Atp1a3-deficient heterozygous mice show lower rank in the hierarchy and altered social behavior.

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Sugimoto, H; Ikeda, K; Kawakami, K

2017-10-23

Atp1a3 is the Na-pump alpha3 subunit gene expressed mainly in neurons of the brain. Atp1a3-deficient heterozygous mice (Atp1a3 +/- ) show altered neurotransmission and deficits of motor function after stress loading. To understand the function of Atp1a3 in a social hierarchy, we evaluated social behaviors (social interaction, aggression, social approach and social dominance) of Atp1a3 +/- and compared the rank and hierarchy structure between Atp1a3 +/- and wild-type mice within a housing cage using the round-robin tube test and barbering observations. Formation of a hierarchy decreases social conflict and promote social stability within the group. The hierarchical rank is a reflection of social dominance within a cage, which is heritable and can be regulated by specific genes in mice. Here we report: (1) The degree of social interaction but not aggression was lower in Atp1a3 +/- than wild-type mice, and Atp1a3 +/- approached Atp1a3 +/- mice more frequently than wild type. (2) The frequency of barbering was lower in the Atp1a3 +/- group than in the wild-type group, while no difference was observed in the mixed-genotype housing condition. (3) Hierarchy formation was not different between Atp1a3 +/- and wild type. (4) Atp1a3 +/- showed a lower rank in the mixed-genotype housing condition than that in the wild type, indicating that Atp1a3 regulates social dominance. In sum, Atp1a3 +/- showed unique social behavior characteristics of lower social interaction and preference to approach the same genotype mice and a lower ranking in the hierarchy. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Ghrelin knockout mice show decreased voluntary alcohol consumption and reduced ethanol-induced conditioned place preference.

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Bahi, Amine; Tolle, Virginie; Fehrentz, Jean-Alain; Brunel, Luc; Martinez, Jean; Tomasetto, Catherine-Laure; Karam, Sherif M

2013-05-01

Recent work suggests that stomach-derived hormone ghrelin receptor (GHS-R1A) antagonism may reduce motivational aspects of ethanol intake. In the current study we hypothesized that the endogenous GHS-R1A agonist ghrelin modulates alcohol reward mechanisms. For this purpose ethanol-induced conditioned place preference (CPP), ethanol-induced locomotor stimulation and voluntary ethanol consumption in a two-bottle choice drinking paradigm were examined under conditions where ghrelin and its receptor were blocked, either using ghrelin knockout (KO) mice or the specific ghrelin receptor (GHS-R1A) antagonist "JMV2959". We showed that ghrelin KO mice displayed lower ethanol-induced CPP than their wild-type (WT) littermates. Consistently, when injected during CPP-acquisition, JMV2959 reduced CPP-expression in C57BL/6 mice. In addition, ethanol-induced locomotor stimulation was lower in ghrelin KO mice. Moreover, GHS-R1A blockade, using JMV2959, reduced alcohol-stimulated locomotion only in WT but not in ghrelin KO mice. When alcohol consumption and preference were assessed using the two-bottle choice test, both genetic deletion of ghrelin and pharmacological antagonism of the GHS-R1A (JMV2959) reduced voluntary alcohol consumption and preference. Finally, JMV2959-induced reduction of alcohol intake was only observed in WT but not in ghrelin KO mice. Taken together, these results suggest that ghrelin neurotransmission is necessary for the stimulatory effect of ethanol to occur, whereas lack of ghrelin leads to changes that reduce the voluntary intake as well as conditioned reward by ethanol. Our findings reveal a major, novel role for ghrelin in mediating ethanol behavior, and add to growing evidence that ghrelin is a key mediator of the effects of multiple abused drugs. Copyright © 2013 Elsevier Inc. All rights reserved.

Minimal Effects of Age and Exposure to a Noisy Environment on Hearing in Alpha9 Nicotinic Receptor Knockout Mice

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Amanda M. Lauer

2017-06-01

Full Text Available Studies have suggested a role of weakened medial olivocochlear (OC efferent feedback in accelerated hearing loss and increased susceptibility to noise. The present study investigated the progression of hearing loss with age and exposure to a noisy environment in medial OC-deficient mice. Alpha9 nicotinic acetylcholine receptor knockout (α9KO and wild types were screened for hearing loss using auditory brainstem responses. α9KO mice housed in a quiet environment did not show increased hearing loss compared to wild types in young adulthood and middle age. Challenging the medial OC system by housing in a noisy environment did not increase hearing loss in α9KO mice compared to wild types. ABR wave 1 amplitudes also did not show differences between α9KO mice and wild types. These data suggest that deficient medial OC feedback does not result in early onset of hearing loss.

Mice doubly-deficient in lysosomal hexosaminidase A and neuraminidase 4 show epileptic crises and rapid neuronal loss.

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Volkan Seyrantepe

2010-09-01

Full Text Available Tay-Sachs disease is a severe lysosomal disorder caused by mutations in the HexA gene coding for the α-subunit of lysosomal β-hexosaminidase A, which converts G(M2 to G(M3 ganglioside. Hexa(-/- mice, depleted of β-hexosaminidase A, remain asymptomatic to 1 year of age, because they catabolise G(M2 ganglioside via a lysosomal sialidase into glycolipid G(A2, which is further processed by β-hexosaminidase B to lactosyl-ceramide, thereby bypassing the β-hexosaminidase A defect. Since this bypass is not effective in humans, infantile Tay-Sachs disease is fatal in the first years of life. Previously, we identified a novel ganglioside metabolizing sialidase, Neu4, abundantly expressed in mouse brain neurons. Now we demonstrate that mice with targeted disruption of both Neu4 and Hexa genes (Neu4(-/-;Hexa(-/- show epileptic seizures with 40% penetrance correlating with polyspike discharges on the cortical electrodes of the electroencephalogram. Single knockout Hexa(-/- or Neu4(-/- siblings do not show such symptoms. Further, double-knockout but not single-knockout mice have multiple degenerating neurons in the cortex and hippocampus and multiple layers of cortical neurons accumulating G(M2 ganglioside. Together, our data suggest that the Neu4 block exacerbates the disease in Hexa(-/- mice, indicating that Neu4 is a modifier gene in the mouse model of Tay-Sachs disease, reducing the disease severity through the metabolic bypass. However, while disease severity in the double mutant is increased, it is not profound suggesting that Neu4 is not the only sialidase contributing to the metabolic bypass in Hexa(-/- mice.

Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation.

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Imai, Rika; Asai, Kanae; Hanai, Jun-ichi; Takenaka, Masaru

2015-07-01

Glia Maturation Factor-β (GMF), a brain specific protein, is induced by proteinuria in renal tubules. Ectopic GMF overexpression causes apoptosisin vitro via cellular vulnerability to oxidative stress. In order to examine the roles of GMF in non-brain tissue, we constructed transgenic mice overexpressing GMF (GMF-TG). The GMF-TG mice exhibited appearance phenotypes associated with premature aging. The GMF-TG mice also demonstrated short lifespans and reduced hair regrowth, suggesting an accelerated aging process. The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies. Importantly, we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice. The GMF-TG mice showed accelerated aging in the kidney, compared with wild-type mice, showing increased TGF-β1, CTGF gene and serum creatinine. The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks. In conclusion, we propose that GMF-TG mice might be a novel mouse model of accelerated aging, due to the abnormal lamin A.

Hes1-deficient mice show precocious differentiation of Paneth cells in the small intestine

International Nuclear Information System (INIS)

Suzuki, Katsumasa; Fukui, Hirokazu; Kayahara, Takahisa; Sawada, Mitsutaka; Seno, Hiroshi; Hiai, Hiroshi; Kageyama, Ryoichiro; Okano, Hideyuki; Chiba, Tsutomu

2005-01-01

We have previously shown that Hes1 is expressed both in putative epithelial stem cells just above Paneth cells and in the crypt base columnar cells between Paneth cells, while Hes1 is completely absent in Paneth cells. This study was undertaken to clarify the role of Hes1 in Paneth cell differentiation, using Hes1-knockout (KO) newborn (P0) mice. Electron microscopy revealed premature appearance of distinct cells containing cytoplasmic granules in the intervillous region in Hes1-KO P0 mice, whereas those cells were absent in wild-type (WT) P0 mice. In Hes1-KO P0 mice, the gene expressions of cryptdins, exclusively present in Paneth cells, were all enhanced compared with WT P0 mice. Immunohistochemistry demonstrated increased number of both lysozyme-positive and cryptdin-4-positive cells in the small intestinal epithelium of Hes1-KO P0 mice as compared to WT P0 mice. Thus, Hes1 appears to have an inhibitory role in Paneth cell differentiation in the small intestine

Zonulin transgenic mice show altered gut permeability and increased morbidity/mortality in the DSS colitis model.

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Sturgeon, Craig; Lan, Jinggang; Fasano, Alessio

2017-06-01

Increased small intestinal permeability (IP) has been proposed to be an integral element, along with genetic makeup and environmental triggers, in the pathogenies of chronic inflammatory diseases (CIDs). We identified zonulin as a master regular of intercellular tight junctions linked to the development of several CIDs. We aim to study the role of zonulin-mediated IP in the pathogenesis of CIDs. Zonulin transgenic Hp2 mice (Ztm) were subjected to dextran sodium sulfate (DSS) treatment for 7 days, followed by 4-7 days' recovery and compared to C57Bl/6 (wild-type (WT)) mice. IP was measured in vivo and ex vivo, and weight, histology, and survival were monitored. To mechanistically link zonulin-dependent impairment of small intestinal barrier function with clinical outcome, Ztm were treated with the zonulin inhibitor AT1001 added to drinking water in addition to DSS. We observed increased morbidity (more pronounced weight loss and colitis) and mortality (40-70% compared with 0% in WT) at 11 days post-DSS treatment in Ztm compared with WT mice. Both in vivo and ex vivo measurements showed an increased IP at baseline in Ztm compared to WT mice, which was exacerbated by DSS treatment and was associated with upregulation of zonulin gene expression (fourfold in the duodenum, sixfold in the jejunum). Treatment with AT1001 prevented the DSS-induced increased IP both in vivo and ex vivo without changing zonulin gene expression and completely reverted morbidity and mortality in Ztm. Our data show that zonulin-dependent small intestinal barrier impairment is an early step leading to the break of tolerance with subsequent development of CIDs. © 2017 New York Academy of Sciences.

Female Nur77-deficient mice show increased susceptibility to diet-induced obesity.

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Sonia Perez-Sieira

Full Text Available Adipose tissue is essential in the regulation of body weight. The key process in fat catabolism and the provision of energy substrate during times of nutrient deprivation or enhanced energy demand is the hydrolysis of triglycerides and the release of fatty acids and glycerol. Nur77 is a member of the NR4A subfamily of nuclear receptors that plays an important metabolic role, modulating hepatic glucose metabolism and lipolysis in muscle. However, its endogenous role on white adipose tissue, as well as the gender dependency of these mechanisms, remains largely unknown. Male and female wild type and Nur77 deficient mice were fed with a high fat diet (45% calories from fat for 4 months. Mice were analyzed in vivo with the indirect calorimetry system, and tissues were analyzed by real-time PCR and Western blot analysis. Female, but not male Nur77 deficient mice, gained more weight and fat mass when compared to wild type mice fed with high fat diet, which can be explained by decreased energy expenditure. The lack of Nur77 also led to a decreased pHSL/HSL ratio in white adipose tissue and increased expression of CIDEA in brown adipose tissue of female Nur77 deficient mice. Overall, these findings suggest that Nur77 is an important physiological modulator of lipid metabolism in adipose tissue and that there are gender differences in the sensitivity to deletion of the Nur77 signaling. The decreased energy expenditure and the actions of Nur77 on liver, muscle, brown and white adipose tissue contribute to the increased susceptibility to diet-induced obesity in females lacking Nur77.

Mu-opioid receptor knockout mice show diminished food-anticipatory activity

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Kas, Martien J H; van den Bos, Ruud; Baars, Annemarie M; Lubbers, Marianne; Lesscher, Heidi M B; Hillebrand, Jacquelien J G; Schuller, Alwin G; Pintar, John E; Spruijt, Berry M

We have previously suggested that during or prior to activation of anticipatory behaviour to a coming reward, mu-opioid receptors are activated. To test this hypothesis schedule induced food-anticipatory activity in mu-opioid receptor knockout mice was measured using running wheels. We hypothesized

Connexin30-deficient mice show increased emotionality and decreased rearing activity in the open-field along with neurochemical changes.

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Dere, E; De Souza-Silva, M A; Frisch, C; Teubner, B; Söhl, G; Willecke, K; Huston, J P

2003-08-01

Gap-junction channels in the brain, formed by connexin (Cx) proteins with a distinct regional/cell-type distribution, allow intercellular electrical and metabolic communication. In astrocytes, mainly the connexins 43, 26 and 30 are expressed. In addition, connexin30 is expressed in ependymal and leptomeningeal cells, as well as in skin and cochlea. The functional implications of the astrocytic gap-junctional network are not well understood and evidence regarding their behavioural relevance is lacking. Thus, we have tested groups of Cx30-/-, Cx30+/-, and Cx30+/+ mice in the open-field, an object exploration task, in the graded anxiety test and on the rotarod. The Cx30-/- mice showed reduced exploratory activity in terms of rearings but not locomotion in the open-field and object exploration task. Furthermore, Cx30-/- mice exhibited anxiogenic behaviour as shown by higher open-field centre avoidance and corner preference. Graded anxiety test and rotarod performance was similar across groups. The Cx30-/- mice had elevated choline levels in the ventral striatum, possibly related to their aberrant behavioural phenotypes. The Cx30+/- mice had lower dopamine and metabolite levels in the amygdala and ventral striatum and lower hippocampal 5-hydroxyindole acid (5-HIAA) concentrations relative to Cx30+/+ mice. Furthermore, the Cx30+/- mice had lower acetylcholine concentrations in the ventral striatum and higher choline levels in the neostriatum, relative to Cx30+/+ mice. Our data suggest that the elimination of connexin30 can alter the reactivity to novel environments, pointing to the importance of gap-junctional signalling in behavioural processes.

Acetaminophen-induced liver damage in mice is associated with gender-specific adduction of peroxiredoxin-6

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Isaac Mohar

2014-01-01

Full Text Available The mechanism by which acetaminophen (APAP causes liver damage evokes many aspects drug metabolism, oxidative chemistry, and genetic-predisposition. In this study, we leverage the relative resistance of female C57BL/6 mice to APAP-induced liver damage (AILD compared to male C57BL/6 mice in order to identify the cause(s of sensitivity. Furthermore, we use mice that are either heterozygous (HZ or null (KO for glutamate cysteine ligase modifier subunit (Gclm, in order to titrate the toxicity relative to wild-type (WT mice. Gclm is important for efficient de novo synthesis of glutathione (GSH. APAP (300 mg/kg, ip or saline was administered and mice were collected at 0, 0.5, 1, 2, 6, 12, and 24 h. Male mice showed marked elevation in serum alanine aminotransferase by 6 h. In contrast, female WT and HZ mice showed minimal toxicity at all time points. Female KO mice, however, showed AILD comparable to male mice. Genotype-matched male and female mice showed comparable APAP–protein adducts, with Gclm KO mice sustaining significantly greater adducts. ATP was depleted in mice showing toxicity, suggesting impaired mitochondria function. Indeed, peroxiredoxin-6, a GSH-dependent peroxiredoxin, was preferentially adducted by APAP in mitochondria of male mice but rarely adducted in female mice. These results support parallel mechanisms of toxicity where APAP adduction of peroxiredoxin-6 and sustained GSH depletion results in the collapse of mitochondria function and hepatocyte death. We conclude that adduction of peroxiredoxin-6 sensitizes male C57BL/6 mice to toxicity by acetaminophen.

Histidine decarboxylase knockout mice, a genetic model of Tourette syndrome, show repetitive grooming after induced fear.

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Xu, Meiyu; Li, Lina; Ohtsu, Hiroshi; Pittenger, Christopher

2015-05-19

Tics, such as are seen in Tourette syndrome (TS), are common and can cause profound morbidity, but they are poorly understood. Tics are potentiated by psychostimulants, stress, and sleep deprivation. Mutations in the gene histidine decarboxylase (Hdc) have been implicated as a rare genetic cause of TS, and Hdc knockout mice have been validated as a genetic model that recapitulates phenomenological and pathophysiological aspects of the disorder. Tic-like stereotypies in this model have not been observed at baseline but emerge after acute challenge with the psychostimulant d-amphetamine. We tested the ability of an acute stressor to stimulate stereotypies in this model, using tone fear conditioning. Hdc knockout mice acquired conditioned fear normally, as manifested by freezing during the presentation of a tone 48h after it had been paired with a shock. During the 30min following tone presentation, knockout mice showed increased grooming. Heterozygotes exhibited normal freezing and intermediate grooming. These data validate a new paradigm for the examination of tic-like stereotypies in animals without pharmacological challenge and enhance the face validity of the Hdc knockout mouse as a pathophysiologically grounded model of tic disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A study on the mechanism by which MDMA protects against dopaminergic dysfunction after minimal traumatic brain injury (mTBI) in mice.

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Edut, S; Rubovitch, V; Rehavi, M; Schreiber, S; Pick, C G

2014-12-01

Driving under methylenedioxymethamphetamine (MDMA) influence increases the risk of being involved in a car accident, which in turn can lead to traumatic brain injury. The behavioral deficits after traumatic brain injury (TBI) are closely connected to dopamine pathway dysregulation. We have previously demonstrated in mice that low MDMA doses prior to mTBI can lead to better performances in cognitive tests. The purpose of this study was to assess in mice the changes in the dopamine system that occurs after both MDMA and minimal traumatic brain injury (mTBI). Experimental mTBI was induced using a concussive head trauma device. One hour before injury, animals were subjected to MDMA. Administration of MDMA before injury normalized the alterations in tyrosine hydroxylase (TH) levels that were observed in mTBI mice. This normalization was also able to lower the elevated dopamine receptor type 2 (D2) levels observed after mTBI. Brain-derived neurotrophic factor (BDNF) levels did not change following injury alone, but in mice subjected to MDMA and mTBI, significant elevations were observed. In the behavioral tests, haloperidol reversed the neuroprotection seen when MDMA was administered prior to injury. Altered catecholamine synthesis and high D2 receptor levels contribute to cognitive dysfunction, and strategies to normalize TH signaling and D2 levels may provide relief for the deficits observed after injury. Pretreatment with MDMA kept TH and D2 receptor at normal levels, allowing regular dopamine system activity. While the beneficial effect we observe was due to a dangerous recreational drug, understanding the alterations in dopamine and the mechanism of dysfunction at a cellular level can lead to legal therapies and potential candidates for clinical use.

Ilexgenin A, a novel pentacyclic triterpenoid extracted from Aquifoliaceae shows reduction of LPS-induced peritonitis in mice.

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Sun, Weidong; Liu, Chang; Zhang, Yaqi; Qiu, Xia; Zhang, Li; Zhao, Hongxia; Rong, Yi; Sun, Yun

2017-02-15

Ilexgenin A (IA) is a novel pentacyclic triterpenoid, which extracted from leaves of Ilex hainanensis Merr. In the present study, we aim to explore anti-inflammatory activity of IA on LPS-induced peritonitis and its underlying molecular mechanism. The results determined that IA was capable of suppressing peritonitis in mice induced by intraperitoneal (i.p.) injection of lipopolysaccaride (LPS). Furthermore, the results showed that IA dramatically inhibited levels of inflammatory cells infiltration in peritoneal cavity and serum in LPS-induced mice peritonitis model. Besides, IA could dramatically inhibit levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) in peritoneal cavity in LPS-induced mice peritonitis model. In vitro study, the results showed that IA inhibited production of IL-1β, IL-6 and TNF-α at transcriptional and translational levels in RAW 264.7 cells induced by LPS. Furthermore, IA could suppress the LPS-induced activation of Akt and downstream degradation and phosphorylation of kappa B-α (IκB-α). Moreover, IA could significantly inhibit ERK 1/2 phosphorylation in RAW 264.7 cells induced by LPS. These results were concurrent with molecular docking which revealed ERK1/2 inhibition. These results demonstrated that IA might as an anti-inflammatory agent candidate for inflammatory disease therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Adolescent C57BL/6J mice show elevated alcohol intake, but reduced taste aversion, as compared to adult mice: a potential behavioral mechanism for binge drinking.

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Holstein, Sarah E; Spanos, Marina; Hodge, Clyde W

2011-10-01

Binge alcohol drinking during adolescence is a serious health problem that may increase future risk of an alcohol use disorder. Although there are several different procedures by which to preclinically model binge-like alcohol intake, limited-access procedures offer the advantage of achieving high voluntary alcohol intake and pharmacologically relevant blood alcohol concentrations (BACs). Therefore, in the current study, developmental differences in binge-like alcohol drinking using a limited-access cycling procedure were examined. In addition, as alcohol drinking has been negatively correlated with sensitivity to the aversive properties of alcohol, we examined developmental differences in sensitivity to an alcohol-induced conditioned taste aversion (CTA). Binge-like alcohol consumption was investigated in adolescent (4 weeks) and adult (10 weeks) male C57BL/6J mice for 2 to 4 h/d for 16 days. Developmental differences in sensitivity to an alcohol-induced CTA were examined in adolescent and adult mice, with saline or alcohol (3 or 4 g/kg) repeatedly paired with the intake of a novel tastant (NaCl). Adolescent mice showed a significant increase in alcohol intake as compared to adults, with adolescents achieving higher BACs and increasing alcohol consumption over successive cycles of the binge procedure. Conversely, adolescent mice exhibited a dose-dependent reduction in sensitivity to the aversive properties of alcohol, as compared to adult mice, with adolescent mice failing to develop a CTA to 3 g/kg alcohol. Finally, extinction of an alcohol CTA was observed following conditioning with a higher dose of alcohol in adolescent, versus adult, mice. These results indicate that adolescent mice consume more alcohol, per kilogram body weight, than adults in a binge-like model of alcohol drinking and demonstrate a blunted sensitivity to the conditioned aversive effects of alcohol. Overall, this supports a behavioral framework by which heightened binge alcohol intake during

Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory

DEFF Research Database (Denmark)

Brakebusch, Cord; Seidenbecher, Constanze I; Asztely, Fredrik

2002-01-01

to be less prominent in mutant than in wild-type mice. Brevican-deficient mice showed significant deficits in the maintenance of hippocampal long-term potentiation (LTP). However, no obvious impairment of excitatory and inhibitory synaptic transmission was found, suggesting a complex cause for the LTP defect....... Detailed behavioral analysis revealed no statistically significant deficits in learning and memory. These data indicate that brevican is not crucial for brain development but has restricted structural and functional roles....

Hearts of dystonia musculorum mice display normal morphological and histological features but show signs of cardiac stress.

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Justin G Boyer

2010-03-01

Full Text Available Dystonin is a giant cytoskeletal protein belonging to the plakin protein family and is believed to crosslink the major filament systems in contractile cells. Previous work has demonstrated skeletal muscle defects in dystonin-deficient dystonia musculorum (dt mice. In this study, we show that the dystonin muscle isoform is localized at the Z-disc, the H zone, the sarcolemma and intercalated discs in cardiac tissue. Based on this localization pattern, we tested whether dystonin-deficiency leads to structural defects in cardiac muscle. Desmin intermediate filament, microfilament, and microtubule subcellular organization appeared normal in dt hearts. Nevertheless, increased transcript levels of atrial natriuretic factor (ANF, 66% beta-myosin heavy chain (beta-MHC, 95% and decreased levels of sarcoplasmic reticulum calcium pump isoform 2A (SERCA2a, 26%, all signs of cardiac muscle stress, were noted in dt hearts. Hearts from two-week old dt mice were assessed for the presence of morphological and histological alterations. Heart to body weight ratios as well as left ventricular wall thickness and left chamber volume measurements were similar between dt and wild-type control mice. Hearts from dt mice also displayed no signs of fibrosis or calcification. Taken together, our data provide new insights into the intricate structure of the sarcomere by situating dystonin in cardiac muscle fibers and suggest that dystonin does not significantly influence the structural organization of cardiac muscle fibers during early postnatal development.

Inner ear dysfunction in caspase-3 deficient mice

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Woo Minna

2011-10-01

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

Experimental Chagas disease in Balb/c mice previously vaccinated with T. rangeli. II. The innate immune response shows immunological memory: reality or fiction?

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Basso, B; Marini, V

2015-03-01

Trypanosoma cruzi is a real challenge to the host's immune system, because it requires strong humoral and cellular immune response to remove circulating trypomastigote forms, and to prevent the replication of amastigote forms in tissues, involving many regulator and effector components. This protozoan is responsible for Chagas disease, a major public health problem in Latinamerica. We have developed a model of vaccination with Trypanosoma rangeli, a parasite closely related to T. cruzi, but nonpathogenic to humans, which reduces the infectiousness in three different species of animals, mice, dogs and guinea pigs, against challenge with T. cruzi. In a previous work, we demonstrated that mice vaccinated with T. rangeli showed important soluble mediators that stimulate phagocytic activity versus only infected groups. The aim of this work was to study the innate immune response in mice vaccinated or not with T. rangeli. Different population cells and some soluble mediators (cytokines) in peritoneal fluid and plasma in mice vaccinated-infected and only infected with T. cruzi were studied. In the first hours of challenge vaccinated mice showed an increase of macrophages, NK, granulocytes, and regulation of IL6, IFNγ, TNFα and IL10, with an increase of IL12, with respect to only infected mice. Furthermore an increase was observed of Li T, Li B responsible for adaptative response. Finally the findings showed that the innate immune response plays an important role in vaccinated mice for the early elimination of the parasites, complementary with the adaptative immune response, suggesting that vaccination with T. rangeli modulates the innate response, which develops some kind of immunological memory, recognizing shared antigens with T. cruzi. These results could contribute to the knowledge of new mechanisms which would have an important role in the immune response to Chagas disease. Copyright © 2014 Elsevier GmbH. All rights reserved.

Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model

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O'Shaughnessy Patrick T

2011-01-01

Full Text Available Abstract Background There is increasing interest in the environmental and health consequences of silver nanoparticles as the use of this material becomes widespread. Although human exposure to nanosilver is increasing, only a few studies address possible toxic effect of inhaled nanosilver. The objective of this study was to determine whether very small commercially available nanosilver induces pulmonary toxicity in mice following inhalation exposure. Results In this study, mice were exposed sub-acutely by inhalation to well-characterized nanosilver (3.3 mg/m3, 4 hours/day, 10 days, 5 ± 2 nm primary size. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage fluid. Lungs were evaluated for histopathologic changes and the presence of silver. In contrast to published in vitro studies, minimal inflammatory response or toxicity was found following exposure to nanosilver in our in vivo study. The median retained dose of nanosilver in the lungs measured by inductively coupled plasma - optical emission spectroscopy (ICP-OES was 31 μg/g lung (dry weight immediately after the final exposure, 10 μg/g following exposure and a 3-wk rest period and zero in sham-exposed controls. Dissolution studies showed that nanosilver did not dissolve in solutions mimicking the intracellular or extracellular milieu. Conclusions Mice exposed to nanosilver showed minimal pulmonary inflammation or cytotoxicity following sub-acute exposures. However, longer term exposures with higher lung burdens of nanosilver are needed to ensure that there are no chronic effects and to evaluate possible translocation to other organs.

Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice

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Mifuji Lira, Roque M.; Limón Flores, Alberto Yairh; Salinas Carmona, Mario César

2016-01-01

Pulmonary nocardiosis is a granulomatous disease with high mortality that affects both immunosuppressed and immunocompetent patients. The mechanisms leading to the establishment and progression of the infection are currently unknown. An animal model to study these mechanisms is sorely needed. We report the first in vivo model of granulomatous pulmonary nocardiosis that closely resembles human pathology. BALB/c mice infected intranasally with two different doses of GFP-expressing Nocardia brasiliensis ATCC700358 (NbGFP), develop weight loss and pulmonary granulomas. Mice infected with 109 CFUs progressed towards death within a week while mice infected with 108 CFUs died after five to six months. Histological examination of the lungs revealed that both the higher and lower doses of NbGFP induced granulomas with NbGFP clearly identifiable at the center of the lesions. Mice exposed to 108 CFUs and subsequently to 109 CFUs were not protected against disease severity but had less granulomas suggesting some degree of protection. Attempts to identify a cellular target for the infection were unsuccessful but we found that bacterial microcolonies in the suspension used to infect mice were responsible for the establishment of the disease. Small microcolonies of NbGFP, incompatible with nocardial doubling times starting from unicellular organisms, were identified in the lung as early as six hours after infection. Mice infected with highly purified unicellular preparations of NbGFP did not develop granulomas despite showing weight loss. Finally, intranasal delivery of nocardial microcolonies was enough for mice to develop granulomas with minimal weight loss. Taken together these results show that Nocardia brasiliensis microcolonies are both necessary and sufficient for the development of granulomatous pulmonary nocardiosis in mice. PMID:27303806

Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice.

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Roque M Mifuji Lira

Full Text Available Pulmonary nocardiosis is a granulomatous disease with high mortality that affects both immunosuppressed and immunocompetent patients. The mechanisms leading to the establishment and progression of the infection are currently unknown. An animal model to study these mechanisms is sorely needed. We report the first in vivo model of granulomatous pulmonary nocardiosis that closely resembles human pathology. BALB/c mice infected intranasally with two different doses of GFP-expressing Nocardia brasiliensis ATCC700358 (NbGFP, develop weight loss and pulmonary granulomas. Mice infected with 109 CFUs progressed towards death within a week while mice infected with 108 CFUs died after five to six months. Histological examination of the lungs revealed that both the higher and lower doses of NbGFP induced granulomas with NbGFP clearly identifiable at the center of the lesions. Mice exposed to 108 CFUs and subsequently to 109 CFUs were not protected against disease severity but had less granulomas suggesting some degree of protection. Attempts to identify a cellular target for the infection were unsuccessful but we found that bacterial microcolonies in the suspension used to infect mice were responsible for the establishment of the disease. Small microcolonies of NbGFP, incompatible with nocardial doubling times starting from unicellular organisms, were identified in the lung as early as six hours after infection. Mice infected with highly purified unicellular preparations of NbGFP did not develop granulomas despite showing weight loss. Finally, intranasal delivery of nocardial microcolonies was enough for mice to develop granulomas with minimal weight loss. Taken together these results show that Nocardia brasiliensis microcolonies are both necessary and sufficient for the development of granulomatous pulmonary nocardiosis in mice.

Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in Mice

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Qingtao Liu

2016-11-01

Full Text Available H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06 virus was highly pathogenic for mice, with a 50% mouse lethal dose of 102.83 50% egg infectious dose, whereas the A/duck/Nanjing/01/1999 (NJ01 virus was low pathogenic for mice, with a 50% mouse lethal dose of >106.81 50% egg infectious dose. Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only twelve different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future.

Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

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Chen, Vicki M; Shelke, Rajani; Nyström, Alexander; Laver, Nora; Sampson, James F; Zhiyi, Cao; Bhat, Najma; Panjwani, Noorjahan

2018-06-16

Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients. Standard treatments are supportive and there is no cure. The immune-histologic and morphologic changes in the corneas of the mouse model for this disease have not been described in the literature. Our purpose is to characterize the eyes of these mice to determine if this is an appropriate model for study of human therapeutics. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to assess the relative collagen VII protein levels and its location within the cornea. Additional IHC for inflammatory and fibrotic biomarkers alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), proteinase 3, tenascin C and collagen III were performed. Clinical photographs documenting opacification of the corneas of animals of differing ages were assessed and scored independently by 2 examiners. Histology was then used to investigate morphologic changes. IHC and WB confirmed that these mice are deficient in collagen VII production at the level of the basement membrane when compared with wild-types. IHC showed anomalous deposition of collagen III throughout the stroma. Of the 5 biomarkers tested, TGF-β showed the strongest and most consistently staining. Photographs documented corneal opacities only in mice older than 10 weeks, opacities were not seen in younger animals. Histology showed multiple abnormalities, including epithelial hyperplasia, ulceration, fibrosis, edema, dysplasia, neovascularization and bullae formation. The collagen VII hypomorphic mouse shows reduced collagen VII production at the level of the corneal basement membrane. Corneal changes are similar to pathology seen in humans with this disease. The presence of anomalous stromal collagen III and TGF-β appear to be

Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows sex-divergent effects on the tissue uptake and distribution pattern of sunitinib in mice.

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Tan, Siok Yean; Wong, Mei Mei; Tiew, Angela Lu Wun; Choo, Yai Wen; Lim, Suat Hun; Ooi, Ing Hong; Modamio, Pilar; Fernández, Cecilia; Mariño, Eduardo L; Segarra, Ignacio

2016-10-01

Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol, mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features. Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed. Ibuprofen halved sunitinib plasma concentration in female mice (p Diclofenac and paracetamol female mice showed 45 and 25 % higher plasma concentrations than male mice which were 27 % lower in mefenamic acid female mice. Paracetamol increased 2.2 (p diclofenac, paracetamol, mefenamic acid and ibuprofen (p diclofenac group in male mice (liver, brain) and female mice (liver, kidney). These results portray gender-based sunitinib pharmacokinetic differences and NSAIDs selective effects on male or female mice, with potential clinical translatability.

Stevia and Saccharin Preferences in Rats and Mice

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Bahrani, Mahsa; Zukerman, Steven; Ackroff, Karen

2010-01-01

Use of natural noncaloric sweeteners in commercial foods and beverages has expanded recently to include compounds from the plant Stevia rebaudiana. Little is known about the responses of rodents, the animal models for many studies of taste systems and food intake, to stevia sweeteners. In the present experiments, preferences of female Sprague–Dawley rats and C57BL/6J mice for different stevia products were compared with those for the artificial sweetener saccharin. The stevia component rebaudioside A has the most sweetness and least off-tastes to human raters. In ascending concentration tests (48-h sweetener vs. water), rats and mice preferred a high-rebaudioside, low-stevioside extract as strongly as saccharin, but the extract stimulated less overdrinking and was much less preferred to saccharin in direct choice tests. Relative to the extract, mice drank more pure rebaudioside A and showed stronger preferences but still less than those for saccharin. Mice also preferred a commercial mixture of rebaudioside A and erythritol (Truvia). Similar tests of sweet receptor T1R3 knockout mice and brief-access licking tests with normal mice suggested that the preferences were based on sweet taste rather than post-oral effects. The preference response of rodents to stevia sweeteners is notable in view of their minimal response to some other noncaloric sweeteners (aspartame and cyclamate). PMID:20413452

A Valepotriate Fraction of Valeriana glechomifolia Shows Sedative and Anxiolytic Properties and Impairs Recognition But Not Aversive Memory in Mice

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Natasha Maurmann

2011-01-01

Full Text Available Plants of the genus Valeriana (Valerianaceae are used in traditional medicine as a mild sedative, antispasmodic and tranquilizer in many countries. This study was undertaken to explore the neurobehavioral effects of systemic administration of a valepotriate extract fraction of known quantitative composition of Valeriana glechomifolia (endemic of southern Brazil in mice. Adult animals were treated with a single intraperitoneal injection of valepotriate fraction (VF in the concentrations of 1, 3 or 10 mg kg-1, or with vehicle in the pre-training period before each behavioral test. During the exploration of an open field, mice treated with 10 mg kg-1 of VF showed reduced locomotion and exploratory behavior. Although overall habituation sessions for locomotion and exploratory behavior among vehicle control and doses of VF were not affected, comparison between open-field and habituation sessions within each treatment showed that VF administration at 1 and 10 mg kg-1 impaired habituation. In the elevated plus-maze test, mice treated with VF (10 mg kg-1 showed a significant increase in the percentage of time spent in the open arms without significant effects in the number of total arm entries. VF at 3 mg kg-1 produced an impairment of novel-object recognition memory. In contrast, VF did not affect fear-related memory assessed in an inhibitory avoidance task. The results indicate that VF can have sedative effects and affect behavioral parameters related to recognition memory.

A novel minimal invasive mouse model of extracorporeal circulation.

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Luo, Shuhua; Tang, Menglin; Du, Lei; Gong, Lina; Xu, Jin; Chen, Youwen; Wang, Yabo; Lin, Ke; An, Qi

2015-01-01

Extracorporeal circulation (ECC) is necessary for conventional cardiac surgery and life support, but it often triggers systemic inflammation that can significantly damage tissue. Studies of ECC have been limited to large animals because of the complexity of the surgical procedures involved, which has hampered detailed understanding of ECC-induced injury. Here we describe a minimally invasive mouse model of ECC that may allow more extensive mechanistic studies. The right carotid artery and external jugular vein of anesthetized adult male C57BL/6 mice were cannulated to allow blood flow through a 1/32-inch external tube. All animals (n = 20) survived 30 min ECC and subsequent 60 min observation. Blood analysis after ECC showed significant increases in levels of tumor necrosis factor α, interleukin-6, and neutrophil elastase in plasma, lung, and renal tissues, as well as increases in plasma creatinine and cystatin C and decreases in the oxygenation index. Histopathology showed that ECC induced the expected lung inflammation, which included alveolar congestion, hemorrhage, neutrophil infiltration, and alveolar wall thickening; in renal tissue, ECC induced intracytoplasmic vacuolization, acute tubular necrosis, and epithelial swelling. Our results suggest that this novel, minimally invasive mouse model can recapitulate many of the clinical features of ECC-induced systemic inflammatory response and organ injury.

A Novel Minimal Invasive Mouse Model of Extracorporeal Circulation

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Shuhua Luo

2015-01-01

Full Text Available Extracorporeal circulation (ECC is necessary for conventional cardiac surgery and life support, but it often triggers systemic inflammation that can significantly damage tissue. Studies of ECC have been limited to large animals because of the complexity of the surgical procedures involved, which has hampered detailed understanding of ECC-induced injury. Here we describe a minimally invasive mouse model of ECC that may allow more extensive mechanistic studies. The right carotid artery and external jugular vein of anesthetized adult male C57BL/6 mice were cannulated to allow blood flow through a 1/32-inch external tube. All animals (n=20 survived 30 min ECC and subsequent 60 min observation. Blood analysis after ECC showed significant increases in levels of tumor necrosis factor α, interleukin-6, and neutrophil elastase in plasma, lung, and renal tissues, as well as increases in plasma creatinine and cystatin C and decreases in the oxygenation index. Histopathology showed that ECC induced the expected lung inflammation, which included alveolar congestion, hemorrhage, neutrophil infiltration, and alveolar wall thickening; in renal tissue, ECC induced intracytoplasmic vacuolization, acute tubular necrosis, and epithelial swelling. Our results suggest that this novel, minimally invasive mouse model can recapitulate many of the clinical features of ECC-induced systemic inflammatory response and organ injury.

Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1 show modestly enhanced alcohol preference and consumption.

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David J Marcus

Full Text Available We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6% but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg, morphine (10 mg/kg, and cocaine (10 mg/kg, demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model.

AβPP/PS1 Transgenic Mice Show Sex Differences in the Cerebellum Associated with Aging.

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Ordoñez-Gutierrez, Lara; Fernandez-Perez, Ivan; Herrera, Jose Luis; Anton, Marta; Benito-Cuesta, Irene; Wandosell, Francisco

2016-09-06

Cerebellar pathology has been related to presenilin 1 mutations in certain pedigrees of familial Alzheimer's disease. However, cerebellum tissue has not been intensively analyzed in transgenic models of mutant presenilins. Furthermore, the effect of the sex of the mice was not systematically analyzed, despite the fact that important gender differences in the evolution of the disease in the human population have been described. We analyzed whether the progression of amyloidosis in a double transgenic mouse, AβPP/PS1, is susceptible to aging and differentially affects males and females. The accumulation of amyloid in the cerebellum differentially affects males and females of the AβPP/PS1 transgenic line, which was found to be ten-fold higher in 15-month-old females. Amyloid-β accumulation was more evident in the molecular layer of the cerebellum, but glia reaction was only observed in the granular layer of the older mice. The sex divergence was also observed in other neuronal, survival, and autophagic markers. The cerebellum plays an important role in the evolution of the pathology in this transgenic mouse model. Sex differences could be crucial for a complete understanding of this disease. We propose that the human population could be studied in this way. Sex-specific treatment strategies in human populations could show a differential response to the therapeutic approach.

Cerebellar nuclei neurons show only small excitatory responses to optogenetic olivary stimulation in transgenic mice: in vivo and in vitro studies

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Huo eLu

2016-03-01

Full Text Available To study the olivary input to the cerebellar nuclei (CN we used optogenetic stimulation in transgenic mice expressing channelrhodopsin-2 (ChR2 in olivary neurons. We obtained in vivo extracellular Purkinje cell (PC and CN recordings in anesthetized mice while stimulating the contralateral inferior olive (IO with a blue laser (single pulse, 10 - 50 ms duration. Peri-stimulus histograms were constructed to show the spike rate changes after optical stimulation. Among 29 CN neurons recorded, 15 showed a decrease in spike rate of variable strength and duration, and only 1 showed a transient spiking response. These results suggest that direct olivary input to CN neurons is usually overridden by stronger Purkinje cell inhibition triggered by climbing fiber responses. To further investigate the direct input from the climbing fiber collaterals we also conducted whole cell recordings in brain slices, where we used local stimulation with blue light. Due to the expression of ChR2 in Purkinje cell axons as well as the IO in our transgenic line, strong inhibitory responses could be readily triggered with optical stimulation (13 of 15 neurons. After blocking this inhibition with GABAzine, only in 5 of 13 CN neurons weak excitatory responses were revealed. Therefore our in vitro results support the in vivo findings that the excitatory input to CN neurons from climbing fiber collaterals in adult mice is masked by the inhibition under normal conditions.

Phosphodiesterase-1b (Pde1b) knockout mice are resistant to forced swim and tail suspension induced immobility and show upregulation of Pde10a.

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Hufgard, Jillian R; Williams, Michael T; Skelton, Matthew R; Grubisha, Olivera; Ferreira, Filipa M; Sanger, Helen; Wright, Mary E; Reed-Kessler, Tracy M; Rasmussen, Kurt; Duman, Ronald S; Vorhees, Charles V

2017-06-01

Major depressive disorder is a leading cause of suicide and disability. Despite this, current antidepressants provide insufficient efficacy in more than 60% of patients. Most current antidepressants are presynaptic reuptake inhibitors; postsynaptic signal regulation has not received as much attention as potential treatment targets. We examined the effects of disruption of the postsynaptic cyclic nucleotide hydrolyzing enzyme, phosphodiesterase (PDE) 1b, on depressive-like behavior and the effects on PDE1B protein in wild-type (WT) mice following stress. Littermate knockout (KO) and WT mice were tested in locomotor activity, tail suspension (TST), and forced swim tests (FST). FST was also used to compare the effects of two antidepressants, fluoxetine and bupropion, in KO versus WT mice. Messenger RNA (mRNA) expression changes were also determined. WT mice underwent acute or chronic stress and markers of stress and PDE1B expression were examined. Pde1b KO mice exhibited decreased TST and FST immobility. When treated with antidepressants, both WT and KO mice showed decreased FST immobility and the effect was additive in KO mice. Mice lacking Pde1b had increased striatal Pde10a mRNA expression. In WT mice, acute and chronic stress upregulated PDE1B expression while PDE10A expression was downregulated after chronic but not acute stress. PDE1B is a potential therapeutic target for depression treatment because of the antidepressant-like phenotype seen in Pde1b KO mice.

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

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Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-12-01

Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

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Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-01-01

Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

Somatostatin receptor 2 knockout/lacZ knockin mice show impaired motor coordination and reveal sites of somatostatin action within the striatum.

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Allen, Jeremy P; Hathway, Gareth J; Clarke, Neil J; Jowett, Mike I; Topps, Stephanie; Kendrick, Keith M; Humphrey, Patrick P A; Wilkinson, Lawrence S; Emson, Piers C

2003-05-01

The peptide somatostatin can modulate the functional output of the basal ganglia. The exact sites and mechanisms of this action, however, are poorly understood, and the physiological context in which somatostatin acts is unknown. Somatostatin acts as a neuromodulator via a family of five 7-transmembrane G protein-coupled receptors, SSTR1-5, one of which, SSTR2, is known to be functional in the striatum. We have investigated the role of SSTR2 in basal ganglia function using mice in which Sstr2 has been inactivated and replaced by the lacZ reporter gene. Analysis of Sstr2lacZ expression in the brain by beta-galactosidase histochemistry demonstrated a widespread pattern of expression. By comparison to previously published in situ hybridization and immunohistochemical data, Sstr2lacZ expression was shown to accurately recapitulate that of Sstr2 and thus provided a highly sensitive model to investigate cell-type-specific expression of Sstr2. In the striatum, Sstr2 expression was identified in medium spiny projection neurons restricted to the matrix compartment and in cholinergic interneurons. Sstr2 expression was not detected in any other nuclei of the basal ganglia except for a sparse number of nondopaminergic neurons in the substantia nigra. Microdialysis in the striatum showed Sstr2-null mice were selectively refractory to somatostatin-induced dopamine and glutamate release. In behavioural tests, Sstr2-null mice showed normal levels of locomotor activity and normal coordination in undemanding tasks. However, in beam-walking, a test of fine motor control, Sstr2-null mice were severely impaired. Together these data implicate an important neuromodulatory role for SSTR2 in the striatum.

HIV-1 Nef mutations abrogating downregulation of CD4 affect other Nef functions and show reduced pathogenicity in transgenic mice

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Hanna, Zaher; Priceputu, Elena; Hu, Chunyan; Vincent, Patrick; Jolicoeur, Paul

2006-01-01

HIV-1 Nef has the ability to downmodulate CD4 cell surface expression. Several studies have shown that CD4 downregulation is required for efficient virus replication and high infectivity. However, the pathophysiological relevance of this phenomenon in vivo, independently of its role in sustaining high virus loads, remains unclear. We studied the impact of the CD4 downregulation function of Nef on its pathogenesis in vivo, in the absence of viral replication, in the CD4C/HIV transgenic (Tg) mouse model. Two independent Nef mutants (RD35/36AA and D174K), known to abrogate CD4 downregulation, were tested in Tg mice. Flow cytometry analysis showed that downregulation of murine CD4 was severely decreased or abrogated on Tg T cells expressing respectively Nef RD35/36AA and Nef D174K . Similarly, the severe depletion of double-positive CD4 + CD8 + and of single-positive CD4 + CD8 - thymocytes, usually observed with Nef Wt , was not detected in Nef RD35/36AA and Nef D174K Tg mice. However, both mutant Tg mice showed a partial depletion of peripheral CD4 + T cells. This was accompanied, as previously reported for Net Wt Tg mice, by the presence of an activated/memory-like phenotype (CD69 + , CD25 + , CD44 + , CD45RB Low , CD62 Low ) of CD4 + T cells expressing Nef RD35/36AA and to a lesser extent Nef D174K . In addition, both mutants retained the ability to block CD4 + T cell proliferation in vitro after anti-CD3 stimulation, but not to enhance apoptosis/death of CD4 + T cells. Therefore, it appears that Nef-mediated CD4 downregulation is associated with thymic defects, but segregates independently of the activated/memory-like phenotype, of the partial depletion and of the impaired in vitro proliferation of peripheral CD4 + T cells. Histopathological assessment revealed the total absence of or decrease severity and frequency of organ AIDS-like diseases (lung, heart and kidney pathologies) in respectively Nef RD35/36AA and Nef D174K Tg mice, relative to those developing in

A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant.

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Mesquita, Leonardo Pereira; Gamon, Thais Helena Martins; Cuevas, Silvia Elena Campusano; Asano, Karen Miyuki; Fahl, Willian de Oliveira; Iamamoto, Keila; Scheffer, Karin Correa; Achkar, Samira Maria; Zanatto, Dennis Albert; Mori, Cláudia Madalena Cabrera; Maiorka, Paulo César; Mori, Enio

2017-12-01

Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD 50 ) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.

Integrated semiconductor optical sensors for chronic, minimally-invasive imaging of brain function.

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Lee, Thomas T; Levi, Ofer; Cang, Jianhua; Kaneko, Megumi; Stryker, Michael P; Smith, Stephen J; Shenoy, Krishna V; Harris, James S

2006-01-01

Intrinsic optical signal (IOS) imaging is a widely accepted technique for imaging brain activity. We propose an integrated device consisting of interleaved arrays of gallium arsenide (GaAs) based semiconductor light sources and detectors operating at telecommunications wavelengths in the near-infrared. Such a device will allow for long-term, minimally invasive monitoring of neural activity in freely behaving subjects, and will enable the use of structured illumination patterns to improve system performance. In this work we describe the proposed system and show that near-infrared IOS imaging at wavelengths compatible with semiconductor devices can produce physiologically significant images in mice, even through skull.

Mice expressing a “hyper-sensitive” form of the CB1 cannabinoid receptor (CB1) show modestly enhanced alcohol preference and consumption

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Gonek, Maciej; Zee, Michael L.; Farnsworth, Jill C.; Amin, Randa A.; Andrews, Mary-Jeanette; Davis, Brian J.; Mackie, Ken; Morgan, Daniel J.

2017-01-01

We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a “hyper-sensitive” form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg), and cocaine (10 mg/kg), demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model. PMID:28426670

Pomegranate (Punica granatum Juice Shows Antioxidant Activity against Cutaneous Leishmaniasis-Induced Oxidative Stress in Female BALB/c Mice

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Badriah Alkathiri

2017-12-01

Full Text Available Leishmania species are parasites that multiply within phagocytes and cause several clinical diseases characterized by single or multiple ulcerations. One of the complications that can induce tissue damage and the resulting scars is caused by secondary bacterial infections. Studies to find new, effective, and safe oral drugs for treating leishmaniasis are being conducted since several decades, owing to the problems associated with the use of antimonials available. Previously, the antiparasitic and antioxidant properties of Punica granatum (pomegranate, P. granatum have been reported. Therefore, in the present study, we aimed to investigate the antileishmanial activity of pomegranate aqueous juice in vitro and in female BALB/c mice. A 3-(4.5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay in Leishmania major promastigotes and alterations in the antioxidant status, liver function, and skin histological changes in L. major-infected mice orally treated with pomegranate juice alone and in combination with the antibiotic ciprofloxacin, were used to investigate the in vitro and in vivo antileishmanial activity of pomegranate juice, respectively. Oral P. granatum juice treatment significantly reduced the average size of cutaneous leishmaniasis lesions compared with that of the untreated mice. This antileishmanial activity of P. granatum was associated with enhanced antioxidant enzyme activities. Histopathological evaluation proved the antileishmanial activity of P. granatum, but did not reveal changes in the treated animals, compared to the positive control. In conclusion, P. granatum shows high and fast antileishmanial activity probably by boosting the endogenous antioxidant activity.

Pomegranate (Punica granatum) Juice Shows Antioxidant Activity against Cutaneous Leishmaniasis-Induced Oxidative Stress in Female BALB/c Mice.

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Alkathiri, Badriah; El-Khadragy, Manal F; Metwally, Dina M; Al-Olayan, Ebtesam M; Bakhrebah, Muhammed A; Abdel Moneim, Ahmed E

2017-12-18

Leishmania species are parasites that multiply within phagocytes and cause several clinical diseases characterized by single or multiple ulcerations. One of the complications that can induce tissue damage and the resulting scars is caused by secondary bacterial infections. Studies to find new, effective, and safe oral drugs for treating leishmaniasis are being conducted since several decades, owing to the problems associated with the use of antimonials available. Previously, the antiparasitic and antioxidant properties of Punica granatum (pomegranate, P. granatum ) have been reported. Therefore, in the present study, we aimed to investigate the antileishmanial activity of pomegranate aqueous juice in vitro and in female BALB/c mice. A 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in Leishmania major promastigotes and alterations in the antioxidant status, liver function, and skin histological changes in L. major -infected mice orally treated with pomegranate juice alone and in combination with the antibiotic ciprofloxacin, were used to investigate the in vitro and in vivo antileishmanial activity of pomegranate juice, respectively. Oral P. granatum juice treatment significantly reduced the average size of cutaneous leishmaniasis lesions compared with that of the untreated mice. This antileishmanial activity of P. granatum was associated with enhanced antioxidant enzyme activities. Histopathological evaluation proved the antileishmanial activity of P. granatum , but did not reveal changes in the treated animals, compared to the positive control. In conclusion, P. granatum shows high and fast antileishmanial activity probably by boosting the endogenous antioxidant activity.

Minimal Surfaces for Hitchin Representations

DEFF Research Database (Denmark)

Li, Qiongling; Dai, Song

2018-01-01

. In this paper, we investigate the properties of immersed minimal surfaces inside symmetric space associated to a subloci of Hitchin component: $q_n$ and $q_{n-1}$ case. First, we show that the pullback metric of the minimal surface dominates a constant multiple of the hyperbolic metric in the same conformal...... class and has a strong rigidity property. Secondly, we show that the immersed minimal surface is never tangential to any flat inside the symmetric space. As a direct corollary, the pullback metric of the minimal surface is always strictly negatively curved. In the end, we find a fully decoupled system...

Global Overexpression of ET-1 Decreases Blood Pressure - A Systematic Review and Meta-Analysis of ET-1 Transgenic Mice.

Science.gov (United States)

Lu, Yong Ping; Tsuprykov, Oleg; Vignon-Zellweger, Nicolas; Heiden, Susi; Hocher, Berthold

2016-01-01

ET-1 has independent effects on blood pressure regulation in vivo, it is involved in tubular water and salt excretion, promotes constriction of smooth muscle cells, modulates sympathetic nerve activity, and activates the liberation of nitric oxide. To determine the net effect of these partially counteracting mechanisms on blood pressure, a systematic meta-analysis was performed. Based on the principles of Cochrane systematic reviews, we searched in major literature databases - MEDLINE (PubMed), Embase, Google Scholar, and the China Biological Medicine Database (CBM-disc) - for articles relevant to the topic of the blood pressure phenotype of endothelin-1 transgenic (ET-1+/+) mice from January 1, 1988 to March 31, 2016. Review Manager Version 5.0 (Rev-Man 5.0) software was applied for statistical analysis. In total thirteen studies reported blood pressure data. The meta-analysis of blood pressure data showed that homozygous ET-1 transgenic mice (ET-1+/+ mice) had a significantly lower blood pressure as compared to WT mice (mean difference: -2.57 mmHg, 95% CI: -4.98∼ -0.16, P = 0.04), with minimal heterogeneity (P = 0.86). A subgroup analysis of mice older than 6 months revealed that the blood pressure difference between ET-1+/+ mice and WT mice was even more pronounced (mean difference: -6.19 mmHg, 95% CI: -10.76∼ -1.62, P = 0.008), with minimal heterogeneity (P = 0.91). This meta-analysis provides robust evidence that global ET-1 overexpression in mice lowers blood pressure in an age-dependent manner. Older ET-1+/+ mice have a somewhat more pronounced reduction of blood pressure. © 2016 The Author(s) Published by S. Karger AG, Basel.

Nuclear triiodothyronine receptor binding characteristics and occupancy in obese (ob/ob) mice

International Nuclear Information System (INIS)

Hillgartner, F.B.; Romsos, D.R.

1987-01-01

Obese (ob/ob) mice exhibit reduced adaptive thermogenesis associated with an impairment of thyroid hormone action. The mechanism underlying the latter defect was investigated by comparing the binding characteristics and occupancy of solubilized nuclear 3,5,3'-triiodothyronine (T 3 ) receptors from livers of lean and obese mice. T 3 concentration was measured by radioimmunoassay. Scatchard analysis showed minimal differences in B/sub max/ and K/sub d/ between phenotypes at both 4 and 8-10 wk of age, indicating that reduced hepatic thyroid hormone expression in obese mice is not caused by alterations in nuclear receptor concentration or affinity. In contrast, nuclear T 3 receptor occupancy (endogenous T 3 associated with the specific receptor divided by B/sub max/) was 14 and 23% lower in 4- and 8- to 10-wk old obese mice, respectively. Together with reported changes in hepatic thyroid hormone-sensitive enzymes, these data are consistent with a diminished nuclear T 3 signal initiating thyroid hormone action in obese mice. Decreased nuclear T 3 receptor occupancy may be secondary to a low transport of plasma T 3 to the nuclear pool. In conclusion, impaired hepatic thyroid hormone action in obese mice is mediated in part at least by a reduction in nuclear T 3 receptor occupancy

Systemic buffers inhibit carcinogenesis in TRAMP mice.

Science.gov (United States)

Ibrahim-Hashim, Arig; Cornnell, Heather H; Abrahams, Dominique; Lloyd, Mark; Bui, Marilyn; Gillies, Robert J; Gatenby, Robert A

2012-08-01

Hypoxia and acidosis develop in in situ tumors as cellular expansion increases the diffusion distance of substrates and metabolites from blood vessels deep to the basement membrane. Prior studies of breast and cervical cancer revealed that cellular adaptation to microenvironmental hypoxia and acidosis is associated with the transition from in situ to invasive cancer. We hypothesized that decreased acidosis in intraductal tumors would alter environmental selection pressures for acid adapted phenotypes and delay or prevent evolution to invasive cancer. A total of 37 C57BL/6 TRAMP mice were randomized to a control group or to 1 of 4 treatment groups. In the latter groups 200 mM sodium bicarbonate were added to drinking water starting between ages 4 and 10 weeks. In all 18 controls prostate cancer developed that was visible on 3-dimensional ultrasound at a mean age of 13 weeks. They died within 52 weeks (median 37). When sodium bicarbonate therapy commenced before age 6 weeks in 10 mice, all reached senescence (age 76 weeks) without radiographic evidence of prostate cancer. Histological sections of the prostates in this cohort showed hyperplasia but no cancer in 70% of mice and minimal well differentiated cancer in the remainder. When therapy commenced after age 6 weeks in 9 mice, prostate cancer development was no different from that in controls. Immunohistochemical staining for carbonic anhydrase 9 in regions of ductal hyperplasia showed increased expression in controls vs the early treatment group. Regional pH perturbation in in situ tumors may be a simple, inexpensive and effective cancer prevention strategy. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The pathology of facial vein blood sampling in mice

DEFF Research Database (Denmark)

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

2014-01-01

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......, and the tissue of the jaw was evaluated. Results: In the 23 mice, from which blood samples had been taken 2 days previously, 5 mice had no signs of gross pathological changes, whereas 12 mice had signs of minimal local subcutaneous bleeding and 6 mice had moderate local subcutaneous bleeding. No additional gross...... pathological changes were observed. In the 23 mice, from which blood samples had been taken 4 weeks earlier, no hemorrhage or signs of scar tissue formation could be observed. Histological slides are currently being processed (HE staining) and will be evaluated and discussed....

Minimal Composite Inflation

DEFF Research Database (Denmark)

Channuie, Phongpichit; Jark Joergensen, Jakob; Sannino, Francesco

2011-01-01

We investigate models in which the inflaton emerges as a composite field of a four dimensional, strongly interacting and nonsupersymmetric gauge theory featuring purely fermionic matter. We show that it is possible to obtain successful inflation via non-minimal coupling to gravity, and that the u......We investigate models in which the inflaton emerges as a composite field of a four dimensional, strongly interacting and nonsupersymmetric gauge theory featuring purely fermionic matter. We show that it is possible to obtain successful inflation via non-minimal coupling to gravity...

Colitic scid mice fed Lactobacillus spp. show an ameliorated gut histopathology and an altered cytokine profile by local T cells

DEFF Research Database (Denmark)

Møller, Peter Lange; Paerregaard, Anders; Gad, Monika

2005-01-01

BACKGROUND: Scid mice transplanted with CD4 T blast cells develop colitis. We investigated if the disease was influenced in colitic mice treated with antibiotic and fed Lactobacillus spp. METHODS: Colitic scid mice were treated for 1 week with antibiotics (vancomycin/meropenem) followed or not fo......-gamma production than mice not fed probiotics. CONCLUSIONS: Our data suggest that probiotics added to the drinking water may ameliorate local histopathological changes and influence local cytokine levels in colitic mice but not alter the colitis-associated weight loss....

Trigeminal ganglion neurons of mice show intracellular chloride accumulation and chloride-dependent amplification of capsaicin-induced responses.

Directory of Open Access Journals (Sweden)

Nicole Schöbel

Full Text Available Intracellular Cl(- concentrations ([Cl(-](i of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG and olfactory sensory neurons (OSNs, Cl(- is accumulated by the Na(+-K(+-2Cl(- cotransporter 1 (NKCC1, resulting in a [Cl(-](i above electrochemical equilibrium and a depolarizing Cl(- efflux upon Cl(- channel opening. Here, we investigate the [Cl(-](i and function of Cl(- in primary sensory neurons of trigeminal ganglia (TG of wild type (WT and NKCC1(-/- mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(-](i of WT TG neurons indicated active NKCC1-dependent Cl(- accumulation. Gamma-aminobutyric acid (GABA(A receptor activation induced a reduction of [Cl(-](i as well as Ca(2+ transients in a corresponding fraction of TG neurons. Ca(2+ transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+ channels (VGCCs. Ca(2+ responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1 were diminished in NKCC1(-/- TG neurons, but elevated under conditions of a lowered [Cl(-](o suggesting a Cl(--dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS, we found expression of different Ca(2+-activated Cl(- channels (CaCCs in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+ imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(-/- mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+-activated Cl(--dependent signal amplification mechanism in TG neurons that requires intracellular Cl(- accumulation by NKCC1 and the activation of CaCCs.

Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

International Nuclear Information System (INIS)

Van der Meeren, A.; Lebaron-Jacobs, L.

2001-01-01

The effects of an 8 Gy γ total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

Energy Technology Data Exchange (ETDEWEB)

Van der Meeren, A.; Lebaron-Jacobs, L. [Inst. de Protection et de Surete Nucleaire, Dept. de Protection de la sante de l' Homme et de Dosimetrie, Section Autonome de Radiobiologie Appliquee a la Medecine, IPSN, Fontenay-aux-Roses (France)

2001-02-01

The effects of an 8 Gy {gamma} total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

Histopathological studies show protective efficacy of Hippophae leaf extract against damage to jejunum in whole body 60Co-a-irradiated mice

International Nuclear Information System (INIS)

Gupta, Manish; Prasad, Jagdish; Madhu Bala

2012-01-01

Background: Ionizing radiation affect living tissue by causing majority of in vivo damage by free radical production. Earlier we reported that our preparation from Hippophae leaf offered survival benefit to >90% mice population which was whole body irradiated ( 60 Co-a-rays, 10 Gy). Objective: This study was planned to examine the protective effects of our drug (from Hippophae leaf) on ( 60 Co-a-ray induced oxidative damage and histopathological changes in jejunum. Methods: Around 2 months old adult male Strain 'A' mice were irradiated (10 Gy). Drug was administered intraperitoneally (-30 mm.). Histological parameters were studied after staining the sections with hematoxylin and eosin. Malondialdehyde formation (index of lipid peroxidation), alkaline phosphatase activity, and total thiol content were determined by biochemical techniques. The data was obtained at different time interval upto 30 days. Results: Biochemical studies showed that in comparison to the untreated controls, in the irradiated (10 Gy) mice, there was significant increase in the alkaline phosphatase activity and level of malondialdehyde whereas decrease in total thiol content within 2 days. Histological studies showed that whole body irradiation (10 Gy), damaged the jejunam crypt cells and decreased the villi height within 2 days. Intra-peritoneal administration of drug, 30 mm prior to irradiation, protected the crypt cells and villi height, countered the radiation induced increase in alkaline phosphatase activity and lipid peroxidation and values were comparable to the level of control in 30 days. Conclusions: These biochemical and histopathological studies suggested that our drug can offer effective radioprotection against the oxidative damage to jejunum in vivo. (author)

Krypton laser-induced photothrombotic distal middle cerebral artery occlusion without craniectomy in mice.

Science.gov (United States)

Sugimori, Hiroshi; Yao, Hiroshi; Ooboshi, Hiroaki; Ibayashi, Setsuro; Iida, Mitsuo

2004-08-01

Recent advances in genetical engineering of the mouse have highlighted the importance of reproducible and less invasive models of cerebral ischemia in mice. In this paper, we developed minimally invasive and reproducible model of distal middle cerebral artery (MCA) occlusion in mice using krypton (Kr) laser-induced photothrombosis. C57BL/6 or BALB mice (n=8 each) were anesthetized with halothane. The skin was cut, the temporal muscle was retracted, and the right distal MCA was observed through the skull. A Kr laser beam of wavelength 568 nm was focused onto the MCA over the intact skull. Upon laser irradiation, intravenous administration of a rose bengal solution was begun. After 4 min of irradiation, the laser beam was refocused on the MCA just proximal to the first spot, and another 4-min irradiation was performed. Then, the right common carotid artery (CCA) was ligated. Three days later, the brain was removed, and infarct volume was determined. Infarction confined almost solely to the cortical area was produced in each mouse. Mean infarct volume in C57BL/6 mice was 25.2+/-13.7 mm3. The BALB mice group showed significantly larger and more reproducible infarction (44.1+/-5.2 mm3; the coefficient of variation was 12%) than did C57BL/6 mice (P<0.005). Our photothrombosis model of stroke in mice can be performed without craniectomy, and its reproducibility is satisfactory when using BALB mice.

Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis

NARCIS (Netherlands)

Zwijnenburg, Petra J. G.; van der Poll, Tom; Florquin, Sandrine; Akira, Shizuo; Takeda, Kiyoshi; Roord, John J.; van Furth, A. Marceline

2003-01-01

To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase. Induction of meningitis resulted in an upregulation of

Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation

DEFF Research Database (Denmark)

Chidgey, M; Brakebusch, C; Gustafsson, E

2001-01-01

epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human...

Interleukin-18 gene-deficient mice show enhanced defense and reduced inflammation during pneumococcal meningitis.

NARCIS (Netherlands)

Zwijnenburg, P.J.G.; Poll, van der T.; Florquin, S; Akira, S; Takeda, K; Roord, J.J.; Furth, van A.M.

2003-01-01

To determine the role of endogenous interleukin-18 (IL-18) in pneumococcal meningitis, meningitis was induced in IL-18 gene-deficient (IL-18(-/-)) and wild-type (WT) mice by intranasal inoculation of Streptococcus pneumoniae with hyaluronidase. Induction of meningitis resulted in an upregulation of

Enhanced endotoxin sensitivity in fps/fes-null mice with minimal defects in hematopoietic homeostasis.

Science.gov (United States)

Zirngibl, Ralph A; Senis, Yotis; Greer, Peter A

2002-04-01

The fps/fes proto-oncogene encodes a cytoplasmic protein tyrosine kinase implicated in growth factor and cytokine receptor signaling and thought to be essential for the survival and terminal differentiation of myeloid progenitors. Fps/Fes-null mice were healthy and fertile, displayed slightly reduced numbers of bone marrow myeloid progenitors and circulating mature myeloid cells, and were more sensitive to lipopolysaccharide (LPS). These phenotypes were rescued using a fps/fes transgene. This confirmed that Fps/Fes is involved in, but not required for, myelopoiesis and that it plays a role in regulating the innate immune response. Bone marrow-derived Fps/Fes-null macrophages showed no defects in granulocyte-macrophage colony-stimulating factor-, interleukin 6 (IL-6)-, or IL-3-induced activation of signal transducer and activator of transcription 3 (Stat3) and Stat5A or LPS-induced degradation of I kappa B or activation of p38, Jnk, Erk, or Akt.

A minimal murine Msx-1 gene promoter. Organization of its cis-regulatory motifs and their role in transcriptional activation in cells in culture and in transgenic mice.

Science.gov (United States)

Takahashi, T; Guron, C; Shetty, S; Matsui, H; Raghow, R

1997-09-05

To dissect the cis-regulatory elements of the murine Msx-1 promoter, which lacks a conventional TATA element, a putative Msx-1 promoter DNA fragment (from -1282 to +106 base pairs (bp)) or its congeners containing site-specific alterations were fused to luciferase reporter and introduced into NIH3T3 and C2C12 cells, and the expression of luciferase was assessed in transient expression assays. The functional consequences of the sequential 5' deletions of the promotor revealed that multiple positive and negative regulatory elements participate in regulating transcription of the Msx-1 gene. Surprisingly, however, the optimal expression of Msx-1 promoter in either NIH3T3 or C2C12 cells required only 165 bp of the upstream sequence to warrant detailed examination of its structure. Therefore, the functional consequences of site-specific deletions and point mutations of the cis-acting elements of the minimal Msx-1 promoter were systematically examined. Concomitantly, potential transcriptional factor(s) interacting with the cis-acting elements of the minimal promoter were also studied by gel electrophoretic mobility shift assays and DNase I footprinting. Combined analyses of the minimal promoter by DNase I footprinting, electrophoretic mobility shift assays, and super shift assays with specific antibodies revealed that 5'-flanking regions from -161 to -154 and from -26 to -13 of the Msx-1 promoter contains an authentic E box (proximal E box), capable of binding a protein immunologically related to the upstream stimulating factor 1 (USF-1) and a GC-rich sequence motif which can bind to Sp1 (proximal Sp1), respectively. Additionally, we observed that the promoter activation was seriously hampered if the proximal E box was removed or mutated, and the promoter activity was eliminated completely if the proximal Sp1 site was similarly altered. Absolute dependence of the Msx-1 minimal promoter on Sp1 could be demonstrated by transient expression assays in the Sp1-deficient

Resistance wheel exercise from mid-life has minimal effect on sciatic nerves from old mice in which sarcopenia was prevented.

Science.gov (United States)

Krishnan, Vidya S; White, Zoe; Terrill, Jessica R; Hodgetts, Stuart I; Fitzgerald, Melinda; Shavlakadze, Tea; Harvey, Alan R; Grounds, Miranda D

2017-10-01

The ability of resistance exercise, initiated from mid-life, to prevent age-related changes in old sciatic nerves, was investigated in male and female C57BL/6J mice. Aging is associated with cellular changes in old sciatic nerves and also loss of skeletal muscle mass and function (sarcopenia). Mature adult mice aged 15 months (M) were subjected to increasing voluntary resistance wheel exercise (RWE) over a period of 8 M until 23 M of age. This prevented sarcopenia in the old 23 M aged male and female mice. Nerves of control sedentary (SED) males at 3, 15 and 23 M of age, showed a decrease in the myelinated axon numbers at 15 and 23 M, a decreased g-ratio and a significantly increased proportion of myelinated nerves containing electron-dense aggregates at 23 M. Myelinated axon and nerve diameter, and axonal area, were increased at 15 M compared with 3 and 23 M. Exercise increased myelinated nerve profiles containing aggregates at 23 M. S100 protein, detected with immunoblotting was increased in sciatic nerves of 23 M old SED females, but not males, compared with 15 M, with no effect of exercise. Other neuronal proteins showed no significant alterations with age, gender or exercise. Overall the RWE had no cellular impact on the aging nerves, apart from an increased number of old nerves containing aggregates. Thus the relationship between cellular changes in aging nerves, and their sustained capacity for stimulation of old skeletal muscles to help maintain healthy muscle mass in response to exercise remains unclear.

Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice

Energy Technology Data Exchange (ETDEWEB)

Guo, S.J. [Beijing Institute of Pharmacology and Toxicology, Beijing (China); Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Qi, C.H.; Zhou, W.X.; Zhang, Y.X. [Beijing Institute of Pharmacology and Toxicology, Beijing (China); Zhang, X.M.; Wang, J.; Wang, H.X. [National Center of Biomedical Analysis, Beijing (China)

2013-04-12

We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2-A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4{sup +} T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.

Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice

International Nuclear Information System (INIS)

Guo, S.J.; Qi, C.H.; Zhou, W.X.; Zhang, Y.X.; Zhang, X.M.; Wang, J.; Wang, H.X.

2013-01-01

We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2-A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4 + T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging

Actions of rilmenidine on neurogenic hypertension in BPH/2J genetically hypertensive mice.

Science.gov (United States)

Jackson, Kristy L; Palma-Rigo, Kesia; Nguyen-Huu, Thu-Phuc; Davern, Pamela J; Head, Geoffrey A

2014-03-01

BPH/2J hypertensive mice have an exaggerated sympathetic contribution to blood pressure (BP). Premotor sympathetic neurons within the rostroventrolateral medulla (RVLM) are a major source of sympathetic vasomotor tone and major site of action of the centrally acting sympatholytic agent, rilmenidine. The relative cardiovascular effect of rilmenidine in BPH/2J versus normotensive BPN/3J mice was used as an indicator of the involvement of the RVLM in the sympathetic contribution to hypertension in BPH/2J mice. BPH/2J and BPN/3J mice were pre-implanted with telemetry devices to measure BP in conscious unrestrained mice. Rilmenidine was administered acutely (n=7-9/group), orally for 14 days, at a wide range of doses (n=5/group), and also infused intracerebroventricularly for 7 days (n=6/group). Acute intraperitoneal rilmenidine induced greater depressor and bradycardic responses in BPH/2J than BPN/3J mice (PstrainBPH/2J mice during the dark (active) period (-6.5 ± 2 mmHg; P=0.006). Chronic orally administered rilmenidine (1-12 mg/kg per day) also had minimal effect on 24-h BP in both strains (P>0.16). The sympathetic vasomotor inhibitory effect of rilmenidine is minimal in both strains and similar in hypertensive BPH/2J and BPN/3J mice. Thus, hypertension in BPH/2J mice is not likely mediated by greater neuronal activity in the RVLM, and agents such as rilmenidine would be an ineffective treatment for this form of neurogenic hypertension.

Global morphological analysis of marine viruses shows minimal regional variation and dominance of non-tailed viruses.

Science.gov (United States)

Brum, Jennifer R; Schenck, Ryan O; Sullivan, Matthew B

2013-09-01

Viruses influence oceanic ecosystems by causing mortality of microorganisms, altering nutrient and organic matter flux via lysis and auxiliary metabolic gene expression and changing the trajectory of microbial evolution through horizontal gene transfer. Limited host range and differing genetic potential of individual virus types mean that investigations into the types of viruses that exist in the ocean and their spatial distribution throughout the world's oceans are critical to understanding the global impacts of marine viruses. Here we evaluate viral morphological characteristics (morphotype, capsid diameter and tail length) using a quantitative transmission electron microscopy (qTEM) method across six of the world's oceans and seas sampled through the Tara Oceans Expedition. Extensive experimental validation of the qTEM method shows that neither sample preservation nor preparation significantly alters natural viral morphological characteristics. The global sampling analysis demonstrated that morphological characteristics did not vary consistently with depth (surface versus deep chlorophyll maximum waters) or oceanic region. Instead, temperature, salinity and oxygen concentration, but not chlorophyll a concentration, were more explanatory in evaluating differences in viral assemblage morphological characteristics. Surprisingly, given that the majority of cultivated bacterial viruses are tailed, non-tailed viruses appear to numerically dominate the upper oceans as they comprised 51-92% of the viral particles observed. Together, these results document global marine viral morphological characteristics, show that their minimal variability is more explained by environmental conditions than geography and suggest that non-tailed viruses might represent the most ecologically important targets for future research.

Enzymatically modified isoquercitrin supplementation intensifies plantaris muscle fiber hypertrophy in functionally overloaded mice.

Science.gov (United States)

Kohara, Akiko; Machida, Masanao; Setoguchi, Yuko; Ito, Ryouichi; Sugitani, Masanori; Maruki-Uchida, Hiroko; Inagaki, Hiroyuki; Ito, Tatsuhiko; Omi, Naomi; Takemasa, Tohru

2017-01-01

Enzymatically modified isoquercitrin (EMIQ) is produced from rutin using enzymatic hydrolysis followed by treatment with glycosyltransferase in the presence of dextrin to add glucose residues. EMIQ is absorbed in the same way as quercetin, a powerful antioxidant reported to prevent disused muscle atrophy by targeting mitochondria and to have ergogenic effects. The present study investigated the effect of EMIQ on skeletal muscle hypertrophy induced by functional overload. In Study 1, 6-week-old ICR male mice were divided into 4 groups: sham-operated control, sham-operated EMIQ, overload-operated control, and overload-operated EMIQ groups. In Study 2, mice were divided into 3 groups: overload-operated whey control, overload-operated whey/EMIQ (low dose), and overload-operated whey/EMIQ (high dose) groups. The functional overload of the plantaris muscle was induced by ablation of the synergist (gastrocnemius and soleus) muscles. EMIQ and whey protein were administered with food. Three weeks after the operation, the cross-sectional area and minimal fiber diameter of the plantaris muscle fibers were measured. In Study 1, functional overload increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ supplementation significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle in both the sham-operated and overload-operated groups. In Study 2, EMIQ supplementation combined with whey protein administration significantly increased the cross-sectional area and minimal fiber diameter of the plantaris muscle. EMIQ, even when administered as an addition to whey protein supplementation, significantly intensified the fiber hypertrophy of the plantaris muscle in functionally overloaded mice. EMIQ supplementation also induced fiber hypertrophy of the plantaris in sham-operated mice.

Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.

Science.gov (United States)

Bour, Alexandra; Grootendorst, Jeannette; Vogel, Elise; Kelche, Christian; Dodart, Jean-Cosme; Bales, Kelly; Moreau, Pierre-Henri; Sullivan, Patrick M; Mathis, Chantal

2008-11-21

Apolipoprotein (apo) E4, one of three human apoE (h-apoE) isoforms, has been identified as a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. However, the biological mechanisms involving apoE in learning and memory processes are unclear. A potential isoform-dependent role of apoE in cognitive processes was studied in human apoE targeted-replacement (TR) mice. These mice express either the human apoE3 or apoE4 gene under the control of endogenous murine apoE regulatory sequences, resulting in physiological expression of h-apoE in both a temporal and spatial pattern similar to humans. Male and female apoE3-TR, apoE4-TR, apoE-knockout and C57BL/6J mice (15-18 months) were tested with spatial memory and avoidance conditioning tasks. Compared to apoE3-TR mice, spatial memory in female apoE4-TR mice was impaired based on their poor performances in; (i) the probe test of the water-maze reference memory task, (ii) the water-maze working memory task and (iii) an active avoidance Y-maze task. Retention performance on a passive avoidance task was also impaired in apoE4-TR mice, but not in other genotypes. These deficits in both spatial and avoidance memory tasks may be related to the anatomical and functional abnormalities previously reported in the hippocampus and the amygdala of apoE4-TR mice. We conclude that the apoE4-TR mice provide an excellent model for understanding the mechanisms underlying apoE4-dependent susceptibility to cognitive decline.

Free-hand ultrasound guidance permits safe and efficient minimally invasive intrathymic injections in both young and aged mice.

Science.gov (United States)

Tuckett, Andrea Z; Zakrzewski, Johannes L; Li, Duan; van den Brink, Marcel R M; Thornton, Raymond H

2015-04-01

The goal of this study was to evaluate whether use of an aseptic free-hand approach to ultrasound-guided injection facilitates injection into the thymic gland in mice. We used this interventional radiology technique in young, aged and immunodeficient mice and found that the thymus was visible in all cases. The mean injection period was 8 seconds in young mice and 19 seconds in aged or immunodeficient mice. Injection accuracy was confirmed by intrathymic location of an injected dye or by in vivo bioluminescence imaging of injected luciferase-expressing cells. Accurate intrathymic injection was confirmed in 97% of cases. No major complications were observed. We conclude that an aseptic freehand technique for ultrasound-guided intrathymic injection is safe and accurate and reduces the time required for intrathymic injections. This method facilitates large-scale experiments and injection of individual thymic lobes and is clinically relevant. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Minimal and non-minimal standard models: Universality of radiative corrections

International Nuclear Information System (INIS)

Passarino, G.

1991-01-01

The possibility of describing electroweak processes by means of models with a non-minimal Higgs sector is analyzed. The renormalization procedure which leads to a set of fitting equations for the bare parameters of the lagrangian is first reviewed for the minimal standard model. A solution of the fitting equations is obtained, which correctly includes large higher-order corrections. Predictions for physical observables, notably the W boson mass and the Z O partial widths, are discussed in detail. Finally the extension to non-minimal models is described under the assumption that new physics will appear only inside the vector boson self-energies and the concept of universality of radiative corrections is introduced, showing that to a large extent they are insensitive to the details of the enlarged Higgs sector. Consequences for the bounds on the top quark mass are also discussed. (orig.)

Feasibility of chemohyperthermia with docetaxel-embedded magnetoliposomes as minimally invasive local treatment for cancer.

Science.gov (United States)

Yoshida, Motohira; Watanabe, Yuji; Sato, Mitsunori; Maehara, Tsunehiro; Aono, Hiromichi; Naohara, Takashi; Hirazawa, Hideyuki; Horiuchi, Atsushi; Yukumi, Shungo; Sato, Koichi; Nakagawa, Hiromichi; Yamamoto, Yuji; Sugishita, Hiroki; Kawachi, Kanji

2010-04-15

Hyperthermia is a minimally invasive approach to cancer treatment, but it is difficult to heat only the tumor without damaging surrounding tissue. To solve this problem, we studied the effectiveness of chemohyperthermia with docetaxel-embedded magnetoliposomes (DMLs) and an applied alternating current (AC) magnetic field. Human MKN45 gastric cancer cells were implanted in the hind limb of Balb-c/nu/nu mice. Various concentrations of docetaxel-embedded DMLs were injected into the tumors and exposed to an AC magnetic field (n = 6, each). For comparison with hyperthermia alone, magnetite-loaded liposome (ML)-injected tumors were exposed to an AC magnetic field. Furthermore, the results of DML without AC treatment and docetaxel diluted into PBS with AC treatment were also compared (n = 10, each). Tumor surface temperature was maintained between 42 and 43 degrees C. Tumor volume was reduced in the DML group with a docetaxel concentration > 56.8 microg/ml, while a docetaxel concentration > 568.5 microg/ml was required for tumor reduction without hyperthermia. Statistically significant differences in tumor volume and survival rate were observed between the DML group exposed to the magnetic field and the other groups. The tumor disappeared in 3 mice in the DML group exposed to the magnetic field; 2 mice survived over 6 months after treatment, whereas all mice of the other groups died by 15 weeks. Histologically, hyperthermia with DML damaged tumor cells and DML diffused homogeneously. To the best of our knowledge, this is the first report to show that hyperthermia using chemotherapeutic agent-embedded magnetoliposomes has an anticancer effect.

Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance.

Science.gov (United States)

Akman, Hasan O; Dorado, Beatriz; López, Luis C; García-Cazorla, Angeles; Vilà, Maya R; Tanabe, Lauren M; Dauer, William T; Bonilla, Eduardo; Tanji, Kurenai; Hirano, Michio

2008-08-15

Mitochondrial DNA (mtDNA) depletion syndrome (MDS), an autosomal recessive condition, is characterized by variable organ involvement with decreased mtDNA copy number and activities of respiratory chain enzymes in affected tissues. MtDNA depletion has been associated with mutations in nine autosomal genes, including thymidine kinase (TK2), which encodes a ubiquitous mitochondrial protein. To study the pathogenesis of TK2-deficiency, we generated mice harboring an H126N Tk2 mutation. Homozygous Tk2 mutant (Tk2(-/-)) mice developed rapidly progressive weakness after age 10 days and died between ages 2 and 3 weeks. Tk2(-/-) animals showed Tk2 deficiency, unbalanced dNTP pools, mtDNA depletion and defects of respiratory chain enzymes containing mtDNA-encoded subunits that were most prominent in the central nervous system. Histopathology revealed an encephalomyelopathy with prominent vacuolar changes in the anterior horn of the spinal cord. The H126N TK2 mouse is the first knock-in animal model of human MDS and demonstrates that the severity of TK2 deficiency in tissues may determine the organ-specific phenotype.

Comprehensive behavioral analysis of Ox1r-/- mice showed implication of orexin receptor-1 in mood, anxiety and social behavior

Directory of Open Access Journals (Sweden)

Md Golam Abbas

2015-12-01

Full Text Available Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R is involved in physiological processes that regulate emotion, the reward system and autonomic nervous system. Here, we examined Ox1r-/- mice with a comprehensive behavioral test battery to screen additional OX1R functions. Ox1r-/- mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behaviour and sensory motor gating in addition to roles in mood and anxiety.

Female Mice Deficient in Alpha-Fetoprotein Show Female-Typical Neural Responses to Conspecific-Derived Pheromones

NARCIS (Netherlands)

Brock, O.; Keller, M.; Douhard, Q.; Bakker, J.

2012-01-01

The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estradiol, that exposure to

Enzyme-treated Asparagus officinalis extract shows neuroprotective effects and attenuates cognitive impairment in senescence-accelerated mice.

Science.gov (United States)

Sakurai, Takuya; Ito, Tomohiro; Wakame, Koji; Kitadate, Kentaro; Arai, Takashi; Ogasawara, Junetsu; Kizaki, Takako; Sato, Shogo; Ishibashi, Yoshinaga; Fujiwara, Tomonori; Akagawa, Kimio; Ishida, Hitoshi; Ohno, Hideki

2014-01-01

Increases in the number of patients with dementia involving Alzheimer's disease (AD) are seen as a grave public health problem. In neurodegenerative disorders involving AD, biological stresses, such as oxidative and inflammatory stress, induce neural cell damage. Asparagus (Asparagus officinalis) is a popular vegetable, and an extract prepared from this reportedly possesses various beneficial biological activities. In the present study, we investigated the effects of enzyme-treated asparagus extract (ETAS) on neuronal cells and early cognitive impairment of senescence-accelerated mouse prone 8 (SAMP8) mice. The expression of mRNAs for factors that exert cytoprotective and anti-apoptotic functions, such as heat-shock protein 70 and heme oxygenase-1, was upregulated in NG108-15 neuronal cells by treatment with ETAS. Moreover, when release of lactate dehydrogenase from damaged NG108-15 cells was increased for cells cultured in medium containing either the nitric oxide donor sodium nitroprusside or the hypoxia mimic reagent cobalt chloride, ETAS significantly attenuated this cell damage. Also, when contextual fear memory, which is considered to be a hippocampus-dependent memory, was significantly impaired in SAMP8 mice, ETAS attenuated the cognitive impairment. These results suggest that ETAS produces cytoprotective effects in neuronal cells and attenuates the effects on the cognitive impairment of SAMP8 mice.

Minimal open strings

International Nuclear Information System (INIS)

Hosomichi, Kazuo

2008-01-01

We study FZZT-branes and open string amplitudes in (p, q) minimal string theory. We focus on the simplest boundary changing operators in two-matrix models, and identify the corresponding operators in worldsheet theory through the comparison of amplitudes. Along the way, we find a novel linear relation among FZZT boundary states in minimal string theory. We also show that the boundary ground ring is realized on physical open string operators in a very simple manner, and discuss its use for perturbative computation of higher open string amplitudes.

The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose

International Nuclear Information System (INIS)

Penza, M.; Jeremic, M.; Marrazzo, E.; Maggi, A.; Ciana, P.; Rando, G.; Grigolato, P.G.; Di Lorenzo, D.

2011-01-01

Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5 μg/kg). At higher doses (50-500 μg/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ERα or ERβ, TBT (in a dose range of 1-100 nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ERα in undifferentiated preadipocytic cells and by ERβ in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. - Research highlights: → The environmental organotin tributyltin chloride shows dose-dependent estrogenic and adipogenic activities in mice. → The duration and extent of these effects depend on the sex and the dose of the compound. → The estrogenic and adipogenic effects of TBT occur at doses closed to the estimated

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

Directory of Open Access Journals (Sweden)

Wael Gamal Nouh

2013-07-01

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

Minimal Webs in Riemannian Manifolds

DEFF Research Database (Denmark)

Markvorsen, Steen

2008-01-01

For a given combinatorial graph $G$ a {\\it geometrization} $(G, g)$ of the graph is obtained by considering each edge of the graph as a $1-$dimensional manifold with an associated metric $g$. In this paper we are concerned with {\\it minimal isometric immersions} of geometrized graphs $(G, g......)$ into Riemannian manifolds $(N^{n}, h)$. Such immersions we call {\\em{minimal webs}}. They admit a natural 'geometric' extension of the intrinsic combinatorial discrete Laplacian. The geometric Laplacian on minimal webs enjoys standard properties such as the maximum principle and the divergence theorems, which...... are of instrumental importance for the applications. We apply these properties to show that minimal webs in ambient Riemannian spaces share several analytic and geometric properties with their smooth (minimal submanifold) counterparts in such spaces. In particular we use appropriate versions of the divergence...

Ruled Laguerre minimal surfaces

KAUST Repository

Skopenkov, Mikhail

2011-10-30

A Laguerre minimal surface is an immersed surface in ℝ 3 being an extremal of the functional ∫ (H 2/K-1)dA. In the present paper, we prove that the only ruled Laguerre minimal surfaces are up to isometry the surfaces ℝ (φλ) = (Aφ, Bφ, Cφ + D cos 2φ) + λ(sin φ, cos φ, 0), where A,B,C,D ε ℝ are fixed. To achieve invariance under Laguerre transformations, we also derive all Laguerre minimal surfaces that are enveloped by a family of cones. The methodology is based on the isotropic model of Laguerre geometry. In this model a Laguerre minimal surface enveloped by a family of cones corresponds to a graph of a biharmonic function carrying a family of isotropic circles. We classify such functions by showing that the top view of the family of circles is a pencil. © 2011 Springer-Verlag.

The Functionality of Minimal PiggyBac Transposons in Mammalian Cells

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Boris Troyanovsky

2016-01-01

Full Text Available Minimal piggyBac vectors are a modified single-plasmid version of the classical piggyBac delivery system that can be used for stable transgene integration. These vectors have a truncated terminal domain in the delivery cassette and thus, integrate significantly less flanking transposon DNA into host cell chromatin than classical piggyBac vectors. Herein, we test various characteristics of this modified transposon. The integration efficiency of minimal piggyBac vectors was inversely related to the size of both the transposon and the entire plasmid, but inserts as large as 15 kb were efficiently integrated. Open and super-coiled vectors demonstrated the same integration efficiency while DNA methylation decreased the integration efficiency and silenced the expression of previously integrated sequences in some cell types. Importantly, the incidence of plasmid backbone integration was not increased above that seen in nontransposon control vectors. In BALB/c mice, we demonstrated prolonged expression of two transgenes (intracellular mCherry and secretable Gaussia luciferase when delivered by the minimal piggyBac that resulted in a more sustained antibody production against the immunogenic luciferase than when delivered by a transient (nontransposon vector plasmid. We conclude that minimal piggyBac vectors are an effective alternative to other integrative systems for stable DNA delivery in vitro and in vivo.

Deletion of the betaine-GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult mice

DEFF Research Database (Denmark)

Lehre, A C; Rowley, N M; Zhou, Y

2011-01-01

of the GAT1 by the clinically available anti-epileptic drug tiagabine has been an effective strategy for the treatment of some patients with partial seizures. Recently, the investigational drug EF1502, which inhibits both GAT1 and BGT1, was found to exert an anti-convulsant action synergistic...... to that of tiagabine, supposedly due to inhibition of BGT1. The present study addresses the role of BGT1 in seizure control and the effect of EF1502 by developing and exploring a new mouse line lacking exons 3-5 of the BGT1 (slc6a12) gene. The deletion of this sequence abolishes the expression of BGT1 mRNA. However......, homozygous BGT1-deficient mice have normal development and show seizure susceptibility indistinguishable from that in wild-type mice in a variety of seizure threshold models including: corneal kindling, the minimal clonic and minimal tonic extension seizure threshold tests, the 6Hz seizure threshold test...

Serotonin augmentation therapy by escitalopram has minimal effects on amyloid-β levels in early-stage Alzheimer's-like disease in mice.

Science.gov (United States)

von Linstow, Christian Ulrich; Waider, Jonas; Grebing, Manuela; Metaxas, Athanasios; Lesch, Klaus Peter; Finsen, Bente

2017-09-12

insoluble/soluble Aβ42 and Aβ40 in both the neocortex and hippocampus. However, levels of soluble amyloid precursor protein α were reduced in the neocortex after 5-HTergic deafferentation. Because this study shows that modulation of the 5-HTergic system has either no effect or increases levels of insoluble/soluble Aβ42 and Aβ40 in the cerebral cortex of APP/PS1 mice, our observations do not support 5-HT augmentation therapy as a preventive strategy for reducing Aβ pathology.

The minimally tuned minimal supersymmetric standard model

International Nuclear Information System (INIS)

Essig, Rouven; Fortin, Jean-Francois

2008-01-01

The regions in the Minimal Supersymmetric Standard Model with the minimal amount of fine-tuning of electroweak symmetry breaking are presented for general messenger scale. No a priori relations among the soft supersymmetry breaking parameters are assumed and fine-tuning is minimized with respect to all the important parameters which affect electroweak symmetry breaking. The superpartner spectra in the minimally tuned region of parameter space are quite distinctive with large stop mixing at the low scale and negative squark soft masses at the high scale. The minimal amount of tuning increases enormously for a Higgs mass beyond roughly 120 GeV

Immobilization induced osteopenia is strain specific in mice

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Andreas Lodberg

2015-06-01

Full Text Available Immobilization causes rapid and massive bone loss. By comparing Botulinum Toxin A (BTX-induced bone loss in mouse strains with different genetic backgrounds we investigated whether the genetic background had an influence on the severity of the osteopenia. Secondly, we investigated whether BTX had systemic effects on bone. Female mice from four inbred mouse strains (BALB/cJ, C57BL/6 J, DBA/2 J, and C3H/HeN were injected unilaterally with BTX (n = 10/group or unilaterally with saline (n = 10/group. Mice were euthanized after 21 days, and the bone properties evaluated using μCT, DXA, bone histomorphometry, and mechanical testing. BTX resulted in substantially lower trabecular bone volume fraction (BV/TV and trabecular thickness in all mouse strains. The deterioration of BV/TV was significantly greater in C57BL/6 J (−57% and DBA/2 J (−60% than in BALB/cJ (−45% and C3H/HeN (−34% mice. The loss of femoral neck fracture strength was significantly greater in C57BL/6 J (−47% and DBA/2 J (−45% than in C3H (−25% mice and likewise the loss of mid-femoral fracture strength was greater in C57BL/6 J (−17%, DBA/2 J (−12%, and BALB/cJ (−9% than in C3H/HeN (−1% mice, which were unaffected. Using high resolution μCT we found no evidence of a systemic effect on any of the microstructural parameters of the contralateral limb. Likewise, there was no evidence of a systemic effect on the bone strength in any mouse strain. We did, however, find a small systemic effect on aBMD in DBA/2 J and C3H/HeN mice. The present study shows that BTX-induced immobilization causes the greatest loss of cortical and trabecular bone in C57BL/6 J and DBA/2 J mice. A smaller loss of bone microstructure and fracture strength was seen in BALB/cJ mice, while the bone microstructure and fracture strength of C3H/HeN mice were markedly less affected. This indicates that BTX-induced loss of bone is mouse strain dependent. We found only minimal systemic

Adolescent mice show anxiety- and aggressive-like behavior and the reduction of long-term potentiation in mossy fiber-CA3 synapses after neonatal maternal separation.

Science.gov (United States)

Shin, S Y; Han, S H; Woo, R-S; Jang, S H; Min, S S

2016-03-01

Exposure to maternal separation (MS) during early life is an identified risk factor for emotional disorders such as anxiety and depression later in life. This study investigated the effects of neonatal MS on the behavior and long-term potentiation (LTP) as well as basic synaptic transmission at hippocampal CA3-CA1 and mossy fiber (MF)-CA3 synapses in adolescent mice for 19days. When mice were adolescents, we measured depression, learning, memory, anxious and aggressive behavior using the forced swimming test (FST), Y-maze, Morris water maze (MWM), elevated plus maze (EPM), three consecutive days of the open field test, the social interaction test, the tube-dominance test and the resident-intruder test. The results showed that there was no difference in FST, Y-maze, and MWM performance. However, MS mice showed more anxiety-like behavior in the EPM test and aggressive-like behavior in the tube-dominance and resident-intruder tests. In addition, the magnitude of LTP and release probability in the MF-CA3 synapses was reduced in the MS group but not in the CA3-CA1 synapse. Our results indicate that early life stress due to MS may induce anxiety- and aggressive-like behavior during adolescence, and these effects are associated with synaptic plasticity at the hippocampal MF-CA3 synapses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

The minimal non-minimal standard model

International Nuclear Information System (INIS)

Bij, J.J. van der

2006-01-01

In this Letter I discuss a class of extensions of the standard model that have a minimal number of possible parameters, but can in principle explain dark matter and inflation. It is pointed out that the so-called new minimal standard model contains a large number of parameters that can be put to zero, without affecting the renormalizability of the model. With the extra restrictions one might call it the minimal (new) non-minimal standard model (MNMSM). A few hidden discrete variables are present. It is argued that the inflaton should be higher-dimensional. Experimental consequences for the LHC and the ILC are discussed

Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC{sup 1638N/+} Mice

Energy Technology Data Exchange (ETDEWEB)

Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Strawn, Steve J.; Thakor, Hemang; Fan, Ziling [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States); Shay, Jerry W. [Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas (United States); Fornace, Albert J. [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia); Datta, Kamal, E-mail: kd257@georgetown.edu [Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia (United States)

2016-05-01

Purpose: There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation. Methods and Materials: Male and female APC{sup 1638N/+} mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, {sup 12}C, {sup 28}Si, or {sup 56}Fe radiation. For the >1 Gy HZE dose, we used γ-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored. Results: The highest number of tumors was observed after {sup 28}Si, followed by {sup 56}Fe and {sup 12}C radiation, and tumorigenesis showed a male preponderance, especially after {sup 28}Si. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest value with {sup 28}Si, and lower doses showed greater RBE relative to higher doses. Conclusions: We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/μm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.

Coumarin Compounds of Biebersteinia Multifida Roots Show Potential Anxiolytic Effects In Mice

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Hamid Reza Monsef-Esfahani

2013-06-01

Full Text Available Background:Traditional preparations of the root of Biebersteinia multifida DC (Geraniaceae, a native medicinal plant of Irano-Turanian floristic region, have been used for the treatment of phobias as anxiolytic herbal preparation.Methods:We utilized the phobic behavior of mice in an elevated plus-maze as a model to evaluate the anxiolytic effect of the plant extract and bio-guided fractionation was applied to isolate the active compounds. Total root extract, alkaline and ether fraction were administered to mice at different doses 30 and 90 min prior to the maze test. Saline and diazepam were administered as negative and positive controls, respectively. The time spent in open and closed arms, an index of anxiety behavior and entry time, was measured as an index of animal activity.Results:The total root extract exhibited anxiolytic effect which was comparable to diazepam but with longer duration. This sustained effect of the crude extract was sustained for 90 min and was even more after injection of 45 mg/kg while the effect of diazepam had been reduced by 90 min. The anxiolytic effect factor was only present in the alkaline fraction and displayed its effect at lower doses than diazepam while pure vasicinone as the previously known alkaloid did not shown anxiolytic effect. The effect of the alkaline fraction was in a dose dependent manner starting at 0.2 mg/kg with a maximum at 1.0 mg/kg. Bio-guided fractionation using a variety of chromatographic methods led to isolation and purification of three coumarin derivatives from the bioactive fraction, including umbelliferone, scopoletin, and ferulic acid.Conclusion:For the first time, bio-guided fractionation of the root extract of B. multifida indicates significant sustained anxiolytic effects which led to isolation of three coumarin derivatives with well-known potent MAO inhibitory and anti-anxiety effects. These data contribute to evidence-based traditional use of B. multifida root for anxiety

Minimal constrained supergravity

Energy Technology Data Exchange (ETDEWEB)

Cribiori, N. [Dipartimento di Fisica e Astronomia “Galileo Galilei”, Università di Padova, Via Marzolo 8, 35131 Padova (Italy); INFN, Sezione di Padova, Via Marzolo 8, 35131 Padova (Italy); Dall' Agata, G., E-mail: dallagat@pd.infn.it [Dipartimento di Fisica e Astronomia “Galileo Galilei”, Università di Padova, Via Marzolo 8, 35131 Padova (Italy); INFN, Sezione di Padova, Via Marzolo 8, 35131 Padova (Italy); Farakos, F. [Dipartimento di Fisica e Astronomia “Galileo Galilei”, Università di Padova, Via Marzolo 8, 35131 Padova (Italy); INFN, Sezione di Padova, Via Marzolo 8, 35131 Padova (Italy); Porrati, M. [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States)

2017-01-10

We describe minimal supergravity models where supersymmetry is non-linearly realized via constrained superfields. We show that the resulting actions differ from the so called “de Sitter” supergravities because we consider constraints eliminating directly the auxiliary fields of the gravity multiplet.

Minimal constrained supergravity

International Nuclear Information System (INIS)

Cribiori, N.; Dall'Agata, G.; Farakos, F.; Porrati, M.

2017-01-01

We describe minimal supergravity models where supersymmetry is non-linearly realized via constrained superfields. We show that the resulting actions differ from the so called “de Sitter” supergravities because we consider constraints eliminating directly the auxiliary fields of the gravity multiplet.

Minimalism

CERN Document Server

Obendorf, Hartmut

2009-01-01

The notion of Minimalism is proposed as a theoretical tool supporting a more differentiated understanding of reduction and thus forms a standpoint that allows definition of aspects of simplicity. This book traces the development of minimalism, defines the four types of minimalism in interaction design, and looks at how to apply it.

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

Directory of Open Access Journals (Sweden)

Sherry L Kurtz

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

Qualifying and quantifying minimal hepatic encephalopathy

DEFF Research Database (Denmark)

Morgan, Marsha Y; Amodio, Piero; Cook, Nicola A

2016-01-01

Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables. There is ......Minimal hepatic encephalopathy is the term applied to the neuropsychiatric status of patients with cirrhosis who are unimpaired on clinical examination but show alterations in neuropsychological tests exploring psychomotor speed/executive function and/or in neurophysiological variables...... analytical techniques may provide better diagnostic information while the advent of portable wireless headsets may facilitate more widespread use. A large number of other diagnostic tools have been validated for the diagnosis of minimal hepatic encephalopathy including Critical Flicker Frequency......, the Inhibitory Control Test, the Stroop test, the Scan package and the Continuous Reaction Time; each has its pros and cons; strengths and weaknesses; protagonists and detractors. Recent AASLD/EASL Practice Guidelines suggest that the diagnosis of minimal hepatic encephalopathy should be based on the PHES test...

Minimal constrained supergravity

Directory of Open Access Journals (Sweden)

N. Cribiori

2017-01-01

Full Text Available We describe minimal supergravity models where supersymmetry is non-linearly realized via constrained superfields. We show that the resulting actions differ from the so called “de Sitter” supergravities because we consider constraints eliminating directly the auxiliary fields of the gravity multiplet.

Sirtuin 1 Agonist Minimizes Injury and Improves the Immune Response Following Traumatic Shock.

Science.gov (United States)

Luciano, Jason A; Kautza, Benjamin; Darwiche, Sophie; Martinez, Silvia; Stratimirovic, Sladjana; Waltz, Paul; Sperry, Jason; Rosengart, Matthew; Shiva, Sruti; Zuckerbraun, Brian S

2015-08-01

Survival from traumatic injury requires a coordinated and controlled inflammatory and immune response. Mitochondrial and metabolic responses to stress have been shown to play a role in these inflammatory and immune responses. We hypothesized that increases in mitochondrial biogenesis via a sirtuin 1 agonist would decrease tissue injury and partially ameliorate the immunosuppression seen following trauma. C57Bl/6 mice were subjected to a multiple trauma model. Mice were pretreated with either 100 mg/kg per day of the sirtuin 1 agonist, Srt1720, via oral gavage for 2 days prior to trauma and extended until the day the animals were killed, or they were pretreated with peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) siRNA via hydrodynamic tail vein injection 48 h prior to trauma. Markers for mitochondrial function and biogenesis were measured in addition to splenocyte proliferative capacity and bacterial clearance. Srt1720 was noted to improve mitochondrial biogenesis, mitochondrial function, and complex IV activity following traumatic injury (P hepatic injury with significant reductions in serum alanine aminotransferase levels seen in mice treated with srt1720. Splenocyte proliferative capacity and intraperitoneal bacterial clearance were evaluated as markers for overall immune function following trauma-hemorrhage. Treatment with Srt1720 minimized the trauma-induced decreases in splenocyte proliferation (P clearance. The PGC1α signaling pathway is an important regulator of mitochondrial function and biogenesis, which can potentially be harnessed to protect against hepatic injury and minimize the immunosuppression that is seen following trauma-hemorrhage.

Minimal Flavor Constraints for Technicolor

DEFF Research Database (Denmark)

Sakuma, Hidenori; Sannino, Francesco

2010-01-01

We analyze the constraints on the the vacuum polarization of the standard model gauge bosons from a minimal set of flavor observables valid for a general class of models of dynamical electroweak symmetry breaking. We will show that the constraints have a strong impact on the self-coupling and mas......We analyze the constraints on the the vacuum polarization of the standard model gauge bosons from a minimal set of flavor observables valid for a general class of models of dynamical electroweak symmetry breaking. We will show that the constraints have a strong impact on the self...

Effects of Breeding Configuration on Maternal and Weanling Behavior in Laboratory Mice.

Science.gov (United States)

Braden, Gillian C; Rasmussen, Skye; Monette, Sebastien; Tolwani, Ravi J

2017-07-01

Although numerous studies have evaluated the effect of housing density on the wellbeing of laboratory mice, little is known about the effect of breeding configuration on mouse behavior. The 8th edition of the Guide for the Care and Use of Laboratory Animals lists the recommended minimal floor area per animal for a female mouse and her litter as 51 in.2 We sought to determine the effects of pair, trio, and harem breeding configurations on the maternal and weanling behavior of C57BL/6J (B6) and 129S6/SvEvTac (129) mice on the basis of nest scores and performance in pup retrieval tests, open-field test (OFT), elevated plus maze, and tail suspension test; we concurrently evaluated cage microenvironment, reproductive indices, and anatomic and clinical pathology. Harem breeding configurations enhanced B6 maternal behaviors as evidenced by significantly shorter pup retrieval times. Trio- and harem-raised B6 weanlings showed increased exploratory behaviors, as evidenced by greater time spent in the center of the OFT, when compared with pair-raised B6 mice. Conversely, breeding configuration did not alter pup retrieval times for 129 mice, and on the day of weaning trio- and harem-raised 129 mice demonstrated increased anxiety-like behavior, as evidenced by greater time spent in the periphery of the OFT, when compared with pair-raised counterparts. Behavioral differences were not noted on subsequent days for either strain. Trio- and harem-raised B6 and 129 weanling mice had significantly higher weaning weights than weanlings raised in a pair breeding configuration. Trio and harem breeding in a standard 67-in.2 shoebox cage did not detrimentally affect the evaluated welfare parameters in either C57BL/6J or 129S6/SvEvTac mice.

Minimal quantization and confinement

International Nuclear Information System (INIS)

Ilieva, N.P.; Kalinowskij, Yu.L.; Nguyen Suan Han; Pervushin, V.N.

1987-01-01

A ''minimal'' version of the Hamiltonian quantization based on the explicit solution of the Gauss equation and on the gauge-invariance principle is considered. By the example of the one-particle Green function we show that the requirement for gauge invariance leads to relativistic covariance of the theory and to more proper definition of the Faddeev - Popov integral that does not depend on the gauge choice. The ''minimal'' quantization is applied to consider the gauge-ambiguity problem and a new topological mechanism of confinement

IFNγ and perforin cooperate to control infection and prevent fatal pathology during persistent gammaherpesvirus infection in mice

DEFF Research Database (Denmark)

Bartholdy, Christina; Høgh-Petersen, Mette; Storm, Pernille

2014-01-01

herpes virus infection, we infected IFNγ/perforin double deficient C57BL/6 mice and followed the outcome of infection. While absence of perforin prevented the splenic atrophy in IFNγ deficient mice, fibrosis did not disappear. Moreover, double deficient mice developed extreme splenomegaly, were unable...... in double deficient mice, other aspects are exaggerated, and the normal architecture of the spleen is completely destroyed. Thus, IFNγ and perforin work in concert to minimize pathology and control the viral load. In the absence of both effector molecules, the balancing race between the virus and the host...

A minimal model of epithelial tissue dynamics and its application to the corneal epithelium

Science.gov (United States)

Henkes, Silke; Matoz-Fernandez, Daniel; Kostanjevec, Kaja; Coburn, Luke; Sknepnek, Rastko; Collinson, J. Martin; Martens, Kirsten

Epithelial cell sheets are characterized by a complex interplay of active drivers, including cell motility, cell division and extrusion. Here we construct a particle-based minimal model tissue with only division/death dynamics and show that it always corresponds to a liquid state with a single dynamic time scale set by the division rate, and that no glassy phase is possible. Building on this, we construct an in-silico model of the mammalian corneal epithelium as such a tissue confined to a hemisphere bordered by the limbal stem cell zone. With added cell motility dynamics we are able to explain the steady-state spiral migration on the cornea, including the central vortex defect, and quantitatively compare it to eyes obtained from mice that are X-inactivation mosaic for LacZ.

Effects of social isolation, re-socialization and age on cognitive and aggressive behaviors of Kunming mice and BALB/c mice.

Science.gov (United States)

An, Dong; Chen, Wei; Yu, De-Qin; Wang, Shi-Wei; Yu, Wei-Zhi; Xu, Hong; Wang, Dong-Mei; Zhao, Dan; Sun, Yi-Ping; Wu, Jun-Cheng; Tang, Yi-Yuan; Yin, Sheng-Ming

2017-05-01

Both Kunming (KM) mice and BALB/c mice have been widely used as rodent models to investigate stress-associated mental diseases. However, little is known about the different behaviors of KM mice and BALB/c mice after social isolation, particularly cognitive and aggressive behaviors. In this study, the behaviors of KM and BALB/c mice isolated for 2, 4 and 8 weeks and age-matched controls were evaluated using object recognition, object location and resident-intruder tests. The recovery of behavioral deficits by re-socialization was also examined for the isolated mice in adolescence. Our study showed that isolation for 2, 4 and 8 weeks led to cognitive deficits and increased aggressiveness for both KM and BALB/c mice. An important finding is that re-socialization could completely recover spatial/non-spatial cognitive deficits resulted from social isolation for both KM and BALB/c mice. In addition, age only impacted aggressiveness of KM mice. Moreover, isolation duration showed different impacts on cognitive and aggressive behaviors for both KM and BALB/c mice. Furthermore, BALB/c mice showed weak spatial/non-spatial memory and low aggressiveness when they were at the same age and isolation duration, compared to KM mice. In conclusion, KM mice and BALB/c mice behaved characteristically under physiology and isolation conditions. © 2016 Japanese Society of Animal Science.

A water-soluble extract of chicken reduced plasma triacylglycerols, but showed no anti-atherosclerotic activity in apoE−/− mice

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Rita Vik

2015-08-01

Conclusion: Chicken protein displayed a slight potential to increase mitochondrial fatty acid oxidation and reduce plasma TAG. However, CP did not affect plasma cholesterol levels, inflammation status or atherosclerotic development in apoE−/− mice. Based on these results, dietary intervention with CP does not have sufficient capacity to influence atherosclerotic development in apoE−/− mice.

Minimal string theory is logarithmic

International Nuclear Information System (INIS)

Ishimoto, Yukitaka; Yamaguchi, Shun-ichi

2005-01-01

We study the simplest examples of minimal string theory whose worldsheet description is the unitary (p,q) minimal model coupled to two-dimensional gravity ( Liouville field theory). In the Liouville sector, we show that four-point correlation functions of 'tachyons' exhibit logarithmic singularities, and that the theory turns out to be logarithmic. The relation with Zamolodchikov's logarithmic degenerate fields is also discussed. Our result holds for generic values of (p,q)

Minimal changes in health status questionnaires: distinction between minimally detectable change and minimally important change

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Knol Dirk L

2006-08-01

Full Text Available Abstract Changes in scores on health status questionnaires are difficult to interpret. Several methods to determine minimally important changes (MICs have been proposed which can broadly be divided in distribution-based and anchor-based methods. Comparisons of these methods have led to insight into essential differences between these approaches. Some authors have tried to come to a uniform measure for the MIC, such as 0.5 standard deviation and the value of one standard error of measurement (SEM. Others have emphasized the diversity of MIC values, depending on the type of anchor, the definition of minimal importance on the anchor, and characteristics of the disease under study. A closer look makes clear that some distribution-based methods have been merely focused on minimally detectable changes. For assessing minimally important changes, anchor-based methods are preferred, as they include a definition of what is minimally important. Acknowledging the distinction between minimally detectable and minimally important changes is useful, not only to avoid confusion among MIC methods, but also to gain information on two important benchmarks on the scale of a health status measurement instrument. Appreciating the distinction, it becomes possible to judge whether the minimally detectable change of a measurement instrument is sufficiently small to detect minimally important changes.

A Wedge Absorber Experiment at MICE

Energy Technology Data Exchange (ETDEWEB)

Neuffer, David [Fermilab; Mohayai, Tanaz [IIT, Chicago; Rogers, Chris [Rutherford; Snopok, Pavel [IIT, Chicago; Summers, Don [Mississippi U.

2017-05-01

Emittance exchange mediated by wedge absorbers is required for longitudinal ionization cooling and for final transverse emittance minimization for a muon collider. A wedge absorber within the MICE beam line could serve as a demonstration of the type of emittance exchange needed for 6-D cooling, including the configurations needed for muon colliders, as well as configurations for low-energy muon sources. Parameters for this test are explored in simulation and possible experimental configurations with simulated results are presented.

Mice with cancer-induced bone pain show a marked decline in day/night activity.

Science.gov (United States)

Majuta, Lisa A; Guedon, Jean-Marc G; Mitchell, Stefanie A T; Kuskowski, Michael A; Mantyh, Patrick W

2017-09-01

Cancer-induced bone pain (CIBP) is the most common type of pain with cancer. In humans, this pain can be difficult to control and highly disabling. A major problem with CIBP in humans is that it increases on weight-bearing and/or movement of a tumor-bearing bone limiting the activity and functional status of the patient. Currently, there is less data concerning whether similar negative changes in activity occur in rodent models of CIBP. To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Osteosarcoma cells were injected and confined to 1 femur of the adult male mouse. Every 7 days, spontaneous horizontal and vertical activities were assessed over a 20-hour day and night period using automated activity boxes. Mechanical hypersensitivity of the hind paw skin was assessed using von Frey testing. As the tumor cells grew within the femur, there was a significant decline in horizontal and vertical activity during the times of the day/night when the mice are normally most active. Mice also developed significant hypersensitivity in the skin of the hind paw in the tumor-bearing limb. Even when the tumor is confined to a single load-bearing bone, CIBP drives a significant loss of activity, which increases with disease progression. Understanding the mechanisms that drive this reduction in activity may allow the development of therapies that allow CIBP patients to better maintain their activity and functional status.

Liver-specific Aquaporin 11 knockout mice show rapid vacuolization of the rough endoplasmic reticulum in periportal hepatocytes after amino acid feeding

DEFF Research Database (Denmark)

Rojek, Aleksandra; Füchtbauer, Ernst-Martin; Füchtbauer, Annette C.

2013-01-01

-specific Aqp11 KO mice, allowing us to study the role of AQP11 protein in liver of mice with normal kidney function. The unchallenged liver-specific Aqp11 KO mice have normal longevity, their livers appeared normal, and the plasma biochemistries revealed only a minor defect in lipid handling. Fasting......Aquaporin 11 (AQP11) is a protein channel expressed intracellularly in multiple organs, yet its physiological function is unclear. Aqp11 knockout (KO) mice die early due to malfunction of the kidney, a result of hydropic degeneration of proximal tubule cells. Here we report the generation of liver...... protein or larger doses of various amino acids. The fasting/refeeding challenge is associated with increased expression of markers of ER stress Grp78 and GADD153 and decreased glutathione levels, suggesting that ER stress may play role in the development of vacuoles in the AQP11-deficient hepatocytes. NMR...

Comprehensive Behavioral Analysis of Male Ox1r−/− Mice Showed Implication of Orexin Receptor-1 in Mood, Anxiety, and Social Behavior

Science.gov (United States)

Abbas, Md. G.; Shoji, Hirotaka; Soya, Shingo; Hondo, Mari; Miyakawa, Tsuyoshi; Sakurai, Takeshi

2015-01-01

Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system, and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R) is involved in physiological processes that regulate emotion, the reward system, and autonomic nervous system. Here, we examined Ox1r−/− mice with a comprehensive behavioral test battery to screen additional OX1R functions. Ox1r−/− mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response, and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behavior and sensory motor gating in addition to roles in mood and anxiety. PMID:26696848

Antigens of worms and eggs showed a differentiated detection of specific IgG according to the time of Schistosoma mansoni infection in mice

Directory of Open Access Journals (Sweden)

Rafaella Fortini Queiroz Grenfell

2012-08-01

Full Text Available INTRODUCTION: The correlation between the immunological assay and the antibody titer can offer a tool for the experimental analysis of different phases of the disease. METHODS: Two simple immunological assays for Schistosoma mansoni in mice sera samples based on specific IgG detection for worms soluble antigens and eggs soluble antigens were standardized and evaluated in our laboratory. Fifty mice were used in negative and positive groups and the results obtained by enzyme-linked immunosorbent assays (ELISA assays were compared with the number of worms counted and the IgG titers at different times of infection. RESULTS: Data showed that ELISA using adult worm antigens (ELISA-SWAP presented a satisfactory correlation between the absorbance value of IgG titers and the individual number of worms counted after perfusion technique (R²=0.62. In addition, ELISA-SWAP differentially detected positive samples with 30 and 60 days post infection (p=0.011 and 0.003, respectively, whereas ELISA using egg antigens (ELISA-SEA detected samples after 140 days (p=0.03. CONCLUSIONS: These data show that the use of different antigens in immunological methods can be used as potential tools for the analysis of the chronological evolution of S. mansoni infection in murine schistosomiasis. Correlations with human schistosomiasis are discussed.

PBI creams: a spontaneously mutated mouse strain showing wild animal-type reactivity.

Science.gov (United States)

Hendrie, C A; Van Driel, K S; Talling, J C; Inglis, I R

2001-01-01

PBI creams are mice derived from warfarin-resistant wild stock that has been maintained under laboratory conditions since the 1970s. This study compares their behaviour to that of laboratory mice and wild house and wood mice. Animals were tested in a black/white box and a 2.64x1.4 m runway. In the black/white box, the behaviour of PBI creams was not significantly different from that of house mice and differed most from that of laboratory mice. Notably, the PBI creams showed the greatest activity and escape-orientated behaviours. When animals were approached by the experimenter in the open runway test, the PBI creams had higher flight speeds than both house and wood mice, whilst laboratory mice failed to respond. In the closed runway test where the animals could not escape, the PBI creams, house mice and wood mice all turned and attempted to run past the approaching experimenter, whilst the laboratory mice again failed to react. At the end of this test session, the time taken to catch each animal was recorded. It took less than 5 s to catch laboratory mice but significantly longer to catch the wild strains and the PBI creams (90-100 s for the latter). In these tests, the PBI creams showed wild animal-type reactivity, and as this behaviour has been retained in the laboratory colony for over 30 years, these animals may be useful in the study of the physiological and genetic basis of fear/anxiety in mice.

Chronic Pelvic Pain Development and Prostate Inflammation in Strains of Mice With Different Susceptibility to Experimental Autoimmune Prostatitis.

Science.gov (United States)

Breser, Maria L; Motrich, Ruben D; Sanchez, Leonardo R; Rivero, Virginia E

2017-01-01

Experimental autoimmune prostatitis (EAP) is an autoimmune inflammatory disease of the prostate characterized by peripheral prostate-specific autoimmune responses associated with prostate inflammation. EAP is induced in rodents upon immunization with prostate antigens (PAg) plus adjuvants and shares important clinical and immunological features with the human disease chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). EAP was induced in young NOD, C57BL/6, and BALB/c male mice by immunization with PAg plus complete Freund́s adjuvant. Tactile allodynia was assessed using Von Frey fibers as a measure of pelvic pain at baseline and at different time points after immunization. Using conventional histology, immunohistochemistry, FACS analysis, and protein arrays, an interstrain comparative study of prostate cell infiltration and inflammation was performed. Chronic pelvic pain development was similar between immunized NOD and C57BL/6 mice, although the severity of leukocyte infiltration was greater in the first case. Coversely, minimal prostate cell infiltration was observed in immunized BALB/c mice, who showed no pelvic pain development. Increased numbers of mast cells, mostly degranulated, were detected in prostate samples from NOD and C57BL/6 mice, while lower total counts and resting were observed in BALB/c mice. Prostate tissue from NOD mice revealed markedly increased expression levels of inflammatory cytokines, chemokines, adhesion molecules, vascular endothelial growth factor, and metalloproteinases. Similar results, but to a lesser extent, were observed when analyzing prostate tissue from C57BL/6 mice. On the contrary, the expression of the above mediators was very low in prostate tissue from immunized BALB/c mice, showing significantly slight increments only for CXCL1 and IL4. Our results provide new evidence indicating that NOD, C57BL/6, and BALB/c mice develop different degrees of chronic pelvic pain, type, and amount of prostate cell infiltration

Expanding the body mass range: associations between BMR and tissue morphology in wild type and mutant dwarf mice (David mice).

Science.gov (United States)

Meyer, Carola W; Neubronner, Juliane; Rozman, Jan; Stumm, Gabi; Osanger, Andreas; Stoeger, Claudia; Augustin, Martin; Grosse, Johannes; Klingenspor, Martin; Heldmaier, Gerhard

2007-02-01

We sought to identify associations of basal metabolic rate (BMR) with morphological traits in laboratory mice. In order to expand the body mass (BM) range at the intra-strain level, and to minimize relevant genetic variation, we used male and female wild type mice (C3HeB/FeJ) and previously unpublished ENU-induced dwarf mutant littermates (David mice), covering a body mass range from 13.5 g through 32.3 g. BMR was measured at 30 degrees C, mice were killed by means of CO(2 )overdose, and body composition (fat mass and lean mass) was subsequently analyzed by dual X-ray absorptiometry (DEXA), after which mice were dissected into 12 (males) and 10 (females) components, respectively. Across the 44 individuals, 43% of the variation in the basal rates of metabolism was associated with BM. The latter explained 47% to 98% of the variability in morphology of the different tissues. Our results demonstrate that sex is a major determinant of body composition and BMR in mice: when adjusted for BM, females contained many larger organs, more fat mass, and less lean mass compared to males. This could be associated with a higher mass adjusted BMR in females. Once the dominant effects of sex and BM on BMR and tissue mass were removed, and after accounting for multiple comparisons, no further significant association between individual variation in BMR and tissue mass emerged.

Loss of PDZK1 causes coronary artery occlusion and myocardial infarction in Paigen diet-fed apolipoprotein E deficient mice.

Directory of Open Access Journals (Sweden)

Ayce Yesilaltay

2009-12-01

Full Text Available PDZK1 is a four PDZ-domain containing protein that binds to the carboxy terminus of the HDL receptor, scavenger receptor class B type I (SR-BI, and regulates its expression, localization and function in a tissue-specific manner. PDZK1 knockout (KO mice are characterized by a marked reduction of SR-BI protein expression ( approximately 95% in the liver (lesser or no reduction in other organs with a concomitant 1.7 fold increase in plasma cholesterol. PDZK1 has been shown to be atheroprotective using the high fat/high cholesterol ('Western' diet-fed murine apolipoprotein E (apoE KO model of atherosclerosis, presumably because of its role in promoting reverse cholesterol transport via SR-BI.Here, we have examined the effects of PDZK1 deficiency in apoE KO mice fed with the atherogenic 'Paigen' diet for three months. Relative to apoE KO, PDZK1/apoE double KO (dKO mice showed increased plasma lipids (33% increase in total cholesterol; 49 % increase in unesterified cholesterol; and 36% increase in phospholipids and a 26% increase in aortic root lesions. Compared to apoE KO, dKO mice exhibited substantial occlusive coronary artery disease: 375% increase in severe occlusions. Myocardial infarctions, not observed in apoE KO mice (although occasional minimal fibrosis was noted, were seen in 7 of 8 dKO mice, resulting in 12 times greater area of fibrosis in dKO cardiac muscle.These results show that Paigen-diet fed PDZK1/apoE dKO mice represent a new animal model useful for studying coronary heart disease and suggest that PDZK1 may represent a valuable target for therapeutic intervention.

Minimal surfaces

CERN Document Server

Dierkes, Ulrich; Sauvigny, Friedrich; Jakob, Ruben; Kuster, Albrecht

2010-01-01

Minimal Surfaces is the first volume of a three volume treatise on minimal surfaces (Grundlehren Nr. 339-341). Each volume can be read and studied independently of the others. The central theme is boundary value problems for minimal surfaces. The treatise is a substantially revised and extended version of the monograph Minimal Surfaces I, II (Grundlehren Nr. 295 & 296). The first volume begins with an exposition of basic ideas of the theory of surfaces in three-dimensional Euclidean space, followed by an introduction of minimal surfaces as stationary points of area, or equivalently

Improved assessment of outcomes following transient global cerebral ischemia in mice

DEFF Research Database (Denmark)

Spray, Stine; Edvinsson, Lars

2016-01-01

by limited neurological assessment protocols and present insufficient reporting of the cumulative survival rate. Therefore, we aim at developing a reproducible and easily implementable model of transient GCI in mice with minimal impact on normal mouse behavior. GCI was induced in male C57BL/6 mice......Mouse models of global cerebral ischemia (GCI) allow experimental examination of cerebral pathophysiology in genetically modified mice and fast screening of new treatment strategies. Various surgical protocols of GCI-induction in mice have been published; however, many of these studies are hindered...... and again daily for up to 7 days after GCI or sham operation and was found to be significantly decreased 1-7 days after GCI compared to sham. Furthermore, we found delayed neuronal cell death in the frontal cortex and hippocampus 5 and 7 days after GCI but not at day 3 or after sham operation. The survival...

The Memory of MICE: The Configuration Database

International Nuclear Information System (INIS)

Wilson, A J; Colling, D J; Hanlet, P

2012-01-01

The configuration database (CDB) is the memory of the Muon Ionisation Cooling Experiment (MICE). Its principle aim is to store temporal data associated with the running of the experiment; these data are used throughout the life cycle of experiment, from running the experiment through data analysis. The CDB also serves as a moderator in the MICE state machine by defining allowable operating states of subsystems depending on the overall state of MICE and other subsystems. Master and slave CDBs, with multiple mirrored pair raid arrays, have been set up in different parts of the site to increase resilience, as well as off site backups. Access to the CDB is via a Python API, which communicates with a WSDL interface provided by a web-service on the CDB. The priority is to ensure availability of the CDB in the experiment control room. The master CDB is located in the MICE control where it is only used by the running experiment. In the event of the failure of the master, the slave can easily be promoted to master. Read only access to the CDB for data analysis and reconstruction is provided by the slave which has an up to the minute copy of the data. As MICE is a precision experiment which will measure a 10% muon cooling effect with 1% precision, it is imperative that we minimize our systematic errors; the CDB will ensure reproducible and documented running conditions in a highly resilient manner. A description of the hardware and software used in the the MICE CDB will be described in what follows.

Thyroid epithelial cell hyperplasia in IFN-gamma deficient NOD.H-2h4 mice.

Science.gov (United States)

Yu, Shiguang; Sharp, Gordon C; Braley-Mullen, Helen

2006-01-01

The role of inflammatory cells in thyroid epithelial cell (thyrocyte) hyperplasia is unknown. Here, we demonstrate that thyrocyte hyperplasia in IFN-gamma-/- NOD.H-2h4 mice has an autoimmune basis. After chronic exposure to increased dietary iodine, 60% of IFN-gamma-/- mice had severe thyrocyte hyperplasia with minimal or moderate lymphocyte infiltration, and thyroid dysfunction with reduced serum T4. All mice produced anti-thyroglobulin autoantibody. Some wild-type NOD.H-2h4 mice had isolated areas of thyrocyte hyperplasia with predominantly lymphocytic infiltration, whereas IL-4-/- and 50% of wild-type NOD.H-2h4 mice developed lymphocytic thyroiditis but no thyrocyte hyperplasia. Both thyroid infiltrating inflammatory cells and environmental factors (iodine) were required to induce thyrocyte hyperplasia. Splenocytes from IFN-gamma-/- mice with thyrocyte hyperplasia, but not splenocytes from naïve IFN-gamma-/- mice, induced hyperplasia in IFN-gamma-/- NOD.H-2h4.SCID mice. These results may provide clues for understanding the mechanisms underlying development of epithelial cell hyperplasia not only in thyroids but also in other tissues and organs.

Methanolic effect of Clerodendrum myricoides root extract on blood, liver and kidney tissues of mice.

Science.gov (United States)

Hayelom, K; Mekbeb, A; Eyasu, M; Wondwossen, E; Kelbesa, U

2012-12-01

The present study deals with the toxicological investigations of chronic treatment with methanol root extract of Clerodendrum myricoides on body weight, hematological and biochemical parameters, and liver and kidney tissue sections. Mice treated with 100mg/kg bw/day of methanol extract showed no behavioral changes. However, there was a general reduction of activity in mice treated with 400mg/kg bw/day methanol extract and LD50 treated mice showed hypoactivity, grooming, prostration, piloroerection and irritation during administration towards the last days of the treatment period. The body weight gain difference in the 100mg/kg bw/day methanol extract treated group was not significant, while those of the others were significant as compared with the controls. Hematological results for the RBC count, HCT, MCV, MCH and MCHC in methanol extract treated mice showed no significant changes at both doses of treatments as compared with the controls. However, the value of lymphocytes was found significantly increased at 100 and 400mg/kg bw/day methanol extract. Similarly, HGB was significantly increased at 100 and 400mg/kg bw/day of methanol extract treated groups. On the other hand, WBC and platelets count were significantly decreased after treatment with 400mg/kg bw/day methanol extract. ALT, ALP, AST and urea values were significantly increased respectively at 100mg/kg bw/day and 400mg/kg bw/day methanol extract. Several histopathological changes of liver and kidney were observed in the extract treated mice as compared to the controls. Such histopathological changes observed in both liver and kidneys were inflammations and hydropic degenerations of hepatocytes at both doses of methanol. In addition, in the LD50 treated mice of the extracts there were also hemorrhages and signs in congestion of glomeruli of the kidney. chronic treatment with Clerodendrum myricoides extracts in mice causes reduction in body weight gain, damage to liver & kidney and changes in some

Production of knock-in mice in a single generation from embryonic stem cells.

Science.gov (United States)

Ukai, Hideki; Kiyonari, Hiroshi; Ueda, Hiroki R

2017-12-01

The system-level identification and analysis of molecular networks in mammals can be accelerated by 'next-generation' genetics, defined as genetics that does not require crossing of multiple generations of animals in order to achieve the desired genetic makeup. We have established a highly efficient procedure for producing knock-in (KI) mice within a single generation, by optimizing the genome-editing protocol for KI embryonic stem (ES) cells and the protocol for the generation of fully ES-cell-derived mice (ES mice). Using this protocol, the production of chimeric mice is eliminated, and, therefore, there is no requirement for the crossing of chimeric mice to produce mice that carry the KI gene in all cells of the body. Our procedure thus shortens the time required to produce KI ES mice from about a year to ∼3 months. Various kinds of KI ES mice can be produced with a minimized amount of work, facilitating the elucidation of organism-level phenomena using a systems biology approach. In this report, we describe the basic technologies and protocols for this procedure, and discuss the current challenges for next-generation mammalian genetics in organism-level systems biology studies.

Wilson loops in minimal surfaces

International Nuclear Information System (INIS)

Drukker, Nadav; Gross, David J.; Ooguri, Hirosi

1999-01-01

The AdS/CFT correspondence suggests that the Wilson loop of the large N gauge theory with N = 4 supersymmetry in 4 dimensions is described by a minimal surface in AdS 5 x S 5 . The authors examine various aspects of this proposal, comparing gauge theory expectations with computations of minimal surfaces. There is a distinguished class of loops, which the authors call BPS loops, whose expectation values are free from ultra-violet divergence. They formulate the loop equation for such loops. To the extent that they have checked, the minimal surface in AdS 5 x S 5 gives a solution of the equation. The authors also discuss the zig-zag symmetry of the loop operator. In the N = 4 gauge theory, they expect the zig-zag symmetry to hold when the loop does not couple the scalar fields in the supermultiplet. They will show how this is realized for the minimal surface

Wilson loops and minimal surfaces

International Nuclear Information System (INIS)

Drukker, Nadav; Gross, David J.; Ooguri, Hirosi

1999-01-01

The AdS-CFT correspondence suggests that the Wilson loop of the large N gauge theory with N=4 supersymmetry in four dimensions is described by a minimal surface in AdS 5 xS 5 . We examine various aspects of this proposal, comparing gauge theory expectations with computations of minimal surfaces. There is a distinguished class of loops, which we call BPS loops, whose expectation values are free from ultraviolet divergence. We formulate the loop equation for such loops. To the extent that we have checked, the minimal surface in AdS 5 xS 5 gives a solution of the equation. We also discuss the zigzag symmetry of the loop operator. In the N=4 gauge theory, we expect the zigzag symmetry to hold when the loop does not couple the scalar fields in the supermultiplet. We will show how this is realized for the minimal surface. (c) 1999 The American Physical Society

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

2016-01-01

, 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...

Supersymmetric hybrid inflation with non-minimal Kahler potential

International Nuclear Information System (INIS)

Bastero-Gil, M.; King, S.F.; Shafi, Q.

2007-01-01

Minimal supersymmetric hybrid inflation based on a minimal Kahler potential predicts a spectral index n s ∼>0.98. On the other hand, WMAP three year data prefers a central value n s ∼0.95. We propose a class of supersymmetric hybrid inflation models based on the same minimal superpotential but with a non-minimal Kahler potential. Including radiative corrections using the one-loop effective potential, we show that the prediction for the spectral index is sensitive to the small non-minimal corrections, and can lead to a significantly red-tilted spectrum, in agreement with WMAP

Fast nonconvex nonsmooth minimization methods for image restoration and reconstruction.

Science.gov (United States)

Nikolova, Mila; Ng, Michael K; Tam, Chi-Pan

2010-12-01

Nonconvex nonsmooth regularization has advantages over convex regularization for restoring images with neat edges. However, its practical interest used to be limited by the difficulty of the computational stage which requires a nonconvex nonsmooth minimization. In this paper, we deal with nonconvex nonsmooth minimization methods for image restoration and reconstruction. Our theoretical results show that the solution of the nonconvex nonsmooth minimization problem is composed of constant regions surrounded by closed contours and neat edges. The main goal of this paper is to develop fast minimization algorithms to solve the nonconvex nonsmooth minimization problem. Our experimental results show that the effectiveness and efficiency of the proposed algorithms.

Chyawanprash, a formulation of traditional Ayurvedic medicine, shows a protective effect on skin photoaging in hairless mice.

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Takauji, Yuki; Morino, Kyoko; Miki, Kensuke; Hossain, Mohammad; Ayusawa, Dai; Fujii, Michihiko

2016-11-01

Chronic exposure to ultraviolet (UV) radiation induces skin photoaging (premature skin aging). UV irradiation generates reactive oxygen species (ROS), which are shown to play a pivotal role in skin photoaging. Ayurveda is a holistic traditional medical system, and Chyawanprash is one of the most popular formulations in Ayurveda. Since maintenance of the function and appearance of skin is important, we examined whether Chyawanprash has a protective effect on skin photoaging. To examine the effect of Chyawanprash on skin photoaging, hairless mice were administered with Chyawanprash in drinking water for 3 weeks, and then repeatedly exposed to ultraviolet light B (UVB) irradiation (225 or 450 mJ/cm 2 ) to induce skin photoaging. To further examine the function of Chyawanprash, its effects were examined in cells cultured in vitro. Chyawanprash was added in culture medium, and examined for the effect on the growth of human keratinocytes, and for the ability to eliminate ROS which generated by paraquat (50 μmol/L) in HeLa cells. UVB irradiation caused symptoms such as rough skin, erythema, and edema on the skin in hairless mice, but administration of Chyawanprash relieved these symptoms. Further, Chyawanprash significantly suppressed epidermal thickening, a typical marker of skin photoaging, in mice. We then analyzed the effect of Chyawanprash in human cells in culture, and found that Chyawanprash enhanced the growth of human keratinocytes, and efficiently eliminated ROS, which are causally involved in skin photoaging, in HeLa cells. These findings suggested that Chyawanprash may have beneficial effects on slowing skin photoaging.

Reduced alcohol consumption in mice lacking preprodynorphin.

Science.gov (United States)

Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

2006-10-01

Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-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 amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

Minimal Dark Matter in the sky

International Nuclear Information System (INIS)

Panci, P.

2016-01-01

We discuss some theoretical and phenomenological aspects of the Minimal Dark Matter (MDM) model proposed in 2006, which is a theoretical framework highly appreciated for its minimality and yet its predictivity. We first critically review the theoretical requirements of MDM pointing out generalizations of this framework. Then we review the phenomenology of the originally proposed fermionic hyperchargeless electroweak quintuplet showing its main γ-ray tests.

Preference for and discrimination of paintings by mice.

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Shigeru Watanabe

Full Text Available I measured preference for paintings (Renoir vs. Picasso or Kandinsky vs. Mondrian in mice. In general mice did not display a painting preference except for two mice: one preferred Renoir to Picasso, and the other preferred Kandinsky to Mondrian. Thereafter, I examined discrimination of paintings with new mice. When exposure to paintings of one artist was associated with an injection of morphine (3.0 mg/kg, mice displayed conditioned preference for those paintings, showing discrimination of paintings by Renoir from those by Picasso, and paintings by Kandinsky from those by Mondrian after the conditioning. They also exhibited generalization of the preference to novel paintings of the artists. After conditioning with morphine for a set of paintings consisting of two artists, mice showed discrimination between two sets of paintings also from the two artists but not in association with morphine. These results suggest that mice can discriminate not only between an artist's style but also among paintings of the same artist. When mice were trained to discriminate a pair of paintings by Kandinsky and Renoir in an operant chamber equipped with a touch screen, they showed transfer of the discrimination to new pairs of the artists, but did not show transfer of discrimination of paintings by other artists, suggesting generalization.

Impaired cutaneous wound healing in mice lacking tetranectin

DEFF Research Database (Denmark)

Iba, Kousuke; Hatakeyama, Naoko; Kojima, Takashi

2009-01-01

disruption of the tetranectin gene to elucidate the biological function of tetranectin. In this study, we showed that wound healing was markedly delayed in tetranectin-null mice compared with wild-type mice. A single full-thickness incision was made in the dorsal skin. By 14 days after the incision......, the wounds fully healed in all wild-type mice based on the macroscopic closure; in contrast, the progress of wound healing in the tetranectin null mice appeared to be impaired. In histological analysis, wounds of wild-type mice showed complete reepithelialization and healed by 14 days after the incision....... However, those of tetranectin-null mice never showed complete reepithelialization at 14 days. At 21 days after the injury, the wound healed and was covered with an epidermis. These results supported the fact that tetranectin may play a role in the wound healing process....

ASIC1a Deficient Mice Show Unaltered Neurodegeneration in the Subacute MPTP Model of Parkinson Disease.

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Daniel Komnig

Full Text Available Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC. Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride.

Pax6 interacts with Iba1 and shows age-associated alterations in brain of aging mice.

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Maurya, Shashank Kumar; Mishra, Rajnikant

2017-07-01

The Pax6, a transcriptional regulator and multifunctional protein, has been found critical for neurogenesis, neuro-degeneration, mental retardation, neuroendocrine tumors, glioblastoma and astrocytomas. The age-associated alteration in the expression of Pax6 in neuron and glia has also been observed in the immunologically privileged brain. Therefore, it is presumed that Pax6 may modulate brain immunity by activation of microglia either directly interacting with genes or proteins of microglia or indirectly though inflammation associated with neurodegeneration. This report describes evaluation of expression, co-localization and interactions of Pax6 with Ionized binding protein1 (Iba1) in brain of aging mice by Immunohistochemistry, Chromatin Immuno-precipitation (ChIP) and Co-immunoprecipitation (Co-IP), respectively. The co-localization of Pax6 with Iba1 was observed in the cerebellum, cerebral cortex, hippocampus, midbrain and olfactory lobe. The Pax6 and Iba1 also interact physically. The age-dependent alteration in their expression and co-localization were also observed in mice. Results indicate Pax6-dependent activities of Iba1 in the remodelling of microglia during immunological surveillance of the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

Rapid learning of magnetic compass direction by C57BL/6 mice in a 4-armed 'plus' water maze.

Science.gov (United States)

Phillips, John B; Youmans, Paul W; Muheim, Rachel; Sloan, Kelly A; Landler, Lukas; Painter, Michael S; Anderson, Christopher R

2013-01-01

Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180(°) so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds.

Cloning Mice.

Science.gov (United States)

Ogura, Atsuo

2017-08-01

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

Comparing Phlebotomy by Tail Tip Amputation, Facial Vein Puncture, and Tail Vein Incision in C57BL/6 Mice by Using Physiologic and Behavioral Metrics of Pain and Distress.

Science.gov (United States)

Moore, Elizabeth S; Cleland, Thomas A; Williams, Wendy O; Peterson, Christine M; Singh, Bhupinder; Southard, Teresa L; Pasch, Bret; Labitt, Rachael N; Daugherity, Erin K

2017-05-01

Tail tip amputation with minimal restraint is not widely used for mouse phlebotomy. In part, this infrequency may reflect policies influenced by tail tip amputation procedures for genotyping, which involve greater handling and tissue removal. To assess tail tip amputation with minimal restraint as a phlebotomy technique, we compared it with 2 more common methods: scruffing with facial vein puncture and lateral tail vein incision with minimal restraint. Blood glucose levels, audible and ultrasonic vocalizations, postphlebotomy activity and grooming behavior, open field and elevated plus maze behaviors, nest-building scores, and histologic changes at the phlebotomy site were evaluated. Mice in the facial vein phlebotomy group produced more audible vocalizations, exhibited lower postphlebotomy activity in the open field, and had more severe histologic changes than did mice in the tail incision and tail tip amputation groups. Facial vein phlebotomy did not affect grooming behavior relative to sham groups, whereas tail vein incision-but not tail tip amputation-increased tail grooming compared with that in control mice. Blood glucose levels, nest-building scores, and elevated plus maze behavior did not differ between groups, and no mice in any group produced ultrasonic vocalizations. Tail tip amputation mice did not perform differently than sham mice in any metric analyzed, indicating that this technique is a potentially superior method of blood collection in mice in terms of animal wellbeing.

On the convergence of nonconvex minimization methods for image recovery.

Science.gov (United States)

Xiao, Jin; Ng, Michael Kwok-Po; Yang, Yu-Fei

2015-05-01

Nonconvex nonsmooth regularization method has been shown to be effective for restoring images with neat edges. Fast alternating minimization schemes have also been proposed and developed to solve the nonconvex nonsmooth minimization problem. The main contribution of this paper is to show the convergence of these alternating minimization schemes, based on the Kurdyka-Łojasiewicz property. In particular, we show that the iterates generated by the alternating minimization scheme, converges to a critical point of this nonconvex nonsmooth objective function. We also extend the analysis to nonconvex nonsmooth regularization model with box constraints, and obtain similar convergence results of the related minimization algorithm. Numerical examples are given to illustrate our convergence analysis.

Minimal-change nephropathy and malignant thymoma.

Science.gov (United States)

Varsano, S; Bruderman, I; Bernheim, J L; Rathaus, M; Griffel, B

1980-05-01

A 56-year-old man had fever, precordial pain, and a mediastinal mass. The mass disappeared two months later and the patient remained asymptomatic for 2 1/2 years. At that time a full-blown nephrotic syndrome developed, with minimal-change glomerulopathy. The chest x-ray film showed the reappearance of a giant mediastinal mass. On biopsy of the mass, malignant thymoma was diagnosed. Association between minimal-change disease and Hodgkin's disease is well known, while the association with malignant thymoma has not been previously reported. The relationship between malignant thymoma and minimal-change disease is discussed, and a possible pathogenic mechanism involving cell-mediated immunity is proposed.

Hypoglycemic and anti-hyperglycemic activity of Triphalādi granules in mice

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Ankush Gunjal

2016-01-01

Conclusion: Triphalādi granules have significant hypoglycemic and anti-hyperglycemic activity in mice with minimal effect on BSL below normal range. The studies suggest the potential role of Triphalādi granules as an alternative adjuvant therapy in diabetic individuals for the control of the blood glucose level.

On the isoperimetric rigidity of extrinsic minimal balls

DEFF Research Database (Denmark)

Markvorsen, Steen; Palmer, V.

2003-01-01

We consider an m-dimensional minimal submanifold P and a metric R-sphere in the Euclidean space R-n. If the sphere has its center p on P, then it will cut out a well defined connected component of P which contains this center point. We call this connected component an extrinsic minimal R-ball of P....... The quotient of the volume of the extrinsic ball and the volume of its boundary is not larger than the corresponding quotient obtained in the space form standard situation, where the minimal submanifold is the totally geodesic linear subspace R-m. Here we show that if the minimal submanifold has dimension...... larger than 3, if P is not too curved along the boundary of an extrinsic minimal R-ball, and if the inequality alluded to above is an equality for the extrinsic minimal ball, then the minimal submanifold is totally geodesic....

Minimal Function Graphs are not Instrumented

DEFF Research Database (Denmark)

Mycroft, Alan; Rosendahl, Mads

1992-01-01

The minimal function graph semantics of Jones and Mycroft is a standard denotational semantics modified to include only `reachable' parts of a program. We show that it may be expressed directly in terms of the standard semantics without the need for instrumentation at the expression level and......, in doing so, bring out a connection with strictness. This also makes it possible to prove a stronger theorem of correctness for the minimal function graph semantics....

Psychological stress exposure to aged mice causes abnormal feeding patterns with changes in the bout number.

Science.gov (United States)

Yamada, Chihiro; Mogami, Sachiko; Hattori, Tomohisa

2017-11-09

Stress responses are affected by aging. However, studies on stress-related changes in feeding patterns with aging subject are minimal. We investigated feeding patterns induced by two psychological stress models, revealing characteristics of stress-induced feeding patterns as "meal" and "bout" (defined as the minimum feeding behavior parameters) in aged mice. Feeding behaviors of C57BL/6J mice were monitored for 24 h by an automatic monitoring device. Novelty stress reduced the meal amount over the 24 h in both young and aged mice, but as a result of a time course study it was persistent in aged mice. In addition, the decreased bout number was more pronounced in aged mice than in young mice. The 24-h meal and bout parameters did not change in either the young or aged mice following water avoidance stress (WAS). However, the meal amount and bout number increased in aged mice for 0-6 h after WAS exposure but remained unchanged in young mice. Our findings suggest that changes in bout number may lead to abnormal stress-related feeding patterns and may be one tool for evaluating eating abnormality in aged mice.

The environmental chemical tributyltin chloride (TBT) shows both estrogenic and adipogenic activities in mice which might depend on the exposure dose.

Science.gov (United States)

Penza, M; Jeremic, M; Marrazzo, E; Maggi, A; Ciana, P; Rando, G; Grigolato, P G; Di Lorenzo, D

2011-08-15

Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5μg/kg). At higher doses (50-500μg/kg), TBT also activated estrogen receptors (ERs) in adipose cells in vitro and in vivo, based on results from acute and longitudinal studies in ERE/luciferase reporter mice. In 3T3-L1 cells (which have no ERs), transiently transfected with the ERE-dependent reporter plus or minus ERα or ERβ, TBT (in a dose range of 1-100nM) directly targets each ER subtype in a receptor-specific manner through a direct mechanism mediated by ERα in undifferentiated preadipocytic cells and by ERβ in differentiating adipocytes. The ER antagonist ICI-182,780 inhibits this effect. In summary, the results of this work suggest that TBT is adipogenic at all ages and in both sexes and that it might be an ER activator in fat cells. These findings might help to resolve the apparent paradox of an adipogenic chemical being also an estrogen receptor activator by showing that the two apparently opposite actions are separated by the different doses to which the organism is exposed. Copyright © 2011 Elsevier Inc. All rights reserved.

Noether symmetry for non-minimally coupled fermion fields

International Nuclear Information System (INIS)

Souza, Rudinei C de; Kremer, Gilberto M

2008-01-01

A cosmological model where a fermion field is non-minimally coupled with the gravitational field is studied. By applying Noether symmetry the possible functions for the potential density of the fermion field and for the coupling are determined. Cosmological solutions are found showing that the non-minimally coupled fermion field behaves as an inflaton describing an inflationary scenario, whereas the minimally coupled fermion field describes a decelerated period, behaving as a standard matter field

Non-minimally coupled tachyon and inflation

International Nuclear Information System (INIS)

Piao Yunsong; Huang Qingguo; Zhang Xinmin; Zhang Yuanzhong

2003-01-01

In this Letter, we consider a model of tachyon with a non-minimal coupling to gravity and study its cosmological effects. Regarding inflation, we show that only for a specific coupling of tachyon to gravity this model satisfies observations and solves various problems which exist in the single and multi tachyon inflation models. But noting in the string theory the coupling coefficient of tachyon to gravity is of order g s , which in general is very small, we can hardly expect that the non-minimally coupling of tachyon to gravity could provide a reasonable tachyon inflation scenario. Our work may be a meaningful try for the cosmological effect of tachyon non-minimally coupled to gravity

Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice.

Science.gov (United States)

Wakayama, Hirotaka; Hashimoto, Naozumi; Matsushita, Yoshihiro; Matsubara, Kohki; Yamamoto, Noriyuki; Hasegawa, Yoshinori; Ueda, Minoru; Yamamoto, Akihito

2015-08-01

Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder characterized by acute respiratory failure, resulting from severe, destructive lung inflammation and irreversible lung fibrosis. We evaluated the use of stem cells derived from human exfoliated deciduous teeth (SHEDs) or SHED-derived serum-free conditioned medium (SHED-CM) as treatments for bleomycin (BLM)-induced mice acute lung injury (ALI), exhibiting several pathogenic features associated with the human disease ARDS. Mice with BLM-induced ALI with or without SHED or SHED-CM treatment were examined for weight loss and survival. The lung tissue was characterized by histological and real-time quantitative polymerase chain reaction analysis. The effects of SHED-CM on macrophage differentiation in vitro were also assessed. A single intravenous administration of either SHEDs or SHED-CM attenuated the lung injury and weight loss in BLM-treated mice and improved their survival rate. Similar recovery levels were seen in the SHEDs and SHED-CM treatment groups, suggesting that SHED improves ALI by paracrine mechanisms. SHED-CM contained multiple therapeutic factors involved in lung-regenerative mechanisms. Importantly, SHED-CM attenuated the BLM-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, accompanied by the induction of anti-inflammatory M2-like lung macrophages. Furthermore, SHED-CM promoted the in vitro differentiation of bone marrow-derived macrophages into M2-like cells, which expressed high levels of Arginase1, CD206 and Ym-1. Our results suggest that SHED-secreted factors provide multifaceted therapeutic effects, including a strong M2-inducing activity, for treating BLM-induced ALI. This work may open new avenues for research on stem cell-based ARDS therapies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The Effects of Minimal Length, Maximal Momentum, and Minimal Momentum in Entropic Force

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Zhong-Wen Feng

2016-01-01

Full Text Available The modified entropic force law is studied by using a new kind of generalized uncertainty principle which contains a minimal length, a minimal momentum, and a maximal momentum. Firstly, the quantum corrections to the thermodynamics of a black hole are investigated. Then, according to Verlinde’s theory, the generalized uncertainty principle (GUP corrected entropic force is obtained. The result shows that the GUP corrected entropic force is related not only to the properties of the black holes but also to the Planck length and the dimensionless constants α0 and β0. Moreover, based on the GUP corrected entropic force, we also derive the modified Einstein’s field equation (EFE and the modified Friedmann equation.

Environmental factors regulate Paneth cell phenotype and host susceptibility to intestinal inflammation in Irgm1-deficient mice

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Allison R. Rogala

2018-02-01

Full Text Available Crohn's disease (CD represents a chronic inflammatory disorder of the intestinal tract. Several susceptibility genes have been linked to CD, though their precise role in the pathogenesis of this disorder remains unclear. Immunity-related GTPase M (IRGM is an established risk allele in CD. We have shown previously that conventionally raised (CV mice lacking the IRGM ortholog, Irgm1 exhibit abnormal Paneth cells (PCs and increased susceptibility to intestinal injury. In the present study, we sought to utilize this model system to determine if environmental conditions impact these phenotypes, as is thought to be the case in human CD. To accomplish this, wild-type and Irgm1−/− mice were rederived into specific pathogen-free (SPF and germ-free (GF conditions. We next assessed how these differential housing environments influenced intestinal injury patterns, and epithelial cell morphology and function in wild-type and Irgm1−/− mice. Remarkably, in contrast to CV mice, SPF Irgm1−/− mice showed only a slight increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF Irgm1−/− mice also displayed minimal abnormalities in PC number and morphology, and in antimicrobial peptide expression. Goblet cell numbers and epithelial proliferation were also unaffected by Irgm1 in SPF conditions. No microbial differences were observed between wild-type and Irgm1−/− mice, but gut bacterial communities differed profoundly between CV and SPF mice. Specifically, Helicobacter sequences were significantly increased in CV mice; however, inoculating SPF Irgm1−/− mice with Helicobacter hepaticus was not sufficient to transmit a pro-inflammatory phenotype. In summary, our findings suggest the impact of Irgm1-deficiency on susceptibility to intestinal inflammation and epithelial function is critically dependent on environmental influences. This work establishes the importance of Irgm1−/− mice as a model to elucidate host

Melatonin Efficacy in Obese Leptin-Deficient Mice Heart

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Alessandra Stacchiotti

2017-12-01

Full Text Available Cardiomyocytes are particularly sensitive to oxidative damage due to the link between mitochondria and sarcoplasmic reticulum necessary for calcium flux and contraction. Melatonin, important indoleamine secreted by the pineal gland during darkness, also has important cardioprotective properties. We designed the present study to define morphological and ultrastructural changes in cardiomyocytes and mainly in mitochondria of an animal model of obesity (ob/ob mice, when treated orally or not with melatonin at 100 mg/kg/day for 8 weeks (from 5 up to 13 week of life. We observed that ob/ob mice mitochondria in sub-sarcolemmal and inter-myofibrillar compartments are often devoid of cristae with an abnormally large size, which are called mega-mitochondria. Moreover, in ob/ob mice the hypertrophic cardiomyocytes expressed high level of 4hydroxy-2-nonenal (4HNE, a marker of lipid peroxidation but scarce degree of mitofusin2, indicative of mitochondrial sufferance. Melatonin oral supplementation in ob/ob mice restores mitochondrial cristae, enhances mitofusin2 expression and minimizes 4HNE and p62/SQSTM1, an index of aberrant autophagic flux. At pericardial fat level, adipose tissue depot strictly associated with myocardium infarction, melatonin reduces adipocyte hypertrophy and inversely regulates 4HNE and adiponectin expressions. In summary, melatonin might represent a safe dietary adjuvant to hamper cardiac mitochondria remodeling and the hypoxic status that occur in pre-diabetic obese mice at 13 weeks of life.

Supersymmetric Hybrid Inflation with Non-Minimal Kähler potential

CERN Document Server

Bastero-Gil, M; Shafi, Q

2007-01-01

Minimal supersymmetric hybrid inflation based on a minimal Kahler potential predicts a spectral index n_s\\gsim 0.98. On the other hand, WMAP three year data prefers a central value n_s \\approx 0.95. We propose a class of supersymmetric hybrid inflation models based on the same minimal superpotential but with a non-minimal Kahler potential. Including radiative corrections using the one-loop effective potential, we show that the prediction for the spectral index is sensitive to the small non-minimal corrections, and can lead to a significantly red-tilted spectrum, in agreement with WMAP.

Validation of 18FDG biodistribution data in healthy mice obtained with G.E. LABPET4

International Nuclear Information System (INIS)

Rocha, Adriana Marcia Guimaraes; Mendes, Bruno Melo; Malamut, Carlos; Silva, Juliana Batista da; Campos, Danielle Cunha; Santos, Priscilla Figueiredo

2013-01-01

The aim of this study is to validate biodistribution data obtained with CDTN's MicroPET. To achieve this goal, correction and image acquisition procedures were established. 1 '8FDG dynamic images of 90 minutes were obtained following these procedures for Swiss healthy mice. Biodistribution data obtained after quantification of acquired images were compared with data available in literature. Considering the uptake time of 60 minutes and similar animal handling, data obtained in this work showed a satisfactory agreement with reference data. Some evaluated organs/tissues showed high interindividual variability. These findings are consistent with those observed in reference literature. However, improvements in VOI positioning VOI technique as well as increasing the number of animals (n) per group can minimize this problem. (author)

Studies on the surface antigenicity and susceptibility to antibody-dependent killing of developing schistosomula using sera from chronically infected mice and mice vaccinated with irradiated cercariae

International Nuclear Information System (INIS)

Bickle, Q.D.; Ford, M.J.

1982-01-01

Changes in the surface antigenicity and susceptibility to in vitro killing during development of schistosomula of Schistosoma mansoni were studied using serum from chronically infected mice (CIS) and from mice vaccinated with highly irradiated (20 krad) cercariae (VS). Binding of these sera was quantitated by counting the number of P388D 1 cells (a transformed, macrophage-like cell of mouse origin, bearing Fc receptors for IgG) binding to the parasite surface. Compared with schistosomula derived in vitro by mechanical transformation (MS), schistosomula recovered 3 hr after skin penetration in vitro (SS) showed a significant loss in surface binding of CIS. Schistosomula recovered 3 hr after skin penetration in vivo (SRS) showed even less binding, and this trend continued such that parasites recovered from the lungs 5 days after infection (LS) showed only minimal binding, and 10-day-old worms from the portal system showed no significant binding. In contrast, VS, which bound significantly less well to MS than CIS, showed enhanced binding to SS, and in the face of their declining antigenicity with respect to CIS, 3- to 24-hr SRS maintained this raised level of antigenicity. Although there appeared to be a decline in binding of VS thereafter, LS remained antigenic, still binding as many cells as MS did despite the fact that they also expressed host antigens detected usng antisera raised against mouse RBC. In spite of this persistence of VS binding up to the lung stage, resistance to eosinophil-mediated killing in vitro had developed by 48 hr post-infection, and LS were totally resistant to both eosinophil- and C-mediated killing

Radioprotection conferred by dextran sulfate given before irradiation in mice

International Nuclear Information System (INIS)

Ross, W.M.; Peeke, J.

1986-01-01

Dextran sulfate (DS) has been observed to cause mobilization (fivefold) of hemopoietic stem cells (HSC) and leukocytes, primarily lymphocytes, into the peripheral blood of mice within 2-3 h after intraperitoneal (i.p.) injection. This effect was dose dependent and was prolonged for several hours when the high-molecular-weight version DS500 (500,000 daltons) was used. When DS500 was given 1-3 days before irradiation, hemopoietic recovery was markedly enhanced. Postirradiation injection was ineffective. By ten days after irradiation (7.0 Gy), the number of endogenous spleen colonies (CFUs) and the splenic mass were much larger if DS pretreatment had been given. This effect was dependent on the dose of DS500 and on the time administered, 60 mg/kg producing a maximal effect when given three days before irradiation. DS500 caused a transient anaphylactoid shock, however, in most mice--mild at low doses but potentially lethal at doses above 40 mg/kg (10% mortality within 1-3 days after 60 mg/kg). The following results were obtained with 50 mg/kg, a compromise dose causing minimal mortality (3%) given three days before irradiation. Reticulocyte reappearance was earlier in irradiated mice given DS500, indicating earlier erythropoietic recovery. Some of these reticulocytes were resistant to lysing agents, so their appearance could be detected using the Coulter electronic cell counter, as well as in stained blood smears. The 30-day mortality due to bone marrow failure after irradiation was significantly decreased in DS-treated mice below 9.5 Gy, and the LD50/30 was increased by 0.5 Gy. This study shows that dextran sulfate exerts a radioprotective influence on the hemopoietic system and hence survival when administered prophylactically

Experimental transmission of M. leprae into the testes of mice born from 60Co-irradiated pregnant mice

International Nuclear Information System (INIS)

Sushida, Kiyo; Tanemura, Mutsuko

1979-01-01

R 1 -mice, which were born from pregnant mice (R-P) irradiated with 60 CO 300 R were inoculated with leprosy bacilli into the testis. Recently, the author reported that the skin homograft survival duration in 60 CO-irradiated mice (R-P) was shown to be longer than the duration in the R 1 -F mice. The acid-fast bacilli, the so-called globi, were often found at the inoculated site of R-P mice, but not in the R 1 -F mice. The R 1 -F females bred with normal males and the R 2 -F females bred with normal males were both irradiated with 60 CO 300 R, and the R 2 -F male offspring from this R 1 -F and the R 3 -F male offspring from this R 2 -F showed the same increase in sensitivity to leprosy bacilli as the R-P generation. Acid-fast bacilli (globi, +G) were also found in the testes of the R 2 -F and R 3 -F males. IR-F mice which had received 131 I-Na 100 μci injections and also 60 CO 300 R irradiations during their fetus-term, showed few increase in sensitivity to infection of leprosy bacilli. (author)

Implementation of minimally invasive and objective humane endpoints in the study of murine Plasmodium infections

DEFF Research Database (Denmark)

Dellavalle, B; Kirchhoff, J; Maretty, L

2014-01-01

SUMMARY Defining appropriate and objective endpoints for animal research can be difficult. Previously we evaluated and implemented a body temperature (BT) of ECM) and were interested in a similar endpoint for a model of severe malarial...... anaemia (SMA). Furthermore, we investigate the potential of a minimally invasive, non-contact infrared thermometer for repeated BT measurement. ECM was induced with Plasmodium berghei ANKA infection in C57Bl/6 mice. SMA was induced with Plasmodium chabaudi AS infection in A/J mice. Our previous published...... endpoint was applied in ECM and 30 °C was pre-determined as the lowest permitted limit for termination in SMA according to consultation with the Danish Animal Inspectorate. Infrared thermometer was compared with the rectal probe after cervical dislocation, ECM and SMA. Linear regression analysis of rectal...

Hyperoxia Inhibits T Cell Activation in Mice

Science.gov (United States)

Hughes-Fulford, M.; Meissler, J.; Aguayo, E. T.; Globus, R.; Aguado, J.; Candelario, T.

2013-02-01

Background: The immune response is blunted in mice and humans in spaceflight. The effects of hyperoxia in mice alter expression of some of the same immune response genes. If these two conditions are additive, there could be an increased risk of infection in long duration missions. Immunosuppression is seen in healthy astronauts who have flown in space; however little is known about the mechanisms that cause the reduced immunity in spaceflight. Here we examine the role of oxidative stress on mice exposed to periods of high O2 levels mimicking pre-breathing protocols and extravehicular activity (EVA). To prevent decompression sickness, astronauts are exposed to elevated oxygen (hyperoxia) before and during EVA activities. Spaceflight missions may entail up to 24 hours of EVA per crewmember per week to perform construction and maintenance tasks. The effectiveness and success of these missions depends on designing EVA systems and protocols that maximize human performance and efficiency while minimizing health and safety risks for crewmembers. To our knowledge, no studies have been conducted on the immune system under 100% oxygen exposures to determine the potential for immune compromise due to prolonged and repeated EVAs. Methods: Animals were exposed to hyperoxic or control conditions for 8 hours per day over a period of 3 days, initiated 4 hours into the dark cycle (12h dark/12h light), using animal environmental control cabinets and oxygen controller (Biospherix, Lacona, NY). Experimental mice were exposed to 98-100% oxygen as a model for pre-breathing and EVA conditions, while control mice were maintained in chambers supplied with compressed air. These are ground control studies where we use real-time RTPCR (qRTPCR) to measure gene expression of the early immune gene expression during bead activation of splenocytes of normoxic and hyperoxic mice. All procedures were reviewed and approved by the IACUC at Ames Research Center. After the last 8h of hyperoxic exposure

Review of Minimal Flavor Constraints for Technicolor

DEFF Research Database (Denmark)

S. Fukano, Hidenori; Sannino, Francesco

2010-01-01

We analyze the constraints on the the vacuum polarization of the standard model gauge bosons from a minimal set of flavor observables valid for a general class of models of dynamical electroweak symmetry breaking. We will show that the constraints have a strong impact on the self-coupling and mas......We analyze the constraints on the the vacuum polarization of the standard model gauge bosons from a minimal set of flavor observables valid for a general class of models of dynamical electroweak symmetry breaking. We will show that the constraints have a strong impact on the self...

Flattening the inflaton potential beyond minimal gravity

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Lee Hyun Min

2018-01-01

Full Text Available We review the status of the Starobinsky-like models for inflation beyond minimal gravity and discuss the unitarity problem due to the presence of a large non-minimal gravity coupling. We show that the induced gravity models allow for a self-consistent description of inflation and discuss the implications of the inflaton couplings to the Higgs field in the Standard Model.

Involvement of interleukin-1 in lead nitrate-induced hypercholesterolemia in mice.

Science.gov (United States)

Kojima, Misaki; Ashino, Takashi; Yoshida, Takemi; Iwakura, Yoichiro; Degawa, Masakuni

2012-01-01

Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and cholesterol 7α-hydroxylase (Cyp7a1) are rate-limiting enzymes for cholesterol biosynthesis and catabolism, respectively. Involvement of inflammatory cytokines, particularly interleukin-1 (IL-1), in alterations of HMGR and Cyp7a1 gene expression during development of lead nitrate (LN)-induced hypercholesterolemia was examined in IL-1α/β-knockout (IL-1-KO) and wild-type (WT) mice. Lead nitrate treatment of WT mice led to not only a marked downregulation of the Cyp7a1 gene at 6-12 h, but also a significant upregulation of the HMGR gene at 12 h. However, such changes were not observed at significant levels in IL-1-KO mice, although a slight, transient downregulation of the Cyp7a1 gene and a minimal upregulation of the HMGR gene occurred at 6 h and 24 h, respectively. Consequently, LN treatment led to development of hypercholesterolemia at 24 h in WT mice, but not in IL-1-KO mice. Furthermore, in WT mice, significant LN-mediated increases were observed at 3-6 h in hepatic IL-1 levels, which can modulate gene expression of Cyp7a1 and HMGR. These findings indicate that, in mice, LN-mediated increases in hepatic IL-1 levels contribute, at least in part, to altered expressions of Cyp7a1 and HMGR genes, and eventually to hypercholesterolemia development.

MicroRNA and Transcriptomic Profiling Showed miRNA-Dependent Impairment of Systemic Regulation and Synthesis of Biomolecules in Rag2 KO Mice.

Science.gov (United States)

Reza, Abu Musa Md Talimur; Choi, Yun-Jung; Kim, Jin-Hoi

2018-02-27

The Rag2 knockout (KO) mouse is a well-established immune-compromised animal model for biomedical research. A comparative study identified the deregulated expression of microRNAs (miRNAs) and messenger RNAs (mRNAs) in Rag2 KO mice. However, the interaction between deregulated genes and miRNAs in the alteration of systemic (cardiac, renal, hepatic, nervous, and hematopoietic) regulations and the synthesis of biomolecules (such as l-tryptophan, serotonin, melatonin, dopamine, alcohol, noradrenaline, putrescine, and acetate) are unclear. In this study, we analyzed both miRNA and mRNA expression microarray data from Rag2 KO and wild type mice to investigate the possible role of miRNAs in systemic regulation and biomolecule synthesis. A notable finding obtained from this analysis is that the upregulation of several genes which are target molecules of the downregulated miRNAs in Rag2 KO mice, can potentially trigger the degradation of l-tryptophan, thereby leading to the systemic impairment and alteration of biomolecules synthesis as well as changes in behavioral patterns (such as stress and fear responses, and social recognition memory) in Rag2 gene-depleted mice. These findings were either not observed or not explicitly described in other published Rag2 KO transcriptome analyses. In conclusion, we have provided an indication of miRNA-dependent regulations of clinical and pathological conditions in cardiac, renal, hepatic, nervous, and hematopoietic systems in Rag2 KO mice. These results may significantly contribute to the prediction of clinical disease caused by Rag2 deficiency.

MicroRNA and Transcriptomic Profiling Showed miRNA-Dependent Impairment of Systemic Regulation and Synthesis of Biomolecules in Rag2 KO Mice

Directory of Open Access Journals (Sweden)

Abu Musa Md Talimur Reza

2018-02-01

Full Text Available The Rag2 knockout (KO mouse is a well-established immune-compromised animal model for biomedical research. A comparative study identified the deregulated expression of microRNAs (miRNAs and messenger RNAs (mRNAs in Rag2 KO mice. However, the interaction between deregulated genes and miRNAs in the alteration of systemic (cardiac, renal, hepatic, nervous, and hematopoietic regulations and the synthesis of biomolecules (such as l-tryptophan, serotonin, melatonin, dopamine, alcohol, noradrenaline, putrescine, and acetate are unclear. In this study, we analyzed both miRNA and mRNA expression microarray data from Rag2 KO and wild type mice to investigate the possible role of miRNAs in systemic regulation and biomolecule synthesis. A notable finding obtained from this analysis is that the upregulation of several genes which are target molecules of the downregulated miRNAs in Rag2 KO mice, can potentially trigger the degradation of l-tryptophan, thereby leading to the systemic impairment and alteration of biomolecules synthesis as well as changes in behavioral patterns (such as stress and fear responses, and social recognition memory in Rag2 gene-depleted mice. These findings were either not observed or not explicitly described in other published Rag2 KO transcriptome analyses. In conclusion, we have provided an indication of miRNA-dependent regulations of clinical and pathological conditions in cardiac, renal, hepatic, nervous, and hematopoietic systems in Rag2 KO mice. These results may significantly contribute to the prediction of clinical disease caused by Rag2 deficiency.

Cdk2-Null Mice Are Resistant to ErbB-2-Induced Mammary Tumorigenesis

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Dipankar Ray

2011-05-01

Full Text Available The concept of targeting G1 cyclin-dependent kinases (CDKs in breast cancer treatments is supported by the fact that the genetic ablation of Cdk4 had minimal impacts on normal cell proliferation in majority of cell types, resulting in near-normal mouse development, whereas such loss of Cdk4 completely abrogated ErbB-2/neu-induced mammary tumorigenesis in mice. In most human breast cancer tissues, another G1-regulatory CDK, CDK2, is also hyperactivated by various mechanisms and is believed to be an important therapeutic target. In this report, we provide genetic evidence that CDK2 is essential for proliferation and oncogenesis of murine mammary epithelial cells. We observed that 87% of Cdk2-null mice were protected from ErbB-2-induced mammary tumorigenesis. Mouse embryonic fibroblasts isolated from Cdk2-null mouse showed resistance to various oncogene-induced transformation. Previously, we have reported that hemizygous loss of Cdc25A, the major activator of CDK2, can also protect mice from ErbB-2-induced mammary tumorigenesis [Cancer Res (2007 67(14: 6605–11]. Thus, we propose that CDC25A-CDK2 pathway is critical for the oncogenic action of ErbB-2 in mammary epithelial cells, in a manner similar to Cyclin D1/CDK4 pathway.

Differences in the immunologic reactivity of mice treated with UVB or methoxsalen plus UVA radiation

International Nuclear Information System (INIS)

Kripke, M.L.; Morison, W.L.; Parrish, J.A.

1981-01-01

Skin tumors induced in mice by chronic exposure to UVB radiation are often highly antigenic and regress when transplanted into normal syngeneic animals, but grow progressively in immunosuppressed mice. Exposure of mice to subtumorigenic doses of UVB radiation can abolish this immunologic rejection phenomenon. In this study, we have investigated the effects of treatment with 8-methoxypsoralen plus UVA radiation (PUVA) on the rejection of antigenic UVB-induced tumors. PUVA treatment, with either topical or systemic administration of the psoralen, did not alter the normal process of rejection of UVB-induced tumors. Mice treated with both minimally and markedly phototoxic doses of PUVA rejected tumors with a frequency similar to that seen in untreated animals, although these tumors grew progressively in UVB-irradiated mice. These results indicate that the effects of PUVA treatment differ from those of UVB irradiation in that PUVA treatment does not alter the immunologic rejection of UVB-induced tumors

MRI of Mouse Models for Gliomas Shows Similarities to Humans and Can Be Used to Identify Mice for Preclinical Trials

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Jason A. Koutcher

2002-01-01

Full Text Available Magnetic resonance imaging (MRI has been utilized for screening and detecting brain tumors in mice based upon their imaging characteristics appearance and their pattern of enhancement. Imaging of these tumors reveals many similarities to those observed in humans with identical pathology. Specifically, high-grade murine gliomas have histologic characteristics of glioblastoma multiforme (GBM with contrast enhancement after intravenous administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, implying disruption of the blood-brain barrier in these tumors. In contrast, low-grade murine oligodendrogliomas do not reveal contrast enhancement, similar to human tumors. MRI can be used to identify mice with brain neoplasms as inclusion criteria in preclinical trials.

Minimal Left-Right Symmetric Dark Matter.

Science.gov (United States)

Heeck, Julian; Patra, Sudhanwa

2015-09-18

We show that left-right symmetric models can easily accommodate stable TeV-scale dark matter particles without the need for an ad hoc stabilizing symmetry. The stability of a newly introduced multiplet either arises accidentally as in the minimal dark matter framework or comes courtesy of the remaining unbroken Z_{2} subgroup of B-L. Only one new parameter is introduced: the mass of the new multiplet. As minimal examples, we study left-right fermion triplets and quintuplets and show that they can form viable two-component dark matter. This approach is, in particular, valid for SU(2)×SU(2)×U(1) models that explain the recent diboson excess at ATLAS in terms of a new charged gauge boson of mass 2 TeV.

Dimensionality of Local Minimizers of the Interaction Energy

KAUST Repository

Balagué , D.; Carrillo, J. A.; Laurent, T.; Raoul, G.

2013-01-01

In this work we consider local minimizers (in the topology of transport distances) of the interaction energy associated with a repulsive-attractive potential. We show how the dimensionality of the support of local minimizers is related to the repulsive strength of the potential at the origin. © 2013 Springer-Verlag Berlin Heidelberg.

Dimensionality of Local Minimizers of the Interaction Energy

KAUST Repository

Balagué, D.

2013-05-22

In this work we consider local minimizers (in the topology of transport distances) of the interaction energy associated with a repulsive-attractive potential. We show how the dimensionality of the support of local minimizers is related to the repulsive strength of the potential at the origin. © 2013 Springer-Verlag Berlin Heidelberg.

Ultrafast mid-IR laser scalpel: protein signals of the fundamental limits to minimally invasive surgery.

Science.gov (United States)

Amini-Nik, Saeid; Kraemer, Darren; Cowan, Michael L; Gunaratne, Keith; Nadesan, Puviindran; Alman, Benjamin A; Miller, R J Dwayne

2010-09-28

Lasers have in principle the capability to cut at the level of a single cell, the fundamental limit to minimally invasive procedures and restructuring biological tissues. To date, this limit has not been achieved due to collateral damage on the macroscale that arises from thermal and shock wave induced collateral damage of surrounding tissue. Here, we report on a novel concept using a specifically designed Picosecond IR Laser (PIRL) that selectively energizes water molecules in the tissue to drive ablation or cutting process faster than thermal exchange of energy and shock wave propagation, without plasma formation or ionizing radiation effects. The targeted laser process imparts the least amount of energy in the remaining tissue without any of the deleterious photochemical or photothermal effects that accompanies other laser wavelengths and pulse parameters. Full thickness incisional and excisional wounds were generated in CD1 mice using the Picosecond IR Laser, a conventional surgical laser (DELight Er:YAG) or mechanical surgical tools. Transmission and scanning electron microscopy showed that the PIRL laser produced minimal tissue ablation with less damage of surrounding tissues than wounds formed using the other modalities. The width of scars formed by wounds made by the PIRL laser were half that of the scars produced using either a conventional surgical laser or a scalpel. Aniline blue staining showed higher levels of collagen in the early stage of the wounds produced using the PIRL laser, suggesting that these wounds mature faster. There were more viable cells extracted from skin using the PIRL laser, suggesting less cellular damage. β-catenin and TGF-β signalling, which are activated during the proliferative phase of wound healing, and whose level of activation correlates with the size of wounds was lower in wounds generated by the PIRL system. Wounds created with the PIRL systsem also showed a lower rate of cell proliferation. Direct comparison of wound

Ultrafast mid-IR laser scalpel: protein signals of the fundamental limits to minimally invasive surgery.

Directory of Open Access Journals (Sweden)

Saeid Amini-Nik

2010-09-01

Full Text Available Lasers have in principle the capability to cut at the level of a single cell, the fundamental limit to minimally invasive procedures and restructuring biological tissues. To date, this limit has not been achieved due to collateral damage on the macroscale that arises from thermal and shock wave induced collateral damage of surrounding tissue. Here, we report on a novel concept using a specifically designed Picosecond IR Laser (PIRL that selectively energizes water molecules in the tissue to drive ablation or cutting process faster than thermal exchange of energy and shock wave propagation, without plasma formation or ionizing radiation effects. The targeted laser process imparts the least amount of energy in the remaining tissue without any of the deleterious photochemical or photothermal effects that accompanies other laser wavelengths and pulse parameters. Full thickness incisional and excisional wounds were generated in CD1 mice using the Picosecond IR Laser, a conventional surgical laser (DELight Er:YAG or mechanical surgical tools. Transmission and scanning electron microscopy showed that the PIRL laser produced minimal tissue ablation with less damage of surrounding tissues than wounds formed using the other modalities. The width of scars formed by wounds made by the PIRL laser were half that of the scars produced using either a conventional surgical laser or a scalpel. Aniline blue staining showed higher levels of collagen in the early stage of the wounds produced using the PIRL laser, suggesting that these wounds mature faster. There were more viable cells extracted from skin using the PIRL laser, suggesting less cellular damage. β-catenin and TGF-β signalling, which are activated during the proliferative phase of wound healing, and whose level of activation correlates with the size of wounds was lower in wounds generated by the PIRL system. Wounds created with the PIRL systsem also showed a lower rate of cell proliferation. Direct

Inflation in non-minimal matter-curvature coupling theories

Energy Technology Data Exchange (ETDEWEB)

Gomes, C.; Bertolami, O. [Departamento de Física e Astronomia and Centro de Física do Porto, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto (Portugal); Rosa, J.G., E-mail: claudio.gomes@fc.up.pt, E-mail: joao.rosa@ua.pt, E-mail: orfeu.bertolami@fc.up.pt [Departamento de Física da Universidade de Aveiro and CIDMA, Campus de Santiago, 3810-183 Aveiro (Portugal)

2017-06-01

We study inflationary scenarios driven by a scalar field in the presence of a non-minimal coupling between matter and curvature. We show that the Friedmann equation can be significantly modified when the energy density during inflation exceeds a critical value determined by the non-minimal coupling, which in turn may considerably modify the spectrum of primordial perturbations and the inflationary dynamics. In particular, we show that these models are characterised by a consistency relation between the tensor-to-scalar ratio and the tensor spectral index that can differ significantly from the predictions of general relativity. We also give examples of observational predictions for some of the most commonly considered potentials and use the results of the Planck collaboration to set limits on the scale of the non-minimal coupling.

Inherent and antigen-induced airway hyperreactivity in NC mice

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Tetsuto Kobayashi

1999-01-01

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

A modified choline-deficient, ethionine-supplemented diet reduces morbidity and retains a liver progenitor cell response in mice

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Adam M. Passman

2015-12-01

Full Text Available The choline-deficient, ethionine-supplemented (CDE dietary model induces chronic liver damage, and stimulates liver progenitor cell (LPC-mediated repair. Long-term CDE administration leads to hepatocellular carcinoma in rodents and lineage-tracing studies show that LPCs differentiate into functional hepatocytes in this model. The CDE diet was first modified for mice by our laboratory by separately administering choline-deficient chow and ethionine in the drinking water (CD+E diet. Although this CD+E diet is widely used, concerns with variability in weight loss, morbidity, mortality and LPC response have been raised by researchers who have adopted this model. We propose that these inconsistencies are due to differential consumption of chow and ethionine in the drinking water, and that incorporating ethionine in the choline-deficient chow, and altering the strength, will achieve better outcomes. Therefore, C57Bl/6 mice, 5 and 6 weeks of age, were fed an all-inclusive CDE diet of various strengths (67% to 100% for 3 weeks. The LPC response was quantitated and cell lines were derived. We found that animal survival, LPC response and liver damage are correlated with CDE diet strength. The 67% and 75% CDE diet administered to mice older than 5 weeks and greater than 18 g provides a consistent and acceptable level of animal welfare and induces a substantial LPC response, permitting their isolation and establishment of cell lines. This study shows that an all-inclusive CDE diet for mice reproducibly induces an LPC response conducive to in vivo studies and isolation, whilst minimizing morbidity and mortality.

Noninvasive Blood-Brain Barrier Opening in Live Mice

Science.gov (United States)

Choi, James J.; Pernot, Mathieu; Small, Scott; Konofagou, Elisa E.

2006-05-01

Most therapeutic agents cannot be delivered to the brain because of brain's natural defense: the Blood-Brain Barrier (BBB). It has recently been shown that Focused Ultrasound (FUS) can produce reversible and localized BBB opening in the brain when applied in the presence of ultrasound contrast agents post-craniotomy in rabbits [1]. However, a major limitation of ultrasound in the brain is the strong phase aberration and attenuation of the skull bone, and, as a result, no study of trans-cranial ultrasound-targeted drug treatment in the brain in vivo has been reported as of yet. In this study, the feasibility of BBB opening in the hippocampus of wildtype mice using FUS through the intact skull and skin was investigated. In order to investigate the effect of the skull, simulations of ultrasound wave propagation (1.5 MHz) through the skull using μCT data, and needle hydrophone measurements through an ex-vivo skull were made. The pressure field showed minimal attenuation (18% of the pressure amplitude) and a well-focused pattern through the left and right halves of the parietal bone. In experiments in vivo, the brains of four mice were sonicated through intact skull and skin. Ultrasound sonications (burst length: 20 ms; duty cycle: 20%; acoustic pressure range: 2.0 to 2.7 MPa) was applied 5 times for 30 s per shot with a 30 s delay between shots. Prior to sonication, ultrasound contrast agents (Optison; 10 μL) were injected intravenously. Contrast material enhanced high resolution MR Imaging (9.4 Tesla) was able to distinguish opening of large vessels in the region of the hippocampus. These results demonstrate the feasibility of locally opening the BBB in the mouse hippocampus using focused ultrasound through intact skull and skin. Future investigations will deal with optimization and reproducibility of the technique as well as application on Alzheimer's-model mice.

A microneedle biosensor for minimally-invasive transdermal detection of nerve agents.

Science.gov (United States)

Mishra, Rupesh K; Vinu Mohan, A M; Soto, Fernando; Chrostowski, Robert; Wang, Joseph

2017-03-13

A microneedle electrochemical biosensor for the minimally invasive detection of organophosphate (OP) chemical agents is described. The new sensor relies on the coupling of the effective biocatalytic action of organophosphorus hydrolase (OPH) with a hollow-microneedle modified carbon-paste array electrode transducer, and involves rapid square-wave voltammetric (SWV) measurements of the p-nitrophenol product of the OPH enzymatic reaction in the presence of the OP substrate. The scanning-potential SWV transduction mode offers an additional dimension of selectivity compared to common fixed-potential OPH-amperometric biosensors. The microneedle device offers a highly linear response for methyl paraoxon (MPOx) over the range of 20-180 μM, high selectivity in the presence of excess co-existing ascorbic acid and uric acid and a high stability sensor upon exposure to the interstitial fluid (ISF). The OPH microneedle sensor was successfully tested ex vivo using mice skin samples exposed to MPOx, demonstrating its promise for minimally-invasive monitoring of OP agents and pesticides and as a wearable sensor for detecting toxic compounds, in general.

Transplacental arsenic carcinogenesis in mice

International Nuclear Information System (INIS)

Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

2007-01-01

Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from days 8 to 18 of gestation, and the offspring were observed for up to 2 years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans

Impairment of visual function and retinal ER stress activation in Wfs1-deficient mice.

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Delphine Bonnet Wersinger

Full Text Available Wolfram syndrome is an early onset genetic disease (1/180,000 featuring diabetes mellitus and optic neuropathy, associated to mutations in the WFS1 gene. Wfs1-/- mouse model shows pancreatic beta cell atrophy, but its visual performance has not been investigated, prompting us to study its visual function and histopathology of the retina and optic nerve. Electroretinogram and visual evoked potentials (VEPs were performed in Wfs1-/- and Wfs1+/+ mice at 3, 6, 9 and 12 months of age. Fundi were pictured with Micron III apparatus. Retinal ganglion cell (RGC abundance was determined from Brn3a immunolabeling of retinal sections. RGC axonal loss was quantified by electron microscopy in transversal optic nerve sections. Endoplasmic reticulum stress was assessed using immunoglobulin binding protein (BiP, protein disulfide isomerase (PDI and inositol-requiring enzyme 1 alpha (Ire1α markers. Electroretinograms amplitudes were slightly reduced and latencies increased with time in Wfs1-/- mice. Similarly, VEPs showed decreased N+P amplitudes and increased N-wave latency. Analysis of unfolded protein response signaling revealed an activation of endoplasmic reticulum stress in Wfs1-/- mutant mouse retinas. Altogether, progressive VEPs alterations with minimal neuronal cell loss suggest functional alteration of the action potential in the Wfs1-/- optic pathways.

Effects of cage density on behavior in young adult mice.

Science.gov (United States)

Davidson, Lauren P; Chedester, Alan L; Cole, Marlene N

2007-08-01

Optimal housing conditions for mice can be achieved by minimizing environmental variables, such as those that may contribute to anxiety-like behavior. This study evaluated the effects of cage size on juvenile mice through assessment of differences in weaning weight, locomotor skills, and anxiety-like behavior. Eighteen pairs of male and pregnant female Swiss-Webster (Cr:SW) mice were housed in 3 different caging scenarios, providing 429, 505, or 729 cm2 of space. Litters were standardized to 10 pups per litter in each cage. Mice reared in each caging scenario were assessed with the open-field, light-dark exploration, and elevated plus-maze tests. No differences in weaning weight were noted. Mice reared in the 505- and 729-cm2 cages explored a significantly larger area of the open-field arena than did those in the 429-cm2 cages. Those reared in the 505-cm2 cages spent more time in the center of the open field than did those in the 729-cm2 cages, suggesting that anxiety-like behavior may be increased in the animals housed in the larger cages. This study did not establish a consistent link between decreased floor space and increased anxiety-like behavior; neither does there appear to be a consistent effect of available floor area on the development of locomotor skills on mouse pups.

Blackfolds, plane waves and minimal surfaces

Science.gov (United States)

Armas, Jay; Blau, Matthias

2015-07-01

Minimal surfaces in Euclidean space provide examples of possible non-compact horizon geometries and topologies in asymptotically flat space-time. On the other hand, the existence of limiting surfaces in the space-time provides a simple mechanism for making these configurations compact. Limiting surfaces appear naturally in a given space-time by making minimal surfaces rotate but they are also inherent to plane wave or de Sitter space-times in which case minimal surfaces can be static and compact. We use the blackfold approach in order to scan for possible black hole horizon geometries and topologies in asymptotically flat, plane wave and de Sitter space-times. In the process we uncover several new configurations, such as black helicoids and catenoids, some of which have an asymptotically flat counterpart. In particular, we find that the ultraspinning regime of singly-spinning Myers-Perry black holes, described in terms of the simplest minimal surface (the plane), can be obtained as a limit of a black helicoid, suggesting that these two families of black holes are connected. We also show that minimal surfaces embedded in spheres rather than Euclidean space can be used to construct static compact horizons in asymptotically de Sitter space-times.

Blackfolds, plane waves and minimal surfaces

Energy Technology Data Exchange (ETDEWEB)

Armas, Jay [Physique Théorique et Mathématique, Université Libre de Bruxelles and International Solvay Institutes, ULB-Campus Plaine CP231, B-1050 Brussels (Belgium); Albert Einstein Center for Fundamental Physics, University of Bern,Sidlerstrasse 5, 3012 Bern (Switzerland); Blau, Matthias [Albert Einstein Center for Fundamental Physics, University of Bern,Sidlerstrasse 5, 3012 Bern (Switzerland)

2015-07-29

Minimal surfaces in Euclidean space provide examples of possible non-compact horizon geometries and topologies in asymptotically flat space-time. On the other hand, the existence of limiting surfaces in the space-time provides a simple mechanism for making these configurations compact. Limiting surfaces appear naturally in a given space-time by making minimal surfaces rotate but they are also inherent to plane wave or de Sitter space-times in which case minimal surfaces can be static and compact. We use the blackfold approach in order to scan for possible black hole horizon geometries and topologies in asymptotically flat, plane wave and de Sitter space-times. In the process we uncover several new configurations, such as black helicoids and catenoids, some of which have an asymptotically flat counterpart. In particular, we find that the ultraspinning regime of singly-spinning Myers-Perry black holes, described in terms of the simplest minimal surface (the plane), can be obtained as a limit of a black helicoid, suggesting that these two families of black holes are connected. We also show that minimal surfaces embedded in spheres rather than Euclidean space can be used to construct static compact horizons in asymptotically de Sitter space-times.

Rapid learning of magnetic compass direction by C57BL/6 mice in a 4-armed 'plus' water maze.

Directory of Open Access Journals (Sweden)

John B Phillips

Full Text Available Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180(° so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1 absence of alternative directional cues (2, rotation of magnetic field alignment, and (3 electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds.

Minimally inconsistent reasoning in Semantic Web.

Science.gov (United States)

Zhang, Xiaowang

2017-01-01

Reasoning with inconsistencies is an important issue for Semantic Web as imperfect information is unavoidable in real applications. For this, different paraconsistent approaches, due to their capacity to draw as nontrivial conclusions by tolerating inconsistencies, have been proposed to reason with inconsistent description logic knowledge bases. However, existing paraconsistent approaches are often criticized for being too skeptical. To this end, this paper presents a non-monotonic paraconsistent version of description logic reasoning, called minimally inconsistent reasoning, where inconsistencies tolerated in the reasoning are minimized so that more reasonable conclusions can be inferred. Some desirable properties are studied, which shows that the new semantics inherits advantages of both non-monotonic reasoning and paraconsistent reasoning. A complete and sound tableau-based algorithm, called multi-valued tableaux, is developed to capture the minimally inconsistent reasoning. In fact, the tableaux algorithm is designed, as a framework for multi-valued DL, to allow for different underlying paraconsistent semantics, with the mere difference in the clash conditions. Finally, the complexity of minimally inconsistent description logic reasoning is shown on the same level as the (classical) description logic reasoning.

Oral lactoferrin protects against experimental candidiasis in mice.

Science.gov (United States)

Velliyagounder, K; Alsaedi, W; Alabdulmohsen, W; Markowitz, K; Fine, D H

2015-01-01

To determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO(-/-)) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO(-/-) mice. Antibiotic-treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO(-/-) I mice showed a 2 log (P = 0·001) higher CFUs of C. albicans in the oral cavity compared to the WT mice infected with C. albicans (WTI). LFKO(-/-) I mice given hLF had a 3 log (P = 0·001) reduction in CFUs in the oral cavity compared to untreated LFKO(-/-) I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO(-/-) I mice showed more white patches compared to WTI and LFKO(-/-) I + hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO(-/-) I mice when compared to WTI or LFKO(-/-) I + hLF mice. Human LF is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. Human LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans. © 2014 The Society for Applied Microbiology.

Post-Coma Persons Emerged from a Minimally Conscious State and Showing Multiple Disabilities Learn to Manage a Radio-Listening Activity

Science.gov (United States)

Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Colonna, Fabio; Buonocunto, Francesca; Sacco, Valentina; Megna, Marisa; Oliva, Doretta

2012-01-01

This study assessed microswitch-based technology to enable three post-coma adults, who had emerged from a minimally conscious state but presented motor and communication disabilities, to operate a radio device. The material involved a modified radio device, a microprocessor-based electronic control unit, a personal microswitch, and an amplified…

Minimal Coleman-Weinberg theory explains the diphoton excess

DEFF Research Database (Denmark)

Antipin, Oleg; Mojaza, Matin; Sannino, Francesco

2016-01-01

It is possible to delay the hierarchy problem, by replacing the standard Higgs-sector by the Coleman-Weinberg mechanism, and at the same time ensure perturbative naturalness through the so-called Veltman conditions. As we showed in a previous study, minimal models of this type require the introdu......It is possible to delay the hierarchy problem, by replacing the standard Higgs-sector by the Coleman-Weinberg mechanism, and at the same time ensure perturbative naturalness through the so-called Veltman conditions. As we showed in a previous study, minimal models of this type require...

An Improved Method for Collection of Cerebrospinal Fluid from Anesthetized Mice

DEFF Research Database (Denmark)

Lim, Nastasia K-H; Moestrup, Visse Theresia Skov; Zhang, Xiao

2017-01-01

a technique that improves on current methods of collection to minimize contamination from blood and allow for the abundant collection of CSF (on average 10-15 µL can be collected). This technique can be used with other dissection methods for tissue collection from mice, as it does not impact any tissues......The cerebrospinal fluid (CSF) is a valuable body fluid for analysis in neuroscience research. It is one of the fluids in closest contact with the central nervous system and thus, can be used to analyze the diseased state of the brain or spinal cord without directly accessing these tissues. However......, in mice it is difficult to obtain from the cisterna magna due to its closeness to blood vessels, which often contaminate samples. The area for CSF collection in mice is also difficult to dissect to and often only small samples are obtained (maximum of 5-7 µL or less). This protocol describes in detail...

The Safe Harbor Mouse Retreat(™) is an innovative enrichment shelter that saves mice and money.

Science.gov (United States)

Froberg-Fejko, Karen M; Lecker, Jaime L

2013-10-01

Environmental enrichment can be defined as altering the living environment of captive animals in order to provide them with opportunities to express their natural behavioral repertoire. As important as offering an enriched environment is assuring lab animals are housed in the safest conditions possible. Cage flooding events are an unfortunate reality; however, technology is advancing to minimize these events. Bio-Serv, in collaboration with Allentown, Inc., has developed an innovative and economical shelter called the Safe Harbor Mouse Retreat (Fig. 1). This shelter offers a life-saving refuge for mice during these occasional, but devastating cage-flooding accidents. Mice will not be lost due to chilling or drowning caused by water exposure. Breeding mice can save their litters by moving their pups to the second level, and all mice can escape to the higher level where they can remain warm and dry until they are rescued. This clever shelter is not only life-saving for mice but offers several other significant benefits as well.

Temporal and Molecular Analyses of Cardiac Extracellular Matrix Remodeling following Pressure Overload in Adiponectin Deficient Mice.

Directory of Open Access Journals (Sweden)

Keith Dadson

Full Text Available Adiponectin, circulating levels of which are reduced in obesity and diabetes, mediates cardiac extracellular matrix (ECM remodeling in response to pressure overload (PO. Here, we performed a detailed temporal analysis of progressive cardiac ECM remodelling in adiponectin knockout (AdKO and wild-type (WT mice at 3 days and 1, 2, 3 and 4 weeks following the induction of mild PO via minimally invasive transverse aortic banding. We first observed that myocardial adiponectin gene expression was reduced after 4 weeks of PO, whereas increased adiponectin levels were detected in cardiac homogenates at this time despite decreased circulating levels of adiponectin. Scanning electron microscopy and Masson's trichrome staining showed collagen accumulation increased in response to 2 and 4 weeks of PO in WT mice, while fibrosis in AdKO mice was notably absent after 2 weeks but highly apparent after 4 weeks of PO. Time and intensity of fibroblast appearance after PO was not significantly different between AdKO and WT animals. Gene array analysis indicated that MMP2, TIMP2, collagen 1α1 and collagen 1α3 were induced after 2 weeks of PO in WT but not AdKO mice. After 4 weeks MMP8 was induced in both genotypes, MMP9 only in WT mice and MMP1α only in AdKO mice. Direct stimulation of primary cardiac fibroblasts with adiponectin induced a transient increase in total collagen detected by picrosirius red staining and collagen III levels synthesis, as well as enhanced MMP2 activity detected via gelatin zymography. Adiponectin also enhanced fibroblast migration and attenuated angiotensin-II induced differentiation to a myofibroblast phenotype. In conclusion, these data indicate that increased myocardial bioavailability of adiponectin mediates ECM remodeling following PO and that adiponectin deficiency delays these effects.

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

Directory of Open Access Journals (Sweden)

Xuesen Li

2014-01-01

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

Minimal canonical comprehensive Gröbner systems

OpenAIRE

Manubens, Montserrat; Montes, Antonio

2009-01-01

This is the continuation of Montes' paper "On the canonical discussion of polynomial systems with parameters''. In this paper, we define the Minimal Canonical Comprehensive Gröbner System of a parametric ideal and fix under which hypothesis it exists and is computable. An algorithm to obtain a canonical description of the segments of the Minimal Canonical CGS is given, thus completing the whole MCCGS algorithm (implemented in Maple and Singular). We show its high utility for applications, suc...

Two-photon calcium imaging in mice navigating a virtual reality environment.

Science.gov (United States)

Leinweber, Marcus; Zmarz, Pawel; Buchmann, Peter; Argast, Paul; Hübener, Mark; Bonhoeffer, Tobias; Keller, Georg B

2014-02-20

In recent years, two-photon imaging has become an invaluable tool in neuroscience, as it allows for chronic measurement of the activity of genetically identified cells during behavior(1-6). Here we describe methods to perform two-photon imaging in mouse cortex while the animal navigates a virtual reality environment. We focus on the aspects of the experimental procedures that are key to imaging in a behaving animal in a brightly lit virtual environment. The key problems that arise in this experimental setup that we here address are: minimizing brain motion related artifacts, minimizing light leak from the virtual reality projection system, and minimizing laser induced tissue damage. We also provide sample software to control the virtual reality environment and to do pupil tracking. With these procedures and resources it should be possible to convert a conventional two-photon microscope for use in behaving mice.

APOA-1Milano muteins, orally delivered via genetically modified rice, show anti-atherogenic and anti-inflammatory properties in vitro and in Apoe-/- atherosclerotic mice.

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Romano, Gabriele; Reggi, Serena; Kutryb-Zajac, Barbara; Facoetti, Amanda; Chisci, Elisa; Pettinato, Mariateresa; Giuffrè, Maria Rita; Vecchio, Federica; Leoni, Silvia; De Giorgi, Marco; Avezza, Federica; Cadamuro, Massimiliano; Crippa, Luca; Leone, Biagio Eugenio; Lavitrano, Marialuisa; Rivolta, Ilaria; Barisani, Donatella; Smolenski, Ryszard Tomasz; Giovannoni, Roberto

2018-06-11

Atherosclerosis is a slowly progressing, chronic multifactorial disease characterized by the accumulation of lipids, inflammatory cells, and fibrous tissue that drives to the formation of asymmetric focal thickenings in the tunica intima of large and mid-sized arteries. Despite the high therapeutic potential of ApoA-1 proteins, the purification and delivery into the disordered organisms of these drugs is still limited by low efficiency in these processes. We report here a novel production and delivery system of anti-atherogenic APOA-1Milano muteins (APOA-1M) by means of genetically modified rice plants. APOA-1M, delivered as protein extracts from transgenic rice seeds, significantly reduced macrophage activation and foam cell formation in vitro in oxLDL-loaded THP-1 model. The APOA-1M delivery method and therapeutic efficacy was tested in healthy mice and in Apoe -/- mice fed with high cholesterol diet (Western Diet, WD). APOA-1M rice milk significantly reduced atherosclerotic plaque size and lipids composition in aortic sinus and aortic arch of WD-fed Apoe -/- mice as compared to wild type rice milk-treated, WD-fed Apoe -/- mice. APOA-1M rice milk also significantly reduced macrophage number in liver of WD-fed Apoe -/- mice as compared to WT rice milk treated mice. The delivery of therapeutic APOA-1M full length proteins via oral administration of rice seeds protein extracts (the 'rice milk') to the disordered organism, without any need of purification, might overcome the main APOA1-based therapies' limitations and improve the use of this molecules as therapeutic agents for cardiovascular patients. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Minimal knotted polygons in cubic lattices

International Nuclear Information System (INIS)

Van Rensburg, E J Janse; Rechnitzer, A

2011-01-01

In this paper we examine numerically the properties of minimal length knotted lattice polygons in the simple cubic, face-centered cubic, and body-centered cubic lattices by sieving minimal length polygons from a data stream of a Monte Carlo algorithm, implemented as described in Aragão de Carvalho and Caracciolo (1983 Phys. Rev. B 27 1635), Aragão de Carvalho et al (1983 Nucl. Phys. B 215 209) and Berg and Foester (1981 Phys. Lett. B 106 323). The entropy, mean writhe, and mean curvature of minimal length polygons are computed (in some cases exactly). While the minimal length and mean curvature are found to be lattice dependent, the mean writhe is found to be only weakly dependent on the lattice type. Comparison of our results to numerical results for the writhe obtained elsewhere (see Janse van Rensburg et al 1999 Contributed to Ideal Knots (Series on Knots and Everything vol 19) ed Stasiak, Katritch and Kauffman (Singapore: World Scientific), Portillo et al 2011 J. Phys. A: Math. Theor. 44 275004) shows that the mean writhe is also insensitive to the length of a knotted polygon. Thus, while these results for the mean writhe and mean absolute writhe at minimal length are not universal, our results demonstrate that these values are quite close the those of long polygons regardless of the underlying lattice and length

Minimal abdominal incisions

Directory of Open Access Journals (Sweden)

João Carlos Magi

2017-04-01

Full Text Available Minimally invasive procedures aim to resolve the disease with minimal trauma to the body, resulting in a rapid return to activities and in reductions of infection, complications, costs and pain. Minimally incised laparotomy, sometimes referred to as minilaparotomy, is an example of such minimally invasive procedures. The aim of this study is to demonstrate the feasibility and utility of laparotomy with minimal incision based on the literature and exemplifying with a case. The case in question describes reconstruction of the intestinal transit with the use of this incision. Male, young, HIV-positive patient in a late postoperative of ileotiflectomy, terminal ileostomy and closing of the ascending colon by an acute perforating abdomen, due to ileocolonic tuberculosis. The barium enema showed a proximal stump of the right colon near the ileostomy. The access to the cavity was made through the orifice resulting from the release of the stoma, with a lateral-lateral ileo-colonic anastomosis with a 25 mm circular stapler and manual closure of the ileal stump. These surgeries require their own tactics, such as rigor in the lysis of adhesions, tissue traction, and hemostasis, in addition to requiring surgeon dexterity – but without the need for investments in technology; moreover, the learning curve is reported as being lower than that for videolaparoscopy. Laparotomy with minimal incision should be considered as a valid and viable option in the treatment of surgical conditions. Resumo: Procedimentos minimamente invasivos visam resolver a doença com o mínimo de trauma ao organismo, resultando em retorno rápido às atividades, reduções nas infecções, complicações, custos e na dor. A laparotomia com incisão mínima, algumas vezes referida como minilaparotomia, é um exemplo desses procedimentos minimamente invasivos. O objetivo deste trabalho é demonstrar a viabilidade e utilidade das laparotomias com incisão mínima com base na literatura e

Low-dose cadmium exposure exacerbates polyhexamethylene guanidine-induced lung fibrosis in mice.

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Kim, Min-Seok; Kim, Sung-Hwan; Jeon, Doin; Kim, Hyeon-Young; Han, Jin-Young; Kim, Bumseok; Lee, Kyuhong

2018-01-01

Cadmium (Cd) is a toxic metal present in tobacco smoke, air, food, and water. Inhalation is an important route of Cd exposure, and lungs are one of the main target organs for metal-induced toxicity. Cd inhalation is associated with an increased risk of pulmonary diseases. The present study aimed to assess the effects of repeated exposure to low-dose Cd in a mouse model of polyhexamethylene guanidine (PHMG)-induced lung fibrosis. Mice were grouped into the following groups: vehicle control (VC), PHMG, cadmium chloride (CdCl 2 ), and PHMG + CdCl 2 . Animals in the PHMG group exhibited increased numbers of total cells and inflammatory cells in the bronchoalveolar lavage fluid (BALF) accompanied by inflammation and fibrosis in lung tissues. These parameters were exacerbated in mice in the PHMG + CdCl 2 group. In contrast, mice in the CdCl 2 group alone displayed only minimal inflammation in pulmonary tissue. Expression of inflammatory cytokines and fibrogenic mediators was significantly elevated in lungs of mice in the PHMG group compared with that VC. Further, expression of these cytokines and mediators was enhanced in pulmonary tissue in mice administered PHMG + CdCl 2 . Data demonstrate that repeated exposure to low-dose Cd may enhance the development of PHMG-induced pulmonary fibrosis.

Social factors modulate restraint stress induced hyperthermia in mice.

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Watanabe, Shigeru

2015-10-22

Stress-induced hyperthermia (SIH) was examined in three different social conditions in mice by thermographic measurement of the body surface temperature. Placing animals in cylindrical holders induced restraint stress. I examined the effect of the social factors in SIH using the thermograph (body surface temperature). Mice restrained in the holders alone showed SIH. Mice restrained in the holders at the same time as other similarly restrained cage mates (social equality condition) showed less hyperthermia. Interestingly, restrained mice with free moving cage mates (social inequality condition) showed the highest hyperthermia. These results are consistent with a previous experiment measuring the memory-enhancing effects of stress and the stress-induced elevation of corticosterone, and suggest that social inequality enhances stress. Copyright © 2015 Elsevier B.V. All rights reserved.

Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.

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Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L; Weis, Joachim; Katona, Istvan; Martini, Rudolf

2018-05-09

Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging

Therapeutic cloning in individual parkinsonian mice

Science.gov (United States)

Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

2009-01-01

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

Minimally inconsistent reasoning in Semantic Web.

Directory of Open Access Journals (Sweden)

Xiaowang Zhang

Full Text Available Reasoning with inconsistencies is an important issue for Semantic Web as imperfect information is unavoidable in real applications. For this, different paraconsistent approaches, due to their capacity to draw as nontrivial conclusions by tolerating inconsistencies, have been proposed to reason with inconsistent description logic knowledge bases. However, existing paraconsistent approaches are often criticized for being too skeptical. To this end, this paper presents a non-monotonic paraconsistent version of description logic reasoning, called minimally inconsistent reasoning, where inconsistencies tolerated in the reasoning are minimized so that more reasonable conclusions can be inferred. Some desirable properties are studied, which shows that the new semantics inherits advantages of both non-monotonic reasoning and paraconsistent reasoning. A complete and sound tableau-based algorithm, called multi-valued tableaux, is developed to capture the minimally inconsistent reasoning. In fact, the tableaux algorithm is designed, as a framework for multi-valued DL, to allow for different underlying paraconsistent semantics, with the mere difference in the clash conditions. Finally, the complexity of minimally inconsistent description logic reasoning is shown on the same level as the (classical description logic reasoning.

Two-year body composition analyses of long-lived GHR null mice.

Science.gov (United States)

Berryman, Darlene E; List, Edward O; Palmer, Amanda J; Chung, Min-Yu; Wright-Piekarski, Jacob; Lubbers, Ellen; O'Connor, Patrick; Okada, Shigeru; Kopchick, John J

2010-01-01

Growth hormone receptor gene-disrupted (GHR-/-) mice exhibit increased life span and adipose tissue mass. Although this obese phenotype has been reported extensively for young adult male GHR-/- mice, data for females and for other ages in either gender are lacking. Thus, the purpose of this study was to evaluate body composition longitudinally in both male and female GHR-/- mice. Results show that GHR-/- mice have a greater percent fat mass with no significant difference in absolute fat mass throughout life. Lean mass shows an opposite trend with percent lean mass not significantly different between genotypes but absolute mass reduced in GHR-/- mice. Differences in body composition are more pronounced in male than in female mice, and both genders of GHR-/- mice show specific enlargement of the subcutaneous adipose depot. Along with previously published data, these results suggest a consistent and intriguing protective effect of excess fat mass in the subcutaneous region.

Paintings discrimination by mice: Different strategies for different paintings.

Science.gov (United States)

Watanabe, Shigeru

2017-09-01

C57BL/6 mice were trained on simultaneous discrimination of paintings with multiple exemplars, using an operant chamber with a touch screen. The number of exemplars was successively increased up to six. Those mice trained in Kandinsky/Mondrian discrimination showed improved learning and generalization, whereas those trained in Picasso/Renoir discrimination showed no improvements in learning or generalization. These results suggest category-like discrimination in the Kandinsky/Mondrian task, but item-to-item discrimination in the Picasso/Renoir task. Mice maintained their discriminative behavior in a pixelization test with various paintings; however, mice in the Picasso/Renoir task showed poor performance in a test that employed scrambling processing. These results do not indicate that discrimination strategy for any Kandinsky/Mondrian combinations differed from that for any Picasso/Monet combinations but suggest the mice employed different strategies of discrimination tasks depending upon stimuli. Copyright © 2017 Elsevier B.V. All rights reserved.

Aging-associated renal disease in mice is fructokinase dependent.

Science.gov (United States)

Roncal-Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Milagres, Tamara; Hernando, Ana Andres; Jensen, Thomas; Miyazaki, Makoto; Doke, Tomohito; Hayasaki, Takahiro; Nakagawa, Takahiko; Marumaya, Shoichi; Long, David A; Garcia, Gabriela E; Kuwabara, Masanari; Sánchez-Lozada, Laura G; Kang, Duk-Hee; Johnson, Richard J

2016-10-01

Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low-level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 yr that had minimal (renal injury was amplified by provision of high-salt diet for 3 wk, as noted by the presence of glomerular hypertrophy, mesangial matrix expansion, and alpha smooth muscle actin expression, and with segmental thrombi. Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. These studies suggest that aging-associated renal disease might be due to activation of specific metabolic pathways that could theoretically be targeted therapeutically, and raise the hypothesis that aging-associated renal injury may represent a disease process as opposed to normal age-related degeneration.

Ghrelin is produced in taste cells and ghrelin receptor null mice show reduced taste responsivity to salty (NaCl and sour (citric acid tastants.

Directory of Open Access Journals (Sweden)

Yu-Kyong Shin

2010-09-01

Full Text Available The gustatory system plays a critical role in determining food preferences, food intake and energy balance. The exact mechanisms that fine tune taste sensitivity are currently poorly defined, but it is clear that numerous factors such as efferent input and specific signal transduction cascades are involved.Using immunohistochemical analyses, we show that ghrelin, a hormone classically considered to be an appetite-regulating hormone, is present within the taste buds of the tongue. Prepro-ghrelin, prohormone convertase 1/3 (PC 1/3, ghrelin, its cognate receptor (GHSR, and ghrelin-O-acyltransferase (GOAT , the enzyme that activates ghrelin are expressed in Type I, II, III and IV taste cells of mouse taste buds. In addition, ghrelin and GHSR co-localize in the same taste cells, suggesting that ghrelin works in an autocrine manner in taste cells. To determine a role for ghrelin in modifying taste perception, we performed taste behavioral tests using GHSR null mice. GHSR null mice exhibited significantly reduced taste responsivity to sour (citric acid and salty (sodium chloride tastants.These findings suggest that ghrelin plays a local modulatory role in determining taste bud signaling and function and could be a novel mechanism for the modulation of salty and sour taste responsivity.

Minimally invasive orthognathic surgery.

Science.gov (United States)

Resnick, Cory M; Kaban, Leonard B; Troulis, Maria J

2009-02-01

Minimally invasive surgery is defined as the discipline in which operative procedures are performed in novel ways to diminish the sequelae of standard surgical dissections. The goals of minimally invasive surgery are to reduce tissue trauma and to minimize bleeding, edema, and injury, thereby improving the rate and quality of healing. In orthognathic surgery, there are two minimally invasive techniques that can be used separately or in combination: (1) endoscopic exposure and (2) distraction osteogenesis. This article describes the historical developments of the fields of orthognathic surgery and minimally invasive surgery, as well as the integration of the two disciplines. Indications, techniques, and the most current outcome data for specific minimally invasive orthognathic surgical procedures are presented.

Regularity of Minimal Surfaces

CERN Document Server

Dierkes, Ulrich; Tromba, Anthony J; Kuster, Albrecht

2010-01-01

"Regularity of Minimal Surfaces" begins with a survey of minimal surfaces with free boundaries. Following this, the basic results concerning the boundary behaviour of minimal surfaces and H-surfaces with fixed or free boundaries are studied. In particular, the asymptotic expansions at interior and boundary branch points are derived, leading to general Gauss-Bonnet formulas. Furthermore, gradient estimates and asymptotic expansions for minimal surfaces with only piecewise smooth boundaries are obtained. One of the main features of free boundary value problems for minimal surfaces is t

A modified choline-deficient, ethionine-supplemented diet reduces morbidity and retains a liver progenitor cell response in mice.

Science.gov (United States)

Passman, Adam M; Strauss, Robyn P; McSpadden, Sarah B; Finch-Edmondson, Megan L; Woo, Ken H; Diepeveen, Luke A; London, Roslyn; Callus, Bernard A; Yeoh, George C

2015-12-01

The choline-deficient, ethionine-supplemented (CDE) dietary model induces chronic liver damage, and stimulates liver progenitor cell (LPC)-mediated repair. Long-term CDE administration leads to hepatocellular carcinoma in rodents and lineage-tracing studies show that LPCs differentiate into functional hepatocytes in this model. The CDE diet was first modified for mice by our laboratory by separately administering choline-deficient chow and ethionine in the drinking water (CD+E diet). Although this CD+E diet is widely used, concerns with variability in weight loss, morbidity, mortality and LPC response have been raised by researchers who have adopted this model. We propose that these inconsistencies are due to differential consumption of chow and ethionine in the drinking water, and that incorporating ethionine in the choline-deficient chow, and altering the strength, will achieve better outcomes. Therefore, C57Bl/6 mice, 5 and 6 weeks of age, were fed an all-inclusive CDE diet of various strengths (67% to 100%) for 3 weeks. The LPC response was quantitated and cell lines were derived. We found that animal survival, LPC response and liver damage are correlated with CDE diet strength. The 67% and 75% CDE diet administered to mice older than 5 weeks and greater than 18 g provides a consistent and acceptable level of animal welfare and induces a substantial LPC response, permitting their isolation and establishment of cell lines. This study shows that an all-inclusive CDE diet for mice reproducibly induces an LPC response conducive to in vivo studies and isolation, whilst minimizing morbidity and mortality. © 2015. Published by The Company of Biologists Ltd.

Improving the performance of minimizers and winnowing schemes.

Science.gov (United States)

Marçais, Guillaume; Pellow, David; Bork, Daniel; Orenstein, Yaron; Shamir, Ron; Kingsford, Carl

2017-07-15

The minimizers scheme is a method for selecting k -mers from sequences. It is used in many bioinformatics software tools to bin comparable sequences or to sample a sequence in a deterministic fashion at approximately regular intervals, in order to reduce memory consumption and processing time. Although very useful, the minimizers selection procedure has undesirable behaviors (e.g. too many k -mers are selected when processing certain sequences). Some of these problems were already known to the authors of the minimizers technique, and the natural lexicographic ordering of k -mers used by minimizers was recognized as their origin. Many software tools using minimizers employ ad hoc variations of the lexicographic order to alleviate those issues. We provide an in-depth analysis of the effect of k -mer ordering on the performance of the minimizers technique. By using small universal hitting sets (a recently defined concept), we show how to significantly improve the performance of minimizers and avoid some of its worse behaviors. Based on these results, we encourage bioinformatics software developers to use an ordering based on a universal hitting set or, if not possible, a randomized ordering, rather than the lexicographic order. This analysis also settles negatively a conjecture (by Schleimer et al. ) on the expected density of minimizers in a random sequence. The software used for this analysis is available on GitHub: https://github.com/gmarcais/minimizers.git . gmarcais@cs.cmu.edu or carlk@cs.cmu.edu. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

PrP0\\0 mice show behavioral abnormalities that suggest PrPC has a role in maintaining the cytoskeleton.

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Background/Introduction. PrPC is highly conserved among mammals, but its natural function is unclear. Prnp ablated mice (PrP0/0) appear to develop normally and are able to reproduce. These observations seem to indicate that the gene is not essential for viability, in spite of it being highly conse...

Minimal Poems Written in 1979 Minimal Poems Written in 1979

Directory of Open Access Journals (Sweden)

Sandra Sirangelo Maggio

2008-04-01

Full Text Available The reading of M. van der Slice's Minimal Poems Written in 1979 (the work, actually, has no title reminded me of a book I have seen a long time ago. called Truth, which had not even a single word printed inside. In either case we have a sample of how often excentricities can prove efficient means of artistic creativity, in this new literary trend known as Minimalism. The reading of M. van der Slice's Minimal Poems Written in 1979 (the work, actually, has no title reminded me of a book I have seen a long time ago. called Truth, which had not even a single word printed inside. In either case we have a sample of how often excentricities can prove efficient means of artistic creativity, in this new literary trend known as Minimalism.

Hydrogen atom in momentum space with a minimal length

International Nuclear Information System (INIS)

Bouaziz, Djamil; Ferkous, Nourredine

2010-01-01

A momentum representation treatment of the hydrogen atom problem with a generalized uncertainty relation, which leads to a minimal length ΔX imin =(ℎ/2π)√(3β+β ' ), is presented. We show that the distance squared operator can be factorized in the case β ' =2β. We analytically solve the s-wave bound-state equation. The leading correction to the energy spectrum caused by the minimal length depends on √(β). An upper bound for the minimal length is found to be about 10 -9 fm.

Low-Voltage Consumption Coordination for Loss Minimization and Voltage Control

DEFF Research Database (Denmark)

Juelsgaard, Morten; Sloth, Christoffer; Wisniewski, Rafal

2014-01-01

This work presents a strategy for minimizing active power losses in low-voltage grids, by coordinating the consumption of electric vehicles and power generation from solar panels. We show that minimizing losses, also reduces voltage variations, and illustrate how this may be employed for increasing...

Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.

Science.gov (United States)

Al Abed, Alice Shaam; Sellami, Azza; Brayda-Bruno, Laurent; Lamothe, Valérie; Noguès, Xavier; Potier, Mylène; Bennetau-Pelissero, Catherine; Marighetto, Aline

2016-07-01

Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as "where I parked" requires abilities to organize/update memories to prevent proactive interference from similar memories of previous "parking events". Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1μM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mapping pathological phenotypes in Reelin mutant mice

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Caterina eMichetti

2014-09-01

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

Correlates of minimal dating.

Science.gov (United States)

Leck, Kira

2006-10-01

Researchers have associated minimal dating with numerous factors. The present author tested shyness, introversion, physical attractiveness, performance evaluation, anxiety, social skill, social self-esteem, and loneliness to determine the nature of their relationships with 2 measures of self-reported minimal dating in a sample of 175 college students. For women, shyness, introversion, physical attractiveness, self-rated anxiety, social self-esteem, and loneliness correlated with 1 or both measures of minimal dating. For men, physical attractiveness, observer-rated social skill, social self-esteem, and loneliness correlated with 1 or both measures of minimal dating. The patterns of relationships were not identical for the 2 indicators of minimal dating, indicating the possibility that minimal dating is not a single construct as researchers previously believed. The present author discussed implications and suggestions for future researchers.

Pengaruh Pelapis Bionanokomposit terhadap Mutu Mangga Terolah Minimal

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Ata Aditya Wardana

2017-04-01

Full Text Available Abstract Minimally-processed mango is a perishable product due to high respiration and transpiration and microbial decay. Edible coating is one of the alternative methods to maintain the quality of minimally - processed mango. The objective of this study was to evaluate the effects of bionanocomposite edible coating from tapioca and ZnO nanoparticles (NP-ZnO on quality of minimally - processed mango cv. Arumanis, stored for 12 days at 8°C. The combination of tapioca and NP-ZnO (0, 1, 2% by weight of tapioca were used to coat minimally processed mango. The result showed that application of bionanocomposite edible coatings were able to maintain the quality of minimally-processed mango during the storage periods. The bionanocomposite from tapioca + NP-ZnO (2% by weight of tapioca was the most effective in reducing weight loss, firmness, browning index, total acidity, total soluble solids ,respiration, and microbial counts. Thus, the use of bionanocomposite edible coating might provide an alternative method to maintain storage quality of minimally-processed mango. Abstrak Mangga terolah minimal merupakan produk yang cepat mengalami kerusakan dikarenakan respirasi yang cepat, transpirasi dan kerusakan oleh mikroba. Edible coating merupakan salah satu alternatif metode untuk mempertahankan mutu mangga terolah minimal. Tujuan dari penelitian ini adalah untuk mengevaluasi pengaruh pelapis bionanokomposit dari tapioka dan nanopartikel ZnO (NP-ZnO terhadap mutu mangga terolah minimal cv. Arumanis yang disimpan selama 12 hari pada suhu 8oC. Kombinasi dari tapioka dan NP-ZnO (0, 1, 2% b/b tapioka digunakan untuk melapisi mangga terolah minimal. Hasil menunjukkan bahwa pelapisan bionanokomposit mampu mempertahankan mutu mangga terolah minimal selama penyimpanan. Bionanokomposit dari tapioka + NP-ZnO (2% b/b tapioka paling efektif dalam menghambat penurunan susut bobot, kekerasan, indeks pencoklatan, total asam, total padatan terlarut, respirasi dan total

Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

Science.gov (United States)

Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

2013-01-01

The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

Inherent and antigen-induced airway hyperreactivity in NC mice

OpenAIRE

Tetsuto Kobayashi; Toru Miura; Tomoko Haba; Miyuki Sato; Masao Takei; Isao Serizawa

1999-01-01

In order to clarify the airway physiology of NC mice, the following experiments were carried out. To investigate inherent airway reactivity, we compared tracheal reactivity to various chemical mediators in NC, BALB/c, C57BL/6 and A/J mice in vitro. NC mice showed significantly greater reactivity to acetylcholine than BALB/c and C57BL/6 mice and a reactivity comparable to that of A/J mice, which are known as high responders. Then, airway reactivity to acetylcholine was investigated in those st...

Minimal Super Technicolor

DEFF Research Database (Denmark)

Antola, M.; Di Chiara, S.; Sannino, F.

2011-01-01

We introduce novel extensions of the Standard Model featuring a supersymmetric technicolor sector (supertechnicolor). As the first minimal conformal supertechnicolor model we consider N=4 Super Yang-Mills which breaks to N=1 via the electroweak interactions. This is a well defined, economical......, between unparticle physics and Minimal Walking Technicolor. We consider also other N =1 extensions of the Minimal Walking Technicolor model. The new models allow all the standard model matter fields to acquire a mass....

CPP2-p16MIS treatment–induced colon carcinoma cell death in vitro and prolonged lifespan of tumor-bearing mice

International Nuclear Information System (INIS)

Wang, Lifeng; Chen, Haijin; Yu, Jinlong; Lin, Xiaohua; Qi, Jia; Cui, Chunhui; Xie, Lang; Huang, Shuxin

2016-01-01

Cell-penetrating peptides (CPPs) are a research hotspot due to their noninvasive delivery ability. Among the identified CPPs, the TAT and R8 peptides have been preferentially applied to transduction into different cells. However, this process is nonselective among various cells. Recent research suggested that CPP2 could selectively penetrate human colorectal cancer (CRC) cells. Using in vitro experiments, the mean fluorescence intensity of fluorescein isothiocyanate–labeled CPPs (CPPs-FITC) incubated with different cell lines was compared to corroborate the colon tumor targeting ability of CPP2. The targeting ability of CPP2 was determined in the same way in tumor-bearing mice. We synthesized antitumor peptides by fusing CPP2 to the minimal inhibitory sequence of p16 (p16MIS), which had the ability to restore the function of lost p16, the expression of which was absent in tumor cell lines of various origins. The antitumor effect of the combined peptide was tested in both CRC cell lines and tumor-bearing mice. In each CRC cell line, the mean fluorescence intensity of CPP2-FITC was higher than that of the TAT-FITC (p < 0.001) and R8-FITC (p < 0.001) groups. CPP2-p16MIS, the targeting carrier, showed a higher antitumor response in the in vitro cell research. CPP2-p16MIS showed a prolonged mean lifespan of tumor-bearing mice, further characterizing its role in specific tumor-targeting ability in vivo. Survival analysis showed that the mice treated with CPP2-p16MIS had significantly longer survival than the mice treated with phosphate-buffered saline (p < 0.05) or those treated with control peptides, including the CPP2 (p < 0.05) and p16MIS (p < 0.05) groups. CPP2 could more selectively penetrate CRC cells than TAT or R8 as well as effectively deliver the p16MIS to the tumor

Teratogenic effect of yogurt in mice fetus (Mus musculus

Directory of Open Access Journals (Sweden)

Dwisari Dillasamola

2018-04-01

Full Text Available Yogurt is one of the dairy products made from lactic acid fermentation by using Lactobacillus bulgaricus and Streptococcus thermophilus. A study on teratogenic effects of yogurt on the white female mice fetus (Mus musculus has been carried out. Pregnant mice used were 20 which divided into 4 groups : the control group, D1, D2, and D3. The treatments giveThe mice were Distidelled water (control, 0.52 yogurt (D1, 1.04  yogurt (D2, and 2.08 g yogurt (D3. Data were analyzed using one-way ANOVA followed by Duncan multiple range test. Results showed that administration of yogurt during pregnancy could affect mother body weight of mice (P 0,05. Observations with Alizarin solution did not show skeletal defects in comparison to the control group. Observations with Bouin’s solution showed defective visceral cleft palate in fetal mice yogurt group D3. This study conclude that yogurt is safe to consume in groups D1 and D2. Yogurt has the potential to cause fetal teratogenic in group D3

On minimal inhibitory rules for almost all k-valued information systems

KAUST Repository

Moshkov, Mikhail; Skowron, Andrzej; Suraj, Zbigniew

2009-01-01

The minimal inhibitory rules for information systems can be used for construction of classifiers. We show that almost all information systems from a certain large class of information systems have relatively short minimal inhibitory rules. However

Toxicity of palmitoyl glycerol to mice: depression of thyroid function

International Nuclear Information System (INIS)

Trumbo, P.R.; Meuten, D.J.; King, M.W.; Tove, S.B.

1987-01-01

Mice given propylthiouracil, a thyroid inhibitor, and fed a diet containing a nontoxic level of rac-1(3)-palmitoyl glycerol showed the hypothermia and mortality expected for a toxic dose, but did not show these signs when linoleate or oleate was added to the diet. Loss of radioiodine from the whole animal and thyroid gland was slower when mice were fed the toxic palmitoyl glycerol diet than when fed the same diet containing 4% safflower oil. However, mice fed the two diets did not differ in the extent of the incorporation of radioiodine, and essentially all was bound to protein in each case. Follicular thyroid cells from mice fed the potentially toxic diet that contained unsaturated fat were normal in appearance. Conversely, cells from mice fed the toxic diet were smaller and more densely stained, showing evidence of glycoprotein inside the cell. These findings show that the thyroid gland is affected by the palmitoyl glycerol diet. However, the thyroid is not the only organ affected, because giving either thyroxine or triiodothyronine had no effect on the toxicity of palmitoyl glycerol

High-Throughput Automatic Training System for Odor-Based Learned Behaviors in Head-Fixed Mice

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Zhe Han

2018-02-01

Full Text Available Understanding neuronal mechanisms of learned behaviors requires efficient behavioral assays. We designed a high-throughput automatic training system (HATS for olfactory behaviors in head-fixed mice. The hardware and software were constructed to enable automatic training with minimal human intervention. The integrated system was composed of customized 3D-printing supporting components, an odor-delivery unit with fast response, Arduino based hardware-controlling and data-acquisition unit. Furthermore, the customized software was designed to enable automatic training in all training phases, including lick-teaching, shaping and learning. Using HATS, we trained mice to perform delayed non-match to sample (DNMS, delayed paired association (DPA, Go/No-go (GNG, and GNG reversal tasks. These tasks probed cognitive functions including sensory discrimination, working memory, decision making and cognitive flexibility. Mice reached stable levels of performance within several days in the tasks. HATS enabled an experimenter to train eight mice simultaneously, therefore greatly enhanced the experimental efficiency. Combined with causal perturbation and activity recording techniques, HATS can greatly facilitate our understanding of the neural-circuitry mechanisms underlying learned behaviors.

Ceftiofur sodium, a broad-spectrum cephalosporin: evaluation in vitro and in vivo in mice.

Science.gov (United States)

Yancey, R J; Kinney, M L; Roberts, B J; Goodenough, K R; Hamel, J C; Ford, C W

1987-07-01

Ceftiofur sodium, a broad-spectrum beta-lactamase-resistant cephalosporin, was evaluated in vitro and in vivo in mice. Ceftiofur is the sodium salt of (6R, 7R)-7[( 2-amino-4-thiazolyl)-Z- (methoxyimino)acetyl]amino)-3-[( (2-furanylcarbonyl)thio]methyl)-8-oxo-5- thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylate. Minimal inhibitory concentration values were obtained with 264 strains representing 9 genera and 17 species of bacterial pathogens from cattle, swine, sheep, horses, poultry, dogs, cats, and human beings. Ceftiofur was more active than was ampicillin against all strains tested including beta-lactamase-producing organisms. In mice with systemic infections, ceftiofur was more active than or equivalent to ampicillin, cephalothin, cefamandole, cloxacillin, cefoperazone, or pirlimycin. These protection tests included infections with Escherichia coli, Haemophilus pleuropneumoniae, H somnus, Pasteurella haemolytica, P multocida, Salmonella typhimurium, or Staphylococcus aureus. In infant mice with E coli-induced lethal diarrhea and in mice with S aureus and E coli-induced mastitis, ceftiofur was comparable or more active than was ampicillin.

Toda theories, W-algebras, and minimal models

International Nuclear Information System (INIS)

Mansfield, P.; Spence, B.

1991-01-01

We discuss the classical W-algebra symmetries of Toda field theories in terms of the pseudo-differential Lax operator associated with the Toda Lax pair. We then show how the W-algebra transformations can be understood as the non-abelian gauge transformations which preserve the form of the Lax pair. This provides a new understanding of the W-algebras, and we discuss their closure and co-cycle structure using this approach. The quantum Lax operator is investigated, and we show that this operator, which generates the quantum W-algebra currents, is conserved in the conformally extended Toda theories. The W-algebra minimal model primary fields are shown to arise naturally in these theories, leading to the conjecture that the conformally extended Toda theories provide a lagrangian formulation of the W-algebra minimal models. (orig.)

Quantum scattering in one-dimensional systems satisfying the minimal length uncertainty relation

Energy Technology Data Exchange (ETDEWEB)

Bernardo, Reginald Christian S., E-mail: rcbernardo@nip.upd.edu.ph; Esguerra, Jose Perico H., E-mail: jesguerra@nip.upd.edu.ph

2016-12-15

In quantum gravity theories, when the scattering energy is comparable to the Planck energy the Heisenberg uncertainty principle breaks down and is replaced by the minimal length uncertainty relation. In this paper, the consequences of the minimal length uncertainty relation on one-dimensional quantum scattering are studied using an approach involving a recently proposed second-order differential equation. An exact analytical expression for the tunneling probability through a locally-periodic rectangular potential barrier system is obtained. Results show that the existence of a non-zero minimal length uncertainty tends to shift the resonant tunneling energies to the positive direction. Scattering through a locally-periodic potential composed of double-rectangular potential barriers shows that the first band of resonant tunneling energies widens for minimal length cases when the double-rectangular potential barrier is symmetric but narrows down when the double-rectangular potential barrier is asymmetric. A numerical solution which exploits the use of Wronskians is used to calculate the transmission probabilities through the Pöschl–Teller well, Gaussian barrier, and double-Gaussian barrier. Results show that the probability of passage through the Pöschl–Teller well and Gaussian barrier is smaller in the minimal length cases compared to the non-minimal length case. For the double-Gaussian barrier, the probability of passage for energies that are more positive than the resonant tunneling energy is larger in the minimal length cases compared to the non-minimal length case. The approach is exact and applicable to many types of scattering potential.

Cassava is not a goitrogen in mice

International Nuclear Information System (INIS)

Hershman, J.M.; Pekary, A.E.; Sugawara, M.; Adler, M.; Turner, L.; Demetriou, J.A.; Hershman, J.D.

1985-01-01

To examine the effect of cassava on the thyroid function of mice, the authors fed fresh cassava root to mice and compared this diet with low iodine diet and Purina. Cassava provided a low iodine intake and increased urine thiocyanate excretion and serum thiocyanate levels. Mice on cassava lost weight. The thyroid glands of mice on cassava were not enlarged, even when normalized for body weight. The 4- and 24-hr thyroid uptakes of mice on cassava were similar to those of mice on low iodine diets. Protein-bound [ 125 I]iodine at 24 hr was high in mice on either the cassava or low iodine diets. The thyroid iodide trap (T/M) was similar in mice on cassava and low iodine diets. When thiocyanate was added in vitro to the incubation medium, T/M was reduced in all groups of mice; under these conditions, thiocyanate caused a dose-related inhibition of T/M. The serum thyroxine (T4) and triiodothyronine (T3) concentrations of mice on cassava were reduced compared with mice on Purina diet. Thyroid T4 and T3 contents of mice on cassava were relatively low compared with mice on Purina diet. Hepatic T3 content and T4 5'-monodeiodination in liver homogenates were reduced in mice on cassava compared with other groups. The data show that cassava does not cause goiter in mice. The thiocyanate formed from ingestation of cassava is insufficient to inhibit thyroid iodide transport or organification of iodide. The cassava diet leads to rapid turnover of hormonal iodine because it is a low iodine diet. It also impairs 5'-monodeiodination of T4 which may be related to nutritional deficiency. These data in mice do not support the concept that cassava per se has goitrogenic action in man

Effects of genistein following fractionated lung irradiation in mice

International Nuclear Information System (INIS)

Para, Andrea E.; Bezjak, Andrea; Yeung, Ivan W.T.; Van Dyk, Jake; Hill, Richard P.

2009-01-01

Background and purpose: This study investigated protection of lung injury by genistein following fractionated doses of radiation and its effect on tumor response. Material and methods: C3H/HeJ mice were irradiated (100 kVp X-rays) with 9 fractions of 3.1 Gy over 30 days (approximately equivalent to 10 Gy single dose) and were maintained on a genistein diet (∼10 mg/kg). Damage was assessed over 28 weeks in lung cells by a cytokinesis block micronucleus (MN) assay and by changes in breathing rate and histology. Tumor protection was assessed using a colony assay to determine cell survival following in situ irradiation of small lung nodules (KHT fibrosarcoma). Results: Genistein caused about a 50% reduction in the MN damage observed during the fractionated radiation treatment and this damage continued to decrease at later times to background levels by 16 weeks. In mice not receiving Genistein MN levels remained well above background out to 28 weeks after irradiation. Genistein reduced macrophage accumulation by 22% and reduced collagen deposition by 28%. There was minimal protection against increases in breathing rate or severe morbidity during pneumonitis. No tumor protection by genistein treatment was observed. Conclusions: Genistein at the dose levels used in this study partially reduced the extent of fibrosis developing in mouse lung caused by irradiation but gave minimal protection against pneumonitis. There was no evidence that genistein caused protection of small tumors growing in the lung.

Sequential unconstrained minimization algorithms for constrained optimization

International Nuclear Information System (INIS)

Byrne, Charles

2008-01-01

The problem of minimizing a function f(x):R J → R, subject to constraints on the vector variable x, occurs frequently in inverse problems. Even without constraints, finding a minimizer of f(x) may require iterative methods. We consider here a general class of iterative algorithms that find a solution to the constrained minimization problem as the limit of a sequence of vectors, each solving an unconstrained minimization problem. Our sequential unconstrained minimization algorithm (SUMMA) is an iterative procedure for constrained minimization. At the kth step we minimize the function G k (x)=f(x)+g k (x), to obtain x k . The auxiliary functions g k (x):D subset of R J → R + are nonnegative on the set D, each x k is assumed to lie within D, and the objective is to minimize the continuous function f:R J → R over x in the set C = D-bar, the closure of D. We assume that such minimizers exist, and denote one such by x-circumflex. We assume that the functions g k (x) satisfy the inequalities 0≤g k (x)≤G k-1 (x)-G k-1 (x k-1 ), for k = 2, 3, .... Using this assumption, we show that the sequence {(x k )} is decreasing and converges to f(x-circumflex). If the restriction of f(x) to D has bounded level sets, which happens if x-circumflex is unique and f(x) is closed, proper and convex, then the sequence {x k } is bounded, and f(x*)=f(x-circumflex), for any cluster point x*. Therefore, if x-circumflex is unique, x* = x-circumflex and {x k } → x-circumflex. When x-circumflex is not unique, convergence can still be obtained, in particular cases. The SUMMA includes, as particular cases, the well-known barrier- and penalty-function methods, the simultaneous multiplicative algebraic reconstruction technique (SMART), the proximal minimization algorithm of Censor and Zenios, the entropic proximal methods of Teboulle, as well as certain cases of gradient descent and the Newton–Raphson method. The proof techniques used for SUMMA can be extended to obtain related results

Radiation carcinogenesis in scid mice

Energy Technology Data Exchange (ETDEWEB)

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

1999-06-01

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

Automated classification of self-grooming in mice using open-source software.

Science.gov (United States)

van den Boom, Bastijn J G; Pavlidi, Pavlina; Wolf, Casper J H; Mooij, Adriana H; Willuhn, Ingo

2017-09-01

Manual analysis of behavior is labor intensive and subject to inter-rater variability. Although considerable progress in automation of analysis has been made, complex behavior such as grooming still lacks satisfactory automated quantification. We trained a freely available, automated classifier, Janelia Automatic Animal Behavior Annotator (JAABA), to quantify self-grooming duration and number of bouts based on video recordings of SAPAP3 knockout mice (a mouse line that self-grooms excessively) and wild-type animals. We compared the JAABA classifier with human expert observers to test its ability to measure self-grooming in three scenarios: mice in an open field, mice on an elevated plus-maze, and tethered mice in an open field. In each scenario, the classifier identified both grooming and non-grooming with great accuracy and correlated highly with results obtained by human observers. Consistently, the JAABA classifier confirmed previous reports of excessive grooming in SAPAP3 knockout mice. Thus far, manual analysis was regarded as the only valid quantification method for self-grooming. We demonstrate that the JAABA classifier is a valid and reliable scoring tool, more cost-efficient than manual scoring, easy to use, requires minimal effort, provides high throughput, and prevents inter-rater variability. We introduce the JAABA classifier as an efficient analysis tool for the assessment of rodent self-grooming with expert quality. In our "how-to" instructions, we provide all information necessary to implement behavioral classification with JAABA. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2016-02-01

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

A cerebellar learning model of vestibulo-ocular reflex adaptation in wild-type and mutant mice.

Science.gov (United States)

Clopath, Claudia; Badura, Aleksandra; De Zeeuw, Chris I; Brunel, Nicolas

2014-05-21

Mechanisms of cerebellar motor learning are still poorly understood. The standard Marr-Albus-Ito theory posits that learning involves plasticity at the parallel fiber to Purkinje cell synapses under control of the climbing fiber input, which provides an error signal as in classical supervised learning paradigms. However, a growing body of evidence challenges this theory, in that additional sites of plasticity appear to contribute to motor adaptation. Here, we consider phase-reversal training of the vestibulo-ocular reflex (VOR), a simple form of motor learning for which a large body of experimental data is available in wild-type and mutant mice, in which the excitability of granule cells or inhibition of Purkinje cells was affected in a cell-specific fashion. We present novel electrophysiological recordings of Purkinje cell activity measured in naive wild-type mice subjected to this VOR adaptation task. We then introduce a minimal model that consists of learning at the parallel fibers to Purkinje cells with the help of the climbing fibers. Although the minimal model reproduces the behavior of the wild-type animals and is analytically tractable, it fails at reproducing the behavior of mutant mice and the electrophysiology data. Therefore, we build a detailed model involving plasticity at the parallel fibers to Purkinje cells' synapse guided by climbing fibers, feedforward inhibition of Purkinje cells, and plasticity at the mossy fiber to vestibular nuclei neuron synapse. The detailed model reproduces both the behavioral and electrophysiological data of both the wild-type and mutant mice and allows for experimentally testable predictions. Copyright © 2014 the authors 0270-6474/14/347203-13$15.00/0.

The role of cilostazol, a phosphodiesterase 3 inhibitor, on oocyte maturation and subsequent pregnancy in mice.

Directory of Open Access Journals (Sweden)

Min Li

Full Text Available It is important to identify effective contraceptive drugs that cause minimal disruption to physiological processes. Phosphodiesterase 3 (PDE3 inhibitors suppress meiosis in oocytes by decreasing the level of cAMP and blocking the extrusion of the first polar body. In this study, we tested the PDE3 inhibitor, cilostazol, as a potential contraceptive agent. The effects of cilostazol treatment in vitro and in vivo on the suppression of oocyte maturation in a mouse model were investigated. The results indicated that treatment with increasing concentrations of cilostazol led to a dose-dependent arrest in meiosis progression. The effective in vitro concentration was 1 µM and was 300 mg/kg in vivo. The effect of cilostazol was reversible. After removal of the drug, meiosis resumed and mouse oocytes matured in vitro, and showed normal chromosome alignment and spindle organization. After fertilization using an ICSI method, the oocytes showed normal morphology, fertilization rate, embryo cleavage, blastocyst formation, and number of viable pups when compared with controls. The offspring showed similar body weight and fertility. In vivo, the mice became infertile if the drug was injected sequentially, and became pregnant following discontinuation of cilostazol. More importantly, no side effects of cilostazol were observed in treated female mice as demonstrated by blood pressure and heart rate monitoring. It is concluded that cilostazol, a drug routinely used for intermittent claudication, can effectively inhibit oocyte maturation in vitro and in vivo, does not affect the developmental potential of oocytes following drug removal and has few side effects in female mice treated with this drug. These findings suggest that cilostazol may be a potential new contraceptive agent that may facilitate an efficacy and safety study of this drug.

[The reproductive correlates of social hierarchy in laboratory male mice].

Science.gov (United States)

Osadchuk, L B; Salomacheva, I N; Bragin, A V; Osadchuk, A V

2007-01-01

In laboratory male mice the effects of social hierarchy on hormonal and spermatogenic testicular function, accessory organs and testicular weights, sexual behaviour have been investigated using an experimental model of social hierarchy, which is characterised by a minimal size (two male mice) and 5 days period of social interactions. The social rank of the partners was detected by asymmetry in aggressive behaviour. Using the experimental condition, when the both partners have no preferences for exclusive use of area we demonstrated that there were no rank differences in the number of mounts and testicular testosterone content. Nevertheless a rank asymmetry in the male sniffing behaviour towards a receptive female, weights of the testes, seminal vesicles, epididymes and the number of epididymal sperm was kept up in a stable social group. Social dominance was found to affect negatively on testicular testosterone increase in response to introduction of a receptive female and sexual attractiveness of male to a receptive female in both dominant and subordinate males. The results obtained demonstrate the impact of social hierarchy on reproduction in laboratory male mice, particular in respect of spermatogenesis and the testicular testosterone in response to a receptive female.

Hexachlorobenzene stimulates uroporphyria in low affinity AHR mice without increasing CYP1A2

International Nuclear Information System (INIS)

Gorman, Nadia; Trask, Heidi S.; Robinson, Susan W.; Sinclair, Jacqueline F.; Gerhard, Glenn S.; Smith, Andrew G.; Sinclair, Peter R.

2007-01-01

Hexachlorobenzene (HCB), a weak ligand of the aryl hydrocarbon receptor (AHR), causes hepatic uroporphyrin (URO) accumulation (uroporphyria) in humans and animals. CYP1A2 has been shown to be necessary in the development of uroporphyria in mice. Using mice expressing the low affinity form of the AH receptor (AHRd), we investigated whether the enhancement of uroporphyria by HCB involves an obligatory increase in CYP1A2 as measured by specific enzyme assays and immunoblotting. We compared the ability of HCB, in combination with iron dextran and the porphyrin precursor, 5-aminolevulinate (ALA), to cause uroporphyria in a strain of mice (C57BL/6) which expresses the high affinity form of the receptor (AHRb 1 ), with three strains of mice (SWR and two 129 sublines) expressing the low affinity AHRd. In C57BL/6 mice, HCB-enhanced uroporphyria was associated with a doubling of CYP1A2. HCB treatment produced uroporphyria in iron-loaded mice expressing AHRd, even though there was little or no increase in CYP1A2. Cyp1a2(-/-) mice in a 129 background were completely resistant to HCB-induced uroporphyria, and female Hfe(-/-) 129 mice, in which the levels of hepatic CYP1A2 were half of those of the male levels, responded poorly. The effect of exogenous iron, administered in the form of iron dextran, on HCB enhancement of uroporphryia could be replicated utilizing the endogenous hepatic iron accumulated in 129 Hfe(-/-) mice. In conclusion, some minimal basal expression of CYP1A2 is essential for HCB-mediated enhancement of uroporphyria, but increases in CYP1A2 above that level are not essential

Neem leaf glycoprotein prevents post-surgical sarcoma recurrence in Swiss mice by differentially regulating cytotoxic T and myeloid-derived suppressor cells.

Directory of Open Access Journals (Sweden)

Madhurima Sarkar

Full Text Available Post-surgical tumor recurrence is a common problem in cancer treatment. In the present study, the role of neem leaf glycoprotein (NLGP, a novel immunomodulator, in prevention of post-surgical recurrence of solid sarcoma was examined. Data suggest that NLGP prevents tumor recurrence after surgical removal of sarcoma in Swiss mice and increases their tumor-free survival time. In NLGP-treated tumor-free mice, increased cytotoxic CD8+ T cells and a decreased population of suppressor cells, especially myeloid-derived suppressor cells (MDSCs was observed. NLGP-treated CD8+ T cells showed greater cytotoxicity towards tumor-derived MDSCs and supernatants from the same CD8+ T cell culture caused upregulation of FasR and downregulation of cFLIP in MDSCs. To elucidate the role of CD8+ T cells, specifically in association with the downregulation in MDSCs, CD8+ T cells were depleted in vivo before NLGP immunization in surgically tumor removed mice and tumor recurrence was noted. These mice also exhibited increased MDSCs along with decreased levels of Caspase 3, Caspase 8 and increased cFLIP expression. In conclusion, it can be stated that NLGP, by activating CD8+ T cells, down regulates the proportion of MDSCs. Accordingly, suppressive effects of MDSCs on CD8+ T cells are minimized and optimum immune surveillance in tumor hosts is maintained to eliminate the residual tumor mass appearing during recurrence.

Behavioral and electrophysiological characterization of Dyt1 heterozygous knockout mice.

Science.gov (United States)

Yokoi, Fumiaki; Chen, Huan-Xin; Dang, Mai Tu; Cheetham, Chad C; Campbell, Susan L; Roper, Steven N; Sweatt, J David; Li, Yuqing

2015-01-01

DYT1 dystonia is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most of the patients have a trinucleotide deletion (ΔGAG) corresponding to a glutamic acid in the C-terminal region (torsinA(ΔE)). Dyt1 ΔGAG heterozygous knock-in (KI) mice, which mimic ΔGAG mutation in the endogenous gene, exhibit motor deficits and deceased frequency of spontaneous excitatory post-synaptic currents (sEPSCs) and normal theta-burst-induced long-term potentiation (LTP) in the hippocampal CA1 region. Although Dyt1 KI mice show decreased hippocampal torsinA levels, it is not clear whether the decreased torsinA level itself affects the synaptic plasticity or torsinA(ΔE) does it. To analyze the effect of partial torsinA loss on motor behaviors and synaptic transmission, Dyt1 heterozygous knock-out (KO) mice were examined as a model of a frame-shift DYT1 mutation in patients. Consistent with Dyt1 KI mice, Dyt1 heterozygous KO mice showed motor deficits in the beam-walking test. Dyt1 heterozygous KO mice showed decreased hippocampal torsinA levels lower than those in Dyt1 KI mice. Reduced sEPSCs and normal miniature excitatory post-synaptic currents (mEPSCs) were also observed in the acute hippocampal brain slices from Dyt1 heterozygous KO mice, suggesting that the partial loss of torsinA function in Dyt1 KI mice causes action potential-dependent neurotransmitter release deficits. On the other hand, Dyt1 heterozygous KO mice showed enhanced hippocampal LTP, normal input-output relations and paired pulse ratios in the extracellular field recordings. The results suggest that maintaining an appropriate torsinA level is important to sustain normal motor performance, synaptic transmission and plasticity. Developing therapeutics to restore a normal torsinA level may help to prevent and treat the symptoms in DYT1 dystonia.

Behavioral and electrophysiological characterization of Dyt1 heterozygous knockout mice.

Directory of Open Access Journals (Sweden)

Fumiaki Yokoi

Full Text Available DYT1 dystonia is an inherited movement disorder caused by mutations in DYT1 (TOR1A, which codes for torsinA. Most of the patients have a trinucleotide deletion (ΔGAG corresponding to a glutamic acid in the C-terminal region (torsinA(ΔE. Dyt1 ΔGAG heterozygous knock-in (KI mice, which mimic ΔGAG mutation in the endogenous gene, exhibit motor deficits and deceased frequency of spontaneous excitatory post-synaptic currents (sEPSCs and normal theta-burst-induced long-term potentiation (LTP in the hippocampal CA1 region. Although Dyt1 KI mice show decreased hippocampal torsinA levels, it is not clear whether the decreased torsinA level itself affects the synaptic plasticity or torsinA(ΔE does it. To analyze the effect of partial torsinA loss on motor behaviors and synaptic transmission, Dyt1 heterozygous knock-out (KO mice were examined as a model of a frame-shift DYT1 mutation in patients. Consistent with Dyt1 KI mice, Dyt1 heterozygous KO mice showed motor deficits in the beam-walking test. Dyt1 heterozygous KO mice showed decreased hippocampal torsinA levels lower than those in Dyt1 KI mice. Reduced sEPSCs and normal miniature excitatory post-synaptic currents (mEPSCs were also observed in the acute hippocampal brain slices from Dyt1 heterozygous KO mice, suggesting that the partial loss of torsinA function in Dyt1 KI mice causes action potential-dependent neurotransmitter release deficits. On the other hand, Dyt1 heterozygous KO mice showed enhanced hippocampal LTP, normal input-output relations and paired pulse ratios in the extracellular field recordings. The results suggest that maintaining an appropriate torsinA level is important to sustain normal motor performance, synaptic transmission and plasticity. Developing therapeutics to restore a normal torsinA level may help to prevent and treat the symptoms in DYT1 dystonia.

Minimizing Mutual Couping

DEFF Research Database (Denmark)

2010-01-01

Disclosed herein are techniques, systems, and methods relating to minimizing mutual coupling between a first antenna and a second antenna.......Disclosed herein are techniques, systems, and methods relating to minimizing mutual coupling between a first antenna and a second antenna....

Brain Lateralization in Mice Is Associated with Zinc Signaling and Altered in Prenatal Zinc Deficient Mice That Display Features of Autism Spectrum Disorder

Directory of Open Access Journals (Sweden)

Stefanie Grabrucker

2018-01-01

Full Text Available A number of studies have reported changes in the hemispheric dominance in autism spectrum disorder (ASD patients on functional, biochemical, and morphological level. Since asymmetry of the brain is also found in many vertebrates, we analyzed whether prenatal zinc deficient (PZD mice, a mouse model with ASD like behavior, show alterations regarding brain lateralization on molecular and behavioral level. Our results show that hemisphere-specific expression of marker genes is abolished in PZD mice on mRNA and protein level. Using magnetic resonance imaging, we found an increased striatal volume in PZD mice with no change in total brain volume. Moreover, behavioral patterns associated with striatal lateralization are altered and the lateralized expression of dopamine receptor 1 (DR1 in the striatum of PZD mice was changed. We conclude that zinc signaling during brain development has a critical role in the establishment of brain lateralization in mice.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie

2016-04-21

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie; Steullet, Pascal; Kulak, Anita; Preitner, Frederic; Do, Kim Q.; Magistretti, Pierre J.

2016-01-01

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

Ultrasound-targeted hepatic delivery of factor IX in hemophiliac mice.

Science.gov (United States)

Anderson, C D; Moisyadi, S; Avelar, A; Walton, C B; Shohet, R V

2016-06-01

Ultrasound-targeted microbubble destruction (UTMD) was used to direct the delivery of plasmid and transposase-based vectors encoding human factor IX (hFIX) to the livers of hemophilia B (FIX-/-) mice. The DNA vectors were incorporated into cationic lipid microbubbles, injected intravenously, and transfected into hepatocytes by acoustic cavitation of the bubbles as they transited the liver. Ultrasound parameters were identified that produced transfection of hepatocytes in vivo without substantial damage or bleeding in the livers of the FIX-deficient mice. These mice were treated with a conventional expression plasmid, or one containing a piggyBac transposon construct, and hFIX levels in the plasma and liver were evaluated at multiple time points after UTMD. We detected hFIX in the plasma by western blotting from mice treated with either plasmid during the 12 days after UTMD, and in the hepatocytes of treated livers by immunofluorescence. Reductions in clotting time and improvements in the percentage of FIX activity were observed for both plasmids, conventional (4.15±1.98%), and transposon based (2.70±.75%), 4 to 5 days after UTMD compared with untreated FIX (-/-) control mice (0.92±0.78%) (P=0.001 and P=0.012, respectively). Reduced clotting times persisted for both plasmids 12 days after treatment (reflecting percentage FIX activity of 3.12±1.56%, P=0.02 and 3.08±0.10%, P=0.001, respectively). Clotting times from an additional set of mice treated with pmGENIE3-hFIX were evaluated for long-term effects and demonstrated a persistent reduction in average clotting time 160 days after a single treatment. These data suggest that UTMD could be a minimally invasive, nonviral approach to enhance hepatic FIX expression in patients with hemophilia.

TRIF Differentially Regulates Hepatic Steatosis and Inflammation/Fibrosis in MiceSummary

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Ling Yang

2017-05-01

Full Text Available Background & Aims: Toll-like receptor 4 (TLR4 signaling is activated through 2 adaptor proteins: MyD88 and TIR-domain containing adaptor-inducing interferon-β (TRIF. TLR4 and MyD88 are crucial in nonalcoholic steatohepatitis (NASH and fibrosis. However, the role of TRIF in TLR4-mediated NASH and fibrosis has been elusive. This study investigated the differential roles of TRIF in hepatic steatosis and inflammation/fibrosis. Methods: A choline-deficient amino acid defined (CDAA diet was used for the mouse NASH model. On this diet, the mice develop hepatic steatosis, inflammation, and fibrosis. TLR4 wild-type and TLR4-/- bone marrow chimeric mice and TRIF-/- mice were fed CDAA or a control diet for 22 weeks. Hepatic steatosis, inflammation, and fibrosis were examined. Results: In the CDAA diet–induced NASH, the mice with wild-type bone marrow had higher alanine aminotransferase and hepatic tumor necrosis factor levels than the mice with TLR4-/- bone marrow. The nonalcoholic fatty liver disease activity score showed that both wild-type and TLR4-/- bone marrow chimeras had reduced hepatic steatosis, and that both types of chimeras had similar levels of inflammation and hepatocyte ballooning to whole-body wild-type mice. Notably, wild-type recipients showed more liver fibrosis than TLR4-/- recipients. Although TRIF-/- mice showed reduced hepatic steatosis, these mice showed more liver injury, inflammation, and fibrosis than wild-type mice. TRIF-/- stellate cells and hepatocytes produced more C-X-C motif chemokine ligand 1 (CXCL1 and C-C motif chemokine ligand than wild-type cells in response to lipopolysaccharide. Consistently, TRIF-/- mice showed increased CXCL1 and CCL3 expression along with neutrophil and macrophage infiltration, which promotes liver inflammation and injury. Conclusions: In TLR4-mediated NASH, different liver cells have distinct roles in hepatic steatosis, inflammation, and fibrosis. TRIF promotes hepatic

Mutagenicity of nicotine in Schistosoma mansoni - infected mice ...

African Journals Online (AJOL)

Analysis of meiotic chromosomes showed significant elevation in the Schistosoma-infected mice. Administration of nicotine to infected mice substantially increased the percentages of micronucleated cells and total CAs. The percentage of chromosomal abnormalities in spermatocyte metaphase-I cells increased significantly ...

BMI1 loss delays photoreceptor degeneration in Rd1 mice. Bmi1 loss and neuroprotection in Rd1 mice.

Science.gov (United States)

Zencak, Dusan; Crippa, Sylvain V; Tekaya, Meriem; Tanger, Ellen; Schorderet, Daniel E; Munier, Francis L; van Lohuizen, Maarten; Arsenijevic, Yvan

2006-01-01

Retinitis pigmentosa (RP) is a heterogeneous group of genetic disorders leading to blindness, which remain untreatable at present. Rd1 mice represent a recognized model of RP, and so far only GDNF treatment provided a slight delay in the retinal degeneration in these mice. Bmi1, a transcriptional repressor, has recently been shown to be essential for neural stem cell (NSC) renewal in the brain, with an increased appearance of glial cells in vivo in Bmi1 knockout (Bmi1-/-) mice. One of the roles of glial cells is to sustain neuronal function and survival. In the view of a role of the retinal Miller glia as a source of neural protection in the retina, the increased astrocytic population in the Bmi1-/- brain led us to investigate the effect of Bmi1 loss in Rd1 mice. We observed an increase of Müller glial cells in Rd1-Bmi1-/- retinas compared to Rd1. Moreover, Rd1-Bmi1-/- mice showed 7-8 rows of photoreceptors at 30 days of age (P30), while in Rd1 littermates there was a complete disruption of the outer nuclear layer (ONL). Preliminary ERG results showed a responsiveness of Rd1-Bmi1-/- mice in scotopic vision at P35. In conclusion, Bmi1 loss prevented, or rescued, photoreceptors from degeneration to an unanticipated extent in Rd1 mice. In this chapter, we will first provide a brief review of our work on the cortical NSCs and introduce the Bmi1 oncogene, thus offering a rational to our observations on the retina.

Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice.

Science.gov (United States)

Xia, Bo; Cai, Guo He; Yang, Hao; Wang, Shu Pei; Mitchell, Grant A; Wu, Jiang Wei

2017-12-01

Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency.

Subspace Correction Methods for Total Variation and $\\ell_1$-Minimization

KAUST Repository

Fornasier, Massimo

2009-01-01

This paper is concerned with the numerical minimization of energy functionals in Hilbert spaces involving convex constraints coinciding with a seminorm for a subspace. The optimization is realized by alternating minimizations of the functional on a sequence of orthogonal subspaces. On each subspace an iterative proximity-map algorithm is implemented via oblique thresholding, which is the main new tool introduced in this work. We provide convergence conditions for the algorithm in order to compute minimizers of the target energy. Analogous results are derived for a parallel variant of the algorithm. Applications are presented in domain decomposition methods for degenerate elliptic PDEs arising in total variation minimization and in accelerated sparse recovery algorithms based on 1-minimization. We include numerical examples which show e.cient solutions to classical problems in signal and image processing. © 2009 Society for Industrial and Applied Physics.

Pre-treatment with antibiotics and Escherichia coli to equalize the gut microbiota in conventional mice.

Science.gov (United States)

Linninge, Caroline; Ahrné, Siv; Molin, Göran

2015-01-01

The composition of the gut microbiota can vary widely between individual mice of the same batch and thereby affect the resulting outcome in experimental studies. Therefore, an efficient method is needed to equalize the gut microbiota prior to the start of critical experiments. In order to minimize variations in gut microbiota between animals and provide the animals with a Gram-negative flora exposing lipopolysaccharides in the cell-walls, C57BL/6 mice were given a mixture of ampicillin, metronidazole and clindamycin in the drinking water for 3 days and then Escherichia coli for two additional days. Treatment with antibiotics alone or with antibiotics in combination with E. coli was well tolerated by all animals. Body weight and liver weight were not affected, although higher hepatic fat content was found in treated animals (p antibiotics and antibiotics in combination with E. coli (p < 0.01), without affecting the total amount of bacteria. Cloned and sequenced 16S rRNA genes showed high presence of Enterobacteriaceae and Porphymonadaceae in the treated animals. Analysis with Principal Component Analysis gave a clear separation of the composition in microbiota between different treatment groups. The described treatment efficiently equalized the gut microbiota and provided the animals with a strong abundance of Enterobacteriaceae without changing the total load of bacteria. This is a straightforward, lenient and efficient method of pre-treatment to equalize the gut microbiota of mice as a starting procedure of animal studies.

SPLEEN-CELLS FROM ANTIGEN-MINIMIZED MICE ARE SUPERIOR TO SPLEEN-CELLS FROM GERM-FREE AND CONVENTIONAL MICE IN THE STIMULATION OF PRIMARY IN-VITRO PROLIFERATIVE RESPONSES TO NOMINAL ANTIGENS

NARCIS (Netherlands)

HOOPER, DC; MOLOWITZ, EH; BOS, NA; PLOPLIS, VA; CEBRA, JJ

T lymphocytes from mice reared under conditions of differential exposure to food, environmental and microbial antigens were compared for phenotypic shifts that may be associated with prior exposure to antigens as well as functional variations in the ability to respond to antigens ne novo. While the

Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

NARCIS (Netherlands)

Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas

Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced

The Mice Drawer System (MDS experiment and the space endurance record-breaking mice.

Directory of Open Access Journals (Sweden)

Ranieri Cancedda

Full Text Available The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS, contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS. The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th, 2009. MDS returned to Earth on November 27(th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice.

Science.gov (United States)

Cancedda, Ranieri; Liu, Yi; Ruggiu, Alessandra; Tavella, Sara; Biticchi, Roberta; Santucci, Daniela; Schwartz, Silvia; Ciparelli, Paolo; Falcetti, Giancarlo; Tenconi, Chiara; Cotronei, Vittorio; Pignataro, Salvatore

2012-01-01

The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

Sex-Specific Diurnal Immobility Induced by Forced Swim Test in Wild Type and Clock Gene Deficient Mice

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Ningyue Li

2015-03-01

Full Text Available Objective: The link between alterations in circadian rhythms and depression are well established, but the underlying mechanisms are far less elucidated. We investigated the circadian characteristics of immobility behavior in wild type (WT mice and mice with mutations in core Clock genes. Methods: All mice were tested with forced swim test (FST at 4 h intervals. Results: These experiments revealed significant diurnal rhythms associated with immobility behavior in both male and female WT mice with sex-different circadian properties. In addition, male mice showed significantly less immobility during the night phase in comparison to female mice. Female Per1Brdm1 mice also showed significant rhythmicity. However, the timing of rhythmicity was very different from that observed in female wild type mice. Male Per1Brdm1 mice showed a pattern of rhythmicity similar to that of wild type mice. Furthermore, female Per1Brdm1 mice showed higher duration of immobility in comparison to male Per1Brdm1 mice in both daytime and early night phases. Neither Per2Brdm1 nor ClockΔ19 mice showed significant rhythmicity, but both female Per2Brdm1 and ClockΔ19 mice had lower levels of immobility, compared to males. Conclusions: This study highlights the differences in the circadian characteristics of immobility induced by FST in WT, ClockΔ19, Per1, and Per2 deficient mice.

Suppressing an anti-inflammatory cytokine reveals a strong age-dependent survival cost in mice.

Directory of Open Access Journals (Sweden)

Virginia Belloni

Full Text Available BACKGROUND: The central paradigm of ecological immunology postulates that selection acts on immunity as to minimize its cost/benefit ratio. Costs of immunity may arise because the energetic requirements of the immune response divert resources that are no longer available for other vital functions. In addition to these resource-based costs, mis-directed or over-reacting immune responses can be particularly harmful for the host. In spite of the potential importance of immunopathology, most studies dealing with the evolution of the immune response have neglected such non resource-based costs. To keep the immune response under control, hosts have evolved regulatory pathways that should be considered when studying the target of the selection pressures acting on immunity. Indeed, variation in regulation may strongly modulate the negative outcome of immune activation, with potentially important fitness consequences. METHODOLOGY/PRINCIPAL FINDINGS: Here, we experimentally assessed the survival costs of reduced immune regulation by inhibiting an anti-inflammatory cytokine (IL-10 with anti-IL-10 receptor antibodies (anti-IL-10R in mice that were either exposed to a mild inflammation or kept as control. The experiment was performed on young (3 months and old (15 months individuals, as to further assess the age-dependent cost of suppressing immune regulation. IL-10 inhibition induced high mortality in old mice exposed to the mild inflammatory insult, whereas no mortality was observed in young mice. However, young mice experienced a transitory lost in body mass when injected with the anti-IL-10R antibodies, showing that the treatment was to a lesser extent also costly for young individuals. CONCLUSIONS: These results suggest a major role of immune regulation that deserves attention when investigating the evolution of immunity, and indicate that the capacity to down-regulate the inflammatory response is crucial for late survival and longevity.

A Prospective Randomized Study on Operative Treatment for Simple Distal Tibial Fractures-Minimally Invasive Plate Osteosynthesis Versus Minimal Open Reduction and Internal Fixation.

Science.gov (United States)

Kim, Ji Wan; Kim, Hyun Uk; Oh, Chang-Wug; Kim, Joon-Woo; Park, Ki Chul

2018-01-01

To compare the radiologic and clinical results of minimally invasive plate osteosynthesis (MIPO) and minimal open reduction and internal fixation (ORIF) for simple distal tibial fractures. Randomized prospective study. Three level 1 trauma centers. Fifty-eight patients with simple and distal tibial fractures were randomized into a MIPO group (treatment with MIPO; n = 29) or a minimal group (treatment with minimal ORIF; n = 29). These numbers were designed to define the rate of soft tissue complication; therefore, validation of superiority in union time or determination of differences in rates of delayed union was limited in this study. Simple distal tibial fractures treated with MIPO or minimal ORIF. The clinical outcome measurements included operative time, radiation exposure time, and soft tissue complications. To evaluate a patient's function, the American Orthopedic Foot and Ankle Society ankle score (AOFAS) was used. Radiologic measurements included fracture alignment, delayed union, and union time. All patients acquired bone union without any secondary intervention. The mean union time was 17.4 weeks and 16.3 weeks in the MIPO and minimal groups, respectively. There was 1 case of delayed union and 1 case of superficial infection in each group. The radiation exposure time was shorter in the minimal group than in the MIPO group. Coronal angulation showed a difference between both groups. The American Orthopedic Foot and Ankle Society ankle scores were 86.0 and 86.7 in the MIPO and minimal groups, respectively. Minimal ORIF resulted in similar outcomes, with no increased rate of soft tissue problems compared to MIPO. Both MIPO and minimal ORIF have high union rates and good functional outcomes for simple distal tibial fractures. Minimal ORIF did not result in increased rates of infection and wound dehiscence. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Increased anxiety-related behaviour in Hint1 knockout mice.

Science.gov (United States)

Varadarajulu, Jeeva; Lebar, Maria; Krishnamoorthy, Gurumoorthy; Habelt, Sonja; Lu, Jia; Bernard Weinstein, I; Li, Haiyang; Holsboer, Florian; Turck, Christoph W; Touma, Chadi

2011-07-07

Several reports have implicated a role for the histidine triad nucleotide-binding protein-1 (Hint1) in psychiatric disorders. We have studied the emotional behaviour of male Hint1 knockout (Hint1 KO) mice in a battery of tests and performed biochemical analyses on brain tissue. The behavioural analysis revealed that Hint1 KO mice exhibit an increased emotionality phenotype compared to wildtype (WT) mice, while no significant differences in locomotion or general exploratory activity were noted. In the elevated plus-maze (EPM) test, the Hint1 KO animals entered the open arms of the apparatus less often than WT littermates. Similarly, in the dark-light box test, Hint1 KO mice spent less time in the lit compartment and the number of entries were reduced, which further confirmed an increased anxiety-related behaviour. Moreover, the Hint1 KO animals showed significantly more struggling and less floating behaviour in the forced swim test (FST), indicating an increased emotional arousal in aversive situations. Hint1 is known as a protein kinase C (PKC) interacting protein. Western blot analysis showed that PKCγ expression was elevated in Hint1 KO compared to WT mice. Interestingly, PKCγ mRNA levels of the two groups did not show a significant difference, implying a post-transcriptional PKCγ regulation. In addition, PKC enzymatic activity was increased in Hint1 KO compared to WT mice. In summary, our results indicate a role for Hint1 and PKCγ in modulating anxiety-related and stress-coping behaviour in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Survival of irradiated mice treated with WR-151327, synthetic trehalose dicorynomycolate, or ofloxacin

Science.gov (United States)

Ledney, G. D.; Elliott, T. B.; Landauer, M. R.; Vigneulle, R. M.; Henderson, P. L.; Harding, R. A.; Tom, S. P.

1994-10-01

Spaceflight personnel need treatment options that would enhance survival from radiation and would not disrupt task performance. Doses of prophylactic or therapeutic agents known to induce significant short-term (30-day) survival with minimal behavioral (locomotor) changes were used for 180-day survival studies. In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD10) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and γ-rays (n/γ = 1) or 60Co γ-rays. In therapy studies, groups of mice received either S-TDCM, the antimicrobial ofloxacin, or S-TDCM plus ofloxacin after irradiation. For WR-151327 treated-mice, survival at 180 days for n/γ = 1 and γ-irradiated mice was 90% and 92%, respectively; for S-TDCM (protection), 57% and 78%, respectively; for S-TDCM (therapy), 20% and 25%, respectively; for ofloxacin, 38% and 5%, respectively; for S-TDCM combined with ofloxacin, 30% and 30%, respectively; and for saline, 8% and 5%, respectively. Ofloxacin or combined ofloxacin and S-TDCM increased survival from the gram-negative bacterial sepsis that predominated in n/γ = 1) irradiated mice. The efficacies of the treatments depended on radiation quality, treatment agent and its mode of use, and microflora of the host.

Relation of type-C RNA virus infectivity and leukemogenesis in rats and mice

International Nuclear Information System (INIS)

Nagao, Kenji; Ito, Takaaki; Yokoro, Kenjiro

1976-01-01

Observation was made as to movement of type-C RNA virus infectivity in the process of leukemogensis induced by Gross virus, N-nitrosoethylurea (NEU), or, x-ray. Total dose of 680 R in 4 times was given to the whole body or parts of the body at intervals of 5 days. Thymic leukemia occurred in 100% or rats which were inoculated with type-C RNA virus at the period of newborn 64 days after, on the average. Infectious titer of virus rose only in thymus toward leukemogenesis. Thymic leukemia was induced 100% in mice by NEU 122 days after, but its incidence was 9% of mice of which thymus was extracted. Leukemia virus was not detected in non-extracted thymus of mice, and pattern of virus infectivity in other organs did not show any difference with that of mice of which thymus was extracted. Virus showed high infectious titer in uterus of mice of both groups. Leukemia occurred 87% in the whole body irradiated mice, 15% in partially irradiated mice, and 39% in mice of which thymus was extracted and the whole body was irradiated. Virus did not show any homeostatic infectious titer in three kinds of leukemia, but it showed high infectious titer in uterus. (Kanao, N.)

Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice

International Nuclear Information System (INIS)

Liu, Zhi-Qin; Liu, Ting; Chen, Chuan; Li, Ming-Yan; Wang, Zi-Yu; Chen, Ruo-song; Wei, Gui-xiang; Wang, Xiao-yi; Luo, Du-Qiang

2015-01-01

Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathways, and its increased activity and expression are implicated in the pathogenesis of insulin resistance. Therefore, the inhibition of PTP1B is anticipated to become a potential therapeutic strategy to treat T2DM. Fumosorinone (FU), a new natural product isolated from insect fungi Isaria fumosorosea, was found to inhibit PTP1B activity in our previous study. Herein, the effects of FU on insulin resistance and mechanism in vitro and in vivo were investigated. FU increased the insulin-provoked glucose uptake in insulin-resistant HepG2 cells, and also reduced blood glucose and lipid levels of type 2 diabetic KKAy mice. FU decreased the expression of PTP1B both in insulin-resistant HepG2 cells and in liver tissues of diabetic KKAy mice. Furthermore, FU increased the phosphorylation of IRβ, IRS-2, Akt, GSK3β and Erk1/2 in insulin-resistant HepG2 cells, as well as the phosphorylation of IRβ, IRS-2, Akt in liver tissues of diabetic KKAy mice. These results showed that FU increased glucose uptake and improved insulin resistance by down-regulating the expression of PTP1B and activating the insulin signaling pathway, suggesting that it may possess antidiabetic properties. - Highlights: • Fumosorinone is a new PTP1B inhibitor isolated from insect pathogenic fungi. • Fumosorinone attenuated the insulin resistance both in vitro and in vivo. • Fumosorinone decreased the expression of PTP1B both in vitro and in vivo. • Fumosorinone activated the insulin signaling pathway both in vitro and in vivo

Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice

Energy Technology Data Exchange (ETDEWEB)

Liu, Zhi-Qin [College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002 (China); College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality control of Hebei province, Hebei University, Baoding 071002 (China); Liu, Ting; Chen, Chuan [College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002 (China); Li, Ming-Yan; Wang, Zi-Yu; Chen, Ruo-song; Wei, Gui-xiang; Wang, Xiao-yi [College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality control of Hebei province, Hebei University, Baoding 071002 (China); Luo, Du-Qiang, E-mail: duqiangluo999@126.com [College of Life Sciences, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding 071002 (China)

2015-05-15

Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathways, and its increased activity and expression are implicated in the pathogenesis of insulin resistance. Therefore, the inhibition of PTP1B is anticipated to become a potential therapeutic strategy to treat T2DM. Fumosorinone (FU), a new natural product isolated from insect fungi Isaria fumosorosea, was found to inhibit PTP1B activity in our previous study. Herein, the effects of FU on insulin resistance and mechanism in vitro and in vivo were investigated. FU increased the insulin-provoked glucose uptake in insulin-resistant HepG2 cells, and also reduced blood glucose and lipid levels of type 2 diabetic KKAy mice. FU decreased the expression of PTP1B both in insulin-resistant HepG2 cells and in liver tissues of diabetic KKAy mice. Furthermore, FU increased the phosphorylation of IRβ, IRS-2, Akt, GSK3β and Erk1/2 in insulin-resistant HepG2 cells, as well as the phosphorylation of IRβ, IRS-2, Akt in liver tissues of diabetic KKAy mice. These results showed that FU increased glucose uptake and improved insulin resistance by down-regulating the expression of PTP1B and activating the insulin signaling pathway, suggesting that it may possess antidiabetic properties. - Highlights: • Fumosorinone is a new PTP1B inhibitor isolated from insect pathogenic fungi. • Fumosorinone attenuated the insulin resistance both in vitro and in vivo. • Fumosorinone decreased the expression of PTP1B both in vitro and in vivo. • Fumosorinone activated the insulin signaling pathway both in vitro and in vivo.

Evaluate the Influence of Eupatorium adenophorum Extract with Mice Organ

Science.gov (United States)

Nong, Xiang; Yang, Can; Yang, Yaojun; Liang, Zi; Hu, Qiang; Zhang, Ting

2018-01-01

In order to study the influence of extract from Eupatorium adenophorum in mice organs, this experiment will be the basis of further study that make Eupatorium adenophorum become Phyto contraceptive, this experiment take the feeding respectively way after the completion of the 1D, 5D, 10d, 15d of Eupatorium adenophorum mice by intragastrical administration of levonorgestrel group and blank control group. After the same operation in different periods of small rat heart and kidney the uterus, testis, and other organs were observed. The results showed that after extraction of E. adenophorum changes in female mice uterus shape was perfused significantly, showed swelling larger. Data analysis of each viscera coefficient was found E. adenophorum had No obvious effect on the heart, kidneys and testicles of mice. but there are obvious differences date between the treatment group and the blank group. (5d: F=10. 800 P=0. 043 cases) from tissue sections we can see female mice uterus cell morphology changes significantly, there was a similar appearance change in the uterus of the female mice with the estradiol For a male mouse testis of E.adenophorum gavage had No obvious effect. And it is found that the heart, the treated mice kidney, testis, ovary and other organs were observed in each period of time the organization had No obvious change; only female mice uterus tissue sections of individual cells became larger, and the organization of the gap larger. This research shows that E.adenophorum extract has the potential to develop botanical contraceptives, we will conduct in-depth study.

Legal incentives for minimizing waste

International Nuclear Information System (INIS)

Clearwater, S.W.; Scanlon, J.M.

1991-01-01

Waste minimization, or pollution prevention, has become an integral component of federal and state environmental regulation. Minimizing waste offers many economic and public relations benefits. In addition, waste minimization efforts can also dramatically reduce potential criminal requirements. This paper addresses the legal incentives for minimizing waste under current and proposed environmental laws and regulations

The Physical Connection and Magnetic Coupling of the MICE Cooling Channel Magnets and the Magnet Forces for Various MICE Operating Modes

International Nuclear Information System (INIS)

Yang, Stephanie Q.; Baynham, D.E.; Fabricatore, Pasquale; Farinon, Stefania; Green, Michael A.; Ivanyushenkov, Yury; Lau, Wing W.; Maldavi, S.M.; Virostek, Steve P.; Witte, Holger

2006-01-01

A key issue in the construction of the MICE cooling channel is the magnetic forces between various elements in the cooling channel and the detector magnets. This report describes how the MICE cooling channel magnets are hooked to together so that the longitudinal magnetic forces within the cooling channel can be effectively connected to the base of the experiment. This report presents a magnetic force and stress analysis for the MICE cooling channel magnets, even when longitudinal magnetic forces as large as 700 kN (70 tons) are applied to the vacuum vessel of various magnets within the MICE channel. This report also shows that the detector magnets can be effectively separated from the central MICE cooling channel magnets without damage to either type of magnet component

Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice.

Science.gov (United States)

Barker-Haliski, Melissa L; Vanegas, Fabiola; Mau, Matthew J; Underwood, Tristan K; White, H Steve

2016-09-01

Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data. ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested. No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice. Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and

MOCUS, Minimal Cut Sets and Minimal Path Sets from Fault Tree Analysis

International Nuclear Information System (INIS)

Fussell, J.B.; Henry, E.B.; Marshall, N.H.

1976-01-01

1 - Description of problem or function: From a description of the Boolean failure logic of a system, called a fault tree, and control parameters specifying the minimal cut set length to be obtained MOCUS determines the system failure modes, or minimal cut sets, and the system success modes, or minimal path sets. 2 - Method of solution: MOCUS uses direct resolution of the fault tree into the cut and path sets. The algorithm used starts with the main failure of interest, the top event, and proceeds to basic independent component failures, called primary events, to resolve the fault tree to obtain the minimal sets. A key point of the algorithm is that an and gate alone always increases the number of path sets; an or gate alone always increases the number of cut sets and increases the size of path sets. Other types of logic gates must be described in terms of and and or logic gates. 3 - Restrictions on the complexity of the problem: Output from MOCUS can include minimal cut and path sets for up to 20 gates

Large non-Gaussianity in non-minimal inflation

CERN Document Server

Gong, Jinn-Ouk

2011-01-01

We consider a simple inflation model with a complex scalar field coupled to gravity non-minimally. Both the modulus and the angular directions of the complex scalar are slowly rolling, leading to two-field inflation. The modulus direction becomes flat due to the non-minimal coupling, and the angular direction becomes a pseudo-Goldstone boson from a small breaking of the global U(1) symmetry. We show that large non-Gaussianity can be produced during slow-roll inflation under a reasonable assumption on the initial condition of the angular direction. This scenario may be realized in particle physics models such as the Standard Model with two Higgs doublets.

Continuous minimally-invasive alcohol monitoring using microneedle sensor arrays.

Science.gov (United States)

Mohan, A M Vinu; Windmiller, Joshua Ray; Mishra, Rupesh K; Wang, Joseph

2017-05-15

The present work describes an attractive skin-worn microneedle sensing device for the minimally invasive electrochemical monitoring of subcutaneous alcohol. The device consists of an assembly of pyramidal microneedle structures integrated with Pt and Ag wires, each with a microcavity opening. The microneedle aperture was modified by electropolymerizing o-phenylene diamine onto the Pt wire microtransducer, followed by the immobilization of alcohol oxidase (AOx) in an intermediate chitosan layer, along with an outer Nafion layer. The resulting microneedle-based enzyme electrode displays an interference-free ethanol detection in artificial interstitial fluid without compromising its sensitivity, stability and response time. The skin penetration ability and the efficaciousness of the biosensor performance towards subcutaneous alcohol monitoring was substantiated by the ex vivo mice skin model analysis. Our results reveal that the new microneedle sensor holds considerable promise for continuous non-invasive alcohol monitoring in real-life situations. Copyright © 2017 Elsevier B.V. All rights reserved.

Is non-minimal inflation eternal?

International Nuclear Information System (INIS)

Feng, Chao-Jun; Li, Xin-Zhou

2010-01-01

The possibility that the non-minimal coupling inflation could be eternal is investigated. We calculate the quantum fluctuation of the inflaton in a Hubble time and find that it has the same value as that in the minimal case in the slow-roll limit. Armed with this result, we have studied some concrete non-minimal inflationary models including the chaotic inflation and the natural inflation, in which the inflaton is non-minimally coupled to the gravity. We find that the non-minimal coupling inflation could be eternal in some parameter spaces.

Seaweed Extracts as Edible Coatings for Minimally Processed Products

Directory of Open Access Journals (Sweden)

Ana Augusto

2014-05-01

The EC containing Codium tomentosum seaweed extract showed the better performance by minimizing physical and chemical changes in RTE apples, namely: minor changes of moisture, total soluble solids and firmness values. In relation to the browning index, after 20 days of storage, RTE apples coated with EC containing Codium tomentosum seaweed extract showed the lowest values, also the results of peroxidase and polyphenoloxidase showed lower activity compared with the EC containing Fucus spirals, Bifurcaria bifurcate and Codium vermilara seaweed extracts, citric acid EC and the control. These results also allowed a pending patent application nº 107369 “Revestimento de origem marinha para aplicação em produtos minimamente processados ou de quarta gama” which is related with an edible coating with the incorporation of bioactive compounds from macroalgae for minimally processed products.

Roughly isometric minimal immersions into Riemannian manifolds

DEFF Research Database (Denmark)

Markvorsen, Steen

of the intrinsic combinatorial discrete Laplacian, and we will show that they share several analytic and geometric properties with their smooth (minimal submanifold) counterparts in $N$. The intrinsic properties thus obtained may hence serve as roughly invariant descriptors for the original metric space $X$....

Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

Science.gov (United States)

Imai, Saki; Kano, Makoto; Nonoyama, Keiko; Ebihara, Shizufumi

2013-01-01

We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system. PMID:23472206

Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice.

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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.

Mice haploinsufficient for Map2k7, a gene involved in neurodevelopment and risk for schizophrenia, show impaired attention, a vigilance decrement deficit and unstable cognitive processing in an attentional task: impact of minocycline.

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Openshaw, R L; Thomson, D M; Penninger, J M; Pratt, J A; Morris, B J

2017-01-01

Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. Attentional function in mice haploinsufficient for Map2k7 (Map2k7 +/- mice) was investigated using the five-choice serial reaction time task (5-CSRTT). Once stable performance had been achieved, Map2k7 +/- mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline-a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia-signs of improvement in attentional performance were detected. Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline.

Minimal families of curves on surfaces

KAUST Repository

Lubbes, Niels

2014-11-01

A minimal family of curves on an embedded surface is defined as a 1-dimensional family of rational curves of minimal degree, which cover the surface. We classify such minimal families using constructive methods. This allows us to compute the minimal families of a given surface.The classification of minimal families of curves can be reduced to the classification of minimal families which cover weak Del Pezzo surfaces. We classify the minimal families of weak Del Pezzo surfaces and present a table with the number of minimal families of each weak Del Pezzo surface up to Weyl equivalence.As an application of this classification we generalize some results of Schicho. We classify algebraic surfaces that carry a family of conics. We determine the minimal lexicographic degree for the parametrization of a surface that carries at least 2 minimal families. © 2014 Elsevier B.V.

Diacylglycerol lipase a knockout mice demonstrate metabolic and behavioral phenotypes similar to those of cannabinoid receptor 1 knockout mice

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David R Powell

2015-06-01

Full Text Available After creating >4650 knockouts (KOs of independent mouse genes, we screened them by high-throughput phenotyping and found that cannabinoid receptor 1 (Cnr1 KO mice had the same lean phenotype published by others. We asked if our KOs of DAG lipase a or b (Dagla or Daglb, which catalyze biosynthesis of the endocannabinoid (EC 2-Arachidonoylglycerol (2-AG, or Napepld, which catalyzes biosynthesis of the EC anandamide, shared the lean phenotype of Cnr1 KO mice. We found that Dagla KO mice, but not Daglb or Napepld KO mice, were among the leanest of 3651 chow-fed KO lines screened. In confirmatory studies, chow- or high fat diet-fed Dagla and Cnr1 KO mice were leaner than wild type (WT littermates; when data from multiple cohorts of adult mice were combined, body fat was 47% and 45% lower in Dagla and Cnr1 KO mice, respectively, relative to WT values. In contrast, neither Daglb nor Napepld KO mice were lean. Weanling Dagla KO mice ate less than WT mice and had body weight similar to pair-fed WT mice, and adult Dagla KO mice had normal activity and VO2 levels, similar to Cnr1 KO mice. Our Dagla and Cnr1 KO mice also had low fasting insulin, triglyceride and total cholesterol levels, and after a glucose challenge had normal glucose but very low insulin levels. Dagla and Cnr1 KO mice also showed similar responses to a battery of behavioral tests. These data suggest: 1 the lean phenotype of young Dagla and Cnr1 KO mice is mainly due to hypophagia; 2 in pathways where ECs signal through Cnr1 to regulate food intake and other metabolic and behavioral phenotypes observed in Cnr1 KO mice, Dagla alone provides the 2-AG that serves as the EC signal; and 3 small molecule Dagla inhibitors with a pharmacokinetic profile similar to that of Cnr1 inverse agonists are likely to mirror the ability of these Cnr1 inverse agonists to lower body weight and improve glycemic control in obese patients with type 2 diabetes, but may also induce undesirable neuropsychiatric

Hexavalent Chromium Minimization Strategy

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2011-05-01

Logistics 4 Initiative - DoD Hexavalent Chromium Minimization Non- Chrome Primer IIEXAVAJ ENT CHRO:M I~UMI CHROMIUM (VII Oil CrfVli.J CANCEfl HAnRD CD...Management Office of the Secretary of Defense Hexavalent Chromium Minimization Strategy Report Documentation Page Form ApprovedOMB No. 0704-0188...00-2011 4. TITLE AND SUBTITLE Hexavalent Chromium Minimization Strategy 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

Conscious visual memory with minimal attention.

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Pinto, Yair; Vandenbroucke, Annelinde R; Otten, Marte; Sligte, Ilja G; Seth, Anil K; Lamme, Victor A F

2017-02-01

Is conscious visual perception limited to the locations that a person attends? The remarkable phenomenon of change blindness, which shows that people miss nearly all unattended changes in a visual scene, suggests the answer is yes. However, change blindness is found after visual interference (a mask or a new scene), so that subjects have to rely on working memory (WM), which has limited capacity, to detect the change. Before such interference, however, a much larger capacity store, called fragile memory (FM), which is easily overwritten by newly presented visual information, is present. Whether these different stores depend equally on spatial attention is central to the debate on the role of attention in conscious vision. In 2 experiments, we found that minimizing spatial attention almost entirely erases visual WM, as expected. Critically, FM remains largely intact. Moreover, minimally attended FM responses yield accurate metacognition, suggesting that conscious memory persists with limited spatial attention. Together, our findings help resolve the fundamental issue of how attention affects perception: Both visual consciousness and memory can be supported by only minimal attention. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

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Biddinger, Jessica E; Fox, Edward A

2010-08-04

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

Symmetry breaking for drag minimization

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Roper, Marcus; Squires, Todd M.; Brenner, Michael P.

2005-11-01

For locomotion at high Reynolds numbers drag minimization favors fore-aft asymmetric slender shapes with blunt noses and sharp trailing edges. On the other hand, in an inertialess fluid the drag experienced by a body is independent of whether it travels forward or backward through the fluid, so there is no advantage to having a single preferred swimming direction. In fact numerically determined minimum drag shapes are known to exhibit almost no fore-aft asymmetry even at moderate Re. We show that asymmetry persists, albeit extremely weakly, down to vanishingly small Re, scaling asymptotically as Re^3. The need to minimize drag to maximize speed for a given propulsive capacity gives one possible mechanism for the increasing asymmetry in the body plans seen in nature, as organisms increase in size and swimming speed from bacteria like E-Coli up to pursuit predator fish such as tuna. If it is the dominant mechanism, then this signature scaling will be observed in the shapes of motile micro-organisms.

Reduced hepatic tumor incidence in cyclin G1-deficient mice

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Jensen, Michael Rugaard; Factor, Valentina M; Fantozzi, Anna

2003-01-01

found that the p53 levels in the cyclin G1-deficient mice are 2-fold higher that in wild-type mice. Moreover, we showed that treatment of mice with the alkylating agent 1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine (Dipin), followed by partial hepatectomy, decreased G1-S transition in cyclin G1-null...

Targeted Deletion of Kynurenine 3-Monooxygenase in Mice

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Giorgini, Flaviano; Huang, Shao-Yi; Sathyasaikumar, Korrapati V.; Notarangelo, Francesca M.; Thomas, Marian A. R.; Tararina, Margarita; Wu, Hui-Qiu; Schwarcz, Robert; Muchowski, Paul J.

2013-01-01

Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the kynurenine pathway (KP) of tryptophan degradation, has been suggested to play a major role in physiological and pathological events involving bioactive KP metabolites. To explore this role in greater detail, we generated mice with a targeted genetic disruption of Kmo and present here the first biochemical and neurochemical characterization of these mutant animals. Kmo−/− mice lacked KMO activity but showed no obvious abnormalities in the activity of four additional KP enzymes tested. As expected, Kmo−/− mice showed substantial reductions in the levels of its enzymatic product, 3-hydroxykynurenine, in liver, brain, and plasma. Compared with wild-type animals, the levels of the downstream metabolite quinolinic acid were also greatly decreased in liver and plasma of the mutant mice but surprisingly were only slightly reduced (by ∼20%) in the brain. The levels of three other KP metabolites: kynurenine, kynurenic acid, and anthranilic acid, were substantially, but differentially, elevated in the liver, brain, and plasma of Kmo−/− mice, whereas the liver and brain content of the major end product of the enzymatic cascade, NAD+, did not differ between Kmo−/− and wild-type animals. When assessed by in vivo microdialysis, extracellular kynurenic acid levels were found to be significantly elevated in the brains of Kmo−/− mice. Taken together, these results provide further evidence that KMO plays a key regulatory role in the KP and indicate that Kmo−/− mice will be useful for studying tissue-specific functions of individual KP metabolites in health and disease. PMID:24189070

Hematopoietic stem cell function in motheaten mice

International Nuclear Information System (INIS)

Shultz, L.D.; Bailey, C.L.; Coman, D.R.

1983-01-01

Mice homozygous for the autosomal recessive mutation ''motheaten'' have normal numbers of multipotential hematopoietic stem cells in the bone marrow and spleen as determined by spleen colony assay. Histologic examination shows no qualitative abnormality in morphology of stem cell colonies in recipients of bone marrow or spleen cells from motheaten mice. Despite the apparently normal ontogeny, distribution, and differentiative capacity of CFU stem cells, bone marrow and spleen cells from motheaten mice fail to save congenic +/+ lethally gamma-irradiated hosts. This impaired lifesparing capacity is not due to defective self-renewal but appears to be due in part to pulmonary hemorrhage from alveolar capillaries in the gamma-irradiated hosts. Treatment of motheaten mice with 500 R gamma-irradiation followed by reconstitution with normal bone marrow cells increases the lifespan of this mutant to 10 months of age. The early onset of pneumonitis and subsequent short lifespan of motheaten mice is determined at the level of progenitor cells in the bone marrow

INFLUENCE OF MICROBIOTA IN EXPERIMENTAL CUTANEOUS LEISHMANIASIS IN SWISS MICE

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OLIVEIRA Marcia Rosa de

1999-01-01

Full Text Available Infection of Swiss/NIH mice with Leishmania major was compared with infection in isogenic resistant C57BL/6 and susceptible BALB/c mice. Swiss/NIH mice showed self-controlled lesions in the injected foot pad. The production of high levels of interferon-g (IFN-g and low levels of interleukin-4 (IL-4 by cells from these animals suggests that they mount a Th1-type immune response. The importance of the indigenous microbiota on the development of murine leishmaniasis was investigated by infecting germfree Swiss/NIH in the hind footpad with L. major and conventionalizing after 3 weeks of infection. Lesions from conventionalized Swiss/NIH mice were significantly larger than conventional mice. Histopathological analysis of lesions from conventionalized animals showed abscesses of variable shapes and sizes and high numbers of parasitized macrophages. In the lesions from conventional mice, besides the absence of abscess formation, parasites were rarely observed. On the other hand, cells from conventional and conventionalized mice produced similar Th1-type response characterized by high levels of IFN-g and low levels of IL-4. In this study, we demonstrated that Swiss/NIH mice are resistant to L. major infection and that the absence of the normal microbiota at the beginning of infection significantly influenced the lesion size and the inflammatory response at the site of infection.

Preparation of slow release anticancer drug by means of radiation technique and IT's therapeutic effect on sold tumor of mice

International Nuclear Information System (INIS)

Li Ximing; Shen Weiming; Liu Chengjie; Hu Xu

1991-01-01

In order to minimize the toxic effect of chemotherapy of malignant tumors, the authors use a method of radiation induced cast polymerization of hydrophilic monomer at low temperature for immobilization the anticancer drug, 5-Fluorouracil, into the polymer matrix. The anticancer drug-polymer composite called slow release anticancer drug was used for treatment the transplantable squamous cell carcinoma in mice 615 and the transplantable sarcoma (S180) in Kunming mice. There were marked difference between the treated group and the control group. That is the higher inhibition ratio and lower toxic effect were reported

Skewed X-inactivation in cloned mice

International Nuclear Information System (INIS)

Senda, Sho; Wakayama, Teruhiko; Yamazaki, Yukiko; Ohgane, Jun; Hattori, Naka; Tanaka, Satoshi; Yanagimachi, Ryuzo; Shiota, Kunio

2004-01-01

In female mammals, dosage compensation for X-linked genes is accomplished by inactivation of one of two X chromosomes. The X-inactivation ratio (a percentage of the cells with inactivated maternal X chromosomes in the whole cells) is skewed as a consequence of various genetic mutations, and has been observed in a number of X-linked disorders. We previously reported that phenotypically normal full-term cloned mouse fetuses had loci with inappropriate DNA methylation. Thus, cloned mice are excellent models to study abnormal epigenetic events in mammalian development. In the present study, we analyzed X-inactivation ratios in adult female cloned mice (B6C3F1). Kidneys of eight naturally produced controls and 11 cloned mice were analyzed. Although variations in X-inactivation ratio among the mice were observed in both groups, the distributions were significantly different (Ansary-Bradley test, P < 0.01). In particular, 2 of 11 cloned mice showed skewed X-inactivation ratios (19.2% and 86.8%). Similarly, in intestine, 1 of 10 cloned mice had a skewed ratio (75.7%). Skewed X-inactivation was observed to various degrees in different tissues of different individuals, suggesting that skewed X-inactivation in cloned mice is the result of secondary cell selection in combination with stochastic distortion of primary choice. The present study is the first demonstration that skewed X-inactivation occurs in cloned animals. This finding is important for understanding both nuclear transfer technology and etiology of X-linked disorders

Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding C3H/HeN mice

DEFF Research Database (Denmark)

Moser, C; Johansen, H K; Song, Z

1997-01-01

model of this infection was established in two strains of mice: C3H/HeN and BALB/c, generally known as Th1 and Th2 responders, respectively, which were challenged with alginate-embedded P. aeruginosa. Mortality was significantly lower in C3H/HeN compared to BALB/c mice (p ... was cleared more efficiently in C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology (p BALB/c mice (p ... from the two strains of mice, the interferon-(IFN-) gamma levels were higher, whereas IL-4 levels were lower in C3H/HeN mice than in BALB/c mice. The implications of these findings for CF patients with chronic P. aeruginosa lung infection are discussed....

Effect of 30-day orbital flight BION M1 on excretion of expired endogenous CO in mice

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Shulagin, Yury; Tatarkin, Sergey; Dyachenko, Alexander

It is known that increased destruction of hem structures is accompanied by increase of the endogenous carbon monoxide excretion rate with respiration (VCO). Changes VCO preceded the observed changes in the blood composition [D’yachenko A. et al., 2010]. Changes in blood composition, i.e. rise of red blood cells content and reduction of reticulocytes content was detected after a 12-day orbital flight (OF) in mice C57BL/6 [Gridley D.et al., 2003]. The purpose of this study was to investigate the effect of 30-day OF on excretion of endogenous CO. The method and apparatus for simultaneous measurement of VCO, and O2 and CO2 exchange were developed. The research consisted of three parts: 1). Measurement of VCO in five C57BL/6 mice after 30-day OF on the Russian satellite BION M1. 2). Measurement of VCO in six C57BL/6 mice after 30-day ground-based experiment (GBE) with simulated flight telemetry environment of BION M1. 3). Measurement of VCO in seven C57BL/6 mice in vivarium The results: Mice weight after OF was 24.3+-3.3 (mean +-SD) with minimal weight 18.1 g, and maximal weight 29.9 g. Vivarium mice weight was 27.0+-1.8 g. KGE mice weight was 25.0+-1.3 g. Mice age in all three groups was the same. We measured and estimated VCO and total CO excretion (MCO) for two gas mixtures ventilated mouse camera: atmospheric CO-contained air and then CO-free air(30 min). The results showed that the average MCO allocated GBE and vivarium mice did not significantly differ. Average MCO in mice after OF was significantly higher then in vivarium group (T=-2,74; p=0.02). MCO after GBE was between the vivarium and OF groups. MCO in OF and KGE groups did not differ ( T=-1,93; p=0,085). Blood tests in mice after OF was not carried out, because the recovery after the OF was studied in this group. The largest excretion of CO was observed in a mouse N39 after the OF. The weight of this mouse was only 18.1 g, i.e. much less than mean weight. Increase of VCO in food-restricted animal is known

Axion dark matter and Planck favor non-minimal couplings to gravity

Energy Technology Data Exchange (ETDEWEB)

Folkerts, Sarah, E-mail: sarah.folkerts@lmu.de [Arnold Sommerfeld Center, Ludwig-Maximilians-University, Theresienstr. 37, 80333 München (Germany); Germani, Cristiano, E-mail: cristiano.germani@lmu.de [Arnold Sommerfeld Center, Ludwig-Maximilians-University, Theresienstr. 37, 80333 München (Germany); Redondo, Javier, E-mail: javier.redondo@lmu.de [Arnold Sommerfeld Center, Ludwig-Maximilians-University, Theresienstr. 37, 80333 München (Germany); Max-Planck-Institut für Physik (Werner-Heisenberg-Institut), Föhringer Ring 6, 80805 München (Germany)

2014-01-20

Constraints on inflationary scenarios and isocurvature perturbations have excluded the simplest and most generic models of dark matter based on QCD axions. Considering non-minimal kinetic couplings of scalar fields to gravity substantially changes this picture. The axion can account for the observed dark matter density avoiding the overproduction of isocurvature fluctuations. Finally, we show that assuming the same non-minimal kinetic coupling to the axion (dark matter) and to the standard model Higgs boson (inflaton) provides a minimal picture of early time cosmology.

Progressive hearing loss and degeneration of hair cell stereocilia in taperin gene knockout mice

International Nuclear Information System (INIS)

Chen, Mo; Wang, Qin; Zhu, Gang-Hua; Hu, Peng; Zhou, Yuan; Wang, Tian; Lai, Ruo-Sha; Xiao, Zi-An; Xie, Ding-Hua

2016-01-01

The TPRN gene encodes taperin, which is prominently present at the taper region of hair cell stereocilia. Mutations in TPRN have been reported to cause autosomal recessive nonsyndromic deafness 79(DFNB 79). To investigate the role of taperin in pathogenesis of hearing loss, we generated TPRN knockout mice using TALEN technique. Sanger sequencing confirmed an 11 bp deletion at nucleotide 177–187 in exon 1 of TPRN, which results in a truncated form of taperin protein. Heterozygous TPRN +/− mice showed apparently normal auditory phenotypes to their wide-type (WT) littermates. Homozygous TPRN −/− mice exhibited progressive sensorineural hearing loss as reflected by auditory brainstem response to both click and tone burst stimuli at postnatal days 15 (P15), 30 (P30), and 60 (P60). Alex Fluor-594 phalloidin labeling showed no obvious difference in hair cell numbers in the cochlea between TPRN −/− mice and WT mice under light microscope. However, scanning electronic microscopy revealed progressive degeneration of inner hair cell stereocilia, from apparently normal at postnatal days 3 (P3) to scattered absence at P15 and further to substantial loss at P30. The outer hair cell stereocilia also showed progressive degeneration, though much less severe, Collectively, we conclude that taperin plays an important role in maintenance of hair cell stereocilia. Establishment of TPRN knockout mice enables further investigation into the function of this gene. - Highlights: • TPRN −/− mice were generated using TALEN technique. • TPRN −/− mice presented progressive hearing loss. • WT and TPRN −/− mice showed no difference in hair cell numbers. • TPRN −/− mice showed progressive degeneration of hair cell stereocilia.

Radioprotective effects of bacterial superoxide dismutase on mice

International Nuclear Information System (INIS)

Hu Tianxi

1992-01-01

The radioprotective effects of bacterial superoxide dismutase (b-SOD) on the mice irradiated by 8 Gy γ-ray were investigated. The results showed that when b-SOD was injected before and after irradiation, the survival fraction of mice is increased 50% and 30% respectively. The former treatment could increase the DNA synthesis of the myeloid cells and spleen's lymphocytes, decrease the LPO of tissue homogenates and the hemolysis of erythrocytes significantly. The mechanism that b-SOD can drop the radiation injury of the mice was discussed

Effect of Home Cage Bedding in the Induction Chamber on Serum Cortisol and Corticosterone Levels in Response to Isoflurane-induced Anesthesia in C57BL/6J Mice.

Science.gov (United States)

Reiter, Cara P; Christy, Amanda C; Olsen, Cara H; Bentzel, David E

2017-03-01

Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to induction of anesthesia. Here we evaluated the potential for familiar surroundings to reduce the adrenocortical response of mice during anesthesia induction with isoflurane. However, adding bedding from the animals' home cage to the induction chamber failed to significantly reduce serum cortisol or corticosterone levels in male and female C57BL/6J mice. These results indicate that familiar surroundings do not appear sufficient to reduce the adrenocortical response of mice during anesthesia induction with isoflurane.

Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

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Chise Tateno

Full Text Available We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID. We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and

Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

Science.gov (United States)

Tateno, Chise; Kawase, Yosuke; Tobita, Yoshimi; Hamamura, Satoko; Ohshita, Hiroki; Yokomichi, Hiroshi; Sanada, Harumi; Kakuni, Masakazu; Shiota, Akira; Kojima, Yuha; Ishida, Yuji; Shitara, Hiroshi; Wada, Naoko A; Tateishi, Hiromi; Sudoh, Masayuki; Nagatsuka, Shin-Ichiro; Jishage, Kou-Ichi; Kohara, Michinori

2015-01-01

We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID) mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps) replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID). We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb) levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and useful hosts for

SAR image regularization with fast approximate discrete minimization.

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Denis, Loïc; Tupin, Florence; Darbon, Jérôme; Sigelle, Marc

2009-07-01

Synthetic aperture radar (SAR) images, like other coherent imaging modalities, suffer from speckle noise. The presence of this noise makes the automatic interpretation of images a challenging task and noise reduction is often a prerequisite for successful use of classical image processing algorithms. Numerous approaches have been proposed to filter speckle noise. Markov random field (MRF) modelization provides a convenient way to express both data fidelity constraints and desirable properties of the filtered image. In this context, total variation minimization has been extensively used to constrain the oscillations in the regularized image while preserving its edges. Speckle noise follows heavy-tailed distributions, and the MRF formulation leads to a minimization problem involving nonconvex log-likelihood terms. Such a minimization can be performed efficiently by computing minimum cuts on weighted graphs. Due to memory constraints, exact minimization, although theoretically possible, is not achievable on large images required by remote sensing applications. The computational burden of the state-of-the-art algorithm for approximate minimization (namely the alpha -expansion) is too heavy specially when considering joint regularization of several images. We show that a satisfying solution can be reached, in few iterations, by performing a graph-cut-based combinatorial exploration of large trial moves. This algorithm is applied to joint regularization of the amplitude and interferometric phase in urban area SAR images.

Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

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Balamurugan Periaswamy

Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

Establishment of a protocol for determining gastrointestinal transit time in mice using barium and radiopaque markers

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Myagmarjaibuu, Bilomaa; Moon, Myeong Ju; Heo, Suk Hee; Jeong, Seo In; Jeong, Yong Yeon; Kang, Heoung Keun [Dept. of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun (Korea, Republic of); Park, Jong Seong [Dept. of Physiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Jun, Jae Yeoul [Dept. of Physiology, College of Medicine, Chosun University, Gwangju (Korea, Republic of)

2013-01-15

The purpose of this study was to establish a minimally invasive and reproducible protocol for estimating the gastrointestinal (GI) transit time in mice using barium and radiopaque markers. Twenty 5- to 6-week-old Balb/C female mice weighing 19-21 g were used. The animals were divided into three groups: two groups that received loperamide and a control group. The control group (n = 10) animals were administered physiological saline (1.5 mL/kg) orally. The loperamide group I (n = 10) and group II (n = 10) animals were administered 5 mg/kg and 10 mg/kg loperamide orally, respectively. Thirty minutes after receiving the saline or loperamide, the mice was administered 80 μL of barium solution and six iron balls (0.5 mm) via the mouth and the upper esophagus by gavage, respectively. Afterwards, the mice were continuously monitored with fluoroscopic imaging in order to evaluate the swallowing of the barium solution and markers. Serial fluoroscopic images were obtained at 5- or 10-min intervals until all markers had been excreted from the anal canal. For analysis, the GI transit times were subdivided into intestinal transit times (ITTs) and colon transit times (CTTs). The mean ITT was significantly longer in the loperamide groups than in the control group (p < 0.05). The mean ITT in loperamide group II (174.5 ± 32.3) was significantly longer than in loperamide group I (133.2 ± 24.2 minute) (p < 0.05). The mean CTT was significantly longer in loperamide group II than in the control group (p < 0.05). Also, no animal succumbed to death after the experimental procedure. The protocol for our study using radiopaque markers and barium is reproducible and minimally invasive in determining the GI transit time of the mouse model.

Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice

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TIAN Bei; LI Xiao-xin; SHEN Li; ZHAO Min; YU Wen-zhen

2010-01-01

Background Hematopoietic stem cells (HSCs) can be used to deliver functionally active angiostatic molecules to the retinal vasculature by targeting active astrocytes and may be useful in targeting pre-angiogenic retinal lesions. We sought to determine whether HSC mobilization can ameliorate early diabetic retinopathy in mice.Methods Mice were devided into four groups: normal mice control group, normal mice HSC-mobilized group, diabetic mice control group and diabetic mice HSC mobilized group. Murine stem cell growth factor (murine SCF) and recombined human granulocyte colony stimulating factor (rhG-csf) were administered to the mice with diabetes and without diabetes for continuous 5 days to induce autologous HSCs mobilization, and subcutaneous injection of physiological saline was used as control. Immunohistochemical double staining was conducted with anti-mouse rat CD31 monoclonal antibody and anti-BrdU rat antibody.Results Marked HSCs clearly increased after SCF plus G-csf-mobilization. Non-mobilized diabetic mice showed more HSCs than normal mice (P=0.032), and peripheral blood significantly increased in both diabetic and normal mice (P=0.000).Diabetic mice showed more CD31 positive capillary vessels (P=0.000) and accelerated endothelial cell regeneration. Only diabetic HSC-mobilized mice expressed both BrdU and CD31 antigens in the endothelial cells of new capillaries.Conclusion Auto-mobilized adult hematopoietic stem cells advance neovasculature in diabetic retinopathy of mice.

Replica Approach for Minimal Investment Risk with Cost

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Shinzato, Takashi

2018-06-01

In the present work, the optimal portfolio minimizing the investment risk with cost is discussed analytically, where an objective function is constructed in terms of two negative aspects of investment, the risk and cost. We note the mathematical similarity between the Hamiltonian in the mean-variance model and the Hamiltonians in the Hopfield model and the Sherrington-Kirkpatrick model, show that we can analyze this portfolio optimization problem by using replica analysis, and derive the minimal investment risk with cost and the investment concentration of the optimal portfolio. Furthermore, we validate our proposed method through numerical simulations.

Spatial learning and memory in male mice with altered growth hormone action.

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Basu, Amrita; McFarlane, Hewlet G; Kopchick, John J

2017-07-01

Growth hormone (GH) has a significant influence on cognitive performance in humans and other mammals. To understand the influence of altered GH action on cognition, we assessed spatial learning and memory using a Barnes maze (BM) comparing twelve-month old, male, bovine GH (bGH) and GH receptor antagonist (GHA) transgenic mice and their corresponding wild type (WT) littermates. During the acquisition training period in the BM, bGH mice showed increased latency, traveled longer path lengths and made more errors to reach the target than WT mice, indicating significantly poorer learning. Short-term memory (STM) and long-term memory (LTM) trials showed significantly suppressed memory retention in bGH mice when compared to the WT group. Conversely, GHA mice showed significantly better learning parameters (latency, path length and errors) and increased use of an efficient search strategy than WT mice. Our study indicates a negative impact of GH excess and a beneficial effect of the inhibition of GH action on spatial learning and memory and, therefore, cognitive performance in male mice. Further research to elucidate GH's role in brain function will facilitate identifying therapeutic applications of GH or GHA for neuropathological and neurodegenerative conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of exercise and enrichment on behaviour in CD-1 mice.

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Aujnarain, Amiirah B; Luo, Owen D; Taylor, Natalie; Lai, Jonathan K Y; Foster, Jane A

2018-04-16

A host of scholarly work has characterized the positive effects of exercise and environmental enrichment on behaviour and cognition in animal studies. The purpose of this study was to investigate the uptake and longitudinal impact of exercise and enrichment on the behavioural phenotype of male and female CD-1 mice. CD-1 mice housed in standard (STD) or exercise and enrichment (EE) conditions post-weaning were tested in the 3-chamber sociability test, open field, and elevated plus maze and exercise activity was monitored throughout the enrichment protocol. Male and female EE mice both showed reduced anxiety and activity in the open field and elevated plus maze relative to sex-matched STD mice. EE altered social behaviours in a sex-specific fashion, with only female EE mice showing increased social preference relative to female STD mice and a preference for social novelty only present in male EE mice. This sexual dimorphism was not observed to be a product of exercise uptake, as CD-1 mice of both sexes demonstrated a consistent trend of wheel rotation frequencies. These findings suggest the importance of considering variables such as sex and strain on experimental design variables in future work on environmental enrichment. Copyright © 2018 Elsevier B.V. All rights reserved.

Adrenal and liver in normal and cld/cld mice synthesize and secrete hepatic lipase, but the lipase is inactive in cld/cld mice.

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Schultz, C J; Blanchette-Mackie, E J; Scow, R O

2000-02-01

Combined lipase deficiency (cld) is a recessive mutation in mice that causes a severe lack of lipoprotein lipase (LPL) and hepatic lipase (HL) activities, hyperlipemia, and death within 3 days after birth. Earlier studies showed that inactive LPL and HL were synthesized by cld/cld tissues and that LPL synthesized by cld/cld brown adipocytes was retained in their ER. We report here a study of HL in liver, adrenal, and plasma of normal newborn and cld/cld mice. Immunofluorescence studies showed HL was present in extracellular space, but not in cells, in liver and adrenal of both normal and cld/cld mice. When protein secretion was blocked with monensin, HL was retained intracellularly in liver cell cultures and in incubated adrenal tissues of both groups of mice. These findings demonstrated that HL was synthesized and secreted by liver and adrenal cells in normal newborn and cld/cld mice. HL activities in liver, adrenal, and plasma in cld/cld mice were very low, cld/cld cells was inactive. Livers of both normal newborn and cld/cld mice synthesized LPL, but the level of LPL activity in cld/cld liver was very low, cld/cld mice, indicating that LPL was synthesized but not secreted by cld/cld liver cells. Immunofluorescent LPL was not found in normal newborn liver cells unless the cells were treated with monensin, thus demonstrating that normal liver cells synthesized and secreted LPL. Livers of both groups of mice contained an unidentified alkaline lipase activity which accounted for 34-54% of alkaline lipase activity in normal and 65% of that in cld/cld livers. Our findings indicate that liver and adrenal cells synthesized and secreted HL in both normal newborn and cld/cld mice, but the lipase was inactive in cld/cld mice. That cld/cld liver cells secreted inactive HL while retaining inactive LPL indicates that these closely related lipases were processed differently.

Kaempferol attenuates acute lung injury in caecal ligation and puncture model of sepsis in mice.

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Rabha, Dipankar Jyoti; Singh, Thakur Uttam; Rungsung, Soya; Kumar, Tarun; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Paul, Avishek; Sahoo, Monalisa; Kumar, Dinesh

2018-03-01

Kaempferol is a flavonoid and important part of the diet. Kaempferol has shown antioxidant, antiinflammatory and antidiabetic activities in various studies. However, protective potential of kaempferol in acute lung injury induced by sepsis and its mechanism remains unclear. The present study was undertaken to evaluate the effect of kaempferol in sepsis-induced acute lung injury in mice and its possible mechanism of action. Acute lung injury was induced by CLP surgery in mice. Kaempferol (100 mg/kg bw) was administered orally one hour before caecal ligation and puncture surgery in mice. Mice were divided into four groups sham, KEM+sham, sepsis (CLP), and KEM+sepsis. Assessment of lung injury was done by estimation of protein content in lung tissue, lung edema, proinflammatory cytokines in plasma and lung tissue, oxidative stress, antioxidant enzymes, nitrite production, and histopathology. Kaempferol pretreated mice showed significant (P Kaempferol pretreatment showed reduction in cytokines IL-6, IL-1β, and TNF-α in plasma as well as in lung tissue in comparison with septic mice without pretreatment. Pretreatment with kaempferol did not show any reduction in MDA level in comparison with septic mice. Antioxidant enzymes SOD and catalase and nonenzymatic antioxidant GSH activities were also increased with kaempferol pretreatment in septic mice. Further, kaempferol pretreatment reduced the lung tissue nitrite level (P Kaempferol pretreatment did not decrease bacterial load in septic mice. Mice pretreated with kaempferol followed by sepsis showed lesser infiltration of cells and more arranged alveolar structure in histopathological analysis. The study suggests that kaempferol showed attenuation in sepsis-induced acute lung injury in mice through suppression of oxidative stress, iNOS, and ICAM-1 pathways.

[Immunodepressant action of cyclophosphamide in different strains of mice].

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Pevnitskiĭ, L A; Telegin, L Iu; Bol'shev, V N

1977-04-01

A study was made of the immunodepressive effect of cyclophosphamide (CP) on mice of 3 strains (BALB/c, CBA, and DBA/2) immunized with sheep red blood cells (SRBC). With the optimal immunizing dose of the antigen (5 X 10(8) SRBC) the most pronounced immunodepression was noted in DBA/2 mice, and with the high dose (6.2 X 10(9))--in DBA/2 and CBA mice. The CP action proved to depend on the dose of the antigen administered; in BALB/c mice a reduction in the number of the antibody-forming cells was the same with both SRBC doses, in DBA/2 mice an increase of the antigen dose led to reduction of immunode pression, and in CBA mice -- to its enhancement (with sufficiently high CP doses). Determination of the rate of oxidative CP hydroxylation by the liver microsomes of mice showed it to be comparatively low in DBA/2 and CBA mice, and much greater in BALB/c mice. It is supposed that the detected differences in the immunodepressive action of CP could be connected with different sensitivity of the target cells and (or) with the peculiarities of its metabolism in mice belonging to different strains.

Neuropathology in mice expressing mouse alpha-synuclein.

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Claus Rieker

Full Text Available α-Synuclein (αSN in human is tightly linked both neuropathologically and genetically to Parkinson's disease (PD and related disorders. Disease-causing properties in vivo of the wildtype mouse ortholog (mαSN, which carries a threonine at position 53 like the A53T human mutant version that is genetically linked to PD, were never reported. To this end we generated mouse lines that express mαSN in central neurons at levels reaching up to six-fold compared to endogenous mαSN. Unlike transgenic mice expressing human wildtype or mutant forms of αSN, these mαSN transgenic mice showed pronounced ubiquitin immunopathology in spinal cord and brainstem. Isoelectric separation of mαSN species revealed multiple isoforms including two Ser129-phosphorylated species in the most severely affected brain regions. Neuronal Ser129-phosphorylated αSN occurred in granular and small fibrillar aggregates and pathological staining patterns in neurites occasionally revealed a striking ladder of small alternating segments staining either for Ser129-phosphorylated αSN or ubiquitin but not both. Axonal degeneration in long white matter tracts of the spinal cord, with breakdown of myelin sheaths and degeneration of neuromuscular junctions with loss of integrity of the presynaptic neurofilament network in mαSN transgenic mice, was similar to what we have reported for mice expressing human αSN wildtype or mutant forms. In hippocampal neurons, the mαSN protein accumulated and was phosphorylated but these neurons showed no ubiquitin immunopathology. In contrast to the early-onset motor abnormalities and muscle weakness observed in mice expressing human αSN, mαSN transgenic mice displayed only end-stage phenotypic alterations that manifested alongside with neuropathology. Altogether these findings show that increased levels of wildtype mαSN does not induce early-onset behavior changes, but drives end-stage pathophysiological changes in murine neurons that are

Linkage disequilibrium in wild mice.

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Cathy C Laurie

2007-08-01

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.

Transgenic Parasites Stably Expressing Full-Length Plasmodium falciparum Circumsporozoite Protein as a Model for Vaccine Down-Selection in Mice Using Sterile Protection as an Endpoint

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Porter, Michael D.; Nicki, Jennifer; Pool, Christopher D.; DeBot, Margot; Illam, Ratish M.; Brando, Clara; Bozick, Brooke; De La Vega, Patricia; Angra, Divya; Spaccapelo, Roberta; Crisanti, Andrea; Murphy, Jittawadee R.; Bennett, Jason W.; Schwenk, Robert J.; Ockenhouse, Christian F.

2013-01-01

Circumsporozoite protein (CSP) of Plasmodium falciparum is a protective human malaria vaccine candidate. There is an urgent need for models that can rapidly down-select novel CSP-based vaccine candidates. In the present study, the mouse-mosquito transmission cycle of a transgenic Plasmodium berghei malaria parasite stably expressing a functional full-length P. falciparum CSP was optimized to consistently produce infective sporozoites for protection studies. A minimal sporozoite challenge dose was established, and protection was defined as the absence of blood-stage parasites 14 days after intravenous challenge. The specificity of protection was confirmed by vaccinating mice with multiple CSP constructs of differing lengths and compositions. Constructs that induced high NANP repeat-specific antibody titers in enzyme-linked immunosorbent assays were protective, and the degree of protection was dependent on the antigen dose. There was a positive correlation between antibody avidity and protection. The antibodies in the protected mice recognized the native CSP on the parasites and showed sporozoite invasion inhibitory activity. Passive transfer of anti-CSP antibodies into naive mice also induced protection. Thus, we have demonstrated the utility of a mouse efficacy model to down-select human CSP-based vaccine formulations. PMID:23536694

Minimal Gromov-Witten rings

International Nuclear Information System (INIS)

Przyjalkowski, V V

2008-01-01

We construct an abstract theory of Gromov-Witten invariants of genus 0 for quantum minimal Fano varieties (a minimal class of varieties which is natural from the quantum cohomological viewpoint). Namely, we consider the minimal Gromov-Witten ring: a commutative algebra whose generators and relations are of the form used in the Gromov-Witten theory of Fano varieties (of unspecified dimension). The Gromov-Witten theory of any quantum minimal variety is a homomorphism from this ring to C. We prove an abstract reconstruction theorem which says that this ring is isomorphic to the free commutative ring generated by 'prime two-pointed invariants'. We also find solutions of the differential equation of type DN for a Fano variety of dimension N in terms of the generating series of one-pointed Gromov-Witten invariants

AGEMAP: a gene expression database for aging in mice.

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Jacob M Zahn

2007-11-01

Full Text Available We present the AGEMAP (Atlas of Gene Expression in Mouse Aging Project gene expression database, which is a resource that catalogs changes in gene expression as a function of age in mice. The AGEMAP database includes expression changes for 8,932 genes in 16 tissues as a function of age. We found great heterogeneity in the amount of transcriptional changes with age in different tissues. Some tissues displayed large transcriptional differences in old mice, suggesting that these tissues may contribute strongly to organismal decline. Other tissues showed few or no changes in expression with age, indicating strong levels of homeostasis throughout life. Based on the pattern of age-related transcriptional changes, we found that tissues could be classified into one of three aging processes: (1 a pattern common to neural tissues, (2 a pattern for vascular tissues, and (3 a pattern for steroid-responsive tissues. We observed that different tissues age in a coordinated fashion in individual mice, such that certain mice exhibit rapid aging, whereas others exhibit slow aging for multiple tissues. Finally, we compared the transcriptional profiles for aging in mice to those from humans, flies, and worms. We found that genes involved in the electron transport chain show common age regulation in all four species, indicating that these genes may be exceptionally good markers of aging. However, we saw no overall correlation of age regulation between mice and humans, suggesting that aging processes in mice and humans may be fundamentally different.

The early effects in the brain after irradiation with carbon ions using mice

International Nuclear Information System (INIS)

Takai, Nobuhiko; Nakamura, Saori; Ohba, Yoshihito; Uzawa, Akiko; Furusawa, Yoshiya; Koike, Sachiko; Matsumoto, Yoshitaka; Hirayama, Ryoichi

2011-01-01

This study investigated both early and late effects in the brain after irradiation with carbon ions using mice. The irradiation dose was set at level known to produce vascular change followed by necrosis, which appeared the late period after irradiation with 30 Gy. The whole of brain was irradiated, excluding eyes and brain stem. The mice irradiated with single dose of 30 Gy showed deficit in short-term working memory assessed at 36 hr after irradiation, whereas mice receiving carbon irradiation showed no deficit in long-term reference memory. At 16 weeks after irradiation, the irradiated mice showed marked learning impairment compared with age-matched controls and the irradiated mice showed substantial impairment of working memory. Histopathological observation revealed no abnormal finding in the irradiated brain at 36 hr after irradiation, although irradiated mice showed marked neuronal degeneration at the hippocampus within CA1 to CA3 layers at 16 weeks after irradiation. In the irradiated group, neuronal cells in the hippocampal CA1-3 areas were reduced by 30-49%. These results suggest that although irradiation-induced hippocampal degeneration is associated with learning disability, cognitive deficits may also be detected on the early stage, not associated with hippocampal degeneration. (author)

Desensitization of delayed-type hypersensitivity in mice: suppressive environment

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Takashi Katsura

1993-01-01

Full Text Available The systemic injection of high doses of antigen into a preimmunized animal results in transient unresponsiveness of cell-mediated immune responses. This phenomenon is known as desensitization. Serum interleukin 2 (IL-2 activity was found transiently in desensitized mice at 3 h after the antigen challenge. These mice could not reveal antigen nonspecific delayed-type hypersensitivity (DTH 1 d after the challenge. Specific suppression of DTH was observed at later stages. Sera from 3 h desensitized mice showed suppressive effects on DTH in preo immunized mice. Administration of recombinant IL-2 into preimmunized mice led to the failure of development of DTH to antigens. These observations suggest that IL-2 plays an important role in the suppressive environment.

Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice.

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Pan, Qiong; Sun, Yiming; Jin, Qili; Li, Qixiang; Wang, Qing; Liu, Hao; Zhao, Surong

2016-11-01

To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice. Fifteen nude mice were grafted subcutaneously in the left flank with MDA-MB-231 cells, then all mice were divided into control group (PBS), 3BP group (8 mg/kg), positive group (DNR: 0.8 mg/kg) when tumor volume reached approximately 100 mm3. 28 days later, tumors, livers and kidneys were stored in 4 % formalin solution and stained with hematoxylin and eosin staining. The Kunming mice experiment included control group (PBS), 3BP group (4mg/kg; 8mg/kg; 16mg/kg), positive group (DNR: 0.8 mg/kg). 24 hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection. 3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues. 3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.

Norm-Minimized Scattering Data from Intensity Spectra

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Alexander Seel

2016-01-01

Full Text Available We apply the l1 minimizing technique of compressive sensing (CS to nonlinear quadratic observations. For the example of coherent X-ray scattering we provide the formulas for a Kalman filter approach to quadratic CS and show how to reconstruct the scattering data from their spatial intensity distribution.

A Matrix Splitting Method for Composite Function Minimization

KAUST Repository

Yuan, Ganzhao

2016-12-07

Composite function minimization captures a wide spectrum of applications in both computer vision and machine learning. It includes bound constrained optimization and cardinality regularized optimization as special cases. This paper proposes and analyzes a new Matrix Splitting Method (MSM) for minimizing composite functions. It can be viewed as a generalization of the classical Gauss-Seidel method and the Successive Over-Relaxation method for solving linear systems in the literature. Incorporating a new Gaussian elimination procedure, the matrix splitting method achieves state-of-the-art performance. For convex problems, we establish the global convergence, convergence rate, and iteration complexity of MSM, while for non-convex problems, we prove its global convergence. Finally, we validate the performance of our matrix splitting method on two particular applications: nonnegative matrix factorization and cardinality regularized sparse coding. Extensive experiments show that our method outperforms existing composite function minimization techniques in term of both efficiency and efficacy.

A Matrix Splitting Method for Composite Function Minimization

KAUST Repository

Yuan, Ganzhao; Zheng, Wei-Shi; Ghanem, Bernard

2016-01-01

Composite function minimization captures a wide spectrum of applications in both computer vision and machine learning. It includes bound constrained optimization and cardinality regularized optimization as special cases. This paper proposes and analyzes a new Matrix Splitting Method (MSM) for minimizing composite functions. It can be viewed as a generalization of the classical Gauss-Seidel method and the Successive Over-Relaxation method for solving linear systems in the literature. Incorporating a new Gaussian elimination procedure, the matrix splitting method achieves state-of-the-art performance. For convex problems, we establish the global convergence, convergence rate, and iteration complexity of MSM, while for non-convex problems, we prove its global convergence. Finally, we validate the performance of our matrix splitting method on two particular applications: nonnegative matrix factorization and cardinality regularized sparse coding. Extensive experiments show that our method outperforms existing composite function minimization techniques in term of both efficiency and efficacy.

Local Community Detection Algorithm Based on Minimal Cluster

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Yong Zhou

2016-01-01

Full Text Available In order to discover the structure of local community more effectively, this paper puts forward a new local community detection algorithm based on minimal cluster. Most of the local community detection algorithms begin from one node. The agglomeration ability of a single node must be less than multiple nodes, so the beginning of the community extension of the algorithm in this paper is no longer from the initial node only but from a node cluster containing this initial node and nodes in the cluster are relatively densely connected with each other. The algorithm mainly includes two phases. First it detects the minimal cluster and then finds the local community extended from the minimal cluster. Experimental results show that the quality of the local community detected by our algorithm is much better than other algorithms no matter in real networks or in simulated networks.

Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice

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Farooqui Amber

2012-06-01

Full Text Available Abstract Background Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established. Results This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA of viral genomes that might correlate with their different phenotypic behavior. Conclusions The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis.

Multi-instantons in R4 and Minimal Surfaces in R2,1

International Nuclear Information System (INIS)

Tekin, Bayram

2000-01-01

It is known that self-duality equations for multi-instantons on a line in four dimensions are equivalent to minimal surface equations in three dimensional Minkowski space. We extend this equivalence beyond the equations of motion and show that topological number, instanton moduli space and anti-self-dual solutions have representations in terms of minimal surfaces. The issue of topological charge is quite subtle because the surfaces that appear are non-compact. This minimal surface/instanton correspondence allows us to define a metric on the configuration space of the gauge fields. We obtain the minimal surface representation of an instanton with arbitrary charge. The trivial vacuum and the BPST instanton as minimal surfaces are worked out in detail. BPS monopoles and the geodesics are also discussed. (author)

Minimal Marking: A Success Story

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McNeilly, Anne

2014-01-01

The minimal-marking project conducted in Ryerson's School of Journalism throughout 2012 and early 2013 resulted in significantly higher grammar scores in two first-year classes of minimally marked university students when compared to two traditionally marked classes. The "minimal-marking" concept (Haswell, 1983), which requires…

Minimal families of curves on surfaces

KAUST Repository

Lubbes, Niels

2014-01-01

A minimal family of curves on an embedded surface is defined as a 1-dimensional family of rational curves of minimal degree, which cover the surface. We classify such minimal families using constructive methods. This allows us to compute the minimal

A novel radial water tread maze tracks age-related cognitive decline in mice

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Christina Pettan-Brewer

2013-10-01

Full Text Available There is currently no treatment and cure for age-related dementia and cognitive impairment in humans. Mice suffer from age-related cognitive decline just as people do, but assessment is challenging because of cumbersome and at times stressful performance tasks. We developed a novel radial water tread (RWT maze and tested male C57BL/6 (B6 and C57BL/6 x Balb/c F1 (CB6F1 mice at ages 4, 12, 20, and 28 months. B6 mice showed a consistent learning experience and memory retention that gradually decreased with age. CB6F1 mice showed a moderate learning experience in the 4 and 12 month groups, which was not evident in the 20 and 28 month groups. In conclusion, CB6F1 mice showed more severe age-related cognitive impairment compared to B6 mice and might be a suitable model for intervention studies. In addition, the RWT maze has a number of operational advantages compared to currently accepted tasks and can be used to assess age-related cognition impairment in B6 and CB6F1 mice as early as 12 months of age.

Mean-field approximation minimizes relative entropy

International Nuclear Information System (INIS)

Bilbro, G.L.; Snyder, W.E.; Mann, R.C.

1991-01-01

The authors derive the mean-field approximation from the information-theoretic principle of minimum relative entropy instead of by minimizing Peierls's inequality for the Weiss free energy of statistical physics theory. They show that information theory leads to the statistical mechanics procedure. As an example, they consider a problem in binary image restoration. They find that mean-field annealing compares favorably with the stochastic approach

Opportunity Loss Minimization and Newsvendor Behavior

Directory of Open Access Journals (Sweden)

Xinsheng Xu

2017-01-01

Full Text Available To study the decision bias in newsvendor behavior, this paper introduces an opportunity loss minimization criterion into the newsvendor model with backordering. We apply the Conditional Value-at-Risk (CVaR measure to hedge against the potential risks from newsvendor’s order decision. We obtain the optimal order quantities for a newsvendor to minimize the expected opportunity loss and CVaR of opportunity loss. It is proven that the newsvendor’s optimal order quantity is related to the density function of market demand when the newsvendor exhibits risk-averse preference, which is inconsistent with the results in Schweitzer and Cachon (2000. The numerical example shows that the optimal order quantity that minimizes CVaR of opportunity loss is bigger than expected profit maximization (EPM order quantity for high-profit products and smaller than EPM order quantity for low-profit products, which is different from the experimental results in Schweitzer and Cachon (2000. A sensitivity analysis of changing the operation parameters of the two optimal order quantities is discussed. Our results confirm that high return implies high risk, while low risk comes with low return. Based on the results, some managerial insights are suggested for the risk management of the newsvendor model with backordering.

Minimizing Symbol Error Rate for Cognitive Relaying with Opportunistic Access

KAUST Repository

Zafar, Ammar

2012-12-29

In this paper, we present an optimal resource allocation scheme (ORA) for an all-participate(AP) cognitive relay network that minimizes the symbol error rate (SER). The SER is derived and different constraints are considered on the system. We consider the cases of both individual and global power constraints, individual constraints only and global constraints only. Numerical results show that the ORA scheme outperforms the schemes with direct link only and uniform power allocation (UPA) in terms of minimizing the SER for all three cases of different constraints. Numerical results also show that the individual constraints only case provides the best performance at large signal-to-noise-ratio (SNR).

Waste minimization assessment procedure

International Nuclear Information System (INIS)

Kellythorne, L.L.

1993-01-01

Perry Nuclear Power Plant began developing a waste minimization plan early in 1991. In March of 1991 the plan was documented following a similar format to that described in the EPA Waste Minimization Opportunity Assessment Manual. Initial implementation involved obtaining management's commitment to support a waste minimization effort. The primary assessment goal was to identify all hazardous waste streams and to evaluate those streams for minimization opportunities. As implementation of the plan proceeded, non-hazardous waste streams routinely generated in large volumes were also evaluated for minimization opportunities. The next step included collection of process and facility data which would be useful in helping the facility accomplish its assessment goals. This paper describes the resources that were used and which were most valuable in identifying both the hazardous and non-hazardous waste streams that existed on site. For each material identified as a waste stream, additional information regarding the materials use, manufacturer, EPA hazardous waste number and DOT hazard class was also gathered. Once waste streams were evaluated for potential source reduction, recycling, re-use, re-sale, or burning for heat recovery, with disposal as the last viable alternative

Westinghouse Hanford Company waste minimization actions

International Nuclear Information System (INIS)

Greenhalgh, W.O.

1988-09-01

Companies that generate hazardous waste materials are now required by national regulations to establish a waste minimization program. Accordingly, in FY88 the Westinghouse Hanford Company formed a waste minimization team organization. The purpose of the team is to assist the company in its efforts to minimize the generation of waste, train personnel on waste minimization techniques, document successful waste minimization effects, track dollar savings realized, and to publicize and administer an employee incentive program. A number of significant actions have been successful, resulting in the savings of materials and dollars. The team itself has been successful in establishing some worthwhile minimization projects. This document briefly describes the waste minimization actions that have been successful to date. 2 refs., 26 figs., 3 tabs

Antistress, Adoptogenic Activity of Sida cordifolia Roots in Mice.

Science.gov (United States)

Sumanth, Meera; Mustafa, S S

2009-05-01

Ethanol extract of roots of Sida cordifolia was evaluated for antistress, adaptogenic activity using cold restraint stress and swim endurance in mice. Mice pretreated with extract of Sida cordifolia showed significant improvement in the swim duration and reduced the elevated WBC, blood glucose and plasma cortisone.

[Experimental study of metabonomics in the diagnosis of allergic rhinitis in mice].

Science.gov (United States)

Wang, A; Li, Q F; Zhang, G Q; Zhao, C Q

2016-02-01

To investigate the application of metabonomics in the diagnosis of allergic rhinitis. Eighty male Kunming mice were randomly divided into two groups, control group (30 mice) and allergic rhinitis (AR) group (50 mice). After modeling, removal behavior score more than 6 and retain 30 mice behavior score equal to 6.Collect the mice peripheral blood and preparate blood serum, using UPLC-MS chromatographic separation and detection. The data were pretreated by SPSS and Excel, after chromatographic peak matching by MZmine. Firstly , delete interference data in accordance with the 80% rule .Then, the investigate data were analyzed by PLS-DA and PCA-X. Three-dimensional view of the control group (30 mice) and AR group (30 mice) blood serum data was drawn using PCA-X and PLS-DA method. The two groups of samples could be completely separated through views, which showed that there was a significant difference between the two groups of data. There were some differences in the blood metabolites between the control group and AR group . The study showed that it was scientific and feasible to diagnose AR using the metabonomics.

Radon inhalation suppresses nephropathy in streptozotocin-induced type-1 diabetic mice

International Nuclear Information System (INIS)

Nishiyama, Yuichi; Kataoka, Takahiro; Yamato, Keiko; Etani, Reo; Taguchi, Takehito; Yamaoka, Kiyonori

2016-01-01

In this study, we investigated the suppressive effects of radon inhalation against nephropathy in C57BL/6J mice with type-1 diabetes induced by intraperitoneal injection of streptozotocin (50 mg/kg weight, given five times). Four weeks after diabetes induction, the diabetic mice were continuously treated with inhaled radon-222 of 2000 Bq/m3 or air only (sham) for four weeks. The results showed that radon inhalation did not affect type-1 diabetic symptoms such as body weight loss, hyperglycemia, and hypoinsulinemia. However, diabetic mice treated with radon showed lower urinary albumin excretion and fibrotic change in renal glomeruli compared with diabetic mice not treated with radon. Furthermore, renal superoxide dismutase activity and glutathione content were significantly higher in diabetic mice treated with radon than in diabetic mice not treated with radon. These findings suggested that radon inhalation enhanced renal antioxidants activities, resulting in the suppression of diabetic nephropathy. This study may contribute to the development of a novel approach in the treatment of nephropathy for diabetic patients. (author)

Protective effect of Hongxue tea mixture against radiation injury in mice

International Nuclear Information System (INIS)

Zhao Chun; Zhang Xuehui; Wang Qi

2005-01-01

Objective: To develop health food of anti-radiation among biological source in Yunnan. Methods: Screening test was done of the health food of biological source of anti-radiation injury in mice. It is indicated that Hong-Xue Tea Mixture among the biological source has the effect against radiation injury, observing experiment of dose-effect of Hong-Xue Tea Mixture was done. Micronuclei in the bone marrow polychromatophilic erythrocytes in each dose group of mice were examined, leucocytes number and 30 day survival rate of mice following whole-body 5.0 Gy γ irradiation were also determined. Results: Research showed that Hong-Xue Tea Mixture and Spirulina Platensis Mixture among the biological source have protective effect against radiation injury in mice. Observing experiment of dose-effect of Hong-Xue Tea Mixture show that low, medium and high dose of Hong-Xue Tea Mixture can significantly decrease bone marrow PECMN rate of mice, increase leucocytes number and 30 day survival rate. Conclusion: Hong-Xue Tea Mixture has potent protective effects against radiation injury in mice. (authors)

Deficits of learning and memory in Hemojuvelin knockout mice.

Science.gov (United States)

Li, Jinglong; Zhang, Peng; Liu, Hongju; Ren, Wei; Song, Jinjing; Rao, Elizabeth; Takahashi, Eiki; Zhou, Ying; Li, Weidong; Chen, Xiaoping

2015-10-01

Iron is involved in various physiological processes of the human body to maintain normal functions. Abnormal iron accumulation in brain has been reported as a pathogenesis of several neurodegenerative disorders and cognitive impairments. Hemojuvelin (HVJ) is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis. Although iron accumulation in brain has been related to neurodegenerative diseases, it remains unknown the effect of mutation of HVJ gene on cognitive performance. In our studies, HJV(-/-) mice showed deficits in novel object recognition and Morris water maze tests. Furthermore, the expression ration of apoptotic marker Bax and anti-apoptotic marker Bcl-2 in the hippocampus and prefrontal cortex showed higher levels in HJV(-/-) mice. Our results suggested that deletion of HJV gene could increase apoptosis in brain which might contribute to learning and memory deficits in mutant mice. These results indicated that HJV(-/-) mice would be a useful model to study cognitive impairment induced by iron overload in brain.

Loss of ATM kinase activity leads to embryonic lethality in mice

DEFF Research Database (Denmark)

Daniel, J.A.; Pellegrini, M.; Filsuf, D.

2012-01-01

whether the functions of ATM are mediated solely by its kinase activity, we generated two mouse models containing single, catalytically inactivating point mutations in Atm. In this paper, we show that, in contrast to Atm-null mice, both D2899A and Q2740P mutations cause early embryonic lethality in mice......, without displaying dominant-negative interfering activity. Using conditional deletion, we find that the D2899A mutation in adult mice behaves largely similar to Atm-null cells but shows greater deficiency in homologous recombination (HR) as measured by hypersensitivity to poly (adenosine diphosphate...

Strategies to rescue the consequences of inducible arginase-1 deficiency in mice.

Directory of Open Access Journals (Sweden)

Laurel L Ballantyne

Full Text Available Arginase-1 catalyzes the conversion of arginine to ornithine and urea, which is the final step of the urea cycle used to remove excess ammonia from the body. Arginase-1 deficiency leads to hyperargininemia in mice and man with severe lethal consequences in the former and progressive neurological impairment to varying degrees in the latter. In a tamoxifen-induced arginase-1 deficient mouse model, mice succumb to the enzyme deficiency within 2 weeks after inducing the knockout and retain <2 % enzyme in the liver. Standard clinical care regimens for arginase-1 deficiency (low-protein diet, the nitrogen-scavenging drug sodium phenylbutyrate, ornithine supplementation either failed to extend lifespan (ornithine or only minimally prolonged lifespan (maximum 8 days with low-protein diet and drug. A conditional, tamoxifen-inducible arginase-1 transgenic mouse strain expressing the enzyme from the Rosa26 locus modestly extended lifespan of neonatal mice, but not that of 4-week old mice, when crossed to the inducible arginase-1 knockout mouse strain. Delivery of an arginase-1/enhanced green fluorescent fusion construct by adeno-associated viral delivery (rh10 serotype with a strong cytomegalovirus-chicken β-actin hybrid promoter rescued about 30% of male mice with lifespan prolongation to at least 6 months, extensive hepatic expression and restoration of significant enzyme activity in liver. In contrast, a vector of the AAV8 serotype driven by the thyroxine-binding globulin promoter led to weaker liver expression and did not rescue arginase-1 deficient mice to any great extent. Since the induced arginase-1 deficient mouse model displays a much more severe phenotype when compared to human arginase-1 deficiency, these studies reveal that it may be feasible with gene therapy strategies to correct the various manifestations of the disorder and they provide optimism for future clinical studies.

Neurogenesis-mediated forgetting minimizes proactive interference.

Science.gov (United States)

Epp, Jonathan R; Silva Mera, Rudy; Köhler, Stefan; Josselyn, Sheena A; Frankland, Paul W

2016-02-26

Established memories may interfere with the encoding of new memories, particularly when existing and new memories overlap in content. By manipulating levels of hippocampal neurogenesis, here we show that neurogenesis regulates this form of proactive interference. Increasing hippocampal neurogenesis weakens existing memories and, in doing so, facilitates the encoding of new, conflicting (but not non-conflicting) information in mice. Conversely, decreasing neurogenesis stabilizes existing memories, and impedes the encoding of new, conflicting information. These results suggest that reduced proactive interference is an adaptive benefit of neurogenesis-induced forgetting.

Immunomodulatory and antioxidative activity of Cordyceps militaris polysaccharides in mice.

Science.gov (United States)

Liu, Jing-yu; Feng, Cui-ping; Li, Xing; Chang, Ming-chang; Meng, Jun-long; Xu, Li-jing

2016-05-01

To evaluate the immune activation and reactive oxygen species scavenging activity of Cordyceps militaris polysaccharides (CMP) in vivo, 24 male and 24 female Kunming mice were randomly divided into four groups. The mice in the four experimental groups were administered 0 (normal control), 50, 100, or 200mg/kg/d body weight CMP via gavage. After 30 days, the viscera index, leukocyte count, differential leukocyte count, immunoglobulin (IgG) levels, and biochemical parameters were measured. The effect of CMP on the expression of tumor necrosis (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β in the spleens of experimental mice was investigated by real-time polymerase chain reaction. The results showed that the administration of CMP improved the immune function in mice, significantly increased the spleen and thymus indices, the spleen lymphocyte activity, the total quantity of white blood cells, and IgG function in mice serum. CMP exhibited significant antioxidative activity in mice, and decreased malondialdehyde levels in vivo. CMP upregulated the expression of TNF-α, IFN-γ, and IL-1β mRNA in high-dose groups compared to that observed for the control mice. We can thus conclude that CMP effectively improved the immune function through protection against oxidative stress. CMP thus shows potential for development as drugs and health supplements. Copyright © 2016 Elsevier B.V. All rights reserved.

Minimal but non-minimal inflation and electroweak symmetry breaking

Energy Technology Data Exchange (ETDEWEB)

Marzola, Luca [National Institute of Chemical Physics and Biophysics,Rävala 10, 10143 Tallinn (Estonia); Institute of Physics, University of Tartu,Ravila 14c, 50411 Tartu (Estonia); Racioppi, Antonio [National Institute of Chemical Physics and Biophysics,Rävala 10, 10143 Tallinn (Estonia)

2016-10-07

We consider the most minimal scale invariant extension of the standard model that allows for successful radiative electroweak symmetry breaking and inflation. The framework involves an extra scalar singlet, that plays the rôle of the inflaton, and is compatibile with current experimental bounds owing to the non-minimal coupling of the latter to gravity. This inflationary scenario predicts a very low tensor-to-scalar ratio r≈10{sup −3}, typical of Higgs-inflation models, but in contrast yields a scalar spectral index n{sub s}≃0.97 which departs from the Starobinsky limit. We briefly discuss the collider phenomenology of the framework.

An experimental analysis of the specificity of actively acquired tolerance in mice

Energy Technology Data Exchange (ETDEWEB)

Doria, G.

1963-08-15

Tolerance to CBA skin was induced in C3H mice by neonatal injection of CBA spleen cells. When two months old, the C3H recipients were grafted with CBA skin. These skin grafts showed no signs of rejection during the observation time of three months, whereas CBA skins grafted onto C3H mice non injected at birth showed complete necrosis in 11.7 days. Normal C3H and C3H mice tolerant to CBA skin were injected with rat RBC and sacrificed 12 days later for serum titration of anti-rat RBC agglutinins. The agglutinin titer was the same in both groups. This indicates that the unresponsiveness of C3H mice to CBA skin was specific, for the tolerant mice were able to respond with normal vigor to antigens (rat RBC) unrelated to C3H and CBA. Whether this response was due to the host immune system or to the CBA spleen cells which may have colonized the C3H newborns was subsequently investigated. Spleen cells from tolerant C3H mice sensitized to rat RBC were injected into two groups of lethally irradiated recipients: C3H mice preimmunized against CBA and CBA mice preimmunized against C3H. Both groups were given rat RBC immediately after the spleen cell transfer from the tolerant mice and sacrified a week later for serum titration of anti-rat RBC agglutinins. These agglutinins, due to the secondary response of the transferred spleen cells, could be detected only in the group of C3H recipients preimmunized against CBA. This shows that anti-rat RBC agglutinins in tolerant mice were produced y the immune system of the C3H host. The theoretical implications of this finding are discussed. (auth)

Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

Science.gov (United States)

Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

2014-01-01

Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA. PMID:24675475

Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action

International Nuclear Information System (INIS)

Currie, Richard A.; Peffer, Richard C.; Goetz, Amber K.; Omiecinski, Curtis J.; Goodman, Jay I.

2014-01-01

Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA

The electroweak phase transition in minimal supergravity models

CERN Document Server

Nanopoulos, Dimitri V

1994-01-01

We have explored the electroweak phase transition in minimal supergravity models by extending previous analysis of the one-loop Higgs potential to include finite temperature effects. Minimal supergravity is characterized by two higgs doublets at the electroweak scale, gauge coupling unification, and universal soft-SUSY breaking at the unification scale. We have searched for the allowed parameter space that avoids washout of baryon number via unsuppressed anomalous Electroweak sphaleron processes after the phase transition. This requirement imposes strong constraints on the Higgs sector. With respect to weak scale baryogenesis, we find that the generic MSSM is {\\it not} phenomenologically acceptable, and show that the additional experimental and consistency constraints of minimal supergravity restricts the mass of the lightest CP-even Higgs even further to $m_h\\lsim 32\\GeV$ (at one loop), also in conflict with experiment. Thus, if supergravity is to allow for baryogenesis via any other mechanism above the weak...

Minimizing convex functions by continuous descent methods

Directory of Open Access Journals (Sweden)

Sergiu Aizicovici

2010-01-01

Full Text Available We study continuous descent methods for minimizing convex functions, defined on general Banach spaces, which are associated with an appropriate complete metric space of vector fields. We show that there exists an everywhere dense open set in this space of vector fields such that each of its elements generates strongly convergent trajectories.

Transient anhedonia phenotype and altered circadian timing of behaviour during night-time dim light exposure in Per3-/- mice, but not wildtype mice.

Science.gov (United States)

Martynhak, Bruno Jacson; Hogben, Alexandra L; Zanos, Panos; Georgiou, Polymnia; Andreatini, Roberto; Kitchen, Ian; Archer, Simon N; von Schantz, Malcolm; Bailey, Alexis; van der Veen, Daan R

2017-01-10

Industrialisation greatly increased human night-time exposure to artificial light, which in animal models is a known cause of depressive phenotypes. Whilst many of these phenotypes are 'direct' effects of light on affect, an 'indirect' pathway via altered sleep-wake timing has been suggested. We have previously shown that the Period3 gene, which forms part of the biological clock, is associated with altered sleep-wake patterns in response to light. Here, we show that both wild-type and Per3 -/- mice showed elevated levels of circulating corticosterone and increased hippocampal Bdnf expression after 3 weeks of exposure to dim light at night, but only mice deficient for the PERIOD3 protein (Per3 -/- ) exhibited a transient anhedonia-like phenotype, observed as reduced sucrose preference, in weeks 2-3 of dim light at night, whereas WT mice did not. Per3 -/- mice also exhibited a significantly smaller delay in behavioural timing than WT mice during weeks 1, 2 and 4 of dim light at night exposure. When treated with imipramine, neither Per3 -/- nor WT mice exhibited an anhedonia-like phenotype, and neither genotypes exhibited a delay in behavioural timing in responses to dLAN. While the association between both Per3 -/- phenotypes remains unclear, both are alleviated by imipramine treatment during dim night-time light.

Minimal-length Synthetic shRNAs Formulated with Lipid Nanoparticles are Potent Inhibitors of Hepatitis C Virus IRES-linked Gene Expression in Mice

Directory of Open Access Journals (Sweden)

Anne Dallas

2013-01-01

Full Text Available We previously identified short synthetic shRNAs (sshRNAs that target a conserved hepatitis C virus (HCV sequence within the internal ribosome entry site (IRES of HCV and potently inhibit HCV IRES-linked gene expression. To assess in vivo liver delivery and activity, the HCV-directed sshRNA, SG220 was formulated into lipid nanoparticles (LNP and injected i.v. into mice whose livers supported stable HCV IRES-luciferase expression from a liver-specific promoter. After a single injection, RNase protection assays for the sshRNA and 3H labeling of a lipid component of the nanoparticles showed efficient liver uptake of both components and long-lasting survival of a significant fraction of the sshRNA in the liver. In vivo imaging showed a dose-dependent inhibition of luciferase expression (>90% 1 day after injection of 2.5 mg/kg sshRNA with t1/2 for recovery of about 3 weeks. These results demonstrate the ability of moderate levels of i.v.-injected, LNP-formulated sshRNAs to be taken up by liver hepatocytes at a level sufficient to substantially suppress gene expression. Suppression is rapid and durable, suggesting that sshRNAs may have promise as therapeutic agents for liver indications.

Preserved dopaminergic homeostasis and dopamine-related behaviour in hemizygous TH-Cre mice

DEFF Research Database (Denmark)

Thomsen, Annika Højrup Runegaard; Jensen, Kathrine L; Fitzpatrick, Ciarán M

2017-01-01

assessment of the dopaminergic system in hemizygous tyrosine hydroxylase (TH)-Cre mice in comparison to wild-type (WT) controls. Our data show that TH-Cre mice display preserved dopaminergic homeostasis with unaltered levels of TH and dopamine as well as unaffected dopamine turnover in striatum. TH-Cre mice...

Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

Directory of Open Access Journals (Sweden)

Miao Long

2016-10-01

Full Text Available Lead is harmful for human health and animals. Proanthocyanidins (PCs, a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER stress-related genes and protein (GRP78 and CHOP. Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress

PERCEPTION OF SWEET TASTE IS IMPORTANT FOR VOLUNTARY ALCOHOL CONSUMPTION IN MICE

OpenAIRE

Blednov, Y.A.; Walker, D.; Martinez, M.; Levine, M.; Damak, S.; Margolskee, R.F.

2007-01-01

To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: α-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solution...

Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender

Directory of Open Access Journals (Sweden)

Pereira Thiago MC

2010-08-01

Full Text Available Abstract Background Although advanced age is considered a risk factor for several diseases, the impact of gender on age-associated cardiovascular diseases, such as atherosclerotic processes and valvular diseases, remains not completely clarified. The present study was designed to assess aortic valve morphology and function and vascular damage in elderly using the apolipoprotein E knockout (ApoE KO mouse. Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice. Methods The grade (0 to 4 of aortic regurgitation was evaluated through angiography. In addition, vascular lipid deposition and senescence were evaluated through histochemical analyses in aged male and female ApoE KO mice, and the results were compared to wild-type C57BL/6J (C57 mice. Results Aortic regurgitation was observed in 92% of the male ApoE KO mice and 100% of the male C57 mice. Comparatively, in age-matched female ApoE KO and C57 mice, aortic regurgitation was observed in a proportion of 58% and 53%, respectively. Histological analysis of the aorta showed an outward (positive remodeling in ApoE KO mice (female: 1.86 ± 0.15; male: 1.89 ± 0.68 using C57 groups as reference values. Histochemical evaluation of the aorta showed lipid deposition and vascular senescence only in the ApoE KO group, which were more pronounced in male mice. Conclusion The data show that male gender contributes to the progression of aortic regurgitation and that hypercholesterolemia and male gender additively contribute to the occurrence of lipid deposition and vascular senescence in elderly mice.

Global Analysis of Minimal Surfaces

CERN Document Server

Dierkes, Ulrich; Tromba, Anthony J

2010-01-01

Many properties of minimal surfaces are of a global nature, and this is already true for the results treated in the first two volumes of the treatise. Part I of the present book can be viewed as an extension of these results. For instance, the first two chapters deal with existence, regularity and uniqueness theorems for minimal surfaces with partially free boundaries. Here one of the main features is the possibility of 'edge-crawling' along free parts of the boundary. The third chapter deals with a priori estimates for minimal surfaces in higher dimensions and for minimizers of singular integ

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

Energy Technology Data Exchange (ETDEWEB)

Kaphalia, Lata [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Boroumand, Nahal [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Hyunsu, Ju [Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Calhoun, William J. [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States)

2014-06-01

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

International Nuclear Information System (INIS)

Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S.; Calhoun, William J.

2014-01-01

Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

International Nuclear Information System (INIS)

Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

1985-01-01

The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae

Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

1985-01-01

The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae.

Waste minimization handbook, Volume 1

Energy Technology Data Exchange (ETDEWEB)

Boing, L.E.; Coffey, M.J.

1995-12-01

This technical guide presents various methods used by industry to minimize low-level radioactive waste (LLW) generated during decommissioning and decontamination (D and D) activities. Such activities generate significant amounts of LLW during their operations. Waste minimization refers to any measure, procedure, or technique that reduces the amount of waste generated during a specific operation or project. Preventive waste minimization techniques implemented when a project is initiated can significantly reduce waste. Techniques implemented during decontamination activities reduce the cost of decommissioning. The application of waste minimization techniques is not limited to D and D activities; it is also useful during any phase of a facility`s life cycle. This compendium will be supplemented with a second volume of abstracts of hundreds of papers related to minimizing low-level nuclear waste. This second volume is expected to be released in late 1996.

Waste minimization handbook, Volume 1

International Nuclear Information System (INIS)

Boing, L.E.; Coffey, M.J.

1995-12-01

This technical guide presents various methods used by industry to minimize low-level radioactive waste (LLW) generated during decommissioning and decontamination (D and D) activities. Such activities generate significant amounts of LLW during their operations. Waste minimization refers to any measure, procedure, or technique that reduces the amount of waste generated during a specific operation or project. Preventive waste minimization techniques implemented when a project is initiated can significantly reduce waste. Techniques implemented during decontamination activities reduce the cost of decommissioning. The application of waste minimization techniques is not limited to D and D activities; it is also useful during any phase of a facility's life cycle. This compendium will be supplemented with a second volume of abstracts of hundreds of papers related to minimizing low-level nuclear waste. This second volume is expected to be released in late 1996

Mice with a targeted disruption of the Fanconi anemia homolog Fanca.

Science.gov (United States)

Cheng, N C; van de Vrugt, H J; van der Valk, M A; Oostra, A B; Krimpenfort, P; de Vries, Y; Joenje, H; Berns, A; Arwert, F

2000-07-22

Fanconi anemia (FA) is a hereditary chromosomal instability syndrome with cancer predisposition. Bone marrow failure resulting in pancytopenia is the main cause of death of FA patients. Diagnosis of FA is based on their cellular hypersensitivity to DNA crosslinking agents and chromosome breakages. Somatic complementation experiments suggest the involvement of at least eight genes in FA. The gene for complementation group A (FANCA) is defective in the majority of FA patients. We show here that mice deficient of FANCA: are viable and have no detectable developmental abnormalities. The hematological parameters showed a slightly decreased platelet count and a slightly increased erythrocyte mean cell volume in mice at young age, but this did not progress to anemia. Consistent with the clinical phenotype of FA patients, both male and female mice showed hypogonadism and impaired fertility. Furthermore, embryonic fibroblasts of the knock-out mice exhibited spontaneous chromosomal instability and were hyper-responsive to the clastogenic effect of the crosslinker mitomycin C.

Thymidine kinase 2 (H126N) knockin mice show the essential role of balanced deoxynucleotide pools for mitochondrial DNA maintenance

OpenAIRE

Akman, Hasan O.; Dorado, Beatriz; López, Luis C.; García-Cazorla, Ángeles; Vilà, Maya R.; Tanabe, Lauren M.; Dauer, William T.; Bonilla, Eduardo; Tanji, Kurenai; Hirano, Michio

2008-01-01

Mitochondrial DNA (mtDNA) depletion syndrome (MDS), an autosomal recessive condition, is characterized by variable organ involvement with decreased mtDNA copy number and activities of respiratory chain enzymes in affected tissues. MtDNA depletion has been associated with mutations in nine autosomal genes, including thymidine kinase (TK2), which encodes a ubiquitous mitochondrial protein. To study the pathogenesis of TK2-deficiency, we generated mice harboring an H126N Tk2 mutation. Homozygous...

Interspecies Variation in the Susceptibility of a Wild-Derived Colony of Mice to Pinworms (Aspiculuris tetraptera).

Science.gov (United States)

Curtis, Ryan C; Murray, Jill K; Campbell, Polly; Nagamori, Yoko; Molnar, Adam; Jackson, Todd A

2017-01-01

Pinworms are common parasites in wild and laboratory rodents. Despite their relative nonpathogenicity in immunocompetent models, pinworm infections add an unwanted variable and may confound some types of research. For this reason, health monitoring programs and biosecurity measures aim to minimize the spread of pinworm infections into colonies free from the organisms. Wild-derived and laboratory strains of mice have shown varied susceptibility to infection with Aspiculuris tetraptera, the most commonly found murine pinworm. In particular, susceptibility is increased in wild-derived mice, young animals, and males. Routine surveillance at our institution revealed pinworm infection (A. tetraptera only) within a colony of multiple, wild-derived species of Mus, although only specific species showed positive results during initial sampling. To assess whether species-associated differences in susceptibility were present, we analyzed fecal egg counts of A. tetraptera in every cage of the colony. Our results revealed significant differences in susceptibility between various species and subspecies of Mus. Egg counts were significantly higher in Mus spicilegus than Mus m. domesticus (WSB/EiJ) and Mus macedonicus. Mus spretus had higher egg counts than M. m. domesticus (WSB/EiJ), M. m. musculus (PWK/PhJ), and M. macedonicus. Egg counts did not differ in regard to age, sex, or number of mice per cage. As wild-derived mouse models continue to compliment research largely based on laboratory strains, it will be important to understand host-parasite interactions and their effects on research, particularly studies evaluating immune responses, behavior, growth, and other physiologic parameters.

Radioprotective effect of RSP-CM on mice irradiated with different doses

International Nuclear Information System (INIS)

Zhang Xia; Yang Rujun; Zhang Xin; Yang Yunfang; Jin Zhijun; Xiang Yingsong

2000-01-01

Objective: To investigate the radioprotective effects of cytokines on hematopoietic impairment of irradiated mice. Methods: Using RSP-CM and LP3-CM respectively originated GM-CSF and G-CSF to treat ICR mice irradiated with different doses of 60 Co γ-rays. The 30-day survival rate of mice, the mean survival days of dead mice were determined and the numbers of peripheral white blood cells and BMC of part of the mice were counted. At the same time, GM clonogenic activity of BM was assayed. Results:RSP-CM could effectively raise 30-day survival rate of mice irradiated with 7.5 Gy. However, LP3-CM had no obvious effect. Judging from the comparative survival ratio, only the RSP-CM treated group showed protective effect on the 8.0 Gy -irradiated mice. The 8.5 Gy-irradiated mice all died within 30 days, indicating that GM-CSF had weak effect on higher dose-irradiated mice. Conclusion: GM-CSF can stimulate the hematopoietic system of irradiated mice, and has dose-effect and time-effect relations. M-CSF used singly has no obvious effect

Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

Science.gov (United States)

Khalifa, Hesham A.; Al-Quraishy, Saleh A.

2017-01-01

The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases. PMID:28819543

Kundt spacetimes minimally coupled to scalar field

Energy Technology Data Exchange (ETDEWEB)

Tahamtan, T. [Charles University, Institute of Theoretical Physics, Faculty of Mathematics and Physics, Prague 8 (Czech Republic); Astronomical Institute, Czech Academy of Sciences, Prague (Czech Republic); Svitek, O. [Charles University, Institute of Theoretical Physics, Faculty of Mathematics and Physics, Prague 8 (Czech Republic)

2017-06-15

We derive an exact solution belonging to the Kundt class of spacetimes both with and without a cosmological constant that are minimally coupled to a free massless scalar field. We show the algebraic type of these solutions and give interpretation of the results. Subsequently, we look for solutions additionally containing an electromagnetic field satisfying nonlinear field equations. (orig.)

Free time minimizers for the three-body problem

Science.gov (United States)

Moeckel, Richard; Montgomery, Richard; Sánchez Morgado, Héctor

2018-03-01

Free time minimizers of the action (called "semi-static" solutions by Mañe in International congress on dynamical systems in Montevideo (a tribute to Ricardo Mañé), vol 362, pp 120-131, 1996) play a central role in the theory of weak KAM solutions to the Hamilton-Jacobi equation (Fathi in Weak KAM Theorem in Lagrangian Dynamics Preliminary Version Number 10, 2017). We prove that any solution to Newton's three-body problem which is asymptotic to Lagrange's parabolic homothetic solution is eventually a free time minimizer. Conversely, we prove that every free time minimizer tends to Lagrange's solution, provided the mass ratios lie in a certain large open set of mass ratios. We were inspired by the work of Da Luz and Maderna (Math Proc Camb Philos Soc 156:209-227, 1980) which showed that every free time minimizer for the N-body problem is parabolic and therefore must be asymptotic to the set of central configurations. We exclude being asymptotic to Euler's central configurations by a second variation argument. Central configurations correspond to rest points for the McGehee blown-up dynamics. The large open set of mass ratios are those for which the linearized dynamics at each Euler rest point has a complex eigenvalue.

Gender affects skin wound healing in plasminogen deficient mice.

Directory of Open Access Journals (Sweden)

Birgitte Rønø

Full Text Available The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin

The regenerative potential of parietal epithelial cells in adult mice

NARCIS (Netherlands)

Berger, K.; Schulte, K.; Boor, P.; Kuppe, C.; Kuppevelt, T.H. van; Floege, J.; Smeets, B.; Moeller, M.J.

2014-01-01

Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman's capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically

Metabolism distribution and transfer of tritium in pregnant mice after exposure to tritium water

International Nuclear Information System (INIS)

Lu Huimin; Zhou Xiangyan; Li Li; Zhang Zhixing

1993-01-01

Tritium water with three kind of different dose was singly injected intraperitoneally to pregnant mice in various time. The tritium concentration in the tissues from mother mice were measured on the 3.5 days after mother mice parturition. Dose rates in baby mice were estimated, as well as the transfer coefficient of tritium from mother mice to baby mice was calculated based on the tritium concentrations. The results of the experiment showed that tritium was almost uniformly distributed among the tissues after exposure to tritiated water at three experimental groups. However, it was found that relative concentrations of tritium in the baby mice tissues were consistently higher than that in mother mice tissues for three experimental groups. The relative concentration of tritium in the tissues was not affected by the different dose but developing on the exposure time. The results of radiation dose rates from baby mice estimation at the end of exposure showed that the higher radiation dose rates was found in the mice exposed to tritiated water during 7.5 days. The transfer coefficient of tritium from mother mice into baby mice was almost no different among the three radiation dose groups. The highest transfer coefficient was observed in mother mice exposed to tritiated baby mice was almost no different among the three radiation dose groups. The highest coefficient was observed in mother mice exposed to tritiated water during 16.5 days, however it was not found that transfer coefficient were higher in the mother mice exposed to tritiated water during 11.5 days than that of 7.5 days

Behavioral phenotyping of mice in pharmacological and toxicological research.

Science.gov (United States)

Karl, Tim; Pabst, Reinhard; von Hörsten, Stephan

2003-07-01

The evaluation of behavioral effects is an important component for the in vivo screening of drugs or potentially toxic compounds in mice. Ideally, such screening should be composed of monitoring general health, sensory functions, and motor abilities, right before specific behavioral domains are tested. A rational strategy in the design and procedure of testing as well as an effective composition of different well-established and reproducible behavioral tests can minimize the risk of false positive and false negative results in drug screening. In the present review we describe such basic considerations in planning experiments, selecting strains of mice, and propose groups of behavioral tasks suitable for a reliable detection of differences in specific behavioral domains in mice. Screening of general health and neurophysiologic functions (reflexes, sensory abilities) and motor function (pole test, wire hang test, beam walking, rotarod, accelerod, and footprint) as well as specific hypothesis-guided testing in the behavioral domains of learning and memory (water maze, radial maze, conditioned fear, and avoidance tasks), emotionality (open field, hole board, elevated plus maze, and object exploration), nociception (tail flick, hot plate), psychiatric-like conditions (porsolt swim test, acoustic startle response, and prepulse inhibition), and aggression (isolation-induced aggression, spontaneous aggression, and territorial aggression) are described in further detail. This review is designed to describe a general approach, which increases reliability of behavioral screening. Furthermore, it provides an overview on a selection of specific procedures suitable for but not limited to behavioral screening in pharmacology and toxicology.

Constructal entransy dissipation minimization for 'volume-point' heat conduction

International Nuclear Information System (INIS)

Chen Lingen; Wei Shuhuan; Sun Fengrui

2008-01-01

The 'volume to point' heat conduction problem, which can be described as to how to determine the optimal distribution of high conductivity material through the given volume such that the heat generated at every point is transferred most effectively to its boundary, has became the focus of attention in the current constructal theory literature. In general, the minimization of the maximum temperature difference in the volume is taken as the optimization objective. A new physical quantity, entransy, has been identified as a basis for optimizing heat transfer processes in terms of the analogy between heat and electrical conduction recently. Heat transfer analyses show that the entransy of an object describes its heat transfer ability, just as the electrical energy in a capacitor describes its charge transfer ability. Entransy dissipation occurs during heat transfer processes, as a measure of the heat transfer irreversibility with the dissipation related thermal resistance. By taking equivalent thermal resistance (it corresponds to the mean temperature difference), which reflects the average heat conduction effect and is defined based on entransy dissipation, as an optimization objective, the 'volume to point' constructal problem is re-analysed and re-optimized in this paper. The constructal shape of the control volume with the best average heat conduction effect is deduced. For the elemental area and the first order construct assembly, when the thermal current density in the high conductive link is linear with the length, the optimized shapes of assembly based on the minimization of entransy dissipation are the same as those based on minimization of the maximum temperature difference, and the mean temperature difference is 2/3 of the maximum temperature difference. For the second and higher order construct assemblies, the thermal current densities in the high conductive link are not linear with the length, and the optimized shapes of the assembly based on the

Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice.

Science.gov (United States)

Ho, Ada Man-Choi; Qiu, Yanyan; Jia, Yun-Fang; Aguiar, Felipe S; Hinton, David J; Karpyak, Victor M; Weinshilboum, Richard M; Choi, Doo-Sup

2016-07-01

Major depression is one of the most prevalent psychiatry comorbidities of alcohol use disorders (AUD). As negative emotions can trigger craving and increase the risk of relapse, treatments that target both conditions simultaneously may augment treatment success. Previous studies showed a potential synergistic effect of Food and Drug Administration approved medication for AUD acamprosate and the antidepressant escitalopram. In this study, we investigated the effects of combining acamprosate and escitalopram on ethanol (EtOH) consumption in stress-induced depressed mice. Forty singly housed C57BL/6J male mice were subjected to chronic unpredictable stress. In parallel, 40 group-housed male mice were subjected to normal husbandry. After 3 weeks, depressive- and anxiety-like behaviors and EtOH consumption were assessed. For the next 7 days, mice were injected with saline, acamprosate (200 mg/kg; twice/d), escitalopram (5 mg/kg; twice/d), or their combination (n = 9 to 11/drug group/stress group). Two-bottle choice limited-access drinking of 15% EtOH and tap water was performed 3 hours into dark phase immediately after the daily dark phase injection. EtOH drinking was monitored for another 7 days without drug administration. Mice subjected to the chronic unpredictable stress paradigm for 3 weeks showed apparent depression- and anxiety-like behaviors compared to their nonstressed counterparts including longer immobility time in the forced swim test and lower sucrose preference. Stressed mice also displayed higher EtOH consumption and preference in a 2-bottle choice drinking test. During the drug administration period, the escitalopram-only and combined drug groups showed significant reduction in EtOH consumption in nonstressed mice, while only the combined drug group showed significantly reduced consumption in stressed mice. However, such reduction did not persist into the postdrug administration period. The combination of acamprosate and escitalopram suppressed

The Regenerative Potential of Parietal Epithelial Cells in Adult Mice

OpenAIRE

Berger, Katja; Schulte, Kevin; Boor, Peter; Kuppe, Christoph; van Kuppevelt, Toin H.; Floege, Jürgen; Smeets, Bart; Moeller, Marcus J.

2014-01-01

Previously, we showed that some podocytes in juvenile mice are recruited from cells lining Bowman’s capsule, suggesting that parietal epithelial cells (PECs) are a progenitor cell population for podocytes. To investigate whether PECs also replenish podocytes in adult mice, PECs were genetically labeled in an irreversible fashion in 5-week-old mice. No significant increase in labeled podocytes was observed, even after 18 months. To accelerate a potential regenerative mechanism, progressive glo...

Cost-effectiveness analysis in minimally invasive spine surgery.

Science.gov (United States)

Al-Khouja, Lutfi T; Baron, Eli M; Johnson, J Patrick; Kim, Terrence T; Drazin, Doniel

2014-06-01

Medical care has been evolving with the increased influence of a value-based health care system. As a result, more emphasis is being placed on ensuring cost-effectiveness and utility in the services provided to patients. This study looks at this development in respect to minimally invasive spine surgery (MISS) costs. A literature review using PubMed, the Cost-Effectiveness Analysis (CEA) Registry, and the National Health Service Economic Evaluation Database (NHS EED) was performed. Papers were included in the study if they reported costs associated with minimally invasive spine surgery (MISS). If there was no mention of cost, CEA, cost-utility analysis (CUA), quality-adjusted life year (QALY), quality, or outcomes mentioned, then the article was excluded. Fourteen studies reporting costs associated with MISS in 12,425 patients (3675 undergoing minimally invasive procedures and 8750 undergoing open procedures) were identified through PubMed, the CEA Registry, and NHS EED. The percent cost difference between minimally invasive and open approaches ranged from 2.54% to 33.68%-all indicating cost saving with a minimally invasive surgical approach. Average length of stay (LOS) for minimally invasive surgery ranged from 0.93 days to 5.1 days compared with 1.53 days to 12 days for an open approach. All studies reporting EBL reported lower volume loss in an MISS approach (range 10-392.5 ml) than in an open approach (range 55-535.5 ml). There are currently an insufficient number of studies published reporting the costs of MISS. Of the studies published, none have followed a standardized method of reporting and analyzing cost data. Preliminary findings analyzing the 14 studies showed both cost saving and better outcomes in MISS compared with an open approach. However, more Level I CEA/CUA studies including cost/QALY evaluations with specifics of the techniques utilized need to be reported in a standardized manner to make more accurate conclusions on the cost effectiveness of

The Effect of Gentle Handling on Depressive-Like Behavior in Adult Male Mice: Considerations for Human and Rodent Interactions in the Laboratory.

Science.gov (United States)

Neely, Caroline; Lane, Christina; Torres, Julio; Flinn, Jane

2018-01-01

Environmental factors play a significant role in well-being of laboratory animals. Regulations and guidelines recommend, if not require, that stressors such as bright lighting, smells, and noises are eliminated or reduced to maximize animal well-being. A factor that is often overlooked is handling and how researchers interact with their animals. Researchers, lab assistants, and husbandry staff in animal facilities may use inconsistent handling methods when interacting with rodents, but humans should be considered a part of the animal's social environment. This study examined the effects of different handling techniques on depressive-like behavior, measured by the Porsolt forced swim test, in adult C57BL/6J male mice. The same two researchers handled the mice in a gentle, aggressive, or minimal (control) fashion over approximately two weeks prior to testing. The results demonstrated a beneficial effect of gentle handling: gentle handling reduced swimming immobility in the forced swim test compared to mice that were aggressively or minimally handled. We argue that gentle handling, rather than methodical handling, can foster a better relationship between the handlers and rodents. Although handling is not standardized across labs, consistent gentle handling allows for less challenging behavioral testing, better data collection, and overall improved animal welfare.

The effects of gliadin on urine metabolome in mice

DEFF Research Database (Denmark)

Roager, Henrik Munch; Zhang, Li; Frandsen, Henrik Lauritz

Gliadin, a proline-rich protein of gluten, is thought to modulate the gut microbiota and affect the intestinal permeability and immune system. However, little is known about the long-term effects of gliadin on the host and microbial metabolism. To study this, we compared the urine metabolome of two...... groups of mice, which were on a high fat diet with and without gliadin, respectively, for 23 weeks. Using liquid chromatography mass-spectrometry (MS) followed by multivariate analyses we were able to show a clear separation of the two groups of mice based on their urine metabolome. Discriminating...... in the gliadin mice. Also, Maillard reaction products and β-oxidized tocopherols were observed in higher levels in the urine of gliadin mice, suggesting increased oxidative stress in the gliadin mice. Indisputably, gliadin affected the urine metabolome. However, the mechanisms behind the observed metabolite...

α7-Nicotinic acetylcholine receptor: role in early odor learning preference in mice.

Directory of Open Access Journals (Sweden)

Jennifer L Hellier

Full Text Available Recently, we have shown that mice with decreased expression of α7-nicotinic acetylcholine receptors (α7 in the olfactory bulb were associated with a deficit in odor discrimination compared to wild-type mice. However, it is unknown if mice with decreased α7-receptor expression also show a deficit in early odor learning preference (ELP, an enhanced behavioral response to odors with attractive value observed in rats. In this study, we modified ELP methods performed in rats and implemented similar conditions in mice. From post-natal days 5-18, wild-type mice were stroked simultaneously with an odor presentation (conditioned odor for 90 s daily. Control mice were only stroked, exposed to odor, or neither. On the day of testing (P21, mice that were stroked in concert with a conditioned odor significantly investigated the conditioned odor compared to a novel odor, as observed similarly in rats. However, mice with a decrease in α7-receptor expression that were stroked during a conditioned odor did not show a behavioral response to that odorant. These results suggest that decreased α7-receptor expression has a role in associative learning, olfactory preference, and/or sensory processing deficits.

Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice

Science.gov (United States)

Levasseur, Regis; Barrios, Roberto; Elefteriou, Florent; Glass, Donald A 2nd; Lieberman, Michael W.; Karsenty, Gerard

2003-01-01

Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.

Effect of spaceflight hardware on the skeletal properties of ground control mice

Science.gov (United States)

Bateman, Ted; Lloyd, Shane; Dunlap, Alex; Ferguson, Virginia; Simske, Steven; Stodieck, Louis; Livingston, Eric

Introduction: Spaceflight experiments using mouse or rat models require habitats that are specifically designed for the microgravity environment. During spaceflight, rodents are housed in a specially designed stainless steel meshed cage with gravity-independent food and water delivery systems and constant airflow to push floating urine and feces towards a waste filter. Differences in the housing environment alone, not even considering the spaceflight environment itself, may lead to physiological changes in the animals contained within. It is important to characterize these cage differences so that results from spaceflight experiments can be more reliably compared to studies from other laboratories. Methods: For this study, we examined the effect of NASA's Animal Enclosure Module (AEM) spaceflight hardware on the skeletal properties of 8-week-old female C57BL/6J mice. This 13-day experiment, conducted on the ground, modeled the flight experiment profile of the CBTM-01 payload on STS-108, with standard vivarium-housed mice being compared to AEM-housed mice (n = 12/group). Functional differences were compared via mechanical testing, micro-hardness indentation, microcomputed tomography, and mineral/matrix composition. Cellular changes were examined by serum chemistry, histology, quantitative histomorphometry, and RT-PCR. A Student's t-test was utilized, with the level of Type I error set at 95 Results: There was no change in elastic, maximum, or fracture force mechanical properties at the femur mid-diaphysis, however, structural stiffness was -17.5 Conclusions: Housing mice in the AEM spaceflight hardware had minimal effects on femur cortical bone properties. However, trabecular bone at the proximal tibia in AEM mice experi-enced large increases in microarchitecture and mineral composition. Increases in bone density were accompanied by reductions in bone-forming osteoblasts and bone-resorbing osteoclasts, representing a general decline in bone turnover at this site

Effects of gamma radiation in cauliflower (Brassica spp) minimally processed

International Nuclear Information System (INIS)

Nunes, Thaise C.F.; Rogovschi, Vladimir D.; Thomaz, Fernanda S.; Trindade, Reginaldo A.; Villavicencio, Anna L.C.H.; Alencar, Severino M.

2007-01-01

Consumers demand for health interests and the latest diet trends. The consumption of vegetables worldwide has increased every year over the past decade, consequently, less extreme treatments or additives are being required. Minimally processed foods have fresh-like characteristics and satisfy the new consumer demand. Food irradiation is an exposure process of the product to controlled sources of gamma radiation with the intention to destroy pathogens and to extend the shelf life. Minimally processed cauliflower (Brassica oleraceae) exposed to low dose of gamma radiation does not show any change in sensory attributes. The aim of this study was to analyze the effects of the low doses of gamma radiation on sensorial aspects like appearance, texture and flavor of minimally processed cauliflower. (author)

Maporal Hantavirus Causes Mild Pathology in Deer Mice (Peromyscus maniculatus

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Amanda McGuire

2016-10-01

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

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

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Morgan Kristen

2011-01-01

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

Transplantation of Gene-Edited Hepatocyte-like Cells Modestly Improves Survival of Arginase-1-Deficient Mice

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Yuan Yan Sin

2018-03-01

Full Text Available Progress in gene editing research has been accelerated by utilizing engineered nucleases in combination with induced pluripotent stem cell (iPSC technology. Here, we report transcription activator-like effector nuclease (TALEN-mediated reincorporation of Arg1 exons 7 and 8 in iPSCs derived from arginase-1-deficient mice possessing Arg1Δ alleles lacking these terminal exons. The edited cells could be induced to differentiate into hepatocyte-like cells (iHLCs in vitro and were subsequently used for transplantation into our previously described (Sin et al., PLoS ONE 2013 tamoxifen-inducible Arg1-Cre arginase-1-deficient mouse model. While successful gene-targeted repair was achieved in iPSCs containing Arg1Δ alleles, only minimal restoration of urea cycle function could be observed in the iHLC-transplanted mice compared to control mice, and survival in this lethal model was extended by up to a week in some mice. The partially rescued phenotype may be due to inadequate regenerative capacity of arginase-1-expressing cells in the correct metabolic zones. Technical hurdles exist and will need to be overcome for gene-edited iPSC to iHLC rescue of arginase-1 deficiency, a rare urea cycle disorder.

Ruled Laguerre minimal surfaces

KAUST Repository

Skopenkov, Mikhail; Pottmann, Helmut; Grohs, Philipp

2011-01-01

A Laguerre minimal surface is an immersed surface in ℝ 3 being an extremal of the functional ∫ (H 2/K-1)dA. In the present paper, we prove that the only ruled Laguerre minimal surfaces are up to isometry the surfaces ℝ (φλ) = (Aφ, Bφ, Cφ + D cos 2φ

Effect of Hibiscus sabdariffa on obesity in MSG mice.

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Alarcon-Aguilar, Francisco J; Zamilpa, Alejandro; Perez-Garcia, Ma Dolores; Almanza-Perez, Julio C; Romero-Nuñez, Eunice; Campos-Sepulveda, Efrain A; Vazquez-Carrillo, Laura I; Roman-Ramos, Ruben

2007-10-08

The aim of the present investigation was determine whether a standardized Hibiscus sabdariffa calyces aqueous extract has an effect on body weight in an obese animal model induced by the administration of monosodium glutamate. Hibiscus sabdariffa aqueous extract, containing 33.64 mg of total anthocyanins per each 120 mg of extract, was orally administered (120 mg/kg/day) for 60 days to healthy and obese mice, and body weight gain, food and liquid intake, aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, and triglycerides levels were measured. Hibiscus sabdariffa administration significantly reduced body weight gain in obese mice and increased liquid intake in healthy and obese mice. ALT levels were significantly increased on the 15th and 45th days in obese mice, but AST levels did not show significant changes. Mortality was not observed in the Hibiscus sabdariffa treated groups. Triglycerides and cholesterol levels showed non-significant reductions in animals treated with Hibiscus sabdariffa. Our data confirm the anti-obesity effect of Hibiscus sabdariffa reported by the Mexican population.

Kinetics of the cells of the hematopoietic system in the course of postradiation regeneration. [Mice

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Kondratenko, N F

1975-01-01

Twenty-four hours after sublethal whole-body irradiation (200 rad) of mice, only 4 percent of the stem cells were viable and continued to differentiate. Exponential growth of these cells started a day later and by week 2 the number was completely restored and stabilized. The kinetics of committed precursors of granulocytes and macrophages was different. Some 20 percent of these cells were viable 24 hours after irradiation and the granulocytes in particular continued to differentiate into mature cellular elements. The total number remained at the minimal level for a week, after which the logarithmic phase began, with complete recovery achieved toward the end of week 2 after irradiation. Thus, the restoration of hematopoiesis in sublethally irradiated mice is due primarily to the exponential growth of surviving stem cells in bone marrow.

Placental and lactating transfer of 147Pm in mice

International Nuclear Information System (INIS)

Tao Feng; Zhu Shoupeng

1990-08-01

The placental and lactating transfer of 147 Pm in late pregnant mice and lactating mice as well as the distribution of 147 Pm in some organs of mother mice were studied and compared. The pregnant mice and lactating mice had intravenous injection with 147 Pm nitrate at the 17th day of gestation and the next day of parturition respectively. The two groups were sacrified at the 1st, 4th, 9th, 14th and 21st day after the injection. The retentions of 147 Pm in the liver, right femur, uterus, spleen, placenta, fetal membrane and litter were determined by the method of liquid scintillation. The results showed that the amount of 147 Pm in litters of both groups was increasing with the days after injection. In the 1st and 4th day of injection the amount of 147 Pm in litters of lactating mice was 20 times higher than those in litters of pregnant mice. The amount of 147 Pm in livers and skeletons and the half-retention time of prenant and lactating dams were much greater than those of control group

Hoelder continuity of energy minimizer maps between Riemannian polyhedra

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Bouziane, Taoufik

2004-10-01

The goal of the present paper is to establish some kind of regularity of an energy minimizer map between Riemannian polyhedra. More precisely, we will show the Hoelder continuity of local energy minimizers between Riemannian polyhedra with the target spaces without focal points. With this new result, we also complete our existence theorem obtained elsewhere, and consequently we generalize completely, to the case of target polyhedra without focal points (which is a weaker geometric condition than the nonpositivity of the curvature), the Eells-Fuglede's existence and regularity theorem which is the new version of the famous Eells-Sampson's theorem. (author)

Minimizing the Pervasiveness of Women's Personal Experiences of Gender Discrimination

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Foster, Mindi D.; Jackson, Lydia C.; Hartmann, Ryan; Woulfe, Shannon

2004-01-01

Given the Rejection-Identification Model (Branscombe, Schmitt, & Harvey, 1999), which shows that perceiving discrimination to be pervasive is a negative experience, it was suggested that there would be conditions under which women would instead minimize the pervasiveness of discrimination. Study 1 (N= 91) showed that when women envisioned…

Long-lived ames dwarf mice are resistant to chemical stressors.

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Bokov, Alex F; Lindsey, Merry L; Khodr, Christina; Sabia, Marian R; Richardson, Arlan

2009-08-01

To probe the connection between longevity and stress resistance, we compared the sensitivity of Ames long-lived dwarf mice and control littermates with paraquat, diquat, and dobutamine. In young adult animals, 95% of male and 39% of female controls died after paraquat administration, but no dwarf animals died. When the experiment was repeated at an older age or a higher dosage of paraquat, dwarf mice still showed greater resistance. Dwarf mice also were more resistant to diquat; 80% of male and 60% of female controls died compared with 40% and 20% of dwarf mice, despite greater sensitivity of dwarf liver to diquat. Dwarf mice were also less sensitive to dobutamine-induced cardiac stress and had lower levels of liver and lung F(2)-isoprostanes. This is the first direct in vivo evidence that long-lived Ames dwarf mice have enhanced resistance to chemical insult, particularly oxidative stressors.

The anti-hypercholesterolemic effect of low p53 expression protects vascular endothelial function in mice.

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Francois Leblond

Full Text Available To demonstrate that p53 modulates endothelial function and the stress response to a high-fat western diet (WD.Three-month old p53+/+ wild type (WT and p53+/- male mice were fed a regular or WD for 3 months. Plasma levels of total cholesterol (TC and LDL-cholesterol were significantly elevated (p<0.05 in WD-fed WT (from 2.1±0.2 mmol/L to 3.1±0.2, and from 0.64±0.09 mmol/L to 1.25±0.11, respectively but not in p53+/- mice. The lack of cholesterol accumulation in WD-fed p53+/- mice was associated with high bile acid plasma concentrations (p53+/- =  4.7±0.9 vs. WT =  3.3±0.2 μmol/L, p<0.05 concomitant with an increased hepatic 7-alpha-hydroxylase mRNA expression. While the WD did not affect aortic endothelial relaxant function in p53+/- mice (WD =  83±5 and RD =  82±4% relaxation, it increased the maximal response to acetylcholine in WT mice (WD =  87±2 vs. RD =  62±5% relaxation, p<0.05 to levels of p53+/-. In WT mice, the rise in TC associated with higher (p<0.05 plasma levels of pro-inflammatory keratinocyte-derived chemokine, and an over-activation (p<0.05 of the relaxant non-nitric oxide/non-prostacyclin endothelial pathway. It is likely that in WT mice, activations of these pathways are adaptive and contributed to maintain endothelial function, while the WD neither promoted inflammation nor affected endothelial function in p53+/- mice.Our data demonstrate that low endogenous p53 expression prevents the rise in circulating levels of cholesterol when fed a WD. Consequently, the endothelial stress of hypercholesterolemia is absent in young p53+/- mice as evidenced by the absence of endothelial adaptive pathway over-activation to minimize stress-related damage.

Activation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in mice

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Blednov, Y.A.; Benavidez, J.M.; Geil, C.; Perra, S.; Morikawa, H.; Harris, R.A.

2011-01-01

Previous studies showed that mice with genetic predisposition for high alcohol consumption as well as human alcoholics show changes in brain expression of genes related to immune signaling. In addition, mutant mice lacking genes related to immune function show decreased alcohol consumption (Blednov et al., in press), suggesting that immune signaling promotes alcohol consumption. To test the possibility that activation of immune signaling will increase alcohol consumption, we treated mice with lipopolysaccaride (LPS; 1 mg/kg, i.p.) and tested alcohol consumption in the continuous two-bottle choice test. To take advantage of the long-lasting activation of brain immune signaling by LPS, we measured drinking beginning one week or one month after LPS treatment and continued the studies for several months. LPS produced persistent increases in alcohol consumption in C57/Bl6 J (B6) inbred mice, FVBxB6F1 and B6xNZBF1 hybrid mice, but not in FVB inbred mice. To determine if this effect of LPS is mediated through binding to TLR4, we tested mice lacking CD14, a key component of TLR4 signaling. These null mutants showed no increase of alcohol intake after treatment with LPS. LPS treatment decreased ethanol-conditioned taste aversion but did not alter ethanol-conditioned place preference (B6xNZBF1 mice). Electro-physiological studies of dopamine neurons in the ventral tegmental area showed that pretreatment of mice with LPS decreased the neuronal firing rate. These results suggest that activation of immune signaling promotes alcohol consumption and alters certain aspects of alcohol reward/aversion. PMID:21266194

Y-12 Plant waste minimization strategy

International Nuclear Information System (INIS)

Kane, M.A.

1987-01-01

The 1984 Amendments to the Resource Conservation and Recovery Act (RCRA) mandate that waste minimization be a major element of hazardous waste management. In response to this mandate and the increasing costs for waste treatment, storage, and disposal, the Oak Ridge Y-12 Plant developed a waste minimization program to encompass all types of wastes. Thus, waste minimization has become an integral part of the overall waste management program. Unlike traditional approaches, waste minimization focuses on controlling waste at the beginning of production instead of the end. This approach includes: (1) substituting nonhazardous process materials for hazardous ones, (2) recycling or reusing waste effluents, (3) segregating nonhazardous waste from hazardous and radioactive waste, and (4) modifying processes to generate less waste or less toxic waste. An effective waste minimization program must provide the appropriate incentives for generators to reduce their waste and provide the necessary support mechanisms to identify opportunities for waste minimization. This presentation focuses on the Y-12 Plant's strategy to implement a comprehensive waste minimization program. This approach consists of four major program elements: (1) promotional campaign, (2) process evaluation for waste minimization opportunities, (3) waste generation tracking system, and (4) information exchange network. The presentation also examines some of the accomplishments of the program and issues which need to be resolved

Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity

International Nuclear Information System (INIS)

Won, Young-Suk; Song, Ji-Won; Lim, Jong-Hwan; Lee, Mee-Young; Moon, Og-Sung; Kim, Hyoung-Chin; Son, Hwa-Young; Kwon, Hyo-Jung

2016-01-01

Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [ 14 C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects. - Highlights: • ob/ob mice are resistant to lethal doses of thioacetamide, compared to ob/+ mice. • ob/ob mice show reduced oxidative stress and enhanced antioxidant enzyme activity. • ob/ob mice exhibit diminished bioactivation of thioacetamide.

Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity

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Won, Young-Suk [Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk (Korea, Republic of); Song, Ji-Won [Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of); Lim, Jong-Hwan [Huons Research Center, Gyonggido (Korea, Republic of); Lee, Mee-Young [Herbal Medicine Formulation Research Group, Korea Institute of Oriental Medicine, Daejeon (Korea, Republic of); Moon, Og-Sung; Kim, Hyoung-Chin [Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk (Korea, Republic of); Son, Hwa-Young [Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of); Kwon, Hyo-Jung, E-mail: hyojung@cnu.ac.kr [Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon (Korea, Republic of)

2016-01-15

Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [{sup 14}C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects. - Highlights: • ob/ob mice are resistant to lethal doses of thioacetamide, compared to ob/+ mice. • ob/ob mice show reduced oxidative stress and enhanced antioxidant enzyme activity. • ob/ob mice exhibit diminished bioactivation of thioacetamide.

Characteristics of gait ataxia in δ2 glutamate receptor mutant mice, ho15J.

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Eri Takeuchi

Full Text Available The cerebellum plays a fundamental, but as yet poorly understood, role in the control of locomotion. Recently, mice with gene mutations or knockouts have been used to investigate various aspects of cerebellar function with regard to locomotion. Although many of the mutant mice exhibit severe gait ataxia, kinematic analyses of limb movements have been performed in only a few cases. Here, we investigated locomotion in ho15J mice that have a mutation of the δ2 glutamate receptor. The cerebellum of ho15J mice shows a severe reduction in the number of parallel fiber-Purkinje synapses compared with wild-type mice. Analysis of hindlimb kinematics during treadmill locomotion showed abnormal hindlimb movements characterized by excessive toe elevation during the swing phase, and by severe hyperflexion of the ankles in ho15J mice. The great trochanter heights in ho15J mice were lower than in wild-type mice throughout the step cycle. However, there were no significant differences in various temporal parameters between ho15J and wild-type mice. We suggest that dysfunction of the cerebellar neuronal circuits underlies the observed characteristic kinematic abnormality of hindlimb movements during locomotion of ho15J mice.

Minimal groups increase young children's motivation and learning on group-relevant tasks.

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Master, Allison; Walton, Gregory M

2013-01-01

Three experiments (N = 130) used a minimal group manipulation to show that just perceived membership in a social group boosts young children's motivation for and learning from group-relevant tasks. In Experiment 1, 4-year-old children assigned to a minimal "puzzles group" persisted longer on a challenging puzzle than children identified as the "puzzles child" or children in a control condition. Experiment 2 showed that this boost in motivation occurred only when the group was associated with the task. In Experiment 3, children assigned to a minimal group associated with word learning learned more words than children assigned an analogous individual identity. The studies demonstrate that fostering shared motivations may be a powerful means by which to shape young children's academic outcomes. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Differential requirement for satellite cells during overload-induced muscle hypertrophy in growing versus mature mice.

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Murach, Kevin A; White, Sarah H; Wen, Yuan; Ho, Angel; Dupont-Versteegden, Esther E; McCarthy, John J; Peterson, Charlotte A

2017-07-10

Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. Pax7 CreER -R26R DTA mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age. Following a 2-week washout, mice were subjected to sham surgery or 10 day synergist ablation overload of the plantaris (n = 6-9 per group). The surgical approach minimized regeneration, de novo fiber formation, and fiber splitting while promoting muscle fiber growth. Satellite cell density (Pax7+ cells/fiber), embryonic myosin heavy chain expression (eMyHC), and muscle fiber cross sectional area (CSA) were evaluated via immunohistochemistry. Myonuclei (myonuclei/100 mm) were counted on isolated single muscle fibers. Tamoxifen treatment depleted satellite cells by ≥90% and prevented myonuclear accretion with overload in young and mature mice (p overload. Average muscle fiber CSA increased ~20% in young SC+ (p = 0.07), mature SC+ (p overload (p overload-induced hypertrophy is dependent on maturational age, and global responses to overload differ in young versus mature mice.

Robust imaging of localized scatterers using the singular value decomposition and ℓ1 minimization

International Nuclear Information System (INIS)

Chai, A; Moscoso, M; Papanicolaou, G

2013-01-01

We consider narrow band, active array imaging of localized scatterers in a homogeneous medium with and without additive noise. We consider both single and multiple illuminations and study ℓ 1 minimization-based imaging methods. We show that for large arrays, with array diameter comparable to range, and when scatterers are sparse and well separated, ℓ 1 minimization using a single illumination and without additive noise can recover the location and reflectivity of the scatterers exactly. For multiple illuminations, we introduce a hybrid method which combines the singular value decomposition and ℓ 1 minimization. This method can be used when the essential singular vectors of the array response matrix are available. We show that with this hybrid method we can recover the location and reflectivity of the scatterers exactly when there is no noise in the data. Numerical simulations indicate that the hybrid method is, in addition, robust to noise in the data. We also compare the ℓ 1 minimization-based methods with others including Kirchhoff migration, ℓ 2 minimization and multiple signal classification. (paper)

Microbiota-Derived Metabolic Factors Reduce Campylobacteriosis in Mice.

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Sun, Xiaolun; Winglee, Kathryn; Gharaibeh, Raad Z; Gauthier, Josee; He, Zhen; Tripathi, Prabhanshu; Avram, Dorina; Bruner, Steven; Fodor, Anthony; Jobin, Christian

2018-05-01

Campylobacter jejuni, a prevalent foodborne bacterial pathogen, exploits the host innate response to induce colitis. Little is known about the roles of microbiota in C jejuni-induced intestinal inflammation. We investigated interactions between microbiota and intestinal cells during C jejuni infection of mice. Germ-free C57BL/6 Il10 -/- mice were colonized with conventional microbiota and infected with a single dose of C jejuni (10 9 colony-forming units/mouse) via gavage. Conventional microbiota were cultured under aerobic, microaerobic, or anaerobic conditions and orally transplanted into germ-free Il10 -/- mice. Colon tissues were collected from mice and analyzed by histology, real-time polymerase chain reaction, and immunoblotting. Fecal microbiota and bile acids were analyzed with 16S sequencing and high-performance liquid chromatography with mass spectrometry, respectively. Introduction of conventional microbiota reduced C jejuni-induced colitis in previously germ-free Il10 -/- mice, independent of fecal load of C jejuni, accompanied by reduced activation of mammalian target of rapamycin. Microbiota transplantation and 16S ribosomal DNA sequencing experiments showed that Clostridium XI, Bifidobacterium, and Lactobacillus were enriched in fecal samples from mice colonized with microbiota cultured in anaerobic conditions (which reduce colitis) compared with mice fed microbiota cultured under aerobic conditions (susceptible to colitis). Oral administration to mice of microbiota-derived secondary bile acid sodium deoxycholate, but not ursodeoxycholic acid or lithocholic acid, reduced C jejuni-induced colitis. Depletion of secondary bile acid-producing bacteria with antibiotics that kill anaerobic bacteria (clindamycin) promoted C jejuni-induced colitis in specific pathogen-free Il10 -/- mice compared with the nonspecific antibiotic nalidixic acid; colitis induction by antibiotics was associated with reduced level of luminal deoxycholate. We identified a

Loss Minimization Sliding Mode Control of IPM Synchronous Motor Drives

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Mehran Zamanifar

2010-01-01

Full Text Available In this paper, a nonlinear loss minimization control strategy for an interior permanent magnet synchronous motor (IPMSM based on a newly developed sliding mode approach is presented. This control method sets force the speed control of the IPMSM drives and simultaneously ensures the minimization of the losses besides the uncertainties exist in the system such as parameter variations which have undesirable effects on the controller performance except at near nominal conditions. Simulation results are presented to show the effectiveness of the proposed controller.

Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice

International Nuclear Information System (INIS)

Noda, Kazuo; Nakamura, Tomoyuki; Komatsu, Yoshihiro

2015-01-01

Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice were less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. - Highlights: • Fibulin-5 is deposited in cranial neural crest-derived mesenchymal tissues. • Fibulin-5-null mice show decreased premaxillary bone growth during postnatal stage. • Fibulin-5 is indispensable for facial suture mesenchymal cell proliferation.

Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice

Energy Technology Data Exchange (ETDEWEB)

Noda, Kazuo, E-mail: knoda@kuhp.kyoto-u.ac.jp [Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030 (United States); Nakamura, Tomoyuki [Department of Pharmacology, Kansai Medical University, Hirakata, Osaka 573-1010 (Japan); Komatsu, Yoshihiro [Department of Pediatrics, The University of Texas Medical School at Houston, Houston, TX 77030 (United States); Graduate Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030 (United States)

2015-10-23

Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice were less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis. - Highlights: • Fibulin-5 is deposited in cranial neural crest-derived mesenchymal tissues. • Fibulin-5-null mice show decreased premaxillary bone growth during postnatal stage. • Fibulin-5 is indispensable for facial suture mesenchymal cell proliferation.

TAM Receptors Are Not Required for Zika Virus Infection in Mice.

Science.gov (United States)

Hastings, Andrew K; Yockey, Laura J; Jagger, Brett W; Hwang, Jesse; Uraki, Ryuta; Gaitsch, Hallie F; Parnell, Lindsay A; Cao, Bin; Mysorekar, Indira U; Rothlin, Carla V; Fikrig, Erol; Diamond, Michael S; Iwasaki, Akiko

2017-04-18

Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl -/- , Mertk -/- , Axl -/- Mertk -/- , and Axl -/- Tyro3 -/- mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR-blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism were observed. These findings indicate that, in mice, TAM receptors are not required for ZIKV entry and infection. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Neonatal periostin knockout mice are protected from hyperoxia-induced alveolar simplication.

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Paul D Bozyk

Full Text Available In bronchopulmonary dysplasia (BPD, alveolar septae are thickened with collagen and α-smooth muscle actin, transforming growth factor (TGF-β-positive myofibroblasts. Periostin, a secreted extracellular matrix protein, is involved in TGF-β-mediated fibrosis and myofibroblast differentiation. We hypothesized that periostin expression is required for hypoalveolarization and interstitial fibrosis in hyperoxia-exposed neonatal mice, an animal model for this disease. We also examined periostin expression in neonatal lung mesenchymal stromal cells and lung tissue of hyperoxia-exposed neonatal mice and human infants with BPD. Two-to-three day-old wild-type and periostin null mice were exposed to air or 75% oxygen for 14 days. Mesenchymal stromal cells were isolated from tracheal aspirates of premature infants. Hyperoxic exposure of neonatal mice increased alveolar wall periostin expression, particularly in areas of interstitial thickening. Periostin co-localized with α-smooth muscle actin, suggesting synthesis by myofibroblasts. A similar pattern was found in lung sections of infants dying of BPD. Unlike wild-type mice, hyperoxia-exposed periostin null mice did not show larger air spaces or α-smooth muscle-positive myofibroblasts. Compared to hyperoxia-exposed wild-type mice, hyperoxia-exposed periostin null mice also showed reduced lung mRNA expression of α-smooth muscle actin, elastin, CXCL1, CXCL2 and CCL4. TGF-β treatment increased mesenchymal stromal cell periostin expression, and periostin treatment increased TGF-β-mediated DNA synthesis and myofibroblast differentiation. We conclude that periostin expression is increased in the lungs of hyperoxia-exposed neonatal mice and infants with BPD, and is required for hyperoxia-induced hypoalveolarization and interstitial fibrosis.

Experimental infection of Balb/c nude mice with Hepatitis E virus

Directory of Open Access Journals (Sweden)

Zhu Jianguo

2009-06-01

Full Text Available Abstract Background Several animal species can reportedly act as reservoirs for Hepatitis E virus (HEV, a zoonotic pathogen. HEV and antibody to the virus have been detected in a variety of animals including rodents. Pig and rat models for HEV have been established for HEV, but a nude mouse has not yet been developed. Methods Balb/c nude mice were inoculated with swine HEV, both orally and via intravenous injection to insure infection. Negative control and experimental contact-exposed groups of mice were also included in the study. The liver, spleen, kidney, jejunum, ileum, cecum and colon of each mouse from all three groups were collected for reverse transcription nested polymerase chain reaction (RT-nPCR detection, indirect immunofluorescence observation and histopathologic examination. The sera from nude mice were tested for anti-HEV IgG by enzyme linked immunosorbent assay (ELISA. Activities of liver enzymes, including alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP, as well as total bilirubin (TBIL were also measured in the sera of the nude mice. Results HEV antigens and HEV RNA were detected in liver, spleen, kidney, jejunum, ileum and colon both by indirect immunofluorescence and by RT-nPCR in all of the inoculated and in one of the contact-exposed nude mice. Histopathological changes were observed in the liver and spleen of these mice. Infected mice showed increased levels of AST, ALP, and anti-HEV IgG in sera. The livers of contact-exposed mice showed obvious histopathological damage. Conclusion Nude mice could be readily infected by HEV isolated from pigs. The nude mouse may therefore be a useful animal model for studying the pathogenesis of HEV.

Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of thrombospondin 2-null mice.

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Kyriakides, T R; Zhu, Y H; Yang, Z; Huynh, G; Bornstein, P

2001-10-01

The matricellular angiogenesis inhibitor, thrombospondin (TSP) 2, has been shown to be an important modulator of wound healing and the foreign body response. Specifically, TSP2-null mice display improved healing with minimal scarring and form well-vascularized foreign body capsules. In this study we performed subcutaneous implantation of sponges and investigated the resulting angiogenic and fibrogenic responses. Histological and immunohistochemical analysis of sponges, excised at 7, 14, and 21 days after implantation, revealed significant differences between TSP2-null and wild-type mice. Most notably, TSP2-null mice exhibited increased angiogenesis and fibrotic encapsulation of the sponge. However, invasion of dense tissue was compromised, even though its overall density was increased. Furthermore, histomorphometry and biochemical assays demonstrated a significant increase in the extracellular distribution of matrix metalloproteinase (MMP) 2, but no change in the levels of active transforming growth factor-beta(1). The alterations in neovascularization, dense tissue invasion, and MMP2 in TSP2-null mice coincided with the deposition of TSP2 in the extracellular matrix of wild-type animals. These observations support the proposed role of TSP2 as a modulator of angiogenesis and matrix remodeling during tissue repair. In addition, they provide in vivo evidence for a newly proposed function of TSP2 as a modulator of extracellular MMP2 levels.

Moro orange juice prevents fatty liver in mice.

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Salamone, Federico; Li Volti, Giovanni; Titta, Lucilla; Puzzo, Lidia; Barbagallo, Ignazio; La Delia, Francesco; Zelber-Sagi, Shira; Malaguarnera, Michele; Pelicci, Pier Giuseppe; Giorgio, Marco; Galvano, Fabio

2012-08-07

To establish if the juice of Moro, an anthocyanin-rich orange, may improve liver damage in mice with diet-induced obesity. Eight-week-old mice were fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk. Liver morphology, gene expression of lipid transcription factors, and metabolic enzymes were assessed. Mice fed HFD displayed increased body weight, insulin resistance and dyslipidemia. Moro juice administration limited body weight gain, enhanced insulin sensitivity, and decreased serum triglycerides and total cholesterol. Mice fed HFD showed liver steatosis associated with ballooning. Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase, a key enzyme of lipid oxidation. Consistently, Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase, and restored liver glycerol-3-phosphate acyltransferase 1 activity. Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.

Impaired baroreflex function in mice overexpressing alpha-synuclein

Directory of Open Access Journals (Sweden)

Sheila eFleming

2013-07-01

Full Text Available Cardiovascular autonomic dysfunction, such as orthostatic hypotension consequent to baroreflex failure and cardiac sympathetic denervation, is frequently observed in the synucleinopathy Parkinson’s disease (PD. In the present study, the baroreceptor reflex was assessed in mice overexpressing human wildtype alpha-synuclein (Thy1-aSyn, a genetic mouse model of synucleinopathy. The beat-to-beat change in heart rate, computed from R-R interval, in relation to blood pressure was measured in anesthetized and conscious mice equipped with arterial blood pressure telemetry transducers during transient bouts of hypertension and hypotension. Compared to wildtype, tachycardia following nitroprusside-induced hypotension was significantly reduced in Thy1-aSyn mice. Thy1-aSyn mice also showed an abnormal cardiovascular response (i.e., diminished tachycardia to muscarinic blockade with atropine. We conclude that Thy1-aSyn mice have impaired basal and dynamic range of sympathetic and parasympathetic-mediated changes in heart rate and will be a useful model for long-term study of cardiovascular autonomic dysfunction associated with PD.

Sensorimotor learning in Dab1(scm) (scrambler) mutant mice.

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Lalonde, R; Strazielle, C

2011-04-15

Homozygous Dab1(scm) mouse mutants with cell ectopias in cerebellar cortex and neocortex were compared with non-ataxic controls on two tests of motor coordination: rotorod and grid climbing. Even at the minimal speed of 4 rpm and unlike controls, none of the Dab1(scm) mutants reached criterion on the constant speed rotorod. In contrast, Dab1(scm) mutants improved their performances on the vertical grid over the course of the same number of trials. Thus, despite massive cerebellar degeneration, sensorimotor learning for equilibrium is still possible, indicating the potential usefulness of the grid-climbing test in determining residual functions in mice with massive cerebellar damage. Copyright © 2010. Published by Elsevier B.V.

Mast cell histamine-mediated transient inflammation following exposure to nickel promotes nickel allergy in mice.