BDNF-Deficient Mice Show Reduced Psychosis-Related Behaviors Following Chronic Methamphetamine.

PubMed

Manning, Elizabeth E; Halberstadt, Adam L; van den Buuse, Maarten

2016-04-01

One of the most devastating consequences of methamphetamine abuse is increased risk of psychosis. Brain-derived neurotrophic factor has been implicated in both psychosis and neuronal responses to methamphetamine. We therefore examined persistent psychosis-like behavioral effects of methamphetamine in brain-derived neurotrophic factor heterozygous mice. Mice were chronically treated with methamphetamine from 6 to 9 weeks of age, and locomotor hyperactivity to an acute D-amphetamine challenge was tested in photocell cages after a 2-week withdrawal period. Methamphetamine-treated wild-type mice, but not brain-derived neurotrophic factor heterozygous mice, showed locomotor sensitization to acute 3mg/kg D-amphetamine. Qualitative analysis of exploration revealed tolerance to D-amphetamine effects on entropy in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice, but not wild-type mice. Chronic methamphetamine exposure induces contrasting profiles of behavioral changes in wild-type and brain-derived neurotrophic factor heterozygous mice, with attenuation of behaviors relevant to psychosis in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice. This suggests that brain-derived neurotrophic factor signalling changes may contribute to development of psychosis in methamphetamine users. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Differential regulation of pathogens: the role of habitat disturbance in predicting prevalence of Sin Nombre virus.

PubMed

Lehmer, Erin M; Clay, Christine A; Pearce-Duvet, Jessica; St Jeor, Stephen; Dearing, M Denise

2008-03-01

Deer mice (Peromyscus maniculatus) are the primary reservoir for Sin Nombre virus (SNV), a North American hantavirus that causes disease with high mortality in humans. Recent studies have proposed that habitat disturbance affects prevalence of SNV in deer mice; however, the outcomes proposed in these studies are in opposition to each other. Our objectives were to test these divergent hypotheses by: (1) measuring SNV infection in deer mice within a patchwork of disturbance; and (2) evaluating the relationships between SNV prevalence, population density and demography as possible mechanisms. In 2003 and 2004, we sampled 1,297 deer mice from 17 sites with varying levels of disturbance in the Great Basin Desert. Across sites and years, SNV prevalence varied from 0.0 to 38.9%. We found a negative relationship between SNV prevalence and disturbance. Although we found no direct relationship between SNV prevalence and deer mouse density, we found that density was highest on sites with the lowest levels of disturbance. The number of deer mice that survived across seasons (e.g., trans-seasonal survivors) differed across levels of disturbance and was greatest on our least disturbed study sites [Formula: see text] moderate on sites with intermediate levels of disturbance (x = 5.61%) and zero on highly disturbed sites. On low-disturbance sites, a greater proportion of trans-seasonal survivors were SNV seropositive (28.80%) compared to the intermediate-disturbance sites (16.67). Collectively, our results indicate that habitat disturbance plays a predictive role in SNV prevalence, with highly disturbed sites having reduced long-term survival of deer mice, including survival of infected individuals.

Peroxiredoxin 6 gene-targeted mice show increased lung injury with paraquat-induced oxidative stress.

PubMed

Wang, Yan; Feinstein, Sheldon I; Manevich, Yefim; Ho, Ye-Shih; Fisher, Aron B

2006-01-01

Mice with knock-out of peroxiredoxin 6 (Prdx6), a recently described antioxidant enzyme, were evaluated for susceptibility to lung injury with paraquat (PQ) administration. With high dose PQ (30 mg/kg i.p.), all Prdx6-/- mice died (LT50 54 +/- 2.05 h, mean +/- SE) by 4 days, whereas 86% of the wild-type (WT) mice (C57BL/6) survived (n = 14). At 2 days after PQ, lung wet/dry weight ratio increased significantly (p < 0.05) to 7.57 +/- 0.37 in Prdx6-/- mice vs. 5.42 +/- 0.25 in WT mice. Total protein and nucleated cells in bronchoalveolar lavage fluid and TBARS and protein carbonyls in lung homogenate also showed more marked increases in Prdx6-/- mice. At 2.5 days after PQ, light microscopy of WT lungs showed mild injury while Prdx6-/- lungs showed epithelial cell necrosis, perivascular edema, and inflammatory cells. With low dose PQ (12.5 mg/kg), mortality and lung injury were less marked but were significantly greater with Prdx6-/- compared to WT mice. These results show that Prdx6-/- mice have increased susceptibility to lung injury with PQ administration. Thus, Prdx6 protects lungs against PQ toxicity as shown previously for hyperoxia, indicating that it functions as an important lung antioxidant enzyme.

Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric

Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 10{sup 6} ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treatedmore » with the cocktail containing 10{sup 6} ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 10{sup 2}–10{sup 3} ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants. - Highlights: • The contamination of drinking water with drugs may have harmful effects on health. • Some drugs can be more hepatotoxic in the context of obesity and fatty liver. • Effects of chronic exposure of trace drugs were studied in lean and obese mouse liver. Drugs and obesity present additive effects on circadian gene expression and toxicity. �

Heparan sulfate deficiency leads to Peters anomaly in mice by disturbing neural crest TGF-β2 signaling

PubMed Central

Iwao, Keiichiro; Inatani, Masaru; Matsumoto, Yoshihiro; Ogata-Iwao, Minako; Takihara, Yuji; Irie, Fumitoshi; Yamaguchi, Yu; Okinami, Satoshi; Tanihara, Hidenobu

2009-01-01

During human embryogenesis, neural crest cells migrate to the anterior chamber of the eye and then differentiate into the inner layers of the cornea, the iridocorneal angle, and the anterior portion of the iris. When proper development does not occur, this causes iridocorneal angle dysgenesis and intraocular pressure (IOP) elevation, which ultimately results in developmental glaucoma. Here, we show that heparan sulfate (HS) deficiency in mouse neural crest cells causes anterior chamber dysgenesis, including corneal endothelium defects, corneal stroma hypoplasia, and iridocorneal angle dysgenesis. These dysfunctions are phenotypes of the human developmental glaucoma, Peters anomaly. In the neural crest cells of mice embryos, disruption of the gene encoding exostosin 1 (Ext1), which is an indispensable enzyme for HS synthesis, resulted in disturbed TGF-β2 signaling. This led to reduced phosphorylation of Smad2 and downregulated expression of forkhead box C1 (Foxc1) and paired-like homeodomain transcription factor 2 (Pitx2), transcription factors that have been identified as the causative genes for developmental glaucoma. Furthermore, impaired interactions between HS and TGF-β2 induced developmental glaucoma, which was manifested as an IOP elevation caused by iridocorneal angle dysgenesis. These findings suggest that HS is necessary for neural crest cells to form the anterior chamber via TGF-β2 signaling. Disturbances of HS synthesis might therefore contribute to the pathology of developmental glaucoma. PMID:19509472

Children with developmental dyslexia showed greater sleep disturbances than controls, including problems initiating and maintaining sleep.

PubMed

Carotenuto, M; Esposito, M; Cortese, S; Laino, D; Verrotti, A

2016-09-01

Although there have been frequent clinical reports about sleep disturbances in children with learning disabilities, no data are available about the prevalence of sleep disturbances in children with developmental dyslexia (DD). This study evaluated sleep disturbances in children with DD referred to a hospital clinic and compared their scores with healthy controls. We consecutively enrolled 147 children (66% male) aged 10.26 ± 2.63 years who were referred by clinical paediatricians to the Clinic for Child and Adolescent Neuropsychiatry at the Second University of Naples with DD and 766 children without DD (60% male) aged 10.49 ± 2.39 years recruited from schools in the same urban area. Sleep disturbances were assessed with the Sleep Disturbances Scale for Children (SDSC), which was filled out by the children's main carers. Compared with the controls, the children with DD showed significantly higher rates of above threshold scores on the total SDSC score (p < 0.001) and on the subscales for disorders in initiating and maintaining sleep (p < 0.001), sleep breathing disorders (p < 0.001) and disorders of arousal (p < 0.001). Sleep disorders were significantly more frequent in children with DD than in healthy controls. A possible relationship between dyslexia and sleep disorders may have relevant clinical implications. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Motivational Disturbances and Effects of L-dopa Administration in Neurofibromatosis-1 Model Mice

PubMed Central

Wozniak, David F.; Diggs-Andrews, Kelly A.; Conyers, Sara; Yuede, Carla M.; Dearborn, Joshua T.; Brown, Jacquelyn A.; Tokuda, Kazuhiro; Izumi, Yukitoshi; Zorumski, Charles F.; Gutmann, David H.

2013-01-01

Children with neurofibromatosis type 1 (NF1) frequently have cognitive and behavioral deficits. Some of these deficits have been successfully modeled in Nf1 genetically-engineered mice that develop optic gliomas (Nf1 OPG mice). In the current study, we show that abnormal motivational influences affect the behavior of Nf1 OPG mice, particularly with regard to their response to novel environmental stimuli. For example, Nf1 OPG mice made fewer spontaneous alternations in a Y-maze and fewer arm entries relative to WT controls. However, analysis of normalized alternation data demonstrated that these differences were not due to a spatial working memory deficit. Other reported behavioral results (e.g., open-field test, below) suggest that differential responses to novelty and/or other motivational influences may be more important determinants of these kinds of behavior than simple differences in locomotor activity/spontaneous movements. Importantly, normal long-term depression was observed in hippocampal slices from Nf1 OPG mice. Results from elevated plus maze testing showed that differences in exploratory activity between Nf1 OPG and WT control mice may be dependent on the environmental context (e.g., threatening or non-threatening) under which exploration is being measured. Nf1 OPG mice also exhibited decreased exploratory hole poking in a novel holeboard and showed abnormal olfactory preferences, although L-dopa (50 mg/kg) administration resolved the abnormal olfactory preference behaviors. Nf1 OPG mice displayed an attenuated response to a novel open field in terms of decreased ambulatory activity and rearing but only during the first 10 min of the session. Importantly, Nf1 OPG mice demonstrated investigative rearing deficits with regard to a novel hanging object suspended on one side of the field which were not rescued by L-dopa administration. Collectively, our results provide new data important for evaluating therapeutic treatments aimed at ameliorating NF1

Heterozygous Che-1 KO mice show deficiencies in object recognition memory persistence.

PubMed

Zalcman, Gisela; Corbi, Nicoletta; Di Certo, Maria Grazia; Mattei, Elisabetta; Federman, Noel; Romano, Arturo

2016-10-06

Transcriptional regulation is a key process in the formation of long-term memories. Che-1 is a protein involved in the regulation of gene transcription that has recently been proved to bind the transcription factor NF-κB, which is known to be involved in many memory-related molecular events. This evidence prompted us to investigate the putative role of Che-1 in memory processes. For this study we newly generated a line of Che-1(+/-) heterozygous mice. Che-1 homozygous KO mouse is lethal during development, but Che-1(+/-) heterozygous mouse is normal in its general anatomical and physiological characteristics. We analyzed the behavioral characteristic and memory performance of Che-1(+/-) mice in two NF-κB dependent types of memory. We found that Che-1(+/-) mice show similar locomotor activity and thigmotactic behavior than wild type (WT) mice in an open field. In a similar way, no differences were found in anxiety-like behavior between Che-1(+/-) and WT mice in an elevated plus maze as well as in fear response in a contextual fear conditioning (CFC) and object exploration in a novel object recognition (NOR) task. No differences were found between WT and Che-1(+/-) mice performance in CFC training and when tested at 24h or 7days after training. Similar performance was found between groups in NOR task, both in training and 24h testing performance. However, we found that object recognition memory persistence at 7days was impaired in Che-1(+/-) heterozygous mice. This is the first evidence showing that Che-1 is involved in memory processes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon

PubMed Central

Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

2015-01-01

Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities. PMID:26304458

Mice repeatedly exposed to Group-A β-Haemolytic Streptococcus show perseverative behaviors, impaired sensorimotor gating, and immune activation in rostral diencephalon.

PubMed

Macrì, Simone; Ceci, Chiara; Onori, Martina Proietti; Invernizzi, Roberto William; Bartolini, Erika; Altabella, Luisa; Canese, Rossella; Imperi, Monica; Orefici, Graziella; Creti, Roberta; Margarit, Immaculada; Magliozzi, Roberta; Laviola, Giovanni

2015-08-25

Repeated exposure to Group-A β-Haemolytic Streptococcus (GAS) may constitute a vulnerability factor in the onset and course of pediatric motor disturbances. GAS infections/colonization can stimulate the production of antibodies, which may cross the blood brain barrier, target selected brain areas (e.g. basal ganglia), and exacerbate motor alterations. Here, we exposed developing SJL male mice to four injections with a GAS homogenate and evaluated the following domains: motor coordination; general locomotion; repetitive behaviors; perseverative responses; and sensorimotor gating (pre-pulse inhibition, PPI). To demonstrate that behavioral changes were associated with immune-mediated brain alterations, we analyzed, in selected brain areas, the presence of infiltrates and microglial activation (immunohistochemistry), monoamines (HPLC), and brain metabolites (in vivo Magnetic Resonance Spectroscopy). GAS-exposed mice showed increased repetitive and perseverative behaviors, impaired PPI, and reduced concentrations of serotonin in prefrontal cortex, a brain area linked to the behavioral domains investigated, wherein they also showed remarkable elevations in lactate. Active inflammatory processes were substantiated by the observation of infiltrates and microglial activation in the white matter of the anterior diencephalon. These data support the hypothesis that repeated GAS exposure may elicit inflammatory responses in brain areas involved in motor control and perseverative behavior, and result in phenotypic abnormalities.

A Pathogen-Selective Antibiotic Minimizes Disturbance to the Microbiome

PubMed Central

Yao, Jiangwei; Carter, Robert A.; Vuagniaux, Grégoire; Barbier, Maryse; Rosch, Jason W.

2016-01-01

Broad-spectrum antibiotic therapy decimates the gut microbiome, resulting in a variety of negative health consequences. Debio 1452 is a staphylococcus-selective enoyl-acyl carrier protein reductase (FabI) inhibitor under clinical development and was used to determine whether treatment with pathogen-selective antibiotics would minimize disturbance to the microbiome. The effect of oral Debio 1452 on the microbiota of mice was compared to the effects of four commonly used broad-spectrum oral antibiotics. During the 10 days of oral Debio 1452 treatment, there was minimal disturbance to the gut bacterial abundance and composition, with only the unclassified S24-7 taxon reduced at days 6 and 10. In comparison, broad-spectrum oral antibiotics caused ∼100- to 4,000-fold decreases in gut bacterial abundance and severely altered the microbial composition. The gut bacterial abundance and composition of Debio 1452-treated mice were indistinguishable from those of untreated mice 2 days after the antibiotic treatment was stopped. In contrast, the bacterial abundance in broad-spectrum-antibiotic-treated mice took up to 7 days to recover, and the gut composition of the broad-spectrum-antibiotic-treated mice remained different from that of the control group 20 days after the cessation of antibiotic treatment. These results illustrate that a pathogen-selective approach to antibiotic development will minimize disturbance to the gut microbiome. PMID:27161626

Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yuehai; Cardiovascular Department, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000; Lu, Huixia

Highlights: • Titers of ANA and anti-dsDNA antibodies were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • The spleen weights and glomerular areas were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • Expressions of IgG and C3 in glomeruli were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • IgG, C3 and macrophage infiltration in aortic plaques were found in ApoE{sup −/−} mice. - Abstract: Background: Apolipoprotein E-knockout (ApoE{sup −/−}) mice is a classic model of atherosclerosis. We have found that ApoE{sup −/−} mice showed splenomegaly, higher titers of serum anti-nuclear antibody (ANA) and anti-dsDNA antibody compared withmore » C57B6/L (B6) mice. However, whether ApoE{sup −/−} mice show autoimmune injury remains unclear. Methods and results: Six females and six males in each group, ApoE{sup −/−}, Fas{sup −/−} and B6 mice, were used in this study. The titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein were measured by ELISA after 4 months of high-fat diet. The spleen weight and the glomerular area were determined. The expressions of IgG, C3 and macrophage in kidney and atherosclerotic plaque were detected by immunostaining followed by morphometric analysis. Similar to the characteristics of Fas{sup −/−} mice, a model of systemic lupus erythematosus (SLE), ApoE{sup −/−} mice, especially female, displayed significant increases of spleen weight and glomerular area when compared to B6 mice. Also, elevated titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein. Moreover, the expressions of IgG, C3 and macrophage in glomeruli and aortic plaques were found in ApoE{sup −/−} mice. In addition, the IgG and C3 expressions in glomeruli and plaques significantly increased (or a trend of increase) in female ApoE{sup −/−} mice compared with males. Conclusions: Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta.« less

Mice subjected to uncontrollable electric shocks show depression-like behaviors irrespective of their state of helplessness.

PubMed

Kim, Jin Yong; Yang, Soo Hyun; Kwon, Jihyun; Lee, Hyun Woo; Kim, Hyun

2017-03-30

The unpredictable and inescapable electric shock-induced "learned helplessness" paradigm has long been used to produce an animal model of depression to identify the molecules associated with depressive symptoms or to assess the efficacy of pharmacological treatments for depression. After exposure to unpredictable and inescapable shocks (uncontrollable stress), most of mice showed defect in escape behavior in active avoidance test (learned helplessness, LH), while others did not (non-learned helplessness, NLH). Here, we investigated whether mice with LH or NLH exhibited depressive symptoms, including anhedonia, anxiety, and despair. We found that compared with control naïve mice, both uncontrollable shocks-induced LH and NLH mice showed increased anhedonia- and anxiety- but not despair-like behaviors. Notably, mice subjected to uncontrollable shocks showed similar behaviors, irrespective of whether they also showed LH or NLH. Furthermore, since both LH and NLH mice showed only anhedonia- and anxiety- but not despair-like behaviors, this model may be generally inadequate for classic depression-like behavior assessment. In conclusion, uncontrollable electric shock induces depression-like behavior, irrespective of the state of helplessness. Copyright © 2017 Elsevier B.V. All rights reserved.

Maternal exposure to benzo[b]fluoranthene disturbs reproductive performance in male offspring mice.

PubMed

Kim, Ahyoung; Park, Mira; Yoon, Tae Ki; Lee, Woo Sik; Ko, Jeong-Jae; Lee, Kangseok; Bae, Jeehyeon

2011-05-30

Polycyclic aromatic hydrocarbons (PAHs) are a large family of environmentally prevalent toxic compounds generated from the combustion of organic materials and diesel exhaust. Humans and wild animals are exposed to PAHs mostly through dietary intake of contaminated food. Benzo[b]fluoranthene (B[b]F) is a common constituent of PAH complexes present in diverse types of food. B[b]F has been found in human milk, raising the demand for the need for risk assessment of offspring after maternal exposure to B[b]F. In the present study, pregnant mice were orally exposed to low doses (2-2000μg/kg body weight) of B[b]F during gestational and lactational periods, and their male offspring were assessed. Maternal B[b]F exposure disturbed normal sperm function in F1 offspring. To understand the molecular and cellular mechanisms by which the perinatal exposure to B[b]F decreased sperm quality, the testes of young adult F1 mice were examined for changes in expression of steroidogenesis-related and testicular apoptosis mediators and found that aryl hydrocarbon receptor, estrogen receptor α, and a set of proapoptotic proteins including Bax, Noxa, Bad, and Bim were significantly upregulated. Therefore, the current transgenerational animal study implies that consumption of PAH-contaminated diets by mothers may possibly influence their offspring to cause dysfunctional male reproductive function in humans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Obese Neuronal PPARγ Knockout Mice Are Leptin Sensitive but Show Impaired Glucose Tolerance and Fertility.

PubMed

Fernandez, Marina O; Sharma, Shweta; Kim, Sun; Rickert, Emily; Hsueh, Katherine; Hwang, Vicky; Olefsky, Jerrold M; Webster, Nicholas J G

2017-01-01

The peroxisome-proliferator activated receptor γ (PPARγ) is expressed in the hypothalamus in areas involved in energy homeostasis and glucose metabolism. In this study, we created a deletion of PPARγ brain-knockout (BKO) in mature neurons in female mice to investigate its involvement in metabolism and reproduction. We observed that there was no difference in age at puberty onset between female BKOs and littermate controls, but the BKOs gave smaller litters when mated and fewer oocytes when ovulated. The female BKO mice had regular cycles but showed an increase in the number of cycles with prolonged estrus. The mice also had increased luteinizing hormone (LH) levels during the LH surge and histological examination showed hemorrhagic corpora lutea. The mice were challenged with a 60% high-fat diet (HFD). Metabolically, the female BKO mice showed normal body weight, glucose and insulin tolerance, and leptin levels but were protected from obesity-induced leptin resistance. The neuronal knockout also prevented the reduction in estrous cycles due to the HFD. Examination of ovarian histology showed a decrease in the number of primary and secondary follicles in both genotypes due to the HFD, but the BKO ovaries showed an increase in the number of hemorrhagic follicles. In summary, our results show that neuronal PPARγ is required for optimal female fertility but is also involved in the adverse effects of diet-induced obesity by creating leptin resistance potentially through induction of the repressor Socs3. Copyright © 2017 by the Endocrine Society.

Socially dominant mice in C57BL6 background show increased social motivation.

PubMed

Kunkel, Thaddeus; Wang, Hongbing

2018-01-15

A series of behavioral tests measuring social dominance, social motivation, and non-social motivation are examined in adult male C57BL6 mice. By using the well-known tube dominance test to determine social dominance and rank, we find that, in the absence of competition for resource and mating, group-housed mouse cage-mates display stable and mostly linear and transitive social hierarchies. Mice with top and bottom social ranks are subjected to a three-chamber social interaction test to measure social motivation. The top ranked mice spend more time interacting with a stranger mouse than the bottom ranked mice, suggesting that social dominance may positively influence social motivation. When subjected to a novel environment, mice with different social ranks show similar locomotion and exploring activity in the open field test, suggesting no detectable difference in certain aspects of non-social motivation. These results demonstrate a behavioral correlation between social dominance and social motivation. Copyright © 2017 Elsevier B.V. All rights reserved.

Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howe, Adina; Ringus, Daina L.; Williams, Ryan J.

To improve our understanding of the stability of mammalian intestinal communities, we characterized the responses of both bacterial and viral communities in murine fecal samples to dietary changes between high- and low-fat (LF) diets. Targeted DNA extraction methods for bacteria, virus-like particles and induced prophages were used to generate bacterial and viral metagenomes as well as 16S ribosomal RNA amplicons. Gut microbiome communities from two cohorts of C57BL/6 mice were characterized in a 6-week diet perturbation study in response to high fiber, LF and high-refined sugar, milkfat (MF) diets. The resulting metagenomes from induced bacterial prophages and extracellular viruses showedmore » significant overlap, supporting a largely temperate viral lifestyle within these gut microbiomes. The resistance of baseline communities to dietary disturbances was evaluated, and we observed contrasting responses of baseline LF and MF bacterial and viral communities. In contrast to baseline LF viral communities and bacterial communities in both diet treatments, baseline MF viral communities were sensitive to dietary disturbances as reflected in their non-recovery during the washout period. Finally, the contrasting responses of bacterial and viral communities suggest that these communities can respond to perturbations independently of each other and highlight the potentially unique role of viruses in gut health.« less

Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice

DOE PAGES

Howe, Adina; Ringus, Daina L.; Williams, Ryan J.; ...

2015-10-16

To improve our understanding of the stability of mammalian intestinal communities, we characterized the responses of both bacterial and viral communities in murine fecal samples to dietary changes between high- and low-fat (LF) diets. Targeted DNA extraction methods for bacteria, virus-like particles and induced prophages were used to generate bacterial and viral metagenomes as well as 16S ribosomal RNA amplicons. Gut microbiome communities from two cohorts of C57BL/6 mice were characterized in a 6-week diet perturbation study in response to high fiber, LF and high-refined sugar, milkfat (MF) diets. The resulting metagenomes from induced bacterial prophages and extracellular viruses showedmore » significant overlap, supporting a largely temperate viral lifestyle within these gut microbiomes. The resistance of baseline communities to dietary disturbances was evaluated, and we observed contrasting responses of baseline LF and MF bacterial and viral communities. In contrast to baseline LF viral communities and bacterial communities in both diet treatments, baseline MF viral communities were sensitive to dietary disturbances as reflected in their non-recovery during the washout period. Finally, the contrasting responses of bacterial and viral communities suggest that these communities can respond to perturbations independently of each other and highlight the potentially unique role of viruses in gut health.« less

Mice lacking GRIP1/2 show increased social interactions and enhanced phosphorylation at GluA2-S880.

PubMed

Han, Mei; Mejias, Rebeca; Chiu, Shu-Ling; Rose, Rebecca; Adamczyk, Abby; Huganir, Richard; Wang, Tao

2017-03-15

Glutamate receptor interacting proteins 1 and 2 (GRIP1/2) play an important role in regulating synaptic trafficking of AMPA receptor 2/3 (GluA2/3) and synaptic strength. Gain-of-function GRIP1 mutations are implicated in social behavioral deficits in autism. To study mechanisms of Grip1/2-mediated AMPA signaling in the regulation of social behaviors, we performed social behavioral testing on neuron-specific Grip1/2-double knockout (DKO) and wild type (WT) mice that are matched for age, sex, and strain background. We determined the expression profile of key signaling proteins in AMPAR, mGluR, mTOR, and GABA pathways in frontal cortex, striatum, and cerebellum of DKO mice. Compared to WT mice, DKO mice show increased sociability in a modified three-chamber social behavioral test [mean±sem for interaction time in seconds; WT: 44.0±5.0; n=10; DKO: 81.0±9.0; n=9; two factor repeated measures ANOVA: F(1,37)=14.45; p<0.01 and planned t-test; p<0.01] and in a dyadic male-male social interaction test (mean±sem for total time in seconds: sniffing, WT-WT, 18.9±1.1; WT-DKO, 42.5±2.1; t-test: p<0.001; following, WT-WT, 7.7±0.72; WT-DKO,14.4±1.8; t-test: p<0.001). Immunoblot studies identified an increase in phosphorylation at GluA2-Serine 880 (GluA2-pS880) in frontal cortex (mean±sem; WT: 0.69±0.06, n=5; DKO: 0.96±0.06, n=6; t-test; p<0.05) and reduced GABAβ3 expression in striatum (mean±sem; WT: 1.16±0.04, n=4; DKO: 0.95±0.06, n=4; t-test; p<0.05) in DKO mice. GluA2-S880 phosphorylation is known to regulate GluA2synaptic recycling, AMPA signaling strength and plasticity. GABAβ3 has been implicated in the etiology and pathogenesis in autism. These data support an important role of Grip1/2-mediated AMPA signaling in regulating social behaviors and disturbance of glutamate- and GABA-signaling in specialized brain regions in autism-related social behavioral deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

Mice lacking the G protein γ3-subunit show resistance to opioids and diet induced obesity

PubMed Central

Schwindinger, William F.; Borrell, Brandon M.; Waldman, Lora C.

2009-01-01

Contributing to the obesity epidemic, there is increasing evidence that overconsumption of high-fat foods may be analogous to drug addiction in that the palatability of these foods is associated with activation of specific reward pathways in the brain. With this perspective, we report that mice lacking the G protein γ3-subunit (Gng3−/− mice) show resistance to high-fat diet-induced weight gain over the course of a 12-wk study. Compared with Gng3+/+ controls, female Gng3−/− mice exhibit a 40% reduction in weight gain and a 53% decrease in fat pad mass, whereas male Gng3−/− mice display an 18% reduction in weight gain and no significant decrease in fat pad mass. The basis for the lowered weight gain is related to reduced food consumption for female and male Gng3−/− mice of 13% and 14%, respectively. Female Gng3−/− mice also show a lesser preference for high-fat chow than their female Gng3+/+ littermates, suggesting an attenuated effect on a reward pathway associated with overconsumption of fat. One possible candidate is the μ-opioid receptor (Oprm1) signaling cascade. Supporting a defect in this signaling pathway, Gng3−/− mice show marked reductions in both acute and chronic morphine responsiveness, as well as increases in endogenous opioid mRNA levels in reward-related regions of the brain. Taken together, these data suggest that the decreased weight gain of Gng3−/− mice may be related to a reduced rewarding effect of the high-fat diet resulting from a defect in Oprm1 signaling and loss of the G protein γ3-subunit. PMID:19759336

Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice.

PubMed

Bedrosian, Tracy A; Herring, Kamillya L; Weil, Zachary M; Nelson, Randy J

2011-07-12

Both normal aging and dementia are associated with dysregulation of the biological clock, which contributes to disrupted circadian organization of physiology and behavior. Diminished circadian organization in conjunction with the loss of cholinergic input to the cortex likely contributes to impaired cognition and behavior. One especially notable and relatively common circadian disturbance among the aged is "sundowning syndrome," which is characterized by exacerbated anxiety, agitation, locomotor activity, and delirium during the hours before bedtime. Sundowning has been reported in both dementia patients and cognitively intact elderly individuals living in institutions; however, little is known about temporal patterns in anxiety and agitation, and the neurobiological basis of these rhythms remains unspecified. In the present study, we explored the diurnal pattern of anxiety-like behavior in aged and amyloid precursor protein (APP) transgenic mice. We then attempted to treat the observed behavioral disturbances in the aged mice using chronic nightly melatonin treatment. Finally, we tested the hypothesis that time-of-day differences in acetylcholinesterase and choline acetyltransferase expression and general neuronal activation (i.e., c-Fos expression) coincide with the behavioral symptoms. Our results show a temporal pattern of anxiety-like behavior that emerges in elderly mice. This behavioral pattern coincides with elevated locomotor activity relative to adult mice near the end of the dark phase, and with time-dependent changes in basal forebrain acetylcholinesterase expression. Transgenic APP mice show a similar behavioral phenomenon that is not observed among age-matched wild-type mice. These results may have useful applications to the study and treatment of age- and dementia-related circadian behavioral disturbances, namely, sundowning syndrome.

Methionine Sulfoxide Reductase A Knockout Mice Show Progressive Hearing Loss and Sensitivity to Acoustic Trauma.

PubMed

Alqudah, Safa; Chertoff, Mark; Durham, Dianne; Moskovitz, Jackob; Staecker, Hinrich; Peppi, Marcello

2018-06-21

Methionine sulfoxide reductases (MsrA and MsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of the MsrA knockout mouse. Young MsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in older MsrA knockout mice. MsrA knockout mice showed an increased sensitivity to noise at young and older ages, suggesting that MsrA is part of a mechanism that protects the cochlea from acoustic damage. MsrA mRNA in the cochlea was increased following acoustic stimulation. Finally, expression of mRNA MsrB1 was compromised at 6 months old, but not in younger MsrA knockout mice (compared to controls). The identification of MsrA in the cochlea as a protective mediator from both early onset hearing loss and acoustic trauma expands our understanding of the pathways that may induce protection from acoustic trauma and foster further studies on how to prevent the damaging effect of noise exposure through Msr-based therapy. © 2018 S. Karger AG, Basel.

Omija fruit ethanol extract improves adiposity and related metabolic disturbances in mice fed a high-fat diet.

PubMed

Park, Hyo Jin; Kim, Hye-Jin; Kim, Sang Ryong; Choi, Myung-Sook; Jung, Un Ju

2017-03-01

This study investigated the biological and molecular mechanisms underlying the antiobesity effect of omija fruit ethanol extract (OFE) in mice fed a high-fat diet (HFD). C57BL/6J mice were fed an HFD (20% fat, w/w) with or without OFE (500 mg/kg body weight) for 16 weeks. Dietary OFE significantly increased brown adipose tissue weight and energy expenditure while concomitantly decreasing white adipose tissue (WAT) weight and adipocyte size by up-regulating the expression of brown fat-selective genes in WAT. OFE also improved hepatic steatosis and dyslipidemia by enhancing hepatic fatty acid oxidation-related enzymes activity and fecal lipid excretion. In addition to steatosis, OFE decreased the expression of pro-inflammatory genes in the liver. Moreover, OFE improved glucose tolerance and lowered plasma glucose, insulin and homeostasis model assessment of insulin resistance, which may be linked to decreases in the activity of hepatic gluconeogenic enzymes and the circulating level of gastric inhibitory polypeptide. These findings suggest that OFE may protect against diet-induced adiposity and related metabolic disturbances by controlling brown-like transformation of WAT, fatty acid oxidation, inflammation in the liver and fecal lipid excretion. Improved insulin resistance may be also associated with its antiobesity effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Fractures in geriatric mice show decreased callus expansion and bone volume.

PubMed

Lopas, Luke A; Belkin, Nicole S; Mutyaba, Patricia L; Gray, Chancellor F; Hankenson, Kurt D; Ahn, Jaimo

2014-11-01

210.79±37.60 mg HA/cm3; p=0.016), and less total cartilage (mean cartilage area at 10 days postfracture, 101,279±46,755 square pixels versus 302,167±137,806 square pixels; p=0.013) and bone content (mean bone volume at 20 days postfracture, 11.68±3.18 mm3 versus 22.34±10.59 mm3; p<0.001) compared with the young adult mice. However, the amount of cartilage and bone relative to the total callus size was similar between the adult and geriatric mice (mean bone volume fraction at 25 days postfracture, 0.48±0.10 versus 0.50±0.13; p=0.793), and the relative expression of chondrogenic (mean fold change in SOX9 at 10 days postfracture, 135+25 versus 90±52; p=0.221) and osteogenic genes (mean fold change in osterix at 20 days postfracture, 22.2±5.3 versus 18.7±5.2; p=0.324) was similar. Analysis of mesenchymal cell proliferation in the geriatric mice relative to adult mice showed a decrease in proliferation (mean percent of undifferentiated mesenchymal cells staining proliferating cell nuclear antigen [PCNA] positive at 10 days postfracture, 25%±6.8% versus 42%±14.5%; p=0.047). Our findings suggest that the molecular program of fracture healing is intact in geriatric mice, as it is in geriatric humans, but callus expansion is reduced in magnitude. Our study showed altered healing capacity in a relevant animal model of geriatric fracture healing. The understanding that callus expansion and bone volume are decreased with aging can help guide the development of targeted therapeutics for these difficult to heal fractures.

Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice after cola beverages drinking.

PubMed

Otero-Losada, Matilde E; Mc Loughlin, Santiago; Rodríguez-Granillo, Gastón; Müller, Angélica; Ottaviano, Graciela; Moriondo, Marisa; Cutrin, Juan C; Milei, José

2013-04-01

Atherosclerosis is a major health burden. Metabolic disorders had been associated with large consumption of soft drinks. The rising incidence of atherosclerosis and metabolic alterations warrants the study of long-term soft drink consumption' effects on metabolism and atherosclerosis in genetic deficiency of apolipoprotein E which typically develops spontaneous atherosclerosis and metabolic alterations. ApoE-/- mice were randomized in 3 groups accordingly with free access to: water (W), regular cola (C) or light cola (L). After 8 weeks, 50% of the animals in each group were euthanized ( W8, C8, L8). The remaining mice (all groups) drank water for 8 weeks and were euthanized (Washout: W16, C16, L16). Body weight and food and drink consumption were periodically measured. Blood was collected (biochemistry). At autopsy, transverse aortic sinus sections were serially cut and stained (histomorphometry); livers and kidneys were processed (microscopy). MANOVA (identification of variance factors) was followed by ANOVA and LSD tests (within-factor differences between levels). Conventionally a p< 0.05 was considered significant. TREATMENT increased drinking volumes (vs W8: 4 fold C8, p<0.0001; +47% L8, p<0.02). Only C reduced eating amounts (-54%, p<0.05 vs W8). I). Compared with W8: C8 developed hyperglycemia (+43%, p<0.03) and increased non-HDL cholesterol (+54%, p<0.05); L8 showed decreased glycemia (-15%, p<0.05 vs W8) and increased creatinine (2.5 fold, p<0.04), urea (+74, p<0.03) and aspartate-aminotransferase (2.8 fold, p<0.05). Hypercreatininemia was observed in L16 (2.7 fold vs W16, p<0.05). Hypertriglyceridemia (+91%, p<0.008) and hyperuremia (+68%, p<0.03) developed over time of study (age). II). TREATMENT caused plaque area increase (vs W8: 28% C8, p<0.02 and 50% L8, p<0.01; vs W16: 43% C16, p<0.05 and 68% L16, p<0.02) and stenosis (vs W8: 38% C8, p<0.04 and 57% L8, p<0.01; vs W16: 71% C16, p<0.01 and 46% L16, p<0.04). Age also caused plaque area increase

Astrocytic leptin-receptor knockout mice show partial rescue of leptin resistance in diet-induced obesity.

PubMed

Jayaram, Bhavaani; Pan, Weihong; Wang, Yuping; Hsuchou, Hung; Mace, Aurelien; Cornelissen-Guillaume, Germaine G; Mishra, Pramod K; Koza, Robert A; Kastin, Abba J

2013-03-15

To determine how astrocytic leptin signaling regulates the physiological response of mice to diet-induced obesity (DIO), we performed metabolic analyses and hypothalamic leptin signaling assays on astrocytic leptin-receptor knockout (ALKO) mice in which astrocytes lack functional leptin receptor (ObR) signaling. ALKO mice and wild-type (WT) littermate controls were studied at different stages of DIO with measurement of body wt, percent fat, metabolic activity, and biochemical parameters. When fed regular chow, the ALKO mice had similar body wt, percent fat, food intake, heat dissipation, respiratory exchange ratio, and activity as their WT littermates. There was no change in blood concentrations of triglyceride, soluble leptin receptor (sObR), mRNA for leptin and uncoupling protein 1 (UCP1) in adipose tissue, and insulin sensitivity. Unexpectedly, in response to a high-fat diet the ALKO mice had attenuated hyperleptinemia and sObR, a lower level of leptin mRNA in subcutaneous fat, and a paradoxical increase in UCP1 mRNA. Thus, ALKO mice did not show the worsening of obesity that occurs with normal WT mice and the neuronal ObR mutation that results in morbid obesity. The findings are consistent with a competing, counterregulatory model between neuronal and astrocytic leptin signaling.

Chronic social stress leads to altered sleep homeostasis in mice.

PubMed

Olini, Nadja; Rothfuchs, Iru; Azzinnari, Damiano; Pryce, Christopher R; Kurth, Salome; Huber, Reto

2017-06-01

Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1-4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Croton grewioides Baill. (Euphorbiaceae) Shows Antidiarrheal Activity in Mice

PubMed Central

da Silva, Anne Dayse Soares; de Melo e Silva, Karoline; Neto, José Clementino; Costa, Vicente Carlos de Oliveira; Pessôa, Hilzeth de Luna F.; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Cavalcante, Fabiana de Andrade

2016-01-01

Based on chemotaxonomy, we decided to investigate the possible antidiarrheal activity in mice of a crude ethanolic extract obtained from aerial parts of Croton grewioides (CG-EtOH). We tested for any possible toxicity in rat erythrocytes and acute toxicity in mice. Antidiarrheal activity was assessed by determining the effect of CG-EtOH on defecation frequency, liquid stool, intestinal motility and intestinal fluid accumulation. CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females. CG-EtOH produced a significant and equipotent antidiarrheal activity, both in defecation frequency (ED50 = 106.0 ± 8.1 mg/kg) and liquid stools (ED50 = 105.0 ± 9.2 mg/kg). However, CG-EtOH (125 mg/kg) decreased intestinal motility by only 22.7% ± 4.4%. Moreover, extract markedly inhibited the castor oil-induced intestinal contents (ED50 = 34.6 ± 5.4 mg/kg). We thus conclude that CG-EtOH is not orally lethal and contains active principles with antidiarrheal activity, and this effect seems to involve mostly changes in intestinal secretion. SUMMARY CG-EtOH showed no in vitro cytotoxicity and was not orally lethal. In contrast, the extract given intraperitoneally (at 2000 mg/kg) was lethal, but only in females.CG-EtOH probably contains active metabolites with antidiarrheal activity.CG-EtOH reduced the frequency and number of liquid stools.Metabolites presents in the CG-EtOH act mainly by reducing intestinal fluid and, to a lesser extent, reducing intestinal motility. Abbreviations Used: CG-EtOH: crude ethanolic extract obtained from the aerial parts of C. grewioides; WHO: World Health Organization; ED50: dose of a drug that produces 50% of its maximum effect; Emax: maximum effect PMID:27365990

Aged mice receiving caffeine since adulthood show distinct patterns of anxiety-related behavior.

PubMed

Botton, Paulo Henrique S; Pochmann, Daniela; Rocha, Andreia S; Nunes, Fernanda; Almeida, Amanda S; Marques, Daniela M; Porciúncula, Lisiane O

2017-03-01

Caffeine is the psychostimulant most consumed worldwide. Anxiogenic effects of caffeine have been described in adult animals with controversial findings about its anxiogenic potential. Besides, the effects of caffeine on anxiety with aging are still poorly known. In this study, adult mice (6months old) started to receive caffeine (0.3 and 1.0mg/mL, drinking water) during 12-14months only in the light cycle and at weekdays. The open field (OF) and elevated plus maze (EPM) testing were used to determine the effects of caffeine on anxiety-related behavior in adult and aged mice (18-20months old). Because aging alters synaptic proteins, we also evaluated SNAP-25 (as a nerve terminals marker), GFAP (as an astrocyte marker) and adenosine A 1 and A 2A receptors levels in the cortex. According to the OF analysis, caffeine did not change both hypolocomotion and anxiety with aging. However, aged mice showed less anxiety behavior in the EPM, but after receiving caffeine (0.3mg/mL) during adulthood they were anxious as adult mice. While SNAP-25 and adenosine A 2A receptors increased with aging, both GFAP and adenosine A 1 receptors were not affected. Caffeine at moderate dose prevented the age-related increase of the SNAP-25, with no effect on adenosine A 2A receptors. The absence of effect for the highest dose suggests that tolerance to caffeine may have developed over time. Aged mice showed high responsiveness to the OF, being difficult to achieve any effect of caffeine. On the other hand this substance sustained the adult anxious behavior over time in a less stressful paradigm, and this effect was coincident with changes in the SNAP-25, suggesting the involvement of this synaptic protein in the ability of caffeine to preserve changes related to emotionality with aging. Copyright © 2016 Elsevier Inc. All rights reserved.

[IMMUNOCYTOCHEMICAL ANALYSIS OF THE DISTURBANCES IN THE STRUCTURE OF SYNAPTONEMAL COMPLEXES IN SPERMATOCYTE NUCLEI IN MICE UNDER EXPOSURE TO ROCKET FUEL COMPONENT].

PubMed

Lovinskaya, A V; Kolumbayeva, S Zh; Abilev, S K; Kolomiets, O L

2016-01-01

There was performed an assessment of genotoxic effects of rocket fuel component--unsymmetrical dimethylhydrazine (UDMH, heptyl)--on forming germ cells of male mice. Immunocytochemically there was studied the structure of meiotic nuclei at different times after the intraperitoneal administration of UDMH to male mice. There were revealed following types of disturbances of the structure of synaptonemal complexes (SCs) of meiotic chromosomes: single and multiple fragments of SCs associations of autosomes with a sex bivalent, atypical structure of the SCs with a frequency higher than the reference level. In addition, there were found the premature desinapsis of sex bivalents, the disorder offormation of the genital corpuscle and ring SCs. Established disorders in SCs of spermatocytes, analyzed at 38th day after the 10-days intoxication of animal by the component of rocket fuel, attest to the risk of permanent persistence of chromosomal abnormalities occurring in the pool of stem cells.

Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice.

PubMed

Kim, Juyoung; Kim, Juhae; Kwon, Young Hye

2016-08-01

Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including LXRα, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging.

PubMed

Wakabayashi, Chisato; Numakawa, Tadahiro; Odaka, Haruki; Ooshima, Yoshiko; Kiyama, Yuji; Manabe, Toshiya; Kunugi, Hiroshi; Iwakura, Yoichiro

2015-07-10

Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

PubMed Central

Umemura, Mariko; Ogura, Tae; Matsuzaki, Ayako; Nakano, Haruo; Takao, Keizo; Miyakawa, Tsuyoshi; Takahashi, Yuji

2017-01-01

Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/-) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders. PMID:28744205

Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yuehai; Huang, Ziyang, E-mail: huangziyang666@126.com; Lu, Huixia

2012-07-13

Highlights: Black-Right-Pointing-Pointer Titers of ANA and anti-dsDNA antibodies were higher in ApoE{sup -/-} than C57B6/L mice. Black-Right-Pointing-Pointer Spleen was greater and splenocyte apoptosis lower in ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer Level of TLR4 was lower in spleen tissue of ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer The TLR4 pathway may participate in maintaining the balance of splenocyte apoptosis. Black-Right-Pointing-Pointer The TLR4 pathway may participate in antibody production in spleen tissue. -- Abstract: Apolipoprotein E-knockout (ApoE{sup -/-}) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE{sup -/-}more » mice. The spleens of all ApoE{sup -/-} and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE{sup -/-} mice after 4 weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE{sup -/-} mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE{sup -/-} than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE{sup -/-} spleen

Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice after cola beverages drinking

PubMed Central

2013-01-01

Background Atherosclerosis is a major health burden. Metabolic disorders had been associated with large consumption of soft drinks. The rising incidence of atherosclerosis and metabolic alterations warrants the study of long-term soft drink consumption’ effects on metabolism and atherosclerosis in genetic deficiency of apolipoprotein E which typically develops spontaneous atherosclerosis and metabolic alterations. Methods ApoE-/- mice were randomized in 3 groups accordingly with free access to: water (W), regular cola (C) or light cola (L). After 8 weeks, 50% of the animals in each group were euthanized (Treatment: W8, C8, L8). The remaining mice (all groups) drank water for 8 weeks and were euthanized (Washout: W16, C16, L16). Body weight and food and drink consumption were periodically measured. Blood was collected (biochemistry). At autopsy, transverse aortic sinus sections were serially cut and stained (histomorphometry); livers and kidneys were processed (microscopy). MANOVA (identification of variance factors) was followed by ANOVA and LSD tests (within-factor differences between levels). Conventionally a p< 0.05 was considered significant. Results Treatment increased drinking volumes (vs W8: 4 fold C8, p<0.0001; +47% L8, p<0.02). Only C reduced eating amounts (–54%, p<0.05 vs W8). I). Compared with W8: C8 developed hyperglycemia (+43%, p<0.03) and increased non-HDL cholesterol (+54%, p<0.05); L8 showed decreased glycemia (–15%, p<0.05 vs W8) and increased creatinine (2.5 fold, p<0.04), urea (+74, p<0.03) and aspartate-aminotransferase (2.8 fold, p<0.05). Hypercreatininemia was observed in L16 (2.7 fold vs W16, p<0.05). Hypertriglyceridemia (+91%, p<0.008) and hyperuremia (+68%, p<0.03) developed over time of study (age). II). Treatment caused plaque area increase (vs W8: 28% C8, p<0.02 and 50% L8, p<0.01; vs W16: 43% C16, p<0.05 and 68% L16, p<0.02) and stenosis (vs W8: 38% C8, p<0.04 and 57% L8, p<0.01; vs W16: 71% C16, p<0.01 and 46% L16, p<0

Rodent models of depression: learned helplessness induced in mice.

PubMed

Anisman, H; Merali, Z

2001-05-01

Uncontrollable stressors induce a variety of behavioral disturbances that are in many ways reminiscent of the symptoms that characterize clinical depression. These deficits are evident across a range of species, including mice. Given the increasing focus on genetic techniques involving mice to identify the mechanisms subserving these behavioral disturbances (e.g., recombinant, knockout, and transgenic strains), it is of particular interest to provide a detailed description of the method to induce behavioral deficits in response to uncontrollable stressors. This unit describes the procedure used to assess the effects of controllable and uncontrollable shock on subsequent shock escape performance in mice using an escape-delay procedure.

Chronic exposure of mice to environmental endocrine-disrupting chemicals disturbs their energy metabolism.

PubMed

Jin, Yuanxiang; Lin, Xiaojian; Miao, Wenyu; Wu, Tao; Shen, Hangjie; Chen, Shan; Li, Yanhong; Pan, Qiaoqiao; Fu, Zhengwei

2014-03-21

We evaluated the effects of a 20-week chronic exposure of mice to a low dose of cypermethrin (CYP), atrazine (ATZ) and 17α-ethynyestradiol (EE2) on energy metabolism. Here, male mice were exposed to 50 μg/kg BW/day CYP, 100 μg/kg BW/day ATZ or 1 μg/kg BW/day EE2 supplied in their drinking water for 20 weeks. During the exposure, mice were fed a high energy diet (HD). The bodyweights were not significantly affected by chronic exposure to EDCs, while the serum-free fatty acids (FFA) levels, hepatic lipid accumulation and triacylglycerol (TG) contents increased significantly in the ATZ- and CYP-HD groups. To determine the mechanism involved, we determined the expression levels of the genes in the glucose and fat metabolism pathways in the liver and adipose tissue. The results showed that chronic exposure to ATZ and CYP increased the mRNA levels of a number of key genes involved in both the de novo FFA synthesis pathway and the transport of FFA from blood. The increased amount of FFA was partially consumed as energy through β-oxidation in the mitochondria. Some of the FFA was used to synthesize TG in the liver by up-regulating primary genes, which resulted in increased TG levels and lipid accumulation. The results indicate that chronic exposure to EDCs has the potential to cause energy metabolic dysregulation and hepatotoxicity in mice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Disturbed Processing of Contextual Information in HCN3 Channel Deficient Mice

PubMed Central

Stieglitz, Marc S.; Fenske, Stefanie; Hammelmann, Verena; Becirovic, Elvir; Schöttle, Verena; Delorme, James E.; Schöll-Weidinger, Martha; Mader, Robert; Deussing, Jan; Wolfer, David P.; Seeliger, Mathias W.; Albrecht, Urs; Wotjak, Carsten T.; Biel, Martin; Michalakis, Stylianos; Wahl-Schott, Christian

2018-01-01

Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) in the nervous system are implicated in a variety of neuronal functions including learning and memory, regulation of vigilance states and pain. Dysfunctions or genetic loss of these channels have been shown to cause human diseases such as epilepsy, depression, schizophrenia, and Parkinson's disease. The physiological functions of HCN1 and HCN2 channels in the nervous system have been analyzed using genetic knockout mouse models. By contrast, there are no such genetic studies for HCN3 channels so far. Here, we use a HCN3-deficient (HCN3−/−) mouse line, which has been previously generated in our group to examine the expression and function of this channel in the CNS. Specifically, we investigate the role of HCN3 channels for the regulation of circadian rhythm and for the determination of behavior. Contrary to previous suggestions we find that HCN3−/− mice show normal visual, photic, and non-photic circadian function. In addition, HCN3−/− mice are impaired in processing contextual information, which is characterized by attenuated long-term extinction of contextual fear and increased fear to a neutral context upon repeated exposure. PMID:29375299

Mice lacking Faim2 show increased cell death in the MPTP mouse model of Parkinson disease.

PubMed

Komnig, Daniel; Schulz, Jörg B; Reich, Arno; Falkenburger, Björn H

2016-12-01

The death receptor Fas/CD95 mediates apoptotic cell death in response to external stimuli. In neurons, Fas-induced apoptosis is prevented by Fas-apoptotic inhibitory molecule 2 (Faim2). Mice lacking Faim2 showed increased neurodegeneration in animal models of stroke and bacterial meningitis. We therefore tested the relevance of Faim2 in a classical animal model of Parkinson disease and determined the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Faim2-deficient mice. Without MPTP treatment, there was no difference in the dopaminergic system between Faim2-deficient mice and control mice. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. Fourteen days after the last MPTP injection, the number of dopaminergic neurons in the lateral substantia nigra, assayed by stereological counting, was reduced by 39% in control mice and 53% in Faim2-deficient mice. The density of dopaminergic fibers in the dorsal striatum was reduced by 36% in control mice and 69% in Faim2-deficient mice, in the ventral striatum 44% in control mice and 76% in Faim2-deficient mice. Fiber density recovered at 90 days after MPTP with similar density in both groups. Striatal catecholamine levels were reduced by 81-84% in both groups and recovered at 90 days. Faim2 expression was documented in mouse midbrain using quantitative reverse transcription-PCR (qRT-PCR) and found decreased after MPTP administration. Taken together, our findings demonstrate increased degeneration of dopaminergic neurons with Faim2 deficiency, indicating that Fas-induced apoptosis contributes to cell death in the MPTP mouse model. Along with the decreased expression of Faim2 after MPTP, this finding indicates that boosting Faim2 function might represent a therapeutic strategy for Parkinson disease. © 2016 International Society for Neurochemistry.

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

PubMed

Sugimoto, H; Ikeda, K; Kawakami, K

2018-06-01

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.

Enhanced Excitatory Connectivity and Disturbed Sound Processing in the Auditory Brainstem of Fragile X Mice.

PubMed

Garcia-Pino, Elisabet; Gessele, Nikodemus; Koch, Ursula

2017-08-02

Hypersensitivity to sounds is one of the prevalent symptoms in individuals with Fragile X syndrome (FXS). It manifests behaviorally early during development and is often used as a landmark for treatment efficacy. However, the physiological mechanisms and circuit-level alterations underlying this aberrant behavior remain poorly understood. Using the mouse model of FXS ( Fmr1 KO ), we demonstrate that functional maturation of auditory brainstem synapses is impaired in FXS. Fmr1 KO mice showed a greatly enhanced excitatory synaptic input strength in neurons of the lateral superior olive (LSO), a prominent auditory brainstem nucleus, which integrates ipsilateral excitation and contralateral inhibition to compute interaural level differences. Conversely, the glycinergic, inhibitory input properties remained unaffected. The enhanced excitation was the result of an increased number of cochlear nucleus fibers converging onto one LSO neuron, without changing individual synapse properties. Concomitantly, immunolabeling of excitatory ending markers revealed an increase in the immunolabeled area, supporting abnormally elevated excitatory input numbers. Intrinsic firing properties were only slightly enhanced. In line with the disturbed development of LSO circuitry, auditory processing was also affected in adult Fmr1 KO mice as shown with single-unit recordings of LSO neurons. These processing deficits manifested as an increase in firing rate, a broadening of the frequency response area, and a shift in the interaural level difference function of LSO neurons. Our results suggest that this aberrant synaptic development of auditory brainstem circuits might be a major underlying cause of the auditory processing deficits in FXS. SIGNIFICANCE STATEMENT Fragile X Syndrome (FXS) is the most common inheritable form of intellectual impairment, including autism. A core symptom of FXS is extreme sensitivity to loud sounds. This is one reason why individuals with FXS tend to avoid social

Proteomic CNS profile of delayed cognitive impairment in mice exposed to Gulf War agents.

PubMed

Abdullah, Laila; Crynen, Gogce; Reed, Jon; Bishop, Alex; Phillips, John; Ferguson, Scott; Mouzon, Benoit; Mullan, Myles; Mathura, Venkatarajan; Mullan, Michael; Ait-Ghezala, Ghania; Crawford, Fiona

2011-12-01

Gulf War Illness (GWI) is a chronic multisymptom condition with a central nervous system (CNS) component, for which there is no treatment available. It is now believed that the combined exposure to Gulf War (GW) agents, including pyridostigmine bromide (PB) and pesticides, such as permethrin (PER), was a key contributor to the etiology of GWI. In this study, a proteomic approach was used to characterize the biomolecular disturbances that accompany neurobehavioral and neuropathological changes associated with combined exposure to PB and PER. Mice acutely exposed to PB and PER over 10 days showed an increase in anxiety-like behavior, psychomotor problems and delayed cognitive impairment compared to control mice that received vehicle only. Proteomic analysis showed changes in proteins associated with lipid metabolism and molecular transport in the brains of GW agent-exposed mice compared to controls. Proteins associated with the endocrine and immune systems were also altered, and dysfunction of these systems is a prominent feature of GWI. The presence of astrogliosis in the GW agent-exposed mice compared to control mice further suggests an immune system imbalance, as is observed in GWI. These studies provide a broad perspective of the molecular disturbances driving the late pathology of this complex illness. Evaluation of the potential role of these biological functions in GWI will be useful in identifying molecular pathways that can be targeted for the development of novel therapeutics against GWI.

The histamine H3 receptor inverse agonist pitolisant reduces body weight in obese mice.

PubMed

Kotańska, Magdalena; Kuder, Kamil J; Szczepańska, Katarzyna; Sapa, Jacek; Kieć-Kononowicz, Katarzyna

2018-05-25

The pharmacological profile of pitolisant, a histamine H 3 receptor antagonist/inverse agonist, indicates that this compound might reduce body weight and metabolic disturbances. Therefore, we studied the influence of pitolisant on body weight, water and sucrose intake as well as metabolic disturbances in the high-fat and high-sugar diet-induced obesity model in mice. To induce obesity, male CD-1 mice were fed a high-fat diet consisting of 40% fat blend for 14 weeks, water and 30% sucrose solution available ad libitum. Glucose tolerance test was performed at the beginning of week 15. Insulin tolerance was tested the day after. At the end of study, plasma levels of triglycerides and cholesterol were determined. Pitolisant at dose of 10 mg/kg bw (ip) was administrated during 14 days, starting from the beginning of week 13. Metformin at dose of 100 mg/kg bw (ip) was used as reference drug. Mice fed with high-fat diet and sucrose solution showed more weight gain throughout the 12-week period of inducing obesity. Animals fed with high-fat diet and treated with pitolisant (for the next 14 days) showed significantly less weight gain than mice from the control group consuming a high-fat feed. In the group treated with pitolisant, glucose levels were significantly lower than glucose levels of control obese mice after glucose load. The plasma triglyceride levels in pitolisant-treated mice were significantly lower compared with those in control obese group. In conclusion, pitolisant has a favorable influence of body weight and improves glucose tolerance and the lipid profile in obese mice.

Irxl1 mutant mice show reduced tendon differentiation and no patterning defects in musculoskeletal system development.

PubMed

Kimura, Wataru; Machii, Masashi; Xue, XiaoDong; Sultana, Nishat; Hikosaka, Keisuke; Sharkar, Mohammad T K; Uezato, Tadayoshi; Matsuda, Masashi; Koseki, Haruhiko; Miura, Naoyuki

2011-01-01

Irxl1 (Iroquois-related homeobox like-1) is a newly identified three amino-acid loop extension (TALE) homeobox gene, which is expressed in various mesoderm-derived tissues, particularly in the progenitors of the musculoskeletal system. To analyze the roles of Irxl1 during embryonic development, we generated mice carrying a null allele of Irxl1. Mice homozygous for the targeted allele were viable, fertile, and showed reduced tendon differentiation. Skeletal morphology and skeletal muscle weight in Irxl1-knockout mice appeared normal. Expression patterns of several marker genes for cartilage, tendon, and muscle progenitors in homozygous mutant embryos were unchanged. These results suggest that Irxl1 is required for the tendon differentiation but dispensable for the patterning of the musculoskeletal system in development. Copyright © 2010 Wiley-Liss, Inc.

Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice.

PubMed

Pilz, Luísa K; Trojan, Yasmine; Quiles, Caroline L; Benvenutti, Radharani; Melo, Gabriela; Levandovski, Rosa; Hidalgo, Maria Paz L; Elisabetsky, Elaine

2015-03-01

Circadian rhythm disturbances are among the risk factors for depression, but specific animal models are lacking. This study aimed to characterize the effects of acute rhythm disruption in mice and investigate the effects of imipramine and N-acetylcysteine (NAC) on rhythm disruption-induced changes. Mice were exposed to 12:12-hour followed by 10:10-hour light:dark cycles (LD); under the latter, mice were treated with saline, imipramine or NAC. Rhythms of rest/activity and temperature were assessed with actigraphs and iButtons, respectively. Hole-board and social preference tests were performed at the beginning of the experiment and again at the 8th 10:10 LD, when plasma corticosterone and IL-6 levels were also assessed. Actograms showed that the 10:10 LD schedule prevents the entrainment of temperature and activity rhythms for at least 13 cycles. Subsequent light regimen change activity and temperature amplitudes showed similar patterns of decline followed by recovery attempts. During the 10:10 LD schedule, activity and temperature amplitudes were significantly decreased (paired t test), an effect exacerbated by imipramine (ANOVA/SNK). The 10:10 LD schedule increased anxiety (paired t test), an effect prevented by NAC (30 mg/kg). This study identified mild but significant behavioral changes at specific time points after light regimen change. We suggest that if repeated overtime, these subtle changes may contribute to lasting behavioral disturbancess relevant to anxiety and mood disorders. Data suggest that imipramine may contribute to sustained rhythm disturbances, while NAC appears to prevent rhythm disruption-induced anxiety. Associations between sleep/circadian disturbances and the recurrence of depressive episodes underscore the relevance of potential drug-induced maintenance of disturbed rhythms.

Altered Cerebellar Organization and Function in Monoamine Oxidase A Hypomorphic Mice

PubMed Central

Alzghoul, Loai; Bortolato, Marco; Delis, Foteini; Thanos, Panayotis K.; Darling, Ryan D.; Godar, Sean C; Zhang, Junlin; Grant, Samuel; Wang, Gene-Jack; Simpson, Kimberly L.; Chen, Kevin; Volkow, Nora D.; Lin, Rick C.S.; Shih, Jean C.

2012-01-01

Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO-ANeo), featuring elevated monoamine levels, social deficits and perseverative behaviors as well as morphological changes in the basolateral amygdala and orbitofrontal cortex. Here we showed that MAO-ANeo mice displayed deficits in motor control, manifested as subtle disturbances in gait, motor coordination, and balance. Furthermore, magnetic resonance imaging of the cerebellum revealed morphological changes and a moderate reduction in the cerebellar size of MAO- ANeo mice compared to wild type (WT) mice. Histological and immunohistochemical analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje cell count and their dendritic density in MAO- ANeo mice compared to WT. Our current findings suggest that congenitally low MAO-A activity leads to abnormal development of the cerebellum. PMID:22971542

Transgenic Mice with Increased Astrocyte Expression of IL-6 Show Altered Effects of Acute Ethanol on Synaptic Function

PubMed Central

Hernandez, Ruben V.; Puro, Alana C.; Manos, Jessica C.; Huitron-Resendiz, Salvador; Reyes, Kenneth C.; Liu, Kevin; Vo, Khanh; Roberts, Amanda J.; Gruol, Donna L.

2015-01-01

A growing body of evidence has revealed that resident cells of the central nervous system (CNS), and particularly the glial cells, comprise a neuroimmune system that serves a number of functions in the normal CNS and during adverse conditions. Cells of the neuroimmune system regulate CNS functions through the production of signaling factors, referred to as neuroimmune factors. Recent studies show that ethanol can activate cells of the neuroimmune system, resulting in the elevated production of neuroimmune factors, including the cytokine interleukin-6 (IL-6). Here we analyzed the consequences of this CNS action of ethanol using transgenic mice that express elevated levels of IL-6 through increased astrocyte expression (IL-6-tg) to model the increased IL-6 expression that occurs with ethanol use. Results show that increased IL-6 expression induces neuroadaptive changes that alter the effects of ethanol. In hippocampal slices from non-transgenic (non-tg) littermate control mice, synaptically evoked dendritic field excitatory postsynaptic potential (fEPSP) and somatic population spike (PS) at the Schaffer collateral to CA1 pyramidal neuron synapse were reduced by acute ethanol (20 or 60 mM). In contrast, acute ethanol enhanced the fEPSP and PS in hippocampal slices from IL-6 tg mice. Long-term synaptic plasticity of the fEPSP (i.e., LTP) showed the expected dose-dependent reduction by acute ethanol in non-tg hippocampal slices, whereas LTP in the IL-6 tg hippocampal slices was resistant to this depressive effect of acute ethanol. Consistent with altered effects of acute ethanol on synaptic function in the IL-6 tg mice, EEG recordings showed a higher level of CNS activity in the IL-6 tg mice than in the non-tg mice during the period of withdrawal from an acute high dose of ethanol. These results suggest a potential role for neuroadaptive effects of ethanol-induced astrocyte production of IL-6 as a mediator or modulator of the actions of ethanol on the CNS, including

Systemic PPARγ deletion causes severe disturbance in fluid homeostasis in mice

PubMed Central

Zhou, Li; Panasiuk, Alexandra; Downton, Maicy; Zhao, Daqiang; Yang, Baoxue; Jia, Zhanjun

2015-01-01

The pharmacological action of peroxisome proliferator-activated receptor (PPAR)γ in promoting sodium and water retention is well documented as highlighted by the major side-effect of body weight gain and edema associated with thiazolidinedione use. However, a possible physiological role of PPARγ in regulation of fluid metabolism has not been reported by previous studies. Here we analyzed fluid metabolism in inducible whole-body PPARγ knockout mice. The null mice developed severe polydipsia and polyuria, reduced urine osmolality, and modest hyperphagia. The phenomenon persisted during 3 days of pair feeding and pair drinking, accompanied by progressive weight loss. After 24 h water deprivation, the null mice had a lower urine osmolality, a higher urine volume, a greater weight loss, and a greater rise in hematocrit than the floxed control. Urinary vasopressin (AVP) excretion was not different between the genotypes under basal condition or after WD. The response of urine osmolality to acute and chronic 1-desamino-8-d-arginine vasopressin treatment was attenuated in the null mice, but the total abundance or phosphorylation of aquaporin 2 (AQP2) in the kidney or AVP-induced cAMP production in inner medullary collecting duct suspensions was unaffected. Overall, PPARγ participates in physiological control of fluid homeostasis through an unknown mechanism involving cAMP/AQP2-independent enhancement of AVP response. PMID:26330489

Disturbed mouse circadian rhythm before the Kobe EQ in 1995

NASA Astrophysics Data System (ADS)

Yokoi, Sayoko

2013-04-01

Legends of macro-anomalies before large earthquakes have been passed down for generations in Asia. Most of the statements on earthquake precursors are considered unreliable afterthoughts by traditional scientists. However, disturbed biological rhythms in mice were observed before the Kobe EQ in 1995 (Yokoi et al, 2003). The records of unusual mouse behavior before the earthquake were obtained to study biological clock at Institute for Protein Research, Osaka University. It is clarified that the disturbance was very rare phenomena statistically. Similar phenomenon was observed before the Wenchuan earthquake in 2008, too (Li et al, 2009). In the presentation, I will discuss the phenomena as one example of preseismic unusual animal behaviors.

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

PubMed

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.

EPA prevents fat mass expansion and metabolic disturbances in mice fed with a Western diet.

PubMed

Pinel, Alexandre; Pitois, Elodie; Rigaudiere, Jean-Paul; Jouve, Chrystele; De Saint-Vincent, Sarah; Laillet, Brigitte; Montaurier, Christophe; Huertas, Alain; Morio, Beatrice; Capel, Frederic

2016-08-01

The impact of alpha linolenic acid (ALA), EPA, and DHA on obesity and metabolic complications was studied in mice fed a high-fat, high-sucrose (HF) diet. HF diets were supplemented with ALA, EPA, or DHA (1% w/w) and given to C57BL/6J mice for 16 weeks and to Ob/Ob mice for 6 weeks. In C57BL/6J mice, EPA reduced plasma cholesterol (-20%), limited fat mass accumulation (-23%) and adipose cell hypertrophy (-50%), and reduced plasma leptin concentration (-60%) compared with HF-fed mice. Furthermore, mice supplemented with EPA exhibited a higher insulin sensitivity (+24%) and glucose tolerance (+20%) compared with HF-fed mice. Similar effects were observed in EPA-supplemented Ob/Ob mice, although fat mass accumulation was not prevented. By contrast, in comparison with HF-fed mice, DHA did not prevent fat mass accumulation, increased plasma leptin concentration (+128%) in C57BL/6J mice, and did not improve glucose homeostasis in C57BL/6J and Ob/Ob mice. In 3T3-L1 adipocytes, DHA stimulated leptin expression whereas EPA induced adiponectin expression, suggesting that improved leptin/adiponectin balance may contribute to the protective effect of EPA. In conclusion, supplementation with EPA, but not ALA and DHA, could preserve glucose homeostasis in an obesogenic environment and limit fat mass accumulation in the early stage of weight gain. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Severe methylenetetrahydrofolate reductase deficiency in mice results in behavioral anomalies with morphological and biochemical changes in hippocampus.

PubMed

Jadavji, Nafisa M; Deng, Liyuan; Leclerc, Daniel; Malysheva, Olga; Bedell, Barry J; Caudill, Marie A; Rozen, Rima

2012-06-01

The brain is particularly sensitive to folate metabolic disturbances, since methyl groups are critical for its functions. Methylenetetrahydrofolate reductase (MTHFR) generates the primary circulatory form of folate required for homocysteine remethylation to methionine. Neurological disturbances have been described in homocystinuria caused by severe MTHFR deficiency. The goal of this study was to determine if behavioral anomalies are present in severe Mthfr-deficient (Mthfr(-/-)) mice and to identify neurobiological changes that could contribute to these anomalies. Adult male mice of 3 Mthfr genotypes (+/+, +/-, -/-) were tested on motor, anxiety, exploratory and cognitive tasks. Volumes (whole brain and hippocampus) and morphology, global DNA methylation, apoptosis, expression of choline acetyltransferase (ChAT) and glucocorticoid receptor (GR), and concentrations of choline metabolites were assessed in hippocampus. Mthfr(-/-) mice had impairments in motor function and in short- and long-term memory, increased exploratory behavior and decreased anxiety. They showed decreased whole brain and hippocampal volumes, reduced thickness of the pyramidal cell layer of CA1 and CA3, and increased apoptosis in hippocampus. There was a disturbance in choline metabolism as manifested by differences in acetylcholine, betaine or glycerophosphocholine concentrations, and by increased ChAT levels. Mthfr(-/-) mice also had increased GR mRNA and protein. Our study has revealed significant anomalies in affective behavior and impairments in memory of Mthfr(-/-) mice. We identified structural changes, increased apoptosis, altered choline metabolism and GR dysregulation in hippocampus. These findings, as well as some similar observations in cerebellum, could contribute to the behavioral changes and suggest that choline is a critical metabolite in homocystinuria. Copyright © 2012 Elsevier Inc. All rights reserved.

K+ channel TASK-1 knockout mice show enhanced sensitivities to ataxic and hypnotic effects of GABA(A) receptor ligands.

PubMed

Linden, Anni-Maija; Aller, M Isabel; Leppä, Elli; Rosenberg, Per H; Wisden, William; Korpi, Esa R

2008-10-01

TASK two-pore-domain leak K(+) channels occur throughout the brain. However, TASK-1 and TASK-3 knockout (KO) mice have few neurological impairments and only mildly reduced sensitivities to inhalational anesthetics, contrasting with the anticipated functions and importance of these channels. TASK-1/-3 channel expression can compensate for the absence of GABA(A) receptors in GABA(A) alpha6 KO mice. To investigate the converse, we analyzed the behavior of TASK-1 and -3 KO mice after administering drugs with preferential efficacies at GABA(A) receptor subtypes: benzodiazepines (diazepam and flurazepam, active at alpha1betagamma2, alpha2betagamma2, alpha3betagamma2, and alpha5betagamma2 subtypes), zolpidem (alpha1betagamma2 subtype), propofol (beta2-3-containing receptors), gaboxadol (alpha4betadelta and alpha6betadelta subtypes), pregnanolone, and pentobarbital (many subtypes). TASK-1 KO mice showed increased motor impairment in rotarod and beam-walking tests after diazepam and flurazepam administration but not after zolpidem. They also showed prolonged loss of righting reflex induced by propofol and pentobarbital. Autoradiography indicated no change in GABA(A) receptor ligand binding levels. These altered behavioral responses to GABAergic drugs suggest functional up-regulation of alpha2beta2/3gamma2 and alpha3beta2/3gamma2 receptor subtypes in TASK-1 KO mice. In addition, female, but not male, TASK-1 KO mice were more sensitive to gaboxadol, suggesting an increased influence of alpha4betadelta or alpha6betadelta subtypes. The benzodiazepine sensitivity of TASK-3 KO mice was marginally increased. Our results underline that TASK-1 channels perform such key functions in the brain that compensation is needed for their absence. Furthermore, because inhalation anesthetics act partially through GABA(A) receptors, the up-regulation of GABA(A) receptor function in TASK-1 KO mice might mask TASK-1 channel's significance as a target for inhalation anesthetics.

Tropical disturbances in relation to general circulation modeling

NASA Technical Reports Server (NTRS)

Estoque, M. A.

1982-01-01

The initial results of an evaluation of the performance of the Goddard Laboratory of Atmospheric Simulation general circulation model depicting the tropical atmosphere during the summer are presented. Because the results show the existence of tropical wave disturbances throughout the tropics, the characteristics of synoptic disturbances over Africa were studied and a synoptic case study of a selected disturbance in this area was conducted. It is shown that the model is able to reproduce wave type synoptic disturbances in the tropics. The findings show that, in one of the summers simulated, the disturbances are predominantly closed vortices; in another summer, the predominant disturbances are open waves.

9 CFR 309.4 - Livestock showing symptoms of certain metabolic, toxic, nervous, or circulatory disturbances...

Code of Federal Regulations, 2010 CFR

2010-01-01

... diseases. 309.4 Section 309.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF..., toxic, nervous, or circulatory disturbances, nutritional imbalances, or infectious or parasitic diseases... the animal is, in fact, infected with such disease. If it is found on such tests to be infected, the...

9 CFR 309.4 - Livestock showing symptoms of certain metabolic, toxic, nervous, or circulatory disturbances...

Code of Federal Regulations, 2011 CFR

2011-01-01

... diseases. 309.4 Section 309.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF..., toxic, nervous, or circulatory disturbances, nutritional imbalances, or infectious or parasitic diseases... the animal is, in fact, infected with such disease. If it is found on such tests to be infected, the...

9 CFR 309.4 - Livestock showing symptoms of certain metabolic, toxic, nervous, or circulatory disturbances...

Code of Federal Regulations, 2014 CFR

2014-01-01

... diseases. 309.4 Section 309.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF..., toxic, nervous, or circulatory disturbances, nutritional imbalances, or infectious or parasitic diseases... the animal is, in fact, infected with such disease. If it is found on such tests to be infected, the...

9 CFR 309.4 - Livestock showing symptoms of certain metabolic, toxic, nervous, or circulatory disturbances...

Code of Federal Regulations, 2013 CFR

2013-01-01

... diseases. 309.4 Section 309.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF..., toxic, nervous, or circulatory disturbances, nutritional imbalances, or infectious or parasitic diseases... the animal is, in fact, infected with such disease. If it is found on such tests to be infected, the...

9 CFR 309.4 - Livestock showing symptoms of certain metabolic, toxic, nervous, or circulatory disturbances...

Code of Federal Regulations, 2012 CFR

2012-01-01

... diseases. 309.4 Section 309.4 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF..., toxic, nervous, or circulatory disturbances, nutritional imbalances, or infectious or parasitic diseases... the animal is, in fact, infected with such disease. If it is found on such tests to be infected, the...

Mouse model for deficiency of methionine synthase reductase exhibits short-term memory impairment and disturbances in brain choline metabolism.

PubMed

Jadavji, Nafisa M; Bahous, Renata H; Deng, Liyuan; Malysheva, Olga; Grand'maison, Marilyn; Bedell, Barry J; Caudill, Marie A; Rozen, Rima

2014-07-15

Hyperhomocysteinaemia can contribute to cognitive impairment and brain atrophy. MTRR (methionine synthase reductase) activates methionine synthase, which catalyses homocysteine remethylation to methionine. Severe MTRR deficiency results in homocystinuria with cognitive and motor impairments. An MTRR polymorphism may influence homocysteine levels and reproductive outcomes. The goal of the present study was to determine whether mild hyperhomocysteinaemia affects neurological function in a mouse model with Mtrr deficiency. Mtrr+/+, Mtrr+/gt and Mtrrgt/gt mice (3 months old) were assessed for short-term memory, brain volumes and hippocampal morphology. We also measured DNA methylation, apoptosis, neurogenesis, choline metabolites and expression of ChAT (choline acetyltransferase) and AChE (acetylcholinesterase) in the hippocampus. Mtrrgt/gt mice exhibited short-term memory impairment on two tasks. They had global DNA hypomethylation and decreased choline, betaine and acetylcholine levels. Expression of ChAT and AChE was increased and decreased respectively. At 3 weeks of age, they showed increased neurogenesis. In the cerebellum, mutant mice had DNA hypomethylation, decreased choline and increased expression of ChAT. Our work demonstrates that mild hyperhomocysteinaemia is associated with memory impairment. We propose a mechanism whereby a deficiency in methionine synthesis leads to hypomethylation and compensatory disturbances in choline metabolism in the hippocampus. This disturbance affects the levels of acetylcholine, a critical neurotransmitter in learning and memory.

Female Nur77-Deficient Mice Show Increased Susceptibility to Diet-Induced Obesity

PubMed Central

Perez-Sieira, Sonia; Martinez, Gloria; Porteiro, Begoña; Lopez, Miguel; Vidal, Anxo; Nogueiras, Ruben; Dieguez, Carlos

2013-01-01

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. PMID:23342015

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

PubMed

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.

Di (2-ethylhexyl) phthalate exposure during pregnancy disturbs temporal sex determination regulation in mice offspring.

PubMed

Wang, Yongan; Liu, Wei; Yang, Qing; Yu, Mingxi; Zhang, Zhou

2015-10-02

Animal researches and clinical studies have supported the relevance between phthalates exposure and testicular dysgenesis syndrome (TDS). These disorders may comprise common origin in fetal life, especially during sex determination and differentiation, where the mechanism remains unclear. The present study evaluated the disturbances in gene regulatory networks of sex determination in fetal mouse by in utero Di (2-ethylhexyl) phthalate (DEHP) exposure. Temporal expression of key sex determination genes were examined during the critical narrow time window, using whole-mount in situ hybridization and quantitative-PCR. DEHP exposure resulted in significant reduction in mRNA of Sry during sex determination from gestation day (GD) 11.0 to 11.5 in male fetal mice, and the increasing of Sry expression to threshold level on GD 11.5 was delayed. Meanwhile, Gadd45g and Gata4, the upstream genes of Sry, and downstream gene Sox9 were also significantly downregulated in expression. In fetal females, the expression of Wnt4 and beta-catenin were up-regulated by DEHP exposure. Taken together, the results suggest that the potential mechanism of gonadal development disorder by DEHP may origin from repression of important male sex determination signaling pathway, involving Gadd45g → Gata4 → Sry → Sox9. The results would promote a better understanding of the association between phthalate esters (PAEs) exposure and the reductive disorder. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The potential role of Morus alba leaves extract on the brain of mice infected with Schistosoma mansoni.

PubMed

Bauomy, Amira A

2014-01-01

Schistosomiasis is a neglected tropical disease which is associated with neuropsychiatric and neuropathological disorders. Herein, the main goal of the presented work is to investigate the effect of Morus alba leaves extract in mice brain infected with Schistosoma mansoni. Since, the resistance of Schistosomes to antischistosomal drug (praziquantel) has been examined, schistosomiasis induced brain oxidative stress as evidenced by the decrease of glutathione level, total antioxidant capacity and the activity of catalase significantly, while a significant elevation in the levels of nitrite/nitrate and malondialdhyde. In addition, the infection resulted in neurochemical disturbances, the main inhibitory amino acid, γ- aminobutyric acid level was decreased. In contrast, the level of chloride ions and acetylcholine esterase activity were significantly increased. Moreover, the histopathological section showed some impairments in the brain. The treatment with Morus alba leaves extract ameliorated the induced disturbances in schistosome-infected mice where the levels of non-enzymatic and enzymatic antioxidants were elevated. On the other hand, the levels of nitrite/nitrate and malondialdhyde were significantly reduced. Likewise, treatment of mice with Morus alba leaves extract improved the altered levels of γ- aminobutyric acid level and chloride ion. Also, it improved the recorded impairments of the histopathological section in the brain of schistosome infected mice.

The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice.

PubMed

Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra; Liu, Jiahui; Pike, Christian J; Smith, Conor; LaDu, Mary Jo; Sullivan, Patrick M; Morgan, Todd E; Dolzhenko, Egor; Charidimou, Andreas; Wahlund, Lars-Olof; Wiberg, Maria Kristofferson; Shams, Sara; Chiang, Gloria Chia-Yi; Finch, Caleb E

2016-01-01

The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD (+/-) /human APOE(+/+)). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Sodium fluoride and sulfur dioxide affected male reproduction by disturbing blood-testis barrier in mice.

PubMed

Zhang, Jianhai; Li, Zhihui; Qie, Mingli; Zheng, Ruibo; Shetty, Jagathpala; Wang, Jundong

2016-08-01

Fluoride and sulfur dioxide (SO2), two well-known environmental toxicants, have been implicated to have adverse effects on male reproductive health in humans and animals. The objective of this study to investigate if the BTB is one of the pathways that lead to reproductive toxicity of sodium fluoride and sulfur dioxide alone or in combination, in view of the key role of blood testis barrier (BTB) in testis. The results showed that a marked decrease in sperm quality, and altered morphology and ultrastructure of BTB in testis of mice exposure to fluoride (100 mg NaF/L in drinking water) or/and sulfur dioxide (28 mg SO2/m(3), 3 h/day). Meanwhile, the mRNA expression levels of some vital BTB-associated proteins, including occluding, claudin-11, ZO-1, Ncadherin, α-catenin, and connexin-43 were all strikingly reduced after NaF exposure, although only the reduction of DSG-2 was statistically significant in all treatment groups. Moreover, the proteins expressions also decreased significantly in claudin-11, N-cadherin, α-catenin, connexin-43 and desmoglein-2 in mice treated with fluoride and/or SO2. These changes in BTB structure and constitutive proteins may therefore be connected with the low sperm quality in these mice. The role of fluoride should deserves more attention in this process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-lived weight-reduced αMUPA mice show higher and longer maternal-dependent postnatal leptin surge

PubMed Central

Pinsky, Mariel; Rauch, Maayan; Abbas, Atallah; Sharabi-Nov, Adi; Tamir, Snait

2017-01-01

We investigated whether long-lived weight-reduced αMUPA mice differ from their wild types in postnatal body composition and leptin level, and whether these differences are affected by maternal-borne factors. Newborn αMUPA and wild type mice had similar body weight and composition up to the third postnatal week, after which αMUPA mice maintained lower body weight due to lower fat-free mass. Both strains showed a surge in leptin levels at the second postnatal week, initiating earlier in αMUPA mice, rising higher and lasting longer than in the wild types, mainly in females. Leptin level in dams’ serum and breast milk, and in their pup’s stomach content were also higher in αMUPA than in the WT during the surge peak. Leptin surge preceded the strain divergence in body weight, and was associated with an age-dependent decrease in the leptin:fat mass ratio—suggesting that postnatal sex and strain differences in leptin ontogeny are strongly influenced by processes independent of fat mass, such as production and secretion, and possibly outside fat tissues. Dam removal elevated corticosterone level in female pups from both strains similarly, yet mitigated the leptin surge only in αMUPA–eliminating the strain differences in leptin levels. Overall, our results indicate that αMUPA’s postnatal leptin surge is more pronounced than in the wild type, more sensitive to maternal deprivation, less related to pup’s total adiposity, and is associated with a lower post-weaning fat-free mass. These strain-related postnatal differences may be related to αMUPA’s higher milk-borne leptin levels. Thus, our results support the use of αMUPA mice in future studies aimed to explore the relationship between maternal (i.e. milk-borne) factors, postnatal leptin levels, and post-weaning body composition and energy homeostasis. PMID:29190757

Relative impact of previous disturbance history on the likelihood of additional disturbance in the Northern United States Forest Service USFS Region

NASA Astrophysics Data System (ADS)

Hernandez, A. J.

2015-12-01

The Landsat archive is increasingly being used to detect trends in the occurrence of forest disturbance. Beyond information about the amount of area affected, forest managers need to know if and how disturbance regimes change. The National Forest System (NFS) has developed a comprehensive plan for carbon monitoring that requires a detailed temporal mapping of forest disturbances across 75 million hectares. A long-term annual time series that shows the timing, extent, and type of disturbance beginning in 1990 and ending in 2011 has been prepared for several USFS Regions, including the Northern Region. Our mapping starts with an automated detection of annual disturbances using a time series of historical Landsat imagery. Automated detections are meticulously inspected, corrected and labeled using various USFS ancillary datasets. The resulting maps of verified disturbance show the timing and types are fires, harvests, insect activity, disease, and abiotic (wind, drought, avalanche) damage. Also, the magnitude of each change event is modeled in terms of the proportion of canopy cover lost. The sequence of disturbances for every pixel since 1990 has been consistently mapped and is available across the entirety of NFS. Our datasets contain sufficient information to describe the frequency of stand replacement, as well as how often disturbance results in only a partial loss of canopy. This information provides empirical insight into how an initial disturbance may predispose a stand to further disturbance, and it also show a climatic signal in the occurrence of processes such as fire and insect epidemics. Thus, we have the information to model the likelihood of occurrence of certain disturbances after a given event (i.e. if we have a fire in the past what does that do to the likelihood of occurrence of insects in the future). Here, we explore if previous disturbance history is a reliable predictor of additional disturbance in the future and we present results of applying

Ocular Phenotype of Fbn2-Null Mice

PubMed Central

Shi, Yanrong; Tu, Yidong; Mecham, Robert P.; Bassnett, Steven

2013-01-01

Purpose. Fibrillin-2 (Fbn2) is the dominant fibrillin isoform expressed during development of the mouse eye. To test its role in morphogenesis, we examined the ocular phenotype of Fbn2−/− mice. Methods. Ocular morphology was assessed by confocal microscopy using antibodies against microfibril components. Results. Fbn2−/− mice had a high incidence of anterior segment dysgenesis. The iris was the most commonly affected tissue. Complete iridal coloboma was present in 37% of eyes. Dyscoria, corectopia and pseudopolycoria were also common (43% combined incidence). In wild-type (WT) mice, fibrillin-2-rich microfibrils are prominent in the pupillary membrane (PM) during development. In Fbn2-null mice, the absence of Fbn2 was partially compensated for by increased expression of fibrillin-1, although the resulting PM microfibrils were disorganized, compared with WTs. In colobomatous adult Fbn2−/− eyes, the PM failed to regress normally, especially beneath the notched region of the iris. Segments of the ciliary body were hypoplastic, and zonular fibers, although relatively plentiful, were unevenly distributed around the lens equator. In regions where the zonular fibers were particularly disturbed, the synchronous differentiation of the underlying lens fiber cells was affected. Conclusions. Fbn2 has an indispensable role in ocular morphogenesis in mice. The high incidence of iris coloboma in Fbn2-null animals implies a previously unsuspected role in optic fissure closure. The observation that fiber cell differentiation was disturbed in Fbn2−/− mice raises the possibility that the attachment of zonular fibers to the lens surface may help specify the equatorial margin of the lens epithelium. PMID:24130178

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

PubMed

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.

In utero arsenic exposure induces early onset of atherosclerosis in ApoE−/− mice

PubMed Central

Srivastava, Sanjay; D’Souza, Stanley E.; Sen, Utpal; States, J. Christopher

2007-01-01

Consumption of arsenic contaminated drinking water has been linked to higher rates of coronary disease, stroke, and peripheral arterial disease. Recent evidence suggests that early life exposures may play a significant role in the onset of chronic adult diseases. To investigate the potential for in utero exposure to accelerate the onset of cardiovascular disease we exposed pregnant ApoE-knockout (ApoE−/−) mice to arsenic in their drinking water and examined the aortic trees of their male offspring for evidence of early disease 10 and 16 weeks after birth. Mice were maintained on normal chow after weaning. ApoE−/− mice are a commonly used model for atherogenesis and spontaneously develop atherosclerotic disease. Mice exposed to arsenic in utero showed a >2-fold increase in lesion formation in the aortic roots as well as the aortic arch compared to control mice at both 10 and 16 weeks of age. The mice exposed to arsenic also had a 20 – 40% decrease in total triglycerides, but no change in total cholesterol, phospholipids and total abundance of VLDL or HDL particles. Subfractionation of VLDL particles showed a decrease in large VLDL particles. In addition, the arsenic exposed mice showed a vasorelaxation defect in response to acetylcholine suggesting disturbance of endothelial cell signalling. These results indicate that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE−/− mice without a hyperlipidemic diet and support the hypothesis that in utero arsenic exposure may be atherogenic in humans. PMID:17317095

Quantification of alcohol drinking patterns in mice.

PubMed

Eisenhardt, Manuela; Leixner, Sarah; Spanagel, Rainer; Bilbao, Ainhoa

2015-11-01

The use of mice in alcohol research provides an excellent model system for a better understanding of the genetics and neurobiology of alcohol addiction. Almost 60 years ago, alcohol researchers began to test strains of mice for alcohol preference and intake. In particular, various voluntary alcohol drinking paradigms in the home cage were developed. In mouse models of voluntary oral alcohol consumption, animals have concurrent access to water and either one or several concentrated alcohol solutions in their home cages. Although these models have high face validity, many experimental conditions require a more precise monitoring of alcohol consumption in mice in order to capture the role of specific strains or genes, or any other manipulation on alcohol drinking behavior. Therefore, we have developed a fully automated, highly precise monitoring system for alcohol drinking in mice in the home cage. This system is now commercially available. We show that this drinkometer system allows for detecting differences in drinking behavior (i) in transgenic mice, (ii) following alcohol deprivation, and (iii) following stress applications that are usually not detected by classical home-cage drinking paradigms. In conclusion, our drinkometer system allows disturbance-free and high resolution monitoring of alcohol drinking behavior. In particular, micro-drinking and circadian drinking patterns can be monitored in genetically modified and inbred strains of mice after environmental and pharmacological manipulation, and therefore this system represents an improvement in measuring behavioral features that are of relevance for the development of alcohol use disorders. © 2015 Society for the Study of Addiction.

Disturbance hydrology: Preparing for an increasingly disturbed future

USGS Publications Warehouse

Mirus, Benjamin B.; Ebel, Brian A.; Mohr, Christian H.; Zegre, Nicolas

2017-01-01

This special issue is the result of several fruitful conference sessions on disturbance hydrology, which started at the 2013 AGU Fall Meeting in San Francisco and have continued every year since. The stimulating presentations and discussions surrounding those sessions have focused on understanding both the disruption of hydrologic functioning following discrete disturbances, as well as the subsequent recovery or change within the affected watershed system. Whereas some hydrologic disturbances are directly linked to anthropogenic activities, such as resource extraction, the contributions to this special issue focus primarily on those with indirect or less pronounced human involvement, such as bark-beetle infestation, wildfire, and other natural hazards. However, human activities are enhancing the severity and frequency of these seemingly natural disturbances, thereby contributing to acute hydrologic problems and hazards. Major research challenges for our increasingly disturbed planet include the lack of continuous pre- and post-disturbance monitoring, hydrologic impacts that vary spatially and temporally based on environmental and hydroclimatic conditions, and the preponderance of overlapping or compounding disturbance sequences. In addition, a conceptual framework for characterizing commonalities and differences among hydrologic disturbances is still in its infancy. In this introduction to the special issue, we advance the fusion of concepts and terminology from ecology and hydrology to begin filling this gap. We briefly explore some preliminary approaches for comparing different disturbances and their hydrologic impacts, which provides a starting point for further dialogue and research progress.

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

PubMed

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

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

PubMed Central

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

2011-01-01

Background Binge alcohol drinking during adolescence is a serious health problem which 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). Methods Binge-like alcohol consumption was investigated in adolescent (4 wk) and adult (10 wk) male C57BL/6J mice for 2-4 h/day for 16 d. 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 intake of a novel tastant (NaCl). Results 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. Conclusions These results indicate that adolescent mice consume more alcohol, per kg 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

Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety.

PubMed

Labarca, C; Schwarz, J; Deshpande, P; Schwarz, S; Nowak, M W; Fonck, C; Nashmi, R; Kofuji, P; Dang, H; Shi, W; Fidan, M; Khakh, B S; Chen, Z; Bowers, B J; Boulter, J; Wehner, J M; Lester, H A

2001-02-27

Knock-in mice were generated that harbored a leucine-to-serine mutation in the alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by normal extracellular choline concentrations. A strain that retains the neo selection cassette in an intron has reduced expression of the hypersensitive receptor and is viable and fertile. The viable mice display increased anxiety, poor motor learning, excessive ambulation that is eliminated by very low levels of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging. These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease.

Mice with mutant Inf2 show impaired podocyte and slit diaphragm integrity in response to protamine-induced kidney injury.

PubMed

Subramanian, Balajikarthick; Sun, Hua; Yan, Paul; Charoonratana, Victoria T; Higgs, Henry N; Wang, Fang; Lai, Ka-Man V; Valenzuela, David M; Brown, Elizabeth J; Schlöndorff, Johannes S; Pollak, Martin R

2016-08-01

Mutations in the INF2 (inverted formin 2) gene, encoding a diaphanous formin family protein that regulates actin cytoskeleton dynamics, cause human focal segmental glomerulosclerosis (FSGS). INF2 interacts directly with certain other mammalian diaphanous formin proteins (mDia) that function as RhoA effector molecules. FSGS-causing INF2 mutations impair these interactions and disrupt the ability of INF2 to regulate Rho/Dia-mediated actin dynamics in vitro. However, the precise mechanisms by which INF2 regulates and INF2 mutations impair glomerular structure and function remain unknown. Here, we characterize an Inf2 R218Q point-mutant (knockin) mouse to help answer these questions. Knockin mice have no significant renal pathology or proteinuria at baseline despite diminished INF2 protein levels. INF2 mutant podocytes do show impaired reversal of protamine sulfate-induced foot process effacement by heparin sulfate perfusion. This is associated with persistent podocyte cytoplasmic aggregation, nephrin phosphorylation, and nephrin and podocin mislocalization, as well as impaired recovery of mDia membrane localization. These changes were partially mimicked in podocyte outgrowth cultures, in which podocytes from knockin mice show altered cellular protrusions compared to those from wild-type mice. Thus, in mice, normal INF2 function is not required for glomerular development but normal INF2 is required for regulation of the actin-based behaviors necessary for response to and/or recovery from injury. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Cytochrome c oxidase subunit 4 isoform 2-knockout mice show reduced enzyme activity, airway hyporeactivity, and lung pathology

PubMed Central

Hüttemann, Maik; Lee, Icksoo; Gao, Xiufeng; Pecina, Petr; Pecinova, Alena; Liu, Jenney; Aras, Siddhesh; Sommer, Natascha; Sanderson, Thomas H.; Tost, Monica; Neff, Frauke; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Naton, Beatrix; Rathkolb, Birgit; Rozman, Jan; Favor, Jack; Hans, Wolfgang; Prehn, Cornelia; Puk, Oliver; Schrewe, Anja; Sun, Minxuan; Höfler, Heinz; Adamski, Jerzy; Bekeredjian, Raffi; Graw, Jochen; Adler, Thure; Busch, Dirk H.; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Wolf, Eckhard; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Weissmann, Norbert; Doan, Jeffrey W.; Bassett, David J. P.; Grossman, Lawrence I.

2012-01-01

Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain. The purpose of this study was to analyze the function of lung-specific cytochrome c oxidase subunit 4 isoform 2 (COX4i2) in vitro and in COX4i2-knockout mice in vivo. COX was isolated from cow lung and liver as control and functionally analyzed. COX4i2-knockout mice were generated and the effect of the gene knockout was determined, including COX activity, tissue energy levels, noninvasive and invasive lung function, and lung pathology. These studies were complemented by a comprehensive functional screen performed at the German Mouse Clinic (Neuherberg, Germany). We show that isolated cow lung COX containing COX4i2 is about twice as active (88 and 102% increased activity in the presence of allosteric activator ADP and inhibitor ATP, respectively) as liver COX, which lacks COX4i2. In COX4i2-knockout mice, lung COX activity and cellular ATP levels were significantly reduced (−50 and −29%, respectively). Knockout mice showed decreased airway responsiveness (60% reduced Penh and 58% reduced airway resistance upon challenge with 25 and 100 mg methacholine, respectively), and they developed a lung pathology deteriorating with age that included the appearance of Charcot-Leyden crystals. In addition, there was an interesting sex-specific phenotype, in which the knockout females showed reduced lean mass (−12%), reduced total oxygen consumption rate (−8%), improved glucose tolerance, and reduced grip force (−14%) compared to wild-type females. Our data suggest that high activity lung COX is a central determinant of airway function and is required for maximal airway responsiveness and healthy lung function. Since airway constriction requires energy, we propose a model in which reduced tissue ATP levels explain protection from airway hyperresponsiveness, i.e., absence of COX4i2 leads to reduced lung COX activity and ATP levels, which results in impaired airway constriction

Peripubertal exposure to the neonicotinoid pesticide dinotefuran affects dopaminergic neurons and causes hyperactivity in male mice.

PubMed

Yoneda, Naoki; Takada, Tadashi; Hirano, Tetsushi; Yanai, Shogo; Yamamoto, Anzu; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Tabuchi, Yoshiaki; Hoshi, Nobuhiko

2018-04-18

Although neonicotinoid pesticides are expected to have harmful influence on mammals, there is little animal experimental data to support the effect and mechanisms. Since acetylcholine causes the release of dopamine, neonicotinoids may confer a risk of developmental disorders via a disturbance in the monoamine systems. Male mice were peripubertally administered dinotefuran (DIN) referring to no observed effect level (NOEL) and performed behavioral and immunohistological analyses. In an open field test, the total locomotor activity was increased in a dose-dependent manner. The immunoreactivity of tyrosine hydroxylase in the substantia nigra was increased in DIN-exposed mice. These results suggest that exposure to DIN in peripubertal male mice causes hyperactivity and a disturbance of dopaminergic signaling.

Restoring Serotonergic Homeostasis in the Lateral Hypothalamus Rescues Sleep Disturbances Induced by Early-Life Obesity.

PubMed

Gazea, Mary; Patchev, Alexandre V; Anderzhanova, Elmira; Leidmaa, Este; Pissioti, Anna; Flachskamm, Cornelia; Almeida, Osborne F X; Kimura, Mayumi

2018-01-10

Early-life obesity predisposes to obesity in adulthood, a condition with broad medical implications including sleep disorders, which can exacerbate metabolic disturbances and disrupt cognitive and affective behaviors. In this study, we examined the long-term impact of transient peripubertal diet-induced obesity (ppDIO, induced between 4 and 10 weeks of age) on sleep-wake behavior in male mice. EEG and EMG recordings revealed that ppDIO increases sleep during the active phase but reduces resting-phase sleep quality. This impaired sleep phenotype persisted for up to 1 year, although animals were returned to a non-obesiogenic diet from postnatal week 11 onwards. To better understand the mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA expression levels of orexin and melanin-concentrating hormone, two peptides that are important for sleep-wake behavior and food intake. Conversely, the LH of ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter involved in both sleep-wake and satiety regulation. Interestingly, an acute peripheral injection of the satiety-signaling peptide YY 3-36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep disturbances, suggesting the therapeutic potential of this peptide. These findings provide new insights into how sleep-wake behavior is programmed during early life and how peripheral and central signals are integrated to coordinate sleep. SIGNIFICANCE STATEMENT Adult physiology and behavior are strongly influenced by dynamic reorganization of the brain during puberty. The present work shows that obesity during puberty leads to persistently dysregulated patterns of sleep and wakefulness by blunting serotonergic signaling in the lateral hypothalamus. It also shows that pharmacological mimicry of satiety with peptide YY 3-36 can reverse this neurochemical imbalance and

Oral intake of beet extract provides protection against skin barrier impairment in hairless mice.

PubMed

Kawano, Ken-Ichi; Umemura, Kazuo

2013-05-01

The epidermis acts as a functional barrier against the external environment. Disturbances in the function of this barrier cause water loss and increase the chances of penetration by various irritable stimuli, leading to skin diseases such as dry skin, atopic dermatitis, and psoriasis. Ceramides are a critical natural element of the protective epidermal barrier. The aim of this study was to evaluate whether the oral intake of beet (Beta vulgaris) extract, a natural product rich in glucosylceramide (GlcCer), may prevent disturbance in skin barrier function. When HR-1 hairless mice were fed a special diet (HR-AD), transepidermal water loss (TEWL) from the dorsal skin increased, with a compensatory increase in water intake after 5 weeks. Mice fed with HR-AD had dry skin with erythema and showed increased scratching behaviour. Histological examinations revealed a remarkable increase in the thickness of the skin at 8 weeks. Supplemental addition of beet extract, which contained GlcCer at a final concentration of 0.1%, significantly prevented an increase TEWL, water intake, cumulative scratching time, and epidermal thickness at 8 weeks. These results indicate that oral intake of beet extract shows potential for preventing skin diseases associated with impaired skin barrier function. Copyright © 2012 John Wiley & Sons, Ltd.

The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer’s Disease of humans and mice

PubMed Central

Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra; Liu, Jiahui; Pike, Christian J.; Sullivan, Patrick M.; Morgan, Todd E.; Dolzhenko, Egor; Charidimou, Andreas; Wahlund, Lars-Olaf; Wiberg, Maria Kristofferson; Shams, Sara; Chiang, Gloria Chia-Yi; Finch, Caleb E.

2015-01-01

The APOE4 allele confers greater risk of Alzheimer’s Disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment (MCI) and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in two clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes. At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy (CAA), plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and CAA increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds vs the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. PMID:26686669

A genetic and pathologic study of a DENV2 clinical isolate capable of inducing encephalitis and hematological disturbances in immunocompetent mice.

PubMed

Amorim, Jaime Henrique; Pereira Bizerra, Raíza Sales; dos Santos Alves, Rúbens Prince; Sbrogio-Almeida, Maria Elisabete; Levi, José Eduardo; Capurro, Margareth Lara; de Souza Ferreira, Luís Carlos

2012-01-01

Dengue virus (DENV) is the causative agent of dengue fever (DF), a mosquito-borne illness endemic to tropical and subtropical regions. There is currently no effective drug or vaccine formulation for the prevention of DF and its more severe forms, i.e., dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). There are two generally available experimental models for the study of DENV pathogenicity as well as the evaluation of potential vaccine candidates. The first model consists of non-human primates, which do not develop symptoms but rather a transient viremia. Second, mouse-adapted virus strains or immunocompromised mouse lineages are utilized, which display some of the pathological features of the infection observed in humans but may not be relevant to the results with regard to the wild-type original virus strains or mouse lineages. In this study, we describe a genetic and pathological study of a DENV2 clinical isolate, named JHA1, which is naturally capable of infecting and killing Balb/c mice and reproduces some of the symptoms observed in DENV-infected subjects. Sequence analyses demonstrated that the JHA1 isolate belongs to the American genotype group and carries genetic markers previously associated with neurovirulence in mouse-adapted virus strains. The JHA1 strain was lethal to immunocompetent mice following intracranial (i.c.) inoculation with a LD(50) of approximately 50 PFU. Mice infected with the JHA1 strain lost weight and exhibited general tissue damage and hematological disturbances, with similarity to those symptoms observed in infected humans. In addition, it was demonstrated that the JHA1 strain shares immunological determinants with the DENV2 NGC reference strain, as evaluated by cross-reactivity of anti-envelope glycoprotein (domain III) antibodies. The present results indicate that the JHA1 isolate may be a useful tool in the study of DENV pathogenicity and will help in the evaluation of anti-DENV vaccine formulations as well as

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

PubMed

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.

Disturbance Hydrology: Preparing for an Increasingly Disturbed Future

NASA Astrophysics Data System (ADS)

Mirus, Benjamin B.; Ebel, Brian A.; Mohr, Christian H.; Zegre, Nicolas

2017-12-01

This special issue is the result of several fruitful conference sessions on disturbance hydrology, which started at the 2013 AGU Fall Meeting in San Francisco and have continued every year since. The stimulating presentations and discussions surrounding those sessions have focused on understanding both the disruption of hydrologic functioning following discrete disturbances, as well as the subsequent recovery or change within the affected watershed system. Whereas some hydrologic disturbances are directly linked to anthropogenic activities, such as resource extraction, the contributions to this special issue focus primarily on those with indirect or less pronounced human involvement, such as bark-beetle infestation, wildfire, and other natural hazards. However, human activities are enhancing the severity and frequency of these seemingly natural disturbances, thereby contributing to acute hydrologic problems and hazards. Major research challenges for our increasingly disturbed planet include the lack of continuous pre and postdisturbance monitoring, hydrologic impacts that vary spatially and temporally based on environmental and hydroclimatic conditions, and the preponderance of overlapping or compounding disturbance sequences. In addition, a conceptual framework for characterizing commonalities and differences among hydrologic disturbances is still in its infancy. In this introduction to the special issue, we advance the fusion of concepts and terminology from ecology and hydrology to begin filling this gap. We briefly explore some preliminary approaches for comparing different disturbances and their hydrologic impacts, which provides a starting point for further dialogue and research progress.

THE EFFECT OF NUTRITIONAL DISTURBANCES ON THE SUSCEPTIBILITY OF MICE TO STAPHYLOCOCCAL INFECTIONS

PubMed Central

Smiths, J. Maclean; Dubos, René J.

1956-01-01

The susceptibility of mice to intravenous injection of coagulase-positive hemolytic staphylococci was estimated by (a) observing the extent and time of mortality of infected animals; (b) determining the number of colonies of cocci that could be recovered from the liver and spleen at various intervals of time after infection. Complete deprival of food for 36 to 48 hours immediately before infection was found to increase susceptibility. This infection-enhancing effect was further increased by allowing the animals to drink a 5 per cent glucose solution instead of water or saline during the fasting period. In contrast, sodium lactate partially corrected the effect of fasting. The infection-enhancing effect of fasting was reversible. Mice prevented from gaining weight for several weeks either by restricting their daily food intake, or by feeding them ad lib. an inadequate diet, appeared just as resistant to staphylococcal infection as did mice that gained weight rapidly on an unrestricted, complete diet. PMID:13278458

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

PubMed Central

Dubey, Mohit; Brouwers, Eelke; Hamilton, Eline M.C.; Stiedl, Oliver; Bugiani, Marianna; Koch, Henner; Kole, Maarten H.P.; Boschert, Ursula; Wykes, Robert C.; Mansvelder, Huibert D.; van der Knaap, Marjo S.

2018-01-01

Objective Loss of function of the astrocyte‐specific protein MLC1 leads to the childhood‐onset leukodystrophy “megalencephalic leukoencephalopathy with subcortical cysts” (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. Methods We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole‐cell patch‐clamp recordings and K+‐sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. Results An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+ dynamics and neuronal network activity are abnormal in MLC mice. Interpretation Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636–649 PMID:29466841

Disturbance History,Spatial Variability, and Patterns of Biodiversity

NASA Astrophysics Data System (ADS)

Bendix, J.; Wiley, J. J.; Commons, M.

2012-12-01

The intermediate disturbance hypothesis predicts that species diversity will be maximized in environments experiencing intermediate intensity disturbance, after an intermediate timespan. Because many landscapes comprise mosaics with complex disturbance histories, the theory implies that each patch in those mosaics should have a distinct level of diversity reflecting combined impact of the magnitude of disturbance and the time since it occurred. We modeled the changing patterns of species richness across a landscape experiencing varied scenarios of simulated disturbance. Model outputs show that individual landscape patches have highly variable species richness through time, with the details reflecting the timing, intensity and sequence of their disturbance history. When the results are mapped across the landscape, the resulting temporal and spatial complexity illustrates both the contingent nature of diversity and the danger of generalizing about the impacts of disturbance.

Species-specific transpiration responses to intermediate disturbance in a northern hardwood forest: Transpiration response to disturbance

DOE PAGES

Matheny, Ashley M.; Bohrer, Gil; Vogel, Christoph S.; ...

2014-12-04

Intermediate disturbances shape forest structure and composition, which may in turn alter carbon, nitrogen, and water cycling. We used a large-scale experiment in a forest in northern lower Michigan where we prescribed an intermediate disturbance by stem girdling all canopy-dominant early successional trees to simulate an accelerated age-related senescence associated with natural succession.Using 3 years of eddy covariance and sap flux measurements in the disturbed area and an adjacent control plot, we analyzed disturbance-induced changes to plot level and species-specific transpiration and stomatal conductance. We found transpiration to be ~15% lower in disturbed plots than in unmanipulated control plots. However,more » species-specific responses to changes in microclimate varied. While red oak and white pine showed increases in stomatal conductance during post disturbance (62.5 and 132.2%, respectively), redmaple reduced stomatal conductance by 36.8%. We used the hysteresis between sap flux and vapor pressure deficit to quantify diurnal hydraulic stress incurred by each species in both plots. Red oak, a ring porousanisohydric species, demonstrated the largest mean relative hysteresis, while red maple, bigtooth aspen, andpaper birch, all diffuse porous species, had the lowest relative hysteresis. We employed the Penman-Monteithmodel for LE to demonstrate that these species-specific responses to disturbance are not well captured using current modeling strategies and that accounting for changes to leaf area index and plot microclimate are insufffcient to fully describe the effects of disturbance on transpiration.« less

Fear-related behaviors in Lurcher mutant mice exposed to a predator.

PubMed

Lorivel, T; Roy, V; Hilber, P

2014-11-01

The Lurcher mutant mice are characterized by massive cerebellar cortex degeneration. Besides their motor and cognitive disturbances, they exhibit both exaggerated blood corticosterone (CORT) level surge and behavioral disinhibition when confronted to anxiogenic conditions (i.e. to a potential threat). In this study, we assessed if such physiological and behavioral hyperactivity was also detectable in a fear-eliciting situation (actual threat). For this purpose, the behaviors and CORT level elevations in Lurcher mice were compared with those of littermate controls in the predator exposure test: mice were exposed either to a rat (exposure) or to a brief wave of the experimenter's hand (sham exposure). While the basal CORT concentrations (24 h before testing) were not significantly different between mice of both genotypes, the post-exposure ones were higher in Lurcher than in control mice whatever the condition of the experimental design (exposure or sham exposure). Predator exposure did not provoke significant increase of CORT levels whatever the genotype. On the contrary, our data clearly showed that fear-related behaviors of cerebellar mutants facing a real threat were exacerbated in comparison to those of control mice. These results suggest that the cerebellar cortex not only participates to fear conditioning and anxiety but also actively contributes to the modulation of the innate fear-related behaviors. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Oxidative Stress Level in the Testes of Mice and Rats during Nickel Intoxication

PubMed Central

Murawska-Ciałowicz, Eugenia; Bal, Wojciech; Januszewska, Lidia; Zawadzki, Marcin; Rychel, Joanna; Zuwała-Jagiełło, Jolanta

2012-01-01

The genotioxic and carcinogenic effect of nickel probably results from its capacity to produce reactive oxygen species (ROS) and disturb the redox balance. The aim of the study was to find out if rats lacking spermatic protamine 2 are less susceptible to Ni(II) than mice. Consequently, the levels of malondialdehyde + 4 hydroxynonenal (MDA+4HDA) − markers of lipid peroxidation, as well as the level of reduced glutathione (GSH) were measured within the rat and mouse testes. Our results showed that the levels of lipid peroxidation markers were elevated in testicular homogenates of intoxicated mice without any changes in rats. GSH level was lower in the group of intoxicated mice comparing to the control without statistically significant changes in rats' homogenates. Moreover, the level of GSH in the testes of intoxicated mice was lower than in rats. On the basis of our results, it appears that Ni(II) can initiate oxidative stress in the testes of mice but not of rats and can reduce GSH level. Consequently, the antioxidative defense of the testes is reduced. Ni(II) that causes oxidative stress in the testes may also contribute to infertility. PMID:22448131

Transience after disturbance: Obligate species recovery dynamics depend on disturbance duration.

PubMed

Singer, Alexander; Johst, Karin

2017-06-01

After a disturbance event, population recovery becomes an important species response that drives ecosystem dynamics. Yet, it is unclear how interspecific interactions impact species recovery from a disturbance and which role the disturbance duration (pulse or press) plays. Here, we analytically derive conditions that govern the transient recovery dynamics from disturbance of a host and its obligately dependent partner in a two-species metapopulation model. We find that, after disturbance, species recovery dynamics depend on the species' role (i.e. host or obligately dependent species) as well as the duration of disturbance. Host recovery starts immediately after the disturbance. In contrast, for obligate species, recovery depends on disturbance duration. After press disturbance, which allows dynamics to equilibrate during disturbance, obligate species immediately start to recover. Yet, after pulse disturbance, obligate species continue declining although their hosts have already begun to increase. Effectively, obligate species recovery is delayed until a necessary host threshold occupancy is reached. Obligates' delayed recovery arises solely from interspecific interactions independent of dispersal limitations, which contests previous explanations. Delayed recovery exerts a two-fold negative effect, because populations continue declining to even smaller population sizes and the phase of increased risk from demographic stochastic extinction in small populations is prolonged. We argue that delayed recovery and its determinants -species interactions and disturbance duration - have to be considered in biodiversity management. Copyright © 2017 Elsevier Inc. All rights reserved.

Hurricane disturbance and tropical tree species diversity.

PubMed

Vandermeer, J; Granzow de la Cerda, I; Boucher, D; Perfecto, I; Ruiz, J

2000-10-27

The debate over the maintenance of high diversity of tree species in tropical forests centers on the role of tree-fall gaps as a primary source of disturbance. Using a 10-year data series accumulated since Hurricane Joan struck the Caribbean coast of Nicaragua in 1988, we examined the pattern of species accumulation over time and with increased sampling of individuals. Our analysis shows that the pattern after a hurricane differs from the pattern after a simple tree-fall disturbance, and we conclude that pioneers are limited in large disturbances and thus do not suppress other species the way they do in smaller disturbances.

GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance.

PubMed

Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

2016-01-01

Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice.

ChAT-ChR2-EYFP mice have enhanced motor endurance but show deficits in attention and several additional cognitive domains.

PubMed

Kolisnyk, Benjamin; Guzman, Monica S; Raulic, Sanda; Fan, Jue; Magalhães, Ana C; Feng, Guoping; Gros, Robert; Prado, Vania F; Prado, Marco A M

2013-06-19

Acetylcholine (ACh) is an important neuromodulator in the nervous system implicated in many forms of cognitive and motor processing. Recent studies have used bacterial artificial chromosome (BAC) transgenic mice expressing channelrhodopsin-2 (ChR2) protein under the control of the choline acetyltransferase (ChAT) promoter (ChAT-ChR2-EYFP) to dissect cholinergic circuit connectivity and function using optogenetic approaches. We report that a mouse line used for this purpose also carries several copies of the vesicular acetylcholine transporter gene (VAChT), which leads to overexpression of functional VAChT and consequently increased cholinergic tone. We demonstrate that these mice have marked improvement in motor endurance. However, they also present severe cognitive deficits, including attention deficits and dysfunction in working memory and spatial memory. These results suggest that increased VAChT expression may disrupt critical steps in information processing. Our studies demonstrate that ChAT-ChR2-EYFP mice show altered cholinergic tone that fundamentally differentiates them from wild-type mice.

Curcumin-treated cancer cells show mitotic disturbances leading to growth arrest and induction of senescence phenotype.

PubMed

Mosieniak, Grażyna; Sliwinska, Małgorzata A; Przybylska, Dorota; Grabowska, Wioleta; Sunderland, Piotr; Bielak-Zmijewska, Anna; Sikora, Ewa

2016-05-01

Cellular senescence is recognized as a potent anticancer mechanism that inhibits carcinogenesis. Cancer cells can also undergo senescence upon chemo- or radiotherapy. Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa, shows anticancer properties both in vitro and in vivo. Previously, we have shown that treatment with curcumin leads to senescence of human cancer cells. Now we identified the molecular mechanism underlying this phenomenon. We observed a time-dependent accumulation of mitotic cells upon curcumin treatment. The time-lapse analysis proved that those cells progressed through mitosis for a significantly longer period of time. A fraction of cells managed to divide or undergo mitotic slippage and then enter the next phase of the cell cycle. Cells arrested in mitosis had an improperly formed mitotic spindle and were positive for γH2AX, which shows that they acquired DNA damage during prolonged mitosis. Moreover, the DNA damage response pathway was activated upon curcumin treatment and the components of this pathway remained upregulated while cells were undergoing senescence. Inhibition of the DNA damage response decreased the number of senescent cells. Thus, our studies revealed that the induction of cell senescence upon curcumin treatment resulted from aberrant progression through the cell cycle. Moreover, the DNA damage acquired by cancer cells, due to mitotic disturbances, activates an important molecular mechanism that determines the potential anticancer activity of curcumin. Copyright © 2016 Elsevier Ltd. All rights reserved.

The MMP-9/TIMP-1 System is Involved in Fluoride-Induced Reproductive Dysfunctions in Female Mice.

PubMed

Wang, Hong-Wei; Zhao, Wen-Peng; Tan, Pan-Pan; Liu, Jing; Zhao, Jing; Zhou, Bian-Hua

2017-08-01

A total of 84 healthy female mice were kept with various concentrations of sodium fluoride (F) (0, 50, 100, 150 mg F - /L in drinking water for 90 days) and were then mated with healthy male mice for 1 week to study the effect of excessive fluoride on female reproductive function, particularly in embryo implantation. The rate of pregnancy, litter size, and the birth weight of female mice were evaluated. Ultrastructural changes of uteri tissues were observed by transmission electron microscopy (TEM). The mRNA expression levels of MMP-9 and TIMP-1 were determined by quantitative real-time PCR. The protein expression levels of MMP-9 and TIMP-1 were analyzed by western blotting. Results showed a significant decrease of litter size in mice exposed to fluoride. TEM images of uteri tissue of mice that underwent a 150 mg/L F - treatment for 90 days showed a vague nucleus, reduced microvilli, increased lysosomes, a dilated endoplasmic reticulum, and a vacuolization mitochondrion when compared with the control group. Following the damage of the structure, the expression levels of MMP-9 and TIMP-1 in uteri tissues were significantly unregulated in the F 150 group. These results show that MMP-9/TIMP-1 system disturbance and changes of histological structure in uteri tissue are involved in fluoride-induced reproductive dysfunctions.

Deficiencies in extrusion of the second polar body due to high calcium concentrations during in vitro fertilization in inbred C3H/He mice.

PubMed

Ohta, Yuki; Nagao, Yoshikazu; Minami, Naojiro; Tsukamoto, Satoshi; Kito, Seiji

2016-08-01

Successful in vitro fertilization (IVF) of all inbred strains of laboratory mice has not yet been accomplished. We have previously shown that a high calcium concentration improved IVF in various inbred mice. However, we also found that in cumulus-free ova of C3H/He mice such IVF conditions significantly increased the deficiency of extrusion of the second polar body (PBII) in a dose-dependent manner (2% at 1.71 mM and 29% at 6.84 mM, P < 0.05) and that PBII extrusion was affected by high calcium levels at 2-3 h post-insemination. While developmental competence of ova without PBII extrusion to blastocysts after 96 h culture was not affected, a significant reduction in the nuclear number of the inner cell mass was observed in blastocyst fertilized under high calcium condition. We also examined how high calcium concentration during IVF affects PBII extrusion in C3H/He mice. Cumulus cells cultured under high calcium conditions showed a significantly alleviated deficient PBII extrusion. This phenomenon is likely to be specific to C3H/He ova because deficient PBII extrusion in reciprocal fertilization between C3H and BDF1 gametes was observed only in C3H/He ova. Sperm factor(s) was still involved in deficient PBII extrusion due to high calcium concentrations, as this phenomenon was not observed in ova activated by ethanol. The cytoskeletal organization of ova without PBII extrusion showed disturbed spindle rotation, incomplete formation of contractile ring and disturbed localization of actin, suggesting that high calcium levels affect the anchoring machinery of the meiotic spindle. These results indicate that in C3H/He mice high calcium levels induce abnormal fertilization, i.e. deficient PBII extrusion by affecting the cytoskeletal organization, resulting in disturbed cytokinesis during the second meiotic division. Thus, use of high calcium media for IVF should be avoided for this strain.

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

PubMed

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

Rhythmicity in Mice Selected for Extremes in Stress Reactivity: Behavioural, Endocrine and Sleep Changes Resembling Endophenotypes of Major Depression

PubMed Central

Ruschel, Jörg; Palme, Rupert; Holsboer, Florian; Kimura, Mayumi; Landgraf, Rainer

2009-01-01

Background Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including hyper- or hypo-activity of the stress hormone system, plays a critical role in the pathophysiology of mood disorders such as major depression (MD). Further biological hallmarks of MD are disturbances in circadian rhythms and sleep architecture. Applying a translational approach, an animal model has recently been developed, focusing on the deviation in sensitivity to stressful encounters. This so-called ‘stress reactivity’ (SR) mouse model consists of three separate breeding lines selected for either high (HR), intermediate (IR), or low (LR) corticosterone increase in response to stressors. Methodology/Principle Findings In order to contribute to the validation of the SR mouse model, our study combined the analysis of behavioural and HPA axis rhythmicity with sleep-EEG recordings in the HR/IR/LR mouse lines. We found that hyper-responsiveness to stressors was associated with psychomotor alterations (increased locomotor activity and exploration towards the end of the resting period), resembling symptoms like restlessness, sleep continuity disturbances and early awakenings that are commonly observed in melancholic depression. Additionally, HR mice also showed neuroendocrine abnormalities similar to symptoms of MD patients such as reduced amplitude of the circadian glucocorticoid rhythm and elevated trough levels. The sleep-EEG analyses, furthermore, revealed changes in rapid eye movement (REM) and non-REM sleep as well as slow wave activity, indicative of reduced sleep efficacy and REM sleep disinhibition in HR mice. Conclusion/Significance Thus, we could show that by selectively breeding mice for extremes in stress reactivity, clinically relevant endophenotypes of MD can be modelled. Given the importance of rhythmicity and sleep disturbances as biomarkers of MD, both animal and clinical studies on the interaction of behavioural, neuroendocrine and sleep parameters may reveal

Regulatory T cell activity in immunosuppresive mice model of pseudomonas aeruginosa pneumonia.

PubMed

Li, Jun-Lu; Chen, Ting-Sang; Yuan, Cong-Cong; Zhao, Guo-Qiang; Xu, Min; Li, Xiao-Yan; Cao, Jie; Xing, Li-Hua

2017-08-01

Pseudomonas aeruginosa (PA) pneumonia is a refractory, even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process. We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells, i.e., Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10). Seventy-two BALB/c mice were divided into four groups randomly: control (A), PA pneumonia (B), immunosuppression (C) and immunosuppression with PA pneumonia (D). Mice were sacrificed at 4, 8 and 24 h after establishing experimental models. The pathological changes of lung tissue were graded, and the FOXP3 mRNA and serum IL-10 levels were detected. Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C, but significantly pathological changes were found in groups B and D, especially in group D at 8 h (P<0.05). The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points, which were significantly lower than those in groups B and D (P<0.05). FOXP3 mRNA levels were lowest at 4 h, and there was significant difference between groups B and D (P<0.05). The serum levels of IL-10 in groups A and C were almost normal at the three time points, but decreased significantly in groups B and D (P<0.05). The serum levels of IL-10 decreased to the lowest at 8 h, especially in group D (P<0.05). The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly, which may be associated with Treg cells function disturbance. And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

Azole-resistant and -susceptible Aspergillus fumigatus isolates show comparable fitness and azole treatment outcome in immunocompetent mice.

PubMed

Lackner, Michaela; Rambach, Günter; Jukic, Emina; Sartori, Bettina; Fritz, Josef; Seger, Christoph; Hagleitner, Magdalena; Speth, Cornelia; Lass-Flörl, Cornelia

2017-12-08

No data are available on the in vivo impact of infections with in vitro azole-resistant Aspergillus fumigatus in immunocompetent hosts. Here, the aim was to investigate fungal fitness and treatment response in immunocompetent mice infected with A. fumigatus (parental strain [ps]) and isogenic mutants carrying either the mutation M220K or G54W (cyp51A). The efficacy of itraconazole (ITC) and posaconazole (PSC) was investigated in mice, intravenously challenged either with a single or a combination of ps and mutants (6 × 105 conidia/mouse). Organ fungal burden and clinical parameters were measured. In coinfection models, no fitness advantage was observed for the ps strain when compared to the mutants (M220K and G54W) independent of the presence or absence of azole-treatment. For G54W, M220K, and the ps, no statistically significant difference in ITC and PSC treatment was observed in respect to fungal kidney burden. However, clinical parameters suggest that in particular the azole-resistant strain carrying the mutation G54W caused a more severe disease than the ps strain. Mice infected with G54W showed a significant decline in body weight and lymphocyte counts, while spleen/body weight ratio and granulocyte counts were increased. In immunocompetent mice, in vitroazole-resistance did not translate into therapeutic failure by either ITC or PSC; the immune system appears to play the key role in clearing the infection. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

PubMed Central

Chao, Jung; Huo, Teh-Ia; Cheng, Hao-Yuan; Tsai, Jen-Chieh; Liao, Jiunn-Wang; Lee, Meng-Shiou; Qin, Xue-Mei; Hsieh, Ming-Tsuen; Pao, Li-Heng; Peng, Wen-Huang

2014-01-01

Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help

Implications of recurrent disturbance for genetic diversity.

PubMed

Davies, Ian D; Cary, Geoffrey J; Landguth, Erin L; Lindenmayer, David B; Banks, Sam C

2016-02-01

Exploring interactions between ecological disturbance, species' abundances and community composition provides critical insights for ecological dynamics. While disturbance is also potentially an important driver of landscape genetic patterns, the mechanisms by which these patterns may arise by selective and neutral processes are not well-understood. We used simulation to evaluate the relative importance of disturbance regime components, and their interaction with demographic and dispersal processes, on the distribution of genetic diversity across landscapes. We investigated genetic impacts of variation in key components of disturbance regimes and spatial patterns that are likely to respond to climate change and land management, including disturbance size, frequency, and severity. The influence of disturbance was mediated by dispersal distance and, to a limited extent, by birth rate. Nevertheless, all three disturbance regime components strongly influenced spatial and temporal patterns of genetic diversity within subpopulations, and were associated with changes in genetic structure. Furthermore, disturbance-induced changes in temporal population dynamics and the spatial distribution of populations across the landscape resulted in disrupted isolation by distance patterns among populations. Our results show that forecast changes in disturbance regimes have the potential to cause major changes to the distribution of genetic diversity within and among populations. We highlight likely scenarios under which future changes to disturbance size, severity, or frequency will have the strongest impacts on population genetic patterns. In addition, our results have implications for the inference of biological processes from genetic data, because the effects of dispersal on genetic patterns were strongly mediated by disturbance regimes.

Continuous uniformly finite time exact disturbance observer based control for fixed-time stabilization of nonlinear systems with mismatched disturbances

PubMed Central

Liu, Chongxin; Liu, Hang

2017-01-01

This paper presents a continuous composite control scheme to achieve fixed-time stabilization for nonlinear systems with mismatched disturbances. The composite controller is constructed in two steps: First, uniformly finite time exact disturbance observers are proposed to estimate and compensate the disturbances. Then, based on adding a power integrator technique and fixed-time stability theory, continuous fixed-time stable state feedback controller and Lyapunov functions are constructed to achieve global fixed-time system stabilization. The proposed control method extends the existing fixed-time stable control results to high order nonlinear systems with mismatched disturbances and achieves global fixed-time system stabilization. Besides, the proposed control scheme improves the disturbance rejection performance and achieves performance recovery of nominal system. Simulation results are provided to show the effectiveness, the superiority and the applicability of the proposed control scheme. PMID:28406966

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

PubMed Central

Maurmann, Natasha; Reolon, Gustavo Kellermann; Rech, Sandra Beatriz; Fett-Neto, Arthur Germano; Roesler, Rafael

2011-01-01

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. PMID:20047889

Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl-CoA dehydrogenase (MCAD)-deficient mice.

PubMed

Herrema, Hilde; Derks, Terry G J; van Dijk, Theo H; Bloks, Vincent W; Gerding, Albert; Havinga, Rick; Tietge, Uwe J F; Müller, Michael; Smit, G Peter A; Kuipers, Folkert; Reijngoud, Dirk-Jan

2008-06-01

Medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD(-/-) mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD(-/-) mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1alpha (Pgc-1alpha) and decreased peroxisome proliferator-activated receptor alpha (Ppar alpha) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD(-/-) mice in both conditions, suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD(-/-) mice. During the APR, however, this flux was significantly decreased (-20%) in MCAD(-/-) mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD(-/-) mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD(-/-) mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD(-/-) mice, was mainly due to enhanced peripheral glucose uptake. Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the

γδ T-cell-deficient mice show alterations in mucin expression, glycosylation, and goblet cells but maintain an intact mucus layer.

PubMed

Kober, Olivia I; Ahl, David; Pin, Carmen; Holm, Lena; Carding, Simon R; Juge, Nathalie

2014-04-01

Intestinal homeostasis is maintained by a hierarchy of immune defenses acting in concert to minimize contact between luminal microorganisms and the intestinal epithelial cell surface. The intestinal mucus layer, covering the gastrointestinal tract epithelial cells, contributes to mucosal homeostasis by limiting bacterial invasion. In this study, we used γδ T-cell-deficient (TCRδ(-/-)) mice to examine whether and how γδ T-cells modulate the properties of the intestinal mucus layer. Increased susceptibility of TCRδ(-/-) mice to dextran sodium sulfate (DSS)-induced colitis is associated with a reduced number of goblet cells. Alterations in the number of goblet cells and crypt lengths were observed in the small intestine and colon of TCRδ(-/-) mice compared with C57BL/6 wild-type (WT) mice. Addition of keratinocyte growth factor to small intestinal organoid cultures from TCRδ(-/-) mice showed a marked increase in crypt growth and in both goblet cell number and redistribution along the crypts. There was no apparent difference in the thickness or organization of the mucus layer between TCRδ(-/-) and WT mice, as measured in vivo. However, γδ T-cell deficiency led to reduced sialylated mucins in association with increased gene expression of gel-secreting Muc2 and membrane-bound mucins, including Muc13 and Muc17. Collectively, these data provide evidence that γδ T cells play an important role in the maintenance of mucosal homeostasis by regulating mucin expression and promoting goblet cell function in the small intestine.

Temporal and Spatial Evolution Characteristics of Disturbance Wave in a Hypersonic Boundary Layer due to Single-Frequency Entropy Disturbance

PubMed Central

Lv, Hongqing; Shi, Jianqiang

2014-01-01

By using a high-order accurate finite difference scheme, direct numerical simulation of hypersonic flow over an 8° half-wedge-angle blunt wedge under freestream single-frequency entropy disturbance is conducted; the generation and the temporal and spatial nonlinear evolution of boundary layer disturbance waves are investigated. Results show that, under the freestream single-frequency entropy disturbance, the entropy state of boundary layer is changed sharply and the disturbance waves within a certain frequency range are induced in the boundary layer. Furthermore, the amplitudes of disturbance waves in the period phase are larger than that in the response phase and ablation phase and the frequency range in the boundary layer in the period phase is narrower than that in these two phases. In addition, the mode competition, dominant mode transformation, and disturbance energy transfer exist among different modes both in temporal and in spatial evolution. The mode competition changes the characteristics of nonlinear evolution of the unstable waves in the boundary layer. The development of the most unstable mode along streamwise relies more on the motivation of disturbance waves in the upstream than that of other modes on this motivation. PMID:25143983

Temporal and spatial evolution characteristics of disturbance wave in a hypersonic boundary layer due to single-frequency entropy disturbance.

PubMed

Wang, Zhenqing; Tang, Xiaojun; Lv, Hongqing; Shi, Jianqiang

2014-01-01

By using a high-order accurate finite difference scheme, direct numerical simulation of hypersonic flow over an 8° half-wedge-angle blunt wedge under freestream single-frequency entropy disturbance is conducted; the generation and the temporal and spatial nonlinear evolution of boundary layer disturbance waves are investigated. Results show that, under the freestream single-frequency entropy disturbance, the entropy state of boundary layer is changed sharply and the disturbance waves within a certain frequency range are induced in the boundary layer. Furthermore, the amplitudes of disturbance waves in the period phase are larger than that in the response phase and ablation phase and the frequency range in the boundary layer in the period phase is narrower than that in these two phases. In addition, the mode competition, dominant mode transformation, and disturbance energy transfer exist among different modes both in temporal and in spatial evolution. The mode competition changes the characteristics of nonlinear evolution of the unstable waves in the boundary layer. The development of the most unstable mode along streamwise relies more on the motivation of disturbance waves in the upstream than that of other modes on this motivation.

Experimental Chagas disease. Innate immune response in Balb/c mice previously vaccinated with Trypanosoma rangeli. I. The macrophage shows immunological memory: Reality or fiction?

PubMed

Basso, B; Marini, V

2014-04-01

Chagas' disease, caused by Trypanosoma cruzi, is a major vector borne health problem in Latin America and an emerging or re-emerging infectious disease in several countries. Immune response to T. cruzi infection is highly complex and involves many components, both regulators and effectors. Although different parasites have been shown to activate different mechanisms of innate immunity, T. cruzi is often able to survive and replicate in its host because they are well adapted to resisting host defences. An experimental model for vaccinating mice with Trypanosoma rangeli, a parasite closely related to T. cruzi, but nonpathogenic to humans, has been designed in our laboratory, showing protection against challenge with T. cruzi infection. The aim of this work was to analyze some mechanisms of the early innate immune response in T. rangeli vaccinated mice challenged with T. cruzi. For this purpose, some interactions were studied between T. cruzi and peritoneal macrophages of mice vaccinated with T. rangeli, infected or not with T. cruzi and the levels of some molecules or soluble mediators which could modify these interactions. The results in vaccinated animals showed a strong innate immune response, where the adherent cells of the vaccinated mice revealed important phagocytic activity, and some soluble mediator (Respiratory Burst: significantly increase, p ≤ 0.03; NO: the levels of vaccinated animals were lower than those of the control group; Arginasa: significantly increase, p ≤ 0.04). The results showed an important role in the early elimination of the parasites and their close relation with the absence of histological lesions that these animals present with regard to the only infected mice. This behaviour reveals that the macrophages act with some type of memory, recognizing the antigens to which they have previously been exposed, in mice were vaccinated with T. rangeli, which shares epitopes with T. cruzi. Copyright © 2013 Elsevier GmbH. All rights reserved.

Non-senescent Hydra tolerates severe disturbances in the nuclear lamina.

PubMed

Klimovich, Alexander; Rehm, Arvid; Wittlieb, Jörg; Herbst, Eva-Maria; Benavente, Ricardo; Bosch, Thomas C G

2018-05-10

The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra . We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization. While Lamin is indispensable for Hydra , the stem cells tolerate overexpression, downregulation and mislocalization of Lamin, and disturbances in the nuclear envelope structure. This extraordinary robustness may underlie the indefinite self-renewal capacity of stem cells and the non-senescence of Hydra . A relatively low complexity of the nuclear envelope architecture in basal Metazoa might allow for their extreme lifespans, while an increasing complexity of the nuclear architecture in bilaterians resulted in restricted lifespans.

Mice with hepatocyte-specific FXR deficiency are resistant to spontaneous but susceptible to cholic acid-induced hepatocarcinogenesis

PubMed Central

Zhu, Yan; Li, Guodong; Williams, Jessica A.; Buckley, Kyle; Tawfik, Ossama; Luyendyk, James P.

2016-01-01

Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily with its endogenous ligands bile acids. Mice with whole body FXR deficiency develop liver tumors spontaneously, but the underlying mechanism is unclear. Moreover, it is unknown whether FXR deficiency in liver alone serves as a tumor initiator or promoter during liver carcinogenesis. This study aims to evaluate the effects of hepatocyte-specific FXR deficiency (FXRhep−/−) in liver tumor formation. The results showed that FXRhep−/− mice did not show spontaneous liver tumorigenesis with aging (up to 24 mo of age). Therefore FXRhep−/− mice were fed a bile acid (cholic acid)-containing diet alone or along with a liver tumor initiator, diethylnitrosamine (DEN). Thirty weeks later, no tumors were found in wild-type or FXRhep−/− mice without any treatment or with DEN only. However, with cholic acid, while only some wild-type mice developed tumors, all FXRhep−/− mice presented with severe liver injury and tumors. Interestingly, FXRhep−/− mouse livers increased basal expression of tumor suppressor p53 protein, apoptosis, and decreased basal cyclin D1 expression, which may prevent tumor development in FXRhep−/− mice. However, cholic acid feeding reversed these effects in FXRhep−/− mice, which is associated with an increased cyclin D1 and decreased cell cycle inhibitors. More in-depth analysis indicates that the increased in cell growth might result from disturbance of the MAPK and JAK/Stat3 signaling pathways. In conclusion, this study shows that hepatic FXR deficiency may only serve as a tumor initiator, and increased bile acids is required for tumor formation likely by promoting cell proliferation. PMID:26744468

Tributyltin exposure induces gut microbiome dysbiosis with increased body weight gain and dyslipidemia in mice.

PubMed

Guo, Hao; Yan, Haotian; Cheng, Dong; Wei, Xinglong; Kou, Ruirui; Si, Jiliang

2018-05-03

Gut microbiome dysbiosis plays a profound role in the pathogenesis of obesity and tributyltin (TBT) has been found as an environmental obesogen. However, whether TBT could disturb gut microbiome and the relationship between obesity induced by TBT exposure and alteration in gut microbiota are still unknown. In order to assess the association between them, mice were exposed to TBTCl (50 μg kg -1 ) once every three days from postnatal days (PNDs) 24 to 54. The results demonstrated that TBT exposure resulted in increased body weight gain, lager visceral fat accumulation and dyslipidemia in male mice on PND 84. Correspondingly, 16S rRNA gene sequencing revealed that TBT treatment decreased gut microbial species and perturbed the microbiome composition in mice. Furthermore, Pearson's corelation coefficient analysis showed a significantly negative correlation between the body weight and the alpha diversity of gut microbiome. These results suggested that TBT exposure could induce gut microbiome dysbiosis in mice, which might contribute to the obesity pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Mice with a fra-1 knock-in into the c-fos locus show impaired spatial but regular contextual learning and normal LTP.

PubMed

Gass, Peter; Fleischmann, Alexander; Hvalby, Oivind; Jensen, Vidar; Zacher, Christiane; Strekalova, Tatyana; Kvello, Ane; Wagner, Erwin F; Sprengel, Rolf

2004-11-04

The immediate early gene c-fos is part of the AP-1 transcription factor complex, which is involved in molecular mechanisms underlying learning and memory. Mice that lack c-Fos in the brain show impairments in spatial reference and contextual learning, and also exhibit a reduced long-term potentiation of synaptic transmission (LTP) at CA3-to-CA1 synapses. In the present study, we investigated mice in which c-fos was deleted and replaced by fra-1 (c-fos(fra-1) mice) to determine whether other members of the c-fos gene family can substitute for the functions of the c-fos gene. In c-fos(fra-1) mice, both CA3-to-CA1 LTP and contextual learning in a Pavlovian fear conditioning task were similar to wild-type littermates, indicating that Fra-1 expression restored the impairments caused by brain-specific c-Fos depletion. However, c-Fos-mediated learning deficits in a reference memory task of the Morris watermaze were also present in c-fos(fra-1) mice. These findings suggest that different c-Fos target genes are involved in LTP, contextual learning, and spatial reference memory formation.

Depression-like behaviour in mice is associated with disrupted circadian rhythms in nucleus accumbens and periaqueductal grey.

PubMed

Landgraf, Dominic; Long, Jaimie E; Welsh, David K

2016-05-01

An association between circadian rhythms and mood regulation is well established, and disturbed circadian clocks are believed to contribute to the development of mood disorders, including major depressive disorder. The circadian system is coordinated by the suprachiasmatic nucleus (SCN), the master pacemaker in the hypothalamus that receives light input from the retina and synchronizes circadian oscillators in other brain regions and peripheral tissues. Lacking the tight neuronal network that couples single-cell oscillators in the SCN, circadian clocks outside the SCN may be less stable and more susceptible to disturbances, for example by clock gene mutations or uncontrollable stress. However, non-SCN circadian clocks have not been studied extensively in rodent models of mood disorders. In the present study, it was hypothesized that disturbances of local circadian clocks in mood-regulating brain areas are associated with depression-like behaviour in mice. Using the learned helplessness procedure, depression-like behaviour was evoked in mice bearing the PER2::LUC circadian reporter, and then circadian rhythms of PER2 expression were examined in brain slices from these mice using luminometry and bioluminescence imaging. It was found that helplessness is associated with absence of circadian rhythms in the nucleus accumbens and the periaqueductal grey, two of the most critical brain regions within the reward circuit. The current study provides evidence that susceptibility of mice to depression-like behaviour is associated with disturbed local circadian clocks in a subset of mood-regulating brain areas, but the direction of causality remains to be determined. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Preferential suppression of limbic Fos expression by intermittent hypoxia in obese diabetic mice.

PubMed

Mukai, Takahiro; Nagao, Yuki; Nishioka, Satoshi; Hayashi, Tetsuya; Shimizu, Saki; Ono, Asuka; Sakagami, Yoshihisa; Watanabe, Sho; Ueda, Yoko; Hara, Madoka; Tokudome, Kentaro; Kato, Ryuji; Matsumura, Yasuo; Ohno, Yukihiro

2013-12-01

Sleep apnea (SA) causes not only sleep disturbances, but also neurocognitive impairments and/or psychoemotional disorders. Here, we studied the effects of intermittent hypoxia (IH) on forebrain Fos expression using obese diabetic db/db mice to explore the pathophysiological alterations in neural activities and the brain regions related to SA syndrome. Male db/db mice were exposed to IH stimuli (repetitive 6-min cycles of 1min with 5% oxygen followed by 5min with 21% oxygen) for 8h (80 cycles) per day or normoxic condition (control group) for 14 days. Fos protein expression was immunohistochemically examined a day after the last IH exposure. Mapping analysis revealed a significant reduction of Fos expression by IH in limbic and paralimbic structures, including the cingulate and piriform cortices, the core part of the nucleus accumbens and most parts of the amygdala (i.e., the basolateral and basomedial amygdaloid nuclei, cortical amygdaloid area and medial amygdaloid nucleus). In the brain stem regions, Fos expression was region-specifically reduced in the ventral tegmental area while other regions including the striatum, thalamus and hypothalamus, were relatively resistant against IH. In addition, db/db mice exposed to IH showed a trend of sedative and/or depressive behavioral signs in the open field and forced swim tests. The present results illustrate that SA in the obese diabetic model causes neural suppression preferentially in the limbic and paralimbic regions, which may be related to the neuropsychological disturbances associated with SA. Copyright © 2013. Published by Elsevier Ireland Ltd.

γδ T-cell-deficient mice show alterations in mucin expression, glycosylation, and goblet cells but maintain an intact mucus layer

PubMed Central

Kober, Olivia I.; Ahl, David; Pin, Carmen; Holm, Lena; Carding, Simon R.

2014-01-01

Intestinal homeostasis is maintained by a hierarchy of immune defenses acting in concert to minimize contact between luminal microorganisms and the intestinal epithelial cell surface. The intestinal mucus layer, covering the gastrointestinal tract epithelial cells, contributes to mucosal homeostasis by limiting bacterial invasion. In this study, we used γδ T-cell-deficient (TCRδ−/−) mice to examine whether and how γδ T-cells modulate the properties of the intestinal mucus layer. Increased susceptibility of TCRδ−/− mice to dextran sodium sulfate (DSS)-induced colitis is associated with a reduced number of goblet cells. Alterations in the number of goblet cells and crypt lengths were observed in the small intestine and colon of TCRδ−/− mice compared with C57BL/6 wild-type (WT) mice. Addition of keratinocyte growth factor to small intestinal organoid cultures from TCRδ−/− mice showed a marked increase in crypt growth and in both goblet cell number and redistribution along the crypts. There was no apparent difference in the thickness or organization of the mucus layer between TCRδ−/− and WT mice, as measured in vivo. However, γδ T-cell deficiency led to reduced sialylated mucins in association with increased gene expression of gel-secreting Muc2 and membrane-bound mucins, including Muc13 and Muc17. Collectively, these data provide evidence that γδ T cells play an important role in the maintenance of mucosal homeostasis by regulating mucin expression and promoting goblet cell function in the small intestine. PMID:24503767

Abnormal circadian locomotor rhythms and Per gene expression in six-month-old triple transgenic mice model of Alzheimer's disease.

PubMed

Wu, Meina; Zhou, Fang; Cao, Xiuli; Yang, Junting; Bai, Yu; Yan, Xudong; Cao, Jimin; Qi, Jinshun

2018-05-29

Circadian rhythm disturbance (CRD) is one of the iconic manifestations in Alzheimer's disease (AD), a disease tightly associated with age, but the characteristics and gender difference of CRD occurred in AD have not been well demonstrated. Using 6-month-old triple transgenic AD mouse model (3xTg-AD) without obvious brain pathological changes, we demonstrated the gender difference of CRD at this age. We further showed abnormal Per gene expression in the central clock suprachiasmatic nucleus (SCN) of the 3xTg-AD mice. Specifically, compared with the wide type (WT) mice, the 3xTg-AD mice showed disrupted circadian locomotor rhythms both at LD (light-dark 12 h:12 h) and DD (constant dark) conditions, such as increased activities in the resting phase, decreased and scattered activities in the active phase, decreased overall activity intensities, amplitude, robustness, and increased intradaily variability. We further observed that 3xTg-AD female mice showed obviously less CRD compared with the 3xTg-AD male mice, and female mice of both WT and 3xTg-AD were more active in locomotor activity. Accordingly, 3xTg-AD mice showed a phase delay in the expression of Per1 and Per2 mRNA in the SCN, with the levels of Per1 and Per2 mRNA were significantly lower than that of WT mice at specific time points. We conclude that 3xTg-AD mice exhibit behavioral CRD at the age of six months with male gender preference, and these phenomena are at least partly associated with the alteration of Per1 and Per2 transcription patterns in the SCN. Copyright © 2018 Elsevier B.V. All rights reserved.

Transmission intensity disturbance in a rotating polarizer

NASA Astrophysics Data System (ADS)

Fan, J. Y.; Li, H. X.; Wu, F. Q.

2008-01-01

Random disturbance was observed in transmission intensity in various rotating prism polarizers when they were used in optical systems. As a result, the transmitted intensity exhibited cyclic significant deviation from the Malus cosine-squared law with rotation of prisms. The disturbance spoils the light quality transmitted through the polarizer thus dramatically depresses the accuracies of measurements when the prim polarizers were used in light path. A rigorous model is presented based on the solid basis of multi-beams interference, and theoretical results show good agreement with measured values and also indicate effective method for reducing the disturbance.

Dioxin pollution disrupts reproduction in male Japanese field mice.

PubMed

Ishiniwa, Hiroko; Sakai, Mizuki; Tohma, Shimon; Matsuki, Hidenori; Takahashi, Yukio; Kajiwara, Hideo; Sekijima, Tsuneo

2013-11-01

Dioxins cause various adverse effects in animals including teratogenesis, induction of drug metabolizing enzymes, tumor promotion, and endocrine disruption. Above all, endocrine disruption is known to disturb reproduction in adult animals and may, also seriously impact their offspring. However, most previous studies have quantified the species-specific accumulation of dioxins, whereas few studies have addressed the physiological impacts of dioxins on wildlife, such as reduced reproductive function. Here we clarify an effect of endocrine disruption caused by dioxins on the Japanese field mouse, Apodemus speciosus. Japanese field mice collected from various sites polluted with dioxins accumulated high concentrations of dioxins in their livers. Some dioxin congeners, especially, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 3,3',4,4',5-pentachloro biphenyl, 1,2,3,4,6,7,8-heptachlorodibenzofuran, and octachlorodibenzo-p-dioxin, which showed high biota-soil accumulation factors, contributed to concentration of dioxins in mouse livers with an increase of accumulation of total dioxins. As for physiological effects on the Japanese field mouse, high levels of cytochrome P450 1A1 (CYP1A1) mRNA, a drug metabolizing enzyme induced by dioxins, were found in the livers of mice captured at polluted sites. Furthermore, at such sites polluted with dioxins, increased CYP1A1 expression coincided with reduced numbers of active spermatozoa in mice. Thus, disruption in gametogenesis observed in these mice suggests that dioxins not only negatively impact reproduction among Japanese field mice, but might also act as a kind of selection pressure in a chemically polluted environment.

vGLUT2 heterozygous mice show more susceptibility to clonic seizures induced by pentylenetetrazol.

PubMed

Schallier, Anneleen; Massie, Ann; Loyens, Ellen; Moechars, Diederik; Drinkenburg, Wilhelmus; Michotte, Yvette; Smolders, Ilse

2009-01-01

Glutamate, the most abundant excitatory neurotransmitter in the central nervous system, is well known to be implicated in epileptic seizures. Therefore, impairments in glutamate transport could have an involvement in the mechanism of epileptogenesis. The uptake of glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (vGLUTs). There are three known vGLUT isoforms, vGLUT1-3. In this study, we are particularly interested in the vGLUT2 isoform. We investigated the possible role of vGLUT2 in pentylenetetrazol (PTZ)-induced seizure generation. Seizure threshold of PTZ was compared in vGLUT2 heterozygous knock out (HET) and wild type (WT) mice. In comparison with their WT littermates a lower dose of PTZ was needed in the vGLUT2 HET mice until the onset of the first myoclonic jerk. The threshold for PTZ-induced clonic seizure activity was also lower in the vGLUT2 HET mice. These results indicate, for the first time, that vGLUT2 is likely involved in the epileptogenesis of generalized seizures.

Novel disturbance-observer-based control for systems with high-order mismatched disturbances

NASA Astrophysics Data System (ADS)

Fang, Xing; Liu, Fei; Wang, Zhiguo; Dong, Na

2018-01-01

A novel disturbance-observer-based control method is investigated to attenuate the high-order mismatched disturbances. First, a finite-time disturbance observer (FTDO) is proposed to estimate the disturbances as well as the derivatives. By incorporating the outputs of FTDO, the original system is then reconstructed, where the mismatched disturbances are transformed to the matched ones that are compensated by feed-forward algorithm. Moreover, a feedback control law is developed to achieve the stability and tracking performance requirements for the systems. Finally, the proposed composite control method is applied to an unmanned helicopter system. The simulation results demonstrate that the proposed control method exhibits excellent control performance in the presence of high-order matched and mismatched disturbances.

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

PubMed

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.

Sustained increase of alpha7 nicotinic receptors and choline-induced improvement of learning deficit in STOP knock-out mice.

PubMed

Bouvrais-Veret, Caroline; Weiss, Stéphanie; Andrieux, Annie; Schweitzer, Annie; McIntosh, J Michael; Job, Didier; Giros, Bruno; Martres, Marie-Pascale

2007-06-01

Mice deficient in the microtubule stabilizing protein STOP (stable tubule only polypeptide) show synaptic plasticity anomalies in hippocampus, dopamine hyper-reactivity in the limbic system and severe behavioral deficits. Some of these disturbances are alleviated by long-term antipsychotic treatment. Therefore, this mouse line represents a pertinent model for some aspects of schizophrenia symptomatology. Numerous data support dysfunction of nicotinic neurotransmission in schizophrenia and epidemiological studies show increased tobacco use in schizophrenic patients, in whom nicotine has been reported to improve cognitive deficits and impairment in sensory gating. In this study, we examined potential alterations in cholinergic (ACh) and nicotinic components and functions in STOP mutant mice. STOP KO mice displayed no variation of the density of ACh esterase and beta2* nicotinic receptors (nAChRs), large reductions in the density of vesicular ACh transporter and alpha6* nAChRs and marked increases in the density of alpha7 nAChRs, in some brain areas. STOP KO mice were hypersensitive to the stimulating locomotor effect of nicotine and, interestingly, their impaired performance in learning the cued version of the water maze were improved by administration of the preferential alpha7 nAChR agonist choline. Altogether, our data show that the deletion of the ubiquitous STOP protein elicited restricted alterations in ACh components. They also suggest that nicotinic neurotransmission can be deficient in STOP KO mice and that mutant mice can represent a meaningful model to study some nicotinic dysfunctions and therapeutic treatments.

Mice heterozygous for cathepsin D deficiency exhibit mania-related behavior and stress-induced depression.

PubMed

Zhou, Rui; Lu, Yi; Han, Yong; Li, Xia; Lou, Huifang; Zhu, Liya; Zhen, Xuechu; Duan, Shumin

2015-12-03

Mutations in cathepsin D (CTSD), an aspartic protease in the endosomal-lysosomal system, underlie congenital neuronal ceroid-lipofuscinosis (cNCL, also known as CLN10), a devastating neurodegenerative disease. CLN10 patients die within the first few days of life, and in the few patients who live into adulthood psychopathological symptoms have not been reported. Extensive neuropathology and altered neurotransmission have been reported in CTSD-deficient mice; however signs of neuropsychiatric behavior in these mice are not well characterized due to the severe movement disorder and premature death of the animal. In the present study, we show that heterozygous CTSD-deficient (CTSD HET) mice display an overall behavioral profile that is similar to human mania, including hyperlocomotion, d-amphetamine-induced hyperactivity, sleep-disturbance, and reduced anxiety-like behavior. However, under stressful conditions CTSD HET mice manifest depressive-like behavior, including anhedonia, behavioral despair, and enhanced learned helplessness. Chronic administration of lithium chloride or valproic acid, two clinically effective mood stabilizers, reverses the majority of these behavioral abnormalities. In addition, CTSD HET mice display stress-induced hypersecretion of corticosterone. These findings suggest an important role for CTSD in the regulation of mood stabilization. Copyright © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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.

Reciprocal relationships and potential feedbacks between biodiversity and disturbance.

PubMed

Hughes, A Randall; Byrnes, Jarrett E; Kimbro, David L; Stachowicz, John J

2007-09-01

Two major foci of ecological research involve reciprocal views of the relationship between biodiversity and disturbance: disturbance determines community diversity or diversity determines realized disturbance severity. Here, we present an initial attempt to synthesize these two approaches in order to understand whether feedbacks occur, and what their effects on patterns of diversity might be. Our review of published experiments shows that (i) disturbance severity can be both a cause and a consequence of local diversity in a wide range of ecosystems and (ii) shapes of the unidirectional relationships between diversity and disturbance can be quite variable. To explore how feedbacks between diversity and disturbance might operate to alter expected patterns of diversity in nature, we develop and then evaluate a conceptual model that decomposes the relationships into component parts, considering sequentially the effect of diversity on disturbance severity, and the effect of realized disturbance on diversity loss, subsequent recruitment, and competitive exclusion. Our model suggests that feedbacks can increase mean values of richness, decrease variability, and alter the patterns of correlation between diversity and disturbance in nature. We close by offering ideas for future research to help fill gaps in our understanding of reciprocal relationships among ecological variables like diversity and disturbance.

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

PubMed Central

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

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.

PubMed

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.

The role of recurrent disturbances for ecosystem multifunctionality.

PubMed

Villnäs, Anna; Norkko, Joanna; Hietanen, Susanna; Josefson, Alf B; Lukkari, Kaarina; Norkko, Alf

2013-10-01

Ecosystem functioning is threatened by an increasing number of anthropogenic stressors, creating a legacy of disturbance that undermines ecosystem resilience. However, few empirical studies have assessed to what extent an ecosystem can tolerate repeated disturbances and sustain its multiple functions. By inducing increasingly recurring hypoxic disturbances to a sedimentary ecosystem, we show that the majority of individual ecosystem functions experience gradual degradation patterns in response to repetitive pulse disturbances. The degradation in overall ecosystem functioning was, however, evident at an earlier stage than for single ecosystem functions and was induced after a short pulse of hypoxia (i.e., three days), which likely reduced ecosystem resistance to further hypoxic perturbations. The increasing number of repeated pulse disturbances gradually moved the system closer to a press response. In addition to the disturbance regime, the changes in benthic trait composition as well as habitat heterogeneity were important for explaining the variability in overall ecosystem functioning. Our results suggest that disturbance-induced responses across multiple ecosystem functions can serve as a warning signal for losses of the adaptive capacity of an ecosystem, and might at an early stage provide information to managers and policy makers when remediation efforts should be initiated.

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

PubMed

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.

Proof of Heisenberg's error-disturbance relation.

PubMed

Busch, Paul; Lahti, Pekka; Werner, Reinhard F

2013-10-18

While the slogan "no measurement without disturbance" has established itself under the name of the Heisenberg effect in the consciousness of the scientifically interested public, a precise statement of this fundamental feature of the quantum world has remained elusive, and serious attempts at rigorous formulations of it as a consequence of quantum theory have led to seemingly conflicting preliminary results. Here we show that despite recent claims to the contrary [L. Rozema et al, Phys. Rev. Lett. 109, 100404 (2012)], Heisenberg-type inequalities can be proven that describe a tradeoff between the precision of a position measurement and the necessary resulting disturbance of momentum (and vice versa). More generally, these inequalities are instances of an uncertainty relation for the imprecisions of any joint measurement of position and momentum. Measures of error and disturbance are here defined as figures of merit characteristic of measuring devices. As such they are state independent, each giving worst-case estimates across all states, in contrast to previous work that is concerned with the relationship between error and disturbance in an individual state.

Freestream Effects on Boundary Layer Disturbances for HIFiRE-5 (Postprint)

DTIC Science & Technology

2015-01-01

hypersonic wind tunnel . For Mach 6.5 and 7, there was no evidence of traveling crossflow waves . However, higher-frequency disturbances were observed. These...disturbances. The structure of these disturbances (phase velocity and wave angle) is similar in both wind tunnels . Coherence measurements in the ACE show that...These include detailed mapping of disturbance fields in the wind tunnel , including higher-frequency measurements, multi-point probe mea- surements to

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

PubMed Central

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

Microbial Mat Compositional and Functional Sensitivity to Environmental Disturbance

PubMed Central

Preisner, Eva C.; Fichot, Erin B.; Norman, Robert S.

2016-01-01

The ability of ecosystems to adapt to environmental perturbations depends on the duration and intensity of change and the overall biological diversity of the system. While studies have indicated that rare microbial taxa may provide a biological reservoir that supports long-term ecosystem stability, how this dynamic population is influenced by environmental parameters remains unclear. In this study, a microbial mat ecosystem located on San Salvador Island, The Bahamas was used as a model to examine how environmental disturbance affects the protein synthesis potential (PSP) of rare and abundant archaeal and bacterial communities and how these changes impact potential biogeochemical processes. This ecosystem experienced a large shift in salinity (230 to 65 g kg-1) during 2011–2012 following the landfall of Hurricane Irene on San Salvador Island. High throughput sequencing and analysis of 16S rRNA and rRNA genes from samples before and after the pulse disturbance showed significant changes in the diversity and PSP of abundant and rare taxa, suggesting overall compositional and functional sensitivity to environmental change. In both archaeal and bacterial communities, while the majority of taxa showed low PSP across conditions, the overall community PSP increased post-disturbance, with significant shifts occurring among abundant and rare taxa across and within phyla. Broadly, following the post-disturbance reduction in salinity, taxa within Halobacteria decreased while those within Crenarchaeota, Thaumarchaeota, Thermoplasmata, Cyanobacteria, and Proteobacteria, increased in abundance and PSP. Quantitative PCR of genes and transcripts involved in nitrogen and sulfur cycling showed concomitant shifts in biogeochemical cycling potential. Post-disturbance conditions increased the expression of genes involved in N-fixation, nitrification, denitrification, and sulfate reduction. Together, our findings show complex community adaptation to environmental change and help

Joint pathology and behavioral performance in autoimmune MRL-lpr Mice.

PubMed

Sakić, B; Szechtman, H; Stead, R H; Denburg, J A

1996-09-01

Young autoimmune MRL-lpr mice perform more poorly than age-matched controls in tests of exploration, spatial learning, and emotional reactivity. Impaired behavioral performance coincides temporally with hyperproduction of autoantibodies, infiltration of lymphoid cells into the brain, and mild arthritic-like changes in hind paws. Although CNS mechanisms have been suggested to mediate behavioral deficits, it was not clear whether mild joint pathology significantly affected behavioral performance. Previously we observed that 11-week-old MRL-lpr mice showed a trend for disturbed performance when crossing a narrow beam. The first aim of the present study was to test the significance of this trend by increasing the sample size and, second, to examine the possibility that arthritis-like changes interfere with performance in brief locomotor tasks. For the purpose of the second goal, 18-week-old mice that differ widely in severity of joint disease were selectively taken from the population and tested in beam walking and swimming tasks. It was expected that the severity of joint inflammation would be positively correlated with the degree of locomotor impairment. The larger sample size revealed that young MRL-lpr mice perform significantly more poorly than controls on the beam-walking test, as evidenced by more foot slips and longer traversing time. However, significant correlation between joint pathology scores and measures of locomotion could not be detected. The lack of such relationship suggests that mild joint pathology does not significantly contribute to impaired performance in young, autoimmune MRL-lpr mice tested in short behavioral tasks.

Non-senescent Hydra tolerates severe disturbances in the nuclear lamina

PubMed Central

Rehm, Arvid; Wittlieb, Jörg; Herbst, Eva-Maria; Benavente, Ricardo

2018-01-01

The cnidarian Hydra is known for its unlimited lifespan and non-senescence, due to the indefinite self-renewal capacity of its stem cells. While proteins of the Lamin family are recognized as critical factors affecting senescence and longevity in human and mice, their putative role in the extreme longevity and non-senescence in long-living animals remains unknown. Here we analyze the role of a single lamin protein in non-senescence of Hydra. We demonstrate that proliferation of stem cells in Hydra is robust against the disturbance of Lamin expression and localization. While Lamin is indispensable for Hydra, the stem cells tolerate overexpression, downregulation and mislocalization of Lamin, and disturbances in the nuclear envelope structure. This extraordinary robustness may underlie the indefinite self-renewal capacity of stem cells and the non-senescence of Hydra. A relatively low complexity of the nuclear envelope architecture in basal Metazoa might allow for their extreme lifespans, while an increasing complexity of the nuclear architecture in bilaterians resulted in restricted lifespans. PMID:29754147

Forest disturbances under climate change

NASA Astrophysics Data System (ADS)

Seidl, Rupert; Thom, Dominik; Kautz, Markus; Martin-Benito, Dario; Peltoniemi, Mikko; Vacchiano, Giorgio; Wild, Jan; Ascoli, Davide; Petr, Michal; Honkaniemi, Juha; Lexer, Manfred J.; Trotsiuk, Volodymyr; Mairota, Paola; Svoboda, Miroslav; Fabrika, Marek; Nagel, Thomas A.; Reyer, Christopher P. O.

2017-06-01

Forest disturbances are sensitive to climate. However, our understanding of disturbance dynamics in response to climatic changes remains incomplete, particularly regarding large-scale patterns, interaction effects and dampening feedbacks. Here we provide a global synthesis of climate change effects on important abiotic (fire, drought, wind, snow and ice) and biotic (insects and pathogens) disturbance agents. Warmer and drier conditions particularly facilitate fire, drought and insect disturbances, while warmer and wetter conditions increase disturbances from wind and pathogens. Widespread interactions between agents are likely to amplify disturbances, while indirect climate effects such as vegetation changes can dampen long-term disturbance sensitivities to climate. Future changes in disturbance are likely to be most pronounced in coniferous forests and the boreal biome. We conclude that both ecosystems and society should be prepared for an increasingly disturbed future of forests.

Forest disturbances under climate change

PubMed Central

Seidl, Rupert; Thom, Dominik; Kautz, Markus; Martin-Benito, Dario; Peltoniemi, Mikko; Vacchiano, Giorgio; Wild, Jan; Ascoli, Davide; Petr, Michal; Honkaniemi, Juha; Lexer, Manfred J.; Trotsiuk, Volodymyr; Mairota, Paola; Svoboda, Miroslav; Fabrika, Marek; Nagel, Thomas A.; Reyer, Christopher P. O.

2017-01-01

Forest disturbances are sensitive to climate. However, our understanding of disturbance dynamics in response to climatic changes remains incomplete, particularly regarding large-scale patterns, interaction effects and dampening feedbacks. Here we provide a global synthesis of climate change effects on important abiotic (fire, drought, wind, snow and ice) and biotic (insects and pathogens) disturbance agents. Warmer and drier conditions particularly facilitate fire, drought and insect disturbances, while warmer and wetter conditions increase disturbances from wind and pathogens. Widespread interactions between agents are likely to amplify disturbances, while indirect climate effects such as vegetation changes can dampen long-term disturbance sensitivities to climate. Future changes in disturbance are likely to be most pronounced in coniferous forests and the boreal biome. We conclude that both ecosystems and society should be prepared for an increasingly disturbed future of forests. PMID:28861124

Recovery of lotic macroinvertebrate communities from disturbance

NASA Astrophysics Data System (ADS)

Wallace, J. Bruce

1990-09-01

Ecosystem disturbances produce changes in macrobenthic community structure (abundances, biomass, and production) that persist for a few weeks to many decades. Examples of disturbances with extremely long-term effects on benthic communities include contamination by persistent toxic agents, physical changes in habitats, and altered energy inputs. Stream size, retention, and local geomorphology may ameliorate the influence of disturbances on invertebrates. Disturbances can alter food webs and may select for favorable genotypes (e.g., insecticidal resistance). Introductions of pesticides into lotic ecosystems, which do not result in major physical changes within habitats, illustrate several factors that influence invertebrate recovery time from disturbance. These include: (1) magnitude of original contamination, toxicity, and extent of continued use; (2) spatial scale of the disturbance; (3) persistence of the pesticide; (4) timing of the contamination in relation to the life history stages of the organisms; (5) vagility of populations influenced by pesticides; and (6) position within the drainage network. The ability of macroinvertebrates to recolonize denuded stream habitats may vary greatly depending on regional life histories, dispersal abilities, and position within the stream network (e.g., headwaters vs larger rivers). Although downstream drift is the most frequently cited mechanism of invertebrate recolonization following disturbance in middle- and larger-order streams, evidence is presented that shows aerial recolonization to be potentially important in headwater streams. There is an apparent stochastic element operating for aerial recolonization, depending on the timing of disturbance and flight periods of various taxa. Available evidence indicates that recolonization of invertebrate taxa without an aerial adult stage requires longer periods of time than for those that possess winged, terrestrial adult stages (i.e., most insects). Innovative, manipulative

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

PubMed Central

Alkathiri, Badriah; Metwally, Dina M.; Al-Olayan, Ebtesam M.; Bakhrebah, Muhammed A.

2017-01-01

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. PMID:29258248

Anthropogenic disturbance homogenizes seagrass fish communities.

PubMed

Iacarella, Josephine C; Adamczyk, Emily; Bowen, Dan; Chalifour, Lia; Eger, Aaron; Heath, William; Helms, Sibylla; Hessing-Lewis, Margot; Hunt, Brian P V; MacInnis, Andrew; O'Connor, Mary I; Robinson, Clifford L K; Yakimishyn, Jennifer; Baum, Julia K

2018-05-01

Anthropogenic activities have led to the biotic homogenization of many ecological communities, yet in coastal systems this phenomenon remains understudied. In particular, activities that locally affect marine habitat-forming foundation species may perturb habitat and promote species with generalist, opportunistic traits, in turn affecting spatial patterns of biodiversity. Here, we quantified fish diversity in seagrass communities across 89 sites spanning 6° latitude along the Pacific coast of Canada, to test the hypothesis that anthropogenic disturbances homogenize (i.e., lower beta-diversity) assemblages within coastal ecosystems. We test for patterns of biotic homogenization at sites within different anthropogenic disturbance categories (low, medium, and high) at two spatial scales (within and across regions) using both abundance- and incidence-based beta-diversity metrics. Our models provide clear evidence that fish communities in high anthropogenic disturbance seagrass areas are homogenized relative to those in low disturbance areas. These results were consistent across within-region comparisons using abundance- and incidence-based measures of beta-diversity, and in across-region comparisons using incidence-based measures. Physical and biotic characteristics of seagrass meadows also influenced fish beta-diversity. Biotic habitat characteristics including seagrass biomass and shoot density were more differentiated among high disturbance sites, potentially indicative of a perturbed environment. Indicator species and trait analyses revealed fishes associated with low disturbance sites had characteristics including stenotopy, lower swimming ability, and egg guarding behavior. Our study is the first to show biotic homogenization of fishes across seagrass meadows within areas of relatively high human impact. These results support the importance of targeting conservation efforts in low anthropogenic disturbance areas across land- and seascapes, as well as managing

Immunopathological Changes in the Brain of Immunosuppressed Mice Experimentally Infected with Toxocara canis

PubMed Central

Eid, Mohamed M.; El-Kowrany, Samy I.; Othman, Ahmad A.; Gendy, Dina I. El; Saied, Eman M.

2015-01-01

Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection. PMID:25748709

Disturbed vesicular trafficking of membrane proteins in prion disease.

PubMed

Uchiyama, Keiji; Miyata, Hironori; Sakaguchi, Suehiro

2013-01-01

The pathogenic mechanism of prion diseases remains unknown. We recently reported that prion infection disturbs post-Golgi trafficking of certain types of membrane proteins to the cell surface, resulting in reduced surface expression of membrane proteins and abrogating the signal from the proteins. The surface expression of the membrane proteins was reduced in the brains of mice inoculated with prions, well before abnormal symptoms became evident. Prions or pathogenic prion proteins were mainly detected in endosomal compartments, being particularly abundant in recycling endosomes. Some newly synthesized membrane proteins are delivered to the surface from the Golgi apparatus through recycling endosomes, and some endocytosed membrane proteins are delivered back to the surface through recycling endosomes. These results suggest that prions might cause neuronal dysfunctions and cell loss by disturbing post-Golgi trafficking of membrane proteins via accumulation in recycling endosomes. Interestingly, it was recently shown that delivery of a calcium channel protein to the cell surface was impaired and its function was abrogated in a mouse model of hereditary prion disease. Taken together, these results suggest that impaired delivery of membrane proteins to the cell surface is a common pathogenic event in acquired and hereditary prion diseases.

Behavioral alterations in cystic fibrosis mice are prevented by cannabinoid treatment in infancy.

PubMed

Bregman, Tatiana; Fride, Ester

2011-06-17

Substantial data have been accumulated regarding the molecular basis of cystic fibrosis (CF) pathogenesis, whereas the influence of biochemical impairments on brain processes has been the focus of much less attention. We have studied some behavioral parameters, such as motor activity and anxiety level, in a mice model of CF. We have assumed that functioning of the endocannabinoid system could be impaired in CF (endocannabinoids are fatty acid derivatives, and fatty acid deficiency is considered a major factor in CF etiology). We have suggested that chronic treatment with cannabinoid receptors agonist during infancy would balance cannabinoid levels and prevent CF-related behavioral alterations. Motor activity and anxiety level were studied in naïve adult CF mice (cftr-deficient mice) and compared with wild-type mice and to CF mice treated chronically with Δ9-tetrahydrocannabinol (Δ9-THC; endocannabinoid receptor agonist) during infancy (from days 7 to 28). Motor activity was tested in the tetrad, and level of anxiety in the plus maze, a month after cessation of treatment. Motor activity decrease and elevated anxiety level were found in adult naïve CF mice compared with wild-type mice. CF mice treated with THC in infancy showed normal motor activity and anxiety levels in adulthood. Motor function alteration and elevated anxiety levels in CF can result from lack of CFTR-channel in neurons and disturbed activity of various brain areas, as well as being secondary and mediated by fatty acids deficiency, altered levels of endocannabinoids and their receptors. It can be suggested that chronic treatment during infancy restores endocannabinoid function and thus prevents behavioral alterations.

Disturbance observer based pitch control of wind turbines for disturbance rejection

NASA Astrophysics Data System (ADS)

Yuan, Yuan; Chen, Xu; Tang, Jiong

2016-04-01

In this research, a disturbance observer based (DOB) control scheme is illustrated to reject the unknown low frequency disturbances to wind turbines. Specifically, we aim at maintaining the constant output power but achieving better generator speed regulation when the wind turbine is operated at time-varying and turbulent wind field. The disturbance observer combined with a filter is designed to asymptotically reject the persistent unknown time-varying disturbances. The proposed algorithm is tested in both linearized and nonlinear NREL offshore 5-MW baseline wind turbine. The application of this DOB pitch controller achieves improved power and speed regulation in Region 3 compared with a baseline gain scheduling PID collective controller both in linearized and nonlinear plant.

Receptivity and Forced Response to Acoustic Disturbances in High-Speed Boundary Layers

NASA Technical Reports Server (NTRS)

Balakumar, P.; King, Rudolph A.; Chou, Amanda; Owens, Lewis R.; Kegerise, Michael A.

2016-01-01

Supersonic boundary-layer receptivity to freestream acoustic disturbances is investigated by solving the Navier-Stokes equations for Mach 3.5 flow over a sharp flat plate and a 7-deg half-angle cone. The freestream disturbances are generated from a wavy wall placed at the nozzle wall. The freestream acoustic disturbances radiated by the wavy wall are obtained by solving the linearized Euler equations. The results for the flat plate show that instability modes are generated at all the incident angles ranging from zero to highly oblique. However, the receptivity coefficient decreases by about 20 times when the incident angle increases from zero to a highly oblique angle of 68 degrees. The results for the cone show that no instability modes are generated when the acoustic disturbances impinge the cone obliquely. The results show that the perturbations generated inside the boundary layer by the acoustic disturbances are the response of the boundary layer to the external forcing. The amplitude of the forced disturbances inside the boundary layer are about 2.5 times larger than the incoming field for zero azimuthal wavenumber and they are about 1.5 times for large azimuthal wavenumbers.

Wildfire disturbance impacts on streamflow from western USA watersheds

NASA Astrophysics Data System (ADS)

Cadol, D.; Wine, M.; Makhnin, O.

2017-12-01

Worldwide rapid changes in climate overlaid on changing land management paradigms have dramatically altered ecological disturbance regimes worldwide including in western North America. Ecological disturbances impacted include woody encroachment, pest pathogen complexes, riparian forest changes, and wildfire. These disturbances impact the hydrologic cycle, though the nature of these impacts has been difficult to quantify. Perhaps the greatest challenge is that most basins worldwide are ungauged. Taking wildfire as a globally relevant example of a key ecological disturbance, even within gauged basins, post-wildfire hydrologic response is spatially and temporally variable, affected by a host of variables including fire frequency, area burned, and recovery trajectory. Hydrologic response to wildfire is further understood to be a non-linear function of watershed characteristics and climate. Here we provide a framework that utilizes remote sensing, statistical modeling, field measurements, and geospatial methods to provide first-order estimates of ecological disturbance hydrologic impacts. We apply this framework to compare ecological disturbance hydrologic impacts amongst selected watersheds in the western USA. Here we show that ecological disturbance impacts on hydrology are highly variable, and in many cases have an effect magnitude similar to that modeled for temperature and precipitation changes.

Clinical investigation of the lesions responsible for sensory disturbance in Minamata disease.

PubMed

Uchino, M; Mita, S; Satoh, H; Hirano, T; Arimura, K; Nakagawa, M; Nakamura, M; Uyama, E; Ando, Y; Wakamiya, J; Futatsuka, M

2001-11-01

To clarify the lesions responsible for sensory disturbance in Minamata disease (MD), we clinically investigated the characteristics of sensory disturbance. In all patients with the classical type MD, two-point discrimination was severely disturbed, but the involvement of superficial sensation was relatively mild. On short-latency somatosensory evoked potential study, the component corresponding to N20 was completely absent with normal N9, N11, and N13 components. Although 14 of 38 chronic MD patients demonstrated intact superficial sensation, 10 of these 14 showed mild to moderate disturbance in two-point discrimination. The two-point discrimination in chronic MD patients was significantly high irrespective of the disturbance of superficial sensation. These findings suggest that the sensory disturbance of MD patients may mainly be caused by a lesion in the sensory cortex rather than in the peripheral nerves. However, other foci could be also responsible for the sensory impairment, since 9 of 38 chronic MD patients showed intact two-point discrimination.

YAC128 Huntington's disease transgenic mice show enhanced short-term hippocampal synaptic plasticity early in the course of the disease.

PubMed

Ghilan, Mohamed; Bostrom, Crystal A; Hryciw, Brett N; Simpson, Jessica M; Christie, Brian R; Gil-Mohapel, Joana

2014-09-18

Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by a polyglutamine expansion in the gene encoding the protein huntingtin. The disease progresses over decades, but often patients develop cognitive impairments that precede the onset of the classical motor symptoms. Similar to the disease progression in humans, the yeast artificial chromosome (YAC) 128 HD mouse model also exhibits cognitive dysfunction that precedes the onset of the neuropathological and motor impairments characteristic of HD. Thus, the purpose of this study was to evaluate whether short- and long-term synaptic plasticity in the hippocampus, two related biological models of learning and memory processes, were altered in YAC128 mice in early stages of disease progression. We show that the YAC128 hippocampal dentate gyrus (DG) displays marked reductions in paired-pulse depression both at 3 and 6 months of age. In addition, significantly enhanced post-tetanic and short-term potentiation are apparent in YAC128 mice after high-frequency stimulation at this time. Early and late forms of long-term plasticity were not altered at this stage. Together these findings indicate that there may be elevated neurotransmitter release in response to synaptic stimulation in YAC128 mice during the initial phase of disease progression. These abnormalities in short-term plasticity detected at this stage in YAC128 HD transgenic mice indicate that aberrant information processing at the level of the synapses may contribute, at least in part, to the early onset of cognitive deficits that are characteristic of this devastating neurodegenerative disorder. Copyright © 2014 Elsevier B.V. All rights reserved.

Gene therapy improves dental manifestations in hypophosphatasia model mice.

PubMed

Okawa, R; Iijima, O; Kishino, M; Okawa, H; Toyosawa, S; Sugano-Tajima, H; Shimada, T; Okada, T; Ozono, K; Ooshima, T; Nakano, K

2017-06-01

Hypophosphatasia is a rare inherited skeletal disorder characterized by defective bone mineralization and deficiency of tissue non-specific alkaline phosphatase (TNSALP) activity. The disease is caused by mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL) encoding TNSALP. Early exfoliation of primary teeth owing to disturbed cementum formation, periodontal ligament weakness and alveolar bone resorption are major complications encountered in oral findings, and discovery of early loss of primary teeth in a dental examination often leads to early diagnosis of hypophosphatasia. Although there are no known fundamental treatments or effective dental approaches to prevent early exfoliation of primary teeth in affected patients, several possible treatments have recently been described, including gene therapy. Gene therapy has also been applied to TNSALP knockout mice (Alpl -/- ), which phenocopy the infantile form of hypophosphatasia, and improved their systemic condition. In the present study, we investigated whether gene therapy improved the dental condition of Alpl -/- mice. Following sublethal irradiation (4 Gy) at the age of 2 d, Alpl -/- mice underwent gene therapy using bone marrow cells transduced with a lentiviral vector expressing a bone-targeted form of TNSALP injected into the jugular vein (n = 3). Wild-type (Alpl +/+ ), heterozygous mice (Alpl +/- ) and Alpl -/- mice were analyzed at 9 d of age (n = 3 of each), while Alpl +/+ mice and treated or untreated Alpl -/- mice were analyzed at 1 mo of age (n = 3 of each), and Alpl +/- mice and Alpl -/- mice with gene therapy were analyzed at 3 mo of age (n = 3 of each). A single mandibular hemi-section obtained at 1 mo of age was analyzed using a small animal computed tomography machine to assess alveolar bone formation. Other mandibular hemi-sections obtained at 9 d, 1 mo and 3 mo of age were subjected to hematoxylin and eosin staining and immunohistochemical analysis of osteopontin, a marker of

Tcf4 transgenic female mice display delayed adaptation in an auditory latent inhibition paradigm.

PubMed

Brzózka, M M; Rossner, M J; de Hoz, L

2016-09-01

Schizophrenia (SZ) is a severe mental disorder affecting about 1 % of the human population. Patients show severe deficits in cognitive processing often characterized by an improper filtering of environmental stimuli. Independent genome-wide association studies confirmed a number of risk variants for SZ including several associated with the gene encoding the transcription factor 4 (TCF4). TCF4 is widely expressed in the central nervous system of mice and humans and seems to be important for brain development. Transgenic mice overexpressing murine Tcf4 (Tcf4tg) in the adult brain display cognitive impairments and sensorimotor gating disturbances. To address the question of whether increased Tcf4 gene dosage may affect cognitive flexibility in an auditory associative task, we tested latent inhibition (LI) in female Tcf4tg mice. LI is a widely accepted translational endophenotype of SZ and results from a maladaptive delay in switching a response to a previously unconditioned stimulus when this becomes conditioned. Using an Audiobox, we pre-exposed Tcf4tg mice and their wild-type littermates to either a 3- or a 12-kHz tone before conditioning them to a 12-kHz tone. Tcf4tg animals pre-exposed to a 12-kHz tone showed significantly delayed conditioning when the previously unconditioned tone became associated with an air puff. These results support findings that associate TCF4 dysfunction with cognitive inflexibility and improper filtering of sensory stimuli observed in SZ patients.

Metabolic, Reproductive, and Neurologic Abnormalities in Agpat1-Null Mice.

PubMed

Agarwal, Anil K; Tunison, Katie; Dalal, Jasbir S; Nagamma, Sneha S; Hamra, F Kent; Sankella, Shireesha; Shao, Xinli; Auchus, Richard J; Garg, Abhimanyu

2017-11-01

Defects in the biosynthesis of phospholipids and neutral lipids are associated with cell membrane dysfunction, disrupted energy metabolism, and diseases including lipodystrophy. In these pathways, the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) enzymes transfer a fatty acid to the sn-2 carbon of sn-1-acylglycerol-3-phosphate (lysophosphatidic acid) to form sn-1, 2-acylglycerol-3-phosphate [phosphatidic acid (PA)]. PA is a precursor for key phospholipids and diacylglycerol. AGPAT1 and AGPAT2 are highly homologous isoenzymes that are both expressed in adipocytes. Genetic defects in AGPAT2 cause congenital generalized lipodystrophy, indicating that AGPAT1 cannot compensate for loss of AGPAT2 in adipocytes. To further explore the physiology of AGPAT1, we characterized a loss-of-function mouse model (Agpat1-/-). The majority of Agpat1-/- mice died before weaning and had low body weight and low plasma glucose levels, independent of plasma insulin and glucagon levels, with reduced percentage of body fat but not generalized lipodystrophy. These mice also had decreased hepatic messenger RNA expression of Igf-1 and Foxo1, suggesting a decrease in gluconeogenesis. In male mice, sperm development was impaired, with a late meiotic arrest near the onset of round spermatid production, and gonadotropins were elevated. Female mice showed oligoanovulation yet retained responsiveness to gonadotropins. Agpat1-/- mice also demonstrated abnormal hippocampal neuron development and developed audiogenic seizures. In summary, Agpat1-/- mice developed widespread disturbances of metabolism, sperm development, and neurologic function resulting from disrupted phospholipid homeostasis. AGPAT1 appears to serve important functions in the physiology of multiple organ systems. The Agpat1-deficient mouse provides an important model in which to study the contribution of phospholipid and triacylglycerol synthesis to physiology and diseases. Copyright © 2017 Endocrine Society.

Laser stimulating ST36 with optical fiber induce blood component changes in mice: a Raman spectroscopy study.

PubMed

Zhang, Heng; Chen, Zhenyi; Wu, Jiping; Chen, Na; Xu, Wenjie; Li, Taihao; Liu, Shupeng

2018-02-15

ST36 is a commonly-used acupoint in traditional Chinese medicine (TCM) for treatment of inflammations, pains and gastrointestinal disturbs. For decades, the low power laser acupuncture has been widely applied as an alternative therapy to traditional metal needle acupuncture and achieved relatively fine therapeutic effect for ST36-related symptoms with reduction of uncomfortableness and infection risks. However its disadvantages of low penetrativity and lack of manipulation skills limit its potential performance. An optical fiber laser acupuncture introduced by the previous study combines traditional needling acupuncture and the laser stimulation together, making a stronger therapeutic effect and showing a potential value in clinical application. To evaluate its acupunctural effect on blood, mice are taken as experimental model and Raman spectroscopic technique is used to analysis the changes of blood components after stimulating on ST36. The results show that both the traditional needling acupuncture and optical fiber acupuncture could lead to some spectral changes of blood in mice. This study explores the optical fiber acupuncture's effect on blood in mice using Raman spectroscopy technique for mechanism of acupuncture therapy. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Trigeminal Ganglion Neurons of Mice Show Intracellular Chloride Accumulation and Chloride-Dependent Amplification of Capsaicin-Induced Responses

PubMed Central

Schöbel, Nicole; Radtke, Debbie; Lübbert, Matthias; Gisselmann, Günter; Lehmann, Ramona; Cichy, Annika; Schreiner, Benjamin S. P.; Altmüller, Janine; Spector, Alan C.; Spehr, Jennifer; Hatt, Hanns; Wetzel, Christian H.

2012-01-01

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 Ca2+ transients in a corresponding fraction of TG neurons. Ca2+ transients were sensitive to inhibition of NKCC1 and voltage-gated Ca2+ channels (VGCCs). Ca2+ 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 Ca2+-activated Cl− channels (CaCCs) in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca2+ 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 Ca2+-activated Cl−-dependent signal amplification mechanism in TG neurons that requires intracellular Cl− accumulation by NKCC1 and the activation of CaCCs. PMID:23144843

Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice.

PubMed

Dorighello, Gabriel G; Rovani, Juliana C; Luhman, Christopher J F; Paim, Bruno A; Raposo, Helena F; Vercesi, Anibal E; Oliveira, Helena C F

2014-03-28

Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-α and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia.

Elegant anti-disturbance control for discrete-time stochastic systems with nonlinearity and multiple disturbances

NASA Astrophysics Data System (ADS)

Wei, Xinjiang; Sun, Shixiang

2018-03-01

An elegant anti-disturbance control (EADC) strategy for a class of discrete-time stochastic systems with both nonlinearity and multiple disturbances, which include the disturbance with partially known information and a sequence of random vectors, is proposed in this paper. A stochastic disturbance observer is constructed to estimate the disturbance with partially known information, based on which, an EADC scheme is proposed by combining pole placement and linear matrix inequality methods. It is proved that the two different disturbances can be rejected and attenuated, and the corresponding desired performances can be guaranteed for discrete-time stochastic systems with known and unknown nonlinear dynamics, respectively. Simulation examples are given to demonstrate the effectiveness of the proposed schemes compared with some existing results.

Absence of collagen IX accelerates hypertrophic differentiation in the embryonic mouse spine through a disturbance of the Ihh-PTHrP feedback loop.

PubMed

Kamper, Matthias; Paulsson, Mats; Zaucke, Frank

2017-02-01

Collagen IX (Col IX) is a component of the cartilage extracellular matrix and contributes to its structural integrity. Polymorphisms in the genes encoding the Col IX ɑ2- and ɑ3-chains are associated with early onset of disc degeneration. Col IX-deficient mice already display changes in the spine at the newborn stage and premature disc degeneration starting at 6 months of age. To determine the role of Col IX in early spine development and to identify molecular mechanisms underlying disc degeneration, the embryonic development of the spine was analyzed in Col IX -/- mice. Histological staining was used to show tissue morphology at different time points. Localization of extracellular matrix proteins as well as components of signaling pathways were analyzed by immunohistochemistry. Developing vertebral bodies of Col IX -/- mice were smaller and already appeared more compact at E12.5. At E15.5, vertebral bodies of Col IX -/- mice revealed an increased number of hypertrophic chondrocytes as well as enhanced staining for the terminal differentiation markers alkaline phosphatase and collagen X. This correlates with an imbalance in the Ihh-PTHrP signaling pathway at this time point, reflected by an increase of Ihh and a concomitant decrease of PTHrP expression. An accelerated hypertrophic differentiation caused by a disturbed Ihh-PTHrP signaling pathway may lead to a higher bone mineral density in the vertebral bodies of newborn Col IX -/- mice and, as a result, to the early onset of disc degeneration.

N-Acetyl-Cysteine Alleviates Gut Dysbiosis and Glucose Metabolic Disorder in High-Fat Diet-Induced Mice.

PubMed

Zheng, Junping; Yuan, Xubing; Zhang, Chen; Jia, Peiyuan; Jiao, Siming; Zhao, Xiaoming; Yin, Heng; Du, Yuguang; Liu, Hongtao

2018-05-30

N-acetyl cysteine (NAC), an anti-oxidative reagent for clinical diseases, shows potential application to diabetes and other metabolic diseases. However, it is unknown how NAC modulates the gut microbiota of mice with metabolic syndrome. In present study, we aim to demonstrate the preventive effect of NAC on intestinal dysbiosis and glucose metabolic disorder. C57BL/6J mice were fed with normal chow diet (NCD), NCD plus NAC, high-fat diet (HFD) or HFD plus NAC for five months. After the treatment, the glucose level, circulating endotoxin and metabolism-related key proteins were determined. The fecal samples were analyzed by 16S rRNA sequencing. A novel analysis was carried out to predict the functional changes of gut microbiota. In addition, Spearman's correlation between metabolic biomarkers and bacterial abundance was also assayed. The results show that NAC treatment significantly reversed the glucose intolerance, fasting glucose level, body weight and plasma endotoxin in HFD-fed mice. Further, NAC upregulated the levels of Occludin protein and mucin glycoproteins in proximal colons of HFD-treated mice. Noticeably, NAC promoted the growth of beneficial bacteria such as Akkermansia, Bifidobacterium, Lactobacillus and Allobaculum, and hampered the population of diabetes-related genera including Desulfovibrio and Blautia. Also, NAC may influence the metabolic pathways of intestinal bacteria including lipopolysaccharide biosynthesis, oxidative stress and bacterial motility. Finally, the modified gut microbiota showed close association with the metabolic changes of the NAC treated HFD-fed mice. In summary, NAC may be a potential drug to prevent glucose metabolic disturbance by reshaping the structure of gut microbiota. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Forest development leading to disturbances

Treesearch

Clinton E. Carlson; Stephen F. Arno; Jimmie Chew; Catherine A. Stewart

1995-01-01

Natural disturbance in western U.S.A. forest ecosystems is related to forest succession, growth, and structural development. Natural disturbance may be biotic (insects and diseases) or abiotic (fire, wind, avalanche, etc.). Natural disturbances are more appropriately thought of as natural processes; disturbance is a social connotation implicating economic loss. Forest...

Map showing areas of visible land disturbances caused by two military training operations in the Mojave Desert, California

USGS Publications Warehouse

Prose, D.V.

1986-01-01

Land disturbances caused by these training exercises are still evident today throughout the designated training areas (Lathrop, 1983; Prose, 1985; Prose and Metzger, 1985). The World War II base-camp locations are easily identified because the networks of dirt roads are still used by campers, hunters, artifact seekers, and other visitors. Vehicle trails and single tracks remain on many relatively stable surfaces and are most conspicuous on surfaces composed of a veneer of stones (desert pavement).

Pregabalin Versus Pramipexole: Effects on Sleep Disturbance in Restless Legs Syndrome

PubMed Central

Garcia-Borreguero, Diego; Patrick, Jeffrey; DuBrava, Sarah; Becker, Philip M.; Lankford, Alan; Chen, Crystal; Miceli, Jeffrey; Knapp, Lloyd; Allen, Richard P.

2014-01-01

Study Objectives: To compare pregabalin versus placebo and pramipexole for reducing restless legs syndrome (RLS)-related sleep disturbance. Design: Randomized, double-blinded, crossover trial. Setting: Twenty-three US sleep centers. Participants: Eighty-five individuals with moderate to severe idiopathic RLS and associated sleep disturbance. Interventions: Participants were randomized across 6 treatment sequences comprising three 4-week periods on pregabalin 300 mg/day (n = 75), pramipexole 0.5 mg/day (n = 76), or placebo (n = 73). Measurements and Results: Polysomnography was conducted over 2 nights at the end of each period. Primary (wake after sleep onset [WASO], pregabalin vs placebo) and key secondary endpoints were analyzed for statistical significance, with descriptive statistics for other endpoints. Pregabalin improved sleep maintenance, demonstrated by reductions in WASO (-27.1 min vs placebo [P < 0.0001]; -26.9 vs pramipexole) and number of awakenings after sleep onset (-2.7 vs placebo; -7.9 vs pramipexole [P < 0.0001]) by polysomnography, and an increase in subjective total sleep time (30.8 min vs placebo [P < 0.0001]; 26.8 vs pramipexole). Pregabalin also increased slow wave sleep duration (20.9 min vs placebo; 32.1 vs pramipexole [P < 0.0001]). Reduction in periodic limb movement arousal index (PLMAI) with pregabalin was similar to pramipexole and greater than placebo (-3.7 PLMA/h [P < 0.0001]), although reduction in total PLM in sleep was less than for pramipexole. Conclusions: This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole. Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole. Trial Registration: ClinicalTrials.gov identifier, NCT00991276; http://clinicaltrials.gov/show/NCT00991276 Citation: Garcia-Borreguero D; Patrick J; DuBrava S; Becker PM; Lankford A; Chen C; Miceli J; Knapp L; Allen

[Effect of trampling disturbance on soil infiltration of biological soil crusts].

PubMed

Shi, Ya Fang; Zhao, Yun Ge; Li, Chen Hui; Wang, Shan Shan; Yang, Qiao Yun; Xie, Shen Qi

2017-10-01

The effect of trampling disturbance on soil infiltration of biological soil crusts was investigated by using simulated rainfall. The results showed that the trampling disturbance significantly increased soil surface roughness. The increasing extent depended on the disturbance intensity. Soil surface roughness values at 50% disturbance increased by 91% compared with the undisturbed treatment. The runoff was delayed by trampling disturbance. A linear increase in the time of runoff yield was observed along with the increasing disturbance intensity within 20%-50%. The time of runoff yield at 50% disturbance increased by 169.7% compared with the undisturbed treatment. Trampling disturbance increased soil infiltration and consequently decreased the runoff coefficient. The cumulative infiltration amount at 50% disturbance increased by 12.6% compared with the undisturbed treatment. Soil infiltration significant decreased when biocrusts were removed. The cumulative infiltration of the treatment of biocrusts removal decreased by 30.2% compared with the undisturbed treatment. Trampling disturbance did not significantly increase the soil loss when the distur bance intensity was lower than 50%, while the biocrusts removal resulted in 10 times higher in soil erosion modulus. The trampling disturbance of lower than 50% on biocrusts might improve soil infiltration and reduce the risk of runoff, thus might improve the soil moisture without obviously increa sing the soil loss.

Disturbance and California riparian tree establishment

NASA Astrophysics Data System (ADS)

Bendix, J.; Cowell, C. M.

2010-12-01

As is the case in many ecosystems, tree establishment in riparian corridors is often episodic, following disturbance events that clear colonization sites. In many riparian settings, flooding is the most obvious, and relevant disturbance agent. However, in Mediterranean-climate regions, fire is an equally important disturbance agent. In California, the frequency and severity of both floods and fire are expected to change with projected climate change, making an understanding of their roles key to understanding future ecological processes in California riparian environments. In this paper, we use tree-ring data from the Transverse Ranges of Southern California to explore the relative importance of fire and flood in the establishment of riparian gallery forest. We examined 42 cores of Alnus rhombifolia, Populus fremontii and Quercus agrifolia from the riparian zone adjacent to Piedra Blanca and Potrero John Creeks in California’s Transverse Ranges, and compared their establishment dates with records of fire and floods, to see how establishment related to disturbance history. Our results show some evidence for major fire having an impact, as all of the largest stems dated to the few years following the 1932 Matilija fire, which had burned all of the sites in our sample. The remainder of the record is less straightforward, although there is an establishment peak in the 1970s, which may be related to a 1975 fire that burned part of the Potrero John watershed. Of note, the establishment chronology shows no relationship to the flood record, as years of major floods do not relate to either prolific or sparse years in the tree-ring record. This record suggests that large fires may serve as a trigger for tree establishment in California riparian settings, but that they are hardly a prerequisite, as many stems germinated between fires. Indeed, ongoing regeneration is apparently independent of disturbance, given the apparent irrelevance of flooding in this regard. The result

Re-establishment of Anxiety in Stress-Sensitized Mice Is Caused by Monocyte Trafficking from the Spleen to the Brain

PubMed Central

Wohleb, Eric S.; McKim, Daniel B.; Shea, Daniel T.; Powell, Nicole D.; Tarr, Andrew J.; Sheridan, John F.; Godbout, Jonathan P.

2014-01-01

Background Persistent anxiety-like symptoms may have an inflammatory-related pathophysiology. Our previous work using repeated social defeat (RSD) in mice showed that recruitment of peripheral myeloid cells to the brain is required for the development of anxiety. Here, we aimed to determine if 1) RSD promotes prolonged anxiety through redistribution of myeloid cells and 2) prior exposure to RSD sensitizes the neuroimmune axis to secondary subthreshold stress. Methods Mice were subjected to RSD and several immune and behavioral parameters were determined 0.5, 8, or 24 days later. In follow-up studies, control and RSD mice were subjected to subthreshold stress at 24 days. Results Repeated social defeat-induced macrophage recruitment to the brain corresponded with development and maintenance of anxiety-like behavior 8 days after RSD, but neither remained at 24 days. Nonetheless, social avoidance and an elevated neuroinflammatory profile were maintained at 24 days. Subthreshold social defeat in RSD-sensitized mice increased peripheral macrophage trafficking to the brain that promoted re-establishment of anxiety. Moreover, subthreshold social defeat increased social avoidance in RSD-sensitized mice compared with naïve mice. Stress-induced monocyte trafficking was linked to redistribution of myeloid progenitor cells in the spleen. Splenectomy before subthreshold stress attenuated macrophage recruitment to the brain and prevented anxiety-like behavior in RSD-sensitized mice. Conclusions These data indicate that monocyte trafficking from the spleen to the brain contributes re-establishment of anxiety in stress-sensitized mice. These findings show that neuroinflammatory mechanisms promote mood disturbances following stress-sensitization and outline novel neuroimmune interactions that underlie recurring anxiety disorders such as posttraumatic stress disorder. PMID:24439304

Re-establishment of anxiety in stress-sensitized mice is caused by monocyte trafficking from the spleen to the brain.

PubMed

Wohleb, Eric S; McKim, Daniel B; Shea, Daniel T; Powell, Nicole D; Tarr, Andrew J; Sheridan, John F; Godbout, Jonathan P

2014-06-15

Persistent anxiety-like symptoms may have an inflammatory-related pathophysiology. Our previous work using repeated social defeat (RSD) in mice showed that recruitment of peripheral myeloid cells to the brain is required for the development of anxiety. Here, we aimed to determine if 1) RSD promotes prolonged anxiety through redistribution of myeloid cells and 2) prior exposure to RSD sensitizes the neuroimmune axis to secondary subthreshold stress. Mice were subjected to RSD and several immune and behavioral parameters were determined .5, 8, or 24 days later. In follow-up studies, control and RSD mice were subjected to subthreshold stress at 24 days. Repeated social defeat-induced macrophage recruitment to the brain corresponded with development and maintenance of anxiety-like behavior 8 days after RSD, but neither remained at 24 days. Nonetheless, social avoidance and an elevated neuroinflammatory profile were maintained at 24 days. Subthreshold social defeat in RSD-sensitized mice increased peripheral macrophage trafficking to the brain that promoted re-establishment of anxiety. Moreover, subthreshold social defeat increased social avoidance in RSD-sensitized mice compared with naïve mice. Stress-induced monocyte trafficking was linked to redistribution of myeloid progenitor cells in the spleen. Splenectomy before subthreshold stress attenuated macrophage recruitment to the brain and prevented anxiety-like behavior in RSD-sensitized mice. These data indicate that monocyte trafficking from the spleen to the brain contributes re-establishment of anxiety in stress-sensitized mice. These findings show that neuroinflammatory mechanisms promote mood disturbances following stress-sensitization and outline novel neuroimmune interactions that underlie recurring anxiety disorders such as posttraumatic stress disorder. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

An interactive survey panel regarding the effects of mice (Microtus spec.) on a young ecosystem

NASA Astrophysics Data System (ADS)

Zaplata, Markus; Maurer, Thomas; Boldt-Burisch, Katja; Schaaf, Wolfgang; Hinz, Christoph

2015-04-01

Apparent disturbance caused by soil megafauna took place for the very first time in 2014, after nine years of spontaneous vegetative succession of the constructed watershed Chicken Creek catchment (6 ha). This watershed was designed to investigate the initial phase of soil and ecosystem development under natural conditions including the detailed study of hydrologic processes and water-substrate-plant-atmosphere interactions. In autumn 2014, we recorded the primarily common vole (Microtus arvalis Pallas) activities (calamity), which altered the microtopography of the substrate surface: We counted mouse holes and diggings (for storage organs) at the same spatial units (permanent plots, >100 # of 5 m × 5 m) where we monitor the vegetation since the onset of the catchment. We are hence capable of analysing the effect of abundant vegetarian mice and biogenic macropores, e.g. on the occurrence and performance of the more than 150 vascular plant species present by comparing the respective coverage in 2013 (the pre-mice year) versus 2014, with or without accounting for the confounding effect of succession. Additionally elaborated insight on the 3-D architecture of the mice underground corridors and the nesting places (in situ) enables to extrapolate mass and volume of the moved substrate and the number of the nests of mice for the whole catchment. We report these results, anticipating a return service: Here, we ask for your expectation regarding the significance of the mice-made disturbance on the vegetation of the young ecosystem.

Unusual subauroral neutral wind disturbances during geomagnetic storms

NASA Astrophysics Data System (ADS)

Zhang, S.; Erickson, P. J.; Holt, J. M.

2016-12-01

Under the influence of geomagnetic storms, general circulation of the global thermosphere undergoes substantial changes that vary with latitudes. High latitude heating processes establish pressure gradients both vertically and horizontally. The equatorward wind surge and the associated westward wind enhancement are a typical disturbance wind characteristic that affacts ionosphere and thermosphere dynamics at mid-, low, and equatorial latitudes. At subauroral latitudes, however, new observations of neutral wind disturbances show some "abnormal" (unusual) behaviors in responding to complicated ion-neutral coupling processes. During the 2015 St. Patrick's Day great geomagnetic storm, incoherent scatter radar measurements at Millstone Hill show the following salient variations: (1) oscillating meridional wind disturbances with the Traveling Atmosphere Disturbance (TAD) feature; (2) vertical wind signature; (3) pre-mindnight poleward wind surges. The latter two variations appear to be associated with strong ion-neutral interaction developed during the subauroral polarization streams (SAPS) presence. Strong frictional heating caused by the relative velocity between the ions with SAPS speed and the neutrals leads to appreciable thermospheric upperwelling. Strong westward ion drifts shown as SAPS also enhance the wseward neutral flow, which subsequently causes a poleward component of the meridional wind due to the Coriolis force. This paper will present these observations of the wind and discuss ion-neutral coupling effects associated with SAPS.

Two-photon imaging in mice shows striosomes and matrix have overlapping but differential reinforcement-related responses

PubMed Central

Sur, Mriganka

2017-01-01

Striosomes were discovered several decades ago as neurochemically identified zones in the striatum, yet technical hurdles have hampered the study of the functions of these striatal compartments. Here we used 2-photon calcium imaging in neuronal birthdate-labeled Mash1-CreER;Ai14 mice to image simultaneously the activity of striosomal and matrix neurons as mice performed an auditory conditioning task. With this method, we identified circumscribed zones of tdTomato-labeled neuropil that correspond to striosomes as verified immunohistochemically. Neurons in both striosomes and matrix responded to reward-predicting cues and were active during or after consummatory licking. However, we found quantitative differences in response strength: striosomal neurons fired more to reward-predicting cues and encoded more information about expected outcome as mice learned the task, whereas matrix neurons were more strongly modulated by recent reward history. These findings open the possibility of harnessing in vivo imaging to determine the contributions of striosomes and matrix to striatal circuit function. PMID:29251596

Disturbance size and severity covary in small and mid-size wind disturbances in Pennsylvania northern hardwoods forests

Treesearch

Chris J. Peterson; Lisa M. Krueger; Alejandro A. Royo; Scott Stark; Walter P. Carson

2013-01-01

Do large disturbances differ from small ones in characteristics other than size? The importance of disturbances in forest dynamics is unquestioned, and the size of the disturbed area (size of gap) is the most common way of differentiating disturbances. But few studies have examined other disturbance characteristics to see if small and large disturbances are different....

Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao Tieqiang; Guo Jun; Li Hui

2006-03-24

Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in clinical practice. It is known to induce life-threatening acute pancreatitis, but its role in atherogenesis remains elusive. Hemorheological abnormality was thought to play an important role in pathogenesis of both pancreatitis and atherosclerosis. However, hemorheology in severe HTG was not well investigated. Recently, we established a severe HTG mouse model deficient in lipoprotein lipase (LPL) in which severe HTG was observed to cause a significant increase in plasma viscosity. Disturbances of erythrocytes were also documented, including decreased deformability, electrophoresis rate, and membrane fluidity, and increased osmotic fragility. Scanning electron microscopymore » demonstrated that most erythrocytes of LPL deficient mice deformed with protrusions, irregular appearances or indistinct concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of membrane lipids may be partially responsible for the hemorheological and morphologic abnormalities of erythrocytes. This study indicated that severe HTG could lead to significant impairment of hemorheology and this model may be useful in delineating the role of severe HTG in the pathogenesis of hyperlipidemic pancreatitis and atherosclerosis.« less

Observation and simulation of the ionosphere disturbance waves triggered by rocket exhausts

NASA Astrophysics Data System (ADS)

Lin, Charles C. H.; Chen, Chia-Hung; Matsumura, Mitsuru; Lin, Jia-Ting; Kakinami, Yoshihiro

2017-08-01

Observations and theoretical modeling of the ionospheric disturbance waves generated by rocket launches are investigated. During the rocket passage, time rate change of total electron content (rTEC) enhancement with the V-shape shock wave signature is commonly observed, followed by acoustic wave disturbances and region of negative rTEC centered along the trajectory. Ten to fifteen min after the rocket passage, delayed disturbance waves appeared and propagated along direction normal to the V-shape wavefronts. These observation features appeared most prominently in the 2016 North Korea rocket launch showing a very distinct V-shape rTEC enhancement over enormous areas along the southeast flight trajectory despite that it was also appeared in the 2009 North Korea rocket launch with the eastward flight trajectory. Numerical simulations using the physical-based nonlinear and nonhydrostatic coupled model of neutral atmosphere and ionosphere reproduce promised results in qualitative agreement with the characteristics of ionospheric disturbance waves observed in the 2009 event by considering the released energy of the rocket exhaust as the disturbance source. Simulations reproduce the shock wave signature of electron density enhancement, acoustic wave disturbances, the electron density depletion due to the rocket-induced pressure bulge, and the delayed disturbance waves. The pressure bulge results in outward neutral wind flows carrying neutrals and plasma away from it and leading to electron density depletions. Simulations further show, for the first time, that the delayed disturbance waves are produced by the surface reflection of the earlier arrival acoustic wave disturbances.

Disturbance rejection performance analyses of closed loop control systems by reference to disturbance ratio.

PubMed

Alagoz, Baris Baykant; Deniz, Furkan Nur; Keles, Cemal; Tan, Nusret

2015-03-01

This study investigates disturbance rejection capacity of closed loop control systems by means of reference to disturbance ratio (RDR). The RDR analysis calculates the ratio of reference signal energy to disturbance signal energy at the system output and provides a quantitative evaluation of disturbance rejection performance of control systems on the bases of communication channel limitations. Essentially, RDR provides a straightforward analytical method for the comparison and improvement of implicit disturbance rejection capacity of closed loop control systems. Theoretical analyses demonstrate us that RDR of the negative feedback closed loop control systems are determined by energy spectral density of controller transfer function. In this manner, authors derived design criteria for specifications of disturbance rejection performances of PID and fractional order PID (FOPID) controller structures. RDR spectra are calculated for investigation of frequency dependence of disturbance rejection capacity and spectral RDR analyses are carried out for PID and FOPID controllers. For the validation of theoretical results, simulation examples are presented. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Wideband Motion Control by Position and Acceleration Input Based Disturbance Observer

NASA Astrophysics Data System (ADS)

Irie, Kouhei; Katsura, Seiichiro; Ohishi, Kiyoshi

The disturbance observer can observe and suppress the disturbance torque within its bandwidth. Recent motion systems begin to spread in the society and they are required to have ability to contact with unknown environment. Such a haptic motion requires much wider bandwidth. However, since the conventional disturbance observer attains the acceleration response by the second order derivative of position response, the bandwidth is limited due to the derivative noise. This paper proposes a novel structure of a disturbance observer. The proposed disturbance observer uses an acceleration sensor for enlargement of bandwidth. Generally, the bandwidth of an acceleration sensor is from 1Hz to more than 1kHz. To cover DC range, the conventional position sensor based disturbance observer is integrated. Thus, the performance of the proposed Position and Acceleration input based disturbance observer (PADO) is superior to the conventional one. The PADO is applied to position control (infinity stiffness) and force control (zero stiffness). The numerical and experimental results show viability of the proposed method.

[Impacts of Ochotona pallasi disturbance on alpine grassland community characteristics].

PubMed

Zhao, Guo-qin; Li, Guang-yong; Ma, Wen-hu; Zhao, Dian-zhi; Li, Xiao-yan

2013-08-01

Plateau pika is the main fossorial mammal in the alpine grassland in Qinghai Lake Watershed of Northwest China. Based on the field investigation data from 18 alpine grassland quadrats in the Watershed, and by using redundancy analysis (RDA) and the surface fitting offered by 'R-Vegan' , the disturbance intensity of plateau pika (Ochotona pallasi) was classified as four levels. In order to explore the impacts of plateau pika disturbance on the alpine grassland ecosystem and its grazing quality, the community characteristics under different disturbance intensities by plateau pika were analyzed, and a conceptual model about the alpine grassland community succession was proposed. The results showed that with the increase of the disturbance intensity, the dominant species changed from Juncus roemerianus to Poa pratensis and Laux maritima. When the disturbance was small, the community had high quantitative values of coverage, aboveground biomass, biodiversity, and species richness, but the proportion of weeds was also high. When the disturbance was large, the quantitative values were the lowest, while the proportion of weeds was the highest. When the disturbance was moderate, the community had relatively high quantitative values, and the proportion of grasses and sedges was the highest. It was concluded that the community' s characteristic values under low plateau pika disturbance intensity were high but the grazing quality was low, while high disturbance intensity resulted in the grassland degradation. Therefore, the disturbance intensity in the threshold could maintain the stability of alpine grassland ecosystem and improve its grazing quality.

Functional hypothalamic amenorrhea due to increased CRH tone in melanocortin receptor 2-deficient mice.

PubMed

Matsuwaki, Takashi; Nishihara, Masugi; Sato, Tsuyoshi; Yoda, Tetsuya; Iwakura, Yoichiro; Chida, Dai

2010-11-01

Exposure to chronic stressors results in dysregulation of the hypothalamic-pituitary-adrenal axis and a disruption in reproduction. CRH, the principal regulator of the hypothalamic-pituitary-adrenal axis induces the secretion of ACTH from the pituitary, which stimulates adrenal steroidogenesis via the specific cell-surface melanocortin 2 receptor (MC2R). Previously, we demonstrated that MC2R(-/-) mice had undetectable levels of corticosterone despite high ACTH levels. Here, we evaluated the reproductive functions of female MC2R(-/-) mice and analyzed the mechanism of the disrupted cyclicity of these mice. The expression of CRH in the paraventricular nucleus was significantly increased in MC2R(-/-) mice under nonstressed conditions. Although MC2R(-/-) females were fertile, they showed a prolonged estrous cycle. After hormonal stimulation, MC2R(-/-) females produced nearly-normal numbers of eggs, but slightly less than MC2R(+/-) females, and showed near-normal ovarian histology. During diestrus, the number of GnRH-positive cells in the medial preoptic area was significantly reduced in MC2R(-/-) females. CRH type 1 receptor antagonist restored estrous cyclicity in MC2R(-/-) females. Kisspeptin-positive areas in the arcuate nucleus were comparable, whereas kisspeptin-positive areas in the anteroventral periventricular nucleus in MC2R(-/-) females were significantly reduced compared with MC2R(+/-) females, suggesting that arcuate nucleus kisspeptin is not involved, but anteroventral periventricular nucleus kisspeptin may be involved, in the maintenance of estrous cyclicity. Our findings show that high levels of hypothalamic CRH disturb estrous cyclicity in the female animals and that the MC2R(-/-) female is a unique animal model of functional hypothalamic amenorrhea.

Response of a hypersonic boundary layer to freestream pulse acoustic disturbance.

PubMed

Wang, Zhenqing; Tang, Xiaojun; Lv, Hongqing

2014-01-01

The response of hypersonic boundary layer over a blunt wedge to freestream pulse acoustic disturbance was investigated. The stability characteristics of boundary layer for freestream pulse wave and continuous wave were analyzed comparatively. Results show that freestream pulse disturbance changes the thermal conductivity characteristics of boundary layer. For pulse wave, the number of main disturbance clusters decreases and the frequency band narrows along streamwise. There are competition and disturbance energy transfer among different modes in boundary layer. The dominant mode of boundary layer has an inhibitory action on other modes. Under continuous wave, the disturbance modes are mainly distributed near fundamental and harmonic frequencies, while under pulse wave, the disturbance modes are widely distributed in different modes. For both pulse and continuous waves, most of disturbance modes slide into a lower-growth or decay state in downstream, which is tending towards stability. The amplitude of disturbance modes in boundary layer under continuous wave is considerably larger than pulse wave. The growth rate for the former is also considerably larger than the later the disturbance modes with higher growth are mainly distributed near fundamental and harmonic frequencies for the former, while the disturbance modes are widely distributed in different frequencies for the latter.

Response of a Hypersonic Boundary Layer to Freestream Pulse Acoustic Disturbance

PubMed Central

Wang, Zhenqing; Tang, Xiaojun; Lv, Hongqing

2014-01-01

The response of hypersonic boundary layer over a blunt wedge to freestream pulse acoustic disturbance was investigated. The stability characteristics of boundary layer for freestream pulse wave and continuous wave were analyzed comparatively. Results show that freestream pulse disturbance changes the thermal conductivity characteristics of boundary layer. For pulse wave, the number of main disturbance clusters decreases and the frequency band narrows along streamwise. There are competition and disturbance energy transfer among different modes in boundary layer. The dominant mode of boundary layer has an inhibitory action on other modes. Under continuous wave, the disturbance modes are mainly distributed near fundamental and harmonic frequencies, while under pulse wave, the disturbance modes are widely distributed in different modes. For both pulse and continuous waves, most of disturbance modes slide into a lower-growth or decay state in downstream, which is tending towards stability. The amplitude of disturbance modes in boundary layer under continuous wave is considerably larger than pulse wave. The growth rate for the former is also considerably larger than the later the disturbance modes with higher growth are mainly distributed near fundamental and harmonic frequencies for the former, while the disturbance modes are widely distributed in different frequencies for the latter. PMID:24737993

Caveolin-1-deficient mice show accelerated mammary gland development during pregnancy, premature lactation, and hyperactivation of the Jak-2/STAT5a signaling cascade.

PubMed

Park, David S; Lee, Hyangkyu; Frank, Philippe G; Razani, Babak; Nguyen, Andrew V; Parlow, Albert F; Russell, Robert G; Hulit, James; Pestell, Richard G; Lisanti, Michael P

2002-10-01

It is well established that mammary gland development and lactation are tightly controlled by prolactin signaling. Binding of prolactin to its cognate receptor (Prl-R) leads to activation of the Jak-2 tyrosine kinase and the recruitment/tyrosine phosphorylation of STAT5a. However, the mechanisms for attenuating the Prl-R/Jak-2/STAT5a signaling cascade are just now being elucidated. Here, we present evidence that caveolin-1 functions as a novel suppressor of cytokine signaling in the mammary gland, akin to the SOCS family of proteins. Specifically, we show that caveolin-1 expression blocks prolactin-induced activation of a STAT5a-responsive luciferase reporter in mammary epithelial cells. Furthermore, caveolin-1 expression inhibited prolactin-induced STAT5a tyrosine phosphorylation and DNA binding activity, suggesting that caveolin-1 may negatively regulate the Jak-2 tyrosine kinase. Because the caveolin-scaffolding domain bears a striking resemblance to the SOCS pseudosubstrate domain, we examined whether Jak-2 associates with caveolin-1. In accordance with this homology, we demonstrate that Jak-2 cofractionates and coimmunoprecipitates with caveolin-1. We next tested the in vivo relevance of these findings using female Cav-1 (-/-) null mice. If caveolin-1 normally functions as a suppressor of cytokine signaling in the mammary gland, then Cav-1 null mice should show premature development of the lobuloalveolar compartment because of hyperactivation of the prolactin signaling cascade via disinhibition of Jak-2. In accordance with this prediction, Cav-1 null mice show accelerated development of the lobuloalveolar compartment, premature milk production, and hyperphosphorylation of STAT5a (pY694) at its Jak-2 phosphorylation site. In addition, the Ras-p42/44 MAPK cascade is hyper-activated. Because a similar premature lactation phenotype is observed in SOCS1 (-/-) null mice, we conclude that caveolin-1 is a novel suppressor of cytokine signaling.

Disturbance Regimes Predictably Alter Diversity in an Ecologically Complex Bacterial System

PubMed Central

Scholz, Monika; Hutchison, Alan L.; Dinner, Aaron R.; Gilbert, Jack A.; Coleman, Maureen L.

2016-01-01

ABSTRACT Diversity is often associated with the functional stability of ecological communities from microbes to macroorganisms. Understanding how diversity responds to environmental perturbations and the consequences of this relationship for ecosystem function are thus central challenges in microbial ecology. Unimodal diversity-disturbance relationships, in which maximum diversity occurs at intermediate levels of disturbance, have been predicted for ecosystems where life history tradeoffs separate organisms along a disturbance gradient. However, empirical support for such peaked relationships in macrosystems is mixed, and few studies have explored these relationships in microbial systems. Here we use complex microbial microcosm communities to systematically determine diversity-disturbance relationships over a range of disturbance regimes. We observed a reproducible switch between community states, which gave rise to transient diversity maxima when community states were forced to mix. Communities showed reduced compositional stability when diversity was highest. To further explore these dynamics, we formulated a simple model that reveals specific regimes under which diversity maxima are stable. Together, our results show how both unimodal and non-unimodal diversity-disturbance relationships can be observed as a system switches between two distinct microbial community states; this process likely occurs across a wide range of spatially and temporally heterogeneous microbial ecosystems. PMID:27999158

Toward a National Early Warning System for Forest Disturbances Using Remotely Sensed Land-Surface Phenology

NASA Astrophysics Data System (ADS)

Hargrove, W. W.; Spruce, J.

2010-12-01

A prototype National Early Warning System (EWS) for Forest Disturbances was established in 2010 by producing national maps showing potential forest disturbance across the conterminous United States at 231m resolution every 8 days. Each map is based on Land-Surface Phenology (LSP), calculated using temporally smoothed MODIS MOD13 imagery obtained over the preceding 24-day analysis window. Potential disturbance maps are generated by comparing a spatially and temporally specific historical expectation of normal NDVI "greenness" with NDVI "greenness" from a series of current satellite views. Three different disturbance products are produced using differing lengths of historical baseline periods to calculate the expected normal greenness. The short-term baseline products show only disturbances newer than one year ago, while the intermediate baseline products show disturbances since the prior three years, and the long-term baseline products show all disturbances over the MODIS historical period. A Forest Change Assessment Viewer website, http://ews.forestthreats.org/NPDE/NPDE.html, showcases the three most recent national disturbance maps in full spatial context. Although 2010 was a wet el Nino year without major forest problems, disturbances in 2010 in MI, NY, CO and LA will be highlighted. Forest disturbances caused by wildfire, hurricanes, tornadoes, hail, ice storms, and defoliating insects, including fall cankerworms, forest tent caterpillars, gypsy moths, baldcypress leafrollers and winter moths were successfully detected during the 2009 and 2010 field seasons. The EWS was used in 2010 to detect and alert Forest Health Monitoring (FHM) Aerial Disturbance Survey personnel to an otherwise-unknown outbreak of forest tent caterpillar and baldcypress leafroller in the Atchafalaya and Pearl River regions of southern Louisiana. A local FHM Program Coordinator verified these EWS-detected outbreaks. Many defoliator-induced disturbances were ephemeral, and were followed by

State Estimation of International Space Station Centrifuge Rotor With Incomplete Knowledge of Disturbance Inputs

NASA Technical Reports Server (NTRS)

Sullivan, Michael J.

2005-01-01

This thesis develops a state estimation algorithm for the Centrifuge Rotor (CR) system where only relative measurements are available with limited knowledge of both rotor imbalance disturbances and International Space Station (ISS) thruster disturbances. A Kalman filter is applied to a plant model augmented with sinusoidal disturbance states used to model both the effect of the rotor imbalance and the 155 thrusters on the CR relative motion measurement. The sinusoidal disturbance states compensate for the lack of the availability of plant inputs for use in the Kalman filter. Testing confirms that complete disturbance modeling is necessary to ensure reliable estimation. Further testing goes on to show that increased estimator operational bandwidth can be achieved through the expansion of the disturbance model within the filter dynamics. In addition, Monte Carlo analysis shows the varying levels of robustness against defined plant/filter uncertainty variations.

Disturbance Distance: Combining a process based ecosystem model and remote sensing data to map the vulnerability of U.S. forested ecosystems to potentially altered disturbance rates

NASA Astrophysics Data System (ADS)

Dolan, K. A.

2015-12-01

Disturbance plays a critical role in shaping the structure and function of forested ecosystems as well as the ecosystem services they provide, including but not limited to: carbon storage, biodiversity habitat, water quality and flow, and land atmosphere exchanges of energy and water. In addition, recent studies suggest that disturbance rates may increase in the future under altered climate and land use scenarios. Thus understanding how vulnerable forested ecosystems are to potential changes in disturbance rates is of high importance. This study calculated the theoretical threshold rate of disturbance for which forest ecosystems could no longer be sustained (λ*) across the Coterminous U.S. using an advanced process based ecosystem model (ED). Published rates of disturbance (λ) in 50 study sites were obtained from the North American Forest Disturbance (NAFD) program. Disturbance distance (λ* - λ) was calculated for each site by differencing the model based threshold under current climate conditions and average observed rates of disturbance over the last quarter century. Preliminary results confirm all sample forest sites have current average rates of disturbance below λ*, but there were interesting patterns in the recorded disturbance distances. In general western sites had much smaller disturbance distances, suggesting higher vulnerability to change, while eastern sites showed larger buffers. Ongoing work is being conducted to assess the vulnerability of these sites in the context of potential future changes by propagating scenarios of future climate and land-use change through the analysis.

Defining Disturbance for Microbial Ecology.

PubMed

Plante, Craig J

2017-08-01

Disturbance can profoundly modify the structure of natural communities. However, microbial ecologists' concept of "disturbance" has often deviated from conventional practice. Definitions (or implicit usage) have frequently included climate change and other forms of chronic environmental stress, which contradict the macrobiologist's notion of disturbance as a discrete event that removes biomass. Physical constraints and disparate biological characteristics were compared to ask whether disturbances fundamentally differ in microbial and macroorganismal communities. A definition of "disturbance" for microbial ecologists is proposed that distinguishes from "stress" and other competing terms, and that is in accord with definitions accepted by plant and animal ecologists.

Using Landsat to Diagnose Trends in Disturbance Magnitude Across the National Forest System

NASA Astrophysics Data System (ADS)

Hernandez, A. J.; Healey, S. P.; Stehman, S. V.; Ramsey, R. D.

2014-12-01

The Landsat archive is increasingly being used to detect trends in the occurrence of forest disturbance. Beyond information about the amount of area affected, forest managers need to know if and how disturbance severity is changing. For example, the United States National Forest System (NFS) has developed a comprehensive plan for carbon monitoring, which requires a detailed temporal mapping of forest disturbance magnitudes across 75 million hectares. To meet this need, we have prepared multitemporal models of percent canopy cover that were calibrated with extensive field data from the USFS Forest Inventory and Analysis Program (FIA). By applying these models to pre- and post-event Landsat images at the site of known disturbances, we develop maps showing first-order estimates of disturbance magnitude on the basis of cover removal. However, validation activities consistently show that these initial estimates under-estimate disturbance magnitude. We have developed an approach, which quantifies this under-prediction at the landscape level and uses empirical validation data to adjust change magnitude estimates derived from initial disturbance maps. In an assessment of adjusted magnitude trends of NFS' Northern Region from 1990 to the present, we observed significant declines since 1990 (p < .01) in harvest magnitude, likely related to known reduction of clearcutting practices in the region. Fire, conversely, did not show strongly significant trends in magnitude, despite an increase in the overall area affected. As Landsat is used to provide increasingly precise maps of the timing and location of historical forest disturbance, a logical next step is to use the archive to generate widely interpretable and objective estimates of disturbance magnitude.

Intermittent Short Sleep Results in Lasting Sleep Wake Disturbances and Degeneration of Locus Coeruleus and Orexinergic Neurons

PubMed Central

Zhu, Yan; Fenik, Polina; Zhan, Guanxia; Somach, Rebecca; Xin, Ryan; Veasey, Sigrid

2016-01-01

Study Objectives: Intermittent short sleep (ISS) is pervasive among students and workers in modern societies, yet the lasting consequences of repeated short sleep on behavior and brain health are largely unexplored. Wake-activated neurons may be at increased risk of metabolic injury across sustained wakefulness. Methods: To examine the effects of ISS on wake-activated neurons and wake behavior, wild-type mice were randomized to ISS (a repeated pattern of short sleep on 3 consecutive days followed by 4 days of recovery sleep for 4 weeks) or rested control conditions. Subsets of both groups were allowed a recovery period consisting of 4-week unperturbed activity in home cages with littermates. Mice were examined for immediate and delayed (following recovery) effects of ISS on wake neuron cell metabolics, cell counts, and sleep/wake patterns. Results: ISS resulted in sustained disruption of sleep/wake activity, with increased wakefulness during the lights-on period and reduced wake bout duration and wake time during the lights-off period. Noradrenergic locus coeruleus (LC) and orexinergic neurons showed persistent alterations in morphology, and reductions in both neuronal stereological cell counts and fronto-cortical projections. Surviving wake-activated neurons evidenced persistent reductions in sirtuins 1 and 3 and increased lipofuscin. In contrast, ISS resulted in no lasting injury to the sleep-activated melanin concentrating hormone neurons. Conclusions: Collectively these findings demonstrate for the first time that ISS imparts significant lasting disturbances in sleep/wake activity, degeneration of wake-activated LC and orexinergic neurons, and lasting metabolic changes in remaining neurons most consistent with premature senescence. Citation: Zhu Y, Fenik P, Zhan G, Somach R, Xin R, Veasey S. Intermittent short sleep results in lasting sleep wake disturbances and degeneration of locus coeruleus and orexinergic neurons. SLEEP 2016;39(8):1601–1611. PMID:27306266

Carbon cycling at the tipping point: Does ecosystem structure predict resistance to disturbance?

NASA Astrophysics Data System (ADS)

Gough, C. M.; Bond-Lamberty, B. P.; Stuart-Haentjens, E.; Atkins, J.; Haber, L.; Fahey, R. T.

2017-12-01

Ecosystems worldwide are subjected to disturbances that reshape their physical and biological structure and modify biogeochemical processes, including carbon storage and cycling rates. Disturbances, including those from insect pests, pathogens, and extreme weather, span a continuum of severity and, accordingly, may have different effects on carbon cycling processes. Some ecosystems resist biogeochemical changes following disturbance, until a critical threshold of severity is exceeded. The ecosystem properties underlying such functional resistance, and signifying when a tipping point will occur, however, are almost entirely unknown. Here, we present observational and experimental results from forests in the Great Lakes region, showing ecosystem structure is closely coupled with carbon cycling responses to disturbance, with shifts in structure predicting thresholds of and, in some cases, increases in carbon storage. We find, among forests in the region, that carbon storage regularly exhibits a non-linear threshold response to increasing disturbance levels, but the severity at which a threshold is reached varies among disturbed forests. More biologically and structurally complex forest ecosystems sometimes exhibit greater functional resistance than simpler forests, and consequently may have a higher disturbance severity threshold. Counter to model predictions but consistent with some theoretical frameworks, empirical data show moderate levels of disturbance may increase ecosystem complexity to a point, thereby increasing rates of carbon storage. Disturbances that increase complexity therefore may stimulate carbon storage, while severe disturbances at or beyond thresholds may simplify structure, leading to carbon storage declines. We conclude that ecosystem structural attributes are closely coupled with biogeochemical thresholds across disturbance severity gradients, suggesting that improved predictions of disturbance-related changes in the carbon cycle require better

Different Facets of Body Image Disturbance in Binge Eating Disorder: A Review

PubMed Central

Lewer, Merle; Bauer, Anika

2017-01-01

The goal of the present review is to give an overview of the current findings on various facets of body image disturbance in Binge Eating Disorder such as body dissatisfaction, overconcern with weight and shape, body-related checking and avoidance behavior, misperception of body size, and body-related cognitive bias. In addition, treatments for a disturbed body image in BED and evidence of body image disturbance in youth with binge eating are reviewed. The results show that a disturbed body image in BED is present in the form of overconcern with weight and shape. Furthermore, there are hints that body dissatisfaction, as well as body-related checking and avoidance behavior, are also impaired. Research concerning misperception of body size in BED has been neglected so far, but first findings show that individuals with BED rate their own body shape rather accurately. Furthermore, there are first hints that body-related cognitive biases are present in individuals with BED. Moreover, in children and adolescents, there are first hints that body dissatisfaction, as well as shape and weight concerns, seem to be associated with loss of control and binge eating. Treatments aimed directly at the convertibility of a disturbed body image in BED have revealed encouraging outcomes. In conclusion, body image disturbance seems to occur in BED, and first studies show that it can be treated effectively. PMID:29182531

Deficiency of prolyl oligopeptidase in mice disturbs synaptic plasticity and reduces anxiety-like behaviour, body weight, and brain volume.

PubMed

Höfling, Corinna; Kulesskaya, Natalia; Jaako, Külli; Peltonen, Iida; Männistö, Pekka T; Nurmi, Antti; Vartiainen, Nina; Morawski, Markus; Zharkovsky, Alexander; Võikar, Vootele; Roßner, Steffen; García-Horsman, J Arturo

2016-06-01

Prolyl oligopeptidase (PREP) has been implicated in neurodegeneration and neuroinflammation and has been considered a drug target to enhance memory in dementia. However, the true physiological role of PREP is not yet understood. In this paper, we report the phenotyping of a mouse line where the PREP gene has been knocked out. This work indicates that the lack of PREP in mice causes reduced anxiety but also hyperactivity. The cortical volumes of PREP knockout mice were smaller than those of wild type littermates. Additionally, we found increased expression of diazepam binding inhibitor protein in the cortex and of the somatostatin receptor-2 in the hippocampus of PREP knockout mice. Furthermore, immunohistochemistry and tail suspension test revealed lack of response of PREP knockout mice to lipopolysaccharide insult. Further analysis revealed significantly increased levels of polysialylated-neural cell adhesion molecule in PREP deficient mice. These findings might be explained as possible alteration in brain plasticity caused by PREP deficiency, which in turn affect behaviour and brain development. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

PubMed

Paredes, João A; Zhou, Xiaoshan; Höglund, Stefan; Karlsson, Anna

2013-01-01

Loss of thymidine kinase 2 (TK2) causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA) depletion syndrome (MDS) in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

Gene Expression Deregulation in Postnatal Skeletal Muscle of TK2 Deficient Mice Reveals a Lower Pool of Proliferating Myogenic Progenitor Cells

PubMed Central

Paredes, João A.; Zhou, Xiaoshan; Höglund, Stefan; Karlsson, Anna

2013-01-01

Loss of thymidine kinase 2 (TK2) causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA) depletion syndrome (MDS) in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue. PMID:23341978

Recombinant influenza H7 hemagglutinin containing CFLLC minidomain in the transmembrane domain showed enhanced cross-protection in mice.

PubMed

Wang, Yang; Zhang, Yun; Wu, Jialing; Lin, Ying; Wu, Zhihui; Wei, Ying; Wei, Xiaona; Qin, Jianru; Xue, Chunyi; Liu, George Dacai; Cao, Yongchang

2017-10-15

Since February 2013, H7N9 influenza virus, causing human infections with high mortality in China, has been a potential pandemic threat. The H7N9 viruses are found to diverge into distinct genotypes as other influenza viruses; thus a vaccine that can provide sufficient cross-protection against different genotypes of H7N9 viruses is urgently needed. Our previous studies demonstrated that the HA-based structural design approach by introducing a CFLLC minidomain into transmembrane domain (TM) of H1, H5 or H9 hemagglutinin (HA) proteins by replacing with H3 subtype HA TM could enhance their cross-protection. In this study, we used Sf9 insect cell expression system to express recombinant H7 HA proteins H7-53WT, in which HA gene was derived from H7N9-53 strain, and H7-53TM containing CFLLC minidomian by replacing its TM domain with H3 HA TM. We investigated whether introduction of CFLLC minidomain into H7 HA (H7-53TM) could increase its cross-reactivity and cross-protection against different genotypes of H7N9 viruses. The results showed that the H7-53TM either with or without squalene adjuvant induced increased HI antibodies, serum IgG antibodies, and IFN-γ production to a panel of 7 H7N9 viruses in mice. Vaccinated animals with H7-53TM alone showed complete protection against challenge with heterologous H7N9-MCX strain, while H7-53WT alone showed incomplete protection (80%). Furthermore, mice vaccinated with H7-53TM HA showed less body weight loss and less pulmonary lesions and inflammation after challenge with homologous or heterologous H7N9 viruses, comparing to H7-53WT. In summary, this study presents a better subunit vaccine candidate (H7-53TM) against potential H7N9 pandemic. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of betel quid on effect of calcium channel blockers on isoprenaline induced myocardial necrosis in mice.

PubMed

Kumar, Vinod; Asdaq, Syed Mohammed Basheeruddin; Asad, Mohammed

2009-09-01

It is known that chewing Betel quid with tobacco (BQT) or without tobacco (BQ) is a major etiological factor for cardiovascular complications and calcium channel blockers (CCBs) are the major class of drugs prescribed widely for myocardial disturbances. The possible pharmacodynamic interaction between CCBs (verapamil, amlodipine and diltiazem) and BQ/BQT was studied on isoproterenol (ISO)-induced myocardial necrosis in mice. Influence of (CCBs) therapy on pretreated animals at times of myocardial stress were determined by estimating diagnostic marker enzymes such as lactate dehydrogenase (LDH) and creatine phosphokinase isoenzyme (CK-MB) in serum and heart tissue homogenate (HTH). Administration of CCBs to mice pretreated with BQ produced a significant decrease and increase in biomarker enzyme levels in serum and HTH respectively. Further, incorporation of diltiazem and amlodipine in BQT pretreated mice significantly elevated enzyme levels in HTH, whereas, amlodipine administration during BQT treatment showed significant fall in enzyme levels in serum. The results indicated that BQT is cardiotoxic and its effect cannot be reversed using CCBs while BQ is cardioprotective, whose activity was further augmented by amlodipine. Histopathological studies confirmed the biochemical findings.

The Essential Role of Mbd5 in the Regulation of Somatic Growth and Glucose Homeostasis in Mice

PubMed Central

Du, Yarui; Liu, Bo; Guo, Fan; Xu, Guifang; Ding, Yuqiang; Liu, Yong; Sun, Xin; Xu, Guoliang

2012-01-01

Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis. PMID:23077600

The essential role of Mbd5 in the regulation of somatic growth and glucose homeostasis in mice.

PubMed

Du, Yarui; Liu, Bo; Guo, Fan; Xu, Guifang; Ding, Yuqiang; Liu, Yong; Sun, Xin; Xu, Guoliang

2012-01-01

Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis.

Thermal structure and dynamics of Saturn's northern springtime disturbance

USGS Publications Warehouse

Fletcher, L.N.; Hesman, B.E.; Irwin, P.G.J.; Baines, K.H.; Momary, T.W.; Sanchez-Lavega, A.; Flasar, F.M.; Read, P.L.; Orton, G.S.; Simon-Miller, A.; Hueso, R.; Bjoraker, G.L.; Mamoutkine, A.; Del, Rio-Gaztelurrutia; Gomez, J.M.; Buratti, B.; Clark, R.N.; Nicholson, P.D.; Sotin, Christophe

2011-01-01

Saturn’s slow seasonal evolution was disrupted in 2010–2011 by the eruption of a bright storm in its northern spring hemisphere. Thermal infrared spectroscopy showed that within a month, the resulting planetary-scale disturbance had generated intense perturbations of atmospheric temperatures, winds, and composition between 20° and 50°N over an entire hemisphere (140,000 kilometers). The tropospheric storm cell produced effects that penetrated hundreds of kilometers into Saturn’s stratosphere (to the 1-millibar region). Stratospheric subsidence at the edges of the disturbance produced “beacons” of infrared emission and longitudinal temperature contrasts of 16 kelvin. The disturbance substantially altered atmospheric circulation, transporting material vertically over great distances, modifying stratospheric zonal jets, exciting wave activity and turbulence, and generating a new cold anticyclonic oval in the center of the disturbance at 41°N.

Disturbed island ecology.

PubMed

Whittaker, R J

1995-10-01

The natural occurrence of significant disturbances to the operation of insular ecosystems has tended to be downplayed in the development of island ecological theory. Despite the importance of events such as Hurricane Hugo, which in 1989 affected islands in the Caribbean, islands that are disturbed tend to be viewed as deviants from the `true path' described by equilibrium models. However, particularly with organisms of long generation times, it is questionable whether such models are applicable. This may be as important for wildlife managers to take account of as for theorists. Disturbance regime should be incorporated into island ecological models alongside other ecological factors structuring colonization patterns and turnover.

Sleep Disturbances in Neurodevelopmental Disorders.

PubMed

Robinson-Shelton, Althea; Malow, Beth A

2016-01-01

Sleep disturbances are extremely prevalent in children with neurodevelopmental disorders compared to typically developing children. The diagnostic criteria for many neurodevelopmental disorders include sleep disturbances. Sleep disturbance in this population is often multifactorial and caused by the interplay of genetic, neurobiological and environmental overlap. These disturbances often present either as insomnia or hypersomnia. Different sleep disorders present with these complaints and based on the clinical history and findings from diagnostic tests, an appropriate diagnosis can be made. This review aims to provide an overview of causes, diagnosis, and treatment of sleep disturbances in neurodevelopmental disorders that present primarily with symptoms of hypersomnia and/or insomnia.

Betacellulin transgenic mice develop urothelial hyperplasia and show sex-dependent reduction in urinary major urinary protein content.

PubMed

Schulz, Helene; Dahlhoff, Maik; Glogowska, Aleksandra; Zhang, Lin; Arnold, Georg J; Fröhlich, Thomas; Schneider, Marlon R; Klonisch, Thomas

2015-08-01

The epidermal growth factor (EGF)-like ligands and their cognate ERBB1-4 receptors represent important signaling pathways that regulate tissue and cell proliferation, differentiation and regeneration in a wide variety of tissues, including the urogenital tract. Betacellulin (BTC) can activate all four ERBB tyrosine kinase receptors and is a multifunctional EGF-like ligand with diverse roles in β cell differentiation, bone maturation, formation of functional epithelial linings and vascular permeability in different organs. Using transgenic BTC mice, we have studied the effect of constitutive systemic BTC over-expression on the urinary bladder. BTC was detected in microvascular structures of the stromal bladder compartment and in umbrella cells representing the protective apical lining of the uroepithelium. ERBB1 and ERBB4 receptors were co-localized in the urothelium. Mice transgenic for BTC and double transgenic for both BTC and the dominant kinase-dead mutant of EGFR (Waved 5) developed hyperplasia of the uroepithelium at 5months of age, suggesting that urothelial hyperplasia was not exclusively dependent on ERBB1/EGFR. Mass spectrometric analysis of urine revealed a significant down-regulation of major urinary proteins in female BTC transgenic mice, suggesting a novel role for systemic BTC in odor-based signaling in female transgenic BTC mice. Copyright © 2015 Elsevier Inc. All rights reserved.

Tropical insular fish assemblages are resilient to flood disturbance

USGS Publications Warehouse

Smith, William E.; Kwak, Thomas J.

2015-01-01

Periods of stable environmental conditions, favoring development of ecological communities regulated by density-dependent processes, are interrupted by random periods of disturbance that may restructure communities. Disturbance may affect populations via habitat alteration, mortality, or displacement. We quantified fish habitat conditions, density, and movement before and after a major flood disturbance in a Caribbean island tropical river using habitat surveys, fish sampling and population estimates, radio telemetry, and passively monitored PIT tags. Native stream fish populations showed evidence of acute mortality and downstream displacement of surviving fish. All fish species were reduced in number at most life stages after the disturbance, but populations responded with recruitment and migration into vacated upstream habitats. Changes in density were uneven among size classes for most species, indicating altered size structures. Rapid recovery processes at the population level appeared to dampen effects at the assemblage level, as fish assemblage parameters (species richness and diversity) were unchanged by the flooding. The native fish assemblage appeared resilient to flood disturbance, rapidly compensating for mortality and displacement with increased recruitment and recolonization of upstream habitats.

Neurologic manifestations of electrolyte disturbances.

PubMed

Riggs, Jack E

2002-02-01

Electrolyte disturbances occur commonly and are associated with a variety of characteristic neurologic manifestations involving both the central and peripheral nervous systems. Electrolyte disturbances are essentially always secondary processes. Effective management requires identification and treatment of the underlying primary disorder. Since neurological symptoms of electrolyte disorders are generally functional rather than structural, the neurologic manifestations of electrolyte disturbances are typically reversible. The neurologic manifestations of serum sodium, potassium, calcium, and magnesium disturbances are reviewed.

Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

PubMed

Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

2018-02-01

The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

Low empathy-like behaviour in male mice associates with impaired sociability, emotional memory, physiological stress reactivity and variations in neurobiological regulations

PubMed Central

Carito, Valentina; Huzard, Damien; Fiore, Marco; Macrì, Simone

2017-01-01

Deficits in empathy have been proposed to constitute a hallmark of several psychiatric disturbances like conduct disorder, antisocial and narcissistic personality disorders. Limited sensitivity to punishment, shallow or deficient affect and reduced physiological reactivity to environmental stressors have been often reported to co-occur with limited empathy and contribute to the onset of antisocial phenotypes. Empathy in its simplest form (i.e. emotional contagion) is addressed in preclinical models through the evaluation of the social transmission of emotional states: mice exposed to a painful stimulus display a higher response if in the presence of a familiar individual experiencing a higher degree of discomfort, than in isolation. In the present study, we investigated whether a reduction of emotional contagion can be considered a predictor of reduced sociality, sensitivity to punishment and physiological stress reactivity. To this aim, we first evaluated emotional contagion in a group of Balb/cJ mice and then discretised their values in four quartiles. The upper (i.e. Emotional Contagion Prone, ECP) and the lower (i.e. Emotional Contagion Resistant, ECR) quartiles constituted the experimental groups. Our results indicate that mice in the lower quartile are characterized by reduced sociability, impaired memory of negative events and dampened hypothalamic-pituitary-adrenocortical reactivity to external stressors. Furthermore, in the absence of changes in oxytocin receptor density, we show that these mice exhibit elevated concentrations of oxytocin and vasopressin and reduced density of BDNF receptors in behaviourally-relevant brain areas. Thus, not only do present results translate to the preclinical investigation of psychiatric disturbances, but also they can contribute to the study of emotional contagion in terms of its adaptive significance. PMID:29200428

Low empathy-like behaviour in male mice associates with impaired sociability, emotional memory, physiological stress reactivity and variations in neurobiological regulations.

PubMed

Laviola, Giovanni; Zoratto, Francesca; Ingiosi, Danilo; Carito, Valentina; Huzard, Damien; Fiore, Marco; Macrì, Simone

2017-01-01

Deficits in empathy have been proposed to constitute a hallmark of several psychiatric disturbances like conduct disorder, antisocial and narcissistic personality disorders. Limited sensitivity to punishment, shallow or deficient affect and reduced physiological reactivity to environmental stressors have been often reported to co-occur with limited empathy and contribute to the onset of antisocial phenotypes. Empathy in its simplest form (i.e. emotional contagion) is addressed in preclinical models through the evaluation of the social transmission of emotional states: mice exposed to a painful stimulus display a higher response if in the presence of a familiar individual experiencing a higher degree of discomfort, than in isolation. In the present study, we investigated whether a reduction of emotional contagion can be considered a predictor of reduced sociality, sensitivity to punishment and physiological stress reactivity. To this aim, we first evaluated emotional contagion in a group of Balb/cJ mice and then discretised their values in four quartiles. The upper (i.e. Emotional Contagion Prone, ECP) and the lower (i.e. Emotional Contagion Resistant, ECR) quartiles constituted the experimental groups. Our results indicate that mice in the lower quartile are characterized by reduced sociability, impaired memory of negative events and dampened hypothalamic-pituitary-adrenocortical reactivity to external stressors. Furthermore, in the absence of changes in oxytocin receptor density, we show that these mice exhibit elevated concentrations of oxytocin and vasopressin and reduced density of BDNF receptors in behaviourally-relevant brain areas. Thus, not only do present results translate to the preclinical investigation of psychiatric disturbances, but also they can contribute to the study of emotional contagion in terms of its adaptive significance.

Automated Detection and Annotation of Disturbance in Eastern Forests

NASA Astrophysics Data System (ADS)

Hughes, M. J.; Chen, G.; Hayes, D. J.

2013-12-01

areas as disturbed, overestimating disturbance and creating ambiguity in the neural network. Even so, total classification error in a neighboring testing region is 22%. Most error comes labeling disturbances that are unknown in the training data as a known disturbance type. Confusion within known disturbance types is low, with 7% misclassification error for southern pine beetle, and 11% misclassification error for fire, which is likely due to over-estimates of disturbance extent in ADS polygons. Additionally, we used the Terrestrial Ecosystem Model (TEM) to quantify the carbon flux associated with a subset of selected disturbances of different severity and type. Early results show that combined disturbances resulted in a net carbon source of 1.27 kg/m2 between 1981 and 2010, which is about 8% of the total carbon storage in forests. This carbon loss offset much of the carbon sink effects resulting from elevated atmospheric CO2 and nitrogen deposition.

CPB-K mice a mouse model of schizophrenia? Differences in dopaminergic, serotonergic and behavioral markers compared to BALB/cJ mice.

PubMed

Panther, P; Nullmeier, S; Dobrowolny, H; Schwegler, H; Wolf, R

2012-04-21

Schizophrenia is characterized by disturbances in social behavior, sensorimotor gating and cognitive function, that are discussed to be caused by a termination of different transmitter systems. Beside morphological alterations in cortical and subcortical areas reduced AMPA- NMDA-, 5-HT2-receptor densities and increased 5-HT1-receptor densities are found in the hippocampus.The two inbred mouse strains CPB-K and BALB/cJ are known to display considerable differences in cognitive function and prepulse inhibition, a stable marker of sensorimotor gating. Furthermore, CPB-K mice exhibit lower NMDA-, AMPA- and increased 5-HT-receptor densities in the hippocampus as compared to BALB/cJ mice. We investigated both mouse strains in social interaction test for differences in social behavior and with immuncytochemical approaches for alterations of dopaminergic and serotonergic parameters. Our results can be summarized as follows: compared to BALB/cJ, CPB-K mice showed:(1) significantly reduced traveling distance and number of contacts in social interaction test, (2) differences in the number of serotonin transporter-immunoreactive neurons and volume of raphe nuclei and a lower serotonergic fiber density in the ventral and dorsal hippocampal subfields CA1 and CA3, (3) no alterations of dopaminergic markers like neuron number, neuron density and volume in subregions of substantia nigra and ventral tegmental area, but a significantly higher dopaminergic fiber density in the dorsal hippocampus, the ventral hippocampus of CA1 and gyrus dentatus, (4) no significant differences in serotonergic and dopaminergic fiber densities in the amygdala.Based on our results and previous studies, CPB-K mice compared to BALB/cJ may serve as an important model to understand the interaction of the serotonergic and dopaminergic system and their impact on sensorimotor gating and cognitive function as related to neuropsychiatric disorders like schizophrenia. 2012 Elsevier B.V. All rights reserved.

Mice Lacking Alternatively Activated (M2) Macrophages Show Impairments in Restorative Sleep after Sleep Loss and in Cold Environment.

PubMed

Massie, Ashley; Boland, Erin; Kapás, Levente; Szentirmai, Éva

2018-06-05

The relationship between sleep, metabolism and immune functions has been described, but the cellular components of the interaction are incompletely identified. We previously reported that systemic macrophage depletion results in sleep impairment after sleep loss and in cold environment. These findings point to the role of macrophage-derived signals in maintaining normal sleep. Macrophages exist either in resting form, classically activated, pro-inflammatory (M1) or alternatively activated, anti-inflammatory (M2) phenotypes. In the present study we determined the contribution of M2 macrophages to sleep signaling by using IL-4 receptor α-chain-deficient [IL-4Rα knockout (KO)] mice, which are unable to produce M2 macrophages. Sleep deprivation induced robust increases in non-rapid-eye-movement sleep (NREMS) and slow-wave activity in wild-type (WT) animals. NREMS rebound after sleep deprivation was ~50% less in IL-4Rα KO mice. Cold exposure induced reductions in rapid-eye-movement sleep (REMS) and NREMS in both WT and KO mice. These differences were augmented in IL-4Rα KO mice, which lost ~100% more NREMS and ~25% more REMS compared to WTs. Our finding that M2 macrophage-deficient mice have the same sleep phenotype as mice with global macrophage depletion reconfirms the significance of macrophages in sleep regulation and suggests that the main contributors are the alternatively activated M2 cells.

Long term sleep disturbance due to traffic noise

NASA Astrophysics Data System (ADS)

Vallet, M.; Gagneux, J.-M.; Blanchet, V.; Favre, B.; Labiale, G.

1983-09-01

This contribution to the evaluation of the effects of traffic noise on sleep disturbance is focused on the responses of people living near a main road. Experiments were carried out in the homes of subjects who had habitually been exposed to noise for periods of more than four years. The chronic changes in overall sleep patterns and the temporary sleep responses to particular noise events caused by traffic are demonstrated. Young people show mainly stage 3 and 4 deficits whilst older people show REM sleep deficits. The cardiac response to noise during sleep was also examined. These results highlight that both long term average and peak levels are important in assessing sleep disturbance. The threshold levels, measured inside the bedroom and above which sleep quality starts to become impaired, are 37 Leq(A) and 45 dB (A) Lp max , respectively. For the type of traffic studied these two levels are coherent and it is therefore possible that a single noise index, Leq(A), is sufficient to scale sleep disturbance.

The strengths of r- and K-selection shape diversity-disturbance relationships.

PubMed

Bohn, Kristin; Pavlick, Ryan; Reu, Björn; Kleidon, Axel

2014-01-01

Disturbance is a key factor shaping species abundance and diversity in plant communities. Here, we use a mechanistic model of vegetation diversity to show that different strengths of r- and K-selection result in different disturbance-diversity relationships. R- and K-selection constrain the range of viable species through the colonization-competition tradeoff, with strong r-selection favoring colonizers and strong K-selection favoring competitors, but the level of disturbance also affects the success of species. This interplay among r- and K-selection and disturbance results in different shapes of disturbance-diversity relationships, with little variation of diversity with no r- and no K-selection, a decrease in diversity with r-selection with disturbance rate, an increase in diversity with K-selection, and a peak at intermediate values with strong r- and K-selection. We conclude that different disturbance-diversity relationships found in observations may reflect different intensities of r- and K-selection within communities, which should be inferable from broader observations of community composition and their ecophysiological trait ranges.

Biweekly disturbance capture and attribution: case study in western Alberta grizzly bear habitat

NASA Astrophysics Data System (ADS)

Hilker, Thomas; Coops, Nicholas C.; Gaulton, Rachel; Wulder, Michael A.; Cranston, Jerome; Stenhouse, Gordon

2011-01-01

An increasing number of studies have demonstrated the impact of landscape disturbance on ecosystems. Satellite remote sensing can be used for mapping disturbances, and fusion techniques of sensors with complimentary characteristics can help to improve the spatial and temporal resolution of satellite-based mapping techniques. Classification of different disturbance types from satellite observations is difficult, yet important, especially in an ecological context as different disturbance types might have different impacts on vegetation recovery, wildlife habitats, and food resources. We demonstrate a possible approach for classifying common disturbance types by means of their spatial characteristics. First, landscape level change is characterized on a near biweekly basis through application of a data fusion model (spatial temporal adaptive algorithm for mapping reflectance change) and a number of spatial and temporal characteristics of the predicted disturbance patches are inferred. A regression tree approach is then used to classify disturbance events. Our results show that spatial and temporal disturbance characteristics can be used to classify disturbance events with an overall accuracy of 86% of the disturbed area observed. The date of disturbance was identified as the most powerful predictor of the disturbance type, together with the patch core area, patch size, and contiguity.

[A review on disturbance ecology of forest].

PubMed

Zhu, Jiaojun; Liu, Zugen

2004-10-01

More than 80% of terrestrial ecosystems have been influenced by natural disasters, human activities and the combination of both natural and human disturbances. Forest ecosystem, as one of the most important terrestrial ecosystems, has also been disturbed without exception. Under the disturbance from natural disasters and human activities, particularly from the unreasonable activities of human beings, forest decline or forest degradation has become more and more severe. For this reason, sustaining or recovering forest service functions is one of the current purposes for managing forest ecosystems. In recent decades, the studies on disturbed ecosystems have been carried out frequently, especially on their ecological processes and their responses to the disturbances. These studies play a very important role in the projects of natural forest conservation and the construction of ecological environment in China. Based on a wide range of literatures collection on forest disturbance research, this paper discussed the fundamental concepts of disturbance ecology, the relationships between forest management and disturbance, and the study contents of forest disturbance ecology. The major research topics of forest disturbance ecology may include: 1) the basic characteristics of disturbed forests; 2) the processes of natural and human disturbances; 3) the responses of forests ecosystem to the disturbances; 4) the main ecological processes or the consequential results of disturbed forests, including the change of biodiversity, soil nutrient and water cycle, eco-physiology and carbon cycle, regeneration mechanism of disturbed forests and so on; 5) the relationships between disturbances and forest management; and 6) the principles and techniques for the management of disturbed forests. This review may be helpful to the management of disturbed forest ecosystem, and to the projects of natural forest conservation in China.

[Automated mapping of urban forests' disturbance and recovery in Nanjing, China].

PubMed

Lyu, Ying-ying; Zhuang, Yi-lin; Ren, Xin-yu; Li, Ming-shi; Xu, Wang-gu; Wang, Zhi

2016-02-01

Using Landsat TM/ETM dense time series observations spanning from 1987 to 2011, taking Laoshan forest farm and Purple Mountain as the research objects, the landsat ecosystem disturbance adaptive processing system (Ledaps) algorithm was used to generate surface reflectance datasets, which were fed to the vegetation change tracker model (VCT) model to derive urban forest disturbance and recovery products over Nanjing, followed by an intensive validation of the products. The results showed that there was a relatively high spatial agreement for forest disturbance products mapped by VCT, ranging from 65.4% to 95.0%. There was an apparent fluctuating forest disturbance and recovery rate over time, and the change trend of forest disturbance occurring at the two sites was roughly similar, but forest recovery was obviously different. Forest coverage in Purple Mountain was less than that in Laoshan forest farm, but the forest disturbance and recovery rates in Laoshan forest farm were larger than those in Purple Mountain.

Determining the size of a complete disturbance landscape: multi-scale, continental analysis of forest change.

PubMed

Buma, Brian; Costanza, Jennifer K; Riitters, Kurt

2017-11-21

The scale of investigation for disturbance-influenced processes plays a critical role in theoretical assumptions about stability, variance, and equilibrium, as well as conservation reserve and long-term monitoring program design. Critical consideration of scale is required for robust planning designs, especially when anticipating future disturbances whose exact locations are unknown. This research quantified disturbance proportion and pattern (as contagion) at multiple scales across North America. This pattern of scale-associated variability can guide selection of study and management extents, for example, to minimize variance (measured as standard deviation) between any landscapes within an ecoregion. We identified the proportion and pattern of forest disturbance (30 m grain size) across multiple landscape extents up to 180 km 2 . We explored the variance in proportion of disturbed area and the pattern of that disturbance between landscapes (within an ecoregion) as a function of the landscape extent. In many ecoregions, variance between landscapes within an ecoregion was minimal at broad landscape extents (low standard deviation). Gap-dominated regions showed the least variance, while fire-dominated showed the largest. Intensively managed ecoregions displayed unique patterns. A majority of the ecoregions showed low variance between landscapes at some scale, indicating an appropriate extent for incorporating natural regimes and unknown future disturbances was identified. The quantification of the scales of disturbance at the ecoregion level provides guidance for individuals interested in anticipating future disturbances which will occur in unknown spatial locations. Information on the extents required to incorporate disturbance patterns into planning is crucial for that process.

The intermediate disturbance hypothesis applies to tropical forests, but disturbance contributes little to tree diversity.

PubMed

Bongers, Frans; Poorter, Lourens; Hawthorne, William D; Sheil, Douglas

2009-08-01

The intermediate disturbance hypothesis (IDH) predicts local species diversity to be maximal at an intermediate level of disturbance. Developed to explain species maintenance and diversity patterns in species-rich ecosystems such as tropical forests, tests of IDH in tropical forest remain scarce, small-scale and contentious. We use an unprecedented large-scale dataset (2504 one-hectare plots and 331,567 trees) to examine whether IDH explains tree diversity variation within wet, moist and dry tropical forests, and we analyse the underlying mechanism by determining responses within functional species groups. We find that disturbance explains more variation in diversity of dry than wet tropical forests. Pioneer species numbers increase with disturbance, shade-tolerant species decrease and intermediate species are indifferent. While diversity indeed peaks at intermediate disturbance levels little variation is explained outside dry forests, and disturbance is less important for species richness patterns in wet tropical rain forests than previously thought.

Forced wave induced by an atmospheric pressure disturbance moving towards shore

NASA Astrophysics Data System (ADS)

Chen, Yixiang; Niu, Xiaojing

2018-05-01

Atmospheric pressure disturbances moving over a vast expanse of water can induce different wave patterns, which can be determined by the Froude number Fr. Generally, Fr = 1 is a critical value for the transformation of the wave pattern and the well-known Proudman resonance happens when Fr = 1. In this study, the forced wave induced by an atmospheric pressure disturbance moving over a constant slope from deep sea to shore is numerically investigated. The wave pattern evolves from a concentric-circle type into a triangular type with the increase of the Froude number, as the local water depth decreases, which is in accord with the analysis in the unbounded flat-bottom cases. However, a hysteresis effect has been observed, which implies the obvious amplification of the forced wave induced by a pressure disturbance can not be simply predicted by Fr = 1. The effects of the characteristic parameters of pressure disturbances and slope gradient have been discussed. The results show that it is not always possible to observe significant peak of the maximum water elevation before the landing of pressure disturbances, and a significant peak can be generated by a pressure disturbance with small spatial scale and fast moving velocity over a milder slope. Besides, an extremely high run-up occurs when the forced wave hits the shore, which is an essential threat to coastal security. The results also show that the maximum run-up is not monotonously varying with the increase of disturbance moving speed and spatial scale. There exists a most dangerous speed and scale which may cause disastrous nearshore surge.

Impaired hippocampus-dependent and -independent learning in IL-6 deficient mice.

PubMed

Baier, Paul Christian; May, Ulrike; Scheller, Jürgen; Rose-John, Stefan; Schiffelholz, Thomas

2009-06-08

Interleukin-6 (IL-6) is a cytokine that, in addition to its essential role in the function of the immune system, is present in the central nervous system (CNS). In particular, pathologically increased CNS IL-6 has been linked to impairments in memory performance. Thus, the aim of our present study was to investigate hippocampus-dependent and -independent memory, in combination with exploratory and anxiety related behaviour in IL-6 knock-out (IL-6KO) mice. The experiments were performed with 9 male IL-6KO and 9 age matched male wild-type (CTRL) mice. Hippocampus-dependent learning was assessed with the Morris water maze (MWM), hippocampus-independent learning with the novel object recognition memory test (NORM). The test-battery for additional behavioural assessments included open field (OF), elevated plus maze (EPM) and forced swim test (FST). IL-6KO mice showed impaired memory processes in the NORM as well in the MWM test. This could not be explained by reduced general activity or increased baseline anxiety. But, there was evidence for a higher susceptibility for stress and reduced exploratory behaviour in IL-6KO mice. In conclusion, absent CNS IL-6 does not lead to an improvement in memory function, but instead to an impairment. As "too little and too much spoils everything", our findings do not contradict the hypothesis of an involvement of IL-6 in memory processes. However, it remains unclear if impairments of memory are a specific result of disturbed IL-6 signalling, or rather an epiphenomenon associated with reduced exploratory behaviour and stress resistance.

Sensitivity of climate mitigation strategies to natural disturbances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le Page, Yannick LB; Hurtt, George; Thomson, Allison M.

2013-02-19

The present and future concentration of atmospheric carbon dioxide depends on both anthropogenic and natural sources and sinks of carbon. Most proposed climate mitigation strategies rely on a progressive transition to carbon12 efficient technologies to reduce industrial emissions, substantially supported by policies to maintain or enhance the terrestrial carbon stock in forests and other ecosystems. This strategy may be challenged if terrestrial sequestration capacity is affected by future climate feedbacks, but how and to what extent is little understood. Here, we show that climate mitigation strategies are highly sensitive to future natural disturbance rates (e.g. fires, hurricanes, droughts), because ofmore » potential effect of disturbances on the terrestrial carbon balance. Generally, altered disturbance rates affect the pace of societal and technological transitions required to achieve the mitigation target, with substantial consequences on the energy sector and on the global economy. Understanding the future dynamics and consequences of natural disturbances on terrestrial carbon balance is thus essential for developing robust climate mitigation strategies and policies« less

Movie-maps of low-latitude magnetic storm disturbance

NASA Astrophysics Data System (ADS)

Love, Jeffrey J.; Gannon, Jennifer L.

2010-06-01

We present 29 movie-maps of low-latitude horizontal-intensity magnetic disturbance for the years 1999-2006: 28 recording magnetic storms and 1 magnetically quiescent period. The movie-maps are derived from magnetic vector time series data collected at up to 25 ground-based observatories. Using a technique similar to that used in the calculation of Dst, a quiet time baseline is subtracted from the time series from each observatory. The remaining disturbance time series are shown in a polar coordinate system that accommodates both Earth rotation and the universal time dependence of magnetospheric disturbance. Each magnetic storm recorded in the movie-maps is different. While some standard interpretations about the storm time equatorial ring current appear to apply to certain moments and certain phases of some storms, the movie-maps also show substantial variety in the local time distribution of low-latitude magnetic disturbance, especially during storm commencements and storm main phases. All movie-maps are available at the U.S. Geological Survey Geomagnetism Program Web site (http://geomag.usgs.gov).

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

PubMed

Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Strawn, Steve J; Thakor, Hemang; Fan, Ziling; Shay, Jerry W; Fornace, Albert J; Datta, Kamal

2016-05-01

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. Male and female APC(1638N/+) mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, (12)C, (28)Si, or (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. The highest number of tumors was observed after (28)Si, followed by (56)Fe and (12)C radiation, and tumorigenesis showed a male preponderance, especially after (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 (28)Si, and lower doses showed greater RBE relative to higher doses. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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.

Disturbance dynamics of forested ecosystems

Treesearch

John A. Stanturf

2004-01-01

Forested ecosystems are dynamic, subject to natural developmental processes as well as natural and anthropogenic stresses and disturbances. Degradation is a related term. for lowered productive capacity from changes to forest structure of function (FAO. 2001). Degradation is not synonymous with disturbance, however; disturbance becomes degradation when natural...

Can you escape the beat? Modelling spatiotemporal biodegradation dynamics during periodic disturbances

NASA Astrophysics Data System (ADS)

König, Sara; Worrich, Anja; Wick, Lukas Y.; Miltner, Anja; Kästner, Matthias; Thullner, Martin; Centler, Florian; Banitz, Thomas; Frank, Karin

2016-04-01

. However, for some specific regimes with highly fragmented disturbance patterns, dispersal networks can in turn decrease the biodegradation performance. Our results show that spatial aspects of the periodic disturbance regime influence the biodegradation dynamics, indicating the relevance of spatial processes for functional stability. The level of connectivity between disturbed and undisturbed areas is crucial for the local and global dynamics of the ecosystem service biodegradation. Networks enhancing bacterial dispersal may often, but not always, increase the functional stability.

Free-stream disturbance, continuous Eigenfunctions, boundary-layer instability and transition

NASA Technical Reports Server (NTRS)

Grosch, C. E.

1980-01-01

A rational foundation is presented for the application of the linear shear flows to transition prediction, and an explicit method is given for carrying out the necessary calculations. The expansions used are shown to be complete. Sample calculations show that a typical boundary layer is very sensitive to vorticity disturbances in the inner boundary layer, near the critical layer. Vorticity disturbances three or four boundary layer thicknesses above the boundary are nearly uncoupled from the boundary layer in that the amplitudes of the discrete Tollmien-Schlicting waves are an extremely small fraction of the amplitude of the disturbance.

Plant hydraulic controls over ecosystem responses to climate-enhanced disturbances

NASA Astrophysics Data System (ADS)

Mackay, D. S.; Ewers, B. E.; Reed, D. E.; Pendall, E.; McDowell, N. G.

2012-12-01

. Disturbances included declining water tables and canopy defoliators (northern temperature forests), bark beetles and associated blue-stain fungi (coniferous forests), and prolonged drought with bark beetles (semi-arid woodland). We show that C dynamics in trees that experience water-limitation, insect attack, or a combination of both disturbance types cannot be explained solely from hydraulic status or NSC, but are better explained by a combination of both in conjunction with N uptake. Results show that the use of plant hydraulics can yield parsimonious explanations of biophysical, ecohydrological, and biogeochemical responses to disturbance.

Climate change and forest disturbances

Treesearch

Virginia H. Dale; Linda A. Joyce; Steve McNulty; Ronald P. Neilson; Matthew P. Ayres; Michael D. Flannigan; Paul J. Hanson; Lloyd C. Irland; Ariel E. Lugo; Chris J. Peterson; Daniel Simberloff; Frederick J. Swanson; Brian J. Stocks; Michael Wotton

2001-01-01

This article examines how eight disturbances influence forest structure, composition, and function, and how climate change may influence the severity, frequency, and magnitude of disturbances to forests. We focus on examples from the United States, although these influences occur worldwide. We also consider options for coping with disturbance under changing climate....

Geomagnetic disturbance and the orientation of nocturnally migrating birds.

PubMed

Moore, F R

1977-05-06

Free-flying passerine migrants respond to natural fluctuations in the earth's magnetic field. The variability in flight directions of nocturnal migrants is significantly correlated with increasing geomagnetic disturbance as measured by both the K index and various components of the earth's magnetic field. The results indicate that such disturbances influence the orientation of free-flying migrants, but the evidence is not sufficient to show that geomagnetism is a cue in their orientation system.

Is passive smoking associated with sleep disturbance among pregnant women?

PubMed

Ohida, Takashi; Kaneita, Yoshitaka; Osaki, Yoneatsu; Harano, Satoru; Tanihata, Takeo; Takemura, Shinji; Wada, Kiyoshi; Kanda, Hideyuki; Hayashi, Kenji; Uchiyama, Makoto

2007-09-01

Pregnant women suffer from sleep disturbance, which may be aggravated by passive smoking. In this study we investigated the effects of passive smoking on sleep disturbance during pregnancy. Two cross-sectional questionnaire surveys conducted in 2002 and 2006. Clinical institutions specializing in obstetrics and gynecology that participated in the nationwide surveys: 260 in the 2002 survey and 344 in the 2006 survey. 16,396 and 19,386 pregnant women in Japan surveyed in 2002 and 2006, respectively. N/A. Pregnant women exposed to passive smoking were likely to have sleep disturbances, such as subjective insufficient sleep, difficulty in initiating sleep, short sleep duration, and snoring loudly/breathing uncomfortably. Smoking pregnant women had the same sleep disturbances and also experienced excessive daytime sleepiness and early morning awakening. The prevalence of 5 types of sleep disturbance (insufficient sleep, difficulty in initiating sleep, short sleep duration, excessive daytime sleepiness, and snoring loudly/breathing uncomfortably) among nonsmokers with environmental tobacco smoke showed a mean value intermediate between that of active smokers and that of nonsmokers without environmental tobacco smoke. Passive smoking is independently associated with increased sleep disturbance during pregnancy.

Endogenous galectin-3 expression levels modulate immune responses in galectin-3 transgenic mice.

PubMed

Chaudhari, Aparna D; Gude, Rajiv P; Kalraiya, Rajiv D; Chiplunkar, Shubhada V

2015-12-01

Galectin-3 (Gal-3), a β-galactoside-binding mammalian lectin, is involved in cancer progression and metastasis. However, there is an unmet need to identify the underlying mechanisms of cancer metastasis mediated by endogenous host galectin-3. Galectin-3 is also known to be an important regulator of immune responses. The present study was aimed at analysing how expression of endogenous galectin-3 regulates host immunity and lung metastasis in B16F10 murine melanoma model. Transgenic Gal-3(+/-) (hemizygous) and Gal-3(-/-) (null) mice exhibited decreased levels of Natural Killer (NK) cells and lower NK mediated cytotoxicity against YAC-1 tumor targets, compared to Gal-3(+/+) (wild-type) mice. On stimulation, Gal-3(+/-) and Gal-3(-/-) mice splenocytes showed increased T cell proliferation than Gal-3(+/+) mice. Intracellular calcium flux was found to be lower in activated T cells of Gal-3(-/-) mice as compared to T cells from Gal-3(+/+) and Gal-3(+/-) mice. In Gal-3(-/-) mice, serum Th1, Th2 and Th17 cytokine levels were found to be lowest, exhibiting dysregulation of pro-inflammatory and anti-inflammatory cytokines balance. Marked decrease in serum IFN-γ levels and splenic IFN-γR1 (IFN-γ Receptor 1) expressing T and NK cell percentages were observed in Gal-3(-/-) mice. On recombinant IFN-γ treatment of splenocytes in vitro, Suppressor of Cytokine Signaling (SOCS) 1 and SOCS3 protein expression was higher in Gal-3(-/-) mice compared to that in Gal-3(+/+) and Gal-3(+/-) mice; suggesting possible attenuation of Signal Transducer and Activator of Transcription (STAT) 1 mediated IFN-γ signaling in Gal-3(-/-) mice. The ability of B16F10 melanoma cells to form metastatic colonies in the lungs of Gal-3(+/+) and Gal-3(-/-) mice remained comparable, whereas it was found to be reduced in Gal-3(+/-) mice. Our data indicates that complete absence of endogenous host galectin-3 facilitates lung metastasis of B16F10 cells in mice, which may be contributed by dysregulated immune

Solar Development on Contaminated and Disturbed Lands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macknick, Jordan; Lee, Courtney; Mosey, Gail

2013-12-01

Land classified as contaminated and disturbed across the United States has the potential to host developments of utility-scale solar power. This report examines the prospect of developing utility- and commercial-scale concentrated solar power (CSP) and solar photovoltaics (PV) technologies on degraded and environmentally contaminated lands. The potential for solar development on contaminated anddisturbed lands was assessed, and for the largest and highest solar resource sites, the economic impacts and feasibility were evaluated. Developing solar power on contaminated and disturbed lands can help create jobs and revitalize local and state economies, and selecting these sites over greenfield sites can potentially havemore » permitting and environmental mitigation advantages. The U.S.Department of Energy (DOE) SunShot goals call for 632 GW of PV and 83 GW of CSP to be deployed by 2050. Conservative land-use estimates of this study (10 acres per megawatt) show that there are disturbed and environmentally contaminated lands throughout the country that could be suitable for utility-scale solar power, and, that there is sufficient land area to meet SunShot solar deployment goals. The purpose of this assessment is to improve the understanding of these sites and facilitate solar developers' selection of contaminated and disturbed sites for development.« less

Disturbing Behavior Checklists" Technical Manual

ERIC Educational Resources Information Center

Algozzine, Bob

2012-01-01

Ecological theorists have suggested that "disturbance" may result from an interaction between a child's behavior and reactions to that behavior within ecosystems such as schools. In this context, behavior is viewed as "disturbing" rather than "disturbed" and equal emphasis is given to the child and to individuals with whom the child interacts when…

Sleep Disturbance Preceding Suicide Among Veterans

PubMed Central

Britton, Peter C.; Ilgen, Mark A.; Chapman, Ben; Conner, Kenneth R.

2012-01-01

Objectives. We examined the role of sleep disturbance in time to suicide since the last treatment visit among veterans receiving Veterans Health Administration (VHA) services. Methods. Among 423 veteran suicide decedents from 2 geographic areas, systematic chart reviews were conducted on the 381 (90.1%) who had a VHA visit in the last year of life. Veteran suicides with a documented sleep disturbance (45.4%) were compared with those without sleep disturbance (54.6%) on time to death since their last VHA visit using an accelerated failure time model. Results. Veterans with sleep disturbance died sooner after their last visit than did those without sleep disturbance, after we adjusted for the presence of mental health or substance use symptoms, age, and region. Conclusions. Findings indicated that sleep disturbance was associated with time to suicide in this sample of veterans who died by suicide. The findings had implications for using the presence of sleep disturbance to detect near-term risk for suicide and suggested that sleep disturbance might provide an important intervention target for a subgroup of at-risk veterans. PMID:22390611

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

PubMed

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.

Intermittent hypoxia induces hyperlipidemia in lean mice.

PubMed

Li, Jianguo; Thorne, Laura N; Punjabi, Naresh M; Sun, Cheuk-Kwan; Schwartz, Alan R; Smith, Philip L; Marino, Rafael L; Rodriguez, Annabelle; Hubbard, Walter C; O'Donnell, Christopher P; Polotsky, Vsevolod Y

2005-09-30

Obstructive sleep apnea, a syndrome leading to recurrent intermittent hypoxia (IH), has been associated previously with hypercholesterolemia, independent of underlying obesity. We examined the effects of experimentally induced IH on serum lipid levels and pathways of lipid metabolism in the absence and presence of obesity. Lean C57BL/6J mice and leptin-deficient obese C57BL/6J-Lep(ob) mice were exposed to IH for five days to determine changes in serum lipid profile, liver lipid content, and expression of key hepatic genes of lipid metabolism. In lean mice, exposure to IH increased fasting serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, phospholipids (PLs), and triglycerides (TGs), as well as liver TG content. These changes were not observed in obese mice, which had hyperlipidemia and fatty liver at baseline. In lean mice, IH increased sterol regulatory element binding protein 1 (SREBP-1) levels in the liver, increased mRNA and protein levels of stearoyl-coenzyme A desaturase 1 (SCD-1), an important gene of TG and PL biosynthesis controlled by SREBP-1, and increased monounsaturated fatty acid content in serum, which indicated augmented SCD-1 activity. In addition, in lean mice, IH decreased protein levels of scavenger receptor B1, regulating uptake of cholesterol esters and HDL by the liver. We conclude that exposure to IH for five days increases serum cholesterol and PL levels, upregulates pathways of TG and PL biosynthesis, and inhibits pathways of cholesterol uptake in the liver in the lean state but does not exacerbate the pre-existing hyperlipidemia and metabolic disturbances in leptin-deficient obesity.

A morphological study of the pacemaker cells of the aganglionic intestine in Hirschsprung's disease utilizing ls/ls model mice.

PubMed

Taniguchi, Kan; Matsuura, Kimio; Matsuoka, Takanori; Nakatani, Hajime; Nakano, Takumi; Furuya, Yasuo; Sugimoto, Takeki; Kobayashi, Michiya; Araki, Keijiro

2005-06-01

Hirschsprung's disease is a congenital aganglionic neural disorder of the segmental distal intestine characterized by unsettled pathogenesis. The relationship between Hirschsprung's disease and pacemaker cells (PMC), which almost corresponds to that of the interstitial cells of Cajal (ICC), was morphologically observed at the level of the intermuscular layer corresponding to Auerbach's plexus using ls/ls mice. These mice are an ideal model because of their large intestinal aganglionosis and gene abnormalities, which are similar to the human form of the disease. Immunostaining using anti-c-kit receptor antibody (ACK2), a marker of PMC, applied to whole-mount muscle-layer specimens, revealed the presence of c-kit immunopositive multipolar cells with many cytoplasmic processes in normal mice. For ls/ls mice, however, there were significantly fewer processes. The average number of processes per positive cell of 2.5 for the aganglionic large intestine was fewer than 3.5 for the large and small intestine of normal mice, indicating the inability to form connections between nerves and PMC in the aganglionic intestine. For normal mice with an Auerbach's plexus, the process attachment of ICC to the Auerbach's plexus was observed by scanning electron microscopy. However, for ls/ls mice no attachment to the intermuscular nerve without Auerbach's plexus was found, although transmission electron microscopy showed no difference in the cell structure and organelles of the c-kit immunopositive cells between the normal and ls/ls mice. These findings suggest that in the aganglionic intestine of Hirschsprung's disease, aplasia of enteric ganglia induces secondary disturbances during the normal development of intestinal PMC.

Altered emotionality, hippocampus-dependent performance and expression of NMDA receptor subunit mRNAs in chronically stressed mice.

PubMed

Costa-Nunes, João; Zubareva, Olga; Araújo-Correia, Margarida; Valença, Andreia; Schroeter, Careen A; Pawluski, Jodi L; Vignisse, Julie; Steinbusch, Hellen; Hermes, Denise; Phillipines, Marjan; Steinbusch, Harry M W; Strekalova, Tatyana

2014-01-01

N-Methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission in the hippocampus is implicated in cognitive and emotional disturbances during stress-related disorders. Here, using quantitative RT-PCR, we investigated the hippocampal expression of NR2A, NR2B and NR1 subunit mRNAs in a mouse stress paradigm that mimics clinically relevant conditions of simultaneously affected emotionality and hippocampus-dependent functions. A 2-week stress procedure, which comprised ethologically valid stressors, exposure to a rat and social defeat, was applied to male C57BL/6J mice. For predation stress, mice were introduced into transparent containers that were placed in a rat home cage during the night; social defeat was applied during the daytime using aggressive CD1 mice. This treatment impaired hippocampus-dependent performance during contextual fear conditioning. A correlation between this behavior and food displacement performance was demonstrated, suggesting that burrowing behavior is affected by the stress procedure and is hippocampus-dependent. Stressed mice (n = 22) showed behavioral invigoration and anomalous anxiolytic-like profiles in the O-maze and brightly illuminated open field, unaltered short-term memory in the step-down avoidance task and enhanced aggressive traits, as compared to non-stressed mice (n = 10). Stressed mice showed increased basal serum corticosterone concentrations, hippocampal mRNA expression for the NR2A subunit of the NMDAR and in the NR2A/NR2B ratio; mRNA expression of NR2B and NR1 was unchanged. Thus, stress-induced aberrations in both hippocampal-dependent performance and emotional abnormalities are associated with alterations in hippocampal mRNA NR2A levels and the NR2A/NR2B ratio and not with mRNA expression of NR2B or NR1.

Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia-reperfusion injury in steatotic livers of ob/ob mice

PubMed Central

Hasegawa, Tadashi; Ito, Yoshiya; Wijeweera, Jayanthika; Liu, Jie; Malle, Ernst; Farhood, Anwar; McCuskey, Robert S.; Jaeschke, Hartmut

2016-01-01

Steatosis is a major risk factor for complications after liver surgery. Since neutrophil cytotoxicity is critical for ischemia-reperfusion injury in normal livers, the aim of the present study was to evaluate whether an exaggerated inflammatory response could cause the increased injury in steatotic livers. In C57Bl/6 mice, 60 min of warm hepatic ischemia triggered a gradual increase in hepatic neutrophil accumulation during reperfusion with peak levels of 100-fold over baseline at 12 h of reperfusion. Neutrophil extravasation and a specific neutrophil-induced oxidant stress (immunostaining for hypochlorous acid-modified epitopes) started at 6 h of reperfusion and peaked at 12–24 h. Ob/ob mice, which had a severe macrovesicular steatosis, suffered significantly higher injury (alanine transaminase activity: 18,000 ± 2,100 U/l; 65% necrosis) compared with lean littermates (alanine transaminase activity: 4,900 ± 720 U/l; 24% necrosis) at 6 h of reperfusion. However, 62% fewer neutrophils accumulated in steatotic livers. This correlated with an attenuated increase in mRNA levels of several proinflammatory genes in ob/ob mice during reperfusion. In contrast, sham-operated ob/ob mice had a 50% reduction in liver blood flow and 35% fewer functional sinusoids compared with lean littermates. These deficiencies in liver blood flow and the microcirculation were further aggravated only in ob/ob mice during reperfusion. The attenuated inflammatory response and reduced neutrophil-induced oxidant stress observed in steatotic livers during reperfusion cannot be responsible for the dramatically increased injury in ob/ob mice. In contrast, the aggravated injury appears to be mediated by ischemic necrosis due to massive impairment of blood and oxygen supply in the steatotic livers. PMID:17307725

Soil disturbance by airbags

NASA Technical Reports Server (NTRS)

1997-01-01

Disturbance of the drift at the Pathfinder landing site reveals a shallow subsurface that is slightly darker but has similar spectral properties. The top set of images, in true color, shows the soils disturbed by the last bounce of the lander on its airbags before coming to rest and the marks created by retraction of the airbags. In the bottom set of images color differences have been enhanced. The mast at center is the Atmospheric Structure Instrument/Meteorology Package (ASI/MET). The ASI/MET is an engineering subsytem that acquired atmospheric data during Pathfinder's descent, and will continue to get more data through the entire landed mission. A shadow of the ASI/MET appears on a rock at left.

Mars Pathfinder was developed and managed by the Jet Propulsion Laboratory (JPL) for the National Aeronautics and Space Administration. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota.

PubMed

Zhou, Da; Pan, Qin; Shen, Feng; Cao, Hai-Xia; Ding, Wen-Jin; Chen, Yuan-Wen; Fan, Jian-Gao

2017-05-08

Non-alcoholic steatohepatitis (NASH) is an epidemic metabolic disease with limited therapeutic strategies. Cumulative data support the pivotal role of gut microbiota in NASH. Here, we investigated the hypothesis regarding whether fecal microbiota transplantation (FMT) is effective in attenuating high-fat diet (HFD)-induced steatohepatitis in mice. Mice were randomized into control, HFD and HFD + FMT groups. After an 8-week HFD, FMT treatment was initiated and carried out for 8 weeks. The gut microbiota structure, butyrate concentrations of the cecal content, liver pathology and intrahepatic lipid and cytokines were examined. Our results showed that after FMT, the gut microbiota disturbance was corrected in HFD-fed mice with elevated abundances of the beneficial bacteria Christensenellaceae and Lactobacillus. FMT also increased butyrate concentrations of the cecal content and the intestinal tight junction protein ZO-1, resulting in relief of endotoxima in HFD-fed mice. Steatohepatitis was alleviated after FMT, as indicated by a significant decrease in intrahepatic lipid accumulation (reduced Oli-red staining, decreased intrahepatic triglyceride and cholesterol), intrahepatic pro-inflammatory cytokines, and the NAS score. Accordingly, intrahepatic IFN-γ and IL-17 were decreased, but Foxp3, IL-4 and IL-22 were increased after FMT intervention. These data indicate that FMT attenuated HFD-induced steatohepatitis in mice via a beneficial effect on the gut microbiota.

Discrepant effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on oxidative stress and energy metabolism in the livers and kidneys of mice.

PubMed

Yan, Jin; Wang, Dezhen; Miao, Jiyan; Liu, Chang; Wang, Yao; Teng, Miaomiao; Zhou, Zhiqiang; Zhu, Wentao

2018-08-01

Endosulfan, an organochloride pesticide, has been used for many commercial purposes. Endosulfan is composed of two isomers, α-endosulfan and β-endosulfan. In biological and soil systems, endosulfan is metabolized into endosulfan sulfate. In this study, the different toxicological effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on the livers and kidneys of mice were comprehensively investigated. The results demonstrated that both endosulfan isomers and endosulfan sulfate disturbed the hepatic and renal antioxidant systems. Furthermore, 1 H NMR metabolomics analysis revealed that endogenous metabolites involved in oxidative stress and energy metabolism were altered after exposure to these compounds. In the liver, the changes in hepatic endogenous metabolites and the induction of hepatic CYP450 mRNA isoforms were similar among mice treated with the three compounds, and the sulfate metabolite was the exclusive exogenous compound detected. Therefore, the metabolism of α- and β-endosulfan to endosulfan sulfate is likely the main cause of toxicological effects in the livers of mice. However, in kidneys, the changes in the metabolome and in CYP450 mRNA expression induced by α-endosulfan and β-endosulfan were stereoselective. Additionally, endosulfan sulfate, which induced a significant increase of renal Cyp3a11, showed a more robust disturbance of renal metabolites than either of the two isomers. These findings revealed that more attention should be given to the toxicological evaluation of endosulfan sulfate in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cyp26b1 within the growth plate regulates bone growth in juvenile mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minegishi, Yoshiki; Department of Plastic and Reconstructive Surgery, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193; Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871

Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, itmore » has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.« less

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

PubMed

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

2016-01-15

Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Dispersal Mutualism Incorporated into Large-Scale, Infrequent Disturbances

PubMed Central

Parker, V. Thomas

2015-01-01

Because of their influence on succession and other community interactions, large-scale, infrequent natural disturbances also should play a major role in mutualistic interactions. Using field data and experiments, I test whether mutualisms have been incorporated into large-scale wildfire by whether the outcomes of a mutualism depend on disturbance. In this study a seed dispersal mutualism is shown to depend on infrequent, large-scale disturbances. A dominant shrubland plant (Arctostaphylos species) produces seeds that make up a persistent soil seed bank and requires fire to germinate. In post-fire stands, I show that seedlings emerging from rodent caches dominate sites experiencing higher fire intensity. Field experiments show that rodents (Perimyscus californicus, P. boylii) do cache Arctostaphylos fruit and bury most seed caches to a sufficient depth to survive a killing heat pulse that a fire might drive into the soil. While the rodent dispersal and caching behavior itself has not changed compared to other habitats, the environmental transformation caused by wildfire converts the caching burial of seed from a dispersal process to a plant fire adaptive trait, and provides the context for stimulating subsequent life history evolution in the plant host. PMID:26151560

A succession of theories: purging redundancy from disturbance theory.

PubMed

Pulsford, Stephanie A; Lindenmayer, David B; Driscoll, Don A

2016-02-01

trait approach is likely to improve the predictive capacity of disturbance theory. Finally, we complement our discussion of theory with a case study which emphasises that many post-disturbance theories apply simultaneously to the same ecosystem. Using the well-studied mountain ash (Eucalyptus regnans) forests of south-eastern Australia, we illustrate phenomena that align with six of the theories described in our model of rationalised disturbance theory. We encourage further work to improve our schematic model, increase coverage of disturbance-related theory, and to show how the model may link to, or integrate with, other domains of ecological theory. © 2014 Cambridge Philosophical Society.

The relative importance of disturbance and exotic-plant abundance in California coastal sage scrub

USGS Publications Warehouse

Fleming, G.M.; Diffendorfer, J.E.; Zedler, P.H.

2009-01-01

Many ecosystems of conservation concern require some level of disturbance to sustain their species composition and ecological function. However, inappropriate disturbance regimes could favor invasion or expansion of exotic species. In southern California coastal sage scrub (CSS) fire is a natural disturbance, but because of human influence, frequencies may now be unnaturally high. Other anthropogenic disturbances such as grazing also occur in reserve areas. Managers charged with imposing or tolerating fire or other disturbance within their reserves are concerned that habitat quality may be degraded by an increasing abundance of exotic plants. We used vegetation monitoring data from Camp Pendleton, California, USA, to assess the correlation between past disturbances (frequent fire, agriculture, or grazing and mechanical disturbances) and current exotic species abundance in CSS. We found that disturbance history was only modestly related to exotic abundance overall, but fire frequency showed the strongest association. We also examined whether cover and richness of various native plant life forms (woody species, perennial herbs, and annual herbs) were more strongly influenced by disturbance history or by exotic-plant abundance. Native plant responses varied among life forms, but woody species and annual herbs were generally more strongly and negatively associated with exotic abundance than with disturbance. Effective CSS conservation will require developing means to curb the negative impacts of exotic plants, which may abound with or without severe or recent disturbance. Additionally, more focus should be given to understory herbs showing sensitivity to invasion. Though understudied, native herbs comprise the greatest portion of plant diversity in CSS and are critical to preservation of the community as a whole. ?? 2009 by the Ecological Society of America.

Disturbance, scale, and boundary in wilderness management

Treesearch

Peter S. White; Jonathan Harrod; Joan L. Walker; Anke Jentsch

2000-01-01

Natural disturbances are critical to wilderness management. This paper reviews recent research on natural disturbance and addresses the problem of managing for disturbances in a world of human-imposed scales and boundaries. The dominant scale issue in disturbance management is the question of patch dynamic equilibrium. The dominant boundary issue in disturbance...

Disturbance, Scale, and Boundary in Wilderness Management

Treesearch

Peter S. White; Jonathan Harrod; Joan L. Walker; Anke Jentsch

2000-01-01

Natural disturbances are critical to wilderness management. This paper reviews recent research on natural disturbance and addresses the problem of managing for disturbances in a world of human-imposed scales and boundaries. The dominant scale issue in disturbance management is the question of patch dynamic equilibrium. The dominant boundary issue in disturbance...

Visually Determined Soil Disturbance Classes Used as Indices of Forest Harvesting Disturbance

Treesearch

W. Michael Aust; James A. Burger; Emily A. Carter; David P. Preston; Steven C. Patterson

1998-01-01

Visual estimates of soil and site disturbances are used by foresters, soil scientists, logging supervisors. and machinery operators to minimize harvest disturbances to forest sites, to evaluate compliance with forestry Best Management Practices (BMPs), and to determine the need for ameliorative practices such as tnechanical site preparation. Although estimates are...

Dysfunctional Muscle and Liver Glycogen Metabolism in mdx Dystrophic Mice

PubMed Central

Stapleton, David I.; Lau, Xianzhong; Flores, Marcelo; Trieu, Jennifer; Gehrig, Stefan M.; Chee, Annabel; Naim, Timur; Lynch, Gordon S.; Koopman, René

2014-01-01

Background Duchenne muscular dystrophy (DMD) is a severe, genetic muscle wasting disorder characterised by progressive muscle weakness. DMD is caused by mutations in the dystrophin (dmd) gene resulting in very low levels or a complete absence of the dystrophin protein, a key structural element of muscle fibres which is responsible for the proper transmission of force. In the absence of dystrophin, muscle fibres become damaged easily during contraction resulting in their degeneration. DMD patients and mdx mice (an animal model of DMD) exhibit altered metabolic disturbances that cannot be attributed to the loss of dystrophin directly. We tested the hypothesis that glycogen metabolism is defective in mdx dystrophic mice. Results Dystrophic mdx mice had increased skeletal muscle glycogen (79%, (P<0.01)). Skeletal muscle glycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (P<0.0001). Glycogen synthase activity was 12% higher (P<0.05) but glycogen branching enzyme activity was 70% lower (P<0.01) in mdx compared with wild-type mice. The rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 62% lower activity (P<0.01) in mdx mice resulting from a 24% reduction in PKA activity (P<0.01). In mdx mice glycogen debranching enzyme expression was 50% higher (P<0.001) together with starch-binding domain protein 1 (219% higher; P<0.01). In addition, mdx mice were glucose intolerant (P<0.01) and had 30% less liver glycogen (P<0.05) compared with control mice. Subsequent analysis of the enzymes dysregulated in skeletal muscle glycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; P<0.05) as a possible cause of this phenotype. Conclusion We identified that mdx mice were glucose intolerant, and had increased skeletal muscle glycogen but reduced amounts of liver glycogen. PMID:24626262

Islets of Langerhans from prohormone convertase-2 knockout mice show α-cell hyperplasia and tumorigenesis with elevated α-cell neogenesis

PubMed Central

Jones, Huw B; Reens, Jaimini; Brocklehurst, Simon R; Betts, Catherine J; Bickerton, Sue; Bigley, Alison L; Jenkins, Richard P; Whalley, Nicky M; Morgan, Derrick; Smith, David M

2014-01-01

Antagonism of the effects of glucagon as an adjunct therapy with other glucose-lowering drugs in the chronic treatment of diabetes has been suggested to aggressively control blood glucose levels. Antagonism of glucagon effects, by targeting glucagon secretion or disabling the glucagon receptor, is associated with α-cell hyperplasia. We evaluated the influence of total glucagon withdrawal on islets of Langerhans using prohormone convertase-2 knockout mice (PC2-ko), in which α-cell hyperplasia is present from a young age and persists throughout life, in order to understand whether or not sustained glucagon deficit would lead to islet tumorigenesis. PC2-ko and wild-type (WT) mice were maintained drug-free, and cohorts of these groups sampled at 3, 12 and 18 months for plasma biochemical and morphological (histological, immunohistochemical, electron microscopical and image analytical) assessments. WT mice showed no islet tumours up to termination of the study, but PC2-ko animals displayed marked changes in islet morphology from α-cell hypertrophy/hyperplasia/atypical hyperplasia, to adenomas and carcinomas, these latter being first encountered at 6–8 months. Islet hyperplasias and tumours primarily consisted of α-cells associated to varying degrees with other islet endocrine cell types. In addition to substantial increases in islet neoplasia, increased α-cell neogenesis associated primarily with pancreatic duct(ule)s was present. We conclude that absolute blockade of the glucagon signal results in tumorigenesis and that the PC2-ko mouse represents a valuable model for investigation of islet tumours and pancreatic ductal neogenesis. PMID:24456331

Prenatal exposure to phencyclidine produces abnormal behaviour and NMDA receptor expression in postpubertal mice.

PubMed

Lu, Lingling; Mamiya, Takayoshi; Lu, Ping; Toriumi, Kazuya; Mouri, Akihiro; Hiramatsu, Masayuki; Kim, Hyoung-Chun; Zou, Li-Bo; Nagai, Taku; Nabeshima, Toshitaka

2010-08-01

Several studies have shown the disruptive effects of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists on neurobehavioural development. Based on the neurodevelopment hypothesis of schizophrenia, there is growing interest in animal models treated with NMDA antagonists at developing stages to investigate the pathogenesis of psychological disturbances in humans. Previous studies have reported that perinatal treatment with phencyclidine (PCP) impairs the development of neuronal systems and induces schizophrenia-like behaviour. However, the adverse effects of prenatal exposure to PCP on behaviour and the function of NMDA receptors are not well understood. This study investigated the long-term effects of prenatal exposure to PCP in mice. The prenatal PCP-treated mice showed hypersensitivity to a low dose of PCP in locomotor activity and impairment of recognition memory in the novel object recognition test at age 7 wk. Meanwhile, the prenatal exposure reduced the phosphorylation of NR1, although it increased the expression of NR1 itself. Furthermore, these behavioural changes were attenuated by atypical antipsychotic treatment. Taken together, prenatal exposure to PCP produced long-lasting behavioural deficits, accompanied by the abnormal expression and dysfunction of NMDA receptors in postpubertal mice. It is worth investigating the influences of disrupted NMDA receptors during the prenatal period on behaviour in later life.

Geranylgeranylacetone prevents stress-induced decline of leptin secretion in mice.

PubMed

Itai, Miki; Kuwano, Yuki; Nishikawa, Tatsuya; Rokutan, Kazuhito; Kensei, Nishida

2018-01-01

Geranylgeranylacetone (GGA) is a chaperon inducer that protects various types of cell and tissue against stress. We examined whether GGA modulated energy intake and expenditure under stressful conditions. After mice were untreated or treated orally with GGA (0.16 g per kg body weight per day) for 10 days, they were subjected to 2-h restraint stress once or once a day for 5 consecutive days. GGA administration did not affect corticosterone response to the stress. Restraint stress rapidly decreased plasma leptin levels in control mice. GGA significantly increased circulating leptin levels without changing food intake and prevented the stress-induced decline of circulating leptin. However GGA-treated mice significantly reduced food intake during the repeated stress, compared with control mice. GGA prevented the stress-induced decline of leptin mRNA and its protein levels in epidydimal adipose tissues. We also found that GGA decreased ghrelin mRNA expression in gastric mucosa before the stress, whereas GGA-treated mice recovered the ghrelin mRNA expression to the baseline level after the repeated stress. Leptin and ghrelin are now recognized as regulators of anxiety and depressive mood. Our results suggest that GGA may regulate food intake and relief stress-induced mood disturbance through regulating leptin and ghrelin secretions. J. Med. Invest. 65:103-109, February, 2018.

Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury

PubMed Central

Gey, Manuel; Wanner, Renate; Schilling, Corinna; Pedro, Maria T.; Sinske, Daniela

2016-01-01

Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce ‘effector’ RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types. PMID:27581653

Impacts of cannabinoid receptor ligands on nicotine- and chronic mild stress-induced cognitive and depression-like effects in mice.

PubMed

Pekala, Karolina; Michalak, Agnieszka; Kruk-Slomka, Marta; Budzynska, Barbara; Biala, Grazyna

2018-07-16

Taking into account the rather frequent concomitance of nicotine abuse and stress, we aimed to research memory- and depression-related effects of nicotine administration in combination with chronic mild unpredictable stress (CMUS) in mice and an involvement of the endocannabinoid system through CB1 and CB2 receptors. Mice were submitted to the CMUS for 4 weeks. Effects on depression-like behaviors and cognition, exerted by a combined administration of CB1, i.e., Oleamide (2.5, 5.0 mg/kg), AM 251 (0.1, 0.25 mg/kg) and CB2, i.e., JWH 133 (0.5, 2.0 mg/kg), AM 630 (0.25, 2.0 mg/kg) receptor ligands and nicotine (0.05, 0.1, 0.2 and 0.5 mg/kg), were then studied in stressed and unstressed mice by the forced swimming test and the passive avoidance paradigm, respectively. The results revealed that the CMUS-exposed mice exhibited depression-like behaviors and memory disturbances, while both effects were alleviated by nicotine. CB1 receptor ligands decreased antidepressive and cognitive (the latter for CB1 receptor antagonist only) effects of subchronic nicotine administration in stressed mice. CB1 and CB2 receptor antagonists exerted themselves some procognitive effects in those mice. Regarding the unstressed mice, CB1 and CB2 receptor ligands reversed the antidepressive effects of subchronic nicotine administration, while nicotine, in an ineffective dose, co-administered with CB2 receptor ligands, improved cognition. We confirmed the role of the two main subtypes of cannabinoid receptors, termed CB1 and CB2, on stress- and nicotine-related behavioral changes in mice. Our study has contributed to the understanding of the mechanisms involved in stress- and nicotine-induced disorders, such as anhedonia and memory disturbances. Copyright © 2018 Elsevier B.V. All rights reserved.

Noise and disturbance of qubit measurements: An information-theoretic characterization

NASA Astrophysics Data System (ADS)

Abbott, Alastair A.; Branciard, Cyril

2016-12-01

Information-theoretic definitions for the noise associated with a quantum measurement and the corresponding disturbance to the state of the system have recently been introduced [F. Buscemi et al., Phys. Rev. Lett. 112, 050401 (2014), 10.1103/PhysRevLett.112.050401]. These definitions are invariant under relabeling of measurement outcomes, and lend themselves readily to the formulation of state-independent uncertainty relations both for the joint estimate of observables (noise-noise relations) and the noise-disturbance tradeoff. Here we derive such relations for incompatible qubit observables, which we prove to be tight in the case of joint estimates, and present progress towards fully characterizing the noise-disturbance tradeoff. In doing so, we show that the set of obtainable noise-noise values for such observables is convex, whereas the conjectured form for the set of obtainable noise-disturbance values is not. Furthermore, projective measurements are not optimal with respect to the joint-measurement noise or noise-disturbance tradeoffs. Interestingly, it seems that four-outcome measurements are needed in the former case, whereas three-outcome measurements are optimal in the latter.

Disturbance to wintering western snowy plovers

USGS Publications Warehouse

Lafferty, Kevin D.

2001-01-01

In order to better understand the nature of disturbances to wintering snowy plovers, I observed snowy plovers and activities that might disturb them at a beach near Devereux Slough in Santa Barbara, California, USA. Disturbance (activity that caused plovers to move or fly) to wintering populations of threatened western snowy plovers was 16 times higher at a public beach than at protected beaches. Wintering plovers reacted to disturbance at half the distance (∼40 m) as has been reported for breeding snowy plovers (∼80 m). Humans, dogs, crows and other birds were the main sources of disturbance on the public beach, and each snowy plover was disturbed, on average, once every 27 weekend min and once every 43 weekday min. Dogs off leash were a disproportionate source of disturbance. Plovers were more likely to fly from dogs, horses and crows than from humans and other shorebirds. Plovers were less abundant near trail heads. Over short time scales, plovers did not acclimate to or successfully find refuge from disturbance. Feeding rates declined with increased human activity. I used data from these observations to parameterize a model that predicted rates of disturbance given various management actions. The model found that prohibiting dogs and a 30 m buffer zone surrounding a 400 m stretch of beach provided the most protection for plovers for the least amount of impact to beach recreation.

Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13-Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation.

PubMed

Liu, Kai-Ming; Chen, Yi-Ju; Shen, Li-Fen; Haddad, Amir N S; Song, I-Wen; Chen, Li-Ying; Chen, Yu-Ju; Wu, Jer-Yuarn; Yen, Jeffrey J Y; Chen, Yuan-Tsong

2015-11-01

Many biochemical pathways involved in hair and skin development have not been investigated. Here, we reported on the lesions and investigated the mechanism underlying hair and skin abnormalities in Zdhhc13(skc4) mice with a deficiency in DHHC13, a palmitoyl-acyl transferase encoded by Zdhhc13. Homozygous affected mice showed ragged and dilapidated cuticle of the hair shaft (CUH, a hair anchoring structure), poor hair anchoring ability, and premature hair loss at early telogen phase of the hair cycle, resulting in cyclic alopecia. Furthermore, the homozygous affected mice exhibited hyperproliferation of the epidermis, disturbed cornification, fragile cornified envelope (CE, a skin barrier structure), and impaired skin barrier function. Biochemical investigations revealed that cornifelin, which contains five palmitoylation sites at cysteine residues (C58, C59, C60, C95, and C101), was a specific substrate of DHHC13 and that it was absent in the CUH and CE structures of the affected mice. Furthermore, cornifelin levels were markedly reduced when two palmitoylated cysteines were replaced with serine (C95S and C101S). Taken together, our results suggest that DHHC13 is important for hair anchoring and skin barrier function and that cornifelin deficiency contributes to cyclic alopecia and skin abnormalities in Zdhhc13(skc4) mice.

Sleep Disturbance after Hospitalization and Critical Illness: A Systematic Review.

PubMed

Altman, Marcus T; Knauert, Melissa P; Pisani, Margaret A

2017-09-01

Sleep disturbance during intensive care unit (ICU) admission is common and severe. Sleep disturbance has been observed in survivors of critical illness even after transfer out of the ICU. Not only is sleep important to overall health and well being, but patients after critical illness are also in a physiologically vulnerable state. Understanding how sleep disturbance impacts recovery from critical illness after hospital discharge is therefore clinically meaningful. This Systematic Review aimed to summarize studies that identify the prevalence of and risk factors for sleep disturbance after hospital discharge for critical illness survivors. PubMed (January 4, 2017), MEDLINE (January 4, 2017), and EMBASE (February 1, 2017). Databases were searched for studies of critically ill adult patients after hospital discharge, with sleep disturbance measured as a primary outcome by standardized questionnaire or objective measurement tools. From each relevant study, we extracted prevalence and severity of sleep disturbance at each time point, objective sleep parameters (such as total sleep time, sleep efficiency, and arousal index), and risk factors for sleep disturbance. A total of 22 studies were identified, with assessment tools including subjective questionnaires, polysomnography, and actigraphy. Subjective questionnaire studies reveal a 50-66.7% (within 1 mo), 34-64.3% (>1-3 mo), 22-57% (>3-6 mo), and 10-61% (>6 mo) prevalence of abnormal sleep after hospital discharge after critical illness. Of the studies assessing multiple time points, four of five questionnaire studies and five of five polysomnography studies show improved aspects of sleep over time. Risk factors for poor sleep varied, but prehospital factors (chronic comorbidity, pre-existing sleep abnormality) and in-hospital factors (severity of acute illness, in-hospital sleep disturbance, pain medication use, and ICU acute stress symptoms) may play a role. Sleep disturbance was frequently associated with

Impaired adiponectin signaling contributes to disturbed catabolism of branched-chain amino acids in diabetic mice.

PubMed

Lian, Kun; Du, Chaosheng; Liu, Yi; Zhu, Di; Yan, Wenjun; Zhang, Haifeng; Hong, Zhibo; Liu, Peilin; Zhang, Lijian; Pei, Haifeng; Zhang, Jinglong; Gao, Chao; Xin, Chao; Cheng, Hexiang; Xiong, Lize; Tao, Ling

2015-01-01

The branched-chain amino acids (BCAA) accumulated in type 2 diabetes are independent contributors to insulin resistance. The activity of branched-chain α-keto acid dehydrogenase (BCKD) complex, rate-limiting enzyme in BCAA catabolism, is reduced in diabetic states, which contributes to elevated BCAA concentrations. However, the mechanisms underlying decreased BCKD activity remain poorly understood. Here, we demonstrate that mitochondrial phosphatase 2C (PP2Cm), a newly identified BCKD phosphatase that increases BCKD activity, was significantly downregulated in ob/ob and type 2 diabetic mice. Interestingly, in adiponectin (APN) knockout (APN(-/-)) mice fed with a high-fat diet (HD), PP2Cm expression and BCKD activity were significantly decreased, whereas BCKD kinase (BDK), which inhibits BCKD activity, was markedly increased. Concurrently, plasma BCAA and branched-chain α-keto acids (BCKA) were significantly elevated. APN treatment markedly reverted PP2Cm, BDK, BCKD activity, and BCAA and BCKA levels in HD-fed APN(-/-) and diabetic animals. Additionally, increased BCKD activity caused by APN administration was partially but significantly inhibited in PP2Cm knockout mice. Finally, APN-mediated upregulation of PP2Cm expression and BCKD activity were abolished when AMPK was inhibited. Collectively, we have provided the first direct evidence that APN is a novel regulator of PP2Cm and systematic BCAA levels, suggesting that targeting APN may be a pharmacological approach to ameliorating BCAA catabolism in the diabetic state. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Sleep disturbance caused by meaningful sounds and the effect of background noise

NASA Astrophysics Data System (ADS)

Namba, Seiichiro; Kuwano, Sonoko; Okamoto, Takehisa

2004-10-01

To study noise-induced sleep disturbance, a new procedure called "noise interrupted method"has been developed. The experiment is conducted in the bedroom of the house of each subject. The sounds are reproduced with a mini-disk player which has an automatic reverse function. If the sound is disturbing and subjects cannot sleep, they are allowed to switch off the sound 1 h after they start to try to sleep. This switch off (noise interrupted behavior) is an important index of sleep disturbance. Next morning they fill in a questionnaire in which quality of sleep, disturbance of sounds, the time when they switched off the sound, etc. are asked. The results showed a good relationship between L and the percentages of the subjects who could not sleep in an hour and between L and the disturbance reported in the questionnaire. This suggests that this method is a useful tool to measure the sleep disturbance caused by noise under well-controlled conditions.

Trophic compensation reinforces resistance: herbivory absorbs the increasing effects of multiple disturbances.

PubMed

Ghedini, Giulia; Russell, Bayden D; Connell, Sean D

2015-02-01

Disturbance often results in small changes in community structure, but the probability of transitioning to contrasting states increases when multiple disturbances combine. Nevertheless, we have limited insights into the mechanisms that stabilise communities, particularly how perturbations can be absorbed without restructuring (i.e. resistance). Here, we expand the concept of compensatory dynamics to include countervailing mechanisms that absorb disturbances through trophic interactions. By definition, 'compensation' occurs if a specific disturbance stimulates a proportional countervailing response that eliminates its otherwise unchecked effect. We show that the compounding effects of disturbances from local to global scales (i.e. local canopy-loss, eutrophication, ocean acidification) increasingly promote the expansion of weedy species, but that this response is countered by a proportional increase in grazing. Finally, we explore the relatively unrecognised role of compensatory effects, which are likely to maintain the resistance of communities to disturbance more deeply than current thinking allows. © 2015 John Wiley & Sons Ltd/CNRS.

Automated attribution of remotely-sensed ecological disturbances using spatial and temporal characteristics of common disturbance classes.

NASA Astrophysics Data System (ADS)

Cooper, L. A.; Ballantyne, A.

2017-12-01

Forest disturbances are critical components of ecosystems. Knowledge of their prevalence and impacts is necessary to accurately describe forest health and ecosystem services through time. While there are currently several methods available to identify and describe forest disturbances, especially those which occur in North America, the process remains inefficient and inaccessible in many parts of the world. Here, we introduce a preliminary approach to streamline and automate both the detection and attribution of forest disturbances. We use a combination of the Breaks for Additive Season and Trend (BFAST) detection algorithm to detect disturbances in combination with supervised and unsupervised classification algorithms to attribute the detections to disturbance classes. Both spatial and temporal disturbance characteristics are derived and utilized for the goal of automating the disturbance attribution process. The resulting preliminary algorithm is applied to up-scaled (100m) Landsat data for several different ecosystems in North America, with varying success. Our results indicate that supervised classification is more reliable than unsupervised classification, but that limited training data are required for a region. Future work will improve the algorithm through refining and validating at sites within North America before applying this approach globally.

Sleep Disturbances in Mood Disorders.

PubMed

Rumble, Meredith E; White, Kaitlin Hanley; Benca, Ruth M

2015-12-01

The article provides an overview of common and differentiating self-reported and objective sleep disturbances seen in mood-disordered populations. The importance of considering sleep disturbances in the context of mood disorders is emphasized, because a large body of evidence supports the notion that sleep disturbances are a risk factor for onset, exacerbation, and relapse of mood disorders. In addition, potential mechanisms for sleep disturbance in depression, other primary sleep disorders that often occur with mood disorders, effects of antidepressant and mood-stabilizing drugs on sleep, and the adjunctive effect of treating sleep in patients with mood disorders are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes

PubMed Central

2014-01-01

Background We previously performed systematic association studies of glutamate receptor gene family members with schizophrenia, and found positive associations of polymorphisms in the GRM3 (a gene of metabotropic glutamate receptor 3: mGluR3) with the disorder. Physiological roles of GRM3 in brain functions and its functional roles in the pathogenesis of schizophrenia remain to be resolved. Results We generated mGluR3 knockout (KO) mice and conducted comprehensive behavioral analyses. KO mice showed hyperactivity in the open field, light/dark transition, and 24-hour home cage monitoring tests, impaired reference memory for stressful events in the Porsolt forced swim test, impaired contextual memory in cued and contextual fear conditioning test, and impaired working memory in the T-Maze forced alternation task test. Hyperactivity and impaired working memory are known as endophenotypes of schizophrenia. We examined long-term synaptic plasticity by assessing long-term potentiation (LTP) in the CA1 region in the hippocampi of KO and wild-type (WT) mice. We observed no differences in the amplitude of LTP between the two genotypes, suggesting that mGluR3 is not essential for LTP in the CA1 region of the mouse hippocampus. As hyperactivity is typically associated with increased dopaminergic transmission, we performed in vivo microdialysis measurements of extracellular dopamine in the nucleus accumbens of KO and WT mice. We observed enhancements in the methamphetamine (MAP)-induced release of dopamine in KO mice. Conclusions These results demonstrate that a disturbance in the glutamate-dopamine interaction may be involved in the pathophysiology of schizophrenia-like behavior, such as hyperactivity in mGluR3 KO mice. PMID:24758191

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penza, M.; Jeremic, M.; Marrazzo, E.

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 estimatedmore » human intake (0.5 {mu}g/kg). At higher doses (50-500 {mu}g/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 ER{alpha} or ER{beta}, 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 ER{alpha} in undifferentiated preadipocytic cells and by ER{beta} 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

Is Passive Smoking Associated With Sleep Disturbance Among Pregnant Women?

PubMed Central

Ohida, Takashi; Kaneita, Yoshitaka; Osaki, Yoneatsu; Harano, Satoru; Tanihata, Takeo; Takemura, Shinji; Wada, Kiyoshi; Kanda, Hideyuki; Hayashi, Kenji; Uchiyama, Makoto

2007-01-01

Study Objective: Pregnant women suffer from sleep disturbance, which may be aggravated by passive smoking. In this study we investigated the effects of passive smoking on sleep disturbance during pregnancy. Design: Two cross-sectional questionnaire surveys conducted in 2002 and 2006. Setting: Clinical institutions specializing in obstetrics and gynecology that participated in the nationwide surveys: 260 in the 2002 survey and 344 in the 2006 survey. Participants: 16,396 and 19,386 pregnant women in Japan surveyed in 2002 and 2006, respectively. Intervention: N/A. Measurements and Results: Pregnant women exposed to passive smoking were likely to have sleep disturbances, such as subjective insufficient sleep, difficulty in initiating sleep, short sleep duration, and snoring loudly/breathing uncomfortably. Smoking pregnant women had the same sleep disturbances and also experienced excessive daytime sleepiness and early morning awakening. The prevalence of 5 types of sleep disturbance (insufficient sleep, difficulty in initiating sleep, short sleep duration, excessive daytime sleepiness, and snoring loudly/breathing uncomfortably) among nonsmokers with environmental tobacco smoke showed a mean value intermediate between that of active smokers and that of nonsmokers without environmental tobacco smoke. Conclusion: Passive smoking is independently associated with increased sleep disturbance during pregnancy. Citation: Ohida T; Kaneita Y; Osaki Y; Harano S; Tanihata T; Takemura S; Wada K; Kanda H; Hayashi K; Uchiyama M. Is passive smoking associated with sleep disturbance among pregnant women? SLEEP 2007;30(9):1155-1161. PMID:17910387

Natural disturbance production functions

Treesearch

Jeffrey P. Prestemon; D. Evan Mercer; John M. Pye

2008-01-01

Natural disturbances in forests are driven by physical and biological processes. Large, landscape scale disturbances derive primarily from weather (droughts, winds, ice storms, and floods), geophysical activities (earthquakes, volcanic eruptions), fires, insects, and diseases. Humans have invented ways to minimize their negative impacts and reduce their rates of...

Physical exercise protects against Alzheimer's disease in 3xTg-AD mice.

PubMed

García-Mesa, Yoelvis; López-Ramos, Juan Carlos; Giménez-Llort, Lydia; Revilla, Susana; Guerra, Rafael; Gruart, Agnès; Laferla, Frank M; Cristòfol, Rosa; Delgado-García, José M; Sanfeliu, Coral

2011-01-01

Physical exercise is considered to exert a positive neurophysiological effect that helps to maintain normal brain activity in the elderly. Expectations that it could help to fight Alzheimer's disease (AD) were recently raised. This study analyzed the effects of different patterns of physical exercise on the 3xTg-AD mouse. Male and female 3xTg-AD mice at an early pathological stage (4-month-old) have had free access to a running wheel for 1 month, whereas mice at a moderate pathological stage(7-month-old) have had access either during 1 or 6 months. The non-transgenic mouse strain was used as a control. Parallel animal groups were housed in conventional conditions. Cognitive loss and behavioral and psychological symptoms of dementia (BPSD)-like behaviors were present in the 3xTg-AD mice along with alteration in synaptic function and ong-term potentiation impairment in vivo. Brain tissue showed AD-pathology and oxidative-related changes. Disturbances were more severe at the older age tested. Oxidative stress was higher in males but other changes were similar or higher in females. Exercise treatment ameliorated cognitive deterioration and BPSD-like behaviors such as anxiety and the startle response. Synaptic changes were partially protected by exercise. Oxidative stress was reduced. The best neuroprotection was generally obtained after 6 months of exercise in 7-month-old 3xTg-AD mice. Improved sensorimotor function and brain tissue antioxidant defence were induced in both 3xTg-AD and NonTg mice. Therefore, the benefits of aerobic physical exercise on synapse, redox homeostasis, and general brain function demonstrated in the 3xTg-AD mouse further support the value of this healthy life-style against neurodegeneration.

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

PubMed Central

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 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. PMID:18467430

Long-term administration of olanzapine induces adiposity and increases hepatic fatty acid desaturation protein in female C57BL/6J mice

PubMed Central

Hou, Po-Hsun; Chang, Geng-Ruei; Chen, Chin-Pin; Lin, Yen-Ling; Chao, I-Shuan; Shen, Ting-Ting; Mao, Frank Chiahung

2018-01-01

Objective(s): Weight gain and metabolic disturbances such as dyslipidemia, are frequent side effects of second-generation antipsychotics, including olanzapine. This study examined the metabolic effects of chronic olanzapine exposure. In addition, we investigated the hepatic fatty acid effects of olanzapine in female C57BL/6J mice fed a normal diet. Materials and Methods: Female C57BL/6J mice orally received olanzapine or normal saline for 7 weeks. The effects of long-term olanzapine exposure on body weight changes, food efficiency, blood glucose, triglyceride (TG), insulin, and leptin levels were observed. Hepatic TG and abdominal fat mass were investigated, and fat cell morphology was analyzed through histopathological methods. The levels of protein markers of fatty acid regulation in the liver, namely fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), were measured. Results: Olanzapine treatment increased the food intake of the mice as well as their body weight. Biochemical analyses showed that olanzapine increased blood TG, insulin, leptin, and hepatic TG. The olanzapine group exhibited increased abdominal fat mass and fat cell enlargement in abdominal fat tissue. Western blotting of the mouse liver revealed significantly higher (1.6-fold) levels of SCD-1 in the olanzapine group relative to the control group; by contrast, FAS levels in the two groups did not differ significantly. Conclusion: Enhanced lipogenesis triggered by increased hepatic SCD-1 activity might be a probable peripheral mechanism of olanzapine-induced dyslipidemia. Some adverse metabolic effects of olanzapine may be related to the disturbance of lipid homeostasis in the liver. PMID:29922430

Glucagon receptor knockout mice are protected against acute olanzapine-induced hyperglycemia.

PubMed

Castellani, Laura N; Peppler, Willem T; Sutton, Charles D; Whitfield, Jamie; Charron, Maureen J; Wright, David C

2017-08-01

To determine if glucagon is involved in mediating the increase in blood glucose levels caused by the second-generation antipsychotic drug olanzapine. Whole body glucagon receptor deficient mice (Gcgr -/- ) or WT littermate controls were injected with olanzapine (5mg/kg BW IP) and changes in blood glucose measured over the following 120min. Separate cohorts of mice were treated with olanzapine and changes in pyruvate tolerance, insulin tolerance and whole body substrate oxidation were determined. Olanzapine treatment increased serum glucagon and lead to rapid increases in blood glucose concentrations in WT mice. Gcgr -/- mice were protected against olanzapine-induced increases in blood glucose but this was not explained by differences in terminal serum insulin concentrations, enhanced AKT phosphorylation in skeletal muscle, adipose tissue or liver or differences in RER. In both genotypes olanzapine induced an equivalent degree of insulin resistance as measured using an insulin tolerance test. Olanzapine treatment led to an exaggerated glucose response to a pyruvate challenge in WT but not Gcgr -/- mice and this was paralleled by reductions in the protein content of PEPCK and G6Pase in livers from Gcgr -/- mice. Gcgr -/- mice are protected against olanzapine-induced increases in blood glucose. This is likely a result of reductions in liver glucose output, perhaps secondary to decreases in PEPCK and G6Pase protein content. Our findings highlight the central role of the liver in mediating olanzapine-induced disturbances in glucose homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Legacy of Pre-Disturbance Spatial Pattern Determines Early Structural Diversity following Severe Disturbance in Montane Spruce Forests

PubMed Central

Bače, Radek; Svoboda, Miroslav; Janda, Pavel; Morrissey, Robert C.; Wild, Jan; Clear, Jennifer L.; Čada, Vojtěch; Donato, Daniel C.

2015-01-01

Background Severe canopy-removing disturbances are native to many temperate forests and radically alter stand structure, but biotic legacies (surviving elements or patterns) can lend continuity to ecosystem function after such events. Poorly understood is the degree to which the structural complexity of an old-growth forest carries over to the next stand. We asked how pre-disturbance spatial pattern acts as a legacy to influence post-disturbance stand structure, and how this legacy influences the structural diversity within the early-seral stand. Methods Two stem-mapped one-hectare forest plots in the Czech Republic experienced a severe bark beetle outbreak, thus providing before-and-after data on spatial patterns in live and dead trees, crown projections, down logs, and herb cover. Results Post-disturbance stands were dominated by an advanced regeneration layer present before the disturbance. Both major species, Norway spruce (Picea abies) and rowan (Sorbus aucuparia), were strongly self-aggregated and also clustered to former canopy trees, pre-disturbance snags, stumps and logs, suggesting positive overstory to understory neighbourhood effects. Thus, although the disturbance dramatically reduced the stand’s height profile with ~100% mortality of the canopy layer, the spatial structure of post-disturbance stands still closely reflected the pre-disturbance structure. The former upper tree layer influenced advanced regeneration through microsite and light limitation. Under formerly dense canopies, regeneration density was high but relatively homogeneous in height; while in former small gaps with greater herb cover, regeneration density was lower but with greater heterogeneity in heights. Conclusion These findings suggest that pre-disturbance spatial patterns of forests can persist through severe canopy-removing disturbance, and determine the spatial structure of the succeeding stand. Such patterns constitute a subtle but key legacy effect, promoting structural

The Disturbing Student and the Judicial Process

ERIC Educational Resources Information Center

Ragle, John D.; Paine, Gage E.

2009-01-01

The Assessment-Intervention of Student Problems (AISP) model is a useful tool for preparing student affairs professionals to assess the problems of disturbed, disturbing, or disturbed/disturbing students and to make appropriate referrals. It is particularly useful because it emphasizes the necessity of developing an integrated system for this…

Increased sensitivity to climate change in disturbed ecosystems.

PubMed

Kröel-Dulay, György; Ransijn, Johannes; Schmidt, Inger Kappel; Beier, Claus; De Angelis, Paolo; de Dato, Giovanbattista; Dukes, Jeffrey S; Emmett, Bridget; Estiarte, Marc; Garadnai, János; Kongstad, Jane; Kovács-Láng, Edit; Larsen, Klaus Steenberg; Liberati, Dario; Ogaya, Romà; Riis-Nielsen, Torben; Smith, Andrew R; Sowerby, Alwyn; Tietema, Albert; Penuelas, Josep

2015-03-24

Human domination of the biosphere includes changes to disturbance regimes, which push many ecosystems towards early-successional states. Ecological theory predicts that early-successional ecosystems are more sensitive to perturbations than mature systems, but little evidence supports this relationship for the perturbation of climate change. Here we show that vegetation (abundance, species richness and species composition) across seven European shrublands is quite resistant to moderate experimental warming and drought, and responsiveness is associated with the dynamic state of the ecosystem, with recently disturbed sites responding to treatments. Furthermore, most of these responses are not rapid (2-5 years) but emerge over a longer term (7-14 years). These results suggest that successional state influences the sensitivity of ecosystems to climate change, and that ecosystems recovering from disturbances may be sensitive to even modest climatic changes. A research bias towards undisturbed ecosystems might thus lead to an underestimation of the impacts of climate change.

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

PubMed

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun

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 equitoxicmore » 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.« less

Comparison study on disturbance estimation techniques in precise slow motion control

NASA Astrophysics Data System (ADS)

Fan, S.; Nagamune, R.; Altintas, Y.; Fan, D.; Zhang, Z.

2010-08-01

Precise low speed motion control is important for the industrial applications of both micro-milling machine tool feed drives and electro-optical tracking servo systems. It calls for precise position and instantaneous velocity measurement and disturbance, which involves direct drive motor force ripple, guide way friction and cutting force etc., estimation. This paper presents a comparison study on dynamic response and noise rejection performance of three existing disturbance estimation techniques, including the time-delayed estimators, the state augmented Kalman Filters and the conventional disturbance observers. The design technique essentials of these three disturbance estimators are introduced. For designing time-delayed estimators, it is proposed to substitute Kalman Filter for Luenberger state observer to improve noise suppression performance. The results show that the noise rejection performances of the state augmented Kalman Filters and the time-delayed estimators are much better than the conventional disturbance observers. These two estimators can give not only the estimation of the disturbance but also the low noise level estimations of position and instantaneous velocity. The bandwidth of the state augmented Kalman Filters is wider than the time-delayed estimators. In addition, the state augmented Kalman Filters can give unbiased estimations of the slow varying disturbance and the instantaneous velocity, while the time-delayed estimators can not. The simulation and experiment conducted on X axis of a 2.5-axis prototype micro milling machine are provided.

Therapeutic effect of Arctium lappa in Schistosoma haematobium associated kidney disturbance: biochemical and molecular effects.

PubMed

Koriem, Khaled M M; Idris, Zulzamri H; Haron, Hasniza F; Omar, Nurulhuda A; Lazain, Halita S

2016-12-01

Schistosoma haematobium ( S. haematobium ) infection has been found to be strongly associated with bladder cancer, which necessitates for discover of a natural new therapeutic agent. The aim of this study was to evaluate the therapeutic effect of Arctium lappa seed extract in S. haematobium associated kidney disturbance. Forty male albino mice were used and divided into four equal groups; group 1 control includes non-infected healthy mice, groups 2, 3 and 4 subcutaneous infected with S. haematobium cercariae. Groups 3 co-treated daily with oral dose of A. lappa seed extract (300 mg/kg, bwt) for 15 days in the same time of S. haematobium infection. Groups 4 post-treated daily for 15 days with oral dose of A. lappa seed extract (300 mg/kg, bwt) after 15 days of S. haematobium infection. The results obtained revealed that S. haematobium significantly decreased kidney weight and serum sodium, potassium and chloride, but increased urinary volume, urinary excretion of sodium, potassium and chloride, serum urea, creatinine and uric acid. Schistosoma haematobium also significantly decreased kidney superoxide dismutase, glutathione peroxidase and reduced glutathione levels while increased kidney lipid peroxidation level. Co- and post-treatment with A. lappa seed extract restore all the above parameters to approach the normal values. These results were supported with histopathological examinations. In conclusion, A. lappa seed extract has therapeutic effect in kidney disturbance caused by S. haematobium where co-treatment of A. lappa seed extract was more effective than post-treatment of the extract.

Pain, Sleep Disturbance, and Quality of Life Among Palestinian Patients Diagnosed with Cancer.

PubMed

Dreidi, Mu'taz M; Hamdan-Mansour, Ayman M

2016-12-01

The objective of this descriptive study is to explore the relationships between pain, sleep disturbance, and quality of life among Palestinian patients diagnosed with cancer in the West Bank. A cross-sectional, descriptive-correlational design was used to collect data from 184 patients with cancer. The quality of life questionnaire, visual analogue pain scale, and physical health status were used in data collection. The results showed that the mean score for pain was 5, the best functioning was for cognitive scale (M = 75, SD = 29), the worst symptoms experienced by patients was appetite loss (M = 47, SD = 35), a moderate global health status (M = 53, SD = 27), and the mean for sleep disturbance was 43 (SD = 35). Pain and sleep disturbance showed high negative correlations with functional scales of quality of life and positive with symptom scales. The findings showed that the co-occurrence of pain and sleep disturbance was negatively correlated with quality of life (QoL) and positively with symptom scales. The regression analysis revealed that pain and sleep disturbance accounted for a significant proportion of variance in the QoL (p < 0.001), and the highest proportion was in predicting global health status (41.9 %). The findings of this study give evidence about the importance of assessing pain and sleep quality among Palestinian patients with cancer.

Relationship between Eating Disturbance and Dementia Severity in Patients with Alzheimer’s Disease

PubMed Central

Kai, Kyoko; Hashimoto, Mamoru; Amano, Koichiro; Tanaka, Hibiki; Fukuhara, Ryuji; Ikeda, Manabu

2015-01-01

Background Eating is one of the most important daily activities in managing patients with dementia. Although various eating disturbance occur as dementia progresses, to our knowledge, most of the studies focused on a part of eating disturbance such as swallowing and appetite. There have been few comprehensive studies including eating habits and food preference in patients with Alzheimer’s disease (AD). The aims of this study were to investigate almost all eating disturbance and to examine the relationship of eating disturbance to dementia stage in AD. Methods A total of 220 patients with AD and 30 normal elderly (NE) subjects were recruited. Eating disturbance was assessed by a comprehensive questionnaire that had been previously validated. Potential relationships between the characteristics of eating disturbance and dementia stage as classified by the Clinical Dementia Rating (CDR) were assessed. Results Overall, 81.4% of patients with AD showed some eating and swallowing disturbance, whereas only 26.7% of the NE subjects had such a disturbance. Even in an early stage, patients with AD had many types of eating disturbance; “Appetite change” was shown in nearly half of the mild AD patients (49.5%). In the moderate stage, the scores of “change of eating habits and food preference” were highest, and in the severe stage “swallowing disturbance” became critical. Conclusion In AD, the relationship of dementia stage to eating disturbance differs according to the type of eating disturbance. The relationships between various eating disturbance and the severity of dementia should be considered. PMID:26266531

Palatable Meal Anticipation in Mice

PubMed Central

Hsu, Cynthia T.; Patton, Danica F.; Mistlberger, Ralph E.; Steele, Andrew D.

2010-01-01

The ability to sense time and anticipate events is a critical skill in nature. Most efforts to understand the neural and molecular mechanisms of anticipatory behavior in rodents rely on daily restricted food access, which induces a robust increase of locomotor activity in anticipation of daily meal time. Interestingly, rats also show increased activity in anticipation of a daily palatable meal even when they have an ample food supply, suggesting a role for brain reward systems in anticipatory behavior, and providing an alternate model by which to study the neurobiology of anticipation in species, such as mice, that are less well adapted to “stuff and starve” feeding schedules. To extend this model to mice, and exploit molecular genetic resources available for that species, we tested the ability of wild-type mice to anticipate a daily palatable meal. We observed that mice with free access to regular chow and limited access to highly palatable snacks of chocolate or “Fruit Crunchies” avidly consumed the snack but did not show anticipatory locomotor activity as measured by running wheels or video-based behavioral analysis. However, male mice receiving a snack of high fat chow did show increased food bin entry prior to access time and a modest increase in activity in the two hours preceding the scheduled meal. Interestingly, female mice did not show anticipation of a daily high fat meal but did show increased activity at scheduled mealtime when that meal was withdrawn. These results indicate that anticipation of a scheduled food reward in mice is behavior, diet, and gender specific. PMID:20941366

32 CFR 643.114 - Civil disturbances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 4 2010-07-01 2010-07-01 true Civil disturbances. 643.114 Section 643.114... ESTATE Additional Authority of Commanders § 643.114 Civil disturbances. Without reference to higher... facilities during civil disturbance for not more than 30 days to the National Guard and to municipal, county...

32 CFR 643.114 - Civil disturbances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 4 2011-07-01 2011-07-01 false Civil disturbances. 643.114 Section 643.114... ESTATE Additional Authority of Commanders § 643.114 Civil disturbances. Without reference to higher... facilities during civil disturbance for not more than 30 days to the National Guard and to municipal, county...

32 CFR 643.114 - Civil disturbances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 4 2014-07-01 2013-07-01 true Civil disturbances. 643.114 Section 643.114... ESTATE Additional Authority of Commanders § 643.114 Civil disturbances. Without reference to higher... facilities during civil disturbance for not more than 30 days to the National Guard and to municipal, county...

32 CFR 643.114 - Civil disturbances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 4 2012-07-01 2011-07-01 true Civil disturbances. 643.114 Section 643.114... ESTATE Additional Authority of Commanders § 643.114 Civil disturbances. Without reference to higher... facilities during civil disturbance for not more than 30 days to the National Guard and to municipal, county...

32 CFR 643.114 - Civil disturbances.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 4 2013-07-01 2013-07-01 false Civil disturbances. 643.114 Section 643.114... ESTATE Additional Authority of Commanders § 643.114 Civil disturbances. Without reference to higher... facilities during civil disturbance for not more than 30 days to the National Guard and to municipal, county...

Water-Pipe Smoke Exposure-Induced Circulatory Disturbances in Mice, and the Influence of Betaine Supplementation Thereon.

PubMed

Nemmar, Abderrahim; Al-Salam, Suhail; Beegam, Sumaya; Yuvaraju, Priya; Oulhaj, Abderrahim; Ali, Badreldin H

2017-01-01

It has been shown, both experimentally and clinically, that water-pipe smoke (WPS) exposure adversely affects the cardiovascular system (CVS) through the generation of oxidative stress and inflammation. Betaine, a naturally occurring compound in common foods, has antioxidant and anti-inflammatory actions. However, its potential to mitigate the adverse effect of WPS on the CVS has never been reported before. This is the subject of this study in mice. Mice were exposed daily for 30 min to either normal air (control), or to WPS for two consecutive weeks. Betaine was administered daily by gavage at a dose of 10mg/kg, 1h before either air or WPS exposure. Betaine mitigated the in vivo prothrombotic effect of WPS in pial arterioles and venules. Moreover, it reversed the WPS-induced decrease in circulating platelets. Likewise, betaine alleviated platelet aggregation in vitro, and the shortening of activated partial thromboplastin time and prothrombin time induced by WPS. Betaine reduced the increase of plasminogen activator inhibitor-1 and fibrinogen concentrations in plasma induced by WPS. Betaine also diminished the WPS-induced increase of plasma concentrations of interleukin 6 and tumor necrosis factor α, and attenuated the increase of lipid peroxidation and superoxide dismutase. Immunohistochemical analysis of the heart revealed an increase in the expression of inducible nitric oxide synthase and cytochrome C by cardiomyocytes of the WPS-exposed mice. These effects were averted by betaine. Our findings suggest that betaine treatment significantly mitigated WPS-induced hypercoagulability, and inflammation, as well as systemic and cardiac oxidative stress. © 2017 The Author(s)Published by S. Karger AG, Basel.

Genetic diversity enhances the resistance of a seagrass ecosystem to disturbance.

PubMed

Hughes, A Randall; Stachowicz, John J

2004-06-15

Motivated by recent global reductions in biodiversity, empirical and theoretical research suggests that more species-rich systems exhibit enhanced productivity, nutrient cycling, or resistance to disturbance or invasion relative to systems with fewer species. In contrast, few data are available to assess the potential ecosystem-level importance of genetic diversity within species known to play a major functional role. Using a manipulative field experiment, we show that increasing genotypic diversity in a habitat-forming species (the seagrass Zostera marina) enhances community resistance to disturbance by grazing geese. The time required for recovery to near predisturbance densities also decreases with increasing eelgrass genotypic diversity. However, there is no effect of diversity on resilience, measured as the rate of shoot recovery after the disturbance, suggesting that more rapid recovery in diverse plots is due solely to differences in disturbance resistance. Genotypic diversity did not affect ecosystem processes in the absence of disturbance. Thus, our results suggest that genetic diversity, like species diversity, may be most important for enhancing the consistency and reliability of ecosystems by providing biological insurance against environmental change.

Using Land Surface Phenology as the Basis for a National Early Warning System for Forest Disturbances

NASA Astrophysics Data System (ADS)

Hargrove, W. W.; Spruce, J.; Norman, S. P.; Hoffman, F. M.

2011-12-01

The National Early Warning System (EWS) provides an 8-day coast-to-coast snapshot of potentially disturbed forests across the U.S.. A prototype system has produced national maps of potential forest disturbances every eight days since January 2010, identifying locations that may require further investigation. Through phenology, the system shows both early and delayed vegetation development and detects all types of unexpected forest disturbances, including insects, disease, wildfires, frost and ice damage, tornadoes, hurricanes, blowdowns, harvest, urbanization, landslides, drought, flood, and climate change. The USDA Forest Service Eastern Forest Environmental Threat Assessment Center is collaborating with NASA Stennis Space Center and the Western Wildland Environmental Threat Assessment Center to develop the tool. The EWS uses differences in phenological responses between an expectation based on historical data and a current view to strategically identify potential forest disturbances and direct attention to locations where forest behavior seems unusual. Disturbance maps are available via the Forest Change Assessment Viewer (FCAV) (http://ews.forestthreats.org/gis), which allows resource managers and other users to see the most current national disturbance maps as soon as they are available. Phenology-based detections show not only vegetation disturbances in the classical sense, but all departures from normal seasonal vegetation behavior. In 2010, the EWS detected a repeated late-frost event at high elevations in North Carolina, USA, that resulted in delayed seasonal development, contrasting with an early spring development at lower elevations, all within close geographic proximity. Throughout 2011, there was a high degree of correspondence between the National Climatic Data Center's North American Drought Monitor maps and EWS maps of phenological drought disturbance in forests. Urban forests showed earlier and more severe phenological drought disturbance than

Conservation of wildlife populations: factoring in incremental disturbance.

PubMed

Stewart, Abbie; Komers, Petr E

2017-06-01

Progressive anthropogenic disturbance can alter ecosystem organization potentially causing shifts from one stable state to another. This potential for ecosystem shifts must be considered when establishing targets and objectives for conservation. We ask whether a predator-prey system response to incremental anthropogenic disturbance might shift along a disturbance gradient and, if it does, whether any disturbance thresholds are evident for this system. Development of linear corridors in forested areas increases wolf predation effectiveness, while high density of development provides a safe-haven for their prey. If wolves limit moose population growth, then wolves and moose should respond inversely to land cover disturbance. Using general linear model analysis, we test how the rate of change in moose ( Alces alces ) density and wolf ( Canis lupus ) harvest density are influenced by the rate of change in land cover and proportion of land cover disturbed within a 300,000 km 2 area in the boreal forest of Alberta, Canada. Using logistic regression, we test how the direction of change in moose density is influenced by measures of land cover change. In response to incremental land cover disturbance, moose declines occurred where <43% of land cover was disturbed; in such landscapes, there were high rates of increase in linear disturbance and wolf density increased. By contrast, moose increases occurred where >43% of land cover was disturbed and wolf density declined. Wolves and moose appeared to respond inversely to incremental disturbance with the balance between moose decline and wolf increase shifting at about 43% of land cover disturbed. Conservation decisions require quantification of disturbance rates and their relationships to predator-prey systems because ecosystem responses to anthropogenic disturbance shift across disturbance gradients.

The timing of life history events in the presence of soft disturbances.

PubMed

Bertacchi, Daniela; Zucca, Fabio; Ambrosini, Roberto

2016-01-21

time shifts of the distribution of the disturbance. We show how the ESS and the average fitness change under the new climate and discuss which is the impact of the new climate on a population that still follows the old strategy. In particular, we show that, at least under some conditions, extreme weather events imply a temporary decrease of the average fitness of the population due to an increased mortality. In addition, if the population adapts to the new climate, the population may have a larger fitness. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cellular mechanisms of cyclophosphamide-induced taste loss in mice.

PubMed

Mukherjee, Nabanita; Pal Choudhuri, Shreoshi; Delay, Rona J; Delay, Eugene R

2017-01-01

Many commonly prescribed chemotherapy drugs such as cyclophosphamide (CYP) have adverse side effects including disruptions in taste which can result in loss of appetite, malnutrition, poorer recovery and reduced quality of life. Previous studies in mice found evidence that CYP has a two-phase disturbance in taste behavior: a disturbance immediately following drug administration and a second which emerges several days later. In this study, we examined the processes by which CYP disturbs the taste system by examining the effects of the drug on taste buds and cells responsible for taste cell renewal using immunohistochemical assays. Data reported here suggest CYP has direct cytotoxic effects on lingual epithelium immediately following administration, causing an early loss of taste sensory cells. Types II and III cells in fungiform taste buds appear to be more susceptible to this effect than circumvallate cells. In addition, CYP disrupts the population of rapidly dividing cells in the basal layer of taste epithelium responsible for taste cell renewal, manifesting a disturbance days later. The loss of these cells temporarily retards the system's capacity to replace Type II and Type III taste sensory cells that survived the cytotoxic effects of CYP and died at the end of their natural lifespan. The timing of an immediate, direct loss of taste cells and a delayed, indirect loss without replacement of taste sensory cells are broadly congruent with previously published behavioral data reporting two periods of elevated detection thresholds for umami and sucrose stimuli. These findings suggest that chemotherapeutic disturbances in the peripheral mechanisms of the taste system may cause dietary challenges at a time when the cancer patient has significant need for well balanced, high energy nutritional intake.

Changing disturbance regimes, ecological memory, and forest resilience

USGS Publications Warehouse

Johnstone, Jill F.; Allen, Craig D.; Franklin, Jerry F.; Frelich, Lee E.; Harvey, Brian J.; Higuera, Philip E.; Mack, Michelle C.; Meentemeyer, Ross K.; Metz, Margaret R.; Perry, George LW; Schoennagel, Tania; Turner, Monica G.

2016-01-01

Ecological memory is central to how ecosystems respond to disturbance and is maintained by two types of legacies – information and material. Species life-history traits represent an adaptive response to disturbance and are an information legacy; in contrast, the abiotic and biotic structures (such as seeds or nutrients) produced by single disturbance events are material legacies. Disturbance characteristics that support or maintain these legacies enhance ecological resilience and maintain a “safe operating space” for ecosystem recovery. However, legacies can be lost or diminished as disturbance regimes and environmental conditions change, generating a “resilience debt” that manifests only after the system is disturbed. Strong effects of ecological memory on post-disturbance dynamics imply that contingencies (effects that cannot be predicted with certainty) of individual disturbances, interactions among disturbances, and climate variability combine to affect ecosystem resilience. We illustrate these concepts and introduce a novel ecosystem resilience framework with examples of forest disturbances, primarily from North America. Identifying legacies that support resilience in a particular ecosystem can help scientists and resource managers anticipate when disturbances may trigger abrupt shifts in forest ecosystems, and when forests are likely to be resilient.

Radio-scintillation observations of interplanetary disturbances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, T.; Kakinuma, T.

1984-01-01

Recent developments in the studies of interplanetary disturbances by scintillation techniques are briefly reviewed. The turbulent postshock region of an interplanetary disturbance produces transient enhancements in the scintillation level and the flow speed in many cases. An empirical method to determine three-dimensional angular distribution of the propagation speed of the disturbance on the basis of interplanetary scintillation measurements of postshock flow speeds is applied to 17 events which took place in 1978-1981. Among them, four representative examples, including two events which were associated with disappearing solar filaments, are described in detail. Several disturbances had oblate configurations the latitudinal extent ismore » smaller than the longitudinal extent. On the average, the angular distribution of the propagation speed at 1-AU heliocentric distance is quasi-isotropic over a longitudinal range of 100 deg centered at the normal of relevant solar phenomenon. The net excess mass and energy in an interplanetary disturbance associated with a disappearing solar filament can be comparable to those of an interplanetary disturbance associated with a large solar flare. 57 references.« less

Interactive effects between N addition and disturbance on boreal forest ecosystem structure and function

NASA Astrophysics Data System (ADS)

Nordin, Annika; Strengbom, Joachim; From, Fredrik

2014-05-01

In management of boreal forests, nitrogen (N) enrichment from atmospheric deposition or from forest fertilization can appear in combination with land-use related disturbances, i.e. tree harvesting by clear-felling. Long-term interactive effects between N enrichment and disturbance on boreal forest ecosystem structure and function are, however, poorly known. We investigated effects of N enrichment by forest fertilization done > 25 years ago on forest understory species composition in old-growth (undisturbed) forests, and in forests clear-felled 10 years ago (disturbed). In clear-felled forests we also investigated effects of the previous N addition on growth of tree saplings. The results show that the N enrichment effect on the understory species composition was strongly dependent on the disturbance caused by clear-felling. In undisturbed forests, there were small or no effects on understory species composition from N addition. In contrast, effects were large in forests first exposed to N addition and subsequently disturbed by clear-felling. Effects of N addition differed among functional groups of plants. Abundance of graminoids increased (+232%) and abundance of dwarf shrubs decreased (-44%) following disturbance in N fertilized forests. For vascular plants, the two perturbations had contrasting effects on α-(within forests) and β-diversity (among forests): in disturbed forests, N addition reduced, or had no effect on α-diversity, while β-diversity increased. For bryophytes, negative effects of disturbance on α-diversity were smaller in N fertilized forests than in forests not fertilized, while neither N addition nor disturbance had any effects on β-diversity. Moreover, sapling growth in forests clear-felled 10 years ago was significantly higher in previously N fertilized forests than in forests not fertilized. Our study show that effects of N addition on plant communities may appear small, short-lived, or even absent until exposed to a disturbance. This

Key landscape and biotic indicators of watersheds sensitivity to forest disturbance identified using remote sensing and historical hydrography data

NASA Astrophysics Data System (ADS)

Buma, Brian; Livneh, Ben

2017-07-01

Water is one of the most critical resources derived from natural systems. While it has long been recognized that forest disturbances like fire influence watershed streamflow characteristics, individual studies have reported conflicting results with some showing streamflow increases post-disturbance and others decreases, while other watersheds are insensitive to even large disturbance events. Characterizing the differences between sensitive (e.g. where streamflow does change post-disturbance) and insensitive watersheds is crucial to anticipating response to future disturbance events. Here, we report on an analysis of a national-scale, gaged watershed database together with high-resolution forest mortality imagery. A simple watershed response model was developed based on the runoff ratio for watersheds (n = 73) prior to a major disturbance, detrended for variation in precipitation inputs. Post-disturbance deviations from the expected water yield and streamflow timing from expected (based on observed precipitation) were then analyzed relative to the abiotic and biotic characteristics of the individual watershed and observed extent of forest mortality. The extent of the disturbance was significantly related to change in post-disturbance water yield (p < 0.05), and there were several distinctive differences between watersheds exhibiting post-disturbance increases, decreases, and those showing no change in water yield. Highly disturbed, arid watersheds with low soil: water contact time are the most likely to see increases, with the magnitude positively correlated with the extent of disturbance. Watersheds dominated by deciduous forest with low bulk density soils typically show reduced yield post-disturbance. Post-disturbance streamflow timing change was associated with climate, forest type, and soil. Snowy coniferous watersheds were generally insensitive to disturbance, whereas finely textured soils with rapid runoff were sensitive. This is the first national

The intermediate disturbance hypothesis should be abandoned.

PubMed

Fox, Jeremy W

2013-02-01

A leading idea about how disturbances and other environmental fluctuations affect species diversity is the intermediate disturbance hypothesis (IDH). The IDH states that diversity of competing species is, or should be expected to be, maximized at intermediate frequencies and/or intensities of disturbance or environmental change. I argue that the IDH has been refuted on both empirical and theoretical grounds, and so should be abandoned. Empirical studies only rarely find the predicted humped diversity-disturbance relationship. Theoretically, the three major mechanisms thought to produce humped diversity-disturbance relationships are logically invalid and do not actually predict what they are thought to predict. Disturbances and other environmental fluctuations can affect diversity, but for different reasons than are commonly recognized. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cathepsin C Aggravates Neuroinflammation Involved in Disturbances of Behaviour and Neurochemistry in Acute and Chronic Stress-Induced Murine Model of Depression.

PubMed

Zhang, Yanli; Fan, Kai; Liu, Yanna; Liu, Gang; Yang, Xiaohan; Ma, Jianmei

2018-01-01

Major depression has been interpreted as an inflammatory disease characterized by cell-mediated immune activation, which is generally triggered by various stresses. Microglia has been thought to be the cellular link between inflammation and depression-like behavioural alterations. The expression of cathepsin C (Cat C), a lysosomal proteinase, is predominantly induced in microglia in neuroinflammation. However, little is known about the role of Cat C in pathophysiology of depression. In the present study, Cat C transgenic mice and wild type mice were subjected to an intraperitoneal injection of LPS (0.5 mg/kg) and 6-week unpredictable chronic mild stress (UCMS) exposure to establish acute and chronic stress-induced depression model. We examined and compared the behavioural and proinflammatory cytokine alterations in serum and depression-targeted brain areas of Cat C differentially expressed mice in stress, as well as indoleamine 2,3-dioxygenase (IDO) and 5-hydroxytryptamine (5HT) levels in brain. The results showed that Cat C overexpression (Cat C OE) promoted peripheral and central inflammatory response with significantly increased TNFα, IL-1β and IL-6 in serum, hippocampus and prefrontal cortex, and resultant upregulation of IDO and downregulation of 5HT expression in brain, and thereby aggravated depression-like behaviours accessed by open field test, forced swim test and tail suspension test. In contrast, Cat C knockdown (Cat C KD) partially prevented inflammation, which may help alleviate the symptoms of depression in mice. To the best of our knowledge, we are the first to demonstrate that Cat C aggravates neuroinflammation involved in disturbances of behaviour and neurochemistry in acute and chronic stress-induced murine model of depression.

Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response.

PubMed

Heritage, Mandy L; Murphy, Therese L; Bridle, Kim R; Anderson, Gregory J; Crawford, Darrell H G; Fletcher, Linda M

2009-08-01

Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-)). Since chronic alcohol consumption is also associated with disturbances in iron metabolism, we investigated the effects of alcohol consumption on hepcidin mRNA expression in Hfe(-/-) mice. Hfe(-/-) and C57BL/6 (wild-type) mice were pair-fed either an alcohol liquid diet or control diet for up to 8 weeks. The mRNA levels of hepcidin and ferroportin were measured at the mRNA level by RT-PCR and protein expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was measured by western blot. Hamp1 mRNA expression was significantly decreased and duodenal ferroportin expression was increased in alcohol-fed wild-type mice at 8 weeks. Time course experiments showed that the decrease in hepcidin mRNA was not immediate, but was significant by 4 weeks. Consistent with the genetic defect, Hamp1 mRNA was decreased and duodenal ferroportin mRNA expression was increased in Hfe(-/-) mice fed on the control diet compared with wild-type animals and alcohol further exacerbated these effects. HIF-1alpha protein levels were elevated in alcohol-fed wild-type animals compared with controls. Alcohol may decrease Hamp1 gene expression independently of the HFE pathway possibly via alcohol-induced hypoxia.

True Triaxial Experimental Study of Rockbursts Induced By Ramp and Cyclic Dynamic Disturbances

NASA Astrophysics Data System (ADS)

Su, Guoshao; Hu, Lihua; Feng, Xiating; Yan, Liubin; Zhang, Gangliang; Yan, Sizhou; Zhao, Bin; Yan, Zhaofu

2018-04-01

A modified rockburst testing system was utilized to reproduce rockbursts induced by ramp and cyclic dynamic disturbances with a low-intermediate strain rate of 2 × 10-3-5 × 10-3 s-1 in the laboratory. The experimental results show that both the ramp and cyclic dynamic disturbances play a significant role in inducing rockbursts. In the tests of rockbursts induced by a ramp dynamic disturbance, as the static stress before the dynamic disturbance increases, both the strength of specimens and the kinetic energy of the ejected fragments first increase and then decrease. In the tests of rockbursts induced by a cyclic dynamic disturbance, there exists a rockburst threshold of the static stress and the dynamic disturbance amplitude, and the kinetic energy of the ejected fragments first increases and then decreases as the cyclic dynamic disturbance frequency increases. The main differences between rockbursts induced by ramp dynamic disturbances and those induced by cyclic dynamic disturbances are as follows: the rockburst development process of the former is characterized by an impact failure feature, while that of the latter is characterized by a fatigue failure feature; the damage evolution curve of the specimen of the former has a leap-developing form with a significant catastrophic feature, while that of the latter has an inverted S-shape with a remarkable fatigue damage characteristic; the energy mechanism of the former involves the ramp dynamic disturbance giving extra elastic strain energy to rocks, while that of the latter involves the cyclic dynamic disturbance decreasing the ultimate energy storage capacity of rocks.

Disturbed Laminar Blood Flow Vastly Augments Lipoprotein Retention in the Artery Wall: A Key Mechanism Distinguishing Susceptible From Resistant Sites.

PubMed

Steffensen, Lasse Bach; Mortensen, Martin Bødtker; Kjolby, Mads; Hagensen, Mette Kallestrup; Oxvig, Claus; Bentzon, Jacob Fog

2015-09-01

Atherosclerosis develops initially at branch points and in areas of high vessel curvature. Moreover, experiments in hypercholesterolemic mice have shown that the introduction of disturbed flow in straight, atherosclerosis-resistant arterial segments turns them highly atherosclerosis susceptible. Several biomechanical mechanisms have been proposed, but none has been demonstrated. In the present study, we examined whether a causal link exists between disturbed laminar flow and the ability of the arterial wall to retain lipoproteins. Lipoprotein retention was detected at natural predilection sites of the murine thoracic aorta 18 hours after infusion of fluorescently labeled low-density lipoprotein. To test for causality between blood flow and the ability of these areas to retain lipoproteins, we manipulated blood flow in the straight segment of the common carotid artery using a constrictive collar. Disturbed laminar flow did not affect low-density lipoprotein influx, but increased the ability of the artery wall to bind low-density lipoprotein. Concordantly, disturbed laminar flow led to differential expression of genes associated with phenotypic modulation of vascular smooth muscle cells, increased expression of proteoglycan core proteins associated with lipoprotein retention, and of enzymes responsible for chondroitin sulfate glycosaminoglycan synthesis and sulfation. Blood flow regulates genes associated with vascular smooth muscle cell phenotypic modulation, as well as the expression and post-translational modification of lipoprotein-binding proteoglycan core proteins, and the introduction of disturbed laminar flow vastly augments the ability of a previously resistant, straight arterial segment to retain lipoproteins. © 2015 American Heart Association, Inc.

Carbon nanotubes introduced into the abdominal cavity of mice show asbestos-like pathogenicity in a pilot study.

PubMed

Poland, Craig A; Duffin, Rodger; Kinloch, Ian; Maynard, Andrew; Wallace, William A H; Seaton, Anthony; Stone, Vicki; Brown, Simon; Macnee, William; Donaldson, Ken

2008-07-01

Carbon nanotubes have distinctive characteristics, but their needle-like fibre shape has been compared to asbestos, raising concerns that widespread use of carbon nanotubes may lead to mesothelioma, cancer of the lining of the lungs caused by exposure to asbestos. Here we show that exposing the mesothelial lining of the body cavity of mice, as a surrogate for the mesothelial lining of the chest cavity, to long multiwalled carbon nanotubes results in asbestos-like, length-dependent, pathogenic behaviour. This includes inflammation and the formation of lesions known as granulomas. This is of considerable importance, because research and business communities continue to invest heavily in carbon nanotubes for a wide range of products under the assumption that they are no more hazardous than graphite. Our results suggest the need for further research and great caution before introducing such products into the market if long-term harm is to be avoided.

Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice

PubMed Central

Logan, Ryan W.; Seggio, Joseph A.; Robinson, Stacy L.; Richard, Gregory R.; Rosenwasser, Alan M.

2010-01-01

Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments, not in the home-cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity relative to plain-air controls that persisted for about one week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior. PMID:20682191

Disturbance Distance: Using a process based ecosystem model to estimate and map potential thresholds in disturbance rates that would give rise to fundamentally altered ecosystems

NASA Astrophysics Data System (ADS)

Dolan, K. A.; Hurtt, G. C.; Fisk, J.; Flanagan, S.; LePage, Y.; Sahajpal, R.

2014-12-01

Disturbance plays a critical role in shaping the structure and function of forested ecosystems as well as the ecosystem services they provide, including but not limited to: carbon storage, biodiversity habitat, water quality and flow, and land atmosphere exchanges of energy and water. As recent studies highlight novel disturbance regimes resulting from pollution, invasive pests and climate change, there is a need to include these alterations in predictions of future forest function and structure. The Ecosystem Demography (ED) model is a mechanistic model of forest ecosystem dynamics in which individual-based forest dynamics can be efficiently implemented over regional to global scales due to advanced scaling methods. We utilize ED to characterize the sensitivity of potential vegetation structure and function to changes in rates of density independent mortality. Disturbance rate within ED can either be altered directly or through the development of sub-models. Disturbance sub-models in ED currently include fire, land use and hurricanes. We use a tiered approach to understand the sensitivity of North American ecosystems to changes in background density independent mortality. Our first analyses were conducted at half-degree spatial resolution with a constant rate of disturbance in space and time, which was altered between runs. Annual climate was held constant at the site level and the land use and fire sub-models were turned off. Results showed an ~ 30% increase in non-forest area across the US when disturbance rates were changed from 0.6% a year to 1.2% a year and a more than 3.5 fold increase in non-forest area when disturbance rates doubled again from 1.2% to 2.4%. Continued runs altered natural background disturbance rates with the existing fire and hurricane sub models turned on as well as historic and future land use. By quantify differences between model outputs that characterize ecosystem structure and function related to the carbon cycle across the US, we

Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects mice from diet-induced obesity and insulin resistance.

PubMed

Nawrocki, Andrea R; Rodriguez, Carlos G; Toolan, Dawn M; Price, Olga; Henry, Melanie; Forrest, Gail; Szeto, Daphne; Keohane, Carol Ann; Pan, Yie; Smith, Karen M; Raheem, Izzat T; Cox, Christopher D; Hwa, Joyce; Renger, John J; Smith, Sean M

2014-01-01

Phosphodiesterase 10A (PDE10A) is a novel therapeutic target for the treatment of schizophrenia. Here we report a novel role of PDE10A in the regulation of caloric intake and energy homeostasis. PDE10A-deficient mice are resistant to diet-induced obesity (DIO) and associated metabolic disturbances. Inhibition of weight gain is due to hypophagia after mice are fed a highly palatable diet rich in fats and sugar but not a standard diet. PDE10A deficiency produces a decrease in caloric intake without affecting meal frequency, daytime versus nighttime feeding behavior, or locomotor activity. We tested THPP-6, a small molecule PDE10A inhibitor, in DIO mice. THPP-6 treatment resulted in decreased food intake, body weight loss, and reduced adiposity at doses that produced antipsychotic efficacy in behavioral models. We show that PDE10A inhibition increased whole-body energy expenditure in DIO mice fed a Western-style diet, achieving weight loss and reducing adiposity beyond the extent seen with food restriction alone. Therefore, chronic THPP-6 treatment conferred improved insulin sensitivity and reversed hyperinsulinemia. These data demonstrate that PDE10A inhibition represents a novel antipsychotic target that may have additional metabolic benefits over current medications for schizophrenia by suppressing food intake, alleviating weight gain, and reducing the risk for the development of diabetes.

Unpredictable chronic mild stress induces anxiety and depression-like behaviors and inactivates AMP-activated protein kinase in mice.

PubMed

Zhu, Shenghua; Wang, Junhui; Zhang, Yanbo; Li, Victor; Kong, Jiming; He, Jue; Li, Xin-Min

2014-08-12

The unpredictable chronic mild stress (UCMS) model was developed based upon the stress-diathesis hypothesis of depression. Most effects of UCMS can be reversed by antidepressants, demonstrating a strong predictive validity of this model for depression. However, the mechanisms underlying the effects induced by UCMS remain incompletely understood. Increasing evidence has shown that AMP-activated protein kinase (AMPK) regulates intracellular energy metabolism and is especially important for neurons because neurons are known to have small energy reserves. Abnormalities in the AMPK pathway disturb normal brain functions and synaptic integrity. In the present study, we first investigated the effects of UCMS on a battery of different tests measuring anxiety and depression-like behaviors in female C57BL/6N mice after 4 weeks of UCMS exposure. Stressed mice showed suppressed body weight gain, heightened anxiety, and increased immobility in the forced swim and tail suspension tests. These results are representative of some of the core symptoms of depression. Simultaneously, we observed decrease of synaptic proteins in the cortex of mice subjected to UCMS, which is associated with decreased levels of phosphorylated AMP-activated protein kinase α (AMPKα) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). Our findings suggest that AMPKα inactivation might be a mechanism by which UCMS causes anxiety/depression-like behaviors in mice. Copyright © 2014 Elsevier B.V. All rights reserved.

The interplay between climate change, forests, and disturbances.

PubMed

Dale, V H; Joyce, L A; McNulty, S; Neilson, R P

2000-11-15

Climate change affects forests both directly and indirectly through disturbances. Disturbances are a natural and integral part of forest ecosystems, and climate change can alter these natural interactions. When disturbances exceed their natural range of variation, the change in forest structure and function may be extreme. Each disturbance affects forests differently. Some disturbances have tight interactions with the species and forest communities which can be disrupted by climate change. Impacts of disturbances and thus of climate change are seen over a board spectrum of spatial and temporal scales. Future observations, research, and tool development are needed to further understand the interactions between climate change and forest disturbances.

Beyond the competition-colonization trade-off: linking multiple trait response to disturbance characteristics.

PubMed

Seifan, Merav; Seifan, Tal; Schiffers, Katja; Jeltsch, Florian; Tielbörger, Katja

2013-02-01

Disturbances' role in shaping communities is well documented but highly disputed. We suggest replacing the overused two-trait trade-off approach with a functional group scheme, constructed from combinations of four key traits that represent four classes of species' responses to disturbances. Using model results and field observations from sites affected by two highly different disturbances, we demonstrated that popular dichotomous trade-offs are not sufficient to explain community dynamics, even if some emerge under certain conditions. Without disturbances, competition was only sufficient to predict species survival but not relative success, which required some escape mechanism (e.g., long-term dormancy). With highly predictable and large-scale disturbances, successful species showed a combination of high individual tolerance to disturbance and, more surprisingly, high competitive ability. When disturbances were less predictable, high individual tolerance and long-term seed dormancy were favored, due to higher environmental uncertainty. Our study demonstrates that theories relying on a small number of predefined trade-offs among traits (e.g., competition-colonization trade-off) may lead to unrealistic results. We suggest that the understanding of disturbance-community relationships can be significantly improved by employing sets of relevant trait assemblies instead of the currently common approach in which trade-offs are assumed in advance.

Disturbance opens recruitment sites for bacterial colonization in activated sludge.

PubMed

Vuono, David C; Munakata-Marr, Junko; Spear, John R; Drewes, Jörg E

2016-01-01

Little is known about the role of immigration in shaping bacterial communities or the factors that may dictate success or failure of colonization by bacteria from regional species pools. To address these knowledge gaps, the influence of bacterial colonization into an ecosystem (activated sludge bioreactor) was measured through a disturbance gradient (successive decreases in the parameter solids retention time) relative to stable operational conditions. Through a DNA sequencing approach, we show that the most abundant bacteria within the immigrant community have a greater probability of colonizing the receiving ecosystem, but mostly as low abundance community members. Only during the disturbance do some of these bacterial populations significantly increase in abundance beyond background levels and in few cases become dominant community members post-disturbance. Two mechanisms facilitate the enhanced enrichment of immigrant populations during disturbance: (i) the availability of resources left unconsumed by established species and (ii) the increased availability of niche space for colonizers to establish and displace resident populations. Thus, as a disturbance decreases local diversity, recruitment sites become available to promote colonization. This work advances our understanding of microbial resource management and diversity maintenance in complex ecosystems. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Serum sialyltransferase and liver catalase activity in cachectic nude mice bearing a human malignant melanoma.

PubMed

Kondo, Y; Sato, K; Ueyama, Y; Ohsawa, N

1981-07-01

Cachexia is rare in nude mice bearing human malignant tumors even when the transplanted tumors become as large as the body size of the host. In our series on heterotransplantation of a variety of human malignant tumors into nude mice, a malignant melanoma (SEKI) was found to induce severe body weight loss in the host at the early stage of transplantation. There was no electrolyte disturbance, hyper- or hypoadrenocorticism, hyperthyroidism, or destruction of cells of vital organs to account for the weight loss. Moreover, no evidence was obtained for concomitant infection with bacteria, Mycoplasma or fungi. These cachectic mice revealed remarkably increased levels of serum sialyltransferase and decreased liver catalase activity. The removal of tumor tissues from these mice resulted in prompt recovery of body weight, serum sialyltransferase, and liver catalase activity within 1 to 2 weeks. On the basis of the results obtained, the SEKI melanoma was thought to have produced a pathophysiological state in host nude mice which was very similar to that of cachexia in cancer patients. Nude mice bearing transplants of SEKI melanoma may provide a useful system for the study of cancer cachexia in humans.

Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

PubMed Central

Sun, Rongli; Zhang, Juan; Yin, Lihong; Pu, Yuepu

2014-01-01

Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of benzene-induced hematotoxicity. Liquid chromatography coupled with time of flight-mass spectrometry (LC-TOF-MS) and principal component analysis (PCA) was applied to investigate the variation of endogenous metabolites in bone marrow cells and plasma of male C3H/He mice. The mice were injected subcutaneously with benzene (0, 300, 600 mg/day) once daily for seven days. The body weights, relative organ weights, blood parameters and bone marrow smears were also analyzed. The results indicated that benzene caused disturbances in the metabolism of oxidation of fatty acids and essential amino acids (lysine, phenylalanine and tyrosine) in bone marrow cells. Moreover, fatty acid oxidation was also disturbed in plasma and thus might be a common disturbed metabolic pathway induced by benzene in multiple organs. This study aims to investigate the underlying molecular mechanisms involved in benzene hematotoxicity, especially in bone marrow cells. PMID:24658442

The implications of recurrent disturbances within the world's hottest coral reef.

PubMed

Bento, Rita; Hoey, Andrew S; Bauman, Andrew G; Feary, David A; Burt, John A

2016-04-30

Determining how coral ecosystems are structured within extreme environments may provide insights into how coral reefs are impacted by future climate change. Benthic community structure was examined within the Persian Gulf, and adjacent Musandam and northern Oman regions across a 3-year period (2008-2011) in which all regions were exposed to major disturbances. Although there was evidence of temporal switching in coral composition within regions, communities predominantly reflected local environmental conditions and the disturbance history of each region. Gulf reefs showed little change in coral composition, being dominated by stress-tolerant Faviidae and Poritidae across the 3 years. In comparison, Musandam and Oman coral communities were comprised of stress-sensitive Acroporidae and Pocilloporidae; Oman communities showed substantial declines in such taxa and increased cover of stress-tolerant communities. Our results suggest that coral communities may persist within an increasingly disturbed future environment, albeit in a much more structurally simple configuration. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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.

MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance.

PubMed

Ogata, Takehiro; Ueyama, Tomomi; Isodono, Koji; Tagawa, Masashi; Takehara, Naofumi; Kawashima, Tsuneaki; Harada, Koichiro; Takahashi, Tomosaburo; Shioi, Tetsuo; Matsubara, Hiroaki; Oh, Hidemasa

2008-05-01

We identified a novel muscle-restricted putative coiled-coil protein, MURC, which is evolutionarily conserved from frog to human. MURC was localized to the cytoplasm with accumulation in the Z-line of the sarcomere in the murine adult heart. MURC mRNA expression in the heart increased during the developmental process from the embryonic stage to adulthood. In response to pressure overload, MURC mRNA expression increased in the hypertrophied heart. Using the yeast two-hybrid system, we identified the serum deprivation response (SDPR) protein, a phosphatidylserine-binding protein, as a MURC-binding protein. MURC induced activation of the RhoA/ROCK pathway, which modulated serum response factor-mediated atrial natriuretic peptide (ANP) expression and myofibrillar organization. SDPR augmented MURC-induced transactivation of the ANP promoter in cardiomyocytes, and RNA interference of SDPR attenuated the action of MURC on the ANP promoter. Transgenic mice expressing cardiac-specific MURC (Tg-MURC) exhibited cardiac contractile dysfunction and atrioventricular (AV) conduction disturbances with atrial chamber enlargement, reduced thickness of the ventricular wall, and interstitial fibrosis. Spontaneous episodes of atrial fibrillation and AV block were observed in Tg-MURC mice. These findings indicate that MURC modulates RhoA signaling and that MURC plays an important role in the development of cardiac dysfunction and conduction disturbance with increased vulnerability to atrial arrhythmias.

Anthropogenic disturbance in tropical forests can double biodiversity loss from deforestation.

PubMed

Barlow, Jos; Lennox, Gareth D; Ferreira, Joice; Berenguer, Erika; Lees, Alexander C; Mac Nally, Ralph; Thomson, James R; Ferraz, Silvio Frosini de Barros; Louzada, Julio; Oliveira, Victor Hugo Fonseca; Parry, Luke; Solar, Ricardo Ribeiro de Castro; Vieira, Ima C G; Aragão, Luiz E O C; Begotti, Rodrigo Anzolin; Braga, Rodrigo F; Cardoso, Thiago Moreira; de Oliveira, Raimundo Cosme; Souza, Carlos M; Moura, Nárgila G; Nunes, Sâmia Serra; Siqueira, João Victor; Pardini, Renata; Silveira, Juliana M; Vaz-de-Mello, Fernando Z; Veiga, Ruan Carlo Stulpen; Venturieri, Adriano; Gardner, Toby A

2016-07-07

Concerted political attention has focused on reducing deforestation, and this remains the cornerstone of most biodiversity conservation strategies. However, maintaining forest cover may not reduce anthropogenic forest disturbances, which are rarely considered in conservation programmes. These disturbances occur both within forests, including selective logging and wildfires, and at the landscape level, through edge, area and isolation effects. Until now, the combined effect of anthropogenic disturbance on the conservation value of remnant primary forests has remained unknown, making it impossible to assess the relative importance of forest disturbance and forest loss. Here we address these knowledge gaps using a large data set of plants, birds and dung beetles (1,538, 460 and 156 species, respectively) sampled in 36 catchments in the Brazilian state of Pará. Catchments retaining more than 69–80% forest cover lost more conservation value from disturbance than from forest loss. For example, a 20% loss of primary forest, the maximum level of deforestation allowed on Amazonian properties under Brazil’s Forest Code, resulted in a 39–54% loss of conservation value: 96–171% more than expected without considering disturbance effects. We extrapolated the disturbance-mediated loss of conservation value throughout Pará, which covers 25% of the Brazilian Amazon. Although disturbed forests retained considerable conservation value compared with deforested areas, the toll of disturbance outside Pará’s strictly protected areas is equivalent to the loss of 92,000–139,000 km2 of primary forest. Even this lowest estimate is greater than the area deforested across the entire Brazilian Amazon between 2006 and 2015 (ref. 10). Species distribution models showed that both landscape and within-forest disturbances contributed to biodiversity loss, with the greatest negative effects on species of high conservation and functional value. These results demonstrate an urgent need

Effect of parsley (Petroselinum crispum, Apiaceae) juice against cadmium neurotoxicity in albino mice (Mus musculus).

PubMed

Maodaa, Saleh N; Allam, Ahmed A; Ajarem, Jamaan; Abdel-Maksoud, Mostafa A; Al-Basher, Gadah I; Wang, Zun Yao

2016-02-04

Parsley was employed as an experimental probe to prevent the behavioral, biochemical and morphological changes in the brain tissue of the albino mice following chronic cadmium (Cd) administration. Non-anesthetized adult male mice were given parsley juice (Petroselinum crispum, Apiaceae) daily by gastric intubation at doses of 10 and 20 g/kg/day. The animals were divided into six groups: Group A, mice were exposed to saline; Groups B and C, were given low and high doses of parsley juice, respectively; Group D, mice were exposed to Cd; Groups E and F, were exposed to Cd and concomitantly given low and high doses of parsley, respectively. Cd intoxication can cause behavioral abnormalities, biochemical and histopathological disturbances in treated mice. Parsley juice has significantly improved the Cd-associated behavioral changes, reduced the elevation of lipid peroxidation and normalized the Cd effect on reduced glutathione and peroxidase activities in the brain of treated mice. Histological data have supported these foundations whereas Cd treatment has induced neuronal degeneration, chromatolysis and pyknosis in the cerebrum, cerebellum and medulla oblongata. The low dose (5 g/kg/day) of parsley exhibited beneficial effects in reducing the deleterious changes associated with Cd treatment on the behavior, neurotransmitters level, oxidative stress and brain neurons of the Cd-treated mice.

Effects of (-)-S-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4,5]decane L-tartrate monohydrate (YM796), a novel muscarinic agonist, on disturbance of passive avoidance learning behavior in drug-treated and senescence-accelerated mice.

PubMed

Suzuki, M; Yamaguchi, T; Ozawa, Y; Ohyama, M; Yamamoto, M

1995-11-01

Effects of YM796 (-)-S-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4,5]decane L-tartrate monohydrate; a novel muscarinic agonist, were observed on disturbance of passive avoidance learning behavior in drug- (protein synthesis inhibitor and anticholinergic drugs) treated and senescence-accelerated mice in comparison with those of a muscarinic agonist (AF102B) and acetylcholinesterase inhibitors (E2020 (1-benzyl-4-[(5,6-dimethoxy-1-indanone-2-yl) methyl] piperidene hydrochloride), NIK247 [9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)-quinoline monohydrate hydrochloride], THA (9-amino-1,2,3,4-tetrahydroacridine) and physostigmine). All tested drugs administered before training significantly prolonged the shortened latency of step-through induced by the protein synthesis inhibitor cycloheximide (150 mg/kg s.c.). This shortened latency was also significantly prolonged when YM796 was administered immediately after training, but not when administered before the test trial. The ameliorating effect of YM796 on the impairment in learning behavior by cycloheximide was significantly suppressed by pirenzepine (0.1 micrograms/mouse i.c.v.). When administered before training, all test drugs prolonged the shortened latency of step-through induced by treatment with the anticholinergic drugs [scopolamine (1 mg/kg s.c.) and hemicholinium-3 (0.3 microgram/mouse i.c.v.)], suggesting that they ameliorated the impairment of learning behavior. This shortened latency in scopolamine-treated mice was also significantly prolonged by YM796, AF102B, E2020, NIK247 and physostigmine when administered immediately after training, but not when administered before the test trial. The pharmacological actions of YM796 administered immediately after training and before the test trial in hemicholinium-3-treated mice were similar to those in scopolamine-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

A Long-term Estrogen Deficiency in Ovariectomized Mice is Associated with Disturbances in Fatty Acid Oxidation and Oxidative Stress.

PubMed

Oliveira, Monique Cristine de; Campos-Shimada, Lilian Brites; Marçal-Natali, Maria Raquel; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

2018-05-01

 The aim of this work was to evaluate the changes caused by estrogen deficiency in lipid metabolism.  This study encompassed direct measurements of plasma biochemical analyses, liver lipid contents, and assessments of the mitochondrial β-oxidation capacity as well as an evaluation of the liver redox status in an animal model of estrogen deficiency.  When compared with control mice, the livers of ovariectomized (OVX) mice presented considerable accretions in their lipid contents, which were accompanied by increased levels of lipid peroxidation in liver homogenates and mitochondria from OVX groups and decreased reduced glutathione (GSH) contents. In isolated mitochondria, estrogen deficiency inhibited mitochondrial β-oxidation of fatty acids irrespective of their chain length. The liver mitochondrial and peroxisomal H 2 O 2 generations in OVX mice were increased. Additionally, the activities of all antioxidant enzymes assessed were decreased.  These data provide one potential explanation for the increased susceptibility to metabolic diseases observed after menopause. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Influence of disturbance on temperate forest productivity

USGS Publications Warehouse

Peters, Emily B.; Wythers, Kirk R.; Bradford, John B.; Reich, Peter B.

2013-01-01

Climate, tree species traits, and soil fertility are key controls on forest productivity. However, in most forest ecosystems, natural and human disturbances, such as wind throw, fire, and harvest, can also exert important and lasting direct and indirect influence over productivity. We used an ecosystem model, PnET-CN, to examine how disturbance type, intensity, and frequency influence net primary production (NPP) across a range of forest types from Minnesota and Wisconsin, USA. We assessed the importance of past disturbances on NPP, net N mineralization, foliar N, and leaf area index at 107 forest stands of differing types (aspen, jack pine, northern hardwood, black spruce) and disturbance history (fire, harvest) by comparing model simulations with observations. The model reasonably predicted differences among forest types in productivity, foliar N, leaf area index, and net N mineralization. Model simulations that included past disturbances minimally improved predictions compared to simulations without disturbance, suggesting the legacy of past disturbances played a minor role in influencing current forest productivity rates. Modeled NPP was more sensitive to the intensity of soil removal during a disturbance than the fraction of stand mortality or wood removal. Increasing crown fire frequency resulted in lower NPP, particularly for conifer forest types with longer leaf life spans and longer recovery times. These findings suggest that, over long time periods, moderate frequency disturbances are a relatively less important control on productivity than climate, soil, and species traits.

Finding disturbances in on-farm biogas production.

PubMed

Antonio, Pereira-Querol Marco; Laura, Seppänen

2012-01-01

When implementing innovations, disturbances are very likely to take place. Disturbances are undesirable because they can lead to unwanted outcomes, such as economic losses and work overload to workers. However, they can be powerful opportunities for learning and re-designing innovations. Here, we will present activity theoretical tools for analyzing disturbances in a way that they could be used as learning opportunities. We illustrate the proposed tools by analyzing a disturbance that took place during the implementation of a project of biogas production. By interpreting the disturbance process with a network of activity systems, we found that on-farm disturbances were formed as ruptures, innovations and asynchronies originated in other activity systems. This finding suggests that disturbances are outcomes of the functioning of networks, rather than simple results of failure of individuals or technical devices. The proposed tools could be used in interventions to help practitioners and ergonomists to recognize the systemic and networked nature of problems, and therefore, realize that they may require the collaboration of actors from different activities. In this sense, disturbances may be turned into opportunities for learning and developing innovations. We conclude by discussing how the method could be used in ergonomic design and intervention.

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

PubMed

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.

Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias

PubMed Central

Hara, Munetsugu; Takahashi, Tomoyuki; Mitsumasu, Chiaki; Igata, Sachiyo; Takano, Makoto; Minami, Tomoko; Yasukawa, Hideo; Okayama, Satoko; Nakamura, Keiichiro; Okabe, Yasunori; Tanaka, Eiichiro; Takemura, Genzou; Kosai, Ken-ichiro; Yamashita, Yushiro; Matsuishi, Toyojiro

2015-01-01

Methyl-CpG-binding protein 2 (MeCP2) is an epigenetic regulator of gene expression that is essential for normal brain development. Mutations in MeCP2 lead to disrupted neuronal function and can cause Rett syndrome (RTT), a neurodevelopmental disorder. Previous studies reported cardiac dysfunction, including arrhythmias in both RTT patients and animal models of RTT. In addition, recent studies indicate that MeCP2 may be involved in cardiac development and dysfunction, but its role in the developing and adult heart remains unknown. In this study, we found that Mecp2-null ESCs could differentiate into cardiomyocytes, but the development and further differentiation of cardiovascular progenitors were significantly affected in MeCP2 deficiency. In addition, we revealed that loss of MeCP2 led to dysregulation of endogenous cardiac genes and myocardial structural alterations, although Mecp2-null mice did not exhibit obvious cardiac functional abnormalities. Furthermore, we detected methylation of the CpG islands in the Tbx5 locus, and showed that MeCP2 could target these sequences. Taken together, these results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure. PMID:26073556

Bisphenol A disrupts glucose transport and neurophysiological role of IR/IRS/AKT/GSK3β axis in the brain of male mice.

PubMed

Li, Jing; Wang, Yixin; Fang, Fangfang; Chen, Donglong; Gao, Yue; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

2016-04-01

Bisphenol A (BPA), one of the most prevalent chemicals for daily use, was recently reported to disturb the homeostasis of energy metabolism and insulin signaling pathways, which might contribute to the increasing prevalence rate of mild cognitive impairment (MCI). However, the underlying mechanisms are remained poorly understood. Here we studied the effects of low dose BPA on glucose transport and the IR/IRS/AKT/GSK3β axis in adult male mice to delineate the association between insulin signaling disruption and neurotoxicity mediated by BPA. Mice were treated with subcutaneous injection of 100μg/kg/d BPA or vehicle for 30 days, then the insulin signaling and glucose transporters in the hippocampus and prefrontal cortex were detected by western blot. Our results showed that mice treated with BPA displayed significant decrease of insulin sensitivity, and in glucose transporter 1, 3 (GLUT1, 3) protein levels in mouse brain. Meanwhile, hyperactivation of IR/IRS/AKT/GSK3β axis was detected in the brain of BPA treated mice. Noteworthily, significant increases of phosphorylated tau and β-APP were observed in BPA treated mice. These results strongly suggest that BPA exposure significantly disrupts brain insulin signaling and might be considered as a potential risk factor for neurodegenerative diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

46 CFR 386.7 - Disturbances.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Disturbances. 386.7 Section 386.7 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MISCELLANEOUS REGULATIONS GOVERNING PUBLIC BUILDINGS AND GROUNDS AT THE UNITED STATES MERCHANT MARINE ACADEMY § 386.7 Disturbances. Any loitering, disorderly conduct or...

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

PubMed Central

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

Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior.

PubMed

Chourbaji, Sabine; Hellweg, Rainer; Brandis, Dorothee; Zörner, Björn; Zacher, Christiane; Lang, Undine E; Henn, Fritz A; Hörtnagl, Heide; Gass, Peter

2004-02-05

The "neurotrophin hypothesis" of depression predicts that depressive disorders in humans coincide with a decreased activity and/or expression of brain-derived neurotrophic factor (BDNF) in the brain. Therefore, we investigated whether mice with a reduced BDNF expression due to heterozygous gene disruption demonstrate depression-like neurochemical changes or behavioral symptoms. BNDF protein levels of adult BDNF(+/-) mice were reduced to about 60% in several brain areas investigated, including the hippocampus, frontal cortex, striatum, and hypothalamus. The content of monoamines (serotonin, norepinephrine, and dopamine) as well as of serotonin and dopamine degradation products was unchanged in these brain regions. By contrast, choline acetyltransferase activity was significantly reduced by 19% in the hippocampus of BDNF(+/-) mice, indicating that the cholinergic system of the basal forebrain is critically dependent on sufficient endogenous BDNF levels in adulthood. Moreover, BDNF(+/-) mice exhibited normal corticosterone and adrenocorticotropic hormone (ACTH) serum levels under baseline conditions and following immobilization stress. In a panel of behavioral tests investigating locomotor activity, exploration, anxiety, fear-associated learning, and behavioral despair, BDNF(+/-) mice were indistinguishable from wild-type littermates. Thus, a chronic reduction of BDNF protein content in adult mice is not sufficient to induce neurochemical or behavioral alterations that are reminiscent of depressive symptoms in humans.

Sex-typed play in gender-disturbed children: a comparison to sibling and psychiatric controls.

PubMed

Zucker, K J; Doering, R W; Bradley, S J; Finegan, J K

1982-08-01

Gender-disturbed children (n = 14) were compared to their preadolescent siblings (n = 16) and psychiatric controls (n = 13) on a sex-typed free-play task previously shown to differentiate gender-disturbed boys from normal boys. On three separate trials totaling 20 minutes, the gender-disturbed children played for a significantly longer period of time with cross-sex toys and for a significantly shorter period of time with same-sex toys than did the two control groups. The gender-disturbed children also showed greater trial-to-trial consistency in their play preferences than the other two groups. The utility of this task in the assessment of childhood gender disturbance is discussed. In addition, the results are discussed in relation to a number of perspectives regarding both typical and atypical gender identity development in childhood.

Work-family conflict and sleep disturbance: the Malaysian working women study

PubMed Central

AAZAMI, Sanaz; MOZAFARI, Mosayeb; SHAMSUDDIN, Khadijah; AKMAL, Syaqirah

2015-01-01

This study aimed at assessing effect of the four dimensions of work-family conflicts (strain and time-based work interference into family and family interference into work) on sleep disturbance in Malaysian working women. This cross-sectional study was conducted among 325 Malaysian married working women. Multiple-stage simple random sampling method was used to recruit women from public service departments of Malaysia. Self-administrated questionnaires were used to measure the study variables and data were analyzed using SPSS version 21. We found that high level of the four dimensions of work-family conflicts significantly increase sleep disturbance. Our analyses also revealed an age-dependent effect of the work-family conflict on sleep disturbance. Women in their 20 to 30 yr old suffer from sleep disturbance due to high level of time-based and strain-based work-interference into family. However, the quality of sleep among women aged 30–39 were affected by strain-based family-interference into work. Finally, women older than 40 yr had significantly disturbed sleep due to strain-based work-interference into family as well as time-based family interference into work. Our findings showed that sleep quality of working women might be disturbed by experiencing high level of work-family conflict. However, the effects of inter-role conflicts on sleep varied among different age groups. PMID:26423332

Work-family conflict and sleep disturbance: the Malaysian working women study.

PubMed

Aazami, Sanaz; Mozafari, Mosayeb; Shamsuddin, Khadijah; Akmal, Syaqirah

2016-01-01

This study aimed at assessing effect of the four dimensions of work-family conflicts (strain and time-based work interference into family and family interference into work) on sleep disturbance in Malaysian working women. This cross-sectional study was conducted among 325 Malaysian married working women. Multiple-stage simple random sampling method was used to recruit women from public service departments of Malaysia. Self-administrated questionnaires were used to measure the study variables and data were analyzed using SPSS version 21. We found that high level of the four dimensions of work-family conflicts significantly increase sleep disturbance. Our analyses also revealed an age-dependent effect of the work-family conflict on sleep disturbance. Women in their 20 to 30 yr old suffer from sleep disturbance due to high level of time-based and strain-based work-interference into family. However, the quality of sleep among women aged 30-39 were affected by strain-based family-interference into work. Finally, women older than 40 yr had significantly disturbed sleep due to strain-based work-interference into family as well as time-based family interference into work. Our findings showed that sleep quality of working women might be disturbed by experiencing high level of work-family conflict. However, the effects of inter-role conflicts on sleep varied among different age groups.

Different Recovery Processes of Soil Ammonia Oxidizers from Flooding Disturbance.

PubMed

Ye, Fei; Ma, Mao-Hua; Op den Camp, Huub J M; Chatzinotas, Antonis; Li, Lei; Lv, Ming-Quan; Wu, Sheng-Jun; Wang, Yu

2018-04-11

Understanding how microorganisms respond to environmental disturbance is one of the key focuses in microbial ecology. Ammonia-oxidizing bacteria (AOB) and archaea (AOA) are responsible for ammonia oxidation which is a crucial step in the nitrogen cycle. Although the physiology, distribution, and activity of AOA and AOB in soil have been extensively investigated, their recovery from a natural disturbance remains largely unknown. To assess the recovery capacities, including resistance and resilience, of AOA and AOB, soil samples were taken from a reservoir riparian zone which experienced periodically water flooding. The samples were classified into three groups (flooding, recovery, and control) for a high-throughput sequencing and quantitative PCR analysis. We used a relative quantitative index of both the resistance (RS) and resilience (RL) to assess the variation of gene abundance, alpha-diversity, and community composition. The AOA generally demonstrated a better recovery capability after the flooding disturbance compared to AOB. In particular, AOA were more resilient after the flooding disturbance. Taxa within the AOA and AOB showed different RS and RL values, with the most abundant taxa showing in general the highest RS indices. Soil NH 4 + and Fe 2+ /Fe 3+ were the main variables controlling the key taxa of AOA and AOB and probably influenced the resistance and resilience properties of AOA and AOB communities. The distinct mechanisms of AOA and AOB in maintaining community stability against the flooding disturbance might be linked to the different life-history strategies: the AOA community was more likely to represent r-strategists in contrast to the AOB community following a K-life strategy. Our results indicated that the AOA may play a vital role in ammonia oxidation in a fluctuating habitat and contribute to the stability of riparian ecosystem.

Trawl disturbance on benthic communities: chronic effects and experimental predictions.

PubMed

Hinz, Hilmar; Prieto, Virginia; Kaiser, Michel J

2009-04-01

Bottom trawling has widespread impacts on benthic communities and habitats. While the direct impacts of trawl disturbances on benthic communities have been extensively studied, the consequences from long-term chronic disturbances are less well understood. The response of benthic macrofauna to chronic otter-trawl disturbance from a Nephrops norvegicus (Norway lobster) fishery was investigated along a gradient of fishing intensity over a muddy fishing ground in the northeastern Irish Sea. Chronic otter trawling had a significant, negative effect on benthic infauna abundance, biomass, and species richness. Benthic epifauna abundance and species richness also showed a significant, negative response, while no such effect was evident for epibenthic biomass. Furthermore, chronic trawl disturbance led to clear changes in community composition of benthic infauna and epifauna. The results presented indicate that otter-trawl impacts are cumulative and can lead to profound changes in benthic communities, which may have far-reaching implications for the integrity of marine food webs. Studies investigating the short-term effects of fishing manipulations previously concluded that otter trawling on muddy substrates had only modest effects on the benthic biota. Hence, the results presented by this study highlight that data from experimental studies can not be readily extrapolated to an ecosystem level and that subtle cumulative effects may only become apparent when fishing disturbances are examined over larger spatial and temporal scales. Furthermore, this study shows that data on chronic effects of bottom trawling on the benthos will be vital in informing the recently advocated move toward an ecosystem approach in fisheries management. As bottom-trawl fisheries are expanding into ever deeper muddy habitats, the results presented here are an important step toward understanding the global ecosystem effects of bottom trawling.

Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice.

PubMed

Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho; Yee, Sung-Tae

2009-03-17

Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

PubMed Central

2009-01-01

Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p < 0.1) and weight (p < 0.1). HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin. PMID:19292900

Multi-dimensional distribution of near-field ionospheric disturbances produced by the 2015 Mw7.8 Nepal earthquake

NASA Astrophysics Data System (ADS)

Tang, Jun; Yuan, Yunbin

2017-10-01

Ionospheric anomalies possibly associated with large earthquakes, particularly coseismic ionospheric disturbances, have been detected by global positioning system (GPS). A large Nepal earthquake with magnitude Mw7.8 occurred on April 25, 2015. In this paper, we investigate the multi-dimensional distribution of near-field coseismic ionospheric disturbances (CIDs) using total electron content (TEC) and computerized ionospheric tomography (CIT) from regional GPS observational data. The results show significant ionospheric TEC disturbances and interesting multi-dimensional structures around the main shock. Regarding the TEC changes, coseismic ionospheric disturbances occur approximately 10-20 min after the earthquake northeast and northwest of epicentre. The maximum ridge-to-trough amplitude of CIDs is up to approximately 0.90 TECU/min. Propagation velocities of the TEC disturbances are 1.27 ± 0.06 km/s and 1.91 ± 0.38 km/s. It is believed that the ionospheric disturbances are triggered by acoustic and Rayleigh waves. Tomographic results show that the three-dimensional distribution of ionospheric disturbances obviously increases at an altitude of 300 km above the surrounding epicentre, predominantly in the entire region between 200 km and 400 km. Significant ionospheric disturbances appear at 06:30 UT from tomographic images. This study reveals characteristics of an ionospheric anomaly caused by the Nepal earthquake.

Are Nested Networks More Robust to Disturbance? A Test Using Epiphyte-Tree, Comensalistic Networks

PubMed Central

Piazzon, Martín; Larrinaga, Asier R.; Santamaría, Luis

2011-01-01

Recent research on ecological networks suggests that mutualistic networks are more nested than antagonistic ones and, as a result, they are more robust against chains of extinctions caused by disturbances. We evaluate whether mutualistic networks are more nested than comensalistic and antagonistic networks, and whether highly nested, host-epiphyte comensalistic networks fit the prediction of high robustness against disturbance. A review of 59 networks including mutualistic, antagonistic and comensalistic relationships showed that comensalistic networks are significantly more nested than antagonistic and mutualistic networks, which did not differ between themselves. Epiphyte-host networks from old-growth forests differed from those from disturbed forest in several topological parameters based on both qualitative and quantitative matrices. Network robustness increased with network size, but the slope of this relationship varied with nestedness and connectance. Our results indicate that interaction networks show complex responses to disturbances, which influence their topology and indirectly affect their robustness against species extinctions. PMID:21589931

[Recognizing and preventing disturbances in eruption].

PubMed

van der Linden, F P G M

2014-04-01

Disturbances in eruption and related problems are quite common in permanent dentition but rare in deciduous dentition. For the timely recognition of disturbances in eruption, knowledge of the normal development of dentition is essential. Disturbances in eruption comprise disturbances in which eruption does not occur at all, in which it is delayed or incomplete, or in which the normal direction of eruption is influenced. If identified early enough, many undesirable dental conditions can be avoided or their seriousness can be limited. A possible impacting of permanent cuspids, for example, can be avoided by extracting the deciduous cuspids at the right moment; in cases of a large overjet or the threat of a cover-bite, lip interference can be prevented.

Effects of spatial disturbance on common loon nest site selection and territory success

USGS Publications Warehouse

McCarthy, K.P.; DeStefano, S.

2011-01-01

The common loon (Gavia immer) breeds during the summer on northern lakes and water bodies that are also often desirable areas for aquatic recreation and human habitation. In northern New England, we assessed how the spatial nature of disturbance affects common loon nest site selection and territory success. We found through classification and regression analysis that distance to and density of disturbance factors can be used to classify observed nest site locations versus random points, suggesting that these factors affect loon nest site selection (model 1: Correct classification = 75%, null = 50%, K = 0.507, P < 0.001; model 2: Correct classification = 78%, null = 50%, K = 0.551, P < 0.001). However, in an exploratory analysis, we were unable to show a relation between spatial disturbance variables and breeding success (P = 0.595, R 2 = 0.436), possibly because breeding success was so low during the breeding seasons of 2007-2008. We suggest that by selecting nest site locations that avoid disturbance factors, loons thereby limit the effect that disturbance will have on their breeding success. Still, disturbance may force loons to use sub-optimal nesting habitat, limiting the available number of territories, and overall productivity. We advise that management efforts focus on limiting disturbance factors to allow breeding pairs access to the best nesting territories, relieving disturbance pressures that may force sub-optimal nest placement. ?? 2011 The Wildlife Society.

Cellular mechanisms of cyclophosphamide-induced taste loss in mice

PubMed Central

Mukherjee, Nabanita; Pal Choudhuri, Shreoshi; Delay, Rona J.

2017-01-01

Many commonly prescribed chemotherapy drugs such as cyclophosphamide (CYP) have adverse side effects including disruptions in taste which can result in loss of appetite, malnutrition, poorer recovery and reduced quality of life. Previous studies in mice found evidence that CYP has a two-phase disturbance in taste behavior: a disturbance immediately following drug administration and a second which emerges several days later. In this study, we examined the processes by which CYP disturbs the taste system by examining the effects of the drug on taste buds and cells responsible for taste cell renewal using immunohistochemical assays. Data reported here suggest CYP has direct cytotoxic effects on lingual epithelium immediately following administration, causing an early loss of taste sensory cells. Types II and III cells in fungiform taste buds appear to be more susceptible to this effect than circumvallate cells. In addition, CYP disrupts the population of rapidly dividing cells in the basal layer of taste epithelium responsible for taste cell renewal, manifesting a disturbance days later. The loss of these cells temporarily retards the system’s capacity to replace Type II and Type III taste sensory cells that survived the cytotoxic effects of CYP and died at the end of their natural lifespan. The timing of an immediate, direct loss of taste cells and a delayed, indirect loss without replacement of taste sensory cells are broadly congruent with previously published behavioral data reporting two periods of elevated detection thresholds for umami and sucrose stimuli. These findings suggest that chemotherapeutic disturbances in the peripheral mechanisms of the taste system may cause dietary challenges at a time when the cancer patient has significant need for well balanced, high energy nutritional intake. PMID:28950008

Disturbance regimes and ecological responses across sites

USDA-ARS?s Scientific Manuscript database

Disturbances affect ecosystems in almost limitless ways. The effects of disturbances extend beyond the initial impacts that are usually visible to the human eye. Therefore, for many disturbances long-term data are needed to unravel their effects. This chapter first presents characteristics of distu...

Potential of Pest and Host Phenological Data in the Attribution of Regional Forest Disturbance Detection Maps According to Causal Agent

NASA Technical Reports Server (NTRS)

Spruce, Joseph; Hargrove, William; Norman Steve; Christie, William

2014-01-01

Near real time forest disturbance detection maps from MODIS NDVI phenology data have been produced since 2010 for the conterminous U.S., as part of the on-line ForWarn national forest threat early warning system. The latter has been used by the forest health community to identify and track many regional forest disturbances caused by multiple biotic and abiotic damage agents. Attribution of causal agents for detected disturbances has been a goal since project initiation in 2006. Combined with detailed cover type maps, geospatial pest phenology data offer a potential means for narrowing the candidate causal agents responsible for a given biotic disturbance. U.S. Aerial Detection Surveys (ADS) employ such phenology data. Historic ADS products provide general locational data on recent insect-induced forest type specific disturbances that may help in determining candidate causal agents for MODIS-based disturbance maps, especially when combined with other historic geospatial disturbance data (e.g., wildfire burn scars and drought maps). Historic ADS disturbance detection polygons can show severe and extensive regional forest disturbances, though they also can show polygons with sparsely scattered or infrequent disturbances. Examples will be discussed that use various historic disturbance data to help determine potential causes of MODIS-detected regional forest disturbance anomalies.

Subclassification of School Phobic Disturbances.

ERIC Educational Resources Information Center

Atkinson, Leslie; And Others

The confusion surrounding all aspects of school refusal may rest partly on the misguided assumption that the disturbance represents a single syndrome. Five consistently emerging variables which may help distinguish among school phobic types were abstracted from the literature: extensiveness of disturbance, mode of onset, age, fear source, and…

Influence of electromagnetic pulse on the offspring sex ratio of male BALB/c mice.

PubMed

Li, Jin-Hui; Jiang, Da-Peng; Wang, Ya-Feng; Yan, Jia-Jia; Guo, Qi-Yan; Miao, Xia; Lang, Hai-Yang; Xu, Sheng-Long; Liu, Jun-Ye; Guo, Guo-Zhen

2017-09-01

Public concern is growing about the exposure to electromagnetic fields (EMF) and its effect on male reproductive health. Detrimental effect of EMF exposure on sex hormones, reproductive performance and sex-ratio was reported. The present study was designed to clarify whether paternal exposure to electromagnetic pulse (EMP) affects offspring sex ratio in mice. 50 male BALB/c mice aged 5-6 weeks were exposed to EMP daily for 2 weeks before mated with non-exposed females at 0d, 7d, 14d, 21d and 28d after exposure. Sex hormones including total testosterone, LH, FSH, and GnRH were detected using radioimmunoassay. The sex ratio was examined by PCR and agarose gel electrophoresis. The results of D0, D21 and D28 showed significant increases compared with sham-exposed groups. The serum testosterone increased significantly in D0, D14, D21, and D28 compared with sham-exposed groups (p<0.05). Overall, this study suggested that EMP exposure may lead to the disturbance of reproductive hormone levels and affect the offspring sex ratio. Copyright © 2017. Published by Elsevier B.V.

Anti-Fatigue Effects of the Unique Polysaccharide Marker of Dendrobium officinale on BALB/c Mice.

PubMed

Wei, Wei; Li, Zhi-Peng; Zhu, Tong; Fung, Hau-Yee; Wong, Tin-Long; Wen, Xin; Ma, Dik-Lung; Leung, Chung-Hang; Han, Quan-Bin

2017-01-18

Dendrobium officinale extract shows potent anti-fatigue effects; however, the active substance responsible for these effects remains undetermined. A glucomannan with a huge molecular size of 730 kDa, called DOP, was identified as the unique authentication marker of this expensive herb. DOP exhibited immunomodulating effects on macrophages and lymphocytes in our previous study. Clinical reports also showed that people with fatigue syndrome have a disturbed immune system. Because DOP is the unique and dominant component of D. officinale , we hypothesize that DOP may also have anti-fatigue activity. The present study aims to evaluate the anti-fatigue activity of DOP on BALB/c mice, with Rhodiola rosea extract as a positive control. DOP and Rhodiola rosea extract were orally administered at doses of 50 mg/kg and 100 mg/kg, respectively, for four weeks, and the anti-fatigue activity of DOP on BALB/c mice was evaluated using the weight-loaded swimming test. The contents of lactic dehydrogenase (LDH), creatine phosphokinase (CK), triglyceride (TG), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA), lactic acid (LD), and glutathione peroxidase (GSH-Px) in serum, glycogen of liver and gastrocnemius muscle were also determined. Their effects on variability of T cells and B cells were determined by using tetrazolium compound (MTS) method. The weight-loaded swimming exercise caused fatigue syndrome, mainly including the decreases of serum SOD/GSH-Px and gastrocnemius glycogen, as well as the increases of LDH, BUN, MDA, CK, TG, and LD in serum. All of these indicators of fatigue were inhibited to a certain extent by both DOP and Rhodiola rosea extract; however, the effects of DOP were much stronger than those of Rhodiola rosea extract. Compared to the positive control, mice dosed with DOP showed increases in endurance, body weight, and food intake. Furthermore, DOP-feeding mice significantly increased the cell variability of T lymphocytes and B

Propagation of Disturbances in AC Electricity Grids.

PubMed

Tamrakar, Samyak; Conrath, Michael; Kettemann, Stefan

2018-04-24

The energy transition towards high shares of renewable energy will affect the stability of electricity grids in many ways. Here, we aim to study its impact on propagation of disturbances by solving nonlinear swing equations describing coupled rotating masses of synchronous generators and motors on different grid topologies. We consider a tree, a square grid and as a real grid topology, the german transmission grid. We identify ranges of parameters with different transient dynamics: the disturbance decays exponentially in time, superimposed by oscillations with the fast decay rate of a single node, or with a smaller decay rate without oscillations. Most remarkably, as the grid inertia is lowered, nodes may become correlated, slowing down the propagation from ballistic to diffusive motion, decaying with a power law in time. Applying linear response theory we show that tree grids have a spectral gap leading to exponential relaxation as protected by topology and independent on grid size. Meshed grids are found to have a spectral gap which decreases with increasing grid size, leading to slow power law relaxation and collective diffusive propagation of disturbances. We conclude by discussing consequences if no measures are undertaken to preserve the grid inertia in the energy transition.

The interplay between climate change, forests, and disturbances

Treesearch

Virginia H. Dale; Linda A. Joyce; Steve McNulty; Ronald P. Neilson

2000-01-01

Climate change affects forests both directly and indirectly through disturbances. Disturbances are a natural and integral part of forest ecosystems, and climate change can alter these natural interactions. When disturbances exceed their natural range of variation, the change in forest structure and function may be extreme. Each disturbance affects forests differently....

Harnessing landscape heterogeneity for managing future disturbance risks in forest ecosystems

PubMed Central

Seidl, Rupert; Albrich, Katharina; Thom, Dominik; Rammer, Werner

2018-01-01

In order to prevent irreversible impacts of climate change on the biosphere it is imperative to phase out the use of fossil fuels. Consequently, the provisioning of renewable resources such as timber and biomass from forests is an ecosystem service of increasing importance. However, risk factors such as changing disturbance regimes are challenging the continuous provisioning of ecosystem services, and are thus a key concern in forest management. We here used simulation modeling to study different risk management strategies in the context of timber production under changing climate and disturbance regimes, focusing on a 8127 ha forest landscape in the Northern Front Range of the Alps in Austria. We show that under a continuation of historical management, disturbances from wind and bark beetles increase by +39.5% on average over 200 years in response to future climate change. Promoting mixed forests and climate-adapted tree species as well as increasing management intensity effectively reduced future disturbance risk. Analyzing the spatial patterns of disturbance on the landscape, we found a highly uneven distribution of risk among stands (Gini coefficients up to 0.466), but also a spatially variable effectiveness of silvicultural risk reduction measures. This spatial variability in the contribution to and control of risk can be used to inform disturbance management: Stands which have a high leverage on overall risk and for which risks can effectively be reduced (24.4% of the stands in our simulations) should be a priority for risk mitigation measures. In contrast, management should embrace natural disturbances for their beneficial effects on biodiversity in areas which neither contribute strongly to landscape-scale risk nor respond positively to risk mitigation measures (16.9% of stands). We here illustrate how spatial heterogeneity in forest landscapes can be harnessed to address both positive and negative effects of changing natural disturbance regimes in

Integrating theory into disturbance interaction experiments to better inform ecosystem management.

PubMed

Foster, Claire N; Sato, Chloe F; Lindenmayer, David B; Barton, Philip S

2016-04-01

Managing multiple, interacting disturbances is a key challenge to biodiversity conservation, and one that will only increase as global change drivers continue to alter disturbance regimes. Theoretical studies have highlighted the importance of a mechanistic understanding of stressor interactions for improving the prediction and management of interactive effects. However, many conservation studies are not designed or interpreted in the context of theory and instead focus on case-specific management questions. This is a problem as it means that few studies test the relationships highlighted in theoretical models as being important for ecological management. We explore the extent of this problem among studies of interacting disturbances by reviewing recent experimental studies of the interaction between fire and grazing in terrestrial ecosystems. Interactions between fire and grazing can occur via a number of pathways; one disturbance can modify the other's likelihood, intensity or spatial distribution, or one disturbance can alter the other's impacts on individual organisms. The strength of such interactions will vary depending on disturbance attributes (e.g. size or intensity), and this variation is likely to be nonlinear. We show that few experiments testing fire-grazing interactions are able to identify the mechanistic pathway driving an observed interaction, and most are unable to detect nonlinear effects. We demonstrate how these limitations compromise the ability of experimental studies to effectively inform ecological management. We propose a series of adjustments to the design of disturbance interaction experiments that would enable tests of key theoretical pathways and provide the deeper ecological understanding necessary for effective management. Such considerations are relevant to studies of a broad range of ecological interactions and are critical to informing the management of disturbance regimes in the context of accelerating global change. © 2015 John

Evolution of the BCG in Disturbed Galaxy Clusters

NASA Astrophysics Data System (ADS)

Ardila, Felipe; Strauss, Michael A.; Lauer, Tod R.; Postman, Marc

2017-01-01

The present paradigm in cosmology tells us that large-scale structures grow hierarchically. This suggests that galaxy clusters grow by accreting mass and merging with other clusters, a process which should be detectable by the presence of substructure within a cluster. Using the Dressler-Shectman (DS) three-dimensional test for dynamical substructure, we determined which clusters showed evidence for disturbance from a set of 227 Abell clusters from Lauer et al. (2014) with at least 50 member galaxies and spectroscopic redshifts, z < 0.08. Our results show that 155 (68.2%) of the clusters showed evidence for substructure at ≥ 95% confidence, while 72 did not. Kolmogorov-Smirnov tests suggest that the two populations of clusters (those with and without detected substructure) are significantly different in their distributions of BCG luminosities (Lm), but not in their BCG stellar velocity dispersions (σ), their BCG spatial offsets from the x-ray centers of the clusters, their BCG velocity offsets from the mean cluster velocity, the logarithmic slopes of their BCG photometric curves of growth (α), their cluster velocity dispersions, or their luminosity differences between the BCG and the second-ranked galaxy in the cluster (M2). Similarly, no significant difference was found in the fitting of the Lm-α-σ metric plane for BCGs of clusters with substructure compared those in which there is not substructure. This is surprising since our hierarchical growth models suggest that some of these BCG/cluster properties would be affected by a disturbance of the cluster, indicating that our understanding of how BCGs evolve with their clusters is incomplete and we should explore other ways to probe the level of disturbance.

Long-Term Simulated Microgravity Causes Cardiac RyR2 Phosphorylation and Arrhythmias in Mice

PubMed Central

Respress, Jonathan L.; Gershovich, Pavel M.; Wang, Tiannan; Reynolds, Julia O.; Skapura, Darlene G.; Sutton, Jeffrey P.; Miyake, Christina Y.; Wehrens, Xander H.T.

2014-01-01

Background Long-term exposure to microgravity during space flight may lead to cardiac remodeling and rhythm disturbances. In mice, hindlimb unloading (HU) mimics the effects of microgravity and stimulates physiological adaptations, including cardiovascular deconditioning. Recent studies have demonstrated an important role played by changes in intracellular Ca handling in the pathogenesis of heart failure and arrhythmia. In this study, we tested the hypothesis that cardiac remodeling following HU in mice involves abnormal intracellular Ca regulation through the cardiac ryanodine receptor (RyR2). Methods and Results Mice were subjected to HU by tail suspension for 28 to 56 days in order to induce cardiac remodeling (n=15). Control mice (n=19) were treated equally, with the exception of tail suspension. Echocardiography revealed cardiac enlargement and depressed contractility starting at 28 days post-HU versus control. Moreover, mice were more susceptible to pacing-induced ventricular arrhythmias after HU. Ventricular myocytes isolated from HU mice exhibited an increased frequency of spontaneous sarcoplasmic reticulum (SR) Ca release events and enhanced SR Ca leak via RyR2. Western blotting revealed increased RyR2 phosphorylation at S2814, and increased CaMKII auto-phosphorylation at T287, suggesting that CaMKII activation of RyR2 might underlie enhanced SR Ca release in HU mice. Conclusion These data suggest that abnormal intracellular Ca handling, likely due to increased CaMKII phosphorylation of RyR2, plays a role in cardiac remodeling following simulated microgravity in mice. PMID:25227892

Radio disturbance warning issuance system

NASA Technical Reports Server (NTRS)

Maeda, R.; Inuki, H.

1979-01-01

A radio disturbance warning issuance system was introduced in the Hiraiso Branch of the Radio Research Laboratories in 1972 to reconstruct the current radio disturbance warning service as a social information service. A description of the new ideas which were experimentally systematized by means of an electronic computer is presented.

CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy.

PubMed

Bechtholt-Gompf, Anita J; Smith, Karen L; John, Catherine S; Kang, Hannah H; Carlezon, William A; Cohen, Bruce M; Ongür, Dost

2011-06-01

In patients, ketamine is a fast-acting antidepressant that can induce long-lasting symptom relief. Similar rapid effects have been reported in rodents, but reports of lasting effects are limited. We sought to extend past findings by examining dose-response curves that overlap with the individual doses previously reported to induce lasting effects in rodents and determining whether effects generalize to the tail suspension test (TST) and Balb/cJ mice. Using common tests of antidepressant efficacy we first confirmed our ability to detect the effects of desipramine, a well-characterized antidepressant drug. Next, we sought to determine whether two non-competitive NMDA antagonists, ketamine and MK-801, had long-lasting antidepressant-like effects in CD-1 mice, a strain that has often been used to demonstrate the short-term antidepressant-like effects of ketamine. Finally, we examined the short- and long-term effects of ketamine in a mouse strain that is more sensitive to antidepressant-like effects, Balb/cJ mice. In CD-1 mice, desipramine treatment yielded significant short-term antidepressant-like effects in the TST and the forced swimming test (FST). However, no significant enduring effects of ketamine or MK-801 were observed 1 week later. Short-term effects of ketamine in the TST were observed in Balb/cJ mice, but lasting effects were absent 1 week later. Although the TST and FST have been widely used to detect antidepressant-like effects in mice, they do not appear to be sensitive to long-lasting antidepressant-like effects of ketamine in mice and, therefore, do not model the therapeutic effects of ketamine that have been reported in humans with major depression.

Endothelial Arginine Resynthesis Contributes to the Maintenance of Vasomotor Function in Male Diabetic Mice

PubMed Central

Chennupati, Ramesh; Meens, Merlijn J. P. M. T.; Marion, Vincent; Janssen, Ben J.; Lamers, Wouter H.; De Mey, Jo G. R.; Köhler, S. Eleonore

2014-01-01

Aim Argininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice. Methods and Results Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/− = Ass-KOTie2) were generated by crossing Assfl/fl mice ( = control) with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP) was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively) in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO) were significantly reduced when compared to diabetic control mice. Conclusions Absence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes. PMID:25033204

Influence of free-stream disturbances on boundary-layer transition

NASA Technical Reports Server (NTRS)

Harvey, W. D.

1978-01-01

Considerable experimental evidence exists which shows that free stream disturbances (the ratio of root-mean-square pressure fluctuations to mean values) in conventional wind tunnels increase with increasing Mach number at low supersonic to moderate hypersonic speeds. In addition to local conditions, the free stream disturbance level influences transition behavior on simple test models. Based on this observation, existing noise transition data obtained in the same test facility were correlated for a large number of reference sharp cones and flat plates and are shown to collapse along a single curve. This result is a significant improvement over previous attempts to correlate noise transition data.

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

PubMed Central

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

2017-01-01

Abstract Introduction: 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. Objectives: To determine whether there are marked changes in activity in a rodent model of CIBP and compare this to changes in skin hypersensitivity. Methods: 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. Results: 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. Conclusion: 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. PMID:29392229

Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice.

PubMed

Stroh, Matthew A; Winter, Michelle K; Swerdlow, Russell H; McCarson, Kenneth E; Zhu, Hao

2016-08-01

Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain. Assessment of molecular markers in the cerebellum of CKO mice revealed changes in pathways associated with cellular and mitochondrial iron homeostasis. (59)Fe pulse-feeding experiments revealed cerebellum-specific increased or decreased uptake of iron by 7 and 16 weeks of age, respectively. Additionally, we characterized behavioral changes associated with loss of NCB5OR in the cerebellum and midbrain in the context of dietary iron deprivation-evoked generalized iron deficiency. Locomotor activity was reduced and complex motor task execution was altered in CKO mice treated with an iron deficient diet. A sucrose preference test revealed that the reward response was intact in CKO mice, but that iron deficient diet consumption altered sucrose preference in all mice. Detailed gait analysis revealed locomotor changes in CKO mice associated with dysfunctional proprioception and locomotor activation independent of dietary iron deficiency. Finally, we demonstrate that loss of NCB5OR in the cerebellum and midbrain exacerbated harmaline-induced tremor activity. Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain.

Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice

PubMed Central

Stroh, Matthew A.; Winter, Michelle K.; Swerdlow, Russell H.; McCarson, Kenneth E.; Zhu, Hao

2018-01-01

Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain. Assessment of molecular markers in the cerebellum of CKO mice revealed changes in pathways associated with cellular and mitochondrial iron homeostasis. 59Fe pulse-feeding experiments revealed cerebellum-specific increased or decreased uptake of iron by 7 weeks and 16 weeks of age, respectively. Additionally, we characterized behavioral changes associated with loss of NCB5OR in the cerebellum and midbrain in the context of dietary iron deprivation-evoked generalized iron deficiency. Locomotor activity was reduced and complex motor task execution was altered in CKO mice treated with an iron deficient diet. A sucrose preference test revealed that the reward response was intact in CKO mice, but that iron deficient diet consumption altered sucrose preference in all mice. Detailed gait analysis revealed locomotor changes in CKO mice associated with dysfunctional proprioception and locomotor activation independent of dietary iron deficiency. Finally, we demonstrate that loss of NCB5OR in the cerebellum and midbrain exacerbated harmaline-induced tremor activity. Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain. PMID:27188291

Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice.

PubMed

Lau, Adeline A; Crawley, Allison C; Hopwood, John J; Hemsley, Kim M

2008-08-05

Mucopolysaccharidosis (MPS) IIIA, or Sanfilippo syndrome, is a lysosomal storage disorder characterized by severe and progressive neuropathology. Following an asymptomatic period, patients may present with sleep disturbances, cognitive decline, aggressive tendencies and hyperactivity. A naturally-occurring mouse model of MPS IIIA also exhibits many of these behavioral features and has been recently back-crossed onto a C57BL/6 genetic background. To more thoroughly characterize the behavioral phenotype of congenic MPS IIIA mice, we assessed exploratory activity and unconditioned anxiety-related behavior in the elevated plus maze (EPM) and open field locomotor activity. Although MPS IIIA male mice were less active in the EPM at 18 and 20 weeks of age, they were more likely to explore the open arms than their normal counter-parts suggesting reduced anxiety. Repeated EPM testing reduced exploration of the open arms in MPS IIIA mice. In the open field test, significant reductions in activity were evident in naïve-tested male MPS IIIA mice from 10 weeks of age. Female normal and MPS IIIA mice displayed similar exploratory activity in the open field test. These differences in anxiety and locomotor activity will allow us to evaluate the efficacy of therapeutic regimes for MPS IIIA as a forerunner to developing safe and effective therapies for Sanfilippo patients.

Altered circadian rhythms of the stress hormone and melatonin response in lupus-prone MRL/MP-fas(Ipr) mice.

PubMed

Lechner, O; Dietrich, H; Oliveira dos Santos, A; Wiegers, G J; Schwarz, S; Harbutz, M; Herold, M; Wick, G

2000-06-01

The immune system interacts with the hypothalamo-pituitary-adrenal axis via so-called glucocorticoid increasing factors, which are produced by the immune system during immune reactions, causing an elevation of systemic glucocorticoid levels that contribute to preservation of the immune reactions specificities. Previous results from our laboratory had already shown an altered immuno-neuroendocrine dialogue via the hypothalamo-pituitary-adrenal axis in autoimmune disease-prone chicken and mouse strains. In the present study, we further investigated the altered glucocorticoid response via the hypothalamo-pituitary-adrenal axis in murine lupus. We established the circadian rhythms of corticosterone, dehydroepiandrosterone-sulfate, adrenocorticotropic hormone and melatonin, as well as the time response curves after injection of interleukin-1 of the first three parameters in normal SWISS and lupus-prone MRL/MP-fas(Ipr) mice. The results show that lupus-prone MRL/ MP-fas(Ipr) mice do not react appropriately to changes of the light/dark cycle, circadian melatonin rhythms seem to uncouple from the light/dark cycle, and plasma corticosterone levels are elevated during the resting phase. Diurnal changes of dehydroepiandrosterone-sulfate and adrenocorticotropic hormone were normal compared to healthy controls. These data indicate that MRL/ MP-fas(Ipr) mice not only show an altered glucocorticoid response mediated via the hypothalamo pituitary adrenal axis to IL-1, but are also affected by disturbances of corticosterone and melatonin circadian rhythms. Our findings may have implications for intrathymic T cell development and the emergence of autoimmune disease.

Receptivity of Hypersonic Boundary Layers to Distributed Roughness and Acoustic Disturbances

NASA Technical Reports Server (NTRS)

Balakumar, P.

2013-01-01

Boundary-layer receptivity and stability of Mach 6 flows over smooth and rough seven-degree half-angle sharp-tipped cones are numerically investigated. The receptivity of the boundary layer to slow acoustic disturbances, fast acoustic disturbances, and vortical disturbances is considered. The effects of three-dimensional isolated roughness on the receptivity and stability are also simulated. The results for the smooth cone show that the instability waves are generated in the leading edge region and that the boundary layer is much more receptive to slow acoustic waves than to the fast acoustic waves. Vortical disturbances also generate unstable second modes, however the receptivity coefficients are smaller than that of the slow acoustic wave. Distributed roughness elements located near the nose region decreased the receptivity of the second mode generated by the slow acoustic wave by a small amount. Roughness elements distributed across the continuous spectrum increased the receptivity of the second mode generated by the slow and fast acoustic waves and the vorticity wave. The largest increase occurred for the vorticity wave. Roughness elements distributed across the synchronization point did not change the receptivity of the second modes generated by the acoustic waves. The receptivity of the second mode generated by the vorticity wave increased in this case, but the increase is lower than that occurred with the roughness elements located across the continuous spectrum. The simulations with an isolated roughness element showed that the second mode waves generated by the acoustic disturbances are not influenced by the small roughness element. Due to the interaction, a three-dimensional wave is generated. However, the amplitude is orders of magnitude smaller than the two-dimensional wave.

Integration of sensory force feedback is disturbed in CRPS-related dystonia.

PubMed

Mugge, Winfred; van der Helm, Frans C T; Schouten, Alfred C

2013-01-01

Complex regional pain syndrome (CRPS) is characterized by pain and disturbed blood flow, temperature regulation and motor control. Approximately 25% of cases develop fixed dystonia. The origin of this movement disorder is poorly understood, although recent insights suggest involvement of disturbed force feedback. Assessment of sensorimotor integration may provide insight into the pathophysiology of fixed dystonia. Sensory weighting is the process of integrating and weighting sensory feedback channels in the central nervous system to improve the state estimate. It was hypothesized that patients with CRPS-related dystonia bias sensory weighting of force and position toward position due to the unreliability of force feedback. The current study provides experimental evidence for dysfunctional sensory integration in fixed dystonia, showing that CRPS-patients with fixed dystonia weight force and position feedback differently than controls do. The study shows reduced force feedback weights in CRPS-patients with fixed dystonia, making it the first to demonstrate disturbed integration of force feedback in fixed dystonia, an important step towards understanding the pathophysiology of fixed dystonia.

Experimental demonstration of the importance of competition under disturbance.

PubMed

Violle, Cyrille; Pu, Zhichao; Jiang, Lin

2010-07-20

Ecologists have long recognized the roles of competition and disturbance in shaping ecological communities, and the combinatorial effects of these two factors have been the subject of substantial ecological research. Nevertheless, it is still unclear whether competition remains as an important structuring force in habitats strongly influenced by disturbance. The conventional belief remains that the importance of competition decreases with increasing disturbance, but limited theory suggests otherwise. Using protist communities established in laboratory microcosms, we demonstrate that disturbance does not diminish the importance of competition. Interspecific competition significantly increased rates of species extinction over a broad disturbance gradient, and increasing disturbance intensities increased, rather than decreased, the tempo of competitive exclusion. This community-level pattern is linked to the species-level pattern that interspecific competition led to most frequent extinctions of each species at the highest level of disturbance that the species can tolerate. Consequently, despite a strong tradeoff between competitive ability and disturbance tolerance across the competing species, species diversity generally declined with disturbance. The consistent structuring role of competition throughout the disturbance gradient underscores the need to understand competitive interactions and their consequences even in highly disturbed habitats.

HDAC Inhibitors Restore the Capacity of Aged Mice to Respond to Haloperidol through Modulation of Histone Acetylation

PubMed Central

Montalvo-Ortiz, Janitza L; Keegan, Jack; Gallardo, Christopher; Gerst, Nicolas; Tetsuka, Kazuhiro; Tucker, Chris; Matsumoto, Mitsuyuki; Fang, Deyu; Csernansky, John G; Dong, Hongxin

2014-01-01

Antipsychotic drugs are widely prescribed to elderly patients for the treatment of a variety of psychopathological conditions, including psychosis and the behavioral disturbances associated with dementia. However, clinical experience suggests that these drugs may be less efficacious in the elderly individuals than in the young. Recent studies suggest that aging may be associated with epigenetic changes and that valproic acid (VPA), a histone deacetylase inhibitor, may reverse such changes. However, it is not yet known whether HDAC inhibitors can modulate age-related epigenetic changes that may impact antipsychotic drug action. In this study, we analyzed conditioned avoidance response (CAR) and c-Fos expression patterns to elucidate the effect of HDAC inhibitors VPA and entinostat (MS-275) on behavioral and molecular markers of the effects of haloperidol (HAL) in aged mice. Our results showed that HAL administration failed to suppress the avoidance response during the CAR test, suggesting an age-related decrease in drug efficacy. In addition, HAL-induced c-Fos expression in the nucleus accumbens shell and prefrontal cortex was significantly lower in aged mice as compared with young mice. Pretreatment with VPA and MS-275 significantly improved HAL effects on the CAR test in aged mice. Also, VPA and MS-275 pretreatment restored HAL-induced increases in c-Fos expression in the nucleus accumbens shell and prefrontal cortex of aged mice to levels comparable with those observed in young mice. Lastly, but most importantly, increases in c-Fos expression and HAL efficacy in the CAR test of the HAL+VPA and HAL+MS-275 groups were correlated with elevated histone acetylation at the c-fos promoter region in aged mice. These findings suggest that pretreatment with VPA or MS-275 increases the behavioral and molecular effects of HAL in aged mice and that these effects occur via modulation of age-related histone hypoacetylation in the nucleus accumbens shell and prefrontal cortex

Receptivity of Hypersonic Boundary Layers to Acoustic and Vortical Disturbances

NASA Technical Reports Server (NTRS)

Balakamar, P.; Kegerise, Michael A.

2011-01-01

Boundary layer receptivity to two-dimensional acoustic disturbances at different incidence angles and to vortical disturbances is investigated by solving the Navier-Stokes equations for Mach 6 flow over a 7deg half-angle sharp-tipped wedge and a cone. Higher order spatial and temporal schemes are employed to obtain the solution. The results show that the instability waves are generated in the leading edge region and that the boundary layer is much more receptive to slow acoustic waves as compared to the fast waves. It is found that the receptivity of the boundary layer on the windward side (with respect to the acoustic forcing) decreases when the incidence angle is increased from 0 to 30 degrees. However, the receptivity coefficient for the leeward side is found to vary relatively weakly with the incidence angle. The maximum receptivity is obtained when the wave incident angle is about 20 degrees. Vortical disturbances also generate unstable second modes, however the receptivity coefficients are smaller than that for the acoustic waves. Vortical disturbances first generate the fast acoustic modes and they switch to the slow mode near the continuous spectrum.

Association between Serum Vitamin D Levels and Sleep Disturbance in Hemodialysis Patients.

PubMed

Han, Bin; Zhu, Fu-Xiang; Shi, Chao; Wu, Heng-Lan; Gu, Xiao-Hong

2017-02-14

Sleep disturbance is a frequent and serious complication of hemodialysis (HD). Low serum vitamin D levels have been associated with sleep quality in non-HD subjects. Our aim was to examine the possible association between serum vitamin D levels and the presence of sleep disturbance in HD patients. We recruited 141 HD patients at the HD center of the First Affiliated Hospital of Jiaxing University during 2014-2015. Serum levels of 25-hydroxyvitamin D (25(OH)D) were determined by the competitive protein-binding assay. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Demographic, clinical and laboratory data were recorded. Meanwhile, 117 healthy control subjects were also recruited and underwent measurement of 25(OH)D. Eighty-eight patients (62.4%) had sleep disturbance (PSQI scores ≥ 5). Patients with sleep disturbance showed lower levels of 25(OH)D as compared to those without sleep disturbance (85.6 ± 37.4 vs. 39.1 ± 29.1 nmol/L, p < 0.001). In multivariate analyses, serum levels of 25(OH)D (≤48.0 nmol/L) were independently associated with sleep disturbance in HD patients (OR 9.897, 95% CI 3.356-29.187, p < 0.001) after adjustment for possible variables. Our study demonstrates that low serum levels of vitamin D are independently associated with sleep disturbance in HD patients, but the finding needs to be confirmed in future experimental and clinical studies.

Species-specific transpiration responses to intermediate disturbance in a northern hardwood forest

NASA Astrophysics Data System (ADS)

Matheny, Ashley M.; Bohrer, Gil; Vogel, Christoph S.; Morin, Timothy H.; He, Lingli; Frasson, Renato Prata de Moraes; Mirfenderesgi, Golnazalsadat; Schäfer, Karina V. R.; Gough, Christopher M.; Ivanov, Valeriy Y.; Curtis, Peter S.

2014-12-01

Intermediate disturbances shape forest structure and composition, which may in turn alter carbon, nitrogen, and water cycling. We used a large-scale experiment in a forest in northern lower Michigan where we prescribed an intermediate disturbance by stem girdling all canopy-dominant early successional trees to simulate an accelerated age-related senescence associated with natural succession. Using 3 years of eddy covariance and sap flux measurements in the disturbed area and an adjacent control plot, we analyzed disturbance-induced changes to plot level and species-specific transpiration and stomatal conductance. We found transpiration to be 15% lower in disturbed plots than in unmanipulated control plots. However, species-specific responses to changes in microclimate varied. While red oak and white pine showed increases in stomatal conductance during postdisturbance (62.5 and 132.2%, respectively), red maple reduced stomatal conductance by 36.8%. We used the hysteresis between sap flux and vapor pressure deficit to quantify diurnal hydraulic stress incurred by each species in both plots. Red oak, a ring porous anisohydric species, demonstrated the largest mean relative hysteresis, while red maple, bigtooth aspen, and paper birch, all diffuse porous species, had the lowest relative hysteresis. We employed the Penman-Monteith model for LE to demonstrate that these species-specific responses to disturbance are not well captured using current modeling strategies and that accounting for changes to leaf area index and plot microclimate are insufficient to fully describe the effects of disturbance on transpiration.

Managing military training-related environmental disturbance.

PubMed

Zentelis, Rick; Banks, Sam; Roberts, J Dale; Dovers, Stephen; Lindenmayer, David

2017-12-15

Military Training Areas (MTAs) cover at least 2 percent of the Earth's terrestrial surface and occur in all major biomes. These areas are potentially important for biodiversity conservation. The greatest challenge in managing MTAs is balancing the disturbance associated with military training and environmental values. These challenges are unique as no other land use is managed for these types of anthropogenic disturbances in a natural setting. We investigated how military training-related disturbance is best managed on MTAs. Specifically, we explored management options to maximise the amount of military training that can be undertaken on a MTA while minimising the amount of environmental disturbance. MTAs comprise of a number of ranges designed to facilitate different types of military training. We simulated military training-related environmental disturbance at different range usage rates under a typical range rotation use strategy, and compared the results to estimated ecosystem recovery rates from training activities. We found that even at relatively low simulated usage rates, random allocation and random spatial use of training ranges within an MTA resulted in environmental degradation under realistic ecological recovery rates. To avoid large scale environmental degradation, we developed a decision-making tool that details the best method for managing training-related disturbance by determining how training activities can be allocated to training ranges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rapid disturbances in Arctic permafrost regions (Invited)

NASA Astrophysics Data System (ADS)

Grosse, G.; Romanovsky, V. E.; Arp, C. D.; Jones, B. M.

2013-12-01

Permafrost thaw is often perceived as a slow process dominated by press disturbances such as gradual active layer thickening. However, various pulse disturbances such as thermokarst formation can substantially increase the rate of permafrost thaw and result in rapid landscape change on sub-decadal to decadal time scales. Other disturbances associated with permafrost thaw are even more dynamic and unfold on sub-annual timescales, such as catastrophic thermokarst lake drainage. The diversity of processes results in complex feedbacks with soil carbon pools, biogeochemical cycles, hydrology, and flora and fauna, and requires a differentiated approach when quantifying how these ecosystem componentsare affected,how vulnerablethey are to rapid change, and what regional to global scale impacts result. Here we show quantitative measurements for three examples of rapid pulse disturbances in permafrost regions as observed with remote sensing data time series: The formation of a mega thaw slump (>50 ha) in syngenetic permafrost in Siberia, the formation of new thermokarst ponds in ice-rich permafrost regions in Alaska and Siberia, and the drainage of thermokarst lakes along a gradient of permafrost extent in Western Alaska. The surprising setting and unabated growth of the mega thaw slump during the last 40 years indicates that limited information on panarctic ground ice distribution, abundance, and vulnerability remains a key gap for reliable projections of thermokarst and thermo-erosion impacts, and that the natural limits on the growth and size of thaw slumps are still poorly understood. Observed thermokarst pond formation and expansion in our study regions was closely tied to ice-rich permafrost terrain, such as syngenetic Yedoma uplands, but was also found in old drained thermokarst lake basins with epigenetic permafrost and shallow drained thermokarst lake basins whose ground ice had not been depleted by the prior lake phase. The very different substrates in which new

Disturbed soil characterization workshop: post-meeting summary

NASA Astrophysics Data System (ADS)

Cathcart, J. Michael

2010-04-01

Disturbance of ground surfaces can arise from a variety of processes, both manmade and natural. Burying landmines, vehicle movement, and walking are representative examples of processes that disturb ground surfaces. The nature of the specific disturbance process can lead to the observables that can aid the detection and identification of that process. While much research has been conducted in this area, fundamental questions related to the remote detection and characterization of disturbed soil surfaces remain unanswered. Under the sponsorship of the Army Research Office (ARO), the Night Vision and Electronic Sensors Directorate (NVESD), and the U.S. Army Corps of Engineers (USACE) Engineering Research and Development Center (ERDC), Georgia Tech hosted a workshop to address Remote Sensing Methods for Disturbed Soil Characterization. The workshop was held January 15-17, 2008 in Atlanta. The primary objective of this workshop was to take a new look at the disturbed soil problem in general as well as its relation to buried explosive detection and other manmade disturbances. In particular, the participants sought to outline the basic science and technology questions that need to be addressed across the full spectrum of military applications to fully exploit this phenomenon. This presentation will outline the approach taken during the workshop and provide a summary of the conclusions.

Anti-disturbance rapid vibration suppression of the flexible aerial refueling hose

NASA Astrophysics Data System (ADS)

Su, Zikang; Wang, Honglun; Li, Na

2018-05-01

As an extremely dangerous phenomenon in autonomous aerial refueling (AAR), the flexible refueling hose vibration caused by the receiver aircraft's excessive closure speed should be suppressed once it appears. This paper proposed a permanent magnet synchronous motor (PMSM) based refueling hose servo take-up system for the vibration suppression of the flexible refueling hose. A rapid back-stepping based anti-disturbance nonsingular fast terminal sliding mode (NFTSM) control scheme with a specially established finite-time convergence NFTSM observer is proposed for the PMSM based hose servo take-up system under uncertainties and disturbances. The unmeasured load torque and other disturbances in the PMSM system are reconstituted by the NFTSM observer and to be compensated during the controller design. Then, with the back-stepping technique, a rapid anti-disturbance NFTSM controller is proposed for the PMSM angular tracking to improve the tracking error convergence speed and tracking precision. The proposed vibration suppression scheme is then applied to PMSM based hose servo take-up system for the refueling hose vibration suppression in AAR. Simulation results show the proposed scheme can suppress the hose vibration rapidly and accurately even the system is exposed to strong uncertainties and probe position disturbances, it is more competitive in tracking accuracy, tracking error convergence speed and robustness.

Integrating multiple disturbance aspects: management of an invasive thistle, Carduus nutans.

PubMed

Zhang, Rui; Shea, Katriona

2012-11-01

Disturbances occur in most ecological systems, and play an important role in biological invasions. We delimit five key disturbance aspects: intensity, frequency, timing, duration and extent. Few studies address more than one of these aspects, yet interactions and interdependence between aspects may lead to complex outcomes. In a two-cohort experimental study, we examined how multiple aspects (intensity, frequency and timing) of a mowing disturbance regime affect the survival, phenology, growth and reproduction of an invasive thistle Carduus nutans (musk thistle). Our results show that high intensity and late timing strongly delay flowering phenology and reduce plant survival, capitulum production and plant height. A significant interaction between intensity and timing further magnifies the main effects. Unexpectedly, high frequency alone did not effectively reduce reproduction. However, a study examining only frequency and intensity, and not timing, would have erroneously attributed the importance of timing to frequency. We used management of an invasive species as an example to demonstrate the importance of a multiple-aspect disturbance framework. Failure to consider possible interactions, and the inherent interdependence of certain aspects, could result in misinterpretation and inappropriate management efforts. This framework can be broadly applied to improve our understanding of disturbance effects on individual responses, population dynamics and community composition.

Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice.

PubMed

Landgraf, Dominic; Long, Jaimie E; Proulx, Christophe D; Barandas, Rita; Malinow, Roberto; Welsh, David K

2016-12-01

Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice

PubMed Central

Landgraf, Dominic; Long, Jaimie E.; Proulx, Christophe D.; Barandas, Rita; Malinow, Roberto; Welsh, David K.

2016-01-01

Background Major depressive disorder is associated with disturbed circadian rhythms. To investigate the causal relationship between mood disorders and circadian clock disruption, previous studies in animal models have employed light/dark manipulations, global mutations of clock genes, or brain area lesions. However, light can impact mood by noncircadian mechanisms; clock genes have pleiotropic, clock-independent functions; and brain lesions not only disrupt cellular circadian rhythms but also destroy cells and eliminate important neuronal connections, including light reception pathways. Thus, a definitive causal role for functioning circadian clocks in mood regulation has not been established. Methods We stereotactically injected viral vectors encoding short hairpin RNA to knock down expression of the essential clock gene Bmal1 into the brain's master circadian pacemaker, the suprachiasmatic nucleus (SCN). Results In these SCN-specific Bmal1-knockdown (SCN-Bmal1-KD) mice, circadian rhythms were greatly attenuated in the SCN, while the mice were maintained in a standard light/dark cycle, SCN neurons remained intact, and neuronal connections were undisturbed, including photic inputs. In the learned helplessness paradigm, the SCN-Bmal1-KD mice were slower to escape, even before exposure to inescapable stress. They also spent more time immobile in the tail suspension test and less time in the lighted section of a light/dark box. The SCN-Bmal1-KD mice also showed greater weight gain, an abnormal circadian pattern of corticosterone, and an attenuated increase of corticosterone in response to stress. Conclusions Disrupting SCN circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression. PMID:27113500

Mouse Cytomegalovirus Infection in BALB/c Mice Resembles Virus-Associated Secondary Hemophagocytic Lymphohistiocytosis and Shows a Pathogenesis Distinct from Primary Hemophagocytic Lymphohistiocytosis.

PubMed

Brisse, Ellen; Imbrechts, Maya; Put, Karen; Avau, Anneleen; Mitera, Tania; Berghmans, Nele; Rutgeerts, Omer; Waer, Mark; Ninivaggi, Marisa; Kelchtermans, Hilde; Boon, Louis; Snoeck, Robert; Wouters, Carine H; Andrei, Graciela; Matthys, Patrick

2016-04-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immunological disorder that is characterized by systemic inflammation, widespread organ damage, and hypercytokinemia. Primary HLH is caused by mutations in granule-mediated cytotoxicity, whereas secondary HLH occurs, without a known genetic background, in a context of infections, malignancies, or autoimmune and autoinflammatory disorders. Clinical manifestations of both HLH subtypes are often precipitated by a viral infection, predominantly with Herpesviridae. Exploiting this knowledge, we established an animal model of virus-associated secondary HLH by infecting immunocompetent wild-type mice with the β-herpesvirus murine CMV. C57BL/6 mice developed a mild inflammatory phenotype, whereas BALB/c mice displayed the clinicopathologic features of HLH, as set forth in the Histiocyte Society diagnostic guidelines: fever, cytopenia, hemophagocytosis, hyperferritinemia, and elevated serum levels of soluble CD25. BALB/c mice also developed lymphadenopathy, liver dysfunction, and decreased NK cell numbers. Lymphoid and myeloid cells were in a hyperactivated state. Nonetheless, depletion of CD8(+) T cells could not inhibit or cure the HLH-like syndrome, highlighting a first dissimilarity from mouse models of primary HLH. Immune cell hyperactivation in BALB/c mice was accompanied by a cytokine storm. Notably, plasma levels of IFN-γ, a key pathogenic cytokine in models of primary HLH, were the highest. Nevertheless, murine CMV-infected IFN-γ-deficient mice still developed the aforementioned HLH-like symptoms. In fact, IFN-γ-deficient mice displayed a more complete spectrum of HLH, including splenomegaly, coagulopathy, and decreased NK cell cytotoxicity, indicating a regulatory role for IFN-γ in the pathogenesis of virus-associated secondary HLH as opposed to its central pathogenic role in primary HLH. Copyright © 2016 by The American Association of Immunologists, Inc.

Effects of spatial disturbance on common loon nest site selection and territory success

USGS Publications Warehouse

McCarthy, Kyle P.; DeStefano, Stephen

2011-01-01

The common loon (Gavia immer) breeds during the summer on northern lakes and water bodies that are also often desirable areas for aquatic recreation and human habitation. In northern New England, we assessed how the spatial nature of disturbance affects common loon nest site selection and territory success. We found through classification and regression analysis that distance to and density of disturbance factors can be used to classify observed nest site locations versus random points, suggesting that these factors affect loon nest site selection (model 1: Correct classification = 75%, null = 50%, K = 0.507, P < 0.001; model 2: Correct classification = 78%, null = 50%, K = 0.551, P < 0.001). However, in an exploratory analysis, we were unable to show a relation between spatial disturbance variables and breeding success (P = 0.595, R2 = 0.436), possibly because breeding success was so low during the breeding seasons of 2007–2008. We suggest that by selecting nest site locations that avoid disturbance factors, loons thereby limit the effect that disturbance will have on their breeding success. Still, disturbance may force loons to use sub-optimal nesting habitat, limiting the available number of territories, and overall productivity. We advise that management efforts focus on limiting disturbance factors to allow breeding pairs access to the best nesting territories, relieving disturbance pressures that may force sub-optimal nest placement.

Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice.

PubMed

Anisimov, V N; Khavinson, V Kh; Alimova, I N; Semchenko, A V; Yashin, A I

2002-08-01

Female transgenic FVB/N mice carrying the breast cancer gene HER-2/neu received epithalon (Ala-Glu-Asp-Gly) in a dose of 1 mg subcutaneously 5 times a week to from the 2nd month of life to death. Epithalon prolonged the average and maximum lifetimes of mice by 13.5 (p<0.05) and 13.9%, respectively. The peptide prolonged the average lifetime of animals without neoplasms (by 34.2%, p<0.05). Epithalon decelerated the development of age-related disturbances in reproductive activity and suppressed the formation of neoplasms. The peptide decreased the incidence of breast adenocarcinomas, lungs metastases (by 1.6 times, p<0.05), and multiple tumors (by 2 times). Epithalon 3.7-fold increased the number of mice without breast tumors (p<0.05), while the number of animals with 6 or more breast tumors decreased by 3 times (p<0.05). Epithalon prolonged the lifetime of mice with breast tumors by 1.4 times (p<0.05). These results indicate that Epithalon possesses geroprotective activity and inhibits breast carcinogenesis in transgenic mice, which is probably related to suppression of HER-2/neu expression.

Mice Lacking EGR1 Have Impaired Clock Gene (BMAL1) Oscillation, Locomotor Activity, and Body Temperature.

PubMed

Riedel, Casper Schwartz; Georg, Birgitte; Jørgensen, Henrik L; Hannibal, Jens; Fahrenkrug, Jan

2018-01-01

Early growth response transcription factor 1 (EGR1) is expressed in the suprachiasmatic nucleus (SCN) after light stimulation. We used EGR1-deficient mice to address the role of EGR1 in the clock function and light-induced resetting of the clock. The diurnal rhythms of expression of the clock genes BMAL1 and PER1 in the SCN were evaluated by semi-quantitative in situ hybridization. We found no difference in the expression of PER1 mRNA between wildtype and EGR1-deficient mice; however, the daily rhythm of BMAL1 mRNA was completely abolished in the EGR1-deficient mice. In addition, we evaluated the circadian running wheel activity, telemetric locomotor activity, and core body temperature of the mice. Loss of EGR1 neither altered light-induced phase shifts at subjective night nor affected negative masking. Overall, circadian light entrainment was found in EGR1-deficient mice but they displayed a reduced locomotor activity and an altered temperature regulation compared to wild type mice. When placed in running wheels, a subpopulation of EGR1-deficient mice displayed a more disrupted activity rhythm with no measurable endogenous period length (tau). In conclusion, the present study provides the first evidence that the circadian clock in the SCN is disturbed in mice deficient of EGR1.

Hydrological disturbance diminishes predator control in wetlands.

PubMed

Dorn, Nathan J; Cook, Mark I

2015-11-01

Effects of predators on prey populations can be especially strong in aquatic ecosystems, but disturbances may mediate the strength of predator limitation and even allow outbreaks of some prey populations. In a two-year study we investigated the numerical responses of crayfish (Procambarus fallax) and small fishes (Poeciliidae and Fundulidae) to a brief hydrological disturbance in replicated freshwater wetlands with an experimental drying and large predatory fish reduction. The experiment and an in situ predation assay tested the component of the consumer stress model positing that disturbances release prey from predator limitation. In the disturbed wetlands, abundances of large predatory fish were seasonally reduced, similar to dynamics in the Everglades (southern Florida). Densities of small fish were unaffected by the disturbance, but crayfish densities, which were similar across all wetlands before drying, increased almost threefold in the year after the disturbance. Upon re-flooding, juvenile crayfish survival was inversely related to the abundance of large fish across wetlands, but we found no evidence for enhanced algal food quality. At a larger landscape scale (500 km2 of the Everglades), crayfish densities over eight years were positively correlated with the severity of local dry disturbances (up to 99 days dry) during the preceding dry season. In contrast, densities of small-bodied fishes in the same wetlands were seasonally depressed by dry disturbances. The results from our experimental wetland drought and the observations of crayfish densities in the Everglades represent a large-scale example of prey population release following a hydrological disturbance in a freshwater ecosystem. The conditions producing crayfish pulses in the Everglades appear consistent with the mechanics of the consumer stress model, and we suggest crayfish pulses may influence the number of nesting wading birds in the Everglades.

Disturbance observer based model predictive control for accurate atmospheric entry of spacecraft

NASA Astrophysics Data System (ADS)

Wu, Chao; Yang, Jun; Li, Shihua; Li, Qi; Guo, Lei

2018-05-01

Facing the complex aerodynamic environment of Mars atmosphere, a composite atmospheric entry trajectory tracking strategy is investigated in this paper. External disturbances, initial states uncertainties and aerodynamic parameters uncertainties are the main problems. The composite strategy is designed to solve these problems and improve the accuracy of Mars atmospheric entry. This strategy includes a model predictive control for optimized trajectory tracking performance, as well as a disturbance observer based feedforward compensation for external disturbances and uncertainties attenuation. 500-run Monte Carlo simulations show that the proposed composite control scheme achieves more precise Mars atmospheric entry (3.8 km parachute deployment point distribution error) than the baseline control scheme (8.4 km) and integral control scheme (5.8 km).

Association between wetland disturbance and biological attributes in floodplain wetlands

USGS Publications Warehouse

Chipps, S.R.; Hubbard, D.E.; Werlin, K.B.; Haugerud, N.J.; Powell, K.A.; Thompson, John; Johnson, T.

2006-01-01

We quantified the influence of agricultural activities on environmental and biological conditions of floodplain wetlands in the upper Missouri River basin. Seasonally-flooded wetlands were characterized as low impact (non-disturbed) or high impact (disturbed) based on local land use. Biological data collected from these wetlands were used to develop a wetland condition index (WCI). Fourteen additional wetlands were sampled to evaluate the general condition of seasonally-flooded floodplain wetlands. Structural and functional attributes of macrophyte, algae, and macroinvertebrate communities were tested as candidate metrics for assessing biotic responses. The WCI we developed used six biological metrics to discriminate between disturbed and non-disturbed wetlands: 1) biomass of Culicidae larvae, 2) abundance of Chironomidae larvae, 3) macroinvertebrate diversity, 4) total number of plant species, 5) the proportion of exotic plant species, and 6) total number of sensitive diatom species. Disturbed wetlands had less taxa richness and species diversity and more exotic and nuisance (e.g., mosquitoes) species. Environmental differences between low and high impact wetlands included measures of total potassium, total phosphorus, total nitrogen, alkalinity, conductance, and sediment phosphorus concentration. Canonical analyses showed that WCI scores were weakly correlated (P = 0.057) with environmental variables in randomly selected wetlands. In addition, mean WCI score for random wetlands was higher than that for high impact wetlands, implying that floodplain wetlands were less impacted by the types of agricultural activities affecting high impact sites. Inter-year sampling of some wetlands revealed that WCI metrics were correlated in 2000 and 2001, implying that biological metrics provided useful indicators of disturbance in floodplain wetlands. ?? 2006, The Society of Wetland Scientists.

Ionospheric disturbances under low solar activity conditions

NASA Astrophysics Data System (ADS)

Buresova, D.; Lastovicka, J.; Hejda, P.; Bochnicek, J.

2014-07-01

The paper is focused on ionospheric response to occasional magnetic disturbances above selected ionospheric stations located at middle latitudes of the Northern and Southern Hemisphere under extremely low solar activity conditions of 2007-2009. We analyzed changes in the F2 layer critical frequency foF2 and the F2 layer peak height hmF2 against 27-days running mean obtained for different longitudinal sectors of both hemispheres for the initial, main and recovery phases of selected magnetic disturbances. Our analysis showed that the effects on the middle latitude ionosphere of weak-to-moderate CIR-related magnetic storms, which mostly occur around solar minimum period, could be comparable with the effects of strong magnetic storms. In general, both positive and negative deviations of foF2 and hmF2 have been observed independent on season and location. However positive effects on foF2 prevailed and were more significant. Observations of stormy ionosphere also showed large departures from the climatology within storm recovery phase, which are comparable with those usually observed during the storm main phase. The IRI STORM model gave no reliable corrections of foF2 for analyzed events.

Midwinter Disturbances in the Middle Atmosphere

NASA Technical Reports Server (NTRS)

Labitzke, K.

1984-01-01

The Middle Atmosphere is coupled to the troposphere during winter because planetary scale waves can propagate upwards if the prevailing winds are from the west. It is during this time of the year that the well-known midwinter disturbances are observed which ultimately affect the whole of the Middle Atmosphere. The mechanism of these disturbances is not completely understood. The large-scale circulation features up to the upper mesosphere are investigated to demonstrate the synoptic-scale behavior of the midwinter disturbances. Ground-based and satellite observations are combined. The interannual variability of the disturbances is discussed briefly. It is shown that the QBO (Quasi Biennial Oscillation) of the equatorial stratosphere appears to modulate the planetary waves during the northern winters, in the troposphere as well as in the Middle Atmosphere.

AmeriFlux US-UMd UMBS Disturbance

DOE Data Explorer

Curtis, Peter [Ohio State University; Gough, Christopher [Virginia Commonwealth University

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-UMd UMBS Disturbance. Site Description - The UMBS Disturbance site is an artificial disturbance site that has recently been created as part of the Forest Accelerate Succession ExperimenT (FASET). In Spring 2008, every aspen and birch tree (>6,700, ~35% canopy LAI), the dominant early successional trees, were girdled over 39 ha of the FASET treatment plot to stimulate a disturbance that will move the forest into a later successional stage, dominated by maples, oaks, and white pine. This treatment caused aspen and birch mortality within 2 - 3 years. As a result of the changed canopy structure, there is a divergence in net ecosystem exchange between the control plot (enhanced carbon uptake) and the treatment plot (reduced carbon uptake).

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

PubMed

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.

Meta-Analysis of the Effects of Xingnaojing Injection on Consciousness Disturbance

PubMed Central

Wu, Lijun; Zhang, Hua; Xing, Yanwei; Gao, Yonghong; Li, Yanda; Ren, Xiaomeng; Li, Jie; Nie, Bo; Zhu, Lingqun; Shang, Hongcai; Gao, Ying

2016-01-01

Abstract Xingnaojing (XNJ) is commonly extracted from Angongniuhuang, a classic Chinese emergency prescription, and widely used in the treatment of nervous system disorders including consciousness disturbance in China. To evaluate the beneficial and adverse effects of XNJ injection, on consciousness disturbance. Seven major electronic databases were searched to retrieve randomized controlled trials designed to evaluate the clinical efficacy of XNJ alone or combined with Western medicine in treating consciousness disturbance caused by conditions such as high fever, poisoning, and stroke. The methodological quality of the included studies was assessed using criteria from the Cochrane Handbook for Systematic Review of Interventions, and analyzed using the RevMan 5.3.0 software. Seventeen randomized controlled trials on XNJ were included in this study and the trials generally showed low methodological quality. The results revealed that XNJ alone or in combination with other medicines and adjuvant methods had a positive effect on patients with fever-, poisoning-, and stroke-induced coma. XNJ effectively treated consciousness disturbances that were caused by high fever, poisoning, or stroke. PMID:26886655

Mice acquire flavor preferences during shipping.

PubMed

Tordoff, Michael G; Alarcón, Laura K; Byerly, Erica A; Doman, Samantha A

2005-11-15

Vigorous motion can cause rodents to develop flavor aversions and show other signs of malaise. We tested whether a flavor aversion could be induced by shipping mice from an animal breeder to a test site. Boxes of 12 male C57BL/6J mice were shipped approximately 950 km from Bar Harbor, ME to Philadelphia, PA by truck. For some boxes, the gel provided for hydration was flavored with almond and for others it was flavored with banana. After the journey, the mice were individually housed and allowed to recover for 5 days. They then received a choice between the two flavors of gel. Contrary to expectations, mice preferred the flavor they had previously ingested during shipping. Controls given flavored gel under similar conditions but while stationary did not show a preference. These results suggest that mice find shipping or its sequelae pleasurable. If mice are travel sick this must be inconsequential relative to other components of the shipping experience.

Norepinephrine in the Medial Pre-frontal Cortex Supports Accumbens Shell Responses to a Novel Palatable Food in Food-Restricted Mice Only

PubMed Central

Latagliata, Emanuele Claudio; Puglisi-Allegra, Stefano; Ventura, Rossella; Cabib, Simona

2018-01-01

Previous findings from this laboratory demonstrate: (1) that different classes of addictive drugs require intact norepinephrine (NE) transmission in the medial pre Frontal Cortex (mpFC) to promote conditioned place preference and to increase dopamine (DA) tone in the nucleus accumbens shell (NAc Shell); (2) that only food-restricted mice require intact NE transmission in the mpFC to develop conditioned preference for a context associated with milk chocolate; and (3) that food-restricted mice show a significantly larger increase of mpFC NE outflow then free fed mice when experiencing the palatable food for the first time. In the present study we tested the hypothesis that only the high levels of frontal cortical NE elicited by the natural reward in food restricted mice stimulate mesoaccumbens DA transmission. To this aim we investigated the ability of a first experience with milk chocolate to increase DA outflow in the accumbens Shell and c-fos expression in striatal and limbic areas of food–restricted and ad-libitum fed mice. Moreover, we tested the effects of a selective depletion of frontal cortical NE on both responses in either feeding group. Only in food-restricted mice milk chocolate induced an increase of DA outflow beyond baseline in the accumbens Shell and a c-fos expression larger than that promoted by a novel inedible object in the nucleus accumbens. Moreover, depletion of frontal cortical NE selectively prevented both the increase of DA outflow and the large expression of c-fos promoted by milk chocolate in the NAc Shell of food-restricted mice. These findings support the conclusion that in food-restricted mice a novel palatable food activates the motivational circuit engaged by addictive drugs and support the development of noradrenergic pharmacology of motivational disturbances. PMID:29434542

Spatio-temporal assessment of ecological disturbance and its intensity in the Mangrove forest using MODIS derived disturbance index

NASA Astrophysics Data System (ADS)

Dutta, D.; Das, P. K.; Paul, S.; Sharma, J. R.; Dadhwal, V. K.

2014-11-01

The mangrove ecosystem of Sundarbans region plays an important ecological and socio-economical role in both India and Bangladesh. The ecological disturbance in the coastal mangrove forests are mainly attributed to the periodic cyclones caused by deep depression formed over the Bay of Bengal. In the present study, three of the major cyclones in the Sundarbans region were analyzed to establish the cause-and-effect relationship between cyclones and the resultant ecological disturbance. The Moderate Resolution Imaging Spectroradiometer (MODIS) time-series data was used to generate MODIS global disturbance index (MGDI) and its potential was explored to assess the instantaneous ecological disturbance caused by cyclones with varying landfall intensities and at different stages of mangrove phenology. The time-series MGDI was converted into the percentage change in MGDI using its multi-year mean for each pixel, and its response towards several cyclonic events was studied. The affected areas were identified by analyzing the Landsat-8 satellite data before and after the cyclone and the MGDI values of the affected areas were utilized to develop the threshold for delineation of the disturbed pixels. The selected threshold was applied on the time-series MGDI images to delineate the disturbed areas for each year individually to identify the frequently disturbed areas. The classified intensity map could able to detect the chronically affected areas, which can serve as a valuable input towards modelling the biomigration of the invasive species and efficient forest management.

Small mammals as indicators of short-term and long-term disturbance in mixed prairie

USGS Publications Warehouse

Leis, S.A.; Leslie, David M.; Engle, David M.; Fehmi, J.S.

2008-01-01

Disturbance by military maneuvers over short and long time scales may have differential effects on grassland communities. We assessed small mammals as indicators of disturbance by military maneuvers in a mixed prairie in southern Oklahoma USA. We examined sites on two soil series, Foard and Lawton, across a gradient of disturbance intensity. A MANOVA showed that abundance of small mammals was associated (p = 0.03) with short-term (cover of vehicle tracks) disturbance but was not associated (p = 0.12) with long-term (loss of soil organic carbon, SOC) disturbance intensity. At the individual species level, Sigmodon hispidus (cotton rat) and Peromyscus maniculatus (deer mouse) occurred across all levels of disturbance and in both soil types. Only P. maniculatus abundance changed (p < 0.01) with short-term disturbance and increased by about one individual per 5% of additional track-cover. Abundance of P. maniculatus also increased (p = 0.04) by about three individuals per 1% increase in soil carbon. Chaetodipus hispidus (hispid pocket mouse) and Reithrodontomys fulvescens (fulvous harvest mouse) only occurred in single soil types limiting their potential as more general indicators. Abundance of P. maniculatus was positively related to shifts in plant species composition and likely reflected changes in vegetation structure (i.e. litter depth) and forage availability resulting from disturbance. Peromyscus maniculatus may be a useful biological indicator of ecosystem change because it responded predictably to both long-term and short-term disturbance and, when coupled with soil, plant, and disturbance history variables, can reveal land condition trends. ?? Springer Science+Business Media B.V. 2007.

Reduced alcohol consumption in mice lacking preprodynorphin.

PubMed Central

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

2007-01-01

Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the κ-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower 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 hours) 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 thath this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability). PMID:17307643

Reduced alcohol consumption in mice lacking preprodynorphin.

PubMed

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).

Production of Mice Deficient in Genes for Interleukin (IL)-1α, IL-1β, IL-1α/β, and IL-1 Receptor Antagonist Shows that IL-1β Is Crucial in Turpentine-induced Fever Development and Glucocorticoid Secretion

PubMed Central

Horai, Reiko; Asano, Masahide; Sudo, Katsuko; Kanuka, Hirotaka; Suzuki, Masatoshi; Nishihara, Masugi; Takahashi, Michio; Iwakura, Yoichiro

1998-01-01

Interleukin (IL)-1 is a major mediator of inflammation and exerts pleiotropic effects on the neuro-immuno-endocrine system. To elucidate pathophysiological roles of IL-1, we have first produced IL-1α/β doubly deficient (KO) mice together with mice deficient in either the IL-1α, IL-1β, or IL-1 receptor antagonist (IL-1ra) genes. These mice were born healthy, and their growth was normal except for IL-1ra KO mice, which showed growth retardation after weaning. Fever development upon injection with turpentine was suppressed in IL-1β as well as IL-1α/β KO mice, but not in IL-1α KO mice, whereas IL-1ra KO mice showed an elevated response. At this time, expression of IL-1β mRNA in the diencephalon decreased 1.5-fold in IL-1α KO mice, whereas expression of IL-1α mRNA decreased >30-fold in IL-1β KO mice, suggesting mutual induction between IL-1α and IL-1β. This mutual induction was also suggested in peritoneal macrophages stimulated with lipopolysaccharide in vitro. In IL-1β KO mice treated with turpentine, the induction of cyclooxygenase-2 (EC 1.14.99.1) in the diencephalon was suppressed, whereas it was enhanced in IL-1ra KO mice. We also found that glucocorticoid induction 8 h after turpentine treatment was suppressed in IL-1β but not IL-1α KO mice. These observations suggest that IL-1β but not IL-1α is crucial in febrile and neuro-immuno-endocrine responses, and that this is because IL-1α expression in the brain is dependent on IL-1β. The importance of IL-1ra both in normal physiology and under stress is also suggested. PMID:9565638

Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion.

PubMed

Horai, R; Asano, M; Sudo, K; Kanuka, H; Suzuki, M; Nishihara, M; Takahashi, M; Iwakura, Y

1998-05-04

Interleukin (IL)-1 is a major mediator of inflammation and exerts pleiotropic effects on the neuro-immuno-endocrine system. To elucidate pathophysiological roles of IL-1, we have first produced IL-1alpha/beta doubly deficient (KO) mice together with mice deficient in either the IL-1alpha, IL-1beta, or IL-1 receptor antagonist (IL-1ra) genes. These mice were born healthy, and their growth was normal except for IL-1ra KO mice, which showed growth retardation after weaning. Fever development upon injection with turpentine was suppressed in IL-1beta as well as IL-1alpha/beta KO mice, but not in IL-1alpha KO mice, whereas IL-1ra KO mice showed an elevated response. At this time, expression of IL-1beta mRNA in the diencephalon decreased 1.5-fold in IL-1alpha KO mice, whereas expression of IL-1alpha mRNA decreased >30-fold in IL-1beta KO mice, suggesting mutual induction between IL-1alpha and IL-1beta. This mutual induction was also suggested in peritoneal macrophages stimulated with lipopolysaccharide in vitro. In IL-1beta KO mice treated with turpentine, the induction of cyclooxygenase-2 (EC 1.14.99.1) in the diencephalon was suppressed, whereas it was enhanced in IL-1ra KO mice. We also found that glucocorticoid induction 8 h after turpentine treatment was suppressed in IL-1beta but not IL-1alpha KO mice. These observations suggest that IL-1beta but not IL-1alpha is crucial in febrile and neuro-immuno-endocrine responses, and that this is because IL-1alpha expression in the brain is dependent on IL-1beta. The importance of IL-1ra both in normal physiology and under stress is also suggested.

The Role of Beta-Adrenergic Receptors in the Regulation of Circadian Intraocular Pressure Rhythm in Mice.

PubMed

Tsuchiya, Shunsuke; Higashide, Tomomi; Toida, Kazunori; Sugiyama, Kazuhisa

2017-07-01

To investigate whether the elimination of β1- and β2-adrenergic receptors alters the diurnal intraocular pressure (IOP) rhythm in mice. β1-/β2-adrenergic receptor double-knockout and C57BL/6J mice were anesthetized intraperitoneally, with their IOPs measured via microneedle method. After entrainment to a 12-h light-dark (LD) cycle (light phase 6:00-18:00), IOPs were measured every 3 h from 9:00 to 24:00 (group 1, β1-/β2-adrenergic receptor double-knockout mice, n = 11; C57BL/6J, n = 15). The IOP measurements at 15:00 and 24:00 under a 12-h LD cycle and in the constant darkness (1 day and 8 days after exposure to darkness, respectively) were performed in another group of β1-/β2-adrenergic receptor double-knockout mice (group 2, n = 12). IOP variance throughout the day and mean IOP differences among time points were evaluated using a linear mixed model. β1-/β2-adrenergic receptor double-knockout and C57BL/6J mice showed biphasic IOP curves, low during the light phase and high during the dark phase; the fluctuation was significant (P < 0.001). The peak IOP (18.7 ± 1.4 mmHg) occurred at 24:00 and the trough IOP (13.5 ± 1.5 mmHg) occurred at 15:00 in β1-/β2-adrenergic receptor double-knockout mice group. IOP curves of β1-/β2-adrenergic receptor double-knockout and C57BL/6J were nearly parallel, and the IOPs of β1-/β2-adrenergic receptor double-knockout mice were significantly higher than those of C57BL/6J mice (P < 0.001). Under constant dark (DD) conditions, IOP at 24:00 (18.1 ± 1.5 mmHg) was significantly higher than that at 15:00 (13.3 ± 1.2 mmHg) (P < 0.001). The transition from the LD cycle to DD environment produced no significant change in IOP (P = 0.728). Elimination of both β1- and β2-adrenergic receptors did not disturb the biphasic diurnal IOP rhythm in mice.