Sample records for cftr-knockout mice subjected

  1. Ileal mucosal bile acid absorption is increased in Cftr knockout mice

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    Somasundaram Sivagurunathan


    Full Text Available Abstract Background Excessive loss of bile acids in stool has been reported in patients with cystic fibrosis. Some data suggest that a defect in mucosal bile acid transport may be the mechanism of bile acid malabsorption in these individuals. However, the molecular basis of this defect is unknown. This study examines the expression of the ileal bile acid transporter protein (IBAT and rates of diffusional (sodium independent and active (sodium dependent uptake of the radiolabeled bile acid taurocholate in mice with targeted disruption of the cftr gene. Methods Wild-type, heterozygous cftr (+/- and homozygous cftr (-/- mice were studied. Five one-cm segments of terminal ileum were excised, everted and mounted onto thin stainless steel rods and incubated in buffer containing tracer 3H-taurocholate. Simultaneously, adjacent segments of terminal ileum were taken and processed for immunohistochemistry and Western blots using an antibody against the IBAT protein. Results In all ileal segments, taurocholate uptake rates were fourfold higher in cftr (-/- and two-fold higher in cftr (+/- mice compared to wild-type mice. Passive uptake was not significantly higher in cftr (-/- mice than in controls. IBAT protein was comparably increased. Immuno-staining revealed that the greatest increases occurred in the crypts of cftr (-/- animals. Conclusions In the ileum, IBAT protein densities and taurocholate uptake rates are elevated in cftr (-/- mice > cftr (+/- > wild-type mice. These findings indicate that bile acid malabsorption in cystic fibrosis is not caused by a decrease in IBAT activity at the brush border. Alternative mechanisms are proposed, such as impaired bile acid uptake caused by the thick mucus barrier in the distal small bowel, coupled with a direct negative regulatory role for cftr in IBAT function.

  2. The "Goldilocks Effect" in Cystic Fibrosis: identification of a lung phenotype in the cftr knockout and heterozygous mouse

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    Bates Jason HT


    Full Text Available Abstract Background Cystic Fibrosis is a pleiotropic disease in humans with primary morbidity and mortality associated with a lung disease phenotype. However, knockout in the mouse of cftr, the gene whose mutant alleles are responsible for cystic fibrosis, has previously failed to produce a readily, quantifiable lung phenotype. Results Using measurements of pulmonary mechanics, a definitive lung phenotype was demonstrated in the cftr-/- mouse. Lungs showed decreased compliance and increased airway resistance in young animals as compared to cftr+/+ littermates. These changes were noted in animals less than 60 days old, prior to any long term inflammatory effects that might occur, and are consistent with structural differences in the cftr-/- lungs. Surprisingly, the cftr+/- animals exhibited a lung phenotype distinct from either the homozygous normal or knockout genotypes. The heterozygous mice showed increased lung compliance and decreased airway resistance when compared to either homozygous phenotype, suggesting a heterozygous advantage that might explain the high frequency of this mutation in certain populations. Conclusions In the mouse the gene dosage of cftr results in distinct differences in pulmonary mechanics of the adult. Distinct phenotypes were demonstrated in each genotype, cftr-/-, cftr +/-, and cftr+/+. These results are consistent with a developmental role for CFTR in the lung.

  3. Bioelectric characterization of epithelia from neonatal CFTR knockout ferrets

    NARCIS (Netherlands)

    J.T. Fisher (John); S.R. Tyler (Scott); Y. Zhang (Yulong); B.J. Lee (Ben); X. Liu (Xiaoming); X. Sun (Xinying); H. Sui (Hongshu); B. Liang (Bo); M. Luo (Ma); W. Xie (Weiliang); I. Yi (Iasson); W. Zhou (Weili); Y. Song (Yiqing); N. Keiser (Nicholas); K. Wang (Kai); H.R. de Jonge (Hugo); J.F. Engelhardt (John)


    textabstractCystic fibrosis (CF) is a life-shortening, recessive, multiorgan genetic disorder caused by the loss of CF transmembrane conductance regulator (CFTR) chloride channel function found in many types of epithelia. Animal models that recapitulate the human disease phenotype are critical to un

  4. Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress. (United States)

    Chhillar, Ritu; Dhingra, Dinesh


    This study was designed to evaluate antidepressant-like activity of gallic acid in Swiss young male albino mice subjected to unpredictable chronic mild stress and to explore the possible underlying mechanisms for this activity. Gallic acid (5, 10, 20 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) per se were administered daily to unstressed mice and other groups of mice subjected to unpredictable mild stress, 30 min after the injection for 21 successive days. The antidepressant-like activity was evaluated using forced swim test (FST) and sucrose preference test. Stress significantly increased immobility period of mice in FST. Gallic acid (10 and 20 mg/kg, i.p.) and fluoxetine significantly decreased immobility period of unstressed and stressed mice in FST and prevented the stress-induced decrease in sucrose preference, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by the drugs. Gallic acid (10 and 20 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in unstressed mice; and significantly prevented the stress-induced decrease in reduced glutathione and catalase activity; and also significantly prevented stress-induced increase in MAO-A activity, malondialdehyde levels, plasma nitrite, and corticosterone levels. Thus, gallic acid showed antidepressant-like activity in unstressed and stressed mice probably due to its antioxidant activity and through inhibition of MAO-A activity and decrease in plasma nitrite levels. In addition, gallic acid also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.

  5. Myricetin Attenuates Depressant-Like Behavior in Mice Subjected to Repeated Restraint Stress

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    Zegang Ma


    Full Text Available Increasing evidence has shown that oxidative stress may be implicated in chronic stress-induced depression. Several flavonoids with anti-oxidative effects have been proved to be anti-depressive. Myricetin is a well-defined flavonoid with the anti-oxidative, anti-inflammatory, anti-apoptotic, and neuroprotective properties. The aim of the present study is to investigate the possible effects of chronic administration of myricetin on depressant-like behaviors in mice subjected to repeated restraint (4 h/day for 21 days. Our results showed that myricetin administration specifically reduced the immobility time in mice exposed to chronic stress, as tested in both forced swimming test and tail suspension test. Myricetin treatment improved activities of glutathione peroxidase (GSH-PX in the hippocampus of stressed mice. In addition, myricetin treatment decreased plasma corticosterone levels of those mice subjected to repeated restraint stress. The effects of myricetin on the brain-derived neurotrophic factor (BDNF levels in hippocampus were also investigated. The results revealed that myricetin normalized the decreased BDNF levels in mice subjected to repeated restraint stress. These findings provided more evidence that chronic administration of myricetin improves helpless behaviors. The protective effects of myricetin might be partially mediated by an influence on BDNF levels and might be attributed to myricetin-mediated anti-oxidative stress in the hippocampus.

  6. Olfactory Sensitivity for Six Predator Odorants in CD-1 Mice, Human Subjects, and Spider Monkeys (United States)

    Sarrafchi, Amir; Odhammer, Anna M. E.; Hernandez Salazar, Laura Teresa; Laska, Matthias


    Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1 mice (Mus musculus) for six sulfur-containing odorants known to be components of the odors of natural predators of the mouse. With all six odorants, the mice discriminated concentrations <0.1 ppm (parts per million) from the solvent, and with five of the six odorants the best-scoring animals were even able to detect concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found to detect the same six odorants at concentrations <0.01 ppm, and with four of the six odorants the best-scoring animals and subjects even detected concentrations <10 ppt. With all three species, the threshold values obtained here are generally lower than (or in the lower range of) those reported for other chemical classes tested previously, suggesting that sulfur-containing odorants may play a special role in olfaction. Across-species comparisons showed that the mice were significantly more sensitive than the human subjects and the spider monkeys with four of the six predator odorants. However, the human subjects were significantly more sensitive than the mice with the remaining two odorants. Human subjects and spider monkeys significantly differed in their sensitivity with only two of the six odorants. These comparisons lend further support to the notion that the number of functional olfactory receptor genes or the relative or absolute size of the olfactory bulbs are poor predictors of a species’ olfactory sensitivity. Analysis of odor structure–activity relationships showed that in both mice and human subjects the type of alkyl rest attached to a thietane and the type of oxygen moiety attached to a thiol significantly affected olfactory sensitivity. PMID:24278296

  7. Pioglitazone attenuates tactile allodynia and thermal hyperalgesia in mice subjected to peripheral nerve injury. (United States)

    Maeda, Takehiko; Kiguchi, Norikazu; Kobayashi, Yuka; Ozaki, Masanobu; Kishioka, Shiroh


    To clarify the role of peroxisome proliferator activated receptor gamma (PPARgamma) in neuropathic pain, we examined the effect of pioglitazone, a PPARgamma agonist, on tactile allodynia and thermal hyperalgesia in a neuropathic pain model. Mice were subjected to partial sciatic nerve ligation (PSL) and given pioglitazone (1 - 25 mg/kg, p.o.) once daily. PPARgamma was distributed in the neurons of the dorsal root ganglion and the dorsal horn of the spinal cord and in the adipocytes at the epineurium of the sciatic nerve in naive mice. PSL elicited tactile allodynia and thermal hyperalgesia for two weeks. Administration of pioglitazone for the first week after PSL attenuated thermal hyperalgesia and tactile allodynia, which was dose-dependent and blocked by GW9662 (2 mg/kg, i.p.), a PPARgamma antagonist. Administration of pioglitazone for the second week also relieved tactile allodynia, but administration one week before PSL had no effect. A single administration of pioglitazone to mice on day 7 of PSL did not alter tactile allodynia and thermal hyperalgesia. PSL-induced upregulation of tumor necrosis factor-alpha and interleukin-6, which are essential for neuropathic pain, was suppressed by pioglitazone for the first week. This suggests that pioglitazone alleviates neuropathic pain through attenuation of proinflammatory cytokine upregulation by PPARgamma stimulation.

  8. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.

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    Emmanuel S Onaivi

    Full Text Available BACKGROUND: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R but not (H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.

  9. Vaccination of healthy subjects and autoantibodies: from mice through dogs to humans. (United States)

    Toplak, N; Avcin, T


    Vaccination against pathogenic microorganisms is one of the major achievements of modern medicine, but due to an increasing number of reports of adverse reactions the vaccination procedure has induced also considerable debate. It is well known that certain infections are involved in triggering the production of autoantibodies, which could lead to autoimmune adverse reactions in genetically predisposed subjects. Based on these findings it was assumed that vaccinations might induce similar autoimmune reactions. At present there is no clear-cut evidence that vaccinations are associated with overt autoimmune diseases but it has been demonstrated that in genetically predisposed persons vaccination can trigger the production of autoantibodies and autoimmune adverse reactions. The first studies investigating the production of autoantibodies following vaccination were done in dogs and mice. Several studies investigated the production of autoantibodies following vaccination in patients with autoimmune diseases, but there are only limited data on the autoimmune responses after vaccinations in apparently healthy humans. This review summarizes current evidence on the vaccination-induced autoantibodies in apparently healthy subjects including studies in animals and humans.

  10. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS.

  11. Peripheral erythrocytes decrease upon specific respiratory challenge with grass pollen allergen in sensitized mice and in human subjects.

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    Galateja Jordakieva

    Full Text Available BACKGROUND AND AIMS: Specific hyper-responsiveness towards an allergen and non-specific airway hyperreactivity both impair quality of life in patients with respiratory allergic diseases. We aimed to investigate cellular responses following specific and non-specific airway challenges locally and systemically in i sensitized BALB/c mice challenged with grass pollen allergen Phl p 5, and in ii grass pollen sensitized allergic rhinitis subjects undergoing specific airway challenge in the Vienna Challenge Chamber (VCC. METHODS AND RESULTS: BALB/c mice (n = 20 were intraperitoneally immunized with grass pollen allergen Phl p 5 and afterwards aerosol challenged with either the specific allergen Phl p 5 (n = 10 or the non-specific antigen ovalbumin (OVA (n = 10. A protocol for inducing allergic asthma as well as allergic rhinitis, according to the united airway concept, was used. Both groups of exposed mice showed significantly reduced physical activity after airway challenge. Specific airway challenge further resulted in goblet cell hyperplasia, enhanced mucous secretion, intrapulmonary leukocyte infiltration and lymphoid follicle formation, associated with significant expression of IL-4, IL-5 and IL-13 in splenocytes and also partially in lung tissue. Concerning circulating blood cell dynamics, we observed a significant drop of erythrocyte counts, hemoglobin and hematocrit levels in both mouse groups, challenged with allergen or OVA. A significant decrease in circulating erythrocytes and hematocrit levels after airway challenges with grass pollen allergen was also found in grass pollen sensitized human rhinitis subjects (n = 42 at the VCC. The effects on peripheral leukocyte counts in mice and humans however were opposed, possibly due to the different primary inflammation sites. CONCLUSION: Our data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens

  12. Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B12-Defective Mice Is Subject to Maternal Influences

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    Lynda Mottram


    Full Text Available Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif, a protein essential for the absorption of vitamin B12/cobalamin (Cbl, have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Giftm1a/tm1a mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1 mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2 equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility.

  13. Analysis of the cerebral transcriptome in mice subjected to traumatic brain injury: importance of IL-6

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    Quintana, Albert; Giralt, Mercedes; Molinero, Amalia


    Traumatic brain injury is one of the leading causes of incapacity and death among young people. Injury to the brain elicits a potent inflammatory response, comprising recruitment of inflammatory cells, reactive astrogliosis and activation of brain macrophages. Under the influence of presumably...... such as microarrays. The combination of these modern techniques with the comparison of normal and genetically modified mice boosts the significance of the results obtained. With this approach, we have demonstrated that a cytokine such as interleukin-6 is one of the key players in the response of the brain to injury....

  14. Measuring aging rates of mice subjected to caloric restriction and genetic disruption of growth hormone signaling (United States)

    Koopman, Jacob J.E.; van Heemst, Diana; van Bodegom, David; Bonkowski, Michael S.; Sun, Liou Y.; Bartke, Andrzej


    Caloric restriction and genetic disruption of growth hormone signaling have been shown to counteract aging in mice. The effects of these interventions on aging are examined through age-dependent survival or through the increase in age-dependent mortality rates on a logarithmic scale fitted to the Gompertz model. However, these methods have limitations that impede a fully comprehensive disclosure of these effects. Here we examine the effects of these interventions on murine aging through the increase in age-dependent mortality rates on a linear scale without fitting them to a model like the Gompertz model. Whereas these interventions negligibly and non-consistently affected the aging rates when examined through the age-dependent mortality rates on a logarithmic scale, they caused the aging rates to increase at higher ages and to higher levels when examined through the age-dependent mortality rates on a linear scale. These results add to the debate whether these interventions postpone or slow aging and to the understanding of the mechanisms by which they affect aging. Since different methods yield different results, it is worthwhile to compare their results in future research to obtain further insights into the effects of dietary, genetic, and other interventions on the aging of mice and other species. PMID:26959761

  15. Initial subjective reward: Single-exposure conditioned place preference to alcohol in mice

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    Judith E. Grisel


    Full Text Available Most adults consume alcohol with relative impunity, but about 10-20% of users persist (or progress in their consumption, despite mounting and serious repercussions. Identifying at-risk individuals before neuroadaptative changes associated with chronic use become well ingrained is thus a key step in mitigating and preventing the end stage disease and its devastating impacts. Explaining liability has been impeded, in part, by the absence of animal models for assessing initial sensitivity to the drug’s reinforcing properties, an important endophenotype in the trajectory toward excessive drinking. Here we assess the initial rewarding effects of the drug in a novel application of the conditioned place preference paradigm. In contrast to previous studies that have all employed repeated drug administration, we demonstrated a robust preference for a context paired with a single exposure to 1.5g/kg EtOH in male and female subjects of three strains. This model validates an assay of initial sensitivity to the subjective rewarding effects of alcohol, a widely used drug with multifarious impacts on both brain and society, and provides a new tool for theory-driven endophenotypic pharmacogenetic approaches to understanding and treating addiction.

  16. Characterization of a critical role for CFTR chloride channels in cardioprotection against ischemia/reperfusion injury

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    Sunny Yang XIANG; Linda L YE; LI-lu Marie DUAN; Li-hui LIU; Zhi-dong GE; John A AUCHAMPACH; Garrett J GROSS; Dayue Darrel DUAN


    Aim: To further characterize the functional role of cystic fibrosis transmembrane conductance regulator (CFTR) in early and late (second window) ischemic preconditioning (IPC)- and postcondtioning (POC)-mediated cardioprotection against ischemia/reperfusion (I/R) injury.Methods: CFTR knockout (CFTR-/-) mice and age- and gender-matched wild-type (CFTR+/+) and heterozygous (CFTR+/-) mice were used.In in vivo studies, the animals were subjected to a 30-min coronary occlusion followed by a 40-min reperfusion. In ex vivo (isolate heart) studies, a 45-min global ischemia was applied. To evaluate apoptosis, the level of activated caspase 3 and TdT-mediated dUTP-X nick end labeling (TUNEL) were examined.Results: In the in vivo I/R models, early IPC significantly reduced the myocardial infarct size in wild-type (CFTR+/+) (from 40.4%±5.3% to 10.4%±2.0%, n=8, P<0.001) and heterozygous (CFTR+/-) littermates (from 39.4%±2.4% to 15.4%±5.1%, n=6, P<0.001) but failed to protect CFTR knockout (CFTR-/-) mice from I/R induced myocardial infarction (46.9%±6.2% vs 55.5%±7.8%, n=6, P>0.5). Similar results were observed in the in vivo late IPC experiments. Furthermore, in both in vivo and ex vivo I/R models, POC significantly reduced myocardial infarction in wild-type mice, but not in CFTR knockout mice. In ex vivo I/R models, targeted inactivation of CFTRgene abolished the protective effects of IPC against I/R-induced apoptosis.Conclusion: These results provide compelling evidence for a critical role for CFTR Cl- channels in IPC- and POC-mediated cardioprotection against I/R-induced myocardial injury.

  17. Types and three-dimensional distribution of neuronal ectopias in the brain of mice prenatally subjected to X-irradiation

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    Sun, Xue-Zhi; Takahashi, Sentaro; Kubota, Yoshihisa; Sato, Hiroshi [National Inst. of Radiological Sciences, Chiba (Japan); Cui, Chun; Fukui, Yoshihiro [Tokushima Univ. (Japan). School of Medicine; Inouye, Minoru [Shin Nippon Biomedical Lab., Ltd., Miyanoura, Kagoshima (Japan)


    The types and three-dimensional distribution of neocortical ectopias following prenatal exposure to X-irradiation were studied by a histological examination and computer reconstruction techniques. Pregnant ICR mice were subjected to X-irradiation at a dose of 1.5 Gy on embryonic day 13. The brains from 30-day-old mice were serially sectioned on the frontal plane at 15 {mu}m, stained with HE and observed with a microscope. The image data for the sections were input to a computer, and then reconstructed to three-dimensional brain structures using the Magellan 3.6 program. Sectional images were then drawn on a computer display at 240 {mu}m intervals, and the positions of the different types of neocortical ectopias were marked using color coding. Three types of neocortical ectopias were recognized in the irradiated brains. Neocortical Lay I ectopias were identified as small patches in the caudal occipital cortex, and were located more laterally in the neocortex in caudal sections than in the rostral sections. Periventricular ectopias were located more rostrally than Lay I ectopias, and were found from the most caudal extent of the presumed motor cortex to the most caudal extent of the lateral ventricle. Hippocampal ectopias appeared as continuous linear bands, and were frequently associated with the anterior parts of the periventricular ectopias. (author)

  18. Intestinal Bicarbonate Secretion in Cystic Fibrosis Mice

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    Clarke LL


    Full Text Available Gene-targeted disruption of the cystic fibrosis transmembrane conductance regulator (CFTR in mice results in an intestinal disease phenotype that is remarkably similar to bowel disease in cystic fibrosis patients. In the intestinal segment downstream from the stomach (i.e., the duodenum, CFTR plays an important role in bicarbonate secretion that protects the epithelium from acidic gastric effluent. In this report, we examine the role of CFTR in cAMP-stimulated bicarbonate secretion in the murine duodenum and the mechanisms of acid-base transport that are revealed in CFTR knockout (CF mice. Ion substitution, channel blocker and pH stat studies comparing duodena from wild-type and CF mice indicate that CFTR mediates a HCO(3(- conductance across the apical membrane of the epithelium. In the presence of a favorable cell-to-lumen HCO(3(- gradient, the CFTR-mediated HCO(3(- current accounts for about 80% of stimulated HCO(3(- secretion. Exposure of the duodenal mucosa to acidic pH reveals another role of CFTR in facilitating HCO(3(- secretion via an electroneutral, 4,4'-diisothiocyanato-stilbene-2,2' disulfonic acid (DIDS sensitive Cl(-/HCO(3(- exchange process. In CF duodenum, other apical membrane acid-base transporters retain function, thereby affording limited control of transepithelial pH. Activity of a Cl(--dependent anion exchanger provides near-constant HCO(3(- secretion in CF intestine, but under basal conditions the magnitude of secretion is lessened by simultaneous activity of a Na(+/H(+ exchanger (NHE. During cAMP stimulation of CF duodenum, a small increase in net base secretion is measured but the change results from cAMP inhibition of NHE activity rather than increased HCO(3(- secretion. Interestingly, a small inward current that is sensitive to the anion channel blocker, 5-nitro-2(3-phenylpropyl amino-benzoate (NPPB, is also activated during cAMP stimulation of the CFTR-null intestine but the identity of the current is yet to be

  19. Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration

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    Laursen, Bettina; Mørk, Arne; Plath, Niels;


    , respectively. Conversely, there was no deterioration of cognitive functioning in sham lesioned Tg2576 mice or wild type littermates (wt) receiving the immunotoxin. At 10 months of age, release of acetylcholine (ACh) was addressed by microdialysis in conscious mice. Scopolamine-induced increases in hippocampal...

  20. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis. (United States)

    Svahn, Sara L; Ulleryd, Marcus A; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov; Johansson, Maria E


    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics,S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival.

  1. Immune responses induced by a Leishmania (Leishmania amazonensis recombinant antigen in mice and lymphocytes from vaccinated subjects

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    Ana Paula FERNANDES


    Full Text Available In the search for Leishmania recombinant antigens that can be used as a vaccine against American Cutaneous Leishmaniasis, we identified a Leishmania (Leishmania amazonensis recombinant protein of 33 kD (Larp33 which is recognized by antibodies and peripheral blood leukocytes (PBL from subjects vaccinated with Leishvacin ®, Larp33 was expressed in Escherichia coli after cloning of a 2,2 kb Sau3A digested genomic fragment of L. (L. amazonensis into the pDS56-6 His vector. Immunoblotting analysis indicated that Larp33 corresponds to an approximately 40-kD native protein expressed in promastigotes of L.(L. amazonensis and L. (Viannia braziliensis. Northern blots of total RNA also demonstrated that the gene coding for this protein is expressed in promastigotes of the major lineages of Leishmania causing American Cutaneous Leishmaniasis. Larp33 induced partial protection in susceptible mouse strains (BALB/c and C57BL/10 against L. (L. amazonensis after vaccination using Bacille Calmette-Guerin (BCG as adjuvant. In vitro stimulation of splenocytes from BALB/c protected mice with Larp33 elicited the secretion of IL-2 and IFN-g, suggesting that a Th1 cell-mediated protective response is associated with the resistance observed in these mice. As revealed by its immunogenic and antigenic properties, this novel recombinant antigen is a suitable candidate to compose a vaccine against cutaneous leishmaniasisA resposta imune induzida por uma proteína recombinante de Leishmania (Leishmania amazonensis de 33 kD (Larp33 foi avaliada em linfócitos de indivíduos vacinados com a Leishvacin® e em camundongos através de vacinação. Larp33 foi expressa em Escherichia coli após clonagem de um fragmento genômico de L. (L. amazonensis de 2,2 kb no vetor pDS56-6His. Larp33 foi reconhecida por anticorpos IgG presentes no soro de indivíduos vacinados com Leishvacin® e induziu proliferação em linfócitos desses indivíduos em níveis comparáveis ao ant

  2. The relationship between the alkaline phosphatase network and the haematopoiesis in mice subjected to whole-body irradiation

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    Almohamad Khaled M.


    Full Text Available Purpose: To investigate the relationship between the alkaline phosphatase (ALP network of the marrow stroma and the haematopoietic regeneration after mice whole-body irradiation. Materials and methods: Three groups of mice were irradiated with a non-lethal ionising radiation dose: the fi rst one received an intraperitoneal injection of Levamisole, ALP inhibitor, 24 h before irradiation; the second one received an intraperitoneal injection of Lisinopril, haematopoiesis inhibitor, 24 h before irradiation; the third was left untreated, but irradiated. The fourth group, untreated and not irradiated, was the control. The total surface occupied by ALP positive processes, revealed by means of ALP cytochemistry in the marrow area, was evaluated semi-quantitively. Nucleated bone marrow cells were also counted. Results: ALP network began to increase 24 h after irradiation to reach a maximum after 72 h, when the bone marrow was almost become completely empty of the haematopoietic cells. This increase advances the haematopoietic recovery. This process was substantially delayed when the mice were injected with Levamisole 24 h before irradiation. On the contrary, ALP network increased strongly since the fi rst day after irradiation when the mice were injected with Lisinopril 24 h before irradiation. Conclusions: These data have indicated that the haematopoietic recovery and repopulation of the bone marrow were advanced by the ALP network recovery.

  3. Post-operative corticosterone levels in plasma and feces of mice subjected to permanent catheterization and automated blood sampling. (United States)

    Sundbom, Renée; Jacobsen, Kirsten R; Kalliokoski, Otto; Hau, Jann; Abelson, Klas S P


    This study investigated the effects of surgical placement of permanent arterial catheters on plasma corticosterone levels, fecal corticosterone excretion and body weight in male BALB/c/Sca mice. In addition, the effects of voluntarily ingested buprenorphine in doses of 0.5 and 1.0 mg/kg body weight on these parameters were studied. A catheter was placed in the carotid artery during isoflurane anesthesia. Immediately after surgery, the mice were connected to an AccuSampler® μ and blood samples for plasma corticosterone quantification were collected automatically during the first 24 h postoperatively. All fecal boli produced 24 h before and 24 h after surgery were collected for fecal corticosterone excretion measures and the pre- and post-operative body weights were registered. Plasma corticosterone levels were in the range of 150-300 ng/ml after the surgical procedure and the body weight was significantly lower 24 h after surgery compared to its pre-operative value. Contrary to what was expected, the total fecal corticosterone excretion was significantly reduced 24 h after surgery, as was the defecation. Buprenorphine treatment significantly lowered the plasma corticosterone levels, but had no effect on fecal corticosterone excretion or body weight change. It was concluded that surgical placement of an arterial catheter induces a significant stress response, as judged by its effect on plasma corticosterone and body weight. Voluntary ingestion of buprenorphine improved postoperative recovery by lowering plasma corticosterone concentrations. Neither fecal corticosterone excretion nor body weight change seems suitable for postoperative stress assessment in mice in the present experimental setup.

  4. Effects of cadmium and monensin on renal and cardiac functions of mice subjected to subacute cadmium intoxication. (United States)

    Ivanova, Juliana; Gluhcheva, Yordanka; Arpadjan, Sonja; Mitewa, Mariana


    Cadmium (Cd) is a well-known nephrotoxic agent. Cd-induced renal dysfunction has been considered as one of the causes leading to the development of hypertension. The correlation between Cd concentration in blood and urine and cardiovascular diseases has been discussed in many epidemiological studies. A therapy with chelating agents is utilized for the treatment of toxic metal intoxication. Herein we present novel information indicating that monensin (applied as tetraethylammonium salt) is a promising chelating agent for the treatment of Cd-induced renal and cardiac dysfunction. The study was performed using the ICR mouse model. Adult ICR male mice were divided into three groups with six animals in each group: control (received distilled water and food ad libitum for 28 days); Cd-intoxicated (treated orally with 20 mg/kg b.w. Cd(II) acetate from day 1 to day 14 of the experimental protocol), and monensin treated group (intoxicated with Cd(II) acetate as described for the Cd-intoxicated group followed by oral treatment with 16 mg/kg b.w. tetraethylammonium salt of monensic acid for 2 weeks). Cd intoxication of the animals resulted in an increase of the organ weight/body weight indexes. Cd elevated significantly creatinine and glucose level in serum. Monensin treatment improved the organ weight/body weight ratios. The therapy of the Cd-intoxicated animals with monensin ameliorated the creatinine and glucose level in serum and decreased the concentration of the toxic metal ions in the heart and kidneys by 54% and 64%, respectively.

  5. Effects of cadmium and monensin on renal and cardiac functions of mice subjected to subacute cadmium intoxication

    Directory of Open Access Journals (Sweden)

    Ivanova Juliana


    Full Text Available Cadmium (Cd is a well-known nephrotoxic agent. Cd-induced renal dysfunction has been considered as one of the causes leading to the development of hypertension. The correlation between Cd concentration in blood and urine and cardiovascular diseases has been discussed in many epidemiological studies. A therapy with chelating agents is utilized for the treatment of toxic metal intoxication. Herein we present novel information indicating that monensin (applied as tetraethylammonium salt is a promising chelating agent for the treatment of Cd-induced renal and cardiac dysfunction. The study was performed using the ICR mouse model. Adult ICR male mice were divided into three groups with six animals in each group: control (received distilled water and food ad libitum for 28 days; Cd-intoxicated (treated orally with 20 mg/kg b.w. Cd(II acetate from day 1 to day 14 of the experimental protocol, and monensin treated group (intoxicated with Cd(II acetate as described for the Cd-intoxicated group followed by oral treatment with 16 mg/kg b.w. tetraethylammonium salt of monensic acid for 2 weeks. Cd intoxication of the animals resulted in an increase of the organ weight/body weight indexes. Cd elevated significantly creatinine and glucose level in serum. Monensin treatment improved the organ weight/body weight ratios. The therapy of the Cd-intoxicated animals with monensin ameliorated the creatinine and glucose level in serum and decreased the concentration of the toxic metal ions in the heart and kidneys by 54 % and 64 %, respectively

  6. H₁ but not H₂ histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing. (United States)

    Serafim, K R; Kishi, M S; Canto-de-Souza, A; Mattioli, R


    This study investigated the role of H₁ and H₂ receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H₁ receptor, but not H₂, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

  7. Investigations on GSK-3β/NF-kB signaling in stress and stress adaptive behavior in electric foot shock subjected mice. (United States)

    Bali, Anjana; Jaggi, Amteshwar Singh


    The present study was designed to explore the role of GSK-3β and NF-kB signaling in electric foot shock-induced stress and stress adaptation. Mice were subjected to foot shocks of 0.5mA intensity and 1s duration of 1h to produce acute stress. Animals were exposed to the same stressor for 5 days to induce stress adaptation. The behavioral alterations were assessed using the actophotometer, hole board, open field and social interaction tests. The serum corticosterone levels were assessed as a marker of the HPA axis. The levels of total GSK-3β, p-GSK-3β-S9 and p-NF-kB were determined in the hippocampus, frontal cortex and amygdala. Acute electric foot shock stress produced behavioral and biochemical changes; decreased the levels of p-GSK-3β-S9, produced no change in total GSK-3β levels and increased p-NF-kB levels in the brain. However, repeated exposure of foot shock stress restored the behavioral and biochemical changes along with normalization of p-GSK-3β-S9 and p-NF-kB levels. Administration of AR-A01, a selective GSK-3β inhibitor, or diethyldithiocarbamic acid (DDTC), a selective NF-kB inhibitor, diminished acute stress-induced behavioral and biochemical changes. Furthermore, AR-A014418 normalized acute stress-induced alterations in p-GSK-3β-S9 and p-NF-kB levels, however, DDTC selectively restored NF-kB levels without any change in p-GSK-3β-S9 levels. It probably suggests that NF-kB is a downstream mediator of the GSK-3 signaling cascade. It may conclude that acute stress associated decrease in p-GSK-3β-S9 and increase in p-NF-kB levels in the brain contribute in the development of behavioral and biochemical alterations and normalization of GSK-3β/NF-kB signaling may contribute in stress adaptive behavior in response to repeated electric foot shock-subjected mice.

  8. Anti-steatotic effects of an n-3 LCPUFA and extra virgin olive oil mixture in the liver of mice subjected to high-fat diet. (United States)

    Valenzuela, Rodrigo; Espinosa, Alejandra; Llanos, Paola; Hernandez-Rodas, Maria Catalina; Barrera, Cynthia; Vergara, Daniela; Romero, Nalda; Pérez, Francisco; Ruz, Manuel; Videla, Luis A


    Non-alcoholic fatty liver disease (NAFLD) is characterized by liver steatosis, oxidative stress, and drastic depletion of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), namely, eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA), which trigger lipolysis stimulation and lipogenesis inhibition. Extra virgin olive oil (EVOO) has important antioxidant effects. This study evaluated the anti-steatotic effects of n-3 LCPUFA plus EVOO in the liver of male C57BL/6J mice subjected to a control diet (CD) (10% fat, 20% protein, 70% carbohydrate) or high fat diet (HFD) (60% fat, 20% protein, 20% carbohydrate), without and with supplementation with n-3 LCPUFA (100 mg per kg per day) plus EVOO (100 mg per kg per day) for 12 weeks. HFD induced (i) liver steatosis (increased total fat, triacylglycerols, and free fatty acid total contents), (ii) higher fasting serum glucose and insulin levels and HOMA index, total cholesterol, triacylglycerols and TNF-α and IL-6, (iii) liver and plasma oxidative stress enhancement, (iv) depletion of the n-3 LCPUFA hepatic content, and (v) increment in lipogenic enzyme activity and reduction in lipolytic enzyme activity. These changes were either reduced (p < 0.05) or normalized to control the values in animals subjected to HFD supplemented with n-3 LCPUFA plus EVOO. In conclusion, n-3 LCPUFA plus EVOO intervention exerts anti-steatotic effects underlying antioxidant and anti-inflammatory responses, improved insulin sensitivity, and recovery of the lipolytic/lipogenic status of the liver altered by HFD, and supports the potential therapeutic use of n-3 LCPUFA plus EVOO supplementation in the treatment of human liver steatosis induced by nutritional factors or other etiologies.

  9. Reduction in the desaturation capacity of the liver in mice subjected to high fat diet: Relation to LCPUFA depletion in liver and extrahepatic tissues. (United States)

    Valenzuela, Rodrigo; Barrera, Cynthia; Espinosa, Alejandra; Llanos, Paola; Orellana, Paula; Videla, Luis A


    α-Linolenic (ALA) and linoleic (LA) acids are precursors of long chain polyunsaturated fatty acids (LCPUFAs), FAs with important biochemical and physiological functions. In this process, desaturation reactions catalyzed by Δ5- and Δ6-desaturase play a major role, enzymes that are subjected to hormonal and dietary regulation. The aim of this study was to assess the influence of a high fat diet (HFD) on activity of liver Δ5 and Δ6 desaturases, in relation to LCPUFA composition in liver and extrahepatic tissues. Male C57BL/6J mice received control diet (CD) (10% fat, 20% protein and 70% carbohydrate) or high fat diet (HFD) (60% fat, 20% protein, and 20% carbohydrate) for 12 weeks. After this time, blood and liver samples were taken for metabolic, morphologic, inflammatory, oxidative stress and desaturase activity assessment, besides FA phospholipid analysis in erythrocytes, heart, adipose tissue and brain. HFD significantly increased hepatic total fat, triacylglycerides and free FA content with macrovesicular steatosis and oxidative stress enhancement, concomitantly with higher fasting serum glucose and insulin levels, HOMA, and serum cholesterol, triacylglycerols, TNF-α, and IL-6. Diminution in liver Δ5- and Δ6-desaturase activities and LCPUFA depletion were induced by HFD, the later finding being also observed in extrahepatic tissues. In conclusion, HFD-induced reduction in the bioavailability of liver LCPUFA is associated with defective desaturation of ALA and LA, with Δ5- and Δ6-desaturase activities being correlated with insulin resistance development. Data analyzed point to the liver as a major organ responsible for extrahepatic LCPUFA homeostasis, which is markedly deranged by HFD.

  10. Comparative assessment of the effects of salinomycin and monensin on the biodistribution of lead and some essential metal ions in mice, subjected to subacute lead intoxication. (United States)

    Ivanova, Juliana; Gluhcheva, Yordanka; Dimova, Donika; Pavlova, Ekaterina; Arpadjan, Sonja


    In this study, we present a comparative assessment of the effects of two polyether ionophorous antibiotics (monensin and salinomycin) on the concentrations of lead (Pb), cooper (Cu), zinc (Zn) and iron (Fe) in the kidneys, spleen, liver and brain of Pb-intoxicated animals. Our data demonstrated that the intoxication of ICR male mice with Pb salt resulted in a significant accumulation of Pb in all studied organs of the mice compared to the untreated control animals. The biodistribution of the toxic metal was in the order kidneys>spleen>liver>brain. The treatment of the Pb-intoxicated animals with tetraethylammonium salts of monensic and salinomycinic acids significantly decreased the concentration of the toxic metal ion compared to the toxic control. The effect varied in the interval 38% (for kidneys) to 52% (for brain) compared to the toxic control group (Pb). The tetraethylammonium salt of salinomycinic acid was more effective in reducing the Pb concentration in the brain of the Pb-treated mice compared to monensin. Pb-intoxication did not affect significantly the Zn endogenous concentration compared to the normal values. The treatment of ICR male mice with Pb-salt decreased the Cu concentration in the spleen and increased the Cu concentration in the liver compared to the untreated control animals. The detoxification of the Pb-intoxicated mice with tetraethylammonium salts of salinomycinic and monensic acids restored the Cu concentration in the spleen, but did not affect the Cu levels in the liver. The Pb-intoxication of the ICR mice resulted in a significant decrease of the Fe-concentration in the spleen and liver compared to the untreated control animals. The administration of the tetraethylammonium salts of salinomycinic and monensic acids to the Pb-treated animals restored the levels of Fe in both organs.

  11. Distribution of selected elements in atherosclerotic plaques of apoE/LDLR-double knockout mice subjected to dietary and pharmacological treatments

    Energy Technology Data Exchange (ETDEWEB)

    Gajda, Mariusz, E-mail: [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Kowalska, Joanna [Institute of Nuclear Physics, Radzikowskiego 152, 31-342 Krakow (Poland); Banas, Agnieszka; Banas, Krzysztof [Singapore Synchrotron Light Source, National University of Singapore, 5 Research Link, 117603 Singapore (Singapore); Kwiatek, Wojciech M. [Institute of Nuclear Physics, Radzikowskiego 152, 31-342 Krakow (Poland); Kostogrys, Renata B. [Department of Human Nutrition, Agricultural University of Krakow, Balicka 122, 30-149, Krakow (Poland); Mateuszuk, Lukasz; ChLopicki, Stefan [Department of Experimental Pharmacology, Jagiellonian University Medical College, Kopernika 7, 31-531 Krakow (Poland); Litwin, Jan A. [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow (Poland); Appel, Karen [Hasylab, DESY, Notkestrasse 85, D-22607, Hamburg (Germany)


    Gene-targeted, apolipoprotein E and LDL receptor-double knockout (apoE/LDLR{sup -/-}) mice represent a new animal model that displays severe hyperlipidemia and atherosclerosis. The aim of the present study was to show changes in histomorphology and in distribution of selected elements in atherosclerotic plaques of apoE/LDLR{sup -/-} mice fed egg-rich proatherosclerotic diet (5% egg-yolk lyophilisate) supplemented or not with perindopril (inhibitor of angiotensin converting enzyme; 2 mg/kg b.w.). Synchrotron radiation micro-X-ray fluorescence spectrometry was combined with histological stainings to determine distribution and concentration of trace and essential elements in atherosclerotic lesions. More advanced atherosclerotic lesions expressed by total area occupied by lipids (oil red-O staining) and by macrophages (CD68 immunohistochemistry) were observed in animals fed egg-rich diet. The perindopril treatment attenuated these effects. No significant differences were observed in the number of intimal smooth muscle cells (smooth muscle actin immunohistochemistry). In animals fed egg-rich diet significantly higher concentrations of Ca and significantly lower contents of S, Cl, , Fe, Cu, Zn and Se in atheromas were seen in comparison to chow diet-fed animals. After pharmacological treatment, concentrations of S, Cl, Fe, Cu, Zn and Se showed the tendency to achieve levels like in animals fed normal diet. K level differed only in group treated with perindopril. Concentration of P did not significantly vary in all experimental groups. Perindopril showed its potency to reduce atherosclerosis, as estimated by the size of the atheroma and content of pro- and antiatherogenic elements.

  12. Purple Tea and Its Extract Suppress Diet-induced Fat Accumulation in Mice and Human Subjects by Inhibiting Fat Absorption and Enhancing Hepatic Carnitine Palmitoyltransferase Expression. (United States)

    Shimoda, Hiroshi; Hitoe, Shoketsu; Nakamura, Seikou; Matsuda, Hisashi


    A number of clinical trials have been completed using green tea and black tea to investigate their effect in controlling weight in overweight adults. The results of these investigations, however, have often been contradictory, with some trials reporting positive effects of tea supplementation and some trials reporting no effect. As a result, the use of these teas for weight loss is controversial. Purple tea is a variety of green tea developed in Kenya (called TRFK306), which in addition to certain tea constituents found in green tea, also contains anthocyanins. The major constituents in the leaves of purple tea are caffeine, theobromine, epigallocatechin (ECG), epigallocatechin gallate (EGCG) and 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-β-D-glucose (GHG). We investigated the efficacy of purple tea extract (PTE) on diet-induced fat accumulation in mice. PTE administration (200 mg/kg) significantly suppressed body weight gain, liver weight, abdominal fat and triglycerides in serum and liver. Protein expression of carnitine palmitoyltransferase (CPT) 1A was also enhanced. In olive oil loaded mice, PTE (100 mg/kg) and caffeine (25 mg/kg) suppressed fat absorption. PTE (10 μg/mL) and GHG (10 μg/mL) also enhanced protein expression of CPT1A in HepG2 hepatoma. Moreover, 4-week daily consumption of purple tea drink in humans improved obesity parameters compared to baseline, including body weight (79.9 ± 3.1 kg vs 80.8 ± 3.2, pweight gain by suppression of fat absorption and enhancement of hepatic fat metabolism.


    Aminova, G G; Sapinj, M R; Yerofeyeva, L M


    The cellular composition of the lamina propria of the mucous membrane of the jejunum was examined in the villi (LPV) and between the crypts (LPC). Two groups of male C57/BL6 mice aged 4-5 months were studied. Experimental group of animals (n=8) for 30 days was living under the terrestrial conditions in "BIOS-SLA" blocks and received a paste-like food made with standard feed containing water and casein. The control group of animals (n=6) were kept in standard vivarium conditions and received standard dry pellets. Studies have shown no significant changes in the content of lymphocytes in LPV and LPC in a terrestrial experiment. LPV was characterized by a sharp reduction in the number of plasma cells. In both LPV and LPC the number of eosinophils was increased, while the content of low differentiated forms of cells (blasts and large lymphocytes) was decreased. It is suggested that the changes in the contents of different cell types in ground-based experiment were due not only to the limited mobility of the animals but also to different composition of the feed.

  14. Depression-like behaviors in mice subjected to co-treatment of high-fat diet and corticosterone are ameliorated by AICAR and exercise. (United States)

    Liu, Weina; Zhai, Xiaofeng; Li, Haipeng; Ji, Liu


    Major depressive disorder (MDD) and type II diabetes mellitus (T2DM) are highly co-morbid, and there may be a bi-directional connection between the two. Herein, we have described a mouse model of a depression-like and insulin-resistant (DIR) state induced by the co-treatment of high-fat diet (HFD) and corticosterone (CORT). 5-Aminoimidazole-4-carboxamide-1-β-d- ribofuranoside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK), was originally used to improve insulin resistance (IR). Interestingly, our results show a clear potential for AICAR as a putative antidepressant with a chronic action on the DIR mice. In contrast to the traditional antidepressants, AICAR as a promising antidepressant avoids reducing insulin actions of skeletal muscle in the context of long-term HFD. Exercise also produced antidepressant effects. Our data suggest that the effects of AICAR and exercise on DIR may further increase our understanding on the link between depression and diabetes.

  15. Expanding subjectivities

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda; Soldz, Stephen


    A major theme in recent psychoanalytic thinking concerns the use of therapist subjectivity, especially “countertransference,” in understanding patients. This thinking converges with and expands developments in qualitative research regarding the use of researcher subjectivity as a tool to understa......-Saxon and continental traditions, this special issue provides examples of the use of researcher subjectivity, informed by psychoanalytic thinking, in expanding research understanding....

  16. Cell Therapy to Obtain Spinal Fusion (United States)


    Mol.Thera. 14, 684-691; 2006. Koehler DR, Sajjan U, Chow YH, Martin B, Kent G, Transwell AK, McKerlie C, Forstner JF, and Hu J. Protection of Cftr ...knockout mice from acute lung infection by a helper-dependent adenoviral vector expressing Cftr in airway epithelia. Proc. Natl. Acad. Sci. USA. 100...with acryloyl chloride as previously described.9 The dried polymers were then dissolved in 10 ml of ultrapure water and purified by dialysis (MWCO 3500

  17. About Subjects

    Institute of Scientific and Technical Information of China (English)


    正During my high school years,I found physics,chemistry and maths specially interesting.Actually,I was interested in many subjects,such as biology,history,geography and English.But somehow I simply couldn't remember the events of history or the facts about geography.I couldn't remember the some of the English idioms well either.On the other hand,physics,chemistry and maths were easy for me to learn.After considering carefully my interests and talents,I felt that science might be the best choice for me.So I was determined to study natural science at college.After graduating from college,I would like to return to school to teach.

  18. Sex differences in depression-like behavior after nerve injury are associated with differential changes in brain-derived neurotrophic factor levels in mice subjected to early life stress. (United States)

    Nishinaka, Takashi; Kinoshita, Megumi; Nakamoto, Kazuo; Tokuyama, Shogo


    We recently demonstrated that exposure to early life stress exacerbates nerve injury-induced thermal and mechanical hypersensitivity in adult male and female mice. Accumulating evidence suggests that chronic pain causes emotional dysfunction, such as anxiety and depression. In the present study, we investigated the impact of early life stress on depression-like behavior after nerve injury in mice. In addition, we examined the expression of brain-derived neurotrophic factor (BDNF), which is known to be involved in the pathogenesis of depression. Early life stress was induced by maternal separation between 2 and 3 weeks of age combined with social isolation after weaning (MSSI). At 9 weeks of age, the sciatic nerve was partially ligated to elicit neuropathic pain. Depression-like behavior was evaluated using the forced swim test at 12 weeks of age. Tissue samples from different regions of the brain were collected at the end of maternal separation (3 weeks of age) or after the forced swim test (12 weeks of age). At 12 weeks of age, immobility time in the forced swim test was increased only in MSSI-stressed female mice with nerve injury. BDNF expression was increased in male, but not female, MSSI-stressed mice at 3 weeks of age. However, MSSI stress did not impact BDNF expression in male or female mice at 12 weeks of age. Our findings suggest that exposure to early life stress exacerbates emotional dysfunction induced by neuropathic pain in a sex-dependent manner. Changes in BDNF expression after early life stress may be associated with neuropathic pain-induced depression-like behavior in adulthood. Furthermore, sex differences in BDNF expression after exposure to early life stress may contribute to sex-specific susceptibility to neuropathic pain-induced emotional dysfunction.

  19. Evaluation of oxidative stress in mice subjected to aerobic exercise Avaliação do estresse oxidativo em camundongos submetidos ao exercício físico aeróbico

    Directory of Open Access Journals (Sweden)

    Mônica Cruvinel de Lima


    Full Text Available PURPOSE: To evaluate the influence of aerobic exercise on oxidative stress in mice. METHODS: The study included twenty female mice Mus musculus-Swiss divided into two groups: sedentary control (GA and exercise (GB, each containing ten animals. All animals underwent an adaptation period of seven days isolated in individual boxes. After this period, the animals in the exercise group (GB were trained in angled running wheel with circumference of 25 cm assembled on an articulated axle during five minutes for three consecutive days. On the fourth day, they underwent an exercise program of one session lasting 45 minutes. The evaluation of oxidative stress was performed by determining the levels of malondialhyde derived of lipid peroxidation by the TBA method. The samples were read in a spectrophotometer at 535 nm. RESULTS: No significant difference was observed in the intergroup comparison of MDA levels in the tissues evaluated. A significant difference was observed in the intragroup comparison of MDA levels in the control group (p = 0.0201.The Tukeys' post hoc test indicated significantly lower values of MDA in the smooth muscle in relation to plasma. In the analysis of variance in the exercise group, a significant difference between tissues (p = 0.0009, with significantly lower values in the smooth muscle in relation to plasma (pOBJETIVO: Avaliar a influência do exercício físico aeróbico sobre o estresse oxidativo em camundongos. MÉTODOS: Participaram do estudo 20 camundongos (Swiss, distribuídos em dois grupos: controle-sedentário (GA e exercício (GB cada um contendo dez animais. Todos os animais passaram por um período de adaptação de sete dias. Após os animais do grupo (GB receberam treinamento em roda giratória angulada montada sobre eixo articulado por cinco minutos durante três dias consecutivos. No quarto dia foram submetidos à única sessão de exercício por 45 minutos. A avaliação do estresse oxidativo foi realizada por

  20. Sensibility and Subjectivity: Levinas’ Traumatic Subject

    Directory of Open Access Journals (Sweden)

    Rashmika Pandya


    Full Text Available The importance of Levinas’ notions of sensibility and subjectivity are evident in the revision of phenomenological method by current phenomenologists such as Jean-Luc Marion and Michel Henry. The criticisms of key tenants of classical phenomenology, intentionality and reduction, are of a particular note. However, there are problems with Levinas’ characterization of subjectivity as essentially sensible. In “Totality and Infinity” and “Otherwise than Being”, Levinas criticizes and recasts a traditional notion of subjectivity, particularly the notion of the subject as the first and foremost rational subject. The subject in Levinas’ works is characterized more by its sensibility and affectedness than by its capacity to reason or affect its world. Levinas ties rationality to economy and suggests an alternative notion of reason that leads to his analysis of the ethical relation as the face-to-face encounter. The ‘origin’ of the social relation is located not in our capacity to know but rather in a sensibility that is diametrically opposed to the reason understood as economy. I argue that the opposition in Levinas’ thought between reason and sensibility is problematic and essentially leads to a self-conflicted subject. In fact, it would seem that violence characterizes the subject’s self-relation and, thus, is also inscribed at the base of the social relation. Rather than overcoming a problematic tendency to dualistic thought in philosophy Levinas merely reverses traditional hierarchies of reason/emotion, subject/object and self/other. 

  1. Compensatory eye movements in mice

    NARCIS (Netherlands)

    A.M. van Alphen (Adriaan)


    textabstractThis thesis will address the generation of compensatory eye movements in naturally mutated or genetically modified mice. The reason for generating compensatory eye movements is solely related to the requirements for good vision. In a subject moving through its environment the projection

  2. A Survey of Subject and Logical Subject

    Institute of Scientific and Technical Information of China (English)



    @@ This paper discusses Subject and Logical Subject of the English language. The grammar rules complied by some grammarians will be focused on and induced in a fuller account of the survey, aiming simply at a common- sense justification of traditional sentence analysis. Subject, a familiar grammatical term, is one of the most basic to thetraditional of grammatical analysis. It reports the concept of the subject and its history conducted with learners of English who are involved in making further English programme in the education with deep grammar explorations. Both the teachers and the students face many problems in this area, which need to be made clear and definite. The non- finite verbs have their specific rules or objective laws stipulated or summed up by grammarians. These areas of intellectual inquiry ,like most other fields of language study, have represented profoundly intelligent and important investigation in to the English deep grammars.

  3. Subject in first person--subject in third person: subject, subjectivity, and intersubjectivity. (United States)

    Lazar, R


    In this article, the author traces the history of the concepts of subject, subjectivity, and intersubjectivity in different psychoanalytic theories in the last decades. She argues that the uniqueness of these concepts and their different implications were not emphasized enough. The author discusses the various implications and contexts of the concept of subject in psychoanalytic theory proper and to relate as to: (1). The need to distinguish between the concepts of subject and subjectivity; (2). The mutual interdependence of the subject and his subjectivity and the intersubjective domain (both in the development of the individual and in theoretical thought pertaining to it). Her point of departure is from the position of the subject as a free creature, the centrality of the experiencing individual, from his/her perspective--the subject in the first person. She tries to explain the paradox implicit in the experiential dimension, the place of the other as participant, as both negating and recognizing--the subject in the third person. She suggests the interdependency of the first-person experience of subjectivity on the intersubjective dimension.

  4. The Subject of Exemption

    DEFF Research Database (Denmark)

    Hamre, Bjørn; Fristrup, Tine; Christensen, Gerd


    This article examines the constructions of the deviant subject in Danish Foucauldian educational research. Following the work of Foucault, we argue that the deviant subject, on the one hand, could be considered as a subject of exemption. In this case, exemption is deduced from Foucault’s understa......This article examines the constructions of the deviant subject in Danish Foucauldian educational research. Following the work of Foucault, we argue that the deviant subject, on the one hand, could be considered as a subject of exemption. In this case, exemption is deduced from Foucault...... discourses of general education. Thus, this article argues that Foucauldian disability studies could benefit from taking into account Foucauldian research in the field of general education. Until recently, the two research fields have been mutually isolated....

  5. Subjective poverty line definitions

    NARCIS (Netherlands)

    J. Flik; B.M.S. van Praag (Bernard)


    textabstractIn this paper we will deal with definitions of subjective poverty lines. To measure a poverty threshold value in terms of household income, which separates the poor from the non-poor, we take into account the opinions of all people in society. Three subjective methods will be discussed a

  6. The Data Subject

    DEFF Research Database (Denmark)

    Blume, Peter


    This article considers whether it is fortunate that data protection rules, as a starting point, apply to all physical persons as data subjects, or whether it would be better to differentiate between kinds of persons on grounds of their ability to act as a data subject. In order to protect all...

  7. Subjective safety in traffic.

    NARCIS (Netherlands)


    The term ‘subjective safety in traffic’ refers to people feeling unsafe in traffic or, more generally, to anxiety regarding being unsafe in traffic for oneself and/or others. Subjective safety in traffic can lead to road users limiting their mobility and social activities, which is one of the reason

  8. Subject (of documents)

    DEFF Research Database (Denmark)

    Hjørland, Birger


    This article presents and discuss the concept “subject” or subject matter (of documents) as it has been examined in library and information science (LIS) for more than 100 years. Different theoretical positions are outlined and it is found that the most important distinction is between document...... such as concepts, aboutness, topic, isness and ofness are also briefly presented. The conclusion is that the most fruitful way of defining “subject” (of a document) is the documents informative or epistemological potentials, that is, the documents potentials of informing users and advance the development......-oriented views versus request-oriented views. The document-oriented view conceive subject as something inherent in documents, whereas the request-oriented view (or the policy based view) understand subject as an attribution made to documents in order to facilitate certain uses of them. Related concepts...

  9. Subjective Rationalizability in Hypergames

    Directory of Open Access Journals (Sweden)

    Yasuo Sasaki


    Full Text Available A new solution concept for hypergames called subjective rationalizability is proposed. Hypergame theory is a game theoretical framework that deals with agents who may misperceive game structures and explicitly takes into account hierarchy of perceptions, that is, an agent’s view about another agent’s view and so on. An action of an agent is called subjectively rationalizable when the agent thinks it can be a best response to the other’s choices, each of which the agent thinks each agent thinks is a best response to the other’s choices, and so on. Then it is proved that subjective rationalizability is equivalent to the standard notion of rationalizability under a condition called inside common knowledge. The result makes the new solution concept a practical tool in hypergame analyses. Theoretically, it is characterized as such a concept that provides the precise implication, that is, predicted outcomes, of a given hypergame structure.

  10. The relationships between Internet addiction, subjective vitality, and subjective happiness. (United States)

    Akın, Ahmet


    The aim of the present study is to examine the relationships between Internet addiction, subjective vitality, and subjective happiness. The participants were 328 university students who completed a questionnaire package that included the Online Cognition Scale, the Subjective Vitality Scale, and the Subjective Happiness Scale. According to the results, subjective vitality and subjective happiness were negatively predicted by Internet addiction. On the other hand, subjective happiness was positively predicted by subjective vitality. In addition, subjective vitality mediated the relationship between Internet addiction and subjective happiness. Results were discussed in light of the literature.

  11. Community, subjectivity, and intersubjectivity. (United States)

    Cronick, Karen


    This paper deals with the notions of "subjectivity," "intersubjectivity," and "community" from several different points of view that include subjective and intersubjective agency, a sense of community, the community as a social institution, and the idea of social justice. The context of these considerations can be found in the Community-Social-Psychological approach to social action as it is often practiced in Latin America. A review of these themes is considered important because different models of community intervention and practice may lead to different expressions of community interaction.

  12. Finitude, Aging and Subjectivity

    Directory of Open Access Journals (Sweden)

    Mariele Rodrigues Correa


    Full Text Available The purpose of this article is to analyze the relationship of man with death and its deployment in subjectivity and in aging. With this intent, we first present a brief history of the vision of death over time and after an analysis of the process of aging and dying according to the logic of biopolitical management. With death and old age increasingly distant from the horizons of life, subjectivity has been weakened. Thus, incorporating these aspects as part of existence constitutes one of the challenges to the thought as well as to the building of the self.  

  13. REVIEW - Thermal Physiology of Laboratory Mice: Defining Thermoneutrality (United States)

    In terms of total number of publications, the laboratory mouse (Mus musculus) has emerged as the most popular test subject in biomedical research. Mice are used as models to study obesity, diabetes, eNS diseases and variety of other pathologies. Mice are classified as homeotherms...

  14. Barron's SAT subject test

    CERN Document Server

    Jansen, MA, Robert


    Includes one diagnostic test and three complete tests, all questions answered and explained, self-assessment guides, and subject reviews. Also features test strategies, QR codes to short instructional videos, and a detailed appendix with equations, physical constants, and a basic math review.

  15. Writing and the 'Subject'

    DEFF Research Database (Denmark)

    Greve, Charlotte

    /page. It is, moreover, an index pointing to the painting/writing subject; it is a special deictic mode of painting/writing. The handwriting of the Russian avant-garde books, the poetics of handwriting, and the way handwriting is represented in poetry emphasize the way the subject (the speaking and the viewing....../reading subject) manifests itself in the material mark on the page. The study shows how this indexical reference to a ‘subject’ is manipulated and used as a mask through which a writer/painter can perform a certain ‘subject’. Through analyses of the various levels on which the ‘subject’ is represented...... in the early as well as the contemporary avant-garde, it becomes clear that the ‘subject’ is an unstable category that can be exposed to manipulation and play. Handwriting is performing as a signature (as an index), but is at the same time similar to the signature of a subject (an icon) and a verbal construct...

  16. Social transfer of pain in mice (United States)

    Smith, Monique L.; Hostetler, Caroline M.; Heinricher, Mary M.; Ryabinin, Andrey E.


    A complex relationship exists between the psychosocial environment and the perception and experience of pain, and the mechanisms of the social communication of pain have yet to be elucidated. The present study examined the social communication of pain and demonstrates that “bystander” mice housed and tested in the same room as mice subjected to inflammatory pain or withdrawal from morphine or alcohol develop corresponding hyperalgesia. Olfactory cues mediate the transfer of hyperalgesia to the bystander mice, which can be measured using mechanical, thermal, and chemical tests. Hyperalgesia in bystanders does not co-occur with anxiety or changes in corticosterone and cannot be explained by visually dependent emotional contagion or stress-induced hyperalgesia. These experiments reveal the multifaceted relationship between the social environment and pain behavior and support the use of mice as a model system for investigating these factors. In addition, these experiments highlight the need for proper consideration of how experimental animals are housed and tested.

  17. Resilience in Aging Mice. (United States)

    Kirkland, James L; Stout, Michael B; Sierra, Felipe


    Recently discovered interventions that target fundamental aging mechanisms have been shown to increase life span in mice and other species, and in some cases, these same manipulations have been shown to enhance health span and alleviate multiple age-related diseases and conditions. Aging is generally associated with decreases in resilience, the capacity to respond to or recover from clinically relevant stresses such as surgery, infections, or vascular events. We hypothesize that the age-related increase in susceptibility to those diseases and conditions is driven by or associated with the decrease in resilience. Thus, a test for resilience at middle age or even earlier could represent a surrogate approach to test the hypothesis that an intervention delays the process of aging itself. For this, animal models to test resilience accurately and predictably are needed. In addition, interventions that increase resilience might lead to treatments aimed at enhancing recovery following acute illnesses, or preventing poor outcomes from medical interventions in older, prefrail subjects. At a meeting of basic researchers and clinicians engaged in research on mechanisms of aging and care of the elderly, the merits and drawbacks of investigating effects of interventions on resilience in mice were considered. Available and potential stressors for assessing physiological resilience as well as the notion of developing a limited battery of such stressors and how to rank them were discussed. Relevant ranking parameters included value in assessing general health (as opposed to focusing on a single physiological system), ease of use, cost, reproducibility, clinical relevance, and feasibility of being repeated in the same animal longitudinally. During the discussions it became clear that, while this is an important area, very little is known or established. Much more research is needed in the near future to develop appropriate tests of resilience in animal models within an aging context

  18. Interaction, transference, and subjectivity

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda


    sense of their lives and which moral, professional, and ethical values seem to guide their behaviour and attitudes. In fieldwork, the researcher has to balance participation and observation in her attempts at representation. Consequently, the researcher’s academic and life-historical subjectivity...... investigate through a case study how the psychoanalytical concepts of “transference” and “institutional transference” can provide insight into the dynamics of efficiency and democracy at a number of Danish human service organisations....

  19. Strain-specific renal toxicity of heterologous antilymphocyte [gamma]-globulin in mice7

    NARCIS (Netherlands)

    Cohen, B.J.; Vries, M.J. de; Noord, M.J. van; Lubbe, F.H.


    Severe glomerulonephritis followed one to five weekly i.p. injections in TLFM mice of rabbit antimouse lymphocyte [gamma]-globulin (ALG). Glomerulonephritis did not occur in C57BL mice subjected to the same regimen. Administration of normal rabbit [gamma]-globulin (NRG) to RFM mice also caused renal

  20. The Subjectivity of Participation

    DEFF Research Database (Denmark)

    Nissen, Morten

    What is a 'we' – a collective – and how can we use such communal self-knowledge to help people? This book is about collectivity, participation, and subjectivity – and about the social theories that may help us understand these matters. It also seeks to learn from the innovative practices and ideas...... of a community of social/youth workers in Copenhagen between 1987 and 2003, who developed a pedagogy through creating collectives and mobilizing young people as participants. The theoretical and practical traditions are combined in a unique methodology viewing research as a contentious modeling of prototypical...

  1. Interview without a subject

    DEFF Research Database (Denmark)

    Rittenhofer, Iris


    for the accomplishment of interviews. The paper focuses on a discussion of theoretical and methodological considerations of design, approach and research strategy. These discussions are specified in relation to a project on gender and ethnicity in cultural encounters at Universities. In the paper, I introduce a research...... design named Cultural interviewing, present an approach to the design of interviews named Interview without a subject, and offer an analytic strategy directed towards the analysis of interview transcripts named Interview on the level of the signifier. The paper concludes that even though it is relevant...

  2. Turning subjective into objective

    DEFF Research Database (Denmark)

    Cardoso, Maria João; Cardoso, Jaime; Amaral, Natália;


    was fair to moderate (k=0.40, wk=0.57). In the objective assessment there was a higher level of concordance between participants (k=0.86, wk=0.90). Agreement between software and consensus classification was fair (k=0.34, wk=0.53), but was higher in the 17 cases that reached first-round consensus (k=0...... and the consensus, for computer evaluation obtained by the different participants and between software and consensus was calculated using multiple kappa (k) and weighted kappa (wk) statistics. In the subjective assessment, first-round consensus was achieved in 17 (57%) cases. Overall interobserver agreement...... for assessment of breast cosmesis in clinical trials, as it can be used simultaneously by a panel of observers from different parts of the world to provide more reliable assessments than has been possible previously...

  3. What captivates the subject?

    DEFF Research Database (Denmark)

    Porsgaard, Kasper

    What can Jacques Lacan tell us about relations of power and figures of authority? – That is the guiding question of "What Captivates the Subject?" The dissertation answers this question by providing a close study of Lacanian texts and seminars from 1953 to 1973, seeking to present not only...... the strong conceptual coherency of Lacan’s theory, but also its fundamental underpinnings in the work of Sigmund Freud. The dissertation thus attempts to pave the way for a renewed engagement between Lacanian theory and social theory in general. This engagement has already proven exceptionally fruitful...... to the establishment and maintenance of power structures, not least within the psychoanalytic clinic itself. Yet his accounts of the concepts remain blurry and tentative throughout his career, and it took a Lacan to finally build a rigorous theoretical framework around these concepts. Throughout the dissertation...

  4. Intestinal microbiota modulates gluten-induced immunopathology in humanized mice. (United States)

    Galipeau, Heather J; McCarville, Justin L; Huebener, Sina; Litwin, Owen; Meisel, Marlies; Jabri, Bana; Sanz, Yolanda; Murray, Joseph A; Jordana, Manel; Alaedini, Armin; Chirdo, Fernando G; Verdu, Elena F


    Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. The recent increase in CD incidence suggests that additional environmental factors, such as intestinal microbiota alterations, are involved in its pathogenesis. However, there is no direct evidence of modulation of gluten-induced immunopathology by the microbiota. We investigated whether specific microbiota compositions influence immune responses to gluten in mice expressing the human DQ8 gene, which confers moderate CD genetic susceptibility. Germ-free mice, clean specific-pathogen-free (SPF) mice colonized with a microbiota devoid of opportunistic pathogens and Proteobacteria, and conventional SPF mice that harbor a complex microbiota that includes opportunistic pathogens were used. Clean SPF mice had attenuated responses to gluten compared to germ-free and conventional SPF mice. Germ-free mice developed increased intraepithelial lymphocytes, markers of intraepithelial lymphocyte cytotoxicity, gliadin-specific antibodies, and a proinflammatory gliadin-specific T-cell response. Antibiotic treatment, leading to Proteobacteria expansion, further enhanced gluten-induced immunopathology in conventional SPF mice. Protection against gluten-induced immunopathology in clean SPF mice was reversed after supplementation with a member of the Proteobacteria phylum, an enteroadherent Escherichia coli isolated from a CD patient. The intestinal microbiota can both positively and negatively modulate gluten-induced immunopathology in mice. In subjects with moderate genetic susceptibility, intestinal microbiota changes may be a factor that increases CD risk.

  5. Laboratory instruction and subjectivity

    Directory of Open Access Journals (Sweden)

    Elisabeth Barolli


    Full Text Available The specific aspects which determined the way some groups of students conducted their work in a university laboratory, made us understand the articulation of these groups´s dynamics, from elements that were beyond the reach of cognition. In more specific terms the conduction and the maintenance of the groups student´s dynamics were explicited based on a intergame between the non conscious strategies, shared anonymously, and the efforts of the individuals in working based on their most objective task. The results and issues we have reached so far, using a reference the work developed by W.R.Bion, with therapeutical groups, gave us the possibility for understanding the dynamics of the student´s experimental work through a new approach that approximates the fields of cognition and subjectivity. This approximation led us to a deeper reflection about the issues which may be involved in the teaching process, particularly in situations which the teacher deals with the class, organised in groups.

  6. Naming the Ethological Subject. (United States)

    Benson, Etienne S


    Argument In recent decades, through the work of Jane Goodall and other ethologists, the practice of giving personal names to nonhuman animals who are the subjects of scientific research has become associated with claims about animal personhood and scientific objectivity. While critics argue that such naming practices predispose the researcher toward anthropomorphism, supporters suggest that it sensitizes the researcher to individual differences and social relations. Both critics and supporters agree that naming tends to be associated with the recognition of individual animal rights. The history of the naming of research animals since the late nineteenth century shows, however, that the practice has served a variety of purposes, most of which have raised few ethical or epistemological concerns. Names have been used to identify research animals who play dual roles as pets, workers, or patients, to enhance their market value, and to facilitate their identification in the field. The multifaceted history of naming suggests both that the use of personal names by Goodall and others is less of a radical break with previous practices than it might first appear to be and that the use of personal names to recognize the individuality, sentience, or rights of nonhuman animals faces inherent limits and contradictions.


    Institute of Scientific and Technical Information of China (English)


    @@ The MICE (Meetings, Incentives, Conventions, and Exhibitions) industry has exploded worldwide over the past decade. The benefits brought by meetings, incentives, conventions, and exhibitions are also benefiting other sectors involved in MICE events, including hotels, travel, and retail. Industry analysts estimate that the income from the global MICE industry will soon exceed USD 220 billion, and is expected to increase by 8-10% each year.


    Directory of Open Access Journals (Sweden)

    IJBE Volume 1


    Full Text Available SUBJECT INDEX IJBE VOLUME 1EPA, 1Agrotourism, 148AHP, 148balance scorecard, 63batik tulis Rolla Junior, 23Broiler, 90business model canvas, 137business performance,32capital structure, 81cashew industry,158CHAID,106CLI,42coal transportation service,63company’s characteristics, 81competitive advantage, 12competitive strategy, 127consumer satisfaction, 51CSI, 42customer loyalty, 42customer satisfaction,42decision of visitors, 72development strategy, 23development,158entrepreneurship, 32Feasibility studies, 90FEM, 81gap analysis, 1Indonesia Stock Exchange, 177Indosat, 137investor,177Kawah Putih, 72kedai sop durian lodaya (KSDL,51klassen typology, 96leading sector, 96less cash society, 137liquidity ratio, 165location quotient, 96logistic regression, 115market, 177marketing development strategy, 148Marketing mix, 72mobile payment, 137modern and Traditional cage, 90multiple regression analyse,165multiple regression, 177net working capital, 165organic tofu product, 115Padang, 106paired comparison, 63partnership, 1, 32Pecking Order Theory, 81PLS, 81Portfolio, 96power, 32product quality, 51profitability ratio, 165Prol Tape Primadona, 127purchase decision, 115purchase intention, 51purchasing interest,115QSPM, 23, 127refilled drinking water, 106seed,1segmentation, 106SEM, 42, 51service quality, 51SMEs, 96specialty coffee, 12stock,177strategic diagnosis,137strategy, 158Sukorambi Botanic Garden, 148SWOT, 23, 127, 148, 158SWOT-AHP, 12tourists,72UD. Primadona, 127value chain, 12VRIO,12 AUTHOR INDEX IJBE VOLUME 1Adiningsih, Kartika Puspitasari,42Aknesia, Vharessa,12Amalia, Firda Rachma,90Andati, Trias, 177Anggraeni, Lukytawati,23Asriani,158Daryanto, Arief,12, 90Djamaludin, MD., 42Djohar, Setiadi,96Fachrodji, Achmad,72Fahmi, Idqan,1, 63, 127Fasyni, Awisal,106Hubeis, Musa,148Iskandar, Dodi,51Juanda, Bambang, 165Kirbrandoko, 12, 106, 115Lumbantoruan, Dewi Margareth,96Maulana, TB Nur Ahmad,81Muksin, 148Mukti Soleh, Cecep,63Najib, Mukhamad,106Noor, Tajudin,81

  9. Mapping pathological phenotypes in Reelin mutant mice

    Directory of Open Access Journals (Sweden)

    Caterina eMichetti


    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

  10. Serum Resistin Levels Are Associated with Adiposity and Insulin Sensitivity in Obese Hispanic Subjects



    Background and Aims: Resistin is involved in the development of obesity and insulin resistance (IR) in mice and may play a similar role in humans through mechanisms that remain unresolved. The objective of this study was to characterize the relationship between resistin levels in obese subjects with and without IR among Hispanic subjects.

  11. Objective Tests versus Subjective tests

    Institute of Scientific and Technical Information of China (English)



    objective test has only one correct answer, while subjective test has a range of possible answers. Because of this feature, reliability will not be difficult to achieve in the marking of the objective item, while the marking of the subjective items is reliable. On the whole, a good test must contain both subjective and objective test items.


    Directory of Open Access Journals (Sweden)

    IJBE Volume 2


    Full Text Available SUBJECT INDEX IJBE VOLUME 2access credit, 93acquisition, 177AHP, 61, 82, 165arena simulation,43BMC, 69Bojonegoro, 69brand choice, 208brand image, 208brand positioning, 208bullwhip effect, 43burger buns, 1business synergy and financial reports, 177capital structure, 130cluster, 151coal reserves, 130coffee plantation, 93competitiveness, 82consumer behaviour, 33consumer complaint behavior, 101cooking spices, 1crackers, 1cross sectional analytical, 139crosstab, 101CSI, 12direct selling, 122discriminant analysis, 33economic value added, 130, 187employee motivation, 112employee performance, 112employees, 139EOQ, 23farmer decisions, 93farmer group, 52financial performance evaluation, 187financial performance, 52, 177financial ratio, 187financial report, 187fiva food, 23food crops, 151horticulture, 151imports, 151improved capital structure, 177IPA, 12leading sector, 151life insurance, 165LotteMart, 43main product, 61marketing mix, 33, 165matrix SWOT, 69MPE, 61multiple linear regression, 122muslim clothing, 197Ogun, 139Pangasius fillet, 82Pati, 93pearson correlation, 101perceived value, 208performance suppy chain, 23PLS, 208POQ, 23portfolio analyzing, 1product, 101PT SKP, 122pulp and papers, 187purchase decision, 165purchase intention, 33remuneration, 112re-purchasing decisions, 197sales performance, 122sawmill, 52SCOR, 23sekolah peternakan rakyat, 69SEM, 112SERVQUAL, 12Sido Makmur farmer groups, 93SI-PUHH Online, 12small and medium industries (IKM, 61socio-demographic, 139sport drink, 208stress, 139supply chain, 43SWOT, 82the mix marketing, 197Tobin’s Q, 130trade partnership, 52uleg chili sauce, 1 AUTHOR INDEX IJBE VOLUME 2Achsani, Noer Azam, 177Andati, Trias, 52, 177Andihka, Galih, 208Arkeman, Yandra, 43Baga, Lukman M, 69Cahyanugroho, Aldi, 112Daryanto, Arief, 12David, Ajibade, 139Djoni, 122Fahmi, Idqan, 1Fattah, Muhammad Unggul Abdul, 61Hakim, Dedi Budiman, 187Harianto, 93Hartoyo, 101Homisah, 1Hubeis, Musa, 112Hutagaol, M. Parulian, 93Jaya, Stevana

  13. A Family of Mice

    Institute of Scientific and Technical Information of China (English)


    @@ 一、故事内容 There is a family of mice in my house. They are father mouse, mother mouse and baby mouse. Baby mouse likes dancing. He is very cute. Father mouse likes watching TV. He likes the sports on TV best. These three mice are clever.

  14. Of mice and men

    CERN Multimedia


    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.

  15. The pathology of facial vein blood sampling in mice

    DEFF Research Database (Denmark)

    Hansen, Ket; Harslund, Jakob le Fèvre; Bollen, Peter


    Introduction: The use of retro-orbital blood sampling is prohibited in Denmark. For this reason, alternative methods are used for obtaining larger blood samples of a good quality. The facial vein is generally recommended for this. However, we have experienced discomfort for mice subjected to facial...... vein blood sampling. Therefore, we investigated if this technique was associated with pathological changes of the jaw region. Methods: 43 NMRI mice were subjected to facial vein blood sampling by using the lancet method during 12 months, starting at the age of 8 weeks. The mice were restrained manually...... by the scruff and a lancet was placed 2-3 mm caudally to the freckle on the lower jaw, and the skin was punctured. After sampling, brief compression by a cotton swab was applied, if bleeding did not stop. Two days after the last blood sampling, the mice were euthanized by an overdose of pentobarbital...

  16. Human subjects research handbook: Protecting human research subjects. Second edition

    Energy Technology Data Exchange (ETDEWEB)



    This handbook serves as a guide to understanding and implementing the Federal regulations and US DOE Orders established to protect human research subjects. Material in this handbook is directed towards new and continuing institutional review board (IRB) members, researchers, institutional administrators, DOE officials, and others who may be involved or interested in human subjects research. It offers comprehensive overview of the various requirements, procedures, and issues relating to human subject research today.

  17. 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.

  18. Subjective and Objective Facial Attractiveness (United States)

    Stillman, Mark A.; Frisina, Andrew C.


    Background: Studies have not adequately compared subjective/objective ratings of female dermatology patients including patients presenting for cosmetic procedures. Objective: To examine objective versus subjective facial attractiveness ratings, demographic variables, and how men versus women judge female facial attractiveness. Methods: Sixty-five women (mean 42 years) presenting to a dermatology office. Subjects filled out a demographic and attractiveness questionnaire and were photographed. Four judges (2 male and 2 female) rated the photographs on a predefined 1 to 7 scale. Results: Mean subjective rating (subjects rating themselves) was 4.85 versus 3.61 for objective rating (judges rating subjects) (p<0.001). The mean age of subjects self-rating (subjective rating) who rated themselves in the 5 to 7 range was 39 years; the mean age of subjects self-rating (subjective rating) who rated themselves in the 3 to 4 range was 45 years (p=0.053). The mean age of subjects objectively rated by judges in the 5 to 7 range was 33 years; the mean age of subjects objectively rated by judges in the 3 to 4 range was 43 years (p<0.001); and the mean age of subjects objectively rated by judges in the 1 to 2 range was 50 years (p<0.001). The mean subjective rating (subjects rating themselves) for married women was 4.55 versus 5.27 for unmarried women (p=0.007); the mean objective rating (judges rating subjects) was 3.22 versus 4.15 (p<0.001). The mean objective rating by male judges was 3.09 versus 4.12 for female judges (p<0.001) Conclusion: Female patients presenting to a dermatology office rated themselves more attractive than did judges who viewed photographs of the subjects. Age and marital status were significant factors, and male judges rated attractiveness lower than female judges. Limitations of the study, implications, and suggestions for future research directions are discussed. PMID:21203353

  19. Acetaminophen-induced acute liver injury in HCV transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U. [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Tech, Katherine; Macdonald, Jeffrey M. [Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States); Boorman, Gary A. [Covance, Chantilly, VA 20151 (United States); Chatterjee, Saurabh; Mason, Ronald P. [Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, RTP, NC 27713 (United States); Melnyk, Stepan B. [Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72201 (United States); Tryndyak, Volodymyr P.; Pogribny, Igor P. [Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Rusyn, Ivan, E-mail: [Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599 (United States)


    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  20. The Subject in Cognitive Psychotherapy

    Directory of Open Access Journals (Sweden)

    Isabel Caro-Gabalda


    Full Text Available This paper discusses the various subjects embedded in cognitive psychotherapy. The cognitive model developed by Beck, considered as a rationalist and modernist model, will exemplify these subjects. Cognitive therapy should be placed in the modernist historical context and related to a subject characterized as having rationality and the ability to observe and detect cognitions, emotions and behaviors. The paper develops this background introducing three main subject types. The first is the introspective and conscious subject, who is able to observe what is within oneself, has free access, and is conscious of one's cognitive world. The second is the cognitive miser that describes the subject who enters into therapy. The final subject identified, is the trained scientist who is able to develop a more objective knowledge, changing faulty schemas and cognitive distortions. This subject is the one most looked for in cognitive therapy. We could connect these subjects to some of the main elements of cognitive therapy such as the concept of ABC, assessment procedures, cognitive techniques or the relevance of schemas. Finally, the paper suggests some issues for study that could contribute to the theoretical and clinical evolution of cognitive psychotherapy.

  1. Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice


    Frye, Cheryl A.


    Progesterone may have actions independent of intracellular progestin receptors (PRs) to influence depressive behavior. To investigate this, we examined effects of progesterone (P; 10 mg/kg, SC) on the depressive behavior of mice in the forced swim test (FST). In Experiment 1, subjects were 4 to 6 months old, intact or ovariectomized (OVX) female and intact or gonadectomized (GDX) male, C57/BL6 mice. Progesterone reduced depressive behavior of young diestrous and OVX mice but male mice were im...

  2. Atopic asthmatic subjects but not atopic subjects without ... (United States)

    BACKGROUND: Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined. OBJECTIVE: We sought to determine whether atopic status modulates ozone response phenotypes in human subjects. METHODS: Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11 atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm ozone exposure protocol. Ozone response was determined based on changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell-surface markers, and cytokine and hyaluronic acid concentrations. RESULTS: All cohorts experienced similar decreases in lung function after ozone. Atopic and atopic asthmatic subjects had increased sputum neutrophil numbers and IL-8 levels after ozone exposure; values did not significantly change in healthy volunteers. After ozone exposure, atopic asthmatic subjects had significantly increased sputum IL-6 and IL-1beta levels and airway macrophage Toll-like receptor 4, Fc(epsilon)RI, and CD23 expression; values in healthy volunteers and atopic nonasthmatic subjects showed no significant change. Atopic asthmatic subjects had significantly decreased IL-10 levels at baseline compared with healthy volunteers; IL-10 levels did not significa

  3. Agreement with Subjects in Lubukusu (United States)

    Diercks, Michael J. K.


    This dissertation examines three topics in the morphosyntax of Lubukusu (Bantu, Kenya), all of which are concerned with agreement with subjects: locative inversion, complementizer agreement, and alternative agreement effects in subject extraction. Each topic reports novel Lubukusu data which are both typologically interesting and theoretically…

  4. The Societal Nature of Subjectivity

    DEFF Research Database (Denmark)

    Olesen, Henning Salling


    . Its particular focus is on subjectivity - as an aspect of the research object and as an aspect of the research process. By the term "approach" is indicated the intrinsic connection between the theorizing of an empirical object and the reflection of the research process and the epistemic subject...

  5. The Object of the Subject

    DEFF Research Database (Denmark)

    Hansen, Brian Benjamin


    The article presents a theory of the subject, based on the work of Jacques Lacan, using the concepts of alienation, separation and liberation.......The article presents a theory of the subject, based on the work of Jacques Lacan, using the concepts of alienation, separation and liberation....

  6. Neuroglobin-overexpression reduces traumatic brain lesion size in mice

    Directory of Open Access Journals (Sweden)

    Zhao Song


    Full Text Available Abstract Background Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb is neuroprotective against hypoxic/ischemic brain injuries. In this study we tested the neuroprotective effects of Ngb over-expression against traumatic brain injury (TBI in mice. Results Both Ngb over-expression transgenic (Ngb-Tg and wild-type (WT control mice were subjected to TBI induced by a controlled cortical impact (CCI device. TBI significantly increased Ngb expression in the brains of both WT and Ngb-Tg mice, but Ngb-Tg mice had significantly higher Ngb protein levels at the pre-injury baseline and post-TBI. Production of oxidative tissue damage biomarker 3NT in the brain was significantly reduced in Ngb-Tg mice compared to WT controls at 6 hours after TBI. The traumatic brain lesion volume was significantly reduced in Ngb Tg mice compared to WT mice at 3 weeks after TBI; however, there were no significant differences in the recovery of sensorimotor and spatial memory functional deficits between Ngb-Tg and WT control mice for up to 3 weeks after TBI. Conclusion Ngb over-expression reduced traumatic lesion volume, which might partially be achieved by decreasing oxidative stress.

  7. Virulence of oral Fusobacterium nucleatum from humans and non-human primates in mice

    Directory of Open Access Journals (Sweden)

    Gaetti-Jardim Júnior Elerson


    Full Text Available The lethal action in Balb/c mice of 80 oral Fusobacterium nucleatum recovered from patients with adult periodontitis, healthy subjects or Cebus apella monkeys was studied. Mice were inoculated intraperitoneally with each bacterial inoculum of 5 x 10(8 CFU/ml. All the clinical isolates induced weight and coordinated movements loss. Pathological alterations in liver, CNS, heart, and kidney with inflammatory reactions or vascular congestion were observed. Of all the tested F. nucleatum isolates, 61.2% from periodontal patients, 57.1% from healthy subjects and 60% from monkeys, were capable of killing the mice in 48h. The clinical isolates were significantly more pathogenic than F. nucleatum ATCC 10953 or ATCC 25586. B. fragilis ATCC 23745 showed lethality against control mice. Our results suggest that LPS could be involved in lethal action against mice and it may play an important role in producing tissue damage or death of mice.

  8. Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice.

    Directory of Open Access Journals (Sweden)

    Zhe Liang

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

  9. Subject Responses to Electrochromic Windows

    Energy Technology Data Exchange (ETDEWEB)

    Clear, Robert; Inkarojrit, Vorapat; Lee, Eleanor


    Forty-three subjects worked in a private office with switchable electrochromic windows, manually-operated Venetian blinds, and dimmable fluorescent lights. The electrochromic window had a visible transmittance range of approximately 3-60%. Analysis of subject responses and physical data collected during the work sessions showed that the electrochromic windows reduced the incidence of glare compared to working under a fixed transmittance (60%) condition. Subjects used the Venetian blinds less often and preferred the variable transmittance condition, but used slightly more electric lighting with it than they did when window transmittance was fixed.

  10. Is Piaget's epistemic subject dead? (United States)

    Lawson, Anton E.

    Niaz (1990) presents arguments in favor of the retention of Piaget's epistemic subject as a theoretical construct to guide research and practice in science education and psychology. The intent of this article is to point out the weaknesses of those arguments and to suggest that the weight of evidence argues against the existence of the logical thinker postulated by Piaget. Therefore, contrary to Niaz's conclusion that the acceptance of Piaget's epistemic subject will facilitate the development of cognitive theories with greater explanatory power, the conclusion is reached that Piaget's epistemic subject is dead and that continued acceptance of this aspect of Piagetian theory would be counterproductive.


    Personal leadership promotes the ethical conduct of human research activities. Leadership entails application of one’s cognitive abilities, technical skills, and emotional intelligence during the conduct of research activities, Personal leadership assures human research subject protection....

  12. The curative activity of thioridazine on mice infected with Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Martins, Marta; Viveiros, Miguel; Kristiansen, Jette E;


    BACKGROUND: The aim of the study was to evaluate the effectiveness of thioridazine (TZ) at different dose levels on mice that had been infected intraperitoneally (i.p.) with a high dose of the Mycobacterium tuberculosis ATCC H37Rv strain. SUBJECTS AND METHODS: Groups of five female BALB/C mice were...

  13. Sub-chronic lung inflammation after airway exposures to Bacillus thuringiensis biopesticides in mice

    DEFF Research Database (Denmark)

    Barfod, Kenneth K; Poulsen, Steen Seier; Hammer, Maria;


    of BALB/c mice were i.t instilled with one bolus (3.5 × 105 or 3.4 × 106 colony forming units (CFU) per mouse) of either biopesticide. Control mice were instilled with sterile water. BALFs were collected and the inflammatory cells were counted and differentiated. The BALFs were also subjected to CFU...

  14. Subjective Illness theory and coping

    Directory of Open Access Journals (Sweden)

    Gessmann H.-W.


    Full Text Available The article presents a view of a problem of subjective illness theory in context of coping behavior. The article compiles the results of the latest studies of coping; discloses the way subjective illness theory affects the illness coping and patient's health; presents the study of differences in coping behaviour of patients at risk of heart attack and oncology. The article is recommended for specialists, concerned with psychological reasons of pathogenic processes and coping strategies of patients.

  15. MICE Particle Identification System

    CERN Document Server

    Bogomilov, M


    The Muon Ionization Cooling Experiment, MICE, at the ISIS accelerator lo- cated at the Rutherford Appleton Laboratory, UK, will be the first experiment to study muon cooling at high precision. Demonstration of muon ionization cooling is an essential step towards the construction of a neutrino factory or a muon collider. Muons are produced by pion decay in a superconducting solenoid and reach MICE with a range of emittances and momenta. The purity of the muon beam is ensured by a system of particle detectors we will briefly describe here.

  16. Subject to Form: Research Interviews, Performative Subjectivity, Professional Development (United States)

    Sarigianides, Sophia Tatiana


    In this dissertation, I analyze teacher, literacy coach and researcher subjectivities in a five-year study of on-site professional development with middle-grade Language Arts teachers in a school designated by its district and state as severely underperforming. Interested in the role of research interviews as both research method and cultural…

  17. Subject position affects EEG magnitudes. (United States)

    Rice, Justin K; Rorden, Christopher; Little, Jessica S; Parra, Lucas C


    EEG (electroencephalography) has been used for decades in thousands of research studies and is today a routine clinical tool despite the small magnitude of measured scalp potentials. It is widely accepted that the currents originating in the brain are strongly influenced by the high resistivity of skull bone, but it is less well known that the thin layer of CSF (cerebrospinal fluid) has perhaps an even more important effect on EEG scalp magnitude by spatially blurring the signals. Here it is shown that brain shift and the resulting small changes in CSF layer thickness, induced by changing the subject's position, have a significant effect on EEG signal magnitudes in several standard visual paradigms. For spatially incoherent high-frequency activity the effect produced by switching from prone to supine can be dramatic, increasing occipital signal power by several times for some subjects (on average 80%). MRI measurements showed that the occipital CSF layer between the brain and skull decreases by approximately 30% in thickness when a subject moves from prone to supine position. A multiple dipole model demonstrated that this can indeed lead to occipital EEG signal power increases in the same direction and order of magnitude as those observed here. These results suggest that future EEG studies should control for subjects' posture, and that some studies may consider placing their subjects into the most favorable position for the experiment. These findings also imply that special consideration should be given to EEG measurements from subjects with brain atrophy due to normal aging or neurodegenerative diseases, since the resulting increase in CSF layer thickness could profoundly decrease scalp potential measurements.

  18. Visual perception of spatial subjects

    Energy Technology Data Exchange (ETDEWEB)

    Osterloh, K.R.S.; Ewert, U. [Federal Institute for Materials Research and Testing (BAM), Berlin (Germany)


    Principally, any imaging technology consists of two consecutive, though strictly separated processes: data acquisition and subsequent processing to generate an image that can be looked at, either on a monitor screen or printed on paper. Likewise, the physiological process of viewing can be separated into vision and perception, though these processes are much more overlapping. Understanding the appearance of a subject requires the entire sequence from receiving the information carried e.g. by photons up to an appropriate processing leading to the perception of the subject shown. As a consequence, the imagination of a subject is a result of both, technological and physiological processes. Whenever an evaluation of an image is critical, also the physiological part of the processing should be considered. However, an image has two dimensions in the first place and reality is spatial, it has three dimensions. This problem has been tackled on a philosophical level at least since Platon's famous discussion on the shadow image in a dark cave. The mere practical point is which structural details can be perceived and what may remain undetected depending on the mode of presentation. This problem cannot be resolved without considering each single step of visual perception. Physiologically, there are three 'tools' available to understanding the spatial structure of a subject: binocular viewing, following the course of perspective projection and motion to collect multiple aspects. Artificially, an object may be cut in various ways to display the interior or covering parts could be made transparent within a model. Samples will be shown how certain details of a subject can be emphasised or hidden depending on the way of presentation. It needs to be discussed what might help to perceive the true spatial structure of a subject with all relevant details and what could be misleading. (authors)

  19. [Psychological problems of thalassemic subjects]. (United States)

    Guasco, G; La Mantia, A; Cuniolo, A


    Analysis of psychological problems of the thalassemic subject shown with these following tests: Der Baumtest, drawing of the human figure. Moreover, we made meetings with all boys and their parents during their stay in the day-hospital. These tests have shown subjective conflicts (fear and uncertainty of future due to illness felt as aggression and fault, depressive moods and loneliness, problems of communication, hope in a magic recovery opposite to the constant discomfort of the therapeutic dependence) and relational conflicts (ambivalence towards parents, difficulties in becoming a part of the social and school environment).

  20. On philosophical subjects and methods

    Institute of Scientific and Technical Information of China (English)

    Peng Fuchun


    With the consideration of some issues in contemporary philosophy,this thesis attempts to analyze being,thinking and language as philosophical subjects,and clear up the multiple meanings for each of them.It will also inquire the traditional methods in both Chinese and Western philosophy,and those in contemporary thinking.Finally,it puts forward a theory of"the critique without principles".The thesis aims to explore a new way to solve the problems of contemporary philosophy by changing its subjects and methods.

  1. Colorful Kindergarten Mice (United States)

    Bobick, Bryna; Wheeler, Elizabeth


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

  2. Subject Departments as Professional Communities? (United States)

    Visscher, Adrie J.; Witziers, Bob


    A growing body of literature suggests that when schools become professional communities there are expected benefits in terms of teacher learning, school improvement and student achievement. In this article the concept of professional communities is examined for certain subject departments in Dutch secondary schools. The authors report on research…

  3. Subject departments as professional communities?

    NARCIS (Netherlands)

    Visscher, Adrie J.; Witziers, Bob


    A growing body of literature suggests that when schools become professional communities there are expected benefits in terms of teacher learning, school improvement and student achievement. In this article the concept of professional communities is examined for certain subject departments in Dutch s

  4. Reliability of subjective wound assessment

    NARCIS (Netherlands)

    M.C.T. Bloemen; P.P.M. van Zuijlen; E. Middelkoop


    Introduction: Assessment of the take of split-skin graft and the rate of epithelialisation are important parameters in burn surgery. Such parameters are normally estimated by the clinician in a bedside procedure. This study investigates whether this subjective assessment is reliable for graft take a

  5. Changes in Dictionary Subject Matter

    DEFF Research Database (Denmark)

    Nielsen, Sandro


    The general content of the three editions of the Duden dictionary has undergone few changes. The most substantial changes are the addition of syllabification and the deletion of antonomy in respect of lemmata in the second and third editions. The concept of dictionary subject matter is questioned...

  6. Subjectivity, objectivity, and triangular space. (United States)

    Britton, Ronald


    The author reviews his ideas on subjectivity, objectivity, and the third position in the psychoanalytic encounter, particularly in clinical work with borderline and narcissistic patients. Using the theories of Melanie Klein and Wilfred Bion as a basis, the author describes his concept of triangular space. A case presentation of a particular type of narcissistic patient illustrates the principles discussed.

  7. Russia needs the Subjective Philosophy

    Directory of Open Access Journals (Sweden)

    S. Z. Gontcharov


    Full Text Available Based on the comparative analysis of different kinds of philosophic thinking, the paper reveals the advantages of subjective philosophy – the most adequate universal essentiality of socialized human being, opening the prospects for Russia as the creative society of cultural spontaneous activity. Objective principle of thinking is limited by the logic of outward definition. According to the above logic, people are regarded as tiny parts of social mechanism, the objects of manipulation. Separating action from spontaneous activity, object changes from self-alteration of human subject, executive functions from norm-creating ones brings about alienated practices and such social situation that makes individuals perceive their own existence as alien non- existence, or opposing existence.Subjectivity is a form of social activity regarding individuals and groups according to their ability in self-definition, self-organizing, self-control, norm-creating, as well as their actual rights and duties in social spheres of needs and objectives, and their feasible power over forces of nature and society. Subjective philosophy perceives the material production as the means for cultivating wholesome and spontaneously active individuals due to educational fundamentality and cultural prosperity. Accordingly, accumulation of capital turns into accumulation of culture and personal creativity growth. The results of the undertaken analysis and its conclusions can be implemented in developing creative anthropological bases for philosophy, pedagogy, psychology, economics, political science, as well as the relating discipline teaching. 

  8. Youth Homelessness and Individualised Subjectivity (United States)

    Farrugia, David


    This article aims to contribute to understandings of youth homelessness and subjectivity by analysing identity construction in terms of young people's negotiation of the structural and institutional environment of youth homelessness. I suggest that while existing literature on this topic concentrates mainly on micro-social encounters, the…

  9. Subjectivity, individuality and singularity in children: a socially constituted subject

    Directory of Open Access Journals (Sweden)

    Alessandra Del Ré


    Full Text Available Considering the hypothesis that Bakhtin and his Circle‟s reflections can help us think about issues involving the field of Language Acquisition, in addition to the fact that there are only a few works developed within this perspective in Brazil, in this article, we intend to discuss the notions of “subject”, “subjectivity”,“individuality” and “singularity”, drawing on Bakhtin‟s theory. Thus, in order to make this discussion clearer, we bring data from the speech of young children, from 1.8 to 3 years old, who were filmed in natural contexts interacting with their parents and relatives. From these data, we could verify, among other things, that children, as individuals who constitute themselves as subjects in and throughlanguage, bring marks to their discourse, revealing their subjectivity (through lexical, morphological, syntactic or genre choices.

  10. Protective Effects of Overexpression of bcl-xl Gene on Local Cerebral Infarction in Transgenic Mice Undergoing Permanent Occlusion of Middle Cerebral Artery

    Institute of Scientific and Technical Information of China (English)

    Furong WANG; Yongsheng JIANG; Suming ZHANG; Wenwu XIAO; Suiqiang ZHU


    In order to investigate the protective effects of the overexpression of bcl-xl gene on local cerebral infarction in the transgenic mice subject to permanent occlusion of middle cerebral artery, the models of bcl-xl transgenic mice were established and subjected to cerebral infarction by intralu- minal occlusion of the middle cerebral artery. The infarct volume and the neurological scores were observed and comparison between the wild type mice and the transgenic mice was made. It was found that the infarct volume and the neurological scores in the transgenic mice were significantly decreased as compared with those in the wild type mice. It was suggested that the overexpression of bcl-xl gene in transgenic mice could reduce the infarct volume and improve the neurological function of the mice.

  11. Mice Drawer System (United States)

    Cancedda, Ranieri


    The Mice Drawer System (MDS) is an Italian Space Agency (ASI) facility which is able to support mice onboard the International Space Station during long-duration exploration missions (from 100 to 150-days) by living space, food, water, ventilation and lighting. Mice can be accommodated either individually (maximum 6) or in groups (4 pairs). MDS is integrated in the Space Shuttle middeck during transportation (uploading and downloading) to the ISS and in an EXPRESS Rack in Destiny, the US Laboratory during experiment execution. Osteoporosis is a debilitating disease that afflicts millions of people worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton. This bone loss experienced by astronauts is similar to osteoporosis in the elderly population. MDS will help investigate the effects of unloading on transgenic (foreign gene that has been inserted into its genome to exhibit a particular trait) mice with the Osteoblast Stimulating Factor-1, OSF-1, a growth and differentiation factor, and to study the genetic mechanisms underlying the bone mass pathophysiology. MDS will test the hypothesis that mice with an increased bone density are likely to be more protected from osteoporosis, when the increased bone mass is a direct effect of a gene involved in skeletogenesis (skeleton formation). Osteoporosis is a debilitating disease that afflicts millions worldwide. One of the physiological changes experienced by astronauts during space flight is the accelerated loss of bone mass due to the lack of gravitational loading on the skeleton, a loss that is similar to osteoporosis in the elderly population on Earth. Osteoblast Stimulating Factor-1 (OSF-1), also known as pleiotrophin (PTN) or Heparin-Binding Growth- Associated Molecule (HB-GAM) belongs to a family of secreted heparin binding proteins..OSF-1 is an extracellular matrix-associated growth and

  12. Using Dragonflies as Common, Flexible & Charismatic Subjects for Teaching the Scientific Process (United States)

    Switzer, Paul V.


    Biology laboratories are usually designed around convenient and available subjects. For example, for animal laboratories "Daphnia magna," "Drosophila melanogaster," frogs, rats, and mice are common animals that are relatively easy to obtain, relatively cheap, and consequently lend themselves well to laboratory experimentation. On many campuses, …

  13. Objective and subjective sleep quality

    DEFF Research Database (Denmark)

    Baandrup, Lone; Glenthøj, Birte Yding; Jennum, Poul Jørgen


    and subjective sleep quality during benzodiazepine discontinuation and whether sleep variables were associated with benzodiazepine withdrawal. Eligible patients included adults with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder and long-term use of benzodiazepines in combination...... with antipsychotics. All participants gradually tapered the use of benzodiazepines after randomization to add-on treatment with melatonin versus placebo. Here we report a subsample of 23 patients undergoing sleep recordings (one-night polysomnography) and 55 patients participating in subjective sleep quality ratings....... Melatonin had no effect on objective sleep efficiency, but significantly improved self-reported sleep quality. Reduced benzodiazepine dosage at the 24-week follow-up was associated with a significantly decreased proportion of stage 2 sleep. These results indicate that prolonged-release melatonin has some...



    Buyukkoyuncu, Maria


    Gertrudis Gómez de Avellaneda's short story, “La dama de Amboto” (TheDame of Mt. Amboto), is classified under the genre of Romantic legends.The authoress develops a fictive narrative in which the theme, characters andmotives inscribe themselves perfectly in the discourse of canonicalRomanticism. However, the reading of this text in the light of the theories offeminist criticism exposes to us a discourse in which develop and take shapea whole network of subject matter and na...

  15. Abnormal Metabolite in Alcoholic Subjects, (United States)


    coated with 3Z Carbowax 20 M. Serum proteins were removed by precipitation with 0.5 M percholoric acid. The clear, protein -free supernatant was...this study included alcoholic hepatitis or cirrhosis of the liver in 29. of the alcoholic subjects; diabetes mellitus in 8 and Korsakoff’s syndrome in ethanol, and who according to the history had been two days without any alcohol intake . DISCUSSION The source of the 2,3-butanediol found in the

  16. Neuroglobin over expressing mice

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Nyengaard, Jens R


    BACKGROUND: Stroke is a major cause of death and severe disability, but effective treatments are limited. Neuroglobin, a neuronal heme-globin, has been advocated as a novel pharmacological target in combating stroke and neurodegenerative disorders based on cytoprotective properties. Using...... thoroughly validated antibodies and oligos, we give a detailed brain anatomical characterization of transgenic mice over expressing Neuroglobin. Moreover, using permanent middle artery occlusion the effect of elevated levels of Neuroglobin on ischemic damage was studied. Lastly, the impact of mouse strain...... genetic background on ischemic damage was investigated. PRINCIPAL FINDINGS: A four to five fold increase in Neuroglobin mRNA and protein expression was seen in the brain of transgenic mice. A β-actin promoter was used to drive Neuroglobin over expression, but immunohistochemistry and in situ hybridization...

  17. The MICE PID Instrumentation

    CERN Document Server

    Bonesini, M


    The international Muon Ionization Cooling Experiment (MICE) will carry out a systematic investigation of ionization cooling of a muon beam. As the emittance measurement will be done on a particle-by-particle basis, sophisticated beam instrumentation is needed to measure particle coordinates and timing vs RF. A PID system based on three time-of-flight stations, two Aerogel Cerenkov detectors and a KLOE-like calorimeter has been constructed in order to keep beam contamination ($e, \\pi$) well below 1%. The MICE time-of-flight system will measure timing with a resolution better than 70 ps per plane, in a harsh environment due to high particle rates, fringe magnetic fields and electron backgrounds from RF dark current.

  18. Psychopharmacological Studies in Mice. (United States)

    Matsuda, Toshio


    Since 1998, when the laboratory of Medicinal Pharmacology was established in the Graduate School of Pharmaceutical Sciences, Osaka University, I have been interested in psychopharmacological research topics. During this period, we identified a number of novel regulatory mechanisms that control the prefrontal dopamine system through functional interaction between serotonin1A and dopamine D2 receptors or between serotonin1A and σ1 receptors. Our findings suggest that strategies that enhance the prefrontal dopamine system may have therapeutic potential in the treatment of psychiatric disorders. We also found that environmental factors during development strongly impact the psychological state in adulthood. Furthermore, we clarified the pharmacological profiles of the acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine, providing novel insights into their mechanisms of action. Finally, we developed the female encounter test, a novel method for evaluating motivation in mice. This simple method should help advance future psychopharmacological research. In this review, we summarize the major findings obtained from our recent studies in mice.

  19. Backward disequilibrium in elderly subjects

    Directory of Open Access Journals (Sweden)

    Patrick Manckoundia


    Full Text Available Patrick Manckoundia1,2, France Mourey1,2, Dominic Pérennou2,3, Pierre Pfitzenmeyer1,21Department of Internal Medicine and Geriatrics, University Hospital, Dijon, France; 2INSERM/ERIT-M 0207 Motricity-Plasticity University of Burgundy, Dijon, France; 3Department of Neurological Rehabilitation, University Hospital, Dijon, FranceAbstract: Backward disequilibrium is observed frequently in daily clinical practice. However, there are no epidemiological data concerning this postural disorder. Defined by a posterior position of the centre of mass with respect to the base of support, backward disequilibrium is abnormal postural behavior, usually characterized by a posterior trunk tilt in standing and sitting positions, which predisposes subjects to backward falls. Many afflictions whether they are somatic (degenerative, ischemic and traumatic brain lesions, psychosomatic (psychomotor disadaptation syndrome, confinement to bed, nonuse situations or psychological (depression can cause backward disequilibrium. A vicious circle of falls, and loss of autonomy can arise and this is the main consequence of backward disequilibrium. Thus, in this paper, we review backward disequilibrium in elderly subjects with regard to the causes, consequences, assessment, and management.Keywords: backward disequilibrium, balance, elderly subject, falls, posture

  20. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. (United States)

    Miyakawa, Tsuyoshi; Leiter, Lorene M; Gerber, David J; Gainetdinov, Raul R; Sotnikova, Tatyana D; Zeng, Hongkui; Caron, Marc G; Tonegawa, Susumu


    Calcineurin (CN), a calcium- and calmodulin-dependent protein phosphatase, plays a significant role in the central nervous system. Previously, we reported that forebrain-specific CN knockout mice (CN mutant mice) have impaired working memory. To further analyze the behavioral effects of CN deficiency, we subjected CN mutant mice to a comprehensive behavioral test battery. Mutant mice showed increased locomotor activity, decreased social interaction, and impairments in prepulse inhibition and latent inhibition. In addition, CN mutant mice displayed an increased response to the locomotor stimulating effects of MK-801. Collectively, the abnormalities of CN mutant mice are strikingly similar to those described for schizophrenia. We propose that alterations affecting CN signaling could comprise a contributing factor in schizophrenia pathogenesis.

  1. Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice

    Institute of Scientific and Technical Information of China (English)

    Tamao Nishihara; Shinji Tamura; Norio Hayashi; Hiroyasu Iishi; Iichiro Shimornura; Miyako Baba; Morihiro Matsuda; Masahiro Inoue; Yasuko Nishizawa; Atsunori Fukuhara; Hiroshi Arald; Shinji Kihara; Tohru Funahashi


    AIM: To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model, and to determine the con-tribution of adiponectin deficiency to colorectal cancer development and proliferation. METHODS: We examined the influence of adiponectin deficiency on colorectal carcinogenesis induced by the administration of azoxymethane (AOM) (7.5 mg/kg, in-traperitoneal injection once a week for 8 wk), by using adiponectin-knockout (KO) mice. RESULTS: At 53 wk after the first AOM treatment, KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type (WT) mice, although the tumor incidence was not different between WT and KO mice. KO mice showed increased cell proliferation of colorec-tal tumor cells, which correlated with the expression levels of cyclooxygenase-2 (COX-2) in the colorectal tumors. In addition, KO mice showed higher incidence and frequency of liver tumors after AOI treatment. Thirteen percent of WT mice developed liver tumors, and these WT mice had only a single tumor. In contrast, 50% of K.O mice developed liver tumors, and 58% of these KO mice had multiple tumors. CONCLUSION: Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice. This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.

  2. Subjective measures of unconscious knowledge. (United States)

    Dienes, Zoltán


    The chapter gives an overview of the use of subjective measures of unconscious knowledge. Unconscious knowledge is knowledge we have, and could very well be using, but we are not aware of. Hence appropriate methods for indicating unconscious knowledge must show that the person (a) has knowledge but (b) does not know that she has it. One way of determining awareness of knowing is by taking confidence ratings after making judgments. If the judgments are above baseline but the person believes they are guessing (guessing criterion) or confidence does not relate to accuracy (zero-correlation criterion) there is evidence of unconscious knowledge. The way these methods can deal with the problem of bias is discussed, as is the use of different types of confidence scales. The guessing and zero-correlation criteria show whether or not the person is aware of knowing the content of the judgment, but not whether the person is aware of what any knowledge was that enabled the judgment. Thus, a distinction is made between judgment and structural knowledge, and it is shown how the conscious status of the latter can also be assessed. Finally, the use of control over the use of knowledge as a subjective measure of judgment knowledge is illustrated. Experiments using artificial grammar learning and a serial reaction time task explore these issues.

  3. [Child's subjectivity in postmodern times]. (United States)

    Lejarraga, Horacio


    From mid ´50s onwards, we witness a change of paradigm in the Western world: the expression of a historical shift from modernity to postmodernity. This new era includes a strong influence of the media on the population, a change from a lineal sense of time to a virtual, punctual one, and a flooding of overwhelming amount of information, mostly irrelevant, broadcasted in a de-contextualized, synchronic, fragmented and senseless fashion. This new age is characterized, above all, by the destitution of the State, the meta- institution source of legitimacy of all modern institutions: citizenship, factory, and mainly, School, an essential determinant this last one in the construction process of child subjectivity. Having lost its modeling power, the School loses its modern meaning, becoming thus a mere physical space in which pupils meet, but where general, transcendent rules, norms and values cannot be built, as in fact happened in modern times. According to Corea and Lewkowicz, school becomes an empty shed in which rules have to be built all the time, and become valid only for a particular occasion. These changes necessarily influence child subjectivity, the way they feel, they behave, and they "live" in contemporary society. Pediatricians have to be aware and try to understand these changes, so that we can help children, and, in doing so, to build a better world for them.

  4. [Dynamic posturography in normal subjects]. (United States)

    Salami, A; Guglielmetti, G; Bindi, G F; Dellepiane, M


    The relative lack of data on the dynamic posturography led us to start a study in order to give our contributions to the standardization of M1, M2, M3, response parameters in normal subjects. Our research was carried out on 35 normal subjects aged 21 to 50. All of them were standing in Romberg's position on a Tönnies model board in a normally lit and ventilated room. We performed two tests: the first one open-eyed staring at no point, the second, 5 minutes later, closed-eyed. The EMG signals were obtained by surface electrodes on triceps sural and front tibial muscles. The EMG recording was determined by a "tilt" movement of the board at a steady speed of 50 per sec. and 4 wide. We use a XT 286 IBM computer with "T POST" software for checking and testing the data. Our results showed a significant variation in the value of the duration parameter in open-eyed and closed-eyed tests. Latency and area values were inferior to those obtained by other authors, except for Diener and Dichgans (3) whose results differ in latency value only.

  5. MPD in Telomerase Null Mice (United States)


    telomere dysfunctional mice will further fuel the genomic instability generated from progressive Figure 5 5FU treated telomere dysfunction bone...marrow has increased megakaryocytic colonies. Equal number of bone marrow cells from the 5FU treated mice of the various indicated cohorts are...We treated the cohorts of the G4 mTerc mutant mice with telomere dysfunction and normal G0 controls with 5FU at (50mg/kg body weight) once every

  6. Subjective wellbeing, health, and ageing. (United States)

    Steptoe, Andrew; Deaton, Angus; Stone, Arthur A


    Subjective wellbeing and health are closely linked to age. Three aspects of subjective wellbeing can be distinguished-evaluative wellbeing (or life satisfaction), hedonic wellbeing (feelings of happiness, sadness, anger, stress, and pain), and eudemonic wellbeing (sense of purpose and meaning in life). We review recent advances in the specialty of psychological wellbeing, and present new analyses about the pattern of wellbeing across ages and the association between wellbeing and survival at older ages. The Gallup World Poll, a continuing survey in more than 160 countries, shows a U-shaped relation between evaluative wellbeing and age in high-income, English speaking countries, with the lowest levels of wellbeing in ages 45-54 years. But this pattern is not universal. For example, respondents from the former Soviet Union and eastern Europe show a large progressive reduction in wellbeing with age, respondents from Latin America also shows decreased wellbeing with age, whereas wellbeing in sub-Saharan Africa shows little change with age. The relation between physical health and subjective wellbeing is bidirectional. Older people with illnesses such as coronary heart disease, arthritis, and chronic lung disease show both increased levels of depressed mood and impaired hedonic and eudemonic wellbeing. Wellbeing might also have a protective role in health maintenance. In an analysis of the English Longitudinal Study of Ageing, we identify that eudemonic wellbeing is associated with increased survival; 29·3% of people in the lowest wellbeing quartile died during the average follow-up period of 8·5 years compared with 9·3% of those in the highest quartile. Associations were independent of age, sex, demographic factors, and baseline mental and physical health. We conclude that the wellbeing of elderly people is an important objective for both economic and health policy. Present psychological and economic theories do not adequately account for the variations in patterns

  7. Persimmon leaf flavonoid induces brain ischemic tolerance in mice

    Institute of Scientific and Technical Information of China (English)

    Mingsan Miao; Xuexia Zhang; Linan Wang


    The persimmon leaf has been shown to improve cerebral ischemic outcomes; however, its mechanism of action remains unclear. In this study, mice were subjected to 10 minutes of ischemic preconditioning, and persimmon leaf flavonoid was orally administered for 5 days. Results showed that the persimmon leaf flavonoid significantly improved the content of tissue type plasminogen activator and 6-keto prostaglandin-F1 α in the cerebral cortex, decreased the content of thromboxane B2, and reduced the content of plasminogen activator inhibitor-1 in mice. Following optical microscopy, persimmon leaf flavonoid was also shown to reduce cell swelling and nuclear hyperchromatism in the cerebral cortex and hippocampus of mice. These results suggested that persimmon leaf flavonoid can effectively inhibit brain thrombosis, improve blood supply to the brain, and relieve ischemia-induced pathological damage, resulting in brain ischemic tolerance.

  8. High dynamic range subjective testing (United States)

    Allan, Brahim; Nilsson, Mike


    This paper describes of a set of subjective tests that the authors have carried out to assess the end user perception of video encoded with High Dynamic Range technology when viewed in a typical home environment. Viewers scored individual single clips of content, presented in High Definition (HD) and Ultra High Definition (UHD), in Standard Dynamic Range (SDR), and in High Dynamic Range (HDR) using both the Perceptual Quantizer (PQ) and Hybrid Log Gamma (HLG) transfer characteristics, and presented in SDR as the backwards compatible rendering of the HLG representation. The quality of SDR HD was improved by approximately equal amounts by either increasing the dynamic range or increasing the resolution to UHD. A further smaller increase in quality was observed in the Mean Opinion Scores of the viewers by increasing both the dynamic range and the resolution, but this was not quite statistically significant.

  9. Scoring Rules for Subjective Probability Distributions

    DEFF Research Database (Denmark)

    Harrison, Glenn W.; Martínez-Correa, Jimmy; Swarthout, J. Todd;

    report the true subjective probability of a binary event, even under Subjective Expected Utility. To address this one can “calibrate” inferences about true subjective probabilities from elicited subjective probabilities over binary events, recognizing the incentives that risk averse agents have...

  10. Empathy is moderated by genetic background in mice.

    Directory of Open Access Journals (Sweden)

    QiLiang Chen

    Full Text Available Empathy, as originally defined, refers to an emotional experience that is shared among individuals. When discomfort or alarm is detected in another, a variety of behavioral responses can follow, including greater levels of nurturing, consolation or increased vigilance towards a threat. Moreover, changes in systemic physiology often accompany the recognition of distressed states in others. Employing a mouse model of cue-conditioned fear, we asked whether exposure to conspecific distress influences how a mouse subsequently responds to environmental cues that predict this distress. We found that mice are responsive to environmental cues that predict social distress, that their heart rate changes when distress vocalizations are emitted from conspecifics, and that genetic background substantially influences the magnitude of these responses. Specifically, during a series of pre-exposure sessions, repeated experiences of object mice that were exposed to a tone-shock (CS-UCS contingency resulted in heart rate deceleration in subjects from the gregarious C57BL/6J (B6 strain, but not in subjects from the less social BALB/cJ (BALB strain. Following the pre-exposure sessions, subjects were individually presented with the CS-only for 5 consecutive trials followed by 5 consecutive pairings of the CS with the UCS. Pre-exposure to object distress increased the freezing responses of B6 mice, but not BALB mice, on both the CS-only and the CS-UCS trials. These physiological and behavioral responses of B6 mice to social distress parallel features of human empathy. Our paradigm thus has construct and face validity with contemporary views of empathy, and provides unequivocal evidence for a genetic contribution to the expression of empathic behavior.

  11. Automatic Assessment of Global Craniofacial Differences between Crouzon mice and Wild-type mice in terms of the Cephalic Index

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Oubel, Estanislao; Frangi, Alejandro F.;


    This paper presents the automatic assessment of differences between Wild-Type mice and Crouzon mice based on high-resolution 3D Micro CT data. One factor used for the diagnosis of Crouzon syndrome in humans is the cephalic index, which is the skull width/length ratio. This index has traditionally...... been computed by time-consuming manual measurements that prevent large-scale populational studies. In this study, an automatic method to estimate cephalic index for this mouse model of Crouzon syndrome is presented. The method is based on constructing a craniofacial atlas of Wild-type mice...... and then registering each mouse to the atlas using affine transformations. The skull length and width are then measured on the atlas and propagated to all subjects to obtain automatic measurements of the cephalic index. The registration accuracy was estimated by RMS landmark errors. Even though the accuracy...

  12. NQO1-Knockout Mice Are Highly Sensitive to Clostridium Difficile Toxin A-Induced Enteritis. (United States)

    Nam, Seung Taek; Hwang, Jung Hwan; Kim, Dae Hong; Lu, Li Fang; Hong, Ji; Zhang, Peng; Yoon, I Na; Hwang, Jae Sam; Chung, Hyo Kyun; Shong, Minho; Lee, Chul-Ho; Kim, Ho


    Clostridium difficile toxin A causes acute gut inflammation in animals and humans. It is known to downregulate the tight junctions between colonic epithelial cells, allowing luminal contents to access body tissues and trigger acute immune responses. However, it is not yet known whether this loss of the barrier function is a critical factor in the progression of toxin A-induced pseudomembranous colitis. We previously showed that NADH:quinone oxidoreductase 1 (NQO1) KO (knockout) mice spontaneously display weak gut inflammation and a marked loss of colonic epithelial tight junctions. Moreover, NQO1 KO mice exhibited highly increased inflammatory responses compared with NQO1 WT (wild-type) control mice when subjected to DSS-induced experimental colitis. Here, we tested whether toxin A could also trigger more severe inflammatory responses in NQO1 KO mice compared with NQO1 WT mice. Indeed, our results show that C. difficile toxin A-mediated enteritis is significantly enhanced in NQO1 KO mice compared with NQO1 WT mice. The levels of fluid secretion, villus disruption, and epithelial cell apoptosis were also higher in toxin A-treated NQO1 KO mice compared with WT mice. The previous and present results collectively show that NQO1 is involved in the formation of tight junctions in the small intestine, and that defects in NQO1 enhance C. difficile toxin A-induced acute inflammatory responses, presumably via the loss of epithelial cell tight junctions.

  13. Authentic subjectivity and social transformation

    Directory of Open Access Journals (Sweden)

    Michael O'Sullivan


    Full Text Available Holiness in the Christian tradition has often been understood in a way that devalues embodiment and practical engagement with the world of one’s time. The latter understanding, for example, led to Marx’s critique and repudiation of Christianity. Both interpretations of holiness can be understood as mistaken efforts to express the dynamism for authenticity in contextualised human subjectivity. Vatican 2 opposed both views by addressing itself to all people of good will, declaring that everyone was called to holiness, and that authentic Christian identity involved solidarity with the world of one’s time, especially those who are poor. Vatican 2, therefore, provided an authoritative faith foundation for holiness expressed through social commitment and for viewing social commitment on the part of people of good will in whatever state of life as a form of holiness. This vision was also the conviction of leading spirituality writers of the period, like Thomas Merton, and inspired liberation theologians and the Latin American Catholic bishops at their conference in Medellín a few years after the Council. The argument of this article is that the emergence and development of a non-dualist Christian spirituality is grounded methodologically in the correct appropriation of the common innate dynamism for authenticity in concrete human persons and lived spiritual experiences consistent with and capable of enhancing this dynamism.

  14. Social stress in male mice impairs long-term antiviral immunity selectively in wounded subjects

    NARCIS (Netherlands)

    de Groot, Johanna; Boersma, Wim J.A.; Scholten, Jan Willem; Koolhaas, Jaap M.


    An important property of the antiviral immune response is its time-dependent character. Beginning with a few antigen-specific cells upon infection, it evolves to a stage where there is an abundance of antigen-specific cells and antibodies that are needed to clear the pathogen, and ends with circulat

  15. Chronic Intermittent Fasting Improves Cognitive Functions and Brain Structures in Mice


    Liaoliao Li; Zhi Wang; Zhiyi Zuo


    Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day) fasting or high fat diet (45% caloric supplied by fat) for 11 months. Mice on intermittent fasting had better learning and me...

  16. Effect of Leukocytes Transfer on the Induction of Liver Damage after Renal Ischemia- Reperfusion in Inbred Mice

    Directory of Open Access Journals (Sweden)

    Hossein Khastar


    Full Text Available Introduction: Renal ischemia-reperfusion (IR induces organ damage in remote organs such as liver, brain and lung. The aim of this study was to assess the role of leukocytes in the induction of liver damage after renal IR injury.Methods: Inbred mice were subjected to either sham operation or bilateral renal IR injury (60 min ischemia followed by 3h reperfusion. Mice were then anesthetized for collection of leukocytes by heart puncture. Isolated leukocytes were transferred to two other groups: intact recipient mice that received leukocytes from IR mice and intact recipient mice that received leukocytes from sham-operated control mice. After 24h, recipient mice were anesthetized and blood and hepatic samples were collected.Results: Alanine aminotransferase (ALT, aspartate aminotransferase (AST and hepatic malondialdehyde (MDA increased significantly in intact recipient mice that received leukocytes from IR mice in comparison to intact recipient mice receiving leukocytes from sham-operated control mice. In addition, loss of normal liver architecture, cytoplasmic vacuolization and focal infiltration of leukocytes were observed.Conclusion: These results suggest that leukocytes are one of the possible factors that contribute to liver damage after renal IR injury and this damage is partly due to the induction of oxidative stress.

  17. Increased seizure susceptibility in mice 30 days after fluid percussion injury.

    Directory of Open Access Journals (Sweden)

    Sanjib eMukherjee


    Full Text Available Traumatic brain injury (TBI has been reported to increase seizure susceptibility and also contribute to the development of epilepsy. However, the mechanistic basis of the development of increased seizure susceptibility and epilepsy is not clear. Though there is substantial work done using rats, data are lacking regarding the use of mice in the fluid percussion injury (FPI model. It is unclear if mice, like rats, will experience increased seizure susceptibility following FPI. The availability of a mouse model of increased seizure susceptibility after FPI would provide a basis for the use of genetically modified mice to study mechanism(s of the development of post-traumatic epilepsy. Therefore, this study was designed to test the hypothesis that, mice subjected to a FPI develop increased seizure susceptibility to a subconvulsive dose of the chemoconvulsant, pentylenetetrazole (PTZ. Three groups of mice were used: FPI, sham and naïve controls. On day thirty after FPI, mice from the three groups were injected with PTZ. The results showed that FPI mice exhibited an increased severity, frequency and duration of seizures in response to PTZ injection compared with the sham and naïve control groups. Histopathological assessment was used to characterize the injury at one, three, seven and thirty days after FPI. The results show that mice subjected to the FPI had a pronounced lesion and glial response that was centered at the FPI focus and peaked at three days. By thirty days, only minimal evidence of a lesion is observed, although there is evidence of a chronic glial response. These data are the first to demonstrate an early increase in seizure susceptibility following fluid percussion injury in mice. Therefore, future studies can incorporate transgenic mice into this model to further elucidate mechanisms of TBI-induced increases in seizure susceptibility.

  18. Weaver mutant mice exhibit long-term learning deficits under several measures of instrumental behavior. (United States)

    Derenne, Adam; Arsenault, Matthew L; Austin, David P; Weatherly, Jeffrey N


    Homozygous weaver mutant mice (wv/wv) exhibit symptoms that parallel Parkinson's disease, including motor deficits and the destruction of dopaminergic neurons as well as degeneration in the cerebellum and hippocampus. To develop a more complete behavioral profile of these organisms, groups of wv/wv, wv/+ mice and C57BL/6 mice were observed on a within-subjects basis under a fixed-interval schedule of reinforcement, a differential-reinforcement-of-low-rate-of-responding schedule, and a discrimination task in which a saccharin solution and tap water were concurrently available from two food cups. Under both reinforcement schedules, the wv/wv mice responded as frequently as the comparison subjects, but they responded in a manner that was inappropriate to the contingencies. Rather than respond with increasing frequency as the upcoming reinforcer became temporally proximate, wv/wv mice responded with decreasing probability as a function of the time since the previous reinforcer. Under the discrimination task, the wv/wv mice, unlike the controls, obtained saccharin over tap water at the level of chance. The findings suggest that weaver mutant mice express learning deficits similar to those found in other dopamine-deficient organisms.




    The paper presents the research on social roots of New European concept of subject. The authors found the basic reason of subject concept change in economical practice of Venetian republic. It was the image of Venetian merchant which not only became the catalyzer of feudal order, but determined the connotations of subsequent New European philosophy of subject.

  20. Sex Education as a Transversal Subject (United States)

    Rabelo, Amanda Oliveira; Pereira, Graziela Raupp; Reis, Maria Amélia; Ferreira, António G.


    Currently, sex education is in many countries a transversal subject, in which the school becomes a privileged place for the implementation of policies that aim at promoting "public health." Its design as a cross-cutting subject envisages fostering the dissemination of these subjects in all pedagogical and curricular fields; however, we…

  1. Promoting Subjective Well-Being at Work (United States)

    Russell, Joyce E. A.


    Research has clearly shown the relationship between subjective well-being and work performance, even though there is debate over the causality of that relationship (i.e., does subjective well-being cause higher work performance or does greater work performance lead to subjective well-being?). Regardless, researchers and practitioners would agree…

  2. Immune function and survival in a long-lived mouse strain subjected to undernutrition. (United States)

    Gerbase-DeLima, M; Liu, R K; Cheney, K E; Mickey, R; Walford, R L


    Functional immune changes were monitored in populations of the long-lived C57BL/6J strain of mice which were subjected to dietary restriction from time of weaning or subjected to such restriction both before and after weaning, along with the appropriate control populations. Responses to T and B cell mitogens (PHA, Con-A, pokeweed, bacterial lipopolysaccharide, and PPD), to injected sheep red blood cells, and measurement of skin allograft rejection rates were followed. Early in life, restricted mice appear immunosuppressed, as judged by all these parameters. Skin allograft rejection remained suppressed until relatively late in life. Other responses tended to reverse from the earlier pattern; by mid-life restricted mice responded better than controls. Dietary restriction profoundly affects the immune system. Mice on such regimes display anatomic and certain immune functional changes which suggest that the immune system may mature less rapidly and stay "younger" longer than in the controls. Furthermore, dietary restriction results in prolongation of life span.

  3. Inborn anemias in mice

    Energy Technology Data Exchange (ETDEWEB)

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


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

  4. Transgenic mice in developmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, R.P.


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

  5. Transgenic mice in developmental toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Woychik, R.P.


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

  6. Mice, men and MHC supertypes

    DEFF Research Database (Denmark)

    Lundegaard, Claus


    vaccine formulations. Toxoplasma gondii, an intracellular parasite, causes severe neurologic and ocular disease in congenitally infected and immunocompromised individuals. No protective vaccine exists against human toxoplasmosis. However, studies with mice have revealed immunodominant cytotoxic T...

  7. Owls and larks in mice

    Directory of Open Access Journals (Sweden)

    Martina ePfeffer


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

  8. The effect of isoflurane anaesthesia and vasectomy on circulating corticosterone and ACTH in BALB/c mice

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten Rosenmaj; Kalliokoski, Otto; Teilmann, Anne Charlotte;


    The use of blood corticosterone and faecal corticosterone metabolites as biomarkers of post-surgical stress and pain in laboratory animals has increased during the last decade. However, many aspects of their reliability in laboratory mice remain uninvestigated. This study investigated serum...... compared to anaesthetised mice not treated with dexamethasone. Thus, dexamethasone effectively inhibited the corticosterone response in the anaesthetised-only mice, but not in the mice subjected to surgery. In conclusion, both isoflurane anaesthesia and vasectomy during isoflurane anaesthesia resulted...... in an increase in serum glucocorticoids, but the negative feedback mechanism of newly operated mice, was altered. This may have consequences for the interpretation of glucocorticoids measurements as a biomarker of post-surgical stress in mice....

  9. Protective effect of berberine on serum glucose levels in non-obese diabetic mice. (United States)

    Chueh, Wei-Han; Lin, Jin-Yuarn


    Among the active components in traditional anti-diabetic herbal plants, berberine which is an isoquinoline alkaloid exhibits promising potential for its potent anti-inflammatory and hypoglycemic effects. However, the berberine effect on serum glucose levels in type 1 diabetes (T1D) subjects still remains unknown. This study investigated berberine's effects on serum glucose levels using non-obese diabetic (NOD) mice that spontaneously develop T1D. The NOD mice were randomly divided into four groups, administered water with 50, 150, and 500 mg berberine/kg bw, respectively, through 14 weeks. ICR mice were also selected as a species control group to compare with the NOD mice. Changes in body weight, oral glucose challenge, and serum glucose levels were determined to identify the protective effect of berberine on T1D. After the 14-week oral supplementation, berberine decreased fasting serum glucose levels in NOD mice close to the levels in normal ICR mice in a dose dependent manner. Serum berberine levels showed a significantly (Pberberine-administered NOD mice. Our results suggested that berberine supplemented at appropriate doses for 14 weeks did not cause toxic side effects, but improved hyperglycemia in NOD mice.

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

    Directory of Open Access Journals (Sweden)

    Koshimizu Hisatsugu


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

  11. The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

    Directory of Open Access Journals (Sweden)

    Mami Shimizu

    Full Text Available Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic β cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C. In addition, injection of high-dose poly(I: C to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

  12. Polytrauma Increases Susceptibility to Pseudomonas Pneumonia in Mature Mice. (United States)

    Turnbull, Isaiah R; Ghosh, Sarbani; Fuchs, Anja; Hilliard, Julia; Davis, Christopher G; Bochicchio, Grant V; Southard, Robert E


    Pneumonia is the most common complication observed in patients with severe injuries. Although the average age of injured patients is 47 years, existing studies of the effect of injury on the susceptibility to infectious complications have focused on young animals, equivalent to a late adolescent human. We hypothesized that mature adult animals are more susceptible to infection after injury than younger counterparts. To test this hypothesis, we challenged 6 to 8-month-old mature mice to a polytrauma injury followed by Pseudomonas aeruginosa pneumonia and compared them to young (8-10-week-old) animals. We demonstrate that polytrauma injury increases mortality from pneumonia in mature animals (sham-pneumonia 21% vs. polytrauma-pneumonia 62%) but not younger counterparts. After polytrauma, pneumonia in mature mice is associated with higher bacterial burden in lung, increased incidence of bacteremia, and elevated levels of bacteria in the blood, demonstrating that injury decreases the ability to control the infectious challenge. We further find that polytrauma did not induce elevations in circulating cytokine levels (TNF-alpha, IL-6, KC, and IL-10) 24  h after injury. However, mature mice subjected to polytrauma demonstrated an exaggerated circulating inflammatory cytokine response to subsequent Pseudomonas pneumonia. Additionally, whereas prior injury increases LPS-stimulated IL-6 production by peripheral blood leukocytes from young (8-10-week-old) mice, injury does not prime IL-6 production by cell from mature adult mice. We conclude that in mature mice polytrauma results in increased susceptibility to Pseudomonas pneumonia while priming an exaggerated but ineffective inflammatory response.

  13. Comprehensive behavioral analysis of cluster of differentiation 47 knockout mice.

    Directory of Open Access Journals (Sweden)

    Hisatsugu Koshimizu

    Full Text Available Cluster of differentiation 47 (CD47 is a member of the immunoglobulin superfamily which functions as a ligand for the extracellular region of signal regulatory protein α (SIRPα, a protein which is abundantly expressed in the brain. Previous studies, including ours, have demonstrated that both CD47 and SIRPα fulfill various functions in the central nervous system (CNS, such as the modulation of synaptic transmission and neuronal cell survival. We previously reported that CD47 is involved in the regulation of depression-like behavior of mice in the forced swim test through its modulation of tyrosine phosphorylation of SIRPα. However, other potential behavioral functions of CD47 remain largely unknown. In this study, in an effort to further investigate functional roles of CD47 in the CNS, CD47 knockout (KO mice and their wild-type littermates were subjected to a battery of behavioral tests. CD47 KO mice displayed decreased prepulse inhibition, while the startle response did not differ between genotypes. The mutants exhibited slightly but significantly decreased sociability and social novelty preference in Crawley's three-chamber social approach test, whereas in social interaction tests in which experimental and stimulus mice have direct contact with each other in a freely moving setting in a novel environment or home cage, there were no significant differences between the genotypes. While previous studies suggested that CD47 regulates fear memory in the inhibitory avoidance test in rodents, our CD47 KO mice exhibited normal fear and spatial memory in the fear conditioning and the Barnes maze tests, respectively. These findings suggest that CD47 is potentially involved in the regulation of sensorimotor gating and social behavior in mice.

  14. The structural neural substrate of subjective happiness. (United States)

    Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Kubota, Yasutaka; Sawada, Reiko; Yoshimura, Sayaka; Toichi, Motomi


    Happiness is a subjective experience that is an ultimate goal for humans. Psychological studies have shown that subjective happiness can be measured reliably and consists of emotional and cognitive components. However, the neural substrates of subjective happiness remain unclear. To investigate this issue, we used structural magnetic resonance imaging and questionnaires that assessed subjective happiness, the intensity of positive and negative emotional experiences, and purpose in life. We found a positive relationship between the subjective happiness score and gray matter volume in the right precuneus. Moreover, the same region showed an association with the combined positive and negative emotional intensity and purpose in life scores. Our findings suggest that the precuneus mediates subjective happiness by integrating the emotional and cognitive components of happiness.

  15. Palatable meal anticipation in mice.

    Directory of Open Access Journals (Sweden)

    Cynthia T Hsu

    Full Text Available The ability to sense time and anticipate events is a critical skill in nature. Most efforts to understand the neural and molecular mechanisms of anticipatory behavior in rodents rely on daily restricted food access, which induces a robust increase of locomotor activity in anticipation of daily meal time. Interestingly, rats also show increased activity in anticipation of a daily palatable meal even when they have an ample food supply, suggesting a role for brain reward systems in anticipatory behavior, and providing an alternate model by which to study the neurobiology of anticipation in species, such as mice, that are less well adapted to "stuff and starve" feeding schedules. To extend this model to mice, and exploit molecular genetic resources available for that species, we tested the ability of wild-type mice to anticipate a daily palatable meal. We observed that mice with free access to regular chow and limited access to highly palatable snacks of chocolate or "Fruit Crunchies" avidly consumed the snack but did not show anticipatory locomotor activity as measured by running wheels or video-based behavioral analysis. However, male mice receiving a snack of high fat chow did show increased food bin entry prior to access time and a modest increase in activity in the two hours preceding the scheduled meal. Interestingly, female mice did not show anticipation of a daily high fat meal but did show increased activity at scheduled mealtime when that meal was withdrawn. These results indicate that anticipation of a scheduled food reward in mice is behavior, diet, and gender specific.

  16. Linkage disequilibrium in wild mice.

    Directory of Open Access Journals (Sweden)

    Cathy C Laurie


    Full Text Available Crosses between laboratory strains of mice provide a powerful way of detecting quantitative trait loci for complex traits related to human disease. Hundreds of these loci have been detected, but only a small number of the underlying causative genes have been identified. The main difficulty is the extensive linkage disequilibrium (LD in intercross progeny and the slow process of fine-scale mapping by traditional methods. Recently, new approaches have been introduced, such as association studies with inbred lines and multigenerational crosses. These approaches are very useful for interval reduction, but generally do not provide single-gene resolution because of strong LD extending over one to several megabases. Here, we investigate the genetic structure of a natural population of mice in Arizona to determine its suitability for fine-scale LD mapping and association studies. There are three main findings: (1 Arizona mice have a high level of genetic variation, which includes a large fraction of the sequence variation present in classical strains of laboratory mice; (2 they show clear evidence of local inbreeding but appear to lack stable population structure across the study area; and (3 LD decays with distance at a rate similar to human populations, which is considerably more rapid than in laboratory populations of mice. Strong associations in Arizona mice are limited primarily to markers less than 100 kb apart, which provides the possibility of fine-scale association mapping at the level of one or a few genes. Although other considerations, such as sample size requirements and marker discovery, are serious issues in the implementation of association studies, the genetic variation and LD results indicate that wild mice could provide a useful tool for identifying genes that cause variation in complex traits.

  17. Nocturnal bruxing events in healthy geriatric subjects. (United States)

    Okeson, J P; Phillips, B A; Berry, D T; Cook, Y; Paesani, D; Galante, J


    Thirty healthy geriatric subjects were studied during a single night of sleep in a sleep laboratory. Unilateral masseter muscle activity was recorded in addition to the standard polysomnographic study. The geriatric subjects in this study exhibited fewer bruxing events than other subjects reported in the literature. Certain conditions that have not been previously investigated, such as sleep position, type of bruxing event, and relationship to the state of the dentition, are reported.

  18. The Analgesic Effect of Pineapple Fruit Juice on Mice

    Directory of Open Access Journals (Sweden)

    Ainul Atiqah binti Hilmi


    Full Text Available Background: Pain is a feeling stimulated by the nervous system which can be suppressed by giving an analgesic agent. Some studies revealed that pineapples have an analgesic effect. This study aim was to determine analgesic effect of pineapple on mice. Methods: In this experimental study, the effect was examined by using a writhing method on the 28 male mice. Subjects were divided into 4 groups with 7 mice each. The control group received aquades and other groups received pineapple fruit juice with 20%, 40% and 80% concentration with the dosage of 10 mL/kg/body weight. After 30 minutes, 3% acetic acid was injected intraperitoneally to induce pain. Writhing responseswere observed every 5 minutes for 30 minutes. Results: The result for mean of total writhing reaction was 2.39±0.40, 1.92±0.40, 1.50±2.13, 1.66±0.11 respectively for group 1 to 4. These data indicated a significant decrease of total writhing response in mice with 20%, 40% and 80% concentration compared to control group (p=0.023;p=0.000 and p=0.000 respectively. Most optimal concentration was40% with the protective percentage equal to 71.8%. Conclusion: Pineapple fruit juice concentrations (20%, 40%, and 80%has an analgesic effect with the most optimal concentration of 40%.

  19. Toxoplasma gondii: sexual transmission in mice


    Asgari, Qasem; Keshavarz Valian, Hossein; REZAEIAN, Mostafa; SHOJAEE, Saeedeh; Mehrabani, Davood


    This study was performed to evaluate sexual transmission of Toxoplasma gondii in mice. RH strain tachyzoites were intraperitoneally inoculated into 10 Balb/C male mice and after 48 h, their semen were collected from epididymis and examined by giemsa staining and PCR. Twenty Balb/C female mice mated with four infected male mice four times and any mating time was 48 h whilst 20 female control mice mated with four uninfected male mice for 8 days. Female mate choice was assessed using a three-cha...

  20. Innovativeness and Subjective Well-Being (United States)

    Binder, Martin


    What are the effects of innovativeness on well-being? This paper argues that research on subjective well-being has progressed to a point where measures of subjective well-being (or: happiness) can usefully be employed to assess the welfare effects of innovative change. Based on a discussion of the prospects and pitfalls associated with subjective…

  1. Preposed Subjects in Questions: Some Considerations (United States)

    Lipski, John M.


    The preposing of subject pronouns in questions containing an interrogative word has become common in several Caribbean countries. Use of preposing with "tu,""usted" and "ustedes" is discussed, including its relation to final "s" aspirated or dropped, preservation of morphological oppositions, and increased use of subject pronouns. (CHK)

  2. Inferring Beliefs as Subjectively Imprecise Probabilities

    DEFF Research Database (Denmark)

    Andersen, Steffen; Fountain, John; Harrison, Glenn W.;


    We propose a method for estimating subjective beliefs, viewed as a subjective probability distribution. The key insight is to characterize beliefs as a parameter to be estimated from observed choices in a well-defined experimental task and to estimate that parameter as a random coefficient. The e...... probabilities are indeed best characterized as probability distributions with non-zero variance....

  3. Essays on subjective expectations and stated preferences

    NARCIS (Netherlands)

    Bissonnette, L.


    This dissertation's unifying theme is the study of subjective data, with particular emphasis on subjective expectations. Eliciting expectations of survey respondents has become a frequent practice in economics over the last decade. This thesis presents studies of such data, analyzing expectations of

  4. Binocular Vision Function Analysis of 75 Subjects

    Institute of Scientific and Technical Information of China (English)

    Ya-ping Gao; Hai-ying Wang; Xiu-rong Tang; Ying Zhang; Xiao-tong Huo


    @@ We randomly chose 75 subjects; 34 men and 41 womenwith an average age of 21 years. Our study method included subject interviews, and evamuination of their refractive and binocular vision functions.We recorded, basic biographical data, medical history, family history, lifestyle factors that relate to their use of vision and history of wearing glasses.

  5. Objective versus Subjective Assessment of Methylphenidate Response (United States)

    Manor, Iris; Meidad, Sheera; Zalsman, Gil; Zemishlany, Zvi; Tyano, Sam; Weizman, Abraham


    Subjective improvement-assessment in attention deficit/hyperactivity disorder (ADHD), following a single dose of methylphenidate (MPH) was compared to performance on the Test-of-Variables-of-Attention (TOVA). Self-perception was assessed with the clinical-global-impression-of-change (CGI-C). Participants included 165 ADHD subjects (M:F ratio…

  6. Subjective Expected Utility Theory with "Small Worlds"

    DEFF Research Database (Denmark)

    Gyntelberg, Jacob; Hansen, Frank

    which is a more general construction than a state space. We retain preference axioms similar in spirit to the Savage axioms and obtain, without abandoning linearity of expectations, a subjective expected utility theory which allows for an intuitive distinction between risk and uncertainty. We also...... obtain separation of subjective probability and utility as in the state space models....

  7. Subject/Author Index 1968-1992. (United States)

    Kupidura, Eva, Ed.; Kupidura, Peter, Ed.


    This 25-year index contains annotations of feature articles by subject and by author. Representative subjects include basic education, development education, empowerment, human rights, lifelong education, peace education, popular education, rural development, social/political action, technological advancement, and transformative research. Articles…

  8. Translator’s Subjectivity From Philosophical Hermeneutics

    Institute of Scientific and Technical Information of China (English)

    徐水乃; 陈兆东


    Traditional translation studies attach great importance to the linguistic level,focusing on translation methods,translation principles and translation standards and the like,while the subject of the translation activity—the translator was neglected,the position of the translator was edged and the subjectivity of the translator was overlooked.With the appearance of the"cultural

  9. Perception, Curriculum, and Subject Matter: Reforming Instruction (United States)

    Hoang, Thienhuong


    The purpose of this study is to illuminate the reciprocal relation between teacher leaders' perception and practice to subject matter. The researcher conducted interviews and observations of 30 teachers from 8 urban elementary schools. The data and results evidently identify those teachers' views of subject matter both shaped and were shaped by…

  10. Interest in Subject Matter: The Mathematics Predicament (United States)

    Rotgans, Jerome I.; Schmidt, Henk G.


    The present study sought to explore (a) the extent to which certain school subjects are perceived "sui generis" more interesting than others and (b) the extent to which students' interest in a subject is related to their study choices. A mixed-methods approach was chosen in which an individual interest questionnaire and an open-ended…

  11. Sliding Subject Positions: Knowledge and Teacher Educators (United States)

    Brown, Tony; Rowley, Harriet; Smith, Kim


    In England, adjustments to policy in teacher education have had implications for how subject knowledge is understood and for how job descriptions are defined. That is, the interface between teacher educator and subject knowledge representation has been changing. This paper reports on a wider study that considers the experience of university…

  12. Virtual materiality, potentiality and gendered subjectivity

    DEFF Research Database (Denmark)

    Søndergaard, Dorte Marie

    How do we conceptualize virtual materiality, in terms of for instance avatars and weapons in computer games, virtual discourse, subjectivity and the enactment of masculinity as phenomena intra-acting with real life materiality, discourse, subjectivity and masculinity in children’s everyday lives...

  13. "Wo Es War": Psychoanalysis, Marxism, and Subjectivity (United States)

    Cho, Daniel


    Subjectivity, for Descartes, emerged when he doubted the veracity of his knowledge. Instead of truth, he counted this knowledge to be inherited myth. Cartesian subjectivity has been helpful for forming a critical education predicated on doubting ideology and hegemony. But Marx indicates a very different kind of knowledge in his analysis of…

  14. The Anatomy of Subjective Well-being

    NARCIS (Netherlands)

    Praag, van B.M.S.; Frijters, P.; Ferrer-i-Carbonell, A.


    This paper contributes to the literature on Subjective Well-Being by taking into account different aspects of life, called domains, such as health, financial situation, job, leisure, housing, and environment. We postulate a two-Iayer model where individual total Subjective Well-Being depends on the

  15. Liquid Hydrogen Absorber for MICE

    Energy Technology Data Exchange (ETDEWEB)

    Ishimoto, S.; Suzuki, S.; Yoshida, M.; Green, Michael A.; Kuno, Y.; Lau, Wing


    Liquid hydrogen absorbers for the Muon Ionization Cooling Experiment (MICE) have been developed, and the first absorber has been tested at KEK. In the preliminary test at KEK we have successfully filled the absorber with {approx}2 liters of liquid hydrogen. The measured hydrogen condensation speed was 2.5 liters/day at 1.0 bar. No hydrogen leakage to vacuum was found between 300 K and 20 K. The MICE experiment includes three AFC (absorber focusing coil) modules, each containing a 21 liter liquid hydrogen absorber made of aluminum. The AFC module has safety windows to separate its vacuum from that of neighboring modules. Liquid hydrogen is supplied from a cryocooler with cooling power 1.5 W at 4.2 K. The first absorber will be assembled in the AFC module and installed in MICE at RAL.

  16. Progress of the MICE experiment

    CERN Document Server

    Bonesini, M


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

  17. Concordance in mate choice in female mound-building mice. (United States)

    Beigneux, Emilie; Féron, Christophe; Gouat, Patrick


    Females must evaluate male quality to perform mate choice. Since females generally base their selection on different male features, individual females may differ in their choice. In this study, we show that concordance between females in mate choice decisions may arise without any experimental maximization of a particular attractive trait. Choice tests were performed in mound-building mice, Mus spicilegus, a monogamous species. Body odours of two male donors were presented to 12 female subjects individually. To determine female choice, the same pair of males was presented three times to a female. Four different pairs of male body odours were used. Male donors, not related to females, were selected at random in our polymorphic breeding stock. Using this two-way choice design, female mice displayed a clear choice and had a similar preference for particular males.

  18. Subjective Wellbeing Among Adults with Diabetes

    DEFF Research Database (Denmark)

    Holmes-Truscott, Elizabeth; Browne, Jessica L; Pouwer, Frans


    duration, body mass index, number of diabetes-related complications, and depression). Furthermore, adults with type 2 diabetes using insulin to manage their condition report the lowest levels of subjective wellbeing, and are also most likely to report dissatisfaction with their current health......This study examines the subjective wellbeing of Australian adults with diabetes who completed the Diabetes MILES—Australia survey, investigating by diabetes type and treatment, and by comparing with the subjective wellbeing of the general Australian adult population. In addition, the extent...... to which depression and socio-demographic factors account for subjective wellbeing is investigated. People with type 1 or type 2 diabetes have significantly lower subjective wellbeing compared to the general population, even after controlling for covariates (demographic and socio-economic status, diabetes...

  19. NF-κB Signaling in the Brain of Autistic Subjects

    Directory of Open Access Journals (Sweden)

    Mazhar Malik


    Full Text Available Autism is a neurodevelopmental disorder characterized by problems in communication, social skills, and repetitive behavior. Recent studies suggest that apoptotic and inflammatory mechanisms may contribute to the pathogenesis of this disorder. Nuclear factor-κB (NF-κB is an important gene transcriptional factor involved in the mediation of inflammation and apoptosis. This study examined the activities of the NF-κB signaling pathway in the brain of autistic subjects and their age-matched controls. The NF-κB activation is also determined in the brain of BTBR mice, which is a promising animal model for study of pathogenic mechanisms responsible for autism. Our results showed that the level of IKKα kinase, which phosphorylates the inhibitory subunit IκBα, is significantly increased in the cerebellum of autistic subjects. However, the expression and phosphorylation of IκBα are not altered. In addition, our results demonstrated that the expression of NF-κB (p65, and the phosphorylation/activation of NF-κB (p65 at Ser536 are not significantly changed in the cerebellum and cortex of both autistic subjects and BTBR mice. Our findings suggest that the NF-κB signaling pathway is not disregulated in the brain of autistic subjects and thus may not be significantly involved in the processes of abnormal inflammatory responses suggested in autistic brain.

  20. Tissue distribution of tritiated digoxin and quabain in mice. [Testing tritium-labeled radiopharmaceuticals in mice

    Energy Technology Data Exchange (ETDEWEB)

    Klopper, J.F.; Atkins, H.L.


    Tissue concentration of tritiated digoxin in human subjects appears to be selective in that after a single dose of the radioactive tracer a myocardial concentration of digoxin on an average 24 to 30 times higher than the serum concentration is reached. In patients studied 3.5 to 84 hours after administration of tritiated digoxin, the dose in the heart was found to vary between 1.95 to 4.83 percent. Should it be possible to label digoxin or another cardiac glycoside with a suitable gamma-emitting tracer, its use as a cardiac imaging agent should thus be feasible. This study was undertaken to determine the tissue distribution in mice of tritiated digoxin at various time intervals post injection; and to determine if these values showed any correlation to the previously determined human data. A preliminary study in mice using /sup 3/H-digitoxin revealed no selective uptake in the heart with high uptakes in the liver and gut. Since ouabain has a more rapid clinical onset of action than digoxin, its tissue distribution was included in the study and compared to that of digoxin.

  1. Piracetam counteracts the effects of amitriptyline on inhibitory avoidance in CD1 mice. (United States)

    Everss, Estrella; Arenas, M Carmen; Vinader-Caerols, Concepción; Monleón, Santiago; Parra, Andrés


    The purpose of the present work was to study the effects of amitriptyline on animal cognition in relation to some characteristics of its therapeutic effects. The modulation of acute and chronic effects of amitriptyline on inhibitory avoidance in male and female mice by piracetam was investigated. In Experiment 1, mice were subjected to the training phase of inhibitory avoidance conditioning 60 min after acute piracetam (100 mg/kg) or physiological saline administration. Immediately after the behavioural task, they received a single injection of the tricyclic antidepressant amitriptyline (30 mg/kg) or physiological saline. Twenty-four hours later, subjects were tested for avoidance. In Experiment 2, the same doses of amitriptyline and piracetam were chronically administered. Mice were subjected to the training phase of inhibitory avoidance on the 22nd day, and to the test phase 24 h later. Forty-five minutes after test, subjects explored the elevated plus-maze for 5 min in order to assess whether the effects of amitriptyline on avoidance performance may reflect general behavioural changes. Results obtained were that: (a) acute and chronic amitriptyline impaired inhibitory avoidance of male and female mice, (b) piracetam counteracted the effect of acutely administered amitriptyline on inhibitory avoidance, and (c) piracetam counteracted the effects of chronically administered amitriptyline in males but not females in the same learning task. These effects do not seem to be mediated by non-specific drug effects on spontaneous motor activity or anxiety.

  2. Evidence that radio-sensitive cells are central to skin-phase protective immunity in CBA/Ca mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni as well as in naive mice protected with vaccine serum

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, V.S.; McLaren, D.J. (National Inst. for Medical Research, London (UK))


    Naive CBA/Ca mice and CBA/ca mice vaccinated 4 weeks previously with radiation-attenuated cercariae of Schistosoma mansoni were subjected to 550 rad of whole body (gamma) irradiation and then challenged 3 days later with normal cercariae. The perfusion recovery data showed that this procedure reduced the primary worm burden in naive mice by 22% and the challence worm burden in vaccinated mice by 82%. Irradiation also ablated the peripheral blood leucocytes of both mouse groups by 90-100% at the time of challenge. Histological data revealed that such treatment caused a dramatic change in number, size and leucocyte composition of cutaneous inflammatory skin reactions that characterize challenged vacccinated mice and are known to entrap invading larvae; cutaneous eosinophils were preferentially abolished by this treatment. Polyvaccine mouse serum that conferred protection passively upon naive recipient mice, failed to protect naive/irradiated mice when administered by the same protocol. Distraction of macrophages by treatment of mice with silica did not affect the establishment of a primary worm burden and reduced the protection exhibited by vaccinated mice by only 16%. These data indicade that radio-sensitive cells are important to both innate and specific acquired resistance in this mouse model and that macrophages contribute only marginally to the expression of vaccine immunity. (author).

  3. Animal neuropsychology: validation of the Intra-Dimensional Extra-Dimensional set shifting task for mice. (United States)

    Garner, Joseph P; Thogerson, Collette M; Würbel, Hanno; Murray, James D; Mench, Joy A


    Research in animal neuropsychology is providing an exciting new generation of behavioral tests for mice that promise to overcome many of the limitations of current high-throughput testing, and provide direct animal homologues of clinically important measures in human research. Set shifting tasks are some of the best understood and widely used human neuropsychological tasks, with clinical relevance to traumatic brain injury, schizophrenia, autism, obsessive compulsive disorder, trichotillomania, and many other disorders. Here we report the first successful modification of a human set shifting neuropsychological task, the Intra-Dimensional Extra-Dimensional (IDED) task, for use with mice. We presented mice with a series of compound discrimination and reversal tasks where one stimulus dimension consistently cued reward. Task performance improved with a new set of compound stimuli, as did reversal performance--indicating the formation of a cognitive-attentional set. We then overtrained a subset of the mice, and presented control and overtrained mice with a new compound discrimination where a novel stimulus dimension cued reward. As is the case in human control subjects, control mice persisted in responding to the now-incorrect stimulus dimension, performing poorly on this extra-dimensional shift compared with the previous intra-dimensional shift, thereby validating the task as a measure of set shifting. Furthermore, overtrained mice were impaired on this extra-dimensional shift compared with controls, further validating the task. The advantages and disadvantages of the IDED task compared to high-throughput approaches are discussed.

  4. Chronic intermittent fasting improves cognitive functions and brain structures in mice.

    Directory of Open Access Journals (Sweden)

    Liaoliao Li

    Full Text Available Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day fasting or high fat diet (45% caloric supplied by fat for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice. Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals.

  5. Detour Behavior of Mice Trained with Transparent, Semitransparent and Opaque Barriers (United States)

    Juszczak, Grzegorz R.; Miller, Michal


    Detour tasks are commonly used to study problem solving skills and inhibitory control in canids and primates. However, there is no comparable detour test designed for rodents despite its significance for studying the development of executive skills. Furthermore, mice offer research opportunities that are not currently possible to achieve when primates are used. Therefore, the aim of the study was to translate the classic detour task to mice and to compare obtained data with key findings obtained previously in other mammals. The experiment was performed with V-shaped barriers and was based on the water escape paradigm. The study showed that an apparently simple task requiring mice to move around a small barrier constituted in fact a challenge that was strongly affected by the visibility of the target. The most difficult task involved a completely transparent barrier, which forced the mice to resolve a conflict between vision and tactile perception. The performance depended both on the inhibitory skills and on previous experiences. Additionally, all mice displayed a preference for one side of the barrier and most of them relied on the egocentric strategy. Obtained results show for the first time that the behavior of mice subjected to the detour task is comparable to the behavior of other mammals tested previously with free-standing barriers. This detailed characterization of the detour behavior of mice constitutes the first step toward the substitution of rodents for primates in laboratory experiments employing the detour task. PMID:27588753

  6. Chronic intermittent fasting improves cognitive functions and brain structures in mice. (United States)

    Li, Liaoliao; Wang, Zhi; Zuo, Zhiyi


    Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day) fasting or high fat diet (45% caloric supplied by fat) for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice). Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals.

  7. Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil.

    Directory of Open Access Journals (Sweden)

    Diansan Su

    Full Text Available Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2% for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE, choline acetylase (ChAT and α7 nicotinic receptor (α7-nAChR were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane.

  8. Physiological and Pathological Impact of Blood Sampling by Retro-Bulbar Sinus Puncture and Facial Vein Phlebotomy in Laboratory Mice

    DEFF Research Database (Denmark)

    Teilmann, Anne Charlotte; Nygaard Madsen, Andreas; Holst, Birgitte;


    collected for histopathological analysis to assess the degree of tissue trauma. Mice subjected to facial vein phlebotomy had significantly elevated plasma corticosterone levels at both time points in contrast to mice subjected to retro-bulbar sinus puncture, which did not. Both groups of sampled mice lost...... extensive tissue trauma after both facial vein phlebotomy and retro-bulbar sinus puncture. This study demonstrates that both blood sampling methods have a considerable impact on the animals' physiological condition, which should be considered whenever blood samples are obtained.......Retro-bulbar sinus puncture and facial vein phlebotomy are two widely used methods for blood sampling in laboratory mice. However, the animal welfare implications associated with these techniques are currently debated, and the possible physiological and pathological implications of blood sampling...

  9. The ideal subject distance for passport pictures. (United States)

    Verhoff, Marcel A; Witzel, Carsten; Kreutz, Kerstin; Ramsthaler, Frank


    In an age of global combat against terrorism, the recognition and identification of people on document images is of increasing significance. Experiments and calculations have shown that the camera-to-subject distance - not the focal length of the lens - can have a significant effect on facial proportions. Modern passport pictures should be able to function as a reference image for automatic and manual picture comparisons. This requires a defined subject distance. It is completely unclear which subject distance, in the taking of passport photographs, is ideal for the recognition of the actual person. We show here that the camera-to-subject distance that is perceived as ideal is dependent on the face being photographed, even if the distance of 2m was most frequently preferred. So far the problem of the ideal camera-to-subject distance for faces has only been approached through technical calculations. We have, for the first time, answered this question experimentally with a double-blind experiment. Even if there is apparently no ideal camera-to-subject distance valid for every face, 2m can be proposed as ideal for the taking of passport pictures. The first step would actually be the determination of a camera-to-subject distance for the taking of passport pictures within the standards. From an anthropological point of view it would be interesting to find out which facial features allow the preference of a shorter camera-to-subject distance and which allow the preference of a longer camera-to-subject distance.

  10. Turning Back the Aging Clock -- in Mice (United States)

    ... 164250.html Turning Back the Aging Clock -- in Mice Elderly rodents treated with cellular therapy regained lost fur, became ... 2017 THURSDAY, March 23, 2017 (HealthDay News) -- Aging mice became more youthful following a new cellular therapy ...

  11. Modified Protein Improves Vitiligo Symptoms in Mice (United States)

    ... 2013 (historical) Modified Protein Improves Vitiligo Symptoms in Mice Altering a key protein involved in the development ... pigmentation loss associated with the skin disorder in mice, according to recent research funded by the NIH’s ...

  12. Nanoparticles Ease Aching Joints in Mice (United States)

    ... page: Nanoparticles Ease Aching Joints in Mice Treatment might one ... News) -- New research in mice suggests that tiny nanoparticles might one day be a better way to ...

  13. Subjective performance evaluations and employee careers

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Lange, Fabian; Kriechell, Ben

    Firms commonly use supervisor evaluations to assess the performance of employees who work in complex environments. Doubts persist whether their subjective nature invalidates using these performance measures to learn about careers of individuals and to inform theory in personnel economics. We...... examine personnel data from six large companies and establish how subjective ratings, interpreted as ordinal rankings of employee performances within narrowly defined peer-groups, correlate with objective career outcomes. We find many similarities across firms in how subjective ratings correlate with base...

  14. Progress on Cherenkov Reconstruction in MICE

    CERN Document Server

    Kaplan, Daniel M; Rajaram, Durga; Winter, Miles; Cremaldi, Lucien; Sanders, David; Summers, Don


    Two beamline Cherenkov detectors (Ckov-a,-b) support particle identification in the MICE beamline. Electrons and high-momentum muons and pions can be identified with good efficiency. We report on the Ckov-a,-b performance in detecting pions and muons with MICE Step I data and derive an upper limit on the pion contamination in the standard MICE muon beam.

  15. Subjective Vitality as Mediator and Moderator of the Relationship between Life Satisfaction and Subjective Happiness (United States)

    Uysal, Recep; Satici, Seydi Ahmet; Satici, Begüm; Akin, Ahmet


    In this study, the mediator and moderator effects of subjective vitality on the relationship between life satisfaction and subjective happiness were investigated. The participants were 378 university students who completed a questionnaire package that included the Subjective Vitality Scale, the Satisfaction with Life Scale, and the Subjective…

  16. Knowing the Subject Matter of a Secondary-School Science Subject (United States)

    Deng, Zongyi


    This paper examines the fundamental yet largely neglected distinction between school subjects and academic disciplines in the discourse on teachers' specialized subject-matter knowledge. It analyses and critiques the curricular positions embedded in that discourse in the light of five possible relationships between school subjects and academic…

  17. Changing from Sears to LC Subject Headings. (United States)

    Schadlich, Thomas


    Briefly discusses factors that might induce a library to consider changing from Sears to Library of Congress subject headings and provides a quantitative evaluation of the compatibility of the two. (Author/FM)

  18. Cardiovascular risk factors in subjects with psoriasis

    DEFF Research Database (Denmark)

    Jensen, Peter; Thyssen, Jacob P; Zachariae, Claus


    smoking status, weight, height, waist and hip circumferences, systolic and diastolic blood pressures, resting heart rate, and plasma lipids, hemoglobin A1c, fasting glucose, and insulin levels. Results Physician-diagnosed psoriasis was reported by 238 (7.1%) of 3374 participants. There were no differences......Background Epidemiological data have established an association between cardiovascular disease and psoriasis. Only one general population study has so far compared prevalences of cardiovascular risk factors among subjects with psoriasis and control subjects. We aimed to determine the prevalence...... of cardiovascular risk factors in subjects with and without psoriasis in the general population. Methods During 2006-2008, a cross-sectional study was performed in the general population in Copenhagen, Denmark. A total of 3471 subjects participated in a general health examination that included assessment of current...

  19. Adult Playfulness, Humor Styles, and Subjective Happiness. (United States)

    Yue, Xiao D; Leung, Chun-Lok; Hiranandani, Neelam A


    Playfulness has been referred to as a disposition that involves reframing a situation to amuse others and to make the situation more stimulating and enjoyable. It may serve to shift one's perspective when dealing with environmental threats. Despite all the benefits of playfulness towards psychological well-being, it remains a largely understudied subject in psychology, particularly in Chinese societies. Hence, this study examined the association between adult playfulness, humor styles, and subjective happiness among a sample of 166 university students in Hong Kong and 159 students in Guangzhou, who completed a self-administered questionnaire, including the Short Measure for Adult Playfulness, the Chinese Humor Styles Questionnaire, and the Subjective Happiness Scale. Results showed that adult playfulness was positively correlated with affiliative humor, self-enhancing humor, and subjective happiness in both Hong Kong and Guangzhou samples. By its implication, highly playful Chinese students preferred using affiliative and self-enhancing humor to amuse themselves and others.

  20. Is Chinese as a Subject Important?

    Institute of Scientific and Technical Information of China (English)


    In January, six universities in Shanghai held independent admission tests to select students from more than 10,000 appli- cants. At four of the universities, Chinese was not a test subject or science students

  1. Cartel Stability with Subjective Detection Beliefs


    Hinloopen, Jeroen


    The condition is derived for Friedman 's trigger strategy to sustaina collusive market equilibrium as a noncooperative Nash equilibriumgiven subjective beliefs as to the antitrust authority's ability of suc-cesfully dissolving the illegal cartel.

  2. Imagery limitations in totally congenitally blind subjects. (United States)

    De Beni, R; Cornoldi, C


    Research on totally blind subjects performing tasks that involve visual imagery has often shown that they do not behave differently from matched sighted subjects, even when their blindness is congenital. If visual imagery is based on visual perception, such tasks may not required visual imagery. In the present article visual images are considered as representations maintaining some properties of visible objects and constructed on the basis of information from various sources. Owing to the absence of visual experience, the limitations of such representations are explored in a series of experiments requiring memorization of single nouns, pairs of nouns, or triplets of nouns associated with a cue noun. Recall by blind subjects was impaired when multiple interactive images (with noun pairs and triplets) are formed. The poorer recall of blind subjects reflected also loss of order information. Recall was better for both groups with locative noun cues and high-imagery targets.

  3. The Major Subjects of Cognitive Linguistics

    Institute of Scientific and Technical Information of China (English)



      Cognitive linguistics is the interdiscipline of cognitive science and linguistics, studying the interrelationship between language and law of human cognition. This paper mainly introduces its several major subjects, hoping to be helpful for some beginners.

  4. Shifting loyalties: reconsidering psychology's subject matter. (United States)

    Beckstead, Zachary


    Schwarz (IPBS: Integrative Psychology & Behavioral Science 43:3, 2009) cogently demonstrates that in conjunction with scientific conventionalism psychology has developed a rather deficient view of their subject matter: the human being. Psychology based on an impoverished notion of empirical has rendered subjectivity or 'the measuring apparatus man' invisible. As his story implicitly demonstrates, psychologists supported by a positivistic view of science (in part to be empirical) and notion of 'objectivity' have learned to trust their 'rigorous' methods instead of their participants as capable of revealing important and interesting phenomena. If we are going to take subjectivity and experience seriously there should be a cultivation of a new attitude or orientation regarding psychology's subject matter (i.e., the human being) and science. This commentary discusses Mark Freeman's (2007) argument that the first requirement of science should be 'fidelity to the phenomena' and elaborates on the implications for psychology grounded in this view of science.

  5. Personality dimensions and subjective well-being. (United States)

    Chico Librán, Eliseo


    This work examines the association between personality dimensions (extraversion and neuroticism) and subjective well-being. Subjective well-being is associated both with extraversion and neuroticism, and currently, neuroticism is generally considered the more important. A total of 368 students from the University of Rovira i Virgili completed the Extraversion and Neuroticism subscales of the revised Eysenck Personality Questionnaire (Eysenck, Eysenck, and Barrett, 1985), the Satisfaction with Life Scale (SWLS; Diener, Emmons, Larsen, and Griffin, 1985), and the Positive and Negative Affect Scale (Watson, Clark, and Tellegen, 1988). Regression analyses revealed the personality variable of neuroticism as one of the most important correlates of subjective well-being. Regression analyses also showed that 44% of the variance of subjective well-being was accounted for by neuroticism, whereas extraversion only explained 8% of the variance.

  6. Subjects of Financial Planning at an Enterprise


    Оверчук, Алла Василівна


    Subjects of financial planning have been considered, users of financial planned information have been determined as well as the analysis of information support of financial planning at an enterprise has been carried out.

  7. Braille character discrimination in blindfolded human subjects. (United States)

    Kauffman, Thomas; Théoret, Hugo; Pascual-Leone, Alvaro


    Visual deprivation may lead to enhanced performance in other sensory modalities. Whether this is the case in the tactile modality is controversial and may depend upon specific training and experience. We compared the performance of sighted subjects on a Braille character discrimination task to that of normal individuals blindfolded for a period of five days. Some participants in each group (blindfolded and sighted) received intensive Braille training to offset the effects of experience. Blindfolded subjects performed better than sighted subjects in the Braille discrimination task, irrespective of tactile training. For the left index finger, which had not been used in the formal Braille classes, blindfolding had no effect on performance while subjects who underwent tactile training outperformed non-stimulated participants. These results suggest that visual deprivation speeds up Braille learning and may be associated with behaviorally relevant neuroplastic changes.

  8. Subjective appraisal of music: neuroimaging evidence. (United States)

    Brattico, Elvira; Jacobsen, Thomas


    In the neurosciences of music, a consensus on the nature of affective states during music listening has not been reached. What is undeniable is that subjective affective states can be triggered by various and even opposite musical events. Here we review the few recent studies on the neural determinants of subjective affective processes of music, contrasted with early automatic neural processes linked to the objective universal properties of music. In particular, we focus on the evaluative judgments of music by subjects according to its aesthetic and structural values, on music-specific emotions felt by listeners, and on conscious liking. We then discuss and seek to stimulate further research on the interplay between the emotional attributes of music and the subjective cognitive, psychological, and biographic factors, such as personality traits and cognitive strategies of listening. We finally draw the neuroscientist's attention to the sociocultural context as a relevant variable to study when considering music as an aesthetic domain.

  9. Universally optimal crossover designs under subject dropout


    Zheng, Wei


    Subject dropout is very common in practical applications of crossover designs. However, there is very limited design literature taking this into account. Optimality results have not yet been well established due to the complexity of the problem. This paper establishes feasible, as well as necessary and sufficient conditions for a crossover design to be universally optimal in approximate design theory in the presence of subject dropout. These conditions are essentially linear equations with re...

  10. Are tent halls subject to property tax?

    Directory of Open Access Journals (Sweden)

    Mariusz Macudziński


    Full Text Available The presented publication is a response to currently asked questions and interpretative doubts of taxpayers and tax authorities, namely whether tent halls are subject to property tax. General issues connected with an entity and a subject of taxation of this tax are presented herein. The answer to the question asked is then provided through the qualification of constructions works and the allocation of tent halls in the proper category of the works, with the use of the current law.

  11. Subjective experience of the creative process


    Kocjan, Maja


    The subject matter of this bachelor's thesis is the creative process. In the first section I present some theoretical knowledge about creativity and the creative process found in literature. The theme of the second section of my thesis is the subjective experience of the creative process. The source of information for this part are the testimonies of artists, in particular of the two world renowned painters – Vincent van Gogh and Francis Bacon. Their statements reveal how far the creative pr...

  12. Vergence adaptation in subjects with convergence excess. (United States)

    Nilsson, Maria; Brautaset, Rune L


    The main purpose of this study was to evaluate the vergence adaptive ability in subjects diagnosed with convergence excess (CE) phoria (ie, subjects with an esophoric shift from distance to near but without an intermittent tropia at near). Vergence adaptation was measured at far and near with both base-in and base-out prisms using a "flashed" Maddox rod technique in 20 control subjects and 16 subjects with CE. In addition, accommodative adaptation and the stimulus AC/A and CA/C cross-links were measured. The AC/A and CA/C ratios were found to be high and low, respectively, and accommodative adaptation was found to be reduced in CE subjects as compared with the controls (P<0.005), all as predicted by the present theory. However, vergence adaptive ability was found to be reduced in the CE subjects at both distance and near and in response to both base-in and base-out prisms (P=0.002). This finding is not in accordance with and is difficult to reconcile with the present theory of CE.

  13. Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice


    Bahi, Amine; Dreyer, Jean-Luc


    Objective: Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP.Methods: Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were s...

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

    Directory of Open Access Journals (Sweden)

    Satoko eHattori


    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

  15. Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yani [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Leu, David [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Palo Alto Institute of Research and Education, Palo Alto, California (United States); Chui, Jennifer [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); Fike, John R. [Departments of Neurosurgery and Radiation Oncology, University of California, San Francisco, California (United States); Huang, Ting-Ting, E-mail: [Department of Neurology and Neurological Sciences, Stanford University, Stanford, California (United States); VA Palo Alto Health Care System, Palo Alto, California (United States)


    Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted.

  16. Intermittent hypoxia can aggravate motor neuronal loss and cognitive dysfunction in ALS mice.

    Directory of Open Access Journals (Sweden)

    Sung-Min Kim

    Full Text Available BACKGROUND: Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained can affect the loss of motor neurons or cognitive function in an in vivo model of ALS. OBJECTIVE: To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice. METHODS: Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation. RESULTS: Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation. CONCLUSIONS: Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in

  17. Oral Self-Administration Of EtOH In Transgenic Mice Lacking Beta-Endorphin

    Directory of Open Access Journals (Sweden)

    Stephani Allen


    Full Text Available EtOH modifies the production and/or release of endogenous opioid peptides, including -endorphin (Gianoulakis, 2004; Przewlocka et al., 1994; Schulz et al., 1980. Opioids subsequently influence the reinforcing properties of EtOH and the development of alcoholism (Terenius, 1996; Van Ree, 1996. In this study, beta-endorphin deficient mutant mice were used to examine the effects of a specific opioid peptide on EtOH consumption. Mice were obtained from The Jackson Laboratory, Bar Harbor, ME, USA. Male and female, adult naïve mice were single housed in Plexiglas cages with corn cob bedding and ad lib access to food (mouse chow and water. A two-bottle free choice EtOH oral self-administration paradigm was administered to homozygous mutant mice (void of all beta-endorphin, heterozygous mice (50% beta-endorphin expression, and sibling wildtype mice (C57BL/6J. Subjects received increasing concentrations of EtOH (0%, 3%, 6%, 12%, and 15% each given over an eight day span, and were evaluated for preference and consumption each day. Bottles were switched every other day to avoid the development of a side preference. Overall, females drank more than males. Homozygous mutant mice (KO showed decreased preference for EtOH at all concentrations, and self-administered significantly less than heterozygous mice (HT and wildtype mice (C57. The HTs had a tendency to drink the most followed by the C57s, and the KOs drank the least. These data support the hypothesis that beta-endorphin influences the reinforcing effects of EtOH.

  18. [Subjectivity sense, language and subject: a new postrationalist perspective in psychotherapy]. (United States)

    González Rey, Fernando


    This paper discusses the philosophical roots of the concept of sense in Russian philosophy and linguistic, analyzing its consequences for the social sciences, in particular for psychology. Starting from the relevance of the Vygotsky's definition of sense, through which that concept became psychological, is discussed its relevance for advancing forward in a proposal about subjectivity from a cultural historical approach. Advancing on this proposal, the concept of subjective sense is defined as a subjective unity whose focus, rather than being on the unity between word and psychological elements, as Vygotsky stated, is on the unity between symbolical processes and emotions. This theoretical account leads to a different representation of the relation between language, subject and subjectivity, which support a non rationalistic reductionism concerning subjectivity. Finally, on the basis of this non individualistic and non essentialist definition of subjectivity are discussed some of its implications for the development of a non rationalistic approach in psychotherapy.

  19. [Model of meningococcal sepsis in mice]. (United States)

    Krasnoproshina, L I; Ermakova, L G; Belova, T N; Filippov, Iu V; Efimov, D D


    The authors studied a possibility of obtaining experimental meningococcus sepsis model on mice. The use of cyclophosphane, iron compounds, yolk medium produced no significant organism. When 4--5% mucine was injected intraperitoneally together with meningococcus culture mice died with sepsis phenomena. Differences were revealed in the sensitivity of linear and mongrel mice to meningococcus infection--AKR mice proved to be more sensitive. At the same time it was found that mongrel mice weighing from 10 to 12 g could be used to induce meningococcus sepsis.

  20. Socially induced morphine pseudosensitization in adolescent mice. (United States)

    Hodgson, Stephen R; Hofford, Rebecca S; Roberts, Kris W; Wellman, Paul J; Eitan, Shoshana


    Given that social influences are among the strongest predictors of adolescents' drug use, this study examined the effect of social interaction on morphine-induced hyperlocomotion in both adolescent and adult mice. Three experimental groups of adolescent and adult male mice were examined (i) morphine-treated mice (twice daily, 10-40 mg/kg, subcutaneous), (ii) saline-injected mice housed together with the morphine-treated mice ('saline cage-mates'), and (iii) saline-injected mice housed physically and visually separated from the morphine-treated mice ('saline alone'). After the treatment period, mice were tested individually for their locomotor response to 10 mg/kg morphine (subcutaneous). Adolescent saline cage-mates, though administered morphine for the very first time, exhibited an enhanced hyperlocomotion response similar to the locomotor sensitization response exhibited by the morphine-treated mice. This was not observed in adults. In adults, there were no significant differences in morphine-induced hyperlocomotion between saline alone and saline cage-mates. As expected, morphine-treated adults and adolescents both exhibited locomotor sensitization. These results show a vulnerability to social influences in adolescent mice, which does not exist in adult mice.

  1. Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

    Directory of Open Access Journals (Sweden)

    Natalia Nuño-Lámbarri


    Full Text Available Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

  2. Extended Cognitive System and Epistemic Subject

    Directory of Open Access Journals (Sweden)

    Trybulec Barbara


    Full Text Available The concept of an extended cognitive system is central to contemporary studies of cognition. In the paper I analyze the place of the epistemic subject within the extended cognitive system. Is it extended as well? In answering this question I focus on the differences between the first and the second wave of arguments for the extended mind thesis. I argue that the position of Cognitive Integration represented by Richard Menary is much more intuitive and fruitful in analyses of cognition and knowledge than the early argument formulated by Andy Clark and David Chalmers. Cognitive Integration is compatible with virtue epistemology of John Greco’s agent reliabilism. The epistemic subject is constituted by its cognitive character composed of an integrated set of cognitive abilities and processes. Some of these processes are extended, they are a manipulation of external informational structures and, as such, they constitute epistemic practices. Epistemic practices are normative; to conduct them correctly the epistemic subject needs to obey epistemic norms embedded in the cultural context. The epistemic subject is not extended because of the casual coupling with external informational artifacts which extend his mind from inside the head and into the world. Rather, cognitive practices constitute the subject’s mind, they transform his cognitive abilities, and this is what makes the mind and epistemic subject “extended”.

  3. Visual impairment in FOXG1-mutated individuals and mice. (United States)

    Boggio, E M; Pancrazi, L; Gennaro, M; Lo Rizzo, C; Mari, F; Meloni, I; Ariani, F; Panighini, A; Novelli, E; Biagioni, M; Strettoi, E; Hayek, J; Rufa, A; Pizzorusso, T; Renieri, A; Costa, M


    The Forkead Box G1 (FOXG1 in humans, Foxg1 in mice) gene encodes for a DNA-binding transcription factor, essential for the development of the telencephalon in mammalian forebrain. Mutations in FOXG1 have been reported to be involved in the onset of Rett Syndrome, for which sequence alterations of MECP2 and CDKL5 are known. While visual alterations are not classical hallmarks of Rett syndrome, an increasing body of evidence shows visual impairment in patients and in MeCP2 and CDKL5 animal models. Herein we focused on the functional role of FOXG1 in the visual system of animal models (Foxg1(+/Cre) mice) and of a cohort of subjects carrying FOXG1 mutations or deletions. Visual physiology of Foxg1(+/Cre) mice was assessed by visually evoked potentials, which revealed a significant reduction in response amplitude and visual acuity with respect to wild-type littermates. Morphological investigation showed abnormalities in the organization of excitatory/inhibitory circuits in the visual cortex. No alterations were observed in retinal structure. By examining a cohort of FOXG1-mutated individuals with a panel of neuro-ophthalmological assessments, we found that all of them exhibited visual alterations compatible with high-level visual dysfunctions. In conclusion our data show that Foxg1 haploinsufficiency results in an impairment of mouse and human visual cortical function.

  4. Effects of ginsenosides on opioid-induced hyperalgesia in mice. (United States)

    Li, Peng; Tang, Minke; Li, Hui; Huang, Xinjie; Chen, Lei; Zhai, Haifeng


    Opioid-induced hyperalgesia (OIH) is characterized by nociceptive sensitization caused by the cessation of chronic opioid use. OIH can limit the clinical use of opioid analgesics and complicate withdrawal from opioid addiction. In this study, we investigated the effects of Re, Rg1, and Rb1 ginsenosides, the bioactive components of ginseng, on OIH. OIH was achieved in mice after subcutaneous administration of morphine for 7 consecutive days three times per day. During withdrawal (days 8 and 9), these mice were administered Re, Rg1, or Rb1 intragastrically two times per day. On the test day (day 10), mice were subjected to the thermal sensitivity test and the acetic acid-induced writhing test. Re (300 mg/kg) inhibited OIH in both the thermal sensitivity test and the acetic acid-induced writhing test. However, the Rg1 and Rb1 ginsenosides failed to prevent OIH in either test. Furthermore, Rg1 showed a tendency to aggravate OIH in the acetic acid-induced writhing test. Our data suggested that the ginsenoside Re, but not Rg1 or Rb1, may contribute toward reversal of OIH.

  5. Suspect Subjects: Affects of Bodily Regulation

    Directory of Open Access Journals (Sweden)

    Kathryn Henne


    Full Text Available There is a growing body of academic literature that scrutinises the effects of technologies deployed to surveil the physical bodies of citizens. This paper considers the role of affect; that is, the visceral and emotive forces underpinning conscious forms of knowing that can drive one’s thoughts, feelings and movements. Drawing from research on two distinctly different groups of surveilled subjects – paroled sex offenders and elite athletes – it examines the effects of biosurveillance in their lives and how their reflections reveal unique insight into how subjectivity, citizenship, harm and deviance become constructed in intimate and public ways vis-à-vis technologies of bodily regulation. Specifically, we argue, their narratives reveal cultural conditions of biosurveillance, particularly how risk becomes embodied and internalised in subjective ways.

  6. A New Kind of Subjective Trust Model

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guangwei; KANG Jianchu; LUO Ziqiang; MENG Xiangyi; FANG Peici; LI Deyi


    Based on the outstanding characteristics of Cloud Model on the process of transforming a qualitative concept to a set of quantitative numerical values, a formalized model of subjective trust is introduced by which we can transform between qualitative reputation and quantitative voting data. The present paper brings forward algorithms to compute direct trust and recommender trust. Further more, an effective similarity measuring method used to distinguish two users'reputation on knowledge level is also proposed. The given model properly settles the uncertainty and fuzziness properties of subjective trust which is always the weakness of traditional subjective trust model, and provides a step in the direction of proper understanding and definition of human trust.

  7. Psychology--tensions between objectivity and subjectivity. (United States)

    Klempe, Sven Hroar


    The self is often defined in terms of its presentational appearances. This may easily end up in a denial of the internal aspects of the self, which is very often related to a tendency to avoid the tension between the internal and the external, but also between subjectivity and objectivity. In this paper this ambition is regarded in a historical perspective, in which Fichte and Hegel both represent attempts at abolishing the tension, whereas Kant and Kierkegaard represent the opposite. History shows that an eradication of the tension between subjectivity and objectivity implies a deterioration of psychology as well. Thus the conclusion is that psychology is primarily to be defined in terms of the tension between subjectivity and objectivity, which requires an accurate understanding and the inclusion of both of them.

  8. Microvascular retinopathy in subjects without diabetes

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Kessel, Line; Borch-Johnsen, Knut


    tolerance testing, clinical and laboratory examinations, non-invasive ocular lens fluorometry and seven-field fundus photography. Results: Retinopathy was present in 8.3% (CI(95) 6.3-10.3%) of subjects. Higher systolic blood pressure (SBP) (p = 0.032), increasing body mass index (BMI) (p = 0.014) and wider......Purpose: Retinal vascular lesions such as microaneurysms and haemorrhages, while typical of diabetic retinopathy, are also seen in subjects without diabetes where they are associated with elevated cardiovascular mortality. In theory, these lesions could be a consequence of past hyperglycaemia. We...... examined the prevalence and risk factors for retinopathy, including lens fluorescence, a biomarker of cumulative life-time glycaemia in adults without diabetes. Methods: Cross-sectional population-based study of 711 subjects without diabetes (WHO 1999 criteria) aged 30-60 years, including oral glucose...

  9. Subject Indexing of children's and juvenile literature

    Directory of Open Access Journals (Sweden)

    Sara Fedeli


    Full Text Available This article tries to highlight some issues related to subject indexing applied to fiction, with a focus on how it could be implemented on children's literature and then also on adults fiction. In fact, Italy is one of the country that does not add subject indexing to fiction, and despite the numerous and ongoing debates on this topic there is not any National plan to solve this issue. Users who requires more this kind of research are children and teenagers: children’s literature, in fact, is involved in some interesting steps on subject indexing applied to fiction, even if this initiative is carried out in an independent way by individual library networks.

  10. Sound quality and subjective hearing perception

    Institute of Scientific and Technical Information of China (English)



    @@ Increasing attention is being paid on sound quality and subjective hearing perception properties of sound/noise signals. While lots of efforts had been done and is being continually done on describing sound character physically, subjective sensation found to be more suitable way reflecting sound character in human related products and environments, demonstrating that human-being is the central object. A wide range of work is being carried out, including subjective evaluation methodology, general sound quality metrics and metrics for special type of noise or products, acoustic comfort and soundscape in living and work spaces and applications in product sound design and product quality evaluation. The aim of this special issue is to reflect the state-of-the-art in sound quality study of Chinese researchers.

  11. Questionnaire on Corporate Income Tax Subjects - Denmark

    DEFF Research Database (Denmark)

    Friis Hansen, Søren; Nielsen, Jacob Graff

    shows that the conditions which must be met in order to be subject to CIT are very different from one country to another. The way tax systems define foreign entities which fall under their CIT may also vary in a significant way, which may in practice give rise to interesting tax planning opportunities...... fundamental idea: while companies limited by shares and limited liability companies should be subject to corporate income tax (CIT), partnerships should be considered fully or partly transparent for tax purposes. This general statement is nevertheless an oversimplification of reality. Comparative law indeed....... Against this background, the EATLP congress devoted to CIT subjects should enhance the main similarities and differences which exist between European countries in order to reach a better understanding of the need (or the absence of need) of increased harmonization in this matter....

  12. Alteration of astrocytes and Wnt/β-catenin signaling in the frontal cortex of autistic subjects

    Directory of Open Access Journals (Sweden)

    Cao Fujiang


    Full Text Available Abstract Background Autism is a neurodevelopmental disorder characterized by impairments in social interaction, verbal communication and repetitive behaviors. To date the etiology of this disorder is poorly understood. Studies suggest that astrocytes play critical roles in neural plasticity by detecting neuronal activity and modulating neuronal networks. Recently, a number of studies suggested that an abnormal function of glia/astrocytes may be involved in the development of autism. However, there is yet no direct evidence showing how astrocytes develop in the brain of autistic individuals. Methods Study subjects include brain tissue from autistic subjects, BTBR T + tfJ (BTBR and Neuroligin (NL-3 knock-down mice. Western blot analysis, Immunohistochemistry and confocal microscopy studies have be used to examine the density and morphology of astrocytes, as well as Wnt and β-catenin protein expression. Results In this study, we demonstrate that the astrocytes in autisitcsubjects exhibit significantly reduced branching processes, total branching length and cell body sizes. We also detected an astrocytosis in the frontal cortex of autistic subjects. In addition, we found that the astrocytes in the brain of an NL3 knockdown mouse exhibited similar alterations to what we found in the autistic brain. Furthermore, we detected that both Wnt and β-catenin proteins are decreased in the frontal cortex of autistic subjects. Wnt/β-catenin pathway has been suggested to be involved in the regulation of astrocyte development. Conclusions Our findings imply that defects in astrocytes could impair neuronal plasticity and partially contribute to the development of autistic-like behaviors in both humans and mice. The alteration of Wnt/β-catenin pathway in the brain of autistic subjects may contribute to the changes of astrocytes.

  13. Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice

    Directory of Open Access Journals (Sweden)

    Dina Silke Malling Damlund


    Full Text Available Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND 1–4 in NOD mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 mice.

  14. Distinct motor impairments of dopamine D1 and D2 receptor knockout mice revealed by three types of motor behavior

    Directory of Open Access Journals (Sweden)

    Toru eNakamura


    Full Text Available Both D1R and D2R knock out (KO mice of the major dopamine receptors show significant motor impairments. However, there are some discrepant reports, which may be due to the differences in genetic background and experimental procedures. In addition, only few studies directly compared the motor performance of D1R and D2R KO mice. In this paper, we examined the behavioral difference among N10 congenic D1R and D2R KO, and wild type (WT mice. First, we examined spontaneous motor activity in the home cage environment for consecutive five days. Second, we examined motor performance using the rota-rod task, a standard motor task in rodents. Third, we examined motor ability with the Step-Wheel task in which mice were trained to run in a motor-driven turning wheel adjusting their steps on foothold pegs to drink water. The results showed clear differences among the mice of three genotypes in three different types of behavior. In monitoring spontaneous motor activities, D1R and D2R KO mice showed higher and lower 24 h activities, respectively, than WT mice. In the rota-rod tasks, at a low speed, D1R KO mice showed poor performance but later improved, whereas D2R KO mice showed a good performance at early days without further improvement. When first subjected to a high speed task, the D2R KO mice showed poorer rota-rod performance at a low speed than the D1R KO mice. In the Step-Wheel task, across daily sessions, D2R KO mice increased the duration that mice run sufficiently close to the spout to drink water, and decreased time to touch the floor due to missing the peg steps and number of times the wheel was stopped, which performance was much better than that of D1R KO mice. These incongruent results between the two tasks for D1R and D2R KO mice may be due to the differences in the motivation for the rota-rod and Step-Wheel tasks, aversion- and reward-driven, respectively. The Step-Wheel system may become a useful tool for assessing the motor ability of WT

  15. Mechanics of composite material subjected to eigenstress

    DEFF Research Database (Denmark)

    Fuglsang Nielsen, L.

    In this SBI Bulletin a theory is presented dealing with the mechanical behavior of composites subjected to hygro-thermal actions such as shrinkage caused by moisture variations and expansion caused by temperature variations of freezing of water in pore systems. Special attention is given to the t......In this SBI Bulletin a theory is presented dealing with the mechanical behavior of composites subjected to hygro-thermal actions such as shrinkage caused by moisture variations and expansion caused by temperature variations of freezing of water in pore systems. Special attention is given...

  16. Early labour market returns to college subjects

    DEFF Research Database (Denmark)

    Buonanno, Paolo; Pozzoli, Dario

    This paper aims at estimating early labour market outcomes  of Italian university graduates across college subjects. We devote great attention to endogenous selection issues using alternative methods to control for potential self-selection associated with the choice of the degree subject in order...... to unravel the causal link between college major and subsequent outcomes in the labour market.  Our results suggest that "quantitative" fields (i.e. Sciences, Engineering and Economics) increase not only the speed of transition into the first job and employment probability but also early earnings...

  17. Early Labour Market Returns to College Subject

    DEFF Research Database (Denmark)

    Buonanno, Paolo; Pozzoli, Dario


    We estimate early labour market outcomes of Italian university  graduates across college subjects. We devote great attention to endogenous selection issues using alternative methods to control for potential self-selection associated with the choice of the degree subject in order to unravel...... the causal link between college major and subsequent outcomes in the labour market. Our results suggest that 'quantitative' fields (i.e. Sciences, Engineering, and Economics) increase not only the speed of transition into the first job and employment probability but also early earnings, conditional...

  18. Early labour market returns to college subject

    DEFF Research Database (Denmark)

    Pozzoli, Dario; Buonanno, Paolo

    This paper aims at estimating early labour market outcomes  of Italian university graduates across college subjects. We devote great attention to endogenous selection issues using alternative methods to control for potential self-selection associated with the choice of the degree subject in order...... to unravel the causal link between college major and subsequent outcomes in the labour market.  Our results suggest that "quantitative" fields (i.e. Sciences, Engineering and Economics) increase not only the speed of transition into the first job and employment probability but also early earnings...

  19. Subjectivities as Centers of Citizen Formation

    Directory of Open Access Journals (Sweden)



    Full Text Available The article presents academic reflections resulting from the teaching work of the authors with students of the Psychology career at the Javeriana University.Beginning from Latinamerica’s sociopolitical reality, it is pointed out that complex views of citizenship are needed that permit the confrontation of the region’s crises, particularly in Colombia, from the educational scenarios. Formative implications of that view for the professional work of Psychologists are reviewed, proposing subject and subjectivity as the heart of formative practices. Finally, some significant challenges to the Psychologists’ task inthe field of civic formation in educational contexts are outlined.

  20. Activation of the central histaminergic system is involved in hypoxia-induced stroke tolerance in adult mice. (United States)

    Fan, Yan-ying; Hu, Wei-wei; Dai, Hai-bin; Zhang, Jian-xiang; Zhang, Lu-yi; He, Ping; Shen, Yao; Ohtsu, Hiroshi; Wei, Er-qing; Chen, Zhong


    We hypothesized that activation of the central histaminergic system is required for neuroprotection induced by hypoxic preconditioning. Wild-type (WT) and histidine decarboxylase knockout (HDC-KO) mice were preconditioned by 3 hours of hypoxia (8% O(2)) and, 48 hours later, subjected to 30 minutes of middle cerebral artery (MCA) occlusion, followed by 24 hours of reperfusion. Hypoxic preconditioning improved neurologic function and decreased infarct volume in WT or HDC-KO mice treated with histamine, but not in HDC-KO or WT mice treated with α-fluoromethylhistidine (α-FMH, an inhibitor of HDC). Laser-Doppler flowmetry analysis showed that hypoxic preconditioning ameliorated cerebral blood flow (CBF) in the periphery of the MCA territory during ischemia in WT mice but not in HDC-KO mice. Histamine decreased in the cortex of WT mice after 2, 3, and 4 hours of hypoxia, and HDC activity increased after 3 hours of hypoxia. Vascular endothelial growth factor (VEGF) mRNA and protein expressions showed a greater increase after hypoxia than those in HDC-KO or α-FMH-treated WT mice. In addition, the VEGF receptor-2 antagonist SU1498 prevented the protective effect of hypoxic preconditioning in infarct volume and reversed increased peripheral CBF in WT mice. Therefore, endogenous histamine is an essential mediator of hypoxic preconditioning. It may function by enhancing hypoxia-induced VEGF expression.

  1. Habituation and memorization of spatial objects' configurations in mice from weaning to adulthood. (United States)

    Chapillon, P; Roullet, P


    This experiment investigated the development of habituation and memorization capacities of C57BL/6 mice. After a first session on a classic open field, four groups of subjects (3, 4, 5 and 9 weeks of age) were exposed to objects arranged in a pre-defined spatial environment during three exploratory sessions. Subsequently, for the test session, half of the mice was exposed to the previous situation, while the other half was exposed to a novel situation with a different spatial configuration for testing animal's abilities to detect and react to a change in their environment. Analysis showed age-related differences in behavioural habituation patterns. Moreover, contrary to our expectancy based on previous studies, the youngest mice (3 week-old) didn't exhibit significant renewal of exploration of the displaced objects during the test session. This results indicated that the youngest mice react differently than the adult mice when they are confronted to a novel environment and especially seem enable to construct a long-lasting representation of their environment when this representation concerns proximal information. The results are discussed in relation to previous studies conducted on the radial maze and the Morris water maze and it seems that the abilities of the youngest mice to construct a representation of their environment are partially dependent upon the type of information available (i.e. proximal versus distal information).

  2. Selective Glucocorticoid Receptor (GR-II Antagonist Reduces Body Weight Gain in Mice

    Directory of Open Access Journals (Sweden)

    Tomoko Asagami


    Full Text Available Previous research has shown that mifepristone can prevent and reverse weight gain in animals and human subjects taking antipsychotic medications. This proof-of-concept study tested whether a more potent and selective glucocorticoid receptor antagonist could block dietary-induced weight gain and increase insulin sensitivity in mice. Ten-week-old, male, C57BL/6J mice were fed a diet containing 60% fat calories and water supplemented with 11% sucrose for 4 weeks. Groups (=8 received one of the following: CORT 108297 (80 mg/kg QD, CORT 108297 (40 mg/kg BID, mifepristone (30 mg/kg BID, rosiglitazone (10 mg/kg QD, or vehicle. Compared to mice receiving a high-fat, high-sugar diet plus vehicle, mice receiving a high-fat, high-sugar diet plus either mifepristone or CORT 108297 gained significantly less weight. At the end of the four week treatment period, mice receiving CORT 108297 40 mg/kg BID or CORT 108297 80 mg/kg QD also had significantly lower steady plasma glucose than mice receiving vehicle. However, steady state plasma glucose after treatment was not highly correlated with reduced weight gain, suggesting that the effect of the glucocorticoid receptor antagonist on insulin sensitivity may be independent of its mitigating effect on weight gain.

  3. Treatment with 4-methylpyrazole modulated stellate cells and natural killer cells and ameliorated liver fibrosis in mice.

    Directory of Open Access Journals (Sweden)

    Hyon-Seung Yi

    Full Text Available Accumulating evidence suggests that retinol and its metabolites are closely associated with liver fibrogenesis. Recently, we demonstrated that genetic ablation of alcohol dehydrogenase 3 (ADH3, a retinol metabolizing gene that is expressed in hepatic stellate cells (HSCs and natural killer (NK cells, attenuated liver fibrosis in mice. In the current study, we investigated whether pharmacological ablation of ADH3 has therapeutic effects on experimentally induced liver fibrosis in mice.Liver fibrosis was induced by intraperitoneal injections of carbon tetrachloride (CCl4 or bile duct ligation (BDL for two weeks. To inhibit ADH3-mediated retinol metabolism, 10 μg 4-methylpyrazole (4-MP/g of body weight was administered to mice treated with CCl4 or subjected to BDL. The mice were sacrificed at week 2 to evaluate the regression of liver fibrosis. Liver sections were stained for collagen and α-smooth muscle actin (α-SMA. In addition, HSCs and NK cells were isolated from control and treated mice livers for molecular and immunological studies.Treatment with 4-MP attenuated CCl4- and BDL-induced liver fibrosis in mice, without any adverse effects. HSCs from 4-MP treated mice depicted decreased levels of retinoic acids and increased retinol content than HSCs from control mice. In addition, the expression of α-SMA, transforming growth factor-β1 (TGF-β1, and type I collagen α1 was significantly reduced in the HSCs of 4-MP treated mice compared to the HSCs from control mice. Furthermore, inhibition of retinol metabolism by 4-MP increased interferon-γ production in NK cells, resulting in increased apoptosis of activated HSCs.Based on our data, we conclude that inhibition of retinol metabolism by 4-MP ameliorates liver fibrosis in mice through activation of NK cells and suppression of HSCs. Therefore, retinol and its metabolizing enzyme, ADH3, might be potential targets for therapeutic intervention of liver fibrosis.

  4. Fluoxetine protection in decompression sickness in mice is enhanced by blocking TREK-1 potassium channel with the spadin antidepressant.

    Directory of Open Access Journals (Sweden)

    Nicolas eVallée


    Full Text Available In mice, disseminated coagulation, inflammation and ischemia induce neurological damages that can lead to the death. These symptoms result from circulating bubbles generated by a pathogenic decompression. An acute fluoxetine treatment or the presence of the TREK-1 potassium channel increased the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50mg/kg in wild-type (WT and TREK-1 deficient mice (Knockout homozygous KO and heterozygous HET. Then, we combined the same fluoxetine treatment with a five-day treatment by spadin, in order to specifically block TREK-1 activity (KO-like mice. KO and KO-like mice could be regarded as antidepressed models.167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux and 4% of mice treated with both spadin and fluoxetine (KO-likeflux died from decompression sickness (DCS symptoms. These values are much lower than those of WT control (62% or KO-like mice (41%. After the decompression protocol, mice showed a significant consumption of their circulating platelets and leukocytes.Spadin antidepressed mice were more likely to declare DCS. Nevertheless, which had both blocked TREK-1 channel and were treated with fluoxetine were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but a concomitant fluoxetine treatment not only decreases DCS severity but increases the survival rate.

  5. Subject Guides: Maintaining Subject Guides Using a Social Bookmarking Site.

    Directory of Open Access Journals (Sweden)

    Edward M. Corrado


    Full Text Available By using Web 2.0 social bookmarking sites, libraries can more easily manage subject guides and other lists of Web resources. Social bookmarking services such as Delicious provide a one-click method to bookmark a Web site, allowing librarians to describe and categorize Web sites. Using a small amount of JavaScript, these bookmarked resources can be dynamically included into subject guides and other Web-based library resources. This paper describes and analyses the use of social bookmarking at a medium-sized comprehensive college library for the creation and maintenance of modern languages subject guides. A brief technical description outlining necessary JavaScript code provides a way for librarians to try this idea elsewhere. This paper examines the initiative at The College of New Jersey (TCNJ Library to utilize the social bookmarking Web site to easily update and maintain modern language subject-specific guides on the library Web site. Previously, the subject guides have proven difficult to maintain and a solution that allowed subject librarians to quickly and easily update subject guides from anywhere was desired. By using, librarians at TCNJ have been able to stream line subject guide maintenance. This paper describes the process used to include resources bookmarked on by librarians from both the subject librarians' and systems librarian's perspectives. Included is a brief technical description that outlines the JavaScript code that needs to be included in the subject guides that other libraries can use as an example if they choose to embark on a similar project. The response from librarians and teaching faculty has been positive. Librarians appreciate the ease of use while teaching faculty appreciate the constantly evolving nature of the subject guides. Recommendations on ways to expand this project, including methods to allowing students and faculty to identify content to be included in subject guides

  6. Vocal development and auditory perception in CBA/CaJ mice (United States)

    Radziwon, Kelly E.

    Mice are useful laboratory subjects because of their small size, their modest cost, and the fact that researchers have created many different strains to study a variety of disorders. In particular, researchers have found nearly 100 naturally occurring mouse mutations with hearing impairments. For these reasons, mice have become an important model for studies of human deafness. Although much is known about the genetic makeup and physiology of the laboratory mouse, far less is known about mouse auditory behavior. To fully understand the effects of genetic mutations on hearing, it is necessary to determine the hearing abilities of these mice. Two experiments here examined various aspects of mouse auditory perception using CBA/CaJ mice, a commonly used mouse strain. The frequency difference limens experiment tested the mouse's ability to discriminate one tone from another based solely on the frequency of the tone. The mice had similar thresholds as wild mice and gerbils but needed a larger change in frequency than humans and cats. The second psychoacoustic experiment sought to determine which cue, frequency or duration, was more salient when the mice had to identify various tones. In this identification task, the mice overwhelmingly classified the tones based on frequency instead of duration, suggesting that mice are using frequency when differentiating one mouse vocalization from another. The other two experiments were more naturalistic and involved both auditory perception and mouse vocal production. Interest in mouse vocalizations is growing because of the potential for mice to become a model of human speech disorders. These experiments traced mouse vocal development from infant to adult, and they tested the mouse's preference for various vocalizations. This was the first known study to analyze the vocalizations of individual mice across development. Results showed large variation in calling rates among the three cages of adult mice but results were highly

  7. Increased intensity discrimination thresholds in tinnitus subjects with a normal audiogram

    DEFF Research Database (Denmark)

    Epp, Bastian; Hots, J.; Verhey, J. L.


    Recent auditory brain stem response measurements in tinnitus subjects with normal audiograms indicate the presence of hidden hearing loss that manifests as reduced neural output from the cochlea at high sound intensities, and results from mice suggest a link to deafferentation of auditory nerve...... fibers. As deafferentation would lead to deficits in hearing performance, the present study investigates whether tinnitus patients with normal hearing thresholds show impairment in intensity discrimination compared to an audiometrically matched control group. Intensity discrimination thresholds were...... significantly increased in the tinnitus frequency range, consistent with the hypothesis that auditory nerve fiber deafferentation is associated with tinnitus....

  8. Political Subjects: Decision and Subjectivity from a Post-Fundational Perspective

    Directory of Open Access Journals (Sweden)

    Martín Retamozo


    Full Text Available The problem of decision and of political subjects was addressed in the field of 20th century political philosophy by authors such as Carl Schmitt, Hannah Arendt, and Jacques Derrida, who related it closely to the concepts of sovereignty, freedom, and contingency. The works of Ernesto Laclau and Slavoj Žižek have currently turnedto the issue of decision in order to address the constitutive spects of the political. In a context dominated by deconstruction, post-Marxism, and post-structuralism,the article inquires into the elation between decision and political subjects in a contemporary setting, examining in depth the difference between subjectivity,subjectivization, and subject.

  9. Acid aspiration-induced airways hyperresponsiveness in mice. (United States)

    Allen, Gilman B; Leclair, Timothy R; von Reyn, Jessica; Larrabee, Yuna C; Cloutier, Mary E; Irvin, Charles G; Bates, Jason H T


    The role of gastroesophageal reflux and micro-aspiration as a trigger of airways hyperresponsiveness (AHR) in patients with asthma is controversial. The role of acid reflux and aspiration as a direct cause of AHR in normal subjects is also unclear. We speculated that aspiration of a weak acid with a pH (1.8) equivalent to the upper range of typical gastric contents would lead to AHR in naive mice. We further speculated that modest reductions in aspirate acidity to a level expected during gastric acid suppression therapy (pH 4.0) would impede aspiration-induced AHR. BALB/c female mice were briefly anesthetized with isoflurane and allowed to aspirate 75 microl of saline with HCl (pH 1.8, 4.0, or 7.4) or underwent sham aspiration. Mice were re-anesthetized 2 or 24 h later, underwent tracheostomy, and were coupled to a mechanical ventilator. Forced oscillations were used to periodically measure respiratory impedance (Zrs) following aerosol delivery of saline and increasing doses of methacholine to measure for AHR. Values for elastance (H), airways resistance (R(N)), and tissue damping (G) were derived from Zrs. Aspirate pH of 1.8 led to a significant overall increase in peak R(N), G, and H compared with pH 4.0 and 7.4 at 2 and 24 h. Differences between pH 7.4 and 4.0 were not significant. In mice aspirating pH 1.8 compared with controls, airway lavage fluid contained more neutrophils, higher protein, and demonstrated higher permeability. We conclude that acid aspiration triggers an acute AHR, driven principally by breakdown of epithelial barrier integrity within the airways.

  10. Human Subjects Issues in AIDS Research. (United States)

    Bayer, Ronald, Ed.


    Six articles are presented on the use of human subjects in research on acquired immune deficiency syndrome (AIDS). Topics include the ethics of human experimentation, female and pediatric AIDS patients, Human Immunodeficiency Virus (HIV) infection and AIDS among correctional inmates, community-based AIDS research, and clinical trials of HIV…

  11. Subject Gateway Sites and Search Engine Ranking. (United States)

    Thelwall, Mike


    Discusses subject gateway sites and commercial search engines for the Web and presents an explanation of Google's PageRank algorithm. The principle question addressed is the conditions under which a gateway site will increase the likelihood that a target page is found in search engines. (LRW)

  12. "Being Good" at Maths: Fabricating Gender Subjectivity (United States)

    Chronaki, Anna; Pechtelidis, Yannis


    Current research in mathematics education places emphasis on the analysis of men and women's accounts about their life trajectories and choices for studying, working and developing a career that involves the learning and teaching of mathematics. Within this realm, the present study aims to highlight how mathematics, gender and subjectivity become…

  13. Subjective sleep efficiency of hemodialysis patients

    NARCIS (Netherlands)

    B.C.P. Koch; J.E. Nagtegaal; E.C. Hagen; W.Th. van Dorp; J.B.S. Boringa; G.A. Kerkhof; P.M. ter Wee


    Background: Sleep disturbances have a major influence on quality of life. A commonly used measure of sleep disturbances is sleep efficiency. The purpose of this study was to investigate the prevalence of decreased subjective sleep efficiency in hemodialysis patients. An additional goal was to identi

  14. The Future for Mathematics Subject Associations (United States)

    Pope, Sue


    Subject associations have developed, over the years, to serve the interests of the mathematics education community. We live in changing times, and education is often at the forefront of such change. So, to remain contemporary, relevant, and to have a regard for the future in a world influenced by technology, it is suggested that there is a need…

  15. Modeling preventive maintenance using subjective data

    Institute of Scientific and Technical Information of China (English)


    Presents the optimal preventive maintenance model establishedwith the target function given through technical economic analysis, and failure rate and delay time distribution estimated from subjective data, which describes the relationship between the total downtime and the preventive maintenance and can be used to determine the rational inspection interval and to minimize the total expected downtime per unit time.

  16. Subjective Quantitative Studies of Human Agency (United States)

    Alkire, Sabina


    Amartya Sen's writings have articulated the importance of human agency, and identified the need for information on agency freedom to inform our evaluation of social arrangements. Many approaches to poverty reduction stress the need for empowerment. This paper reviews "subjective quantitative measures of human agency at the individual level." It…

  17. Is Chinese as a Subject Important?

    Institute of Scientific and Technical Information of China (English)


    @@ In January,six universities in Shanghai held independent admission tests to select students from more than 10,000 applicants.At four of the universities,Chinese was not a test subject or science students were exempted from being tested in Chinese.

  18. Subjective evaluation of HEVC in mobile devices (United States)

    Garcia, Ray; Kalva, Hari


    Mobile compute environments provide a unique set of user needs and expectations that designers must consider. With increased multimedia use in mobile environments, video encoding methods within the smart phone market segment are key factors that contribute to positive user experience. Currently available display resolutions and expected cellular bandwidth are major factors the designer must consider when determining which encoding methods should be supported. The desired goal is to maximize the consumer experience, reduce cost, and reduce time to market. This paper presents a comparative evaluation of the quality of user experience when HEVC and AVC/H.264 video coding standards were used. The goal of the study was to evaluate any improvements in user experience when using HEVC. Subjective comparisons were made between H.264/AVC and HEVC encoding standards in accordance with Doublestimulus impairment scale (DSIS) as defined by ITU-R BT.500-13. Test environments are based on smart phone LCD resolutions and expected cellular bit rates, such as 200kbps and 400kbps. Subjective feedback shows both encoding methods are adequate at 400kbps constant bit rate. However, a noticeable consumer experience gap was observed for 200 kbps. Significantly less H.264 subjective quality is noticed with video sequences that have multiple objects moving and no single point of visual attraction. Video sequences with single points of visual attraction or few moving objects tended to have higher H.264 subjective quality.

  19. Neuropsychological test performance in illiterate subjects. (United States)

    Ostrosky-Solis, F; Ardila, A; Rosselli, M; Lopez-Arango, G; Uriel-Mendoza, V


    The purpose of this study was to further analyze the effects of education across different age ranges on neuropsychological test performance. Two different analyses were performed. The first analysis was conducted in order to pinpoint the impact of school attendance on neuropsychological testing. A group of 64 illiterate normal subjects was selected in the Mexican Republic. Their performance was compared with two barely schooled control groups (1-2 and 3-4 years of schooling). The subjects' ages ranged from 16 to 85 years. In the second analysis, the illiterate subjects were further matched by age and sex with individuals with 1 to 4, 5 to 9, and 10 to 19 years of formal education. The Spanish version of the NEUROPSI neuropsychological test battery (Ostrosky, Ardila, & Rosselli, 1997) was used. Results indicated a significant educational effect on most of the tests. Largest educational effect was noted in constructional abilities (copying of a figure), language (comprehension), phonological verbal fluency, and conceptual functions (similarities, calculation abilities, and sequences). Aging effect was noted in visuoperceptual (visual detection) and memory scores. In the first subject sample, it was evident that, despite using such limited educational range (from 0-4 years of formal education), and such a wide age range (from 16-85 years), schooling represented a stronger variable than age. It is proposed that education effect on neuropsychological test performance represents a negatively accelerated curve, tending to a plateau.

  20. Economic Shocks and Subjective Well-Being

    DEFF Research Database (Denmark)

    Hariri, Jacob Gerner; Bjørnskov, Christian; Justesen, Mogens Kamp

    -treatment respondents, surveyed after the devaluation. Our estimates show that the devaluation had a large and significantly negative effect on individuals’ evaluations of subjective well-being. These results suggest that macroeconomic shocks, such as unanticipated currency devaluations, may have significant short...

  1. Psychology or semiotics: persons or subjects? (United States)

    Bell, Philip


    Cultural studies and especially semiological theory has recently sought to re-conceptualise classical problems considered in academic psychology such as perception, identity, and "subjectivity". It is argued that these theorizations are reductionist and/or theoretically incoherent without an adequate epistemology. Yet they have become for many students of the human sciences the conventional modes of analyzing such questions as personal identity.

  2. Human Subjects Research and the Physics Classroom (United States)

    Kubitskey, Beth W.; Thomsen, Marshall


    Physics Education Research is a form of social science research in that it uses human subjects. As physicists we need to be aware of the ethical and legal ramifications of performing this research, taking into account the fundamental differences between working with substances and working with people. For several decades, the federal government…

  3. A Shallow Approach to Subjectivity Classification

    NARCIS (Netherlands)

    Raaijmakers, S.A.; Kraaij, W.


    We present a shallow linguistic approach to subjectivity classification. Using multinomial kernel machines, we demonstrate that a data representation based on counting character n-grams is able to improve on results previously attained on the MPQA corpus using word-based n-grams and syntactic inform

  4. Are Subject Small Clauses Really Small Clauses? (United States)

    Kubo, Miori


    This paper discusses the ongoing debate over small clauses concerning the structure of the verb phrase in "I consider Bill smart." It is demonstrated that the subject constituent in question is not a small clause, but a Noun Phrase (NP), following Noun (N). It is shown that some peculiar phenomena under the small clause analysis are natural…

  5. Subjectivity and intersubjectivity of clinical facts. (United States)

    Mayer, E L


    The author has learned a great deal from the IJPA 75th Anniversary Issue, particularly regarding ways in which psychoanalysts across the world are consensually re-defining psychoanalysis as a quintessentially subjective and intersubjective endeavour. In summarising her response to the Issue, she addresses the ways in which its focus on psychoanalytic subjectivity and intersubjectivity helps to define the nature of psychoanalysis as a scientific endeavour. In addition, she identifies an area that she wished had been more developed in the Issue: some further specification of the cognitive and communicative processes that make for psychoanalytic subjectivity and intersubjectivity. She speculates that, as we continue our attempts further to understand those processes, we may find it valuable to look towards a body of research that is absent from consideration in the 75th Anniversary Issue (and is, for that matter, absent from serious and scientific consideration by psychoanalysts in general): research on mental effects currently considered 'anomalous', or outside the bounds of conventionally defined human mental function and capacity. She describes briefly some of that research in the context of its possible relevance to issues of psychoanalytic subjectivity and intersubjectivity. She takes up the specific relevance of that research to phenomena we have traditionally subsumed under categories of experience like intuition, empathic attunement and unconscious communication.

  6. Religious Culture as a School Subject (United States)

    Kozyrev, F. N.; Avest, K. H. ter


    In Russia a new school subject has been introduced in order to facilitate educators in shaping the enculturation process of the autonomous student into the cumulative tradition. In this article the Russian societal and educational context is described and the concepts "religion" and "culture" are clarified. Together they build the concentric…

  7. Career Construction and Subjective Well-Being (United States)

    Hartung, Paul J.; Taber, Brian J.


    Experienced happiness and reported life contentment represent cardinal elements of subjective well-being (SWB). Achieving happiness and contentment with work and other domains, such as love, play, and community, constitute fundamental life goals. Career construction offers a developmental theory of vocational behavior and a career assessment and…

  8. Subjective performance evaluations and employee careers

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Lange, Fabian; Kriechel, Ben

    such data are for evaluating theories in personnel economics and whether findings from such data generalize to the labor force at large. In this paper, we examine personnel data from six large companies and establish how subjective ratings, interpreted as ordinal rankings of employees within narrowly...

  9. Subject Matter Knowledge for Teaching Statistical Association (United States)

    Casey, Stephanie A.


    This study seeks to describe the subject matter knowledge needed for teaching statistical association at the secondary level. Taking a practice-based qualitative approach, three experienced teachers were observed as they taught statistical association and interviewed immediately following each observation. Records of practice were assembled to…

  10. Primary Teachers' Subject Matter Knowledge: Decimals (United States)

    Ubuz, Behiye; Yayan, Betul


    The main objective of this study was to investigate primary teachers' subject matter knowledge in the domain of decimals and more elaborately to investigate their performance and difficulties in reading scale, ordering numbers, finding the nearest decimal and doing operations, such as addition and subtraction. The difficulties in these particular…

  11. On the subjectivity of personality theory. (United States)

    Atwood, G E; Tomkins, S S


    Every theorist of personality views the human condition from the unique perspective of his own individuality. As a consequence, personality theories are strongly influenced by personal and subjective factors. These influences are partially responsible for the present day lack of consensus in psychology as to basic conceptual frameworks for the study of man. The science of human personality can achieve a greater degree of consensus and generality only if it begins to turn back on itself and question its own psychological foundations. The role of subjective and personal factors in this field can be studied and made more explicit by means of a psychobiographical method which interprets the major ideas of personality theories in the light of the formative experiences in the respective theorists' lives. This method is briefly illustrated by an examination of the influence of personal experiences on theoretical concepts in the work of Carl Jung, Carl Rogers, Wilhelm Reich, and Gordon Allport. The subjective factors disclosed by psychobiographical analysis can bee seen to interact with influences stemming from the intellectual and historical context within which the theorist work. The psychobiographical study of personality theory is only one part of a larger discipline, the psychology of knowledge, which would study the role of subjective and personal factors in the structure of man's knowledge in general.


    Directory of Open Access Journals (Sweden)

    Olesya Vyacheslavovna Sulina


    Full Text Available The author highlights the media discourse of the budget process in its subject-temporal dimension. Place and role of the subjects of media discourse of the budget process are determined on the basis of the analysis of budgetary legislation, practical implementation of the budgeting process in the executive and legislative bodies and its reflection in the media. Public discourse of budgeting process includes not only participants, who are legally empowered, but also other actors involved in the formation of the informational agenda regarding the budget. For example, the subjects of media discourse of the budget process are executive and legislative bodies, regulatory authorities, recipients of budgetary funds, political parties, professional and expert communities, civil society activists. Sociocommunicative description of the budgeting process and its subjects is presented based on analytical and inductive methods. At the same time political journalism is not only a space for the formation of media discourse and reflection of the budgetary process, but also one of the indicators of the state of the political system as a whole. The conclusions present methodological aids for the media discourse analysis of specific cases of the budgeting process and may be used for scientific and practical research.

  13. Essays on subjective expectations and mortality trends

    NARCIS (Netherlands)

    Niu, G.


    This thesis consists of four chapters on two topics. The first topic, covered in chapter 2, 3, and 4, is about subjective expectations. Economists have long understood that expectations are important determinants of economic decisions. However, expectations are rarely observed. One way to overcome t

  14. Subjective Expected Utility Theory with "Small Worlds"

    DEFF Research Database (Denmark)

    Gyntelberg, Jacob; Hansen, Frank

    which is a more general construction than a state space. We retain preference axioms similar in spirit to the Savage axioms and obtain, without abandoning linearity of expectations, a subjective expected utility theory which allows for an intuitive distinction between risk and uncertainty. We also...

  15. A Subject Clitic in Child Catalan

    Directory of Open Access Journals (Sweden)

    Anna Gavarró


    Full Text Available In this paper we examine an instance of subject cliticisation in child Catalan previously unattested in the literature (1,. Given the lack of an adult counterpart to (1 in the input the child is exposed to, the claim is made that its occurrence, far from being accidental, must result from deep properties of grammar, also detectable in other Romance varieties. (1M'he vist una pel.lícula.    (Lena, 5;9 1sCL have seen a film 'I have seen a film.' This subject clitic is sensitive to the presence of a person feature - it is limited to first person singular - and tense-sensitive - it is only found in the present perfect. The subject clitic is analysed as a means to identify the empty subject of the sentence in cases where incorporation of be to yield have is taking place, along the lines of Kayne (1993. The analysis extends to also previously unattested existential constructions found in child Catalan, which involve instances of be instead of have (Hi era un caçador instead of Hi havia un caçador 'There was a hunter' (Joan 3;5 , but not vice-versa.

  16. [Traits of personality in hypochondriacal subjects]. (United States)

    De Vanna, M; Cauzer, M; Spreafichi, A


    Among the several mental originated clinical syndromes, hypochondria is not still well understood and listed. Indeed, hypochondria is often a complicating element in other psychopathological pictures; a slight form of hypochondria can appear in phobic-obsessing neurosis, and a worse one at the beginning of psychosis. The Authors, trying to explain the complex questions about diagnosis and prognosis of hypochondria, look for common personality traits in these patients. The research instrument was the Adjective Check List (ACL), a psychological test highly standardized and diffused, composed of 300 adjectives, or adjectival sentences, used to describe a person's attributes. The ACL was given to 65 subjects divided into two groups. The first group was made of 15 subjects, 10 women and 5 men, ambulatory treated at the Psychiatric Clinic in Trieste for the following diagnosis: psychosis (4 persons), depressing syndrome (3 persons), hypochondria (6 persons), obsessive neurosis (1 persons), anxiety syndrome (1 person). The second group was made of 50 subjects, 28 women and 22 men, diagnosed as hypochondriac by their medical officers. The results point out that some personality traits rising above the others are suggesting for an apathetical patient, not ready to accept himself, easily overcome by everyday life problems. These subjects are introverted, intolerant to frustrations, and inclined to take refuge in their own imaginary world, not able to self-governing. In the considered group the Authors find a moderate tendency to change, and it could be interpreted like a good prognostic element for a psychotherapeutic treatment.

  17. Subjective Well-Being Around Retirement

    NARCIS (Netherlands)

    Abolhassani, Marzieh; Alessie, Rob


    This paper studies the effect of both retirement and unemployment on life satisfaction, using subjective satisfaction indicators from the German Socio-Economic Panel. Moreover, we analyze how accurate individuals anticipate changes in satisfaction around retirement, as well as the correlation betwee

  18. National accounts of subjective well-being. (United States)

    Diener, Ed; Oishi, Shigehiro; Lucas, Richard E


    Diener (2000) proposed that National Accounts of Well-Being be created to complement existing economic and social indicators that reflect the quality of life in nations. These national accounts can provide valuable information to policymakers and other leaders. Systematic measurement of subjective well-being provides novel information about the quality of life in societies, and it allows for the accumulation of detailed information regarding the circumstances that are associated with high subjective well-being. Thus, accounts of subjective well-being can help decision makers evaluate policies that improve societies beyond economic development. Progress with well-being accounts has been notable: Prestigious scientific and international institutions have recommended the creation of such national accounts, and these recommendations have been adopted in some form in over 40 nations. In addition, increasing research into policy-relevant questions reveals the importance of the accounts for policy. Psychologists can enlarge their role in the formulation and adoption of policies by actively studying and using accounts of subjective well-being to evaluate and support the policies they believe are needed.

  19. Homeownership and subjective well-being

    DEFF Research Database (Denmark)

    Bloze, Gintautas; Skak, Morten

    Favouring homeownership is an important part of housing policies in many countries. Although this may be explained by the preferences of the majority of voters, it may also be because homeownership is believed to have positive effects on individuals’ behaviour and welfare. Previous research seems...... and subjective well-being....

  20. Effects of subchronic exposures to concentrated ambient particles in mice. IX. Integral assessment and human health implications of subchronic exposures of mice to CAPs. (United States)

    Lippmann, Morton; Gordon, Terry; Chen, Lung Chi


    In order to examine the biologic plausibility of adverse chronic cardiopulmonary effects in humans associated with ambient particulate matter (PM) exposure, we exposed groups of normal mice (C57) and knockout mice that develop atherosclerotic plaque (ApoE-/- and ApoE-/- LDLr-/-) for 6 h/day, 5 days/wk for 5 or 6 mo during the spring/summer of 2003 to either filtered air or 10-fold concentrated ambient particles (CAPs) in Tuxedo, NY (average PM2.5 concentration during exposure = 110 microg/m3). Some of the mice had implanted electrocardiographic monitors. We demonstrated that: (1) this complex interdisciplinary study was technically feasible in terms of daily exposure, collection of air quality monitoring data, the collection, analysis, and interpretation of continuous data on cardiac function, and the collection and analyses of tissues of the animals sacrificed at the end of the study; (2) the daily variations in CAPs were significantly associated, in ApoE-/- mice, with daily variations in cardiac functions; (3) there were significant differences between CAPs and sham-exposed ApoE-/- mice in terms of cardiac function after the end of exposure period, as well as small differences in atherosclerotic plaque density, coronary artery disease, and cell density in the substantia nigra in the brain in the ApoE-/- mice; (4) there are suggestive indications of gene expression changes for genes associated with the control of circadian rhythm in the ApoE-/- LDLr-/- double knockout (DK) mice. These various CAPs-related effects on cardiac function and the development of histological evidence of increased risk of clinically significant disease at the end of exposures in animal models of atherosclerosis provide biological plausibility for the premature mortality associated with PM2.5 exposure in human subjects and provide suggestive evidence for neurogenic disease as well.

  1. Construction of Subjectivity in Social Media

    Directory of Open Access Journals (Sweden)

    Anže Dolinar


    Full Text Available Social media are a phenomenon that came about with the Web 2.0. The essential characteristic of social media is the so-called user-generated content, which means that individuals and their lives are entangled in a social interaction in which their identity is to some extent subsumed under the logic of the production of profit. From the standpoint of the critique of political economy, the phenomenon of digital labor can be tackled with a digital labor theory of value. On the other hand, a question of a subjective aspect remains open. The initial hypothesis is that an analysis of a dynamic character of capitalism is necessarily connected with historical transformations of subjectivity. I will inspect which type of subjectivity is produced during the “process of production” on Facebook, how relations of the exchange of information and meaning take place inside this medium, and what kind of consciousness comes with this virtual identity. I will attempt to address this question with an explication of social forms of sharing amongst individuals on this social network. I will focus on how photos, notifications and comments structure web subjectivity and its function. Answers to such questions can help us in understanding a certain aspect of a socioeconomic structure of contemporary capitalism and bear an emancipatory potential in a possibility of negation of such social relations. The article will limit itself to the exploration of subjectivity in social media, which will be dealt with in a dynamic sense and in regard to formal conditions of communication inside social media, and in respect to a social situation in which they are.


    Directory of Open Access Journals (Sweden)

    M. G. Abdulmutalibov


    Full Text Available Aim. The article considers a notion of subject of such crime as illegal hunting. Only a man can be a subject of this crime. The content of such crime is revealed with the help of such properties as guilt, motive and aim. The article considers different properties of a subject of crime: 1 Physical nature Illegal actions can be committed by a man directly or indirectly. If during hunting a dog without its master’s command got a wild animal, the hunter is not liable as here intentional crime is absent. Juridical entities also are not admitted a subject of crime, only their representative if he committed this crime. 2 Criminal capacity. A person is not liable for this crime if he committed it in the state of criminal incapacity (CC Art.21. If illegal hunting is committed by a person in the state of drunkenness he is admitted capable and is liable for the crime(Criminal Code art.23. 3 A definite age. According to Art.23 of RF CC criminal responsibility for illegal hunting comes from the age of 16 . Performance of art.11, 12, 13 of CC concerns citizens of Russia, foreign citizens and persons without citizenship who committed poaching on the territory of Russia. Thus, the subject of poaching is a capable physical person reached the age of 16 by the moment of committing the crime. Methods. questionnaire method was applied for finding out the predominant motive and aim of illegal hunting. Result. 82% of pollee officials of hunting supervision bodies indicated the motive of profit as a predominant in committing illegal hunting.Location. Pskovskaya, Tulskaya, Moskovskaya regions. Conclusions. 1.Illegal hunting is committed only intentionally.2.The aim of poaching is killing wild animals and further use of their meat, skin, down, and active rest3.The more spread motives of poaching are: mercenary motives (35% and hunting passion

  3. Ischemia-reperfusion injury leads to distinct temporal cardiac remodeling in normal versus diabetic mice.

    Directory of Open Access Journals (Sweden)

    Megumi Eguchi

    Full Text Available Diabetes is associated with higher incidence of myocardial infarction (MI and increased propensity for subsequent events post-MI. Here we conducted a temporal analysis of the influence of diabetes on cardiac dysfunction and remodeling after ischemia reperfusion (IR injury in mice. Diabetes was induced using streptozotocin and IR performed by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for up to 42 days. We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV in both control and diabetic mice. The longitudinal systolic and diastolic strain rate were altered after IR, but there were no significant differences between diabetic mice and controls. However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-((18Ffluoro-D-glucose. Interestingly, after 24 hours reperfusion diabetic mice showed a reduced infarct size and less apoptosis indicated by TUNEL analysis in heart sections. This may be explained by increased levels of autophagy detected in diabetic mice hearts. Similar increases in IR-induced macrophage infiltration detected by CD68 staining indicated no change in inflammation between control and diabetic mice. Over time, control mice subjected to IR developed mild left ventricular dilation whereas diabetic mice exhibited a decrease in both end diastolic left ventricular volume and LVESV with a decreased intraventricular space and thicker left ventricular wall, indicating concentric hypertrophy. This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group. In summary, we demonstrate that diabetes principally influences distinct IR-induced chronic changes

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

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


    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. Multi-tissue computational modeling analyzes pathophysiology of type 2 diabetes in MKR mice.

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    Full Text Available Computational models using metabolic reconstructions for in silico simulation of metabolic disorders such as type 2 diabetes mellitus (T2DM can provide a better understanding of disease pathophysiology and avoid high experimentation costs. There is a limited amount of computational work, using metabolic reconstructions, performed in this field for the better understanding of T2DM. In this study, a new algorithm for generating tissue-specific metabolic models is presented, along with the resulting multi-confidence level (MCL multi-tissue model. The effect of T2DM on liver, muscle, and fat in MKR mice was first studied by microarray analysis and subsequently the changes in gene expression of frank T2DM MKR mice versus healthy mice were applied to the multi-tissue model to test the effect. Using the first multi-tissue genome-scale model of all metabolic pathways in T2DM, we found out that branched-chain amino acids' degradation and fatty acids oxidation pathway is downregulated in T2DM MKR mice. Microarray data showed low expression of genes in MKR mice versus healthy mice in the degradation of branched-chain amino acids and fatty-acid oxidation pathways. In addition, the flux balance analysis using the MCL multi-tissue model showed that the degradation pathways of branched-chain amino acid and fatty acid oxidation were significantly downregulated in MKR mice versus healthy mice. Validation of the model was performed using data derived from the literature regarding T2DM. Microarray data was used in conjunction with the model to predict fluxes of various other metabolic pathways in the T2DM mouse model and alterations in a number of pathways were detected. The Type 2 Diabetes MCL multi-tissue model may explain the high level of branched-chain amino acids and free fatty acids in plasma of Type 2 Diabetic subjects from a metabolic fluxes perspective.

  6. CETP Expression Protects Female Mice from Obesity-Induced Decline in Exercise Capacity.

    Directory of Open Access Journals (Sweden)

    David A Cappel

    Full Text Available Pharmacological approaches to reduce obesity have not resulted in dramatic reductions in the risk of coronary heart disease (CHD. Exercise, in contrast, reduces CHD risk even in the setting of obesity. Cholesteryl Ester Transfer Protein (CETP is a lipid transfer protein that shuttles lipids between serum lipoproteins and tissues. There are sexual-dimorphisms in the effects of CETP in humans. Mice naturally lack CETP, but we previously reported that transgenic expression of CETP increases muscle glycolysis in fasting and protects against insulin resistance with high-fat diet (HFD feeding in female but not male mice. Since glycolysis provides an important energy source for working muscle, we aimed to define if CETP expression protects against the decline in exercise capacity associated with obesity. We measured exercise capacity in female mice that were fed a chow diet and then switched to a HFD. There was no difference in exercise capacity between lean, chow-fed CETP female mice and their non-transgenic littermates. Female CETP transgenic mice were relatively protected against the decline in exercise capacity caused by obesity compared to WT. Despite gaining similar fat mass after 6 weeks of HFD-feeding, female CETP mice showed a nearly two-fold increase in run distance compared to WT. After an additional 6 weeks of HFD-feeding, mice were subjected to a final exercise bout and muscle mitochondria were isolated. We found that improved exercise capacity in CETP mice corresponded with increased muscle mitochondrial oxidative capacity, and increased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α. These results suggest that CETP can protect against the obesity-induced impairment in exercise capacity and may be a target to improve exercise capacity in the context of obesity.

  7. CETP Expression Protects Female Mice from Obesity-Induced Decline in Exercise Capacity. (United States)

    Cappel, David A; Lantier, Louise; Palmisano, Brian T; Wasserman, David H; Stafford, John M


    Pharmacological approaches to reduce obesity have not resulted in dramatic reductions in the risk of coronary heart disease (CHD). Exercise, in contrast, reduces CHD risk even in the setting of obesity. Cholesteryl Ester Transfer Protein (CETP) is a lipid transfer protein that shuttles lipids between serum lipoproteins and tissues. There are sexual-dimorphisms in the effects of CETP in humans. Mice naturally lack CETP, but we previously reported that transgenic expression of CETP increases muscle glycolysis in fasting and protects against insulin resistance with high-fat diet (HFD) feeding in female but not male mice. Since glycolysis provides an important energy source for working muscle, we aimed to define if CETP expression protects against the decline in exercise capacity associated with obesity. We measured exercise capacity in female mice that were fed a chow diet and then switched to a HFD. There was no difference in exercise capacity between lean, chow-fed CETP female mice and their non-transgenic littermates. Female CETP transgenic mice were relatively protected against the decline in exercise capacity caused by obesity compared to WT. Despite gaining similar fat mass after 6 weeks of HFD-feeding, female CETP mice showed a nearly two-fold increase in run distance compared to WT. After an additional 6 weeks of HFD-feeding, mice were subjected to a final exercise bout and muscle mitochondria were isolated. We found that improved exercise capacity in CETP mice corresponded with increased muscle mitochondrial oxidative capacity, and increased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). These results suggest that CETP can protect against the obesity-induced impairment in exercise capacity and may be a target to improve exercise capacity in the context of obesity.

  8. Tau hyperphosphorylation in apolipoprotein E-deficient and control mice after closed head injury. (United States)

    Genis, L; Chen, Y; Shohami, E; Michaelson, D M


    Apolipoprotein E (apoE)-deficient mice have learning and memory impairments that are associated with specific neurochemical changes and hyperphosphorylation of distinct epitopes of the cytoskeletal protein tau. Furthermore, such mice are highly susceptible to the sequelae of brain trauma and their ability to recover from head injury is impaired. In the present study we investigated the extent that the neuronal maintenance and repair impairments of apoE-deficient mice are related to aberrations at the tau phosphorylation level. This was pursued by subjecting control and apoE-deficient mice to closed head injury (CHI) and examination, utilizing immunoblot assays, of the resulting effects on tau phosphorylation. The results thus obtained revealed that tau of apoE-deficient mice is hyperphosphorylated before CHI and that this insult results in transient tau hyperphosphorylation, whose extent and time course in the two mouse groups varied markedly. Tau hyperphosphorylation in the injured controls was maximal by about 4 hr after injury and reverted to basal levels by 24 hr. In contrast, almost no head injury-induced tau hyperphosphorylation was observed in the apoE-deficient mice at 4 hr after injury. Some tau hyper-phosphorylation was detected in the head-injured apoE-deficient mice after longer time intervals, but its extent was markedly lower than the maximal values obtained in the head injured controls. These findings show that the chronic neuronal impairments brought about by apoE deficiency and the acute response to head injury are both associated with hyperphosphorylation of the same tau domain and that the ability of apoE-deficient mice to mount the acute tau hyperphosphorylation response to head injury is impaired.

  9. Hypertension is a conditional factor for the development of cardiac hypertrophy in type 2 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Marc van Bilsen

    Full Text Available BACKGROUND: Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice. METHODS: Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII for 4 wks to induce mild hypertension (n = 9-10 per group. Left ventricular (LV function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immunohistochemical analysis to assess effects on hypertrophy, fibrosis and inflammation. RESULTS: Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01 and cardiomyocyte size (+53% and +31%, p<0.001. This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK, while accumulation of Advanced Glycation End products (AGEs and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice. CONCLUSIONS: Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling.

  10. Cyclosporin A promotes in vivo myogenic response in collagen VI deficient myopathic mice

    Directory of Open Access Journals (Sweden)

    Francesca eGattazzo


    Full Text Available Mutations of genes encoding for collagen VI cause various muscle diseases in humans, including Bethlem myopathy and Ullrich congenital muscular dystrophy. Collagen VI null (Col6a1–/– mice are affected by a myopathic phenotype with mitochondrial dysfunction, spontaneous apoptosis of muscle fibers and defective autophagy. Moreover, Col6a1–/– mice display impaired muscle regeneration and defective self-renewal of satellite cells after injury. Treatment with cyclosporin A (CsA is effective in normalizing the mitochondrial, apoptotic and autophagic defects of myofibers in Col6a1–/– mice. A pilot clinical trial with CsA in Ullrich patients suggested that CsA may increase the number of regenerating myofibers. Here we report the effects of CsA administration at 5 mg/kg body weight every 12 hr in Col6a1–/– mice on muscle regeneration under physiological conditions and after cardiotoxin (CdTx-induced muscle injury. Our findings indicate that CsA influences satellite cell activity and triggers the formation of regenerating fibers in Col6a1–/– mice. Data obtained on injured muscles show that under appropriate administration regimens CsA is able to stimulate myogenesis in Col6a1–/– mice by significantly increasing the number of myogenin (MyoG-positive cells and of regenerating myofibers at the early stages of muscle regeneration. CsA is also able to ameliorate muscle regeneration of Col6a1–/– mice subjected to multiple CdTx injuries, with a concurrent maintenance of the satellite cell pool. Our data show that CsA is beneficial for muscle regeneration in Col6a1–/– mice.

  11. Sulfonylurea therapy improves glucose disposal without changing skeletal muscle GLUT4 levels in noninsulin-dependent diabetes mellitus subjects

    DEFF Research Database (Denmark)

    Vestergaard, H; Weinreb, J E; Rosen, A S


    A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus......, longitudinal studies are needed to assess whether changes in GLUT4 expression in muscle of NIDDM subjects could be responsible for changes in glucose disposal. The question is timely because recent studies in transgenic mice show that increasing GLUT4 expression can increase insulin-stimulated glucose uptake...... in vivo and in vitro. Here we use a longitudinal design to investigate the effects of 8 weeks of therapy with the sulfonylurea gliclazide on glycemic control, glucose tolerance, insulin-stimulated glucose disposal, and GLUT4 expression in muscle of 10 obese NIDDM subjects. Subjects were on a weight...

  12. Effects of chronic doxepin and amitriptyline administration in naïve mice and in neuropathic pain mice model. (United States)

    Mika, J; Jurga, A M; Starnowska, J; Wasylewski, M; Rojewska, E; Makuch, W; Kwiatkowski, K; Malek, N; Przewlocka, B


    Neuropathic pain is a severe clinical problem, often appearing as a co-symptom of many diseases or manifesting as a result of damage to the nervous system. Many drugs and agents are currently used for the treatment of neuropathic pain, such as tricyclic antidepressants (TCAs). The aims of this paper were to test the effects of two classic TCAs, doxepin and amitriptyline, in naïve animals and in a model of neuropathic pain and to determine the role of cytokine activation in the effects of these drugs. All experiments were carried out with Albino-Swiss mice using behavioral tests (von Frey test and the cold plate test) and biochemical analyses (qRT-PCR and Western blot). In the mice subjected to chronic constriction injury (CCI), doxepin and amitriptyline attenuated the symptoms of neuropathic pain and diminished the CCI-induced increase in the levels of spinal interleukin (IL)-6 and -1β mRNA, but not the protein levels of these cytokines, measured on day 12. Unexpectedly, chronic administration of doxepin or amitriptyline for 12 days produced allodynia and hyperalgesia in naïve mice. The treatment with these drugs did not influence the spinal levels of IL-1β and IL-6 mRNA, however, the protein levels of these pronociceptive factors were increased. The administration of ondansetron (5-HT3 receptor antagonist) significantly weakened the allodynia and hyperalgesia induced by both antidepressants in naïve mice; in contrast, yohimbine (α2-adrenergic receptors antagonist) did not influence these effects. Allodynia and hyperalgesia induced in naïve animals by amitriptyline and doxepin may be associated with an increase in the levels of pronociceptive cytokines resulting from 5-HT3-induced hypersensitivity. Our results provide new and important information about the possible side effects of antidepressants. Further investigation of these mechanisms may help to guide decisions about the use of classic TCAs for therapy.

  13. Effects of Subject-Area Degree and Classroom Experience on New Chemistry Teachers' Subject Matter Knowledge (United States)

    Nixon, Ryan S.; Campbell, Benjamin K.; Luft, Julie A.


    Science teachers need to understand the subject matter they teach. While subject matter knowledge (SMK) can improve with classroom teaching experience, it is problematic that many secondary science teachers leave the profession before garnering extensive classroom experience. Furthermore, many new science teachers are assigned to teach science…

  14. Contemporary native American fiction (1968-2001) : subject-ivity and identity

    NARCIS (Netherlands)

    Peraino, S.E.


    This study is a literary critical analysis of post-1960s Native American fiction and its engagement in the concepts of subject-ivity and identity in relation to both tribal- and Euroamerican -generated socio-cultural discourses and paradigms. This study adds to the critical enquiry of previous studi

  15. The origin of the Northern Subject Rule : subject positions and verbal morphosyntax in older English

    NARCIS (Netherlands)

    de Haas, Nynke; van Kemenade, Ans


    This article presents new evidence for the early history of the Northern Subject Rule in the form of an exhaustive corpus study of plural present-tense indicative verb forms in Northern and Northern Midlands early Middle English, analysed in relation to their syntactic context, including subject typ

  16. Night-vision goggles for night-blind subjects : subjective evaluation after 2 years of use

    NARCIS (Netherlands)

    Hartong, D. T.; Kooijman, A. C.


    Purpose: To evaluate the usefulness of night-vision goggles (NVG) for night-blind subjects after 1 and 2 years of use. Methods: Eleven night-blind subjects with retinitis pigmentosa used NVG for a 2-year period. At the end of each year, they were requested to fill-in two questionnaires regarding the

  17. Introduction to Subject Indexing; A Programmed Text. Volume One: Subject Analysis and Practical Classification. (United States)

    Brown, Alan George

    This programed text presents the basic principles and practices of subject indexing--limited to the area of precoordinate indexing. This first of two volumes deals with the subject analysis of documents, primarily at the level of summarization, and the basic elements of translation into classification schemes. The text includes regular self-tests…

  18. The Automatic indexing of Grey Literature by Subject Headings of the Polythematic Structured Subject Heading System


    Kocourek, Pavel


    The contribution is devoted to the automatic indexing of grey literature by subject headings of the Polythematic Structured Subject Heading System in the National repository of grey literature. The paper describes the initial situation, previous experience, analysis, stages of implementation and demonstration of indexing.

  19. Introduction to Subject Indexing; a Programmed Text. Volume Two: UDC and Chain Procedure in Subject Cataloguing. (United States)

    Brown, A. G.; And Others

    This is the second of two volumes dealing with practical classification and subject indexing. The programed text considers use of the Universal Decimal Classification (UDC) and techniques of cross referencing based on UDC in the construction of classified and alphabetical subject catalogs. (Author/LS)

  20. Effects of Chronic Mild Stress on the Development of Atherosclerosis and Expression of Toll-Like Receptor 4 Signaling Pathway in Adolescent Apolipoprotein E Knockout Mice

    Directory of Open Access Journals (Sweden)

    Hongfeng Gu


    Full Text Available Here, we investigated the effect of chronic mild stress (CMS on the development of atherosclerosis as well as the expression of Toll-like receptors (TLRs signaling pathway in adolescent apolipoprotein E knockout (apoE-/- mice. Mice were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein E knockout mice subjected to CMS, we compared gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87 genes. We found that atherosclerosis lesions both in aortic tress and sinuses of CMS mice were significantly increased linearly in response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88 (MyD88, and IL-1β, and 28 genes were downregulated compared with nonstressed mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were associated with significant increases in levels of expression of TLR4, MyD88, nuclear factor κB (NF-κB, MCP-1, IL-1β, TNF-α, and sICAM-1. Taken together, our results suggest an important role for TLR4 signaling pathway in atherosclerosis in a CMS mouse model.

  1. The subjective brain, identity, and neuroethics. (United States)

    Gillett, Grant R


    The human brain is subjective and reflects the life of a being-in-the-world-with-others whose identity reflects that complex engaged reality. Human subjectivity is shaped and in-formed (formed by inner processes) that are adapted to the human life-world and embody meaning and the relatedness of a human being. Questions of identity relate to this complex and dynamic reality to reflect the fact that biology, human ecology, culture, and one's historic-political situation are inscribed in one's neural network and have configured its architecture so that it is a unique and irreplaceable phenomenon. So much is a human individual a relational being whose own understanding and ownership of his or her life is both situated and distinctive that neurophilosophical conceptions of identity and human activity that neglect these features of our being are quite inadequate to ground a robust neuroethics.


    Directory of Open Access Journals (Sweden)

    Lourdete Rejane Ferro Zago


    Full Text Available The family, first family group of human beings, is the collective dimension of human existence and becomes responsible for the formation of the first social identity, as well as the constitution of subjectivity. Subjectivity is the inner world of each and every human being. This inner world is made up of emotions, feelings and thoughts. It is through this inner world that the individual relates to the social world, appointed by the outside world. This relationship follows the individual characteristics that mark the individual as unique, originated in shaping the individual, when they built the knowledge and beliefs. social representation as a form of knowledge, socially elaborated, shared with a practical purpose, contributing to the construction of a common reality to a social group. Is thus built up the social representation of the family.

  3. Vulnerable Subjects: Why Does Informed Consent Matter? (United States)

    Goodwin, Michele


    This special issue of the Journal Law, Medicine & Ethics takes up the concern of informed consent, particularly in times of controversy. The dominant moral dilemmas that frame traditional bioethical concerns address medical experimentation on vulnerable subjects; physicians assisting their patients in suicide or euthanasia; scarce resource allocation and medical futility; human trials to develop drugs; organ and tissue donation; cloning; xenotransplantation; abortion; human enhancement; mandatory vaccination; and much more. The term "bioethics" provides a lens, language, and guideposts to the study of medical ethics. It is worth noting, however, that medical experimentation is neither new nor exclusive to one country. Authors in this issue address thorny subjects that span borders and patients: from matters dealing with children and vaccination to the language and perception of consent.

  4. Teaching physics as a service subject (United States)

    Lowe, T. L.; Hayes, M.


    At South Glamorgan Institute of Higher Education physics is taught over a wide range of courses. In addition to the more conventional courses found in science, technology and education faculties there is a physics input into areas such as beauty therapy, applied biology, catering, chiropody, dental technology, environmental health, food technology, hairdressing, human-movement studies, industrial design, applied life sciences, marine technology, medical laboratory science, physiological measurement, nursing and speech therapy. Due to the fundamental differences in emphasis required when teaching physics as a 'minor' subject on these types of courses, and since the authors have no courses which lead to a 'major' physics qualification, it is necessary to develop a rational strategy for teaching physics as a 'service' subject. If this is not achieved then staff satisfaction and student interest are likely to suffer. They describe their strategy.

  5. Subjective Information Measure and Rate Fidelity Theory

    CERN Document Server

    Lu, Chenguang


    Using fish-covering model, this paper intuitively explains how to extend Hartley's information formula to the generalized information formula step by step for measuring subjective information: metrical information (such as conveyed by thermometers), sensory information (such as conveyed by color vision), and semantic information (such as conveyed by weather forecasts). The pivotal step is to differentiate condition probability and logical condition probability of a message. The paper illustrates the rationality of the formula, discusses the coherence of the generalized information formula and Popper's knowledge evolution theory. For optimizing data compression, the paper discusses rate-of-limiting-errors and its similarity to complexity-distortion based on Kolmogorov's complexity theory, and improves the rate-distortion theory into the rate-fidelity theory by replacing Shannon's distortion with subjective mutual information. It is proved that both the rate-distortion function and the rate-fidelity function ar...

  6. Family Support and Subjective Well-Being

    DEFF Research Database (Denmark)

    Schnettler, Berta; Denegri, Marianela; Miranda, Horacio


    In order to distinguish typologies of university students based on family support received in the form of tangible and intangible resources, their level of satisfaction with life and food-related life as well as subjective happiness, a survey was applied to a non-probabilistic sample of 347...... students in southern Chile. The questionnaire included the following scales: Family Resources scale, Satisfaction with Life Scale, Satisfaction with Food-related Life and Subjective Happiness Scale (SHS). Using factor analysis, two dimensions were detected on the Family Resources scale: intangible...... resources (Cronbach’s α = 0.886) and tangible resources (Cronbach’s α = 0.824). A cluster analysis applied to the Z-scores from the factor analysis classified three typologies: students with high support in tangible resources, satisfied with their life and their food-related life (18.2 %), students with low...

  7. [Risk profiles of hypertension in normotensive subjects]. (United States)

    Ducher, M; Fauvel, J P; Cerutti, C


    The aim of this study was to evaluate the influence of 10 factors suspected to be involved in hypertension genesis (age, body mass index, alcohol consumption, sodium to potassium urinary excretion ratio, systolic BP and heart rate response to mental stress, baroreflex sensitivity (BRS), job demand, job latitude (Karasec's questionnaire), and personality (Bortner's score). A cohort of 213 normotensive healthy subjects was followed during five years. Using K-means clustering technique we have defined 7 homogeneous groups of subjects. Four groups with different combinations of these factors had a significantly higher 5-year systolic BP increase. The common characteristic of these groups was a low BRS. In conclusion, cluster analysis is well suited to analyse combined effect of factors on hypertension genesis. Only low BRS seems to be the common factor involved in hypertension development.



    Guiot, Denis


    International audience; Until now, the concept of subjective age has only been used to segment the mature market. Research on consumer behavior has shown the effects of a youthful bias, the tendency to see oneself as younger. Using a conceptual framework based on self-concept, social comparison, and symbolic consumption, this research proposes to characterize the antecedents and the effects of an analogous but opposed tendency: an older bias among adolescent girls. An empirical study carried ...

  9. Optimization of laminates subjected to failure criterion

    Directory of Open Access Journals (Sweden)

    E. Kormaníková


    Full Text Available The paper is aimed on laminate optimization subjected to maximum strain criterion. The optimization problem is based on the use of continuous design variables. The thicknesses of layers with the known orientation are used as design variables. The optimization problem with strain constraints are formulated to minimize the laminate weight. The design of the final thickness is rounded off to integer multiples of the commercially available layer thickness.

  10. The responsible subject in the global age. (United States)

    Pulcini, Elena


    The first thesis of this article is that the concept of responsibility takes on an unprecedented meaning in the twentieth century resulting from the emergence of a new dimension of the other: to be responsible comes to mean not just to account for oneself in relation to the other, but also to take the other into account, to take care of the other-what I call responsibility towards (the other). The main reason for this change consists in the emergence of global risks and the necessity, as underlined by Hans Jonas, to be responsible for the destiny of the world and future generations. The problem, as explored in the article's second thesis, is that this implies the existence of a subject who is capable of responsibility. Jonas's insights on this point are insufficient, since he only recognizes duty as the fundament for his ethics of responsibility and thus neglects the problem of motivation. This is a particularly crucial problem today as we are witnessing the presence of a pathological subject, characterized by a split in his faculties (between doing and imagining, knowing and feeling). To underline this fact, this article makes use of Günther Anders's reflections, which provide a psycho-anthropological analysis of the subject, showing his pathologies and the necessity, from a moral perspective, to overcome his scission. Finally, this author suggests, as the article's third thesis, that this overcoming is the necessary fundament for the perception of risk, which in turn reinstates the subject's perception of his own vulnerability. Responsibility thus finds a motivation, which is neither altruistic nor duty-centred, in the awareness of our own vulnerability and the bond with the destiny of humankind as a whole.

  11. The Death of Narcissus: On Musical Subjectivity

    Directory of Open Access Journals (Sweden)

    James Currie


    Full Text Available On the first page of the preface to Michael Steinberg’s excellent book, Listening to Reason: Culture, Subjectivity, and Nineteenth-Century Music, the author states that the book’s origin can be located specifically to “August 1990,” when he was giving “a short preconcert lecture on Brahms at the first Bard Music Festival.”

  12. A Subjective Report of Pragmalinguistic Failure



    This paper begins with a subjective history of the writer's L2 (Japanese) learning experience. It i followed by a detailed description of three instances of pragmalinguistic failure, each related to th correct use of keigo (honourific formal Japanese according to many definitions). Keigo is both a indispensable part of sociolinguistic life in Japan and a major linguistic challenge to almost all foreig Japanese language learners, and even some native Japanese speakers. To be exact, the speech ...

  13. The neural substrates of subjective time dilation

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    Marc Wittmann


    Full Text Available An object moving towards an observer is subjectively perceived as longer in duration than the same object that is static or moving away. This 'time dilation effect' has been shown for a number of stimuli that differ from standard events along different feature dimensions (e.g. color, size, and dynamics. We performed an event-related functional magnetic resonance imaging (fMRI, while subjects viewed a stream of five visual events, all of which were static and of identical duration except the fourth one, which was a deviant target consisting of either a looming or a receding disc. The duration of the target was systematically varied and participants judged whether the target was shorter or longer than all other events. A time dilation effect was observed only for looming targets. Relative to the static standards, the looming as well as the receding targets induced increased activation of the anterior insula and anterior cingulate cortices (the “core control network”. The decisive contrast between looming and receding targets representing the time dilation effect showed strong asymmetric activation and, specifically, activation of cortical midline structures (the “default network”. These results provide the first evidence that the illusion of temporal dilation is due to activation of areas that are important for cognitive control and subjective awareness. The involvement of midline structures in the temporal dilation illusion is interpreted as evidence that time perception is related to self-referential processing.

  14. Subjective alertness rhythms in elderly people (United States)

    Monk, T. H.; Buysse, D. J.; Reynolds, C. F. 3rd; Kupfer, D. J.; Houck, P. R.


    The aim of this study was to evaluate age-related changes in the circadian rhythm of subjective alertness and to explore the circadian mechanisms underlying such changes. Using a visual analogue scale (VAS) instrument, 25 older men and women (71 y and older; 15 female, 10 male) rated their subjective alertness about 7 times per day during 5 baseline days of temporal isolation during which habitual bedtimes and waketimes were enforced. Comparisons were made with 13 middle-aged men (37-52 y) experiencing the same protocol. Advancing age (particularly in the men) resulted in less rhythmic alertness patterns, as indicated by lower amplitudes and less reliability of fitted 24-h sinusoids. This appeared in spite of the absence of any reliable age-related diminution in circadian temperature rhythm amplitude, thus suggesting the effect was not due to SCN weakness per se, but to weakened transduction of SCN output. In a further experiment, involving 36 h of constant wakeful bedrest, differences in the amplitude of the alertness rhythm were observed between 9 older men (79 y+), 7 older women (79 y+), and 17 young controls (9 males, 8 females, 19-28 y) suggesting that with advancing age (particularly in men) there is less rhythmic input into subjective alertness from the endogenous circadian pacemaker. These results may explain some of the nocturnal insomnia and daytime hypersomnia that afflict many elderly people.

  15. Review Essay: Knowledge, Subjectivity and Politics

    Directory of Open Access Journals (Sweden)

    Thomas Pfister


    Full Text Available The main interest of the study reviewed in this essay is in manifestations of subjectivity in the knowledge society. The first part demonstrates how the discourse on a knowledge society also constructs the dominant notion of an autonomous, self-reliant and intellectually capable subject. Then, the book traces how individuals act and constitute themselves in response to the discursive call for specific forms of subjectivity, focusing on a set of citizen conferences on biomedical issues. It thus, especially in its latter part, provides original and surprising insights, but this part is given too little space compared to the first part, leaving the reader wanting more. The essay then engages in a broader debate, discussing two further points in addition to the insights of the review. First, it scrutinises the function of science, which plays a key role in those negotiations where the knowledge society is constituted and shaped. Secondly, it seeks to refine the notion of politics, which should be comprehensive yet not too general. It therefore suggests understanding politics as a gradual phenomenon, which might be omnipresent but becomes particularly manifest in certain situations. In order to analyze politics in the context of pluralizing knowledges, it especially recommends focusing on situations where agency and agonistic contestations become visible. URN: urn:nbn:de:0114-fqs1003207

  16. From land to sea: unsettling subjectivities

    Directory of Open Access Journals (Sweden)

    Patrick Bresnihan


    Full Text Available In this paper I trace an important conceptual shift which emerged during my fieldwork with fishermen in the South West of Ireland. I begin by describing how my role as a social researcher was interpreted as a valuable ‘bridge’ between different (epistemological positions, namely the fishermen and scientists. This approach rests on the belief that individual actors occupy discrete subject-positions capable of being articulated and understood within consensus-making processes. Going to sea marked, for me, a literal and metaphorical departure from this understanding. Rather than thinking of fishermen as bounded, individual subjects acting on and in a ‘dumb’ external world, and thus having a ‘position’ from which to make themselves understood, I began to attend to experiences which extended across and between people, places and things. In part two I analyze how the concept of ‘continuous experience’ helps us to think about experience as relational and contingent, unsettling the (governing call to identify one’s position. Attending to the ways in which experience unfolds through the immediate mattering of relations between people, places and things also allows us to move beyond explanatory modes which seek to identify how subjects are produced through particular structuring relations. In the final part of the paper I describe how the excess of sociability can suspend normal roles and relations, including those which exist between ‘researcher’ and ‘subject’.

  17. Subjective refraction: the mechanism underlying the routine. (United States)

    Harris, W F


    The routine of subjective refraction is usually understood, explained and taught in terms of the relative positions of line or point foci and the retina. This paper argues that such an approach makes unnecessary and sometimes invalid assumptions about what is actually happening inside the eye. The only assumption necessary in fact is that the subject is able to guide the refractionist to (or close to) the optimum power for refractive compensation. The routine works even in eyes in which the interval of Sturm does not behave as supposed; it would work, in fact, regardless of the structure of the eye. The idealized subjective refraction routine consists of two steps: the first finds the best sphere (the stigmatic component) and the second finds the remaining Jackson cross-cylinder (the antistigmatic component). The model makes use of the concept of symmetric dioptric power space. The second part of the refraction routine can be performed with Jackson cross-cylinders alone. However, it is usually taught and practiced using spheres, cylinders and Jackson cross-cylinders in a procedure that is not easy to understand and learn. Recognizing that this part of the routine is equivalent to one involving Jackson cross-cylinders only allows one to teach and understand the procedure more naturally and easily.

  18. No effect of ablation of surfactant protein-D on acute cerebral infarction in mice

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Østergaard, Kamilla; Clausen, Bettina Hjelm;


    -induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected...... were comparable in SP-D KO and WT mice. CONCLUSIONS: SP-D synthesis in middle cerebral artery cells is consistent with SP-D conceivably leaking into the infarcted area and affecting local cytokine production. However, there was no SP-D synthesis in parenchymal brain cells and ablation of SP-D had...

  19. Radioiodinated Naphthylalanine Derivatives Targeting Pancreatic Beta Cells in Normal and Nonobese Diabetic Mice (United States)

    Amartey, John K.; Shi, Yufei; Al-Jammaz, Ibrahim; Esguerra, Celestina; Al-Otaibi, Basem; Al-Mohanna, Futwan


    An imaging method capable of using a signal from pancreatic beta cells to determine their mass would be of immense value in monitoring the progression of diabetes as well as response to treatment. Somatostatin receptors (SSTRs) are expressed on beta cells and are a potential target for imaging. The main objective of this study was to investigate whether pancreatic beta cells are a target for radiolabeled naphthylalanine derivatives. The molecules were subjected to in vitro and ex vivo evaluations. Pancreatic uptake of radioactivity was lower in nonobese diabetic (NOD) mice than normal mice at all time points investigated (P < .05) and correlated with the number of islets in tissue sections of both control and NOD mice. Immunohistochemical and confocal fluorescent microscopic studies showed colocalization of insulin and the conjugate radioligand in the pancreas. The results demonstrated that pancreatic uptake is receptor-mediated, and that beta cells are the primary target. PMID:18483609

  20. Postnatal hematopoiesis and gut microbiota in NOD mice deviate from C57BL/6 mice

    DEFF Research Database (Denmark)

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss


    Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate f...

  1. High-energy proton irradiation of C57Bl6 mice under hindlimb unloading (United States)

    Mendonca, Marc; Todd, Paul; Orschell, Christie; Chin-Sinex, Helen; Farr, Jonathan; Klein, Susan; Sokol, Paul


    Solar proton events (SPEs) pose substantial risk for crewmembers on deep space missions. It has been shown that low gravity and ionizing radiation both produce transient anemia and immunodeficiencies. We utilized the C57Bl/6 based hindlimb suspension model to investigate the consequences of hindlimb-unloading induced immune suppression on the sensitivity to whole body irradiation with modulated 208 MeV protons. Eight-week old C57Bl/6 female mice were conditioned by hindlimb-unloading. Serial CBC and hematocrit assays by HEMAVET were accumulated for the hindlimb-unloaded mice and parallel control animals subjected to identical conditions without unloading. One week of hindlimb-unloading resulted in a persistent, statistically significant 10% reduction in RBC count and a persistent, statistically significant 35% drop in lymphocyte count. This inhibition is consistent with published observations of low Earth orbit flown mice and with crewmember blood analyses. In our experiments the cell count suppression was sustained for the entire six-week period of observation and persisted for at least 7 days beyond the period of active hindlimb-unloading. C57Bl/6 mice were also irradiated with 208 MeV Spread Out Bragg Peak (SOBP) protons at the Midwest Proton Radiotherapy Institute at the Indiana University Cyclotron Facility. We found that at 8.5 Gy hindlimb-unloaded mice were significantly more radiation sensitive with 35 lethalities out of 51 mice versus 15 out of 45 control (non-suspended) mice within 30 days of receiving 8.5 Gy of SOBP protons (p =0.001). Both control and hindlimb-unloaded stocktickerCBC analyses of 8.5 Gy proton irradiated and control mice by HEMAVET demonstrated severe reductions in WBC counts (Lymphocytes and PMNs) by day 2 post-irradiation, followed a week to ten days later by reductions in platelets, and then reductions in RBCs about 2 weeks post-irradiation. Recovery of all blood components commenced by three weeks post-irradiation. CBC analyses of 8

  2. Mast cells and gastrointestinal dysmotility in the cystic fibrosis mouse.

    Directory of Open Access Journals (Sweden)

    Robert C De Lisle

    Full Text Available BACKGROUND: Cystic fibrosis (CF has many effects on the gastrointestinal tract and a common problem in this disease is poor nutrition. In the CF mouse there is an innate immune response with a large influx of mast cells into the muscularis externa of the small intestine and gastrointestinal dysmotility. The aim of this study was to evaluate the potential role of mast cells in gastrointestinal dysmotility using the CF mouse (Cftr(tm1UNC, Cftr knockout. METHODOLOGY: Wild type (WT and CF mice were treated for 3 weeks with mast cell stabilizing drugs (ketotifen, cromolyn, doxantrazole or were treated acutely with a mast cell activator (compound 48/80. Gastrointestinal transit was measured using gavage of a fluorescent tracer. RESULTS: In CF mice gastric emptying at 20 min post-gavage did not differ from WT, but was significantly less than in WT at 90 min post-gavage. Gastric emptying was significantly increased in WT mice by doxantrazole, but none of the mast cell stabilizers had any significant effect on gastric emptying in CF mice. Mast cell activation significantly enhanced gastric emptying in WT mice but not in CF mice. Small intestinal transit was significantly less in CF mice as compared to WT. Of the mast cell stabilizers, only doxantrazole significantly affected small intestinal transit in WT mice and none had any effect in CF mice. Mast cell activation resulted in a small but significant increase in small intestinal transit in CF mice but not WT mice. CONCLUSIONS: The results indicate that mast cells are not involved in gastrointestinal dysmotility but their activation can stimulate small intestinal transit in cystic fibrosis.

  3. Environmental Health Research Involving Human Subjects: Ethical Issues

    Directory of Open Access Journals (Sweden)

    David B. Resnik


    Full Text Available This article reviews some of the ethical issues that arise in environmental health research with human subjects, such as minimizing risks to subjects, balancing benefits and risks in research, intentional exposure studies with human subjects, protecting third parties in research, informing subjects about environmental hazards, communicating health information to subjects, and protecting privacy and confidentiality.

  4. Identification of subjects at risk of developing irritable bowel syndrome



    Described is the use of enterotyping of the gut microbiota for identifying a subject at risk of developing Irritable Bowel Syndrome (IBS) and/or diagnosing a subject suffering from IBS, as well as method for identifying a subject at risk of developing IBS and/or diagnosing a subject suffering from IBS by enterotypes a test sample derived from a subject

  5. Identificationof subjects at risk of developing irritable bowel syndrome



    Described is the use of enterotyping of the gut microbiota for identifying a subject at risk of developing Irritable Bowel Syndrome (IBS) and/or diagnosing a subject suffering from IBS, as well as method for identifying a subject at risk of developing IBS and/or diagnosing a subject suffering from IBS by enterotypes a test sample derived from a subject

  6. Reduction of Subjective and Objective System Complexity (United States)

    Watson, Michael D.


    Occam's razor is often used in science to define the minimum criteria to establish a physical or philosophical idea or relationship. Albert Einstein is attributed the saying "everything should be made as simple as possible, but not simpler". These heuristic ideas are based on a belief that there is a minimum state or set of states for a given system or phenomena. In looking at system complexity, these heuristics point us to an idea that complexity can be reduced to a minimum. How then, do we approach a reduction in complexity? Complexity has been described as a subjective concept and an objective measure of a system. Subjective complexity is based on human cognitive comprehension of the functions and inter relationships of a system. Subjective complexity is defined by the ability to fully comprehend the system. Simplifying complexity, in a subjective sense, is thus gaining a deeper understanding of the system. As Apple's Jonathon Ive has stated," It's not just minimalism or the absence of clutter. It involves digging through the depth of complexity. To be truly simple, you have to go really deep". Simplicity is not the absence of complexity but a deeper understanding of complexity. Subjective complexity, based on this human comprehension, cannot then be discerned from the sociological concept of ignorance. The inability to comprehend a system can be either a lack of knowledge, an inability to understand the intricacies of a system, or both. Reduction in this sense is based purely on a cognitive ability to understand the system and no system then may be truly complex. From this view, education and experience seem to be the keys to reduction or eliminating complexity. Objective complexity, is the measure of the systems functions and interrelationships which exist independent of human comprehension. Jonathon Ive's statement does not say that complexity is removed, only that the complexity is understood. From this standpoint, reduction of complexity can be approached

  7. Long-Lived αMUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection.

    Directory of Open Access Journals (Sweden)

    Esther Levy

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

  8. Expression of Attractin in male reproductive tract of human and mice and its correlation with male reproduction. (United States)

    Cheng, Dan; Ming, Yu; Li, Jie; Chi, Yan; Li, Hong-Gang; Zou, Yu-Jie; Xiong, Cheng-Liang


    The expression of Attractin mRNA and protein in testis and semen of human and male mice was investigated. Human testis and semen samples were all collected from Reproductive Center of Renmin Hospital, Wuhan University in December, 2012. Testis samples were collected from 7 cases of obstructive azoospermias when they were subjected to diagnosed testis biopsy, and 30 normal human semen samples were obtained from those cases of semen analysis. Adult mice testis tissues were obtained from 10 2-month-old male BALB/c mice, and 60 male mice at different ages were classified into 10 groups (day 1, 5, 10, 15, 21, 28, 35, 42, 56, and 120 respectively, n=6 each). The expression of Attractin mRNA and protein in testis was detected by RT-PCR and Western blotting respectively. Human semen samples were centrifuged into sperm plasma (SP) and sperm extract (SE), and mice sperm samples were collected from the epididymis of 10 adult male BALB/c mice. Western blotting was used to determine the Attractin protein expression level. Attractin mRNA and protein were expressed in the testis of both patients with obstructive azoospermias and adult Bcl/B mice. Quantitative RT-PCR revealed that no Attractin mRNA was detectable in day 1 male BALB/c mice group. The Attractin mRNA and protein levels were low on the day 10, and increased with age until day 56. On the day 120, the expression levels of Attractin were decreased. As for human semen samples, Attractin protein was expressed in both SP and SE, but didn't exist in samples from the epididymis of male BALB/c mice. It was suggested that Attractin acted as a novel active substance and was involved in male reproduction in both human and BALB/c mice, but it exerted a different expression profile in different mammal species.


    Directory of Open Access Journals (Sweden)

    D. Cinghiţă


    Full Text Available In this work we study agonistic behavior of laboratory white mice when they are kept in captivity. For all this experimental work we used direct observation of mice, in small lists, because we need a reduced space to emphasize characteristics of agonistic behavior. Relations between members of the same species that live in organized groups are based in most cases on hierarchical structure. Relations between leader and subservient, decided by fighting, involve a thorough observation between individuals. Each member of a group has its own place on the ierarchical scale depending on resultes of fhights – it can be leader or it can be subsurvient, depending on if it wines or looses the fight. Once hierarchical scale made, every animal will adjust its behavior. After analyzing the obtained data we have enough reasons to believe that after fights the winner, usually, is the massive mouse, but it is also very important the sexual ripeness, so the immature male will be beaten. The leader male had a big exploring area and it checks up all territory.The females can be more aggressive, its fights are more brutal, than male fights are, when they fight for supremacy, but in this case fights are not as frequent as in the case of males. Always the superior female, on hierarchical scale, shows males its own statute, so the strongest genes will be perpetuated.

  10. Mice embryology: a microscopic overview. (United States)

    Salvadori, Maria Letícia Baptista; Lessa, Thais Borges; Russo, Fabiele Baldino; Fernandes, Renata Avancini; Kfoury, José Roberto; Braga, Patricia Cristina Baleeiro Beltrão; Miglino, Maria Angélica


    In this work, we studied the embryology of mice of 12, 14, and 18 days of gestation by gross observation, light microscopy, and scanning electron microscopy. Grossly, the embryos of 12 days were observed in C-shaped region of the brain, eye pigmentation of the retina, first, second, and third pharyngeal arches gill pit nasal region on the fourth ventricle brain, cervical curvature, heart, liver, limb bud thoracic, spinal cord, tail, umbilical cord, and place of the mesonephric ridge. Microscopically, the liver, cardiovascular system and spinal cord were observed. In the embryo of 14 days, we observed structures that make up the liver and heart. At 18 days of gestation fetuses, it was noted the presence of eyes, mouth, and nose in the cephalic region, chest and pelvic region with the presence of well-developed limbs, umbilical cord, and placenta. Scanning electron microscopy in 18 days of gestation fetuses evidenced head, eyes closed eyelids, nose, vibrissae, forelimb, heart, lung, kidney, liver, small bowel, diaphragm, and part of the spine. The results obtained in this work describe the internal and external morphology of mice, provided by an integration of techniques and review of the morphological knowledge of the embryonic development of this species, as this animal is of great importance to scientific studies.

  11. Amylin induces hypoglycemia in mice

    Directory of Open Access Journals (Sweden)

    Luiz H. Guerreiro


    Full Text Available Amylin is a 37-aminoacid pancreatic protein that exerts control over several metabolic events such as glycemia and lacticemia. Amylin has long been shown to induce increases in arterial plasma glucose. We decided to investigate whether amylin plays additional roles in the glucose metabolism. We evaluated glucose homeostasis using whole blood from the tail tip of fasting, conscious, unrestrained normal and streptozotocyn-induced diabetic mice following subcutaneous administration of mouse amylin. Subcutaneous injection of 1 μg mouse amylin caused a transient decrease in whole blood glucose in both normal and diabetic mice in the absence of insulin. The blood glucose levels were lowest approximately 2 hours after amylin administration, after that they gradually recovered to the levels of the control group. The hypoglycemic effect followed a dose-dependent response ranging from 0.1 to 50 µg / mouse. These results reveal the ability for amylin in the direct control of glycemia at low doses in the absence of insulin.

  12. Effects of sleep disruption and high fat intake on glucose metabolism in mice. (United States)

    Ho, Jacqueline M; Barf, R Paulien; Opp, Mark R


    Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this

  13. Comparison of techniques for morphologic evaluation of glycerol-preserved human skim subjected to gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Bringel, Fabiana de A. [Faculty of Humanities, Economic and Health Sciences of Araguaina ITPAC (FAHESA/ITPAC/TO) Araguaina, TO (Brazil); Isaac, Cesar [Faculty of Medicine, University of Sao Paulo (FMUSP/SP) Sao Paulo, SP (Brazil); Herson, Marisa R., E-mail: [Tissue Bank of Victoria, Victoria (Australia); Freitas, Anderson Z. de; Martinho Junior, Antonio C.; Mathor, Monica B., E-mail:, E-mail: [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Radiation Technology Centre; Oliveira, Sergio F. de [Institute of Biomedical Sciences, University of Sao Paulo (ICB-USP/SP), SP (Brazil)


    Extensive skin lesions expose the body to damaging agents, which makes spontaneous regeneration difficult and, in many cases, leads patient to death. In such cases, if there are no donating areas for auto graft, allografts can be used. In this type of graft, tissue is processed in tissue banks, where it can be subjected to radiosterilization. According to in vitro studies, gamma radiation, in doses higher than 25 kGy, causes breakdown of collagen I fibrils in the skin preserved in glycerol at 85% and this change influences fibroblast migration and deposition of new collagen. In order to assess if the alterations observed in vitro, would compromise in vivo use, transplants of human tissue, irradiated or not, were performed in Nude mice. After the surgery the skins of the mice was subjected to macroscopic analysis on the 3{sup rd}, 7{sup th}, 21{sup st} and 90{sup th} days; optical coherence tomography on the 90{sup th} day and histological assay on the 3{sup rd}, 7{sup th}, 21{sup st} days to compare the results of the repair process among the techniques, considering that the OCT allows in vivo and not destructive morphological analysis. According to the results obtained through OCT it was possible to observe a more organized repair process in the animals which received irradiated grafts (25 and 50 kGy) if compared to unirradiated grafts. It was not possible to observe such phenomena through macroscopic or histological evaluation. (author)

  14. Adaptation to experimental jet-lag in R6/2 mice despite circadian dysrhythmia.

    Directory of Open Access Journals (Sweden)

    Nigel I Wood

    Full Text Available The R6/2 transgenic mouse model of Huntington's disease (HD shows a disintegration of circadian rhythms that can be delayed by pharmacological and non-pharmacological means. Since the molecular machinery underlying the circadian clocks is intact, albeit progressively dysfunctional, we wondered if light phase shifts could modulate the deterioration in daily rhythms in R6/2 mice. Mice were subjected to four x 4 hour advances in light onset. R6/2 mice adapted to phase advances, although angles of entrainment increased with age. A second cohort was subjected to a jet-lag paradigm (6 hour delay or advance in light onset, then reversal after 2 weeks. R6/2 mice adapted to the original shift, but could not adjust accurately to the reversal. Interestingly, phase shifts ameliorated the circadian rhythm breakdown seen in R6/2 mice under normal LD conditions. Our previous finding that the circadian period (tau of 16 week old R6/2 mice shortens to approximately 23 hours may explain how they adapt to phase advances and maintain regular circadian rhythms. We tested this using a 23 hour period light/dark cycle. R6/2 mice entrained to this cycle, but onsets of activity continued to advance, and circadian rhythms still disintegrated. Therefore, the beneficial effects of phase-shifting are not due solely to the light cycle being closer to the tau of the mice. Our data show that R6/2 mice can adapt to changes in the LD schedule, even beyond the age when their circadian rhythms would normally disintegrate. Nevertheless, they show abnormal responses to changes in light cycles. These might be caused by a shortened tau, impaired photic re-synchronization, impaired light detection and/or reduced masking by evening light. If similar abnormalities are present in HD patients, they may suffer exaggerated jet-lag. Since the underlying molecular clock mechanism remains intact, light may be a useful treatment for circadian dysfunction in HD.

  15. Enhanced self-administration of alcohol in muscarinic acetylcholine M4 receptor knockout mice

    DEFF Research Database (Denmark)

    de la Cour, Cecilie; Sørensen, Gunnar; Wörtwein, Gitta


    Modulation of cholinergic neurotransmission via nicotinic acetylcholine receptors is known to alter alcohol-drinking behavior. It is not known if muscarinic acetylcholine receptor subtypes have similar effects. The muscarinic M4 receptor is highly expressed in the brain reinforcement system......% and 10% alcohol in 60min sessions, 6 days/week, after having undergone a standard sucrose fading training procedure on a fixed ratio schedule. The mice were further subjected to an extinction period followed by a 1 day reinstatement trial. M4-/- mice consumed more alcohol at 5% and 8% compared to their M......-established. Moreover, the M4-/- mice displayed a reduced capacity to extinguish their alcohol-seeking behavior. Taken together, alcohol consumption is elevated in M4-/- mice, indicating that the M4 receptor is involved in mediating the reinforcing effects of alcohol. The M4 receptor should be further explored...

  16. Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Mensink, R.P.; Hof, H.B. van 't; Offermans, R.F.G.; Hofker, M.H.; Havekes, L.M.


    Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidentic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VDL) r

  17. Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet. (United States)

    Douris, Nicholas; Melman, Tamar; Pecherer, Jordan M; Pissios, Pavlos; Flier, Jeffrey S; Cantley, Lewis C; Locasale, Jason W; Maratos-Flier, Eleftheria


    Ingestion of very low-carbohydrate ketogenic diets (KD) is associated with weight loss, lowering of glucose and insulin levels and improved systemic insulin sensitivity. However, the beneficial effects of long-term feeding have been the subject of debate. We therefore studied the effects of lifelong consumption of this diet in mice. Complete metabolic analyses were performed after 8 and 80weeks on the diet. In addition we performed a serum metabolomic analysis and examined hepatic gene expression. Lifelong consumption of KD had no effect on morbidity or mortality (KD vs. Chow, 676 vs. 630days) despite hepatic steatosis and inflammation in KD mice. The KD fed mice lost weight initially as previously reported (Kennnedy et al., 2007) and remained lighter and had less fat mass; KD consuming mice had higher levels of energy expenditure, improved glucose homeostasis and higher circulating levels of β-hydroxybutyrate and triglycerides than chow-fed controls. Hepatic expression of the critical metabolic regulators including fibroblast growth factor 21 were also higher in KD-fed mice while expression levels of lipogenic enzymes such as stearoyl-CoA desaturase-1 was reduced. Metabolomic analysis revealed compensatory changes in amino acid metabolism, primarily involving down-regulation of catabolic processes, demonstrating that mice eating KD can shift amino acid metabolism to conserve amino acid levels. Long-term KD feeding caused profound and persistent metabolic changes, the majority of which are seen as health promoting, and had no adverse effects on survival in mice.

  18. Role of melatonin in reducing hypoxia-induced oxidative stress and morphological changes in the liver of male mice. (United States)

    El-Sokkary, Gamal H; Khidr, Bothaina M; Younes, Hala A


    Oxygen deficiency during critical illness may cause profound changes in cellular metabolism and subsequent tissue and organ dysfunction. Thus, the present study was designed to determine the effects of hypoxia and reoxygenation on the levels of lipid peroxidation and the morphological changes in the liver of male mice as well as the protective role of melatonin as an antioxidant. Two experiments were carried out in this study. Experiment I includes three groups of mice (control, hypoxic, and hypoxic+melatonin) while the experiment II includes two groups (reoxygenated and reoxygenated+melatonin). The levels of oxidized lipids were measured and the morphological changes were investigated using light and electron microscopy. In experiment I, hypoxia strongly stimulated lipid peroxidation levels (88%) while melatonin administration inhibited this increase (69%). Severe morphological changes (necrosis, dilated congested blood vessels, collection of inflammatory cells, condensed heterochromatic with irregular outlines nuclei, and mitochondrial degeneration) were detected in the liver of hypoxic mice. In experiment II, reoxygenation inhibited the levels of oxidized lipids (42%) versus hypoxic mice and some morphological changes were detected. When melatonin was given before reoxygenation, it inhibited the levels of lipid peroxidation by 66% versus hypoxic mice. Also, melatonin enhanced the recovery profile by 41% when compared with mice that reoxygenated with room air only. All morphological alterations that detected in both hypoxic and reoxygenated mice were repaired when melatonin administered. These results indicate that hypoxia and reoxygenation induce severe alterations in the liver and that melatonin exerts beneficial role in restoring tissue alterations after subjection to hypoxia.

  19. Lagged association between geomagnetic activity and diminished nocturnal pain thresholds in mice. (United States)

    Galic, M A; Persinger, M A


    A wide variety of behaviors in several species has been statistically associated with the natural variations in geomagnetism. To examine whether changes in geomagnetic activity are associated with pain thresholds, adult mice were exposed to a hotplate paradigm once weekly for 52 weeks during the dark cycle. Planetary A index values from the previous 6 days of a given hotplate session were correlated with the mean response latency for subjects to the thermal stimulus. We found that hotplate latency was significantly (P geomagnetic intensity 3 days prior to testing. Therefore, if the geomagnetic activity was greater 3 days before a given hotplate trial, subjects tended to exhibit shorter response latencies, suggesting lower pain thresholds or less analgesia. These results are supported by related experimental findings and suggest that natural variations in geomagnetic intensity may influence nociceptive behaviors in mice.

  20. Bacterial infections in Myd88-deficient mice. (United States)

    Villano, Jason S; Rong, Fang; Cooper, Timothy K


    Three breeding colonies of Myd88(-/-) mice had a history of significant morbidity and mortality. Although strain-specific poor reproductive performance might explain neonatal death and dystocia, mice were found dead or required euthanasia because of moribundity, distended abdomen, head tilt, and seizures. Histopathology results included bacteremia, placentitis, metritis, peritonitis with abscess formation, and suppurative meningoencephalitis. Intralesional gram-negative coccobacilli were present, often in extremely high number. Cultures of samples of the cardiac blood of a mouse and from water-bottle sipper tubes provided to some affected mice grew Pseudomonas aeruginosa. In addition, affected tissues from 2 mice and feces from a third tested PCR-positive for P. aeruginosa. Although the mice had received autoclaved reverse-osmosis-purified drinking water, we suspect that the mice were inoculated with P. aeruginosa through contaminated sipper tubes. Because of the deficiency in most of the Toll-like receptor signaling pathways, these Myd88(-/-) mice were unlikely to have developed competitive innate and adaptive immune responses, resulting in bacterial infections. These clinical cases underscore the importance of understanding how genotype, phenotype and environment affect animal health. Sound husbandry and experimental practices are needed to prevent the exposure of immuno-deficient mice to pathogens.

  1. Euthanasia of neonatal mice with carbon dioxide (United States)

    Pritchett, K.; Corrow, D.; Stockwell, J.; Smith, A.


    Exposure to carbon dioxide (CO2) is the most prevalent method used to euthanize rodents in biomedical research. The purpose of this study was to determine the time of CO2 exposure required to euthanize neonatal mice (0 to 10 days old). Multiple groups of mice were exposed to 100% CO 2 for time periods between 5 and 60 min. Mice were placed in room air for 10 or 20 min after CO2 exposure, to allow for the chance of recovery. If mice recovered at one time point, a longer exposure was examined. Inbred and outbred mice were compared. Results of the study indicated that time to death varied with the age of the animals and could be as long as 50 min on the day of birth and differed between inbred and outbred mice. Institutions euthanizing neonatal mice with CO2 may wish to adjust their CO 2 exposure time periods according the age of the mice and their genetic background. Copyright 2005 by the American Association for Laboratory Animal Science.

  2. The subjective importance of noise spectral content (United States)

    Baxter, Donald; Phillips, Jonathan; Denman, Hugh


    This paper presents secondary Standard Quality Scale (SQS2) rankings in overall quality JNDs for a subjective analysis of the 3 axes of noise, amplitude, spectral content, and noise type, based on the ISO 20462 softcopy ruler protocol. For the initial pilot study, a Python noise simulation model was created to generate the matrix of noise masks for the softcopy ruler base images with different levels of noise, different low pass filter noise bandwidths and different band pass filter center frequencies, and 3 different types of noise: luma only, chroma only, and luma and chroma combined. Based on the lessons learned, the full subjective experiment, involving 27 observers from Google, NVIDIA and STMicroelectronics was modified to incorporate a wider set of base image scenes, and the removal of band pass filtered noise masks to ease observer fatigue. Good correlation was observed with the Aptina subjective noise study. The absence of tone mapping in the noise simulation model visibly reduced the contrast at high levels of noise, due to the clipping of the high levels of noise near black and white. Under the 34-inch viewing distance, no significant difference was found between the luma only noise masks and the combined luma and chroma noise masks. This was not the intuitive expectation. Two of the base images with large uniform areas, `restaurant' and `no parking', were found to be consistently more sensitive to noise than the texture rich scenes. Two key conclusions are (1) there are fundamentally different sensitivities to noise on a flat patch versus noise in real images and (2) magnification of an image accentuates visual noise in a way that is non-representative of typical noise reduction algorithms generating the same output frequency. Analysis of our experimental noise masks applied to a synthetic Macbeth ColorChecker Chart confirmed the color-dependent nature of the visibility of luma and chroma noise.

  3. The Subject Analysis of Payment Systems Characteristics

    Directory of Open Access Journals (Sweden)

    Korobeynikova Olga Mikhaylovna


    Full Text Available The article deals with the analysis of payment systems aimed at identifying the categorical terminological apparatus, proving their specific features and revealing the impact of payment systems on the state of money turnover. On the basis of the subject analysis, the author formulates the definitions of a payment system (characterized by increasing speed of effecting payments, by the reduction of costs, by high degree of payments convenience for subjects of transactions, by security of payments, by acceptable level of risks and by social efficiency, a national payment system, and a local payment system (characterized by the growth of economic and social efficiency of systems participants, by the process of money turnover optimization on the basis of saving transaction costs and increasing speed of money flows within the local payment systems. According to the economic levels, the payment systems are divided to macrosystems (national payment systems, mezosystems (payment systems localized on the operational and territorial basis, microsystems (payments by individual economic subjects. The establishment of qualitative features of payment systems, which is a basis of the author’s terminological interpretation, gave a possibility to reveal the cause-effect relations of payment systems influence on the state of money turnover in the involved subjects, and on the economy as a whole. The result of the present research consists in revealing the payment systems influence on the state of money turnover which is significant: at the state and regional level – in the optimization of budget and inter-budgetary relations, in acceleration of the money turnover, in deceleration of the money supply and inflation rate, in reduced need in money emission; at the level of economic entities – in accelerating the money turnover and accounts receivable, in the reduction of debit and credit loans, in the growth of profit (turnover; at the household level – in

  4. [The Frankfurt-Pamplona subjective experience scale]. (United States)

    Cuesta Zorita, M J; Peralta Martín, V; Irigoyen Recalde, I


    Several instruments have been designed to assess subjective experiences (SE). The Frankfurt Complaint Questionnaire (FCQ) is the most widely used scale to assess SE. This study was aimed to replicate the factor validation of the scale in a Spanish sample. A factor analysis we carried out on the 98-items of FCQ. No a four-factor solution was found, as initially it had been proposed by authors of the scale. A simplified version of the FCQ was derived through procedures of unidimensionality analysis of factors.

  5. Personality as a Subject of Managerial Activity

    Directory of Open Access Journals (Sweden)

    Tytova Kateryna V.


    Full Text Available Psychological science, along with many other natural and social sciences, studies a person and personality, but it allocates in them its own specific aspect. The psychological science has a big number of approaches to understanding essence of the personality. Professionally important qualities are individual qualities of a subject of activity, which influence efficiency of activity and success of its mastering. The considered concepts are efforts to put in order various sociological and psychological knowledge about the personality and unite the personality theory with the theory of professional choice. The problem of professional formation of the personality belongs to actively developed psychological problems.

  6. Suction caissons subjected to monotonic combined loading

    DEFF Research Database (Denmark)

    Penzes, P.; Jensen, M.R.; Zania, Varvara


    Suction caissons are being increasingly used as offshore foundation solutions in shallow and intermediate water depths. The convenient installation method through the application of suction has rendered this type of foundation as an attractive alternative to the more traditional monopile foundation...... for offshore wind turbines. The combined loading imposed typically to a suction caisson has led to the estimation of their bearing capacity by means of 3D failure envelopes. This study aims to analyse the behaviour of suction caissons for offshore wind turbines subjected to combined loading. Finite element...

  7. Subjectivity and intersubjectivity between semiotics and phenomenology

    Directory of Open Access Journals (Sweden)

    Francesco Marsciani


    Full Text Available A semiotic theory of subjectivity cannot prescind from a radical consideration of the intersubjective dimension, which, from the phenomenological perspective, represents the constitutive instance of the meaning of the world. The theory of signification has yet to come to terms with this fundamental option: the theory of enunciation, for example, is still tied to the alternative between an egological perception of the production of meaning and a truly intersubjective conception. A radically intersubjective understanding of the constitution of meaning must, in the theory of enunciation, include an authentic theory of alterity in which the production of communicative intentions can be described based on a more fundamental transcendental intentionality.

  8. Handbook of statistical methods single subject design

    CERN Document Server

    Satake, Eiki; Maxwell, David L


    This book is a practical guide of the most commonly used approaches in analyzing and interpreting single-subject data. It arranges the methodologies used in a logical sequence using an array of research studies from the existing published literature to illustrate specific applications. The book provides a brief discussion of each approach such as visual, inferential, and probabilistic model, the applications for which it is intended, and a step-by-step illustration of the test as used in an actual research study.

  9. Acquisition in different and special subject areas

    CERN Document Server

    Katz, Linda S


    Learn how acquisitions librarians successfully serve specialized users! In this book, you'll find profiles, methods, and processes for acquisitions in specialized subject areas, such as local and regional poetry, oceanography, educational information in electronic formats, popular fiction, regional and ethnic materials, and more. Seasoned acquisitions librarians share their experiences in gathering the hard-to-find materials their libraries' highly specialized clients need to access. You'll also examine issues surrounding the acquisition of new reference tools that are vital in today's emergi

  10. Sick Leave and Subjective Health Complaints


    Tveito, Torill Helene


    The aims of this thesis were to identify risk factors for high levels of sick leave and investigate what – if anything – can be done to reduce sick leave. What is the role of “subjective health complaints”, coping, and psychosocial work factors in relation to sick leave, and to what extent do these factors and the sick leave relate to quality of life? Are there any interventions with a documented effect on sick leave in the literature? Is it possible to influence sick leave thr...

  11. Asperger's Syndrome, Subjectivity and the Senses. (United States)

    Badone, Ellen; Nicholas, David; Roberts, Wendy; Kien, Peter


    Situated at the intersection of anthropological work on illness narratives and research on the anthropology of autism, this paper is a close reading of an autobiographical narrative recounted by Peter, a young man diagnosed with Asperger's Syndrome, a type of autism spectrum disorder (ASD). Responding to Solomon's (2010a:252) call for phenomenologically grounded accounts of "the subjective, sensory, and perceptual experiences of autism … based on personal narratives and practices of being and self-awareness," this paper calls into question key assumptions in the clinical and popular literature about ASD relating to theory of mind, empathy, capacity for metaphorical thinking, and ASD as a life-long condition.

  12. The subject matter of an action

    Institute of Scientific and Technical Information of China (English)



    The subject matter of an action theory is the core of the civil procedure law theory. In the civil action sign theory development, appeared the old substantive law theory, the new lawsuit sign theory as well as the new substantive law theory three kin-ds of theories successively. In recent years, many jurists in our country also carried on the discussion to this question, this article have carried on the analysis in many theory foundations, looking for our country national condition the lawsuit sign theory.

  13. Economic Shocks and Subjective Well-being

    DEFF Research Database (Denmark)

    Hariri, Jacob Gerner; Bjørnskov, Christian; Justesen, Mogens Kamp

    -treatment respondents, surveyed after the devaluation. Our estimates show that the devaluation had a large and significantly negative effect on individuals’ evaluations of subjective well-being. These results suggest that macroeconomic shocks, such as unanticipated currency devaluations, may have significant short......This paper examines how economic shocks affect individual well-being in developing countries. Using the case of a sudden and unanticipated currency devaluation in Botswana as a quasi-experiment, we examine how this monetary shock affects individuals’ evaluations of well-being. We do so by using......-term costs in the form of reductions in people’s sense of well-being....

  14. Watching neutral and threatening movies: subjective experience and autonomic responses in subjects with different hypnotizability levels. (United States)

    Santarcangelo, E L; Paoletti, G; Balocchi, R; Scattina, E; Ghelarducci, B; Varanini, M


    Subjects with high hypnotizability scores (Highs) have been considered more prone to experience negative affect and more vulnerable to its autonomic effects with respect to low hypnotizable individuals (Lows). The aim of the study was to analyze the subjective experience, tonic skin conductance (SC), respiratory frequency (RF), heart rate (HR) and heart rate variability (HRV) of healthy Highs and Lows during a long-lasting, emotionally neutral task (Session R, 46 subjects) and a moderately threatening one (Session T, 35 subjects). At the end of the relaxing Session R, all participants reported an increased relaxation. At the end of the threatening Session T, only 20 subjects reported a decreased relaxation (effective T: eT subsample). Highs and Lows of this subsample reported a similarly reduced relaxation and showed a similarly increased skin conductance. HR and HRV did not differ between the two sessions and between Highs and Lows. Among the subjects not reporting decreased relaxation at the end of Session T (ineffective T: iT subsample, n=15), relaxation was deeper and associated with lower skin conductance in Highs, although HR and HRV did not differ between Highs and Lows. All together, the results do not support the hypothesis of higher proneness of Highs to experience negative affect and to exhibit the autonomic correlates of negative emotion.

  15. Surfactant protein D is proatherogenic in mice

    DEFF Research Database (Denmark)

    Sorensen, Grith L; Madsen, Jens; Kejling, Karin


    Surfactant protein D (SP-D) is an important innate immune defense molecule that mediates clearance of pathogens and modulates the inflammatory response. Moreover, SP-D is involved in lipid homeostasis, and pulmonary accumulation of phospholipids has previously been observed in SP-D-deficient (Spd......-/-) mice. Atherogenesis involves both inflammation and lipid deposition, and we investigated the role of SP-D in the development of atherosclerosis. SP-D synthesis was localized to vascular endothelial cells. Atherosclerotic lesion areas were 5.6-fold smaller in the aortic roots in Spd-/- mice compared...... with wild-type C57BL/6N mice on an atherogenic diet. HDL cholesterol (HDL-C) was significantly elevated in Spd-/- mice. Treatment of Spd-/- mice with a recombinant fragment of human SP-D resulted in decreases of HDL-C (21%) as well as total cholesterol (26%), and LDL cholesterol (28%). Plasma TNF...

  16. Pion contamination in the MICE muon beam (United States)

    Adams, D.; Alekou, A.; Apollonio, M.; Asfandiyarov, R.; Barber, G.; Barclay, P.; de Bari, A.; Bayes, R.; Bayliss, V.; Bertoni, R.; Blackmore, V. J.; Blondel, A.; Blot, S.; Bogomilov, M.; Bonesini, M.; Booth, C. N.; Bowring, D.; Boyd, S.; Brashaw, T. W.; Bravar, U.; Bross, A. D.; Capponi, M.; Carlisle, T.; Cecchet, G.; Charnley, C.; Chignoli, F.; Cline, D.; Cobb, J. H.; Colling, G.; Collomb, N.; Coney, L.; Cooke, P.; Courthold, M.; Cremaldi, L. M.; DeMello, A.; Dick, A.; Dobbs, A.; Dornan, P.; Drews, M.; Drielsma, F.; Filthaut, F.; Fitzpatrick, T.; Franchini, P.; Francis, V.; Fry, L.; Gallagher, A.; Gamet, R.; Gardener, R.; Gourlay, S.; Grant, A.; Greis, J. R.; Griffiths, S.; Hanlet, P.; Hansen, O. M.; Hanson, G. G.; Hart, T. L.; Hartnett, T.; Hayler, T.; Heidt, C.; Hills, M.; Hodgson, P.; Hunt, C.; Iaciofano, A.; Ishimoto, S.; Kafka, G.; Kaplan, D. M.; Karadzhov, Y.; Kim, Y. K.; Kuno, Y.; Kyberd, P.; Lagrange, J.-B.; Langlands, J.; Lau, W.; Leonova, M.; Li, D.; Lintern, A.; Littlefield, M.; Long, K.; Luo, T.; Macwaters, C.; Martlew, B.; Martyniak, J.; Mazza, R.; Middleton, S.; Moretti, A.; Moss, A.; Muir, A.; Mullacrane, I.; Nebrensky, J. J.; Neuffer, D.; Nichols, A.; Nicholson, R.; Nugent, J. C.; Oates, A.; Onel, Y.; Orestano, D.; Overton, E.; Owens, P.; Palladino, V.; Pasternak, J.; Pastore, F.; Pidcott, C.; Popovic, M.; Preece, R.; Prestemon, S.; Rajaram, D.; Ramberger, S.; Rayner, M. A.; Ricciardi, S.; Roberts, T. J.; Robinson, M.; Rogers, C.; Ronald, K.; Rubinov, P.; Rucinski, P.; Sakamato, H.; Sanders, D. A.; Santos, E.; Savidge, T.; Smith, P. J.; Snopok, P.; Soler, F. J. P.; Speirs, D.; Stanley, T.; Stokes, G.; Summers, D. J.; Tarrant, J.; Taylor, I.; Tortora, L.; Torun, Y.; Tsenov, R.; Tunnell, C. D.; Uchida, M. A.; Vankova-Kirilova, G.; Virostek, S.; Vretenar, M.; Warburton, P.; Watson, S.; White, C.; Whyte, C. G.; Wilson, A.; Winter, M.; Yang, X.; Young, A.; Zisman, M.


    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240 MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than ~1% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is fπ < 1.4% at 90% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.

  17. Pion contamination in the MICE muon beam

    CERN Document Server

    Bogomilov, M.; Vankova-Kirilova, G.; Bertoni, R.; Bonesini, M.; Chignoli, F.; Mazza, R.; Palladino, V.; de Bari, A.; Cecchet, G.; Capponi, M.; Iaciofano, A.; Orestano, D.; Pastore, F.; Tortora, L.; Kuno, Y.; Sakamoto, H.; Ishimoto, S.; Japan, Ibaraki; Filthaut, F.; Hansen, O.M.; Ramberger, S.; Vretenar, M.; Asfandiyarov, R.; Blondel, A.; Drielsma, F.; Karadzhov, Y.; Charnley, G.; Collomb, N.; Gallagher, A.; Grant, A.; Griffiths, S.; Hartnett, T.; Martlew, B.; Moss, A.; Muir, A.; Mullacrane, I.; Oates, A.; Owens, P.; Stokes, G.; Warburton, P.; White, C.; Adams, D.; Barclay, P.; Bayliss, V.; Bradshaw, T.W.; Courthold, M.; Francis, V.; Fry, L.; Hayler, T.; Hills, M.; Lintern, A.; Macwaters, C.; Nichols, A.; Preece, R.; Ricciardi, S.; Rogers, C.; Stanley, T.; Tarrant, J.; Watson, S.; Wilson, A.; Bayes, R.; Nugent, J.C.; Soler, F.J.P.; Cooke, P.; Gamet, R.; Alekou, A.; Apollonio, M.; Barber, G.; Colling, D.; Dobbs, A.; Dornan, P.; Hunt, C.; Lagrange, J-B.; Long, K.; Martyniak, J.; Middleton, S.; Pasternak, J.; Santos, E.; Savidge, T.; Uchida, M.A.; Blackmore, V.J.; Carlisle, T.; Cobb, J.H.; Lau, W.; Rayner, M.A.; Tunnell, C.D.; Booth, C.N.; Hodgson, P.; Langlands, J.; Nicholson, R.; Overton, E.; Robinson, M.; Smith, P.J.; Dick, A.; Ronald, K.; Speirs, D.; Whyte, C.G.; Young, A.; Boyd, S.; Franchini, P.; Greis, J.R.; Pidcott, C.; Taylor, I.; Gardener, R.; Kyberd, P.; Littlefield, M.; Nebrensky, J.J.; Bross, A.D.; Fitzpatrick, T.; Leonova, M.; Moretti, A.; Neuffer, D.; Popovic, M.; Rubinov, P.; Rucinski, R.; Roberts, T.J.; Bowring, D.; DeMello, A.; Gourlay, S.; Li, D.; Prestemon, S.; Virostek, S.; Zisman, M.; Drews, M.; Hanlet, P.; Kafka, G.; Kaplan, D.M.; Rajaram, D.; Snopok, P.; Torun, Y.; Winter, M.; Blot, S.; Kim, Y.K.; Bravar, U.; Onel, Y.; Cremaldi, L.M.; Hart, T.L.; Luo, T.; Sanders, D.A.; Summers, D.J.; Cline, D.; Yang, X.; Coney, L.; Hanson, G.G.; Heidt, C.


    The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240\\,MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than $\\sim$1\\% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is $f_\\pi < 1.4\\%$ at 90\\% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.

  18. The immunosuppressive effects of phthalocyanine photodynamic therapy in mice are mediated by CD4+ and CD8+ T cells and can be adoptively transferred to naive recipients. (United States)

    Yusuf, Nabiha; Katiyar, Santosh K; Elmets, Craig A


    Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors but it is also immunosuppressive which may reduce its therapeutic efficacy. The purpose of our study was to elucidate the role of CD4+ and CD8+ T cells in PDT immunosuppression. Using silicon phthalocyanine 4 (Pc4) as photosensitizer, nontumor-bearing CD4 knockout (CD4-/-) mice and their wild type (WT) counterparts were subjected to Pc4-PDT in a manner identical to that used for tumor regression (1 cm spot size, 0.5 mg kg(-1) Pc4, 110 J cm(-2) light) to assess the effect of Pc4-PDT on cell-mediated immunity. There was a decrease in immunosuppression in CD4-/- mice compared with WT mice. We next examined the role of CD8+ T cells in Pc4-PDT-induced immunosuppression using CD8-/- mice following the same treatment regimen used for CD4-/- mice. Similar to CD4-/- mice, CD8-/- mice exhibited less immunosuppression than WT mice. Pc4-PDT-induced immunosuppression could be adoptively transferred with spleen cells from Pc4-PDT treated donor mice to syngenic naive recipients (P PDT-induced immunosuppression but do not affect PDT-induced regression of tumors may prove superior to PDT alone in promoting long-term antitumor responses.

  19. Role of state-dependent learning in the cognitive effects of caffeine in mice


    Sanday, Leandro [UNIFESP; Zanin, Karina Agustini [UNIFESP; Patti, Camilla de Lima [UNIFESP; Fernandes-Santos, Luciano [UNIFESP; Oliveira, Larissa C. [UNIFESP; Longo, Beatriz Monteiro; Andersen, Monica Levy [UNIFESP; Tufik, Sergio; Frussa-Filho, Roberto


    Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine be...

  20. Tumour necrosis factor alpha causes hypoferraemia and reduced intestinal iron absorption in mice


    Laftah, Abas H; SHARMA, NAVEEN; Matthew J Brookes; McKie, Andrew T; Simpson, Robert J; Tariq H Iqbal; Tselepis, Chris


    Abstract Cytokines are implicated in the anaemia of chronic disease by reducing erythropoiesis and increasing iron sequestration in the reticuloendotheial system. However, the effect of cytokines in particular TNF-{alpha} on small bowel iron uptake and iron transporter expression remains unclear. In this study we subjected CD1 male mice to intra-peritoneal injection with TNF-{alpha} (10ng/mouse) and then examined the expression and localisation of DMT1, Ireg1, and ferritin in duode...

  1. Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV knockout mice.

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    Keizo Takao

    Full Text Available Calcium-calmodulin dependent protein kinase IV (CaMKIV is a protein kinase that activates the transcription factor CREB, the cyclic AMP-response element binding protein. CREB is a key transcription factor in synaptic plasticity and memory consolidation. To elucidate the behavioral effects of CaMKIV deficiency, we subjected CaMKIV knockout (CaMKIV KO mice to a battery of behavioral tests. CaMKIV KO had no significant effects on locomotor activity, motor coordination, social interaction, pain sensitivity, prepulse inhibition, attention, or depression-like behavior. Consistent with previous reports, CaMKIV KO mice exhibited impaired retention in a fear conditioning test 28 days after training. In contrast, however, CaMKIV KO mice did not show any testing performance deficits in passive avoidance, one of the most commonly used fear memory paradigms, 28 days after training, suggesting that remote fear memory is intact. CaMKIV KO mice exhibited intact spatial reference memory learning in the Barnes circular maze, and normal spatial working memory in an eight-arm radial maze. CaMKIV KO mice also showed mildly decreased anxiety-like behavior, suggesting that CaMKIV is involved in regulating emotional behavior. These findings indicate that CaMKIV might not be essential for fear memory or spatial memory, although it is possible that the activities of other neural mechanisms or signaling pathways compensate for the CaMKIV deficiency.

  2. A proposal for refining the forced swim test in Swiss mice. (United States)

    Costa, Ana Paula Ramos; Vieira, Cintia; Bohner, Lauren O L; Silva, Cristiane Felisbino; Santos, Evelyn Cristina da Silva; De Lima, Thereza Christina Monteiro; Lino-de-Oliveira, Cilene


    The forced swim test (FST) is a preclinical test to the screening of antidepressants based on rats or mice behaviours, which is also sensitive to stimulants of motor activity. This work standardised and validated a method to register the active and passive behaviours of Swiss mice during the FST in order to strength the specificity of the test. Adult male Swiss mice were subjected to the FST for 6 min without any treatment or after intraperitoneal injection of saline (0.1 ml/10 g), antidepressants (imipramine, desipramine, or fluoxetine, 30 mg/kg) or stimulants (caffeine, 30 mg/kg or apomorphine, 10mg/kg). The latency, frequency and duration of behaviours (immobility, swimming, and climbing) were scored and summarised in bins of 6, 4, 2 or 1 min. Parameters were first analysed using Principal Components Analysis generating components putatively related to antidepressant (first and second) or to stimulant effects (third). Antidepressants and stimulants affected similarly the parameters grouped into all components. Effects of stimulants on climbing were better distinguished of antidepressants when analysed during the last 4 min of the FST. Surprisingly, the effects of antidepressants on immobility were better distinguished from saline when parameters were scored in the first 2 min. The method proposed here is able to distinguish antidepressants from stimulants of motor activity using Swiss mice in the FST. This refinement should reduce the number of mice used in preclinical evaluation of antidepressants.

  3. Lack of Melanopsin Is Associated with Extreme Weight Loss in Mice upon Dietary Challenge.

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    Didem Göz Aytürk

    Full Text Available Metabolic disorders have been established as major risk factors for ocular complications and poor vision. However, little is known about the inverse possibility that ocular disease may cause metabolic dysfunction. To test this hypothesis, we assessed the metabolic consequences of a robust dietary challenge in several mouse models suffering from retinal mutations. To this end, mice null for melanopsin (Opn4-/-, the photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs, were subjected to five weeks of a ketogenic diet. These mice lost significantly more weight than wild-type controls or mice lacking rod and cone photoreceptors (Pde6brd1/rd1. Although ipRGCs are critical for proper circadian entrainment, and circadian misalignment has been implicated in metabolic pathology, we observed no differences in entrainment between Opn4-/- and control mice. Additionally, we observed no differences in any tested metabolic parameter between these mouse strains. Further studies are required to establish the mechanism giving rise to this dramatic phenotype observed in melanopsin-null mice. We conclude that the causality between ocular disease and metabolic disorders merits further investigation due to the popularity of diets that rely on the induction of a ketogenic state. Our study is a first step toward understanding retinal pathology as a potential cause of metabolic dysfunction.

  4. Behavioral and Biochemical Evidences for Antidepressant-Like Activity of Celastrus Paniculatus Seed Oil in Mice (United States)

    Valecha, Rekha; Dhingra, Dinesh


    Introduction: Celastrus paniculatus seed oil, commonly known as Malkangni or Jyotishmati, was in use from time immemorial to treat brain related disorders. Celastrus paniculatus seed oil has significant antidepressant-like activity in chronic unpredictable stressed mice. The present study was undertaken to evaluate the antidepressant-like effect of Celastrus paniculatus seed oil in unstressed mice and to explore its mechanism of action. Methods: The seed oil (50, 100, and 200 mg/kg, PO) and fluoxetine per se were administered for 14 successive days to Swiss young albino mice. On the 14th day, 60 min after drug administration, animals were subjected to Tail Suspension Test (TST) and Forced Swim Test (FST). The mechanism of action was also studied. Results: The oil significantly decreased immobility period of mice in both tail suspension test and forced swim test, indicating its significant antidepressant-like activity. The efficacy was found to be comparable to fluoxetine (PSulpiride (selective D2-receptor antagonist), p-CPA (tryptophan hydroxylase inhibitor), and baclofen (GABAB agonist) significantly attenuated the oil-induced antidepressant-like effect, when assessed during TST. Discussion: Celastrus paniculatus seed oil produced significant antidepressant-like effect in mice possibly through interaction with dopamine D2, serotonergic, and GABAB receptors; as well as inhibition of MAO–A activity and decrease in plasma corticosterone levels. PMID:27303599

  5. Characterization of cognitive deficits in mice with an alternating hemiplegia-linked mutation. (United States)

    Kirshenbaum, Greer S; Dachtler, James; Roder, John C; Clapcote, Steven J


    Cognitive impairment is a prominent feature in a range of different movement disorders. Children with Alternating Hemiplegia of Childhood are prone to developmental delay, with deficits in cognitive functioning becoming progressively more evident as they grow older. Heterozygous mutations of the ATP1A3 gene, encoding the Na+,K+-ATPase α3 subunit, have been identified as the primary cause of Alternating Hemiplegia. Heterozygous Myshkin mice have an amino acid change (I810N) in Na+,K+-ATPase α3 that is also found in Alternating Hemiplegia. To investigate whether Myshkin mice exhibit learning and memory deficits resembling the cognitive impairments of patients with Alternating Hemiplegia, we subjected them to a range of behavioral tests that interrogate various cognitive domains. Myshkin mice showed impairments in spatial memory, spatial habituation, locomotor habituation, object recognition, social recognition, and trace fear conditioning, as well as in the visible platform version of the Morris water maze. Increasing the duration of training ameliorated the deficit in social recognition but not in spatial habituation. The deficits of Myshkin mice in all of the learning and memory tests used are consistent with the cognitive impairment of the vast majority of AHC patients. These mice could thus help advance our understanding of the underlying neural mechanisms influencing cognitive impairment in patients with ATP1A3-related disorders.

  6. Preserved recovery of cardiac function following ischemia-reperfusion in mice lacking SIRT3. (United States)

    Koentges, Christoph; Pfeil, Katharina; Meyer-Steenbuck, Maximilian; Lother, Achim; Hoffmann, Michael M; Odening, Katja E; Hein, Lutz; Bode, Christoph; Bugger, Heiko


    Lack of the mitochondrial deacetylase sirtuin 3 (SIRT3) impairs mitochondrial function and increases the susceptibility to induction of the mitochondrial permeability transition pore. Because these alterations contribute to myocardial ischemia-reperfusion (IR) injury, we hypothesized that SIRT3 deficiency may increase cardiac injury following myocardial IR. Hearts of 10-week-old mice were perfused in the isolated working mode and subjected to 17.5 min of global no-flow ischemia, followed by 30 min of reperfusion. Measurements before ischemia revealed a decrease in cardiac power (-20%) and rate pressure product (-15%) in SIRT3(-/-) mice. Mitochondrial state 3 respiration (-15%), ATP synthesis (-39%), and ATP/O ratios (-29%) were decreased in hearts of SIRT3(-/-) mice. However, percent recovery of cardiac power (WT 94% ± 9%; SIRT3(-/-) 89% ± 9%) and rate pressure product (WT 89% ± 16%; SIRT3(-/-) 96% ± 3%) following IR was similar in both groups. Myocardial infarct size was not increased in SIRT3(-/-) mice following permanent ligation of the left anterior descending coronary artery (LAD). Left ventricular pressure and dP/dtmax, and mitochondrial respiration and ATP synthesis were not different between groups following LAD ligation. Thus, despite pre-existing defects in cardiac function and mitochondrial respiratory capacity in SIRT3(-/-) mice, SIRT3 deficiency does not additionally impair cardiac function following IR or following myocardial infarction.

  7. A Cmv2 QTL on chromosome X affects MCMV resistance in New Zealand male mice. (United States)

    Rodriguez, Marisela R; Lundgren, Alyssa; Sabastian, Pearl; Li, Qian; Churchill, Gary; Brown, Michael G


    NK cell-mediated resistance to viruses is subject to genetic control in humans and mice. Here we used classical and quantitative genetic strategies to examine NK-mediated murine cytomegalovirus (MCMV) control in genealogically related New Zealand white (NZW) and black (NZB) mice. NZW mice display NK cell-dependent MCMV resistance while NZB NK cells fail to limit viral replication after infection. Unlike Ly49H(+) NK resistance in C57BL/6 mice, NZW NK-mediated MCMV control was Ly49H-independent. Instead, MCMV resistance in NZW (Cmv2) involves multiple genetic factors. To establish the genetic basis of Cmv2 resistance, we further characterized a major chromosome X-linked resistance locus (DXMit216) responsible for innate MCMV control in NZW x NZB crosses. We found that the DXMit216 locus affects early MCMV control in New Zealand F(2) crosses and demonstrate that the NZB-derived DXMit216 allele enhances viral resistance in F(2) males. The evolutionary conservation of the DXMit216 region in mice and humans suggests that a Cmv2-related mechanism may affect human antiviral responses.

  8. Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine induced amnesia in mice. (United States)

    Ghumatkar, Priya J; Patil, Sachin P; Jain, Pankaj D; Tambe, Rufi M; Sathaye, Sadhana


    Phloretin (PHL), a dihydrochalcone flavonoid usually present in the roots and leaves of apple tree. In vitro study on GT1-7 immortalized hypothalamic neurons exposed to amyloid beta (25-35), demonstrated that PHL significantly influenced membrane fluidity and potential. PHL also significantly decreased excitotoxicity by restoring the calcium homeostasis in the same. Thus, PHL proves to be a promising therapeutic moiety which should be further screened in the treatment of Alzheimer's disease. The objective of the present study was to evaluate the nootropic, neuroprotective and neurotrophic roles of PHL in the subacute scopolamine induced amnesia in mice. In this study, mice were pretreated with PHL 2.5mg/kg, 5mg/kg, 10mg/kg and Donepezil (DON) 1mg/kg intraperitoneally (i.p) for 14days. The last 7days of treatment regimen included daily injection of SCP 1.5mg/kg to induce cognitive deficits. Mice were subjected to behavioral analysis. Biochemical estimation of the brain homogenates for acetylcholinesterase and oxidative stress biomarkers were conducted. Furthermore, immunohistochemical analysis for the brain derived neurotrophic factor (BDNF) was carried out particularly in the hippocampus. PHL was found to significantly improve the performance of mice in Morris water maze test (Pnootropic, neuroprotective and neurotrophic activities in SCP induced memory impaired mice and hence, is a promising therapeutic moiety in the treatment of AD.

  9. Plasminogen deficiency causes reduced corticospinal axonal plasticity and functional recovery after stroke in mice.

    Directory of Open Access Journals (Sweden)

    Zhongwu Liu

    Full Text Available Tissue plasminogen activator (tPA has been implicated in neurite outgrowth and neurological recovery post stroke. tPA converts the zymogen plasminogen (Plg into plasmin. In this study, using plasminogen knockout (Plg-/- mice and their Plg-native littermates (Plg+/+, we investigated the role of Plg in axonal remodeling and neurological recovery after stroke. Plg+/+ and Plg-/- mice (n = 10/group were subjected to permanent intraluminal monofilament middle cerebral artery occlusion (MCAo. A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA was injected into the left motor cortex to anterogradely label the corticospinal tract (CST. Animals were euthanized 4 weeks after stroke. Neurite outgrowth was also measured in primary cultured cortical neurons harvested from Plg+/+ and Plg-/- embryos. In Plg+/+ mice, the motor functional deficiency after stroke progressively recovered with time. In contrast, recovery in Plg-/- mice was significantly impaired compared to Plg+/+ mice (p0.82, p<0.01. Plg-/- neurons exhibited significantly reduced neurite outgrowth. Our data suggest that plasminogen-dependent proteolysis has a beneficial effect during neurological recovery after stroke, at least in part, by promoting axonal remodeling in the denervated spinal cord.

  10. Chronic exercise ameliorates the neuroinflammation in mice carrying NSE/htau23

    Energy Technology Data Exchange (ETDEWEB)

    Leem, Yea-Hyun, E-mail: [Exercise Biochemistry Laboratory, Korea National Sport University, Seoul 138-763 (Korea, Republic of); Lee, Young-Ik, E-mail: [Department of Oriental Sports Medicine, Daegu Hanny University, Daegu 712-715 (Korea, Republic of); Son, Hee-Jeong, E-mail: [Exercise Physiology Laboratory, Korea National Sport University, Seoul 138-763 (Korea, Republic of); Lee, Sang-Ho, E-mail: [Department of Sports for All, Kangnam University, Yongin 446-702 (Korea, Republic of)


    Research highlights: {yields} The progress of neurodegeration are directly linked to the neuroinflammatory response. {yields} We investigate whether exercise improves the neuroinflammation using T{sub g}-NSE/htau23 mice. {yields} This provides insights that exercise may beneficial effects on the neuroinflammatory disorders. -- Abstract: The objective of the present study was to investigate whether chronic endurance exercise attenuates the neuroinflammation in the brain of mice with NSE/htau23. In this study, the tau-transgenic (Tg) mouse, Tg-NSE/htau23, which over expresses human Tau23 in its brain, was subjected to chronic exercise for 3 months, from 16 months of age. The brains of Tg mice exhibited increased immunoreactivity and active morphological changes in GFAP (astrocyte marker) and MAC-1 (microglia marker) expression in an age-dependent manner. To identify the effects of chronic exercise on gliosis, the exercised Tg mice groups were treadmill run at a speed of 12 m/min (intermediate exercise group) or 19 m/min (high exercise group) for 1 h/day and 5 days/week during the 3 month period. The neuroinflammatory response characterized by activated astroglia and microglia was significantly repressed in the exercised Tg mice in an exercise intensity-dependent manner. In parallel, chronic exercise in Tg mice reduced the increased expression of TNF-{alpha}, IL-6, IL-1{beta}, COX-2, and iNOS. Consistently with these changes, the levels of phospho-p38 and phospho-ERK were markedly downregulated in the brain of Tg mice after exercise. In addition, nuclear NF-{kappa}B activity was profoundly reduced after chronic exercise in an exercise intensity-dependent manner. These findings suggest that chronic endurance exercise may alleviate neuroinflammation in the Tau pathology of Alzheimer's disease.

  11. Relaxin-3 receptor (RXFP3 signalling mediates stress-related alcohol preference in mice.

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    Andrew W Walker

    Full Text Available Stressful life events are causally linked with alcohol use disorders (AUDs, providing support for a hypothesis that alcohol consumption is aimed at stress reduction. We have previously shown that expression of relaxin-3 mRNA in rat brain correlates with alcohol intake and that central antagonism of relaxin-3 receptors (RXFP3 prevents stress-induced reinstatement of alcohol-seeking. Therefore the objectives of these studies were to investigate the impact of Rxfp3 gene deletion in C57BL/6J mice on baseline and stress-related alcohol consumption. Male wild-type (WT and Rxfp3 knockout (KO (C57/B6JRXFP3TM1/DGen littermate mice were tested for baseline saccharin and alcohol consumption and preference over water in a continuous access two-bottle free-choice paradigm. Another cohort of mice was subjected to repeated restraint followed by swim stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde dehydrogenase activity was assessed in mice following chronic alcohol intake and in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice displayed a stress-induced reduction in alcohol preference that was not observed in WT littermates. Notably, this phenotype, once established, persisted for at least six weeks after cessation of stress exposure. These findings suggest that in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol preference during and after stress, but does not appear to strongly regulate the primary reinforcing effects of alcohol.

  12. Agmatine increases proliferation of cultured hippocampal progenitor cells and hippocampal neurogenesis in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Yun-feng LI; Hong-xia CHEN; Ying LIU; You-zhi ZHANG; Yan-qin LIU; Jin LI


    Aim:To explore the mechanism of agmatine's antidepressant action.Methods: Male mice were subjected to a variety of unpredictable stressors on a daily basis over a 24-d period.The open-field behaviors of the mice were displayed and recorded using a Videomex-V image analytic system automatically.For bromodeoxyuridine (BrdU;thymidine analog as a marker for dividing cells) labeling,the mice were injected with BrdU (100 mg/kg,ip,twice per d for 2 d),and the hippocampal neurogenesis in stressed mice was measured by immunohistochemistry.The proliferation of cultured hippocampal progenitor cells from neonatal rats was determined by colorimetric assay (cell counting kit-8) and 3H-thymidine incorporation assay.Results:After the onset of chronic stress,the locomotor activity of the mice in the open field significantly decreased,while coadministration of agmatine 10 mg/kg (po) blocked it.Furthermore,the number of BrdU-labeled cells in the hippocampal dentate gyrus significantly decreased in chronically stressed mice, which was also blocked by chronic coadministration with agmatine 10 mg/kg (po). Four weeks after the BrdU injection, some of the new born cells matured and became neurons, as determined by double labeling for BrdU and neuron specific enolase (NSE), a marker for mature neurons.In vitro treatment with agmatine 0.1-10 μmo1/L for 3 d significantly increased the proliferation of the cultured hippocampal progenitor cells in a dose-dependent manner.Conclusion:We have found that agmatine increases proliferation of hippocampal progenitor cells in vitro and the hippocampal neurogenesis in vivo in chronically stressed mice.This may be one of the important mechanisms involved in agmatine's antidepressant action.

  13. Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice.

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    Kazuyoshi Aso

    Full Text Available It has been shown that adipose-derived mesenchymal stem cells (AMSCs can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>18 mo old mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA plus cholera toxin (CT three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA and plasma IgG antibody (Ab responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. When cytokine production was examined, OVA-stimulated Peyer's patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA- or CT-B-specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice.

  14. Nation, Identity, and Subjectivity in Globalizing Literature

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    Yasue Arimitsu


    Full Text Available Since the end of the 20th century, particularly after the Cold War ended, national borderlines have been redrawn many times in the areas of the Eastern Europe, the Middle East, and a wide range of Asia, and people started crossing national borderlines to immigrate to other countries. As a result, the definition of a modern nation with one ethnicity, one language, and one culture collapsed. Under the policy of multiculturalism, Australia accepts immigrants from all over the world, and Australian literature at present is characterized as being ethnically, culturally, and linguistically hybrid. In this paper I look at Australian writers such as Brian Castro and Nam Le and compare them with other writers who are considered post-colonial writers, such as Salman Rushdie, V.S. Naipaul and Kazuo Ishiguro. I focus on how these writers attempt to present their identities along with their subjectivities. I also compare them with a Japanese writer, Haruki Murakami, whose literary works are widely read throughout the world, crossing cultural, ethnic, and language barriers, even though he writes in Japanese and has a mono-cultural background. I investigate the reason why Murakami’s works are accepted by many contemporary readers worldwide. I finally explore the meaning of national identity and subjectivity in the globalizing world, and clarify the transformation of modern literature.

  15. Including subjectivity in the teaching of Psychopathology

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    Octavio Domont de Serpa Junior


    Full Text Available Current psychopathology studies have often been presented in their descriptive dimension. This perspective is important for teaching because it helps the students to recognize and identify the symptomatology of each psychopathology case. However, subjectivity, the experience of suffering and interpersonal aspects are all lost in this perspective. Coming from another psychopathology tradition - existential anthropology - this paper presents practical psychopathology teaching experience which considers such dimensions as being relevant to the understanding of mental suffering. The features and limitations of such traditions are briefly reviewed to support this teaching experience. Two new modalities of practical teaching, used in the discipline of "Special Psychopathology I" offered by the Department of Psychiatry and Forensic Medicine at the medical school of the Federal University of Rio de Janeiro for students of psychology, will be presented according to descriptive case study methodology. With these activities we also expect to change the practice of teaching. Traditionally, interviewing of in-patients by a large group of students who observe passively what is happening is the center of this kind of education. We intend to develop a model of teaching which is closer to the proposal of the Brazilian Psychiatric Reform which views mental illness as a complex phenomenon, always involving the relationship that the subject establishes with the world.

  16. Curriculum and the production of indigenous subjects

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    Adir Casaro Nascimento


    Full Text Available The policy on school education has always been explicit in its intentions to produce identities for indigenous peoples. The Federal Constitution of 1988 broke with the assimilationist/integrationist/colonizing proposal of curricula imposed on indigenous people and recognizes the ethnic identities of indigenous people inserted within the context of their cultural relations and the right to their customs, values, traditions, languages and knowledge. The use of the mother tongue and of learning processes has been orienting categories in the curricula of their schools. With culture as the focal point of discussion, this text is supported on testimonies by indigenous teachers from Terena, Guarani and Kaiowá tribes, subjects living the ambiguities and conflicts as well as their identities and the identities of those looking for schooling in different communities. Despite the difficulties that the indigenous school still faces, indigenous movements question homogenous and colonizing schooling models. This school is part of their lives and plays its social role of working with knowledge without excluding cultures as producers of sense and meaning, their knowledge that guarantees the difference in curriculum, area of struggle, and in the production of indigenous subjects.

  17. Subjectivity and intersubjectivity in psychiatric diagnosis. (United States)

    Fuchs, Thomas


    The establishment of criteriological diagnostic systems since the 1980s has increased the reliability of psychiatric diagnosis. On the other hand, the limits of this approach for clinicians and researchers are becoming increasingly apparent. In particular, the assessment of subjective experience is nearly excluded on the theoretical level and undervalued on the pragmatic level, with detrimental consequences for the validity of psychiatric diagnosis, empirical research and therapeutic purposes. To correct this unfavourable development, three major approaches to the assessment of mental illness should be equally taken into account: (1) the positivistic, objectifying or 3rd-person approach as endorsed by DSM-IV and ICD-10, focusing mainly on observable behavioural symptoms; (2) the phenomenological, subject-oriented or 1st-person approach, focusing on the patient's self-experience and exploring its basic structures, and (3) the hermeneutic, intersubjective or 2nd-person approach, mainly aiming at the co-construction of narratives and interpretations regarding the patient's self-concept, relationships and conflicts. These three approaches will be compared regarding their respective values for psychopathological description, diagnosis, research and therapeutic purposes.

  18. Capitalist Discourse, Subjectivity and Lacanian Psychoanalysis (United States)

    Vanheule, Stijn


    This paper studies how subjectivity in capitalist culture can be characterized. Building on Lacan's later seminars XVI, XVII, XVIII, and XIX, the author first outlines Lacan's general discourse theory, which includes four characteristic discourses: the discourse of the master, the discourse of the university, the discourse of the hysteric and the discourse of the analyst. Next, the author explores the subjectivity and the mode of dealing with jouissance and semblance, which is entailed in a fifth type of discourse, the capitalist discourse, discussed by Lacan (1972). Indeed, like the other discourses that Lacan discerns, the discourse of the capitalist can be thought of as a mode of dealing with the sexual non-rapport. It is argued that in the case of neurosis the discourse of the capitalist functions as an attempt to ignore the sexual non-rapport and the dimension of the unconscious. Psychosis, by contrast, is marked by an a priori exclusion from discourse. In that case, consumerist ways of relating to the other might offer a semblance, and thus the possibility of inventing a mode of relating to the other. Two clinical vignettes are presented to illustrate this perspective: one concerning the neurotic structure and one concerning the psychotic structure. PMID:28018280

  19. Mechanisms of dyspnea in healthy subjects

    Directory of Open Access Journals (Sweden)

    Gigliotti Francesco


    Full Text Available Abstract Dyspnea is a general term used to characterize a range of different descriptors; it varies in intensity, and is influenced by a wide variety of factors such as cultural expectations and the patient's experiences. Healthy subjects can experience dyspnea in different situations, e.g. at high altitude, after breath-holding, during stressful situations that cause anxiety or panic, and more commonly during strenuous exercise. Discussing the mechanisms of dyspnea we need to briefly take into account the physiological mechanisms underlying the sensation of dyspnea: the functional status of the respiratory muscles, the role of chemoreceptors and mechanoreceptors, and how the sense of respiratory motor output reaches a level of conscious awareness. We also need to take into account theories on the pathophysiological mechanisms of the sensation of dyspnea and the possibility that each pathophysiological mechanism produces a distinct quality of breathing discomfort. The terms used by subjects to identify different characteristics of breathing discomfort - dyspnea descriptors - may contribute to understanding the mechanisms of dyspnea and providing the rationale for a specific diagnosis.

  20. Pharmacokinetics of rilmenidine in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Genissel, P.; Bromet, N.; Fourtillan, J.B.; Mignot, A.; Albin, H.


    Rilmenidine is a novel alpha 2-adrenoceptor agonist, used in the treatment of mild or moderate hypertension at the oral dose of 1 mg once or twice daily. The pharmacokinetic parameters were investigated after single or repeated administration in healthy subjects, using labeled and unlabeled compounds. Rilmenidine was rapidly and extensively absorbed, with an absolute bioavailability factor close to 1 and a maximal plasma concentration achieved within 2 hours. Rilmenidine was not subject to presystemic metabolism. Distribution was independent of the free fraction because rilmenidine was weakly bound to plasma proteins (less than 10%). The volume of distribution was approximately 5 (315 liters). Elimination was rapid with a total body plasma clearance of approximately 450 ml.min-1 and an elimination half-life of approximately 8 hours. Renal excretion was the major elimination process (two-thirds of the total clearance). Metabolism was very poor, with a renal elimination of rilmenidine as the parent drug (urinary fraction of rilmenidine was about 65% and no metabolite plasma levels were detected). Linear pharmacokinetics were demonstrated for rilmenidine from 0.5 to 2 mg but, at 3 mg, a slight deviation from linearity was observed. In repeated administration, the linear disposition of rilmenidine with dose was confirmed.

  1. Subjective evidence based ethnography: method and applications. (United States)

    Lahlou, Saadi; Le Bellu, Sophie; Boesen-Mariani, Sabine


    Subjective Evidence Based Ethnography (SEBE) is a method designed to access subjective experience. It uses First Person Perspective (FPP) digital recordings as a basis for analytic Replay Interviews (RIW) with the participants. This triggers their memory and enables a detailed step by step understanding of activity: goals, subgoals, determinants of actions, decision-making processes, etc. This paper describes the technique and two applications. First, the analysis of professional practices for know-how transferring purposes in industry is illustrated with the analysis of nuclear power-plant operators' gestures. This shows how SEBE enables modelling activity, describing good and bad practices, risky situations, and expert tacit knowledge. Second, the analysis of full days lived by Polish mothers taking care of their children is described, with a specific focus on how they manage their eating and drinking. This research has been done on a sub-sample of a large scale intervention designed to increase plain water drinking vs sweet beverages. It illustrates the interest of SEBE as an exploratory technique in complement to other more classic approaches such as questionnaires and behavioural diaries. It provides the detailed "how" of the effects that are measured at aggregate level by other techniques.

  2. Anaerobic performances of sedentary and trained subjects. (United States)

    Serresse, O; Ama, P F; Simoneau, J A; Lortie, G; Bouchard, C; Boulay, M R


    The objective of this report was to compare the performance of sedentary individuals, physical education students, and athletes of various disciplines in 10 s and 90 s maximal cycle ergometer tests. The 10 s power was the highest power output in one second from the 10 s test, while capacities were defined as the total work output during the best 10 s trial and the 90 s test. ANOVA and Duncan multiple range test indicated that the mean values of the 10 S power and capacity and the 90 S capacity tests were significantly higher in sprinter than in sedentary groups. Sprinters performed significantly better than marathon runners only in the 10 s capacity and power. Bodybuilders and sedentary subjects had similar results in the 90 s capacity test. Mean performance values per kilogram of body weight in sedentary females reached about 60% of sedentary males while marathon runners, physical education students and sprinter females reached about 80% of the male performances for the three indicators. When expressed per kilogram of fat-free mass, females reached a higher proportion of the male values for all performances. These results indicate that: a) there are differences for the power and capacity measured in predominantly anaerobic tests between athletes from different disciplines and sedentary individuals, and b) gender differences exist for these anaerobic performance indicators, but they appear attenuated in trained subjects.

  3. Sensitization, subjective health complaints, and sustained arousal. (United States)

    Ursin, H; Eriksen, H R


    The purpose of this presentation is to discuss the possibility that sensitization is a psychobiological mechanism underlying not only multiple chemical sensitivity (MCS), but a much more general cluster of illness, referred to as "subjective health complaints". Sustained arousal, or sustained "stress" responses, may be an important factor for the development of these conditions. Patients with subjective complaints without objective changes are sometimes referred to as having "fashionable diagnoses" or "unexplained symptoms". They may be given diagnoses like MCS, epidemic fatigue, chronic fatigue syndrome, burnout, stress, a variety of intoxications, environmental illness, radiation, multiple chemical hypersensitivity, food intolerance, functional dyspepsia, irritable bowel, myalgic encephalitis, postviral syndrome, yuppie flu, fibromyalgia, or vital exhaustion. One issue is whether this is one general condition or separate entities. Another issue is whether sensitization may be the psychobiological mechanism for most or all of these conditions. Finally, is it likely that sustained arousal may facilitate the development of sensitization in some or many neural circuits? In this review, the main emphasis will be on musculoskeletal pain. This is the most frequent and most expensive condition for sickness compensation and disability. The comorbidity of other complaints, however, will also be taken into account.

  4. International Energy: Subject Thesaurus. Revision 1

    Energy Technology Data Exchange (ETDEWEB)


    The International Energy Agency: Subject Thesaurus contains the standard vocabulary of indexing terms (descriptors) developed and structured to build and maintain energy information databases. Involved in this cooperative task are (1) the technical staff of the USDOE Office of Scientific and Technical Information (OSTI) in cooperation with the member countries of the International Energy Agency`s Energy Technology Data Exchange (ETDE) and (2) the International Atomic Energy Agency`s International Nuclear Information System (INIS) staff representing the more than 100 countries and organizations that record and index information for the international nuclear information community. ETDE member countries are also members of INIS. Nuclear information prepared for INIS by ETDE member countries is included in the ETDE Energy Database, which contains the online equivalent of the printed INIS Atomindex. Indexing terminology is therefore cooperatively standardized for use in both information systems. This structured vocabulary reflects thscope of international energy research, development, and technological programs. The terminology of this thesaurus aids in subject searching on commercial systems, such as ``Energy Science & Technology`` by DIALOG Information Services, ``Energy`` by STN International and the ``ETDE Energy Database`` by SilverPlatter. It is also the thesaurus for the Integrated Technical Information System (ITIS) online databases of the US Department of Energy.

  5. Estradiol enhances object recognition memory in Swiss female mice by activating hippocampal estrogen receptor α. (United States)

    Pereira, Luciana M; Bastos, Cristiane P; de Souza, Jéssica M; Ribeiro, Fabíola M; Pereira, Grace S


    In rodents, 17β-estradiol (E2) enhances hippocampal function and improves performance in several memory tasks. Regarding the object recognition paradigm, E2 commonly act as a cognitive enhancer. However, the types of estrogen receptor (ER) involved, as well as the underlying molecular mechanisms are still under investigation. In the present study, we asked whether E2 enhances object recognition memory by activating ERα and/or ERβ in the hippocampus of Swiss female mice. First, we showed that immediately post-training intraperitoneal (i.p.) injection of E2 (0.2 mg/kg) allowed object recognition memory to persist 48 h in ovariectomized (OVX) Swiss female mice. This result indicates that Swiss female mice are sensitive to the promnesic effects of E2 and is in accordance with other studies, which used C57/BL6 female mice. To verify if the activation of hippocampal ERα or ERβ would be sufficient to improve object memory, we used PPT and DPN, which are selective ERα and ERβ agonists, respectively. We found that PPT, but not DPN, improved object memory in Swiss female mice. However, DPN was able to improve memory in C57/BL6 female mice, which is in accordance with other studies. Next, we tested if the E2 effect on improving object memory depends on ER activation in the hippocampus. Thus, we tested if the infusion of intra-hippocampal TPBM and PHTPP, selective antagonists of ERα and ERβ, respectively, would block the memory enhancement effect of E2. Our results showed that TPBM, but not PHTPP, blunted the promnesic effect of E2, strongly suggesting that in Swiss female mice, the ERα and not the ERβ is the receptor involved in the promnesic effect of E2. It was already demonstrated that E2, as well as PPT and DPN, increase the phospho-ERK2 level in the dorsal hippocampus of C57/BL6 mice. Here we observed that PPT increased phospho-ERK1, while DPN decreased phospho-ERK2 in the dorsal hippocampus of Swiss female mice subjected to the object recognition sample phase

  6. Cannabinoids & Stress: impact of HU-210 on behavioral tests of anxiety in acutely stressed mice. (United States)

    Kinden, Renee; Zhang, Xia


    Anxiety disorders are one of the most prevalent classes of mental disorders affecting the general population, but current treatment strategies are restricted by their limited efficacy and side effect profiles. Although the cannabinoid system is speculated to be a key player in the modulation of stress responses and emotionality, the vast majority of current research initiatives had not incorporated stress exposure into their experimental designs. This study was the first to investigate the impact of exogenous cannabinoid administration in an acutely stressed mouse model, where CD1 mice were pre-treated with HU-210, a potent CB1R agonist, prior to acute stress exposure and subsequent behavioral testing. Exogenous cannabinoid administration induced distinct behavioral phenotypes in stressed and unstressed mice. While low doses of HU-210 were anxiolytic in unstressed subjects, this effect was abolished when mice were exposed to an acute stressor. The administration of higher HU-210 doses in combination with acute stress exposure led to severe locomotor deficits that were not previously observed at the same dose in unstressed subjects. These findings suggest that exogenous cannabinoids and acute stress act synergistically in an anxiogenic manner. This study underlies the importance of including stress exposure into future anxiety-cannabinoid research due to the differential impact of cannabinoid administration on stressed and unstressed subjects.

  7. The effects of growth hormone (GH) treatment on GH and insulin/IGF-1 signaling in long-lived Ames dwarf mice. (United States)

    Masternak, Michal M; Panici, Jacob A; Wang, Feiya; Wang, Zhihui; Spong, Adam


    The disruption of the growth hormone (GH) axis in mice promotes insulin sensitivity and is strongly correlated with extended longevity. Ames dwarf (Prop1(df), df/df) mice are GH, prolactin (PRL), and thyrotropin (TSH) deficient and live approximately 50% longer than their normal siblings. To investigate the effects of GH on insulin and GH signaling pathways, we subjected these dwarf mice to twice-daily GH injections (6 microg/g/d) starting at the age of 2 weeks and continuing for 6 weeks. This produced the expected activation of the GH signaling pathway and stimulated somatic growth of the Ames dwarf mice. However, concomitantly with increased growth and increased production of insulinlike growth factor-1, the GH treatment strongly inhibited the insulin signaling pathway by decreasing insulin sensitivity of the dwarf mice. This suggests that improving growth of these animals may negatively affect both their healthspan and longevity by causing insulin resistance.

  8. Glucose homeostasis in mice is transglutaminase 2 independent.

    Directory of Open Access Journals (Sweden)

    Siiri E Iismaa

    Full Text Available Transglutaminase type 2 (TG2 has been reported to be a candidate gene for maturity onset diabetes of the young (MODY because three different mutations that impair TG2 transamidase activity have been found in 3 families with MODY. TG2 null (TG2(-/- mice have been reported to be glucose intolerant and have impaired glucose-stimulated insulin secretion (GSIS. Here we rigorously evaluated the role of TG2 in glucose metabolism using independently generated murine models of genetic TG2 disruption, which show no compensatory enhanced expression of other TGs in pancreatic islets or other tissues. First, we subjected chow- or fat-fed congenic SV129 or C57BL/6 wild type (WT and TG2(-/- littermates, to oral glucose gavage. Blood glucose and serum insulin levels were similar for both genotypes. Pancreatic islets isolated from these animals and analysed in vitro for GSIS and cholinergic potentiation of GSIS, showed no significant difference between genotypes. Results from intraperitoneal glucose tolerance tests (GTTs and insulin tolerance tests (ITTs were similar for both genotypes. Second, we directly investigated the role of TG2 transamidase activity in insulin secretion using a coisogenic model that expresses a mutant form of TG2 (TG2(R579A, which is constitutively active for transamidase activity. Intraperitoneal GTTs and ITTs revealed no significant differences between WT and TG2(R579A/R579A mice. Given that neither deletion nor constitutive activation of TG2 transamidase activity altered basal responses, or responses to a glucose or insulin challenge, our data indicate that glucose homeostasis in mice is TG2 independent, and question a link between TG2 and diabetes.

  9. Mangafodipir protects against hepatic ischemia-reperfusion injury in mice.

    Directory of Open Access Journals (Sweden)

    Romain Coriat

    Full Text Available INTRODUCTION AND AIM: Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. METHODS: Mice were subjected to 70% hepatic ischemia (continuous ischemia for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity. The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. RESULTS: Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01, in liver tissue damages, in markers of apoptosis (P<0.01, and by higher rates of survival in treated than in untreated animals (P<0.001. The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. CONCLUSIONS: Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.

  10. Effect of Chronic Lead Intoxication on Risky Behavior in Mice

    Directory of Open Access Journals (Sweden)

    L Mohammadyar


    Full Text Available Introduction: With industrialization of human societies, pollutants like lead have entered in the life cycle, causing harmful effects on body organs. No sufficient studies have been done on the effects of pollutants on behavior. The aim of this study was to investigate possible effects of lead on some measurable behaviors of an animal model. Methods: Forty eight male adult mice were divided into 4 groups of 12 each. Lead acetate was added at concentrations of 0, 5, 50, or 500 ppm to the drinking water of the animals for 4 weeks (28 days. On day 29, animals were placed on an Elevated Plus maze (EPM for 5 min and the time in sec spent was measured on closed arms, open arms and the end 1/3rd of the open arms. Increased time on open arms, particularly the end 1/3rd was considered to reflect an enhanced risk-accepting behavior. Results: In this study, it was shown that lead exposure caused an increased number of entrance (P=0.006 and time spent (P=0.034 by mice on open arms of the EPM. There was a positive correlation between the concentration of lead acetate and those two effects. Conclusion: The present study demonstrated that lead poisoning may decrease normal anxiety in mice and increase risky behavior in this species. Clinical studies on human subjects with risky behavior are strongly suggested in order to find a possible relation between chronic exposures to lead as well as plasma concentration of lead with the extent of this kind of behavior.

  11. Subject subjected - Sexualised coercion, agency and the reorganisation and reformulation of life strategies

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    Rikke Spjæt Salkvist


    Full Text Available When not acting in ways that are recognised as physicalself-defence, women are often – in psychology and inother dominant discourses – generalised as inherentlypassive during subjection to sexualised coercion (rapeand attempted rape. Likewise, in the aftermaths, their(inactions are frequently pathologised as ‘maladaptivecoping strategies’.We present theoretically and empirically based argumentsfor an agency-oriented approach to women’sperspectives on sexualised coercion. Agency is understoodas intentional, situated and strategic. Sexualisedcoercion is not generalised as a single “traumatic”event, but conceptualised as life events. Meanings ofcoercion are embedded in social activities connectedto discourses on ‘rape’ and ‘trauma’. Thus personalmeanings of subjection are understood as developed inand through participation in trajectories across diversecontexts.Adopted in our study, this approach points to thegreat diversity of personal meanings of sexualised coercion.Moreover, it reveals intimate connections betweensituated, personal and dominant discursive meanings ofcoercion, and women’s strategies of (inactions duringand in the aftermaths of the events.Our analysis of participants’ perspectives also indicatesan imperative need for reinterpreting conceptssuch as ‘victim’ and ‘passivity’. In a reinterpretationwomen, although subjected to sexualised coercion,emerge as subjects both during subjection and in theaftermaths. Furthermore their seemingly pathologicalbehaviour may be re-conceptualised as personally sense-making strategies of action in reflected attemptsat (reformulating and (reorganising their lifestrategies.

  12. Effects of subject-area degree and classroom experience on new chemistry teachers' subject matter knowledge (United States)

    Nixon, Ryan S.; Campbell, Benjamin K.; Luft, Julie A.


    Science teachers need to understand the subject matter they teach. While subject matter knowledge (SMK) can improve with classroom teaching experience, it is problematic that many secondary science teachers leave the profession before garnering extensive classroom experience. Furthermore, many new science teachers are assigned to teach science subjects for which they do not hold a degree. This study investigates the SMK of new secondary science teachers assigned to teach chemistry in their first three years of teaching. These new teachers do not have the advantage of years of experience to develop their SMK and half hold a degree in biology rather than chemistry. This qualitative study explores the effects of holding a degree in the subject area one teaches as well as classroom teaching experience on teachers' SMK for two chemistry topics, conservation of mass and chemical equilibrium. Qualitative analysis of semi-structured interviews indicated that the SMK of teachers who had a chemistry degree and more extensive classroom experience was more coherent, chemistry-focused, and sophisticated than that of teachers who lacked this preparation and experience. This study provides evidence that new science teachers' SMK is influenced by both holding a degree in the subject area and having classroom experience.


    Directory of Open Access Journals (Sweden)

    Marlon Xavier


    Full Text Available Abstract This theoretical work discusses consumerism's processes of subjectivation and their psychological consequences. Its regime is studied through its social imaginary and its totalitarian character: the discourse of advertising, as a global hegemon, absorbs all forms of discourse and signification, thereby actualizing capitalism's telos - the colonization of the Lebenswelt under a great imperative: everything must become a commodity, especially the subject. A process of totalization of subjectivity occurs under a commodification logic centered on the representation: every image must be transformed into commodity-signs. Thus the consumption imaginary appears as a totalizing ideology, functioning as archaic représentations collectives (Durkheim and simulating a religious imaginary. It mass-produces subjectivity through participation mystique (Lévy-Bruhl with its commodity-signs (and their fetish and the whole imaginary. Its subject is defined as a bricolage of consumable commodity-signs, being therefore eternally fluid, performative, and ethereal. Thus it produces an anthropological mutation, the commodity-subject: a disposable, empty, thoroughly commodified self.

  14. IL-6 Compared to Young Mice

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    Jihyun Park


    Full Text Available Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly.

  15. Leukemogenesis in heterozygous PU.1 knockout mice. (United States)

    Genik, Paula C; Vyazunova, Irina; Steffen, Leta S; Bacher, Jeffery W; Bielefeldt-Ohmann, Helle; McKercher, Scott; Ullrich, Robert L; Fallgren, Christina M; Weil, Michael M; Ray, F Andrew


    Most murine radiation-induced acute myeloid leukemias involve biallelic inactivation of the PU.1 gene, with one allele being lost through a radiation-induced chromosomal deletion and the other allele affected by a recurrent point mutation in codon 235 that is likely to be spontaneous. The short latencies of acute myeloid leukemias occurring in nonirradiated mice engineered with PU.1 conditional knockout or knockdown alleles suggest that once both copies of PU.1 have been lost any other steps involved in leukemogenesis occur rapidly. Yet, spontaneous acute myeloid leukemias have not been reported in mice heterozygous for a PU.1 knockout allele, an observation that conflicts with the understanding that the PU.1 codon 235 mutation is spontaneous. Here we describe experiments that show that the lack of spontaneous leukemia in PU.1 heterozygous knockout mice is not due to insufficient monitoring times or mouse numbers or the genetic background of the knockout mice. The results reveal that spontaneous leukemias that develop in mice of the mixed 129S2/SvPas and C57BL/6 background of knockout mice arise by a pathway that does not involve biallelic PU.1 mutation. In addition, the latency of radiation-induced leukemia in PU.1 heterozygous mice on a genetic background susceptible to radiation-induced leukemia indicates that the codon 235 mutation is not a rate-limiting step in radiation leukemogenesis driven by PU.1 loss.

  16. Life Events and Subjective Well-being

    DEFF Research Database (Denmark)

    Pedersen, Peder J.; Schmidt, Torben Dall


    we focus on the eventual impact on SWB from having children. The dominant result in the rather few studies until now is the finding of no – or even a negative – impact on subjective well being following birth of a child. We focus on the impact from having children using two very big panel data sets.......The first is the European Community Household Panel (ECHP) with data collected over 8 annual waves from 1994 to 2001 in 15 EU member countries. Observations are available for up to 15 countries with big differences in fertility levels, child care institutions and labour force participation for married women....... At the same time, the ECHP data contains a lot of relevant demographic and labour market background variables to be included in the econometric analyses of the SWB impact from children. The second data set is The German Socio Economic Panel (GSOEP). Like the ECHP, the GSOEP data contains many relevant...

  17. Objective and subjective time in anthropic reasoning

    CERN Document Server

    Carter, Brandon


    The original formulation of the (weak) anthropic principle was prompted by a question about objective time at a macroscopic level, namely the age of the universe when ``anthropic'' observers such as ourselves would be most likely to emerge. Theoretical interpretation of what one observes requires the theory to indicate what is expected, which will commonly depend on where, and particularly when, the observation can be expected to occur. In response to the question of where and when, the original version of the anthropic principle proposed an {it a priori} probability weighting proportional to the number of ``anthropic'' observers present. The present discussion takes up the question of the time unit characterising the biological clock controlling our subjective internal time, using a revised alternative to a line of argument due to Press, who postulated that animal size is limited by the brittleness of bone. On the basis of a static support condition depending on the tensile strength of flesh rather than bone...

  18. Nonspecific eating disorders - a subjective review

    Directory of Open Access Journals (Sweden)

    Aneta Michalska


    Full Text Available Aim. The aim of this paper was to characterise nonspecific eating disorders (other than anorexia nervosa and bulimia nervosa. Method. The Medline database was searched for articles on nonspecific eating disorders. The following disorders were described: binge eating disorder (BED, pica, rumination disorder, avoidant/restrictive food intake disorder, night eating syndrome (NES, sleep-related eating disorder (SRED, bigorexia, orthorexia, focusing on diagnosis, symptoms, assessment, comorbidities, clinical implications and treatment. Results. All of the included disorders may have dangerous consequences, both somatic and psychological. They are often comorbid with other psychiatric disorders. Approximately a few percent of general population can be diagnosed with each disorder, from 0.5–4.7% (SRED to about 7% (orthorexia. With the growing literature on the subject and changes in DSM-5, clinicians recognise and treat those disorders more often. Conclusions. More studies have to be conducted in order to differentiate disorders and treat or prevent them appropriately.


    Institute of Scientific and Technical Information of China (English)

    Yan LU; Yongjun LU; Xingnong ZHANG


    The stability of riverbanks subject to seepage is studied experimentally and theoretically in this paper. By including seepage in a 3-dimensional theoretical analysis, the study first shows how the critical slope or angle of repose of a cohesionless material is related to the ratio of the hydraulic gradient of seepage to its critical value under the fluidization condition. The critical stable slope is shown to be related to not only the hydraulic gradient but also the seepage direction. Measured laboratory data reasonably fit well with the theoretical relationship for the case of injection and suction. The data reveal that the slope is reduced with injection and increased with suction, respectively. Additionally, the study identifies the seepage direction which results in a minimum critical stable slope for a certain hydraulic gradient of seepage.

  20. Multiple modernities, modern subjectivities and social order

    DEFF Research Database (Denmark)

    Jung, Dietrich; Sinclair, Kirstine


    to modern subjectivity formation. In combining conceptual tools from these strands of social theory, we argue that the emergence of multiple modernities should be understood as a historical result of idiosyncratic social constructions combining global social imaginaries with religious and other cultural......Taking its point of departure in the conceptual debate about modernities in the plural, this article presents a heuristic framework based on an interpretative approach to modernity. The article draws on theories of multiple modernities, successive modernities and poststructuralist approaches...... traditions. In the second part of the article we illustrate this argument with three short excursions into the history of Islamic reform in the 19th and 20th centuries. In this way we interpret the modern history of Muslim societies as based on cultural conflicts between different forms of social order...

  1. The malleable meaning of subjective ease. (United States)

    Briñol, Pablo; Petty, Richard E; Tormala, Zakary L


    People can generate the same thoughts or process the same information with different degrees of ease, and this subjective experience has implications for attitudes and social judgment. In prior research, it has generally been assumed that the experience of ease or fluency is interpreted by people as something good. In the two experiments reported here, the meaning or value of ease was directly manipulated, and the implications for evaluative judgments were explored. Across experiments, we replicated the traditional ease-of-retrieval effect (more thought-congruent attitudes when thoughts were easy rather than difficult to generate) when ease was described as positive, but we reversed this effect when ease was described as negative. These findings suggest that it is important to consider both the content of metacognition (e.g., "those thoughts were easy to generate") and the value associated with that content (e.g., "ease is good" or "ease is bad").


    Directory of Open Access Journals (Sweden)



    Full Text Available The problem of leadership (a management phenomenon has attracted a lot of interest thought time, from theoreticians and scholars to practicians skilled in wide range of science subjects. (sociology, political science, philosophy, organizational management etc. The leader is generally defined as an individual of a person which has been given the task of coordinating and directing the group’s activities, or who, in the absence of an elected leader, has the greatest responsibility in achieving these group functions. The leadership represents nothing more than manner or way of achieving those responsibilities that were taken in charge by the leader. Leadership in practice results in successfully carrying out a task or designing a behavior that will allow the group to remain closely bounded.

  3. Subjective Oral Health in Dutch Adults

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    Gijsbert H.W. Verrips


    Full Text Available Aim: To determine whether the subjective oral health (SOH of the Dutch adult population was associated with clinical and demographic variables. Methods: A clinical examination was conducted in a sample of 1,018 people from the Dutch city of ‘s-Hertogenbosch. SOH was measured using the Dutch translation of the short form of the Oral Health Impact Profile (OHIP-NL14. Results: The average score on the OHIP-NL14 was 2.8 ± 5.9 and 51% of the respondents had a score of 0. Dental status was the most important predictor of SOH. Conclusions:  The SOH in the Dutch adult population was much better than in groups of adults in Australia, the United Kingdom and New Zealand. Nevertheless, there were important variations in SOH related to dental and socio-economic status.

  4. On confessional dialogue and collective subjects

    DEFF Research Database (Denmark)

    Olsson, Ulf; Petersson, Kenneth; Krejsler, John B.


    The concept of dialogue as an ideal for face-to face relationships in education has a long history in Western societies. Dialogue, however, does not only opeate in face-to-face relationships but also between collective subjects such as national states. The focus of this chapter is to discuss...... the operation of dialogue as a governmental practice in the construction of the contemporary European Higher Educational Area (EHEA) as a transnational political space. In this context the Bologna Process, as an expression of the rationalities of Open Method of Coordination, operates as a goal directed...... machinery or, as we prefer to call it, as a dialogic dispositive for the governmentalisation of Europe as a transnational political space. Dialogue operates as a means to reaching a form of unity in diversity considered inevitable if the hope for a future Europe with smart, sustainable and inclusive growth...

  5. Radiologists: The Unsuspecting Subject Matter Experts. (United States)

    McGann, Camille; Miaullis, Aaron; Page, Neil


    The social and political climates are changing rapidly in the United States and the world at large. The threat of a chemical, biologic, radiologic, and/or nuclear event is a rising concern to many. The current Ebola crisis has shed light on health care providers' preparedness for such an event. Radiologists, including radiation oncologists, nuclear medicine specialists, and all radiology subspecialists are considered "subject matter experts" in this area and are likely to be called upon in response to a radiation incident. Although others, such as radiation safety officers, provide important expertise, the clinical leadership will be the responsibility of physicians and other health care providers. However, many radiologists are unaware that they are considered subject matter experts who may be called on to assist, should their local hospital's emergency department need to take care of casualties from a radiation incident. A mass-casualty situation with hundreds of patients would require the immediate assistance of all available medical providers. Radiologists are primed and positioned to take the lead in ensuring preparedness of their local hospital and community, through emergency planning for a radiologic incident, given their combined medical and radiation physics knowledge. Therefore, increasing the skills of radiologists first is the more prudent approach in such planning. This preparation can be done through understanding of the critical components of such scenarios: the threat, types of radiation incidents, contamination, detection, decontamination, and acute radiation syndrome and its treatment. Once the necessary knowledge supplementation has been completed, radiologists can participate in educating their fellow medical colleagues and health care staff, and assist in the radiation-related aspects of an "all hazards" emergency department response, decreasing "radiophobia" in the process.

  6. Congenital pouch colon in female subjects

    Directory of Open Access Journals (Sweden)

    Sarin Y


    Full Text Available Over a period of 5-year (May 2000 to April 2005 29 patients of congenital pouch colon (CPC were managed by single pediatric surgeon in the Department of Pediatric Surgery of a tertiary hospital. Of these, 11 were girls (M: F: 1.6:1. Detailed anatomy could be studied in nine patients, were included in this study. Age of presentation in female subjects ranged 1 day to 8 years. On examination, eight of the nine patients had single perineal opening suggesting a very high incidence of association of cloaca in female subjects with CPC. Four had short urogenital sinus with colonic pouch opening in the posterior wall of urinary bladder. In other two patients, CPC terminated in short cloaca. Anomalies of mullerian structures such as uterus didelphus and septate vagina ware commonly encountered. Proximal diversion with or without pouch excision was done as the initial preliminary treatment for all those patients who presented in early life. Of the nine girls, two died after the preliminary surgery. Only five patients have undergone definitive surgery. Definitive surgery included abdomino-perineal pull-through of proximal normal colon ( n =2, tubularization of pouch with abdomino- posterior sagittal- pull through ( n =2 and abdomino-posterior sagittal urethra-vaginoanorectoplasty with pull through of tapered pouch colon in one patient. Two of these patients had concomitant bowel vaginoplasty. Three patients with tubularized pouches had constipation and spurious diarrhea. However, good pseudo-continence of bowel was achieved on regular bowel washes. The cosmetic appearance of perineum in all these three patients was acceptable. The patients in whom pouch excision was done had diarrhea and severe perineal excoriation resistant to conservative management.

  7. Modification of female and male social behaviors in estrogen receptor beta knockout mice by neonatal maternal separation

    Directory of Open Access Journals (Sweden)

    Mumeko C Tsuda


    Full Text Available Maternal separation (MS is an animal model mimicking the effects of early life stress on the development of emotional and social behaviors. Recent studies revealed that MS stress increased social anxiety levels in female mice and reduced peri-pubertal aggression in male mice. Estrogen receptor (ER β plays a pivotal role in the regulation of stress responses and anxiety-related and social behaviors. Behavioral studies using ERβ knockout (βERKO mice reported increased social investigation and decreased social anxiety in βERKO females, and elevated aggression levels in βERKO males compared to wild-type (WT mice. In the present study, using βERKO and WT mice, we examined whether ERβ contributes to MS effects on anxiety and social behaviors. βERKO and WT mice were separated from their dam daily (4 h from postnatal day 1 to 14 and control groups were left undisturbed. First, MS and ERβ gene deletion individually increased anxiety-related behaviors in the open field test, but only in female mice. Anxiety levels were not further modified in βERKO female mice subjected to MS stress. Second, βERKO female mice showed higher levels of social investigation compared with WT in the social investigation test and long-term social preference test. However, MS greatly reduced social investigation duration and elevated number of stretched approaches in WT and βERKO females in the social investigation test, suggesting elevated levels of social anxiety in both genotypes. Third, peri-pubertal and adult βERKO male mice were more aggressive than WT mice as indicated by heightened aggression duration. On the other hand, MS significantly decreased aggression duration in both genotypes, but only in peri-pubertal male mice. Altogether, these results suggest that βERKO mice are sensitive to the adverse effects of MS stress on subsequent female and male social behaviors, which could then have overrode the ERβ effects on female social anxiety and male aggression.

  8. Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Jamie K Wong

    Full Text Available Stroke results in brain tissue damage from ischemia and oxidative stress. Molecular regulators of the protective versus deleterious cellular responses after cerebral ischemia remain to be identified. Here, we show that deletion of Smad1, a conserved transcription factor that mediates canonical bone morphogenetic protein (BMP signaling, results in neuroprotection in an ischemia-reperfusion (I/R stroke model. Uninjured mice with conditional deletion of Smad1 in the CNS (Smad1 cKO displayed upregulation of the reactive astrocyte marker GFAP and hypertrophic morphological changes in astrocytes compared to littermate controls. Additionally, cultured Smad1(-/- astrocytes exhibited an enhanced antioxidant capacity. When subjected to I/R injury by transient middle cerebral artery occlusion (tMCAO, Smad1 cKO mice showed enhanced neuronal survival and improved neurological recovery at 7 days post-stroke. This neuroprotective phenotype is associated with attenuated reactive astrocytosis and neuroinflammation, along with reductions in oxidative stress, p53 induction, and apoptosis. Our data suggest that Smad1-mediated signaling pathway is involved in stroke pathophysiology and may present a new potential target for stroke therapy.

  9. Effects of slightly acidic electrolysed drinking water on mice. (United States)

    Inagaki, Hideaki; Shibata, Yoshiko; Obata, Takahiro; Kawagoe, Masami; Ikeda, Katsuhisa; Sato, Masayoshi; Toida, Kazumi; Kushima, Hidemi; Matsuda, Yukihisa


    Slightly acidic electrolysed (SAE) water is a sanitizer with strong bactericidal activity due to hypochlorous acid. We assessed the safety of SAE water as drinking water for mice at a 5 ppm total residual chlorine (TRC) concentration to examine the possibility of SAE water as a labour- and energy-saving alternative to sterile water. We provided SAE water or sterile water to mice for 12 weeks, during which time we recorded changes in body weight and weekly water and food intakes. At the end of the experiment, all of the subject animals were sacrificed to assess serum aspartate aminotransferase, alanine aminotransferase and creatinine levels and to examine the main organs histopathologically under a light microscope. In addition, we investigated the bacteria levels of both types of water. We found no difference in functional and morphological health condition indices between the groups. Compared with sterile water, SAE water had a relatively higher ability to suppress bacterial growth. We suggest that SAE water at 5 ppm TRC is a safe and useful alternative to sterile water for use as drinking water in laboratory animal facilities.

  10. Protective effects of fluoxetine on decompression sickness in mice.

    Directory of Open Access Journals (Sweden)

    Jean-Eric Blatteau

    Full Text Available Massive bubble formation after diving can lead to decompression sickness (DCS that can result in central nervous system disorders or even death. Bubbles alter the vascular endothelium and activate blood cells and inflammatory pathways, leading to a systemic pathophysiological process that promotes ischemic damage. Fluoxetine, a well-known antidepressant, is recognized as having anti-inflammatory properties at the systemic level, as well as in the setting of cerebral ischemia. We report a beneficial clinical effect associated with fluoxetine in experimental DCS. 91 mice were subjected to a simulated dive at 90 msw for 45 min before rapid decompression. The experimental group received 50 mg/kg of fluoxetine 18 hours before hyperbaric exposure (n = 46 while controls were not treated (n = 45. Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine IL-6 detection. There were significantly fewer manifestations of DCS in the fluoxetine group than in the controls (43.5% versus 75.5%, respectively; p = 0.004. Survivors showed a better and significant neurological recovery with fluoxetine. Platelets and red cells were significantly decreased after decompression in controls but not in the treated mice. Fluoxetine reduced circulating IL-6, a relevant marker of systemic inflammation in DCS. We concluded that fluoxetine decreased the incidence of DCS and improved motor recovery, by limiting inflammation processes.

  11. Identification of subjects at risk of developing irritable bowel syndrome

    NARCIS (Netherlands)

    Tuk, L.; Rajilic-Stojanovic, M.; Vos, de W.M.


    Described is the use of enterotyping of the gut microbiota for identifying a subject at risk of developing Irritable Bowel Syndrome (IBS) and/or diagnosing a subject suffering from IBS, as well as method for identifying a subject at risk of developing IBS and/or diagnosing a subject suffering from I

  12. 14 CFR Appendix B to Part 147 - General Curriculum Subjects (United States)


    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false General Curriculum Subjects B Appendix B to... to Part 147—General Curriculum Subjects This appendix lists the subjects required in at least 400 hours in general curriculum subjects. The number in parentheses before each item listed under...

  13. Blood and urinary concentrations of salbutamol in asthmatic subjects

    DEFF Research Database (Denmark)

    Elers, Jimmi; Pedersen, Lars; Henninge, John;


    Data on blood and urinary concentrations of salbutamol after inhalation and oral administration in healthy subjects are scarce. Accordingly, we examined the pharmacokinetics of inhaled and oral salbutamol in asthmatic subjects.......Data on blood and urinary concentrations of salbutamol after inhalation and oral administration in healthy subjects are scarce. Accordingly, we examined the pharmacokinetics of inhaled and oral salbutamol in asthmatic subjects....

  14. 29 CFR 4211.21 - Changes subject to PBGC approval. (United States)


    ... method or modification to an allocation method that is not permitted under § 4211.12 if the method or... 29 Labor 9 2010-07-01 2010-07-01 false Changes subject to PBGC approval. 4211.21 Section 4211.21... Subject to PBGC Approval § 4211.21 Changes subject to PBGC approval. (a) General rule. Subject to...

  15. 45 CFR 703.3 - Scope of subject matter. (United States)


    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Scope of subject matter. 703.3 Section 703.3... AND FUNCTIONS OF STATE ADVISORY COMMITTEES § 703.3 Scope of subject matter. The scope of the subject matter to be dealt with by Advisory Committees shall be those subjects of inquiry or study with which...

  16. Endocrine therapy of human breast cancer grown in nude mice

    DEFF Research Database (Denmark)

    Brünner, N; Osborne, C K; Spang-Thomsen, M


    Although there have been extensive studies of rodent breast tumor models, and of human breast cancer cell lines in culture, there is still need for a human tumor model which can be manipulated experimentally but also provides a valid expression of the tumor cells in a host environment. Athymic nude...... mice bearing transplanted human breast tumors have been proposed as such a model. This review therefore discusses the use of the athymic nude mouse model of the study of human breast cancer biology, and focuses on four subjects: 1. biological characteristics of heterotransplanted breast tumors; 2....... endocrinology and pharmacology of hormonal agents in the nude mouse; 3. endocrine sensitivity of heterotransplanted tumors; and 4. applicability and limitations of this model for the study of human breast cancer....

  17. Congenic mice: cutting tools for complex immune disorders. (United States)

    Rogner, Ute C; Avner, Philip


    Autoimmune diseases are, in general, under complex genetic control and subject to strong interactions between genetics and the environment. Greater knowledge of the underlying genetics will provide immunologists with a framework for study of the immune dysregulation that occurs in such diseases. Ascertaining the number of genes that are involved and their characterization have, however, proven to be difficult. Improved methods of genetic analysis and the availability of a draft sequence of the complete mouse genome have markedly improved the outlook for such research, and they have emphasized the advantages of mice as a model system. In this review, we provide an overview of the genetic analysis of autoimmune diseases and of the crucial role of congenic and consomic mouse strains in such research.

  18. Empathy and reversed empathy of stress in mice.

    Directory of Open Access Journals (Sweden)

    Shigeru Watanabe

    Full Text Available Empathy is an emotional response to display of distress in others and reversed-empathy is an emotional response to non-distressed others in distressed subjects. Stress has memory enhancing effect on aversive experience. Here, I examine empathy and reversed empathy using the memory enhancing effects of stress in mice. Restrain stress enhanced aversive memory of a floor with electric shock, but restrain stress, with cage mates also restrained, reduced the enhancing effect. On the other hand, restrain stress with free-moving cage mates increased the memory enhancing effect, suggesting the stronger stress. This is the reversed-empathy. Level of corticosterone is the highest after the restrain with free-moving mates and lowest after the restrain with restrained mates.

  19. Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. (United States)

    Guilloux, J-P; Douillard-Guilloux, G; Kota, R; Wang, X; Gardier, A M; Martinowich, K; Tseng, G C; Lewis, D A; Sibille, E


    Women are twice as likely as men to develop major depressive disorder (MDD) and are more prone to recurring episodes. Hence, we tested the hypothesis that the illness may associate with robust molecular changes in female subjects, and investigated large-scale gene expression in the post-mortem brain of MDD subjects paired with matched controls (n=21 pairs). We focused on the lateral/basolateral/basomedian complex of the amygdala as a neural hub of mood regulation affected in MDD. Among the most robust findings were downregulated transcripts for genes coding for γ-aminobutyric acid (GABA) interneuron-related peptides, including somatostatin (SST), tachykinin, neuropeptide Y (NPY) and cortistatin, in a pattern reminiscent to that previously reported in mice with low brain-derived neurotrophic factor (BDNF). Changes were confirmed by quantitative PCR and not explained by demographic, technical or known clinical parameters. BDNF itself was significantly downregulated at the RNA and protein levels in MDD subjects. Investigating putative mechanisms, we show that this core MDD-related gene profile (including SST, NPY, TAC1, RGS4 and CORT) is recapitulated by complementary patterns in mice with constitutive (BDNF-heterozygous) or activity-dependent (exon IV knockout) decreases in BDNF function, with a common effect on SST and NPY. Together, these results provide both direct (low RNA/protein) and indirect (low BDNF-dependent gene pattern) evidence for reduced BDNF function in the amygdala of female subjects with MDD. Supporting studies in mutant mice models suggest a complex mechanism of low constitutive and activity-dependent BDNF function in MDD, particularly affecting SST/NPY-related GABA neurons, thus linking the neurotrophic and GABA hypotheses of depression.

  20. Biological Effect of Magnetic Field in Mice

    Institute of Scientific and Technical Information of China (English)

    Zhao-Wei ZENG


    Objective: To study the biological effect of magnetic field in mice bodies. Method: With a piece of permanent magnet embeded in mice bodies beside the femoral artery and vein to measure the electrophoretic velocity(um/s). Result: The magnetic field in mice bodies on the experiment group that the electrophoretic velocity is faster more than control and free group.Conclusion:The magnetic field in animal's body can raise the negative electric charges on the surface of erythrocyte to improve the microcirculation, this is the biological effect of magnetic field.

  1. Autonomy, subject-relativity, and subjective and objective theories of well-being in bioethics. (United States)

    Varelius, Jukka


    Among the different approaches to questions of biomedical ethics, there is a view that stresses the importance of a patient's right to make her own decisions in evaluative questions concerning her own well-being. This approach, the autonomy-based approach to biomedical ethics, has usually led to the adoption of a subjective theory of well-being on the basis of its commitment to the value of autonomy and to the view that well-being is always relative to a subject. In this article, it is argued that these two commitments need not lead to subjectivism concerning the nature of well-being.

  2. Experimental osteoarthritis models in mice. (United States)

    Lorenz, Julia; Grässel, Susanne


    Osteoarthritis (OA) is a slowly progressing, degenerative disorder of synovial joints culminating in the irreversible destruction of articular cartilage and subchondral bone. It affects almost everyone over the age of 65 and influences life quality of affected individuals with enormous costs to the health care system. Current therapeutic strategies seek to ameliorate pain and increase mobility; however, to date none of them halts disease progression or regenerates damaged cartilage or bone. Thus, there is an ultimate need for the development of new, noninvasive treatments that could substitute joint replacement for late- or end-stage patients. Therefore, osteoarthritis animal models for mimicking of all OA features are important. Mice develop an OA pathology that is comparable to humans, rapidly develop OA due to the short lifetime and show reproducible OA symptoms. They provide a versatile and widely used animal model for analyzing molecular mechanisms of OA pathology. One major advantage over large animal models is the availability of knockout or transgenic mice strains to examine genetic predispositions/contributions to OA.In this chapter, we describe three widely used instability-inducing murine osteoarthritis models. The most common two methods for surgical induction are: (1) destabilization of the medial meniscus (DMM) and (2) anterior cruciate ligament transection (ACLT). In the DMM model, the medial meniscotibial ligament is transected while in the ACLT model the anterior cruciate ligament is destroyed. In the third, chemical induced instability method, intraarticular collagenase is injected into the knee joint. Intraarticular collagenase weakens articular ligaments which cause instability of the joint, and full-blown OA develops within 6 weeks. For morphological evaluation, we correspond mainly to the recommendations of OARSI for histological assessment of osteoarthritis in mouse. For statistical evaluation summed or mean scores of all four knee areas

  3. Pyridostigmine restores cardiac autonomic balance after small myocardial infarction in mice.

    Directory of Open Access Journals (Sweden)

    Marina T Durand

    Full Text Available The effect of pyridostigmine (PYR--an acetylcholinesterase inhibitor--on hemodynamics and cardiac autonomic control, was never studied in conscious myocardial infarcted mice. Telemetry transmitters were implanted into the carotid artery under isoflurane anesthesia. Seven to ten days after recovery from the surgery, basal arterial pressure and heart rate were recorded, while parasympathetic and sympathetic tone (ΔHR was evaluated by means of methyl atropine and propranolol. After the basal hemodynamic recording the mice were subjected to left coronary artery ligation for producing myocardial infarction (MI, or sham operation, and implantation of minipumps filled with PYR or saline. Separate groups of anesthetized (isoflurane mice previously (4 weeks subjected to MI, or sham coronary artery ligation, were submitted to cardiac function examination. The mice exhibited an infarct length of approximately 12%, no change in arterial pressure and increased heart rate only in the 1st week after MI. Vagal tone decreased in the 1st week, while the sympathetic tone was increased in the 1st and 4th week after MI. PYR prevented the increase in heart rate but did not affect the arterial pressure. Moreover, PYR prevented the increase in sympathetic tone throughout the 4 weeks. Concerning the parasympathetic tone, PYR not only impaired its attenuation in the 1st week, but enhanced it in the 4th week. MI decreased ejection fraction and increased diastolic and systolic volume. Therefore, the pharmacological increase of peripheral acetylcholine availability by means of PYR prevented tachycardia, increased parasympathetic and decreased sympathetic tone after MI in mice.

  4. Neurobehavioral development of CD-1 mice after combined gestational and postnatal exposure to ozone

    Energy Technology Data Exchange (ETDEWEB)

    Dell`Omo, G. [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Fiore, M. [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Petruzzi, S. [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Alleva, E. [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy); Bignami, G. [Section of Behavioral Pathophysiology, Lab. di Fisiopatologia di Organo e di Sistema, Istituto Superiore di Sanita, Rome (Italy)


    Outbred CD-1 mice were exposed continuously to ozone (O{sub 3}, 0.6 ppm) from 6 days prior to the formation of breeding pairs to the time of weaning of the offspring on postnatal day 22 (PND 22) or to PND 26. One half of the mice in each of eight O{sub 3} and eight control litters were subjected on PND 24 to a 20-min open-field test after IP treatment by either saline or scopolamine (2 mg/kg). The remaining mice (those exposed until PND 26) were subjected on PNDs 28-31 to a conditioned place preference (CPP) test, using a short schedule with a single IP injection on PND 29 of either d-amphetamine (3.3 mg/kg) or saline. Subsequently, the saline mice of the open-field experiment were used on PND 59 for an activity test in one of the CPP apparatus compartments after IP treatment by either d-amphetamine (same dose) or saline. In addition, the saline mice of the CPP experiment underwent a multitrial, step-through passive avoidance (PA) acquisition test on PND 59 or 60, followed 24 h later by a single-trial retention test. In the absence of effects on reproductive performance (proportion of successful pregnancies, litter size, offspring viability, and sex ratio), O{sub 3} offspring showed a long-lasting reduction in body weight without modification of sec differences. Ozone effects on neurobehavioral development were not large and quite selective, including: attenuation of the sex differences in several responses (rearing and sniffing in the open-field, activity in the final CPP test session); a change in response choices in the final CPP test, in the absence of a main effect on conditioning; a reduction of grooming in the activity test on PND 29; and impairment of PA acquisition limited to the initial period of training. (orig.)

  5. Intravenous injections in neonatal mice. (United States)

    Gombash Lampe, Sara E; Kaspar, Brian K; Foust, Kevin D


    Intravenous injection is a clinically applicable manner to deliver therapeutics. For adult rodents and larger animals, intravenous injections are technically feasible and routine. However, some mouse models can have early onset of disease with a rapid progression that makes administration of potential therapies difficult. The temporal (or facial) vein is just anterior to the ear bud in mice and is clearly visible for the first two days after birth on either side of the head using a dissecting microscope. During this window, the temporal vein can be injected with volumes up to 50 μl. The injection is safe and well tolerated by both the pups and the dams. A typical injection procedure is completed within 1-2 min, after which the pup is returned to the home cage. By the third postnatal day the vein is difficult to visualize and the injection procedure becomes technically unreliable. This technique has been used for delivery of adeno-associated virus (AAV) vectors, which in turn can provide almost body-wide, stable transgene expression for the life of the animal depending on the viral serotype chosen.

  6. Mice lacking neurofibromin develop gastric hyperplasia (United States)

    Lin, Lu; Chen, Jian; Richardson, James A.


    Gastrointestinal (GI) neoplasms are among many manifestations of the genetic disease neurofibromatosis type 1 (NF1). However, the physiological and pathological functions of the Nf1 gene in the GI system have not been fully studied, possibly because of a lack of mouse models. In this study, we generated conditional knockout mice with Nf1 deficiency in the GI tract. These mice develop gastric epithelial hyperplasia and inflammation together with increased cell proliferation and apoptosis. The gastric phenotypes observed in these mutant mice seem to be the consequence of loss of Nf1 in gastric fibroblasts, resulting in paracrine hyperactivation of the ERK pathway in the gastric epithelium. These mice provide a useful model to study the pathogenesis of GI lesions in a subset of patients with NF1 and to investigate the role of the Nf1 gene in the development of GI neoplasms. PMID:19661150

  7. Zika Infection Shrinks Testicles in Mice (United States)

    ... page: Zika Infection Shrinks Testicles in Mice Study authors unsure ... 22, 2017 WEDNESDAY, Feb. 22, 2017 (HealthDay News) -- Zika virus can be sexually transmitted through semen, and ...

  8. Electroencephalographic changes with age in male mice. (United States)

    Eleftheriou, B E; Zolovick, A J; Elias, M F


    Electroencephalographic (EEG) changes, as measured by the awake state, slow-wave sleep (SWS), rapid-eye movement (REM) patterns and ratio of REM/total sleep, were recorded in aging male mice of DBA/2J and C57BL/6J strains. Results indicate that there is a significant increase in the awake state accompanied by significant decrease in SWS with advancing age for both strains, although these changes appear more pronounced in DBA/2J mice than C57BL/6J mice. Of considerable significance is the finding that REM sleep is absent in mice of DBA/2J strain at 23.5 months of age. Based on these findings, the conclusion was reached that strain DBA/2J ages significantly faster than C57BL/6J. The difference in aging between the two strains emphasizes the need for additional studies dealing with genetic aspects of aging.

  9. Sex-specific association of ACAT-1 rs1044925 SNP and serum lipid levels in the hypercholesterolemic subjects

    Directory of Open Access Journals (Sweden)

    Wu Dong-Feng


    Full Text Available Abstract Background Acyl-CoA:cholesterol acyltransferase (ACAT is a key enzyme in cellular cholesterol homeostasis and in atherosclerosis. The cellular cholesterol efflux correlated with serum high-density lipoprotein cholesterol (HDL-C concentrations has shown to be impaired in hyperlipidemic mice. The present study was carried out to clarify the association of ACAT-1 rs1044925 single nucleotide polymorphism (SNP and serum lipid levels in the hyperlipidemic subjects. Methods A total of 821 unrelated subjects (hyperlipidemia, 476; normolipidemia, 345 aged 15-80 were included in the study. Genotyping of the ACAT-1 rs1044925 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results There was no significant difference in the genotypic and allelic frequencies of ACAT-1 rs1044925 SNP between the normolipidemic and hyperlipidemic subjects. The levels of total cholesterol (TC, HDL-C and apolipoprotein (Apo AI in hyperlipidemic subjects were different between the AA and AC/CC genotypes in male but not in female (P Conclusions The present study shows that the C allele carriers of ACAT-1 rs1044925 SNP in male hyperlipidemic subjects had higher serum TC, HDL-C and ApoAI levels than the C allele noncarriers. There is a sex (male-specific association of ACAT-1 rs1044925 SNP and serum HDL-C and ApoAI levels in the hypercholesterolemic subjects.

  10. Cotinine reduces depressive-like behavior and hippocampal vascular endothelial growth factor downregulation after forced swim stress in mice. (United States)

    Grizzell, J Alex; Mullins, Michelle; Iarkov, Alexandre; Rohani, Adeeb; Charry, Laura C; Echeverria, Valentina


    Cotinine, the predominant metabolite of nicotine, appears to act as an antidepressant. We have previously shown that cotinine reduced immobile postures in Porsolt's forced swim (FS) and tail suspension tests while preserving the synaptic density in the hippocampus as well as prefrontal and entorhinal cortices of mice subjected to chronic restraint stress. In this study, we investigated the effect of daily oral cotinine (5 mg/kg) on depressive-like behavior induced by repeated, FS stress for 6 consecutive days in adult, male C57BL/6J mice. The results support our previous report that cotinine administration reduces depressive-like behavior in mice subjected or not to high salience stress. In addition, cotinine enhanced the expression of the vascular endothelial growth factor (VEGF) in the hippocampus of mice subjected to repetitive FS stress. Altogether, the results suggest that cotinine may be an effective antidepressant positively influencing mood through a mechanism involving the preservation of brain homeostasis and the expression of critical growth factors such as VEGF. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  11. Velopharyngeal mucosal surface topography in healthy subjects and subjects with obstructive sleep apnea. (United States)

    Lambeth, Christopher; Amatoury, Jason; Wang, Ziyu; Foster, Sheryl; Amis, Terence; Kairaitis, Kristina


    Macroscopic pharyngeal anatomical abnormalities are thought to contribute to the pathogenesis of upper airway (UA) obstruction in obstructive sleep apnea (OSA). Microscopic changes in the UA mucosal lining of OSA subjects are reported; however, the impact of these changes on UA mucosal surface topography is unknown. This study aimed to 1) develop methodology to measure UA mucosal surface topography, and 2) compare findings from healthy and OSA subjects. Ten healthy and eleven OSA subjects were studied. Awake, gated (end expiration), head and neck position controlled magnetic resonance images (MRIs) of the velopharynx (VP) were obtained. VP mucosal surfaces were segmented from axial images, and three-dimensional VP mucosal surface models were constructed. Curvature analysis of the models was used to study the VP mucosal surface topography. Principal, mean, and Gaussian curvatures were used to define surface shape composition and surface roughness of the VP mucosal surface models. Significant differences were found in the surface shape composition, with more saddle/spherical and less flat/cylindrical shapes in OSA than healthy VP mucosal surface models (P surface models were also found to have more mucosal surface roughness (P surface models. Our novel methodology was utilized to model the VP mucosal surface of OSA and healthy subjects. OSA subjects were found to have different VP mucosal surface topography, composed of increased irregular shapes and increased roughness. We speculate increased irregularity in VP mucosal surface may increase pharyngeal collapsibility as a consequence of friction-related pressure loss.NEW & NOTEWORTHY A new methodology was used to model the upper airway mucosal surface topography from magnetic resonance images of patients with obstructive sleep apnea and healthy adults. Curvature analysis was used to analyze the topography of the models, and a new metric was derived to describe the mucosal surface roughness. Increased roughness was

  12. Dream as a subject of psychological research

    Directory of Open Access Journals (Sweden)

    P.A. Egorova,


    Full Text Available We discuss the main theoretical concepts of a dream: dream definitions, ideas about its genesis, functions, dream location in the structure of activity. We analyze the similarities and differences between the approaches. The results of empirical studies of adolescent and adult dreams are generalized, dream functions in adolescence are analyzed. Based on the analysis of different approaches, we chose theoretical basis of our own research – A. Leontiev activity theory, L.S. Vygotsky concept, K. Lewin's model. We formulated and substantiated the definition of dream as emotionally colored image of the desired future, having a subjective significance. We show the significance and hypotheses of our research: 1 the content of dreams is connected not only with a situation of frustration, but also with the teenager abilities, 2 the dream is involved in regulating of values choice; 3 restoration and development of the ability to dream can be used in the practice of counseling and psychotherapy as an effective tool to help adolescents and adults

  13. Subjective risk assessment for planning conservation projects (United States)

    Game, Edward T.; Fitzsimons, James A.; Lipsett-Moore, Geoff; McDonald-Madden, Eve


    Conservation projects occur under many types of uncertainty. Where this uncertainty can affect achievement of a project’s objectives, there is risk. Understanding risks to project success should influence a range of strategic and tactical decisions in conservation, and yet, formal risk assessment rarely features in the guidance or practice of conservation planning. We describe how subjective risk analysis tools can be framed to facilitate the rapid identification and assessment of risks to conservation projects, and how this information should influence conservation planning. Our approach is illustrated with an assessment of risks to conservation success as part of a conservation plan for the work of The Nature Conservancy in northern Australia. Risks can be both internal and external to a project, and occur across environmental, social, economic and political systems. Based on the relative importance of a risk and the level of certainty in its assessment we propose a series of appropriate, project level responses including research, monitoring, and active amelioration. Explicit identification, prioritization, and where possible, management of risks are important elements of using conservation resources in an informed and accountable manner.

  14. Dietary management for older subjects with obesity. (United States)

    Chernoff, Ronni


    In recent years, obesity has been recognized as a form of malnutrition in older adults and a continuing risk factor for serious health problems. Weight reduction in older adults is not as reliable a recommendation as it is for younger adults; a decreased body mass index (BMI) seems to be associated with a higher incidence of stroke, and a normal or slightly elevated BMI has been linked to greater reserve capacity. Weight loss in older adults requires strategies that consider health status, functional ability, and rational targets. Strategies may include behavior modification, dietary alterations, exercise or physical activity, and reasonable goals that do not put the individual at nutritional risk. Studies that examine different approaches to weight reduction rarely include older subjects, so it is difficult to make judgments about various interventions (surgery, exercise, drugs, or diet) and their efficacy in this population. Fad diets may be lacking in essential nutrients and may prove to be risky for elderly people. Weight loss programs for older adults should focus on maintaining adequate intake of essential nutrients while reducing calories by controlling dietary fat intake.

  15. Subjectivity, Identity and Violence: Masculinity Crossroads

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    Javier Pineda Duque


    Full Text Available This article explores elements of masculine subjectivity and identity based on interviews with men from median and low income groups whose spouses pressed charges against them with the Family Commissioners (comisaría de familia of Bogota. Based on the poststructuralist tradition in social sciences and pro-feminist studies about masculinities, the article examines the significances and representations of the men about the occurrences of intrafamilial violence, in the context of the negotiation of homes in front of family judges. The article points out properties of the accounts related to everyday practices that represent a tactical character in the negotiation of the representation of self, and are codified expressions of cultural constructs that configure the relationships between intrafamilial violence and masculinity. It is shown how intervention processes in matters that traditionally were reserved for private consideration, have allowed to evidence the ambivalence of masculine identities to get rid of the stigma of having been reported and consolidate images that result in accordance with hegemonic patterns of representation and power.

  16. The effect of predictability on subjective duration.

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    Vani Pariyadath

    Full Text Available Events can sometimes appear longer or shorter in duration than other events of equal length. For example, in a repeated presentation of auditory or visual stimuli, an unexpected object of equivalent duration appears to last longer. Illusions of duration distortion beg an important question of time representation: when durations dilate or contract, does time in general slow down or speed up during that moment? In other words, what entailments do duration distortions have with respect to other timing judgments? We here show that when a sound or visual flicker is presented in conjunction with an unexpected visual stimulus, neither the pitch of the sound nor the frequency of the flicker is affected by the apparent duration dilation. This demonstrates that subjective time in general is not slowed; instead, duration judgments can be manipulated with no concurrent impact on other temporal judgments. Like spatial vision, time perception appears to be underpinned by a collaboration of separate neural mechanisms that usually work in concert but are separable. We further show that the duration dilation of an unexpected stimulus is not enhanced by increasing its saliency, suggesting that the effect is more closely related to prediction violation than enhanced attention. Finally, duration distortions induced by violations of progressive number sequences implicate the involvement of high-level predictability, suggesting the involvement of areas higher than primary visual cortex. We suggest that duration distortions can be understood in terms of repetition suppression, in which neural responses to repeated stimuli are diminished.

  17. Peripapillary choroidal thickness in healthy Turkish subjects

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    Erbagci H


    Full Text Available Hulya Erbagci,1 Burak Oren,2 Seydi Okumus,3 Serhat Kenan,3 Pelin Celemler,3 Ibrahim Erbagci3 1Department of Anatomy, Medical Faculty, Zirve University Emine Bahattin Nakiboglu, Gaziantep, 2Department of Ophthalmology, Kilis State Hospital, Kilis, 3Department of Ophthalmology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey Aim: The objective of the study reported here was to investigate the normal peripapillary choroidal thickness (CT, measured by enhanced depth imaging optical coherence tomography (EDI-OCT, in healthy Turkish volunteers. Materials and methods: In this prospective cross-sectional study, 57 eyes of 57 healthy Turkish subjects were enrolled. Each participant underwent a comprehensive ophthalmic examination and peripapillary CT measurement using EDI-OCT. Results: The mean age of the 25 female and 32 male patients in the study was 30.9±10.6 years (range, 18–56 years. The mean peripapillary CT at the superior, inferior, nasal, and temporal sites was 225±57, 183±47, 220±57, and 233±59 µm, respectively. The inferior peripapillary CT value was significantly lower than the peripapillary CT values (P<0.001 for all, whereas no significant differences were found between the superior, nasal, and temporal peripapillary CT values. Conclusion: The findings of the study revealed that Turkish people had significantly lower peripapillary CT values in the inferior quadrant than in the superior, nasal, and temporal quadrants. Keywords: peripapillary choroidal thickness, enhanced depth imaging optical coherence tomography, EDI-OCT

  18. Family farmers as subjects of rights

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    Everton Lazzaretti Picolotto


    Full Text Available The process of the family farmers' recognition as individuals with rights demonstrates having their first roots, in spite of being recent, if compared to the history of the Brazilian rural syndicalism, still in the constitution of the labor-syndical legislation in 1930. Therefore, seeking to explore that process the present paper has as objective to analyze the family farmers' emergence as individuals of rights in the contemporary Brazilian society, analyzing the processes of formation of the rural syndicalism and the expansion of the labor law for the rural workers as a form of accomplishment of a “regulated citizens hip” until the decade of 1970; the urge to the official syndicalism, the structuring of a “new syndicalism” and the new social actors' appearance in the field, which made possible the enlargement of the citizenship spaces in the period of re-democratization in Brazil; the “crisis” of the new syndicalism, the creation of new syndical structures “apart” of the official structure (syndicalism of the family agriculture and the emergency of the “family farmers” as subject of rights in the recent period.

  19. Classifying anatomical subtypes of subjective memory impairment. (United States)

    Jung, Na-Yeon; Seo, Sang Won; Yoo, Heejin; Yang, Jin-Ju; Park, Seongbeom; Kim, Yeo Jin; Lee, Juyoun; Lee, Jin San; Jang, Young Kyoung; Lee, Jong Min; Kim, Sung Tae; Kim, Seonwoo; Kim, Eun-Joo; Na, Duk L; Kim, Hee Jin


    We aimed to categorize subjective memory impairment (SMI) individuals based on their patterns of cortical thickness and to propose simple models that can classify each subtype. We recruited 613 SMI individuals and 613 age- and gender-matched normal controls. Using hierarchical agglomerative cluster analysis, SMI individuals were divided into 3 subtypes: temporal atrophy (12.9%), minimal atrophy (52.4%), and diffuse atrophy (34.6%). Individuals in the temporal atrophy (Alzheimer's disease-like atrophy) subtype were older, had more vascular risk factors, and scored the lowest on neuropsychological tests. Combination of these factors classified the temporal atrophy subtype with 73.2% accuracy. On the other hand, individuals with the minimal atrophy (non-neurodegenerative) subtype were younger, were more likely to be female, and had depression. Combination of these factors discriminated the minimal atrophy subtype with 76.0% accuracy. We suggest that SMI can be largely categorized into 3 anatomical subtypes that have distinct clinical features. Our models may help physicians decide next steps when encountering SMI patients and may also be used in clinical trials.

  20. Antifatigue effect of Gracilaria eucheumoides in mice


    SHAO, JIN-TING; Wang, Mei-Yan; ZHENG, LU-BIN


    Gracilaria eucheumoides Linn (Gracilariaceae; G. eucheumoides) is abundant in dietary fiber, which aids the clearance of excess cholesterol from the blood and maintains stable blood glucose levels. The aim of the present study was to investigate the antifatigue effect of G. eucheumoides in mice and the physiological and molecular mechanisms underlying this effect. Mice were randomly divided into four groups and three of the groups were administered different doses of G. eucheumoides extract. ...

  1. Metabolic characteristics of long-lived mice

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    Andrzej eBartke


    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

  2. Pregnant phenotype in aquaporin 8-deficient mice

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan SHA; Zheng-fang XIONG; Hui-shu LIU; Zheng ZHENG; Tong-hui MA


    Aim: Aquaporin 8 (AQP8) is expressed within the female reproductive system but its physiological function reminds to be elucidated.This study investigates the role of AQP8 during pregnancy using AQP8-knockout (AQP8-KO) mice.Methods: Homozygous AQP8-KO mice were mated, and the conception rate was recorded. AQP8-KO pregnant mice or their offspring were divided into 5 subgroups according to fetal gestational day (7, 13, 16, 18 GD) and newborn. Wild type C57 pregnant mice served as the control group. The number of pregnant mice, total embryos and atrophic embryos, as well as fetal weight, placental weight and placental area were recorded for each subgroup. The amount of amniotic fluid in each sac at 13, 16, and 18 GD was calculated. Statistical significance was determined by analysis of variance of factorial design and chi-square tests.Results: Conception rates did not differ significantly between AQP8-KO and wild type mice. AQP8-KO pregnant mice had a significantly higher number of embryos compared to wild type controls. Fetal/neonatal weight was also significantly greater in the AQP8-KO group compared to age-matched wild type controls. The amount of amniotic fluid was greater in AQP8-KO pregnant mice than wild type controis, although the FM/AFA (fetal weight/amniotic fluid amount) did not differ. While AQP8-KO placental weight was significantly larger than wild type controls, there was no evidence of placental pathology in either group.Conclusion: The results suggest that AQP8 deficiency plays an important role in pregnancy outcome.

  3. Reduced alcohol consumption in mice lacking preprodynorphin.


    Blednov, Yuri A.; Walker, Danielle; Martinez, Marni; Harris, R. Adron


    Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the κ-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower a...

  4. Serum amyloid A regulates monopoiesis in hyperlipidemic Ldlr(-/-) mice. (United States)

    Krishack, Paulette A; Sontag, Timothy J; Getz, Godfrey S; Reardon, Catherine A


    We previously showed that feeding a Western-type diet (WTD) to Ldlr(-/-) mice lacking serum amyloid A (SAA) (Saa(-/-) Ldlr(-/-) mice), the level of total blood monocytes was higher than in Ldlr(-/-) mice. In this investigation we demonstrate that higher levels of bone marrow monocytes and macrophage-dendritic cell progenitor (MDP) cells were found in WTD-fed Saa(-/-) Ldlr(-/-) mice compared to Ldlr(-/-) mice and lower levels of GMP cells and CMP cells in Ldlr(-/-) mice. These data indicate that SAA regulates the level of bone marrow monocytes and their myeloid progenitors in hyperlipidemic Ldlr(-/-) mice.

  5. Deficiency of complement receptors CR2/CR1 in Cr2⁻/⁻ mice reduces the extent of secondary brain damage after closed head injury. (United States)

    Neher, Miriam D; Rich, Megan C; Keene, Chesleigh N; Weckbach, Sebastian; Bolden, Ashley L; Losacco, Justin T; Patane, Jenée; Flierl, Michael A; Kulik, Liudmila; Holers, V Michael; Stahel, Philip F


    Complement activation at the C3 convertase level has been associated with acute neuroinflammation and secondary brain injury after severe head trauma. The present study was designed to test the hypothesis that Cr2-/- mice, which lack the receptors CR2/CD21 and CR1/CD35 for complement C3-derived activation fragments, are protected from adverse sequelae of experimental closed head injury. Adult wild-type mice and Cr2-/- mice on a C57BL/6 genetic background were subjected to focal closed head injury using a standardized weight-drop device. Head-injured Cr2-/- mice showed significantly improved neurological outcomes for up to 72 hours after trauma and a significantly decreased post-injury mortality when compared to wild-type mice. In addition, the Cr2-/- genotype was associated with a decreased extent of neuronal cell death at seven days post-injury. Western blot analysis revealed that complement C3 levels were reduced in the injured brain hemispheres of Cr2-/- mice, whereas plasma C3 levels remained unchanged, compared to wild-type mice. Finally, head-injured Cr2-/- had an attenuated extent of post-injury C3 tissue deposition, decreased astrocytosis and microglial activation, and attenuated immunoglobulin M deposition in injured brains compared to wild-type mice. Targeting of these receptors for complement C3 fragments (CR2/CR1) may represent a promising future approach for therapeutic immunomodulation after traumatic brain injury.

  6. Liver-derived IGF-I regulates cortical bone mass but is dispensable for the osteogenic response to mechanical loading in female mice. (United States)

    Svensson, Johan; Windahl, Sara H; Saxon, Leanne; Sjögren, Klara; Koskela, Antti; Tuukkanen, Juha; Ohlsson, Claes


    Low circulating IGF-I is associated with increased fracture risk. Conditional depletion of IGF-I produced in osteoblasts or osteocytes inhibits the bone anabolic effect of mechanical loading. Here, we determined the role of endocrine IGF-I for the osteogenic response to mechanical loading in young adult and old female mice with adult, liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice, serum IGF-I reduced by ≈70%) and control mice. The right tibia was subjected to short periods of axial cyclic compressive loading three times/wk for 2 wk, and measurements were performed using microcomputed tomography and mechanical testing by three-point bending. In the nonloaded left tibia, the LI-IGF-I(-/-) mice had lower cortical bone area and increased cortical porosity, resulting in reduced bone mechanical strength compared with the controls. Mechanical loading induced a similar response in LI-IGF-I(-/-) and control mice in terms of cortical bone area and trabecular bone volume fraction. In fact, mechanical loading produced a more marked increase in cortical bone mechanical strength, which was associated with a less marked increase in cortical porosity, in the LI-IGF-I(-/-) mice compared with the control mice. In conclusion, liver-derived IGF-I regulates cortical bone mass, cortical porosity, and mechanical strength under normal (nonloaded) conditions. However, despite an ∼70% reduction in circulating IGF-I, the osteogenic response to mechanical loading was not attenuated in the LI-IGF-I(-/-) mice.

  7. Palmoplantar keratoderma in Slurp2-deficient mice (United States)

    Allan, Christopher M.; Procaccia, Shiri; Tran, Deanna; Tu, Yiping; Barnes, Richard H.; Larsson, Mikael; Allan, Bernard B.; Young, Lorraine C.; Hong, Cynthia; Tontonoz, Peter; Fong, Loren G.; Young, Stephen G.; Beigneux, Anne P.


    SLURP1, a member of the Ly6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Another secreted Ly6 protein, SLURP2, is encoded by a gene located ~20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2–3 sequences had been replaced with lacZ and neo cassettes. Slurp2−/− mice exhibited hyperkeratosis on the volar surface of the paws (i.e., PPK), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are very similar to those of Slurp1−/− mice. To solidify a link between Slurp2 deficiency and PPK and to be confident that the disease phenotypes in Slurp2−/− mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X−/−) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X−/− mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes. PMID:26967477


    Directory of Open Access Journals (Sweden)

    V.V. Mikheev


    Full Text Available The role of the left and right hemispheres in realization of behavior for SHR, DBA/2 and C57BL/6 males mice in open field was studied. All three lines of mice differed each from other in elements of individual behavior. Comparison of effects of unilateral inactivation in SHR mice revealed domination of the right hemisphere in regulation of total duration of rearings and grooming, the most specialization of hemispheres being registered in regulation of temporary parameters of behavioral reactions. In DBA/2 mice, the left hemisphere dominated in control of rearings, and the right one did on seating. In C57BL/6 mice, the right hemisphere dominated only on locomotion. Therefore, the cortex of the brain (after inactivation did not participate in regulation of individual behavior in the majority of the experiments (11 from 18. In two cases, the symmetric participation of hemispheres in regulation of behavioral reactions was obtained, and in 5 cases, the unilateral domination of hemispheres in control of behavioral elements was registered. Thus, in three lines of mice, the pattern of interhemispheric asymmetry of individual behavior is principally different.

  9. Evaluation of social and physical enrichment in modulation of behavioural phenotype in C57BL/6J female mice.

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    Natalia Kulesskaya

    Full Text Available Housing conditions represent an important environmental variable playing a critical role in the assessment of mouse behaviour. In the present study the effects of isolation and nesting material on the behaviour of female C57BL/6J mice were evaluated. The mice were subjected to different rearing conditions from weaning (at the age of 3 weeks. The study groups were group- and single-housed mice, divided further into groups with or without nesting material (species-specific enrichment. After 8 weeks spent in respective conditions the behavioural testing began. Both factors (social conditions and nesting material appeared to have a significant impact on the behavioural phenotype. However, it is important to stress that the interaction between the factors was virtually absent. We established that isolation increased locomotor activity and reduced anxiety-like behaviour in several tests of exploration. In contrast, absence of nesting material increased anxiety-like behaviour. Neither factor affected rota-rod performance, nociception and prepulse inhibition. Contextual fear memory was significantly reduced in single-housed mice, and interestingly, in mice with nesting material. Cued fear memory was reduced by single-housing, but not affected by enrichment. Mice from enriched cages displayed faster and better learning and spatial search strategy in the water maze. In contrast, isolation caused significant impairment in the water maze. In conclusion, both isolation and species-specific enrichment have profound effects on mouse behaviour and should be considered in design of the experiments and in assessment of animal welfare issues.

  10. Long-term Autophagy and Nrf2 Signaling in the Hippocampi of Developing Mice after Carbon Ion Exposure (United States)

    Ye, Fei; Zhao, Ting; Liu, Xiongxiong; Jin, Xiaodong; Liu, Xinguo; Wang, Tieshan; Li, Qiang


    To explore charged particle radiation-induced long-term hippocampus damage, we investigated the expression of autophagy and antioxidant Nrf2 signaling-related proteins in the mouse hippocampus after carbon ion radiation. Heads of immature female Balb/c mice were irradiated with carbon ions of different LETs at various doses. Behavioral tests were performed on the mice after maturation. Acute and chronic expression of LC3-II, p62/SQSTM1, nuclear Nrf2, activated caspase-3 and the Bax/Bcl-2 ratio were measured in the hippocampi. Secondary X-ray insult was adopted to amplify potential damages. Long-term behavioral changes were observed in high-LET carbon ion-irradiated mice. There were no differences in the rates of LC3-II induction and p62/SQSTM1 degradation compared to the control group regardless of whether the mice received the secondary X-ray insult. A high nuclear Nrf2 content and low apoptosis level in hippocampal cells subjected to secondary X-rays were observed for the mice exposed to relatively low-LET carbon ions. Therefore, carbon ion exposure in the immature mouse led to an LET-dependent behavioral change after maturation. Although autophagy was intact, the persistently high nuclear Nrf2 content in the hippocampus might account for the unchanged behavioral pattern in mice exposed to the relatively low-LET carbon ions and the subsequent increased radioresistance of the hippocampus.

  11. Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice. (United States)

    Ong, Qi-Rui; Chan, Elizabeth S; Lim, Mei-Li; Cole, Gregory M; Wong, Boon-Seng


    Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content.

  12. Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects

    DEFF Research Database (Denmark)

    Zhu, Xiaorong; Zhou, An; Dey, Arunangsu


    ., Rouille, Y., Holst, J., Carroll, R., Ravazzola, M., Orci, L., Furuta, H. & Steiner, D. (1997) Proc. Natl. Acad. Sci. USA 94, 6646-6651). The PC1/3-null mice differ from a human subject reported with compound heterozygosity for defects in this gene, who was of normal stature but markedly obese from early...... life. The PC1/3-null mice are not obese. The basis for these phenotypic differences is an interesting topic for further study. These findings prove the importance of PC1/3 as a key neuroendocrine convertase....

  13. Time restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high fat diet


    Hatori, Megumi; Vollmers, Christopher; Zarrinpar, Amir; DiTacchio, Luciano; Bushong, Eric A.; Gill, Shubhroz; Leblanc, Mathias; Chaix, Amandine; Joens, Matthew; Fitzpatrick, James A. J.; Ellisman, Mark H.; Panda, Satchidananda


    While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed high fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time restricted feeding (tRF) of a HFD for 8 h/day. Mice under tRF consume equivalent calories from HFD as those with ad lib access, ye...

  14. Improvement of skin wound healing in diabetic mice by kinin B2 receptor blockade. (United States)

    Desposito, Dorinne; Chollet, Catherine; Taveau, Christopher; Descamps, Vincent; Alhenc-Gelas, François; Roussel, Ronan; Bouby, Nadine; Waeckel, Ludovic


    Impaired skin wound healing is a major medical problem in diabetic subjects. Kinins exert a number of vascular and other actions limiting organ damage in ischaemia or diabetes, but their role in skin injury is unknown. We investigated, through pharmacological manipulation of bradykinin B1 and B2 receptors (B1R and B2R respectively), the role of kinins in wound healing in non-diabetic and diabetic mice. Using two mouse models of diabetes (streptozotocin-induced and db/db mice) and non-diabetic mice, we assessed the effect of kinin receptor activation or inhibition by subtype-selective pharmacological agonists (B1R and B2R) and antagonist (B2R) on healing of experimental skin wounds. We also studied effects of agonists and antagonist on keratinocytes and fibroblasts in vitro. Levels of Bdkrb1 (encoding B1R) and Bdkrb2 (encoding B2R) mRNAs increased 1-2-fold in healthy and wounded diabetic skin compared with in non-diabetic skin. Diabetes delayed wound healing. The B1R agonist had no effect on wound healing. In contrast, the B2R agonist impaired wound repair in both non-diabetic and diabetic mice, inducing skin disorganization and epidermis thickening. In vitro, B2R activation unbalanced fibroblast/keratinocyte proliferation and increased keratinocyte migration. These effects were abolished by co-administration of B2R antagonist. Interestingly, in the two mouse models of diabetes, the B2R antagonist administered alone normalized wound healing. This effect was associated with the induction of Ccl2 (encoding monocyte chemoattractant protein 1)/Tnf (encoding tumour necrosis factor α) mRNAs. Thus stimulation of kinin B2 receptor impairs skin wound healing in mice. B2R activation occurs in the diabetic skin and delays wound healing. B2R blockade improves skin wound healing in diabetic mice and is a potential therapeutic approach to diabetic ulcers.

  15. Environmental Enrichment Blunts Ethanol Consumption after Restraint Stress in C57BL/6 Mice (United States)

    Marianno, Priscila; Abrahao, Karina Possa


    Elevated alcohol intake after abstinence is a key feature of the addiction process. Some studies have shown that environmental enrichment (EE) affects ethanol intake and other reinforcing effects. However, different EE protocols may vary in their ability to influence alcohol consumption and stress-induced intake. The present study evaluated whether short (3 h) or continuous (24 h) EE protocols affect ethanol consumption after periods of withdrawal. Mice were challenged with stressful stimuli (24 h isolation and restraint stress) to evaluate the effects of stress on drinking. Male C57BL/6 mice were subjected to a two-bottle choice drinking-in-the-dark paradigm for 15 days (20% ethanol and water, 2 h/day, acquisition phase). Control mice were housed under standard conditions (SC). In the first experiment, one group of mice was housed under EE conditions 24 h/day (EE24h). In the second experiment, the exposure to EE was reduced to 3 h/day (EE3h). After the acquisition phase, the animals were deprived of ethanol for 6 days, followed by 2 h ethanol access once a week. Animals were tested in the elevated plus maze (EPM) during ethanol withdrawal. During the last 2 weeks, the mice were exposed to 24 h ethanol access. A 1-h restraint stress test was performed immediately before the last ethanol exposure. EE24h but not EE3h increased anxiety-like behavior during withdrawal compared to controls. Neither EE24h nor EE3h affected ethanol consumption during the 2 h weekly exposure periods. However, EE24h and EE3h mice that were exposed to acute restraint stress consumed less ethanol than controls during a 24 h ethanol access. These results showed that EE reduces alcohol intake after an acute restraint stress. PMID:28107511

  16. Food restriction increases long-term memory persistence in adult or aged mice. (United States)

    Talhati, F; Patti, C L; Zanin, K A; Lopes-Silva, L B; Ceccon, L M B; Hollais, A W; Bizerra, C S; Santos, R; Tufik, S; Frussa-Filho, R


    Food restriction (FR) seems to be the unique experimental manipulation that leads to a remarkable increase in lifespan in rodents. Evidences have suggested that FR can enhance memory in distinct animal models mainly during aging. However, only few studies systemically evaluated the effects FR on memory formation in both adult (3-month-old) and aged (18-24-month-old) mice. Thus, the aim of the present study was to investigate the effects of acute (12h) or repeated (12h/day for 2days) FR protocols on learning and memory of adult and aged mice evaluated in the plus-maze discriminative avoidance task (PM-DAT), an animal model that concurrently (but independently) evaluates learning and memory, anxiety and locomotion. We also investigated the possible role of FR-induced stress by the corticosterone concentration in adult mice. Male mice were kept at home cage with food ad libitum (CTRL-control condition) or subjected to FR during the dark phase of the cycle for 12h/day or 12h/2days. The FR protocols were applied before training, immediately after it or before testing. Our results demonstrated that only FR for 2days enhanced memory persistence when applied before training in adults and before testing in aged mice. Conversely, FR for 2days impaired consolidation and exerted no effects on retrieval irrespective of age. These effects do not seem to be related to corticosterone concentration. Collectively, these results indicate that FR for 2days can promote promnestic effects not only in aged mice but also in adults.

  17. Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit

    Institute of Scientific and Technical Information of China (English)

    Hongkai Wang; Chengren Li; Hanzhi Wang; Feng Mei; Zhi Liu; Hai-Ying Shen; Lan Xiao


    Schizophrenia is a mental disease that mainly affects young individuals (15 to 35 years old) but its etiology remains largely undefined.Recently,accumulating evidence indicated that demyelination and/or dysfunction of oligodendrocytes is an important feature of its pathogenesis.We hypothesized that the vulnerability of young individuals to demyelination may contribute to the onset of schizophrenia.In the present study,three different age cohorts of mice,i.e.juvenile (3 weeks),young-adult (6 weeks) and middle-aged (8months),were subjected to a 6-week diet containing 0.2% cuprizone (CPZ) to create an animal model of acute demyelination.Then,age-related vulnerability to CPZ-induced demyelination,behavioral outcomes,and myelination-related molecular biological changes were assessed.We demonstrated:(1) CPZ treatment led to more severe demyelination in juvenile and young-adult mice than in middle-aged mice in the corpus callosum,a region closely associated with the pathophysiology of schizophrenia; (2)the higher levels of demyelination in juvenile and young-adult mice were correlated with a greater reduction of myelin basic protein,more loss of CC-1-positive mature oligodendrocytes,and higher levels of astrocyte activation; and (3) CPZ treatment resulted in a more prominent exploratory behavior deficit in juvenile and young-adult mice than in middle-aged mice.Together,our data demonstrate an age-related vulnerability to demyelination with a concurrent behavioral deficit,providing supporting evidence for better understanding the susceptibility of the young to the onset of schizophrenia.

  18. Ozone-Induced Type 2 Immunity in Nasal Airways. Development and Lymphoid Cell Dependence in Mice. (United States)

    Ong, Chee Bing; Kumagai, Kazuyoshi; Brooks, Phillip T; Brandenberger, Christina; Lewandowski, Ryan P; Jackson-Humbles, Daven N; Nault, Rance; Zacharewski, Timothy R; Wagner, James G; Harkema, Jack R


    Inhalation exposures to ozone commonly encountered in photochemical smog cause airway injury and inflammation. Elevated ambient ozone concentrations have been epidemiologically associated with nasal airway activation of neutrophils and eosinophils. In the present study, we elucidated the temporal onset and lymphoid cell dependency of eosinophilic rhinitis and associated epithelial changes in mice repeatedly exposed to ozone. Lymphoid cell-sufficient C57BL/6 mice were exposed to 0 or 0.5 parts per million (ppm) ozone for 1, 2, 4, or 9 consecutive weekdays (4 h/d). Lymphoid cell-deficient, Rag2(-/-)Il2rg(-/-) mice were similarly exposed for 9 weekdays. Nasal tissues were taken at 2 or 24 hours after exposure for morphometric and gene expression analyses. C57BL/6 mice exposed to ozone for 1 day had acute neutrophilic rhinitis, with airway epithelial necrosis and overexpression of mucosal Ccl2 (MCP-1), Ccl11 (eotaxin), Cxcl1 (KC), Cxcl2 (MIP-2), Hmox1, Il1b, Il5, Il6, Il13, and Tnf mRNA. In contrast, 9-day ozone exposure elicited type 2 immune responses in C57BL/6 mice, with mucosal mRNA overexpression of Arg1, Ccl8 (MCP-2), Ccl11, Chil4 (Ym2), Clca1 (Gob5), Il5, Il10, and Il13; increased density of mucosal eosinophils; and nasal epithelial remodeling (e.g., hyperplasia/hypertrophy, mucous cell metaplasia, hyalinosis, and increased YM1/YM2 proteins). Rag2(-/-)Il2rg(-/-) mice exposed to ozone for 9 days, however, had no nasal pathology or overexpression of transcripts related to type 2 immunity. These results provide a plausible paradigm for the activation of eosinophilic inflammation and type 2 immunity found in the nasal airways of nonatopic individuals subjected to episodic exposures to high ambient ozone.

  19. Donor MHC gene to mitigate rejection of transplantation in recipient mice

    Institute of Scientific and Technical Information of China (English)

    LI Tong; ZHANG Zhi-tai; LI Hui; YAN Jun; TAN Jia-li; L(U) Yue-ping; HOU Sheng-cai; LI Shen-tao; XU Qing; TONG Xue-hong; DING Jie


    Background Donor organ rejection continues to be a significant problem for patients receiving transplants.We therefore tested whether transferring a donor's major histocompatibility complex (MHC) gene to the recipient would mitigate the rejection of transplanted hearts in mice.Methods H-2Kkgene from donor mice was amplified using nested polymerase chain reaction (PCR) and ligated into a mammalian expression vector,which was then transfected into thymus ground mass cells collected from the recipients.Clones stably expressing the transgene were then injected into the recipients' thymus visualized using ultrasound.Control mice were administered cells previously transfected with empty vector.Following heart transplantation,cardiac activity was monitored electrocardiographically.Recipient thymus cells were tested for MHC antigenicity using flow cytometry and spleen cells were subjected to mixed lymphocyte culture tests.Finally,the transplanted hearts were sectioned,stained and examined under light microscopy.Results Southern analysis following nested PCR revealed clear expression of H-2Kk gene.Following transplantation,electrocardiosignals were detectable highly significantly longer in recipients administered thymal cells expressing donor H-2Kk than in those receiving control cells.Flow cytometric analysis using an anti-H-2Kk antibody confirmed its expression in H-2Kk treated recipients but not in control mice.Mixed lymphocyte cultures containing H-2Kk treated cells showed significantly less proliferation than those containing control cells.Hearts from control mice showed substantially greater lymphocyte infiltration than those from H-2Kk treated mice and large areas of necrosis.Conclusion Rejection of transplanted hearts can be mitigated substantially by introducing the donor's MHC into the recipient.

  20. Mitochondrial mutations in subjects with psychiatric disorders.

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    Adolfo Sequeira

    Full Text Available A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C. Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA.

  1. From Perception to Subject: The Bergsonian Reversal

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    Messay Kebede


    Full Text Available In lieu of an abstract, here is the opening paragraph to the essay:What singles out philosophical analyses of perception is the challenge to common sense, that is, to the spontaneous, instinctive belief that an external world exists and that it is similar to the perception we have of it. Even those theories that refrain from questioning the independent existence of the world concede that the resemblance of whatever is out there to the perceived reality is anything but assured. Henri Bergson proposes a theory of perception that not only restores the common belief in the existence of an external world, but also goes a long way in narrowing the alleged disparity between perception and the objective world. With few exceptions, Bergson’s theory of perception has been either ignored or misunderstood. Through a close reading of the first chapter of Matter and Memory, the paper argues, in addition to correcting misreadings, that the strength and originality of Bergson’s theory lie in the reversal of the method of explaining perception from the premise of a given subject, a premise shared by all idealist and realist theories as well as phenomenology. This de-subjectification proposes an approach deriving perception from the interactions of objects while countering the materialist theory of the brain as an organ of representation. The paper contends that the Bergsonian elucidation of the brain as an organ of simulation both anticipates the findings of the sensorimotor theory and overcomes its limitation by showing how simulation inserts indetermination into materiality, thereby actualizing consciousness.

  2. Ventilatory efficiency during exercise in healthy subjects. (United States)

    Sun, Xing-Guo; Hansen, James E; Garatachea, Nuria; Storer, Thomas W; Wasserman, Karlman


    When evaluating dyspnea in patients with heart or lung disease it is useful to measure the quantity of ventilation needed to eliminate metabolically produced CO2 (i.e., the ventilatory efficiency). Mathematically, the relationship between ventilation (VE) and CO2 output is determined by the arterial CO2 pressure and the physiologic dead space-tidal volume ratio. We decided to determine how age, sex, size, fitness, and the type of ergometer influenced ventilatory efficiency in normal subjects. Three methods were compared for expressing this relationship: (1) the VE versus CO2 output slope below the ventilatory compensation point, commonly used by cardiologists for estimating the severity of heart failure; (2) the VE/CO2 output ratio at the anaerobic threshold, commonly used by pulmonologists; and (3) the lowest VE/CO2 output ratio during exercise, the latter parameter not previously reported. We studied 474 healthy adults, between 17 and 78 years of age during incremental cycle and treadmill cardiopulmonary exercise tests at three test sites, correcting the total VE for the equipment dead space. The lowest VE/CO2 output ratio was insignificantly different from the ratio at the anaerobic threshold, less variable than that for the slope relationship, and unaffected by the site, ergometer, and gas exchange measurement systems. The regression equation for the lowest VE/CO2 output ratio was 27.94 + 0.108 x age + (0.97 = F, 0.0 = M) - 0.0376 x height, where age is in years and height is in centimeters. We conclude that the lowest VE/CO2 output ratio is the preferred noninvasive method to estimate ventilatory inefficiency.

  3. Comparison of Subjective and Objective Sleep Estimations in Patients with Bipolar Disorder and Healthy Control Subjects (United States)

    Sauer, Cathrin; Pfeiffer, Steffi; Bauer, Michael; Pfennig, Andrea


    Background. Several studies have described but not formally tested discrepancies between subjective and objective measures of sleep. Study Objectives. To test the hypothesis that patients with bipolar disorder display a systematic bias to underestimate sleep duration and overestimate sleep latency. Methods. Actimetry was used to assess sleep latency and duration in 49 euthymic participants (bipolar = 21; healthy controls = 28) for 5–7 days. Participants simultaneously recorded estimated sleep duration and sleep latency on a daily basis via an online sleep diary. Group differences in the discrepancy between subjective and objective parameters were calculated using t-tests and corrected for multiple comparisons. Results. Patients with bipolar disorder significantly underestimated their sleep duration but did not overestimate their sleep latency compared to healthy controls. Conclusions. Studies utilizing diaries or questionnaires alone in patients with bipolar disorders may systematically underestimate sleep duration compared to healthy controls. The additional use of objective assessment methods such as actimetry is advisable. PMID:27891255

  4. CFTR is a tumor suppressor gene in murine and human intestinal cancer. (United States)

    Than, B L N; Linnekamp, J F; Starr, T K; Largaespada, D A; Rod, A; Zhang, Y; Bruner, V; Abrahante, J; Schumann, A; Luczak, T; Niemczyk, A; O'Sullivan, M G; Medema, J P; Fijneman, R J A; Meijer, G A; Van den Broek, E; Hodges, C A; Scott, P M; Vermeulen, L; Cormier, R T


    CFTR, the cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regulation and tissue homeostasis of various epithelia. In the gastrointestinal (GI) tract CFTR promotes chloride and bicarbonate secretion, playing an essential role in ion and acid-base homeostasis. Cftr has been identified as a candidate driver gene for colorectal cancer (CRC) in several Sleeping Beauty DNA transposon-based forward genetic screens in mice. Further, recent epidemiological and clinical studies indicate that CF patients are at high risk for developing tumors in the colon. To investigate the effects of CFTR dysregulation on GI cancer, we generated Apc(Min) mice that carried an intestinal-specific knockout of Cftr. Our results indicate that Cftr is a tumor suppressor gene in the intestinal tract as Cftr mutant mice developed significantly more tumors in the colon and the entire small intestine. In Apc(+/+) mice aged to ~1 year, Cftr deficiency alone caused the development of intestinal tumors in >60% of mice. Colon organoid formation was significantly increased in organoids created from Cftr mutant mice compared with wild-type controls, suggesting a potential role of Cftr in regulating the intestinal stem cell compartment. Microarray data from the Cftr-deficient colon and the small intestine identified dysregulated genes that belong to groups of immune response, ion channel, intestinal stem cell and other growth signaling regulators. These associated clusters of genes were confirmed by pathway analysis using Ingenuity Pathway Analysis and gene set enrichment analysis (GSEA). We also conducted RNA Seq analysis of tumors from Apc(+/+) Cftr knockout mice and identified sets of genes dysregulated in tumors including altered Wnt β-catenin target genes. Finally we analyzed expression of CFTR in early stage human CRC patients stratified by risk of recurrence and found that loss of expression of CFTR was significantly associated with poor disease

  5. Subject subjected - Sexualised coercion, agency and the reorganisation and reformulation of life strategies


    Rikke Spjæt Salkvist; Bodil Pedersen


    When not acting in ways that are recognised as physicalself-defence, women are often – in psychology and inother dominant discourses – generalised as inherentlypassive during subjection to sexualised coercion (rapeand attempted rape). Likewise, in the aftermaths, their(in)actions are frequently pathologised as ‘maladaptivecoping strategies’.We present theoretically and empirically based argumentsfor an agency-oriented approach to women’sperspectives on sexualised coercion. Agency is understoo...

  6. Repeated acquisition and performance chamber for mice: a paradigm for assessment of spatial learning and memory. (United States)

    Brooks, A I; Cory-Slechta, D A; Murg, S L; Federoff, H J


    Molecular genetic manipulation of the mouse offers the possibility of elucidating the function of individual gene products in neural systems underlying learning and memory. Many extant learning paradigms for mice rely on negative reinforcement, involve simple problems that are relatively rapidly acquired and thus preclude time-course assessment, and may impose the need to undertake additional experiments to determine the extent to which noncognitive behaviors influence the measures of learning. To overcome such limitations, a multiple schedule of repeated acquisition and performance was behaviorally engineered to assess learning vs rote performance within-behavioral test session and within-subject utilizing an apparatus modified from the rat (the repeated acquisition and performance chamber; RAPC). The multiple schedule required mice to learn a new sequence of door openings leading to saccharin availability in the learning component during each session, while the sequence of door openings for the performance component remained constant across sessions. The learning and performance components alternated over the course of each test session, with different auditory stimuli signaling which component was currently in effect. To validate this paradigm, learning vs performance was evaluated in two inbred strains of mice: C57BL/6J and 129/SvJ. The hippocampal dependence of this measure was examined in lesioned C57BL/6J mice. Both strains exhibited longer latencies and higher errors in the learning compared to the performance component and evidenced declines in both measures across the trials of each session, consistent with an acquisition phenomenon. These same measures showed little or no evidence of change in the performance component. Whereas three trials per session were utilized with C57BL/65 mice in each component, behavior of 129/SvJ mice could only be sustained for two trials per component per session, demonstrating differences in testing capabilities between


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    Ismara Eliane Vidal de Souza TASSO


    Full Text Available Given the uniqueness of the gaze regime to people with disabilities in contemporary, this study focuses on the identity constitution of this subject as it is transformed into discourse from complex relationships among the domain of knowledge, power and ethics. Such restlessness, leads us to undertake a gesture of reading about the documentary “Seeing and believing”, showed in films festival “So we live” (2007. Based on the theoretical assumptions of Cultural Studies, on the question of identity and its relationship with the notions of subjectivity and practices of themselves, from epistemological ground of Discourse Analysis of Foucault perspective, we aim at understanding how the identity constitution is given from the relationships established between visual representation and conditions (co existence enunciative on the disabled body. On the movie materiality, object of this analysis, the linguistic-discursive strategies and the mechanisms employed in the documentary give visibility to the exercise of a government on the other, legitimized by the culture of inclusion. Mind yourself is the guiding principle of the discourse about the relationship between subjectivity and truth, which permeates the will of truth about the inclusion constructed in contemporary society.

  8. Subjective Visual Vertical during Caloric Stimulation in Healthy Subjects: Implications to Research and Neurorehabilitation

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    Martha Funabashi


    Full Text Available Background. The subjective visual vertical (SVV is a perception often impaired in patients with neurologic disorders and is considered a sensitive tool to detect otolithic dysfunctions. However, it remains unclear whether the semicircular canals (SCCs are also involved in the visual vertical perception. Objective. The aim of this study was to analyze the influence of horizontal SCCs on SVV by caloric stimulation in healthy subjects. Methods. SVV was performed before and during the ice-cold caloric stimulation (4°C, right ear in 30 healthy subjects. Results. The mean SVV tilts before and during the caloric stimulation were 0.31° ± 0.39 and −0.28° ± 0.40, respectively. There was no significant difference between the mean SVV tilts before and during stimulation p=0.113. Conclusion. These results suggest that horizontal SCCs do not influence SVV. Therefore, investigations and rehabilitation approaches for SVV misperceptions should be focused on otolithic and cognitive strategies.

  9. Defective CFTR-dependent CREB activation results in impaired spermatogenesis and azoospermia.

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    Wen Ming Xu

    Full Text Available Cystic fibrosis (CF is the most common life-limiting recessive genetic disease among Caucasians caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR with over 95% male patients infertile. However, whether CFTR mutations could affect spermatogenesis and result in azoospermia remains an open question. Here we report compromised spermatogenesis, with significantly reduced testicular weight and sperm count, and decreased cAMP-responsive element binding protein (CREB expression in the testes of CFTR knockout mice. The involvement of CFTR in HCO(3 (- transport and the expression of the HCO(3 (- sensor, soluble adenylyl cyclase (sAC, are demonstrated for the first time in the primary culture of rat Sertoli cells. Inhibition of CFTR or depletion of HCO(3 (- could reduce FSH-stimulated, sAC-dependent cAMP production and phosphorylation of CREB, the key transcription factor in spermatogenesis. Decreased CFTR and CREB expression are also observed in human testes with azoospermia. The present study reveals a previously undefined role of CFTR and sAC in regulating the cAMP-CREB signaling pathway in Sertoli cells, defect of which may result in impaired spermatogenesis and azoospermia. Altered CFTR-sAC-cAMP-CREB functional loop may also underline the pathogenesis of various CF-related diseases.

  10. Efficacy of Spirulina platensis in improvement of the reproductive performance and easing teratogenicity in hyperglycemic albino mice (United States)

    Pankaj, Pranay Punj


    Objectives: The present study evaluates the therapeutic efficacy of cell suspension of Spirulina platensis (SP) on estrous cycle, fetal development and embryopathy in alloxan (AXN) induced hyperglycemic mice. Materials and Methods: Diabetes was induced by intra-peritoneal administration of AXN. Mice with blood glucose level above 200 mg/dl were divided into Group I (control), Group II (diabetic control), Group III (diabetic control mice fed with SP), and Group IV (control mice fed with SP). Litter counts, estrous cycles, percent survival of litter, and gestation length were recorded. Results: In hyperglycemic mice, a significant (P < 0.05) increase in duration of diestrus (14.48%), estrus (84.21%), and metestrus (164.15%) with concomitant decrease in proestrus phase by 26.13% was recorded when compared with control. Reduction in litter count and survival of litter was 68.67% and 88.38%, respectively, whereas gestation length increased to 14.51% day in diabetic mice, but recovery in these parameters was observed (P < 0.05) when subjected to SP treatment. SP resulted in increased fertility rate from 77.5% to 82.5% and dropped off resorption of the fetus to 33.73% while the survival rate of offspring of diabetic mice went up to 88.89% from 83.61%. Conclusions: These findings suggest that SP is effective in improving the reproductive performance and easing teratogenic effects in diabetic mice and hence warrants further detailed dose-dependent studies to understand its mechanism of action. PMID:26285837

  11. Trypanosoma cruzi Infection through the Oral Route Promotes a Severe Infection in Mice: New Disease Form from an Old Infection?

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    Juliana Barreto-de-Albuquerque


    Full Text Available Oral transmission of Chagas disease has been documented in Latin American countries. Nevertheless, significant studies on the pathophysiology of this form of infection are largely lacking. The few studies investigating oral route infection disregard that inoculation in the oral cavity (Oral infection, OI or by gavage (Gastrointestinal infection, GI represent different infection routes, yet both show clear-cut parasitemia and heart parasitism during the acute infection. Herein, BALB/c mice were subjected to acute OI or GI infection using 5x10(4 culture-derived Trypanosoma cruzi trypomastigotes. OI mice displayed higher parasitemia and mortality rates than their GI counterparts. Heart histopathology showed larger areas of infiltration in the GI mice, whereas liver lesions were more severe in the OI animals, accompanied by higher Alanine Transaminase and Aspartate Transaminase serum contents. A differential cytokine pattern was also observed because OI mice presented higher pro-inflammatory cytokine (IFN-γ, TNF serum levels than GI animals. Real-time PCR confirmed a higher TNF, IFN-γ, as well as IL-10 expression in the cardiac tissue from the OI group compared with GI. Conversely, TGF-β and IL-17 serum levels were greater in the GI animals. Immunolabeling revealed macrophages as the main tissue source of TNF in infected mice. The high mortality rate observed in the OI mice paralleled the TNF serum rise, with its inhibition by an anti-TNF treatment. Moreover, differences in susceptibility between GI versus OI mice were more clearly related to the host response than to the effect of gastric pH on parasites, since infection in magnesium hydroxide-treated mice showed similar results. Overall, the present study provides conclusive evidence that the initial site of parasite entrance critically affects host immune response and disease outcome. In light of the occurrence of oral Chagas disease outbreaks, our results raise important implications in terms

  12. Soluble epoxide hydrolase gene deletion improves blood flow and reduces infarct size after cerebral ischemia in reproductively senescent female mice

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    Kristen L Zuloaga


    Full Text Available Soluble epoxide hydrolase (sEH, a key enzyme in the metabolism of vasodilatory epoxyeicosatrienoic acids (EETs, is sexually dimorphic, suppressed by estrogen, and contributes to underlying sex differences in cerebral blood flow and injury after cerebral ischemia. We tested the hypothesis that sEH inhibition or gene deletion in reproductively senescent (RS female mice would increase cerebral perfusion and decrease infarct size following stroke. RS (15-18 month old and young (3-4 month old female sEH knockout (sEHKO mice and wild type (WT mice were subjected to 45 min middle cerebral artery occlusion (MCAO with laser Doppler perfusion monitoring. WT mice were treated with vehicle or a sEH inhibitor t-AUCB at the time of reperfusion and every 24hrs thereafter for 3 days. Differences in regional cerebral blood flow were measured in vivo using optical microangiography. Infarct size was measured 3 days after reperfusion. Infarct size and cerebral perfusion 24h after MCAO were not altered by age. Both sEH gene deletion and sEH inhibition increased cortical perfusion 24h after MCAO. Neither sEH gene deletion nor sEH inhibition reduced infarct size in young mice. However, sEH gene deletion, but not sEH inhibition of the hydrolase domain of the enzyme, decreased infarct size in RS mice. Results of these studies show that sEH gene deletion and sEH inhibition enhance cortical perfusion following MCAO and sEH gene deletion reduces damage after ischemia in RS female mice; however this neuroprotection in absent is young mice.

  13. IgG variable region and VH CDR3 diversity in unimmunized mice analyzed by massively parallel sequencing. (United States)

    Lu, Jin; Panavas, Tadas; Thys, Kim; Aerssens, Jeroen; Naso, Michael; Fisher, Jamie; Rycyzyn, Michael; Sweet, Raymond W


    Most antigen-specific mouse antibodies have been derived by hybridoma technology, predominantly through use of the Balb/c strain. Much of the Balb/c germline repertoire of variable genes (V regions) is known. However, there is little information about the background expressed repertoire of IgG antibodies in mice, which reflects the baseline against which antigen-specific antibodies are generated through immunization. To assess this baseline repertoire, RNA was isolated from splenic B-cells enriched for expression of IgG from three mice. The RNA was individually amplified with three distinct PCR primer sets for comprehensive recovery of the heavy and light chain variable regions. Each PCR product was independently subjected to deep sequencing using 454 pyro-sequencing technology and analysed for redundancy, open reading frame, germline representation, and CDR3 sequence of the heavy chain variable region (VH CDR3) within and across the primer sets and mice. A highly skewed abundance of heavy and light chain variable gene usage was observed for all three primers in all three mice. While showing considerable overlap, there were differences among these profiles indicative of primer bias and animal-to-animal variation. VH CDR3 sequences were likewise highly skewed indicating that the heavy chain genes profiles substantially reflected individual antibodies. This observation was confirmed through analysis of randomly selected complete heavy chain variable sequences. However, there was very little redundancy in VH CDR3 sequences across the different mice. We conclude that the background IgG repertoire in young, unimmunized mice is highly skewed within individual mice and is diverse among them, a pattern similar to that observed in highly immunized mice.

  14. Reduced fasting-induced activation of hypothalamic arcuate neurons is associated with hyperleptinemia and increased leptin sensitivity in obese mice. (United States)

    Becskei, Csilla; Lutz, Thomas A; Riediger, Thomas


    Fasting increases c-Fos expression in neuropeptide Y (NPY) neurons of the hypothalamic arcuate nucleus (ARC) in lean, but not in hyperleptinemic mice with late-onset obesity (LOO). Although obesity is associated with leptin resistance, we hypothesized that under fasting conditions, leptin sensitivity might be restored and that hyperleptinemia may counteract the neuronal response to fasting. We investigated whether the reduced fasting response of ARC neurons in LOO is paralleled by an increase in leptin sensitivity, as measured by leptin-induced STAT-3 phosphorylation. To assess leptin's role in the modulation of the fasting-induced ARC activation, we investigated c-Fos responses and hormone and metabolite levels in hyperleptinemic diet-induced obese (DIO) and in leptin-deficient ob/ob mice. Leptin induced a stronger STAT-3 phosphorylation in fasted LOO and lean mice than in ad libitum-fed animals. Similar to LOO, hyperleptinemic DIO mice showed no c-Fos response after fasting, while ob/ob mice showed a stronger response than lean control mice. Mimicking hyperleptinemia by repeated leptin injections in lean mice during fasting attenuated the fasting-induced c-Fos expression. Our findings indicate that high leptin levels prevent the fasting-induced activation of ARC neurons in mice. Moreover, leptin sensitivity is dynamic in obese subjects and depends on the feeding status. During short-term increases in leptin sensitivity, e.g., during fasting, leptin signaling appears to be effective, even in hyperleptinemic obesity. As reflected by the blockade of the fasting-induced ARC activation, fasting seems to interfere with the responsiveness of the ARC to signals related to the status of energy intake.

  15. Sustained protection in mice immunized with fractional doses of Salmonella Enteritidis core and O polysaccharide-flagellin glycoconjugates.

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    Raphael Simon

    Full Text Available Non-typhoidal Salmonella (NTS serovars S. Enteritidis and S. Typhimurium are a major cause of invasive bacterial disease (e.g., bacteremia, meningitis in infants and young children in sub-Saharan Africa and also occasionally cause invasive disease in highly susceptible hosts (young infants, the elderly, and immunocompromised subjects in industrialized countries. No licensed vaccines exist against human NTS infections. NTS core and O polysaccharide (COPS and FliC (Phase 1 flagellin subunits each constitute protective antigens in murine models. S. Enteritidis COPS conjugated to FliC represents a promising vaccine approach that elicits binding and opsonophagocytic antibodies and protects mice against lethal challenge with virulent S. Enteritidis. We examined the protective efficacy of fractional dosages of S. Enteritidis COPS:FliC conjugate vaccines in mice, and also established that protection can be passively transferred to naïve mice by administering sera from mice immunized with conjugate. Mice were immunized with three doses of either 10 µg, 2.5 µg (full dose, 0.25 µg, or 0.025 µg S. Enteritidis COPS:FliC conjugate at 28 day intervals. Antibody titers to COPS and FliC measured by ELISA fell consonant with progressively smaller vaccine dosage levels; anti-FliC IgG responses remained robust at fractional dosages for which anti-COPS serum IgG titers were decreased. Nevertheless, >90% protection against intraperitoneal challenge was observed in mice immunized with fractional dosages of conjugate that elicited diminished titers to both FliC and COPS. Passive transfer of immune sera from mice immunized with the highest dose of COPS:FliC to naïve mice was also protective, demonstrating the role of antibodies in mediating protection. These results provide important insights regarding the potency of Salmonella glycoconjugate vaccines that use flagellin as a carrier protein.

  16. Efficacy of Spirulina platensis in improvement of the reproductive performance and easing teratogenicity in hyperglycemic albino mice

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    Pranay Punj Pankaj


    Full Text Available Objectives: The present study evaluates the therapeutic efficacy of cell suspension of Spirulina platensis (SP on estrous cycle, fetal development and embryopathy in alloxan (AXN induced hyperglycemic mice. Materials and Methods: Diabetes was induced by intra-peritoneal administration of AXN. Mice with blood glucose level above 200 mg/dl were divided into Group I (control, Group II (diabetic control, Group III (diabetic control mice fed with SP, and Group IV (control mice fed with SP. Litter counts, estrous cycles, percent survival of litter, and gestation length were recorded. Results: In hyperglycemic mice, a significant (P < 0.05 increase in duration of diestrus (14.48%, estrus (84.21%, and metestrus (164.15% with concomitant decrease in proestrus phase by 26.13% was recorded when compared with control. Reduction in litter count and survival of litter was 68.67% and 88.38%, respectively, whereas gestation length increased to 14.51% day in diabetic mice, but recovery in these parameters was observed (P < 0.05 when subjected to SP treatment. SP resulted in increased fertility rate from 77.5% to 82.5% and dropped off resorption of the fetus to 33.73% while the survival rate of offspring of diabetic mice went up to 88.89% from 83.61%. Conclusions: These findings suggest that SP is effective in improving the reproductive performance and easing teratogenic effects in diabetic mice and hence warrants further detailed dose-dependent studies to understand its mechanism of action.

  17. 48 CFR 1352.235-70 - Protection of human subjects. (United States)


    ... subjects research involves pregnant women, prisoners, or children, the contractor is also required to... subjects research protocol, all questionnaires, surveys, advertisements, and informed consent forms..., questionnaires, surveys, advertisements, and informed consent forms by the cognizant IRB; (3) Documentation...

  18. Dysfunctional dopaminergic neurotransmission in asocial BTBR mice. (United States)

    Squillace, M; Dodero, L; Federici, M; Migliarini, S; Errico, F; Napolitano, F; Krashia, P; Di Maio, A; Galbusera, A; Bifone, A; Scattoni, M L; Pasqualetti, M; Mercuri, N B; Usiello, A; Gozzi, A


    Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits and stereotyped behaviours. Recent psychosocial and neuroimaging studies have highlighted reward-processing deficits and reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological and molecular determinants of these deficits remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about the origin and neurophysiological underpinnings of clinically relevant traits. Here we used functional magnetic resonance imaging (fMRI), behavioural and molecular readouts to probe dopamine neurotransmission responsivity in BTBR T(+) Itpr3(tf)/J mice (BTBR), an inbred mouse line widely used to model ASD-like symptoms owing to its robust social and communication deficits, and high level of repetitive stereotyped behaviours. C57BL/6J (B6) mice were used as normosocial reference comparators. DA reuptake inhibition with GBR 12909 produced significant striatal DA release in both strains, but failed to elicit fMRI activation in widespread forebrain areas of BTBR mice, including mesolimbic reward and striatal terminals. In addition, BTBR mice exhibited no appreciable motor responses to GBR 12909. DA D1 receptor-dependent behavioural and signalling responses were found to be unaltered in BTBR mice, whereas dramatic reductions in pre- and postsynaptic DA D2 and adenosine A2A receptor function was observed in these animals. Overall these results document profoundly compromised DA D2-mediated neurotransmission in BTBR mice, a finding that is likely to have a role in the distinctive social and behavioural deficits exhibited by these mice. Our results call for a deeper investigation of the role of dopaminergic dysfunction in mouse lines exhibiting ASD-like phenotypes, and possibly in ASD patient populations.

  19. Lovastatin protects against experimental plague in mice.

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    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.

  20. Laparotomy in mice induces blood cell expression of inflammatory and stress genes. (United States)

    Ko, Fred; Isoda, Fumiko; Mobbs, Charles


    Surgical trauma induces immune and stress responses although its effects on postsurgical inflammatory and stress gene expression remain poorly characterized. This study sought to improve current scientific knowledge by investigating the effects of laparotomy on mouse blood cell inflammatory and stress gene expression. Three-month-old male C57BL/6J mice were subjected to 2% isoflurane or 2% isoflurane with laparotomy and sacrificed 4 h postintervention. Blood was collected and blood cell expression of 158 genes central to inflammatory and stress responses was assayed using quantitative polymerase chain reaction arrays. Mice subjected to isoflurane with laparotomy, compared with mice receiving isoflurane alone, had >2-fold upregulation of genes in inflammation (Osm, IL1rn, IL1b, and Csf1), oxidative stress (Hmox1), heat shock (Hspa1b), growth arrest (Cdkn1a), and DNA repair (Ugt1a2). These genes demonstrated similar expression patterns by Pearson correlation and cluster analysis. Thus, laparotomy induces coordinated, postsurgical blood cell expression of unique inflammatory and stress genes whose roles in influencing surgical outcomes need further investigation.

  1. Antioxidant effects of nerolidol in mice hippocampus after open field test. (United States)

    Nogueira Neto, José Damasceno; de Almeida, Antonia Amanda Cardoso; da Silva Oliveira, Johanssy; Dos Santos, Pauline Sousa; de Sousa, Damião Pergentino; de Freitas, Rivelilson Mendes


    The aim of this study was to evaluate the neuroprotective effects of nerolidol in mice hippocampus against oxidative stress in neuronal cells compared to ascorbic acid (positive control) as well as evaluated the nerolidol sedative effects by open field test compared to diazepam (positive control). Thirty minutes prior to behavioral observation on open field test, mice were intraperitoneally treated with vehicle, nerolidol (25, 50 and 75 mg/kg), diazepam (1 mg/kg) or ascorbic acid (250 mg/kg). To clarify the action mechanism of of nerolidol on oxidative stress in animals subjected to the open field test, Western blot analysis of Mn-superoxide dismutase and catalase in mice hippocampus were performed. In nerolidol group, there was a significant decrease in lipid peroxidation and nitrite levels when compared to negative control (vehicle). However, a significant increase was observed in superoxide dismutase and catalase activities in this group when compared to the other groups. Vehicle, diazepam, ascorbic acid and nerolidol groups did not affected Mn-superoxide dismutase, catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus. Nerolidol showed sedative effects in animals subjected to the open field test. Oxidative process plays a crucial role on neuronal pathological consequence, and implies that antioxidant effects could be achieved using this sesquiterpene.

  2. Low dose effects of a Withania somnifera extract on altered marble burying behavior in stressed mice (United States)

    Dey, Amitabha; Chatterjee, Shyam Sunder; Kumar, Vikas


    Aim: Withania somnifera root (WSR) extracts are often used in traditionally known Indian systems of medicine for prevention and cure of psychosomatic disorders. The reported experiment was designed to test whether low daily oral doses of such extracts are also effective in suppressing marble burying behavior in stressed mice or not. Materials and Methods: Groups of mice treated with 10, 20, or 40 mg/kg daily oral doses of WSR were subjected to a foot shock stress-induced hyperthermia test on the 1st, 5th, 7th, and 10th day of the experiment. On the 11th and 12th treatment days, they were subjected to marble burying tests. Stress response suppressing effects of low dose WSR were estimated by its effects on body weight and basal core temperature of animals during the course of the experiment. Results: Alterations in bodyweight and basal core temperature triggered by repeated exposures to foot shock stress were absent even in the 10 mg/kg/day WSR treated group, whereas the effectiveness of the extract in foot shock stress-induced hyperthermia and marble burying tests increased with its increasing daily dose. Conclusion: Marble burying test in stressed mice is well suited for identifying bioactive constituents of W. somnifera like medicinal plants with adaptogenic, anxiolytic and antidepressant activities, or for quantifying pharmacological interactions between them. PMID:27366354

  3. Overt and Null Subject Pronouns in Jordanian Arabic

    Directory of Open Access Journals (Sweden)

    Islam M. Al-Momani


    Full Text Available The paper aims at examining the role that morphology plays in allowing and/or motivating sentences in Jordanian Arabic (hereafter JA to be formed with or without subject pronouns. It also aims at giving a comprehensive and descriptive presentation of the distribution of overt and null subject pronouns in JA, and tries to determine to what extent there is optionality in its system. Keywords: null subject pronouns, overt subjects, pro-drop languages, verbal inflectional morphology

  4. Assessment of nicotine dependence in subjects with vascular dementia



    Background: Nicotine Dependence is an important public health issue. Nicotine Dependence is a risk factor for vascular diseases like Myocardial Infarction and Vascular dementia. The rate of nicotine dependence in Indian subjects with Vascular Dementia is not known. Hence we decided to assess Nicotine Dependence in subjects with Vascular Dementia Methods: Nicotine Dependence in subjects with Vascular Dementia was assessed among subjects presenting to Memory Clinic of a tertiary car...

  5. Blockade of glucocorticoid receptors improves cutaneous wound healing in stressed mice. (United States)

    de Almeida, Taís Fontoura; de Castro Pires, Taiza; Monte-Alto-Costa, Andréa


    Stress is an important condition of modern life. The successful wound healing requires the execution of three major overlapping phases: inflammation, proliferation, and remodeling, and stress can disturb this process. Chronic stress impairs wound healing through the activation of the hypothalamic-pituitary-adrenal axis, and the glucocorticoids (GCs) hormones have been shown to delay wound closure. Therefore, the aim of this study was to investigate the effects of a GC receptor antagonist (RU486) treatment on cutaneous healing in chronically stressed mice. Male mice were submitted to rotational stress, whereas control animals were not subjected to stress. Stressed and control animals were treated with RU486. A full-thickness excisional lesion was generated, and seven days later, lesions were recovered. The RU486 treatment improves wound healing since contraction takes place earlier in RU486-treated in comparison to non-treated mice, and the RU486 treatment also improves the angiogenesis in Stress+RU486 mice when compared to stressed animals. The Stress+RU486 group showed a decrease in inflammatory cell infiltration and in hypoxia-inducible factor-1α and inducible nitric oxide synthase expression; meanwhile, there was an increase in myofibroblasts quantity. In conclusion, blockade of GC receptors with RU486 partially ameliorates stress-impaired wound healing, suggesting that stress inhibits healing through more than one functional pathway.

  6. Risk Assessment of Neonatal Exposure to Low Frequency Noise Based on Balance in Mice (United States)

    Ohgami, Nobutaka; Oshino, Reina; Ninomiya, Hiromasa; Li, Xiang; Kato, Masashi; Yajima, Ichiro; Kato, Masashi


    General electric devices and ventilation systems are known to generate low frequency noise (LFN) with frequencies of risk to be exposed to LFN in the NICU. However, the risk of neonatal exposure to LFN remains unclear in humans and mice. In this study, male ICR mice were exposed to LFN at 100 Hz for 4 weeks after birth and then subjected to rotarod and beam crossing tests in order to assess LFN-mediated risk of imbalance during the neonatal period. Exposure to LFN at 70 dB, but not exposure to LFN up to 60 dB, during the neonatal period significantly decreased performance scores for rotarod and beam crossing tests compared to the scores of the control group. The number of calbindin-positive hair cells in the saccule and utricle was decreased in mice exposed to LFN at 70 dB for 4 weeks in the neonatal phase. Cessation of exposure for 10 weeks did not result in recovery of the decreased performance in rotarod and beam crossing tests. Thus, our results suggest that 70 dB is a possible threshold for exposure to LFN for 4 weeks during the neonatal period causing unrecoverable imbalance in mice. PMID:28275341

  7. Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

    Directory of Open Access Journals (Sweden)

    Teruaki Toyota


    Full Text Available We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT, glutamic pyruvic transaminase (GPT in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

  8. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji


    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  9. Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice. (United States)

    Zhang, Ming-Zhi; Yao, Bing; Wang, Suwan; Fan, Xiaofeng; Wu, Guanqing; Yang, Haichun; Yin, Huiyong; Yang, Shilin; Harris, Raymond C


    In addition to its role as an essential neurotransmitter, dopamine serves important physiologic functions in organs such as the kidney. Although the kidney synthesizes dopamine through the actions of aromatic amino acid decarboxylase (AADC) in the proximal tubule, previous studies have not discriminated between the roles of extrarenal and intrarenal dopamine in the overall regulation of renal function. To address this issue, we generated mice with selective deletion of AADC in the kidney proximal tubules (referred to herein as ptAadc-/- mice), which led to selective decreases in kidney and urinary dopamine. The ptAadc-/- mice exhibited increased expression of nephron sodium transporters, decreased natriuresis and diuresis in response to l-dihydroxyphenylalanine, and decreased medullary COX-2 expression and urinary prostaglandin E2 excretion and developed salt-sensitive hypertension. They had increased renin expression and altered renal Ang II receptor (AT) expression, with increased AT1b and decreased AT2 and Mas expression, associated with increased renal injury in response to Ang II. They also exhibited a substantially shorter life span compared with that of wild-type mice. These results demonstrate the importance of the intrarenal dopaminergic system in salt and water homeostasis and blood pressure control. Decreasing intrarenal dopamine subjects the kidney to unbuffered responses to Ang II and results in the development of hypertension and a dramatic decrease in longevity.

  10. Inhalation developmental toxicology studies: Teratology study of 1,3-butadiene in mice: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Hackett, P.L.; Sikov, M.R.; Mast, T.J.; Brown, M.G.; Buschbom, R.L.; Clark, M.L.; Decker, J.R.; Evanoff, J.J.; Rommereim, R.L.; Rowe, S.E.; Westerberg, R.B.


    Maternal toxicity, reproductive performance and developmental toxicology were evaluated in CD-1 mice following whole-body, inhalation exposures to 0, 40, 200 and 1000 ppM of 1,3-butadiene. The female mice, which had mated with unexposed males were exposed to the chemical for 6 hours/day on 6 through 15 dg and sacrificed on 18 dg. Maternal animals were weighed prior to mating and on 0, 6, 11 and 18 dg; the mice were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies. Significant concentration-related decreases were detected in a number of maternal body weight measures. There was a significant concentration-related depression of fetal body weights and placental weights. Body weights of male fetuses of all exposed groups were significantly lower than values for control fetuses; weights of female fetuses were significantly depressed in the mice exposed to 200 and 1000 ppM. In the 200- and 1000-ppM exposure groups, weights of placentas of male fetuses were significantly decreased, but placental weights of female fetuses were significantly affected only in litters exposed to the highest 1,3-butadiene concentration. This exposure regimen produced significant signs of maternal toxicity at concentrations of 200 and 1000 ppM 1,3-butadiene.

  11. Tauroursodeoxycholic acid prevents hearing loss and hair cell death in Cdh23(erl/erl) mice. (United States)

    Hu, J; Xu, M; Yuan, J; Li, B; Entenman, S; Yu, H; Zheng, Q Y


    Sensorineural hearing loss has long been the subject of experimental and clinical research for many years. The recently identified novel mutation of the Cadherin23 (Cdh23) gene, Cdh23(erl/erl), was proven to be a mouse model of human autosomal recessive nonsyndromic deafness (DFNB12). Tauroursodeoxycholic acid (TUDCA), a taurine-conjugated bile acid, has been used in experimental research and clinical applications related to liver disease, diabetes, neurodegenerative diseases, and other diseases associated with apoptosis. Because hair cell apoptosis was implied to be the cellular mechanism leading to hearing loss in Cdh23(erl/erl) mice (erl mice), this study investigated TUDCA's otoprotective effects in erl mice: preventing hearing impairment and protecting against hair cell death. Our results showed that systemic treatment with TUDCA significantly alleviated hearing loss and suppressed hair cell death in erl mice. Additionally, TUDCA inhibited apoptotic genes and caspase-3 activation in erl mouse cochleae. The data suggest that TUDCA could be a potential therapeutic agent for human DFNB12.

  12. Moderate exercise prevents neurodegeneration in D-galactose-induced aging mice

    Institute of Scientific and Technical Information of China (English)

    Li Li; Meng Xu; Bo Shen; Man Li; Qian Gao; Shou-gang Wei


    D-galactose has been widely used in aging research because of its efifcacy in inducing senescence and accelerating aging in animal models. The present study investigated the beneifts of exercise for preventing neurodegeneration, such as synaptic plasticity, spatial learning and memory abilities, in mouse models of aging. D-galactose-induced aging mice were administered daily subcutaneous injections of D-ga-lactose at the base of the neck for 10 consecutive weeks. Then, the mice were subjected to exercise training by running on a treadmill for 6 days a week. Shortened escape latency in a Morris water maze test indicated that exercise improved learning and memory in aging mice. The ameliorative changes were likely induced by an upregulation of Bcl-2 and brain-derived neurotrophic factor, the repression of apop-tosis factors such as Fas and Bax, and an increase in the activity of glucose transporters-1 and 4. The data suggest moderate exercise may retard or inhibit neurodegeneration in D-galactose-induced aging mice.

  13. Sodium hydrosulfide prevents hypoxia-induced behavioral impairment in neonatal mice. (United States)

    Wang, Zhen; Zhan, Jingmin; Wang, Xueer; Gu, Jianhua; Xie, Kai; Zhang, Qingrui; Liu, Dexiang


    Hypoxic encephalopathy is a common cause of neonatal seizures and long-term neurological abnormalities. Endogenous hydrogen sulfide (H2S) may have multiple functions in brain. The aim of this study is to investigate whether sodium hydrosulfide (NaHS), a H2S donor, provides protection against neonatal hypoxia-induced neurobehavioral deficits. Neonatal mice were subjected to hypoxia (5% oxygen for 120min) at postnatal day 1 and received NaHS (5.6mg/kg) once daily for 3d. Neurobehavioral toxicity was examined at 3-30d after hypoxia. Treatment with NaHS significantly attenuated the delayed development of sensory and motor reflexes induced by hypoxia up to two weeks after the insult. Moreover, NaHS improved the learning and memory performance of hypoxic animals as indicated in Morris water maze test at 30d after hypoxia. In mice exposed to hypoxia, treatment with NaHS enhanced expression of brain derived neurotrophic factor (BDNF) in the hippocampus. Furthermore, the protective effects of NaHS were associated with its ability to repress the hypoxia-induced nitric oxide synthase (NOS) activity and nitric oxide production in the hippocampus of mice brain. Taken together, these results suggest that the long-lasting beneficial effects of NaHS on hypoxia-induced neurobehavioral deficits are mediated, at least in part, by inducing BDNF expression and suppressing NOS activity in the brain of mice.

  14. Translation and Validation of the Malay Subjective Happiness Scale (United States)

    Swami, Viren


    The Subjective Happiness Scale (Lyubomirsky and Lepper, "Social Indicators Research," 46, 137-155, 1999) is a brief measure for assessing subjective happiness. The reliability and validity of the Malay version of the Subjective Happiness Scale was investigated in a community sample of 290 Chinese and 227 Malays in Malaysia. Results…

  15. 14 CFR Appendix D to Part 147 - Powerplant Curriculum Subjects (United States)


    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Powerplant Curriculum Subjects D Appendix D... Appendix D to Part 147—Powerplant Curriculum Subjects This appendix lists the subjects required in at least 750 hours of each powerplant curriculum, in addition to at least 400 hours in general...

  16. Descriptive Analysis of Single Subject Research Designs: 1983-2007 (United States)

    Hammond, Diana; Gast, David L.


    Single subject research methodology is commonly used and cited in special education courses and journals. This article reviews the types of single subject research designs published in eight refereed journals between 1983 and 2007 used to answer applied research questions. Single subject designs were categorized as withdrawal/reversal, time…

  17. The Acquisition of Jamaican Creole: Null Subject Phenomenon (United States)

    De Lisser, Tamirand Nnena; Durrleman, Stephanie; Rizzi, Luigi; Shlonsky, Ur


    This article provides the first systematic analysis of early subject omission in a creole language. Basing our analysis on a longitudinal corpus of natural production of Jamaican Creole (JC), we observe that early subject drop is robustly attested for several months. Early subject omission is basically confined to the clause initial position,…

  18. Do Null Subjects (Mis-)Trigger Pro-Drop Grammars? (United States)

    Frazier, Lyn


    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [[superscript -]pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing…

  19. Creating Subjects: The Language of the Stage 6 English Syllabus (United States)

    Anson, Daniel W. J.


    This paper investigates the language of the 2009 NSW Stage 6 English Syllabus. I argue that the language of the syllabus aims to create two distinct subjects: Subject English, that is, what students learn; and the subject position of its students, that is, what students are expected to become. Analysis reveals themes of personal development and…

  20. 1 CFR 6.2 - Analytical subject indexes. (United States)


    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Analytical subject indexes. 6.2 Section 6.2 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER INDEXES AND ANCILLARIES § 6.2 Analytical subject indexes. Analytical subject indexes covering the contents of the...