations, but only one location among them displayed both. Displays on the actual use of X-radiation were found at 4 locations. Needs to prepare further improved displays exist at the sites visited. (S. Ohno)

  6. CERN Inspires Art in Major New Exhibition

    CERN Document Server

    2001-01-01

    Signatures of the Invisible, an exhibition inspired by CERN, opened at the Atlantis Gallery in London on Thursday, 1 March before going on a world tour. The fruit of a close collaboration between CERN and the London Institute, the exhibition brings together works from many leading European contemporary artists. White wooden boxes on a grey floor... the lids opened, unveiling brilliant white light from a bunch of optical fibres carefully stuck together in the shape of a square. Another holds a treasure of lead glass surrounded by enigmatic black mirrors. What's it all about? Signatures of the Invisible, that's what, a joint project organised by the London Institute, one of the world's largest college of art, and our Laboratory. Damien Foresy from the EST workshop putting finishing touches to the spinning tops of French artist Jérôme Basserode. Monica Sand's boxes are just one of the many works based around materials used in particle detection at CERN that was admired at the opening o...

  7. Children's drawings exhibited in the Globe

    CERN Multimedia

    Elizabeth Roe

    2010-01-01

    "Draw Me A Physicist" has been a success. Members of the public visiting the exhibition in the Globe of Science and Innovation have praised the scientific and creative balance the children of neighbouring France and the Canton of Geneva have obtained through their visit to CERN.   The Draw Me a Physicist exhibition in the Globe For a six-month period 9 to 11-year olds from the Pays de Gex, Meyrin, Satigny and Vernier have been able to enjoy a balance between science and art, through drawing and defining their interpretations of a physicist. In May, eight pairs of drawings from each participating class were selected by the schools to be displayed on the second floor of the Globe. Since the images have been put up, the viewers have enjoyed the contrast between the "before" pictures of vibrant Albert Einsteins to the "after" pictures of casual people sitting in an office. The large room in the Globe has been transformed from a hollow shell int...

  8. Exhibiting the Human/Exhibiting the Cyborg: “Who Am I?”

    Directory of Open Access Journals (Sweden)

    Sophia C. Vackimes

    2013-08-01

    Full Text Available The role of the museum in shaping our relationship to science and technology, particularly cyborgization, is illuminated by a close examination of the Who Am I permanent exhibition in the Wellcome Wing of the Science Museum of London. This innovative exhibition raises real questions both about the human-technology-science relationship but also about museography. In the context of the history and current practices of museums engaging contemporary technological developments the evidence suggest that even as the Who am I? exhibit did break somewhat from previous approaches, especially the didactic presentation of the socially useful, it has not changed the feld as a whole.

  9. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

    Science.gov (United States)

    Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

    2017-09-01

    Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

  10. Comparison of the quick mild cognitive impairment (Qmci) screen and the SMMSE in screening for mild cognitive impairment.

    LENUS (Irish Health Repository)

    O'Caoimh, Rónán

    2012-09-01

    differentiating mild cognitive impairment (MCI) from normal cognition (NC) is difficult. The AB Cognitive Screen (ABCS) 135, sensitive in differentiating MCI from dementia, was modified to improve sensitivity and specificity, producing the quick mild cognitive impairment (Qmci) screen.

  11. Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Atsuko Hayashi

    2015-09-01

    Full Text Available Background/Aims: We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI and mild Alzheimer's disease (AD. To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji. Methods: A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. Results: For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. Conclusions: The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

  12. Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease.

    Science.gov (United States)

    Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

    2015-01-01

    We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

  13. Wild-type male offspring of fmr-1+/- mothers exhibit characteristics of the fragile X phenotype.

    Science.gov (United States)

    Zupan, Bojana; Toth, Miklos

    2008-10-01

    Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Males are more severely affected than heterozygote (H) females, who, as carriers, have a 50% chance of transmitting the mutated allele in each pregnancy. fmr-1 knockout (KO) mice reproduce fragile X symptoms, including hyperactivity, seizures, and abnormal sensory processing. In contrast to the expectation that wild-type (WT) males born to H (fmr-1(+/-)) mothers (H>WT) are behaviorally normal and indistinguishable from WT males born to WT mothers (WT>WT); here, we show that H>WT offspring are more active than WT>WT offspring and that their hyperactivity is similar to male KO mice born to H or KO (fmr-1(-/-)) mothers (H>KO/KO>KO). H>WT mice, however, do not exhibit seizures or abnormal sensory processing. Consistent with their hyperactivity, the effect of the D2 agonist quinpirole is reduced in H>WT as well as in H>KO and KO>KO mice compared to WT>WT offspring, suggesting a diminished feedback inhibition of dopamine release. Our data indicate that some aspects of hyperactivity and associated dopaminergic changes in 'fragile X' mice are a maternal fmr-1 genotype rather than an offspring fmr-1 genotype effect.

  14. Inherent and antigen-induced airway hyperreactivity in NC mice

    Directory of Open Access Journals (Sweden)

    Tetsuto Kobayashi

    1999-01-01

    Full Text Available In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those strains in vivo. NC mice again showed comparable airway reactivity to that seen in A/J mice and a significantly greater reactivity than that seen in BALB/c and C57BL/6 mice. To investigate the effects of airway inflammation on airway reactivity to acetylcholine in vivo, NC and BALB/c mice were sensitized to and challenged with antigen. Sensitization to and challenge with antigen induced accumulation of inflammatory cells, especially eosinophils, in lung and increased airway reactivity in NC and BALB/c mice. These results indicate that NC mice exhibit inherent and antigen-induced airway hyperreactivity. Therefore, NC mice are a suitable strain to use in investigating the mechanisms underlying airway hyperreactivity and such studies will provide beneficial information for understanding the pathophysiology of asthma.

  15. Inner ear dysfunction in caspase-3 deficient mice

    Directory of Open Access Journals (Sweden)

    Woo Minna

    2011-10-01

    Full Text Available Abstract Background Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/- mouse strain. Results Average ABR thresholds of Casp3-/- mice were significantly elevated (P Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers. Conclusions These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule.

  16. Shape-Memory PVDF Exhibiting Switchable Piezoelectricity.

    Science.gov (United States)

    Hoeher, Robin; Raidt, Thomas; Novak, Nikola; Katzenberg, Frank; Tiller, Joerg C

    2015-12-01

    In this study, a material is designed which combines the properties of shape-memory and electroactive polymers. This is achieved by covalent cross-linking of polyvinylidene fluoride. The resulting polymer network exhibits excellent shape-memory properties with a storable strain of 200%, and fixity as well as recovery values of 100%. Programming upon rolling induces the transformation from the nonelectroactive α-phase to the piezoelectric β-phase. The highest β-phase content is found to be 83% for a programming strain of 200% affording a d33 value of -30 pm V(-1). This is in good accordance with literature known values for piezoelectric properties. Thermal triggering this material does not only result in a shape change but also renders the material nonelectroactive. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Applied Gamification in Self-guided Exhibitions

    DEFF Research Database (Denmark)

    Vistisen, Peter; Selvadurai, Vashanth; Krishnasamy, Rameshnath Kala

    2018-01-01

    This paper contributes to the current understanding of applied digital gamification by providing insights from two design cases from the Danish aqua zoo, the North Sea Oceanarium, concerned with self-facilitated exhibitions. Grounded in a short review of the current state of art, we provide two...... empirical case examples, concerning a mobile augmented reality design and an Instagram service. Analyzing the design process behind these cases, we identify some of the challenges arising from applying gamification in practice, and whether these insights verify, extents or contradicts current examples...... of applied gamification research. Specifically, the cases provide insights to the challenge of on-boarding visitors into participating and using the designed products during their visit. In both cases, providing certain incentives for using the app or participating in the Instagram challenge, seemed...

  18. Exhibiting health and medicine as culture

    DEFF Research Database (Denmark)

    Whiteley, Louise; Tybjerg, Karin; Pedersen, Bente Vinge

    2017-01-01

    -being of their visitors, we instead focus on how museums should communicate about health and medicine. Methods: The paper describes three examples of exhibitions at Medical Museion that attempt to display medicine as culture, and draws out three of the key strategies they employ. Results: The three key strategies are: (1......Introduction: This paper discusses the potential role of medical museums in public engagement with health and medicine, based on the work of Medical Museion at the University of Copenhagen. Rather than asking whether cultural venues such as museums can directly improve the well......: There is increasing emphasis on the need for health communication to recognize people’s multiple, lived cultures. We argue that we should also recognize that medical research and practice is itself a form of culture, and as such is multiple and historically shifting. This paper demonstrates that museums are an ideal...

  19. The coordination office at SIREME 2008 exhibition

    International Nuclear Information System (INIS)

    Grotz, Claudia; Cassin, Fabrice; Evrard, Aurelien; Froeding, Veronique; Galaup, Serge; Kaelble, Laure; Persem, Melanie; Regnier, Yannick; )

    2008-01-01

    The French-German office for Renewable energies (OFAEnR) organised several presentations at the occasion of the SIREME International exhibition of renewable energies and energy management. This document brings together these presentations (slides) dealing with: 1 - The new German Renewable Energy Sources Act (EEG) and its impact on wind energy (Claudia Grotz); 2 - Consequences of the July 10, 2006 wind energy tariff bylaw cancelling (Fabrice Cassin); 3 - Wind energy trajectory in France and Germany: a political perspective (Aurelien Evrard); 4 - The wind energy development areas (Veronique Froeding); 5 - A commitment at the heart of our business: renewable energy sources (Serge Galaup); 6 - The wind energy coordination office (Laure Kaelble); 7 - New challenges of the German wind energy market (Melanie Persem); 8 - An industry - a qualification standard (Yannick Regnier)

  20. The Road Transport world exhibition in Paris

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    Following the agreement between French and German professionals of automobile and industrial vehicle, the Road Transport world exhibition will take place alternatively in Paris and Hanover. The 1995 meeting has taken place in Paris (September 15-21) and about 20 countries were represented. Road transport is the principal way of goods transportation in France and represent 88% of the traffic explained in tons gross and 70% in tons km. The petroleum dependence of the transportation sector is becoming a worrying problem as the gasoline and diesel fuels taxes will be discussed in the 1996 financial laws project. According to the last ''Worldwide energetic perspectives'' report published by the IEA, in 2010 the transportation sector could absorb more than 60% of the worldwide petroleum consumption. This increase represents a challenge to the petroleum industry to increase the energetic efficiency of the vehicle fuels and the production of diesel fuels, and conversely to reduce the pollution effluents. (J.S.). 4 tabs

  1. Application of an imaging system to a museum exhibition for developing interactive exhibitions

    Science.gov (United States)

    Miyata, Kimiyoshi; Inoue, Yuka; Takiguchi, Takahiro; Tsumura, Norimichi; Nakaguchi, Toshiya; Miyake, Yoichi

    2009-10-01

    In the National Museum of Japanese History, 215,759 artifacts are stored and used for research and exhibitions. In museums, due to the limitation of space in the galleries, a guidance system is required to satisfy visitors' needs and to enhance their understanding of the artifacts. We introduce one exhibition using imaging technology to improve visitors' understanding of a kimono (traditional Japanese clothing) exhibition. In the imaging technology introduced, one data projector, one display with touch panel interface, and magnifiers were used as exhibition tools together with a real kimono. The validity of this exhibition method was confirmed by results from a visitors' interview survey. Second, to further develop the interactive guidance system, an augmented reality system that consisted of cooperation between the projector and a digital video camera was also examined. A white paper board in the observer's hand was used as a projection screen and also as an interface to control the images projected on the board. The basic performance of the proposed system was confirmed; however continuous development was necessary for applying the system to actual exhibitions.

  2. Conserved role of unc-79 in ethanol responses in lightweight mutant mice.

    Directory of Open Access Journals (Sweden)

    David J Speca

    2010-08-01

    Full Text Available The mechanisms by which ethanol and inhaled anesthetics influence the nervous system are poorly understood. Here we describe the positional cloning and characterization of a new mouse mutation isolated in an N-ethyl-N-nitrosourea (ENU forward mutagenesis screen for animals with enhanced locomotor activity. This allele, Lightweight (Lwt, disrupts the homolog of the Caenorhabditis elegans (C. elegans unc-79 gene. While Lwt/Lwt homozygotes are perinatal lethal, Lightweight heterozygotes are dramatically hypersensitive to acute ethanol exposure. Experiments in C. elegans demonstrate a conserved hypersensitivity to ethanol in unc-79 mutants and extend this observation to the related unc-80 mutant and nca-1;nca-2 double mutants. Lightweight heterozygotes also exhibit an altered response to the anesthetic isoflurane, reminiscent of unc-79 invertebrate mutant phenotypes. Consistent with our initial mapping results, Lightweight heterozygotes are mildly hyperactive when exposed to a novel environment and are smaller than wild-type animals. In addition, Lightweight heterozygotes exhibit increased food consumption yet have a leaner body composition. Interestingly, Lightweight heterozygotes voluntarily consume more ethanol than wild-type littermates. The acute hypersensitivity to and increased voluntary consumption of ethanol observed in Lightweight heterozygous mice in combination with the observed hypersensitivity to ethanol in C. elegans unc-79, unc-80, and nca-1;nca-2 double mutants suggests a novel conserved pathway that might influence alcohol-related behaviors in humans.

  3. Mild trigonocephaly. Report of 300 operative cases

    International Nuclear Information System (INIS)

    Shimoji, Takeyoshi; Yamashiro, Katsumi; Nagamine, Tomoaki; Kawakubo, Junichi; Shimoji, Kazuaki

    2009-01-01

    Since 1999, we have reported mild trigonocephaly with symptoms mainly accompanied with developmental delays. We would like to report the operative results of 300 patients. All patients had some kind of clinical symptoms. The diagnosis made recognizing ridge of the fused metopic suture by palpation and a three-dimensional computed tomography (3D-CT). Most patients (287 among 300) could not be diagnosed because of the mild changes of their facial features and their natural development as infants. They suffered from symptoms such as mental retardation, delayed language development, hyperactivity, autistic tendencies, panic and irritability, motor dysfunctions, self-mutilation and sleeping disturbances. Two hundred thirteen patients were recorded intracranial pressure (ICP). Developmental quotients (D.Q) were also measured. Two hundred fifteen (73.6%) of 292 patients with delays of language development were improved within a year after surgery. Other symptoms also improved: 91.6% in hyperactivity, 76.5% in autistic tendencies, 92% in panic, 90.4% in motor dysfunctions, 88.6% in self-mutilation and 93% in sleeping disturbances. The chronological scores in D.Q maintained parallel in most patients. Measurements of ICP resulted in 10 cases (5%) under mean 10 mmHg, 33 cases (15%) between 11 to 15 mmHg and 170 cases (80%) over 16 mmHg. The mean pulse pressure calculated around 9 mmHg in each group. Decompressive cranioplasty was applied to all patients. Patients with mild trigonocephaly may have a possibility to show clinical symptoms. Since the ICP seems to be high, decompressive cranioplasty may be a reasonable treatment for these patients. (author)

  4. Mild Cognitive Impairment Status and Mobility Performance

    DEFF Research Database (Denmark)

    Pedersen, Mette; Holt, Nicole E; Grande, Laura

    2014-01-01

    : An analysis was conducted on baseline data from the Boston Rehabilitative Impairment Study in the Elderly study, a cohort study of 430 primary care patients aged 65 or older. Neuropsychological tests identified participants with MCI and further subclassified those with impairment in memory domains (a......BACKGROUND: The prevalence of mild cognitive impairment (MCI) and mobility limitations is high among older adults. The aim of this study was to investigate the association between MCI status and both performance-based and self-report measures of mobility in community-dwelling older adults. METHODS...

  5. Thyroid disorders in mild iodine deficiency

    DEFF Research Database (Denmark)

    Laurberg, P; Nøhr, S B; Pedersen, K M

    2000-01-01

    in elderly subjects, especially women, with risk of cardiac arrhythmias, osteoporosis, and muscle wasting. The hyperthyroidism is caused by autonomous nodular growth and function of the thyroid gland and it is accompanied by a high frequency of goiter. Pregnant women and small children are not immediately...... endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine...

  6. Factors controlling nitrate cracking of mild steel

    International Nuclear Information System (INIS)

    Donovan, J.A.

    1977-01-01

    Nitrite and hydroxide ions inhibit the growth of nitrate stress corrosion cracks in mild steel. Crack growth measurements showed that sufficient concentrations of nitrite and hydroxide ions can prevent crack growth; however, insufficient concentrations of these ions did not influence the Stage II growth rate or the threshold stress intensity, but extended the initiation time. Stage III growth was discontinuous. Oxide formed in the grain boundaries ahead of the crack tip and oxide dissolution (Stage II) and fracture (Stage III) are the proposed mechanisms of nitrate stress corrosion crack growth

  7. Eddy current inspection of mildly ferromagnetic tubing

    International Nuclear Information System (INIS)

    Mayo, W.R.; Carter, J.R.

    1984-02-01

    The past decade has seen the development of eddy current probes for inspection of the mildly ferro-magnetic alloy Monel 400. Due to the rapid advances in permanent magnet technology similar probes have been upgraded to magnetically saturate, and hence inspect, the duplex stainless steel Sandvik 3RE60, which has saturation induction more than twice that of Monel 400. Prototypes of these probes have been tested in three ways: saturation capability, quality of typical eddy current data, and ability to eliminate permeability induced signals. Successful laboratory testing, potential applications, and limitations of these type probes are discussed

  8. Serial position effects in mild cognitive impairment.

    Science.gov (United States)

    Howieson, Diane B; Mattek, Nora; Seeyle, Adriana M; Dodge, Hiroko H; Wasserman, Dara; Zitzelberger, Tracy; Jeffrey, Kaye

    2011-03-01

    Mild cognitive impairment (MCI) is often associated with the preclinical phase of Alzheimer's disease (AD). Special scoring of word-list recall data for serial position has been suggested to improve discrimination of normal aging from dementia. We examined serial position effects in word-list recall for MCI participants compared to Alzheimer patients and controls. Individuals with MCI, like Alzheimer patients, had a diminished primacy effect in recalling words from a list. No alternative scoring system was better than standard scoring of word-list recall in distinguishing MCI patients from controls. Retention weighted scoring improved the discrimination of MCI and AD groups.

  9. Exhibition of Stochastic Resonance in Vestibular Perception

    Science.gov (United States)

    Galvan-Garza, R. C.; Clark, T. K.; Merfeld, D. M.; Bloomberg, J. J.; Oman, C. M.; Mulavara, A. P.

    2016-01-01

    Astronauts experience sensorimotor changes during spaceflight, particularly during G-transitions. Post flight sensorimotor changes include spatial disorientation, along with postural and gait instability that may degrade operational capabilities of the astronauts and endanger the crew. A sensorimotor countermeasure that mitigates these effects would improve crewmember safety and decrease risk. The goal of this research is to investigate the potential use of stochastic vestibular stimulation (SVS) as a technology to improve sensorimotor function. We hypothesize that low levels of SVS will improve sensorimotor perception through the phenomenon of stochastic resonance (SR), when the response of a nonlinear system to a weak input signal is enhanced by the application of a particular nonzero level of noise. This study aims to advance the development of SVS as a potential countermeasure by 1) demonstrating the exhibition of stochastic resonance in vestibular perception, a vital component of sensorimotor function, 2) investigating the repeatability of SR exhibition, and 3) determining the relative contribution of the semicircular canals (SCC) and otolith (OTO) organs to vestibular perceptual SR. A constant current stimulator was used to deliver bilateral bipolar SVS via electrodes placed on each of the mastoid processes, as previously done. Vestibular perceptual motion recognition thresholds were measured using a 6-degree of freedom MOOG platform and a 150 trial 3-down/1-up staircase procedure. In the first test session, we measured vestibular perceptual thresholds in upright roll-tilt at 0.2 Hz (SCC+OTO) with SVS ranging from 0-700 µA. In a second test session a week later, we re-measured roll-tilt thresholds with 0, optimal (from test session 1), and 1500 µA SVS levels. A subset of these subjects, plus naive subjects, participated in two additional test sessions in which we measured thresholds in supine roll-rotation at 0.2 Hz (SCC) and upright y-translation at 1 Hz

  10. Repeated Exposition to Mercury (II Chloride Enhances Susceptibility to S. schenckii sensu stricto Infection in Mice

    Directory of Open Access Journals (Sweden)

    Alexander Batista-Duharte

    2018-05-01

    Full Text Available Sporotrichosis is a subcutaneous mycosis that has re-emerged in several tropical and subtropical regions over the last decades. Growing findings suggest that the interplay of host, pathogen, and environment has a determinant effect on the diversity, local distribution, and virulence of Sporothrix schenckii sensu lato, the etiologic agent. Among the environmental factors, we have studied the potential role of repeated exposures to mercury (Hg, a known immunotoxic xenobiotic that is widely used in gold mining regions where sporotrichosis outbreaks are frequently reported. In this study, male Swiss mice received subcutaneous injections of either 300 or 1200 µg/kg of mercury (II chloride (HgCl2 for 14 days, three times a week. A control group was injected with the vehicle Phosphate Buffered Saline (PBS. Treatment with HgCl2 impaired several immunologic parameters that are involved in host response to Sporothrix infection, such as the production of TNFα, IL-1, and nitric oxide by macrophages, and Th1/Th2/Th17 populations and their respective cytokines. The consequences of these effects on the host resistance to S. schenckii infection were subsequently evaluated. Hg-exposed mice exhibited a higher fungal load in the fungal inoculation site associated to systemic dissemination to spleen and liver on 14 days post-infection and a higher production of specific IgG1 and mild reduction of IgG2a. These findings suggest that repeated exposition to Hg enhances susceptibility to S. schenckii infection in mice and can be a factor associated to sporotrichosis outbreaks in endemic and highly Hg-polluted areas.

  11. A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice.

    Science.gov (United States)

    Abulizi, Abudukadier; Perry, Rachel J; Camporez, João Paulo G; Jurczak, Michael J; Petersen, Kitt Falk; Aspichueta, Patricia; Shulman, Gerald I

    2017-07-01

    Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes. After 4 wk of oral CRMP (2 mg/kg body weight per day) or vehicle treatment, mice underwent hyperinsulinemic-euglycemic clamps combined with radiolabeled glucose to assess liver and muscle insulin responsiveness and tissue lipid measurements. CRMP treatment reversed hypertriglyceridemia and insulin resistance in liver and skeletal muscle. Reversal of insulin resistance could be attributed to reductions in diacylglycerol content and reduced PKC-ε and PKC-θ activity in liver and muscle respectively. CRMP treatment also reversed NASH as reflected by reductions in plasma aspartate aminotransferase and alanine aminotransferase concentrations; hepatic steatosis; and hepatic expression of IL-1α, -β, -2, -4, -6, -10, -12, CD69, and caspase 3 and attenuated activation of the IRE-1α branch of the unfolded protein response. Taken together, these results provide proof of concept for the development of liver-targeted mitochondrial uncoupling agents as a potential novel therapy for lipodystrophy-associated hypertriglyceridemia, NASH and diabetes.-Abulizi, A., Perry, R. J., Camporez, J. P. G., Jurczak, M. J., Petersen, K. F., Aspichueta, P., Shulman, G. I. A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice. © FASEB.

  12. Preclinical cerebral network connectivity evidence of deficits in mild white matter lesions

    Directory of Open Access Journals (Sweden)

    Ying eLiang

    2016-02-01

    Full Text Available White matter lesions (WMLs are notable for their high prevalence and have been demonstrated to be a potential neuroimaging biomarker of early diagnosis of Alzheimer’s disease. This study aimed to identify the brain functional and structural mechanisms underlying cognitive decline observed in mild WMLs. Multi-domain cognitive tests, as well as resting-state, diffusion tensor and structural images were obtained on 42 mild WMLs and 42 age/sex-matched healthy controls. For each participant, we examined the functional connectivity of three resting-state networks related to the changed cognitive domains: the default mode network (DMN and the bilateral fronto-parietal network (FPN. We also performed voxel-based morphometry analysis to compare whole-brain gray matter volume, atlas-based quantification of the white matter tracts interconnecting the RSNs, and the relationship between functional connectivity and structural connectivity. We observed functional connectivity alterations in the DMN and the right FPN combined with related white matter integrity disruption in mild WMLs. However, no significant gray matter atrophy difference was found. Furthermore, the right precuneus functional connectivity in the DMN exhibited a significantly negative correlation with the memory test scores. Our study suggests that in mild WMLs, dysfunction of RSNs might be a consequence of decreased white matter structural connectivity, which further affects cognitive performance.

  13. VIRTUAL EXHIBITION AND FRUITION OF ARCHAEOLOGICAL FINDS

    Directory of Open Access Journals (Sweden)

    A. M. Manferdini

    2012-09-01

    Full Text Available During the last two decades, since digital technologies have become more sophisticated in acquiring real data and building faithful copies of them, their improvements have suggested interesting applications in the field of valorisation of Historical, Cultural and Artistic Heritage, with significant consequences in the share and widespread of knowledge. But although several technologies and methodologies for 3d digitization have recently been developed and improved, the lack of a standard procedure and the costs connected to their use still doesn't encourage the systematic digital acquisition of wide collections and heritage. The aim of this paper is to show the state of the art of a project whose aim is to provide a methodology and a procedure to create digital reproductions of artefacts for Institutions called to preserve, manage and enhance the fruition of archaeological finds inside museums or through digital exhibitions. Our project’s aim is to find the most suitable procedure to digitally acquire archaeo logical artefacts that usually have small dimensions and have very complex and detailed surfaces. Within our methodology, particular attention has been paid to the use of widely shared and open-source visualization systems that enhance the involvement of the user by emphasizing three-dimensional characteristics of artefacts through virtual reality.

  14. Decreased hedonic responsiveness following chronic mild stress is not secondary to loss of body weight.

    Science.gov (United States)

    Willner, P; Moreau, J L; Nielsen, C K; Papp, M; Sluzewska, A

    1996-07-01

    Chronic exposure to mild unpredictable stress (CMS) has previously been found to decrease hedonic responsiveness, as measured by the consumption of palatable sweet solutions or sensitivity to brain stimulation reward. These effects are reversed by chronic treatment with antidepressant drugs, and the CMS procedure has been proposed as a relatively valid animal model of depression. It has recently been suggested that the behavioural effects of CMS may be secondary to loss of body weight. This article collates data from five laboratories using the CMS procedure. Data are presented from seven studies using five different rat strains, as well as CD1 mice. Three-week exposure to CMS significantly decreased sucrose consumption by Lister hooded, PVG hooded, Wistar, and Wistar WU rats, and by CD1 mice, and sensitivity to brain stimulation reward in Ibm:Ro Ro rats. Weight loss in different experiments varied between 0 and 10%. Hedonic sensitivity relative to body weight (e.g., mg sucrose/g body weight) decreased significantly in all experiments. Animals maintained on a restricted feeding regime lost weight but did not show decreases in sucrose intake. It is concluded that decreased hedonic sensitivity following chronic mild stress cannot be attributed to loss of body weight.

  15. Thyroid disorders in mild iodine deficiency.

    Science.gov (United States)

    Laurberg, P; Nøhr, S B; Pedersen, K M; Hreidarsson, A B; Andersen, S; Bülow Pedersen, I; Knudsen, N; Perrild, H; Jørgensen, T; Ovesen, L

    2000-11-01

    Comparative epidemiologic studies in areas with low and high iodine intake and controlled studies of iodine supplementation have demonstrated that the major consequence of mild-to-moderate iodine deficiency for the health of the population is an extraordinarily high occurrence of hyperthyroidism in elderly subjects, especially women, with risk of cardiac arrhythmias, osteoporosis, and muscle wasting. The hyperthyroidism is caused by autonomous nodular growth and function of the thyroid gland and it is accompanied by a high frequency of goiter. Pregnant women and small children are not immediately endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine deficiency should be corrected. However, there is evidence that a high iodine intake may be associated with more autoimmune hypothyroidism, and that Graves' disease may manifest at a younger age and be more difficult to treat. Hence, the iodine intake should be brought to a level at which iodine deficiency disorders are avoided but not higher. Iodine supplementation programs should aim at relatively uniform iodine intake, avoiding deficient or excessive iodine intake in subpopulations. To adopt such a strategy, surveillance programs are needed.

  16. DESIGN AND DEVELOPMENT OF MILD COMBUSTION BURNER

    Directory of Open Access Journals (Sweden)

    M.M. Noor

    2013-12-01

    Full Text Available This paper discusses the design and development of the Moderate and Intense Low oxygen Dilution (MILD combustion burner using Computational Fluid Dynamics (CFD simulations. The CFD commercial package was used to simulate preliminary designs for the burner before the final design was sent to the workshop for fabrication. The burner is required to be a non-premixed and open burner. To capture and use the exhaust gas, the burner was enclosed within a large circular shaped wall with an opening at the top. An external EGR pipe was used to transport the exhaust gas which was mixed with the fresh oxidant. To control the EGR and exhaust flow, butterfly valves were installed at the top opening as a damper to close the exhaust gas flow at a certain ratio for EGR and exhaust out to the atmosphere. High temperature fused silica glass windows were installed to view and capture images of the flame and analyze the flame propagation. The burner simulation shows that MILD combustion was achieved for the oxygen mole fraction of 3-13%. The final design of the burner was fabricated and ready for the experimental validation.

  17. The Magnolia Bioactive Constituent 4-O-Methylhonokiol Protects against High-Fat Diet-Induced Obesity and Systemic Insulin Resistance in Mice

    Directory of Open Access Journals (Sweden)

    Zhiguo Zhang

    2014-01-01

    Full Text Available Obesity is caused by a combination of both genetic and environmental risks. Disruption in energy balance is one of these risk factors. In the present study, the preventive effect on high-fat diet- (HFD- induced obesity and insulin resistance in mice by Magnolia bioactive constituent 4-O-methylhonokiol (MH was compared with Magnolia officinalis extract BL153. C57BL/6J mice were fed by normal diet or by HFD with gavage-administered vehicle, BL153, low-dose MH, and high-dose MH simultaneously for 24 weeks, respectively. Either MH or BL153 slightly inhibited body-weight gain of mice by HFD feeding although the food intake had no obvious difference. Body fat mass and the epididymal white adipose tissue weight were also mildly decreased by MH or BL153. Moreover, MH significantly lowered HFD-induced plasma triglyceride, cholesterol levels and activity of alanine transaminase (ALT, liver weight and hepatic triglyceride level, and ameliorated hepatic steatosis. BL153 only significantly reduced ALT and liver triglyceride level. Concurrently, low-dose MH improved HFD-induced hyperinsulinemia and insulin resistance. Furthermore, the infiltration of mast cells in adipose tissue was decreased in MH or in BL153 treatment. These results suggested that Magnolia bioactive constituent MH might exhibit potential benefits for HFD-induced obesity by improvement of lipid metabolism and insulin resistance.

  18. Analysis of the T Cell Response to Zika Virus and Identification of a Novel CD8+ T Cell Epitope in Immunocompetent Mice.

    Directory of Open Access Journals (Sweden)

    Ryan D Pardy

    2017-02-01

    Full Text Available Zika virus (ZIKV is an emerging arbovirus of the Flaviviridae family. Although ZIKV infection is typically mild and self-limiting in healthy adults, infection has been associated with neurological symptoms such as Guillain-Barré syndrome, and a causal link has been established between fetal microcephaly and ZIKV infection during pregnancy. These risks, and the magnitude of the ongoing ZIKV pandemic, have created an urgent need for the development of animal models to study the immune response to ZIKV infection. Previous animal models have primarily focused on pathogenesis in immunocompromised mice. In this study, we provide a model of ZIKV infection in wild-type immunocompetent C57BL/6 mice, and have provided an analysis of the immune response to infection. We evaluated the activation of several innate immune cell types, and studied the kinetics, phenotype, and functionality of T cell responses to ZIKV infection. Our results demonstrate that ZIKV infection is mild in wild-type immunocompetent C57BL/6 mice, resulting in minimal morbidity. Our data establish that at the peak of the adaptive response, antigen-experienced CD4+ T cells polarize to a Th1 phenotype, and antigen-experienced CD8+ T cells exhibit an activated effector phenotype, producing both effector cytokines and cytolytic molecules. Furthermore, we have identified a novel ZIKV CD8+ T cell epitope in the envelope protein that is recognized by the majority of responding cells. Our model provides an important reference point that will help dissect the impact of polymorphisms in the circulating ZIKV strains on the immune response and ZIKV pathogenesis. In addition, the identification of a ZIKV epitope will allow for the design of tetramers to study epitope-specific T cell responses, and will have important implications for the design and development of ZIKV vaccine strategies.

  19. Rapid hemostatic and mild polyurethane-urea foam wound dressing for promoting wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiangyu; Niu, Yuqing [College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060 (China); Nanshan District Key lab for Biopolymers and Safety Evaluation, Shenzhen 518060 (China); Shenzhen Key Laboratory of Polymer Science and Technology, Shenzhen 518060 (China); Guangdong Research Center for Interfacial Engineering of Functional Materials, Shenzhen 518060 (China); Chen, Kevin C. [Multidisciplinary Research Center, Shantou University, Shantou, Guangdong 515063 (China); Chen, Shiguo, E-mail: csg@szu.edu.cn [College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060 (China); Nanshan District Key lab for Biopolymers and Safety Evaluation, Shenzhen 518060 (China); Shenzhen Key Laboratory of Polymer Science and Technology, Shenzhen 518060 (China); Guangdong Research Center for Interfacial Engineering of Functional Materials, Shenzhen 518060 (China)

    2017-02-01

    A novel rapid hemostatic and mild polyurethane-urea foam (PUUF) wound dressing was prepared by the particle leaching method and vacuum freeze-drying method using 4, 4-Methylenebis(cyclohexyl isocyanate), 4,4-diaminodicyclohexylmethane and poly (ethylene glycol) as raw materials. And X-ray diffraction (XRD), tensile test, differential scanning calorimetry (DSC) and thermogravimetry (TG) were used to its crystallinity, stress and strain behavior, and thermal properties, respectively. Platelet adhesion, fibrinogen adhesion and blood clotting were performed to evaluate its hemostatic effect. And H&E staining and Masson Trichrome staining were used to its wound healing efficacy. The results revealed the pore size of PUUF is 50–130 μm, and its porosity is 71.01%. Porous PUUF exhibited good water uptake that was benefit to adsorb abundant wound exudates to build a regional moist environment beneficial for wound healing. The PUUF wound dressing exhibit better blood coagulation effect than commercial polyurethane dressing (CaduMedi). Though both PUUF and CaduMedi facilitated wound healing generating full re-epithelialization within 13 days, PUUF was milder and lead to more slight inflammatory response than CaduMedi. In addition, PUUF wound dressing exhibited lower cytotoxicity than CaduMedi against NIH3T3 cells. Overall, porous PUUF represents a novel mild wound dressing with excellent water uptake, hemostatic effect and low toxicity, and it can promote wound healing and enhance re-epithelialization. - Highlights: • Rapid hemostatic and mild PUUF wound dressing was fabricated. • Low-toxic PUUF exhibited good water uptake that could build a regional moist environment beneficial for wound healing. • PUUF could promote wound healing and enhance re-epithelialization.

  20. 77 FR 31420 - Culturally Significant Objects Imported for Exhibition

    Science.gov (United States)

    2012-05-25

    ... also determine that the exhibition or display of the exhibit objects at The Museum of Modern Art, New...: Game Plan'' imported from abroad for temporary exhibition within the United States, are of cultural...

  1. Radiation sensitivity of T-lymphocytes from immunodeficient wasted mice

    International Nuclear Information System (INIS)

    Padilla, M.; Libertin, C.; Krco, C.; Woloschak, G.E.

    1990-01-01

    Mice with the autosomal recessive gene wasted (wst/wst) exhibit neurologic disorders, reduced mucosal immune responses, and abnormal DNA repair mechanisms. The wst/wst mouse has been proposed as a murine model for the human disorder ataxia telangiectasia. Experiments were designed to examine the sensitivity of T-cells from wasted mice to ionizing radiation. Results demonstrated that T-cell clones derived from wasted mice are more sensitive to the killing effects of gamma-rays than similar T-cell clones from control mice. Bulk thymocyte and splenic cell cultures demonstrated similar radiation sensitivity. Both thymic and splenic lymphocytes from wasted mice also expressed low proliferative responses to mitogenic stimulation with concanavalin A (Con A) that could not be attributed to an absence or reduction in T-cell number. However, following activation with Con A, cell cultures exhibited a marked decrease in the percentage of Thyl + cells in wasted mice, in contrast to cultures from control mice in which significant increases in Thyl + cells were observed. Furthermore, when cells were treated with gamma-rays in combination with Con A, Thyl + cells were decreased in control spleen and thymus, but were elevated in similarly treated wasted cultures. These changes were accompanied by an increase in cell volume in T-cells from wasted but not from control mice. These results describe the sensitivity of T-cells from wasted mice to ionizing radiation; in addition, they suggest that the wst/wst abnormality may be associated with cell cycle aberrancies

  2. GH and IGF1: Roles in Energy Metabolism of Long-Living GH Mutant Mice

    OpenAIRE

    Brown-Borg, Holly M.; Bartke, Andrzej

    2012-01-01

    Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of t...

  3. Overexpression of TIMP-1 under the MMP-9 promoter interferes with wound healing in transgenic mice

    OpenAIRE

    Salonurmi, T.; Parikka, M.; Kontusaari, S.; Pirila, E.; Munaut, Carine; Salo, T.; Tryggvason, K.

    2004-01-01

    We have generated transgenic mice harboring the murine matrix metalloproteinase 9 (MMP-9) promoter cloned in front of human TIMP-1 cDNA. The transgenic mice were viable and fertile and exhibited normal growth and general development. During wound healing the mice were shown to express human TIMP-1 in keratinocytes that normally express MMP-9. However, the healing of skin wounds was significantly retarded with slow migration of keratinocytes over the wound in transgenic mice. In situ zymograph...

  4. Mapping pathological phenotypes in Reelin mutant mice

    Directory of Open Access Journals (Sweden)

    Caterina eMichetti

    2014-09-01

    Full Text Available Autism Spectrum Disorders (ASD are neurodevelopmental disorders with multifactorial origin characterized by social communication and behavioural perseveration deficits. 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 investigated the behavioural, neurochemical and brain morphological features of reeler male mice. We recently reported a genotype-dependent deviation in ultrasonic vocal repertoire and a general delay in motor development in reeler pups. We now report that adult male heterozygous reeler mice did not show social behaviour and communication deficits during male-female social interactions. Wildtype and heterozygous mice also 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 heterozygous mice showed an over response to stress. At the end of the behavioural 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 heterozygous 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

  5. Swimming and Persons with Mild Persistant Asthma

    Directory of Open Access Journals (Sweden)

    Mirjana Arandelovic

    2007-01-01

    Full Text Available The aim of our study was to analyze the effect of recreational swimming on lung function and bronchial hyperresponsiveness (BHR in patients with mild persistent asthma. This study included 65 patients with mild persistent asthma, who were divided into two groups: experimental group A (n = 45 and control group B (n = 20. Patients from both groups were treated with low doses of inhaled corticosteroids (ICS and short-acting β2 agonists salbutamol as needed. Our program for patients in group A was combined asthma education with swimming (twice a week on a 1-h basis for the following 6 months. At the end of the study, in Group A, we found a statistically significant increase of lung function parameters FEV1 (forced expiratory volume in 1 sec (3.55 vs. 3.65 (p < 0.01, FVC (forced vital capacity (4.27 vs. 4.37 (p < 0.05, PEF (peak expiratory flow (7.08 vs. 7.46 (p < 0.01, and statistically significant decrease of BHR (PD20 0.58 vs. 2.01 (p < 0.001. In Group B, there was a statistically significant improvement of FEV1 3.29 vs. 3.33 (p < 0.05 and although FVC, FEV1/FVC, and PEF were improved, it was not significant. When Groups A and B were compared at the end of the study, there was a statistically significant difference of FVC (4.01 vs. 4.37, FEV1 (3.33 vs. 3.55, PEF (6.79 vs.7.46, and variability (p <0.001, and statistically significantly decreased BHR in Group A (2.01 vs. 1.75 (p < 0.001. Engagement of patients with mild persistent asthma in recreational swimming in nonchlorinated pools, combined with regular medical treatment and education, leads to better improvement of their parameters of lung function and also to more significant decrease of their airway hyperresponsiveness compared to patients treated with traditional medicine

  6. Zinc translocation accelerates infarction after mild transient focal ischemia.

    Science.gov (United States)

    Lee, J-M; Zipfel, G J; Park, K H; He, Y Y; Hsu, C Y; Choi, D W

    2002-01-01

    Excess release of chelatable zinc (Zn(2+)) from central synaptic vesicles may contribute to the pathogenesis of selective neuronal cell death following transient forebrain ischemia, but a role in neurodegeneration after focal ischemia has not been defined. Adult male Long-Evans rats subjected to middle cerebral artery occlusion (MCAO) for 30 min followed by reperfusion developed delayed cerebral infarction reaching completion 3 days after the insult. One day after the insult, many degenerating cerebral neurons exhibited increased intracellular Zn(2+), and some labeled with the antibody against activated caspase-3. I.c.v. administration of the Zn(2+) chelator, EDTA saturated with equimolar Ca(2+) (CaEDTA), 15 min prior to ischemia attenuated subsequent Zn(2+) translocation into cortical neurons, and reduced infarct volume measured 3 days after ischemia. Although the protective effect of CaEDTA at this endpoint was substantial (about 70% infarct reduction), it was lost when insult severity was increased (from 30 to 60 min MCAO), or when infarct volume was measured at a much later time point (14 days instead of 3 days after ischemia). These data suggest that toxic Zn(2+) translocation, from presynaptic terminals to post-synaptic cell bodies, may accelerate the development of cerebral infarction following mild transient focal ischemia.

  7. Catalase deletion promotes prediabetic phenotype in mice.

    Science.gov (United States)

    Heit, Claire; Marshall, Stephanie; Singh, Surrendra; Yu, Xiaoqing; Charkoftaki, Georgia; Zhao, Hongyu; Orlicky, David J; Fritz, Kristofer S; Thompson, David C; Vasiliou, Vasilis

    2017-02-01

    Hydrogen peroxide is produced endogenously and can be toxic to living organisms by inducing oxidative stress and cell damage. However, it has also been identified as a signal transduction molecule. By metabolizing hydrogen peroxide, catalase protects cells and tissues against oxidative damage and may also influence signal transduction mechanisms. Studies suggest that acatalasemic individuals (i.e., those with very low catalase activity) have a higher risk for the development of diabetes. We now report catalase knockout (Cat -/- ) mice, when fed a normal (6.5% lipid) chow, exhibit an obese phenotype that manifests as an increase in body weight that becomes more pronounced with age. The mice demonstrate altered hepatic and muscle lipid deposition, as well as increases in serum and hepatic triglycerides (TGs), and increased hepatic transcription and protein expression of PPARγ. Liver morphology revealed steatosis with inflammation. Cat -/- mice also exhibited pancreatic morphological changes that correlated with impaired glucose tolerance and increased fasting serum insulin levels, conditions consistent with pre-diabetic status. RNA-seq analyses revealed a differential expression of pathways and genes in Cat -/- mice, many of which are related to metabolic syndrome, diabetes, and obesity, such as Pparg and Cidec. In conclusion, the results of the present study show mice devoid of catalase develop an obese, pre-diabetic phenotype and provide compelling evidence for catalase (or its products) being integral in metabolic regulation. Copyright © 2016. Published by Elsevier Inc.

  8. Postpartum estrogen withdrawal impairs hippocampal neurogenesis and causes depression- and anxiety-like behaviors in mice.

    Science.gov (United States)

    Zhang, Zhuan; Hong, Juan; Zhang, Suyun; Zhang, Tingting; Sha, Sha; Yang, Rong; Qian, Yanning; Chen, Ling

    2016-04-01

    Postpartum estrogen withdrawal is known to be a particularly vulnerable time for depressive symptoms. Ovariectomized adult mice (OVX-mice) treated with hormone-simulated pregnancy (HSP mice) followed by a subsequent estradiol benzoate (EB) withdrawal (EW mice) exhibited depression- and anxiety-like behaviors, as assessed by forced swim, tail suspension and elevated plus-maze, while HSP mice, OVX mice or EB-treated OVX mice (OVX/EB mice) did not. The survival and neurite growth of newborn neurons in hippocampal dentate gyrus were examined on day 5 after EW. Compared with controls, the numbers of 28-day-old BrdU(+) and BrdU(+)/NeuN(+) cells were increased in HSP mice but significantly decreased in EW mice; the numbers of 10-day-old BrdU(+) cells were increased in HSP mice and OVX/EB mice; and the density of DCX(+) fibers was reduced in EW mice and OVX mice. The phosphorylation of hippocampal NMDA receptor (NMDAr) NR2B subunit or Src was increased in HSP mice but decreased in EW mice. NMDAr agonist NMDA prevented the loss of 28-day-old BrdU(+) cells and the depression- and anxiety-like behaviors in EW mice. NR2B inhibitor Ro25-6981 or Src inhibitor dasatinib caused depression- and anxiety-like behaviors in HSP mice with the reduction of 28-day-old BrdU(+) cells. The hippocampal BDNF levels were reduced in EW mice and OVX mice. TrkB receptor inhibitor K252a reduced the density of DCX(+) fibers in HSP mice without the reduction of 28-day-old BrdU(+) cells, or the production of affective disorder. Collectively, these results indicate that postpartum estrogen withdrawal impairs hippocampal neurogenesis in mice that show depression- and anxiety-like behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Electrodeposition of zinc-doped silane films for corrosion protection of mild steels

    International Nuclear Information System (INIS)

    Wu Liankui; Hu Jiming; Zhang Jianqing

    2012-01-01

    Highlights: ► Metallic zinc is doped into organosilane films by one-step electrodeposition. ► The composite films exhibit the improved corrosion resistance of mild steels. ► Zinc-doping provides additional cathodic protection to the mild steels. - Abstract: Organosilane/zinc composite films are prepared by one-step electrodeposition onto cold-rolled steels for corrosion protection. Electrochemical impedance spectroscopy measurement, bulk solution immersion and wet heat tests all show that the composite films have improved corrosion performance. X-ray photoelectron spectroscopy measurement suggests the successful encapsulation of metallic zinc. The embedding of metallic zinc results in negative shift in open-circuit potential of the film-covered electrodes. Such cathodic protection effect given by the metallic zinc provides the improved corrosion resistance of the composite films.

  10. Improved stability of OLEDs with mild oxygen plasma treated PEDOT:PSS

    International Nuclear Information System (INIS)

    Zhou Yunfei; Yuan Yongbo; Cao Lingfang; Zhang Jie; Pang Hongqi; Lian Jiarong; Zhou Xiang

    2007-01-01

    We demonstrate improved stability of OLEDs with mild oxygen plasma-treated poly (3,4-ethylenedioxythiophene) doped with poly (styrenesulfonate) (PEDOT:PSS) as anode buffer layer. The devices with treated PEDOT:PSS layer exhibited dramatically enhanced lifetime by a factor of 9 compared to the control devices. We investigated the substantial changes in surface morphology of PEDOT:PSS layer after the mild oxygen plasma treatment by scanning electron microscopy and atomic force microscopy. We found that the appropriate treatment can form uniformly distributed nano scaled hillocks/islands on the surface of PEDOT:PSS layer, which possibly result in improved contact to hole transport layer and thus enhanced lifetime of the devices

  11. Studies on the Inhibition of Mild Steel Corrosion by Rauvolfia serpentina in Acid Media

    Science.gov (United States)

    Bothi Raja, P.; Sethuraman, M. G.

    2010-07-01

    Alkaloid extract of Rauvolfia serpentina was tested as corrosion inhibitor for mild steel in 1 M HCl and H2SO4 using weight loss method at three different temperatures, viz., 303, 313, and 323 K, potentiodynamic polarization, electrochemical impedance spectroscopy and scanning electron microscope (SEM) studies. It is evident from the results of this study that R. serpentina effectively inhibits the corrosion in both the acids through adsorption process following Tempkin adsorption isotherm. The protection efficiency increased with increase in inhibitor concentration and temperature. Free energy of adsorption calculated from the temperature studies also revealed the chemisorption. The mixed mode of action exhibited by the inhibitor was confirmed by the polarization studies while SEM analysis substantiated the formation of protective layer over the mild steel surface.

  12. Delayed epidural hematoma after mild head injury

    Directory of Open Access Journals (Sweden)

    Radulović Danilo

    2005-01-01

    Full Text Available Background. Traumatic delayed epidural hematoma (DEH can be defined as insignificant or not seen on the initial CT scan performed after a trauma but seen on the subsequent CT scan as a “massive” epidural bleeding. Case report. We presented two cases of traumatic DEH after mild head injury. Both patients were conscious and without neurological deficit on the admission. Initial CT scan did not reveal intracranial hematoma. Repeated CT scan, that was performed after neurological deterioration, revealed epidural hematoma in both cases. The patients were operated with a favorable surgical outcome. Conclusion. Traumatic DEH could occur in the patients with head injuries who were conscious on the admission with a normal initial CT scan finding. Early detection of DEH and an urgent surgical evacuation were essential for a good outcome.

  13. Atmospheric corrosion of mild steel in Oman

    Energy Technology Data Exchange (ETDEWEB)

    Gismelseed, Abbasher, E-mail: abbasher@squ.edu.om; Al-Harthi, S. H.; Elzain, M.; Al-Rawas, A. D.; Yousif, A.; Al-Saadi, S.; Al-Omari, I.; Widatallah, H.; Bouziane, K. [College of Science, Department of Physics (Oman)

    2006-01-15

    A systematic study has been made of the initial corrosion products which form on mild steel capons exposed near the coastal region of Oman and at some industrial areas. The phases and compositions of the products formed at different periods of exposure were examined by using Moessbauer spectroscopy (295 and 78 K) and X-ray diffraction (XRD) techniques. The results show that lepidocorcite and maghemite are early corrosion products and goethite starts to form after 2 months of metal exposure to the atmosphere. Akaganeite is an early corrosion product but it forms in marine environments only, which reflects the role of chlorine effect in the atmosphere. The 12 months coupons showed the presence of goethite, lepidocorcite and maghemite, but no akaganeite being seen in the products of one of the studied areas.

  14. Atmospheric corrosion of mild steel in Oman

    International Nuclear Information System (INIS)

    Gismelseed, Abbasher; Al-Harthi, S. H.; Elzain, M.; Al-Rawas, A. D.; Yousif, A.; Al-Saadi, S.; Al-Omari, I.; Widatallah, H.; Bouziane, K.

    2006-01-01

    A systematic study has been made of the initial corrosion products which form on mild steel capons exposed near the coastal region of Oman and at some industrial areas. The phases and compositions of the products formed at different periods of exposure were examined by using Moessbauer spectroscopy (295 and 78 K) and X-ray diffraction (XRD) techniques. The results show that lepidocorcite and maghemite are early corrosion products and goethite starts to form after 2 months of metal exposure to the atmosphere. Akaganeite is an early corrosion product but it forms in marine environments only, which reflects the role of chlorine effect in the atmosphere. The 12 months coupons showed the presence of goethite, lepidocorcite and maghemite, but no akaganeite being seen in the products of one of the studied areas.

  15. Functional Hubs in Mild Cognitive Impairment

    Science.gov (United States)

    Navas, Adrián; Papo, David; Boccaletti, Stefano; Del-Pozo, F.; Bajo, Ricardo; Maestú, Fernando; Martínez, J. H.; Gil, Pablo; Sendiña-Nadal, Irene; Buldú, Javier M.

    We investigate how hubs of functional brain networks are modified as a result of mild cognitive impairment (MCI), a condition causing a slight but noticeable decline in cognitive abilities, which sometimes precedes the onset of Alzheimer's disease. We used magnetoencephalography (MEG) to investigate the functional brain networks of a group of patients suffering from MCI and a control group of healthy subjects, during the execution of a short-term memory task. Couplings between brain sites were evaluated using synchronization likelihood, from which a network of functional interdependencies was constructed and the centrality, i.e. importance, of their nodes was quantified. The results showed that, with respect to healthy controls, MCI patients were associated with decreases and increases in hub centrality respectively in occipital and central scalp regions, supporting the hypothesis that MCI modifies functional brain network topology, leading to more random structures.

  16. A mild Grave's ophthalmopathy during pregnancy.

    Science.gov (United States)

    Abbouda, Alessandro; Trimboli, Pierpaolo; Bruscolini, Alice

    2014-01-01

    Thyroid ophthalmopathy is a complication most commonly associated with Grave's disease. The disease course ranges from mild to severe, with severe cases resulting in major visual impairment. A complete ophthalmic examination in a 35-year-old secundigravida to 14 weeks of gestation presented to the hospital for a routine ophthalmological examination with eyelid retraction in the right eye was made. We studied the course of ocular disease through the gestation with orbit ecography and a 3T MRI. A diagnosis of Grave's Ophthalmopathy was made. This case presents an unusual course of the GD during pregnancy and a normal post-partum relapse, according to the Th1/Th2 balance. The frequent follow-up and the use of MRI allowed a prompt identification and complete control of the disease.

  17. Prevention of Chronic Experimental Colitis Induced by Dextran Sulphate Sodium (DSS in Mice Treated with FR91

    Directory of Open Access Journals (Sweden)

    Valter R. M. Lombardi

    2012-01-01

    Full Text Available One of the main treatments currently used in humans to fight cancer is chemotherapy. A huge number of compounds with antitumor activity are present in nature, and many of their derivatives are produced by microorganisms. However, the search for new drugs still represents a main objective for cancer therapy, due to drug toxicity and resistance to multiple chemotherapeutic drugs. In animal models, a short-time oral administration of dextran sulfate sodium (DSS induces colitis, which exhibits several clinical and histological features similar to ulcerative colitis (UC. However, the pathogenic factors responsible for DSS-induced colitis and the subsequent colon cancer also remain unclear. We investigated the effect of FR91, a standardized lysate of microbial cells belonging to the Bacillus genus which has been previously shown to have significant immunomodulatory effects, against intestinal inflammation. Colitis was induced in mice during 5 weeks by oral administration 2% (DSS. Morphological changes in the colonic mucosa were evaluated by hematoxylin-eosin staining and immunohistochemistry methods. Adenocarcinoma and cryptal cells of the dysplastic epithelium showed cathenin-β, MLH1, APC, and p53 expression, together with increased production of IFN-γ. In our model, the optimal dose response was the 20% FR91 concentration, where no histological alterations or mild DSS-induced lesions were observed. These results indicate that FR91 may act as a chemopreventive agent against inflammation in mice DSS-induced colitis.

  18. Bex1 knock out mice show altered skeletal muscle regeneration

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  19. Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

    Science.gov (United States)

    Imai, Saki; Kano, Makoto; Nonoyama, Keiko; Ebihara, Shizufumi

    2013-01-01

    We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system. PMID:23472206

  20. Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice.

    Directory of Open Access Journals (Sweden)

    Saki Imai

    Full Text Available We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92, and mice with this mutation (MT mice, as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system.

  1. Normal macrophage function in copper deficient mice

    International Nuclear Information System (INIS)

    Lukasewycz, O.A.; Kolquist, K.L.; Prohaska, J.R.

    1986-01-01

    Copper deficiency (-Cu) was produced in C57 BL and C58 mice by feeding a low copper diet (modified AIN-76A) from birth. Mice given supplemental copper in the drinking water (+Cu) served as controls. Copper status was monitored by assay of ceruloplasmin (CP) activity. Macrophages (M0) were obtained from matched +Cu and -Cu male 7 week-old mice by peritoneal lavage 3 days after thioglycollate stimulation. M0 were assayed in terms of lipopolysaccharide-induced hexose monophosphate shunt activity by monitoring 14 CO 2 production from [1- 14 C]-glucose and by the determination of phagocytic index using fluorescein labelled latex bead ingestion. M0 from -Cu mice were equivalent to those of +Cu mice in both these parameters. However, superoxide dismutase and cytochrome oxidase activities were both significantly lower in -Cu M0, confirming a functional copper deficiency. Previous results from this laboratory have shown that -Cu mice have a decreased antibody response to sheep erythrocyte antigens and a diminished reactivity to B and T cell mitogens. These immunological insufficiencies appear to be proportional to the severity of copper depletion as determined by CP levels. Furthermore, -Cu lymphocytes exhibit depressed mixed lymphocyte reactivity consistent with alterations at the membrane surface. The present results suggest that M0/monocytes are less severely affected than lymphocytes in copper deficiency states

  2. Synthesis and corrosion inhibition application of NATN on mild steel surface in acidic media complemented with DFT studies

    Directory of Open Access Journals (Sweden)

    Shaimaa B. Al-Baghdadi

    2018-03-01

    Full Text Available The corrosion inhibition effectiveness of thiosemicarbazide compound, namely 3-nitro-5-(2-amino-1,3,4-thiadiazolylnitrobenzene (NATN, on mild steel in 1 M hydrochloric acid media has been investigated by weight loss technique. The results exhibit that the corrosion ratio of mild steel was reduced regarding to adding NATN. The corrosion inhibition rate for the NATN was 92.3% at the highest investigated NATN concentration. From the weight loss results it could be concluded that NATN with sulfur, nitrogen and oxygen atoms has clarified best corrosion inhibition achievement comparing to 3,5-dinitrobenzoic acid. Regarding to theoretical studies, DFT was employee to figured geometrical structure and electronic characteristics on NATN. The investigation have been extensive to the HOMO and LUMO analysis to evaluate the energy gap, Ionization potential, Electron Affinity, Global Hardness, Chemical Potential, Electrophilicity, Electronegativity and Polarizability. Keywords: NATN, Mild steel, Weight loss, Dinitrobenzoic acid

  3. 77 FR 31909 - Culturally Significant Objects Imported for Exhibition

    Science.gov (United States)

    2012-05-30

    ... exhibition ``50th Anniversary Remembrance of the Tragedy at Orly,'' imported from abroad by the High Museum of Art for temporary exhibition within the United States, is of cultural significance. The object is... exhibition or display of the exhibit object at the High Museum of Art in Atlanta, Georgia from on or about...

  4. Temporary and Travelling Exhibitions. Museums and Monuments, X.

    Science.gov (United States)

    Daifuku, Hiroshi; And Others

    The permanent exhibition, the most typical form of museum exhibition, has failed to attract repeated visitation, since visitors quickly become familiar with the objects shown. The temporary exhibition evolved as a result for the need of repeated visitation. The temporary exhibition, set up for a period of one to six months, introduces fresh…

  5. Designing immersion exhibits as border-crossing environments

    DEFF Research Database (Denmark)

    Mortensen, Marianne Foss

    2010-01-01

    be applied to achieve an understanding of the immersion exhibit form. The argument proceeds by demonstrating how the characteristics of immersion exhibits, and visitors to them, classify them as microcultures, and examining the implications of this for exhibit design using a hypothetical immersion exhibit...

  6. Comparing Cognitive Profiles of Licensed Drivers with Mild Alzheimer’s Disease and Mild Dementia with Lewy Bodies

    Directory of Open Access Journals (Sweden)

    Stephanie Yamin

    2016-01-01

    Full Text Available Purpose. Alzheimer’s disease (AD and dementia with Lewy Bodies (DLB constitute two of the most common forms of dementia in North America. Driving is a primary means of mobility among older adults and the risk of dementia increases with advanced age. The purpose of this paper is to describe the cognitive profile of licensed drivers with mild AD and mild DLB. Method. Licensed drivers with mild AD, mild DLB, and healthy controls completed neuropsychological tests measuring general cognition, attention, visuospatial/perception, language, and cognitive fluctuations. Results. The results showed differences between healthy controls and demented participants on almost all neuropsychological measures. Participants with early DLB were found to perform significantly worse on some measures of attention and visuospatial functioning in comparison with early AD. Discussion. Future research should examine the relationship between neuropsychological measures and driving outcomes among individuals with mild AD and mild DLB.

  7. Neurotropism In Vitro and Mouse Models of Severe and Mild Infection with Clinical Strains of Enterovirus 71

    Directory of Open Access Journals (Sweden)

    Pin Yu

    2017-11-01

    Full Text Available Enterovirus 71 (EV71 is a common etiological agent of hand, foot, and mouth disease and fatal neurological diseases in children. The neuropathogenicity of severe EV71 infection has been documented, but studies comparing mouse models of severe and mild EV71 infection are lacking. The aim of the study was to investigate the neurovirulence of EV71 strains and the differences in serum cytokine and chemokine levels in mouse models of severe and mild EV71 infection. Nine EV71 isolates belonging to the C4 subgenogroup (proposed as genotype D displayed infectivity in human neuroblastoma SK-N-SH cells; moreover, ultrastructural observation confirmed viral particle replication. The survival rate of the severe model was 71.43% (5/7, and 60% (3/5 of the surviving severe model mice displayed sequelae of paralysis, whereas the only symptom in mild model mice was ruffled fur. Dynamic detection of serum cytokine and chemokine levels demonstrated that interleukin (IL-5, IL-13, IL-6, monocyte chemotactic protein 1 (MCP-1, and chemokine (C-C motif ligand 5 (also called Regulated upon Activation, Normal T-cell Expressed, and Secreted (CCL5/RANTES were significantly up-regulated at the early period of infection, indicating that these factors might herald a severe outcome. Our findings suggest that elevated cytokines and chemokines may have potential value as prognostic markers in mouse models.

  8. Cimetidine attenuates vinorelbine-induced phlebitis in mice by militating E-selectin expression.

    Science.gov (United States)

    Wang, Zhuo; Ma, Lijuan; Wang, Xuebin; Cai, Heping; Huang, Jin; Liu, Jiyong; Hu, Jinhong; Su, Dingfeng

    2014-08-01

    We investigated E-selectin expression in mice and rabbits with vinorelbine-induced phlebitis and the effect of cimetidine. To find the relationship between E-selectin expression and vinorelbine-induced phlebitis. Mouse and rabbit model of vinorelbine-induced phlebitis was established by intravenous infusion of vinorelbine. Pathological observation, molecular-biological determination of E-selectin and protein function of it was evaluated. Grossly, we observed swelling, edema and cord-like vessel changes in mice receiving vinorelbine but only mild edema in mice pretreated with cimetidine. Pathological scoring yielded a total score of 37 for vinorelbine-treated mice and 17 for mice pretreated with cimetidine (P phlebitis in mice probably by suppressing increased expression of E-selectin.

  9. Chronic Co-species Housing Mice and Rats Increased the Competitiveness of Male Mice.

    Science.gov (United States)

    Liu, Ying-Juan; Li, Lai-Fu; Zhang, Yao-Hua; Guo, Hui-Fen; Xia, Min; Zhang, Meng-Wei; Jing, Xiao-Yuan; Zhang, Jing-Hua; Zhang, Jian-Xu

    2017-03-01

    Rats are predators of mice in nature. Nevertheless, it is a common practice to house mice and rats in a same room in some laboratories. In this study, we investigated the behavioral and physiological responsively of mice in long-term co-species housing conditions. Twenty-four male mice were randomly assigned to their original raising room (control) or a rat room (co-species-housed) for more than 6 weeks. In the open-field and light-dark box tests, the behaviors of the co-species-housed mice and controls were not different. In a 2-choice test of paired urine odors [rabbit urine (as a novel odor) vs. rat urine, cat urine (as a natural predator-scent) vs. rabbit urine, and cat urine vs. rat urine], the co-species-housed mice were more ready to investigate the rat urine odor compared with the controls and may have adapted to it. In an encounter test, the rat-room-exposed mice exhibited increased aggression levels, and their urines were more attractive to females. Correspondingly, the levels of major urinary proteins were increased in the co-species-housed mouse urine, along with some volatile pheromones. The serum testosterone levels were also enhanced in the co-species-housed mice, whereas the corticosterone levels were not different. The norepinephrine, dopamine, and 5-HT levels in the right hippocampus and striatum were not different between the 2. Our findings indicate that chronic co-species housing results in adaptation in male mice; furthermore, it appears that long-term rat-odor stimuli enhance the competitiveness of mice, which suggests that appropriate predator-odor stimuli may be important to the fitness of prey animals. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Memory complaints in subjective cognitive impairment, amnestic mild cognitive impairment and mild Alzheimer's disease.

    Science.gov (United States)

    Ryu, Seon Young; Lee, Sang Bong; Kim, Tae Woo; Lee, Taek Jun

    2016-12-01

    Memory complaints are a frequent phenomenon in elderly individuals and can lead to opportunistic help-seeking behavior. The aim of this study was to compare different aspects of memory complaints (i.e., prospective versus retrospective complaints) in individuals with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (aMCI), and mild Alzheimer's disease (AD). The study included a total of 115 participants (mean age: 68.82 ± 8.83 years) with SCI (n = 34), aMCI (n = 46), and mild AD (n = 35). Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which consists of 16 items that describe everyday memory failure of both prospective memory (PM) and retrospective memory (RM). For aMCI and AD subjects, informants also completed an informant-rating of the PRMQ. All participants completed detailed neuropsychological tests. Results show that PM complaints were equivalent among the three groups. However, RM complaints differed. Specifically, RM complaints in aMCI were higher than SCI, but similar to AD. Informant-reported memory complaints were higher for AD than aMCI. Our study suggests that RM complaints of memory complaints may be helpful in discriminating between SCI and aMCI, but both PM and RM complaints are of limited value in differentiating aMCI from AD.

  11. Creating Virtual Exhibitions for Educational and Cultural Development

    Directory of Open Access Journals (Sweden)

    Gabriela DUMITRESCU

    2014-01-01

    Full Text Available The paper presents different tools and mechanisms to implement a virtual exhibition in different cultural areas, such as museums and libraries. Quality characteristics of virtual exhibitions are identified and described. The possibility to create native mobile applications for virtual exhibitions presentation is analyzed. The functional flow of creating a virtual exhibition is presented and discussed. The Seals - History Treasure exhibition is presented and significant historical documents are revealed.

  12. Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

    Science.gov (United States)

    Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

    2018-04-02

    Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Retinoic acid attenuates the mild hyperoxic lung injury in newborn mice

    Czech Academy of Sciences Publication Activity Database

    Zimová-Herknerová, M.; Mysliveček, J.; Potměšil, Petr

    2008-01-01

    Roč. 57, č. 1 (2008), s. 33-40 ISSN 0862-8408 Institutional research plan: CEZ:AV0Z50390512 Keywords : Retionic acid * Hyperoxia * Lung injury Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.653, year: 2008

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Alterations in urine, serum and brain metabolomic profiles exhibit sexual dimorphism during malaria disease progression

    Directory of Open Access Journals (Sweden)

    Sharma Shobhona

    2010-04-01

    Full Text Available Abstract Background Metabolic changes in the host in response to Plasmodium infection play a crucial role in the pathogenesis of malaria. Alterations in metabolism of male and female mice infected with Plasmodium berghei ANKA are reported here. Methods 1H NMR spectra of urine, sera and brain extracts of these mice were analysed over disease progression using Principle Component Analysis and Orthogonal Partial Least Square Discriminant Analysis. Results Analyses of overall changes in urinary profiles during disease progression demonstrate that females show a significant early post-infection shift in metabolism as compared to males. In contrast, serum profiles of female mice remain unaltered in the early infection stages; whereas that of the male mice changed. Brain metabolite profiles do not show global changes in the early stages of infection in either sex. By the late stages urine, serum and brain profiles of both sexes are severely affected. Analyses of individual metabolites show significant increase in lactate, alanine and lysine, kynurenic acid and quinolinic acid in sera of both males and females at this stage. Early changes in female urine are marked by an increase of ureidopropionate, lowering of carnitine and transient enhancement of asparagine and dimethylglycine. Several metabolites when analysed individually in sera and brain reveal significant changes in their levels in the early phase of infection mainly in female mice. Asparagine and dimethylglycine levels decrease and quinolinic acid increases early in sera of infected females. In brain extracts of females, an early rise in levels is also observed for lactate, alanine and glycerol, kynurenic acid, ureidopropionate and 2-hydroxy-2-methylbutyrate. Conclusions These results suggest that P. berghei infection leads to impairment of glycolysis, lipid metabolism, metabolism of tryptophan and degradation of uracil. Characterization of early changes along these pathways may be crucial for

  16. Long duration mild temperature hyperthermia and brachytherapy.

    Science.gov (United States)

    Armour, E P; Raaphorst, G P

    2004-03-01

    Combining long duration mild temperature hyperthermia (LDMH) and low dose-rate (LDR) brachytherapy to enhance therapeutic killing of cancer cells was proposed many years ago. The cellular and tumour research that supports this hypothesis is presented in this review. Research describing LDMH interaction with pulsed brachytherapy and high dose-rate brachytherapy using clinically relevant parameters are compared with LDMH/LDR brachytherapy. The mechanism by which LDMH sensitizes LDR has been established as the inhibition of sublethal damage repair. The molecular mechanisms have been shown to involve DNA repair enzymes, but the exact nature of these processes is still under investigation. The relative differences between LDMH interactions with human and rodent cells are presented to help in the understanding of possible roles of LDMH in clinical application. The role of LDMH in modifying tumour blood flow and its possible role in LDR sensitization of tumours is also presented. The positive aspects of LDMH-brachytherapy for clinical application are sixfold; (1) the thermal goals (temperature, time and volume) are achievable with currently available technology, (2) the hyperthermia by itself has no detectable toxic effects, (3) thermotolerance appears to play a minor if any role in radiation sensitization, (4) TER of around 2 can be expected, (5) hypoxic fraction may be decreased due to blood flow modification and (6) simultaneous chemotherapy may also be sensitized. Combined LDMH and brachytherapy is a cancer therapy that has established biological rationale and sufficient technical and clinical advancements to be appropriately applied. This modality is ripe for clinical testing.

  17. A sibship with a mild variant of Zellweger syndrome

    NARCIS (Netherlands)

    Barth, P. G.; Schutgens, R. B.; Wanders, R. J.; Heymans, H. S.; Moser, A. E.; Moser, H. W.; Bleeker-Wagemakers, E. M.; Jansonius-Schultheiss, K.; Derix, M.; Nelck, G. F.

    1987-01-01

    A mild variant of Zellweger (cerebro-hepato-renal) syndrome was diagnosed in male and female siblings aged 7 and 2 years. They had mild facial dysmorphia, moderate psychomotor retardation, tapetoretinal degeneration, sensorineural deafness and hepatomegaly. Ultrastructural examination of a liver

  18. Mild Aphasia: Is This the Place for an Argument?

    Science.gov (United States)

    Armstrong, Elizabeth; Fox, Sarah; Wilkinson, Ray

    2013-01-01

    Purpose: Individuals with mild aphasia often report significant disruption to their communication despite seemingly minor impairment. This study explored this phenomenon through examining conversations of a person with mild aphasia engaging in argumentation--a skill she felt had significantly deteriorated after her stroke. Method: A person with…

  19. Efficacy of psychosocial intervention in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Waldorff, F B; Buss, D V; Eckermann, A

    2012-01-01

    To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers.......To assess the efficacy at 12 months of an early psychosocial counselling and support programme for outpatients with mild Alzheimer's disease and their primary care givers....

  20. Digit Symbol Performance in Mild Dementia and Depression.

    Science.gov (United States)

    Hart, Robert P.; And Others

    1987-01-01

    Patients with mild dementia of the Alzheimer's type (DAT), patients with major depression, and normal control subjects completed the Wechsler Adult Intelligence Scale (WAIS) Digit Symbol test of incidental memory. Though mild DAT and depressed patients had equivalent deficits in psychomotor speed, DAT patients recalled fewer digit-symbol items.…

  1. Heterogeneity in executive impairment in patients with very mild Alzheimer's

    DEFF Research Database (Denmark)

    Stokholm, J.; Gade, Anders; Vogel, A.

    2006-01-01

    The presence of executive impairment in mild Alzheimer's disease (AD) has primarily been demonstrated by means of group comparison. Whether executive dysfunction is a common feature of mild AD or only present in a subgroup of patients remains unclear. The aim of this study was to describe...

  2. Anticorrosion potential of hydralazine for corrosion of mild steel in ...

    African Journals Online (AJOL)

    Anticorrosion potential of mild steel by Hydralazine as corrosion inhibitor for mild steel in 1M hydrochloric acid was investigated by chemical and electrochemical measurements at 303-333 K temperature. The maximum inhibition efficiency of inhibitor by Weight loss method is around 90%, Tafel polarization method is ...

  3. Reliability and performance evaluation of stainless and mild steel ...

    African Journals Online (AJOL)

    Reliability and performance of stainless and mild steel products in methanolic and aqueous sodium chloride media have been investigated. Weight-loss and pre-exposure methods were used. There was a higher rate of weight-loss of mild steels and stainless steels in 1% HCl methanolic solution than in aqueous NaCl ...

  4. A mouse model of the schizophrenia-associated 1q21.1 microdeletion syndrome exhibits altered mesolimbic dopamine transmission

    DEFF Research Database (Denmark)

    Nielsen, Jacob; Fejgin, Kim; Sotty, Florence

    2017-01-01

    on schizophrenia-related assays. Df(h1q21)/+ mice displayed increased hyperactivity in response to amphetamine challenge and increased sensitivity to the disruptive effects of amphetamine and phencyclidine hydrochloride (PCP) on prepulse inhibition. Probing of the direct dopamine (DA) pathway using the DA D1...... and basic functions such as reflexes, ASR, thermal pain sensitivity, and motor performance were unaltered. Similarly, anxiety related measures, baseline prepulse inhibition, and seizure threshold were unaltered. In addition to the central nervous system-related phenotypes, Df(h1q21)/+ mice exhibited reduced...

  5. A content-oriented model for science exhibit engineering

    DEFF Research Database (Denmark)

    Achiam, Marianne

    2013-01-01

    Recently, science museums have begun to review their educational purposes and redesign their pedagogies. At the most basic level, this entails accounting for the performance of individual exhibits, and indeed, in some cases, research indicates shortcomings in exhibit design: While often successful......: as a means to operationalize the link between exhibit features and visitor activities; and as a template to transform scientists’ practices in the research context into visitors’ activities in the exhibit context. The resulting model of science exhibit engineering is presented and exemplified, and its...... implications for science exhibit design are discussed at three levels: the design product, the design process, and the design methodology....

  6. Mechanical behaviour of Zn-Fe alloy coated mild steel

    International Nuclear Information System (INIS)

    Panagopoulos, C.N.; Georgiou, E.P.; Agathocleous, P.E.; Giannakopoulos, K.I.

    2009-01-01

    Zinc alloy coatings containing various amounts of Fe were deposited by electrodeposition technique on a mild steel substrate. The concentration of Fe in the produced alloy coatings ranged from 0 to 14 wt.%, whereas the thickness of the coatings was about 50 μm. Structural and metallurgical characterization of the produced coatings was performed with the aid of X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) techniques. This study aims in investigating the mechanical behaviour of Zn-Fe coated mild steel specimens, as no research investigation concerning the tensile behaviour of Zn alloy coated ferrous alloys has been reported in the past. The experimental results indicated that the ultimate tensile strength of the Zn-Fe coated mild steel was lower than the bare mild steel. In addition, the ductility of the Zn-Fe coated mild steel was found to decrease significantly with increasing Fe content in the coating.

  7. Lipid metabolism and body composition in Gclm(-/-) mice

    Energy Technology Data Exchange (ETDEWEB)

    Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

  8. Multiple alterations of platelet functions dominated by increased secretion in mice lacking Cdc42 in platelets

    DEFF Research Database (Denmark)

    Pleines, Irina; Eckly, Anita; Elvers, Margitta

    2010-01-01

    formation and exocytosis in various cell types, but its exact function in platelets is not established. Here, we show that the megakaryocyte/platelet-specific loss of Cdc42 leads to mild thrombocytopenia and a small increase in platelet size in mice. Unexpectedly, Cdc42-deficient platelets were able to form...

  9. Efficacy of On-Demand Therapy Using 20-mg Vonoprazan for Mild Reflux Esophagitis.

    Science.gov (United States)

    Umezawa, Mariko; Kawami, Noriyuki; Hoshino, Shintaro; Hoshikawa, Yoshimasa; Koizumi, Eriko; Takenouchi, Nana; Hanada, Yuriko; Kaise, Mitsuru; Iwakiri, Katsuhiko

    2018-01-01

    The study aimed to evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for mild reflux esophagitis (RE). On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 24 weeks using 30 patients with mild RE who were receiving maintenance therapy with proton pomp inhibitors (PPIs). The presence or absence of RE, degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin level before breakfast were examined before and after on-demand therapy. The number of tablets taken during the 24-week period was also noted. One of the 30 patients dropped out of on-demand therapy 1 week after its initiation. Remission was maintained in 25 (86.2%) of the 29 patients (all 10 [100%] Los Angeles classification grade A patients and 15 (78.9%) of the 19 grade B patients). However, 4 grade B patients exhibited grade B relapse. There were no differences in the degree of overall satisfaction, score of symptoms or the gastrin level between PPI and on-demand therapies. The number of vonoprazan tablets taken during the observation period was 33 tablets (median)/24 weeks. On-demand therapy using 20-mg vonoprazan tablets is an effective alternative maintenance therapy for mild RE. © 2018 S. Karger AG, Basel.

  10. Infanticide: accounting for genetic variation in mice.

    Science.gov (United States)

    Svare, B; Kinsley, C H; Mann, M A; Broida, J

    1984-07-01

    Infanticide, the killing of young, is one of a number of sexually-dimorphic traits in mice that is dependent upon androgen stimulation during perinatal life and during adulthood. Genotype also influences infanticide in that males of some strains of mice (C57BL/6J) exhibit high levels of this behavior while males of other strains (DBA/2J) seldom kill young. The experiments conducted here show that strain differences in pup killing behavior exhibited by males are not related to postweaning social factors nor are they due to differences in perinatal, pubertal, or adult levels of circulating hormones. These results, in combination with those previously reported, suggest that strain differences in the tendency of mice to kill young may instead depend upon the interaction of genotypic features such as prenatal hormone titers and/or sensitivity to these hormones, as well as on extra organismic factors such as intrauterine position. A model for understanding the manner in which genes and hormones may interact to influence infanticide and other hormone dependent sexually-dimorphic behaviors in mice is presented.

  11. Nicotinamide pharmacokinetics in humans and mice

    International Nuclear Information System (INIS)

    Horsman, M.R.; Hoyer, M.; Overgaard, J.; Honess, D.J.; Dennis, A.F.

    1993-01-01

    Healthy human volunteers orally ingested escalating doses of up to 6 g nicotinamide in capsule form on an empty stomach. Some side-effects were seen although these were mild and transient. HPLC analysis of blood samples showed peak plasma levels, typically within 45 min after ingestion, which were linearly dependent on dose ingested. The elimination half-life and AUC were also found to increase with drug dose, although these increases were non-linear. Pharmacokinetic studies were also performed to female CDF1 mice with C3H mammary carcinomas grown in the right rear foot. Analysis of blood and tumour samples taken from mice injected i.p. with nicotinamide doses between 100-1000 mg/kg showed similar characteristics as the human data, although the elimination half-lives were not dose-dependent. The average peak plasma concentration of 160 μg/ml measured in humans after taking 6 g of nicotinamide was equivalent to that seen in mice after injecting 171 mg/kg. Using a regrowth delay assay the enhancement of radiation damage by nicotinamide in this mouse tumour was found to be independent of drug dose from 100-1000 mg/kg, resulting in a constant 1.3-fold increase in radiation response. Doses of nicotinamide that can be tolerated clinically should therefore produce adequate enhancements of radiation damage in human tumours. (author)

  12. Variation in Resistance of Natural Isolates of Escherichia coli O157 to High Hydrostatic Pressure, Mild Heat, and Other Stresses

    OpenAIRE

    Benito, Amparo; Ventoura, Georgia; Casadei, Maria; Robinson, Tobin; Mackey, Bernard

    1999-01-01

    Strains of Escherichia coli O157 isolated from patients with clinical cases of food-borne illness and other sources exhibited wide differences in resistance to high hydrostatic pressure. The most pressure-resistant strains were also more resistant to mild heat than other strains. Strain C9490, a representative pressure-resistant strain, was also more resistant to acid, oxidative, and osmotic stresses than the pressure-sensitive strain NCTC 12079. Most of these differences in resistance were o...

  13. A Novel mouse model of enhanced proteostasis: Full-length human heat shock factor 1 transgenic mice

    International Nuclear Information System (INIS)

    Pierce, Anson; Wei, Rochelle; Halade, Dipti; Yoo, Si-Eun; Ran, Qitao; Richardson, Arlan

    2010-01-01

    Research highlights: → Development of mouse overexpressing native human HSF1 in all tissues including CNS. → HSF1 overexpression enhances heat shock response at whole-animal and cellular level. → HSF1 overexpression protects from polyglutamine toxicity and favors aggresomes. → HSF1 overexpression enhances proteostasis at the whole-animal and cellular level. -- Abstract: The heat shock response (HSR) is controlled by the master transcriptional regulator heat shock factor 1 (HSF1). HSF1 maintains proteostasis and resistance to stress through production of heat shock proteins (HSPs). No transgenic model exists that overexpresses HSF1 in tissues of the central nervous system (CNS). We generated a transgenic mouse overexpressing full-length non-mutant HSF1 and observed a 2-4-fold increase in HSF1 mRNA and protein expression in all tissues studied of HSF1 transgenic (HSF1 +/0 ) mice compared to wild type (WT) littermates, including several regions of the CNS. Basal expression of HSP70 and 90 showed only mild tissue-specific changes; however, in response to forced exercise, the skeletal muscle HSR was more elevated in HSF1 +/0 mice compared to WT littermates and in fibroblasts following heat shock, as indicated by levels of inducible HSP70 mRNA and protein. HSF1 +/0 cells elicited a significantly more robust HSR in response to expression of the 82 repeat polyglutamine-YFP fusion construct (Q82YFP) and maintained proteasome-dependent processing of Q82YFP compared to WT fibroblasts. Overexpression of HSF1 was associated with fewer, but larger Q82YFP aggregates resembling aggresomes in HSF1 +/0 cells, and increased viability. Therefore, our data demonstrate that tissues and cells from mice overexpressing full-length non-mutant HSF1 exhibit enhanced proteostasis.

  14. Neuropathology of mild cognitive impairment (MCI)

    International Nuclear Information System (INIS)

    Murayama, Shigeo; Saito, Yuko

    2007-01-01

    Described are retrospective pathological studies on mild cognitive impairment (MCI) of brain specimens in the brain bank of authors' institute and current clinical studies of outpatients for screening of MCI based on those pathological findings. The study projects, aided by Ministry of Health, Labour and Welfare (MHLW) from 2003 and from 2007, have aimed to develop the optimal way for prophylaxis of dementia. In the former autopsy, about 10% of the elderly dead registered in the institute are found to have pathological changes of the clinical dementia rating 0.5, in whom the early Alzheimer disease (AD), Lewy body dementia, argentaffin granular disease and neurofibrillary tangle dominant disease are involved in a similar ratio to each other. Clinically, new patients with memory complaint are first screened by neurological tests involving CT, and then those with suspicious dementia undergo the second screening (2-day hospitalization) involving MRI with VSRAD (Voxel-based Specific Regional Analysis System for AD), ECD single photon emission computed tomography (SPECT) with eZis (easy Z-score imaging system), myocardial scintigraphy with homovanillic acid (HVA)/m-iodobenzylguanidine (MIBG), and if necessary, PET with fluorodeoxyglucose (FDG), PIB (Pittsburgh Compound B, an amyloid prove) and/or 11 C-CFT and 11 C-raclopride. Further, new patients with suspicious Parkinson disease undergo the screening (3-day) of various tests involving MRI with voxel-based morphometry and VSRAD, cerebral blood flow ECD SPECT with eZis and MIBG myocardial scintigraphy. It is concluded that AD is the most important subject in MCI and systemic diseases can also affect the cognitive ability as well. (R.T.)

  15. Myogenin regulates exercise capacity but is dispensable for skeletal muscle regeneration in adult mdx mice.

    Directory of Open Access Journals (Sweden)

    Eric Meadows

    Full Text Available Duchenne muscular dystrophy (DMD is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenic regulatory factor, is best known for its role in embryonic myogenesis, but its role in adult muscle maintenance and regeneration is still poorly understood. Here, we generated an mdx:Myog(flox/flox mouse harboring a tamoxifen-inducible Cre recombinase transgene, which was used to conditionally delete Myog during adult life. After tamoxifen treatment, three groups of mice were created to study the effects of Myog deletion: mdx:Myog(flox/flox mice (mdx, Myog(flox/flox mice (wild-type, and mdx:Myog(floxΔ/floxΔ:Cre-ER mice (mdx:Myog-deleted. mdx:Myog-deleted mice exhibited no adverse phenotype and behaved normally. When run to exhaustion, mdx:Myog-deleted mice demonstrated an enhanced capacity for exercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, we found that myogenin was dispensable for muscle regeneration. Factors associated with muscle fatigue, metabolism, and proteolysis were significantly altered in mdx:Myog-deleted mice, and this might contribute to their increased exercise capacity. Our results reveal novel functions for myogenin in adult muscle and suggest that reducing Myog expression in other muscle disease models may partially restore muscle function.

  16. Dissociation of hepatic insulin resistance from susceptibility of nonalcoholic fatty liver disease induced by a high-fat and high-carbohydrate diet in mice.

    Science.gov (United States)

    Asai, Akihiro; Chou, Pauline M; Bu, Heng-Fu; Wang, Xiao; Rao, M Sambasiva; Jiang, Anthony; DiDonato, Christine J; Tan, Xiao-Di

    2014-03-01

    Liver steatosis in nonalcoholic fatty liver disease is affected by genetics and diet. It is associated with insulin resistance (IR) in hepatic and peripheral tissues. Here, we aimed to characterize the severity of diet-induced steatosis, obesity, and IR in two phylogenetically distant mouse strains, C57BL/6J and DBA/2J. To this end, mice (male, 8 wk old) were fed a high-fat and high-carbohydrate (HFHC) or control diet for 16 wk followed by the application of a combination of classic physiological, biochemical, and pathological studies to determine obesity and hepatic steatosis. Peripheral IR was characterized by measuring blood glucose level, serum insulin level, homeostasis model assessment of IR, glucose intolerance, insulin intolerance, and AKT phosphorylation in adipose tissues, whereas the level of hepatic IR was determined by measuring insulin-triggered hepatic AKT phosphorylation. We discovered that both C57BL/6J and DBA/2J mice developed obesity to a similar degree without the feature of liver inflammation after being fed an HFHC diet for 16 wk. C57BL/6J mice in the HFHC diet group exhibited severe pan-lobular steatosis, a marked increase in hepatic triglyceride levels, and profound peripheral IR. In contrast, DBA/2J mice in the HFHC diet group developed only a mild degree of pericentrilobular hepatic steatosis that was associated with moderate changes in peripheral IR. Interestingly, both C57BL/6J and DBA/2J developed severe hepatic IR after HFHC diet treatment. Collectively, these data suggest that the severity of diet-induced hepatic steatosis is correlated to the level of peripheral IR, not with the severity of obesity and hepatic IR. Peripheral rather than hepatic IR is a dominant factor of pathophysiology in nonalcoholic fatty liver disease.

  17. Short-term vitamin E treatment impairs reactive oxygen species signaling required for adipose tissue expansion, resulting in fatty liver and insulin resistance in obese mice.

    Directory of Open Access Journals (Sweden)

    Martin Alcala

    Full Text Available The use of antioxidant therapy in the treatment of oxidative stress-related diseases such as cardiovascular disease, diabetes or obesity remains controversial. Our aim is to demonstrate that antioxidant supplementation may promote negative effects if used before the establishment of oxidative stress due to a reduced ROS generation under physiological levels, in a mice model of obesity.C57BL/6J mice were fed with a high-fat diet for 14 weeks, with (OE group or without (O group vitamin E supplementation.O mice developed a mild degree of obesity, which was not enough to induce metabolic alterations or oxidative stress. These animals exhibited a healthy expansion of retroperitoneal white adipose tissue (rpWAT and the liver showed no signs of lipotoxicity. Interestingly, despite achieving a similar body weight, OE mice were insulin resistant. In the rpWAT they presented a reduced generation of ROS, even below physiological levels (C: 1651.0 ± 212.0; O: 3113 ± 284.7; OE: 917.6 ±104.4 RFU/mg protein. C vs OE p< 0.01. ROS decay may impair their action as second messengers, which could account for the reduced adipocyte differentiation, lipid transport and adipogenesis compared to the O group. Together, these processes limited the expansion of this fat pad and as a consequence, lipid flux shifted towards the liver, causing steatosis and hepatomegaly, which may contribute to the marked insulin resistance.This study provides in vivo evidence for the role of ROS as second messengers in adipogenesis, lipid metabolism and insulin signaling. Reducing ROS generation below physiological levels when the oxidative process has not yet been established may be the cause of the controversial results obtained by antioxidant therapy.

  18. 76 FR 68808 - Culturally Significant Objects Imported for Exhibition

    Science.gov (United States)

    2011-11-07

    ... also determine that the exhibition or display of the exhibit objects at the Onassis Cultural Center... Century AD,'' imported from abroad for temporary exhibition within the United States, are of cultural... Cultural Affairs, Department of State. [FR Doc. 2011-28805 Filed 11-4-11; 8:45 am] BILLING CODE 4710-05-P ...

  19. 78 FR 7849 - Culturally Significant Objects Imported for Exhibition

    Science.gov (United States)

    2013-02-04

    ... Century,'' imported from abroad for temporary exhibition within the United States, are of cultural... also determine that the exhibition or display of the exhibit objects at The Yale Center for British Art..., Bureau of Educational and Cultural Affairs, Department of State. [FR Doc. 2013-02401 Filed 2-1-13; 8:45...

  20. A Salamander Tale: Effective Exhibits and Attitude Change

    Science.gov (United States)

    Rollins, Jeffrey; Watson, Sunnie Lee

    2017-01-01

    Little information exists regarding intention behind the design and development of Extension outreach and educational exhibits. An evaluation of response to the exhibit "A Salamander Tale" indicates that the methods used to develop the exhibit resulted in an effective way to present information to an adult audience. Survey questions were…

  1. Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

    Science.gov (United States)

    Cerqueira, Fernanda M; Laurindo, Francisco R M; Kowaltowski, Alicia J

    2011-03-31

    Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

  2. Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis.

    Directory of Open Access Journals (Sweden)

    Fernanda M Cerqueira

    2011-03-01

    Full Text Available Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR. Since treatment of mice with dinitrophenol (DNP promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

  3. Otolith dysfunction alters exploratory movement in mice.

    Science.gov (United States)

    Blankenship, Philip A; Cherep, Lucia A; Donaldson, Tia N; Brockman, Sarah N; Trainer, Alexandria D; Yoder, Ryan M; Wallace, Douglas G

    2017-05-15

    The organization of rodent exploratory behavior appears to depend on self-movement cue processing. As of yet, however, no studies have directly examined the vestibular system's contribution to the organization of exploratory movement. The current study sequentially segmented open field behavior into progressions and stops in order to characterize differences in movement organization between control and otoconia-deficient tilted mice under conditions with and without access to visual cues. Under completely dark conditions, tilted mice exhibited similar distance traveled and stop times overall, but had significantly more circuitous progressions, larger changes in heading between progressions, and less stable clustering of home bases, relative to control mice. In light conditions, control and tilted mice were similar on all measures except for the change in heading between progressions. This pattern of results is consistent with otoconia-deficient tilted mice using visual cues to compensate for impaired self-movement cue processing. This work provides the first empirical evidence that signals from the otolithic organs mediate the organization of exploratory behavior, based on a novel assessment of spatial orientation. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Uterine dysfunction in biglycan and decorin deficient mice leads to dystocia during parturition.

    Directory of Open Access Journals (Sweden)

    Zhiping Wu

    Full Text Available Cesarean birth rates are rising. Uterine dysfunction, the exact mechanism of which is unknown, is a common indication for Cesarean delivery. Biglycan and decorin are two small leucine-rich proteoglycans expressed in the extracellular matrix of reproductive tissues and muscle. Mice deficient in biglycan display a mild muscular dystrophy, and, along with mice deficient in decorin, are models of Ehlers-Danlos Syndrome, a connective tissue anomaly associated with uterine rupture. As a variant of Ehlers-Danlos Syndrome is caused by a genetic mutation resulting in abnormal biglycan and decorin secretion, we hypothesized that biglycan and decorin play a role in uterine function. Thus, we assessed wild-type, biglycan, decorin and double knockout pregnancies for timing of birth and uterine function. Uteri were harvested at embryonic days 12, 15 and 18. Nonpregnant uterine samples of the same genotypes were assessed for tissue failure rate and spontaneous and oxytocin-induced contractility. We discovered that biglycan/decorin mixed double-knockout dams displayed dystocia, were at increased risk of delayed labor onset, and showed increased tissue failure in a predominantly decorin-dependent manner. In vitro spontaneous uterine contractile amplitude and oxytocin-induced contractile force were decreased in all biglycan and decorin knockout genotypes compared to wild-type. Notably, we found no significant compensation between biglycan and decorin using quantitative real time PCR or immunohistochemistry. We conclude that the biglycan/decorin mixed double knockout mouse is a model of dystocia and delayed labor onset. Moreover, decorin is necessary for uterine function in a dose-dependent manner, while biglycan exhibits partial compensatory mechanisms in vivo. Thus, this model is poised for use as a model for testing novel targets for preventive or therapeutic manipulation of uterine dysfunction.

  5. Uterine Dysfunction in Biglycan and Decorin Deficient Mice Leads to Dystocia during Parturition

    Science.gov (United States)

    Wu, Zhiping; Aron, Abraham W.; Macksoud, Elyse E.; Iozzo, Renato V.; Hai, Chi-Ming; Lechner, Beatrice E.

    2012-01-01

    Cesarean birth rates are rising. Uterine dysfunction, the exact mechanism of which is unknown, is a common indication for Cesarean delivery. Biglycan and decorin are two small leucine-rich proteoglycans expressed in the extracellular matrix of reproductive tissues and muscle. Mice deficient in biglycan display a mild muscular dystrophy, and, along with mice deficient in decorin, are models of Ehlers-Danlos Syndrome, a connective tissue anomaly associated with uterine rupture. As a variant of Ehlers-Danlos Syndrome is caused by a genetic mutation resulting in abnormal biglycan and decorin secretion, we hypothesized that biglycan and decorin play a role in uterine function. Thus, we assessed wild-type, biglycan, decorin and double knockout pregnancies for timing of birth and uterine function. Uteri were harvested at embryonic days 12, 15 and 18. Nonpregnant uterine samples of the same genotypes were assessed for tissue failure rate and spontaneous and oxytocin-induced contractility. We discovered that biglycan/decorin mixed double-knockout dams displayed dystocia, were at increased risk of delayed labor onset, and showed increased tissue failure in a predominantly decorin-dependent manner. In vitro spontaneous uterine contractile amplitude and oxytocin-induced contractile force were decreased in all biglycan and decorin knockout genotypes compared to wild-type. Notably, we found no significant compensation between biglycan and decorin using quantitative real time PCR or immunohistochemistry. We conclude that the biglycan/decorin mixed double knockout mouse is a model of dystocia and delayed labor onset. Moreover, decorin is necessary for uterine function in a dose-dependent manner, while biglycan exhibits partial compensatory mechanisms in vivo. Thus, this model is poised for use as a model for testing novel targets for preventive or therapeutic manipulation of uterine dysfunction. PMID:22253749

  6. Lovastatin protects against experimental plague in mice.

    Directory of Open Access Journals (Sweden)

    Saravanan Ayyadurai

    Full Text Available BACKGROUND: Plague is an ectoparasite-borne deadly infection caused by Yersinia pestis, a bacterium classified among the group A bioterrorism agents. Thousands of deaths are reported every year in some African countries. Tetracyclines and cotrimoxazole are used in the secondary prophylaxis of plague in the case of potential exposure to Y. pestis, but cotrimoxazole-resistant isolates have been reported. There is a need for additional prophylactic measures. We aimed to study the effectiveness of lovastatin, a cholesterol-lowering drug known to alleviate the symptoms of sepsis, for plague prophylaxis in an experimental model. METHODOLOGY: Lovastatin dissolved in Endolipide was intraperitoneally administered to mice (20 mg/kg every day for 6 days prior to a Y. pestis Orientalis biotype challenge. Non-challenged, lovastatin-treated and challenged, untreated mice were also used as control groups in the study. Body weight, physical behavior and death were recorded both prior to infection and for 10 days post-infection. Samples of the blood, lungs and spleen were collected from dead mice for direct microbiological examination, histopathology and culture. The potential antibiotic effect of lovastatin was tested on blood agar plates. CONCLUSIONS/SIGNIFICANCE: Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5% and lovastatin-treated mice (3/15; 20% was significant (P<0.004; Mantel-Haenszel test. Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague. Field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague.

  7. Functional Disorganization of Small-World Brain Networks in mild Alzheimer’s Disease and amnestic Mild Cognitive Impairment: An EEG Study using Relative Wavelet Entropy (RWE

    Directory of Open Access Journals (Sweden)

    Christos A. Frantzidis

    2014-08-01

    Full Text Available Previous neuroscientific findings have linked Alzheimer’s disease (AD with less efficient information processing and brain network disorganization. However, pathological alterations of the brain networks during the preclinical phase of amnestic Mild Cognitive Impairment (aMCI remain largely unknown. The present study aimed at comparing patterns of the detection of functional disorganization in MCI relative to Mild Dementia (MD. Participants consisted of 23 cognitively healthy adults, 17 aMCI and 24 mild AD patients who underwent electroencephalographic (EEG data acquisition during a resting-state condition. Synchronization analysis through the Orthogonal Discrete Wavelet Transform (ODWT, and directional brain network analysis were applied on the EEG data. This computational model was performed for networks that have the same number of edges (N=500, 600, 700, 800 edges across all participants and groups (fixed density values. All groups exhibited a small-world (SW brain architecture. However, we found a significant reduction in the SW brain architecture in both aMCI and MD patients relative to the group of Healthy controls. This functional disorganization was also correlated with the participant’s generic cognitive status. The deterioration of the network’s organization was caused mainly by deficient local information processing as quantified by the mean cluster coefficient value. Functional hubs were identified through the normalized betweenness centrality metric. Analysis of the local characteristics showed relative hub preservation even with statistically significant reduced strength. Compensatory phenomena were also evident through the formation of additional hubs on left frontal and parietal regions. Our results indicate a declined functional network organization even during the prodromal phase. Degeneration is evident even in the preclinical phase and coexists with transient network reorganization due to compensation.

  8. GH and IGF1: roles in energy metabolism of long-living GH mutant mice.

    Science.gov (United States)

    Brown-Borg, Holly M; Bartke, Andrzej

    2012-06-01

    Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of these pathways are suppressed. Core body temperature is markedly lower in dwarf mice, yet whole-body metabolism, as measured by indirect calorimetry, is surprisingly higher in Ames dwarf and Ghr-/- mice compared with normal controls. Elevated adiponectin, a key antiinflammatory cytokine, is also very likely to contribute to longevity in these mice. Thus, several important components related to energy metabolism are altered in GH mutant mice, and these differences are likely critical in aging processes and life-span extension.

  9. Ccr2 deletion dissociates cavity size and tau pathology after mild traumatic brain injury.

    Science.gov (United States)

    Gyoneva, Stefka; Kim, Daniel; Katsumoto, Atsuko; Kokiko-Cochran, O Nicole; Lamb, Bruce T; Ransohoff, Richard M

    2015-12-03

    Millions of people experience traumatic brain injury (TBI) as a result of falls, car accidents, sports injury, and blast. TBI has been associated with the development of neurodegenerative conditions such as Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). In the initial hours and days, the pathology of TBI comprises neuronal injury, breakdown of the blood-brain barrier, and inflammation. At the cellular level, the inflammatory reaction consists of responses by brain-resident microglia, astrocytes, and vascular elements as well as infiltration of peripheral cells. After TBI, signaling by chemokine (C-C motif) ligand 2 (CCL2) to the chemokine (C-C motif) receptor 2 (CCR2) is a key regulator of brain infiltration by monocytes. We utilized mice with one or both copies of Ccr2 disrupted by red fluorescent protein (RFP, Ccr2 (RFP/+) and Ccr2 (RFP/RFP) ). We subjected these mice to the mild lateral fluid percussion model of TBI and examined several pathological outcomes 3 days later in order to determine the effects of altered monocyte entry into the brain. Ccr2 deletion reduced monocyte infiltration, diminished lesion cavity volume, and lessened axonal damage after mild TBI, but the microglial reaction to the lesion was not affected. We further examined phosphorylation of the microtubule-associated protein tau, which aggregates in brains of people with TBI, AD, and CTE. Surprisingly, Ccr2 deletion was associated with increased tau mislocalization to the cell body in the cortex and hippocampus by tissue staining and increased levels of phosphorylated tau in the hippocampus by Western blot. Disruption of CCR2 enhanced tau pathology and reduced cavity volume in the context of TBI. The data reveal a complex role for CCR2(+) monocytes in TBI, as monitored by cavity volume, axonal damage, and tau phosphorylation.

  10. Hepatic steatosis in transgenic mice overexpressing human histone deacetylase 1

    International Nuclear Information System (INIS)

    Wang, Ai-Guo; Seo, Sang-Beom; Moon, Hyung-Bae; Shin, Hye-Jun; Kim, Dong Hoon; Kim, Jin-Man; Lee, Tae-Hoon; Kwon, Ho Jeong; Yu, Dae-Yeul; Lee, Dong-Seok

    2005-01-01

    It is generally thought that histone deacetylases (HDACs) play important roles in the transcriptional regulation of genes. However, little information is available concerning the specific functions of individual HDACs in disease states. In this study, two transgenic mice lines were established which harbored the human HDAC1 gene. Overexpressed HDAC1 was detected in the nuclei of transgenic liver cells, and HDAC1 enzymatic activity was significantly higher in the transgenic mice than in control littermates. The HDAC1 transgenic mice exhibited a high incidence of hepatic steatosis and nuclear pleomorphism. Molecular studies showed that HDAC1 may contribute to nuclear pleomorphism through the p53/p21 signaling pathway

  11. Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis

    DEFF Research Database (Denmark)

    Martel, Britta Cathrina; Litman, Thomas; Hald, Andreas

    2016-01-01

    Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared...... with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation-associated genes found among...... patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD....

  12. Farmakologisk behandling af mild ukompliceret hypertension i almen praksis

    DEFF Research Database (Denmark)

    Paulsen, Maja Skov; Christensen, Bo; Søndergaard, Jens

    2013-01-01

    pressure 90-99 mmHg; no diabetes or cardiovascular disease) did not reduce mortality or morbidity. The evidence for pharmacotherapy in patients having mild/uncomplicated hypertension is weak. However, current Danish guidelines have taken this into consideration in their recommendations of pharmacotherapy......Hypertension is an important risk factor for cardiovascular disease. In Denmark, patients with hypertension are primarily managed in primary care. A recent Cochrane review concluded that pharmacotherapy of patients with mild hypertension (systolic blood pressure 140-159 mmHg; diastolic blood...... to patients with mild/uncomplicated hypertension....

  13. Of mice and men

    CERN Multimedia

    1973-01-01

    At the end of March , sixty mice were irradiated at the synchro-cyclotron in the course of an experimental programme studying radiation effects on mice and plants (Vicia faba bean roots) being carried out by the CERN Health Physics Group.

  14. Digital Natives: Creating Emergent Exhibitions through Digital Technologies

    DEFF Research Database (Denmark)

    Smith, Rachel Charlotte; Iversen, Ole Sejer; Dindler, Christian

    2011-01-01

    . In this way, digital technology can contribute to the creation of emergent exhibitions in which the exhibition is created in dialogue between audiences and the museum. We present experiences from a current research project, the Digital Natives exhibition, in which digital technology was designed......Digital Technology can support the creation of dialogical spaces in the museum, both playful and reflective, that allow audiences to engage in the ongoing construction and reproduction of cultural heritage creating novel connections between self and others and between past, present and future...... as an integral part of the exhibition to encourage dialogue between audiences and the exhibition materials and thereby investigate how the exhibition emerge as a result of this dialogic co-construction inside the exhibition space. In short, the opportunities offered by digital technologies prompts us to consider...

  15. A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

    Directory of Open Access Journals (Sweden)

    Mirjam Frischknecht

    Full Text Available We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2. It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA and collagen alpha-2(XI chain gene (COL11A2, respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

  16. A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

    Science.gov (United States)

    Frischknecht, Mirjam; Niehof-Oellers, Helena; Jagannathan, Vidhya; Owczarek-Lipska, Marta; Drögemüller, Cord; Dietschi, Elisabeth; Dolf, Gaudenz; Tellhelm, Bernd; Lang, Johann; Tiira, Katriina; Lohi, Hannes; Leeb, Tosso

    2013-01-01

    We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

  17. Cost-effectiveness of a mild compared with a standard strategy for IVF : a randomized comparison using cumulative term live birth as the primary endpoint

    NARCIS (Netherlands)

    Polinder, S.; Heijnen, E. M. E. W.; Macklon, N. S.; Habbema, J. D. F.; Fauser, B. J. C. M.; Eijkemans, M. J. C.

    Background: Conventional ovarian stimulation and the transfer of two embryos in IVF exhibits an inherent high probability of multiple pregnancies, resulting in high costs. We evaluated the cost-effectiveness of a mild compared with a conventional strategy for IVF. Methods: Four hundred and four

  18. AGEMAP: a gene expression database for aging in mice.

    Directory of Open Access Journals (Sweden)

    Jacob M Zahn

    2007-11-01

    Full Text Available We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project gene expression database, which is a resource that catalogs changes in gene expression as a function of age in mice. The AGEMAP database includes expression changes for 8,932 genes in 16 tissues as a function of age. We found great heterogeneity in the amount of transcriptional changes with age in different tissues. Some tissues displayed large transcriptional differences in old mice, suggesting that these tissues may contribute strongly to organismal decline. Other tissues showed few or no changes in expression with age, indicating strong levels of homeostasis throughout life. Based on the pattern of age-related transcriptional changes, we found that tissues could be classified into one of three aging processes: (1 a pattern common to neural tissues, (2 a pattern for vascular tissues, and (3 a pattern for steroid-responsive tissues. We observed that different tissues age in a coordinated fashion in individual mice, such that certain mice exhibit rapid aging, whereas others exhibit slow aging for multiple tissues. Finally, we compared the transcriptional profiles for aging in mice to those from humans, flies, and worms. We found that genes involved in the electron transport chain show common age regulation in all four species, indicating that these genes may be exceptionally good markers of aging. However, we saw no overall correlation of age regulation between mice and humans, suggesting that aging processes in mice and humans may be fundamentally different.

  19. Time estimation in mild Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Nichelli Paolo

    2009-07-01

    Full Text Available Abstract Background Time information processing relies on memory, which greatly supports the operations of hypothetical internal timekeepers. Scalar Expectancy Theory (SET postulates the existence of a memory component that is functionally separated from an internal clock and other processing stages. SET has devised several experimental procedures to map these cognitive stages onto cerebral regions and neurotransmitter systems. One of these, the time bisection procedure, has provided support for a dissociation between the clock stage, controlled by dopaminergic systems, and the memory stage, mainly supported by cholinergic neuronal networks. This study aimed at linking the specific memory processes predicted by SET to brain mechanisms, by submitting time bisection tasks to patients with probable Alzheimer's disease (AD, that are known to present substantial degeneration of the fronto-temporal regions underpinning memory. Methods Twelve mild AD patients were required to make temporal judgments about intervals either ranging from 100 to 600 ms (short time bisection task or from 1000 to 3000 ms (long time bisection task. Their performance was compared with that of a group of aged-matched control participants and a group of young control subjects. Results Long time bisection scores of AD patients were not significantly different from those of the two control groups. In contrast, AD patients showed increased variability (as indexed by increased WR values in timing millisecond durations and a generalized inconsistency of responses over the same interval in both the short and long bisection tasks. A similar, though milder, decreased millisecond interval sensitivity was found for elderly subjects. Conclusion The present results, that are consistent with those of previous timing studies in AD, are interpreted within the SET framework as not selectively dependent on working or reference memory disruptions but as possibly due to distortions in different

  20. Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Mariko Umemura

    2017-07-01

    Full Text Available Activating transcription factor 5 (ATF5 is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/- mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders.

  1. The MICE Online Systems

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    The Muon Ionization Cooling Experiment (MICE) is designed to test transverse cooling of a muon beam, demonstrating an important step along the path toward creating future high intensity muon beam facilities. Protons in the ISIS synchrotron impact a titanium target, producing pions which decay into muons that propagate through the beam line to the MICE cooling channel. Along the beam line, particle identification (PID) detectors, scintillating fiber tracking detectors, and beam diagnostic tools identify and measure individual muons moving through the cooling channel. The MICE Online Systems encompass all tools; including hardware, software, and documentation, within the MLCR (MICE Local Control Room) that allow the experiment to efficiently record high quality data. Controls and Monitoring (C&M), Data Acquisition (DAQ), Online Monitoring and Reconstruction, Data Transfer, and Networking all fall under the Online Systems umbrella. C&M controls all MICE systems including the target, conventional an...

  2. Traumatic brain injury precipitates cognitive impairment and extracellular Aβ aggregation in Alzheimer's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Naoki Tajiri

    Full Text Available 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 (Aβ-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 Aβ 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 Aβ 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 Aβ deposition in the brain.

  3. Increased Cortical Gamma-Aminobutyric Acid Precedes Incomplete Extinction of Conditioned Fear and Increased Hippocampal Excitatory Tone in a Mouse Model of Mild Traumatic Brain Injury.

    Science.gov (United States)

    Schneider, Brandy L; Ghoddoussi, Farhad; Charlton, Jennifer L; Kohler, Robert J; Galloway, Matthew P; Perrine, Shane A; Conti, Alana C

    2016-09-01

    Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and functional changes in brain regions mediating fear learning, including prefrontal cortex (PFC), amygdala (AMYG), and hippocampus (HC). These changes may reflect loss of top-down control by which PFC normally exhibits inhibitory influence over AMYG reactivity to fearful stimuli, with HC contribution. Considering the susceptibility of these regions to injury, we examined fear conditioning (FC) in the delayed post-injury period, using a mouse model of mTBI. Mice with mTBI displayed enhanced acquisition and delayed extinction of FC. Using proton magnetic resonance spectroscopy ex vivo, we examined PFC, AMYG, and HC levels of gamma-aminobutyric acid (GABA) and glutamate as surrogate measures of inhibitory and excitatory neurotransmission, respectively. Eight days post-injury, GABA was increased in PFC, with no significant changes in AMYG. In animals receiving FC and mTBI, glutamate trended toward an increase and the GABA/glutamate ratio decreased in ventral HC at 25 days post-injury, whereas GABA decreased and GABA/glutamate decreased in dorsal HC. These neurochemical changes are consistent with early TBI-induced PFC hypoactivation facilitating the fear learning circuit and exacerbating behavioral fear responses. The latent emergence of overall increased excitatory tone in the HC, despite distinct plasticity in dorsal and ventral HC fields, may be associated with disordered memory function, manifested as incomplete extinction and enhanced FC recall.

  4. Biomass, virus concentration, and symptomatology of cucurbits infected by mild and severe strains of Papaya ringspot virus

    Directory of Open Access Journals (Sweden)

    Pacheco Davi Andrade

    2003-01-01

    Full Text Available Pre-immunization with mild strains of Papaya ringspot virus - type W (PRWV-W has allowed the mosaic disease to be controlled in different cucurbit species, with increases in marketable fruit yield. The objective of this study was to compare virus concentration, biomass and symptomatology of 'Caserta' zucchini squash, 'Menina Brasileira' long-neck squash and 'Crimson Sweet' watermelon plants infected by three mild strains and one severe strain of PRSV-W. Plants were inoculated at the cotyledonary stage, under greenhouse conditions, sampled at 7, 14, 21, 28 and 35 days after inoculation (DAI, and analyzed by PTA-ELISA. The severity of the symptoms was scored according to a scale from 1 to 5, and the fresh and dry biomass of the aerial part of the plants were evaluated at 40 DAI. Concentrations of the mild strains, based on absorbance values of the PTA-ELISA, were lower than the concentration of the severe strain for all species. The mild strains did not cause mosaic in infected plants of all species. Plants of zucchini squash and watermelon infected by the severe strain exhibited severe mosaic symptoms, but the same was not noticed for infected long-neck squash plants. Biomass values from zucchini squash and watermelon plants infected by the mild strains were 1.7 % to 12.4 % lower as compared to healthy plants. Biomass values of zucchini squash and watermelon plants infected by the severe strain presented greater reduction, varying from 29 % to 74 %. However, biomass values of long-neck squash plants infected by the mild and severe strains were similar for all treatments.

  5. Cognitive Profile of Elderly Patients with Mild Stroke

    Directory of Open Access Journals (Sweden)

    Arne Gramstad

    2011-11-01

    Full Text Available Background: A pattern characterizing cognitive deficits in mild stroke could help in differential diagnosis and rehabilitation planning. Methods: Fifty patients with mild stroke (modified Rankin scale ≤2 at discharge aged >60 years were given the Mini Mental State Examination (MMSE, the Hopkins Verbal Learning Test-Revised (HVLT-R and the Stroop test. Results: On HVLT-R, significant impairments were found in learning and recall, but not in delayed recall. The Stroop test revealed significant impairments in reading speed, but not in color-word interference. Using the MMSE, significant deficits were only found in the youngest age group. Conclusion: Elderly patients with mild stroke show deficits in verbal learning/recall and in reading speed, but not in the MMSE, delayed recall or color-word interference. The deficits are consistent with a mild-to-moderate brain dysfunction, with relative sparing of medial brain structures.

  6. Development of mild steel exposure chart for neutron radiography application

    International Nuclear Information System (INIS)

    Hafizal Yazid; Rafhayudi Jamro; Hishamuddin Husain; Muhammad Rawi Mohd Zin; Razali Kassim; Abd Aziz Mohamed; Azali Muhammad

    2004-01-01

    A neutron radiography exposure chart for mild steel was developed to facilitate the determination of exposure time when producing neutron radiographs for any given mild steel thickness. A mild steel sample in the form of step wedge (1-10 mm thick) was exposed to thermal neutron using Direct technique. This technique involves exposing x-ray film-Gadolinium converter housed in one film cassette simultaneously to thermal neutron beam. Gadolinium converters with thickness of 0.025 mm and 0.5 mm were used to observe the effect of converter thickness on radiographic density and exposure time. Collected radiographic density data is then calculated based on manufacturer's film characteristic chart and finally exposure chart for mild steel was plotted. This chart could later be used as a guide for estimating exposure time for any given sample thickness providing other conditions are similar (material, film processing, neutron flux, film density and converter thickness). (Author)

  7. ALMOST AUTOMORPHIC MILD SOLUTIONS TO SOME FRACTIONAL DELAY DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    In this paper,a new and general existence and uniqueness theorem of almost automorphic mild solutions is obtained for some fractional delay differential equations,using sectorial operators and the Banach contraction principle.

  8. Reflections on "Multisensory Mathematics for Children with Mild Disabilities."

    Science.gov (United States)

    Scott, Kristin S.

    1993-01-01

    The author of EC 606 784 describes the background of her research, noting her experience with the "TOUCH MATH" manipulative materials to help students with mild disabilities acquire math facts and computational skills. (DB)

  9. Recent neuroimaging techniques in mild traumatic brain injury.

    Science.gov (United States)

    Belanger, Heather G; Vanderploeg, Rodney D; Curtiss, Glenn; Warden, Deborah L

    2007-01-01

    Mild traumatic brain injury (TBI) is characterized by acute physiological changes that result in at least some acute cognitive difficulties and typically resolve by 3 months postinjury. Because the majority of mild TBI patients have normal structural magnetic resonance imaging (MRI)/computed tomography (CT) scans, there is increasing attention directed at finding objective physiological correlates of persistent cognitive and neuropsychiatric symptoms through experimental neuroimaging techniques. The authors review studies utilizing these techniques in patients with mild TBI; these techniques may provide more sensitive assessment of structural and functional abnormalities following mild TBI. Particular promise is evident with fMRI, PET, and SPECT scanning, as demonstrated by associations between brain activation and clinical outcomes.

  10. Preliminary questions before studying mild traumatic brain injury outcome.

    Science.gov (United States)

    Fayol, P; Carrière, H; Habonimana, D; Dumond, J-J

    2009-07-01

    To point out from the literature the issues in mild traumatic brain injury outcome. METHODOLOGY-RESULTS: The literature review allows to point out several different factors involved in the difficulty to study mild traumatic brain injury: mild traumatic brain injury definition, postconcussional syndrome definition, diagnosis threshold, severity and functional symptoms outcome, neuropsychological tests, unspecific syndrome feature, individual factors, confounding factors and treatment interventions. The mild traumatic brain injury outcome study is complicated by the definitions issues and especially their practical use and by the multiplicity and the intricate interrelationships among involved factors. The individual outcome and social cost weight is widely emphasized for an event still considered as medically trivial. The well-ordered preventive interventions necessity and the targeted treatment programs need for the persisting postconcussive symptoms complete our critical review.

  11. Simulation of MILD combustion using Perfectly Stirred Reactor model

    KAUST Repository

    Chen, Z.; Vanteru, Mahendra Reddy; Ruan, S.; Doan, N. A K; Roberts, William L.; Swaminathan, N.

    2016-01-01

    A simple model based on a Perfectly Stirred Reactor (PSR) is proposed for moderate or intense low-oxygen dilution (MILD) combustion. The PSR calculation is performed covering the entire flammability range and the tabulated chemistry approach is used

  12. Perioperative corticosteroids for intermittent and mild persistent asthma

    OpenAIRE

    Hiroto Matsuse; Terufumi Shimoda; Ikuko Machida; Yuki Kondo; Tetsuya Kawano; Sachiko Saeki; Shinya Tomari; Kazuko Mitsuta; Chizu Fukushima; Yasushi Obase; Shigeru Kohno

    2002-01-01

    Objectives: Asthmatics are considered to be at high risk for pulmonary complications during general anesthesia with tracheal intubation. The purpose of the present study was to determine the usefulness of perioperative corticosteroids for mild asthmatics in preventing perioperative exacerbation of asthma. Methods: Airway hyperresponsiveness to inhaled methacholine was determined in patients with intermittent (n = 27) and mild persistent (n = 48) asthma before general anesthesia who underwe...

  13. Ventilatory sensitivity to mild asphyxia: prone versus supine sleep position

    OpenAIRE

    Galland, B; Bolton, D; Taylor, B; Sayers, R; Williams, S

    2000-01-01

    AIMS—To compare the effects of prone and supine sleep position on the main physiological responses to mild asphyxia: increase in ventilation and arousal.
METHODS—Ventilatory and arousal responses to mild asphyxia (hypercapnia/hypoxia) were measured in 53 healthy infants at newborn and 3 months of age, during quiet sleep (QS) and active sleep (AS), and in supine and prone sleep positions. The asphyxial test mimicked face down rebreathing by slowly altering the inspired air: C...

  14. Sinalbin degradation products in mild yellow mustard paste

    OpenAIRE

    Paunović, Dragana; Šolević-Knudsen, Tatjana; Krivokapić, Mirjana; Zlatković, Branislav; Antić, Mališa

    2012-01-01

    Sinalbin degradation products in mild yellow mustard paste were investigated. The analyzed material consisted of a mild yellow mustard paste condiment and ground white mustard seeds which were originally used in the mustard paste production process. The samples were extracted in a Soxhlet extraction system and analyzed by gas chromatography - mass spectrometry (GC-MS) technique. The only sinalbin degradation product in ground mustard seeds was 2-(4-hydroxyphenyl)acetonitrile. The most a...

  15. Human thrombomodulin knock-in mice reveal differential effects of human thrombomodulin on thrombosis and atherosclerosis.

    Science.gov (United States)

    Raife, Thomas J; Dwyre, Denis M; Stevens, Jeff W; Erger, Rochelle A; Leo, Lorie; Wilson, Katina M; Fernández, Jose A; Wilder, Jennifer; Kim, Hyung-Suk; Griffin, John H; Maeda, Nobuyo; Lentz, Steven R

    2011-11-01

    We sought to develop a murine model to examine the antithrombotic and antiinflammatory functions of human thrombomodulin in vivo. Knock-in mice that express human thrombomodulin from the murine thrombomodulin gene locus were generated. Compared with wild-type mice, human thrombomodulin knock-in mice exhibited decreased protein C activation in the aorta (Pknock-in mice compared with wild-type mice (Pknock-in mice (12±3 minutes) than in wild-type mice (31±6 minutes; Pknock-in and wild-type mice after injection of endotoxin. When crossed with apolipoprotein E-deficient mice and fed a Western diet, knock-in mice had a further decrease in protein C activation but did not exhibit increased atherosclerosis. Expression of human thrombomodulin in place of murine thrombomodulin produces viable mice with a prothrombotic phenotype but unaltered responses to systemic inflammatory or atherogenic stimuli. This humanized animal model will be useful for investigating the function of human thrombomodulin under pathophysiological conditions in vivo.

  16. Updating the mild encephalitis hypothesis of schizophrenia.

    Science.gov (United States)

    Bechter, K

    2013-04-05

    Schizophrenia seems to be a heterogeneous disorder. Emerging evidence indicates that low level neuroinflammation (LLNI) may not occur infrequently. Many infectious agents with low overall pathogenicity are risk factors for psychoses including schizophrenia and for autoimmune disorders. According to the mild encephalitis (ME) hypothesis, LLNI represents the core pathogenetic mechanism in a schizophrenia subgroup that has syndromal overlap with other psychiatric disorders. ME may be triggered by infections, autoimmunity, toxicity, or trauma. A 'late hit' and gene-environment interaction are required to explain major findings about schizophrenia, and both aspects would be consistent with the ME hypothesis. Schizophrenia risk genes stay rather constant within populations despite a resulting low number of progeny; this may result from advantages associated with risk genes, e.g., an improved immune response, which may act protectively within changing environments, although they are associated with the disadvantage of increased susceptibility to psychotic disorders. Specific schizophrenic symptoms may arise with instances of LLNI when certain brain functional systems are involved, in addition to being shaped by pre-existing liability factors. Prodrome phase and the transition to a diseased status may be related to LLNI processes emerging and varying over time. The variability in the course of schizophrenia resembles the varying courses of autoimmune disorders, which result from three required factors: genes, the environment, and the immune system. Preliminary criteria for subgrouping neurodevelopmental, genetic, ME, and other types of schizophrenias are provided. A rare example of ME schizophrenia may be observed in Borna disease virus infection. Neurodevelopmental schizophrenia due to early infections has been estimated by others to explain approximately 30% of cases, but the underlying pathomechanisms of transition to disease remain in question. LLNI (e.g. from

  17. CERN exhibition attracts over 100,000 visitors in Belgrade

    CERN Multimedia

    Antonella Del Rosso

    2012-01-01

    “This must be an 'all-time record',” says Ray Lewis, CERN travelling exhibition manager. “In all my time with the various permanent and travelling exhibitions that have taken place locally and within our Member States I have never experienced such figures.”   Zarko Obradovic (left), Serbian Minister of Education, Science and Technology, and Rolf Heuer (right), CERN Director-General, at the CERN travelling exhibition in Belgrade. Indeed, in approximately 20 days of exhibition time about 120,000 people, mainly school visiters and the general public, visited the 100 m2 CERN mini-exhibition. It was set up in the centre of Belgrade in October, in association with the meeting of the Restricted European Committee for Future Accelerators (RECFA). After attending the RECFA meeting, CERN's Director-General Rofl Heuer opened the CERN exhibition on the evening of 19 October. Lectures about CERN were held every afternoon, and two public de...

  18. Maintaining students’ Speaking Fluency through Exhibition Examination in Sociolinguistic Studies

    Directory of Open Access Journals (Sweden)

    Khusnul Qhotimah Yuliatuty

    2013-07-01

    Full Text Available Using exhibition for the final project in Sociolinguistic study is really interesting for Universitas Siswa Bangsa Internasional students, especially for 2011 English Department students. Exhibition becomes interesting because this is the new thing to conduct the final project for English Department students’ cohort 2011 at Universitas Siswa Bangsa Internasional. The lecturer divides the students into pairs and each pairs should master one content or topic in Sociolinguistic study.  The students will do the exhibition about the topic that they get in a pairs. The lecturer also gives the students rubric sheet to fill by the visitors. The exhibition will make the students prepare themselves well because they will face many questions about the content which will be delivered by them. Beside, this exhibition also maintains students’ fluency in speaking English because they will explain and answer the questions from visitors with English. This paper tries to focus on how exhibition examination can maintain students’ fluency in speaking English.

  19. The Eugenides Foundation Interactive Exhibition of Science and Technology

    Science.gov (United States)

    Kontogiannis, Ioannis

    2010-01-01

    The Interactive Exhibition of Science and Technology is installed in an area of 1200 m2 at the Eugenides Foundation. 65 interactive exhibits, designed by the "Cites des Science et de l' Industrie" are organised in themes, stimulate the visitors' mind and provoke scientific thinking. Parallel activities take place inside the exhibition, such as live science demonstrations, performed by young scientists. Extra material such as news bulletins (short news, science comics and portraits), educational paths and treasure-hunting based games, all available online as well, are prepared on a monthly basis and provided along with the visit to the exhibition. Through these exhibits and activities, scientific facts are made simple and easy to comprehend using modern presentation tools. We present details on how this exhibition acts complementary to the science education provided by schools, making it a highly sophisticated educational tool.

  20. Students-exhibits interaction at a science center

    Science.gov (United States)

    Botelho, Agostinho; Morais, Ana M.

    2006-12-01

    In this study we investigate students' learning during their interaction with two exhibits at a science center. Specifically, we analyze both students' procedures when interacting with exhibits and their understanding of the scientific concepts presented therein. Bernstein's theory of pedagogic discourse (1990, 2000) provided the sociological foundation to assess the exhibit-student interaction and allowed analysis of the influence of the characteristics of students, exhibits, and interactions on students' learning. Eight students (ages 12ndash;13 years of age) with distinct sociological characteristics participated in the study. Several findings emerged from the results. First, the characteristics of the students, exhibits, and interactions appeared to influence student learning. Second, to most students, what they did interactively (procedures) seems not to have had any direct consequence on what they learned (concept understanding). Third, the data analysis suggest an important role for designers and teachers in overcoming the limitations of exhibit-student interaction.

  1. A REVIEW OF MILD COMBUSTION AND OPEN FURNACE DESIGN CONSIDERATION

    Directory of Open Access Journals (Sweden)

    M.M. Noor

    2012-12-01

    Full Text Available Combustion is still very important to generate energy. Moderate or Intense Low-oxygen Dilution (MILD combustion is one of the best new technologies for clean and efficient combustion. MILD combustion has been proven to be a promising combustion technology in industrial applications with decreased energy consumption due to the uniformity of its temperature distribution. It is clean compared to traditional combustion due to producing low NOx and CO emissions. This article provides a review and discussion of recent research and developments in MILD. The issue and applications are summarized, with some suggestions presented on the upgrading and application of MILD in the future. Currently MILD combustion has been successfully applied in closed furnaces. The preheating of supply air is no longer required since the recirculation inside the enclosed furnace already self-preheats the supply air and self-dilutes the oxygen in the combustion chamber. The possibility of using open furnace MILD combustion will be reviewed. The design consideration for open furnace with exhaust gas re-circulation (EGR was discussed.

  2. Detection of Mild Emphysema by Computed Tomography Density Measurements

    International Nuclear Information System (INIS)

    Vikgren, J.; Friman, O.; Borga, M.; Boijsen, M.; Gustavsson, S.; Bake, B.; Tylen, U.; Ekberg-Jansson, A.

    2005-01-01

    Purpose: To assess the ability of a conventional density mask method to detect mild emphysema by high-resolution computed tomography (HRCT); to analyze factors influencing quantification of mild emphysema; and to validate a new algorithm for detection of mild emphysema. Material and Methods: Fifty-five healthy male smokers and 34 never-smokers, 61-62 years of age, were examined. Emphysema was evaluated visually, by the conventional density mask method, and by a new algorithm compensating for the effects of gravity and artifacts due to motion and the reconstruction algorithm. Effects of the reconstruction algorithm, slice thickness, and various threshold levels on the outcome of the density mask area were evaluated. Results: Forty-nine percent of the smokers had mild emphysema. The density mask area was higher the thinner the slice irrespective of the reconstruction algorithm and threshold level. The sharp algorithm resulted in increased density mask area. The new reconstruction algorithm could discriminate between smokers with and those without mild emphysema, whereas the density mask method could not. The diagnostic ability of the new algorithm was dependent on lung level. At about 90% specificity, sensitivity was 65-100% in the apical levels, but low in the rest of the lung. Conclusion: The conventional density mask method is inadequate for detecting mild emphysema, while the new algorithm improves the diagnostic ability but is nevertheless still imperfect

  3. Development of Zn50 Brazing Alloy for Joining Mild Steel to Mild Steel (SAE1018

    Directory of Open Access Journals (Sweden)

    S.C. Nwigbo

    2014-09-01

    Full Text Available This work has developed new brazing alloys for joining mild steel to mild steel (SAE1018 at a lower temperature. The alloys blends and error analysis were done by experimental design software (Design Expert 8.0.7.1. Design of experiments was done by Scheffe quadratic mixture method. The liquidus temperatures were predicted by calculation of phase diagrams of the alloying metals. The brazing alloys were produced by gravity technique and melted using silicon carbide graphite crucible. The quality of the brazing alloys was analyzed by optical microscopy (OM, atomic absorption spectroscopy (AAS and fourier transform infrared spectroscopy (FT-IR. Brazed joints were produced by torch method with a commercial flux. Brazing temperatures (liquidus were tracked by a digital infrared/laser pyrometer. Some mechanical properties studied were tensile strength and hardness. Finally, brazed joints produced from the developed brazing alloys were compared to that produced from muntz brass. Six (6 brazing alloys were successfully developed. Zinc and manganese were the main components, to which were added; 3 to 4 %wt silver and 11 to15 %wt modifying element. The microstructure showed a typical eutectic structure with zinc-rich phase distributed uniformly in the matrix with a combination of different sizes of dendrite, rounded blocks of compounds and hypoeutectic structures. AAS results indicated minimal out-gassing of zinc and FT-IR results indicated very low presence of atmospheric gas. The range of brazing temperature for best results was recorded from 690.90 to 735.10 0C. The joints produced from the developed brazing alloys had acceptable strengths with improved stress-strain behaviour compared to muntz brass.

  4. Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

    Directory of Open Access Journals (Sweden)

    Yun Seong-Jo

    2012-01-01

    Full Text Available Abstract Background Dimeric human erythropoietin (dHuEPO peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg mice expressing dHuEPO and to investigate the characteristics of these mice. Methods A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile, was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice. Results A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47 of tg mice expressing the dHuEPO gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11. We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764. Reverse transcriptase-polymerase chain reaction (RT-PCR and quantitative real-time PCR (qRT-PCR were used for validating the results of the microarray

  5. Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress.

    Science.gov (United States)

    Song, Li; Che, Wang; Min-Wei, Wang; Murakami, Yukihisa; Matsumoto, Kinzo

    2006-02-01

    Increasing evidences indicate the concurrence and interrelationship of depression and cognitive impairments. The present study was undertaken to investigate the effects of two depressive animal models, learned helplessness (LH) and chronic mild stress (CMS), on the cognitive functions of mice in the Morris water maze task. Our results demonstrated that both LH and CMS significantly decreased the cognitive performance of stressed mice in the water maze task. The escaping latency to the platform was prolonged and the probe test percentage in the platform quadrant was reduced. These two models also increased the plasma corticosterone concentration and decreased the brain derived neurotrophic factor (BDNF) and cAMP-response element-biding protein (CREB) messenger ribonucleic acid (mRNA) levels in hippocampus, which might cause the spatial cognition deficits. Repeated treatment with antidepressant drugs, imipramine (Imi) and fluoxetine (Flu), significantly reduced the plasma corticosterone concentration and enhanced the BDNF and CREB levels. Furthermore, antidepressant treated animals showed an ameliorated cognitive performance compared with the vehicle treated stressed animals. These data suggest that both LH and CMS impair the spatial cognitive function and repeated treatment with antidepressant drugs decreases the prevalence of cognitive impairments induced by these two animal models. Those might in part be attributed to the reduced plasma corticosterone and enhanced hippocampal BDNF and CREB expressions. This study provided a better understanding of molecular mechanisms underlying interactions of depression and cognitive impairments, although animal models used in this study can mimic only some aspects of depression or cognition of human.

  6. A new disease? Persistent isolated beta.hydroxybutyrate ketosis and mild congenital hyperinsulinism

    DEFF Research Database (Denmark)

    Christesen, Henrik Thybo; Brusgaard, Klaus; Ditkovskaya, L

    A new disease? Persistent isolated beta.hydroxybutyrate ketosis and mild congenital hyperinsulinism.......A new disease? Persistent isolated beta.hydroxybutyrate ketosis and mild congenital hyperinsulinism....

  7. Creating National Narrative: The Red Guard Art Exhibitions and the National Exhibitions in the Chinese Cultural Revolution 1966 - 1976

    Directory of Open Access Journals (Sweden)

    Winnie Tsang

    2014-06-01

    Full Text Available The artistic development in China experienced drastic changes during the Cultural Revolution from 1966 to 1976. Traditional Chinese art was denounced, whereas propaganda art became predominant in shaping the public’s loyalty towards the Communist Party and the country. Two major groups of art exhibitions emerged during the Revolution—the unofficial Red Guard art exhibitions organized by student activists in collaboration with local communes and art schools between 1966 and 1968, and the state-run national exhibitions from 1972 to 1975. These exhibitions were significant to this period because they were held frequently in the capital city Beijing and occasionally elsewhere, and through art they presented unique revolutionary beliefs to the Chinese people in a public setting. While the Red Guard art exhibitions and the national exhibitions certainly created different national narratives, I argue that the national exhibitions were in fact an attempt to revise the national narrative created by the Red Guard art exhibitions in order to re-establish a more utopian, consistent, and official national narrative. This paper unravels the intricate relationship between the two groups of exhibitions by comparing their exhibition venues, ideological focuses, work selection and quality editing. 

  8. Preference for and discrimination of paintings by mice.

    Directory of Open Access Journals (Sweden)

    Shigeru Watanabe

    Full Text Available I measured preference for paintings (Renoir vs. Picasso or Kandinsky vs. Mondrian in mice. In general mice did not display a painting preference except for two mice: one preferred Renoir to Picasso, and the other preferred Kandinsky to Mondrian. Thereafter, I examined discrimination of paintings with new mice. When exposure to paintings of one artist was associated with an injection of morphine (3.0 mg/kg, mice displayed conditioned preference for those paintings, showing discrimination of paintings by Renoir from those by Picasso, and paintings by Kandinsky from those by Mondrian after the conditioning. They also exhibited generalization of the preference to novel paintings of the artists. After conditioning with morphine for a set of paintings consisting of two artists, mice showed discrimination between two sets of paintings also from the two artists but not in association with morphine. These results suggest that mice can discriminate not only between an artist's style but also among paintings of the same artist. When mice were trained to discriminate a pair of paintings by Kandinsky and Renoir in an operant chamber equipped with a touch screen, they showed transfer of the discrimination to new pairs of the artists, but did not show transfer of discrimination of paintings by other artists, suggesting generalization.

  9. Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice.

    Science.gov (United States)

    Pan, Qiong; Sun, Yiming; Jin, Qili; Li, Qixiang; Wang, Qing; Liu, Hao; Zhao, Surong

    2016-11-01

    To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice. Fifteen nude mice were grafted subcutaneously in the left flank with MDA-MB-231 cells, then all mice were divided into control group (PBS), 3BP group (8 mg/kg), positive group (DNR: 0.8 mg/kg) when tumor volume reached approximately 100 mm3. 28 days later, tumors, livers and kidneys were stored in 4 % formalin solution and stained with hematoxylin and eosin staining. The Kunming mice experiment included control group (PBS), 3BP group (4mg/kg; 8mg/kg; 16mg/kg), positive group (DNR: 0.8 mg/kg). 24 hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection. 3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues. 3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.

  10. Masking responses to light in period mutant mice.

    Science.gov (United States)

    Pendergast, Julie S; Yamazaki, Shin

    2011-10-01

    Masking is an acute effect of an external signal on an overt rhythm and is distinct from the process of entrainment. In the current study, we investigated the phase dependence and molecular mechanisms regulating masking effects of light pulses on spontaneous locomotor activity in mice. The circadian genes, Period1 (Per1) and Per2, are necessary components of the timekeeping machinery and entrainment by light appears to involve the induction of the expression of Per1 and Per2 mRNAs in the suprachiasmatic nuclei (SCN). We assessed the roles of the Per genes in regulating masking by assessing the effects of light pulses on nocturnal locomotor activity in C57BL/6J Per mutant mice. We found that Per1(-/-) and Per2(-/-) mice had robust negative masking responses to light. In addition, the locomotor activity of Per1(-/-)/Per2(-/-) mice appeared to be rhythmic in the light-dark (LD) cycle, and the phase of activity onset was advanced (but varied among individual mice) relative to lights off. This rhythm persisted for 1 to 2 days in constant darkness in some Per1(-/-)/Per2(-/-) mice. Furthermore, Per1(-/-)/Per2(-/-) mice exhibited robust negative masking responses to light. Negative masking was phase dependent in wild-type mice such that maximal suppression was induced by light pulses at zeitgeber time 14 (ZT14) and gradually weaker suppression occurred during light pulses at ZT16 and ZT18. By measuring the phase shifts induced by the masking protocol (light pulses were administered to mice maintained in the LD cycle), we found that the phase responsiveness of Per mutant mice was altered compared to wild-types. Together, our data suggest that negative masking responses to light are robust in Per mutant mice and that the Per1(-/-)/Per2(-/-) SCN may be a light-driven, weak/damping oscillator.

  11. Regional analysis of the magnetization transfer ratio of the brain in mild Alzheimer disease and amnestic mild cognitive impairment.

    Science.gov (United States)

    Mascalchi, M; Ginestroni, A; Bessi, V; Toschi, N; Padiglioni, S; Ciulli, S; Tessa, C; Giannelli, M; Bracco, L; Diciotti, S

    2013-01-01

    Manually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment. Twenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs. Voxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine-based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio-related features, especially between patients with Alzheimer disease versus healthy subjects. Bilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the

  12. Gait, dual task and history of falls in elderly with preserved cognition, mild cognitive impairment, and mild Alzheimer's disease

    OpenAIRE

    Ansai, Juliana H.; Andrade, Larissa P.; Rossi, Paulo G.; Takahashi, Anielle C.M.; Vale, Francisco A.C.; Rebelatto, Jos? R.

    2017-01-01

    Background Studies with functional and applicable methods and new cognitive demands involving executive function are needed to improve screening, prevention and rehabilitation of cognitive impairment and falls. Objective to identify differences in gait, dual task performances, and history of falls between elderly people with preserved cognition, mild cognitive impairment and mild Alzheimer's disease. Method A cross-sectional study was conducted. The sample consisted of 40 community-dwelling o...

  13. Hepatic changes in metabolic gene expression in old ghrelin and ghrelin receptor knockout mice

    Science.gov (United States)

    Ghrelin knockout (GKO) and ghrelin receptor (growth hormone secretagogue receptor) knockout (GHSRKO) mice exhibit enhanced insulin sensitivity, but the mechanism is unclear. Insulin sensitivity declines with age and is inversely associated with accumulation of lipid in liver, a key glucoregulatory ...

  14. Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

    Science.gov (United States)

    Liang, Zhe; Xie, Yan; Dominguez, Jessica A; Breed, Elise R; Yoseph, Benyam P; Burd, Eileen M; Farris, Alton B; Davidson, Nicholas O; Coopersmith, Craig M

    2014-01-01

    Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO) exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week) Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis. Aged (20-24 months) Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival. In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005). Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice. Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

  15. Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

    Directory of Open Access Journals (Sweden)

    Zhe Liang

    Full Text Available Mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO exhibit a complete block in chylomicron assembly together with lipid malabsorption. Young (8-10 week Mttp-IKO mice have improved survival when subjected to a murine model of Pseudomonas aeruginosa-induced sepsis. However, 80% of deaths in sepsis occur in patients over age 65. The purpose of this study was to determine whether age impacts outcome in Mttp-IKO mice subjected to sepsis.Aged (20-24 months Mttp-IKO mice and WT mice underwent intratracheal injection with P. aeruginosa. Mice were either sacrificed 24 hours post-operatively for mechanistic studies or followed seven days for survival.In contrast to young septic Mttp-IKO mice, aged septic Mttp-IKO mice had a significantly higher mortality than aged septic WT mice (80% vs. 39%, p = 0.005. Aged septic Mttp-IKO mice exhibited increased gut epithelial apoptosis, increased jejunal Bax/Bcl-2 and Bax/Bcl-XL ratios yet simultaneously demonstrated increased crypt proliferation and villus length. Aged septic Mttp-IKO mice also manifested increased pulmonary myeloperoxidase levels, suggesting increased neutrophil infiltration, as well as decreased systemic TNFα compared to aged septic WT mice.Blocking intestinal chylomicron secretion alters mortality following sepsis in an age-dependent manner. Increases in gut apoptosis and pulmonary neutrophil infiltration, and decreased systemic TNFα represent potential mechanisms for why intestine-specific Mttp deletion is beneficial in young septic mice but harmful in aged mice as each of these parameters are altered differently in young and aged septic WT and Mttp-IKO mice.

  16. Effect of coating mild steel with CNTs on its mechanical properties and corrosion behaviour in acidic medium

    Science.gov (United States)

    Abdulmalik Abdulrahaman, Mahmud; Kamaldeeen Abubakre, Oladiran; Ambali Abdulkareem, Saka; Oladejo Tijani, Jimoh; Aliyu, Ahmed; Afolabi, Ayo Samuel

    2017-03-01

    The study investigated the mechanical properties and corrosion behaviour of mild steel coated with carbon nanotubes at different coating conditions. Multi-walled carbon nanotubes (MWCNTs) were synthesized via the conventional chemical vapour deposition reaction using bimetallic Fe-Ni catalyst supported on kaolin, with acetylene gas as a carbon source. The HRSEM/HRTEM analysis of the purified carbon materials revealed significant reduction in the diameters of the purified MWCNT bundles from 50 nm to 2 nm and was attributed to the ultrasonication assisted dispersion with surfactant (gum arabic) employed in purification process. The network of the dispersed MWCNTs was coated onto the surfaces of mild steel samples, and as the coating temperature and holding time increased, the coating thickness reduced. The mechanical properties (tensile strength, yield strength, hardness value) of the coated steel samples increased with increase in coating temperature and holding time. Comparing the different coating conditions, coated mild steels at the temperature of 950 °C for 90 min holding time exhibited high hardness, yield strength and tensile strength values compared to others. The corrosion current and corrosion rate of the coated mild steel samples decreased with increase in holding time and coating temperature. The lowest corrosion rate was observed on sample coated at 950 °C for 90 min.

  17. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    Science.gov (United States)

    Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

    2017-09-01

    Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

  18. Impaired bone formation in Pdia3 deficient mice.

    Directory of Open Access Journals (Sweden)

    Yun Wang

    Full Text Available 1α,25-Dihydroxyvitamin D3 [1α,25(OH2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3 mediates 1α,25(OH2D3 initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/- heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality. Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis of the tibias. In comparison to wild type mice, Pdia3 heterozygous mice displayed expanded growth plates associated with decreased tether formation. Histomorphometry also showed that the hypertrophic zone in Pdia3+/- mice was more cellular than seen in wild type growth plates. Metaphyseal trabecular bone in Pdia3+/- mice exhibited an age-dependent phenotype with lower BV/TV and trabecular numbers, which was most pronounced at 15 weeks of age. Bone marrow cells from Pdia3+/- mice exhibited impaired osteoblastic differentiation, based on reduced expression of osteoblast markers and mineral deposition compared to cells from wild type animals. Collectively, our findings provide in vivo evidence that PDIA3 is essential for normal skeletal development. The fact that the Pdia3+/- heterozygous mice share a similar growth plate and bone phenotype to nVdr knockout mice, suggests that PDIA3-mediated rapid membrane signaling might be an alternative mechanism responsible for 1α,25(OH2D3's actions in regulating skeletal development.

  19. Synthesis of ultrasmall Li-Mn spinel oxides exhibiting unusual ion exchange, electrochemical, and catalytic properties

    Science.gov (United States)

    Miyamoto, Yumi; Kuroda, Yoshiyuki; Uematsu, Tsubasa; Oshikawa, Hiroyuki; Shibata, Naoya; Ikuhara, Yuichi; Suzuki, Kosuke; Hibino, Mitsuhiro; Yamaguchi, Kazuya; Mizuno, Noritaka

    2015-10-01

    The efficient surface reaction and rapid ion diffusion of nanocrystalline metal oxides have prompted considerable research interest for the development of high functional materials. Herein, we present a novel low-temperature method to synthesize ultrasmall nanocrystalline spinel oxides by controlling the hydration of coexisting metal cations in an organic solvent. This method selectively led to Li-Mn spinel oxides by tuning the hydration of Li+ ions under mild reaction conditions (i.e., low temperature and short reaction time). These particles exhibited an ultrasmall crystallite size of 2.3 nm and a large specific surface area of 371 ± 15 m2 g-1. They exhibited unique properties such as unusual topotactic Li+/H+ ion exchange, high-rate discharge ability, and high catalytic performance for several aerobic oxidation reactions, by creating surface phenomena throughout the particles. These properties differed significantly from those of Li-Mn spinel oxides obtained by conventional solid-state methods.

  20. Synthesis of ultrasmall Li–Mn spinel oxides exhibiting unusual ion exchange, electrochemical, and catalytic properties

    Science.gov (United States)

    Miyamoto, Yumi; Kuroda, Yoshiyuki; Uematsu, Tsubasa; Oshikawa, Hiroyuki; Shibata, Naoya; Ikuhara, Yuichi; Suzuki, Kosuke; Hibino, Mitsuhiro; Yamaguchi, Kazuya; Mizuno, Noritaka

    2015-01-01

    The efficient surface reaction and rapid ion diffusion of nanocrystalline metal oxides have prompted considerable research interest for the development of high functional materials. Herein, we present a novel low-temperature method to synthesize ultrasmall nanocrystalline spinel oxides by controlling the hydration of coexisting metal cations in an organic solvent. This method selectively led to Li–Mn spinel oxides by tuning the hydration of Li+ ions under mild reaction conditions (i.e., low temperature and short reaction time). These particles exhibited an ultrasmall crystallite size of 2.3 nm and a large specific surface area of 371 ± 15 m2 g−1. They exhibited unique properties such as unusual topotactic Li+/H+ ion exchange, high-rate discharge ability, and high catalytic performance for several aerobic oxidation reactions, by creating surface phenomena throughout the particles. These properties differed significantly from those of Li–Mn spinel oxides obtained by conventional solid-state methods. PMID:26456216