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Sample records for mice show disturbances

  1. 9 CFR 309.4 - Livestock showing symptoms of certain metabolic, toxic, nervous, or circulatory disturbances...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Livestock showing symptoms of certain metabolic, toxic, nervous, or circulatory disturbances, nutritional imbalances, or infectious or parasitic..., toxic, nervous, or circulatory disturbances, nutritional imbalances, or infectious or parasitic...

  2. Gelsemine alleviates both neuropathic pain and sleep disturbance in partial sciatic nerve ligation mice

    PubMed Central

    Wu, Yu-er; Li, Ya-dong; Luo, Yan-jia; Wang, Tian-xiao; Wang, Hui-jing; Chen, Shuo-nan; Qu, Wei-min; Huang, Zhi-li

    2015-01-01

    Aim: Gelsemine, an alkaloid from the Chinese herb Gelsemium elegans (Gardn & Champ) Benth., is effective in mitigating chronic pain in rats. In the present study we investigated whether the alkaloid improved sleep disturbance, the most common comorbid symptoms of chronic pain, in a mouse model of neuropathic pain. Methods: Mice were subjected to partial sciatic nerve ligation (PSNL). After the mice were injected with gelsemine or pregabalin (the positive control) intraperitoneally, mechanical allodynia and thermal hyperalgesia were assessed, and electroencephalogram (EEG)/electromyogram (EMG) recording was performed. Motor performance of the mice was assessed using rota-rod test. c-Fos expression in the brain was analyzed with immunohistochemical staining. Results: In PSNL mice, gelsemine (2 and 4 mg/kg) increased the mechanical threshold for 4 h and prolonged the thermal latencies for 3 h. Furthermore, gelsemine (4 mg/kg, administered at 6:30 AM) increased non-rapid eye movement (non-REM, NREM) sleep, decreased wakefulness, but did not affect REM sleep during the first 3 h in PSNL mice. Sleep architecture analysis showed that gelsemine decreased the mean duration of wakefulness and increased the total number of episodes of NREM sleep during the first 3 h after the dosing. Gelsemine (4 mg/kg) did not impair motor coordination in PSNL mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of the anterior cingulate cortex, and gelsemine (4 mg/kg) decreased c-Fos expression by 58%. Gelsemine (4 mg/kg, administered at either 6:30 AM or 8:30 PM) did not produce hypnotic effect in normal mice. Pregabalin produced similar antinociceptive and hypnotic effects, but impaired motor coordination in PSNL mice. Conclusion: Gelsemine is an effective agent for treatment of both neuropathic pain and sleep disturbance in PSNL mice; anterior cingulate cortex might play a role in the hypnotic effects of gelsemine. PMID:26388157

  3. Bex1 knock out mice show altered skeletal muscle regeneration

    SciTech Connect

    Koo, Jae Hyung Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

    2007-11-16

    Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca{sup 2+}/CaM may be involved in skeletal muscle regeneration.

  4. Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response

    PubMed Central

    Ojeda-Fernández, Luisa; Recio-Poveda, Lucía; Aristorena, Mikel; Lastres, Pedro; Blanco, Francisco J.; Sanz-Rodríguez, Francisco; Gallardo-Vara, Eunate; de las Casas-Engel, Mateo; Corbí, Ángel; Arthur, Helen M.; Bernabeu, Carmelo; Botella, Luisa M.

    2016-01-01

    Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-Osler-Weber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Engfl/flLysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Engfl/flLysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients. PMID:27010826

  5. Environmental enrichment induces behavioural disturbances in neuropeptide Y knockout mice

    PubMed Central

    Reichmann, Florian; Wegerer, Vanessa; Jain, Piyush; Mayerhofer, Raphaela; Hassan, Ahmed M.; Fröhlich, Esther E.; Bock, Elisabeth; Pritz, Elisabeth; Herzog, Herbert; Holzer, Peter; Leitinger, Gerd

    2016-01-01

    Environmental enrichment (EE) refers to the provision of a complex and stimulating housing condition which improves well-being, behaviour and brain function of laboratory animals. The mechanisms behind these beneficial effects of EE are only partially understood. In the current report, we describe a link between EE and neuropeptide Y (NPY), based on findings from NPY knockout (KO) mice exposed to EE. Relative to EE-housed wildtype (WT) animals, NPY KO mice displayed altered behaviour as well as molecular and morphological changes in amygdala and hippocampus. Exposure of WT mice to EE reduced anxiety and decreased central glucocorticoid receptor expression, effects which were absent in NPY KO mice. In addition, NPY deletion altered the preference of EE items, and EE-housed NPY KO mice responded to stress with exaggerated hyperthermia, displayed impaired spatial memory, had higher hippocampal brain-derived neurotrophic factor mRNA levels and altered hippocampal synaptic plasticity, effects which were not seen in WT mice. Accordingly, these findings suggest that NPY contributes to the anxiolytic effect of EE and that NPY deletion reverses the beneficial effects of EE into a negative experience. The NPY system could thus be a target for “enviromimetics”, therapeutics which reproduce the beneficial effects of enhanced environmental stimulation. PMID:27305846

  6. 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

  7. The effect of daily disturbance on the breeding performance of mice.

    PubMed

    Peters, Alan G; Bywater, Peter M; Festing, Michael F W

    2002-04-01

    The United Kingdom Home Office Code of Practice for the housing and care of breeding animals requires that, 'the general well-being of all animals must be checked at least once daily'. However, excessive daily disturbance of rodent breeding colonies could be counter-productive to animal welfare if it increases pre-weaning mortality. An experiment involving 100 breeding cages of BALB/c mice compared daily inspection of the mouse cages, but without disturbing the mice within the nest, with daily inspection in which every individual was studied even if this involved removing the cage lid and disturbing the nest. No statistically significant differences were found between the two groups in breeding performance or pre-weaning mortality, though the disturbed group produced marginally fewer offspring and had slightly higher mortality. Average weaning weight did not differ between the groups, but sexual dimorphism at weaning was significantly increased in the disturbed group. It is concluded that there are unlikely to be any welfare benefits in an inspection regimen that involves disturbance of breeding mice, provided the cage is inspected daily.

  8. Impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen metabolism

    SciTech Connect

    Kirfel, Jutta Pantelis, Dimitrios; Kabba, Mustapha; Kahl, Philip; Roeper, Anke; Kalff, Joerg C.; Buettner, Reinhard

    2008-12-10

    Four and one half LIM domain protein FHL2 participates in many cellular processes involved in tissue repair such as regulation of gene expression, cytoarchitecture, cell adhesion, migration and signal transduction. The repair process after wounding is initiated by the release of peptides and bioactive lipids. These molecules induce synthesis and deposition of a provisional extracellular matrix. We showed previously that sphingosine-1-phosphate (S1P) triggers a signal transduction cascade mediating nuclear translocation of FHL2 in response to activation of the RhoA GTPase. Our present study shows that FHL2 is an important signal transducer influencing the outcome of intestinal anastomotic healing. Early wound healing is accompanied by reconstitution and remodelling of the extracellular matrix and collagen is primarily responsible for wound strength. Our results show that impaired intestinal wound healing in Fhl2-deficient mice is due to disturbed collagen III metabolism. Impaired collagen III synthesis reduced the mechanical stability of the anastomoses and led to lower bursting pressure in Fhl2-deficient mice after surgery. Our data confirm that FHL2 is an important factor regulating collagen expression in the early phase of wound healing, and thereby is critically involved in the physiologic process of anastomosis healing after bowel surgery and thus may represent a new therapeutic target.

  9. Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice

    PubMed Central

    Harry, Brian L.; Sanders, John M.; Feaver, Ryan E.; Lansey, Melissa; Deem, Tracy L.; Zarbock, Alexander; Bruce, Anthony C.; Pryor, Andrew W.; Gelfand, Bradley D.; Blackman, Brett R.; Schwartz, Martin A.; Ley, Klaus

    2009-01-01

    Objective Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) has recently been shown to form an essential element of a mechanosensory complex that mediates endothelial responses to fluid shear stress. The aim of this study was to determine the in vivo role of PECAM-1 in atherosclerosis. Methods and Results We crossed C57BL/6 Pecam1−/− mice with apolipoprotein E–deficient (Apoe−/−) mice. On a Western diet, Pecam1−/−Apoe−/− mice showed reduced atherosclerotic lesion size compared to Apoe−/− mice. Striking differences were observed in the lesser curvature of the aortic arch, an area of disturbed flow, but not in the descending thoracic or abdominal aorta. Vascular cell adhesion molecule-1 (VCAM-1) expression, macrophage infiltration, and endothelial nuclear NF-κB were all reduced in Pecam1−/−Apoe−/− mice. Bone marrow transplantation suggested that endothelial PECAM-1 is the main determinant of atherosclerosis in the aortic arch, but that hematopoietic PECAM-1 promotes lesions in the abdominal aorta. In vitro data show that siRNA-based knockdown of PECAM-1 attenuates endothelial NF-κB activity and VCAM-1 expression under conditions of atheroprone flow. Conclusion These results indicate that endothelial PECAM-1 contributes to atherosclerotic lesion formation in regions of disturbed flow by regulating NF-κB–mediated gene expression. PMID:18688018

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

    SciTech Connect

    Howe, Adina; Ringus, Daina L.; Williams, Ryan J.; Choo, Zi -Ning; Greenwald, Stephanie M.; Owens, Sarah M.; Coleman, Maureen L.; Meyer, Folker; Chang, Eugene B.

    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 showed 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.

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

    PubMed Central

    Howe, Adina; Ringus, Daina L; Williams, Ryan J; Choo, Zi-Ning; Greenwald, Stephanie M; Owens, Sarah M; Coleman, Maureen L; Meyer, Folker; Chang, Eugene B

    2016-01-01

    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 showed 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. 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. PMID:26473721

  12. Disturbance gradient shows logging affects plant functional groups more than fire.

    PubMed

    Blair, David P; McBurney, Lachlan M; Blanchard, Wade; Banks, Sam C; Lindenmayer, David B

    2016-10-01

    Understanding the impacts of natural and human disturbances on forest biota is critical for improving forest management. Many studies have examined the separate impacts on fauna and flora of wildfire, conventional logging, and salvage logging, but empirical comparisons across a broad gradient of simultaneous disturbances are lacking. We quantified species richness and frequency of occurrence of vascular plants, and functional group responses, across a gradient of disturbances that occurred concurrently in 2009 in the mountain ash forests of southeastern Australia. Our study encompassed replicated sites in undisturbed forest (~70 yr post fire), forest burned at low severity, forest burned at high severity, unburned forest that was clearcut logged, and forest burned at high severity that was clearcut salvage logged post-fire. All sites were sampled 2 and 3 yr post fire. Mean species richness decreased across the disturbance gradient from 30.1 species/site on low-severity burned sites and 28.9 species/site on high-severity burned sites, to 25.1 species/site on clearcut sites and 21.7 species/site on salvage logged sites. Low-severity burned sites were significantly more species-rich than clearcut sites and salvage logged sites; high-severity burned sites supported greater species richness than salvage logged sites. Specific traits influenced species' sensitivity to disturbance. Resprouting species dominated undisturbed mountain ash forests, but declined significantly across the gradient. Fern and midstory trees decreased significantly in frequency of occurrence across the gradient. Ferns (excluding bracken) decreased from 34% of plants in undisturbed forest to 3% on salvage logged sites. High-severity burned sites supported a greater frequency of occurrence and species richness of midstory trees compared to clearcut and salvage logged sites. Salvage logging supported fewer midstory trees than any other disturbance category, and were distinctly different from

  13. 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,...

  14. 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,...

  15. 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,...

  16. 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,...

  17. Treatment of GABA from Fermented Rice Germ Ameliorates Caffeine-Induced Sleep Disturbance in Mice

    PubMed Central

    Mabunga, Darine Froy N.; Gonzales, Edson Luck T.; Kim, Hee Jin; Choung, Se Young

    2015-01-01

    γ-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is involved in sleep physiology. Caffeine is widely used psychoactive substance known to induce wakefulness and insomnia to its consumers. This study was performed to examine whether GABA extracts from fermented rice germ ameliorates caffeine-induced sleep disturbance in mice, without affecting spontaneous locomotor activity and motor coordination. Indeed, caffeine (10 mg/kg, i.p.) delayed sleep onset and reduced sleep duration of mice. Conversely, rice germ ferment extracts-GABA treatment (10, 30, or 100 mg/kg, p.o.), especially at 100 mg/kg, normalized the sleep disturbance induced by caffeine. In locomotor tests, rice germ ferment extracts-GABA slightly but not significantly reduced the caffeine-induced increase in locomotor activity without affecting motor coordination. Additionally, rice germ ferment extracts-GABA per se did not affect the spontaneous locomotor activity and motor coordination of mice. In conclusion, rice germ ferment extracts-GABA supplementation can counter the sleep disturbance induced by caffeine, without affecting the general locomotor activities of mice. PMID:25995826

  18. Disturbances in the secretion of neurotransmitters in IA-2/IA-2beta null mice: changes in behavior, learning and lifespan.

    PubMed

    Nishimura, T; Kubosaki, A; Ito, Y; Notkins, A L

    2009-03-17

    Islet-associated protein 2 (IA-2) and IA-2beta are major autoantigens in type 1 diabetes and transmembrane proteins in dense core secretory vesicles (DCV) of neuroendocrine cells. The deletion of these genes results in a decrease in insulin secretion. The present study was initiated to test the hypothesis that this deletion not only affects the secretion of insulin, but has a more global effect on neuroendocrine secretion that leads to disturbances in behavior and learning. Measurement of neurotransmitters showed that norepinephrine, dopamine and 5-HT were significantly decreased in the brain of double knockout (DKO) mice (P<0.05 to <0.001). In tests evaluating anxiety-like behavior and conditioned-learning, the DKO mice showed a highly significant increase in anxiety-like behavior (P<0.01 to <0.001) and impairment of conditioned learning (P<0.01) as compared to WT mice. The DKO mice also displayed an increase in spontaneous and induced seizures (P<0.01) and age-related death. Contrary to the generally held view that IA-2 and IA-2beta are expressed exclusively in DCV, subcellular fractionation studies revealed that IA-2beta, but not IA-2, co-purifies with fractions rich in synaptic vesicles (SV), and that the secretion of dopamine, GABA and glutamate from the synaptosomes of the DKO mice was significantly decreased as was the number of SV (P<0.01). Taken together, these findings show that IA-2beta is present in both DCV and SV, and that the deletion of IA-2/IA-2beta has a global effect on the secretion of neurotransmitters. The impairment of secretion leads to behavioral and learning disturbances, seizures and reduced lifespan.

  19. Disturbance of aerobic metabolism accompanies neurobehavioral changes induced by nickel in mice.

    PubMed

    He, Min-Di; Xu, Shang-Cheng; Zhang, Xin; Wang, Yan; Xiong, Jia-Chuan; Zhang, Xiao; Lu, Yong-Hui; Zhang, Lei; Yu, Zheng-Ping; Zhou, Zhou

    2013-09-01

    The oral ingestion of soluble nickel compounds leads to neurological symptoms in humans. Deficiencies in aerobic metabolism induced by neurotoxic stimulus can cause an energy crisis in the brain that results in a variety of neurotoxic effects. In the present study, we focused on the aerobic metabolic states to investigate whether disturbance of aerobic metabolism was involved in nickel-induced neurological effects in mice. Mice were orally administered nickel chloride, and neurobehavioral performance was evaluated using the Morris water maze and open field tests at different time points. Aerobic metabolic states in the cerebral cortex were analyzed at the same time points at which neurobehavioral changes were evident. We found that nickel exposure caused deficits in both spatial memory and exploring activity in mice and that nickel was deposited in their cerebral cortex. Deficient aerobic metabolism manifested as decreased O2 consumption and ATP concentrations, lactate and NADH accumulation, and oxidative stress. Meanwhile, the activity of prototypical iron-sulfur clusters (ISCs) containing enzymes that are known to control aerobic metabolism, including complex I and aconitase, and the expression of ISC assembly scaffold protein (ISCU) were inhibited following nickel deposition. Overall, these data suggest that aerobic metabolic disturbances, which accompanied the neurobehavioral changes, may participate in nickel-induced neurologic effects. The inactivation of ISC containing metabolic enzymes may result in the disturbance of aerobic metabolism. A better understanding of how nickel impacts the energy metabolic processes may provide insight into the prevention of nickel neurotoxicity.

  20. The Mediterranean Benthic Herbivores Show Diverse Responses to Extreme Storm Disturbances

    PubMed Central

    Pagès, Jordi F.; Gera, Alessandro; Romero, Javier; Farina, Simone; Garcia-Rubies, Antoni; Hereu, Bernat; Alcoverro, Teresa

    2013-01-01

    Catastrophic storms have been observed to be one of the major elements in shaping the standing structure of marine benthic ecosystems. Yet, little is known about the effect of catastrophic storms on ecosystem processes. Specifically, herbivory is the main control mechanism of macrophyte communities in the Mediterranean, with two main key herbivores: the sea urchin Paracentrotus lividus and the fish Sarpa salpa. Consequently, the effects of extreme storm events on these two herbivores (at the population level and on their behaviour) may be critical for the functioning of the ecosystem. With the aim of filling this gap, we took advantage of two parallel studies that were conducted before, during and after an unexpected catastrophic storm event. Specifically, fish and sea urchin abundance were assessed before and after the storm in monitored fixed areas (one site for sea urchin assessment and 3 sites for fish visual transects). Additionally, we investigated the behavioural response to the disturbance of S. salpa fishes that had been tagged with acoustic transmitters. Given their low mobility, sea urchins were severely affected by the storm (ca. 50% losses) with higher losses in those patches with a higher density of sea urchins. This may be due to a limited availability of refuges within each patch. In contrast, fish abundance was not affected, as fish were able to move to protected areas (i.e. deeper) as a result of the high mobility of this species. Our results highlight that catastrophic storms differentially affect the two dominant macroherbivores of rocky macroalgal and seagrass systems due to differences in mobility and escaping strategies. This study emphasises that under catastrophic disturbances, the presence of different responses among the key herbivores of the system may be critical for the maintenance of the herbivory function. PMID:23667512

  1. The Mediterranean benthic herbivores show diverse responses to extreme storm disturbances.

    PubMed

    Pagès, Jordi F; Gera, Alessandro; Romero, Javier; Farina, Simone; Garcia-Rubies, Antoni; Hereu, Bernat; Alcoverro, Teresa

    2013-01-01

    Catastrophic storms have been observed to be one of the major elements in shaping the standing structure of marine benthic ecosystems. Yet, little is known about the effect of catastrophic storms on ecosystem processes. Specifically, herbivory is the main control mechanism of macrophyte communities in the Mediterranean, with two main key herbivores: the sea urchin Paracentrotus lividus and the fish Sarpa salpa. Consequently, the effects of extreme storm events on these two herbivores (at the population level and on their behaviour) may be critical for the functioning of the ecosystem. With the aim of filling this gap, we took advantage of two parallel studies that were conducted before, during and after an unexpected catastrophic storm event. Specifically, fish and sea urchin abundance were assessed before and after the storm in monitored fixed areas (one site for sea urchin assessment and 3 sites for fish visual transects). Additionally, we investigated the behavioural response to the disturbance of S. salpa fishes that had been tagged with acoustic transmitters. Given their low mobility, sea urchins were severely affected by the storm (ca. 50% losses) with higher losses in those patches with a higher density of sea urchins. This may be due to a limited availability of refuges within each patch. In contrast, fish abundance was not affected, as fish were able to move to protected areas (i.e. deeper) as a result of the high mobility of this species. Our results highlight that catastrophic storms differentially affect the two dominant macroherbivores of rocky macroalgal and seagrass systems due to differences in mobility and escaping strategies. This study emphasises that under catastrophic disturbances, the presence of different responses among the key herbivores of the system may be critical for the maintenance of the herbivory function.

  2. Narp knockout mice show normal reactivity to novelty but attenuated recovery from neophobia.

    PubMed

    Blouin, Ashley M; Lee, Jongah J; Tao, Bo; Smith, Dani R; Johnson, Alexander W; Baraban, Jay M; Reti, Irving M

    2013-11-15

    Narp knockout (KO) mice demonstrate cognitive inflexibility and addictive behavior, which are associated with abnormal reactivity to a novel stimulus. To assess reactivity to novelty, we tested Narp KO and wild-type (WT) mice on a neophobia procedure. Both Narp KO and WT mice showed a similar decrease in consumption upon initial exposure to a novel flavor, but Narp KO mice did not increase consumption with subsequent exposures to the novel flavor like the WT mice. Therefore, Narp KO mice do not have abnormal reactivity to novelty but show deficits in adapting behavior to reflect the updated value of a stimulus.

  3. Factor XIII-A transglutaminase deficient mice show signs of metabolically healthy obesity on high fat diet

    PubMed Central

    Myneni, Vamsee D.; Mousa, Aisha; Kaartinen, Mari T.

    2016-01-01

    F13A1 gene, which encodes for Factor XIII-A blood clotting factor and a transglutaminase enzyme, was recently identified as a potential causative gene for obesity in humans. In our previous in vitro work, we showed that FXIII-A regulates preadipocyte differentiation and modulates insulin signaling via promoting plasma fibronectin assembly into the extracellular matrix. To understand the role of FXIII-A in whole body energy metabolism, here we have characterized the metabolic phenotype of F13a1−/− mice. F13a1−/− and F13a1+/+ type mice were fed chow or obesogenic, high fat diet for 20 weeks. Weight gain, total fat mass and fat pad mass, glucose handling, insulin sensitivity, energy expenditure and, morphological and biochemical analysis of adipose tissue was performed. We show that mice lacking FXIII-A gain weight on obesogenic diet, similarly as wild type mice, but exhibit a number of features of metabolically healthy obesity such as protection from developing diet-induced insulin resistance and hyperinsulinemia. Mice also show normal fasting glucose levels, larger adipocytes, decreased extracellular matrix accumulation and inflammation of adipose tissue, as well as decreased circulating triglycerides. This study reveals that FXIII-A transglutaminase can regulate whole body insulin sensitivity and may have a role in the development of diet-induced metabolic disturbances. PMID:27759118

  4. Proteomic Analysis of Aortae from Human Lipoprotein(a) Transgenic Mice Shows an Early Metabolic Response Independent of Atherosclerosis

    PubMed Central

    Rodger, Euan J.; Suetani, Rachel J.; Jones, Gregory T.; Kleffmann, Torsten; Carne, Alan; Legge, Michael; McCormick, Sally P. A.

    2012-01-01

    Background Elevated low density lipoprotein (LDL) and lipoprotein(a) are independent risk factors for the development of atherosclerosis. Using a proteomic approach we aimed to determine early changes in arterial protein expression in transgenic mice containing both human LDL and lipoprotein(a) in circulation. Methods and Results Plasma lipid analyses showed the lipoprotein(a) transgenic mice had significantly higher lipid levels than wildtype, including a much increased LDL and high density lipoprotein (HDL) cholesterol. Analysis of aortae from lipoprotein(a) mice showed lipoprotein(a) accumulation but no lipid accumulation or foam cells, leaving the arteries essentially atherosclerosis free. Using two-dimensional gel electrophoresis and mass spectrometry, we identified 34 arterial proteins with significantly altered abundance (P<0.05) in lipoprotein(a) transgenic mice compared to wildtype including 17 that showed a ≥2 fold difference. Some proteins of interest showed a similarly altered abundance at the transcript level. These changes collectively indicated an initial metabolic response that included a down regulation in energy, redox and lipid metabolism proteins and changes in structural proteins at a stage when atherosclerosis had not yet developed. Conclusions Our study shows that human LDL and lipoprotein(a) promote changes in the expression of a unique set of arterial proteins which may be early indicators of the metabolic disturbances preceding atherosclerosis. PMID:22276189

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

    PubMed

    Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima; Trak-Smayra, Viviane; Martinais, Sophie; Porceddu, Mathieu; Robin, Marie-Anne; Fromenty, Bernard

    2014-04-01

    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 10⁶ ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 10⁶ 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 10²-10³ 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.

  6. 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

  7. Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy.

    PubMed

    Mader, Jessica R; Resch, Zachary T; McLean, Gary R; Mikkelsen, Jakob H; Oxvig, Claus; Marler, Ronald J; Conover, Cheryl A

    2013-10-01

    We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic nephropathy. Normal human kidney showed specific staining for PAPP-A in glomeruli, and this staining was markedly increased in diabetic kidney. To assess the possible contribution of PAPP-A in the development of diabetic nephropathy, we induced diabetes with streptozotocin in 14-month-old WT and Papp-A knockout (KO) mice. Renal histopathology was evaluated after 4 months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman's capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration to those of diabetic WT mice, indicating that these changes were predominantly age-related. However, thickened Bowman's capsule and increased glomerular size appeared specific for the experimental diabetes. Kidneys from diabetic Papp-A KO mice had significantly reduced or no evidence of changes in Bowman's capsule thickening and glomerular size. There was also a shift to larger mesangial area and increased macrophage staining in diabetic WT mice compared with Papp-A KO mice. In summary, elevated PAPP-A expression in glomeruli is associated with diabetic nephropathy in humans and absence of PAPP-A is associated with resistance to the development of indicators of diabetic nephropathy in mice. These data suggest PAPP-A as a potential therapeutic target for diabetic nephropathy.

  8. 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

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

    SciTech Connect

    Anthérieu, Sébastien; Le Guillou, Dounia; Coulouarn, Cédric; Begriche, Karima; Trak-Smayra, Viviane; Martinais, Sophie; Porceddu, Mathieu; Robin, Marie-Anne; Fromenty, Bernard

    2014-04-01

    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 treated 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. • Trace

  10. Mice lacking components of adaptive immunity show increased Brucella abortus virB mutant colonization.

    PubMed

    Rolán, Hortensia García; Tsolis, Renée M

    2007-06-01

    The Brucella abortus type IV secretion system (T4SS), encoded by the virB genes, is essential for survival in mononuclear phagocytes in vitro. In the mouse model, a B. abortus virB mutant was initially able to colonize the spleen at the level of the wild type for approximately 3 to 5 days, which coincided with the development of adaptive immunity. To investigate the relationship between survival in macrophages cultivated in vitro and persistence in tissues in vivo, we tested the ability of mutant mice lacking components of adaptive immunity to eliminate the virB mutant from the spleen during a mixed infection with the B. abortus wild type. Ifng(-/-) or beta(2)m(-/-) mice were able to clear the virB mutant to the same degree as control mice. However, spleens of Rag1(-/-) mice and Igh6(-/-) mice were more highly colonized by the virB mutant than control mice after 14 to 21 days, suggesting that, in these mice, there is not an absolute requirement for the T4SS to mediate persistence of B. abortus in the spleen. Macrophages isolated from Igh6(-/-) mice killed the virB mutant to the same extent as macrophages from control mice, showing that the reduced ability of these mice to clear the virB mutant from the spleen does not correlate with diminished macrophage function in vitro. These results show that in the murine model host, the T4SS is required for persistence beyond 3 to 5 days after infection and suggest that the T4SS may contribute to evasion of adaptive immune mechanisms by B. abortus.

  11. H3 histamine receptor antagonist pitolisant reverses some subchronic disturbances induced by olanzapine in mice.

    PubMed

    Dudek, Magdalena; Kuder, Kamil; Kołaczkowski, Marcin; Olczyk, Adrian; Żmudzka, Elżbieta; Rak, Aleksandra; Bednarski, Marek; Pytka, Karolina; Sapa, Jacek; Kieć-Kononowicz, Katarzyna

    2016-10-01

    The use of atypical antipsychotic drugs like olanzapine is associated with side effects such as sedation and depression-like symptoms, especially during the initial period of the use. It is believed that the occurrence of these undesirable effectsis mainly the result of the histamine H1receptors blockade by olanzapine. In addition, use of olanzapine increases the level of triglycerides in the blood, which correlates with growing obesity. The aim of this study was to investigate the influence of pitolisant - H3 histamine antagonist - on subchronic olanzapine-induced depresion-like symptoms, sedation and hypertriglicerydemia. Forced swim test was conducted to determinate depressive-like effect of olanzapine and antidepressive-like activity during the co-administered pitolisant. The test was performed after the first and fifteenth day of the treatment of the mice. The spontaneous activity of the mice was measured on the fourteenth day of the treatment with a special, innovative RFID-system (Radio-frequency identification system) - TraffiCage (TSE-Systems, Germany). Triglyceride levels were determined on the sixteenth day of the experiment after 15 cycles of drug administration. Daily olanzapine treatment (4 mg/kg b.w., i.p., d.p.d) for 15 days significantly induces sedation (p < 0.05) and prolongs immobility time in forced swim tests (FST) in mice (p < 0.05); and also elevates the level of triglycerides (p < 0.05). Administration of pitolisant (10 mg/kg b.w., i.p.) subsequentto olanzapine normalizes these adverse effects. This study presents a promising alternative for counteracting some behavioral changes and metabolic disturbances which occur in the early period of treatment with antipsychotic drugs.

  12. Effects of voluntary running and soy supplementation on diet-induced metabolic disturbances and inflammation in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of voluntary running and soy supplementation on diet-induced metabolic disturbance and inflammation in male C57BL/6 mice using a 2x2x2 design in which the effects of diet (AIN93G or its modification with 45% calories from fat), activity level (sedentary or ...

  13. β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes

    PubMed Central

    Shi, Chang-Xiang; Zhao, Ming-Xia; Shu, Xiao-Dong; Xiong, Xiao-Qing; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-01-01

    β-aminoisobutyric acid (BAIBA) is a nature thymine catabolite, and contributes to exercise-induced protection from metabolic diseases. Here we show the therapeutical effects of BAIBA on hepatic endoplasmic reticulum (ER) stress and glucose/lipid metabolic disturbance in diabetes. Type 2 diabetes was induced by combined streptozotocin (STZ) and high-fat diet (HFD) in mice. Oral administration of BAIBA for 4 weeks reduced blood glucose and lipids levels, hepatic key enzymes of gluconeogenesis and lipogenesis expressions, attenuated hepatic insulin resistance and lipid accumulation, and improved insulin signaling in type 2 diabetic mice. BAIBA reduced hepatic ER stress and apoptosis in type 2 diabetic mice. Furthermore, BAIBA alleviated ER stress in human hepatocellular carcinoma (HepG2) cells with glucosamine-induced insulin resistance. Hepatic AMPK phosphorylation was reduced in STZ/HFD mice and glucosamine-treated HepG2 cells, which were restored by BAIBA treatment. The suppressive effects of BAIBA on glucosamine-induced ER stress were reversed by knockdown of AMPK with siRNA. In addition, BAIBA prevented thapsigargin- or tunicamycin-induced ER stress, and tunicamycin–induced apoptosis in HepG2 cells. These results indicate that BAIBA attenuates hepatic ER stress, apoptosis and glucose/lipid metabolic disturbance in mice with type 2 diabetes. AMPK signaling is involved to the role of BAIBA in attenuating ER stress. PMID:26907958

  14. β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes.

    PubMed

    Shi, Chang-Xiang; Zhao, Ming-Xia; Shu, Xiao-Dong; Xiong, Xiao-Qing; Wang, Jue-Jin; Gao, Xing-Ya; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-02-24

    β-aminoisobutyric acid (BAIBA) is a nature thymine catabolite, and contributes to exercise-induced protection from metabolic diseases. Here we show the therapeutical effects of BAIBA on hepatic endoplasmic reticulum (ER) stress and glucose/lipid metabolic disturbance in diabetes. Type 2 diabetes was induced by combined streptozotocin (STZ) and high-fat diet (HFD) in mice. Oral administration of BAIBA for 4 weeks reduced blood glucose and lipids levels, hepatic key enzymes of gluconeogenesis and lipogenesis expressions, attenuated hepatic insulin resistance and lipid accumulation, and improved insulin signaling in type 2 diabetic mice. BAIBA reduced hepatic ER stress and apoptosis in type 2 diabetic mice. Furthermore, BAIBA alleviated ER stress in human hepatocellular carcinoma (HepG2) cells with glucosamine-induced insulin resistance. Hepatic AMPK phosphorylation was reduced in STZ/HFD mice and glucosamine-treated HepG2 cells, which were restored by BAIBA treatment. The suppressive effects of BAIBA on glucosamine-induced ER stress were reversed by knockdown of AMPK with siRNA. In addition, BAIBA prevented thapsigargin- or tunicamycin-induced ER stress, and tunicamycin-induced apoptosis in HepG2 cells. These results indicate that BAIBA attenuates hepatic ER stress, apoptosis and glucose/lipid metabolic disturbance in mice with type 2 diabetes. AMPK signaling is involved to the role of BAIBA in attenuating ER stress.

  15. Localized brain differences in Arc expression between mice showing low vs. high propensity to ethanol sensitization.

    PubMed

    Nona, Christina N; Lam, Marcus; Nobrega, José N

    2016-03-01

    Behavioral sensitization to ethanol (EtOH) manifests as a progressive and enduring increase in locomotor activity with repeated drug exposure. However, not all mice sensitize to EtOH and the neuronal mechanisms mediating vulnerability and resistance to EtOH sensitization remain unclear. We examined regional brain expression of the immediate early gene activity-regulated cytoskeleton-associated protein (Arc) in order to identify brain areas in which neuroplastic changes may contribute to the development and expression of EtOH sensitization. Male DBA/2J mice received 5 biweekly injections of EtOH (2.2g/kg, i.p.) or saline (SAL). They were categorized as high- (HS) or low-sensitized (LS) on the basis of final locomotor activity scores. In both LS and HS mice sacrificed after the last sensitization injection, Arc expression was decreased throughout the brain in comparison to SAL animals. A similar pattern was seen in mice sacrificed after an EtOH challenge two weeks after the last sensitization injection. However in this cohort, Arc expression was significantly increased in the central amygdala (CeA) in LS mice and in SAL mice receiving EtOH for the first time. No significant increases in Arc expression were seen in brains of sensitized (HS) animals. These results indicate an acute EtOH challenge results in different patterns of Arc expression in brains of LS, HS, and SAL mice. The dramatic increases in Arc expression in the CeA in LS and SAL mice showing little or no behavioral activation suggests that neural activity in this region may serve to inhibit the stimulant effects of EtOH. The observation that HS mice do not show increases in Arc expression with an EtOH challenge suggests the possibility that increased tolerance to the Arc-inducing effects of EtOH may be a factor in behavioral sensitization.

  16. Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference.

    PubMed

    Neugebauer, Nichole M; Henehan, Robert M; Hales, Claire A; Picciotto, Marina R

    2011-03-01

    Previous work has indicated that the neuropeptide galanin decreases sensitivity to the rewarding effects of morphine and cocaine, but increases alcohol drinking. The aim of the current study was to examine the role of galanin signaling in nicotine reward by testing the effects of nicotine in mice lacking galanin peptide (GAL-/-) as compared to wild-type (GAL+/+) controls. Using an unbiased, three-chamber conditioned place preference (CPP) paradigm the dose-response function for nicotine CPP was tested in GAL-/- and GAL+/+ mice. Since activation of extracellular signal-related kinase (ERK2) is involved in the rewarding effects of several classes of drugs of abuse, we then measured the level of ERK2 phosphorylation in the nucleus accumbens shell (NACsh) and core (NACco) of GAL-/- and GAL+/+ mice following re-exposure to the CPP chamber previously paired with nicotine as a marker of mesolimbic system activation. Finally, we examined whether acute nicotine administration affects ERK2 activity in GAL-/- and GAL+/+ mice. GAL-/- mice required a higher dose of nicotine to induce a significant CPP compared to GAL+/+ mice. In the conditioning groups showing significant expression of nicotine CPP, only GAL+/+ mice showed ERK2 activation in the NACsh. This suggests that the nicotine CPP observed in GAL+/+ mice resulted in differential recruitment of ERK signaling in the NACsh compared to GAL-/- mice. In addition, no activation of ERK2 was observed following acute nicotine administration in either genotype. These data, along with prior results, suggest that galanin alters sensitivity to drugs of abuse differentially, with morphine, cocaine and amphetamine place preference suppressed, and nicotine and alcohol preference increased, by galanin signaling.

  17. 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.

  18. Meal time shift disturbs circadian rhythmicity along with metabolic and behavioral alterations in mice.

    PubMed

    Yoon, Ji-Ae; Han, Dong-Hee; Noh, Jong-Yun; Kim, Mi-Hee; Son, Gi Hoon; Kim, Kyungjin; Kim, Chang-Ju; Pak, Youngmi Kim; Cho, Sehyung

    2012-01-01

    In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s) underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA), body temperature (BT), blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42%) of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR) as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers.

  19. 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.

  20. 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.

  1. Role of stress system disturbance and enhanced novelty response in spatial learning of NCAM-deficient mice.

    PubMed

    Brandewiede, Joerg; Jakovcevski, Mira; Stork, Oliver; Schachner, Melitta

    2013-11-01

    The neural cell adhesion molecule (NCAM) plays a crucial role in stress-related brain function, emotional behavior and memory formation. In this study, we investigated the functions of the glucocorticoid and serotonergic systems in mice constitutively deficient for NCAM (NCAM-/- mice). Our data provide evidence for a hyperfunction of the hypothalamic-pituitary-adrenal axis, with enlarged adrenal glands and increased stress-induced corticosterone release, but reduced hippocampal glucocorticoid receptor expression in NCAM-/- mice when compared to NCAM+/+ mice. We also obtained evidence for a hypofunction of 5-HT1A autoreceptors as indicated by increased 8-0H-DPAT-induced hypothermia. These findings suggest a disturbance of both humoral and neural stress systems in NCAM-/- mice. Accordingly, we not only confirmed previously observed hyperarousal of NCAM-/- mice in various anxiety tests, but also observed an increased response to novelty exposure in these animals. Spatial learning deficits of the NCAM-/- mice in a Morris Water maze persisted, even when mice were pretrained to prevent effects of novelty or stress. We suggest that NCAM-mediated processes are involved in both novelty/stress-related emotional behavior and in cognitive function during spatial learning.

  2. Pancreas-specific aquaporin 12 null mice showed increased susceptibility to caerulein-induced acute pancreatitis.

    PubMed

    Ohta, Eriko; Itoh, Tomohiro; Nemoto, Tomomi; Kumagai, Jiro; Ko, Shigeru B H; Ishibashi, Kenichi; Ohno, Mayuko; Uchida, Keiko; Ohta, Akihito; Sohara, Eisei; Uchida, Shinichi; Sasaki, Sei; Rai, Tatemitsu

    2009-12-01

    Aquaporin 12 (AQP12) is the most recently identified member of the mammalian AQP family and is specifically expressed in pancreatic acinar cells. In vitro expression studies have revealed that AQP12 is localized at intracellular sites. To determine the physiological roles of AQP12 in the pancreas, we generated knockout mice for this gene (AQP12-KO). No obvious differences were observed under normal conditions between wild-type (WT) and AQP12-KO mice in terms of growth, blood chemistry, pancreatic fluid content, or histology. However, when we induced pancreatitis through the administration of a cholecystokinin-8 (CCK-8) analog, the AQP12-KO mice showed more severe pathological damage to this organ than WT mice. Furthermore, when we analyzed exocytosis in the pancreatic acini using a two-photon excitation imaging method, the results revealed larger exocytotic vesicles (vacuoles) in the acini of AQP12-KO mice at a high CCK-8 dose (100 nM). From these results, we conclude that AQP12 may function in the mechanisms that control the proper secretion of pancreatic fluid following rapid and intense stimulation.

  3. Meal Time Shift Disturbs Circadian Rhythmicity along with Metabolic and Behavioral Alterations in Mice

    PubMed Central

    Noh, Jong-Yun; Kim, Mi-Hee; Son, Gi Hoon; Kim, Kyungjin; Kim, Chang-Ju; Pak, Youngmi Kim; Cho, Sehyung

    2012-01-01

    In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s) underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA), body temperature (BT), blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42%) of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR) as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers. PMID:22952870

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

    PubMed

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

    2013-05-01

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

  5. 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).

  6. 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 A1 and A2A 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 A2A receptors increased with aging, both GFAP and adenosine A1 receptors were not affected. Caffeine at moderate dose prevented the age-related increase of the SNAP-25, with no effect on adenosine A2A 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.

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

    PubMed

    Chidgey, M; Brakebusch, C; Gustafsson, E; Cruchley, A; Hail, C; Kirk, S; Merritt, A; North, A; Tselepis, C; Hewitt, J; Byrne, C; Fassler, R; Garrod, D

    2001-11-26

    The desmosomal cadherin desmocollin (Dsc)1 is expressed in upper epidermis where strong adhesion is required. To investigate its role in vivo, we have genetically engineered mice with a targeted disruption in the Dsc1 gene. Soon after birth, null mice exhibit flaky skin and a striking punctate epidermal barrier defect. The epidermis is fragile, and acantholysis in the granular layer generates localized lesions, compromising skin barrier function. Neutrophils accumulate in the lesions and further degrade the tissue, causing sloughing (flaking) of lesional epidermis, but rapid wound healing prevents the formation of overt lesions. Null epidermis is hyperproliferative and overexpresses keratins 6 and 16, indicating abnormal differentiation. From 6 wk, null mice develop ulcerating lesions resembling chronic dermatitis. We speculate that ulceration occurs after acantholysis in the fragile epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human blistering diseases is discussed. These results show that Dsc1 is required for strong adhesion and barrier maintenance in epidermis and contributes to epidermal differentiation.

  8. Mice deficient in dihydrolipoyl succinyltransferase show increased vulnerability to mitochondrial toxins

    PubMed Central

    Yang, Lichuan; Shi, Qingli; Ho, Daniel J.; Starkov, Anatoly A.; Wille, Elizabeth J.; Xu, Hui; Chen, HL; Zhang, Steven; Stack, Cliona M.; Calingasan, Noel Y.; Gibson, Gary E.; Beal, M. Flint

    2013-01-01

    The activity of a key mitochondrial tricarboxylic acid cycle enzyme, α-ketoglutarate dehydrogenase complex (KGDHC), declines in many neurodegenerative diseases. KGDHC consists of three subunits. The dihydrolipoyl succinyltransferase (DLST) component is unique to KGDHC. DLST+/- mice showed reduced mRNA and protein levels and decreased brain mitochondrial KGDHC activity. Neurotoxic effects of mitochondrial toxins were exacerbated in DLST+/- mice. MPTP produced a significantly greater reduction of striatal dopamine and tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta of DLST+/- mice. DLST deficiency enhanced the severity of lipid peroxidation in the substantia nigra after MPTP treatment. Striatal lesions induced by either malonate or 3-nitropropionic acid (3-NP) were significantly larger in DLST+/- mice than in wildtype controls. DLST deficiency enhanced the 3-NP inhibition of mitochondria enzymes, and 3-NP induced protein and DNA oxidations. These observations support the hypothesis that reductions in KGDHC may impair the adaptability of the brain and contribute to the pathogenesis of neurodegenerative diseases. PMID:19660549

  9. Juvenile mice show greater flexibility in multiple choice reversal learning than adults

    PubMed Central

    Johnson, Carolyn; Wilbrecht, Linda

    2011-01-01

    We hypothesized that decision-making strategies in juvenile animals, rather than being immature, are optimized to navigate the uncertainty and instability likely to be encountered in the environment at the time of the animal’s transition to independence. We tested juvenile and young adult mice on discrimination and reversal of a 4-choice and 2-choice odor-based foraging task. Juvenile mice (P26–27) learned a 4-choice discrimination and reversal faster than adults (P60–70), making fewer perseverative and distraction errors. Juvenile mice had shorter choice latencies and more focused search strategies. In both ages, performance of the task was significantly impaired by a lesion of the dorsomedial frontal cortex. Our data show that the frontal cortex can support highly flexible behavior in juvenile mice at a time coincident with weaning and first independence. The unexpected developmental decline in flexibility of behavior one month later suggests that frontal cortex based executive function may not inevitably become more flexible with age, but rather may be developmentally tuned to optimize exploratory and exploitative behavior for each life stage. PMID:21949556

  10. PFOS induced lipid metabolism disturbances in BALB/c mice through inhibition of low density lipoproteins excretion

    NASA Astrophysics Data System (ADS)

    Wang, Ling; Wang, Yu; Liang, Yong; Li, Jia; Liu, Yuchen; Zhang, Jie; Zhang, Aiqian; Fu, Jianjie; Jiang, Guibin

    2014-04-01

    Male BALB/c mice fed with either a regular or high fat diet were exposed to 0, 5 or 20 mg/kg perfluorooctane sulfonate (PFOS) for 14 days. Increased body weight, serum glucose, cholesterol and lipoprotein levels were observed in mice given a high fat diet. However, all PFOS-treated mice got reduced levels of serum lipid and lipoprotein. Decreasing liver glycogen content was also observed, accompanied by reduced serum glucose levels. Histological and ultrastructural examination detected more lipid droplets accumulated in hepatocytes after PFOS exposure. Moreover, transcripitonal activity of lipid metabolism related genes suggests that PFOS toxicity is probably unrelevant to PPARα's transcription. The present study demonstrates a lipid disturbance caused by PFOS and thus point to its role in inhibiting the secretion and normal function of low density lipoproteins.

  11. PFOS induced lipid metabolism disturbances in BALB/c mice through inhibition of low density lipoproteins excretion

    PubMed Central

    Wang, Ling; Wang, Yu; Liang, Yong; Li, Jia; Liu, Yuchen; Zhang, Jie; Zhang, Aiqian; Fu, Jianjie; Jiang, Guibin

    2014-01-01

    Male BALB/c mice fed with either a regular or high fat diet were exposed to 0, 5 or 20 mg/kg perfluorooctane sulfonate (PFOS) for 14 days. Increased body weight, serum glucose, cholesterol and lipoprotein levels were observed in mice given a high fat diet. However, all PFOS-treated mice got reduced levels of serum lipid and lipoprotein. Decreasing liver glycogen content was also observed, accompanied by reduced serum glucose levels. Histological and ultrastructural examination detected more lipid droplets accumulated in hepatocytes after PFOS exposure. Moreover, transcripitonal activity of lipid metabolism related genes suggests that PFOS toxicity is probably unrelevant to PPARα's transcription. The present study demonstrates a lipid disturbance caused by PFOS and thus point to its role in inhibiting the secretion and normal function of low density lipoproteins. PMID:24694979

  12. Ghrelin O-acyltransferase knockout mice show resistance to obesity when fed high-sucrose diet.

    PubMed

    Kouno, Tetsuya; Akiyama, Nobuteru; Ito, Takahito; Okuda, Tomohiko; Nanchi, Isamu; Notoya, Mitsuru; Oka, Shogo; Yukioka, Hideo

    2016-02-01

    Ghrelin is an appetite-stimulating hormone secreted from stomach. Since the discovery that acylation of the serine-3 residue by ghrelin O-acyltransferase (GOAT) is essential for exerting its functions, GOAT has been regarded as an therapeutic target for attenuating appetite, and thus for the treatment of obesity and diabetes. However, contrary to the expectations, GOAT-knockout (KO) mice have not shown meaningful body weight reduction, under high-fat diet. Here, in this study, we sought to determine whether GOAT has a role in body weight regulation and glucose metabolism with a focus on dietary sucrose, because macronutrient composition of diet is important for appetite regulation. We found that peripherally administered acylated-ghrelin, but not unacylated one, stimulated sucrose consumption in a two-bottle-drinking test. The role of acylated-ghrelin in sucrose preference was further supported by the finding that GOAT KO mice consumed less sucrose solution compared with WT littermates. Then, we investigated the effect of dietary composition of sucrose on food intake and body weight in GOAT KO and WT mice. As a result, when fed on high-fat diet, food intake and body weight were similar between GOAT KO and WT mice. However, when fed on high-fat, high-sucrose diet, GOAT KO mice showed significantly reduced food intake and marked resistance to obesity, leading to amelioration of glucose metabolism. These results suggest that blockade of acylated-ghrelin production offers therapeutic potential for obesity and metabolic disorders caused by overeating of palatable food.

  13. 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.

  14. Continuous administration of polyphenols from aqueous rooibos (Aspalathus linearis) extract ameliorates dietary-induced metabolic disturbances in hyperlipidemic mice.

    PubMed

    Beltrán-Debón, R; Rull, A; Rodríguez-Sanabria, F; Iswaldi, I; Herranz-López, M; Aragonès, G; Camps, J; Alonso-Villaverde, C; Menéndez, J A; Micol, V; Segura-Carretero, A; Joven, J

    2011-03-15

    The incidence of obesity and related metabolic diseases is increasing globally. Current medical treatments often fail to halt the progress of such disturbances, and plant-derived polyphenols are increasingly being investigated as a possible way to provide safe and effective complementary therapy. Rooibos (Aspalathus linearis) is a rich source of polyphenols without caloric and/or stimulant components. We have tentatively characterized 25 phenolic compounds in rooibos extract and studied the effects of continuous aqueous rooibos extract consumption in mice. The effects of this extract, which contained 25% w/w of total polyphenol content, were negligible in animals with no metabolic disturbance but were significant in hyperlipemic mice, especially in those in which energy intake was increased via a Western-type diet that increased the risk of developing metabolic complications. In these mice, we found hypolipemiant activity when given rooibos extract, with significant reductions in serum cholesterol, triglyceride and free fatty acid concentrations. Additionally, we found changes in adipocyte size and number as well as complete prevention of dietary-induced hepatic steatosis. These effects were not related to changes in insulin resistance. Among other possible mechanisms, we present data indicating that the activation of AMP-activated protein kinase (AMPK) and the resulting regulation of cellular energy homeostasis may play a significant role in these effects of rooibos extract. Our findings suggest that adding polyphenols to the daily diet is likely to help in the overall management of metabolic diseases.

  15. Aged PrP null mice show defective processing of neuregulins in the peripheral nervous system.

    PubMed

    Benvegnù, Stefano; Gasperini, Lisa; Legname, Giuseppe

    2011-05-01

    A prion, a protease-resistant conformer of the cellular prion protein (PrP(C)), is the causative agent of transmissible spongiform encephalopathies or prion diseases. While this property is well established for the aberrantly folded protein, the physiological function of PrP(C) remains elusive. Among different putative functions, the non-pathogenic protein isoform PrP(C) is involved in several cellular processes. Here, we show that PrP(C) regulates the cleavage of neuregulin-1 proteins (NRG1). Neuregulins provide key axonal signals that regulate several processes, including glial cells proliferation, survival and myelination. Interestingly, mice devoid of PrP(C) (Prnp⁰/⁰) were recently shown to have a late-onset demyelinating disease in the peripheral nervous system (PNS) but not in the central nervous system (CNS). We found that NRG1 processing is developmentally regulated in the PNS and, by comparing wildtype and Prnp⁰/⁰ mice, that PrP(C) influences NRG1 processing in old, but not in young, animals. In addition, we found that also the processing of neuregulin-3, another neuregulin family member, is altered in the PNS of Prnp⁰/⁰ mice. These differences in neuregulin proteins processing are not paralleled in the CNS, thus suggesting a different cellular function for PrP(C) between the CNS and the PNS.

  16. Immunization with recombinant leucine aminopeptidase showed protection against Fasciola gigantica in mice.

    PubMed

    Changklungmoa, Narin; Kueakhai, Pornanan; Riengrojpitak, Suda; Chaithirayanon, Kulathida; Chaichanasak, Pannigan; Preyavichyapugdee, Narin; Chantree, Pathanin; Sansri, Veerawat; Itagaki, Tadashi; Sobhon, Prasert

    2013-10-01

    Leucine aminopeptidase (LAP) is expressed in all stages of Fasciola gigantica and, hence, is considered as a potential vaccine candidate. In this study, we have tested a vaccine potential of LAP and the types of immune responses it elicited in vaccinated mice. Recombinant F. gigantica leucine aminopeptidase (rFgLAP) was expressed in Escherichia coli, BL21 (DE3). The imprinting control region mice subcutaneously immunized with 50 μg of rFgLAP combined with Freund's adjuvant (n = 10) exhibited a significant reduction in worm recoveries when compared with non-immunized and Freund's adjuvant controls at 60.8 and 64.3%, respectively, and both T helper (Th)1 and Th2 humoral immune responses were elicited in the hosts as reflected by the levels of IgG1 and IgG2a, with Th2 predominating. The levels of IgG1- and IgG2a-specific antibodies to rFgLAP were inversely and significantly correlated with the numbers of worm recoveries. The rFgLAP-vaccinated mice showed significantly reduced levels of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase and liver damage. These indicated that rFgLAP has a potential as a vaccine candidate against F. gigantica, whose efficacy will be studied further in economic animals including cattle, sheep, and goat.

  17. Mice lacking brain-type creatine kinase activity show defective thermoregulation

    PubMed Central

    Streijger, Femke; Pluk, Helma; Oerlemans, Frank; Beckers, Gaby; Bianco, Antonio C.; Ribeiro, Miriam O.; Wieringa, Bé; Van der Zee, Catharina E.E.M.

    2010-01-01

    The cytosolic brain-type creatine kinase and mitochondrial ubiquitous creatine kinase (CK-B and UbCKmit) are expressed during the prepubescent and adult period of mammalian life. These creatine kinase (CK) isoforms are present in neural cell types throughout the central and peripheral nervous system and in smooth muscle containing tissues, where they have an important role in cellular energy homeostasis. Here, we report on the coupling of CK activity to body temperature rhythm and adaptive thermoregulation in mice. With both brain-type CK isoforms being absent, the body temperature reproducibly drops ~1.0°C below normal during every morning (inactive) period in the daily cycle. Facultative non-shivering thermogenesis is also impaired, since CK−−/−− mice develop severe hypothermia during 24 h cold exposure. A relationship with fat metabolism was suggested because comparison of CK−−/−− mice with wildtype controls revealed decreased weight gain associated with less white and brown fat accumulation and smaller brown adipocytes. Also, circulating levels of glucose, triglycerides and leptin are reduced. Extensive physiological testing and uncoupling protein1 analysis showed, however, that the thermogenic problems are not due to abnormal responsiveness of brown adipocytes, since noradrenaline infusion produced a normal increase of body temperature. Moreover, we demonstrate that the cyclic drop in morning temperature is also not related to altered rhythmicity with reduced locomotion, diminished food intake or increased torpor sensitivity. Although several integral functions appear altered when CK is absent in the brain, combined findings point into the direction of inefficient neuronal transmission as the dominant factor in the thermoregulatory defect. PMID:19419668

  18. MRL/MpJ-Fas(lpr) mice show abnormalities in ovarian function and morphology with the progression of autoimmune disease.

    PubMed

    Otani, Yuki; Ichii, Osamu; Otsuka-Kanazawa, Saori; Chihara, Masataka; Nakamura, Teppei; Kon, Yasuhiro

    2015-01-01

    The immune system is known to affect reproductive function, and maternal-fetal immune tolerance is essential for a successful pregnancy. To investigate the relationship between autoimmune disease and female reproductive function, we performed a comparative analysis of the ovarian phenotypes for C57BL/6 mice, autoimmune disease-prone MRL/MpJ (MRL/+) mice and congenic MRL/MpJ-Fas(lpr) (MRL/lpr) mice harboring a mutation in the Fas gene that speeds disease onset. Both MRL-background strains showed earlier vaginal opening than C57BL/6 mice. The estrous cycle became irregular by 6 and 12 months of age in MRL/lpr mice and mice of the other two strains, respectively. Histological analysis at 3 months revealed that the number of primordial follicles was smaller in MRL-background mice than in C57BL/6 mice after 3 months. In addition, MRL/lpr and MRL/+ mice displayed lower numbers of ovarian follicles and corpora lutea at 3 and 6 months, and 6 and 12 months, respectively, than that in age-matched C57BL/6 mice. MRL/lpr and MRL/+ mice developed ovarian interstitial glands after 3 and 6 months, respectively. In particular, MRL/lpr mice showed numerous infiltrating lymphocytes within the ovarian interstitia, and partially stratified ovarian surface epithelia with more developed microvilli than that observed in C57BL/6 mice at 6 months. No significant differences in serum hormone levels were observed between the strains. In conclusion, MRL/lpr mice display altered ovarian development, morphology and function consistent with the progression of severe autoimmune disease, as these findings are less severe in MRL/+ counterparts.

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

    PubMed Central

    Liu, Qingtao; Liu, Yuzhuo; Yang, Jing; Huang, Xinmei; Han, Kaikai; Zhao, Dongmin; Bi, Keran; Li, Yin

    2016-01-01

    H9N2 Avian influenza virus has repeatedly infected humans and other mammals, which highlights the need to determine the pathogenicity and the corresponding mechanism of this virus for mammals. In this study, we found two H9N2 viruses with similar genetic background but with different pathogenicity in mice. The A/duck/Nanjing/06/2003 (NJ06) virus was highly pathogenic for mice, with a 50% mouse lethal dose (MLD50) of 102.83 50% egg infectious dose (EID50), whereas the A/duck/Nanjing/01/1999 (NJ01) virus was low pathogenic for mice, with a MLD50 of >106.81 EID50. Further studies showed that the NJ06 virus grew faster and reached significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06 virus induced more severe lung lesions, and higher levels of inflammatory cellular infiltration and cytokine response in lungs than NJ01 did. However, only 12 different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2-K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N) were found between the two viruses, and all these residues except for NA-R435K were located in the known functional regions involved in interaction of viral proteins or between the virus and host factors. Summary, our results suggest that multiple amino acid differences may be responsible for the higher pathogenicity of the NJ06 virus for mice, resulting in lethal infection, enhanced viral replication, severe lung lesions, and excessive inflammatory cellular infiltration and cytokine response in lungs. These observations will be helpful for better understanding the pathogenic potential and the corresponding molecular basis of H9N2 viruses that might pose threats to human health in the future. PMID:27867373

  20. Mice lacking GD3 synthase display morphological abnormalities in the sciatic nerve and neuronal disturbances during peripheral nerve regeneration.

    PubMed

    Ribeiro-Resende, Victor Túlio; Araújo Gomes, Tiago; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration.

  1. Mice Lacking GD3 Synthase Display Morphological Abnormalities in the Sciatic Nerve and Neuronal Disturbances during Peripheral Nerve Regeneration

    PubMed Central

    Ribeiro-Resende, Victor Túlio; Gomes, Tiago Araújo; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration. PMID:25330147

  2. "Binge" drinking experience in adolescent mice shows sex differences and elevated ethanol intake in adulthood.

    PubMed

    Strong, Moriah N; Yoneyama, Naomi; Fretwell, Andrea M; Snelling, Chris; Tanchuck, Michelle A; Finn, Deborah A

    2010-06-01

    Binge drinking, defined as achieving blood ethanol concentrations (BEC) of 80 mg%, has been increasing in adolescents and was reported to predispose later physical dependence. The present experiments utilized an animal model of binge drinking to compare the effect of ethanol "binge" experience during adolescence or adulthood on subsequent ethanol intake in male and female C57BL/6 mice. Adolescent and adult mice were initially exposed to the scheduled high alcohol consumption procedure, which produces BECs that exceed the levels for binge drinking following a 30-min ethanol session every third day. Ethanol intake and BECs were significantly higher in the adolescent ( approximately 3 g/kg, 199 mg%) versus adult ( approximately 2 g/kg, 135 mg%) mice during the first three ethanol sessions, but were more equivalent during the final two ethanol sessions (1.85-2.0 g/kg, 129-143 mg%). Then, separate groups of the ethanol-experienced mice were tested with ethanol naïve adolescent and adult mice for 2-h limited access (10% and 20% solutions) or 24-h (5%, 10% and 20% solutions) ethanol preference drinking. Limited access ethanol intake was significantly higher in female versus male mice, but was not altered by age or ethanol experience. In contrast, 24-h ethanol intake was significantly higher in the adolescent versus adult mice and in female versus male mice. Furthermore, binge drinking experience in the adolescent mice significantly increased subsequent ethanol intake, primarily due to intake in female mice. Thus, adolescent binge drinking significantly increased unlimited ethanol intake during adulthood, with female mice more susceptible to this effect.

  3. Metabolic and structural bone disturbances induced by hyperlipidic diet in mice treated with simvastatin

    PubMed Central

    Soares, Evelise Aline; Novaes, Rômulo Dias; Nakagaki, Wilson Romero; Fernandes, Geraldo José Medeiros; Garcia, José Antônio Dias; Camilli, José Angelo

    2015-01-01

    Simvastatin can modulate lipid and bone metabolism. However, information related to the interaction between diet and simvastatin on bone structure and biomechanics is scarce. Thus, this study evaluated the effects of simvastatin on femoral biomechanics and cortical/trabecular bone structure in wild-type mice nourished with a hyperlipidic diet. Three-month-old male wild-type mice (C57BL6 strain) were divided into four groups: (1) group W, nourished with a standard diet; (2) group WH, fed a hyperlipidic diet; (3) group WS, nourished with a standard diet plus oral simvastatin (20 mg/kg/day); and (4) group WHS, fed a hyperlipidic diet plus oral simvastatin (20 mg/kg/day). All animals received only their specific diet and water for 60 days. Blood samples were collected for the analysis of calcium, triglycerides, total cholesterol (TC) and fraction serum levels. Diet manipulation was able to induce a dyslipidaemic status in mice, characterized by triglyceride and TC rise in WH animals. Simvastatin prevented hypercholesterolaemia and reduced TC and LDL serum levels, but did not prevent hypertriglyceridaemia and HDL serum levels in the WHS group. In the WH mice the hyperlipidaemia was associated with reduction in trabecular bone thickness, femur structural and material property alterations. Simvastatin prevented these morphological alterations and minimized femur biomechanical changes in WHS mice. Taken together, the results indicated that the hyperlipidic diet intake acts as a risk factor for bone integrity, generating bones with reduced resistance and more susceptible to fractures, an effect attenuated by simvastatin that is potentially related to the modulatory action of this drug on lipid and bone metabolism. PMID:26175225

  4. Ceruloplasmin gene-deficient mice with experimental autoimmune encephalomyelitis show attenuated early disease evolution.

    PubMed

    Gresle, Melissa M; Schulz, Katrin; Jonas, Anna; Perreau, Victoria M; Cipriani, Tania; Baxter, Alan G; Miranda-Hernandez, Socorro; Field, Judith; Jokubaitis, Vilija G; Cherny, Robert; Volitakis, Irene; David, Samuel; Kilpatrick, Trevor J; Butzkueven, Helmut

    2014-06-01

    We conducted a microarray study to identify genes that are differentially regulated in the spinal cords of mice with the inflammatory disease experimental autoimmune encephalomyelitis (EAE) relative to healthy mice. In total 181 genes with at least a two-fold increase in expression were identified, and most of these genes were associated with immune function. Unexpectedly, ceruloplasmin (Cp), a ferroxidase that converts toxic ferrous iron to its nontoxic ferric form and also promotes the efflux of iron from astrocytes in the CNS, was shown to be highly upregulated (13.2-fold increase) in EAE spinal cord. Expression of Cp protein is known to be increased in several neurological conditions, but the role of Cp regulation in CNS autoimmune disease is not known. To investigate this, we induced EAE in Cp gene knockout, heterozygous, and wild-type mice. Cp knockout mice were found to have slower disease evolution than wild-type mice (EAE days 13-17; P = 0.05). Interestingly, Cp knockout mice also exhibited a significant increase in the number of astrocytes with reactive morphology in early EAE compared with wild-type mice at the same stage of disease. CNS iron levels were not increased with EAE in these mice. Based on these observations, we propose that an increase in Cp expression could contribute to tissue damage in early EAE. In addition, endogenous CP either directly or indirectly inhibits astrocyte reactivity during early disease, which could also worsen early disease evolution.

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

    SciTech Connect

    Wang, Yuehai; Lu, Huixia; Huang, Ziyang; Lin, Huili; Lei, Zhenmin; Tang, Mengxiong; Gao, Fei; Dong, Mei; Li, Rongda; Lin, Ling

    2014-07-18

    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 with 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.

  6. Disturbed flow induces systemic changes in metabolites in mouse plasma: a metabolomics study using ApoE⁻/⁻ mice with partial carotid ligation.

    PubMed

    Go, Young-Mi; Kim, Chan Woo; Walker, Douglas I; Kang, Dong Won; Kumar, Sandeep; Orr, Michael; Uppal, Karan; Quyyumi, Arshed A; Jo, Hanjoong; Jones, Dean P

    2015-01-01

    Disturbed blood flow (d-flow) occurring in branched and curved arteries promotes endothelial dysfunction and atherosclerosis, in part, by altering gene expression and epigenomic profiles in endothelial cells. While a systemic metabolic change is known to play a role in atherosclerosis, it is unclear whether it can be regulated by local d-flow. Here, we tested this hypothesis by carrying out a metabolomics study using blood plasma samples obtained from ApoE(-/-) mice that underwent a partial carotid ligation surgery to induce d-flow. Mice receiving sham ligation were used as a control. To study early metabolic changes, samples collected from 1 wk after partial ligation when endothelial dysfunction occurs, but before atheroma develops, were analyzed by high-resolution mass spectrometry. A metabolome-wide association study showed that 128 metabolites were significantly altered in the ligated mice compared with the sham group. Of these, sphingomyelin (SM; m/z 703.5747), a common mammalian cell membrane sphingolipid, was most significantly increased in the ligated mice. Of the 128 discriminatory metabolites, 18 and 41 were positively and negatively correlated with SM, respectively. The amino acids methionine and phenylalanine were increased by d-flow, while phosphatidylcholine and phosphatidylethanolamine were decreased by d-flow, and these metabolites were correlated with SM. Other significantly affected metabolites included dietary and environmental agents. Pathway analysis showed that the metabolic changes of d-flow impacted broad functional networks. These results suggest that signaling from d-flow occurring in focal regions induces systemic metabolic changes associated with atherosclerosis.

  7. Behavioral Disturbances in Estrogen-Related Receptor alpha-Null Mice

    PubMed Central

    Cui, Huxing; Lu, Yuan; Khan, Michael Z.; Anderson, Rachel M.; McDaniel, Latisha; Wilson, Hannah E.; Yin, Terry C.; Radley, Jason J.; Pieper, Andrew A.; Lutter, Michael

    2015-01-01

    SUMMARY Eating disorders, such as anorexia nervosa and bulimia nervosa, are common and severe mental illnesses of unknown etiology. Recently, we identified a rare missense mutation in the transcription factor estrogen-related receptor alpha (ESRRA) that is associated with the development of eating disorders. However, little is known about ESRRA function in the brain. Here, we report that Esrra is expressed in the mouse brain and demonstrate that Esrra levels are regulated by energy reserves. Esrra-null female mice display a reduced operant response to a high-fat diet, compulsivity/behavioral rigidity, and social deficits. Selective Esrra knockdown in the prefrontal and orbitofrontal cortices of adult female mice recapitulates reduced operant response and increased compulsivity, respectively. These results indicate that Esrra deficiency in the mouse brain impairs behavioral responses in multiple functional domains. PMID:25865889

  8. Effects of voluntary running and soy supplementation on diet-induced metabolic disturbance and inflammation in mice.

    PubMed

    Yan, Lin; Graef, George L; Claycombe, Kate J; Johnson, LuAnn K

    2013-10-02

    We investigated the effects of diet (AIN93G or high-fat), physical activity (sedentary or voluntary running), and protein source (casein or soy protein isolate (SPI)) and their interactions on metabolic disturbance and inflammation in mice. After 14 weeks of feeding, the high-fat diet increased body weight gain by 34.5% (p < 0.01), whereas running reduced weight gain by 30.5% (p < 0.01) compared to their respective AIN93G and sedentary controls; SPI did not affect weight gain. The high-fat diet significantly increased plasma concentrations of insulin, glucose, triglycerides, leptin, and monocyte chemotactic protein-1 (MCP-1); running and SPI significantly reduced these parameters compared to their respective controls. The high-fat diet significantly increased and running significantly reduced plasma plasminogen activator inhibitor-1. A unique finding was that SPI supplementation to the high-fat diet reduced plasma insulin by 11% (p < 0.05), MCP-1 by 21% (p = 0.03), and tumor necrosis factor-α (TNF-α) by 50% (p = 0.05) compared to casein. As adipose tissues produce many adipocytokines, including MCP-1 and TNF-α, that contribute to a state of chronic low grade systemic inflammation and facilitate metabolic disturbance in obesity, further investigations are warranted into the roles of soy protein in reducing the risk of obesity.

  9. Ultrasonic Vocalizations of Male Mice Differ among Species and Females Show Assortative Preferences for Male Calls

    PubMed Central

    Musolf, Kerstin; Meindl, Stefanie; Larsen, Angela L.; Kalcounis-Rueppell, Matina C.; Penn, Dustin J.

    2015-01-01

    Male house mice (Mus musculus) emit ultrasonic vocalizations (USVs) during courtship, which attract females, and we aimed to test whether females use these vocalizations for species or subspecies recognition of potential mates. We recorded courtship USVs of males from different Mus species, Mus musculus subspecies, and populations (F1 offspring of wild-caught Mus musculus musculus, Mus musculus domesticus (and F1 hybrid crosses), and Mus spicilegus), and we conducted playback experiments to measure female preferences for male USVs. Male vocalizations contained at least seven distinct syllable types, whose frequency of occurrence varied among species, subspecies, and populations. Detailed analyses of multiple common syllable types indicated that Mus musculus and Mus spicilegus could be discriminated based on spectral and temporal characteristics of their vocalizations, and populations of Mus musculus were also distinctive regardless of the classification model used. Females were able to discriminate USVs from different species, and showed assortative preferences for conspecific males. We found no evidence that females discriminate USVs of males from a different subspecies or separate populations of the same species, even though our spectral analyses identified acoustic features that differ between species, subspecies, and populations of the same species. Our results provide the first comparison of USVs between Mus species or between Mus musculus subspecies, and the first evidence that male USVs potentially facilitate species recognition. PMID:26309246

  10. NCAM-deficient mice show prominent abnormalities in serotonergic and BDNF systems in brain - Restoration by chronic amitriptyline.

    PubMed

    Aonurm-Helm, Anu; Anier, Kaili; Zharkovsky, Tamara; Castrén, Eero; Rantamäki, Tomi; Stepanov, Vladimir; Järv, Jaak; Zharkovsky, Alexander

    2015-12-01

    Mood disorders are associated with alterations in serotonergic system, deficient BDNF (brain-derived neurotrophic factor) signaling and abnormal synaptic plasticity. Increased degradation and reduced functions of NCAM (neural cell adhesion molecule) have recently been associated with depression and NCAM deficient mice show depression-related behavior and impaired learning. The aim of the present study was to investigate potential changes in serotonergic and BDNF systems in NCAM knock-out mice. Serotonergic nerve fiber density and SERT (serotonin transporter) protein levels were robustly reduced in the hippocampus, prefrontal cortex and basolateral amygdala of adult NCAM(-)(/-) mice. This SERT reduction was already evident during early postnatal development. [(3)H]MADAM binding experiments further demonstrated reduced availability of SERT in cell membranes of NCAM(-)(/-) mice. Moreover, the levels of serotonin and its major metabolite 5-HIAA were down regulated in the brains of NCAM(-)(/-) mice. NCAM(-)(/-) mice also showed a dramatic reduction in the BDNF protein levels in the hippocampus and prefrontal cortex. This BDNF deficiency was associated with reduced phosphorylation of its receptor TrkB. Importantly, chronic administration of antidepressant amitriptyline partially or completely restored these changes in serotonergic and BDNF systems, respectively. In conclusion, NCAM deficiency lead to prominent and persistent abnormalities in brain serotonergic and BDNF systems, which likely contributes to the behavioral and neurobiological phenotype of NCAM(-/-) mice.

  11. 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.

  12. Young MLP deficient mice show diastolic dysfunction before the onset of dilated cardiomyopathy

    PubMed Central

    Lorenzen-Schmidt, Ilka; Stuyvers, Bruno D.; ter Keurs, Henk E.D.J.; Date, Moto-o; Hoshijima, Masahiko; Chien, Kenneth R.; McCulloch, Andrew D.; Omens, Jeffrey H.

    2015-01-01

    Targeted deletion of cytoskeletal muscle LIM protein (MLP) in mice consistently leads to dilated cardiomyopathy (DCM) after one or more months. However, next to nothing is known at present about the mechanisms of this process. We investigated whether diastolic performance including passive mechanics and systolic behavior are altered in 2-week-old MLP knockout (MLPKO) mice, in which heart size, fractional shortening and ejection fraction are still normal. Right ventricular trabeculae were isolated from 2-week-old MLPKO and wildtype mice and placed in an apparatus that allowed force measurements and sarcomere length measurements using laser diffraction. During a twitch from the unloaded state at 1 Hz, MLPKO muscles relengthened to slack length more slowly than controls, although the corresponding force relaxation time was unchanged. Active developed stress at a diastolic sarcomere length of 2.00 μm was preserved in MLPKO trabeculae over a wide range of pacing frequencies. Force relaxation under the same conditions was consistently prolonged compared with wildtype controls, whereas time to peak and maximum rate of force generation were not significantly altered. Ca2+ content of the sarcoplasmic reticulum (SR) and the quantities of Ca2+ handling proteins were similar in both genotypes. In summary, young MLPKO mice revealed substantial alterations in passive myocardial properties and relaxation time, but not in most systolic characteristics. These results indicate that the progression to heart failure in the MLPKO model may be driven by diastolic myocardial dysfunction and abnormal passive properties rather than systolic dysfunction. PMID:15978612

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

    SciTech Connect

    Wang, Yuehai; Huang, Ziyang; Lu, Huixia; Lin, Huili; Wang, Zhenhua; Chen, Xiaoqing; Ouyang, Qiufang; Tang, Mengxiong; Hao, Panpan; Ni, Jingqin; Xu, Dongming; Zhang, Mingxiang; Zhang, Qunye; Lin, Ling; and others

    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 -/-} 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 tissue. The

  14. PACAP-deficient mice show attenuated corticosterone secretion and fail to develop depressive behavior during chronic social defeat stress.

    PubMed

    Lehmann, Michael L; Mustafa, Tomris; Eiden, Adrian M; Herkenham, Miles; Eiden, Lee E

    2013-05-01

    The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) regulates activation of the hypothalamic-pituitary-adrenal (HPA) axis and the adrenal gland in response to various stressors. We previously found that in response to acute psychological stress (restraint), elevated corticotrophin-releasing hormone (CRH) mRNA levels in the hypothalamic paraventricular nucleus (PVN) as well as elevated plasma corticosterone (CORT) were profoundly attenuated in PACAP-deficient mice. To determine whether HPA axis responses and stress-induced depressive-like behaviors in a chronic stress paradigm are affected by PACAP deficiency, we subjected mice to 14 days of social defeat stress. Defeat-exposed PACAP-/- mice showed a marked attenuation of stress-induced increases in serum CORT levels, cellular PVN ΔFosB immunostaining, and depressive-like behaviors (social interaction and forced swim tests) compared to wild-type control mice. The PACAP-/- mice showed reduced PVN FosB-positive cell numbers, but relatively elevated cell counts in several forebrain areas including the medial prefrontal cortex, after social stress. PACAP appears to be specific for mediating HPA activation only in psychological stress because marked elevations in plasma CORT after a systemic stressor (lipopolysaccharide administration) occurred regardless of genotype. We conclude that chronically elevated CORT is a key component of depressive effects of social defeat, and that attenuation of the CORT response at the level of the PVN, as well as extrahypothalamic forebrain regions, in PACAP-deficient mice protects from development of depressive behavior.

  15. Mice lacking hypertension candidate gene ATP2B1 in vascular smooth muscle cells show significant blood pressure elevation.

    PubMed

    Kobayashi, Yusuke; Hirawa, Nobuhito; Tabara, Yasuharu; Muraoka, Hidenori; Fujita, Megumi; Miyazaki, Nobuko; Fujiwara, Akira; Ichikawa, Yasuhiro; Yamamoto, Yuichiro; Ichihara, Naoaki; Saka, Sanae; Wakui, Hiromichi; Yoshida, Shin-ichiro; Yatsu, Keisuke; Toya, Yoshiyuki; Yasuda, Gen; Kohara, Katsuhiko; Kita, Yoshikuni; Takei, Kohtaro; Goshima, Yoshio; Ishikawa, Yoshihiro; Ueshima, Hirotsugu; Miki, Tetsuro; Umemura, Satoshi

    2012-04-01

    We reported previously that ATP2B1 was one of the genes for hypertension receptivity in a large-scale Japanese population, which has been replicated recently in Europeans and Koreans. ATP2B1 encodes the plasma membrane calcium ATPase isoform 1, which plays a critical role in intracellular calcium homeostasis. In addition, it is suggested that ATP2B1 plays a major role in vascular smooth muscle contraction. Because the ATP2B1 knockout (KO) mouse is embryo-lethal, we generated mice with vascular smooth muscle cell-specific KO of ATP2B1 using the Cre-loxP system to clarify the relationship between ATP2B1 and hypertension. The KO mice expressed significantly lower levels of ATP2B1 mRNA and protein in the aorta compared with control mice. KO mice showed significantly higher systolic blood pressure as measured by tail-cuff method and radiotelemetric method. Similar to ATP2B1, the expression of the Na(+)-Ca(2+) exchanger isoform 1 mRNA was decreased in vascular smooth muscle cells of KO mice. However, ATP2B4 expression was increased in KO mice. The cultured vascular smooth muscle cells of KO mice showed increased intracellular calcium concentration not only in basal condition but also in phenylephrine-stimulated condition. Furthermore, phenylephrine-induced vasoconstriction was significantly increased in vascular rings of the femoral artery of KO mice. These results suggest that ATP2B1 plays important roles in the regulation of blood pressure through alteration of calcium handling and vasoconstriction in vascular smooth muscle cells.

  16. Disturbed sleep/wake rhythms and neuronal cell loss in lateral hypothalamus and retina of mice with a spontaneous deletion in the ubiquitin carboxyl-terminal hydrolase L1 gene.

    PubMed

    Pfeffer, Martina; Plenzig, Stefanie; Gispert, Suzana; Wada, Keiji; Korf, Horst-Werner; Von Gall, Charlotte

    2012-02-01

    Many neurodegenerative disorders including Parkinson's disease (PD) and Alzheimer's disease (AD) are associated with sleep disturbances with presumably multifactorial etiology. Ubiquitin C-terminal hydrolase L1 (UCH-L1) is involved in the pathophysiology of PD and AD. In the present study, we analyzed locomotor rhythms, orexin A-immunoreaction (Ir) in the lateral hypothalamus (LH) and melanopsin-Ir in the retina of gracile axonal dystrophy (gad) mice with a spontaneous deletion in the Uch-l1 gene. In constant darkness, gad mice showed circadian rhythms in locomotor activity, indicating the integrity of the endogenous circadian rhythm generator. However, gad mice showed an increased activity during subjective day and a decreased number of orexin A-immunoreactive neurons in the LH compared with the wild type (WT). In addition, gad mice showed increased locomotor activity in the light period when kept in a standard photoperiod and entrainment to phase shifts was significantly slower than in WT. Moreover, melanopsin-Ir was significantly reduced in the retina of gad mice, suggesting an impairment of circadian light perception in gad mice.

  17. Female mice lacking Xist RNA show partial dosage compensation and survive to term

    PubMed Central

    Yang, Lin; Kirby, James E.; Sunwoo, Hongjae; Lee, Jeannie T.

    2016-01-01

    X-chromosome inactivation (XCI) compensates for differences in X-chromosome number between male and female mammals. XCI is orchestrated by Xist RNA, whose expression in early development leads to transcriptional silencing of one X chromosome in the female. Knockout studies have established a requirement for Xist with inviability of female embryos that inherit an Xist deletion from the father. Here, we report that female mice lacking Xist RNA can, surprisingly, develop and survive to term. Xist-null females are born at lower frequency and are smaller at birth, but organogenesis is mostly normal. Transcriptomic analysis indicates significant overexpression of hundreds of X-linked genes across multiple tissues. Therefore, Xist-null mice can develop to term in spite of a deficiency of dosage compensation. However, the degree of X-autosomal dosage imbalance was less than anticipated (1.14-fold to 1.36-fold). Thus, partial dosage compensation can be achieved without Xist, supporting the idea of inherent genome balance. Nevertheless, to date, none of the mutant mice has survived beyond weaning stage. Sudden death is associated with failure of postnatal organ maturation. Our data suggest Xist-independent mechanisms of dosage compensation and demonstrate that small deviations from X-autosomal balance can have profound effects on overall fitness. PMID:27542829

  18. IL1RAPL1 knockout mice show spine density decrease, learning deficiency, hyperactivity and reduced anxiety-like behaviours.

    PubMed

    Yasumura, Misato; Yoshida, Tomoyuki; Yamazaki, Maya; Abe, Manabu; Natsume, Rie; Kanno, Kouta; Uemura, Takeshi; Takao, Keizo; Sakimura, Kenji; Kikusui, Takefumi; Miyakawa, Tsuyoshi; Mishina, Masayoshi

    2014-10-14

    IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety.

  19. IL1RAPL1 knockout mice show spine density decrease, learning deficiency, hyperactivity and reduced anxiety-like behaviours

    PubMed Central

    Yasumura, Misato; Yoshida, Tomoyuki; Yamazaki, Maya; Abe, Manabu; Natsume, Rie; Kanno, Kouta; Uemura, Takeshi; Takao, Keizo; Sakimura, Kenji; Kikusui, Takefumi; Miyakawa, Tsuyoshi; Mishina, Masayoshi

    2014-01-01

    IL-1 receptor accessory protein-like 1 (IL1RAPL1) is responsible for nonsyndromic intellectual disability and is associated with autism. IL1RAPL1 mediates excitatory synapse formation through trans-synaptic interaction with PTPδ. Here, we showed that the spine density of cortical neurons was significantly reduced in IL1RAPL1 knockout mice. The spatial reference and working memories and remote fear memory were mildly impaired in IL1RAPL1 knockout mice. Furthermore, the behavioural flexibility was slightly reduced in the T-maze test. Interestingly, the performance of IL1RAPL1 knockout mice in the rotarod test was significantly better than that of wild-type mice. Moreover, IL1RAPL1 knockout mice consistently exhibited high locomotor activity in all the tasks examined. In addition, open-space and height anxiety-like behaviours were decreased in IL1RAPL1 knockout mice. These results suggest that IL1RAPL1 ablation resulted in spine density decrease and affected not only learning but also behavioural flexibility, locomotor activity and anxiety. PMID:25312502

  20. 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.

  1. 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

  2. Disturbed synthesis of type II collagen interferes with rate of bone formation and growth and increases bone resorption in transgenic mice.

    PubMed

    Nieminen, Jyrki; Sahlman, Janne; Hirvonen, Teemu; Lapveteläinen, Tuomo; Miettinen, Markku; Arnala, Ilkka; Malluche, Hartmut H; Helminen, Heikki J

    2008-03-01

    Transgenic mice carrying an internally deleted human type II collagen gene (COL2A1) were used to study bone growth and development. This mutation has previously been shown to disturb the development of collagen fibrils in articular cartilage, causing chondrodysplasia and osteoarthritis. Type II collagen expression in bones was investigated with immunohistochemistry. The development and mineralization of the skeleton and anthropometric measurements on bones were evaluated using X-rays and dynamic histomorphometry. Type II collagen was expressed in the cartilage of developing bones. The bones of transgenic mice were smaller compared with the controls. The bone mass remained almost unchanged in transgenic mice after 1 month of age, leading to differences of 47% in trabecular bone volume (P = 0.012) and 40% in trabecular thickness (P < 0.01) at the age of 3 months compared with controls. At the age of 3 months the eroded surface per bone volume was 31% greater in transgenic mice compared with controls (P < 0.05). Trabecular thickness correlated positively with body weight (R = 0.71, P < 0.001). Interestingly, body weight correlated with bone volume in control mice (R = 0.27, P < 0.01), but no correlation was observed in transgenic mice. The disturbed synthesis of cartilage-specific type II collagen in growing transgenic mice retarded bone development, increased bone resorption, and altered tissue properties. This led to a negative net bone balance and small bone size. The results support the idea that an altered synthesis of cartilage-specific molecule(s) can disturb postnatal bone development and growth.

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

    PubMed Central

    Komnig, Daniel; Imgrund, Silke; Reich, Arno; Gründer, Stefan; Falkenburger, Björn H.

    2016-01-01

    Inflammation contributes to the death of dopaminergic neurons in Parkinson disease and can be accompanied by acidification of extracellular pH, which may activate acid-sensing ion channels (ASIC). Accordingly, amiloride, a non-selective inhibitor of ASIC, was protective in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease. To complement these findings we determined MPTP toxicity in mice deficient for ASIC1a, the most common ASIC isoform in neurons. MPTP was applied i.p. in doses of 30 mg per kg on five consecutive days. We determined the number of dopaminergic neurons in the substantia nigra, assayed by stereological counting 14 days after the last MPTP injection, the number of Nissl positive neurons in the substantia nigra, and the concentration of catecholamines in the striatum. There was no difference between ASIC1a-deficient mice and wildtype controls. We are therefore not able to confirm that ASIC1a are involved in MPTP toxicity. The difference might relate to the subacute MPTP model we used, which more closely resembles the pathogenesis of Parkinson disease, or to further targets of amiloride. PMID:27820820

  4. Central administration of obestatin fails to show inhibitory effects on food and water intake in mice.

    PubMed

    Van Dijck, Annemie; Annemie, Van Dijck; Van Dam, Debby; Debby, Van Dam; Vergote, Valentijn; Valentijn, Vergote; De Spiegeleer, Bart; Bart, De Spiegeleer; Luyten, Walter; Walter, Luyten; Schoofs, Liliane; Liliane, Schoofs; De Deyn, Peter Paul; Peter Paul, De Deyn

    2009-08-07

    Obestatin is a ghrelin-associated peptide hormone with presumed anorexigenic and inhibitory effect on gastric propulsive motility activity. Recent literature, however, discloses much contestation over satiety and gastrointestinal motility-related functionalities of obestatin. In addition, antidipsinogenic effects in rodents by obestatin were recently reported. The present study was set up to bring more clarity into the contested effects of obestatin on food and water intake. Additionally, the stability of obestatin in brain tissue homogenate was investigated. The in vitro incubation of obestatin in brain homogenates revealed disappearance half-life times of 19 min for crude brain homogenate to 27 min for brain membrane homogenate. For the behavioural studies, male C57Bl/6 mice were intracerebroventricularly treated with 0.2 nmol murine amidated obestatin or vehicle at the age of 3 months. An additional group of mice was treated with 0.3 nmol of corticotropin releasing factor (CRF) as a positive control of suppression of food intake. Food and water intake were studied over a period of 5 h in metabolic cages. Under our experimental conditions, no suppressive effects of obestatin on food or water intake were observed, whereas CRF evoked a significant suppression of food intake, which proves the internal validity of the study design.

  5. Habituation under stress: shocked mice show nonassociative learning in a T-maze.

    PubMed

    Mitchell, D; Osborne, E W; O'Boyle, M W

    1985-03-01

    Conflicting predictions of reinforcement and neophobia-arousal theories were evaluated in a simple choice task. Four groups of C57BL/6J mice were administered daily two-trial tests in a uniform T-maze for 10 consecutive days. For three groups, the contingencies of footshock treatments were manipulated to reinforce alternation, perseveration, or both. A control group that was not administered footshock alternated, but all three groups that were stressed perseverated more and more across tests, despite the differences in reinforcement contingencies. These results are inconsistent with the predictions of reinforcement theory but consistent with the view that stressed or aroused animals are neophobic and use nonassociative learning (habituation) to distinguish between novel and familiar alternatives.

  6. Nanoemulsified green tea extract shows improved hypocholesterolemic effects in C57BL/6 mice.

    PubMed

    Kim, Young Jun; Houng, Soung-Jin; Kim, Jae Hoon; Kim, Young-Rok; Ji, Hong Geun; Lee, Sung-Joon

    2012-02-01

    Nanoemulsification of nutrients could improve bioavailability by enhancing intestinal uptake. We investigated the antioxidant and hypolipidemic effects of nanoemulsified green tea extract (NGTE). Antioxidant effect was measured by 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assay and dichlorofluorescein diacetate (DCFH-DA) assay. C57BL/6 mice were fed a control high-fat diet, green tea extract (GTE), or NGTE diet for 4 weeks. In composition analysis, GTE and NGTE contained similar total catechin concentrations. The antioxidative effect of GTE was comparable with that of NGTE. In the ABTS assay, GTE had a marked effect, although NGTE was more effective than GTE in the DCFH-DA assay. In the mouse feeding experiment, total and low-density lipoprotein (LDL) cholesterol concentrations were significantly reduced after NGTE treatment in comparison with GTE treatment in high-fat-fed C57BL/6J mice over the course of 4 weeks. The hypocholesterolemic effects were greater in the NGTE group compared with the GTE group (24% vs. 15.4% LDL cholesterol reduction compared with the control). Expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase was significantly down-regulated. Protein expression of LDL receptor was significantly increased in the livers of both the GTE- and NGTE-treated groups (+234.1%, P<.01 and +274.7%, P<.001), with a greater effect in the NGTE than in the GTE group. Cholesterol 7α-hydroxylase gene expression was similarly increased in both the GTE and NGTE groups. These results suggest that nanoemulsification significantly increased hypocholesterolemic effects of GTE in vivo due to increased bioavailability.

  7. MRL/MpJ mice show unique pathological features after experimental kidney injury.

    PubMed

    Shiozuru, Daichi; Ichii, Osamu; Kimura, Junpei; Nakamura, Teppei; Elewa, Yaser Hosny Ali; Otsuka-Kanazawa, Saori; Kon, Yasuhiro

    2016-02-01

    Clarification of the renal repair process is crucial for developing novel therapeutic strategies for kidney injury. MRL/MpJ mice have a unique repair process characterized by low scar formation. The pathological features of experimentally injured MRL/MpJ and C57BL/6 mouse kidneys were compared to examine the renal repair process. The dilation and atrophy of renal tubules were observed in folic acid (FA)-induced acute kidney injury (AKI) in both strains, and the histopathological injury scores and number of interleukin (IL)-1F6-positive damaged distal tubules and kidney injury molecule 1 (KIM-1)-positive damaged proximal tubules drastically increased 1 day after AKI induction. However, KIM-1-positive tubules and the elevation of serum renal function markers were significantly fewer and lower, respectively, in MRL/MpJ mice at days 2 and 7 after AKI. After traumatic kidney injury (TKI) via needle puncture, severe tubular necrotic lesions in the punctured area and fibrosis progressed in both strains. Indices for fibrosis such as aniline blue-positive area, number of alpha smooth muscle actin-positive myofibroblasts, and messenger RNA expression levels of Tgfb1 and Mmp2 indicated lower fibrotic activity in MRL/MpJ kidneys. Characteristically, only MRL/MpJ kidneys manifested remarkable calcification around the punctured area beginning 7 days after TKI. The pathological features of injured MRL/MpJ and C57BL/6 kidneys differed, especially those of kidneys with mild proximal tubular injuries after FA-induced AKI. Lower fibrotic activity and increased calcification after TKI were observed in MRL/MpJ kidneys. These findings clarified the unique pathological characteristics of MRL/MpJ mouse kidneys and contribute to understanding of the renal repair process after kidney injury.

  8. Degeneration and energy shortage in the suprachiasmatic nucleus underlies the circadian rhythm disturbance in ApoE−/− mice: implications for Alzheimer’s disease

    PubMed Central

    Zhou, Lan; Gao, Qian; Nie, Meng; Gu, Jing-Li; Hao, Wei; Wang, Lin; Cao, Ji-Min

    2016-01-01

    Alzheimer’s disease (AD) patients suffer sleep disorders and circadian rhythm disturbances (CRDs). The underlying mechanisms are incompletely understood, and treatments are lacking. In this study, we characterized the locomotor activity, clock gene expression, morphological degeneration and energy metabolism of suprachiasmatic nucleus (SCN), together with retinal light sensing, in ApoE−/− mice, a model for AD. Compared with the control C57BL/6J mice, ApoE−/− mice exhibited disordered circadian locomotor activity under dim light and constant darkness, with impaired re-entrainment to phase change schedules. Decreased retinal melanopsin expression, together with amyloidosis and tau deposition, was evident in ApoE−/− mice. Mitochondrial and synaptic deterioration, altered SIRT1-mediated energy metabolism and clock gene expression were also observed in ApoE−/− SCN. Supplementation with fat or ketone bodies but not glucose, or intraperitoneal administration of nicotinamide, restored the locomotor rhythmicity and circadian expression of SIRT1 and clock genes, as well as reducing neurodegeneration. Taken together, ApoE deficiency induced degeneration and a significant disturbance in the SCN rhythmicity. Decline of retinal light sensing and SCN structural and metabolic deteriorations represented the major pathologies accounting for the CRDs in ApoE−/− mice. Our curative experiments may help develop future therapies to treat the CRDs and sleep disorders in AD patients. PMID:27824104

  9. CD38 Knockout Mice Show Significant Protection Against Ischemic Brain Damage Despite High Level Poly-ADP-Ribosylation.

    PubMed

    Long, Aaron; Park, Ji H; Klimova, Nina; Fowler, Carol; Loane, David J; Kristian, Tibor

    2017-01-01

    Several enzymes in cellular bioenergetics metabolism require NAD(+) as an essential cofactor for their activity. NAD(+) depletion following ischemic insult can result in cell death and has been associated with over-activation of poly-ADP-ribose polymerase PARP1 as well as an increase in NAD(+) consuming enzyme CD38. CD38 is an NAD(+) glycohydrolase that plays an important role in inflammatory responses. To determine the contribution of CD38 activity to the mechanisms of post-ischemic brain damage we subjected CD38 knockout (CD38KO) mice and wild-type (WT) mice to transient forebrain ischemia. The CD38KO mice showed a significant amelioration in both histological and neurologic outcome following ischemic insult. Decrease of hippocampal NAD(+) levels detected during reperfusion in WT mice was only transient in CD38KO animals, suggesting that CD38 contributes to post-ischemic NAD(+) catabolism. Surprisingly, pre-ischemic poly-ADP-ribose (PAR) levels were dramatically higher in CD38KO animals compared to WT animals and exhibited reduction post-ischemia in contrast to the increased levels in WT animals. The high PAR levels in CD38 mice were due to reduced expression levels of poly-ADP-ribose glycohydrolase (PARG). Thus, the absence of CD38 activity can not only directly affect inflammatory response, but also result in unpredicted alterations in the expression levels of enzymes participating in NAD(+) metabolism. Although the CD38KO mice showed significant protection against ischemic brain injury, the changes in enzyme activity related to NAD(+) metabolism makes the determination of the role of CD38 in mechanisms of ischemic brain damage more complex.

  10. PACAP-deficient mice show attenuated corticosterone secretion and fail to develop depressive behavior during chronic social defeat stress

    PubMed Central

    Lehmann, Michael L.; Mustafa, Tomris; Eiden, Adrian M.; Herkenham, Miles; Eiden, Lee E.

    2012-01-01

    Summary The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) regulates activation of the hypothalamic-pituitary-adrenal (HPA) axis and the adrenal gland in response to various stressors. We previously found that in response to acute psychological stress (restraint), elevated corticotrophin-releasing hormone (CRH) mRNA levels in the hypothalamic paraventricular nucleus (PVN) as well as elevated plasma corticosterone (CORT) were profoundly attenuated in PACAP-deficient mice. To determine whether HPA axis responses and stress-induced depressive-like behaviors in a chronic stress paradigm are affected by PACAP deficiency, we subjected mice to 14 days of social defeat stress. Defeat-exposed PACAP−/− mice showed a marked attenuation of stress-induced increases in serum CORT levels, cellular PVN ΔFosB immunostaining, and depressive-like behaviors (social interaction and forced swim tests) compared to wild-type control mice. The PACAP−/− mice showed reduced PVN FosB-positive cell numbers, but relatively elevated cell counts in several forebrain areas including the medial prefrontal cortex, after social stress. PACAP appears to be specific for mediating HPA activation only in psychological stress because marked elevations in plasma CORT after a systemic stressor (lipopolysaccharide administration) occurred regardless of genotype. We conclude that chronically elevated CORT is a key component of depressive effects of social defeat, and that attenuation of the CORT response at the level of the PVN, as well as extrahypothalamic forebrain regions, in PACAP-deficient mice protects from development of depressive behavior. PMID:23062748

  11. Otx1 null mutant mice show partial segregation of sensory epithelia comparable to lamprey ears

    NASA Technical Reports Server (NTRS)

    Fritzsch, B.; Signore, M.; Simeone, A.

    2001-01-01

    We investigated the development of inner ear innervation in Otx1 null mutants, which lack a horizontal canal, between embryonic day 12 (E12) and postnatal day 7 (P7) with DiI and immunostaining for acetylated tubulin. Comparable to control animals, horizontal crista-like fibers were found to cross over the utricle in Otx1 null mice. In mutants these fibers extend toward an area near the endolymphatic duct, not to a horizontal crista. Most Otx1 null mutants had a small patch of sensory hair cells at this position. Measurement of the area of the utricular macula suggested it to be enlarged in Otx1 null mutants. We suggest that parts of the horizontal canal crista remain incorporated in the utricular sensory epithelium in Otx1 null mutants. Other parts of the horizontal crista appear to be variably segregated to form the isolated patch of hair cells identifiable by the unique fiber trajectory as representing the horizontal canal crista. Comparison with lamprey ear innervation reveals similarities in the pattern of innervation with the dorsal macula, a sensory patch of unknown function. SEM data confirm that all foramina are less constricted in Otx1 null mutants. We propose that Otx1 is not directly involved in sensory hair cell formation of the horizontal canal but affects the segregation of the horizontal canal crista from the utricle. It also affects constriction of the two main foramina in the ear, but not their initial formation. Otx1 is thus causally related to horizontal canal morphogenesis as well as morphogenesis of these foramina.

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

    PubMed

    Seyrantepe, Volkan; Lema, Pablo; Caqueret, Aurore; Dridi, Larbi; Bel Hadj, Samar; Carpentier, Stephane; Boucher, Francine; Levade, Thierry; Carmant, Lionel; Gravel, Roy A; Hamel, Edith; Vachon, Pascal; Di Cristo, Graziella; Michaud, Jacques L; Morales, Carlos R; Pshezhetsky, Alexey V

    2010-09-16

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

  13. 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

  14. Transgenic mice with increased astrocyte expression of IL-6 show altered effects of acute ethanol on synaptic function.

    PubMed

    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

    2016-04-01

    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

  15. Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes.

    PubMed Central

    Reis, L F; Ruffner, H; Stark, G; Aguet, M; Weissmann, C

    1994-01-01

    The transcription factor interferon regulatory factor 1 (IRF-1) binds tightly to the interferon (IFN)-beta promoter and has been implicated in the induction of type I IFNs. We generated mice devoid of functional IRF-1 by targeted gene disruption. As reported by others, IRF-1-deficient mice showed a discrete phenotype: the CD4/CD8 ratio was increased and IFN-gamma-induced levels of macrophage iNO synthase mRNA were strongly diminished. However, type I IFN induction in vivo by virus or double-stranded RNA was unimpaired, as evidenced by serum IFN titers and IFN mRNA levels in spleen, liver and lung. There was also no impairment in the response of type I IFN-inducible genes. Therefore, IRF-1 is not essential for these processes in vivo. Images PMID:7957048

  16. Mice with Deficient BK Channel Function Show Impaired Prepulse Inhibition and Spatial Learning, but Normal Working and Spatial Reference Memory

    PubMed Central

    Azzopardi, Erin; Ruettiger, Lukas; Ruth, Peter; Schmid, Susanne

    2013-01-01

    Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this model for cognitive testing. Auditory brain stem responses to click stimuli showed no threshold differences between knockout mice and their wild-type littermates. Despite of muscular tremor, reduced grip force, and impaired gait, knockout mice exhibited normal locomotion. These findings allowed for testing of sensorimotor gating using the acoustic startle reflex, as well as of working memory, spatial learning and memory in the Y-maze and the Morris water maze, respectively. Prepulse inhibition on the first day of testing was normal, but the knockout mice did not improve over the days of testing as their wild-type littermates did. Spontaneous alternation in the y-maze was normal as well, suggesting that the BK channel knock-out does not impair working memory. In the Morris water maze knock-out mice showed significantly slower acquisition of the task, but normal memory once the task was learned. Thus, we propose a crucial role of the BK channels in learning, but not in memory storage or recollection. PMID:24303038

  17. Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice.

    PubMed

    Enquist, Johan; Ferwerda, Madeline; Milan-Lobo, Laura; Whistler, Jennifer L

    2012-02-01

    Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

  18. Heterozygous caveolin-3 mice show increased susceptibility to palmitate-induced insulin resistance.

    PubMed

    Talukder, M A Hassan; Preda, Marilena; Ryzhova, Larisa; Prudovsky, Igor; Pinz, Ilka M

    2016-03-01

    Insulin resistance and diabetes are comorbidities of obesity and affect one in 10 adults in the United States. Despite the high prevalence, the mechanisms of cardiac insulin resistance in obesity are still unclear. We test the hypothesis that the insulin receptor localizes to caveolae and is regulated through binding to caveolin-3 (CAV3). We further test whether haploinsufficiency forCAV3 increases the susceptibility to high-fat-induced insulin resistance. We used in vivo and in vitro studies to determine the effect of palmitate exposure on global insulin resistance, contractile performance of the heart in vivo, glucose uptake in the heart, and on cellular signaling downstream of theIR We show that haploinsufficiency forCAV3 increases susceptibility to palmitate-induced global insulin resistance and causes cardiomyopathy. On the basis of fluorescence energy transfer (FRET) experiments, we show thatCAV3 andIRdirectly interact in cardiomyocytes. Palmitate impairs insulin signaling by a decrease in insulin-stimulated phosphorylation of Akt that corresponds to an 87% decrease in insulin-stimulated glucose uptake inHL-1 cardiomyocytes. Despite loss of Akt phosphorylation and lower glucose uptake, palmitate increased insulin-independent serine phosphorylation ofIRS-1 by 35%. In addition, we found lipid induced downregulation ofCD36, the fatty acid transporter associated with caveolae. This may explain the problem the diabetic heart is facing with the simultaneous impairment of glucose uptake and lipid transport. Thus, these findings suggest that loss ofCAV3 interferes with downstream insulin signaling and lipid uptake, implicatingCAV3 as a regulator of theIRand regulator of lipid uptake in the heart.

  19. Plgf-/-eNos-/- mice show defective angiogenesis associated with increased oxidative stress in response to tissue ischemia.

    PubMed

    Gigante, Bruna; Morlino, Giulia; Gentile, Maria Teresa; Persico, Maria Graziella; De Falco, Sandro

    2006-05-01

    Neo-angiogenesis is a complex phenomenon modulated by the concerted action of several molecular factors. We have generated a congenic line of knockout mice carrying null mutations of both placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS), two genes that play a pivotal role in the regulation of pathological angiogenesis. In the present study, we describe the phenotype of this new experimental animal model after surgically induced hind-limb ischemia. Plgf-/-, eNos-/-, Plgf-/- eNos-/-, and wild-type C57BL/6J mice were studied. Plgf-/- eNos-/- mice showed the most severe phenotype: self-amputation, and death occurred in up to 47% of the animals studied; in ischemic legs, capillary density was severely reduced; macrophage infiltration and oxidative stress increased as compared to the other groups of animals. These changes were associated with an up-regulation of both inducible NOS (iNOS) expression and vascular endothelial growth factor (VEGF) protein levels in ischemic limbs, and to an increased extent of protein nitration. Our results demonstrate that the deletion of these two genes, Plgf, which acts in synergism with VEGF, and eNos, a downstream mediator of VEGF, determines a significant change in the vascular response to an ischemic stimulus and that oxidative stress within the ischemic tissue represents a crucial factor to maintain tissue homeostasis.

  20. Di(2-Ethylhexyl) Phthalate Exposure In Utero Damages Sertoli Cell Differentiation Via Disturbance of Sex Determination Pathway in Fetal and Postnatal Mice.

    PubMed

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

    2016-07-01

    Mice may share similar mechanism with human underlying reproductive toxicity induced by di(2-ethylhexyl) phthalate (DEHP), which is not supposed to be associated with decreased testicular testosterone. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure level. After in utero DEHP exposure, loss of Sertoli cells and germ cells were observed in the male pups at postnatal days 21. And SRY-related HMG box 9 (SOX9), Fibroblast growth factor-9 (FGF9), and Double-sex and Mab-3 related transcripttion factor 1 (DMRT1) proteins were significantly downregulated by DEHP at 2 mg/kg/d and above, suggesting the depression of Sertoli cell differentiation. The repression of Sox9 genes expression was supported by whole-mount in situ hybridization and real-time real-time-quantitative PCR. The expressions of Cyp11α1 and Star were not significantly affected by in utero DEHP exposure, indicating the absence of effects on testosterone biosynthesis. Furthermore, the testosterone-independent pathway regulating Sertoli cells differentiation was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination, involving Gadd45g → Gata4/Fog2 → Sry → Sox9 → Fgf9 The results suggest that in utero DEHP exposure damaged Sertoli cells in the postnatal life of mice offspring via disturbance of the differentiation regulating pathway, potentially inducing declines in spermatogenesis.

  1. 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

  2. A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice.

    PubMed

    Jahagirdar, Ravi; Zhang, Haiyan; Azhar, Salman; Tobin, Jennifer; Attwell, Sarah; Yu, Raymond; Wu, Jin; McLure, Kevin G; Hansen, Henrik C; Wagner, Gregory S; Young, Peter R; Srivastava, Rai Ajit K; Wong, Norman C W; Johansson, Jan

    2014-09-01

    Despite the benefit of statins in reducing cardiovascular risk, a sizable proportion of patients still remain at risk. Since HDL reduces CVD risk through a process that involves formation of pre-beta particles that facilitates the removal of cholesterol from the lipid-laden macrophages in the arteries, inducing pre-beta particles, may reduce the risk of CVD. A novel BET bromodomain antagonist, RVX-208, was reported to raise apoA-I and increase preβ-HDL particles in non-human primates and humans. In the present study, we investigated the effect of RVX-208 on aortic lesion formation in hyperlipidemic apoE(-/-) mice. Oral treatments of apoE(-/-) mice with 150 mg/kg b.i.d RVX-208 for 12 weeks significantly reduced aortic lesion formation, accompanied by 2-fold increases in the levels of circulating HDL-C, and ∼50% decreases in LDL-C, although no significant changes in plasma apoA-I were observed. Circulating adhesion molecules as well as cytokines also showed significant reduction. Haptoglobin, a proinflammatory protein, known to bind with HDL/apoA-I, decreased >2.5-fold in the RVX-208 treated group. With a therapeutic dosing regimen in which mice were fed Western diet for 10 weeks to develop lesions followed by switching to a low fat diet and concurrent treatment with RVX-208 for 14 weeks, RVX-208 similarly reduced lesion formation by 39% in the whole aorta without significant changes in the plasma lipid parameters. RVX-208 significantly reduced the proinflammatory cytokines IP-10, MIP1(®) and MDC. These results show that the antiatherogenic activity of BET inhibitor, RVX-208, occurs via a combination of lipid changes and anti-inflammatory activities.

  3. [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.

  4. Dynamic studies of positron-emitting putative tumor marker /sup 132/Cs in mice show differential tumor and regional uptake

    SciTech Connect

    McKee, J.S.; Durocher, J.J.; Bose, R.; Gusdal, M.I.; Sharma, G.P.; Pinsky, C.; Gallop, D.

    1985-01-01

    Positron-emitting /sup 132/Cs (t1/2 = 6.47 days) was generated from stable /sup 133/CsCl via the /sup 133/Cs (p,pn) /sup 132/Cs reaction. BALB/c mice, bearing implanted MT296 mammary tumors, were given 4.6 mEq kg-1 of /sup 132/CsCl via a single intraperitoneal injection. Postinjection uptake of /sup 132/Cs into body regions was monitored in vivo with external detectors. Positron emission from the tumor region was continuously greater than that from the head, the numerical ratio of mean emission intensities being fourfold at 10 min postinjection. Tissues excised from these mice postmortem showed sequence of relative tissue cesium uptake rates to be kidney 1.8, small intestine 1.7, tumor 1.0, skin 0.75, liver 0.75, skeletal muscle 0.4, and brain 0.28. Comparative studies with multiple injections of stable cesium and rubidium showed this sequence to be ion-specific. These observations suggest that positron-emitting isotopes of cesium could provide useful markers for tumors of several tissues.

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

    SciTech Connect

    Hanna, Zaher . E-mail: Zaher.Hanna@ircm.qc.ca; Priceputu, Elena; Hu, Chunyan; Vincent, Patrick; Jolicoeur, Paul

    2006-03-01

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

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

    PubMed

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

    2006-03-01

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

  7. 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

  8. Mice overexpressing 70-kDa heat shock protein show increased resistance to malonate and 3-nitropropionic acid.

    PubMed

    Dedeoglu, Alpaslan; Ferrante, Robert J; Andreassen, Ole A; Dillmann, Wolfgang H; Beal, M Flint

    2002-07-01

    Heat shock proteins (HSPs) are induced in response to oxidative stress, hypoxia-ischemia, and neuronal injury and play a protective role. Malonate and 3-nitropropionic acid (3-NP) are well-characterized animal models of Huntington's Disease (HD). They inhibit succinate dehydrogenase, inducing mitochondrial dysfunction, which triggers the generation of superoxide radicals, secondary excitotoxicity, and apoptosis. In this study, we examined whether the 70-kDa heat shock protein (HSP-70) is protective against neurotoxicity induced by malonate and 3-NP. Homozygous and heterozygous HSP-70 overexpressing mice (HSP-70+/+, HSP-70+/-) and wild-type controls received 3-NP or malonate and striatal lesion sizes were evaluated by stereology. Compared to HSP-70+/+ and HSP-70+/-, wild-type controls showed significantly larger striatal lesions following 3-NP or malonate injections. These findings support the idea that HSP-70 has a neuroprotective role that may be useful in the treatment of neurodegenerative diseases.

  9. Severe SMA mice show organ impairment that cannot be rescued by therapy with the HDACi JNJ-26481585.

    PubMed

    Schreml, Julia; Riessland, Markus; Paterno, Mario; Garbes, Lutz; Roßbach, Kristina; Ackermann, Bastian; Krämer, Jan; Somers, Eilidh; Parson, Simon H; Heller, Raoul; Berkessel, Albrecht; Sterner-Kock, Anja; Wirth, Brunhilde

    2013-06-01

    Spinal muscular atrophy (SMA) is the leading genetic cause of early childhood death worldwide and no therapy is available today. Many drugs, especially histone deacetylase inhibitors (HDACi), increase SMN levels. As all HDACi tested so far only mildly ameliorate the SMA phenotype or are unsuitable for use in humans, there is still need to identify more potent drugs. Here, we assessed the therapeutic power of the pan-HDACi JNJ-26481585 for SMA, which is currently used in various clinical cancer trials. When administered for 64 h at 100 nM, JNJ-26481585 upregulated SMN levels in SMA fibroblast cell lines, including those from non-responders to valproic acid. Oral treatment of Taiwanese SMA mice and control littermates starting at P0 showed no overt extension of lifespan, despite mild improvements in motor abilities and weight progression. Many treated and untreated animals showed a very rapid decline or unexpected sudden death. We performed exploratory autopsy and histological assessment at different disease stages and found consistent abnormalities in the intestine, heart and lung and skeletal muscle vasculature of SMA animals, which were not prevented by JNJ-26481585 treatment. Interestingly, some of these features may be only indirectly caused by α-motoneuron function loss but may be major life-limiting factors in the course of disease. A better understanding of - primary or secondary - non-neuromuscular organ involvement in SMA patients may improve standard of care and may lead to reassessment of how to investigate SMA patients clinically.

  10. Abnormal Mammary Adipose Tissue Environment of Brca1 Mutant Mice Show a Persistent Deposition of Highly Vascularized Multilocular Adipocytes.

    PubMed

    Jones, Laundette P; Buelto, Destiney; Tago, Elaine; Owusu-Boaitey, Kwadwo E

    2011-12-08

    A major challenge to breast cancer research is the identification of alterations in the architecture and composition of the breast that are associated with breast cancer progression. The aim of the present investigation was to characterize the mammary adipose phenotype from Brca1 mutant mice in the expectation that this would shed light on the role of the mammary tissue environment in the early stages of breast tumorigenesis. We observed that histological sections of mammary tissue from adult Brca1 mutant mice abnormally display small, multilocular adipocytes that are reminiscent of brown adipose tissue (BAT) as compared to wildtype mice. Using a marker for BAT, the uncoupling protein 1 (UCP1), we demonstrated that these multilocular adipose regions in Brca1 mutant mice stain positive for UCP1. Transcriptionally, UCP1 mRNA levels in the Brca1 mutant mice were elevated greater than 50-fold compared to age-matched mammary glands from wildtype mice. Indeed, BAT has characteristics that are favorable for tumor growth, including high vascularity. Therefore, we also demonstrated that the multilocular brown adipose phenotype in the mammary fat pad of Brca1 mutant mice displayed regions of increased vascularity as evidenced by a significant increase in the protein expression of CD31, a marker for angiogenesis. This Brca1 mutant mouse model should provide a physiologically relevant context to determine whether brown adipose tissue can play a role in breast cancer development.

  11. T cells from baxalpha transgenic mice show accelerated apoptosis in response to stimuli but do not show restored DNA damage-induced cell death in the absence of p53.

    PubMed Central

    Brady, H J; Salomons, G S; Bobeldijk, R C; Berns, A J

    1996-01-01

    Baxalpha was isolated due to its interaction with Bcl-2. Baxalpha overexpression in an interleukin (IL)-3 dependent cell line accelerates apoptosis upon removal of the cytokine. The ratio of Baxalpha to Bcl-2 appears to be crucial for the effect. To study the action of the bax gene product in vivo, we have generated transgenic mice overexpressing Baxalpha specifically in T cells. Such T cells show accelerated apoptosis in response to gamma-radiation, dexamethasone and etoposide. By crossing baxalpha mice with bcl-2 transgenics we show that the critical nature of the Baxalpha:Bcl-2 ratio holds in primary T cells and that it can be manipulated to elicit a strong response to previously resisted stimuli. p53 has a role in the regulation of apoptosis in response to DNA-damaging agents. p53 directly activates transcription of the bax gene. The presence of the baxalpha transgene accelerated apoptosis in thymocytes from both p53-l- and p53+l- mice in response to dexamethasone. Thymocytes from p53-l- mice with the baxalpha transgene showed similar resistance to apoptosis by DNA-damaging agents as did p53-l- mice without the transgene. Baxalpha overexpression alone cannot restore the DNA damage apoptosis pathway, suggesting that p53 is required to induce or activate other factor(s) to reconstitute the response fully. Images PMID:8635454

  12. Transmembrane domain Nrg1 mutant mice show altered susceptibility to the neurobehavioural actions of repeated THC exposure in adolescence.

    PubMed

    Long, Leonora E; Chesworth, Rose; Huang, Xu-Feng; McGregor, Iain S; Arnold, Jonathon C; Karl, Tim

    2013-02-01

    Heavy cannabis abuse increases the risk of developing schizophrenia. Adolescents appear particularly vulnerable to the development of psychosis-like symptoms after cannabis use. To test whether the schizophrenia candidate gene neuregulin 1 (NRG1) modulates the effects of cannabinoids in adolescence, we tested male adolescent heterozygous transmembrane domain Nrg1 mutant (Nrg1 TM HET) mice and wild type-like littermates (WT) for their neurobehavioural response to repeated Δ(9)-tetrahydrocannabinol (THC, 10 mg/kg i.p. for 21 d starting on post-natal day 31). During treatment and 48 h after treatment withdrawal, we assessed several behavioural parameters relevant to schizophrenia. After behavioural testing we measured autoradiographic CB(1), 5-HT(2A) and NMDA receptor binding. The hyperlocomotor phenotype typical of Nrg1 mutants emerged after drug withdrawal and was more pronounced in vehicle than THC-treated Nrg1 TM HET mice. All mice were equally sensitive to THC-induced suppression of locomotion. However, mutant mice appeared protected against inhibiting effects of repeated THC on investigative social behaviours. Neither THC nor Nrg1 genotype altered prepulse inhibition. Repeated adolescent THC promoted differential effects on CB(1) and 5-HT(2A) receptor binding in the substantia nigra and insular cortex respectively, decreasing binding in WT while increasing it in Nrg1 TM HET mice. THC also selectively affected 5-HT(2A) receptor binding in several other regions in WT mice, whereas NMDA receptor binding was only affected in mutant mice. Overall, Nrg1 mutation does not appear to increase the induction of psychotomimetic symptoms by repeated adolescent THC exposure but may attenuate some of its actions on social behaviour and schizophrenia-relevant neurotransmitter receptor profiles.

  13. Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats.

    PubMed

    Jelovac, N; Sikiric, P; Rucman, R; Petek, M; Marovic, A; Perovic, D; Seiwerth, S; Mise, S; Turkovic, B; Dodig, G; Miklic, P; Buljat, G; Prkacin, I

    1999-08-20

    A gastric pentadecapeptide, BPC 157, with the amino acid sequence, Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, MW 1419, known to have a variety of protective effects in gastrointestinal tract and other organs, was recently shown to particularly affect dopamine systems. For instance, it blocks the stereotypy produced acutely by amphetamine in rats, and the development of haloperidol-induced supersensitivity to amphetamine in mice. Consequently, whether pentadecapeptide BPC 157, that by itself has no cataleptogenic effect in normal animals, may attenuate the immediate effects of neuroleptics application, particularly catalepsy, was the focus of the present report. Prominent catalepsy, otherwise consistently seen in the mice treated with haloperidol (0.625, 1.25, 2.5, 5.0 and 10.0 mg/kg b.w., i.p.) and fluphenazine (0.3125, 0.625, 1.25, 2.5 and 5.0 mg/kg b.w., i.p.) after 1.5, 3, 4.5, 6 and 7.5 h following administration, was markedly attenuated when pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w., i.p.) was coadministered with the neuroleptic. The number of cataleptic mice was markedly lower throughout most of the experimental period. Moreover, on challenge with lower doses of neuroleptics, catalepsy appearance was postponed and the mice, otherwise cataleptic since the earliest period, became cataleptic later, not before 3 or 4.5 h after neuroleptic administration, especially if protected with higher pentadecapeptide dose. Besides catalepsy, coadministration of the pentadecapeptide BPC 157, given in the above mentioned doses, reduced not only catalepsy but somatosensory disorientation (for 7.5 h after administration of a neuroleptic, assessed at intervals of 1.5 h, by a simple scoring system [0-5]) in haloperidol- or fluphenazine-challenged mice as it did in mice treated with sulpiride (20, 40, 80 and 160 mg/kg b.w., i.p.) or with clozapine (25, 50 and 100 mg/kg b.w., i.p.), in which case catalepsy was absent. In other experiments, considering

  14. 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.

  15. Elastin-insufficient mice show normal cardiovascular remodeling in 2K1C hypertension despite higher baseline pressure and unique cardiovascular architecture.

    PubMed

    Wagenseil, Jessica E; Knutsen, Russell H; Li, Dean Y; Mecham, Robert P

    2007-07-01

    Mice heterozygous for the elastin gene (ELN(+/-)) show unique cardiovascular properties, including increased blood pressure and smaller, thinner arteries with an increased number of lamellar units. Some of these properties are also observed in humans with supravalvular aortic stenosis, a disease caused by functional heterozygosity of the elastin gene. The arterial geometry in ELN(+/-) mice is contrary to the increased thickness that would be expected in an animal demonstrating hypertensive remodeling. To determine whether this is due to a decreased capability for cardiovascular remodeling or to a novel adaptation of the ELN(+/-) cardiovascular system, we increased blood pressure in adult ELN(+/+) and ELN(+/-) mice using the two-kidney, one-clip Goldblatt model of hypertension. Successfully clipped mice have a systolic pressure increase of at least 15 mmHg over sham-operated animals. ELN(+/+) and ELN(+/-)-clipped mice show significant increases over sham-operated mice in cardiac weight, arterial thickness, and arterial cross-sectional area with no changes in lamellar number. There are no significant differences in most mechanical properties with clipping in either genotype. These results indicate that ELN(+/+) and ELN(+/-) hearts and arteries remodel similarly in response to adult induced hypertension. Therefore, the cardiovascular properties of ELN(+/-) mice are likely due to developmental remodeling in response to altered hemodynamics and reduced elastin levels.

  16. Lectin-like, oxidized low-density lipoprotein receptor-1-deficient mice show resistance to age-related knee osteoarthritis

    PubMed Central

    Hashimoto, Kazuhiko; Oda, Yutaka; Nakamura, Fumihisa; Kakinoki, Ryosuke; Akagi, Masao

    2017-01-01

    The lectin-like, oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system contributes to atherosclerosis and may be involved in cartilage degeneration. The purpose of this study was to determine whether the LOX-1/ox-LDL system contributes to age-related osteoarthritis (OA) in vivo, using LOX-1 knockout (LOX-1 KO) mice. Knee cartilage from 6, 12, and 18-month old (n = 10/group) C57Bl/6 wild-type (WT) and LOX-1 KO mice was evaluated by determining the Osteoarthritis Research Society International (OARSI) score of Safranin-O stained samples. The prevalence of knee OA in both mouse strains was also investigated. Expression levels of LOX-1, ox-LDL, runt-related transcription factor-2 (Runx2), type-X collagen (COL X), and matrix metalloproteinase-13 (MMP-13) in the articular chondrocytes were analyzed immunohistologically. No significant difference was observed in the mean scores of WT (2.00±0.61) and LOX-1 KO mice (2.00±0.49) at 6 months of age (P=1.00, n=10). At 12 and 18 months of age, the mean scores of LOX-1 KO mice (3.75±0.93 and 5.50±0.78) were significantly lower than those of WT mice (5.25±1.14 and 9.00±1.01; P<0.001 in both cases; n=10). The prevalence of OA in LOX-1 KO mice was lower than that in WT mice at 12 and 18 months of age (40 vs 70%, 70 vs 90%, respectively; n=10). The expression levels of Runx2, COL X, and MMP-13 in articular chondrocytes significantly decreased in LOX-1 KO, mice compared with those in WT mice. The study indicated that the LOX-1/ox-LDL system in chondrocytes plays a role in the pathogenesis of age-related knee OA, which is potentially a target for preventing OA progression. PMID:28348422

  17. Forebrain-specific constitutively active CaMKKα transgenic mice show deficits in hippocampus-dependent long-term memory.

    PubMed

    Kaitsuka, Taku; Li, Sheng-Tian; Nakamura, Kenji; Takao, Keizo; Miyakawa, Tsuyoshi; Matsushita, Masayuki

    2011-09-01

    The Ca(2+)/calmodulin (CaM) kinase cascade is activated by Ca(2+) influx through the voltage-dependent Ca(2+) channels and the NMDA receptor. CaM kinase kinase (CaMKK), the most upstream kinase of the CaM kinase cascade, phosphorylates and activates both CaM kinase I (CaMKI) and CaMKIV, resulting in activation of cyclic AMP-responsive element binding protein (CREB)-dependent gene transcription. Using transgenic techniques, we created mutant mice in which a constitutively active form of CaMKK1, the autoinhibitory domain truncated protein, is over-expressed specifically in the forebrain. In these mice, although performance was normal in basal activity and short-term memory, specific impairments were shown in hippocampus-dependent long-term memory after training in spatial memory tasks and after contextual fear conditioning. In cultured neurons of these mice, phosphorylation of CaMKI was significantly increased in basal states, whereas the activity range of CaMKI phosphorylation by brain-derived neurotrophic factor (BDNF) and KCl stimulation was significantly diminished in mutant mice. Our results define a critical role for CaMKKα in synaptic plasticity and the retention of hippocampus-dependent long-term memory.

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

    PubMed

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

    2014-01-01

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

  19. Mice Deficient in GEM GTPase Show Abnormal Glucose Homeostasis Due to Defects in Beta-Cell Calcium Handling

    PubMed Central

    Gunton, Jenny E.; Sisavanh, Mary; Stokes, Rebecca A.; Satin, Jon; Satin, Leslie S.; Zhang, Min; Liu, Sue M.; Cai, Weikang; Cheng, Kim; Cooney, Gregory J.; Laybutt, D. Ross; So, Trina; Molero, Juan-Carlos; Grey, Shane T.; Andres, Douglas A.

    2012-01-01

    Aims and Hypothesis Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo. Methods Gem-deficient mice were generated and their metabolic phenotype characterised by in vivo testing of glucose tolerance, insulin tolerance and insulin secretion. Calcium flux was measured in isolated islets. Results Gem-deficient mice were glucose intolerant and had impaired glucose stimulated insulin secretion. Furthermore, the islets of Gem-deficient mice exhibited decreased free calcium responses to glucose and the calcium oscillations seen upon glucose stimulation were smaller in amplitude and had a reduced frequency. Conclusions These results suggest that Gem plays an important role in normal beta-cell function by regulation of calcium signalling. PMID:22761801

  20. 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.

  1. Mice lacking acid-sensing ion channels (ASIC) 1 or 2, but not ASIC3, show increased pain behaviour in the formalin test.

    PubMed

    Staniland, Amelia A; McMahon, Stephen B

    2009-07-01

    Extracellular acidification is a component of the inflammatory process and may be a factor driving the pain accompanying it. Acid-sensing ion channels (ASICs) are neuronal proton sensors and evidence suggests they are involved in signalling inflammatory pain. The aims of this study were to (1) clarify the role of ASICs in nociception and (2) confirm their involvement in inflammatory pain and determine whether this was subunit specific. This was achieved by (1) direct comparison of the sensitivity of ASIC1, ASIC2, ASIC3 and TRPV1 knockout mice versus wildtype littermates to acute thermal and mechanical noxious stimuli and (2) studying the behavioural responses of each transgenic strain to hind paw inflammation with either complete Freund's adjuvant (CFA) or formalin. Naïve ASIC1(-/-) and ASIC2(-/-) mice responded normally to acute noxious stimuli, whereas ASIC3(-/-) mice were hypersensitive to high intensity thermal stimuli. CFA injection decreased mechanical and thermal withdrawal thresholds for up to 8 days. ASIC2(-/-) mice had increased mechanical sensitivity on day 1 post-CFA compared to wildtype controls. TRPV1(-/-) mice had significantly reduced thermal, but not mechanical, hyperalgesia on all days after inflammation. Following formalin injection, ASIC1(-/-) and ASIC2(-/-), but not ASIC3(-/-) or TRPV1(-/-), mice showed enhanced pain behaviour, predominantly in the second phase of the test. These data suggest that whilst ASICs may play a role in mediating inflammatory pain, this role is likely to be modulatory and strongly dependent on channel subtype.

  2. Mice Homozygous for a Deletion in the Glaucoma Susceptibility Locus INK4 Show Increased Vulnerability of Retinal Ganglion Cells to Elevated Intraocular Pressure.

    PubMed

    Gao, Shan; Jakobs, Tatjana C

    2016-04-01

    A genomic region located on chromosome 9p21 is associated with primary open-angle glaucoma and normal tension glaucoma in genome-wide association studies. The genomic region contains the gene for a long noncoding RNA called CDKN2B-AS, two genes that code for cyclin-dependent kinase inhibitors 2A and 2B (CDKN2A/p16(INK4A) and CDKN2B/p15(INK4B)) and an additional protein (p14(ARF)). We used a transgenic mouse model in which 70 kb of murine chromosome 4, syntenic to human chromosome 9p21, are deleted to study whether this deletion leads to a discernible phenotype in ocular structures implicated in glaucoma. Homozygous mice of this strain were previously reported to show persistent hyperplastic primary vitreous. Fundus photography and optical coherence tomography confirmed that finding but showed no abnormalities for heterozygous mice. Optokinetic response, eletroretinogram, and histology indicated that the heterozygous and mutant retinas were normal functionally and morphologically, whereas glial cells were activated in the retina and optic nerve head of mutant eyes. In quantitative PCR, CDKN2B expression was reduced by approximately 50% in the heterozygous mice and by 90% in the homozygous mice, which suggested that the CDKN2B knock down had no deleterious consequences for the retina under normal conditions. However, compared with wild-type and heterozygous animals, the homozygous mice are more vulnerable to retinal ganglion cell loss in response to elevated intraocular pressure.

  3. Neuropeptide Y Overexpressing Female and Male Mice Show Divergent Metabolic but Not Gut Microbial Responses to Prenatal Metformin Exposure

    PubMed Central

    Salomäki-Myftari, Henriikka; Vähätalo, Laura H.; Ailanen, Liisa; Pietilä, Sami; Laiho, Asta; Hänninen, Arno; Pursiheimo, Juha-Pekka; Munukka, Eveliina; Rintala, Anniina; Savontaus, Eriika; Pesonen, Ullamari; Koulu, Markku

    2016-01-01

    Background Prenatal metformin exposure has been shown to improve the metabolic outcome in the offspring of high fat diet fed dams. However, if this is evident also in a genetic model of obesity and whether gut microbiota has a role, is not known. Methods The metabolic effects of prenatal metformin exposure were investigated in a genetic model of obesity, mice overexpressing neuropeptide Y in the sympathetic nervous system and in brain noradrenergic neurons (OE-NPYDβH). Metformin was given for 18 days to the mated female mice. Body weight, body composition, glucose tolerance and serum parameters of the offspring were investigated on regular diet from weaning and sequentially on western diet (at the age of 5–7 months). Gut microbiota composition was analysed by 16S rRNA sequencing at 10–11 weeks. Results In the male offspring, metformin exposure inhibited weight gain. Moreover, weight of white fat depots and serum insulin and lipids tended to be lower at 7 months. In contrast, in the female offspring, metformin exposure impaired glucose tolerance at 3 months, and subsequently increased body weight gain, fat mass and serum cholesterol. In the gut microbiota, a decline in Erysipelotrichaceae and Odoribacter was detected in the metformin exposed offspring. Furthermore, the abundance of Sutterella tended to be decreased and Parabacteroides increased. Gut microbiota composition of the metformin exposed male offspring correlated to their metabolic phenotype. Conclusion Prenatal metformin exposure caused divergent metabolic phenotypes in the female and male offspring. Nevertheless, gut microbiota of metformin exposed offspring was similarly modified in both genders. PMID:27681875

  4. Influence of gender and time diet exposure on endocrine pancreas remodeling in response to high fat diet-induced metabolic disturbances in mice.

    PubMed

    Oliveira, R B; Maschio, D A; Carvalho, C P F; Collares-Buzato, C B

    2015-07-01

    In this study, we investigated a possible sexual dimorphism regarding metabolic response and structural and functional adaptations of the endocrine pancreas after exposure to a high-fat diet (HFd). On chow diet, male and female C57BL/6/JUnib mice showed similar metabolic and morphometric parameters, except that female islets displayed a relatively lower β-cell:non-β-cell ratio. After 30 days on HFd, both male and female mice showed increased weight gain, however only the males displayed glucose intolerance associated with high postprandial glycemia when compared to their controls. After 60 days on HFd, both genders became obese, hyperglycemic, hyperinsulinemic, insulin resistant and glucose intolerant, although the metabolic changes were more pronounced in males, while females displayed greater weight gain. In both genders, insulin resistance induced by HFd feeding was compensated by expansion of β-cell mass without changes in islet cytoarchitecture. Interestingly, we found a strong correlation between the degree of β-cell expansion and the levels of hyperglycemia in the fed state: male mice fed a 60d-HFd, showing higher glycemic levels also displayed a greater β-cell mass increase in comparison with female mice. Additionally, sexual dimorphism was also observed regarding the source of β-cell mass expansion following 60d-HFd: while in males, both hypertrophy and hyperplasia (revealed by morphometry and Ki67 immunoreaction) of β-cells were observed, female islets displayed only a significant increase in β-cell size. In conclusion, this study describes gender differences in metabolic response to high fat diet, paralleled by distinct compensatory morphometric changes in pancreatic islets.

  5. Mandibular coronoid process in parathyroid hormone-related protein-deficient mice shows ectopic cartilage formation accompanied by abnormal bone modeling.

    PubMed

    Shibata, Shunichi; Suda, Naoto; Fukada, Kenji; Ohyama, Kimie; Yamashita, Yasuo; Hammond, Vicki E

    2003-07-01

    Parathyroid hormone-related protein (PTHrP) null mutant mice were analyzed to investigate an additional role for PTHrP in cell differentiation. We found ectopic cartilage formation in the mandibular coronoid process in newborn mice. While many previous studies involving PTHrP gene knockout mouse have shown that the cartilage in various regions becomes smaller, this is the first report showing an "increase" of cartilage volume. Investigations of mandibular growth using normal mice indicated that coronoid secondary cartilage never formed from E 15 to d 4, but small amount of cartilage temporally formed at d 7, and this also applies to PTHrP-wild type mice. Therefore, PTHrP deficiency consequently advanced the secondary cartilage formation, which is a novel role of PTHrP in chondrocyte differentiation. In situ hybridization of matrix proteins showed that this coronoid cartilage had characteristics of the lower hypertrophic cell zone usually present at the site of endochondral bone formation and/or "chondroid bone" occasionally found in distraction osteogenesis. In addition, the coronoid process in the PTHrP-deficient mouse also showed abnormal expansion of bone marrow and an increase in the number of multinucleated osteoclasts, an indication of abnormal bone modeling. These results indicate that PTHrP is involved in bone modeling as well as in chondrocyte differentiation. In situ hybridization of matrix protein mRNAs in the abnormal mandibular condylar cartilage revealed that this cartilage was proportionally smaller, supporting previous immunohistochemical results.

  6. Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-β Signaling.

    PubMed

    van der Pluijm, I; van Vliet, N; von der Thusen, J H; Robertus, J L; Ridwan, Y; van Heijningen, P M; van Thiel, B S; Vermeij, M; Hoeks, S E; Buijs-Offerman, R M G B; Verhagen, H J M; Kanaar, R; Bertoli-Avella, A M; Essers, J

    2016-10-01

    Aneurysm-osteoarthritis syndrome characterized by unpredictable aortic aneurysm formation, is caused by SMAD3 mutations. SMAD3 is part of the SMAD2/3/4 transcription factor, essential for TGF-β-activated transcription. Although TGF-β-related gene mutations result in aneurysms, the underlying mechanism is unknown. Here, we examined aneurysm formation and progression in Smad3(-/-) animals. Smad3(-/-) animals developed aortic aneurysms rapidly, resulting in premature death. Aortic wall immunohistochemistry showed no increase in extracellular matrix and collagen accumulation, nor loss of vascular smooth muscle cells (VSMCs) but instead revealed medial elastin disruption and adventitial inflammation. Remarkably, matrix metalloproteases (MMPs) were not activated in VSMCs, but rather specifically in inflammatory areas. Although Smad3(-/-) aortas showed increased nuclear pSmad2 and pErk, indicating TGF-β receptor activation, downstream TGF-β-activated target genes were not upregulated. Increased pSmad2 and pErk staining in pre-aneurysmal Smad3(-/-) aortas implied that aortic damage and TGF-β receptor-activated signaling precede aortic inflammation. Finally, impaired downstream TGF-β activated transcription resulted in increased Smad3(-/-) VSMC proliferation. Smad3 deficiency leads to imbalanced activation of downstream genes, no activation of MMPs in VSMCs, and immune responses resulting in rapid aortic wall dilatation and rupture. Our findings uncover new possibilities for treatment of SMAD3 patients; instead of targeting TGF-β signaling, immune suppression may be more beneficial.

  7. Maneb disturbs expression of superoxide dismutase and glutathione peroxidase, increases reactive oxygen species production, and induces genotoxicity in liver of adult mice.

    PubMed

    Ben Amara, Ibtissem; Ben Saad, Hajer; Hamdaoui, Latifa; Karray, Aida; Boudawara, Tahia; Ben Ali, Yassine; Zeghal, Najiba

    2015-08-01

    Maneb (MB), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. However there is a lack of informations regarding the risks arising from MB exposure on non target organisms, especially mammals. The aim of this study was to investigate the morphological, biochemical and molecular aspects of liver injury after exposure of mice to MB. Four doses of MB corresponding to 1/8 (group D1), 1/6 (group D2), 1/4 (group D3), and 1/2 (group D4) of lethal dose (DL50 = 1500 mg/kg body weight) were administered to adult mice. Oxidative stress parameters were also objectified by molecular and histological endpoints in the liver. Maneb caused hepatotoxicity as characterized by the significant increase in the levels of malondialdehyde and protein oxidation marker, advanced oxidation protein products (AOPP). The activities of catalase, glutathione peroxidase, superoxide dismutase and the levels of glutathione decreased significantly in all treated mice, while vitamin C levels decreased only in group D4. We also noted a significant decrease in gene expression of superoxide dismutase and glutathione peroxidase enzymes. Maneb caused nucleic acids degradation testifying its genotoxicity. Yet, biochemical markers in plasma showed a decrease in total protein and an increase in aspartate, alanine amino transferases and bilirubin levels in all treatment groups. Moreover, plasma levels of cholesterol, triglycerides and low density lipoprotein-cholesterol significantly increased, while those of high density lipoprotein-cholesterol decreased. These biochemical alterations were correlated with significantly histological changes. Our data showed, for the first time, that intraperitoneal injection of very high non environmentally relevant MB concentrations to adult mice resulted in oxidative stress leading to hepatotoxicity and the impairment of defense systems, confirming the

  8. Anxious and Nonanxious Mice Show Similar Hippocampal Sensory Evoked Oscillations under Urethane Anesthesia: Difference in the Effect of Buspirone

    PubMed Central

    Horváth, János; Barkóczi, Balázs; Müller, Géza

    2015-01-01

    Hippocampal oscillations recorded under urethane anesthesia are proposed to be modulated by anxiolytics. All classes of clinically effective anxiolytics were reported to decrease the frequency of urethane theta; however, recent findings raise concerns about the direct correlation of anxiolysis and the frequency of hippocampal theta. Here, we took advantage of our two inbred mouse strains displaying extremes of anxiety (anxious (AX) and nonanxious (nAX)) to compare the properties of hippocampal activity and to test the effect of an anxiolytic drugs. No difference was observed in the peak frequency or in the peak power between AX and nAX strains. Buspirone (Bus) applied in 2.5 mg/kg decreased anxiety of AX but did not have any effect on nAX as was tested by elevated plus maze and open field. Interestingly, Bus treatment increased hippocampal oscillatory frequency in the AX but left it unaltered in nAX mice. Saline injection did not have any effect on the oscillation. Paired-pulse facilitation was enhanced by Bus in the nAX, but not in the AX strain. Collectively, these results do not support the hypothesis that hippocampal activity under urethane may serve as a marker for potential anxiolytic drugs. Moreover, we could not confirm the decrease of frequency after anxiolytic treatment. PMID:25949829

  9. Size does not always matter: Ts65Dn Down syndrome mice show cerebellum-dependent motor learning deficits that cannot be rescued by postnatal SAG treatment.

    PubMed

    Gutierrez-Castellanos, Nicolas; Winkelman, Beerend H J; Tolosa-Rodriguez, Leonardo; Devenney, Benjamin; Reeves, Roger H; De Zeeuw, Chris I

    2013-09-25

    Humans with Down syndrome (DS) and Ts65Dn mice both show a reduced volume of the cerebellum due to a significant reduction in the density of granule neurons. Recently, cerebellar hypoplasia in Ts65Dn mice was rescued by a single treatment with SAG, an agonist of the Sonic hedgehog pathway, administered on the day of birth. In addition to normalizing cerebellar morphology, this treatment restored the ability to learn a spatial navigation task, which is associated with hippocampal function. It is not clear to what extent this improved performance results from restoration of the cerebellar architecture or a yet undefined role of Sonic hedgehog (Shh) in perinatal hippocampal development. The absence of a clearly demonstrated deficit in cerebellar function in trisomic mice exacerbates the problem of discerning how SAG acts to improve learning and memory. Here we show that phase reversal adaptation and consolidation of the vestibulo-ocular reflex is significantly impaired in Ts65Dn mice, providing for the first time a precise characterization of cerebellar functional deficits in this murine model of DS. However, these deficits do not benefit from the normalization of cerebellar morphology following treatment with SAG. Together with the previous observation that the synaptic properties of Purkinje cells are also unchanged by SAG treatment, this lack of improvement in a region-specific behavioral assay supports the possibility that a direct effect of Shh pathway stimulation on the hippocampus might explain the benefits of this potential approach to the improvement of cognition in DS.

  10. FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

    PubMed Central

    Kuroda, Kumi O; Ornthanalai, Veravej G; Kato, Tadafumi; Murphy, Niall P

    2010-01-01

    Previous studies show that (1) two members of fos family transcription factors, c-Fos and FosB, are induced in frontal brain regions by methamphetamine; (2) null mutation of c-Fos exacerbates methamphetamine-induced neurotoxicity; and (3) null mutation of FosB enhances behavioral responses to cocaine. Here we sought a role of FosB in responses to methamphetamine by studying FosB null mutant (−/−) mice. After a 10 mg/kg methamphetamine injection, FosB(−/−) mice were more prone to self-injury. Concomitantly, the intracellular feedback regulators of Sprouty and Rad-Gem-Kir (RGK) family transcripts had lower expression profiles in the frontoparietal cortex and striatum of the FosB(−/−) mice. Three days after administration of four 10 mg/kg methamphetamine injections, the frontoparietal cortex and striatum of FosB(−/−) mice contained more degenerated neurons as determined by Fluoro-Jade B staining. The abundance of the small neutral amino acids, serine, alanine, and glycine, was lower and/or was poorly induced after methamphetamine administration in the frontoparietal cortex and striatum of FosB(−/−) mice. In addition, methamphetamine-treated FosB(−/−) frontoparietal and piriform cortices showed more extravasation of immunoglobulin, which is indicative of blood–brain barrier dysfunction. Methamphetamine-induced hyperthermia, brain dopamine content, and loss of tyrosine hydroxylase immunoreactivity in the striatum, however, were not different between genotypes. These data indicate that FosB is involved in thermoregulation-independent protective functions against methamphetamine neurotoxicity in postsynaptic neurons. Our findings suggest two possible mechanisms of FosB-mediated neuroprotection: one is induction of negative feedback regulation within postsynaptic neurons through Sprouty and RGK. Another is supporting astroglial function such as maintenance of the blood–brain barrier, and metabolism of serine and glycine, which are important

  11. FosB null mutant mice show enhanced methamphetamine neurotoxicity: potential involvement of FosB in intracellular feedback signaling and astroglial function.

    PubMed

    Kuroda, Kumi O; Ornthanalai, Veravej G; Kato, Tadafumi; Murphy, Niall P

    2010-02-01

    Previous studies show that (1) two members of fos family transcription factors, c-Fos and FosB, are induced in frontal brain regions by methamphetamine; (2) null mutation of c-Fos exacerbates methamphetamine-induced neurotoxicity; and (3) null mutation of FosB enhances behavioral responses to cocaine. Here we sought a role of FosB in responses to methamphetamine by studying FosB null mutant (-/-) mice. After a 10 mg/kg methamphetamine injection, FosB(-/-) mice were more prone to self-injury. Concomitantly, the intracellular feedback regulators of Sprouty and Rad-Gem-Kir (RGK) family transcripts had lower expression profiles in the frontoparietal cortex and striatum of the FosB(-/-) mice. Three days after administration of four 10 mg/kg methamphetamine injections, the frontoparietal cortex and striatum of FosB(-/-) mice contained more degenerated neurons as determined by Fluoro-Jade B staining. The abundance of the small neutral amino acids, serine, alanine, and glycine, was lower and/or was poorly induced after methamphetamine administration in the frontoparietal cortex and striatum of FosB(-/-) mice. In addition, methamphetamine-treated FosB(-/-) frontoparietal and piriform cortices showed more extravasation of immunoglobulin, which is indicative of blood-brain barrier dysfunction. Methamphetamine-induced hyperthermia, brain dopamine content, and loss of tyrosine hydroxylase immunoreactivity in the striatum, however, were not different between genotypes. These data indicate that FosB is involved in thermoregulation-independent protective functions against methamphetamine neurotoxicity in postsynaptic neurons. Our findings suggest two possible mechanisms of FosB-mediated neuroprotection: one is induction of negative feedback regulation within postsynaptic neurons through Sprouty and RGK. Another is supporting astroglial function such as maintenance of the blood-brain barrier, and metabolism of serine and glycine, which are important glial modulators of nerve cells.

  12. 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.

  13. 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

  14. Prion Protein (PrP) Knock-Out Mice Show Altered Iron Metabolism: A Functional Role for PrP in Iron Uptake and Transport

    PubMed Central

    Singh, Ajay; Kong, Qingzhong; Luo, Xiu; Petersen, Robert B.; Meyerson, Howard; Singh, Neena

    2009-01-01

    Despite overwhelming evidence implicating the prion protein (PrP) in prion disease pathogenesis, the normal function of this cell surface glycoprotein remains unclear. In previous reports we demonstrated that PrP mediates cellular iron uptake and transport, and aggregation of PrP to the disease causing PrP-scrapie (PrPSc) form results in imbalance of iron homeostasis in prion disease affected human and animal brains. Here, we show that selective deletion of PrP in transgenic mice (PrPKO) alters systemic iron homeostasis as reflected in hematological parameters and levels of total iron and iron regulatory proteins in the plasma, liver, spleen, and brain of PrPKO mice relative to matched wild type controls. Introduction of radiolabeled iron (59FeCl3) to Wt and PrPKO mice by gastric gavage reveals inefficient transport of 59Fe from the duodenum to the blood stream, an early abortive spike of erythropoiesis in the long bones and spleen, and eventual decreased 59Fe content in red blood cells and all major organs of PrPKO mice relative to Wt controls. The iron deficient phenotype of PrPKO mice is reversed by expressing Wt PrP in the PrPKO background, demonstrating a functional role for PrP in iron uptake and transport. Since iron is required for essential metabolic processes and is also potentially toxic if mismanaged, these results suggest that loss of normal function of PrP due to aggregation to the PrPSc form induces imbalance of brain iron homeostasis, resulting in disease associated neurotoxicity. PMID:19568430

  15. Emotional Disturbance

    MedlinePlus

    ... Resources of More Information References Back to top Definition We’ve chosen to use the term “emotional ... to top Characteristics As is evident in IDEA’s definition, emotional disturbances can affect an individual in areas ...

  16. Caveolin-1-deficient Mice Show Accelerated Mammary Gland Development During Pregnancy, Premature Lactation, and Hyperactivation of the Jak-2/STAT5a Signaling Cascade

    PubMed Central

    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.

    2002-01-01

    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. PMID:12388746

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

    PubMed

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

    2016-03-01

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

  18. The characterization of the first anti-mouse Muc6 antibody shows an increased expression of the mucin in pancreatic tissue of Cftr-knockout mice.

    PubMed

    Gouyer, Valérie; Leir, Shih-Hsing; Tetaert, Daniel; Liu, Yamin; Gottrand, Frédéric; Harris, Ann; Desseyn, Jean-Luc

    2010-05-01

    Gel-forming mucins are large high-molecular weight secreted O-glycoproteins responsible for the gel-properties of the mucus blanket. Five orthologous gel-forming mucins have been cloned in human and mouse. Among them, the mucin MUC6 has been less studied, particularly in rodents and no anti rodent-Muc6 antibody has been reported yet. In order to further study Muc6 in mice, our aims were to obtain a specific Muc6 antibody, to validate it and to test it in Cftr deficient mice. A polyclonal serum named CP4 was isolated from a rabbit immunized by a mouse Muc6 peptide. In Western blot experiments, the antibody detected a high-molecular weight molecule secreted by the gastric tissue. Using immunohistochemistry, we showed that the antibody reacted strongly with deep glands of duodenum and ileum and mucous neck cells of gastric body. CP4 also recognized Muc6 protein secreted at the surface of the stomach and renal collecting tubules. The centroacinar cells of pancreatic tissue also reacted with the antibody. Cftr-/- mice showed a higher expression of Muc6 at both protein and RNA levels compared with their control Cftr+/+ littermates suggesting that as in the human disease, Muc6 may contribute to the formation of materials that block pancreatic acini and ducts in mouse models of cystic fibrosis. The rabbit anti-mouse Muc6 polyclonal antibody seems highly specific to the mouse mucin and will be useful to study pancreatic pathology in cystic fibrosis.

  19. Viable RNaseH1 knockout mice show RNaseH1 is essential for R loop processing, mitochondrial and liver function

    PubMed Central

    Lima, Walt F.; Murray, Heather M.; Damle, Sagar S.; Hart, Christopher E.; Hung, Gene; De Hoyos, Cheryl Li; Liang, Xue-Hai; Crooke, Stanley T.

    2016-01-01

    Viable constitutive and tamoxifen inducible liver-specific RNase H1 knockout mice that expressed no RNase H1 activity in hepatocytes showed increased R-loop levels and reduced mitochondrial encoded DNA and mRNA levels, suggesting impaired mitochondrial R-loop processing, transcription and mitochondrial DNA replication. These changes resulted in mitochondrial dysfunction with marked changes in mitochondrial fusion, fission, morphology and transcriptional changes reflective of mitochondrial damage and stress. Liver degeneration ensued, as indicated by apoptosis, fibrosis and increased transaminase levels. Antisense oligonucleotides (ASOs) designed to serve as substrates for RNase H1 were inactive in the hepatocytes from the RNase H1 knockout mice and in vivo, demonstrating that RNase H1 is necessary for the activity of DNA-like ASOs. During liver regeneration, a clone of hepatocytes that expressed RNase H1 developed and partially restored mitochondrial and liver function. PMID:27131367

  20. Exposure of Neonatal Mice to Tobacco Smoke Disturbs Synaptic Proteins and Spatial Learning and Memory from Late Infancy to Early Adulthood.

    PubMed

    Torres, Larissa Helena; Garcia, Raphael C T; Blois, Anne M M; Dati, Lívia M M; Durão, Ana Carolina; Alves, Adilson Silva; Pacheco-Neto, Maurílio; Mauad, Thais; Britto, Luiz R G; Xavier, Gilberto Fernando; Camarini, Rosana; Marcourakis, Tania

    2015-01-01

    Exposure to environmental tobacco smoke (ETS) in the early postnatal period has been associated with several diseases; however, little is known about the brain effects of ETS exposure during this critical developmental period or the long-term consequences of this exposure. This study investigated the effects of the early postnatal ETS exposure on both reference and working memory, synaptic proteins and BDNF from late infancy to early adulthood (P3-P73). BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes (0.73 mg of nicotine/cigarette) from P3 to P14. Spatial reference and working memory were evaluated in the Morris water maze during infancy (P20-P29), adolescence (P37-P42) and adulthood (P67-P72). Synapsin, synaptophysin, PSD95 and brain-derived neurotrophic factor (BDNF) were assessed at P15, P35 and P65 by immunohistochemistry and immunoblotting. Mice that were exposed to ETS during the early postnatal period showed poorer performance in the spatial reference memory task. Specifically, the ETS-exposed mice exhibited a significantly reduced time and distance traveled in the target quadrant and in the platform location area than the controls at all ages evaluated. In the spatial working memory task, ETS disrupted the maintenance but not the acquisition of the critical spatial information in both infancy and adolescence. ETS also induced changes in synaptic components, including decreases in synapsin, synaptophysin, PSD95 and BDNF levels in the hippocampus. Exposure to ETS in the early postnatal period disrupts both spatial reference and working memory; these results may be related to changes in synaptogenesis in the hippocampus. Importantly, most of these effects were not reversed even after a long exposure-free period.

  1. Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice.

    PubMed

    Zhang, Hua; Liu, Lian; Li, Xin; Busayavalasa, Kiran; Shen, Yan; Hovatta, Outi; Gustafsson, Jan-Åke; Liu, Kui

    2014-12-16

    Whether or not oocyte regeneration occurs in adult life has been the subject of much debate. In this study, we have traced germ-cell lineages over the life spans of three genetically modified mouse models and provide direct evidence that oogenesis does not originate from any germline stem cells (GSCs) in adult mice. By selective ablation of all existing oocytes in a Gdf9-Cre;iDTR mouse model, we have demonstrated that no new germ cells were ever regenerated under pathological conditions. By in vivo tracing of oocytes and follicles in the Sohlh1-CreER(T2);R26R and Foxl2-CreER(T2);mT/mG mouse models, respectively, we have shown that the initial pool of oocytes is the only source of germ cells throughout the life span of the mice and that no adult oogenesis ever occurs under physiological conditions. Our findings clearly show that there are no GSCs that contribute to adult oogenesis in mice and that the initial pool of oocytes formed in early life is the only source of germ cells throughout the entire reproductive life span.

  2. 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.

  3. Male mice housed in groups engage in frequent fighting and show a lower response to additional bone loading than females or individually housed males that do not fight.

    PubMed

    Meakin, Lee B; Sugiyama, Toshihiro; Galea, Gabriel L; Browne, William J; Lanyon, Lance E; Price, Joanna S

    2013-05-01

    Experiments to investigate bone's physiological adaptation to mechanical loading frequently employ models that apply dynamic loads to bones in vivo and assess the changes in mass and architecture that result. It is axiomatic that bones will only show an adaptive response if the applied artificial loading environment differs in a significant way from that to which the bones have been habituated by normal functional loading. It is generally assumed that this normal loading is similar between experimental groups. In the study reported here we found that this was not always the case. Male and female 17-week-old C57BL/6 mice were housed in groups of six, and a single episode (40 cycles) of non-invasive axial loading, engendering 2,200 με on the medial surface of the proximal tibiae in sample mice, was applied to right tibiae on alternate days for two weeks. This engendered an adaptive increase in bone mass in females, but not males. Observation revealed the main difference in behaviour between males and females was that males were involved in fights 1.3 times per hour, whereas the females never fought. We therefore housed all mice individually. In females, there was a similar significant osteogenic response to loading in cortical and trabecular bone of both grouped and individual mice. In contrast, in males, adaptive increases in the loaded compared with non-loaded control bones was only apparent in animals housed individually. Our interpretation of these findings is that the frequent vigorous fighting that occurs between young adult males housed in groups could be sufficient to engender peak strains and strain rates that equal or exceed the stimulus derived from artificial loading. This indicates the importance of ensuring that physical activity is consistent between groups. Reducing the background level of the naturally engendered strain environment allows adaptive responses to artificial loading to be demonstrated at lower loads.

  4. 55P0110, a Novel Synthetic Compound Developed from a Plant Derived Backbone Structure, Shows Promising Anti-Hyperglycaemic Activity in Mice.

    PubMed

    Brunmair, Barbara; Lehner, Zsuzsanna; Stadlbauer, Karin; Adorjan, Immanuel; Frobel, Klaus; Scherer, Thomas; Luger, Anton; Bauer, Leonhardt; Fürnsinn, Clemens

    2015-01-01

    Starting off with a structure derived from the natural compound multiflorine, a derivatisation program aimed at the discovery and initial characterisation of novel compounds with antidiabetic potential. Design and discovery of the structures was guided by oral bioactivities obtained in oral glucose tolerance tests in mice. 55P0110, one among several new compounds with distinct anti-hyperglycaemic activity, was further examined to characterise its pharmacology and mode of action. Whereas a single oral dose of 55P0110 did not affect basal glycaemia, it markedly improved the glucose tolerance of healthy and diabetic mice (peak blood glucose in glucose tolerance test, mmol/l: healthy mice with 90 mg/kg 55P0110, 17.0 ± 1.2 vs. 10.1 ± 1.1; diabetic mice with 180 mg/kg 55P0110, 23.1 ± 0.9 vs. 11.1 ± 1.4; p<0.001 each). Closer examination argued against retarded glucose resorption from the gut, increased glucose excretion in urine, acute insulin-like or insulin sensitising properties, and direct inhibition of dipeptidyl peptidase-4 as the cause of glucose lowering. Hence, 55P0110 seems to act via a target not exploited by any drug presently approved for the treatment of diabetes mellitus. Whereas the insulinotropic sulfonylurea gliclazide (16 mg/kg) distinctly increased the circulating insulin-per-glucose ratio under basal conditions, 55P0110 (90 mg/kg) lacked such an effect (30 min. after dosing, nmol/mol: vehicle, 2.49 ± 0.27; 55P0110, 2.99 ± 0.35; gliclazide, 8.97 ± 0.49; p<0.001 each vs. gliclazide). Under an exogenous glucose challenge, however, 55P0110 increased this ratio to the same extent as gliclazide (20 min. after glucose feeding: vehicle, 2.53 ± 0.41; 55P0110, 3.80 ± 0.46; gliclazide, 3.99 ± 0.26; p<0.05 each vs. vehicle). By augmenting the glucose stimulated increase in plasma insulin, 55P0110 thus shows distinct anti-hyperglycaemic action in combination with low risk for fasting hypoglycaemia in mice. In summary, we have discovered a novel class of

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

    PubMed

    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

    2014-02-01

    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.

  6. 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.

  7. Cannabinoid receptor 1 antagonist treatment induces glucagon release and shows an additive therapeutic effect with GLP-1 agonist in diet-induced obese mice.

    PubMed

    Patel, Kartikkumar Navinchandra; Joharapurkar, Amit Arvind; Patel, Vishal; Kshirsagar, Samadhan Govind; Bahekar, Rajesh; Srivastava, Brijesh Kumar; Jain, Mukul R

    2014-12-01

    Cannabinoid 1 (CB1) receptor antagonists reduce body weight and improve insulin sensitivity. Preclinical data indicates that an acute dose of CB1 antagonist rimonabant causes an increase in blood glucose. A stable analog of glucagon-like peptide 1 (GLP-1), exendin-4 improves glucose-stimulated insulin secretion in pancreas, and reduces appetite through activation of GLP-1 receptors in the central nervous system and liver. We hypothesized that the insulin secretagogue effect of GLP-1 agonist exendin-4 may synergize with the insulin-sensitizing action of rimonabant. Intraperitoneal as well as intracerebroventricular administration of rimonabant increased serum glucose upon glucose challenge in overnight fasted, diet-induced obese C57 mice, with concomitant rise in serum glucagon levels. Exendin-4 reversed the acute hyperglycemia induced by rimonabant. The combination of exendin-4 and rimonabant showed an additive effect in the food intake, and sustained body weight reduction upon repeated dosing. The acute efficacy of both the compounds was additive for inducing nausea-like symptoms in conditioned aversion test in mice, whereas exendin-4 treatment antagonized the effect of rimonabant on forced swim test upon chronic dosing. Thus, the addition of exendin-4 to rimonabant produces greater reduction in food intake owing to increased aversion, but reduces the other central nervous system side effects of rimonabant. The hyperglucagonemia induced by rimonabant is partially responsible for enhancing the antiobesity effect of exendin-4.

  8. Artificial sweetener neohesperidin dihydrochalcone showed antioxidative, anti-inflammatory and anti-apoptosis effects against paraquat-induced liver injury in mice.

    PubMed

    Shi, Qiong; Song, Xiufang; Fu, Juanli; Su, Chuanyang; Xia, Xiaomin; Song, Erqun; Song, Yang

    2015-12-01

    The present study evaluated the protective effect of artificial sweetener neohesperidin dihydrochalcone (NHDC) against paraquat (PQ)-induced acute liver injury in mice. A single dose of PQ (75mg/kg body weight, i.p.) induced acute liver toxicity with the evidences of increased liver damage biomarkers, aspartate transaminase (AST) and alanine transaminase (ALT) activities in serum. Consistently, PQ decreased the antioxidant capacity by reducing glutathione peroxidase (GP-X), glutathione-S-transferase (GST) and catalase (CAT) activities, glutathione (GSH) level and total antioxidant capacity (T-AOC), as well as increasing reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels. Histopathological examination revealed that PQ induced numerous changes in the liver tissues. Immunochemical staining assay indicated the upregulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. However, NHDC ameliorates PQ-induced hepatic toxicity in mice by reversing these parameters. Additionally, NHDC significantly inhibited PQ-induced nuclear factor-kappa B (NF-κB) expression and mitochondrial-driven apoptotic signaling. TUNEL assay confirmed that PQ-induced apoptosis was relieved by NHDC. In conclusion, these findings suggested that NHDC showed potent antioxidant, anti-inflammatory and anti-apoptotic effects against PQ-induced acute liver damage.

  9. T-type calcium channel Cav3.2 deficient mice show elevated anxiety, impaired memory and reduced sensitivity to psychostimulants

    PubMed Central

    Gangarossa, Giuseppe; Laffray, Sophie; Bourinet, Emmanuel; Valjent, Emmanuel

    2014-01-01

    The fine-tuning of neuronal excitability relies on a tight control of Ca2+ homeostasis. The low voltage-activated (LVA) T-type calcium channels (Cav3.1, Cav3.2 and Cav3.3 isoforms) play a critical role in regulating these processes. Despite their wide expression throughout the central nervous system, the implication of T-type Cav3.2 isoform in brain functions is still poorly characterized. Here, we investigate the effect of genetic ablation of this isoform in affective disorders, including anxiety, cognitive functions as well as sensitivity to drugs of abuse. Using a wide range of behavioral assays we show that genetic ablation of the cacna1h gene results in an anxiety-like phenotype, whereas novelty-induced locomotor activity is unaffected. Deletion of the T-type channel Cav3.2 also triggers impairment of hippocampus-dependent recognition memories. Acute and sensitized hyperlocomotion induced by d-amphetamine and cocaine are dramatically reduced in T-type Cav3.2 deficient mice. In addition, the administration of the T-type blocker TTA-A2 prevented the expression of locomotor sensitization observed in wildtype mice. In conclusion, our data reveal that physiological activity of this specific Ca2+ channel is required for affective and cognitive behaviors. Moreover, our work highlights the interest of T-type channel blockers as therapeutic strategies to reverse drug-associated alterations. PMID:24672455

  10. Octaphlorethol A: a potent α-glucosidase inhibitor isolated from Ishige foliacea shows an anti-hyperglycemic effect in mice with streptozotocin-induced diabetes.

    PubMed

    Lee, Seung-Hong; Kang, Sung-Myung; Ko, Seok-Chun; Moon, Sang-Ho; Jeon, Byong-Tae; Lee, Dae Ho; Jeon, You-Jin

    2014-10-01

    α-Glucosidase inhibitors are important agents for decreasing postprandial hyperglycemia. The current study examined the inhibitory effects of octaphlorethol A (OPA) isolated from Ishige foliacea, a brown alga, on α-glucosidase, and analyzed the inhibitor's binding modes using the crystal structure of α-glucosidase. The effects of OPA on postprandial blood glucose levels after meals were also investigated. The IC50 value of OPA against α-glucosidase was 0.11 mM, which is higher than that of the commercial inhibitor acarbose. For further insights, we predicted the 3D structure of α-glucosidase and used a docking algorithm to simulate binding between α-glucosidase and OPA. These molecular modeling studies were successful, and indicated that OPA interacts with Phe575, His600, Arg526, Met444, Asp542, Tyr605, Ser448, Asp203, Lys480, and Phe450. Furthermore, increases in postprandial blood glucose levels were significantly suppressed in the OPA-treated group compared with those in the streptozotocin-induced diabetic or normal mice. Additionally, the area under the curve was significantly reduced following OPA administration (907 versus 1034 mg h dL(-1)) in the diabetic mice, along with a delay in the absorption of dietary carbohydrates. Collectively, these results indicated that OPA is a potent inhibitor of α-glucosidase, and shows potential to be used as an anti-diabetic agent.

  11. Mice deficient for the type II topoisomerase-like DNA transesterase Spo11 show normal immunoglobulin somatic hypermutation and class switching.

    PubMed

    Klein, Ulf; Esposito, Gloria; Baudat, Frédéric; Keeney, Scott; Jasin, Maria

    2002-02-01

    Somatic hypermutation in B cells undergoing T cell dependent immune responses generates high affinity antibodies that provide protective immunity. B cells also switch from the expression of immunoglobulin (Ig) M and IgD to that of other Ig classes through somatic DNA recombination. Recent work has implicated DNA strand breaks, possibly DNA double strand breaks (DSB), as the initiating lesions in both class switch recombination and hypermutation, although the etiology of these lesions is not understood. Spo11, a protein structurally related to archaeal type II topoisomerases, generates DSB that initiate meiotic recombination. This characteristic, together with its expression pattern, marks this enzyme as a potential candidate for the initiation of hypermutation, and perhaps also for Ig class switching. To investigate whether Spo11 is involved in these processes, we studied the T cell dependent immune response of Spo11-deficient (Spo11(-/-)) mice against the hapten nitrophenyl (NP). We found that V186.2-bearing IgG1 transcripts had normal levels and patterns of somatic hypermutation. Furthermore, Spo11(-/-) mice showed normal serum levels of all Ig isotypes. These results indicate that Spo11 is not required for Ig hypermutation or class switch recombination.

  12. Disturbances in cholesterol, bile acid and glucose metabolism in peroxisomal 3-ketoacylCoA thiolase B deficient mice fed diets containing high or low fat contents.

    PubMed

    Nicolas-Francès, Valérie; Arnauld, Ségolène; Kaminski, Jacques; Ver Loren van Themaat, Emiel; Clémencet, Marie-Claude; Chamouton, Julie; Athias, Anne; Grober, Jacques; Gresti, Joseph; Degrace, Pascal; Lagrost, Laurent; Latruffe, Norbert; Mandard, Stéphane

    2014-03-01

    The peroxisomal 3-ketoacyl-CoA thiolase B (ThB) catalyzes the thiolytic cleavage of straight chain 3-ketoacyl-CoAs. Up to now, the ability of ThB to interfere with lipid metabolism was studied in mice fed a laboratory chow enriched or not with the synthetic agonist Wy14,643, a pharmacological activator of the nuclear hormone receptor PPARα. The aim of the present study was therefore to determine whether ThB could play a role in obesity and lipid metabolism when mice are chronically fed a synthetic High Fat Diet (HFD) or a Low Fat Diet (LFD) as a control diet. To investigate this possibility, wild-type (WT) mice and mice deficient for Thb (Thb(-/-)) were subjected to either a synthetic LFD or a HFD for 25 weeks, and their responses were compared. First, when fed a normal regulatory laboratory chow, Thb(-/-) mice displayed growth retardation as well as a severe reduction in the plasma level of Growth Hormone (GH) and Insulin Growth Factor-I (IGF-I), suggesting alterations in the GH/IGF-1 pathway. When fed the synthetic diets, the corrected energy intake to body mass was significantly higher in Thb(-/-) mice, yet those mice were protected from HFD-induced adiposity. Importantly, Thb(-/-) mice also suffered from hypoglycemia, exhibited reduction in liver glycogen stores and circulating insulin levels under the LFD and the HFD. Thb deficiency was also associated with higher levels of plasma HDL (High Density Lipoproteins) cholesterol and increased liver content of cholesterol under both the LFD and the HFD. As shown by the plasma lathosterol to cholesterol ratio, a surrogate marker for cholesterol biosynthesis, whole body cholesterol de novo synthesis was increased in Thb(-/-) mice. By comparing liver RNA from WT mice and Thb(-/-) mice using oligonucleotide microarray and RT-qPCR, a coordinated decrease in the expression of critical cholesterol synthesizing genes and an increased expression of genes involved in bile acid synthesis (Cyp7a1, Cyp17a1, Akr1d1) were

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

    SciTech Connect

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

    2011-08-15

    Exposure during early development to chemicals with hormonal action may be associated with weight gain during adulthood because of altered body homeostasis. It is known that organotins affect adipose mass when exposure occurs during fetal development, although no knowledge of effects are available for exposures after birth. Here we show that the environmental organotin tributyltin chloride (TBT) exerts adipogenic action when peripubertal and sexually mature mice are exposed to the chemical. The duration and extent of these effects depend on the sex and on the dose of the compound, and the effects are relevant at doses close to the estimated human intake (0.5 {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 closed to

  14. A Dominant Mutation in Rpe65, D477G, Delays Dark Adaptation and Disturbs the Visual Cycle in the Mutant Knock-In Mice.

    PubMed

    Shin, Younghwa; Moiseyev, Gennadiy; Chakraborty, Dibyendu; Ma, Jian-Xing

    2017-03-01

    RPE65 is an indispensable component of the retinoid visual cycle in vertebrates, through which the visual chromophore 11-cis-retinal (11-cis-RAL) is generated to maintain normal vision. Various blinding conditions in humans, such as Leber congenital amaurosis and retinitis pigmentosa (RP), are attributed to either homozygous or compound heterozygous mutations in RPE65. Herein, we investigated D477G missense mutation, an unprecedented dominant-acting mutation of RPE65 identified in patients with autosomal dominant RP. We generated a D477G knock-in (KI) mouse and characterized its phenotypes. Although RPE65 protein levels were decreased in heterozygous KI mice, their scotopic, maximal, and photopic electroretinography responses were comparable to those of wild-type (WT) mice in stationary condition. As shown by high-performance liquid chromatography analysis, levels of 11-cis-RAL in fully dark-adapted heterozygous KI mice were similar to that in WT mice. However, kinetics of 11-cis-RAL regeneration after light exposure were significantly slower in heterozygous KI mice compared with WT and RPE65 heterozygous knockout mice. Furthermore, heterozygous KI mice exhibited lower A-wave recovery compared with WT mice after photobleaching, suggesting a delayed dark adaptation. Taken together, these observations suggest that D477G acts as a dominant-negative mutant of RPE65 that delays chromophore regeneration. The KI mice provide a useful model for further understanding of the pathogenesis of RP associated with this RPE65 mutant and for the development of therapeutic strategies.

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

    PubMed

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

    2011-08-15

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

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

    PubMed

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

    2014-07-03

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

  17. Chitosan dressing promotes healing in third degree burns in mice: gene expression analysis shows biphasic effects for rapid tissue regeneration and decreased fibrotic signaling.

    PubMed

    Baxter, Ruth M; Dai, Tianhong; Kimball, Jess; Wang, Eugenia; Hamblin, Michael R; Wiesmann, William P; McCarthy, Simon J; Baker, Shenda M

    2013-02-01

    Burns are a significant health challenge and healing can result in scar formation. Chitosan, a derivative of chitin, has been used to promote wound healing. In this study we used gene expression profiling in a mouse model of full thickness cutaneous burn to assess the benefits of treating with a chitosan lactate dressing. Three days after wounding mice treated with chitosan showed increased expression of genes associated with formation of granulation tissue. At a later time point, seven days after wounding, genes that initially showed increased expression were now down-regulated, and there was increased expression of genes involved in remodeling suggesting that the chitosan treatment results in accelerated healing. Quantitative RT-PCR showed modulated mRNA levels for TGFβ1 by the chitosan dressing. TGFβ1 initially promotes healing but extended activity can result in scarring. Importantly we found that expression was elevated at day three, but decreased at day seven suggesting that chitosan treatment will not result in scar formation, and may even be beneficial in preventing scar formation. Additionally, the biphasic regulation of expression of TGFβ1 could be a powerful biomarker for future studies of the wound-healing potential of chitosan based and other treatments for burn wounds.

  18. iNOS null MRL+/+ mice show attenuation of trichloroethene-mediated autoimmunity: contribution of reactive nitrogen species and lipid-derived reactive aldehydes

    PubMed Central

    Wang, Gangduo; Wakamiya, Maki; Wang, Jianling; Ansari, G.A.S.; Khan, M. Firoze

    2015-01-01

    Earlier studies from our laboratory in MRL+/+ mice suggest that free radicals, especially overproduction of reactive nitrogen species (RNS) and lipid-derived reactive aldehydes (LDRAs), are associated with trichloroethene (TCE)-mediated autoimmune response. The current study was undertaken to further assess the contribution of RNS and LDRAs in TCE-mediated autoimmunity by using iNOS-null MRL+/+ mice. iNOS-null MRL+/+ mice were obtained by backcrossing iNOS-null mice (B6.129P2-Nos2tm1Lau/J) to MRL +/+ mice. Female MRL+/+ and iNOS-null MRL+/+ mice were given TCE (10 mmol/kg, i.p., every 4th day) for 6 weeks; their respective controls received corn oil only. TCE exposure led to significantly increased iNOS mRNA in livers, iNOS protein in livers and sera, increased nitrotyrosine (NT) formation in both livers and sera, induction of MDA-/HNE-protein adducts in livers and their respective antibodies in sera along with significant increases in serum antinuclear antibodies (ANA) and anti-dsDNA in MRL+/+ mice. Even though in iNOS-null MRL+/+ mice, the iNOS and NT levels were negligible in both TCE-treated and untreated groups, TCE treatment still led to significant increases in MDA-/HNE-protein adducts and their respective antibodies along with increases in serum ANA and anti-dsDNA compared to controls. Most remarkably, the increases in serum ANA and anti-dsDNA induced by TCE in the iNOS-null MRL+/+ mice were significantly less pronounced compared to that in MRL+/+ mice. Our results provide further evidence that both RNS and LDRAs contribute to TCE-induced autoimmunity in MRL+/+ mice, and iNOS deficiency attenuates this autoimmune response. PMID:26472195

  19. iNOS null MRL+/+ mice show attenuation of trichloroethene-mediated autoimmunity: contribution of reactive nitrogen species and lipid-derived reactive aldehydes.

    PubMed

    Wang, Gangduo; Wakamiya, Maki; Wang, Jianling; Ansari, G A S; Firoze Khan, M

    2015-12-01

    Earlier studies from our laboratory in MRL+/+ mice suggest that free radicals, especially overproduction of reactive nitrogen species (RNS) and lipid-derived reactive aldehydes (LDRAs), are associated with trichloroethene (TCE)-mediated autoimmune response. The current study was undertaken to further assess the contribution of RNS and LDRAs in TCE-mediated autoimmunity by using iNOS-null MRL+/+ mice. iNOS-null MRL+/+ mice were obtained by backcrossing iNOS-null mice (B6.129P2-Nos2(tm1Lau)/J) to MRL +/+ mice. Female MRL+/+ and iNOS-null MRL+/+ mice were given TCE (10 mmol/kg, i.p., every 4(th) day) for 6 weeks; their respective controls received corn oil only. TCE exposure led to significantly increased iNOS mRNA in livers, iNOS protein in livers and sera, increased nitrotyrosine (NT) formation in both livers and sera, induction of MDA-/HNE-protein adducts in livers and their respective antibodies in sera along with significant increases in serum antinuclear antibodies (ANA) and anti-dsDNA in MRL+/+ mice. Even though in iNOS-null MRL+/+ mice, the iNOS and NT levels were negligible in both TCE-treated and untreated groups, TCE treatment still led to significant increases in MDA-/HNE-protein adducts and their respective antibodies along with increases in serum ANA and anti-dsDNA compared to controls. Most remarkably, the increases in serum ANA and anti-dsDNA induced by TCE in the iNOS-null MRL+/+ mice were significantly less pronounced compared to that in MRL+/+ mice. Our results provide further evidence that both RNS and LDRAs contribute to TCE-induced autoimmunity in MRL+/+ mice, and iNOS deficiency attenuates this autoimmune response.

  20. SrGAP3 knockout mice display enlarged lateral ventricles and specific cilia disturbances of ependymal cells in the third ventricle.

    PubMed

    Koschützke, Leif; Bertram, Jonathan; Hartmann, Bianca; Bartsch, Dusan; Lotze, Martin; von Bohlen und Halbach, Oliver

    2015-08-01

    In several mouse models of mental retardation, ventricular enlargements have been observed. Mutation in the SrGAP3 gene residing on chromosome 3p25 has previously been associated with intellectual disability in humans. In addition, SrGAP3 is related to Rho-GAPs signaling pathways, which play essential roles in the development and plasticity of the nervous system. About 10 % of postnatal homozygous SrGAP3-deficient mice die due to hydrocephalus, whereas the remaining mice survive into adulthood but display enlarged ventricles. We analyze the ventricular enlargement of these mice by performing a post-mortem MRI approach. We found a more than 15-fold enlargement of the lateral ventricles of homozygous SrGAP3-deficient mice. Moreover, we demonstrate that this phenotype was not accompanied by a stenosis of the aqueduct. Instead, SrGAP3 knockout mice displayed reduced densities of cilia of ependymal cells in These third ventricle compared to age-matched controls. This results indicate that the ventricular enlargement may be due to ciliopathy.

  1. In Situ Fluorescence Measurement of Tear Film [Na+], [K+], [Cl−], and pH in Mice Shows Marked Hypertonicity in Aquaporin-5 Deficiency

    PubMed Central

    Ruiz-Ederra, Javier; Levin, Marc H.; Verkman, A. S.

    2009-01-01

    Purpose Tear film composition depends on water and ion transport across ocular surface epithelia and on fluid secretion by lacrimal glands. The purpose of this study was to establish in situ fluorescence methods to measure tear film ionic concentrations and pH in mice and to determine whether tear film composition is sensitive to deficiency of the major ocular surface aquaporin water channels. Methods Tear film ionic concentrations and pH were measured in anesthetized mice by ratio imaging fluorescence microscopy after topical application of ion/pH-sensing, dual-wavelength fluorescent indicators. [Na+], [K+], and [Cl−] were measured with membrane-impermeant indicators developed by our laboratory, and pH was measured with bis(carboxyethyl)-carboxyfluorescein fluorescence-conjugated dextran. Measurements were performed on wild-type mice and on knockout mice lacking aquaporins AQP1, AQP3, and AQP5. Results In wild-type mice, tear film [Na+] was 139 ± 8 mM, [K+] was 48 ± 1 mM, [Cl−] was 127 ± 4 mM, and pH was 7.59 ± 0.2 (SE; n = 5–8). pH did not differ significantly in the AQP knockout mice. [Na+] was increased by approximately twofold in AQP5 null mice (230 ± 20 mM) and was greatly reduced after exposure of the ocular surface to a humidified atmosphere. [K+] was mildly reduced in AQP1 null mice. Conclusions These results establish an in situ optical methodology to measure tear film [Na+], [K+], [Cl−], and pH in living mice, without the need for fluid sampling. Tear film hypertonicity in AQP5 deficiency is likely caused by reduced transcorneal water secretion in response to evaporative water loss. PMID:19136711

  2. 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.

  3. Infection of mice with oocysts of Toxoplasma gondii by oral route showed differences of virulence from Brazilian RFLP genotypes BrI and BrIII.

    PubMed

    Chiebao, Daniela Pontes; Pena, Hilda Fátima de Jesus; Cabral, Aline Diniz; Rocca, Mayra Pereira; Lopes, Estela Gallucci; Valadas, Samantha Yuri Oshiro Branco; Keid, Lara Borges; Grisi Filho, José Henrique Hildebrand; Soares, Rodrigo Martins

    2016-08-01

    South American strains of Toxoplasma gondii present higher genetic diversity than classical European strains. We compared the virulence of two non-archetypal Brazilian genotypes of T. gondii to mice. Oocysts of four isolates, two genotype BrI (TgCatBr71 and TgShBr11) and two BrIII (TgCatBr74 and TgCatBr60) were obtained from cats fed experimentally infected mice. After sporulation, 5.0×10(1) and 1.0×10(2) oocysts were orally administrated to Swiss albine mice in Experiments #1 and #2, respectively (4-10 mice/group). Humoral response from dead and surviving mice was analyzed on days 9 to 35 post-infection. Microscopic observations of lungs and brains were performed for tachyzoites and cysts visualization in fresh preparations. Negative results were tested by PCR. Virulence after infection with oocysts is dose dependent for genotype BrIII isolates, but not for BrI. Differences in mortality were observed among isolates from genotype BrIII on Experiment #1. Intra-genotype phenotypic variation related to the parasite stage of infection was demonstrated and this characteristic should be further studied and may influence future work regarding the role of virulence amid hosts.

  4. ILDR1 null mice, a model of human deafness DFNB42, show structural aberrations of tricellular tight junctions and degeneration of auditory hair cells.

    PubMed

    Morozko, Eva L; Nishio, Ayako; Ingham, Neil J; Chandra, Rashmi; Fitzgerald, Tracy; Martelletti, Elisa; Borck, Guntram; Wilson, Elizabeth; Riordan, Gavin P; Wangemann, Philine; Forge, Andrew; Steel, Karen P; Liddle, Rodger A; Friedman, Thomas B; Belyantseva, Inna A

    2015-02-01

    In the mammalian inner ear, bicellular and tricellular tight junctions (tTJs) seal the paracellular space between epithelial cells. Tricellulin and immunoglobulin-like (Ig-like) domain containing receptor 1 (ILDR1, also referred to as angulin-2) localize to tTJs of the sensory and non-sensory epithelia in the organ of Corti and vestibular end organs. Recessive mutations of TRIC (DFNB49) encoding tricellulin and ILDR1 (DFNB42) cause human nonsyndromic deafness. However, the pathophysiology of DFNB42 deafness remains unknown. ILDR1 was recently reported to be a lipoprotein receptor mediating the secretion of the fat-stimulated cholecystokinin (CCK) hormone in the small intestine, while ILDR1 in EpH4 mouse mammary epithelial cells in vitro was shown to recruit tricellulin to tTJs. Here we show that two different mouse Ildr1 mutant alleles have early-onset severe deafness associated with a rapid degeneration of cochlear hair cells (HCs) but have a normal endocochlear potential. ILDR1 is not required for recruitment of tricellulin to tTJs in the cochlea in vivo; however, tricellulin becomes mislocalized in the inner ear sensory epithelia of ILDR1 null mice after the first postnatal week. As revealed by freeze-fracture electron microscopy, ILDR1 contributes to the ultrastructure of inner ear tTJs. Taken together, our data provide insight into the pathophysiology of human DFNB42 deafness and demonstrate that ILDR1 is crucial for normal hearing by maintaining the structural and functional integrity of tTJs, which are critical for the survival of auditory neurosensory HCs.

  5. The C57BL/6J mice offspring originated from a parental generation exposed to tannery effluents shows object recognition deficits.

    PubMed

    Guimarães, Abraão Tiago Batista; Ferreira, Raíssa de Oliveira; Rabelo, Letícia Martins; E Silva, Bianca Costa; de Souza, Joyce Moreira; da Silva, Wellington Alves Mizael; de Menezes, Ivandilson Pessoa Pinto; Rodrigues, Aline Sueli de Lima; Vaz, Boniek Gontijo; de Oliveira Costa, Denys Ribeiro; Pereira, Igor; da Silva, Anderson Rodrigo; Malafaia, Guilherme

    2016-12-01

    The main aim of the present paper is to assess whether the parental generation exposure to such discharges could cause object recognition deficits in their offspring. Male and female C57Bl/6J mice were put to mate after they were exposed to 7.5% and 15% tannery effluents or water (control group), for 60 days. The male mice were withdrawn from the boxes after 15 days and the female mice remained exposed to the treatment during the gestation and lactation periods. The offspring were subjected to the object recognition test after weaning in order to assess possible cognition losses. The results of the analysis of the novel object recognition index found in the testing session (performed 1 h after the training session) applied to offspring from different experimental groups appeared to be statistically different. The novel object recognition index of the offspring from female mice exposed to tannery effluents (7.5% and 15% groups) was lower than that of the control group, and it demonstrated object recognition deficit in the studied offspring. The present study is the first to report evidences that parental exposure to effluent of tannery (father and mother) can cause object recognition deficit in the offspring, which is related to problems in the central nervous system.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  7. Sterilizing Immunity Elicited by Neisseria meningitidis Carriage Shows Broader Protection than Predicted by Serum Antibody Cross-Reactivity in CEACAM1-Humanized Mice

    PubMed Central

    McCaw, Shannon E.; Strobel, Lea; Frosch, Matthias

    2014-01-01

    Neisseria meningitidis asymptomatically colonizes the human upper respiratory tract but is also the cause of meningitis and severe septicemia. Carriage or disease evokes an immune response against the infecting strain. Hitherto, we have known little about the breadth of immunity induced by natural carriage of a single strain or its implications for subsequent infectious challenge. In this study, we establish that transgenic mice expressing human CEACAM1 support nasal colonization by a variety of strains of different capsular types. Next, we nasally challenged these mice with either of the N. meningitidis strains H44/76 (serogroup B, ST-32) and 90/18311 (serogroup C, ST-11), while following the induction of strain-specific immunoglobulin. When these antisera were tested for reactivity with a diverse panel of N. meningitidis strains, very low levels of antibody were detected against all meningococcal strains, yet a mutually exclusive “fingerprint” of high-level cross-reactivity toward certain strains became apparent. To test the efficacy of these responses for protection against subsequent challenge, CEACAM1-humanized mice exposed to strain 90/18311 were then rechallenged with different N. meningitidis strains. As expected, the mice were immune to challenge with the same strain and with a closely related ST-11 strain, 38VI, while H44/76 (ST-32) could still colonize these animals. Notably, however, despite the paucity of detectable humoral response against strain 196/87 (ST-32), this strain was unable to colonize the 90/18311-exposed mice. Combined, our data suggest that current approaches may underestimate the actual breadth of mucosal protection gained through natural exposure to N. meningitidis strains. PMID:25368118

  8. In Utero and Lactational Exposure to PCBs in Mice: Adult Offspring Show Altered Learning and Memory Depending on Cyp1a2 and Ahr Genotypes

    PubMed Central

    Curran, Christine P.; Genter, Mary Beth; Patel, Krishna V.; Schaefer, Tori L.; Skelton, Matthew R.; Williams, Michael T.; Vorhees, Charles V.

    2011-01-01

    Background: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response. Objectives: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs. Methods: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity–AHR Cyp1a2 wild-type [Ahrb1_Cyp1a2(+/+)], poor-affinity–AHR Cyp1a2 wild-type [Ahrd_Cyp1a2(+/+)], and high-affinity–AHR Cyp1a2 knockout [Ahrb1_Cyp1a2(–/–)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189–208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors. Results: We observed the most significant deficits in response to PCB treatment in Ahrb1_Cyp1a2(–/–) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on

  9. RAG2−/−γc−/− Mice Transplanted with CD34+ Cells from Human Cord Blood Show Low Levels of Intestinal Engraftment and Are Resistant to Rectal Transmission of Human Immunodeficiency Virus▿

    PubMed Central

    Hofer, Ursula; Baenziger, Stefan; Heikenwalder, Mathias; Schlaepfer, Erika; Gehre, Nadine; Regenass, Stephan; Brunner, Thomas; Speck, Roberto F.

    2008-01-01

    Rectal transmission is one of the main routes of infection by human immunodeficiency virus type 1 (HIV-1). To efficiently study transmission mechanisms and prevention strategies, a small animal model permissive for rectal transmission of HIV is mandatory. We tested the susceptibility of RAG2−/−γc−/− mice transplanted with human cord blood hematopoietic stem cells to rectal infection with HIV. We rectally exposed these humanized mice to cell-free and cell-associated HIV. All mice remained HIV negative as assessed by plasma viral load. The same mice infected intraperitoneally showed high levels of HIV replication. In the gut-associated lymphatic tissue, we found disproportionately smaller numbers of human cells than in other lymphoid organs. This finding may explain the observed resistance to rectal transmission of HIV. To increase the numbers of local HIV target cells and the likelihood of HIV transmission, we treated mice with different proinflammatory stimuli: local application of interleukin-1β, addition of seminal plasma to the inoculum, or induction of colitis with dextran sodium sulfate. These procedures attracted some human leukocytes, but the transmission rate was still very low. The humanized mice showed low levels of human engraftment in the intestinal tract and seem to be resistant to rectal transmission of HIV, and thus they are an unsuitable model for this application. PMID:18842716

  10. Novel dual agonist peptide analogues derived from dogfish glucagon show promising in vitro insulin releasing actions and antihyperglycaemic activity in mice.

    PubMed

    O'Harte, F P M; Ng, M T; Lynch, A M; Conlon, J M; Flatt, P R

    2016-08-15

    The antidiabetic potential of thirteen novel dogfish glucagon derived analogues were assessed in vitro and in acute in vivo studies. Stable peptide analogues enhanced insulin secretion from BRIN-BD11 β-cells (p < 0.001) and reduced acute glycaemic responses following intraperitoneal glucose (25 nmol/kg) in healthy NIH Swiss mice (p < 0.05-p<0.001). The in vitro insulinotropic actions of [S2a]dogfish glucagon, [S2a]dogfish glucagon-exendin-4(31-39) and [S2a]dogfish glucagon-Lys(30)-γ-glutamyl-PAL, were blocked (p < 0.05-p<0.001) by the specific GLP-1 and glucagon receptor antagonists, exendin-4(9-39) and (desHis(1)Pro(4)Glu(9))glucagon amide but not by (Pro(3))GIP, indicating lack of GIP receptor involvement. These analogues dose-dependently stimulated cAMP production in GLP-1 and glucagon (p < 0.05-p<0.001) but not GIP-receptor transfected cells. They improved acute glycaemic and insulinotropic responses in high-fat fed diabetic mice and in wild-type C57BL/6J and GIPR-KO mice (p < 0.05-p<0.001), but not GLP-1R-KO mice, confirming action on GLP-1 but not GIP receptors. Overall, dogfish glucagon analogues have potential for diabetes therapy, exerting beneficial metabolic effects via GLP-1 and glucagon receptors.

  11. Photoreceptor phagosome processing defects and disturbed autophagy in retinal pigment epithelium of Cln3Δex1-6 mice modelling juvenile neuronal ceroid lipofuscinosis (Batten disease)

    PubMed Central

    Wavre-Shapton, Silène T.; Calvi, Alessandra A.; Turmaine, Mark; Seabra, Miguel C.; Cutler, Daniel F.; Futter, Clare E.; Mitchison, Hannah M.

    2015-01-01

    Retinal degeneration and visual impairment are the first signs of juvenile neuronal ceroid lipofuscinosis caused by CLN3 mutations, followed by inevitable progression to blindness. We investigated retinal degeneration in Cln3Δex1-6 null mice, revealing classic ‘fingerprint’ lysosomal storage in the retinal pigment epithelium (RPE), replicating the human disease. The lysosomes contain mitochondrial F0-ATP synthase subunit c along with undigested membranes, indicating a reduced degradative capacity. Mature autophagosomes and basal phagolysosomes, the terminal degradative compartments of autophagy and phagocytosis, are also increased in Cln3Δex1-6 RPE, reflecting disruption to these key pathways that underpin the daily phagocytic turnover of photoreceptor outer segments (POS) required for maintenance of vision. The accumulated autophagosomes have post-lysosome fusion morphology, with undigested internal contents visible, while accumulated phagosomes are frequently docked to cathepsin D-positive lysosomes, without mixing of phagosomal and lysosomal contents. This suggests lysosome-processing defects affect both autophagy and phagocytosis, supported by evidence that phagosomes induced in Cln3Δex1-6-derived mouse embryonic fibroblasts have visibly disorganized membranes, unprocessed internal vesicles and membrane contents, in addition to reduced LAMP1 membrane recruitment. We propose that defective lysosomes in Cln3Δex1-6 RPE have a reduced degradative capacity that impairs the final steps of the intimately connected autophagic and phagocytic pathways that are responsible for degradation of POS. A build-up of degradative organellar by-products and decreased recycling of cellular materials is likely to disrupt processes vital to maintenance of vision by the RPE. PMID:26450516

  12. Carcinogenicity study of 3-monochloropropane-1, 2-diol (3-MCPD) administered by drinking water to B6C3F1 mice showed no carcinogenic potential.

    PubMed

    Jeong, Jayoung; Han, Beom Seok; Cho, Wan-Seob; Choi, Mina; Ha, Chang-Su; Lee, Byoung-Seok; Kim, Yong-Bum; Son, Woo-Chan; Kim, Choong-Yong

    2010-09-01

    3-Monochloropropane-1, 2-diol (or 3-chloro-1,2-propanediol, 3-MCPD) is a well-known food processing contaminant found in a wide range of foods and ingredients. It has been classified as non-genotoxic carcinogen but its carcinogenic potential in the rodents has been controversial. The carcinogenicity to B6C3F1 mice by drinking water administration was assessed over a period of 104 weeks. Three groups, each comprising 50 male and 50 female mice received 3-MCPD at dosages of 30, 100 or 300 ppm up to Day 100 and 200 ppm onward (4.2, 14.3 and 33.0 mg/kg for males; 3.7, 12.2, and 31.0 mg/kg for females), were allocated. Survival was good, with at least 80% of males and 72% of females in each group surviving 104 weeks. Body weights and body weight gain were decreased in males and females receiving 200 ppm. Water and food consumptions of both sexes at 300/200 ppm were lowered. Emaciated or crouching position was observed for animals of both sexes exposed to 200 ppm. There were some differences in hematology and serum biochemistry compared with controls, although there was no histopathological evidence to support those changes. Histopathological examination did not reveal any neoplastic or non-neoplastic findings attributable to treatment with 3-MCPD. It is concluded that drinking water administration of 3-MCPD for 104 weeks revealed no evidence of carcinogenic potential.

  13. Microbial Anti-Inflammatory Molecule (MAM) from Faecalibacterium prausnitzii Shows a Protective Effect on DNBS and DSS-Induced Colitis Model in Mice through Inhibition of NF-κB Pathway

    PubMed Central

    Breyner, Natalia M.; Michon, Cristophe; de Sousa, Cassiana S.; Vilas Boas, Priscilla B.; Chain, Florian; Azevedo, Vasco A.; Langella, Philippe; Chatel, Jean M.

    2017-01-01

    Faecalibacterium prausnitzii and its supernatant showed protective effects in different chemically-induced colitis models in mice. Recently, we described 7 peptides found in the F. prausnitzii supernatant, all belonging to a protein called Microbial Anti-inflammatory Molecule (MAM). These peptides were able to inhibit NF-κB pathway in vitro and showed anti-inflammatory properties in vivo in a DiNitroBenzene Sulfate (DNBS)-induced colitis model. In this current proof we tested MAM effect on NF-κB pathway in vivo, using a transgenic model of mice producing luciferase under the control of NF-κB promoter. Moreover, we tested this protein on Dextran Sodium Sulfate (DSS)-induced colitis in mice. To study the effect of MAM we orally administered to the mice a Lactococcus lactis strain carrying a plasmid containing the cDNA of MAM under the control of a eukaryotic promoter. L. lactis delivered plasmids in epithelial cells of the intestinal membrane allowing thus the production of MAM directly by host. We showed that MAM administration inhibits NF-κB pathway in vivo. We confirmed the anti-inflammatory properties of MAM in DNBS-induced colitis but also in DSS model. In DSS model MAM was able to inhibit Th1 and Th17 immune response while in DNBS model MAM reduced Th1, Th2, and Th17 immune response and increased TGFβ production. PMID:28203226

  14. Microbial Anti-Inflammatory Molecule (MAM) from Faecalibacterium prausnitzii Shows a Protective Effect on DNBS and DSS-Induced Colitis Model in Mice through Inhibition of NF-κB Pathway.

    PubMed

    Breyner, Natalia M; Michon, Cristophe; de Sousa, Cassiana S; Vilas Boas, Priscilla B; Chain, Florian; Azevedo, Vasco A; Langella, Philippe; Chatel, Jean M

    2017-01-01

    Faecalibacterium prausnitzii and its supernatant showed protective effects in different chemically-induced colitis models in mice. Recently, we described 7 peptides found in the F. prausnitzii supernatant, all belonging to a protein called Microbial Anti-inflammatory Molecule (MAM). These peptides were able to inhibit NF-κB pathway in vitro and showed anti-inflammatory properties in vivo in a DiNitroBenzene Sulfate (DNBS)-induced colitis model. In this current proof we tested MAM effect on NF-κB pathway in vivo, using a transgenic model of mice producing luciferase under the control of NF-κB promoter. Moreover, we tested this protein on Dextran Sodium Sulfate (DSS)-induced colitis in mice. To study the effect of MAM we orally administered to the mice a Lactococcus lactis strain carrying a plasmid containing the cDNA of MAM under the control of a eukaryotic promoter. L. lactis delivered plasmids in epithelial cells of the intestinal membrane allowing thus the production of MAM directly by host. We showed that MAM administration inhibits NF-κB pathway in vivo. We confirmed the anti-inflammatory properties of MAM in DNBS-induced colitis but also in DSS model. In DSS model MAM was able to inhibit Th1 and Th17 immune response while in DNBS model MAM reduced Th1, Th2, and Th17 immune response and increased TGFβ production.

  15. AAV2/8-humanFOXP3 gene therapy shows robust anti-atherosclerosis efficacy in LDLR-KO mice on high cholesterol diet.

    PubMed

    Cao, M; Theus, S A; Straub, K D; Figueroa, J A; Mirandola, L; Chiriva-Internati, M; Hermonat, P L

    2015-07-18

    Inflammation is a key etiologic component in atherogenesis. Previously we demonstrated that adeno-associated virus (AAV) 2/8 gene delivery of Netrin1 inhibited atherosclerosis in the low density lipoprotein receptor knockout mice on high-cholesterol diet (LDLR-KO/HCD). One important finding from this study was that FOXP3 was strongly up-regulated in these Netrin1-treated animals, as FOXP3 is an anti-inflammatory gene, being the master transcription factor of regulatory T cells. These results suggested that the FOXP3 gene might potentially be used, itself, as an agent to limit atherosclerosis. To test this hypothesis AAV2/8 (AAV)/hFOXP3 or AAV/Neo (control) gene therapy virus were tail vein injected into the LDLR-KO/HCD animal model. It was found that hFOXP3 gene delivery was associated with significantly lower HCD-induced atherogenesis, as measured by larger aortic lumen cross sectional area, thinner aortic wall thickness, and lower aortic systolic blood velocity compared with Neo gene-HCD-treated controls. Moreover these measurements taken from the hFOXP3/HCD-treated animals very closely matched those measurements taken from the normal diet (ND) control animals. These data strongly suggest that AAV/hFOXP3 delivery gave a robust anti-atherosclerosis therapeutic effect and further suggest that FOXP3 be examined more stringently as a therapeutic gene for clinical use.

  16. Mice deficient for the extracellular matrix glycoprotein tenascin-r show physiological and structural hallmarks of increased hippocampal excitability, but no increased susceptibility to seizures in the pilocarpine model of epilepsy.

    PubMed

    Brenneke, F; Bukalo, O; Dityatev, A; Lie, A A

    2004-01-01

    Recognition molecules provide important cues for neuronal survival, axonal fasciculation, axonal pathfinding, synaptogenesis, synaptic plasticity, and regeneration. Our previous studies revealed a link between perisomatic inhibition and the extracellular matrix glycoprotein tenascin-R (TN-R). Therefore, we here studied neuronal excitability and epileptic susceptibility in mice constitutively deficient in TN-R. In vitro analysis of populational spikes in hippocampal slices of TN-R-deficient mice revealed a significant increase in multiple spikes in the CA1 region, as compared with wild-type mice. This difference between genotypes was only partially reduced after blockade of GABA(A) receptors with picrotoxin, indicating a deficit in GABAergic inhibition and an increase in intrinsic excitability of CA1 pyramidal cells in TN-R-deficient mice. Using a battery of immunohistochemical markers and histological stainings, we were able to identify two abnormalities in the hippocampus of TN-R-deficient mice possibly related to increased excitability: the high number of glial fibrillary acidic protein-positive astrocytes and low number of calretinin-positive interneurons in the CA1 and CA3 regions. In order to test whether the revealed abnormalities give rise to increased susceptibility to seizures in TN-R-deficient mice, we used the pilocarpine model of epilepsy. No genotype-specific differences were found with regard to the time-course of pilocarpine-induced and spontaneous seizures, neuronal cell loss, aberrant sprouting and distribution of synaptic and inhibitory interneuron markers. However, pilocarpine-induced astrogliosis and reduction in calretinin-positive interneurons were less pronounced in TN-R mutants, thereby resulting in an occlusion of effects induced by TN-R deficiency and pilocarpine. Thus, TN-R-deficient mutants show several electrophysiological and morphological hallmarks of increased neuronal excitability, which, however, do not give rise to more

  17. Intracranial administration of vaccinia virus complement control protein in Mo/Hu APPswe PS1dE9 transgenic mice at an early age shows enhanced performance at a later age using a cheese board maze test.

    PubMed

    Kulkarni, Amod P; Pillay, Nirvana S; Kellaway, Lauriston A; Kotwal, Girish J

    2008-12-01

    One of the key pro-inflammatory mediators activated by amyloid protein in neurodegenerative disorders of the brain, such as Alzheimer's disease is the complement system. Vaccinia virus complement control protein secreted by vaccinia virus, commonly known as VCP, was found to inhibit amyloid protein mediated up-regulation of complement system in vitro. In the current research investigation, VCP was administered twice (First dose at 3 weeks and the second dose at 6-7 months) intracranially into the parietal cortical area of Mo/Hu APPswe transgenic mice. At the age of 2 years or more, the same mice were subjected to cued-learning, spatial learning, probe and reverse probe trial paradigms of cheese board maze tasks for cognitive assessment. A significant difference was observed between VCP treated mice and the transgenic controls on days two and three of the cued trials and probe trials. The VCP treated group showed a similar trend as revealed during the spatial learning trial and reverse probe trial. A differential pattern of thioflavine S staining was observed in the VCP treated group. These results suggest that administration of VCP at an early age in transgenic mice may be effective in regulating the progression to the familial form of Alzheimer's disease at a later age.

  18. 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.

  19. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the…

  20. New Hippocampal Neurons Are Not Obligatory for Memory Formation; Cyclin D2 Knockout Mice with No Adult Brain Neurogenesis Show Learning

    ERIC Educational Resources Information Center

    Jaholkowski, Piotr; Kiryk, Anna; Jedynak, Paulina; Abdallah, Nada M. Ben; Knapska, Ewelina; Kowalczyk, Anna; Piechal, Agnieszka; Blecharz-Klin, Kamilla; Figiel, Izabela; Lioudyno, Victoria; Widy-Tyszkiewicz, Ewa; Wilczynski, Grzegorz M.; Lipp, Hans-Peter; Kaczmarek, Leszek; Filipkowski, Robert K.

    2009-01-01

    The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs…

  1. 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.

  2. Regional boreal biodiversity peaks at intermediate human disturbance.

    PubMed

    Mayor, S J; Cahill, J F; He, F; Sólymos, P; Boutin, S

    2012-01-01

    The worldwide biodiversity crisis has intensified the need to better understand how biodiversity and human disturbance are related. The 'intermediate disturbance hypothesis' suggests that disturbance regimes generate predictable non-linear patterns in species richness. Evidence often contradicts intermediate disturbance hypothesis at small scales, and is generally lacking at large regional scales. Here, we present the largest extent study of human impacts on boreal plant biodiversity to date. Disturbance extent ranged from 0 to 100% disturbed in vascular plant communities, varying from intact forest to agricultural fields, forestry cut blocks and oil sands. We show for the first time that across a broad region species richness peaked in communities with intermediate anthropogenic disturbance, as predicted by intermediate disturbance hypothesis, even when accounting for many environmental covariates. Intermediate disturbance hypothesis was consistently supported across trees, shrubs, forbs and grasses, with temporary and perpetual disturbances. However, only native species fit this pattern; exotic species richness increased linearly with disturbance.

  3. Sleep disturbance induces neuroinflammation and impairment of learning and memory.

    PubMed

    Zhu, Biao; Dong, Yuanlin; Xu, Zhipeng; Gompf, Heinrich S; Ward, Sarah A P; Xue, Zhanggang; Miao, Changhong; Zhang, Yiying; Chamberlin, Nancy L; Xie, Zhongcong

    2012-12-01

    Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients.

  4. Induction of Heat-Shock Protein 70 Expression by Geranylgeranylacetone Shows Cytoprotective Effects in Cardiomyocytes of Mice under Humid Heat Stress

    PubMed Central

    Wang, Xiaowu; Yuan, Binbin; Dong, Wenpeng; Yang, Bo; Yang, Yongchao; Lin, Xi; Gong, Gu

    2014-01-01

    Background Increasing evidence has revealed that humid heat stress (HHS) causes considerable damage to human health. The cardiovascular system has been suggested to be the primary target of heat stress, which results in serious cardiovascular diseases. However, there is still a lack of effective approaches for the prevention and treatment of cardiovascular diseases induced by HHS. Objective Heat-shock proteins (Hsps), especially Hsp70, are reported to provide effective cytoprotection under various stress stimuli. In the present study, we evaluated the cytoprotective effect of geranylgeranylacetone (GGA), which was previously been reported to induce Hsp70 expression in cardiomyocytes under HHS. Methods and Principal Findings Using a mouse model of HHS, we showed that the pretreatment of GGA enhanced Hsp70 expression under HHS, as examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. We then examined the effect of GGA pretreatment on the cardiomyocyte apoptosis induced by HHS using terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining, and found that GGA pretreatment inhibited mitochondria-mediated apoptosis. GGA pretreatment could reverse the effect of HHS on cell apoptosis by increasing expression of Bcl-2, decreasing cytochrome c in cytosol, and increasing cytochrome c in mitochondria. However, GGA pretreatment had no effect on the oxidative stress induced by HHS as determined by levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH). Conclusion We have demonstrated that GGA pretreatment suppressed HHS-induced apoptosis of cardiomyocytes through the induction of Hsp70 overexpression. PMID:24695789

  5. Fossil Mice and Rats Show Isotopic Evidence of Niche Partitioning and Change in Dental Ecomorphology Related to Dietary Shift in Late Miocene of Pakistan

    PubMed Central

    Kimura, Yuri; Jacobs, Louis L.; Cerling, Thure E.; Uno, Kevin T.; Ferguson, Kurt M.; Flynn, Lawrence J.; Patnaik, Rajeev

    2013-01-01

    Stable carbon isotope analysis in tooth enamel is a well-established approach to infer C3 and C4 dietary composition in fossil mammals. The bulk of past work has been conducted on large herbivorous mammals. One important finding is that their dietary habits of fossil large mammals track the late Miocene ecological shift from C3 forest and woodland to C4 savannah. However, few studies on carbon isotopes of fossil small mammals exist due to limitations imposed by the size of rodent teeth, and the isotopic ecological and dietary behaviors of small mammals to climate change remain unknown. Here we evaluate the impact of ecological change on small mammals by fine-scale comparisons of carbon isotope ratios (δ13C) with dental morphology of murine rodents, spanning 13.8 to ∼2.0 Ma, across the C3 to C4 vegetation shift in the Miocene Siwalik sequence of Pakistan. We applied in-situ laser ablation GC-IRMS to lower first molars and measured two grazing indices on upper first molars. Murine rodents yield a distinct, but related, record of past ecological conditions from large herbivorous mammals, reflecting available foods in their much smaller home ranges. In general, larger murine species show more positive δ13C values and have higher grazing indices than smaller species inhabiting the same area at any given age. Two clades of murine rodents experienced different rates of morphological change. In the faster-evolving clade, the timing and trend of morphological innovations are closely tied to consumption of C4 diet during the vegetation shift. This study provides quantitative evidence of linkages among diet, niche partitioning, and dental morphology at a more detailed level than previously possible. PMID:23936324

  6. Fossil mice and rats show isotopic evidence of niche partitioning and change in dental ecomorphology related to dietary shift in Late Miocene of Pakistan.

    PubMed

    Kimura, Yuri; Jacobs, Louis L; Cerling, Thure E; Uno, Kevin T; Ferguson, Kurt M; Flynn, Lawrence J; Patnaik, Rajeev

    2013-01-01

    Stable carbon isotope analysis in tooth enamel is a well-established approach to infer C3 and C4 dietary composition in fossil mammals. The bulk of past work has been conducted on large herbivorous mammals. One important finding is that their dietary habits of fossil large mammals track the late Miocene ecological shift from C3 forest and woodland to C4 savannah. However, few studies on carbon isotopes of fossil small mammals exist due to limitations imposed by the size of rodent teeth, and the isotopic ecological and dietary behaviors of small mammals to climate change remain unknown. Here we evaluate the impact of ecological change on small mammals by fine-scale comparisons of carbon isotope ratios (δ(13)C) with dental morphology of murine rodents, spanning 13.8 to ∼2.0 Ma, across the C3 to C4 vegetation shift in the Miocene Siwalik sequence of Pakistan. We applied in-situ laser ablation GC-IRMS to lower first molars and measured two grazing indices on upper first molars. Murine rodents yield a distinct, but related, record of past ecological conditions from large herbivorous mammals, reflecting available foods in their much smaller home ranges. In general, larger murine species show more positive δ(13)C values and have higher grazing indices than smaller species inhabiting the same area at any given age. Two clades of murine rodents experienced different rates of morphological change. In the faster-evolving clade, the timing and trend of morphological innovations are closely tied to consumption of C4 diet during the vegetation shift. This study provides quantitative evidence of linkages among diet, niche partitioning, and dental morphology at a more detailed level than previously possible.

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

    PubMed

    Liu, Zhi-Qin; Liu, Ting; Chen, Chuan; Li, Ming-Yan; Wang, Zi-Yu; Chen, Ruo-Song; Wei, Gui-Xiang; Wang, Xiao-Yi; Luo, Du-Qiang

    2015-05-15

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

  8. Optimal Tuning for Disturbance Suppression Mechanism for Model Predictive Control

    NASA Astrophysics Data System (ADS)

    Tange, Yoshio; Nakazawa, Chikashi

    Disturbance suppression is one of most required performances in process control. We recently proposed a new disturbance suppression mechanism applicable for model predictive control in order to enhance disturbance suppression performance for ramp-like disturbances. The proposed method utilized the prediction error of controlled values and generates a disturbance compensation signal by a constant gain feedback. In this paper, we propose an improved version of the disturbance suppression mechanism by applying a low-pass filter and parameter tuning methods by which we can make the mechanism more tolerant to various disturbances such as ramp, step, and other supposable ones. We also show numerical simulation results with an oil distillation tower plant.

  9. Anthropogenic habitat disturbance and the dynamics of hantavirus using remote sensing, GIS, and a spatially explicit agent-based model

    NASA Astrophysics Data System (ADS)

    Cao, Lina

    Sin Nombre virus (SNV), a strain of hantavirus, causes hantavirus pulmonary syndrome (HPS) in humans, a deadly disease with high mortality rate (>50%). The primary virus host is deer mice, and greater deer mice abundance has been shown to increase the human risk of HPS. There is a great need in understanding the nature of the virus host, its temporal and spatial dynamics, and its relation to the human population with the purpose of predicting human risk of the disease. This research studies SNV dynamics in deer mice in the Great Basin Desert of central Utah, USA using multiyear field data and integrated geospatial approaches including remote sensing, Geographic Information System (GIS), and a spatially explicit agent-based model. The goal is to advance our understanding of the important ecological and demographic factors that affect the dynamics of deer mouse population and SNV prevalence. The primary research question is how climate, habitat disturbance, and deer mouse demographics affect deer mouse population density, its movement, and SNV prevalence in the sagebrush habitat. The results show that the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI) can be good predictors of deer mouse density and the number of infected deer mice with a time lag of 1.0 to 1.3 years. This information can be very useful in predicting mouse abundance and SNV risk. The results also showed that climate, mouse density, sex, mass, and SNV infection had significant effects on deer mouse movement. The effect of habitat disturbance on mouse movement varies according to climate conditions with positive relationship in predrought condition and negative association in postdrought condition. The heavier infected deer mice moved the most. Season and disturbance alone had no significant effects. The spatial agent-based model (SABM) simulation results show that prevalence was negatively related to the disturbance levels and the sensitivity analysis showed that

  10. 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.

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

    SciTech Connect

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

    2015-05-15

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

  12. Disturbance and change in biodiversity.

    PubMed

    Dornelas, Maria

    2010-11-27

    Understanding how disturbance affects biodiversity is important for both fundamental and applied reasons. Here, I investigate how disturbances with different ecological effects change biodiversity metrics. I define three main types of disturbance effects: D disturbance (shifts in mortality rate), B disturbance (shifts in reproductive rates) and K disturbance (shifts in carrying capacity). Numerous composite disturbances can be defined including any combination of these three types of ecological effects. The consequences of D, B and K disturbances, as well as of composite DBK disturbances are examined by comparing metrics before and after a disturbance, in disturbed and undisturbed communities. I use simulations of neutral communities and examine species richness, total abundance and species abundance distributions. The patterns of change in biodiversity metrics are consistent among different types of disturbance. K disturbance has the most severe effects, followed by D disturbance, and B disturbance has nearly negligible effects. Consequences of composite DBK disturbances are more complex than any of the three types of disturbance, with unimodal relationships along a disturbance gradient arising when D, B and K are negatively correlated. Importantly, regardless of disturbance type, community isolation enhances the negative consequences and hinders the positive effects of disturbances.

  13. Indicators: Human Disturbance

    EPA Pesticide Factsheets

    Human disturbance is a measure of the vulnerability of aquatic resources to a variety of harmful human activities such as tree removal, road building, construction near shorelines/streambanks, and artificial hardening of lakeshores with retaining walls.

  14. Amphetamine withdrawal and sleep disturbance.

    PubMed

    Gossop, M R; Bradley, B P; Brewis, R K

    1982-01-01

    Sleep duration and indices of disturbed sleep, such as night-time waking and day-time sleep, were investigated in amphetamine users following hospital admission and withdrawal from the drug. Compared to controls, the amphetamine group showed an initial period of oversleeping and, towards the end of the first week, they showed a considerable degree of reduced sleep which persisted for the 20 days of this study. There was greater variability in sleep duration within the amphetamine group on almost all nights, and the variability in sleep duration from one night to the next was also greater. More night-time sleep disturbance was evident among the amphetamine ex-users. These results are discussed with respect to previous work and the pattern is seen to be more complex than had been imagined. A tentative neurochemical model is suggested and clinical implications are considered.

  15. A robust disturbance reduction scheme for linear small delay systems with disturbances of unknown frequencies.

    PubMed

    Tsai, Ming-Hau; Tung, Pi-Cheng

    2012-05-01

    A robust disturbance reduction scheme for linear small delay systems with disturbances of unknown frequencies is presented in this paper. Unlike other methods, the proposed scheme does not require disturbance frequencies to be known. The linear systems modeled in this study are nominally stable and minimum phase systems with relative degree. The control structure is an integration of Astrom's modified Smith predictor and the proposed scheme. The proposed scheme consists of an input disturbance reduction controller (IDRC) and a residual disturbance reduction controller (RDRC). The IDRC using an artificial neural network (ANN) is proposed to reduce unknown load disturbances and modeling uncertainties in stable systems and unstable systems. The ANN can appropriately approximate the product of an inverse time delay and a nonnegative gain in the IDRC. The residual signals including residual disturbances and residual uncertainties are suppressed by the RDRC based on a disturbance observer. Simulation examples are illustrated to show the effectiveness of the proposed robust disturbance reduction scheme for linear delay uncertain systems with periodic or non-periodic unknown load disturbances.

  16. 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

  17. Sleep disturbances in Parkinsonism.

    PubMed

    Askenasy, J J M

    2003-02-01

    The present article is meant to suggest an approach to the guidelines for the therapy of sleep disturbances in Parkinson's Disease (PD) patients.The factors affecting the quality of life in PD patients are depression, sleep disturbances and dependence. A large review of the literature on sleep disturbances in PD patients, provided the basis for the following classification of the sleep-arousal disturbances in PD patients. We suggest a model based on 3 steps in the treatment of sleep disturbances in PD patients. This model allowing the patient, the spouse or the caregiver a quiet sleep at night, may postpone the retirement and the institutionalization of the PD patient. I. Correct diagnosis of sleep disorders based on detailed anamnesis of the patient and of the spouse or of the caregiver. One week recording on a symptom diary (log) by the patient or the caregiver. Correct diagnosis of sleep disorders co morbidities. Selection of the most appropriate sleep test among: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), Epworth Sleepiness Scale, actigraphy or video-PSG. II. The nonspecific therapeutic approach consists in: a) Checking the sleep effect on motor performance, is it beneficial, worse or neutral. b) Psycho-physical assistance. c) Dopaminergic adjustment is necessary owing to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals, which alter the normal modulator mechanisms of the motor centers in PD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and NonREM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates PD motor symptoms. L-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. The permanent adjustment

  18. 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.

  19. A Mixture of Ethanol Extracts of Persimmon Leaf and Citrus junos Sieb Improves Blood Coagulation Parameters and Ameliorates Lipid Metabolism Disturbances Caused by Diet-Induced Obesity in C57BL/6J Mice.

    PubMed

    Kim, Ae Hyang; Kim, Hye Jin; Ryu, Ri; Han, Hye Jin; Han, Young Ji; Lee, Mi-Kyung; Choi, Myung-Sook; Park, Yong Bok

    2016-02-01

    This study investigated the effects of a flavonoid-rich ethanol extract of persimmon leaf (PL), an ethanol extract of Citrus junos Sieb (CJS), and a PL-CJS mixture (MPC) on mice fed a highfat diet (HFD). We sought to elucidate the mechanisms of biological activity of these substances using measurements of blood coagulation indices and lipid metabolism parameters. C57BL/6J mice were fed a HFD with PL (0.5% (w/w)), CJS (0.1% (w/w)), or MPC (PL 0.5%, CJS 0.1% (w/w)) for 10 weeks. In comparison with data obtained for mice in the untreated HFD group, consumption of MPC remarkably prolonged the activated partial thromboplastin time (aPTT) and prothrombin time (PT), whereas exposure to PL prolonged aPTT only. Lower levels of plasma total cholesterol, hepatic cholesterol, and erythrocyte thiobarbituric acid-reactive substances, hepatic HMG-CoA reductase, and decreased SREBP-1c gene expression were observed in mice that received PL and MPC supplements compared with the respective values detected in the untreated HFD animals. Our results indicate that PL and MPC may have beneficial effects on blood circulation and lipid metabolism in obese mice.

  20. Chronic social stress leads to altered sleep homeostasis in mice.

    PubMed

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

    2017-03-15

    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.

  1. Identification of a male meiosis-specific gene, Tcte2, which is differentially spliced in species that form sterile hybrids with laboratory mice and deleted in t chromosomes showing meiotic drive.

    PubMed

    Braidotti, G; Barlow, D P

    1997-06-01

    Tcte2 (t complex testes expressed 2) is a male meiosis-specific gene that maps to band 3.3 of mouse chromosome 17. Two distinct male fertility defects, hybrid sterility and transmission ratio distortion, have previously been mapped to this region. Hybrid sterility arises in crosses between different mouse species and the F1 generation males have defects in the first meiotic division and are sterile. Transmission ratio distortion is shown by males heterozygous for the t haplotype form of chromosome 17 and is a type of meiotic drive in which male gametes function unequally at fertilization. The Tcte2 gene expresses a coding mRNA and a number of putative non-ORF transcripts in meiosis I. A deletion of the 5' part of the locus abolishes Tcte2 expression on the t haplotype form of chromosome 17. Additionally, the series of putative non-ORF RNAs at the Tcte2 locus are differentially spliced in species that show hybrid sterility when crossed to laboratory mice. The identification of polymorphisms in t haplotypes and in different mouse species allows alleles of Tcte2 to be proposed as candidates for loci which contribute to both meiotic drive and hybrid sterility phenotypes. While theoretical considerations have previously been used to propose that speciation and meiotic drive involve alleles of the same genes, Tcte2 is the first cloned candidate gene to support this link at a molecular level.

  2. 300 Area Disturbance Report

    SciTech Connect

    LL Hale; MK Wright; NA Cadoret

    1999-01-07

    The objective of this study was to define areas of previous disturbance in the 300 Area of the U.S. Department of Energy (DOE) Hanford Site to eliminate these areas from the cultural resource review process, reduce cultural resource monitoring costs, and allow cultural resource specialists to focus on areas where subsurface disturbance is minimal or nonexistent. Research into available sources suggests that impacts from excavations have been significant wherever the following construction activities have occurred: building basements and pits, waste ponds, burial grounds, trenches, installation of subsurface pipelines, power poles, water hydrants, and well construction. Beyond the areas just mentioned, substrates in the' 300 Area consist of a complex, multidimen- sional mosaic composed of undisturbed stratigraphy, backfill, and disturbed sediments; Four Geographic Information System (GIS) maps were created to display known areas of disturbance in the 300 Area. These maps contain information gleaned from a variety of sources, but the primary sources include the Hanford GIS database system, engineer drawings, and historic maps. In addition to these maps, several assumptions can be made about areas of disturbance in the 300 Area as a result of this study: o o Buried pipelines are not always located where they are mapped. As a result, cultural resource monitors or specialists should not depend on maps depicting subsurface pipelines for accurate locations of previous disturbance. Temporary roads built in the early 1940s were placed on layers of sand and gravel 8 to 12 in. thick. Given this information, it is likely that substrates beneath these early roads are only minimally disturbed. Building foundations ranged from concrete slabs no more than 6 to 8 in. thick to deeply excavated pits and basements. Buildings constructed with slab foundations are more numerous than may be expected, and minimally disturbed substrates may be expected in these locations. Historic black

  3. Waveguide disturbance detection method

    DOEpatents

    Korneev, Valeri A.; Nihei, Kurt T.; Myer, Larry R.

    2000-01-01

    A method for detection of a disturbance in a waveguide comprising transmitting a wavefield having symmetric and antisymmetric components from a horizontally and/or vertically polarized source and/or pressure source disposed symmetrically with respect to the longitudinal central axis of the waveguide at one end of the waveguide, recording the horizontal and/or vertical component or a pressure of the wavefield with a vertical array of receivers disposed at the opposite end of the waveguide, separating the wavenumber transform of the wavefield into the symmetric and antisymmetric components, integrating the symmetric and antisymmetric components over a broad frequency range, and comparing the magnitude of the symmetric components and the antisymmetric components to an expected magnitude for the symmetric components and the antisymmetric components for a waveguide of uniform thickness and properties thereby determining whether or not a disturbance is present inside the waveguide.

  4. Atmospheric Disturbance Environment Definition

    NASA Technical Reports Server (NTRS)

    Tank, William G.

    1994-01-01

    Traditionally, the application of atmospheric disturbance data to airplane design problems has been the domain of the structures engineer. The primary concern in this case is the design of structural components sufficient to handle transient loads induced by the most severe atmospheric "gusts" that might be encountered. The concern has resulted in a considerable body of high altitude gust acceleration data obtained with VGH recorders (airplane velocity, V, vertical acceleration, G, altitude, H) on high-flying airplanes like the U-2 (Ehernberger and Love, 1975). However, the propulsion system designer is less concerned with the accelerations of the airplane than he is with the airflow entering the system's inlet. When the airplane encounters atmospheric turbulence it responds with transient fluctuations in pitch, yaw, and roll angles. These transients, together with fluctuations in the free-stream temperature and pressure will disrupt the total pressure, temperature, Mach number and angularity of the inlet flow. For the mixed compression inlet, the result is a disturbed throat Mach number and/or shock position, and in extreme cases an inlet unstart can occur (cf. Section 2.1). Interest in the effects of inlet unstart on the vehicle dynamics of large, supersonic airplanes is not new. Results published by NASA in 1962 of wind tunnel studies of the problem were used in support of the United States Supersonic Transport program (SST) (White, at aI, 1963). Such studies continued into the late 1970's. However, in spite of such interest, there never was developed an atmospheric disturbance database for inlet unstart analysis to compare with that available for the structures load analysis. Missing were data for the free-stream temperature and pressure disturbances that also contribute to the unStart problem.

  5. Global Scale Solar Disturbances

    NASA Astrophysics Data System (ADS)

    Title, A. M.; Schrijver, C. J.; DeRosa, M. L.

    2013-12-01

    The combination of the STEREO and SDO missions have allowed for the first time imagery of the entire Sun. This coupled with the high cadence, broad thermal coverage, and the large dynamic range of the Atmospheric Imaging Assembly on SDO has allowed discovery of impulsive solar disturbances that can significantly affect a hemisphere or more of the solar volume. Such events are often, but not always, associated with M and X class flares. GOES C and even B class flares are also associated with these large scale disturbances. Key to the recognition of the large scale disturbances was the creation of log difference movies. By taking the log of images before differencing events in the corona become much more evident. Because such events cover such a large portion of the solar volume their passage can effect the dynamics of the entire corona as it adjusts to and recovers from their passage. In some cases this may lead to a another flare or filament ejection, but in general direct causal evidence of 'sympathetic' behavior is lacking. However, evidence is accumulating these large scale events create an environment that encourages other solar instabilities to occur. Understanding the source of these events and how the energy that drives them is built up, stored, and suddenly released is critical to understanding the origins of space weather. Example events and comments of their relevance will be presented.

  6. Integrating Landscape Disturbance and Indicator Species in Conservation Studies

    PubMed Central

    Fattorini, Simone; Terzopoulou, Sofia; Borges, Paulo A. V.

    2013-01-01

    Successful conservation plans are conditioned by our ability to detect anthropogenic change in space and time and various statistical analyses have been developed to handle this critical issue. The main objective of this paper is to illustrate a new approach for spatial analysis in conservation biology. Here, we propose a two-step protocol. First, we introduce a new disturbance metric which provides a continuous measure of disturbance for any focal communities on the basis of the surrounding landscape matrix. Second, we use this new gradient to estimate species and community disturbance thresholds by implementing a recently developed method called Threshold Indicator Taxa ANalysis (TITAN). TITAN detects changes in species distributions along environmental gradients using indicators species analysis and assesses synchrony among species change points as evidence for community thresholds. We demonstrate our method with soil arthropod assemblages along a disturbance gradient in Terceira Island (Azores, Portugal). We show that our new disturbance metric realistically reflects disturbance patterns, especially in buffer zones (ecotones) between land use categories. By estimating species disturbance thresholds with TITAN along the disturbance gradient in Terceira, we show that species significantly associated with low disturbance differ from those associated with high disturbance in their biogeographical origin (endemics, non-endemic natives and exotics) and taxonomy (order). Finally, we suggest that mapping the disturbance community thresholds may reveal areas of primary interest for conservation, since these may host indigenous species sensitive to high disturbance levels. This new framework may be useful when: (1) both local and regional processes are to be reflected on single disturbance measures; (2) these are better quantified in a continuous gradient; (3) mapping disturbance of large regions using fine scales is necessary; (4) indicator species for disturbance are

  7. Integrating landscape disturbance and indicator species in conservation studies.

    PubMed

    Cardoso, Pedro; Rigal, François; Fattorini, Simone; Terzopoulou, Sofia; Borges, Paulo A V

    2013-01-01

    Successful conservation plans are conditioned by our ability to detect anthropogenic change in space and time and various statistical analyses have been developed to handle this critical issue. The main objective of this paper is to illustrate a new approach for spatial analysis in conservation biology. Here, we propose a two-step protocol. First, we introduce a new disturbance metric which provides a continuous measure of disturbance for any focal communities on the basis of the surrounding landscape matrix. Second, we use this new gradient to estimate species and community disturbance thresholds by implementing a recently developed method called Threshold Indicator Taxa ANalysis (TITAN). TITAN detects changes in species distributions along environmental gradients using indicators species analysis and assesses synchrony among species change points as evidence for community thresholds. We demonstrate our method with soil arthropod assemblages along a disturbance gradient in Terceira Island (Azores, Portugal). We show that our new disturbance metric realistically reflects disturbance patterns, especially in buffer zones (ecotones) between land use categories. By estimating species disturbance thresholds with TITAN along the disturbance gradient in Terceira, we show that species significantly associated with low disturbance differ from those associated with high disturbance in their biogeographical origin (endemics, non-endemic natives and exotics) and taxonomy (order). Finally, we suggest that mapping the disturbance community thresholds may reveal areas of primary interest for conservation, since these may host indigenous species sensitive to high disturbance levels. This new framework may be useful when: (1) both local and regional processes are to be reflected on single disturbance measures; (2) these are better quantified in a continuous gradient; (3) mapping disturbance of large regions using fine scales is necessary; (4) indicator species for disturbance are

  8. The response of avian feeding guilds to tropical forest disturbance.

    PubMed

    Gray, Michael A; Baldauf, Sandra L; Mayhew, Peter J; Hill, Jane K

    2007-02-01

    Anthropogenic habitat disturbance is a major threat to tropical forests and understanding the ecological consequences of this disturbance is crucial for the conservation of biodiversity. There have been many attempts to determine the ecological traits associated with bird species' vulnerability to disturbance, but no attempt has been made to synthesize these studies to show consensus. We analyzed data from 57 published studies (covering 1214 bird species) that investigated the response of tropical bird assemblages to moderate forest disturbance (e.g., selective logging). Our results show that the mean abundance of species from six commonly reported feeding guilds responded differently to disturbance and that species' ecological traits (body size, local population size, and geographic range size) and evolutionary relationships may influence responses in some guilds. Granivore abundance increased significantly and insectivore and frugivore abundance decreased significantly following disturbance. These general conclusions were robust to the effects of ecological traits and phylogeny. Responses of carnivores, nectarivores, and omnivores were less clear, but analyses that accounted for phylogeny indicated that these guilds declined following disturbance. In contrast to the other guilds, the reported responses of carnivores and nectarivores differed among regions (Asia vs. Neotropics) and were influenced by the sampling protocols used in different studies (e.g., time since disturbance), which may explain the difficulty in detecting general responses to disturbance in these guilds. Overall, general patterns governed the responses of species to habitat disturbance, and the differential responses of guilds suggested that disturbance affects trophic organization and thus ecosystem functioning.

  9. Model of traveling ionospheric disturbances

    NASA Astrophysics Data System (ADS)

    Fedorenko, Yury P.; Tyrnov, Oleg F.; Fedorenko, Vladimir N.; Dorohov, Vasiliy L.

    2013-10-01

    A multiscale semi-empirical model of traveling ionospheric disturbances (TIDs) is developed. The model is based on the following assumptions: (1) TIDs are generated by acoustic-gravity waves (AGWs) and propagate as pressure waves; (2) time intervals between adjacent extrema of atmospheric pressure oscillations in a disturbance source are constant; (3) the pressure extrema propagate from the source up to ~14 000 km at a constant horizontal velocity; (4) the velocity of each extremum is determined only by its number in a TID train. The model was validated using literature data on disturbances generated by about 20 surface and high-altitude nuclear explosions, two volcano explosions, one earthquake and by energetic proton precipitation events in the magnetospheric cusp of the northern hemisphere. Model tests using literature data show that the spatial and temporal TID periods may be predicted with an accuracy of 12%. Adequacy of the model was also confirmed by our observations collected using transionospheric sounding. The following TID parameters: amplitudes, horizontal spatial periods, and a TID front inclination angle in a vertical plane are increasing as the distance between an AGW and the excitation source is increasing. Diurnal and seasonal variability of the TID occurrence, defined as ratio of TID events to the total number of observations for the corresponding period, is not observed. However, the TID occurrence was growing from ~50% in 1987 to ~98% in 2010. The results of other studies asserting that the TID occurrence does not depend on the number of sunspots and magnetic activity are confirmed. The TID occurrence has doubled over the period from 1987 to 2010 indicating increasing solar activity which is not associated with sunspot numbers. The dynamics of spatial horizontal periods was studied in a range of 150-35 000 km.

  10. 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.

  11. Vehicle Disturbance Test

    NASA Astrophysics Data System (ADS)

    Clapp, Brian

    2009-07-01

    The purpose of the VDT is to measure and characterize uncompensated environmental disturbances acting upon the HST during normal operation. The VDT is a passive test {not a forced-response test} used to obtain signatures for both externally induced {e.g. SCM, SA-3, SSM thermal gradients} and internally induced {e.g. HGA, RWA, COS and WFC3 mechanisms} disturbances affecting HST LOS pointing. The disturbances observed will be used as the nominal on-orbit disturbances in pointing control simulations until the next VDT is run.The test occurs after release, and most of the VDT can be run during the BEA period. The ?V1 sunpoint portion of the VDT usually occurs after the BEA period is complete. The VDT shall consist of two separate tests that need not occur consecutively. The overall duration of the VDT is at least 13 orbits of spacecraft time including {1} at least 8 orbits at +V3 sunpoint after achieving thermal equilibrium {at least 36-hours at +V3 sunpoint} and three out of 8-orbits have RWA Friction Compensation turned Off, and {2} at least 5 orbits at ?V1 sunpoint {all or part of this segment have RWA Friction Compensation turned Off}. At the beginning of each test, the attitude control law gains are switched to maneuver gains, and the gyros are commanded to low mode. The nominal attitude control law configuration will be restored at the end of each test.Each test is initiated via SMS execution of stored program macros in the HST flight computer to switch the attitude control law gains to low-bandwidth maneuver gains, command the gyros into low mode, terminate Velocity aberration and parallax {VAP} processing, and manage the status of on-board RWA Friction Compensation. The nominal attitude control law configuration will be restored at the end of each test via SMS execution of stored program macros. The stored program command macros are developed specifically for the VDT by the Flight Software and Pointing Control System groups.

  12. 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.

  13. [Relation between dementia and circadian rhythm disturbance].

    PubMed

    Nakamura, Kei; Meguro, Kenichi

    2014-03-01

    Dementia and circadian rhythm disturbance are closely linked. First, dementia patient shows circadian rhythm disorders (e.g. insomnia, night wandering, daytime sleep). These symptoms are a burden for caregivers. Circadian rhythm disturbance of dementia relates ADL and cognitive impairment, and diurnal rhythm disorder of blood pressure and body temperature. Some study shows that circadian rhythm disorders in dementia are a disturbance of neural network between suprachiasmatic nucleus and cerebral white matter, and involvement of both frontal lobes, left parietal and occipital cortex, left temporoparietal region. The first-line treatment of circadian rhythm disturbance should be non-drug therapy (e.g. exercise, bright light exposure, reduce caffeine intake, etc.). If physician prescribe drugs, keep the rule of low-dose and short-term and avoid benzodiazepines. Atypical antipsychotic drugs like risperidone and some antidepressants are useful for treatment of insomnia in dementia. But this usage is off-label. So we must well inform to patient and caregiver, and get consent about treatment. Second, some study shows circadian rhythm disorder is a risk factor of dementia. However, we should discuss that circadian rhythm disturbance is "risk factor of dementia" or "prodromal symptom of dementia". If a clinician finds circadian rhythm disorder in elderly people, should be examined cognitive and ADL function, and careful about that patients have dementia or will develop dementia.

  14. Unloading stress disturbs muscle regeneration through perturbed recruitment and function of macrophages.

    PubMed

    Kohno, Shohei; Yamashita, Yui; Abe, Tomoki; Hirasaka, Katsuya; Oarada, Motoko; Ohno, Ayako; Teshima-Kondo, Shigetada; Higashibata, Akira; Choi, Inho; Mills, Edward M; Okumura, Yuushi; Terao, Junji; Nikawa, Takeshi

    2012-05-01

    Skeletal muscle is one of the most sensitive tissues to mechanical loading, and unloading inhibits the regeneration potential of skeletal muscle after injury. This study was designed to elucidate the specific effects of unloading stress on the function of immunocytes during muscle regeneration after injury. We examined immunocyte infiltration and muscle regeneration in cardiotoxin (CTX)-injected soleus muscles of tail-suspended (TS) mice. In CTX-injected TS mice, the cross-sectional area of regenerating myofibers was smaller than that of weight-bearing (WB) mice, indicating that unloading delays muscle regeneration following CTX-induced skeletal muscle damage. Delayed infiltration of macrophages into the injured skeletal muscle was observed in CTX-injected TS mice. Neutrophils and macrophages in CTX-injected TS muscle were presented over a longer period at the injury sites compared with those in CTX-injected WB muscle. Disturbance of activation and differentiation of satellite cells was also observed in CTX-injected TS mice. Further analysis showed that the macrophages in soleus muscles were mainly Ly-6C-positive proinflammatory macrophages, with high expression of tumor necrosis factor-α and interleukin-1β, indicating that unloading causes preferential accumulation and persistence of proinflammatory macrophages in the injured muscle. The phagocytic and myotube formation properties of macrophages from CTX-injected TS skeletal muscle were suppressed compared with those from CTX-injected WB skeletal muscle. We concluded that the disturbed muscle regeneration under unloading is due to impaired macrophage function, inhibition of satellite cell activation, and their cooperation.

  15. 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

  16. Reaction Wheel Disturbance Reduction Method Using Disturbance Measurement Table

    NASA Astrophysics Data System (ADS)

    Cheon, Dong-Ik; Jang, Eun-Jeong; Oh, Hwa-Suk

    2011-12-01

    Momentum changing actuators like reaction wheels and control moment gyros are generally used for spacecraft attitude control. This type of actuators produces force and torque disturbances. These disturbances must be reduced since they degrade the quality of spacecraft attitude control. Major disturbances are mainly due to static and dynamic imbalances. This paper gives attention to the reduction of the static and dynamic imbalance. Force/torque measurement system is used to measure the disturbance of the test reaction wheel. An identification method for the location and magnitude of the imbalance is suggested, and the corrections of the imbalance are performed using balancing method. Through balancing, the static and dynamic imbalance is remarkably reduced

  17. Human ABCA1 BAC transgenic mice show increased high density lipoprotein cholesterol and ApoAI-dependent efflux stimulated by an internal promoter containing liver X receptor response elements in intron 1.

    PubMed

    Singaraja, R R; Bocher, V; James, E R; Clee, S M; Zhang, L H; Leavitt, B R; Tan, B; Brooks-Wilson, A; Kwok, A; Bissada, N; Yang, Y Z; Liu, G; Tafuri, S R; Fievet, C; Wellington, C L; Staels, B; Hayden, M R

    2001-09-07

    By using BAC transgenic mice, we have shown that increased human ABCA1 protein expression results in a significant increase in cholesterol efflux in different tissues and marked elevation in high density lipoprotein (HDL)-cholesterol levels associated with increases in apoAI and apoAII. Three novel ABCA1 transcripts containing three different transcription initiation sites that utilize sequences in intron 1 have been identified. In BAC transgenic mice there is an increased expression of ABCA1 protein, but the distribution of the ABCA1 product in different cells remains similar to wild type mice. An internal promoter in human intron 1 containing liver X response elements is functional in vivo and directly contributes to regulation of the human ABCA1 gene in multiple tissues and to raised HDL cholesterol, apoAI, and apoAII levels. A highly significant relationship between raised protein levels, increased efflux, and level of HDL elevation is evident. These data provide proof of the principle that increased human ABCA1 efflux activity is associated with an increase in HDL levels in vivo.

  18. Disturbance maintains alternative biome states.

    PubMed

    Dantas, Vinícius de L; Hirota, Marina; Oliveira, Rafael S; Pausas, Juli G

    2016-01-01

    Understanding the mechanisms controlling the distribution of biomes remains a challenge. Although tropical biome distribution has traditionally been explained by climate and soil, contrasting vegetation types often occur as mosaics with sharp boundaries under very similar environmental conditions. While evidence suggests that these biomes are alternative states, empirical broad-scale support to this hypothesis is still lacking. Using community-level field data and a novel resource-niche overlap approach, we show that, for a wide range of environmental conditions, fire feedbacks maintain savannas and forests as alternative biome states in both the Neotropics and the Afrotropics. In addition, wooded grasslands and savannas occurred as alternative grassy states in the Afrotropics, depending on the relative importance of fire and herbivory feedbacks. These results are consistent with landscape scale evidence and suggest that disturbance is a general factor driving and maintaining alternative biome states and vegetation mosaics in the tropics.

  19. Fractional active disturbance rejection control.

    PubMed

    Li, Dazi; Ding, Pan; Gao, Zhiqiang

    2016-05-01

    A fractional active disturbance rejection control (FADRC) scheme is proposed to improve the performance of commensurate linear fractional order systems (FOS) and the robust analysis shows that the controller is also applicable to incommensurate linear FOS control. In FADRC, the traditional extended states observer (ESO) is generalized to a fractional order extended states observer (FESO) by using the fractional calculus, and the tracking differentiator plus nonlinear state error feedback are replaced by a fractional proportional-derivative controller. To simplify controller tuning, the linear bandwidth-parameterization method has been adopted. The impacts of the observer bandwidth ωo and controller bandwidth ωc on system performance are then analyzed. Finally, the FADRC stability and frequency-domain characteristics for linear single-input single-output FOS are analyzed. Simulation results by FADRC and ADRC on typical FOS are compared to demonstrate the superiority and effectiveness of the proposed scheme.

  20. Hypertrophic lagoon management by sediment disturbance.

    PubMed

    Lenzi, Mauro; Birardi, Francesca; Calzolai, Roberto; Finoia, Maria Grazia; Marcone, Francesco; Nocciolini, Stefano; Roffilli, Rugiada; Sgroi, Sergio; Solari, Duccio

    2010-01-01

    Experimental control of eutrophication in a small coastal lagoon was attempted by means of sediment disturbance. A specially designed boat was used to resuspend the top 3 cm of sediment by a jets of air-water directed towards the bottom. This disturbance was carried out for 3 months in each of two areas with a surface area of 24 and 20 hectares respectively. In a total of 80 stations in these two areas and in two undisturbed areas of 16 and 20 ha, organic matter, porosity, density and redox potential were monitored in sediment bimonthly and free sulphides were monitored in water close to the bottom. Before, during and after disturbance, the impact of daily sediment resuspension on the water column was monitored monthly, as ammonium nitrogen (N-NH4), soluble reactive phosphorus (SRP), dissolved oxygen (DO) and pH. In the whole lagoon, sediment texture was determined at the start and at the end of the experiment in 120 stations, and seaweed (mainly Chaetomorpha linum and Lophosiphonia subadunca) and seagrass (Ruppia cirrhosa) biomasses were estimated in 42 stations every month. The results showed a stable organic matter content in disturbed areas and an increase in undisturbed areas, as well as an increase in seaweed in areas distant from disturbed areas. No significant effect of sediment resuspension on water column N-NH4, SRP, DO or pH was found.

  1. 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.

  2. Climate Change and Disturbance Interactions

    NASA Astrophysics Data System (ADS)

    McKenzie, Don; Allen, Craig D.

    2007-05-01

    Workshop on Climate Change and Disturbance Interactions in Western North America, Tucson, Ariz., 12-15 February 2007 Warming temperatures across western North America, coupled with increased drought, are expected to exacerbate disturbance regimes, particularly wildfires, insect outbreaks, and invasions of exotic species. Many ecologists and resource managers expect ecosystems to change more rapidly from disturbance effects than from the effects of a changing climate by itself. A particular challenge is to understand the interactions among disturbance regimes; for example, how will massive outbreaks of bark beetles, which kill drought-stressed trees by feeding on cambial tissues, increase the potential for large severe wildfires in a warming climate?

  3. Nonunity gain minimal-disturbance measurement

    SciTech Connect

    Sabuncu, Metin; Andersen, Ulrik L.; Mista, Ladislav Jr.; Fiurasek, Jaromir; Filip, Radim; Leuchs, Gerd

    2007-09-15

    We propose and experimentally demonstrate an optimal nonunity gain Gaussian scheme for partial measurement of an unknown coherent state that causes minimal disturbance of the state. The information gain and the state disturbance are quantified by the noise added to the measurement outcomes and to the output state, respectively. We derive the optimal trade-off relation between the two noises and we show that the tradeoff is saturated by nonunity gain teleportation. Optimal partial measurement is demonstrated experimentally using a linear optics scheme with feedforward.

  4. Cognitive deficiencies in emotionally disturbed children.

    PubMed

    Curley, J F; Pabis, R

    1978-01-01

    This research investigated development of cognitive abilities in a normal vs. emotionally disturbed school age population (N = 240) ages 6-12. The Ss had to display skills on the Southern Illinois University Test necessary to show understanding of Piagetian concepts of class inclusion, class exclusion, and complement of set. A three way analysis of variance indicated significant main effects for age, sex, and emotionality factors. There were, however, no significant interactions among these factors. Emotionally disturbed children were not only deficient in the measured cognitive skills, but even the rate of development of these cognitive skills was inferior to that of the normal population.

  5. [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.

  6. Disturbances of spatial perception in children.

    PubMed

    Meerwaldt, J D; van Dongen, H R

    1988-12-01

    Spatial perception was tested in 12 children with a localized brain lesion by means of the rod orientation test, line orientation test and facial recognition test. Only children with a lesion of the right hemisphere showed a disturbance of spatial perception.

  7. The High-Risk (Disturbed and Disturbing) College Student

    ERIC Educational Resources Information Center

    Hollingsworth, Kathy R.; Dunkle, John H.; Douce, Louise

    2009-01-01

    The disturbed and disturbing college student causes the most vexing concerns for student affairs administrators. The Assessment-Intervention of Student Problems (AISP) model offers a useful and easily understood framework for dealing with the various challenges of this high-risk student population. This chapter focuses on changes that have…

  8. Impaired glucose and lipid metabolism in ageing aryl hydrocarbon receptor deficient mice

    PubMed Central

    Biljes, Daniel; Hammerschmidt-Kamper, Christiane; Kadow, Stephanie; Diel, Patrick; Weigt, Carmen; Burkart, Volker; Esser, Charlotte

    2015-01-01

    Disturbed homeostasis of glucose and lipid metabolism are dominant features of the so-called metabolic syndrome (MetS) and can increase the risk for the development of type 2 diabetes (T2D), a severe metabolic disease. T2D prevalence increases with age. The aryl hydrocarbon receptor (AHR) is a sensor of small molecules including dietary components. AHR has been identified as potential regulator of glucose homeostasis and lipid metabolism. Epidemiologically, exposure to xenobiotic AHR ligands such as polycyclic aromatic hydrocarbons is linked to T2D. We assess here the potential role of the AHR in disturbances of glucose and lipid metabolism in young (age 2-5 months) and old (age > 1,5 years) AHR-deficient (AHR KO) mice. Fasted young wildtype (WT) and AHR-KO mice displayed similar blood glucose kinetics after challenge with intra-peritoneal glucose injection. However, old AHR-KO mice showed lower tolerance than WT to i.p. administered glucose, i.e. glucose levels rose higher and returned more slowly to normal levels. Old mice had overall higher insulin levels than young mice, and old AHR-KO had a somewhat disturbed insulin kinetic in the serum after glucose challenge. Surprisingly, young AHR-KO mice had significantly lower triglycerides, cholesterol, high density lipoprotein values than WT, i.e., a dyslipidemic profile. With ageing, AHR-KO and WT mice did not differ in these lipid levels, except for slightly reduced levels of triglycerides and cholesterol. In conclusion, our findings in AHR KO mice suggest that AHR expression is relevant for the maintenance of glucose and lipid homeostasis in old mice. PMID:26664351

  9. Ionospheric disturbance dynamo

    SciTech Connect

    Blanc, M.; Richmond, A.D.

    1980-04-01

    A numerical simulation study of the thermospheric winds produced by auroral heating during magnetic storms, and of their global dynamo effects, establishes the main features of the ionospheric disturbanc dynamo. Driven by auroral heating, a Hadley cell is created with equatorward winds blowing above about 120 km at mid-latitudes. The transport of angular momentum by these winds produces a subrotation of the midlatitude thermosphere, or westward motion with respect to the earth. The westward winds in turn drive equatorward Pedersen currents which accumulate charge toward the equator, resulting in the generation of a poleward electric field, a westward E x B drift, and an eastward current. When realistic local time conductivity variations are simulated, the eastward mid-latitude current is found to close partly via lower latitudes, resulting in an 'anti-Sq' type of current vortex. Both electric field and current at low latitudes thus vary in opposition to their normal quiet-day behavior. This total pattern of distrubance winds, electric fields, and currents is superimposed upon the background quiet-day pattern. When the neutral winds are artificially confined on the nightside, the basic pattern of predominantly westward E x B plasma drifts still prevails on the nightside but no longer extends into the dayside. Considerable observational evidence exists, suggesting that the ionospheric disturbance dynamo has an appreciable influence on storm-time ionospheric electric fields at middle and low latitudes.

  10. Autonomic disturbances in narcolepsy.

    PubMed

    Plazzi, Giuseppe; Moghadam, Keivan Kaveh; Maggi, Leonardo Serra; Donadio, Vincenzo; Vetrugno, Roberto; Liguori, Rocco; Zoccoli, Giovanna; Poli, Francesca; Pizza, Fabio; Pagotto, Uberto; Ferri, Raffaele

    2011-06-01

    Narcolepsy is a clinical condition characterized mainly by excessive sleepiness and cataplexy. Hypnagogic hallucinations and sleep paralysis complete the narcoleptic tetrad; disrupted night sleep, automatic behaviors and weight gain are also usual complaints. Different studies focus on autonomic changes or dysfunctions among narcoleptic patients, such as pupillary abnormalities, fainting spells, erectile dysfunction, night sweats, gastric problems, low body temperature, systemic hypotension, dry mouth, heart palpitations, headache and extremities dysthermia. Even if many studies lack sufficient standardization or their results have not been replicated, a non-secondary involvement of the autonomic nervous system in narcolepsy is strongly suggested, mainly by metabolic and cardiovascular findings. Furthermore, the recent discovery of a high risk for overweight and for metabolic syndrome in narcoleptic patients represents an important warning for clinicians in order to monitor and follow them up for their autonomic functions. We review here studies on autonomic functions and clinical disturbances in narcoleptic patients, trying to shed light on the possible contribute of alterations of the hypocretin system in autonomic pathophysiology.

  11. 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.

  12. Humanized mice dually challenged with R5 and X4 HIV-1 show preferential R5 viremia and restricted X4 infection of CCR5(+)CD4(+) T cells.

    PubMed

    Terahara, Kazutaka; Ishige, Masayuki; Ikeno, Shota; Okada, Seiji; Kobayashi-Ishihara, Mie; Ato, Manabu; Tsunetsugu-Yokota, Yasuko

    2015-05-01

    CCR5-tropic (R5) immunodeficiency virus type 1 (HIV-1) strains are highly transmissible during the early stage of infection in humans, whereas CXCR4-tropic (X4) strains are less transmissible. This study aimed to explore the basis for early phase R5 and X4 HIV-1 infection in vivo by using humanized mice dually challenged with R5 HIV-1NLAD8-D harboring DsRed and X4 HIV-1(NL-E) harboring EGFP. Whereas R5 HIV-1 replicated well, X4 HIV-1 caused only transient viremia with variable kinetics; however, this was distinct from the low level but persistent viremia observed in mice challenged with X4 HIV-1 alone. Flow cytometric analysis of HIV-1-infected cells revealed that X4 HIV-1 infection of CCR5(+)CD4(+) T cells was significantly suppressed in the presence of R5 HIV-1. X4 HIV-1 was more cytopathic than R5 HIV-1; however, this was not the cause of restricted X4 HIV-1 infection because there were no significant differences in the mortality rates of CCR5(+) and CCR5(-) cells within the X4 HIV-1-infected cell populations. Taken together, these results suggest that restricted infection of CCR5(+)CD4(+) T cells by X4 HIV-1 (occurring via a still-to-be-identified mechanism) might contribute to the preferential transmission of R5 HIV-1 during the early phase of infection.

  13. Patients with chronic pancreatitis have islet progenitor cells in their ducts, but reversal of overt diabetes in NOD mice by anti-CD3 shows no evidence for islet regeneration.

    PubMed

    Phillips, Jenny M; O'Reilly, Lorraine; Bland, Chris; Foulis, Alan K; Cooke, Anne

    2007-03-01

    Monoclonal antibodies to T-cell coreceptors have been shown to tolerise autoreactive T-cells and prevent or even reverse autoimmune pathology. In type 1 diabetes, there is a loss of insulin-secreting beta-cells, and a cure for type 1 diabetes would require not only tolerance induction but also recovery of the functional beta-cell mass. Although we have previously shown that diabetic mice have increased numbers of ductal progenitors in the pancreas, there is no evidence of any increase of insulin-secreting cells in the ducts. In contrast, in the adult human pancreas of patients with chronic pancreatitis, we can demonstrate, in the ducts, increased numbers of insulin-containing cells, as well as cells containing other endocrine and exocrine markers. There are also significantly increased numbers of cells expressing the homeodomain protein, pancreatic duodenal homeobox-1. Anti-CD3 has been shown to reverse overt diabetes in NOD mice; thus, we have used this model to ask whether monoclonal antibody-mediated inhibition of ongoing beta-cell destruction enables islet regeneration to occur. We find no evidence that such monoclonal antibody therapy results in either regeneration of insulin-secreting beta-cells or of increased proliferation of islet beta-cells.

  14. 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…

  15. Educating Emotionally Disturbed Children: Readings.

    ERIC Educational Resources Information Center

    Dupont, Henry, Ed.

    Designed to introduce the classroom teacher to a clinical teaching approach with the emotionally disturbed child and to encourage critical discussion of current practices and theories, the collection of readings presents selected dimensions of emotional disturbance such as personality patterns, learning disabilities, and minimal brain damage.…

  16. Beam sensorimotor learning and habituation to motor activity in lurcher mutant mice.

    PubMed

    Lalonde, R; Joyal, C C; Thifault, S

    1996-01-01

    Lurcher mutant mice lose cerebellar granule cells and Purkinje cells. The mutants were compared to normal mice in a beam-walking task. Normal mice were placed on a slippery bridge while lurchers, because of their severe ataxia, were placed on a bridge with the same diameter, but enveloped with surgical tape to improve traction. The performance of both groups improved with repeated trials. In an activity box, lurcher mutants were as active as normal mice, showed normal intrasession habituation, and emerged from a toy object as easily as normal mice. These results indicate that the cerebellar damage in lurchers does not prevent the acquisition of a motor skill task requiring balance in an immobile apparatus. Ataxia was not accompanied by hypoactivity, inhibition or disturbances in intrasession habituation.

  17. Western Disturbances: A review

    NASA Astrophysics Data System (ADS)

    Dimri, A. P.; Niyogi, D.; Barros, A. P.; Ridley, J.; Mohanty, U. C.; Yasunari, T.; Sikka, D. R.

    2015-06-01

    Cyclonic storms associated with the midlatitude Subtropical Westerly Jet (SWJ), referred to as Western Disturbances (WDs), play a critical role in the meteorology of the Indian subcontinent. WDs embedded in the southward propagating SWJ produce extreme precipitation over northern India and are further enhanced over the Himalayas due to orographic land-atmosphere interactions. During December, January, and February, WD snowfall is the dominant precipitation input to establish and sustain regional snowpack, replenishing regional water resources. Spring melt is the major source of runoff to northern Indian rivers and can be linked to important hydrologic processes from aquifer recharge to flashfloods. Understanding the dynamical structure, evolution-decay, and interaction of WDs with the Himalayas is therefore necessary to improve knowledge which has wide ranging socioeconomic implications beyond short-term disaster response including cold season agricultural activities, management of water resources, and development of vulnerability-adaptive measures. In addition, WD wintertime precipitation provides critical mass input to existing glaciers and modulates the albedo characteristics of the Himalayas and Tibetan Plateau, affecting large-scale circulation and the onset of the succeeding Indian Summer Monsoon. Assessing the impacts of climate variability and change on the Indian subcontinent requires fundamental understanding of the dynamics of WDs. In particular, projected changes in the structure of the SWJ will influence evolution-decay processes of the WDs and impact Himalayan regional water availability. This review synthesizes past research on WDs with a perspective to provide a comprehensive assessment of the state of knowledge to assist both researchers and policymakers, and context for future research.

  18. Asian plantain (Plantago asiatica) essential oils suppress 3-hydroxy-3-methyl-glutaryl-co-enzyme A reductase expression in vitro and in vivo and show hypocholesterolaemic properties in mice.

    PubMed

    Chung, Mi Ja; Park, Kuen Woo; Kim, Kyoung Heon; Kim, Cheong-Tae; Baek, Jun Pill; Bang, Kyong-Hwan; Choi, Young-Mi; Lee, Sung-Joon

    2008-01-01

    Asian plantain (Plantago asiatica) essential oil (PAEO) contains multiple bioactive compounds, but its potential effects on lipid metabolism have not been examined. PAEO was found to be mostly composed of oxygenated monoterpenes, with linalool as the major component (82.5 %, w/w), measured using GC-MS. Incubation of 0-200 microg PAEO/ml with HepG2 cells for 24 h resulted in no significant toxicity. Incubation with 0.2 mg PAEO/ml altered the expression of LDL receptor (+83 %; P < 0.05) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase ( - 37 %; P < 0.05), as assessed using RT-PCR. LDL oxidation was markedly inhibited by PAEO treatment due to the prevalence of linalool compounds in PAEO. Oral administration of PAEO for 3 weeks in C57BL/6 mice significantly reduced plasma total cholesterol and TAG concentrations by 29 and 46 %, respectively. The mRNA (+58 %; P < 0.05), but not protein, levels of the LDL receptor were significantly higher, whereas both mRNA and protein levels of HMG-CoA reductase were significantly lower ( - 46 and - 11 %, respectively; P < 0.05) in the liver of PAEO-fed than of control mice. The mRNA levels of CYP7A1 were marginally reduced in HepG2 cells, but not in mouse liver after PAEO treatment. Thus, PAEO may have hypocholesterolaemic effects by altering the expression of HMG-CoA reductase. Reduced TAG and oxidised LDL may provide additional cardiovascular protective benefits.

  19. Dietary restriction protects against diethylnitrosamine-induced hepatocellular tumorigenesis by restoring the disturbed gene expression profile

    PubMed Central

    Duan, Ting; Sun, Wenjie; Zhang, Mohan; Ge, Juan; He, Yansu; Zhang, Jun; Zheng, Yifan; Yang, Wei; Shen, Han-ming; Yang, Jun; Zhu, Xinqiang; Yu, Peilin

    2017-01-01

    Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent malignancies, worse still, there are very limited therapeutic measures with poor clinical outcomes. Dietary restriction (DR) has been known to inhibit spontaneous and induced tumors in several species, but the mechanisms are little known. In the current study, by using a diethylnitrosamine (DEN)-induced HCC mice model, we found that DR significantly reduced the hepatic tumor number and size, delayed tumor development, suppressed proliferation and promoted apoptosis. Further transcriptome sequencing of liver tissues from the DEN and the DEN accompanied with DR (DEN+DR) mice showed that DEN induced profound changes in the gene expression profile, especially in cancer-related pathways while DR treatment reversed most of the disturbed gene expression induced by DEN. Finally, transcription factor enrichment analysis uncovered the transcription factor specificity protein 1 (SP1) probably functioned as the main regulator of gene changes, orchestrating the protective effects of DR on DEN induced HCC. Taken together, by the first comprehensive transcriptome analysis, we elucidate that DR protects aginst DEN-induced HCC by restoring the disturbed gene expression profile, which holds the promise to provide effective molecular targets for cancer therapies. PMID:28262799

  20. Solar Development on Contaminated and Disturbed Lands

    SciTech Connect

    Macknick, Jordan; Lee, Courtney; Mosey, Gail; Melius, Jenny

    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 have 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.

  1. Disturbance Increases Microbial Community Diversity and Production in Marine Sediments

    PubMed Central

    Galand, Pierre E.; Lucas, Sabrina; Fagervold, Sonja K.; Peru, Erwan; Pruski, Audrey M.; Vétion, Gilles; Dupuy, Christine; Guizien, Katell

    2016-01-01

    Disturbance strongly impacts patterns of community diversity, yet the shape of the diversity-disturbance relationship remains a matter of debate. The topic has been of interest in theoretical ecology for decades as it has practical implications for the understanding of ecosystem services in nature. One of these processes is the remineralization of organic matter by microorganisms in coastal marine sediments, which are periodically impacted by disturbances across the sediment-water interface. Here we set up an experiment to test the hypothesis that disturbance impacts microbial diversity and function during the anaerobic degradation of organic matter in coastal sediments. We show that during the first 3 weeks of the experiment, disturbance increased both microbial production, derived from the increase in microbial abundance, and diversity of the active fraction of the community. Both community diversity and phylogenetic diversity increased, which suggests that disturbance promoted the cohabitation of ecologically different microorganisms. Metagenome analysis also showed that disturbance increased the relative abundance of genes diagnostic of metabolism associated with the sequential anaerobic degradation of organic matter. However, community composition was not impacted in a systematic way and changed over time. In nature, we can hypothesize that moderate storm disturbances, which impact coastal sediments, promote diverse, and productive communities. These events, rather than altering the decomposition of organic matter, may increase the substrate turnover and, ultimately, remineralization rates. PMID:27994581

  2. No energetic cost of anthropogenic disturbance in a songbird

    PubMed Central

    Bisson, Isabelle-Anne; Butler, Luke K.; Hayden, Tim J.; Romero, L. Michael; Wikelski, Martin C.

    2008-01-01

    Anthropogenic or natural disturbances can have a significant impact on wild animals. Therefore, understanding when, how and what type of human and natural events disturb animals is a central problem in wildlife conservation. However, it can be difficult to identify which particular environmental stressor affects an individual most. We use heart rate telemetry to quantify the energy expenditure associated with different types of human-mediated and natural disturbances in a breeding passerine, the white-eyed vireo (Vireo griseus). We fitted 0.5 g heart rate transmitters to 14 male vireos and continuously recorded heart rate and activity for two days and three nights on a military installation. We calibrated heart rate to energy expenditure for five additional males using an open-flow, push-through respirometry system showing that heart rate predicted 74 per cent of energy expenditure. We conducted standardized disturbance trials in the field to experimentally simulate a natural stressor (predator presence) and two anthropogenic stressors. Although birds initially showed behavioural and heart rate reactions to some disturbances, we could not detect an overall increase in energy expenditure during 1- or 4-hours disturbances. Similarly, overall activity rates were unaltered between control and experimental periods, and birds continued to perform parental duties despite the experimental disturbances. We suggest that vireos quickly determined that disturbances were non-threatening and thus showed no (costly) physiological response. We hypothesize that the lack of a significant response to disturbance in vireos is adaptive and may be representative of animals with fast life histories (e.g. short lifespan, high reproductive output) so as to maximize energy allocation to reproduction. Conversely, we predict that energetic cost of human-mediated disturbances will be significant in slow-living animals. PMID:19129135

  3. No energetic cost of anthropogenic disturbance in a songbird.

    PubMed

    Bisson, Isabelle-Anne; Butler, Luke K; Hayden, Tim J; Romero, L Michael; Wikelski, Martin C

    2009-03-07

    Anthropogenic or natural disturbances can have a significant impact on wild animals. Therefore, understanding when, how and what type of human and natural events disturb animals is a central problem in wildlife conservation. However, it can be difficult to identify which particular environmental stressor affects an individual most. We use heart rate telemetry to quantify the energy expenditure associated with different types of human-mediated and natural disturbances in a breeding passerine, the white-eyed vireo (Vireo griseus). We fitted 0.5g heart rate transmitters to 14 male vireos and continuously recorded heart rate and activity for two days and three nights on a military installation. We calibrated heart rate to energy expenditure for five additional males using an open-flow, push-through respirometry system showing that heart rate predicted 74 per cent of energy expenditure. We conducted standardized disturbance trials in the field to experimentally simulate a natural stressor (predator presence) and two anthropogenic stressors. Although birds initially showed behavioural and heart rate reactions to some disturbances, we could not detect an overall increase in energy expenditure during 1- or 4-hours disturbances. Similarly, overall activity rates were unaltered between control and experimental periods, and birds continued to perform parental duties despite the experimental disturbances. We suggest that vireos quickly determined that disturbances were non-threatening and thus showed no (costly) physiological response. We hypothesize that the lack of a significant response to disturbance in vireos is adaptive and may be representative of animals with fast life histories (e.g. short lifespan, high reproductive output) so as to maximize energy allocation to reproduction. Conversely, we predict that energetic cost of human-mediated disturbances will be significant in slow-living animals.

  4. Monitoring Mars for Electrostatic Disturbances

    NASA Technical Reports Server (NTRS)

    Compton, D.

    2011-01-01

    The DSN radio telescope DSS-13 was used to monitor Mars for electrostatic discharges from 17 February to 11 April, 2010, and from 19 April to 4 May, 2011, over a total of 72 sessions. Of these sessions, few showed noteworthy results and no outstanding electrostatic disturbances were observed on Mars from analyzing the kurtosis of radio emission from Mars. Electrostatic discharges on mars were originally detected in June of 2006 by Ruf et al. using DSS-13. he kurtosis (normalized fourth moment of the electrical field strength) is sensitive to non-thermal radiation. Two frequencies bands, either 2.4 and 8.4 GHz or 8.4 and 32 GHz were used. The non-thermal radiation spectrum should have peaks at the lowest three modes of the theoretical Schumann Resonances of Mars. The telescope was pointed away from Mars every 5 minutes for 45 seconds to confirm if Mars was indeed the sources of any events. It was shown that by including a down-link signal in one channel and by observing when the kurtosis changed as the telescope was pointed away from the source that the procedure can monitor Mars without the need of extra equipment monitoring a control source.

  5. Sleep disturbances and PTSD: a perpetual circle?

    PubMed Central

    van Liempt, Saskia

    2012-01-01

    subjective and objective sleep parameters. Only a few RCTs have been published. They show promising results for atypical antipsychotics and prazosin, the latter especially on nightmare reduction. Conclusions Disturbed sleep due to nightmares increases the risk for PTSD. PTSD in turn leads to increased sleep fragmentation, decreased GH secretion, and frequent nightmares, which may again compromise fear extinction, synaptic plasticity, and recovery. This suggests that disturbed sleep is a precipitating and perpetuating factor in PTSD symptomatology, creating a perpetual circle. This dissertation suggests that activity of the hypothalamic–pituitary–adrenal axis and the sympathetic nervous system (SNS) is involved in disturbed sleep in patients with PTSD. PMID:23050070

  6. 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

  7. Disturbance regime and disturbance interactions in Rocky Mountain subalpine forest

    USGS Publications Warehouse

    Veblen, Thomas T.; Hadley, Keith S.; Nel, Elizabeth M.; Kitzberger, Thomas; Reid, Marion; Villalba, Ricardo

    1994-01-01

    1 The spatial and temporal patterns of fire, snow avalanches and spruce beetle out-breaks were investigated in Marvine Lakes Valley in the Colorado Rocky Mountains in forests of Picea engelmannii, Abies lasiocarpa, Pseudotsuga menziesiiand Populus tremuloides. Dates and locations of disturbances were determined by dendrochronological techniques. A geographic information system (GIS) was used to calculate areas affected by the different disturbance agents and to examine the spatial relationships of the different disturbances. 2 In the Marvine Lakes Valley, major disturbance was caused by fire in the 1470s, the 1630s and the 1870s and by spruce beetle outbreak in c. 1716, 1827 and 1949. 3 Since c. 1633, 9% of the Marvine Lakes Valley has been affected by snow avalanches, 38.6% by spruce beetle outbreak and 59.1% by fire. At sites susceptible to avalanches, avalanches occur at a near-annual frequency. The mean return intervals for fire and spruce beetle outbreaks are 202 and 116.5 years, respectively. Turnover times for fire and spruce beetle outbreaks are 521 and 259 years, respectively. 4 Several types of disturbance interaction were identified. For example, large and severe snow avalanches influence the spread of fire. Similarly, following a stand-devastating fire or avalanche, Picea populations will not support a spruce beetle outbreak until individual trees reach a minimum diameter which represents at least 70 years' growth. Thus, recent fires and beetle outbreaks have nonoverlapping distributions.

  8. Disturbance detection and isolation in the activated sludge process.

    PubMed

    Yoo, C K; Choi, S W; Lee, I

    2002-01-01

    This paper proposes a new fault detection and isolation (FDI) method. This method monitors the distribution of process data and detects changes in this distribution, which reflect changes in the corresponding operating condition. A modified dissimilarity index and a FDI technique are defined to quantitatively evaluate the difference between data sets. This technique considers the importance of each transformed variable in the multivariate system. The FDI technique is applied to a benchmark simulation and to data from a real wastewater treatment plant. Simulation results show that it immediately detects disturbances and automatically distinguishes between serious and minor anomalies for various types of fault. The method not only detects the disturbances, but also isolates the scale of the disturbance, facilitating the interpretation of the disturbance source. The proposed monitoring technique is found to be appropriate for analyzing the biological wastewater treatment process, which is characterized by a variety of fault and disturbance sources and non-stationary characteristics.

  9. Environmental Disturbances Decrease the Variability of Microbial Populations within Periphyton

    PubMed Central

    Webert, Kyle C.; McMahon, Katherine D.

    2016-01-01

    ABSTRACT A central pursuit of microbial ecology is to accurately model changes in microbial community composition in response to environmental factors. This goal requires a thorough understanding of the drivers of variability in microbial populations. However, most microbial ecology studies focus on the effects of environmental factors on mean population abundances, rather than on population variability. Here, we imposed several experimental disturbances upon periphyton communities and analyzed the variability of populations within disturbed communities compared with those in undisturbed communities. We analyzed both the bacterial and the diatom communities in the periphyton under nine different disturbance regimes, including regimes that contained multiple disturbances. We found several similarities in the responses of the two communities to disturbance; all significant treatment effects showed that populations became less variable as the result of environmental disturbances. Furthermore, multiple disturbances to these communities were often interactive, meaning that the effects of two disturbances could not have been predicted from studying single disturbances in isolation. These results suggest that environmental factors had repeatable effects on populations within microbial communities, thereby creating communities that were more similar as a result of disturbances. These experiments add to the predictive framework of microbial ecology by quantifying variability in microbial populations and by demonstrating that disturbances can place consistent constraints on the abundance of microbial populations. Although models will never be fully predictive due to stochastic forces, these results indicate that environmental stressors may increase the ability of models to capture microbial community dynamics because of their consistent effects on microbial populations. IMPORTANCE There are many reasons why microbial community composition is difficult to model. For example

  10. Disturbance and Recovery in Terrestrial Ecosystem Carbon Cycling-a Global Synthesis

    NASA Astrophysics Data System (ADS)

    Niu, S.; Li, D.; Hararuk, O.; Yan, L.; Chen, X.; Ali, E.; Luo, Y.

    2012-04-01

    Disturbances have been shown by many studies to trigger the release of large amounts of carbon and then influence climate change. Ecosystems usually recover after disturbances, potentially compensating the released carbon. However, it's not clear what states the ecosystems would recover to after disturbances and how long it takes to recover. We synthesized results from peer-reviewed papers that examined ecosystem recovery following disturbances. A total of 94 case studies that had complete cycles of predistrubance-disturbance-recovery were included in this synthesis. Disturbance severity, recovery time, and state shifts were quantified for each variable. The results showed that most variables recovered to their pre-disturbance states. But the recovery time changed greatly among variables, ecosystems, and disturbance types, with long recovery time for soil C (101 years) and short time for NPP (56 years) and litter accumulation (34 years) after fire. Recovery time was shorter in grasslands than forests, and shorter from droughts (climate extremes) than fire and deforestation. Moreover, the recovery time was related to disturbance severity. The severer the disturbance, the longer the recovery time is. State changes that after disturbances ecosystems recovered to states that differ from the pre-disturbance ones was detected for many variables. NPP and litter accumulation after the full recovery following fire disturbances exceeded the pre-disturbance states while the fully recovered total aboveground biomass and soil carbon after the disturbances differed little from the pre-disturbance ones. The results indicate that it's crucial to quantify the disturbance impacts on ecosystems by considering the disturbance severity and state shifts.

  11. Composite disturbance rejection control based on generalized extended state observer.

    PubMed

    Zhang, Yanjun; Zhang, Jun; Wang, Lu; Su, Jianbo

    2016-07-01

    Traditional extended state observer (ESO) design method does not focus on analysis of system reconstruction strategy. The prior information of the controlled system cannot be used for ESO implementation to improve the control accuracy. In this paper, composite disturbance rejection control strategy is proposed based on generalized ESO. First, the disturbance rejection performance of traditional ESO is analyzed to show the essence of the reconstruction strategy. Then, the system is reconstructed based on the equivalent disturbance model. The generalized ESO is proposed based on the reconstructed model, while convergence of the proposed ESO is analyzed along with the outer loop feedback controller. Simulation results on a second order mechanical system show that the proposed generalized ESO can deal with the external disturbance with known model successfully. Experiment of attitude tracking task on an aircraft is also carried out to show the effectiveness of the proposed method.

  12. Polar Disturbance Surrounding a Long Living Cyclone in Saturn's Atmosphere

    NASA Astrophysics Data System (ADS)

    del Rio-Gaztelurrutia, T.; Sanchez-Lavega, A.; Antuñano, A.; Hueso, R.; Perez-Hoyos, S.; Rojas, J. F.; Wong, M. H.; Simon, A. A.; De Pater, I.; Gomez-Forrelad, J. M.; Legarreta, J.

    2015-12-01

    In 2014 and 2015 a large 'dark spot' about 6,000 km in length and located at planetocentric latitude +58.5º (+63º N planetographic) was tracked on the best ground-based amateur images of Saturn, revealing a long-lived feature, an uncommon phenomenon in Saturn's atmosphere. Images captured by the Imaging Science Subsystem (ISS) onboard Cassini spacecraft showed the feature as a very contrasted dark spot in the MT3 filter, and barely visible in the deep sounding filters CB2 and CB3. On mid-May 2015 ground-based observations obtained by amateur astronomers operating small telescopes started to show a disturbance around this dark spot. Following the onset of this disturbance the drift of the dark spot remained unaltered and equal to the motion it had previously, but the disturbance evolved zonally in a complex manner, giving hints of a kind of large scale phenomena in Saturn's atmosphere of an unprecedented type. Unfortunately the orbital path of the Cassini spacecraft was not appropriate to see details of the disturbance at that time. Images by the Hubble Space Telescope (HST) WFC3 instrument obtained in director's time (DDT) allow us to describe the detailed dynamics of the disturbance, while the study of its long-term evolution is possible thanks to the efforts of the community of amateur astronomers. In this work we analyse the dynamics of the region before the start of the disturbance and the dynamics and evolution of the disturbance after its onset.

  13. Melatonin ameliorates chronic mild stress induced behavioral dysfunctions in mice.

    PubMed

    Haridas, Seenu; Kumar, Mayank; Manda, Kailash

    2013-07-02

    Melatonin, a neurohormone, is known to regulate several physiological functions, especially the circadian homeostasis, mood and behavior. Chronic exposure to stress is involved in the etiology of human affective disorders, and depressed patients have been reported to show changes in the circadian rhythms and nocturnal melatonin concentration. The present study was conducted to evaluate a possible beneficial action of chronic night-time melatonin treatment against chronic mild stress (CMS) induced behavioral impairments. As expected in the present study, the stress exposed mice showed reduced weight gain, hedonic deficit, cognitive deficits and decreased mobility in behavioral despair test. Interestingly, CMS exposed mice showed less anxiety. Chronic night-time melatonin administration significantly ameliorated the stress-induced behavioral disturbances, especially the cognitive dysfunction and depressive phenotypes. In conclusion, the present findings suggest the mitigating role of melatonin against CMS-induced behavioral changes, including the cognitive dysfunctions and reaffirm its potential role as an antidepressant.

  14. Protecting coherence by reservoir engineering: intense bath disturbance

    NASA Astrophysics Data System (ADS)

    Zhou, Zixian; Lü, Zhiguo; Zheng, Hang

    2016-08-01

    We put forward a scheme based on reservoir engineering to protect quantum coherence from leaking to bath, in which we intensely disturb the Lorentzian bath by N harmonic oscillators. We show that the intense disturbance changes the spectrum of the bath and reduces the qubit-bath interaction. Furthermore, we give the exact time evolution with the Lorentzian spectrum by a master equation and calculate the concurrence and survival probability of the qubits to demonstrate the effect of the intense bath disturbance on the protection of coherence. Meanwhile, we reveal the dynamic effects of counter-rotating interaction on the qubits as compared to the results of the rotating-wave approximation.

  15. Stronger error disturbance relations for incompatible quantum measurements

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Chiranjib; Shukla, Namrata; Pati, Arun Kumar

    2016-03-01

    We formulate a new error-disturbance relation, which is free from explicit dependence upon variances in observables. This error-disturbance relation shows improvement over the one provided by the Branciard inequality and the Ozawa inequality for some initial states and for a particular class of joint measurements under consideration. We also prove a modified form of Ozawa's error-disturbance relation. The latter relation provides a tighter bound compared to the Ozawa and the Branciard inequalities for a small number of states.

  16. Imaging of growth disturbance in children.

    PubMed

    Ecklund, K; Jaramillo, D

    2001-07-01

    Growth disturbance of the long bones in children is frequently post-traumatic but also occurs because of physeal, epiphyseal, or metaphyseal ischemia. The imaging features of growth arrest depend more on the anatomic site involved than on the cause. The physes of the distal tibia and femur and proximal tibia are disproportionately at risk because of their complex geometry. The central undulation in the distal femur and the bump in the anteromedial physis (Kump's bump) in the distal tibia are the sites of initial physiologic closure and the most frequent areas of premature fusion. The MR imaging features of growth disturbance are characteristic. T1-weighted images show low signal intensity GRL and variable signal intensity bony bridges. On GRE sequences, a bridge appears as low signal intensity interruption in the otherwise high signal intensity physeal cartilage. Physeal widening on GRE and T2-weighted images implies physeal dysfunction without bridge formation. Proton density and T2-weighted images best reveal associated metaphyseal and soft tissue changes. Regardless of the cause, MR imaging exquisitely depicts cartilaginous pathology at the physis. MR evaluation should be considered in patients at high risk for growth disturbance including young children with extensive residual growth potential; those with involvement of particularly vulnerable growth plates; and those with severe, complex fractures.

  17. State Definitions of Emotional Disturbance

    ERIC Educational Resources Information Center

    Wery, Jessica J.; Cullinan, Douglas

    2013-01-01

    This article examines definitions state education agencies use to describe the federal education disability called "emotional disturbance." State definitions were collected so that various aspects of them could be analyzed and compared with results of similar studies completed in the 1970s and 1980s. Among results are that state definitions have…

  18. Disturbed by Meta-Analysis?

    ERIC Educational Resources Information Center

    Wachter, Kenneth W.

    1988-01-01

    Defines meta-analysis as statistical procedures for combining results from previous separate studies. Discusses four charges promoted by some skeptics as it relates to this statistical procedure. States that many of the trends making a place for meta-analysis are disturbing. (RT)

  19. RESILIENCE OF ECOSYSTEMS TO DISTURBANCES

    EPA Science Inventory

    Resilience, in an ecological context, is one of several terms that characterize the response of an ecosystem to disturbance. Other such terms include persistence, resistance and stability. Two definitions of resilience have become prominent in the literature, both of which derive...

  20. Linking disturbance intensity and carbon cycle in forest ecosystems

    NASA Astrophysics Data System (ADS)

    Gielen, B.; Hudiburg, T.; Law, B. E.; Luyssaert, S.

    2011-12-01

    There is increasing awareness that natural and anthropogenic disturbance in forests forest affects exchange of CO2, H2O and energy between the ecosystem and the atmosphere. Furthermore, severe disturbance may result in substantial emissions of greenhouse gasses to the atmosphere. Consequently quantification of land use and disturbance intensity (LUDI) is one of the next steps needed to improve our understanding of the carbon cycle, its interactions with the atmosphere and its main drivers at local as well as at global level. The conventional NPP-based approaches to quantify the intensity of land management are limited because they lack a sound ecological basis. Here we apply a new way of characterising the degree of management and disturbance in forest. The index called LUDI: land use and disturbance intensity makes use of the self thinning theory and observations of diameter at breast height and stand density. The application of LUDI was demonstrated by using a very extensive dataset from the Pacific Northwest region (PNW) in North America containing more than 5000 inventory plots. Results show significant relationships between LUDI and forest productivity (NPP) and Carbon uptake (NEP) for seven different forest types in the PNW. In addition the relationships suggest a maximal productivity at mild disturbance. These results further confirm the link between forest disturbance and carbon cycling in forest ecosystems.

  1. A Landsat Record of North American Forest Disturbance

    NASA Astrophysics Data System (ADS)

    Masek, J.; Hall, F. G.; Huang, C.; Wolfe, R.

    2005-12-01

    The Landsat Ecosystem Disturbance Adaptive Processing System (LEDAPS) is generating a decadal, wall-to-wall analysis of forest disturbance and recovery from Landsat satellite imagery for the period 1975-2000. The intent is to provide an accurate, high-resolution view of forest disturbance to support biogeochemical modeling and carbon accounting for the North American Carbon Program (NACP). Through the NASA Science Data Purchase program, substantially cloud-free Landsat MSS, TM, and ETM+ data were selected from the global archive and orthorectified to a UTM map base. The LEDAPS project has calibrated and atmospherically corrected these data (~2100 TM and ETM+ scenes to date) using the MODIS/6S radiative transfer approach. Forest disturbance and recovery is then calculated from the surface reflectance images using change detection techniques. An empirical spectral index (the `Disturbance Index') is used to classify pixels into classes exhibiting high rates of biomass loss over ten years (disturbance) or high rates of biomass gain (recovery). Initial results from North America show good correlation with areas of known harvest activity (Southeastern US, Maine, Pacific Northwest) and fire activity (Boreal forests). Additional work is concentrating on the use of canopy reflectance models to quantify changes in canopy properties in order to identify more subtle changes due to partial harvest and thinning. Initial versions of the surface reflectance and Disturbance Index products were released during 2005 (http://ledaps.nascom.nasa.gov/ledaps/ledaps_NorthAmerica.html).

  2. 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.

  3. Effects of gabapentin on brain hyperactivity related to pain and sleep disturbance under a neuropathic pain-like state using fMRI and brain wave analysis.

    PubMed

    Takemura, Yoshinori; Yamashita, Akira; Horiuchi, Hiroshi; Furuya, Masaharu; Yanase, Makoto; Niikura, Keiichi; Imai, Satoshi; Hatakeyama, Noboru; Kinoshita, Hiroyuki; Tsukiyama, Yoshi; Senba, Emiko; Matoba, Motohiro; Kuzumaki, Naoko; Yamazaki, Mitsuaki; Suzuki, Tsutomu; Narita, Minoru

    2011-07-01

    Neuropathic pain is the most difficult pain to manage in the pain clinic, and sleep problems are common among patients with chronic pain including neuropathic pain. In the present study, we tried to visualize the intensity of pain by assessing neuronal activity and investigated sleep disturbance under a neuropathic pain-like state in mice using functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG)/electromyogram (EMG), respectively. Furthermore, we investigated the effect of gabapentin (GBP) on these phenomena. In a model of neuropathic pain, sciatic nerve ligation caused a marked decrease in the latency of paw withdrawal in response to a thermal stimulus only on the ipsilateral side. Under this condition, fMRI showed that sciatic nerve ligation produced a significant increase in the blood oxygenation level-dependent (BOLD) signal intensity in the pain matrix, which was significantly decreased 2 h after the i.p. injection of GBP. Based on the results of an EEG/EMG analysis, sciatic nerve-ligated animals showed a statistically significant increase in wakefulness and a decrease in non-rapid eye movement (NREM) sleep during the light phase, and the sleep disturbance was almost completely alleviated by a higher dose of GBP in nerve-ligated mice. These findings suggest that neuropathic pain associated with sleep disturbance can be objectively assessed by fMRI and EEG/EMG analysis in animal models. Furthermore, GBP may improve the quality of sleep as well as control pain in patients with neuropathic pain.

  4. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  5. 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

  6. [Disturbance assessment of urban wetland ecosystem services: a case study in Pingshan watershed of Shenzhen City].

    PubMed

    Zhang, Wen-juan; Li, Gui-cai; Zeng, Hui

    2010-05-01

    To understand the wetland ecosystem services in urbanizing area is much needed in wetland assessment. Currently, the dominant approach in assessing wetland value is the assessment model using environmental economic analysis. However, this approach can not reflect the impact of human disturbance. This paper introduced the connotation of wetland ecosystem services and the patterns of human disturbance, established an evaluation index system which could characterize the disturbance impact, and determined the weight of each index by using analytic hierarchy process. Moreover, a dual-grade fuzzy comprehensive evaluation model was applied to analyze the spatial heterogeneity of human disturbance. Our case study in Pingshan River Basin, a typical urbanizing area of Shenzhen, showed that geographic condition was the primary factor in determining the intensity of human disturbance on wetland ecosystem services. The main disturbance pattern in the south hilly area was vegetation degeneration, but the disturbance intensity was low. Even so, the vegetation protection and management in this area shouldn't be ignored though. The disturbance pattern in north valley area was diverse, and the disturbance intensity was much higher than that south hilly area. From the upper reach to the lower reach of the main stream, the impact of human disturbance increased first and decreased then, being accorded with the characteristics of land use pattern, but the disturbance pattern didn't have a continuous distribution. Our study showed that fuzzy comprehensive evaluation model had good performance in the disturbance assessment of wetland ecosystem services.

  7. 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.

  8. Increased tolerance to humans among disturbed wildlife.

    PubMed

    Samia, Diogo S M; Nakagawa, Shinichi; Nomura, Fausto; Rangel, Thiago F; Blumstein, Daniel T

    2015-11-16

    Human disturbance drives the decline of many species, both directly and indirectly. Nonetheless, some species do particularly well around humans. One mechanism that may explain coexistence is the degree to which a species tolerates human disturbance. Here we provide a comprehensive meta-analysis of birds, mammals and lizards to investigate species tolerance of human disturbance and explore the drivers of this tolerance in birds. We find that, overall, disturbed populations of the three major taxa are more tolerant of human disturbance than less disturbed populations. The best predictors of the direction and magnitude of bird tolerance of human disturbance are the type of disturbed area (urbanized birds are more tolerant than rural or suburban populations) and body mass (large birds are more tolerant than small birds). By identifying specific features associated with tolerance, these results guide evidence-based conservation strategies to predict and manage the impacts of increasing human disturbance on birds.

  9. Increased tolerance to humans among disturbed wildlife

    PubMed Central

    Samia, Diogo S. M.; Nakagawa, Shinichi; Nomura, Fausto; Rangel, Thiago F.; Blumstein, Daniel T.

    2015-01-01

    Human disturbance drives the decline of many species, both directly and indirectly. Nonetheless, some species do particularly well around humans. One mechanism that may explain coexistence is the degree to which a species tolerates human disturbance. Here we provide a comprehensive meta-analysis of birds, mammals and lizards to investigate species tolerance of human disturbance and explore the drivers of this tolerance in birds. We find that, overall, disturbed populations of the three major taxa are more tolerant of human disturbance than less disturbed populations. The best predictors of the direction and magnitude of bird tolerance of human disturbance are the type of disturbed area (urbanized birds are more tolerant than rural or suburban populations) and body mass (large birds are more tolerant than small birds). By identifying specific features associated with tolerance, these results guide evidence-based conservation strategies to predict and manage the impacts of increasing human disturbance on birds. PMID:26568451

  10. 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

  11. Central ghrelin signaling mediates the metabolic response of C57BL/6 male mice to chronic social defeat stress.

    PubMed

    Patterson, Z R; Khazall, R; Mackay, H; Anisman, H; Abizaid, A

    2013-03-01

    Chronic stressors promote metabolic disturbances, including obesity and metabolic syndrome. Ghrelin, a peptide that promotes appetite and the accumulation of adipose tissue, is also secreted in response to stressors to protect the brain and peripheral tissues from the effects of these stressors. Here we demonstrate that elevated ghrelin levels produced by chronic exposure to social stress are associated with increased caloric intake and body weight gain in male C57BL mice. In contrast, stressed mice lacking ghrelin receptors (GHSR KO mice) or C57BL mice receiving chronic intracerebroventricular delivery of the ghrelin receptor antagonist [d-Lys(3)]-GHRP-6 show attenuated weight gain and feeding responses under the same social stress paradigm. Interestingly, stressed GHSR KO mice showed depleted sc and intrascapular brown fat depots, whereas stressed young wild-type mice did not. In old wild-type mice, chronic social defeat increased visceral and intrascapular brown fat depots in association with increases in obesity markers like hyperleptinemia and hyperinsulinemia along with increased hypothalamic expression of neuropeptide Y and Agouti related peptide. Importantly, the elevated expression of these peptides persisted least for 2 weeks after cessation of the stressor regimen. In contrast, old GHSR KO mice did not show these alterations after chronic social defeat. These results suggest that ghrelin plays an important role in the metabolic adaptations necessary to meet the energetic demands posed by stressors, but chronic exposure to stress-induced ghrelin elevations ultimately could lead to long lasting metabolic dysfunctions.

  12. Global ionospheric disturbances during super magnetic storms

    NASA Astrophysics Data System (ADS)

    Huang, C.; Foster, J.; Rideout, W.; Zhang, Y.; Paxton, L.

    2005-12-01

    Magnetic storms represent the largest disturbances in the magnetosphere and ionosphere. We will present the ionospheric observations by the Millstone Hill incoherent scatter radar, global GPS network, and TIMED GUVI instrument during two super storms. The sudden commencement (SSC) of the 15 July 2000 storm occurred at 19 UT, and the minimum Dst reached -301 nT. The dayside midlatitude ionospheric F region electron density showed a sudden decrease at Millstone Hill and Eglin in response to the SSC. The elevation scan measurements of the Millstone HIll radar show that the sudden decrease in the ionospheric electron density was related to an electron density trough which had an equatorward boundary at Eglin (magnetic latitude 41 degree) at 16 MLT. The formation of the trough may be related to equatorward incursion of the disturbance SAPS electric field. The dayside TEC decreased significantly at the equatorial and upper midlatitudes, and an enhanced TEC band occurred between the depleted regions. The SSC of the 29 October 2003 storm occurred at 07 UT, the storm was further enhanced at 18 UT, and the minimum Dst reached -363 nT. The Millstone Hill radar also detected a sudden decrease of the dayside F region electron density immediately after the storm enhancement. The simultaneous TIMED GUVI measurements show a significant decrease in the O/N2 ratio over the Atlantic sector from the auroral zone to anomaly latitudes, and large TEC depletions occurred coincidentally with the O/N2 decrease. In this second case, both the enhanced electric field and decrease of O/N2 ratio contributed to the depletion of the dayside midlatitude F-region electron density and TEC. The multiple measurements during the two storms reveal the distinct properties and mechanisms of the global ionospheric disturbances.

  13. Intact theory of mind in TBI with behavioural disturbance.

    PubMed

    Bach, L J; Happe, F; Fleminger, S; David, A S

    2006-03-01

    Behavioural disturbance following TBI is common. Theory of mind(ToM) deficits have been noted in autism where difficulties with social interaction and communication are evident. It was hypothesised that TBI patients with behavioural disturbance would show deficits on ToM tasks independent of executive function. Twenty TBI patients with behavioural disturbance and 20 TBI patients without were assessed on verbal (stories) and non-verbal (cartoons) ToM tasks,standard psychometry, and measures of executive function.TBI patients were unimpaired on the ToM tasks. Both groups were unimpaired on standard tests of executive function (verbal fluency and trail making test) but were impaired on the Behavioural Assessment of Dysexecutive Syndrome (BADS). Groups did not differ significantly on these tests. It is concluded that ToM ability does not predict behavioural disturbance and may be independent of executive functioning.

  14. Robust uncalibrated visual servoing control based on disturbance observer.

    PubMed

    Ma, Zhe; Su, Jianbo

    2015-11-01

    In this paper, an uncalibrated visual servoing scheme with optimal disturbance rejection performance is proposed based on disturbance observer (DOB). Comparing with traditional uncalibrated methods, which estimate online the hand-eye relationship characterized by varying image Jacobian, the uncertainty of image Jacobian is eliminated via DOB to approach a given nominal model in this paper. By solving a constrained optimization problem transformed into an H∞ control framework, the disturbance rejection performance is optimized while ensuring the robust stability of the closed-loop visual servoing system. The controller is based on the nominal image Jacobian matrix, thus avoiding singularities and local minima. Simulations and experiments show that the proposed scheme performs better in tracking an object than traditional algorithms. The disturbance and image noise rejection performance is verified.

  15. 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, C.

    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.

  16. Extended active disturbance rejection controller

    NASA Technical Reports Server (NTRS)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2012-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  17. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2014-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  18. Extended Active Disturbance Rejection Controller

    NASA Technical Reports Server (NTRS)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2016-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  19. 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.

  20. Natural and Human-induced Disturbances and Their Impacts on Forest Carbon Budgets in North America

    NASA Astrophysics Data System (ADS)

    Pan, Y.; Birdsey, R.; Chen, J. M.; McCullough, K.; Zhang, F.

    2014-12-01

    Natural and human-induced disturbances have profound impacts on forest carbon dynamics, and may cause the greatest uncertainty in estimating forest carbon budgets. In North America, three countries show very different forest disturbance patterns: Canadian forests are dominated by natural disturbances such as wildfires and insect outbreaks; forests of Mexico are more affected by human-induced land disturbances such as land-use change; while US forests are equally affected by human-induced and natural disturbances. As human-induced disturbances are closely linked to socioeconomic factors, natural disturbances are usually viewed as a natural process in forests and have equilibrium impacts on forests over the long run. However, with climate change and related changes in natural disturbance regimes in terms of frequency, intensity and scale, there are now fundamental changes in the nature of the impact of natural disturbances on forest carbon dynamics and even greater uncertainty about forest carbon budgets and feedbacks to the atmosphere and climate. In this study, we synthesize disturbance information for North America based on existing remote-sensing products, ground-based observations and modeling studies, evaluating impacts of disturbances on forest carbon budgets that are relevant to disturbance types, scales, frequency and intensity. The work represents the initial step of a more ambitious project tackling this research challenge for North America that crosses a broad climate gradient and diverse socioeconomic entities. The goal is to ultimately improve the estimates of forest carbon budgets and their potential for climate mitigation under changing environments.

  1. 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.

  2. A Genetic Mouse Model of Parkinson's Disease Shows Involuntary Movements and Increased Postsynaptic Sensitivity to Apomorphine.

    PubMed

    Brehm, N; Bez, F; Carlsson, T; Kern, B; Gispert, S; Auburger, G; Cenci, M A

    2015-12-01

    Alpha-synuclein (SNCA) protein aggregation plays a causal role in Parkinson's disease (PD). The SNCA protein modulates neurotransmission via the SNAP receptor (SNARE) complex assembly and presynaptic vesicle trafficking. The striatal presynaptic dopamine deficit is alleviated by treatment with levodopa (L-DOPA), but postsynaptic plastic changes induced by this treatment lead to a development of involuntary movements (dyskinesia). While this process is currently modeled in rodents harboring neurotoxin-induced lesions of the nigrostriatal pathway, we have here explored the postsynaptic supersensitivity of dopamine receptor-mediated signaling in a genetic mouse model of early PD. To this end, we used mice with prion promoter-driven overexpression of A53T-SNCA in the nigrostriatal and corticostriatal projections. At a symptomatic age (18 months), mice were challenged with apomorphine (5 mg/kg s.c.) and examined using both behavioral and molecular assays. After the administration of apomorphine, A53T-transgenic mice showed more severe stereotypic and dystonic movements in comparison with wild-type controls. Molecular markers of extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation and dephosphorylation, and Fos messenger RNA (mRNA), were examined in striatal tissue at 30 and 100 min after apomorphine injection. At 30 min, wild-type and transgenic mice showed a similar induction of phosphorylated ERK1/2, Dusp1, and Dusp6 mRNA (two MAPK phosphatases). At the same time point, Fos mRNA was induced more strongly in mutant mice than in wild-type controls. At 100 min after apomorphine treatment, the induction of both Fos, Dusp1, and Dusp6 mRNA was significantly larger in mutant mice than wild-type controls. At this time point, apomorphine caused a reduction in phospho-ERK1/2 levels specifically in the transgenic mice. Our results document for the first time a disturbance of ERK1/2 signaling regulation associated with apomorphine-induced involuntary movements

  3. Showing What They Know

    ERIC Educational Resources Information Center

    Cech, Scott J.

    2008-01-01

    Having students show their skills in three dimensions, known as performance-based assessment, dates back at least to Socrates. Individual schools such as Barrington High School--located just outside of Providence--have been requiring students to actively demonstrate their knowledge for years. The Rhode Island's high school graduating class became…

  4. The Ozone Show.

    ERIC Educational Resources Information Center

    Mathieu, Aaron

    2000-01-01

    Uses a talk show activity for a final assessment tool for students to debate about the ozone hole. Students are assessed on five areas: (1) cooperative learning; (2) the written component; (3) content; (4) self-evaluation; and (5) peer evaluation. (SAH)

  5. What Do Maps Show?

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet, appropriate for grades 4-8, features a teaching poster which shows different types of maps (different views of Salt Lake City, Utah), as well as three reproducible maps and reproducible activity sheets which complement the maps. The poster provides teacher background, including step-by-step lesson plans for four geography…

  6. Show Me the Way

    ERIC Educational Resources Information Center

    Dicks, Matthew J.

    2005-01-01

    Because today's students have grown up steeped in video games and the Internet, most of them expect feedback, and usually gratification, very soon after they expend effort on a task. Teachers can get quick feedback to students by showing them videotapes of their learning performances. The author, a 3rd grade teacher describes how the seemingly…

  7. Chemistry Game Shows

    NASA Astrophysics Data System (ADS)

    Campbell, Susan; Muzyka, Jennifer

    2002-04-01

    We present a technological improvement to the use of game shows to help students review for tests. Our approach uses HTML files interpreted with a browser on a computer attached to an LCD projector. The HTML files can be easily modified for use of the game in a variety of courses.

  8. Honored Teacher Shows Commitment.

    ERIC Educational Resources Information Center

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  9. Talk Show Science.

    ERIC Educational Resources Information Center

    Moore, Mitzi Ruth

    1992-01-01

    Proposes having students perform skits in which they play the roles of the science concepts they are trying to understand. Provides the dialog for a skit in which hot and cold gas molecules are interviewed on a talk show to study how these properties affect wind, rain, and other weather phenomena. (MDH)

  10. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

    In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

  11. 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,...

  12. 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,...

  13. Recovery of methanotrophs from disturbance: population dynamics, evenness and functioning.

    PubMed

    Ho, Adrian; Lüke, Claudia; Frenzel, Peter

    2011-04-01

    Biodiversity is claimed to be essential for ecosystem functioning, but is threatened by anthropogenic disturbances. Prokaryotes have been assumed to be functionally redundant and virtually inextinguishable. However, recent work indicates that microbes may well be sensitive to environmental disturbance. Focusing on methane-oxidizing bacteria as model organisms, we simulated disturbance-induced mortality by mixing native with sterilized paddy soil in two ratios, 1:4 and 1:40, representing moderate and severe die-offs. Disturbed microcosms were compared with an untreated control. Recovery of activity and populations was followed over 4 months by methane uptake measurements, pmoA-qPCR, pmoA-based terminal restriction fragment length polymorphism and a pmoA-based diagnostic microarray. Diversity and evenness of methanotrophs decreased in disturbed microcosms, but functioning was not compromised. We consistently observed distinctive temporal shifts between type I and type II methanotrophs, and a rapid population growth leading to even higher cell numbers comparing disturbed microcosms with the control. Overcompensating mortality suggested that population size in the control was limited by competition with other bacteria. Overall, methanotrophs showed a remarkable ability to compensate for die-offs.

  14. [Sedimentary Phosphorus Forms Under Disturbances and Algae in Taihu Lake].

    PubMed

    Chen, Jun; Li, Da-peng; Zhu, Pei-ying; Huang, Yong; Wang, Ren

    2015-12-01

    Sedimentary phosphorus forms were investigated to clarify the release of sedimentary phosphorus forms under the repeated disturbance with the addition of algae at different initial concentrations. The sediments and overlying water were taken from the Meiliang Bay in Taihu Lake. The results showed that the concentrations of NH₄ Cl-P and Res-P decreased, while the content of Fe/Al-P and Ca-P increased without disturbance. In addition, the Ca-P increased with the increase of the initial concentration of algae and the net increase of Ca-P increased by 48% (30 µg · L⁻¹), 66% (60 µg · L⁻¹), 74% (120 µg · L⁻¹), respectively. However, under the disturbance, the NH₄Cl-P and Res-P were significantly reduced, the Fe/Al-P increased significantly. The percentage of Fe/Al-P to Tot-P was up to 66. 2% (average of the 3 experiments with the addition of algae of 30 µg · L⁻¹, 60 µg · L⁻¹ and 120 µg L-¹), it was higher than the value (53.%, average of the 3 experiments) without the disturbance. Moreover, under the disturbance, the percentage of Ca-P to Tot-P was 24.1% (average of the 3 experiments with the addition of algae of 30 µg · L⁻¹, 60 µg⁻¹ and 120 µg · L⁻¹) and it was slightly lower than that (33.0%, average of the 3 experiments) without the disturbance. It is suggested that the coexistence of disturbance and algae facilitated the formation of Fe/Al-P, but the algae accelerated the formation of Ca-P without disturbance.

  15. Exposure of cerium oxide nanoparticles to kidney bean shows disturbance in the plant defense mechanisms.

    PubMed

    Majumdar, Sanghamitra; Peralta-Videa, Jose R; Bandyopadhyay, Susmita; Castillo-Michel, Hiram; Hernandez-Viezcas, Jose-Angel; Sahi, Shivendra; Gardea-Torresdey, Jorge L

    2014-08-15

    Overwhelming use of engineered nanoparticles demands rapid assessment of their environmental impacts. The transport of cerium oxide nanoparticles (nCeO2) in plants and their impact on cellular homeostasis as a function of exposure duration is not well understood. In this study, kidney bean plants were exposed to suspensions of ∼ 8 ± 1 nm nCeO2 (62.5 to 500 mg/L) for 15 days in hydroponic conditions. Plant parts were analyzed for cerium accumulation after one, seven, and 15 days of nCeO2 exposure. The primary indicators of stress like lipid peroxidation, antioxidant enzyme activities, total soluble protein and chlorophyll contents were studied. Cerium in tissues was localized using scanning electron microscopy and synchrotron μ-XRF mapping, and the chemical forms were identified using μ-XANES. In the root epidermis, cerium was primarily shown to exist as nCeO2, although a small fraction (12%) was biotransformed to Ce(III) compound. Cerium was found to reach the root vascular tissues and translocate to aerial parts with time. Upon prolonged exposure to 500 mg nCeO2/L, the root antioxidant enzyme activities were significantly reduced, simultaneously increasing the root soluble protein by 204%. In addition, leaf's guaiacol peroxidase activity was enhanced with nCeO2 exposure in order to maintain cellular homeostasis.

  16. Frequency and duration of disturbances in the mid-latitude F region of the ionosphere

    SciTech Connect

    Lambert, S.

    1988-08-01

    Disturbances of the ionospheric F region at two well-separated midlatitude stations were identified on rapid run ionograms by spread echoes, blackouts, and anomalies in structure or critical frequency. The diurnal variation in the probability of disturbance consistently shows minima around sunrise and sunset. Details such as a brief postsunset enhancement in winter are revealed by the fine time resolution of the data. Disturbance probabilities were lowest in autumn and spring (8 and 9 percent), while that for winter (33 percent) exceeded the summer level (20 percent). Spread F constituted 32 percent of the events, and disturbances producing sharply defined ionogram signatures 77 percent, with some overlapping of types. The majority of disturbances were not correlated with geomagnetic phenomena. Disturbances at the two stations were essentially independent (spatial correlation of 0.15). Spread F events were of longer duration (25 min) than sharp disturbances (20 min). 24 references.

  17. Determination of travelling ionospheric disturbances

    NASA Technical Reports Server (NTRS)

    Degenhardt, W.; Hartmann, G. H.; Davies, K.

    1978-01-01

    A total of 35 days of Faraday rotation data was obtained from the ATS-6 radio beacon experiment operating with the closely spaced network of Elbert, Table Mountain, and Fort Morgan. The 140-MHz Faraday bandpass data are uncorrelated in the transmission range from 8 to 45 minutes. There are distinct, well correlated, and time-displaced maxima and minima that allow the calculation of the speed and direction of horizontal motions of plane fronts of disturbances in the ionosphere. For some selected events, velocities between 88 and 278 m/sec were obtained.

  18. Vulnerability of conditional NCAM-deficient mice to develop stress-induced behavioral alterations.

    PubMed

    Bisaz, Reto; Sandi, Carmen

    2012-03-01

    Previous studies in rodents showed that chronic stress induces structural and functional alterations in several brain regions, including shrinkage of the hippocampus and the prefrontal cortex, which are accompanied by cognitive and emotional disturbances. Reduced expression of the neural cell adhesion molecule (NCAM) following chronic stress has been proposed to be crucially involved in neuronal retraction and behavioral alterations. Since NCAM gene polymorphisms and altered expression of alternatively spliced NCAM isoforms have been associated with bipolar depression and schizophrenia in humans, we hypothesized that reduced expression of NCAM renders individuals more vulnerable to the deleterious effects of stress on behavior. Here, we specifically questioned whether mice in which the NCAM gene is inactivated in the forebrain by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter (conditional NCAM-deficient mice), display increased vulnerability to stress. We assessed the evolving of depressive-like behaviors and spatial learning and memory impairments following a subchronic stress protocol (2 weeks) that does not result in behavioral dysfunction, nor in altered NCAM expression, in wild-type mice. Indeed, while no behavioral alterations were detected in wild-type littermates after subchronic stress, conditional NCAM-deficient mice showed increased immobility in the tail suspension test and deficits in reversal spatial learning in the water maze. These findings indicate that diminished NCAM expression might be a critical vulnerability factor for the development of behavioral alterations by stress and further support a functional involvement of NCAM in stress-induced cognitive and emotional disturbances.

  19. A direct relationship between aggressive behavior in the resident/intruder test and cell oxidative status in adult male mice.

    PubMed

    Rammal, Hassan; Bouayed, Jaouad; Soulimani, Rachid

    2010-02-10

    Disturbances in oxidative metabolism are involved in many acute and chronic diseases, as well as in several other conditions. The objective of the present study was to examine the relationship between the level of intracellular reactive oxygen species in the peripheral blood granulocytes of mice, as evaluated by 2',7'-dichlorofluorescin diacetate (DCFH-DA), a sensor of reactive oxygen species, and the aggressive behavior of these mice, as estimated by the resident/intruder test. Our results showed a significant, linear and positive relationship (P<0.001) between the intracellular redox status of peripheral blood granulocytes and the aggressive behavior levels of adult male mice (correlation coefficients (R(2)) ranging from 0.75 to 0.77). This suggests that the granulocytes of aggressively behaving mice have high levels of oxidative stress.

  20. Not a "reality" show.

    PubMed

    Wrong, Terence; Baumgart, Erica

    2013-01-01

    The authors of the preceding articles raise legitimate questions about patient and staff rights and the unintended consequences of allowing ABC News to film inside teaching hospitals. We explain why we regard their fears as baseless and not supported by what we heard from individuals portrayed in the filming, our decade-long experience making medical documentaries, and the full un-aired context of the scenes shown in the broadcast. The authors don't and can't know what conversations we had, what documents we reviewed, and what protections we put in place in each televised scene. Finally, we hope to correct several misleading examples cited by the authors as well as their offhand mischaracterization of our program as a "reality" show.

  1. 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

  2. Pulse homodyne field disturbance sensor

    DOEpatents

    McEwan, T.E.

    1997-10-28

    A field disturbance sensor operates with relatively low power, provides an adjustable operating range, is not hypersensitive at close range, allows co-location of multiple sensors, and is inexpensive to manufacture. The sensor includes a transmitter that transmits a sequence of transmitted bursts of electromagnetic energy. The transmitter frequency is modulated at an intermediate frequency. The sequence of bursts has a burst repetition rate, and each burst has a burst width and comprises a number of cycles at a transmitter frequency. The sensor includes a receiver which receives electromagnetic energy at the transmitter frequency, and includes a mixer which mixes a transmitted burst with reflections of the same transmitted burst to produce an intermediate frequency signal. Circuitry, responsive to the intermediate frequency signal indicates disturbances in the sensor field. Because the mixer mixes the transmitted burst with reflections of the transmitted burst, the burst width defines the sensor range. The burst repetition rate is randomly or pseudo-randomly modulated so that bursts in the sequence of bursts have a phase which varies. A second range-defining mode transmits two radio frequency bursts, where the time spacing between the bursts defines the maximum range divided by two. 12 figs.

  3. Pulse homodyne field disturbance sensor

    DOEpatents

    McEwan, Thomas E.

    1997-01-01

    A field disturbance sensor operates with relatively low power, provides an adjustable operating range, is not hypersensitive at close range, allows co-location of multiple sensors, and is inexpensive to manufacture. The sensor includes a transmitter that transmits a sequence of transmitted bursts of electromagnetic energy. The transmitter frequency is modulated at an intermediate frequency. The sequence of bursts has a burst repetition rate, and each burst has a burst width and comprises a number of cycles at a transmitter frequency. The sensor includes a receiver which receives electromagnetic energy at the transmitter frequency, and includes a mixer which mixes a transmitted burst with reflections of the same transmitted burst to produce an intermediate frequency signal. Circuitry, responsive to the intermediate frequency signal indicates disturbances in the sensor field. Because the mixer mixes the transmitted burst with reflections of the transmitted burst, the burst width defines the sensor range. The burst repetition rate is randomly or pseudo-randomly modulated so that bursts in the sequence of bursts have a phase which varies. A second range-defining mode transmits two radio frequency bursts, where the time spacing between the bursts defines the maximum range divided by two.

  4. Street lighting disturbs commuting bats.

    PubMed

    Stone, Emma Louise; Jones, Gareth; Harris, Stephen

    2009-07-14

    Anthropogenic disturbance is a major cause of worldwide declines in biodiversity. Understanding the implications of this disturbance for species and populations is crucial for conservation biologists wishing to mitigate negative effects. Anthropogenic light pollution is an increasing global problem, affecting ecological interactions across a range of taxa and impacting negatively upon critical animal behaviors including foraging, reproduction, and communication (for review see). Almost all bats are nocturnal, making them ideal subjects for testing the effects of light pollution. Previous studies have shown that bat species adapted to foraging in open environments feed on insects attracted to mercury vapor lamps. Here, we use an experimental approach to provide the first evidence of a negative effect of artificial light pollution on the commuting behavior of a threatened bat species. We installed high-pressure sodium lights that mimic the intensity and light spectra of streetlights along commuting routes of lesser horseshoe bats (Rhinolophus hipposideros). Bat activity was reduced dramatically and the onset of commuting behavior was delayed in the presence of lighting, with no evidence of habituation. These results demonstrate that light pollution may have significant negative impacts upon the selection of flight routes by bats.

  5. 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.

  6. Transient Effects and Disturbed Conditions

    NASA Astrophysics Data System (ADS)

    Wibberenz, G.; Le Roux, J. A.; Potgieter, M. S.; Bieber, J. W.

    1998-01-01

    In the present phase of the solar cycle no big transients leading to strong modulation had been observed after 1991. Apart from a few minor disturbances cosmic rays were still recovering to a new intensity maximum. It was suggested, therefore, that existing literature from previous cycles should be critically reviewed. The scene was set by the introductory papers on - phenomenology of cosmic ray modulation in successive solar cycles throughout the heliosphere, - the present state of models for long term modulation and their shortcomings, - the relation between cosmic ray variations and the magnitude of the interplanetary magnetic field (the CR-B-relation), - charge dependent effects. In the discussions, the study of propagating diffusive disturbances and the CR-B-relation played a central role. The difference was stressed between isolated transient disturbances in the inner solar system (Forbush decreases), and the long lasting, step-like decreases caused by merged interaction regions in the outer heliosphere. The recovery rates following the step-like decreases vary with the phase in the 22-year solar cycle. In some cases this requires a modification of existing drift models. In the outer heliosphere, the CR-B-relation leads to the result Κ alpha 1/Β between the diffusion coefficient Κ and the field magnitude Β. This simple result is a challenge for theoreticians to derive the perpendicular diffusion coefficient fromfirst principles. The three articles in this report essentially follow the list of open points and arguments just presented. The article "Observations and Simple Models" is organised around the model of a propagating diffusive barrier, its application to Forbush effects in the inner heliosphere and to decreases caused by merged interaction regions in the outer heliosphere. Acomparison of observed Forbush decreases with model predictions requires a careful separation of the two steps related to the turbulent region behind the shock front and the

  7. Public medical shows.

    PubMed

    Walusinski, Olivier

    2014-01-01

    In the second half of the 19th century, Jean-Martin Charcot (1825-1893) became famous for the quality of his teaching and his innovative neurological discoveries, bringing many French and foreign students to Paris. A hunger for recognition, together with progressive and anticlerical ideals, led Charcot to invite writers, journalists, and politicians to his lessons, during which he presented the results of his work on hysteria. These events became public performances, for which physicians and patients were transformed into actors. Major newspapers ran accounts of these consultations, more like theatrical shows in some respects. The resultant enthusiasm prompted other physicians in Paris and throughout France to try and imitate them. We will compare the form and substance of Charcot's lessons with those given by Jules-Bernard Luys (1828-1897), Victor Dumontpallier (1826-1899), Ambroise-Auguste Liébault (1823-1904), Hippolyte Bernheim (1840-1919), Joseph Grasset (1849-1918), and Albert Pitres (1848-1928). We will also note their impact on contemporary cinema and theatre.

  8. The Great Cometary Show

    NASA Astrophysics Data System (ADS)

    2007-01-01

    its high spatial and spectral resolution, it was possible to zoom into the very heart of this very massive star. In this innermost region, the observations are dominated by the extremely dense stellar wind that totally obscures the underlying central star. The AMBER observations show that this dense stellar wind is not spherically symmetric, but exhibits a clearly elongated structure. Overall, the AMBER observations confirm that the extremely high mass loss of Eta Carinae's massive central star is non-spherical and much stronger along the poles than in the equatorial plane. This is in agreement with theoretical models that predict such an enhanced polar mass-loss in the case of rapidly rotating stars. ESO PR Photo 06c/07 ESO PR Photo 06c/07 RS Ophiuchi in Outburst Several papers from this special feature focus on the later stages in a star's life. One looks at the binary system Gamma 2 Velorum, which contains the closest example of a star known as a Wolf-Rayet. A single AMBER observation allowed the astronomers to separate the spectra of the two components, offering new insights in the modeling of Wolf-Rayet stars, but made it also possible to measure the separation between the two stars. This led to a new determination of the distance of the system, showing that previous estimates were incorrect. The observations also revealed information on the region where the winds from the two stars collide. The famous binary system RS Ophiuchi, an example of a recurrent nova, was observed just 5 days after it was discovered to be in outburst on 12 February 2006, an event that has been expected for 21 years. AMBER was able to detect the extension of the expanding nova emission. These observations show a complex geometry and kinematics, far from the simple interpretation of a spherical fireball in extension. AMBER has detected a high velocity jet probably perpendicular to the orbital plane of the binary system, and allowed a precise and careful study of the wind and the shockwave

  9. 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.

  10. Forest response and recovery following disturbance (Invited)

    NASA Astrophysics Data System (ADS)

    Schafer, K. V.; Clark, K. L.; Renninger, H. J.; Carlo, N.; Medvigy, D.

    2013-12-01

    Forest management and global climate change may modulate forest responses to disturbances such as drought, insect infestation or windthrow. Forest responses to drought and gypsy moth defoliation measured from 2005 to present in an oak/pine ecosystem in the Atlantic Coastal Plain (New Jersey Pinelands) show a relative conservatism of water use but longer lasting effects on carbon balance. While post-defoliation transpiration and evapotranspiration were similar to pre-defoliation levels, post-defoliation carbon fluxes have not returned to pre-disturbance levels even after five years of recovery due to a 25% reduction in basal area following tree mortality. Defoliation frequency also affects recovery with modeled carbon fluxes under various defoliation scenarios, showing pronounced reduction in productivity under frequent defoliation, but no effect if defoliation occurs at a rate of less than 15 years. Despite a relatively consistent seasonal water use through various disturbances, defoliation and drought affect water use differently. For example, canopy transpiration (EC) after defoliation and subsequent re-sprouting, was reduced by 25% compared to pre-defoliation levels, even though only half of the leaf area was replaced. However under severe drought conditions in 2006 and 2010, EC was only reduced by 8% and 18% respectively. Therefore, prolonged drought had a lesser effect on EC than reduced foliage or episodic defoliation, suggesting these trees have access to deeper soil moisture. These data also suggest that defoliation may make trees more sensitive to drought as evidenced by the higher reduction of Ec in 2010 compared to 2006 (pre-defoliation). Differential physiological responses of the various oak species as well as pitch pine may also create a species shift in an ecosystem that is also prone to fire. In this ecosystem, Quercus prinus showed consistently lower stomatal conductance, photosynthesis and maximum carboxylation rate compared to Quercus velutina

  11. 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

  12. Stretched View Showing 'Victoria'

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Stretched View Showing 'Victoria'

    This pair of images from the panoramic camera on NASA's Mars Exploration Rover Opportunity served as initial confirmation that the two-year-old rover is within sight of 'Victoria Crater,' which it has been approaching for more than a year. Engineers on the rover team were unsure whether Opportunity would make it as far as Victoria, but scientists hoped for the chance to study such a large crater with their roving geologist. Victoria Crater is 800 meters (nearly half a mile) in diameter, about six times wider than 'Endurance Crater,' where Opportunity spent several months in 2004 examining rock layers affected by ancient water.

    When scientists using orbital data calculated that they should be able to detect Victoria's rim in rover images, they scrutinized frames taken in the direction of the crater by the panoramic camera. To positively characterize the subtle horizon profile of the crater and some of the features leading up to it, researchers created a vertically-stretched image (top) from a mosaic of regular frames from the panoramic camera (bottom), taken on Opportunity's 804th Martian day (April 29, 2006).

    The stretched image makes mild nearby dunes look like more threatening peaks, but that is only a result of the exaggerated vertical dimension. This vertical stretch technique was first applied to Viking Lander 2 panoramas by Philip Stooke, of the University of Western Ontario, Canada, to help locate the lander with respect to orbiter images. Vertically stretching the image allows features to be more readily identified by the Mars Exploration Rover science team.

    The bright white dot near the horizon to the right of center (barely visible without labeling or zoom-in) is thought to be a light-toned outcrop on the far wall of the crater, suggesting that the rover can see over the low rim of Victoria. In figure 1, the northeast and southeast rims are labeled

  13. Medium term ecohydrological response of peatland bryophytes to canopy disturbance

    NASA Astrophysics Data System (ADS)

    Leonard, Rhoswen; Kettridge, Nick; Krause, Stefan; Devito, Kevin; Granath, Gustaf; Petrone, Richard; Mandoza, Carl; Waddington, James Micheal

    2016-04-01

    Canopy disturbance in northern forested peatlands is widespread. Canopy changes impact the ecohydrological function of moss and peat, which provide the principal carbon store within these carbon rich ecosystems. Different mosses have contrasting contributions to carbon and water fluxes (e.g. Sphagnum fuscum and Pleurozium schreberi) and are strongly influenced by canopy cover. As a result, changes in canopy cover lead to long-term shifts in species composition and associated ecohydrological function. Despite this, the medium-term response to such disturbance, the associated lag in this transition to a new ecohydrological and biogeochemical regime, is not understood. Here we investigate this medium term ecohydrological response to canopy removal using a randomised plot design within a north Albertan peatland. We show no significant ecohydrological change in treatment plots four years after canopy removal. Notably, Pleurozium schreberi and Sphagnum fuscum remained within respective plots post treatment and there was no significant difference in plot resistance to evapotranspiration or carbon exchange. Our results show that canopy removal alone has little impact on bryophyte ecohydrology in the short/medium term. This resistance to disturbance contrasts strongly with dramatic short-term changes observed within mineral soils suggesting that concurrent shifts in the large scale hydrology induced within such disturbances are necessary to cause rapid ecohydrological transitions. Understanding this lagged response is critical to determine the decadal response of carbon and water fluxes in response to disturbance and the rate at which important medium term ecohydrological feedbacks are invoked.

  14. 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

  15. A Bioenergetics Approach to Understanding the Population Consequences of Disturbance: Elephant Seals as a Model System.

    PubMed

    Costa, Daniel P; Schwarz, Lisa; Robinson, Patrick; Schick, Robert S; Morris, Patricia A; Condit, Richard; Crocker, Daniel E; Kilpatrick, A Marm

    2016-01-01

    Using long-term empirical data, we developed a complete population consequences of acoustic disturbance (PCAD) model and application for northern elephant seals. We assumed that the animals would not successfully forage while in a 100-km-diameter disturbance region within their foraging and transit paths. The decrease in lipid gain due to exposure was then translated to changes in birth rate and pup survival. Given their large foraging range, elephant seals were resilient to such a disturbance, showing no population-level effects. However, similar track analysis showed that given their more coastal nature, California sea lions were within a 25-km-diameter region of disturbance more often.

  16. Fire disturbance and climate change: implications for Russian forests

    NASA Astrophysics Data System (ADS)

    Shuman, Jacquelyn K.; Foster, Adrianna C.; Shugart, Herman H.; Hoffman-Hall, Amanda; Krylov, Alexander; Loboda, Tatiana; Ershov, Dmitry; Sochilova, Elena

    2017-03-01

    Change in the Russian boreal forest has the capacity to alter global carbon and climate dynamics. Fire disturbance is an integral determinant of the forest’s composition and structure, and changing climate conditions are expected to create more frequent and severe fires. Using the individual tree-based forest gap model UVAFME, along with an updated fire disturbance module that tracks mortality based on tree-species and –size level effects, biomass and species dynamics are simulated across Russia for multiple scenarios: with and without fire, and with and without altered climate. Historical fire return intervals and percent of forest stand mortality are calculated for the Russian eco-regions and applied to 31 010 simulation points across Russia. Simulation results from the scenarios are compared to assess changes in biomass, composition, and stand structure after 600 years of successional change following bare-ground initiation. Simulations that include fire disturbance show an increase in biomass across the region compared to equivalent simulations without fire. Fire disturbance allows the deciduous needle-leaved conifer larch to maintain dominance across much of the region due to their high growth rate and fire tolerance relative to other species. Larch remain dominant under the scenario of altered climate conditions with fire disturbance. The distribution of age cohorts shifts for the scenario of altered climate with fire disturbance, displaying a bimodal distribution with a peak of 280-year-old trees and another of 100-year-old cohorts. In these simulations, fire disturbance acts to increase the turnover rate and patterns of biomass accumulation, though species and tree size are also important factors in determining mortality and competitive success. These results reinforce the importance of the inclusion of complex competition at the species level in evaluating forest response to fire and climate.

  17. Are old Mediterranean grasslands resilient to human disturbances?

    NASA Astrophysics Data System (ADS)

    Coiffait-Gombault, Clémentine; Buisson, Elise; Dutoit, Thierry

    2012-08-01

    Many dry herbaceous ecosystems suffer damage and are characterized by low resilience after disturbance. Among these forms of disturbance, soil excavation due to the construction of underground pipelines affects vegetation at plant community and landscape scales. Synchronic studies are the best approach for more rapid study of plant succession on ecosystems with low resilience. In order to better understand plant succession in a Mediterranean dry grassland, we compared the effect of a recent disturbance caused by the digging of a pipeline in 2006 with that of a pipeline created in 1972 in the same area. Surveys of floristic composition and richness were carried out along both pipelines in order to understand the succession after this single disturbance, one that does not drastically change soil chemical properties unlike former agricultural practices. Nevertheless, this type of disturbance still changes the floristic composition in the long term (>30 years). The first stage begins just after disturbance with the occurrence of many weed species. Another level between the first and the mature stage was characterized in our study, 30 years after the disturbance, by an assemblage of annual and perennial species but still lacking species typical of the reference steppe. The reference steppe is described as the mature level of the succession with an assemblage of typical grasses, forbs and a few small chamaephytes and, in particular, by the presence of Brachypodium retusum. This community corresponds to a very old Mediterranean grassland that has evolved under the Mediterranean climate and traditional sheep grazing management systems since the Neolithic Age. This study confirms the low resilience of this steppe community and shows the importance of pursuing research on this steppe and in particular on the biotic and abiotic processes involved in community assembly.

  18. 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.

  19. Gait disturbances in dystrophic hamsters.

    PubMed

    Hampton, Thomas G; Kale, Ajit; Amende, Ivo; Tang, Wenlong; McCue, Scott; Bhagavan, Hemmi N; VanDongen, Case G

    2011-01-01

    The delta-sarcoglycan-deficient hamster is an excellent model to study muscular dystrophy. Gait disturbances, important clinically, have not been described in this animal model. We applied ventral plane videography (DigiGait) to analyze gait in BIO TO-2 dystrophic and BIO F1B control hamsters walking on a transparent treadmill belt. Stride length was ∼13% shorter (P < .05) in TO-2 hamsters at 9 months of age compared to F1B hamsters. Hindlimb propulsion duration, an indicator of muscle strength, was shorter in 9-month-old TO-2 (247 ± 8 ms) compared to F1B hamsters (272 ± 11 ms; P < .05). Braking duration, reflecting generation of ground reaction forces, was delayed in 9-month-old TO-2 (147 ± 6 ms) compared to F1B hamsters (126 ± 8 ms; P < .05). Hindpaw eversion, evidence of muscle weakness, was greater in 9-month-old TO-2 than in F1B hamsters (17.7 ± 1.2° versus 8.7 ± 1.6°; P < .05). Incline and decline walking aggravated gait disturbances in TO-2 hamsters at 3 months of age. Several gait deficits were apparent in TO-2 hamsters at 1 month of age. Quantitative gait analysis demonstrates that dystrophic TO-2 hamsters recapitulate functional aspects of human muscular dystrophy. Early detection of gait abnormalities in a convenient animal model may accelerate the development of therapies for muscular dystrophy.

  20. 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

  1. 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

  2. Robertson-Schrödinger-type formulation of Ozawa's noise-disturbance uncertainty principle

    NASA Astrophysics Data System (ADS)

    Bastos, Catarina; Bernardini, Alex E.; Bertolami, Orfeu; Costa Dias, Nuno; Prata, João Nuno

    2014-04-01

    In this work we derive a matrix formulation of a noise-disturbance uncertainty relation, which is akin to the Robertson-Schrödinger uncertainty principle. Our inequality is stronger than Ozawa's uncertainty principle and takes noise-disturbance correlations into account. Moreover, we show that for certain types of measurement interactions it is covariant with respect to linear symplectic transformations of the noise and disturbance operators. Finally, we also study the tightness of our matrix inequality.

  3. Systematic Disturbance Of Optimal Rotational Trajectory

    NASA Technical Reports Server (NTRS)

    Grunwald, Arthur J.; Kaiser, Mary K.

    1992-01-01

    Algorithm introduces systematic disturbance into otherwise optimal rotation of body from prescribed initial to prescribed final orientation. Disturbance introduced as deviation of actual axis of rotation from optimal one, like wobble of top. Algorithm effects rotational transformations and solves differential equations necessary to compute disturbed trajectory. Devised for use with motion-control program and three-dimensional computer-graphical display to study ability of observers to distinguish between optimal and suboptimal rotational trajectories.

  4. Piston core properties and disturbance effects.

    USGS Publications Warehouse

    Olsen, H.W.; Rice, T.L.; Mayne, P.W.; Singh, R.D.

    1986-01-01

    Laboratory geotechnical data on piston cores for 31 sites on the mid-Atlantic Upper Continental Slope show the near-surface sediments vary from normally consolidated to somewhat overconsolidated clayey silts and silty clays of low to high plasticity. They also exhibit normalized behavior and their index property correlations with the effective-stress friction angle, the undrained strength ratio, and the compression index are reasonably consistent with existing knowledge. Because existing knowledge concerning disturbance effect suggests that in-situ preconsolidation stress values should lie between those derived from the triaxial and laboratory vane data, the preconsolidation stress values obtained from the consolidation data appear to be appreciably smaller than in-situ values. -from ASCE Publications Information

  5. Numerical computation of steady-state acoustic disturbances in flow

    NASA Technical Reports Server (NTRS)

    Watson, W. R.; Myers, M. K.

    1992-01-01

    Two time domain methods for computing two dimensional steady-state acoustic disturbances propagating through internal subsonic viscous flow fields in the presence of variable area are investigated. The first method solves the Navier-Stokes equations for the combined steady and acoustic field together and subtracts the steady flow to obtain the acoustic field. The second method solves a system of perturbation equations to obtain the acoustic disturbances, making use of a separate steady flow computation as input to the system. In each case the periodic steady-state acoustic fluctuations are obtained numerically on a supercomputer using a second order unsplit explicit MacCormack predictor-corrector method. Results show that the first method is not very effective for computing acoustic disturbances of even moderate amplitude. It appears that more accurate steady flow algorithms are required for this method to succeed. On the other hand, linear and nonlinear acoustic disturbances extracted from the perturbation approach are shown to exhibit expected behavior for the problems considered. It is also found that inflow boundary conditions for an equivalent uniform duct can be successfully applied to a nonuniform duct to obtain steady-state acoustic disturbances.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. An experimental disturbance alters fish size structure but not food chain length in streams.

    PubMed

    Walters, Annika W; Post, David M

    2008-12-01

    Streams experience frequent natural disturbance and are undergoing considerable anthropogenic disturbance due to dam construction and water diversion. Disturbance is known to impact community structure, but its effect on food chain length is still a matter of considerable debate. Theoretical models show that longer food chains are less resilient to disturbance, so food chain length is predicted to be shorter following a disturbance event. Here we experimentally test the effect of disturbance on food chain length in streams by diverting stream flow. We found that our experimental low-flow disturbance did not alter food chain length. We did see an effect on body-size structure in our food webs suggesting that food chain length may be an insensitive indicator of disturbance. We suggest that habitat heterogeneity and food web complexity buffer the effect of disturbance on food chain length. The theoretical predictions of disturbance on food chain length are only likely to be seen in homogeneous systems that closely approximate the linear food chains the models are based upon.

  12. Anthropogenic disturbance and the risk of flea-borne disease transmission.

    PubMed

    Friggens, Megan M; Beier, Paul

    2010-11-01

    Anthropogenic disturbance may lead to the spread of vector-borne diseases through effects on pathogens, vectors, and hosts. Identifying the type and extent of vector response to habitat change will enable better and more accurate management strategies for anthropogenic disease spread. We compiled and analyzed data from published empirical studies to test for patterns among flea and small mammal diversity, abundance, several measures of flea infestation, and host specificity in 70 small mammal communities of five biomes and three levels of human disturbance: remote/wild areas, agricultural areas, and urban areas. Ten of 12 mammal and flea characteristics showed a significant effect of disturbance category (six), biome (four), or both (two). Six variables had a significant interaction effect. For mammal-flea communities in forest habitats (39 of the 70 communities), disturbance affected all 12 characteristics. Overall, flea and mammal richness were higher in remote versus urban sites. Most measures of flea infestation, including percent of infested mammals and fleas/mammal and fleas/mammal species increased with increasing disturbance or peaked at intermediate levels of disturbance. In addition, host use increased, and the number of specialist fleas decreased, as human disturbance increased. Of the three most common biomes (forest, grassland/savanna, desert), deserts were most sensitive to disturbance. Finally, sites of intermediate disturbance were most diverse and exhibited characteristics associated with increased disease spread. Anthropogenic disturbance was associated with conditions conducive to increased transmission of flea-borne diseases.

  13. 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.

  14. Evidence of directional filtering of travelling ionospheric disturbances.

    NASA Technical Reports Server (NTRS)

    Yeh, K. C.; Webb, H. D.; Cowling, D. H.

    1972-01-01

    Traveling disturbance data obtained by Munro (1953, 1958) in Australia are used to test the concept that thermospheric winds act as a directional filter for gravitational waves. Diurnal contours for winter are presented graphically, showing the number of hours required for gravity waves to reach a height of 300 km.

  15. Disturbance frequency and vertical distribution of seeds affect long-term population dynamics: a mechanistic seed bank model.

    PubMed

    Eager, Eric Alan; Haridas, Chirakkal V; Pilson, Diana; Rebarber, Richard; Tenhumberg, Brigitte

    2013-08-01

    Seed banks are critically important for disturbance specialist plants because seeds of these species germinate only in disturbed soil. Disturbance and seed depth affect the survival and germination probability of seeds in the seed bank, which in turn affect population dynamics. We develop a density-dependent stochastic integral projection model to evaluate the effect of stochastic soil disturbances on plant population dynamics with an emphasis on mimicking how disturbances vertically redistribute seeds within the seed bank. We perform a simulation analysis of the effect of the frequency and mean depth of disturbances on the population's quasi-extinction probability, as well as the long-term mean and variance of the total density of seeds in the seed bank. We show that increasing the frequency of disturbances increases the long-term viability of the population, but the relationship between the mean depth of disturbance and the long-term viability of the population are not necessarily monotonic for all parameter combinations. Specifically, an increase in the probability of disturbance increases the long-term viability of the total seed bank population. However, if the probability of disturbance is too low, a shallower mean depth of disturbance can increase long-term viability, a relationship that switches as the probability of disturbance increases. However, a shallow disturbance depth is beneficial only in scenarios with low survival in the seed bank.

  16. Network response to disturbances in large sand-bed braided rivers

    NASA Astrophysics Data System (ADS)

    Schuurman, F.; Kleinhans, M. G.; Middelkoop, H.

    2016-01-01

    The reach-scale effects of human-induced disturbances on the channel network in large braided rivers are a challenge to understand and to predict. In this study, we simulated different types of disturbances in a large braided river to get insight into the propagation of disturbances through a braided channel network. The results showed that the disturbances initiate an instability that propagates in the downstream direction by means of alteration of water and sediment division at bifurcations. These adjustments of the bifurcations change the migration and shape of bars, with a feedback to the upstream bifurcation and alteration of the approaching flow to the downstream bifurcation. This way, the morphological effect of a disturbance amplifies in the downstream direction. Thus, the interplay of bifurcation instability and asymmetrical reshaping of bars was found to be essential for propagation of the effects of a disturbance. The study also demonstrated that the large-scale bar statistics are hardly affected.

  17. Solar-Array-Induced Disturbance of the Hubble Space Telescope Pointing System

    NASA Technical Reports Server (NTRS)

    Foster, Carlton L.; Tinker, Michael L.; Nurre, Gerald S.; Till, William A.

    1995-01-01

    The investigation of the vibrational disturbances of the Hubble Space Telescope that were discovered soon after deployment in orbit is described in detail. It was found that the disturbances were particularly evident during orbital day-night crossings, and that the magnitude of the disturbances was considerably larger than the design jitter requirement. This paper describes the process by which the vibrations were characterized and isolated to a particular mechanism. The analysis of the flight data and comparisons with computer simulation results showed that the source of the disturbances was the thermally driven deformation of the solar arrays in conjunction with frictional effects in the array mechanisms. The control system was successfully modified to attenuate the disturbances to tolerable levels pending mechanical and thermal redesign of the solar arrays. The new arrays were installed during the first Space Telescope servicing mission, and in combination with the enhanced control system algorithm reduced the disturbances to satisfactory levels.

  18. The solar array-induced disturbance of the Hubble Space Telescope pointing system

    NASA Technical Reports Server (NTRS)

    Foster, C. L.; Tinker, M. L.; Nurre, G. S.; Till, W. A.

    1995-01-01

    The investigation of the vibrational disturbances of the Hubble Space Telescope that were discovered soon after deployment in orbit is described in detail. It was found that the disturbances were particularly evident during orbital day-night crossings, and that the magnitudes of the disturbances were considerably larger than the design jitter requirements. This paper describes the process by which the vibrations were characterized and isolated to a particular mechanism. The analysis of the flight data and comparisons with computer simulation results showed that the source of the disturbances was the thermally driven deformation of the solar arrays in conjunction with frictional effects in the array mechanisms. The control system was successfully modified to attenuate the disturbances to tolerable levels pending mechanical and thermal redesign of the solar arrays. The new arrays were installed during the first space telescope servicing mission and, in combination with the enhanced control system algorithm, reduced the disturbances to satisfactory levels.

  19. Temporal change in the diversity-invasibility relationship in the presence of a disturbance regime.

    PubMed

    Clark, Graeme F; Johnston, Emma L

    2011-01-01

    Disturbance can affect both the diversity and invasibility of communities. Many field studies have found correlations between diversity and susceptibility to invasion, but if both factors independently respond to disturbance then spurious non-causal relationships may be observed. Here, we show that disturbance can cause a temporal shift in the diversity-invasibility relationship. In a field experiment using sessile marine communities, disturbance strongly affected both diversity and invasion such that they were highly correlated. Disturbance facilitated initial invasion, creating a negative diversity-invasibility relationship when the invader first arrived. Over time, disturbance hindered the persistence of invaders, creating a positive diversity-invasibility relationship. We suggest that temporal changes in the diversity-invasibility relationship may have contributed to the 'invasion paradox', a term for the contrasting patterns of experimental and observational studies of the diversity-invasibility relationship.

  20. Social reinforcement in block design performance by brain-damaged, emotionally disturbed, and non-disturbed retardates.

    PubMed

    Lehinger, S; McManis, D L

    1976-12-01

    48 retarded adults, equally divided by sex in three diagnostic categories (brain-damaged, nondamaged disturbed, and nondamaged-nondisturbed) were assigned to posttest reinforcement or control conditions on the basis of CA, IQ, and pretest performance on the Block Design. Reinforced subjects were praised for each individual correct block placement on the posttrest; control subjects repeated the test without reinforcement. Both brain-damaged and non-damaged-nondisturbed subjects showed accuracy gains under reinforcement, while nondamaged-disturbed subjects decreased in accuracy. Failure to replicate previous differential reinforcement effects with brain-damaged and nondamaged-nondisturbed subjects, and the discrepant reinforcement effect on nondamaged-disturbed subjects, did not support the use of reinforcement of performance on the Block Design test as an aid in detecting organic damage.

  1. Effects of disturbances in the magnetosheath on the EMIC wave and its characteristics

    NASA Astrophysics Data System (ADS)

    Lee, S. H.; Lee, D. H.; Choi, J.; Sung, S. K.; Kim, H.; Kim, E. H.; Johnson, J.; Kim, K. H.; Lee, E.

    2015-12-01

    It is generally believed that electromagnetic ion cyclotron (EMIC) waves are generated by temperature anisotropy. However, statistical studies have shown the high occurrence rate of EMIC waves in the outer magnetosphere without temperature anisotropy. Recently, it is suggested that the disturbances in the magnetosheath flow can excite broadband EMIC sources by using both theoretical and numerical models. We investigate with spacecraft data whether disturbances in the magnetosheath and EMIC waves in the outer magnetosphere are correlated. We present that the flow disturbances affect EMIC wave occurrences and the EMIC frequencies are sensitive to the size and/or intervals of disturbances. Our results show that observational features are consistent with the models above.

  2. Circadian-dependent learning and memory enhancement in nociceptin receptor-deficient mice with a novel KUROBOX apparatus using stress-free positive cue task.

    PubMed

    Nagai, Jun; Kurokawa, Mamoru; Takeshima, Hiroshi; Kieffer, Brigitte L; Ueda, Hiroshi

    2007-04-01

    Using the novel apparatus KUROBOX, learning and memory behaviors, as well as various parameters of movement activity, were reevaluated in mice deficient for nociceptin/orphanin FQ receptor (NOP-/- mice) or mu-opioid receptor (MOP-/- mice). This method has the advantages that no handling procedures are required throughout the experiments performed over 3 days, positive cue paradigms are used without water or shock stress, and the method does not disturb the nocturnal habit of mice. NOP-/- mice displayed a significant enhancement of learning and memory under stress-free conditions, but there were no changes in the various physical and psychological parameters of movement activity (nest stay ratio, distance moved, speed and angle in the movement) and biological rhythm that were measured. Enhancement of nocturnal learning was observed during the first 12-h dark cycle, and enhancement of memory was observed at the beginning of the second dark cycle in NOP-/- mice. In contrast, MOP-/- mice showed no significant change in learning and memory behaviors or in physical and psychological parameters of movement activity, except for speed, MOP-/- mice showed a significant decrease in speed of movement. Thus, the KUROBOX apparatus provides a useful alternative method to evaluate learning and memory activity under the more physiological conditions. In addition, this apparatus has an advantage that various physical and psychological parameters of movement activity affecting learning and memory behavior are also evaluated at the same time.

  3. Invasive plants on disturbed Korean sand dunes

    NASA Astrophysics Data System (ADS)

    Kim, Kee Dae

    2005-01-01

    The sand dunes in coastal regions of South Korea are important ecosystems because of their small size, the rare species found in this habitat, and the beautiful landscapes they create. This study investigated the current vegetative status of sand dunes on three representative coasts of the Korean peninsula, and on the coasts of Cheju Island, and assessed the conditions caused by invasive plants. The relationships between the degree of invasion and 14 environmental variables were studied. Plots of sand dunes along line transects perpendicular to the coastal lines were established to estimate vegetative species coverage. TWINSPAN (Two-Way Indicator Species Analysis), CCA (Canonical Correspondence Analysis), and DCCA (Detrended Canonical Correspondence Analysis) were performed to classify communities on sand dunes and assess species composition variation. Carex kobomugi, Elymus mollis, and Vitex rotundifolia were found to be the dominant species plotted on the east, the west, and the peripheral coasts of Cheju Island, respectively. Vegetation on the south coast was totally extinct. The 19 communities, including representative C. kobomugi, C. kobomugi- Ixeris repens, C. kobomugi- Oenothera biennis, E. mollis, Lolium multiflorum- Calystegia soldanella, and V. rotundifolia- C. kobomugi, were all classified according to TWINSPAN. Oenothera biennis and L. multiflorum were exotics observed within these native communities. CCA showed that invasive native and exotic species distribution was segregated significantly, according to disturbance level, exotic species number, gravel, sand and silt contents, as well as vegetation size. It further revealed that human disturbance can strongly favor the settlement of invasive and exotic species. Restoration options to reduce exotic plants in the South Korean sand dune areas were found to be the introduction of native plant species from one sand dune into other sand dune areas, prohibition of building and the introduction of exotic

  4. 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.

  5. Disturbance, the uncertainty principle and quantum optics

    NASA Technical Reports Server (NTRS)

    Martens, Hans; Demuynck, Willem M.

    1993-01-01

    It is shown how a disturbance-type uncertainty principle can be derived from an uncertainty principle for joint measurements. To achieve this, we first clarify the meaning of 'inaccuracy' and 'disturbance' in quantum mechanical measurements. The case of photon number and phase is treated as an example, and it is applied to a quantum non-demolition measurement using the optical Kerr effect.

  6. Monitoring response to disturbance in dynamic rangelands

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Arid and semi-arid rangelands worldwide provide important ecosystem services and see a diversity of land uses. To maintain the health of these lands, it is necessary to monitor rangeland conditions in response to management and disturbance. Spatial patterns from disturbance are superimposed on patte...

  7. 38 CFR 4.62 - Circulatory disturbances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances. The circulatory disturbances, especially of the lower extremity following injury in the popliteal... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Circulatory...

  8. 38 CFR 4.62 - Circulatory disturbances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances. The circulatory disturbances, especially of the lower extremity following injury in the popliteal... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Circulatory...

  9. 38 CFR 4.62 - Circulatory disturbances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances. The circulatory disturbances, especially of the lower extremity following injury in the popliteal... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Circulatory...

  10. 38 CFR 4.62 - Circulatory disturbances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances. The circulatory disturbances, especially of the lower extremity following injury in the popliteal... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Circulatory...

  11. 38 CFR 4.62 - Circulatory disturbances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... FOR RATING DISABILITIES Disability Ratings The Musculoskeletal System § 4.62 Circulatory disturbances. The circulatory disturbances, especially of the lower extremity following injury in the popliteal... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Circulatory...

  12. Remote Sensing Analysis of Forest Disturbances

    NASA Technical Reports Server (NTRS)

    Asner, Gregory P. (Inventor)

    2015-01-01

    The present invention provides systems and methods to automatically analyze Landsat satellite data of forests. The present invention can easily be used to monitor any type of forest disturbance such as from selective logging, agriculture, cattle ranching, natural hazards (fire, wind events, storms), etc. The present invention provides a large-scale, high-resolution, automated remote sensing analysis of such disturbances.

  13. Remote sensing analysis of forest disturbances

    NASA Technical Reports Server (NTRS)

    Asner, Gregory P. (Inventor)

    2012-01-01

    The present invention provides systems and methods to automatically analyze Landsat satellite data of forests. The present invention can easily be used to monitor any type of forest disturbance such as from selective logging, agriculture, cattle ranching, natural hazards (fire, wind events, storms), etc. The present invention provides a large-scale, high-resolution, automated remote sensing analysis of such disturbances.

  14. 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.

  15. Disturbance observer based control system design for inertially stabilized platform

    NASA Astrophysics Data System (ADS)

    Wu, Chunnan; Lin, Zhe

    2012-09-01

    Inertially stabilized platform (ISP) is indispensable for various imaging systems to segregate the base angular movement and achieve high LOS (Line-Of-Sight) stability. The disturbance rejection ratio and command following performance are of primary concern in designing ISP control systems. In this paper, the redundant gimbals ISP system is considered and it is shown to experience complex disturbance and parameter variation during operation. To meet advanced LOS stabilization requirement, a disturbance observer based (DOB) dual-loop controller design for ISP is proposed of which the DOB is the internal-loop. Using a nominal plant model and a low-pass filter, the disturbance signal is estimated and used as a cancellation input added to the current command of torque motor. If the DOB works well, the disturbance torque and mismatch between nominal plant and actual plant will be compensated and the internal-loop will behave as nominal model parameters. On the other hand, the external-loop will be designed for nominal model parameters to meet stabilization requirements. This paper will mainly focus on the DOB design method. Since the low-pass filter of DOB determines the sensitivity and complementary sensitivity function as will be shown in this paper, designing the filter is the most important consideration. In this paper, an optimal low-pass filter design method is proposed. The method is intuitive, simple to implement and allows on-line tuning. Simulation results show the performance enhancement of our control structure in the presence of disturbance and measurement noise.

  16. Somatosensory disturbance by methylmercury exposure.

    PubMed

    Takaoka, Shigeru; Kawakami, Yoshinobu; Fujino, Tadashi; Oh-ishi, Fumihiro; Motokura, Fukuo; Kumagai, Yoshio; Miyaoka, Tetsu

    2008-05-01

    Minamata disease is methylmercury poisoning from consuming fish and shellfish contaminated by industrial waste. The polluted seafood was widely consumed in the area around Minamata, but many individuals were never examined for or classified as having Minamata disease. Following the determination of the Supreme Court of Japan in October 2004 that the Japanese Government was responsible for spreading Minamata disease, over 13,000 residents came forward to be examined for Minamata disease. We studied 197 residents from the Minamata area who had a history of fish consumption during the polluted period to determine the importance of sensory symptoms and findings in making a diagnosis of Minamata disease. We divided the exposed subjects into non-complicated (E) and complicated (E+N) groups based on the absence or presence of other neurological or neurologically related disorders and compared them to residents in control area (C) after matching for age and sex. We quantitatively measured four somatosensory modalities (minimal tactile sense by Semmes-Weinstein monofilaments, vibration sense, position sense, and two-point discrimination) and did psychophysical tests of fine-surface-texture discrimination. Subjective complaints were higher in groups E and E+N than C. Over 90% of E+N and E subjects displayed a sensory disturbance on conventional neurological examination and 28% had visual constriction. About 50% of the E and E +N groups had upper and lower extremity ataxia and about 70% had truncal ataxia. The prevalence of these neurological findings was significantly higher in exposed subjects than controls. All sensory modalities were impaired in the E and E+N groups. All four quantitatively measured sensory modalities were correlated. The prevalence of complaints, neurological findings, and sensory impairment was similar or a little worse in group E+N than in group E. We conclude that sensory symptoms and findings are important in making the diagnosis of Minamata disease

  17. Behavioral and EEG changes in male 5xFAD mice.

    PubMed

    Schneider, F; Baldauf, K; Wetzel, W; Reymann, K G

    2014-08-01

    Transgenic animal models of Alzheimer's disease (AD) are widely used to investigate mechanisms of pathophysiology and cognitive dysfunctions. A model with a very early development of parenchymal plaque load at the age of 2months is the 5xFAD mouse (Tg6799, Oakley et al. 2006). These 5xFAD mice over-express both human amyloid precursor protein (APP) and human presenilin 1 (PS1). Mice from this line have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-β (Aβ). The aim of this study was the behavioral and functional investigations of 5xFAD males because in most studies females of this strain were characterized. In comparison to literature of transgenic 5xFAD females, transgenic 5xFAD males showed decreased anxiety in the elevated plus maze, reduced locomotion and exploration in the open field and disturbances in learning performance in the Morris water maze starting at 9months of age. Electroencephalogram (EEG) recordings on 6month old transgenic mice revealed a decrease of delta, theta, alpha, beta and gamma frequency bands whereas the subdelta frequency was increased. EEG recordings during sleep showed a reduction of rapid eye movement sleep in relation to the amount of total sleep. Thus, 5xFAD males develop early functional disturbances and subsequently behavioral deficits and therefore they are a good mouse model for studying Alzheimer's disease.

  18. Macromegakaryocytosis after hydroxyurea. [Mice

    SciTech Connect

    Ebbe, S.; Phalen, E.

    1982-11-01

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

  19. Statistics of ionospheric disturbances over the Antarctic Peninsula as derived from TEC measurements

    NASA Astrophysics Data System (ADS)

    Galushko, V. G.; Paznukhov, V. V.; Sopin, A. A.; Yampolski, Y. M.

    2016-04-01

    Results of ionospheric disturbances observations using multisite total electron content (TEC) measurements over the Antarctic Peninsula for the period from 2009 to 2012 are presented. Diurnal dependencies of the disturbance occurrence frequency, velocity, and direction of motion are established. Parameters of the disturbances are calculated using dynamic approach to the problem of ionospheric disturbances diagnostics which has been extended to allow for an arbitrary waveform of TEC perturbations. Specific data quality constraints are introduced to determine the presence of wavelike disturbances in the TEC records and to satisfy the required accuracy of parameter reconstruction. Statistical treatment of the results shows that during the daytime disturbances propagate predominantly in the northern and northeastern directions. In the evening and nocturnal hours the northwestern direction is prevailing, with the characteristic disturbance velocities ranging from 10 to 250 m/s. The most probable velocities are tens of meters per second, while the mean values are equal to about 100-130 m/s. In the daytime the velocities of the ionospheric disturbances are even higher. During the Antarctic winter time disturbances are usually observed at local noon time, in sharp contrast with the summer time, when they are present during the nights and mornings.

  20. Simulation of the low latitude ionosphere response to disturbed winds and electric fields: Brazilian region

    NASA Astrophysics Data System (ADS)

    Batista, Inez S.; Souza, Jonas; Bailey, Graham; Bravo, Manuel

    2016-07-01

    Modeling the ionosphere during disturbed periods is one of the most challenging tasks due to the complexity of the phenomena that affect the electric fields and the thermosphere environment as whole. It is well known that depending on the direction of the interplanetary magnetic field disturbance electric fields (undershielding or overshielding) can penetrate from high to low latitudes causing significant disturbances in the electron density distribution and in the equatorial ionization anomaly (EIA) development. Besides that, the large amount of energy deposited in the polar region during disturbed periods will be responsible for the generation of disturbed winds that will flow towards the equator where they produce a disturbance dynamo which also affects the EIA density distribution. The TIDs and TADs are also sources of disturbances that propagate at high velocity reaching the equator 2-3 hours after the beginning of the magnetic storm. In this work we use the Sheffield University Plasmasphere-Ionosphere Model at INPE (SUPIM-INPE), to simulate the drastic effects that were observed at the low latitude ionosphere in the Brazilian region during a very intense magnetic storm event. A few models are tested for the disturbed electric field and wind. The simulation results showed that the observations are better explained when considering a traveling waveform disturbance propagating from north to south at a velocity equal to 200 m/s.

  1. Anti-disturbance control theory for systems with multiple disturbances: a survey.

    PubMed

    Guo, Lei; Cao, Songyin

    2014-07-01

    The problem of anti-disturbance control has been an eternal topic along with the development of the control theory. However, most methodologies can only deal with systems subject to a single equivalent disturbance which was merged by various types of uncertainties. In this paper, a review on anti-disturbance control is presented for systems with multiple disturbances. First, the classical control methods are briefly reviewed for disturbance attenuation or rejection problems. Then, recent advances in disturbance observer based control (DOBC) theory are introduced and especially, the composite hierarchical anti-disturbance control (CHADC) is firstly addressed. A comparison of different approaches is briefly carried out. Finally, focuses in the field on the current research are also addressed with emphasis on the practical application of the techniques.

  2. 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.

  3. Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction.

    PubMed

    Park, Jeehye; Kim, Sung Yun; Cha, Guang-Ho; Lee, Sung Bae; Kim, Sunhong; Chung, Jongkyeong

    2005-11-21

    DJ-1 is linked to an early-onset autosomal recessive Parkinson's disease (PD) characterized primarily by selective loss of dopaminergic (DA) neurons, which results in motor disturbances. However, our understanding on how mutations in DJ-1 are related to PD is unclear. Here, we isolated the DJ-1 orthologue, DJ-1beta, in Drosophila and characterized its expression and loss-of-function mutants. We observed its strongest expression in the adult stage of development and ubiquitous expression in the larval brain. Our homozygous mutants showed severe defects in locomotor ability without loss of DA neurons, consistent with the previous mice DJ-1 mutant studies ([Goldberg, M.S., Pisani, A., Haburcak, M., Vortherms, T.A., Kitada, T., Costa, C., Tong, Y., Martella, G., Tscherter, A., Martins, A., et al., 2005. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45, 489-496.]; [Kim, R.H., Smith, P.D., Aleyasin, H., Hayley, S., Mount, M.P., Pownall, S., Wakeham, A., You-Ten, A.J., Kalia, S.K., Horne, P., Westaway, D., Lozano, A.M., Anisman, H., Park, D.S., Mak, T.W., 2005. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and oxidative stress. Proc. Natl. Acad. Sci. USA 102, 5215-5220.]; [Chen, L., Cagniard, B., Mathews, T., Jones, S., Koh, H.C., Ding, Y., Carvey, P.M., Ling, Z., Kang, U.J., Zhuang, X., 2005. Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J. Biol. Chem. 280, 21418-21426.]). The locomotor activity of DJ-1beta mutants was further decreased by paraquat-induced oxidative stress. Moreover, we found that Drosophila DJ-1 is prominently localized in mitochondria, suggesting that DJ-1 functions as a protector against oxidative stress in mitochondria.

  4. Cyp26b1 within the growth plate regulates bone growth in juvenile mice.

    PubMed

    Minegishi, Yoshiki; Sakai, Yasuo; Yahara, Yasuhito; Akiyama, Haruhiko; Yoshikawa, Hideki; Hosokawa, Ko; Tsumaki, Noriyuki

    2014-11-07

    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, it 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(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.

  5. Generation of induced pluripotent stem cell-derived mice by reprogramming of a mature NKT cell.

    PubMed

    Ren, Yue; Dashtsoodol, Nyambayar; Watarai, Hiroshi; Koseki, Haruhiko; Quan, Chengshi; Taniguchi, Masaru

    2014-10-01

    NKT cells are characterized by their expression of an NKT-cell-specific invariant antigen-receptor α chain encoded by Vα14Jα18 gene segments. These NKT cells bridge the innate and acquired immune systems to mediate effective and augmented responses; however, the limited number of NKT cells in vivo hampers their analysis. Here, two lines of induced pluripotent stem cell-derived mice (NKT-iPSC-derived mice) were generated by reprogramming of mature NKT cells, where one harbors both rearranged Vα14Jα18 and Vβ7 genes and the other carries rearranged Vα14Jα18 on both alleles but germline Vβ loci. The analysis of NKT-iPSC-derived mice showed a significant increase in NKT cell numbers with relatively normal frequencies of functional subsets, but significantly enhanced in some cases, and acquired functional NKT cell maturation in peripheral lymphoid organs. NKT-iPSC-derived mice also showed normal development of other immune cells except for the absence of γδT cells and disturbed development of conventional CD4 αβT cells. These results suggest that the NKT-iPSC-derived mice are a better model for NKT cell development and function study rather than transgenic mouse models reported previously and also that the presence of a pre-rearranged Vα14Jα18 in the natural chromosomal context favors the developmental fate of NKT cells.

  6. Heparanase Regulates Thrombosis in Vascular Injury and Stent-Induced Flow Disturbance

    PubMed Central

    Baker, Aaron B.; Gibson, William J.; Kolachalama, Vijaya B.; Golomb, Mordechai; Indolfi, Laura; Spruell, Christopher; Zcharia, Eyal; Vlodavsky, Israel; Edelman, Elazer R.

    2014-01-01

    Objectives The purpose of this study was to examine the role of heparanase in controlling thrombosis following vascular injury or endovascular stenting. Background The use of endovascular stents are a common clinical intervention for the treatment of arteries occluded due to vascular disease. Both heparin and heparan sulfate are known to be potent inhibitors of thrombosis. Heparanase is the major enzyme that degrades heparan sulfate in mammalian cells. This study examined the role of heparanase in controlling thrombosis following vascular injury and stent-induced flow disturbance. Methods This study used mice overexpressing human heparanase and examined the time to thrombosis using a laser-induced arterial thrombosis model in combination with vascular injury. An ex vivo system was used to examine the formation of thrombus to stent-induced flow disturbance. Results In the absence of vascular injury, wild type and heparanase overexpressing (HPA Tg) mice had similar times to thrombosis in a laser-induced arterial thrombosis model. However, in the presence of vascular injury, the time to thrombosis was dramatically reduced in HPA Tg mice. An ex vivo system was used to flow blood from wild type and HPA Tg mice over stents and stented arterial segments from both animal types. These studies demonstrate markedly increased thromboses on stents with blood isolated from HPA Tg mice in comparison to blood from wild type animals. We found that blood from HPA Tg animals had markedly increased thrombosis when applied to stented arterial segments from either wild type or HPA Tg mice. Conclusions Taken together, this study’s results indicate that heparanase is a powerful mediator of thrombosis in the context of vascular injury and stent-induced flow disturbance. PMID:22516446

  7. Ectomycorrhizal Fungal Communities of Red Pine (Pinus densiflora) Seedlings in Disturbed Sites and Undisturbed Old Forest Sites.

    PubMed

    Lee, Eun-Hwa; Eom, Ahn-Heum

    2013-06-01

    This study aimed to investigate differences in ectomycorrhizal (ECM) fungal communities between disturbed sites and undisturbed old forest sites. ECM root tips of Pinus densiflora were collected from 4 sites disturbed by human activities and 3 undisturbed old forest sites adjacent to the disturbed sites. Results in this study showed that the number of ECM root tips, species diversity, and number of species were significantly higher in the disturbed sites than in the undisturbed sites, suggesting that the ECM fungal community structure was affected by the degree of disturbance.

  8. Disturbance Dynamics in Transitional and Turbulent Flows

    NASA Technical Reports Server (NTRS)

    Grosch, Chester E.

    1999-01-01

    In order to expand the predictive capability of single-point turbulence closure models to account for the early-stage transition regime, a methodology for the formulation and calibration of model equations for the ensemble-averaged disturbance kinetic energy and energy dissipation rate is presented. First the decay of laminar disturbances and turbulence in mean shear-free flows is studied. In laminar flows, such disturbances are linear superpositions of modes governed by the Orr-Sommerfeld equation. In turbulent flows, disturbances are described through transport equations for representative mean quantities. The link between a description based on a deterministic evolution equation and a probability based mean transport equation is established. Because an uncertainty in initial conditions exists in the laminar as well as the turbulent regime, a probability distribution must be defined even in the laminar case. Using this probability distribution, it is shown that the exponential decay of the linear modes in the laminar regime can be related to a power law decay of both the (ensemble) mean disturbance kinetic energy and the dissipation rate. The evolution of these mean disturbance quantities is then described by transport equations similar to those for the corresponding turbulent decaying flow. Second, homogeneous shear flow, where disturbances can be described by rapid distortion theory (RDT), is studied. The relationship between RDT and linear stability theory is exploited in order to obtain a closed set of modeled equations. The linear disturbance equations are solved directly so that the numerical simulation yields a database from which the closure coefficients in the ensemble-averaged disturbance equations can be determined.

  9. 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.

  10. Effect of unilateral testicular rupture on histopathology and germ cell delayed-type hypersensitivity in C3H/He and A/J mice.

    PubMed

    Naito, Munekazu; Sakamoto, Yasuki; Terayama, Hayato; Hirai, Shuichi; Ning, Qu; Aota, Yoichi; Itoh, Masahiro

    2009-07-01

    Contralateral orchitis induced by unilateral testicular injury has been reported as sympathetic orchitis in men and experimental animals. In mice, experimental sympathetic orchitis (ESO) was first demonstrated in the C3H/He strain after experimental testicular trauma. Delayed-typed hypersensitivity (DTH) to testicular germ cells is induced by testicular trauma and treatment with cyclophosphamide before the trauma further enhances anti-testicular germ cell DTH. In the present study we investigated ESO induction with or without cyclophosphamide pretreatment in two murine strains, C3H/He and A/J mice, that are susceptible to testicular autoimmunity. The results show that traumatized testes undergo early degeneration of the seminiferous epithelium followed by neutrophilic inflammation and later fibrosis with little lymphocytic infiltration, in both murine strains. In the contralateral testes, ESO characterized by both lymphocytic inflammation and spermatogenic disturbance was induced in both strains. However, the incidence and severity of ESO in A/J mice tended to be higher than in C3H/He mice. In contrast, cyclophosphamide pretreatment significantly augmented both pathological stages of ESO and anti-testicular germ cell DTH in C3H/He mice, while those in A/J mice were fully developed by testicular rupture alone and were not further augmented by cyclophosphamide pretreatment. We conclude that A/J mice are more sensitive to trauma-induced testicular autoimmunity than C3H/He mice.

  11. 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.

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

    PubMed

    Fleming, Genie M; Diffendorfer, James E; Zedler, Paul H

    2009-12-01

    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.

  13. Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance

    PubMed Central

    Ferreyra, Jessica A.; Wu, Katherine J.; Hryckowian, Andrew J.; Bouley, Donna M.; Weimer, Bart C.; Sonnenburg, Justin L.

    2016-01-01

    Summary Clostridium difficile is a leading cause of antibiotic-associated diarrhea. The mechanisms underlying C. difficile expansion after microbiota disturbance are just emerging. We assessed the gene expression profile of C. difficile within the intestine of gnotobiotic mice to identify genes regulated in response to either dietary or microbiota compositional changes. In the presence of the gut symbiont Bacteroides thetaiotaomicron, C. difficile induces a pathway that metabolizes the microbiota fermentation end-product succinate to butyrate. The low concentration of succinate in the microbiota of conventional mice is transiently elevated upon antibiotic treatment or chemically-induced intestinal motility disturbance, and C. difficile exploits this succinate spike to expand in the perturbed intestine. A C. difficile mutant compromised in succinate utilization is at a competitive disadvantage during these perturbations. Understanding the metabolic mechanisms involved in microbiota-C. difficile interactions may help to identify approaches for the treatment and prevention of C. difficile-associated diseases. PMID:25498344

  14. Vertical distribution of soil removed by four species of burrowing rodents in disturbed and undisturbed soils

    SciTech Connect

    Reynolds, T.D.; Laundre, J.W.

    1988-04-01

    Burrow volumes were determined in disturbed and undisturbed soils for four species of rodents in southeastern Idaho. Comparisons were made between soil types for the average volume and the proportion of the total volume of soil excavated from 10-cm increments for each species, and the relative number of burrows and proportion of total soil removed from beneath the minimum thickness of soil covers over buried low-level radioactive wastes. Burrows of montane voles (Microtus montanus) and deer mice (Peromyscus maniculatus) rarely extended below 50 cm and neither volumes nor depths were influenced by soil disturbance. Townsend's ground squirrels (Spermophilus townsendii) had the deepest and most voluminous burrows that, along with Ord's kangaroo rat (Dipodomys ordii) burrows, were more prevalent beneath 50 cm in disturbed soils.

  15. Sensitivity of climate mitigation strategies to natural disturbances

    SciTech Connect

    Le Page, Yannick LB; Hurtt, George; Thomson, Allison M.; Bond-Lamberty, Benjamin; Patel, Pralit L.; Wise, Marshall A.; Calvin, Katherine V.; Kyle, G. Page; Clarke, Leon E.; Edmonds, James A.; Janetos, Anthony C.

    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 of 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

  16. [Accessing Disturbances of Attachment Symptoms Using Interview Technique].

    PubMed

    Kliewer-Neumann, Josephine; Bovenschen, Ina; Lang, Katrin; Spangler, Gottfried; Nowacki, Katja; Roland, Inga C

    2015-01-01

    Disturbances of attachment represent a clinically significant disorder and seriously impair social behavioural functioning. To date there has been little research and valid diagnostic methods are lacking. In the present study a German Version of the Disturbances of Attachment Interview developed by Smyke and Zeanah (1999) was used to assess disturbances of attachment in a sample of foster children and the validity of the translation is investigated. Furthermore, the Strengths and Difficulties Questionnaire (Goodman, 1997) was used to examine the discriminative validity. The results show a satisfying reliability and the scales of attachment disorders declare the main of the variance. There is a weak association between the disinhibited scale and hyperactivity in the SDQ. Overall the disinhibited disorder can be distinguished from other behaviour patterns. Regarding the inhibited scale there are associations with all SDQ scales and the inhibited category seems harder to distinguish from other deviant developmental issues. The method is evaluated as a qualified approach to the diagnosis of attachment disorders in the context of a multimethodical approach. Furthermore, the findings suggest further examination of the construct of attachment disturbances.

  17. A meta-analysis of bees' responses to anthropogenic disturbance.

    PubMed

    Winfree, Rachael; Aguilar, Ramiro; Vázquez, Diego P; LeBuhn, Gretchen; Aizen, Marcelo A

    2009-08-01

    Pollinators may be declining globally, a matter of concern because animal pollination is required by most of the world's plant species, including many crop plants. Human land use and the loss of native habitats is thought to be an important driver of decline for wild, native pollinators, yet the findings of published studies on this topic have never been quantitatively synthesized. Here we use meta-analysis to synthesize the literature on how bees, the most important group of pollinators, are affected by human disturbances such as habitat loss, grazing, logging, and agriculture. We obtained 130 effect sizes from 54 published studies recording bee abundance and/or species richness as a function of human disturbance. Both bee abundance and species richness were significantly, negatively affected by disturbance. However, the magnitude of the effects was not large. Furthermore, the only disturbance type showing a significant negative effect, habitat loss and fragmentation, was statistically significant only in systems where very little natural habitat remains. Therefore, it would be premature to draw conclusions about habitat loss having caused global pollinator decline without first assessing the extent to which the existing studies represent the status of global ecosystems. Future pollinator declines seem likely given forecasts of increasing land-use change.

  18. 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.

  19. 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.

  20. Cobalt-induced changes in the spleen of mice from different stages of development.

    PubMed

    Gluhcheva, Yordanka; Atanasov, Vasil; Ivanova, Juliana; Mitewa, Mariana

    2012-01-01

    Cobalt(II) accumulates in organs such as spleen, kidneys, heart, and liver. The aim of the present study was to investigate the effects of cobalt ethylenediamine tetraacetic acid (Co-EDTA) on spleen of developing mice. Pregnant BALB/c mice in late gestation were subjected to Co-EDTA treatment at daily doses of 75 or 125 mg/kg in drinking water, which continued until d 90 of the newborn pups. The newborn pups were sacrificed on d 18, 25, 30, 45, 60, and 90, which correspond to different stages of development. Spleens were excised, weighed, and processed for histological analysis. Spleen index (SI) was calculated as a ratio of spleen weight to body weight. Cobalt(II) bioaccumulation in spleen was determined using flame atomic absorption spectrometry (FAAS). Preliminary results showed that chronic treatment of mice with low- or high-dose Co-EDTA disturbed extramedullary hematopoiesis in the spleen. The number of megakaryocytes was reduced compared to controls. SI was also reduced in d 18 mice treated with low- or high-dose Co-EDTA. However, exposure to 75 mg/kg led to an increase of SI in all other experimental groups. FAAS analysis revealed significant cobalt(II) accumulation in spleen of treated mice. The Co(II) levels in spleens of d 18 mice were highest compared to other experimental groups, indicating that at this period mice are more sensitive to treatment. Exposure to cobalt-EDTA resulted in accumulation of Co(II) in spleen, altered SI, and hematopoiesis. Immature mice appear to be more sensitive to chronic treatment than adults.

  1. 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.

  2. The atypical antipsychotic olanzapine disturbs depotentiation by modulating mAChRs and impairs reversal learning.

    PubMed

    Song, Woo Seok; Cha, Jin Hee; Yoon, Sang Ho; Cho, Young Seon; Park, Kyeong-Yeol; Kim, Myoung-Hwan

    2017-03-01

    Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown. Here we show that Olz interrupts depotentiation (reversal of long-term potentiation) without disturbing de novo LTP (long-term potentiation) and LTD (long-term depression). At hippocampal SC-CA1 synapses, inhibition of NMDARs (N-methyl-d-aspartate receptors), mGluRs (metabotropic glutamate receptors), or mAChRs (muscarinic acetylcholine receptors) disrupted depotentiation. In addition, co-activation of NMDARs, mGluRs, and mAChRs reversed stably expressed LTP. Olz inhibits the activation of mAChRs, which amplifies glutamate signaling through enhanced NMDAR opening and Gq (Gq class of G protein)-mediated signal transduction. Behaviorally, Olz impairs spatial reversal learning of mice in the Morris water maze test. Our results uncover a novel mechanism underpinning the cognitive modulation of Olz and show that the anticholinergic property of Olz affects glutamate signaling and synaptic plasticity.

  3. 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

  4. Hardy's paradox and measurement-disturbance relations

    NASA Astrophysics Data System (ADS)

    Fujikawa, Kazuo; Oh, C. H.; Yu, Sixia

    2015-01-01

    We establish a quantitative relation between Hardy's paradox and the breaking of the uncertainty principle in the sense of measurement-disturbance relations in the conditional measurement of noncommuting operators. The analysis of the inconsistency of local realism with entanglement by Hardy is simplified if this breaking of measurement-disturbance relations is taken into account, and a much simplified experimental test of local realism is illustrated in the framework of Hardy's thought experiment. The essence of Hardy's model is identified as a combination of two conditional measurements, which give rise to definite eigenvalues to two noncommuting operators simultaneously in hidden-variables models. Better understanding of the intimate interplay of entanglement and measurement disturbance is crucial in the current discussions of Hardy's paradox using the idea of weak measurement, which is based on a general analysis of measurement-disturbance relations.

  5. Sleep Disturbances Associated with Parkinson's Disease

    PubMed Central

    Suzuki, Keisuke; Miyamoto, Masayuki; Miyamoto, Tomoyuki; Iwanami, Masaoki; Hirata, Koichi

    2011-01-01

    Sleep disturbances are common problems affecting the quality life of Parkinson's disease (PD) patients and are often underestimated. The causes of sleep disturbances are multifactorial and include nocturnal motor disturbances, nocturia, depressive symptoms, and medication use. Comorbidity of PD with sleep apnea syndrome, restless legs syndrome, rapid eye movement sleep behavior disorder, or circadian cycle disruption also results in impaired sleep. In addition, the involvement of serotoninergic, noradrenergic, and cholinergic neurons in the brainstem as a disease-related change contributes to impaired sleep structures. Excessive daytime sleepiness is not only secondary to nocturnal disturbances or dopaminergic medication but may also be due to independent mechanisms related to impairments in ascending arousal system and the orexin system. Notably, several recent lines of evidence suggest a strong link between rapid eye movement sleep behavior disorder and the risk of neurodegenerative diseases such as PD. In the present paper, we review the current literature concerning sleep disorders in PD. PMID:21876839

  6. Evolution of disturbances in stagnation point flow

    NASA Technical Reports Server (NTRS)

    Criminale, William O.; Jackson, Thomas L.; Lasseigne, D. Glenn

    1993-01-01

    The evolution of three-dimensional disturbances in an incompressible three-dimensional stagnation-point flow in an inviscid fluid is investigated. Since it is not possible to apply classical normal mode analysis to the disturbance equations for the fully three-dimensional stagnation-point flow to obtain solutions, an initial-value problem is solved instead. The evolution of the disturbances provide the necessary information to determine stability and indeed the complete transient as well. It is found that when considering the disturbance energy, the planar stagnation-point flow, which is independent of one of the transverse coordinates, represents a neutrally stable flow whereas the fully three-dimensional flow is either stable or unstable, depending on whether the flow is away from or towards the stagnation point in the transverse direction that is neglected in the planar stagnation point.

  7. Landsat Ecosystem Disturbance Adaptive Processing System (LEDAPS)

    NASA Technical Reports Server (NTRS)

    Masek, Jeffrey G.

    2006-01-01

    The Landsat Ecosystem Disturbance Adaptive Processing System (LEDAPS) project is creating a record of forest disturbance and regrowth for North America from the Landsat satellite record, in support of the carbon modeling activities. LEDAPS relies on the decadal Landsat GeoCover data set supplemented by dense image time series for selected locations. Imagery is first atmospherically corrected to surface reflectance, and then change detection algorithms are used to extract disturbance area, type, and frequency. Reuse of the MODIS Land processing system (MODAPS) architecture allows rapid throughput of over 2200 MSS, TM, and ETM+ scenes. Initial ("Beta") surface reflectance products are currently available for testing, and initial continental disturbance products will be available by the middle of 2006.

  8. Effects of disturbance on small mammal community structure in the New Jersey Pinelands, USA.

    PubMed

    Shenko, Alicia N; Bien, Walter F; Spotila, James R; Avery, Harold W

    2012-03-01

    We compared small mammal community composition among undisturbed habitats and habitats disturbed by military operations on Warren Grove Gunnery Range (WGR) in the New Jersey Pinelands. WGR is one of the largest tracts of protected land within this globally rare ecosystem. Disturbance in the form of fire, mowing, soil disruption and logging has had a large effect on small mammal occurrence and distribution. Of the 14 small mammal species that occur in the Pinelands, 9 live on WGR, including large populations of the southern bog lemming (Synaptomys cooperi Baird, 1858) and meadow jumping mouse [Zapus hudsonius (Zimmermann, 1780)]. Simpson's Index of Diversity was 0 for most disturbed sites and was generally greater in wetlands than in uplands. White-footed mouse [Peromyscus leucopus (Rafinesque, 1818)] was the most common species on WGR and had a dominant effect on species diversity and community similarity indices. It dominated upland habitats and was the only species to occur in several disturbed habitats, whereas all 9 species occurred in wetlands. Principal components analysis indicated that most variation in species diversity was explained by disturbance and differences between upland and wetland habitats, due to presence of white-footed mice in disturbed and upland sites. Meadow jumping mice, southern bog lemmings and red-back voles [Myodes gapperi (Vigors, 1830)] were positively correlated with wetland habitats, and pine voles [Microtus pinetorum (Le Conte, 1830)], short-tail shrews [Blarina brevicauda (Say, 1823)] and eastern chipmunks [Tamias striatus (Linnaeus, 1758)] were associated with uplands. Habitat heterogeneity at WGR, including extensive undisturbed wetlands and uplands supported a rich diversity of small mammal species.

  9. Optimal disturbance rejecting control of hyperbolic systems

    NASA Technical Reports Server (NTRS)

    Biswas, Saroj K.; Ahmed, N. U.

    1994-01-01

    Optimal regulation of hyperbolic systems in the presence of unknown disturbances is considered. Necessary conditions for determining the optimal control that tracks a desired trajectory in the presence of the worst possible perturbations are developed. The results also characterize the worst possible disturbance that the system will be able to tolerate before any degradation of the system performance. Numerical results on the control of a vibrating beam are presented.

  10. Mapping surface disturbance from wind farms

    NASA Astrophysics Data System (ADS)

    Diffendorfer, James E.

    2013-04-01

    Wind energy is one of the fastest growing segments of the electricity market and this trend will likely continue as countries strive to reduce CO2 production while meeting growing energy demands. One impact of wind facilities is surface disturbance, including roads, that lead to habitat loss and fragmentation. Numerous studies of wind power utilize estimates of surface disturbance for GIS-based modeling or basic calculations of the land area required to generate energy using wind. However published estimates of the land use required for a MW of electricity from wind facilities vary by more than 10 times (0.83 to 250 MW/Km2). We report results from a geospatial analysis of 39 wind facilities in the United States that we fully digitized using high resolution photo-imagery. The selected sites and analyses were designed to elucidate the effects of turbine size, topography, and land use on the area requirements of wind facilities. The results indicate point estimates of average surface disturbance/MW have wide levels of variation, explained primarily by Landcover and Topography. Wind facilities in agricultural landscapes had smaller surface disturbance/ha than facilities in forests and shrublands, and facilities in relatively flat topography had smaller surface disturbance/ha than facilities on hills, ridges, or mesas. Land use, topography, and turbine size all influenced turbine spacing. The statistical models suggest we can predict geographic locations where new wind facilities could be placed with minimized surface disturbance.

  11. [Correlation between eating disorders and sleep disturbances].

    PubMed

    Eiber, R; Friedman, S

    2001-01-01

    Anorectics and bulimics often complain sleep onset insomnia and disrupted sleep. During awakenings bulimics can have binges. Conversely, eating disorders can be a clinical expression of a concomitantly occurring sleep disorder. Two clinical entities have been recently described: the Night Eating Syndrome (NES) and the Sleep Related Eating Disorders. The main goal of this literature review was to better characterize the relationships between eating disorders and sleep disturbances. No specific EEG sleep pattern emerges in anorectic and bulimic patients. However, all studies include several methodological limitations: a few number of patients, heterogeneous patient groups, various diagnostic criteria. The results of studies evaluating the impact of depression on sleep EEG in eating disorder patients are also subject to controversy. The only study examining the relationship between sleep EEG and morphological alterations in anorectics and normal weight bulimics shows that patients with enlarged cerebrospinal fluid spaces spent more time in slow wave sleep and that the duration of rapid eye movement (REM) sleep was reduced. The ventricular brain ratio was negatively correlated with REM sleep. The Night Eating Syndrome consists in insomnia, binge eating and morning anorexia. Other criteria are proposed to characterize the NES: more than 50% of the daily energy intake is consumed after the last evening meal, awakenings at least once a night, repetition of the provisional criteria for more than 3 months, subjects do not meet criteria for bulimia nervosa or binge eating disorder. Patients have no amnesia nor alteration of alertness, and no other sleep disorder. There is no modification of sleep EEG except sleep maintenance. The prevalence of the NES is 1.5% in the general population. Some neuroendocrine disturbances have been found in the NES. The delimitation with eating disorders is not yet clearly established. If it shares the compulsive features with eating disorders

  12. [Distribution of Phosphorus Forms in the Overlying Water Under Disturbance with the Addition of Algae].

    PubMed

    Chen, Jun; Li, Yong; Li, Da-peng; Huang, Yong; Zhu, Pei-ying

    2016-04-15

    Distribution of different phosphorus (P) forms in the overlying water and the contribution of different algae to the P disappearance were investigated under disturbance with the addition of algae (Microcystis aeruginosa and Selenastrum capricornutum, respectively). The sediments and overlying water were taken from Meiliang Bay in Taihu Lake. The results showed that the concentrations of total P (TP), dissolved total P (DTP), dissolved inorganic P (DIP) and biavailable P (BAP) decreased with and without disturbance. The uptake of DTP and DIP by Microcystis aeruginosa was better than that of Selenastrum capricornutum under the disturbance, but it was the opposite without the disturbance. The disappearance of P in the overlying water was attributed completely to the physico-chemical adsorption of the suspended solids and the uptake of algae. But the contribution of suspended solids and algae depended on the disturbance. The contribution of Microcystis aeruginosa and Selenastrum capricornutum to DTP and DIP absorption was about 60% without disturbance. However, the value was reduced to 40% (Microcystis aeruginosa) and 25% ( Selenastrum capricornutum) under the disturbance. Under the disturbance and the action of algae, the distribution of sedimentary P forms changed. NH4 Cl-P and Ca-P release and Fe/Al-P increase were observed with and without disturbance. The decrease of NH4 Cl-P and Ca-P and the increase of Fe/Al-P were more obvious with disturbance than without disturbance. Selenastrum capricornutum was favor of the release of Ca-P and the formation of Fe/Al-P.

  13. Scales of Stream Disturbance Patterns and Population Structure in Bull Trout

    NASA Astrophysics Data System (ADS)

    Luce, C. H.; Rieman, B. E.; Dunham, J. B.

    2005-05-01

    Ecological theory proposes that the geometry and dynamics of suitable habitats are important predictors for the persistence of a population or metapopulation. A key finding supporting a metapopulation-like conceptualization of extinction and colonization in fragmented salmonid populations is that individuals of particular species are more likely to be absent from small patches of suitable habitat than from large patches. Extinctions from small patches occur for a few reasons that can be roughly classed as physical catastrophic causes (e.g. a major channel reorganizing event) or as biological small-population effects related to genetics and demographics. One important question with implications for land management is how strong of a role physical disturbances play in determining presence and absence of a species within a patch. If disturbance plays a key role in structuring populations, then we would expect to observe two patterns. First the spatial scale of disturbance should be on the order of the size of patches that are commonly unoccupied. The second prediction would be that the spatial scale of genetic variability should show strong gene flow at scales smaller than the scale of disturbance. We examined aerial photography over the last 40 years in central Idaho to measure the scale of stream disturbance patches. The scale of stream disturbances was on the same order of magnitude as the divide between commonly occupied and unoccupied patches, and was smaller than scales of high gene flow among bull trout populations, failing to reject the possibility that disturbance plays an important role in structuring populations in this basin. Management for persistence of the species must consider both the likelihood of decreased habitat patch sizes and increased disturbance scales with global warming. Knowing disturbance patch scales and how disturbance operates to structure populations can be used to consider a disturbance based paradigm for management of sensitive

  14. Detection and Analyses of Traveling Ionospheric Disturbances from two Successive Earthquakes and Tsunami Waves

    NASA Astrophysics Data System (ADS)

    Yang, Y.; Garrison, J. L.; Komjathy, A.

    2012-12-01

    Traveling ionospheric disturbances (TIDs), induced by acoustic-gravity waves (AGWs) in the neutral atmosphere, are observable in trans-ionospheric Global Navigation Satellite System (GNSS) measurements. Previous studies on the GNSS-derived ionospheric disturbances have been presented for studying the interactions between ionospheric perturbations associated with the 2011 Japan Tohoku Earthquakes and Tsunamis. Three different types of TIDs were observed. Short-period disturbances (2 - 8 minutes) with speeds up to 2300 km/s were observed in the near-field, and the long-period (8-22 minutes) disturbances with speeds (195 - 354m/s) were identified in both near- and far-fields. In this study, identification and classification of ionospheric disturbances was conducted using a wavelet detection method in combination with a cross-correlation technique estimating the propagation speeds and directions of atmosphere wave-induced disturbances in dual frequency IEC time series collected form GNSS networks near the epicenter of the March 11, 2011 Japan Tohoku earthquake and the subsequent tsunami induced by it. Through the use of the wavelet detection process, we are able to find major wave trains, present in the data collected from these networks, with two dominate frequency bands corresponding to the disturbances from two successive earthquakes and tsunami propagations. Additionally, the comparative observations and model predictions, including ground motions and tsunami propagations calculated by JPL using the MOST model are used to understand and perceive the dominant properties (propagation speeds, directions, periods and occurrence times) of the GPS-derived ionospheric disturbances. This analysis is demonstrated on data from 1235 stations in the Japanese GEONET GPS network. A comparison between GNSS-derived disturbances, ground motions and tsunami propagations shows that the propagation directions and speeds of short-period disturbances are consistent with the acoustic

  15. Developing versus Non-Developing Tropical Disturbances over the South China Sea

    NASA Astrophysics Data System (ADS)

    Li, W.; Guo, Z.; Wang, L.

    2012-12-01

    Developing and non-developing tropical disturbances over the South China Sea (SCS) are investigated and compared utilizing the QuikSCAT (Quick Scatterometer) wind, Outgoing Longwave Radiation (OLR) and other auxiliary atmospheric data. The results show that: (1) the developing disturbances exhibit remarkable regional features and seasonal variations over the SCS. Most of the developing disturbances occur only over the middle to northern SCS, especially around the Zhongsha, Nansha and Huangyan Islands. In addition, the developing disturbances occur only during May to October even though the tropical disturbances exist all the year around over the SCS; (2) there are substantial differences in the motions between the developing and non-developing tropical disturbances. The movements of the disturbances are significantly slower in the developing cases than in the non-developing cases. Whereas most of the non-developing disturbances move west ward, most of the developing disturbances move north ward or north-west ward; (3) analyses of the box difference index (BDI) reveal significant differences in the environmental factors between the developing and non-developing disturbances. It seems that the dynamic factors are more important than the thermodynamic factors in controlling the development of tropical disturbances over the SCS. In order of importance, they are: 850 hPa relative vorticity, OLR, 850-200hPa vertical wind shear, temperature differences between 850hPa and 500hPa, water vapor content within low layer. The above five parameters are identified as the best predictors for cyclogenesis in the SCS.

  16. Metabolic Disturbances Associated with Systemic Lupus Erythematosus

    PubMed Central

    Wu, Tianfu; Xie, Chun; Han, Jie; Ye, Yujin; Weiel, Jim; Li, Quan; Blanco, Irene; Ahn, Chul; Olsen, Nancy; Putterman, Chaim; Saxena, Ramesh; Mohan, Chandra

    2012-01-01

    The metabolic disturbances that underlie systemic lupus erythematosus are currently unknown. A metabolomic study was executed, comparing the sera of 20 SLE patients against that of healthy controls, using LC/MS and GC/MS platforms. Validation of key differences was performed using an independent cohort of 38 SLE patients and orthogonal assays. SLE sera showed evidence of profoundly dampened glycolysis, Krebs cycle, fatty acid β oxidation and amino acid metabolism, alluding to reduced energy biogenesis from all sources. Whereas long-chain fatty acids, including the n3 and n6 essential fatty acids, were significantly reduced, medium chain fatty acids and serum free fatty acids were elevated. The SLE metabolome exhibited profound lipid peroxidation, reflective of oxidative damage. Deficiencies were noted in the cellular anti-oxidant, glutathione, and all methyl group donors, including cysteine, methionine, and choline, as well as phosphocholines. The best discriminators of SLE included elevated lipid peroxidation products, MDA, gamma-glutamyl peptides, GGT, leukotriene B4 and 5-HETE. Importantly, similar elevations were not observed in another chronic inflammatory autoimmune disease, rheumatoid arthritis. To sum, comprehensive profiling of the SLE metabolome reveals evidence of heightened oxidative stress, inflammation, reduced energy generation, altered lipid profiles and a pro-thrombotic state. Resetting the SLE metabolome, either by targeting selected molecules or by supplementing the diet with essential fatty acids, vitamins and methyl group donors offers novel opportunities for disease modulation in this disabling systemic autoimmune ailment. PMID:22723834

  17. Role of cannabis in psychiatric disturbance.

    PubMed

    Knight, F

    1976-01-01

    Clinical observation suggests that cannabis is implicated in some types of psychiatric disturbance. A record of admissions to two urban and four rural hospitals in Jamaica is examined along with details of individual cases. One-third of male admissions to the psychiatric hospital have used cannabis. Of 74 males admitted to another psychiatric service over a 12-month period, 29 had used cannabis. Ten of these patients were diagnosed as "ganja psychosis," and four others were classified as "marijuana-modified mania." At another psychiatric service, 54 of 223 admissions (24.2%) for functional psychosis presented with cannabis usage as a comtributory factor. These 54 patients included 14 and seven cases of hypomanic and depressive reactions, respectively. At three other rural general hospitals, psychiatric admissions for psychosis showed 11 of 51, seven of 18, and 39 of 75 patients, respectively, in whom cannabis was considered directly responsible. These findings lend support to the idea of causation of illness or modification of existing illness. The negative findings of controlled studies in the same country are not inconsistent. A suggested classification for adverse reactions to cannabis offered by one author is recommended, because it is in accord with common local clinical experience.

  18. Parkinson's disease: disturbed vestibular function and levodopa.

    PubMed

    Lithgow, Brian J; Shoushtarian, Mehrnaz

    2015-01-01

    Evidence indicates Levodopa effects central postural control. As electrophysiological postural control biomarkers, sensory oto-acoustic features were extracted from Electrovestibulography (EVestG) data to identify 20 healthy age and gender matched individuals as Controls from 20 PD subjects before (PDlowmed) and 18 after (PDmed) morning doses of Levodopa. EVestG data was collected using a single tilt stimulus applied in the pitch plane. The extracted features were based on the measured firing pattern, interval histogram and the shape of the average field potential response. An unbiased cross validated classification accuracy of 88%, 88% and 79% was achieved using combinations of 2 features for separating PDlowmed from control, control from PD (combined PDlowmed and PDmed), and PDlowmed from PDmed groups respectively. One feature showed significant correlations (p<0.05) with the Modified Hoehn and Yahr PD staging scale. The results indicate disturbed vestibular function is observed in both the PDmed and PDlowmed conditions, and these are separable. The implication is that Levodopa may also affect peripheral as well as central postural control.

  19. Disturbance Rejection Control for The Green Bank Telescope

    NASA Astrophysics Data System (ADS)

    Ranka, Trupti

    The GBT is a single dish, receiving radio telescope. It is capable of receiving radio waves in the frequency range of 300 MHz to 115 GHz. The off-axis primary reflector of the telescope is 100 meters in diameter. A truss boom (feedarm) extends about 60 meters perpendicular to the primary reflector and is supported at the edge of the reflector. A subreflector is placed at the tip of the feedarm, which directs the focused radio waves from the primary reflector to the radio receivers placed on the feedarm. At high radio frequencies of observation, the uncorrected pointing and tracking errors become limiting factors for making useful scientific observations. The primary reflector and subreflector servo systems need to reduce the pointing and tracking errors due to torque disturbances acting on the system. The overall aim of this research is to redesign the servo control systems such that they are able to give a superior disturbance rejection performance. The 4 contributions of this research are: 1) Verifying the dynamical model of the structure using system identification experiments. 2) The unique reformulation of the extended state observer (ESO) design as a quantitative feedback design problem in frequency domain and splitting the design of the ESO as a feedback observer and a feedforward filter. This formulation gives a more systematic way of designing an ESO as compared to the current technique used for the ESO design. This method is then used to design the ESO based controller for the primary reflector position loop. The ESO based controller provides more than 50% improvement in disturbance rejection in the primary reflector servo loop, as compared to the legacy PID controller. 3) The innovative use of extremum seeking controller (ESC) with a disturbance feedforward signal. We investigate the use of disturbance feedforward with ESC and show that disturbance feedforward improves the speed of the ESC loop by improving the initial condition of the ESC loop and by

  20. Chronic Low Back Pain, Sleep Disturbance, and Interleukin-6

    PubMed Central

    Heffner, Kathi L.; France, Christopher R.; Trost, Zina; Mei Ng, H.; Pigeon, Wilfred R.

    2010-01-01

    Objectives Sleep disturbance is a common co-morbidity of chronic pain. Inflammatory processes are dysregulated in sleep disturbance and also contribute to pain sensitivity. Thus, inflammation may play an important role in bi-directional associations between pain and sleep. Little is known about concurrent relationships among chronic pain, sleep, and inflammation. The aim of our study was to examine associations among sleep disturbance and circulating levels of the inflammatory cytokine, interleukin-6 (IL-6), in individuals with and without chronic low back pain. Methods Gender and age-matched adults with chronic low back pain (CLBP; n = 25) or without chronic pain (controls; n = 25) completed measures of sleep quality in the past month and depressive symptoms in the past week, and provided a blood draw for IL-6. The next morning, participants reported their sleep quality the previous night and their current experience of morning pain. Results Individuals with CLBP had more sleep disturbance than controls. Circulating IL-6 levels were similar for the two groups; however, in adults with CLBP, poorer sleep quality was associated with higher IL-6 levels, and both sleep and IL-6 related to pain reports. Unlike CLBP participants, controls showed normal, age-related increases in IL-6 levels, whereas sleep quality was unrelated to IL-6 levels. Depressive symptoms could not fully explain the observed associations. Discussion Inflammatory processes may play a significant role in cycles of pain and sleep disturbance. Clinical interventions that improve sleep and reduce concomitant inflammatory dysregulation hold promise for chronic pain management. PMID:21188850

  1. Flow disturbances generated by feeding and swimming zooplankton.

    PubMed

    Kiørboe, Thomas; Jiang, Houshuo; Gonçalves, Rodrigo Javier; Nielsen, Lasse Tor; Wadhwa, Navish

    2014-08-12

    Interactions between planktonic organisms, such as detection of prey, predators, and mates, are often mediated by fluid signals. Consequently, many plankton predators perceive their prey from the fluid disturbances that it generates when it feeds and swims. Zooplankton should therefore seek to minimize the fluid disturbance that they produce. By means of particle image velocimetry, we describe the fluid disturbances produced by feeding and swimming in zooplankton with diverse propulsion mechanisms and ranging from 10-µm flagellates to greater than millimeter-sized copepods. We show that zooplankton, in which feeding and swimming are separate processes, produce flow disturbances during swimming with a much faster spatial attenuation (velocity u varies with distance r as u ∝ r(-3) to r(-4)) than that produced by zooplankton for which feeding and propulsion are the same process (u ∝ r(-1) to r(-2)). As a result, the spatial extension of the fluid disturbance produced by swimmers is an order of magnitude smaller than that produced by feeders at similar Reynolds numbers. The "quiet" propulsion of swimmers is achieved either through swimming erratically by short-lasting power strokes, generating viscous vortex rings, or by "breast-stroke swimming." Both produce rapidly attenuating flows. The more "noisy" swimming of those that are constrained by a need to simultaneously feed is due to constantly beating flagella or appendages that are positioned either anteriorly or posteriorly on the (cell) body. These patterns transcend differences in size and taxonomy and have thus evolved multiple times, suggesting a strong selective pressure to minimize predation risk.

  2. Flow disturbances generated by feeding and swimming zooplankton

    PubMed Central

    Kiørboe, Thomas; Jiang, Houshuo; Gonçalves, Rodrigo Javier; Nielsen, Lasse Tor; Wadhwa, Navish

    2014-01-01

    Interactions between planktonic organisms, such as detection of prey, predators, and mates, are often mediated by fluid signals. Consequently, many plankton predators perceive their prey from the fluid disturbances that it generates when it feeds and swims. Zooplankton should therefore seek to minimize the fluid disturbance that they produce. By means of particle image velocimetry, we describe the fluid disturbances produced by feeding and swimming in zooplankton with diverse propulsion mechanisms and ranging from 10-µm flagellates to greater than millimeter-sized copepods. We show that zooplankton, in which feeding and swimming are separate processes, produce flow disturbances during swimming with a much faster spatial attenuation (velocity u varies with distance r as u ∝ r−3 to r−4) than that produced by zooplankton for which feeding and propulsion are the same process (u ∝ r−1 to r−2). As a result, the spatial extension of the fluid disturbance produced by swimmers is an order of magnitude smaller than that produced by feeders at similar Reynolds numbers. The “quiet” propulsion of swimmers is achieved either through swimming erratically by short-lasting power strokes, generating viscous vortex rings, or by “breast-stroke swimming.” Both produce rapidly attenuating flows. The more “noisy” swimming of those that are constrained by a need to simultaneously feed is due to constantly beating flagella or appendages that are positioned either anteriorly or posteriorly on the (cell) body. These patterns transcend differences in size and taxonomy and have thus evolved multiple times, suggesting a strong selective pressure to minimize predation risk. PMID:25071196

  3. Antinociceptive and hypnotic activities of pregabalin in a neuropathic pain-like model in mice.

    PubMed

    Wang, Tian-Xiao; Yin, Dou; Guo, Wei; Liu, Yuan-Yuan; Li, Ya-Dong; Qu, Wei-Min; Han, Wu-Jian; Hong, Zong-Yuan; Huang, Zhi-Li

    2015-08-01

    To evaluate the antinociceptive and hypnotic effects of pregabalin, we established a neuropathic pain-like model in mice using partial sciatic nerve ligation (PSNL), and examined thermal hyperalgesia, mechanical allodynia, electroencephalogram, rota-rod testing, and c-Fos expression in the anterior cingulate cortex. Gabapentin was used as a reference drug in the study. Pregabalin administered i.g. at 12.5 and 25mg/kg prolonged the duration of thermal latencies by 1.4- and 1.6-fold and increased the mechanical threshold by 2.2- and 3.1-fold 3h after administration, respectively, but did not affect motor coordination in PSNL mice, compared with vehicle control. Pregabalin (12.5 and 25mg/kg) given at 6:30 increased the amount of non-rapid eye movement sleep in a 4-h period by 1.3- and 1.4-fold, respectively, in PSNL mice. However, pregabalin (25mg/kg) given at 20:30 did not alter the sleep pattern in normal mice. Immunohistochemical study showed that PSNL increased c-Fos expression in the neurons of anterior cingulate cortex by 2.1-fold, which could be reversed by pregabalin. These results indicate that pregabalin is an effective treatment for both neuropathic pain and sleep disturbance in PSNL mice.

  4. 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

  5. Obesity impairs lactation performance in mice by inducing prolactin resistance

    PubMed Central

    Buonfiglio, Daniella C.; Ramos-Lobo, Angela M.; Freitas, Vanessa M.; Zampieri, Thais T.; Nagaishi, Vanessa S.; Magalhães, Magna; Cipolla-Neto, Jose; Cella, Nathalie; Donato Jr., Jose

    2016-01-01

    Obesity reduces breastfeeding success and lactation performance in women. However, the mechanisms involved are not entirely understood. In the present study, female C57BL/6 mice were chronically exposed to a high-fat diet to induce obesity and subsequently exhibited impaired offspring viability (only 15% survival rate), milk production (33% reduction), mammopoiesis (one-third of the glandular area compared to control animals) and postpartum maternal behaviors (higher latency to retrieving and grouping the pups). Reproductive experience attenuated these defects. Diet-induced obese mice exhibited high basal pSTAT5 levels in the mammary tissue and hypothalamus, and an acute prolactin stimulus was unable to further increase pSTAT5 levels above basal levels. In contrast, genetically obese leptin-deficient females showed normal prolactin responsiveness. Additionally, we identified the expression of leptin receptors specifically in basal/myoepithelial cells of the mouse mammary gland. Finally, high-fat diet females exhibited altered mRNA levels of ERBB4 and NRG1, suggesting that obesity may involve disturbances to mammary gland paracrine circuits that are critical in the control of luminal progenitor function and lactation. In summary, our findings indicate that high leptin levels are a possible cause of the peripheral and central prolactin resistance observed in obese mice which leads to impaired lactation performance. PMID:26926925

  6. Least Disturbed Condition for European Mediterranean rivers.

    PubMed

    Feio, M J; Aguiar, F C; Almeida, S F P; Ferreira, J; Ferreira, M T; Elias, C; Serra, S R Q; Buffagni, A; Cambra, J; Chauvin, C; Delmas, F; Dörflinger, G; Erba, S; Flor, N; Ferréol, M; Germ, M; Mancini, L; Manolaki, P; Marcheggiani, S; Minciardi, M R; Munné, A; Papastergiadou, E; Prat, N; Puccinelli, C; Rosebery, J; Sabater, S; Ciadamidaro, S; Tornés, E; Tziortzis, I; Urbanič, G; Vieira, C

    2014-04-01

    The present report describes a three-step approach that was used to characterize and define thresholds for the Least Disturbed Condition in Mediterranean streams of four different types, regarding organic pollution and nutrients, hydrological and morphological alterations, and land use. For this purpose, a common database composed of national reference sites (929 records) from seven countries, sampled for invertebrates, diatoms and macrophytes was used. The analyses of reference sites showed that small (catchment <100 km(2)) siliceous and non-siliceous streams were mainly affected by channelization, bank alteration and hydropeaking. Medium-sized siliceous rivers were the most affected by stressors: 25-43% of the samples showed at least slight alterations regarding channelization, connectivity, upstream dam influence, hydropeaking and degradation of riparian vegetation. Temporary streams were the least affected by hydromorphological changes, but they were nevertheless affected by alterations in riparian vegetation. There were no major differences between all permanent stream types regarding water quality, but temporary streams showed lower values for oxygenation (DO) and wider ranges for other variables, such as nitrates. A lower threshold value for DO (60%) was determined for this stream type and can be attributed to the streams' natural characteristics. For all other river types, common limits were found for the remaining variables (ammonium, nitrate, phosphate, total P, % of artificial areas, % of intensive and extensive agriculture, % of semi-natural areas in the catchment). These values were then used to select the list of reference sites. The biological communities were characterized, revealing the existence of nine groups of Mediterranean invertebrate communities, six for diatoms and five for macrophytes: each group was characterized by specific indicator taxa that highlighted the differences between groups.

  7. Comparison of methods for determining the hydrologic recovery time after forest disturbance

    NASA Astrophysics Data System (ADS)

    Oda, T.; Green, M.; Ohte, N.; Urakawa, R.; Endo, I.; Scanlon, T. M.; Sebestyen, S. D.; McGuire, K. J.; Katsuyama, M.; Fukuzawa, K.; Tague, C.; Hiraoka, M.; Fukushima, K.; Giambelluca, T. W.

    2013-12-01

    Changes in forest hydrology changes after forest disturbance vary among catchments. Although studies have summarized the initial runoff changes following forest disturbance, the estimates of long-term recovery time are less frequently reported. To understand the mechanisms of long-term recovery processes and to predict the long-term changes in streamflow after forest disturbance, it is important to compare recovery times after disturbance. However, there is no clear consensus regarding the best methodology for such research, especially for watershed studies that were not designed as paired watersheds. We compared methods of determining the hydrologic recovery time to determine if there is a common method for sites in any hydroclimatic setting. We defined the hydrologic recovery time to be the time of disturbance to the time when hydrological factors first recovered to pre-disturbance levels. We acquired data on long-term rainfall and runoff at 16 sites in northeastern USA and Japan that had at least 10 years (and up to 50 years) of post disturbance data. The types of disturbance include harvesting, diseases and insect damages. We compared multiple indices of hydrological response including annual runoff, annual runoff ratio (annual runoff/annual rainfall), annual loss (annual rainfall-annual runoff), fiftieth-percentile annual flow, and seasonal water balance. The results showed that comparing annual runoff to a reference site was most robust at constraining the recovery time, followed by using pre-disturbance data as reference data and calculating the differences in annual runoff from pre-disturbance levels. However, in case of small disturbance at sites without reference data or long-term pre-disturbance data, the inter-annual variation of rainfall makes the effect of disturbance unclear. We found that annual loss had smaller inter-annual variation, and defining recovery time with annual loss was best in terms of matching the results from paired watersheds. The

  8. Implementation of a Compressor Face Boundary Condition Based on Small Disturbances

    NASA Technical Reports Server (NTRS)

    Slater, John W.; Paynter, Gerald C.

    2000-01-01

    A compressor-face boundary condition that models the unsteady interactions of acoustic and convective velocity disturbances with a compressor has been implemented into a three-dimensional computational fluid dynamics code. Locally one-dimensional characteristics along with a small-disturbance model are used to compute the acoustic response as a function of the local stagger angle and the strength and direction of the disturbance. Simulations of the inviscid flow in a straight duct, a duct coupled to a compressor, and a supersonic inlet demonstrate the behavior of the boundary condition in relation to existing boundary conditions. Comparisons with experimental data show a large improvement in accuracy over existing boundary conditions in the ability to predict the reflected disturbance from the interaction of an acoustic disturbance with a compressor.

  9. Information-disturbance tradeoff in estimating a unitary transformation

    SciTech Connect

    Bisio, Alessandro; D'Ariano, Giacomo Mauro; Perinotti, Paolo; Chiribella, Giulio

    2010-12-15

    We address the problem of the information-disturbance tradeoff associated to the estimation of a quantum transformation and show how the extraction of information about a black box causes a perturbation of the corresponding input-output evolution. In the case of a black box performing a unitary transformation, randomly distributed according to the invariant measure, we give a complete solution of the problem, deriving the optimal tradeoff curve and presenting an explicit construction of the optimal quantum network.

  10. Prevalence of feral swine disturbance at important archaeological sites over a large landscape in Florida.

    PubMed

    Engeman, Richard M; Meyer, Joseph S; Allen, John B

    2017-01-10

    Feral swine are globally known as one of the most destructive invasive vertebrates, damaging native habitats, native plants and animals, agriculture, infrastructure, spreading diseases. There has been little quantification on their disturbance to archaeological sites across a broad landscape. Over 6 years we inspected 293 significant archaeological sites for swine disturbance across a vast area. We found a 42% prevalence of swine disturbance among all sites, with prevalence not distinguishable among prehistoric sites, historic sites, and sites with both components. The areas of disturbance mapped within three historic homestead sites showed 5-26% of total site surface area rooted. Disturbance was not evident upon re-inspection of one of these sites after 18 months, indicating how evidence of disturbance can be obscured in this environment. Thus, our observed 42% prevalence of disturbance should be considered a minimum for disturbance occurring through time. Artifacts depths were <10 cm of the surface at 85% of the sites and <20 cm of the surface for 90% of the sites. Feral swine rooting commonly exceeds 20 cm in depth, especially in soft sandy substrates typical of Florida, making the great majority of the studied sites highly vulnerable to artifact damage or displacement.

  11. Prevalence of feral swine disturbance at important archaeological sites over a large landscape in Florida

    PubMed Central

    Engeman, Richard M.; Meyer, Joseph S.; Allen, John B.

    2017-01-01

    Feral swine are globally known as one of the most destructive invasive vertebrates, damaging native habitats, native plants and animals, agriculture, infrastructure, spreading diseases. There has been little quantification on their disturbance to archaeological sites across a broad landscape. Over 6 years we inspected 293 significant archaeological sites for swine disturbance across a vast area. We found a 42% prevalence of swine disturbance among all sites, with prevalence not distinguishable among prehistoric sites, historic sites, and sites with both components. The areas of disturbance mapped within three historic homestead sites showed 5–26% of total site surface area rooted. Disturbance was not evident upon re-inspection of one of these sites after 18 months, indicating how evidence of disturbance can be obscured in this environment. Thus, our observed 42% prevalence of disturbance should be considered a minimum for disturbance occurring through time. Artifacts depths were <10 cm of the surface at 85% of the sites and <20 cm of the surface for 90% of the sites. Feral swine rooting commonly exceeds 20 cm in depth, especially in soft sandy substrates typical of Florida, making the great majority of the studied sites highly vulnerable to artifact damage or displacement. PMID:28071758

  12. Prevalence of feral swine disturbance at important archaeological sites over a large landscape in Florida

    NASA Astrophysics Data System (ADS)

    Engeman, Richard M.; Meyer, Joseph S.; Allen, John B.

    2017-01-01

    Feral swine are globally known as one of the most destructive invasive vertebrates, damaging native habitats, native plants and animals, agriculture, infrastructure, spreading diseases. There has been little quantification on their disturbance to archaeological sites across a broad landscape. Over 6 years we inspected 293 significant archaeological sites for swine disturbance across a vast area. We found a 42% prevalence of swine disturbance among all sites, with prevalence not distinguishable among prehistoric sites, historic sites, and sites with both components. The areas of disturbance mapped within three historic homestead sites showed 5–26% of total site surface area rooted. Disturbance was not evident upon re-inspection of one of these sites after 18 months, indicating how evidence of disturbance can be obscured in this environment. Thus, our observed 42% prevalence of disturbance should be considered a minimum for disturbance occurring through time. Artifacts depths were <10 cm of the surface at 85% of the sites and <20 cm of the surface for 90% of the sites. Feral swine rooting commonly exceeds 20 cm in depth, especially in soft sandy substrates typical of Florida, making the great majority of the studied sites highly vulnerable to artifact damage or displacement.

  13. 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.

  14. Boswellic acids synergize antitumor activity and protect against the cardiotoxicity of doxorubicin in mice bearing Ehrlich's carcinoma.

    PubMed

    Ali, Shimaa A; Zaitone, Sawsan A; Moustafa, Yasser M

    2015-08-01

    This study aimed to test whether boswellic acids add to the antitumor effects of doxorubicin against solid tumors of Ehrlich's ascites carcinoma (EAC) grown in mice, and to investigate the protective effects of boswellic acids against doxorubicin-induced cardiotoxicity. Sixty-four female Swiss albino mice bearing EAC solid tumors were distributed among 8 groups as follows: group 1, EAC control group; group 2, doxorubicin treatment group [mice were injected with doxorubicin (6 mg·(kg body mass)(-1)·week(-1)) for 3 weeks]; groups 3-5, these mice were treated with boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively; groups 6-8, these mice were treated with a combination of doxorubicin and boswellic acids (125, 250, or 500 mg·kg(-1)·day(-1)), respectively, for 3 weeks. The results indicated that boswellic acids synergized the antitumor activity of doxorubicin. Doxorubicin-treated mice showed elevated serum activities of lactate dehydrogenase and creatine kinase isoenzyme MB as well as cardiac malondialdehyde. Further, decreases in cardiac levels of reduced glutathione, superoxide dismutase, and catalase activities were observed. These effects were accompanied by an increase in cardiac expression of caspase 3. Thus, treatment with boswellic acids attenuated doxorubicin-evoked disturbances in the above-mentioned parameters, highlighting antioxidant and antiapoptotic activities. Therefore, boswellic acids could be potential candidates for ameliorating the cardiotoxicity of doxorubicin.

  15. Proteomic analysis of mouse testis reveals perfluorooctanoic acid-induced reproductive dysfunction via direct disturbance of testicular steroidogenic machinery.

    PubMed

    Zhang, Hongxia; Lu, Yin; Luo, Bin; Yan, Shengmin; Guo, Xuejiang; Dai, Jiayin

    2014-07-03

    Perfluorooctanoic acid (PFOA) is a ubiquitous environmental pollutant suspected of being an endocrine disruptor; however, mechanisms of male reproductive disorders induced by PFOA are poorly understood. In this study, male mice were exposed to 0, 0.31, 1.25, 5, and 20 mg PFOA/kg/day by oral gavage for 28 days. PFOA significantly damaged the seminiferous tubules and reduced testosterone and progesterone levels in the testis in a dose-dependent manner. Furthermore, PFOA exposure reduced sperm quality. We identified 93 differentially expressed proteins between the control and the 5 mg/kg/d PFOA treated mice using a quantitative proteomic approach. Among them, insulin like-factor 3 (INSL3) and cytochrome P450 cholesterol side-chain cleavage enzyme (CYP11A1) as Leydig-cell-specific markers were significantly decreased. We examined in detail the expression patterns of CYP11A1 and associated genes involved in steroidogenesis in the mouse testis. PFOA inhibited the mRNA and protein levels of CYP11A1 and the mRNA levels of 17β-hydroxysteroid dehydrogenase (17β-HSD) in a dose-dependent manner. Moreover, in vitro study showed the reduction in progesterone levels was accompanied by decreased expression of CYP11A1 in cAMP-stimulated mLTC-1 cells. Our findings indicate that PFOA exposure can impair male reproductive function, possibly by disturbing testosterone levels, and CPY11A1 may be a major steroidogenic enzyme targeted by PFOA.

  16. Adaptive immune response in JAM-C-deficient mice: normal initiation but reduced IgG memory.

    PubMed

    Zimmerli, Claudia; Lee, Boris P L; Palmer, Gaby; Gabay, Cem; Adams, Ralf; Aurrand-Lions, Michel; Imhof, Beat A

    2009-04-15

    We have recently shown that junctional adhesion molecule (JAM)-C-deficient mice have leukocytic pulmonary infiltrates, disturbed neutrophil homeostasis, and increased postnatal mortality. This phenotype was partially rescued when mice were housed in ventilated isolators, suggesting an inability to cope with opportunistic infections. In the present study, we further examined the adaptive immune responses in JAM-C(-/-) mice. We found that murine conventional dendritic cells express in addition to Mac-1 and CD11c also JAM-B as ligand for JAM-C. By in vitro adhesion assay, we show that murine DCs can interact with recombinant JAM-C via Mac-1. However, this interaction does not seem to be necessary for dendritic cell migration and function in vivo, even though JAM-C is highly expressed by lymphatic sinuses of lymph nodes. Nevertheless, upon immunization and boosting with a protein Ag, JAM-C-deficient mice showed decreased persistence of specific circulating Abs although the initial response was normal. Such a phenotype has also been observed in a model of Ag-induced arthritis, showing that specific IgG2a Ab titers are reduced in the serum of JAM-C(-/-) compared with wild-type mice. Taken together, these data suggest that JAM-C deficiency affects the adaptive humoral immune response against pathogens, in addition to the innate immune system.

  17. 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

    2017-01-07

    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.

  18. 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.

  19. Multi-Omics Reveals that Lead Exposure Disturbs Gut Microbiome Development, Key Metabolites, and Metabolic Pathways.

    PubMed

    Gao, Bei; Chi, Liang; Mahbub, Ridwan; Bian, Xiaoming; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

    2017-03-16

    Lead exposure remains a global public health issue, and the recent Flint water crisis has renewed public concern about lead toxicity. The toxicity of lead has been well established in a variety of systems and organs. The gut microbiome has been shown to be highly involved in many critical physiological processes, including food digestion, immune system development, and metabolic homeostasis. However, despite the key role of the gut microbiome in human health, the functional impact of lead exposure on the gut microbiome has not been studied. The aim of this study is to define gut microbiome toxicity induced by lead exposure in C57BL/6 mice using multiomics approaches, including 16S rRNA sequencing, whole genome metagenomics sequencing, and gas chromatography-mass spectrometry (GC-MS) metabolomics. 16S rRNA sequencing revealed that lead exposure altered the gut microbiome trajectory and phylogenetic diversity. Metagenomics sequencing and metabolomics profiling showed that numerous metabolic pathways, including vitamin E, bile acids, nitrogen metabolism, energy metabolism, oxidative stress, and the defense/detoxification mechanism, were significantly disturbed by lead exposure. These perturbed molecules and pathways may have important implications for lead toxicity in the host. Taken together, these results demonstrated that lead exposure not only altered the gut microbiome community structures/diversity but also greatly affected metabolic functions, leading to gut microbiome toxicity.

  20. Using Actiwatch to monitor circadian rhythm disturbance in Huntington’ disease: A cautionary note

    PubMed Central

    Townhill, Jenny; Hughes, Alis C.; Thomas, Benny; Busse, Monica E.; Price, Kathy; Dunnett, Stephen B.; Hastings, Michael H.; Rosser, Anne E.

    2016-01-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder that is well recognised as producing progressive deterioration of motor function, including dyskinetic movements, as well as deterioration of cognition and ability to carry out activities of daily living. However, individuals with HD commonly suffer from a wide range of additional symptoms, including weight loss and sleep disturbance, possibly due to disruption of circadian rhythmicity. Disrupted circadian rhythms have been reported in mice models of HD and in humans with HD. One way of assessing an individual's circadian rhythmicity in a community setting is to monitor their sleep/wake cycles, and a convenient method for recording periods of wakefulness and sleep is to use accelerometers to discriminate between varied activity levels (including sleep) during daily life. Here we used Actiwatch® Activity monitors alongside ambulatory EEG and sleep diaries to record wake/sleep patterns in people with HD and normal volunteers. We report that periods of wakefulness during the night, as detected by activity monitors, agreed poorly with EEG recordings in HD subjects, and unsurprisingly sleep diary findings showed poor agreement with both EEG recordings and activity monitor derived sleep periods. One explanation for this is the occurrence of ‘break through’ involuntary movements during sleep in the HD patients, which are incorrectly assessed as wakeful periods by the activity monitor algorithms. Thus, care needs to be taken when using activity monitors to assess circadian activity in individuals with movement disorders. PMID:26774754

  1. Increased neuronal death and disturbed axonal growth in the Polμ-deficient mouse embryonic retina

    PubMed Central

    Baleriola, Jimena; Álvarez-Lindo, Noemí; de la Villa, Pedro; Bernad, Antonio; Blanco, Luis; Suárez, Teresa; de la Rosa, Enrique J.

    2016-01-01

    Programmed cell death occurs naturally at different stages of neural development, including neurogenesis. The functional role of this early phase of neural cell death, which affects recently differentiated neurons among other cell types, remains undefined. Some mouse models defective in DNA double-strand break (DSB) repair present massive cell death during neural development, occasionally provoking embryonic lethality, while other organs and tissues remain unaffected. This suggests that DSBs occur frequently and selectively in the developing nervous system. We analyzed the embryonic retina of a mouse model deficient in the error-prone DNA polymerase μ (Polμ), a key component of the non-homologous end-joining (NHEJ) repair system. DNA DSBs were increased in the mutant mouse at embryonic day 13.5 (E13.5), as well as the incidence of cell death that affected young neurons, including retinal ganglion cells (RGCs). Polμ−/− mice also showed disturbed RGC axonal growth and navigation, and altered distribution of the axonal guidance molecules L1-CAM and Bravo (also known as Nr-CAM). These findings demonstrate that Polμ is necessary for proper retinal development, and support that the generation of DSBs and their repair via the NHEJ pathway are genuine processes involved in neural development. PMID:27172884

  2. Predicting Solar Disturbance Effects on Navigation Systems

    NASA Astrophysics Data System (ADS)

    Lockwood, M.; Wild, M. N.; Stamper, R.; Davis, C. J.; Grande, M.

    A variety of operational systems are vulnerable to disruption by solar disturbances brought to the Earth by the solar wind. Of particular importance to navigation systems are energetic charged particles which can generate temporary malfunctions and permanent damage in satellites. Modern spacecraft technology may prove to be particularly at risk during the next maximum of the solar cycle. In addition, the associated ionospheric disturbances cause phase shifts of transionospheric and ionosphere-reflected signals, giving positioning errors and loss of signal for GPS and Loran-C positioning systems and for over-the-horizon radars. We now have sufficient understanding of the solar wind, and how it interacts with the Earth's magnetic field, to predict statistically the likely effects on operational systems over the next solar cycle. We also have a number of advanced ways of detecting and tracking these disturbances through space but we cannot, as yet, provide accurate forecasts of individual disturbances that could be used to protect satellites and to correct errors. In addition, we have recently discovered long-term changes in the Sun, which mean that the number and severity of the disturbances to operational systems are increasing.

  3. Sleep disturbance in Mowat-Wilson syndrome.

    PubMed

    Evans, Elizabeth; Mowat, David; Wilson, Meredith; Einfeld, Stewart

    2016-03-01

    Mowat-Wilson syndrome (MWS) is a multiple congenital anomaly syndrome caused by a heterozygous mutation or deletion of the ZEB2 gene. It is characterized by a distinctive facial appearance in association with intellectual disability (ID) and variable other features including agenesis of the corpus callosum, seizures, congenital heart defects, microcephaly, short stature, hypotonia, and Hirschsprung disease. The current study investigated sleep disturbance in people with MWS. In a series of unstructured interviews focused on development and behaviors in MWS, family members frequently reported sleep disturbance, particularly early-morning waking and frequent night waking. The Sleep Disturbance Scale for Children (SDSC) was therefore administered to a sample of 35 individuals with MWS, along with the Developmental Behaviour Checklist (DBC) to measure behavioral and emotional disturbance. A high level of sleep disturbance was found in the MWS sample, with 53% scoring in the borderline range and 44% in the clinical disorder range for at least one subscale of the SDSC. Scores were highest for the Sleep-wake transition disorders subscale, with 91% of participants reaching at least the borderline disorder range. A significant positive association was found between total scores on the SDSC and the DBC Total Behaviour Problem Score. These results suggest that sleep disorders should be screened for in people with MWS, and where appropriate, referrals to sleep specialists made for management of sleep problems.

  4. Growth disturbances after distal tibial physeal fractures.

    PubMed

    Berson, L; Davidson, R S; Dormans, J P; Drummond, D S; Gregg, J R

    2000-01-01

    Twenty-four patients with distal tibial growth disturbance were reviewed. Disturbances were classified as physeal bar (prior to deformity), angular, linear or combined deformities. Treatment consisted of osteotomy in fourteen, epiphyseodesis in seven, excision of bony bar in two, and observation in one patient. Follow up was an average 36.6 months (range 4-129 months) after treatment of growth disturbance. The age at time of injury was 10.4 years of age average (range 3-15 years). There were 12 SH2, 2 SH3, 7 SH4, and 3 SH5 distal tibial physeal fractures. Thirteen of 15 fractures considered high energy and only 1 of 9 fractures considered low energy resulted in angular deformity. Angular and linear deformities presented an average 46 months (range 12-120 months) and physeal bars at an average 14 months (range 6-25 months) after injury. Patients with a delay in presentation of growth disturbance greater than 24 months had angular deformities in 92% compared with 33% in children presenting less than or at 24 months. Treatment based on type of deformity, age at time of injury, and growth remaining was considered successful in 83%. Patients with angular or linear deformities were more likely to present late, have high energy injuries, be male patients and have Salter-Harris types IV and V. Early diagnosis and treatment of growth disturbance can prevent severe deformity.

  5. Recurrence and Frequency of Disturbance have Cumulative Effect on Methanotrophic Activity, Abundance, and Community Structure

    PubMed Central

    Ho, Adrian; van den Brink, Erik; Reim, Andreas; Krause, Sascha M. B.; Bodelier, Paul L. E.

    2016-01-01

    Alternate prolonged drought and heavy rainfall is predicted to intensify with global warming. Desiccation-rewetting events alter the soil quality and nutrient concentrations which drive microbial-mediated processes, including methane oxidation, a key biogeochemical process catalyzed by methanotrophic bacteria. Although aerobic methanotrophs showed remarkable resilience to a suite of physical disturbances induced as a single event, their resilience to recurring disturbances is less known. Here, using a rice field soil in a microcosm study, we determined whether recurrence and frequency of desiccation-rewetting impose an accumulating effect on the methanotrophic activity. The response of key aerobic methanotroph subgroups (type Ia, Ib, and II) were monitored using qPCR assays, and was supported by a t-RFLP analysis. The methanotrophic activity was resilient to recurring desiccation-rewetting, but increasing the frequency of the disturbance by twofold significantly decreased methane uptake rate. Both the qPCR and t-RFLP analyses were congruent, showing the dominance of type Ia/Ib methanotrophs prior to disturbance, and after disturbance, the recovering community was predominantly comprised of type Ia (Methylobacter) methanotrophs. Both type Ib and type II (Methylosinus/Methylocystis) methanotrophs were adversely affected by the disturbance, but type II methanotrophs showed recovery over time, indicating relatively higher resilience to the disturbance. This revealed distinct, yet unrecognized traits among the methanotroph community members. Our results show that recurring desiccation-rewetting before a recovery in community abundance had an accumulated effect, compromising methanotrophic activity. While methanotrophs may recover well following sporadic disturbances, their resilience may reach a ‘tipping point’ where activity no longer recovered if disturbance persists and increase in frequency. PMID:26779148

  6. Speckle disturbance limit in laser-based cinema projection systems

    NASA Astrophysics Data System (ADS)

    Verschaffelt, Guy; Roelandt, Stijn; Meuret, Youri; van den Broeck, Wendy; Kilpi, Katriina; Lievens, Bram; Jacobs, An; Janssens, Peter; Thienpont, Hugo

    2015-09-01

    In a multi-disciplinary effort, we investigate the level of speckle that can be tolerated in a laser cinema projector based on a quality of experience experiment with movie clips shown to a test audience in a real-life movie theatre setting. We identify a speckle disturbance threshold by statistically analyzing the observers’ responses for different values of the amount of speckle, which was monitored using a well-defined speckle measurement method. The analysis shows that the speckle perception of a human observer is not only dependent on the objectively measured amount of speckle, but it is also strongly influenced by the image content. The speckle disturbance limit for movies turns out to be substantially larger than that for still images, and hence is easier to attain.

  7. Learning experiences in dance class predict adult eating disturbance.

    PubMed

    Annus, Agnes; Smith, Gregory T

    2009-01-01

    Elite dancers are at increased risk of eating disorders. The authors hypothesized that specific learning about thinness in dance class, rather than simple participation in dance training, tends to be an important aspect of the risk process. Approximately 500 college women reported on their previous dance experiences, their dance-related learning about thinness, their eating behaviours and attitudes and their thinness expectancies. Results showed that lifetime amount of time spent in dance class was unrelated to adult eating disturbance, women's reports of learning experiences concerning thinness during their dance classes predicted adult disordered eating concurrently, and thinness expectancies appeared to mediate the relationship between learning about thinness and adult eating disturbance. Learning experiences about thinness in dance class seem more important than time spent in dance class when examining the relationship between dance study and eating disorders.

  8. Speckle disturbance limit in laser-based cinema projection systems

    PubMed Central

    Verschaffelt, Guy; Roelandt, Stijn; Meuret, Youri; Van den Broeck, Wendy; Kilpi, Katriina; Lievens, Bram; Jacobs, An; Janssens, Peter; Thienpont, Hugo

    2015-01-01

    In a multi-disciplinary effort, we investigate the level of speckle that can be tolerated in a laser cinema projector based on a quality of experience experiment with movie clips shown to a test audience in a real-life movie theatre setting. We identify a speckle disturbance threshold by statistically analyzing the observers’ responses for different values of the amount of speckle, which was monitored using a well-defined speckle measurement method. The analysis shows that the speckle perception of a human observer is not only dependent on the objectively measured amount of speckle, but it is also strongly influenced by the image content. The speckle disturbance limit for movies turns out to be substantially larger than that for still images, and hence is easier to attain. PMID:26370531

  9. Affective and personality disturbances among female former microelectronics workers.

    PubMed

    Bowler, R M; Mergler, D; Rauch, S S; Harrison, R; Cone, J

    1991-01-01

    The production and manufacture of microelectronic components, carried out primarily by women workers, require extensive use of organic solvents. Affective and personality disturbances frequently have been associated with organic solvent toxicity. A group of women, former microelectronics workers (N = 70), primarily of Hispanic origin (77.1%) but raised in the United States, were evaluated for affective and personality disturbance with the MMPI. Profiles were analyzed, and diagnostic classification was performed blind. Results showed that (1) 85.7% of the profiles indicated abnormally high clinical elevations; and (2) MMPI profile classification revealed four clinical diagnostic groups: somatoform (24.3%), depression (15.7%), anxiety (28.6%), and psychotic (14.3%). These findings indicate significant psychopathology among these women, who formerly had worked in a microelectronics plant. The patterns of impairment present similarities to previous reports of organic solvent toxicity.

  10. Modified active disturbance rejection control for time-delay systems.

    PubMed

    Zhao, Shen; Gao, Zhiqiang

    2014-07-01

    Industrial processes are typically nonlinear, time-varying and uncertain, to which active disturbance rejection control (ADRC) has been shown to be an effective solution. The control design becomes even more challenging in the presence of time delay. In this paper, a novel modification of ADRC is proposed so that good disturbance rejection is achieved while maintaining system stability. The proposed design is shown to be more effective than the standard ADRC design for time-delay systems and is also a unified solution for stable, critical stable and unstable systems with time delay. Simulation and test results show the effectiveness and practicality of the proposed design. Linear matrix inequality (LMI) based stability analysis is provided as well.

  11. 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

  12. Ionospheric and geomagnetic disturbances during the 2005 Sumatran earthquakes

    NASA Astrophysics Data System (ADS)

    Hasbi, Alina Marie; Momani, Mohammed Awad; Mohd Ali, Mohd Alauddin; Misran, Norbahiah; Shiokawa, Kazuo; Otsuka, Yuichi; Yumoto, Kiyohumi

    2009-12-01

    This paper investigates the ionospheric and geomagnetic responses during the 28 March 2005 and 14 May 2005 Sumatran earthquakes using GPS and magnetometer stations located in the near zone of the epicenters. These events occurred during low solar and geomagnetic activity. TEC oscillations with periods of 5-10 min were observed about 10-24 min after the earthquakes and have horizontal propagation velocities of 922-1259 m/s. Ionospheric disturbances were observed at GPS stations located to the northeast of the epicenters, while no significant disturbances were seen relatively east and south of the epicenters. The magnetic field measurements show rapid fluctuations of 4-5 s shortly after the earthquake, followed by a Pc5 pulsation of 4.8 min about 11 min after the event. The correlation between the ionospheric and geomagnetic responses shows a good agreement in the period and time lag of the peak disturbance arrival, i.e. about 11-13 min after the earthquake.

  13. 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.

  14. Transient disturbance growth in a corrugated channel

    NASA Astrophysics Data System (ADS)

    Szumbarski, J.; Floryan, J. M.

    2006-12-01

    Transient growth of small disturbances may lead to the initiation of the laminar turbulent transition process. Such growth in a two-dimensional laminar flow in a channel with a corrugated wall is analysed. The corrugation has a wavy form that is completely characterized by its wavenumber and amplitude. The maximum possible growth and the form of the initial disturbance that leads to such growth have been identified for each form of the corrugation. The form that leads to the largest growth for a given corrugation amplitude, i.e. the optimal corrugation, has been found. It is shown that the corrugation acts as an amplifier for disturbances that are approximately optimal in the smooth channel case but has little effect in the other cases. The interplay between the modal (asymptotic) instability and the transient growth, and the use of the variable corrugation for modulation of the growth are discussed.

  15. MERCURY RELEASE FROM DISTURBED ANOXIC SOILS

    SciTech Connect

    Jaroslav Solc; Bethany A. Bolles

    2001-07-16

    The primary objectives of experiments conducted at the Energy & Environmental Research Center (EERC) were to provide information on the secondary release of mercury from contaminated anoxic sediments to an aqueous environment after disturbance/change of in situ physical conditions and to evaluate its migration and partitioning under controlled conditions, including implications of these processes for treatment of contaminated soils. Experimental work included (1) characterization of the mercury-contaminated sediment; (2) field bench-scale dredging simulation; (3) laboratory column study to evaluate a longer-term response to sediment disturbance; (4) mercury volatilization from sediment during controlled drying; (5) resaturation experiments to evaluate the potential for secondary release of residual mercury after disturbance, transport, drying, and resaturation, which simulate a typical scenario during soil excavation and transport to waste disposal facilities; and (6) mercury speciation and potential for methylation during column incubation experiments.

  16. Robust fuzzy logic stabilization with disturbance elimination.

    PubMed

    Danapalasingam, Kumeresan A

    2014-01-01

    A robust fuzzy logic controller is proposed for stabilization and disturbance rejection in nonlinear control systems of a particular type. The dynamic feedback controller is designed as a combination of a control law that compensates for nonlinear terms in a control system and a dynamic fuzzy logic controller that addresses unknown model uncertainties and an unmeasured disturbance. Since it is challenging to derive a highly accurate mathematical model, the proposed controller requires only nominal functions of a control system. In this paper, a mathematical derivation is carried out to prove that the controller is able to achieve asymptotic stability by processing state measurements. Robustness here refers to the ability of the controller to asymptotically steer the state vector towards the origin in the presence of model uncertainties and a disturbance input. Simulation results of the robust fuzzy logic controller application in a magnetic levitation system demonstrate the feasibility of the control design.

  17. Robust Fuzzy Logic Stabilization with Disturbance Elimination

    PubMed Central

    Danapalasingam, Kumeresan A.

    2014-01-01

    A robust fuzzy logic controller is proposed for stabilization and disturbance rejection in nonlinear control systems of a particular type. The dynamic feedback controller is designed as a combination of a control law that compensates for nonlinear terms in a control system and a dynamic fuzzy logic controller that addresses unknown model uncertainties and an unmeasured disturbance. Since it is challenging to derive a highly accurate mathematical model, the proposed controller requires only nominal functions of a control system. In this paper, a mathematical derivation is carried out to prove that the controller is able to achieve asymptotic stability by processing state measurements. Robustness here refers to the ability of the controller to asymptotically steer the state vector towards the origin in the presence of model uncertainties and a disturbance input. Simulation results of the robust fuzzy logic controller application in a magnetic levitation system demonstrate the feasibility of the control design. PMID:25177713

  18. Sleep disturbances in eating disorders: a review.

    PubMed

    Cinosi, E; Di Iorio, G; Acciavatti, T; Cornelio, M; Vellante, F; De Risio, L; Martinotti, G

    2011-01-01

    Psychiatric disorders are frequently associated with disturbances of sleep and circadian rhythms. This review focus on the relationship between sleep disturbances and eating disorders. In the first part are discussed the presence of sleep disorders among patients suffering from anorexia nervosa and bulimia nervosa, the macrostructure and microstructure of theirs sleep, the differences between the various subtypes in ED patients, the dreams of eating disordered patients and their recurrent contents. In the second part, there are treated sleep disturbances in binge eating disorder and other eating disorders not otherwise specified, such as nocturnal (night) eating syndrome and sleep-related eating disorder. In the third part, there are presented data concerning the neurobiological and neuroendocrinological correlates between feeding, metabolism, weight restoration and the processes regulating sleep. In conclusion, possible future investigations are proposed.

  19. Geomagnetic Disturbances Caused by Internal Atmospheric Dynamics

    NASA Technical Reports Server (NTRS)

    Sonneman, G.

    1984-01-01

    It is commonly believed that geomagnetic disturbances are caused by external influences connected with the solar wind. The 27-day recurrence of perturbations seems to be a strong hint for this interaction. But frequently geomagnetic disturbances occur without any relation to sunspot numbers or radiowave fluxes. This was one of the reasons for introducing hypothetical M-regions on the Sun and their relation to solar wind activities. Only one half of the variance of the geomagnetic AL-index could be related to the solar wind. Therefore it is concluded that internal processes of the magnetosphere were responsible for additional geomagnetic activity. Arguments, which might lead to the suggestion of geomagnetic disturbances as being caused by internal atmospheric dynamics are discussed and a rather preliminary scenario of those processes is proposed.

  20. 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

  1. High-Resolution Modeling Disturbance-Induced Forest Carbon Dynamics with Lidar and Landsat Observations

    NASA Astrophysics Data System (ADS)

    Zhao, M.; Huang, C.; Hurtt, G. C.; Dubayah, R.; Fisk, J.; Sahajpal, R.; Flanagan, S.; Swatantran, A.; Huang, W.; Tang, H.; ONeil-Dunne, J.; Johnson, K. D.

    2015-12-01

    Forest stands are dynamic in a status from severely, partially disturbed, or undisturbed to different stages of recovery towards maturity and equilibrium. Forest ecosystem models generally use potential biomass (an assumption of equilibrium status) as initial biomass, which is unrealistic and could result in unreliable estimates of disturbance-induced carbon changes. To accurately estimate spatiotemporal changes of forest carbon stock and fluxes, it requires accurate information on initial biomass, the extent and severity of disturbance, and following land use. We demonstrate a prototype system to achieve this goal by integrating 1-m small footprint Lidar acquired in year 2004, 30-m Landsat disturbances from 1984 to 2011, and an individual-based structure height Ecosystem Demography (ED) model. Lidar provides critical information on forest canopy height, improving the accuracy of initial forest biomass estimates; impervious surfaces data and yearly disturbance data from Landsat provide information on wall-to-wall yearly natural and anthropogenic disturbances and their severity (on average 0.32% for the natural and 0.19% for the anthropogenic for below test area); ED model plays a central role by linking both Lidar canopy height and Landsat disturbances with ecosystem processes. We tested the system at 90-m spatial resolution in Charles County, Maryland, by running ED model for six experiments, the combinations of three initial biomass (potential, moderate and low initial biomass constrained by Lidar canopy height) with two disturbance scenarios (with and without anthropogenic disturbances). Our experiments show that estimated changes of carbon stock and flux are sensitive to initial biomass status and human-induced land cover change. Our prototype system can assess regional carbon dynamics at local scale under changing climate and disturbance regimes, and provide useful information for forest management and land use policies.

  2. 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.

  3. Are forest disturbances amplifying or canceling out climate change-induced productivity changes in European forests?

    NASA Astrophysics Data System (ADS)

    Reyer, Christopher P. O.; Bathgate, Stephen; Blennow, Kristina; Borges, Jose G.; Bugmann, Harald; Delzon, Sylvain; Faias, Sonia P.; Garcia-Gonzalo, Jordi; Gardiner, Barry; Gonzalez-Olabarria, Jose Ramon; Gracia, Carlos; Guerra Hernández, Juan; Kellomäki, Seppo; Kramer, Koen; Lexer, Manfred J.; Lindner, Marcus; van der Maaten, Ernst; Maroschek, Michael; Muys, Bart; Nicoll, Bruce; Palahi, Marc; Palma, João HN; Paulo, Joana A.; Peltola, Heli; Pukkala, Timo; Rammer, Werner; Ray, Duncan; Sabaté, Santiago; Schelhaas, Mart-Jan; Seidl, Rupert; Temperli, Christian; Tomé, Margarida; Yousefpour, Rasoul; Zimmermann, Niklaus E.; Hanewinkel, Marc

    2017-03-01

    Recent studies projecting future climate change impacts on forests mainly consider either the effects of climate change on productivity or on disturbances. However, productivity and disturbances are intrinsically linked because 1) disturbances directly affect forest productivity (e.g. via a reduction in leaf area, growing stock or resource-use efficiency), and 2) disturbance susceptibility is often coupled to a certain development phase of the forest with productivity determining the time a forest is in this specific phase of susceptibility. The objective of this paper is to provide an overview of forest productivity changes in different forest regions in Europe under climate change, and partition these changes into effects induced by climate change alone and by climate change and disturbances. We present projections of climate change impacts on forest productivity from state-of-the-art forest models that dynamically simulate forest productivity and the effects of the main European disturbance agents (fire, storm, insects), driven by the same climate scenario in seven forest case studies along a large climatic gradient throughout Europe. Our study shows that, in most cases, including disturbances in the simulations exaggerate ongoing productivity declines or cancel out productivity gains in response to climate change. In fewer cases, disturbances also increase productivity or buffer climate-change induced productivity losses, e.g. because low severity fires can alleviate resource competition and increase fertilization. Even though our results cannot simply be extrapolated to other types of forests and disturbances, we argue that it is necessary to interpret climate change-induced productivity and disturbance changes jointly to capture the full range of climate change impacts on forests and to plan adaptation measures.

  4. Towards the planning and design of disturbance patterns across scales to counter biological invasions.

    PubMed

    Zurlini, Giovanni; Petrosillo, Irene; Jones, Kenneth Bruce; Li, Bai-Lian; Riitters, Kurt Hans; Medagli, Pietro; Marchiori, Silvano; Zaccarelli, Nicola

    2013-10-15

    The way in which disturbances from human land use are patterned in space across scales can have important consequences for efforts to govern human/environment with regard to, but not only, invasive spread-dispersal processes. In this context, we explore the potential of disturbance patterns along a continuum of scales as proxies for identifying the geographical regions prone to spread of invasive plant species. To this end, we build on a previous framework of cross-scale disturbance patterns, exercising the approach for the Apulia region (South Italy). We first review procedures and results introducing disturbance maps and sliding windows to measure composition (amount) and configuration (contagion) of disturbance patterns both for real and simulated landscapes from random, multifractal and hierarchical neutral models. We introduce cross-scale disturbance profiles obtained by clustering locations from real and simulated landscapes, which are used as foils for comparison to the real landscapes on the same pattern transition space. Critical percolation thresholds derived from landscape observations and theoretical works are discussed in order to identify critical scale domains. With reference to the actual land use and invasive alien flora correlates of disturbance patterns, a cross-scale "invasibility" map of the Apulia region is derived, which shows sub-regions and scale domains with different potentials for the invasive spread of undesirable species. We discuss the potential effect of contagious and non-contagious disturbances like climate change and why multifractal-like disturbance patterns might be more desirable than others to counter biological invasions in a multi-scale and multi-level context of adaptive planning, design and management of disturbance.

  5. 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

  6. Self-reported sleep disturbances in renal transplant recipients

    PubMed Central

    2013-01-01

    Background Poor sleep quality (SQ) and daytime sleepiness (DS) are common in renal transplant (RTx) recipients; however, related data are rare. This study describes the prevalence and frequency of self-reported sleep disturbances in RTx recipients. Methods This cross-sectional study included 249 RTx recipients transplanted at three Swiss transplant centers. All had reported poor SQ and / or DS in a previous study. With the Survey of Sleep (SOS) self-report questionnaire, we screened for sleep and health habits, sleep history, main sleep problems and sleep-related disturbances. To determine a basis for preliminary sleep diagnoses according to the International Classification of Sleep Disorders (ICSD), 164 subjects were interviewed (48 in person, 116 via telephone and 85 refused). Descriptive statistics were used to analyze the data and to determine the frequencies and prevalences of specific sleep disorders. Results The sample had a mean age of 59.1 ± 11.6 years (60.2% male); mean time since Tx was 11.1 ± 7.0 years. The most frequent sleep problem was difficulty staying asleep (49.4%), followed by problems falling asleep (32.1%). The most prevalent sleep disturbance was the need to urinate (62.9%), and 27% reported reduced daytime functionality. Interview data showed that most suffered from the first ICSD category: insomnias. Conclusion Though often disregarded in RTx recipients, sleep is an essential factor of wellbeing. Our findings show high prevalences and incidences of insomnias, with negative impacts on daytime functionality. This indicates a need for further research on the clinical consequences of sleep disturbances and the benefits of insomnia treatment in RTx recipients. PMID:24112372

  7. Operational constraints on state-dependent formulations of quantum error-disturbance trade-off relations

    NASA Astrophysics Data System (ADS)

    Korzekwa, Kamil; Jennings, David; Rudolph, Terry

    2014-05-01

    We argue for an operational requirement that all state-dependent measures of disturbance should satisfy. Motivated by this natural criterion, we prove that in any d-dimensional Hilbert space and for any pair of noncommuting operators, A and B, there exists a set of at least 2d -1 zero-noise, zero-disturbance (ZNZD) states, for which the first observable can be measured without noise and the second will not be disturbed. Moreover, we show that it is possible to construct such ZNZD states for which the expectation value of the commutator [A,B] does not vanish. Therefore any state-dependent error-disturbance relation, based on the expectation value of the commutator as a lower bound, must violate the operational requirement. We also discuss Ozawa's state-dependent error-disturbance relation in light of our results and show that the disturbance measure used in this relation exhibits unphysical properties. We conclude that the trade-off is inevitable only between state-independent measures of error and disturbance.

  8. Increasing forest disturbances in Europe and their impact on carbon storage

    PubMed Central

    Seidl, Rupert; Schelhaas, Mart-Jan; Rammer, Werner; Verkerk, Pieter Johannes

    2015-01-01

    Disturbances from wind, bark beetles, and wildfires have increased in Europe’s forests throughout the 20th century 1. Climatic changes were identified as a main driver behind this increase 2, yet how the expected continuation of climate change will affect Europe’s forest disturbance regime remains unresolved. Increasing disturbances could strongly impact the forest carbon budget 3,4, and are hypothesized to contribute to the recently observed carbon sink saturation in Europe’s forests 5. Here we show that forest disturbance damage in Europe has continued to increase in the first decade of the 21st century. Based on an ensemble of climate change scenarios we find that damage from wind, bark beetles, and forest fires is likely to increase further in coming decades, and estimate the rate of increase to +0.91·106 m3 of timber per year until 2030. We show that this intensification can offset the effect of management strategies aiming to increase the forest carbon sink, and calculate the disturbance-related reduction of the carbon storage potential in Europe’s forests to be 503.4 Tg C in 2021-2030. Our results highlight the considerable carbon cycle feedbacks of changing disturbance regimes, and underline that future forest policy and management will require a stronger focus on disturbance risk and resilience. PMID:25737744

  9. A novel testate amoebae trait-based approach to infer environmental disturbance in Sphagnum peatlands

    NASA Astrophysics Data System (ADS)

    Marcisz, Katarzyna; Colombaroli, Daniele; Jassey, Vincent E. J.; Tinner, Willy; Kołaczek, Piotr; Gałka, Mariusz; Karpińska-Kołaczek, Monika; Słowiński, Michał; Lamentowicz, Mariusz

    2016-09-01

    Species’ functional traits are closely related to ecosystem processes through evolutionary adaptation, and are thus directly connected to environmental changes. Species’ traits are not commonly used in palaeoecology, even though they offer powerful advantages in understanding the impact of environmental disturbances in a mechanistic way over time. Here we show that functional traits of testate amoebae (TA), a common group of palaeoecological indicators, can serve as an early warning signal of ecosystem disturbance and help determine thresholds of ecosystem resilience to disturbances in peatlands. We analysed TA traits from two Sphagnum-dominated mires, which had experienced different kinds of disturbances in the past 2000 years – fire and peat extraction, respectively. We tested the effect of disturbances on the linkages between TA community structure, functional trait composition and functional diversity using structural equation modelling. We found that traits such as mixotrophy and small hidden apertures (plagiostomic apertures) are strongly connected with disturbance, suggesting that these two traits can be used as palaeoecological proxies of peatland disturbance. We show that TA functional traits may serve as a good proxy of past environmental changes, and further analysis of trait-ecosystem relationships could make them valuable indicators of the contemporary ecosystem state.

  10. Cooperation and competition shape ecological resistance during periodic spatial disturbance of engineered bacteria.

    PubMed

    Wilson, Cortney E; Lopatkin, Allison J; Craddock, Travis J A; Driscoll, William W; Eldakar, Omar Tonsi; Lopez, Jose V; Smith, Robert P

    2017-03-27

    Cooperation is fundamental to the survival of many bacterial species. Previous studies have shown that spatial structure can both promote and suppress cooperation. Most environments where bacteria are found are periodically disturbed, which can affect the spatial structure of the population. Despite the important role that spatial disturbances play in maintaining ecological relationships, it remains unclear as to how periodic spatial disturbances affect bacteria dependent on cooperation for survival. Here, we use bacteria engineered with a strong Allee effect to investigate how the frequency of periodic spatial disturbances affects cooperation. We show that at intermediate frequencies of spatial disturbance, the ability of the bacterial population to cooperate is perturbed. A mathematical model demonstrates that periodic spatial disturbance leads to a tradeoff between accessing an autoinducer and accessing nutrients, which determines the ability of the bacteria to cooperate. Based on this relationship, we alter the ability of the bacteria to access an autoinducer. We show that increased access to an autoinducer can enhance cooperation, but can also reduce ecological resistance, defined as the ability of a population to resist changes due to disturbance. Our results may have implications in maintaining stability of microbial communities and in the treatment of infectious diseases.

  11. How Disturbance Influences Community Composition at Hydrothermal Vents: a Theoretical Model of Macrofaunal Coexistence

    NASA Astrophysics Data System (ADS)

    Miller, A. D.; Hsing, P.; Roxburgh, S. H.; Shea, K.; Fisher, C. R.

    2012-12-01

    Biological communities at spreading centers experience a continuum of disturbance regimes, with fast spreading ridges characterized by relatively frequent tectonic and magmatic events, and slow spreading ridges displaying more stable environmental conditions. We develop a theoretical model to show how disturbance (or lack thereof) can influence the composition of biological communities at hydrothermal vents. Our model assumptions are based on empirical data, which show that macrofaunal species of interest (Riftia pachyptila, Bathymodiolus thermophilus, Calyptogena magnifica) establish in distinct microhabitats, based on availability of vent fluids that nourish endosymbiotic chemoautotrophs. We focus on how these establishment strategies interact with species fecundity, and with disturbance frequency and intensity, to determine what types of strategies can coexist in the system. We find that species must adopt sufficiently different fecundity-establishment strategies to coexist in the community, though strict tradeoffs between fecundity and establishment ability are not required. Additionally, we describe how the strategies that lead to coexistence depend on habitat availability and disturbance regime. Though other coexistence mechanisms may also play a role, our findings suggest why communities within a single biogeographic province may vary with spreading rate (as from N to S along the East Pacific Rise), and what strategies will allow coexistence under different disturbance regimes. Understanding how changes to disturbance regimes influence community composition is very important, as commercial mining interests are rapidly developing plans to exploit the rich mineral resources associated with hydrothermal vents and their activities will change the disturbance regime.

  12. A novel testate amoebae trait-based approach to infer environmental disturbance in Sphagnum peatlands

    PubMed Central

    Marcisz, Katarzyna; Colombaroli, Daniele; Jassey, Vincent E. J.; Tinner, Willy; Kołaczek, Piotr; Gałka, Mariusz; Karpińska-Kołaczek, Monika; Słowiński, Michał; Lamentowicz, Mariusz

    2016-01-01

    Species’ functional traits are closely related to ecosystem processes through evolutionary adaptation, and are thus directly connected to environmental changes. Species’ traits are not commonly used in palaeoecology, even though they offer powerful advantages in understanding the impact of environmental disturbances in a mechanistic way over time. Here we show that functional traits of testate amoebae (TA), a common group of palaeoecological indicators, can serve as an early warning signal of ecosystem disturbance and help determine thresholds of ecosystem resilience to disturbances in peatlands. We analysed TA traits from two Sphagnum-dominated mires, which had experienced different kinds of disturbances in the past 2000 years – fire and peat extraction, respectively. We tested the effect of disturbances on the linkages between TA community structure, functional trait composition and functional diversity using structural equation modelling. We found that traits such as mixotrophy and small hidden apertures (plagiostomic apertures) are strongly connected with disturbance, suggesting that these two traits can be used as palaeoecological proxies of peatland disturbance. We show that TA functional traits may serve as a good proxy of past environmental changes, and further analysis of trait-ecosystem relationships could make them valuable indicators of the contemporary ecosystem state. PMID:27658521

  13. Impact of monocarboxylate transporter-8 deficiency on the hypothalamus-pituitary-thyroid axis in mice.

    PubMed

    Trajkovic-Arsic, Marija; Müller, Julia; Darras, Veerle M; Groba, Claudia; Lee, Sooyeon; Weih, Debra; Bauer, Karl; Visser, Theo J; Heuer, Heike

    2010-10-01

    In patients, inactivating mutations in the gene encoding the thyroid hormone-transporting monocarboxylate transporter 8 (Mct8) are associated with severe mental and neurological deficits and disturbed thyroid hormone levels. The latter phenotype characterized by high T3 and low T4 serum concentrations is replicated in Mct8 knockout (ko) mice, indicating that MCT8 deficiency interferes with thyroid hormone production and/or metabolism. Our studies of Mct8 ko mice indeed revealed increased thyroidal T3 and T4 concentrations without overt signs of a hyperactive thyroid gland. However, upon TSH stimulation Mct8 ko mice showed decreased T4 and increased T3 secretion compared with wild-type littermates. Moreover, similar changes in the thyroid hormone secretion pattern were observed in Mct8/Trhr1 double-ko mice, which are characterized by normal serum T3 levels and normal hepatic and renal D1 expression in the presence of very low T4 serum concentrations. These data strongly indicate that absence of Mct8 in the thyroid gland affects thyroid hormone efflux by shifting the ratio of the secreted hormones toward T3. To test this hypothesis, we generated Mct8/Pax8 double-mutant mice, which in addition to Mct8 lack a functional thyroid gland and are therefore completely athyroid. Following the injection of these animals with either T4 or T3, serum analysis revealed T3 concentrations similar to those observed in Pax8 ko mice under thyroid hormone replacement, indicating that indeed increased thyroidal T3 secretion in Mct8 ko mice represents an important pathogenic mechanism leading to the high serum T3 levels.

  14. 15. Detail showing lower chord pinconnected to vertical member, showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Detail showing lower chord pin-connected to vertical member, showing floor beam riveted to extension of vertical member below pin-connection, and showing brackets supporting cantilevered sidewalk. View to southwest. - Selby Avenue Bridge, Spanning Short Line Railways track at Selby Avenue between Hamline & Snelling Avenues, Saint Paul, Ramsey County, MN

  15. Phase-OFDR for distributed disturbance measurement

    NASA Astrophysics Data System (ADS)

    Liehr, Sascha; Krebber, Katerina

    2016-05-01

    We introduce the optical frequency domain reflectometry (OFDR) technique based on intensity modulation frequency sweep measurement for distributed disturbance measurement in optical fibres. By evaluating interferometric Rayleigh scattering changes along the fibre, strain and temperature changes are detected with 100 n(epsilon) sensitivity and 10 mK resolution. The vibration frequencies for low frequencies and up to the kHz-range can be obtained from power change evaluation in the spatial domain. This novel OFDR approach is a low-cost alternative for distributed disturbance measurement up to distances of several kilometres.

  16. Human disturbances of waterfowl: An annotated bibliography

    USGS Publications Warehouse

    Dahlgren, R.B.; Korschgen, C.E.

    1992-01-01

    The expansion of outdoor recreation greatly increased the interaction between the public, waterfowl, and waterfowl habitat. The effects of these interactions on waterfowl habitats are visible and obvious, whereas the effects of interactions that disrupt the normal behavior of waterfowl are subtle and often overlooked, but perhaps no less harmful than destruction of habitat. Resource managers and administrators require information on the types, magnitude, and effect of disturbances from human contact with wildlife. This bibliography contains annotations for 211 articles with information about effects of human disturbances on waterfowl. Indexes are provided by subject or key words, geographic locations, species of waterfowl, and authors.

  17. From one to one million: How does community structure track disturbance across time and space?

    NASA Astrophysics Data System (ADS)

    Webb, A. E.

    2012-12-01

    ) result in more extensive faunal turnover, thereby reducing the utility of ordinations that require at least some faunal similarity. Rank-abundance curves can be applied even in intervals of complete taxonomic turnover; curve shape is quantified by kurtosis, a statistical measure of whether a distribution is more (>3) or less (<3) peaked than a Gaussian distribution (kurtosis = 3). Rank-abundance curve kurtosis values are always greater than 3 for disturbed communities (n=20), and pre-disturbance and recovered communities generally range from 0 to 4. The average kurtosis for a pre-disturbance or recovered community is unique for each type of community (taxonomically or environmentally defined), requiring the establishment of a baseline for rank-abundance curve analysis. In each dataset, both rank-abundance curves and ordinations show a similar pattern of change in community structure during a disturbance. The rate and pattern of recovery varies relative to the spatial and temporal extent of the disturbance. The results of this study reveal that community structure is a useful measure of the impact of a disturbance, both in terms of the severity of the disturbance and in measuring the subsequent recovery. The methods and results of this research are applicable to multiple fields, from conservation biology to ecosystem health to paleoceanography and paleobiology.

  18. 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.

  19. Anthropogenic disturbances are key to maintaining the biodiversity of grasslands.

    PubMed

    Yuan, Z Y; Jiao, F; Li, Y H; Kallenbach, Robert L

    2016-02-23

    Although anthropogenic disturbances are often perceived as detrimental to plant biodiversity, the relationship between biodiversity and disturbance remains unclear. Opinions diverge on how natural diversity is generated and maintained. We conducted a large-scale investigation of a temperate grassland system in Inner Mongolia and assessed the richness-disturbance relationship using grazing intensity, the primary anthropogenic disturbance in the region. Vascular plant-species richness peaked at an intermediate level of anthropogenic disturbance. Our results support the Intermediate Disturbance Hypothesis, which provides a valid and useful measure of biodiversity at a metacommunity scale, indicating that anthropogenic disturbances are necessary to conserve the biodiversity of grassland systems.

  20. Anthropogenic disturbances are key to maintaining the biodiversity of grasslands

    PubMed Central

    Yuan, Z. Y.; Jiao, F.; Li, Y. H.; Kallenbach, Robert L.

    2016-01-01

    Although anthropogenic disturbances are often perceived as detrimental to plant biodiversity, the relationship between biodiversity and disturbance remains unclear. Opinions diverge on how natural diversity is generated and maintained. We conducted a large-scale investigation of a temperate grassland system in Inner Mongolia and assessed the richness-disturbance relationship using grazing intensity, the primary anthropogenic disturbance in the region. Vascular plant-species richness peaked at an intermediate level of anthropogenic disturbance. Our results support the Intermediate Disturbance Hypothesis, which provides a valid and useful measure of biodiversity at a metacommunity scale, indicating that anthropogenic disturbances are necessary to conserve the biodiversity of grassland systems. PMID:26903041

  1. Anthropogenic disturbances are key to maintaining the biodiversity of grasslands

    NASA Astrophysics Data System (ADS)

    Yuan, Z. Y.; Jiao, F.; Li, Y. H.; Kallenbach, Robert L.

    2016-02-01

    Although anthropogenic disturbances are often perceived as detrimental to plant biodiversity, the relationship between biodiversity and disturbance remains unclear. Opinions diverge on how natural diversity is generated and maintained. We conducted a large-scale investigation of a temperate grassland system in Inner Mongolia and assessed the richness-disturbance relationship using grazing intensity, the primary anthropogenic disturbance in the region. Vascular plant-species richness peaked at an intermediate level of anthropogenic disturbance. Our results support the Intermediate Disturbance Hypothesis, which provides a valid and useful measure of biodiversity at a metacommunity scale, indicating that anthropogenic disturbances are necessary to conserve the biodiversity of grassland systems.

  2. Ionospheric disturbances and gravity waves

    NASA Technical Reports Server (NTRS)

    Eun, H.; Gross, S. H.

    1976-01-01

    The response of ionization to a gravity wave moving through the ionosphere is studied. Hydrodynamic equations are used, and local thermodynamic equilibrium is imposed for simplicity. The treatment involves a perturbation analysis, and the background medium is assumed to be time stationary, horizontally stratified, and known. It is shown that ionization may be locally resonant at each level for certain frequencies and directions, for which condition neutral and ionized particles are considered closely or critically coupled. The phase direction for this critical coupling is always downward in the absence of a magnetic field. A magnetic field results in two resonant directions for the same frequency, and these directions are mostly downward. Observed TID's associated with gravity waves may be indicative of such resonances. It is also noted that strong coupling may occur to neutral acoustic waves at high altitudes. Previous investigations restrict their use of momentum equations to the diffusion equation. The analysis also shows that such restrictions result in the neglect of terms arising from momentum transport due to any background ambipolar diffusion velocity and wave motion. These terms are mostly relevant at higher altitudes.

  3. Free-stream disturbances, continuous eigenfunctions, boundary-layer instability and transition

    NASA Technical Reports Server (NTRS)

    Salwen, H.

    1980-01-01

    A rational foundation is provided for the application of the linear stability theory of parallel shear flows to transition prediction. An explicit method is given for carrying out the necessary calculations. The expansions are shown to be complete. Sample calculations show that a typical boundary layer is very sensitive to vorticity disturbance 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 Tollmein-Schlichting waves are an extremely small fraction of the amplitude of the disturbance.

  4. Modeling and Simulation of Upset-Inducing Disturbances for Digital Systems in an Electromagnetic Reverberation Chamber

    NASA Technical Reports Server (NTRS)

    Torres-Pomales, Wilfredo

    2014-01-01

    This report describes a modeling and simulation approach for disturbance patterns representative of the environment experienced by a digital system in an electromagnetic reverberation chamber. The disturbance is modeled by a multi-variate statistical distribution based on empirical observations. Extended versions of the Rejection Samping and Inverse Transform Sampling techniques are developed to generate multi-variate random samples of the disturbance. The results show that Inverse Transform Sampling returns samples with higher fidelity relative to the empirical distribution. This work is part of an ongoing effort to develop a resilience assessment methodology for complex safety-critical distributed systems.

  5. The Feasibility of the Disturbance Accommodating Controller for Precision Antenna Pointing

    NASA Technical Reports Server (NTRS)

    Gresham, L. L.; Lansing, F. L.; Guiar, C. N.

    1988-01-01

    The objective of this study is to investigate the feasibility of a pointing (position loop) controller for the NASA-JPL Deep Space Network (DSN) antennas using the Disturbance Accommodating Control (DAC) theory. A model that includes state dependent disturbances was developed, and an example demonstrating the noise estimator is presented as an initial phase in the controller design. The goal is to improve pointing accuracy by the removal of the systematic errors caused by the antenna misalignment as well as sensor noise and random wind and thermal disturbances. Preliminary simulation results show that the DAC technique is successful in both cancelling the imposed errors and maintaining an optimal control policy.

  6. The linear stability of plane stagnation-point flow against general disturbances

    NASA Astrophysics Data System (ADS)

    Brattkus, K.; Davis, S. H.

    1991-02-01

    The linear-stability theory of plane stagnation-point flow against an infinite flat plate is re-examined. Disturbances are generalized from those of Goertler type to include other types of variations along the plate. It is shown that Hiemenz flow is linearly stable and that the Goertler-type modes are those that decay slowest. This work then rationalizes the use of such self-similar disturbances on Hiemenz flow and shows how questions of disturbance structure can be approached on other self-similar flows.

  7. The linear stability of plane stagnation-point flow against general disturbances

    NASA Technical Reports Server (NTRS)

    Brattkus, K.; Davis, S. H.

    1991-01-01

    The linear-stability theory of plane stagnation-point flow against an infinite flat plate is re-examined. Disturbances are generalized from those of Goertler type to include other types of variations along the plate. It is shown that Hiemenz flow is linearly stable and that the Goertler-type modes are those that decay slowest. This work then rationalizes the use of such self-similar disturbances on Hiemenz flow and shows how questions of disturbance structure can be approached on other self-similar flows.

  8. 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.

  9. A hybrid disturbance rejection control solution for variable valve timing system of gasoline engines.

    PubMed

    Xie, Hui; Song, Kang; He, Yu

    2014-07-01

    A novel solution for electro-hydraulic variable valve timing (VVT) system of gasoline engines is proposed, based on the concept of active disturbance rejection control (ADRC). Disturbances, such as oil pressure and engine speed variations, are all estimated and mitigated in real-time. A feed-forward controller was added to enhance the performance of the system based on a simple and static first principle model, forming a hybrid disturbance rejection control (HDRC) strategy. HDRC was validated by experimentation and compared with an existing manually tuned proportional-integral (PI) controller. The results show that HDRC provided a faster response and better tolerance of engine speed and oil pressure variations.

  10. Hyperphosphatemia, hypocalcemia and increased serum potassium concentration as distinctive features of early hypomagnesemia in magnesium-deprived mice.

    PubMed

    Ortega, Bernardo; MacWilliams, Jacob R; Dey, Jason M; Courtright, Valerie B

    2015-12-01

    Magnesium-deficient patients show dysfunctional calcium (Ca(2+)) metabolism due to defective parathyroid hormone (PTH) secretion. In mice and rats, long-term magnesium (Mg(2+)) deprivation causes hyperphosphaturia and increases fibroblast growth factor 23 (FGF23) secretion, despite normal serum phosphate (Pi) and Ca(2+). Electrolyte disturbances during early hypomagnesemia may explain the response of mice to long-term Mg(2+) deprivation, but our knowledge of electrolyte homeostasis during this stage is limited. This study compares the effect of both short- and long-term Mg(2+) restriction on the electrolyte balance in mice. Mice were fed control or Mg(2+)-deficient diets for one to three days, one week, or three weeks. Prior to killing the mice, urine was collected over 24 h using metabolic cages. Within 24 h of Mg(2+) deprivation, hypomagnesemia, hypocalcemia and hyperphosphatemia developed, and after three days of Mg(2+) deprivation, serum potassium (K(+)) was increased. These changes were accompanied by a reduction in urinary volume, hyperphosphaturia, hypocalciuria and decreased Mg(2+), sodium (Na(+)) and K(+) excretion. Surprisingly, after one week of Mg(2+) deprivation, serum K(+), Pi and Ca(2+) had normalized, showing that mineral homeostasis is most affected during early hypomagnesemia. Serum Pi and K(+) are known to stimulate secretion of FGF23 and aldosterone, which are usually elevated during Mg(2+) deficiency. Thus, the hyperphosphatemia and increased serum K(+) concentration observed during short-term Mg(2+) deprivation may help our understanding of adaptation to chronic Mg(2+) deficiency.

  11. Rates of disturbance vary by data resolution: implications for conservation schedules using the Alberta boreal forest as a case study.

    PubMed

    Komers, P E; Stanojevic, Z

    2013-09-01

    Investigations of biophysical changes on earth caused by anthropogenic disturbance provide governments with tools to generate sustainable development policy. Canada currently experiences one of the fastest rates of boreal forest disturbance in the world. Plans to conserve the 330 000 km(2) boreal forest in the province of Alberta exist but conservation targets and schedules must be aligned with rates of forest disturbance. We explore how disturbance rate, and the accuracy with which we detect it, may affect conservation success. We performed a change detection analysis from 1992 to 2008 using Landsat and SPOT satellite image data processing. Canada's recovery strategy for boreal caribou (Rangifer tarandus caribou) states that ≤35% of a caribou range can be either burned or within 500 m of a man-made feature for caribou to recover. Our analyses show that by 2008 78% of the boreal forest was disturbed and that, if the current rate continues, 100% would be disturbed by 2028. Alberta plans to set aside 22% for conservation in a region encompassing oil sands development to balance economic, environmental, and traditional indigenous land-use goals. Contrary to the federal caribou recovery strategy, provincial conservation plans do not consider wildfire a disturbance. Based on analyses used in the provincial plan, we apply a 250 m buffer around anthropogenic footprints. Landsat image analysis indicates that the yearly addition of disturbance is 714 km(2) (0.8%). The higher resolution SPOT images show fine-scale disturbance indicating that actual disturbance was 1.28 times greater than detected by Landsat. If the SPOT image based disturbance rates continue, the 22% threshold may be exceeded within the next decade, up to 20 years earlier than indicated by Landsat-based analysis. Our results show that policies for sustainable development will likely fail if governments do not develop time frames that are grounded by accurate calculations of disturbance rates.

  12. Slow recovery in desert perennial vegetation following prolonged human disturbance

    USGS Publications Warehouse

    Guo, Q.

    2004-01-01

    Questions: How long may it take for desert perennial vegetation to recover from prolonged human disturbance and how do different plant community variables (i.e. diversity, density and cover) change during the recovery process? Location: Sonoran Desert, Arizona, USA. Methods: Since protection from grazing from 1907 onwards, plant diversity, density and cover of perennial species were monitored intermittently on ten 10 m x 10 m permanent plots on Tumamoc Hill, Tucson, Arizona, USA. Results: The study shows an exceptionally slow recovery of perennial vegetation from prolonged heavy grazing and other human impacts. Since protection, overall species richness and habitat heterogeneity at the study site continued to increase until the 1960s when diversity, density and cover had been stabilized. During the same period, overall plant density and cover also increased. Species turnover increased gradually with time but no significant relation between any of the three community variables and precipitation or Palmer Drought Severity Index (PDSI) was detected. Conclusions: It took more than 50 yr for the perennial vegetation to recover from prolonged human disturbance. The increases in plant species richness, density, and cover of the perennial vegetation were mostly due to the increase of herbaceous species, especially palatable species. The lack of a clear relationship between environment (e.g. precipitation) and community variabl