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  1. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington's disease.

    Science.gov (United States)

    Zeng, Yixuan; Guo, Wenyuan; Xu, Guangqing; Wang, Qinmei; Feng, Luyang; Long, Simei; Liang, Fengyin; Huang, Yi; Lu, Xilin; Li, Shichang; Zhou, Jiebin; Burgunder, Jean-Marc; Pang, Jiyan; Pei, Zhong

    2016-01-01

    Huntington's disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt). Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington's disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson's and Alzheimer's diseases. To identify potential neuroprotective molecules for Huntington's disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington's disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a stable trimeric complex that can prevent the formation of mutant Htt aggregates. Taken together, we conclude that xyloketal derivatives could be novel drug candidates for treating Huntington's disease. Molecular target analysis is a good method to simulate the interaction between proteins and drug compounds. Further, protective candidate drugs could be designed in future using the guidance of molecular docking results.

  2. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Science.gov (United States)

    Zeng, Yixuan; Guo, Wenyuan; Xu, Guangqing; Wang, Qinmei; Feng, Luyang; Long, Simei; Liang, Fengyin; Huang, Yi; Lu, Xilin; Li, Shichang; Zhou, Jiebin; Burgunder, Jean-Marc; Pang, Jiyan; Pei, Zhong

    2016-01-01

    Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt). Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a stable trimeric complex that can prevent the formation of mutant Htt aggregates. Taken together, we conclude that xyloketal derivatives could be novel drug candidates for treating Huntington’s disease. Molecular target analysis is a good method to simulate the interaction between proteins and drug compounds. Further, protective candidate drugs could be designed in future using the guidance of molecular docking results. PMID:27110099

  3. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Zeng YX

    2016-04-01

    Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

  4. NASA Images Show Decreased Clarity in Lake Tahoe's Water

    Science.gov (United States)

    2002-01-01

    Images from the Advanced Spaceborne Thermal Emission and Reflection Radiometer aboard NASA's Terra satellite, launched in 1999, illustrate the state of gradually decreasing water clarity at Lake Tahoe, one of the clearest lakes in the world. The images are available at: http://asterweb.jpl.nasa.gov/default.htm.In the image on the left, acquired in November 2000, vegetation can be seen in red. The image on the right, acquired at the same time by a different spectral band of the instrument, is color-coded to show the bottom of the lake around the shoreline. Where the data are black, the bottom cannot be seen.Scientists monitoring the lake's water clarity from boat measurements obtained since 1965 have discovered that the lake along the California-Nevada border has lost more than one foot of visibility each year, according to the Lake Tahoe Watershed Assessment, a review of scientific information about the lake undertaken at the request of President Clinton and published in February 2000. The most likely causes are increases in algal growth, sediment washed in from surrounding areas and urban growth and development.By combining historical and current ground-based measurements with space measurements from new instruments like the Advanced Spaceborne Thermal Emission and Reflection Radiometer, scientists are now continuously monitoring and better understanding the circulation and changes in Lake Tahoe's water clarity. Images like these from satellites, which are able to capture entire views of the lake and its 63 contributing streams, can be used to determine and monitor spatial variations in the lake's clarity over time. These images complement 'point' measurements, made by boats from one spot in the lake. Rafts and buoys verify the satellite images, and help scientists develop and test circulation models.The Advanced Spaceborne Thermal Emission and Reflection Radiometer is one of five Earth-observing instruments on Terra, launched in 1999, and is its only high

  5. Functional diversity and community assembly of river invertebrates show globally consistent responses to decreasing glacier cover.

    Science.gov (United States)

    Brown, Lee E; Khamis, Kieran; Wilkes, Martin; Blaen, Phillip; Brittain, John E; Carrivick, Jonathan L; Fell, Sarah; Friberg, Nikolai; Füreder, Leopold; Gislason, Gisli M; Hainie, Sarah; Hannah, David M; James, William H M; Lencioni, Valeria; Olafsson, Jon S; Robinson, Christopher T; Saltveit, Svein J; Thompson, Craig; Milner, Alexander M

    2018-02-01

    Global change threatens invertebrate biodiversity and its central role in numerous ecosystem functions and services. Functional trait analyses have been advocated to uncover global mechanisms behind biodiversity responses to environmental change, but the application of this approach for invertebrates is underdeveloped relative to other organism groups. From an evaluation of 363 records comprising >1.23 million invertebrates collected from rivers across nine biogeographic regions on three continents, consistent responses of community trait composition and diversity to replicated gradients of reduced glacier cover are demonstrated. After accounting for a systematic regional effect of latitude, the processes shaping river invertebrate functional diversity are globally consistent. Analyses nested within individual regions identified an increase in functional diversity as glacier cover decreases. Community assembly models demonstrated that dispersal limitation was the dominant process underlying these patterns, although environmental filtering was also evident in highly glacierized basins. These findings indicate that predictable mechanisms govern river invertebrate community responses to decreasing glacier cover globally.

  6. X-ray sensitive strains of CHO cells show decreased frequency of stable transfection

    International Nuclear Information System (INIS)

    Jeggo, P.; Smith, J.

    1987-01-01

    Six X-ray sensitive (xrs) strains of the Chinese hamster ovary cell line have previously been isolated and shown to have a defect in double strand break rejoining. In this study, these strains have been investigated for their ability to take up and integrate foreign DNA. All the xrs strains investigated so far have shown a decreased frequency of stable transfectants compared to their parent line, in experiments using the plasmid pSV2gpt, which contains the selectable bacterial gene, guanine phosphoribosyl transferase. This decreased frequency is observed over a wide range of DNA concentrations (0.1 to 20 μg DNA) but is more pronounced at higher DNA concentrations. In contrast, these xrs strains show the same level of transfection proficiency as the wild type parent using a transient transfection system with a plasmid containing the bacterial CAT (chloramphenicol acetyl transferase) gene. Since the level of CAT activity does not depend on integration of foreign DNA, this suggests that the xrs strains are able to take up the same amount of DNA as the parent strains, but have a defect in the integration of foreign DNA. Since this integration of foreign DNA probably occurs by non-homologous recombination, this may indicate a role of the xrs gene product in this process

  7. Interleukin-1 receptor null mutant mice show decreased anxiety-like behavior and enhanced fear memory

    Science.gov (United States)

    Koo, Ja Wook; Duman, Ronald S.

    2013-01-01

    IL-1β is a proinflammatory cytokine that contributes to psychological stress responses and has been implicated in various psychiatric disorders most notably depression. Preclinical studies also demonstrate that IL-1β modulates anxiety- and fear-related behaviors, although these findings are difficult to assess because IL-1β infusions influence locomotor activity and nociception. Here we demonstrate that IL-1RI null mice exhibit a behavioral phenotype consistent with a decrease in anxiety-related behaviors. This includes significant effects in the elevated plus maze, light–dark, and novelty-induced hypophagia tests compared to wild-type mice, with no differences in locomotor activity. With regard to fear conditioning, IL-1RI null mice showed more freezing in auditory and contextual fear conditioning tests, and there was no effect on pain sensitivity. Taken together, the results indicate that the IL-1β/IL-1RI signaling pathway induces anxiety-related behaviors and impairs fear memory. PMID:19429130

  8. Pregnant rats show enhanced spatial memory, decreased anxiety, and altered levels of monoaminergic neurotransmitters

    Science.gov (United States)

    Macbeth, A.H.; Gautreaux, C.; Luine, V.N.

    2008-01-01

    Spatial memory, anxiety and central monoaminergic activities were measured in non-pregnant (NP) and pregnant females during two time periods of pregnancy: gestational day 7–9 (GD7, GD9) & gestation day 16–18 (GD16, GD18). Pregnant females discriminated between object locations on both test days on an object placement task, whereas NP females were unable to discriminate between locations. Pregnant females displayed decreased anxiety on the elevated plus maze on GD9 compared to NP females, followed by increased anxiety-like behavior on the elevated plus maze on GD18. Monoamine levels and activity (as indexed by turnover ratio) were measured in prefrontal cortex (PFC), CA1 and CA3 regions of the hippocampus (areas important for memory), and medial preoptic area (mPOA, an area important in display of maternal behaviors). In the PFC, NP females generally had higher monoamine levels and turnover ratios; however, norepinephrine (NE) turnover was higher in pregnant females at GD18. In the CA1 and CA3 regions of the hippocampus, monoamine levels and turnover ratios were generally higher during pregnancy, particularly on GD9. In the mPOA, pregnancy was associated with increases in NE activity, a previously unreported finding. The present study expands upon existing research indicating that pregnancy is beneficial to spatial memory and may decrease anxiety. Changes in monoamine levels and activity in specific brain regions indicate that the dopamine, norepinephrine and serotonin systems may contribute to the observed behavioral differences. PMID:18823955

  9. Failure to show decrease in small pulmonary blood vessels in rats with experimental pulmonary hypertension.

    OpenAIRE

    Kay, J M; Suyama, K L; Keane, P M

    1982-01-01

    We induced chronic pulmonary hypertension in one group of rats by exposing them to chronic hypobaric hypoxia (380 mm Hg for three weeks) and in another group by administering a single subcutaneous dose of monocrotaline (60 mg/kg body weight). Both groups of rats showed increase of the right ventricular mean systolic blood pressure and right ventricular hypertrophy. We measured the surface area of histological sections of the left or right lungs and counted all small blood vessels with an exte...

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

    Science.gov (United States)

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

    2013-05-01

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

  11. Simulations show decreasing carbon stocks and potential for carbon emissions in Rocky Mountain forests over the next century.

    Science.gov (United States)

    Boisvenue, Céline; Running, Steven W

    2010-07-01

    Climate change has altered the environment in which forests grow, and climate change models predict more severe alterations to come. Forests have already responded to these changes, and the future temperature and precipitation scenarios are of foremost concern, especially in the mountainous western United States, where forests occur in the dry environments that interface with grasslands. The objective of this study was to understand the trade-offs between temperature and water controls on these forested sites in the context of available climate projections. Three temperature and precipitation scenarios from IPCC AR4 AOGCMs ranging in precipitation levels were input to the process model Biome-BGC for key forested sites in the northern U.S. Rocky Mountains. Despite the omission of natural and human-caused disturbances in our simulations, our results show consequential effects from these conservative future temperature and precipitation scenarios. According to these projections, if future precipitation and temperatures are similar to or drier than the dry scenario depicted here, high-elevation forests on both the drier and wetter sites, which have in the absence of disturbance accumulated carbon, will reduce their carbon accumulation. Under the marginally drier climate projections, most forests became carbon sources by the end of the simulation horizon (2089). Under all three scenarios, growing season lengthened, the number of days with snow on the ground decreased, peak snow occurred earlier, and water stress increased through the projection horizon (1950-2089) for all sites, which represent the temperature and precipitation spectrum of forests in this region. The quantity, form, and timing of precipitation ultimately drive the carbon accumulation trajectory of forests in this region.

  12. Dryland biological soil crust cyanobacteria show unexpected decreases in abundance under long-term elevated CO2

    Science.gov (United States)

    Steven, Blaire; Gallegos-Graves, La Verne; Yeager, Chris M.; Belnap, Jayne; Evans, R. David; Kuske, Cheryl R.

    2012-01-01

    Biological soil crusts (biocrusts) cover soil surfaces in many drylands globally. The impacts of 10 years of elevated atmospheric CO2 on the cyanobacteria in biocrusts of an arid shrubland were examined at a large manipulated experiment in Nevada, USA. Cyanobacteria-specific quantitative PCR surveys of cyanobacteria small-subunit (SSU) rRNA genes suggested a reduction in biocrust cyanobacterial biomass in the elevated CO2 treatment relative to the ambient controls. Additionally, SSU rRNA gene libraries and shotgun metagenomes showed reduced representation of cyanobacteria in the total microbial community. Taxonomic composition of the cyanobacteria was similar under ambient and elevated CO2 conditions, indicating the decline was manifest across multiple cyanobacterial lineages. Recruitment of cyanobacteria sequences from replicate shotgun metagenomes to cyanobacterial genomes representing major biocrust orders also suggested decreased abundance of cyanobacteria sequences across the majority of genomes tested. Functional assignment of cyanobacteria-related shotgun metagenome sequences indicated that four subsystem categories, three related to oxidative stress, were differentially abundant in relation to the elevated CO2 treatment. Taken together, these results suggest that elevated CO2 affected a generalized decrease in cyanobacteria in the biocrusts and may have favoured cyanobacteria with altered gene inventories for coping with oxidative stress.

  13. Model sensitivity studies of the decrease in atmospheric carbon tetrachloride

    Directory of Open Access Journals (Sweden)

    M. P. Chipperfield

    2016-12-01

    Full Text Available Carbon tetrachloride (CCl4 is an ozone-depleting substance, which is controlled by the Montreal Protocol and for which the atmospheric abundance is decreasing. However, the current observed rate of this decrease is known to be slower than expected based on reported CCl4 emissions and its estimated overall atmospheric lifetime. Here we use a three-dimensional (3-D chemical transport model to investigate the impact on its predicted decay of uncertainties in the rates at which CCl4 is removed from the atmosphere by photolysis, by ocean uptake and by degradation in soils. The largest sink is atmospheric photolysis (74 % of total, but a reported 10 % uncertainty in its combined photolysis cross section and quantum yield has only a modest impact on the modelled rate of CCl4 decay. This is partly due to the limiting effect of the rate of transport of CCl4 from the main tropospheric reservoir to the stratosphere, where photolytic loss occurs. The model suggests large interannual variability in the magnitude of this stratospheric photolysis sink caused by variations in transport. The impact of uncertainty in the minor soil sink (9 % of total is also relatively small. In contrast, the model shows that uncertainty in ocean loss (17 % of total has the largest impact on modelled CCl4 decay due to its sizeable contribution to CCl4 loss and large lifetime uncertainty range (147 to 241 years. With an assumed CCl4 emission rate of 39 Gg year−1, the reference simulation with the best estimate of loss processes still underestimates the observed CCl4 (overestimates the decay over the past 2 decades but to a smaller extent than previous studies. Changes to the rate of CCl4 loss processes, in line with known uncertainties, could bring the model into agreement with in situ surface and remote-sensing measurements, as could an increase in emissions to around 47 Gg year−1. Further progress in constraining the CCl4 budget is partly limited by

  14. Brief Report: Application of Proposed Model of Decreasing Reinforcement Intensity

    Science.gov (United States)

    Cautilli, Joseph

    2005-01-01

    LaBlanc, Hagopian, Malieri, and Poling (2002) proposed a model for decreasing reinforcement intensity in clinical practice. This paper applies that model to the fading of a point system for a nine-year-old boy who displayed escape behavior around nightly homework assignments. Using a hanging criterion design, the author was able to track the…

  15. Nogo-A-deficient transgenic rats show deficits in higher cognitive functions, decreased anxiety and altered circadian activity patterns

    Directory of Open Access Journals (Sweden)

    Tomas ePetrasek

    2014-03-01

    Full Text Available Decreased levels of Nogo-A dependent signaling have been shown to affect behavior and cognitive functions. In Nogo-A knockout and knock-down laboratory rodents, behavioral alterations were observed, possibly corresponding with human neuropsychiatric diseases of neurodevelopmental origin, particularly schizophrenia. This study offers further insight into behavioral manifestations of Nogo-A knockdown in laboratory rats, focusing on spatial and non-spatial cognition, anxiety levels, circadian rhythmicity and activity patterns. Demonstrated is an impairment of cognitive functions and behavioral flexibility in a spatial active avoidance task, while non-spatial memory in a step-through avoidance task was spared. No signs of anhedonia, typical for schizophrenic patients, were observed in the animals. Some measures indicated lower anxiety levels in the Nogo-A deficient group. Circadian rhythmicity in locomotor activity was preserved in the Nogo-A-knockout rats and their circadian period (tau did not differ from controls. However, daily activity patterns were slightly altered in the knockdown animals. We conclude that a reduction of Nogo-A levels induces changes in CNS development, manifested as subtle alterations in cognitive functions, emotionality and activity patterns.

  16. Dynamics of myelin content decrease in the rat stroke model

    Science.gov (United States)

    Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

    2017-08-01

    The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

  17. Idosos hipertensos apresentam menor desempenho cognitivo do que idosos normotensos Elderly hypertensives show decreased cognitive performance compared with elderly normotensives

    Directory of Open Access Journals (Sweden)

    Juliana Magalhães Duarte Matoso

    2013-05-01

    Full Text Available FUNDAMENTO: A hipertensão arterial tem sido associada à redução do desempenho cognitivo, contudo a literatura é conflitante. OBJETIVO: Comparar o desempenho cognitivo entre idosos normotensos ("N"; n = 17; idade 68 ± 1; pressão arterial = 133 ± 3/74 ± 2 mmHg e hipertensos ("H"; n = 28; idade 69 ± 1, pressão arterial = 148 ± 4/80 ± 1 mmHg com pelo menos cinco anos de escolaridade. MÉTODOS: A avaliação neuropsicológica ampla constou do "Cambridge Cognition-Revised" (CAMCOG-R, dos "Trail Making Test A and B" (TMT A e B e do "Rey Auditory Verbal Learning Test" (RAVLT. RESULTADOS: Os idosos hipertensos apresentaram menor escore do CAMCOG-R (N = 87,6 ± 1,8; H = 78,6 ± 1,4; p = 0,002. Os idosos hipertensos necessitaram de maior tempo para realizar o TMT A e B (TMT A: N = 39 ± 3s; H = 57 ± 3,4s; p = 0,001; TMT B: N = 93 ± 7s; H = 124 ± 7s; p = 0,006, o que também é demonstrado pelos percentis significativamente menores obtidos nestes testes. O somatório do RAVLT foi significativamente menor nos idosos hipertensos (N = 51,8 ± 1,7; H = 40,7 ± 1,5; p BACKGROUND: Essential hypertension has been associated with decreased cognitive performance; however, the literature is conflicting. OBJECTIVE: This study aims at comparing cognitive performance between elderly normotensives ("N"; n = 17; age 68 ± 1; blood pressure = 133 ± 3/74 ±2 mmHg and hypertensives ("H"; n = 28; age 69 ± 1, blood pressure = 148 ± 4/80 ± 1mmHg with at least 5 years of education. METHODS: The comprehensive neuropsychological assessment was comprised of the Cambridge Cognition-Revised (CAMCOG-R, the Trail Making Test A and B (TMT A and B and the Rey Auditory Verbal Learning Test (RAVLT. RESULTS: Elderly hypertensives presented lower CAMCOG-R global scores (N = 87.6 ± 1.8; H = 78.6 ± 1.4; p = 0.002. The hypertensive's performance was slower in the TMT A and B (TMT A: N = 39 ± 3s; H = 57 ± 3s; p = 0.001; TMT B: N = 93 ± 7s; H = 124 ± 7s; p = 0.006, which

  18. Non-expert listeners show decreased heart rate and increased blood pressure (fear bradycardia in response to atonal music

    Directory of Open Access Journals (Sweden)

    Alice Mado eProverbio

    2015-10-01

    Full Text Available Previous studies suggested that listening to different types of music may modulate differently psychological mood and physiological responses associated with the induced emotions. In this study the effect of listening to instrumental classical vs. atonal contemporary music was examined in a group of 50 non-expert listeners. The subjects’ heart rate and diastolic and systolic blood pressure values were measured while they listened to music of different style and emotional typologies. Pieces were selected by asking a group of composers and conservatory professors to suggest a list of the most emotional music pieces (from Renaissance to present time. A total of 214 suggestions from 20 respondents was received. Then it was asked them to identify which pieces best induced in the listener feelings of agitation, joy or pathos and the number of suggested pieces per style was computed. Atonal pieces were more frequently indicated as agitating, and tonal pieces as joyful. The presence/absence of tonality in a musical piece did not affect the affective dimension of pathos (being touching. Among the most frequently cited six pieces were selected that were comparable for structure and style, to represent each emotion and style. They were equally evaluated as unfamiliar by an independent group of 10 students of the same cohort and were then used as stimuli for the experimental session in which autonomic parameters were recorded. Overall, listening to atonal music (independent of the pieces’ emotional characteristics was associated with a reduced heart rate (fear bradycardia and increased blood pressure (both diastolic and systolic, possibly reflecting an increase in alertness and attention, psychological tension, and anxiety. This evidence fits with the results of the aesthetical assessment showing how, overall, atonal music is perceived as more agitating and less joyful than tonal one.

  19. Non-expert listeners show decreased heart rate and increased blood pressure (fear bradycardia) in response to atonal music

    Science.gov (United States)

    Proverbio, Alice M.; Manfrin, Luigi; Arcari, Laura A.; De Benedetto, Francesco; Gazzola, Martina; Guardamagna, Matteo; Lozano Nasi, Valentina; Zani, Alberto

    2015-01-01

    Previous studies suggested that listening to different types of music may modulate differently psychological mood and physiological responses associated with the induced emotions. In this study the effect of listening to instrumental classical vs. atonal contemporary music was examined in a group of 50 non-expert listeners. The subjects’ heart rate and diastolic and systolic blood pressure values were measured while they listened to music of different style and emotional typologies. Pieces were selected by asking a group of composers and conservatory professors to suggest a list of the most emotional music pieces (from Renaissance to present time). A total of 214 suggestions from 20 respondents were received. Then it was asked them to identify which pieces best induced in the listener feelings of agitation, joy or pathos and the number of suggested pieces per style was computed. Atonal pieces were more frequently indicated as agitating, and tonal pieces as joyful. The presence/absence of tonality in a musical piece did not affect the affective dimension of pathos (being touching). Among the most frequently cited six pieces were selected that were comparable for structure and style, to represent each emotion and style. They were equally evaluated as unfamiliar by an independent group of 10 students of the same cohort) and were then used as stimuli for the experimental session in which autonomic parameters were recorded. Overall, listening to atonal music (independent of the pieces’ emotional characteristics) was associated with a reduced heart rate (fear bradycardia) and increased blood pressure (both diastolic and systolic), possibly reflecting an increase in alertness and attention, psychological tension, and anxiety. This evidence fits with the results of the esthetical assessment showing how, overall, atonal music is perceived as more agitating and less joyful than tonal one. PMID:26579029

  20. Non-expert listeners show decreased heart rate and increased blood pressure (fear bradycardia) in response to atonal music.

    Science.gov (United States)

    Proverbio, Alice M; Manfrin, Luigi; Arcari, Laura A; De Benedetto, Francesco; Gazzola, Martina; Guardamagna, Matteo; Lozano Nasi, Valentina; Zani, Alberto

    2015-01-01

    Previous studies suggested that listening to different types of music may modulate differently psychological mood and physiological responses associated with the induced emotions. In this study the effect of listening to instrumental classical vs. atonal contemporary music was examined in a group of 50 non-expert listeners. The subjects' heart rate and diastolic and systolic blood pressure values were measured while they listened to music of different style and emotional typologies. Pieces were selected by asking a group of composers and conservatory professors to suggest a list of the most emotional music pieces (from Renaissance to present time). A total of 214 suggestions from 20 respondents were received. Then it was asked them to identify which pieces best induced in the listener feelings of agitation, joy or pathos and the number of suggested pieces per style was computed. Atonal pieces were more frequently indicated as agitating, and tonal pieces as joyful. The presence/absence of tonality in a musical piece did not affect the affective dimension of pathos (being touching). Among the most frequently cited six pieces were selected that were comparable for structure and style, to represent each emotion and style. They were equally evaluated as unfamiliar by an independent group of 10 students of the same cohort) and were then used as stimuli for the experimental session in which autonomic parameters were recorded. Overall, listening to atonal music (independent of the pieces' emotional characteristics) was associated with a reduced heart rate (fear bradycardia) and increased blood pressure (both diastolic and systolic), possibly reflecting an increase in alertness and attention, psychological tension, and anxiety. This evidence fits with the results of the esthetical assessment showing how, overall, atonal music is perceived as more agitating and less joyful than tonal one.

  1. Showing that the race model inequality is not violated

    DEFF Research Database (Denmark)

    Gondan, Matthias; Riehl, Verena; Blurton, Steven Paul

    2012-01-01

    When participants are asked to respond in the same way to stimuli from different sources (e. g., auditory and visual), responses are often observed to be substantially faster when both stimuli are presented simultaneously (redundancy gain). Different models account for this effect, the two most...

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

    Science.gov (United States)

    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. Copyright © 2012 Wiley Periodicals, Inc.

  3. Decreases in 15-lipoxygenase metabolites in Olmsted syndrome model rats.

    Science.gov (United States)

    Wakabayashi, Masato; Yoshioka, Takeshi; Higashino, Kenichi; Numata, Yoshito; Igarashi, Yasuyuki; Kihara, Akio

    2017-03-01

    Olmsted syndrome (OS) is a congenital dermatosis characterized by palmoplantar keratoderma and periorificial keratotic plaque. TRPV3 (transient receptor potential vanilloid subtype 3) encodes a thermosensitive Ca 2+ channel and is the causative gene of OS. However, the molecular mechanism that causes the pathological development of OS is unclear. We aimed to investigate the molecular mechanisms underlying OS pathology from the perspective of lipid metabolism. Comprehensive lipidomics and microarray analyses were conducted on tissue samples from a non-lesional skin area of OS model rats (Ht rats) and from wild type (WT) rats as the control. Infiltration of leukocytes such as eosinophils and neutrophils and an increase in the fibrotic region were detected in the unaffected skin area of Ht rats compared with the WT rats. Among about 600 lipid species examined, the levels of 15-lipoxygenase (LOX) metabolites, the precursors of anti-inflammatory and pro-resolving lipid mediators, and dihydroceramides decreased by ≥16-fold in Ht rats compared with WT rats. Consistent with the decreases in the 15-LOX metabolites, expression levels of the genes that encode the 15-LOXs, Alox15 and Alox15b, were largely reduced. Conversely, increased expression levels were detected of Il36b, Ccl20, Cxcl1, and Cxcl2, which encode cytokines/chemokines, and S100a8 and S100a9, which encode the Ca 2+ binding proteins that are implicated in epidermal proliferation. The pro-inflammatory state in the unaffected skin of Ht rats caused by decreases in 15-LOX metabolites and increases in cytokines/chemokines may contribute to the pathogenesis of OS. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  4. High resolution modelling of the decreasing Arctic sea ice

    DEFF Research Database (Denmark)

    Madsen, K. S.; Rasmussen, T. A. S.; Blüthgen, Jonas

    2012-01-01

    The Arctic sea ice cover has been rapidly decreasing and thinning over the last decade, with minimum ice extent in 2007 and almost as low extent in 2011. This study investigates two aspects of the decreasing ice cover; first the large scale thinning and changing dynamics of the polar sea ice, and...

  5. Theoretical model of CR Forbush-decrease and precursors effects

    Science.gov (United States)

    Lev, Dorman

    The understanding of the mechanism of CR Forbush decrease and precursor effects is important for forecasting of the great magnetic storms by using on-line one hour CR observation data. We consider in details the situation with CR distribution inside CME and how it changed with time. We suppose that shock wave before CME is semi-transpired and the coefficient of transparence depends from the CR particles rigidity. One differential equation determined the change of CR intensity inside CME by the particle energy decrease in the expanding volume and by exchange with CR particles outside the CME. The other differential equation determined the outside CR particles drift acceleration by interaction with the shock wave before CME (this effect gives increase of CR intensity before magnetic storm sudden commencement) as well as exchange with CR particles inside the CME along the IMF lines (what gives the decrease of CR intensity before the start of magnetic storm on the Earth). We calculate also the expected CR anisotropy. Obtained results we compare with observation data. It is obvious now that according to data from the past on big variations of planetary surface temperature on scales of many millions and thousands of years, the Earth’s global climate change is determined mostly by space factors, including: the moving of the Solar system around the center of our galaxy, the crossing of galactic arms and molecular dust clouds, nearby supernova and supernova remnants. Another important space factor is the cyclic variations of solar activity and the solar wind (mostly on the scale of hundreds of years and decades). The effects of space factors on the Earth’s climate are realized mostly through cosmic rays (CR) and space dust influencing the formation of clouds, thereby controlling the total energy input from the Sun into the Earth’s atmosphere. The propagation and modulation of galactic CR (generated mostly during supernova explosions and in supernova remnants in our

  6. The Solow model in discrete time and decreasing population growth rate

    OpenAIRE

    Juan Sebastián Pereyra; Juan Gabriel Brida

    2008-01-01

    This paper reformulates the neoclassical Solow-Swan model of economic growth in discrete time by introducing a generic population growth law that verifies the following properties: 1) population is strictly increasing and bounded 2) the rate of growth of population is decreasing to zero as time tends to infinity. We show that in the long run the capital per worker of the model converges to the non-trivial steady state of the Solow Swan model with zero labor growth rate. In addition we prove t...

  7. Non-demented Parkinson's disease patients with apathy show decreased grey matter volume in key executive and reward-related nodes.

    Science.gov (United States)

    Martinez-Horta, Saul; Sampedro, Frederic; Pagonabarraga, Javier; Fernandez-Bobadilla, Ramón; Marin-Lahoz, Juan; Riba, Jordi; Kulisevsky, Jaime

    2017-10-01

    Apathy is a common but poorly understood neuropsychiatric disturbance in Parkinson's disease (PD). In a recent study using event-related brain potentials we demonstrated impaired reward processing and compromised mesocortico-limbic pathways in PD patients with clinical symptoms of apathy. Here we aimed to further investigate the involvement of reward circuits in apathetic PD patients by assessing potential differences in brain structure. Using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) we quantified grey matter volume (GMV) in a sample of 18 non-demented and non-depressed PD patients with apathy, and 18 matched non-apathetic patients. Both groups were equivalent in terms of sociodemographic characteristics, disease stage, cognitive performance and L-Dopa equivalent daily dose. Apathetic patients showed significant GMV loss in cortical and subcortical brain structures. Various clusters of cortical GMV decrease were found in the parietal, lateral prefrontal cortex, and orbitofrontal cortex (OFC). The second largest cluster of GMV loss was located in the left nucleus accumbens (NAcc), a subcortical structure that is a key node of the human reward circuit. Isolated apathy in our sample is explained by the combined GMV loss in regions involved in executive functions, and cortical and subcortical structures of the mesolimbic reward pathway. The correlations observed between apathy and cognition suggests apathy as a marker of more widespread brain degeneration even in a sample of non-demented PD patients.

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

    Directory of Open Access Journals (Sweden)

    S.J. Guo

    2013-05-01

    Full Text Available We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8 mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m to age-matched SAM-resistant 1 (SAMR1 mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413, chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2_A, alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.

  9. Modeling Nitrogen Decrease in Water Lettuce Ponds from Waste Stabilization Ponds

    Science.gov (United States)

    Putri, Gitta Agnes; Sunarsih

    2018-02-01

    This paper presents about the dynamic modeling of the Water Lettuce ponds as a form of improvement from the Water Hyacinth ponds. The purpose of this paper is to predict nitrogen decrease and nitrogen transformation in Water Lettuce ponds integrated with Waste Stabilization Ponds. The model consists of 4 mass balances, namely Dissolved Organic Nitrogen (DON), Particulate Organic Nitrogen (PON), ammonium (NH4+), Nitrate and Nitrite (NOx). The process of nitrogen transformation which considered in a Water Lettuce ponds, namely hydrolysis, mineralization, nitrification, denitrification, plant and bacterial uptake processes. Numerical simulations are performed by giving the values of parameters and the initial values of nitrogen compounds based on a review of previous studies. Numerical results show that the rate of change in the concentration of nitrogen compounds in the integration ponds of waste stabilization and water lettuce decreases and reaches stable at different times.

  10. Acute myocardial infarction: serial cardiac MR imaging shows a decrease in delayed enhancement of the myocardium during the 1st week after reperfusion.

    Science.gov (United States)

    Ibrahim, Tareq; Hackl, Thomas; Nekolla, Stephan G; Breuer, Martin; Feldmair, Michael; Schömig, Albert; Schwaiger, Markus

    2010-01-01

    To evaluate the time course of delayed gadolinium enhancement of infarcted myocardium by using serial contrast agent-enhanced (CE) cardiac magnetic resonance (MR) images obtained during the acute, subacute, and chronic stages of infarction. The study protocol was reviewed and approved by the local ethics committee, and written informed consent was obtained. Seventeen patients with reperfused acute myocardial infarction (AMI) underwent cine and CE cardiac MR a median of 1, 7, 35, and 180 days after reperfusion. Infarct size determined on the basis of delayed enhancement MR imaging at different times was compared by using nonparametric tests and Bland-Altman analysis. Extent of myocardial enhancement was compared with single photon emission computed tomographic (SPECT) measures of infarct size with Spearman correlation. Regional myocardial enhancement extent and contractility were analyzed with nonparametric tests. Infarct size was 18.3% of total myocardial LV volume on day 1 after AMI and decreased to 12.9% on day 7, 11.3% on day 35, and 11.6% on day 180 (all P infarct size on day 7, as compared with day 1 enhancement size, declined by 57.1% within the epicardium and by 6.3% within the endocardium (both P Infarct size on day 7 showed only minor changes at subsequent imaging and yielded a high correlation with SPECT measurements of infarct size (r = 0.84). Infarct size on day 7 inversely correlated with long-term wall thickening (P infarction. Thus, timing of CE cardiac MR imaging is crucial for accurate measurement of myocardial infarct size early after AMI.

  11. Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6.

    Directory of Open Access Journals (Sweden)

    Chaman Saini

    2016-04-01

    Full Text Available 50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR and Type 2/ Erythema Nodosum Leprosum (ENL reactions which lead to morbidity and nerve damage. CD4+ subsets of Th17 cells and CD25+FOXP3+ regulatory T cells (Tregs have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions.Quantitative reverse transcribed PCR (qPCR, flowcytometry and ELISA were used to respectively investigate gene expression, cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC cultures in patients with stable disease and those undergoing leprosy reactions. Both types of reactions are associated with significant increase of Th17 cells and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22 as compared to matching stable forms of leprosy. Concurrently patients in reactions show reduction in FOXP3+ Treg cells as well as reduction in TGF-β and increase in IL-6. Moreover, expression of many T cell markers, cytokines, chemokines and signaling factors were observed to be increased in RR as compared to ENL reaction patients.Patients with leprosy reactions show an imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity is associated withhigherTh17cell activity. The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases. The increase in Th17 cell associated cytokines may contribute to lesional inflammation.

  12. Ebola Virus Makona Shows Reduced Lethality in an Immune-deficient Mouse Model.

    Science.gov (United States)

    Smither, Sophie J; Eastaugh, Lin; Ngugi, Sarah; O'Brien, Lyn; Phelps, Amanda; Steward, Jackie; Lever, Mark Stephen

    2016-10-15

    Ebola virus Makona (EBOV-Makona; from the 2013-2016 West Africa outbreak) shows decreased virulence in an immune-deficient mouse model, compared with a strain from 1976. Unlike other filoviruses tested, EBOV-Makona may be slightly more virulent by the aerosol route than by the injected route, as 2 mice died following aerosol exposure, compared with no mortality among mice that received intraperitoneal injection of equivalent or higher doses. Although most mice did not succumb to infection, the detection of an immunoglobulin G antibody response along with observed clinical signs suggest that the mice were infected but able to clear the infection and recover. We hypothesize that this may be due to the growth rates and kinetics of the virus, which appear slower than that for other filoviruses and consequently give more time for an immune response that results in clearance of the virus. In this instance, the immune-deficient mouse model is unlikely to be appropriate for testing medical countermeasures against this EBOV-Makona stock but may provide insight into pathogenesis and the immune response to virus. © Crown copyright 2016.

  13. The galactose-induced decrease in phosphate levels leads to toxicity in yeast models of galactosemia.

    Science.gov (United States)

    Machado, Caio M; De-Souza, Evandro A; De-Queiroz, Ana Luiza F V; Pimentel, Felipe S A; Silva, Guilherme F S; Gomes, Fabio M; Montero-Lomelí, Mónica; Masuda, Claudio A

    2017-06-01

    Classic galactosemia is an inborn error of metabolism caused by deleterious mutations in the GALT gene. A number of evidences indicate that the galactose-1-phosphate accumulation observed in patient cells is a cause of toxicity in this disease. Nevertheless, the consequent molecular events caused by the galactose-1-phosphate accumulation remain elusive. Here we show that intracellular inorganic phosphate levels decreased when yeast models of classic galactosemia were exposed to galactose. The decrease in phosphate levels is probably due to the trapping of phosphate in the accumulated galactose-1-phosphate since the deletion of the galactokinase encoding gene GAL1 suppressed this phenotype. Galactose-induced phosphate depletion caused an increase in glycogen content, an expected result since glycogen breakdown by the enzyme glycogen phosphorylase is dependent on inorganic phosphate. Accordingly, an increase in intracellular phosphate levels suppressed the galactose effect on glycogen content and conferred galactose tolerance to yeast models of galactosemia. These results support the hypothesis that the galactose-induced decrease in phosphate levels leads to toxicity in galactosemia and opens new possibilities for the development of better treatments for this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. An asthma patient with steroid-resistant decrease in peak expiratory flow after the Great East Japan earthquake showing spontaneous recovery after 1 month.

    Science.gov (United States)

    Yanagimoto, Shintaro; Haida, Michiko; Suko, Matsunobu

    2012-01-01

    People living in Japan were affected in various ways after the Great East Japan earthquake of March 11, 2011. A 52-year-old female asthma patient not directly affected by the disaster experienced a decrease in peak expiratory flow (PEF) immediately after the earthquake. Despite increasing the inhaled and oral corticosteroid doses, her PEF did not recover. One month later, her PEF level abruptly returned to normal with minimal medications, which were previously ineffective, and the asthma-related symptoms vanished. The stabilization of her state of mind and actual social state seemed to be a part of the reason for the patient's recovery.

  15. A snapshot of 3649 Web-based services published between 1994 and 2017 shows a decrease in availability after 2 years.

    Science.gov (United States)

    Osz, Ágnes; Pongor, Lorinc Sándor; Szirmai, Danuta; Gyorffy, Balázs

    2017-12-08

    The long-term availability of online Web services is of utmost importance to ensure reproducibility of analytical results. However, because of lack of maintenance following acceptance, many servers become unavailable after a short period of time. Our aim was to monitor the accessibility and the decay rate of published Web services as well as to determine the factors underlying trends changes. We searched PubMed to identify publications containing Web server-related terms published between 1994 and 2017. Automatic and manual screening was used to check the status of each Web service. Kruskall-Wallis, Mann-Whitney and Chi-square tests were used to evaluate various parameters, including availability, accessibility, platform, origin of authors, citation, journal impact factor and publication year. We identified 3649 publications in 375 journals of which 2522 (69%) were currently active. Over 95% of sites were running in the first 2 years, but this rate dropped to 84% in the third year and gradually sank afterwards (P Web services is 10.39 years. Working Web services were published in journals with higher impact factors (P = 4.8e-04). Services published before the year 2000 received minimal attention. The citation of offline services was less than for those online (P = 0.022). The majority of Web services provide analytical tools, and the proportion of databases is slowly decreasing. Conclusions. Almost one-third of Web services published to date went out of service. We recommend continued support of Web-based services to increase the reproducibility of published results. © The Author 2017. Published by Oxford University Press.

  16. Coronary revascularization does not decrease cardiac events in patients with stable ischemic heart disease but might do in those who showed moderate to severe ischemia.

    Science.gov (United States)

    Moroi, Masao; Yamashina, Akira; Tsukamoto, Kazumasa; Nishimura, Tsunehiko

    2012-07-12

    As an initial management strategy for stable ischemic heart disease (IHD), coronary revascularization therapy is thought to be equal to optimal medical therapy alone regarding prognosis. Whether or not the effects of revascularization on the prognosis of patients with stable IHD are associated with the amount of ischemic myocardium detected by nuclear stress imaging was evaluated. This retrospective study analyzed data from 4629 patients with suspected or known IHD who underwent gated stress myocardial-perfusion SPECT at 117 hospitals in Japan. The follow-up periods were three years and the combined endpoints consisted of cardiac death, nonfatal myocardial infarction, and congestive heart failure requiring hospitalization. After matching propensity scores between patients who underwent early revascularization and those who did not (n=316 per group), we compared cardiac event rates in relation to the amount of ischemic myocardium. Cardiac event rates did not significantly differ between patients who underwent early revascularization and those who did not (5.4% vs. 6.4%). Among patients with ≤ 5%, 6-10%, and >10% ischemic myocardium, cardiac event rates were 8%, 3% and 0% respectively, who underwent early revascularization compared with 4.5%, 6.1%, and 12.3%, respectively, among those who did not. Cardiac event rates were significantly lower among patients with >10% ischemic myocardium who underwent early revascularization compared with those who did not (0% vs. 12.3%, p=0.0062). Coronary revascularization for stable IHD does not decrease major cardiac events in all patients but might do in patients with moderate to severe ischemia. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Rifalazil and derivative compounds show potent efficacy in a mouse model of H. pylori colonization.

    Science.gov (United States)

    Rothstein, David M; Mullin, Steve; Sirokman, Klari; Söndergaard, Karen L; Johnson, Starrla; Gwathmey, Judith K; van Duzer, John; Murphy, Christopher K

    2008-08-01

    The rifamycin rifalazil (RFZ), and derivatives (NCEs) were efficacious in a mouse model of Helicobacter pylori colonization. Select NCEs were more active in vitro and showed greater efficacy than RFZ. A systemic component contributes to efficacy.

  18. Vegetation succession as affected by decreasing nitrogen deposition, soil characteristics and site management: A modelling approach

    NARCIS (Netherlands)

    Wamelink, G.W.W.; Dobben, van H.F.; Berendse, F.

    2009-01-01

    After many years of increasing nitrogen deposition, the deposition rates are now decreasing. A major question is whether this will result in the expected positive effects on plant species diversity. Long-term experiments that investigate the effects of decreasing deposition are not available. Model

  19. Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

    Science.gov (United States)

    Adhikari, Mohit H; Hacker, Carl D; Siegel, Josh S; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo; Corbetta, Maurizio

    2017-04-01

    While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to

  20. GRAPH-ORIENTED MODEL FOR NEO4J. A FREE ALTERNATIVE TO DECREASE TEMPORAL COMPLEXITY

    Directory of Open Access Journals (Sweden)

    Cleger, Eliober

    2017-06-01

    Full Text Available The University of Informatics Science uses the system of software project management (XedroGESPRO for monitoring and control the activities related to the production of software. The reports are based on a series of indicators to measure the progress of projects managed, among which those related to performance human resources. This system uses the relational model as the basis for storing information and indicators calculated by the technique of artificial intelligence "fuzzy logic" and stored procedures in the database manager PostgreSQL. All this meant a breakthrough and has produced satisfactory results in the last three years of operation, however significant delays are beginning to appear in the retrieval of information in those tables whose growth increases exponentially compared to the rest. This led to the creation of an oriented-graph model using the tool Neo4J, which reduces response times of queries needed to respond to each indicator. This paper presents the results of applying the model in a scenario closer to reality, which shows the decrease in temporal complexity.

  1. Classifying Multi-Model Wheat Yield Impact Response Surfaces Showing Sensitivity to Temperature and Precipitation Change

    Science.gov (United States)

    Fronzek, Stefan; Pirttioja, Nina; Carter, Timothy R.; Bindi, Marco; Hoffmann, Holger; Palosuo, Taru; Ruiz-Ramos, Margarita; Tao, Fulu; Trnka, Miroslav; Acutis, Marco; hide

    2017-01-01

    Crop growth simulation models can differ greatly in their treatment of key processes and hence in their response to environmental conditions. Here, we used an ensemble of 26 process-based wheat models applied at sites across a European transect to compare their sensitivity to changes in temperature (minus 2 to plus 9 degrees Centigrade) and precipitation (minus 50 to plus 50 percent). Model results were analysed by plotting them as impact response surfaces (IRSs), classifying the IRS patterns of individual model simulations, describing these classes and analysing factors that may explain the major differences in model responses. The model ensemble was used to simulate yields of winter and spring wheat at four sites in Finland, Germany and Spain. Results were plotted as IRSs that show changes in yields relative to the baseline with respect to temperature and precipitation. IRSs of 30-year means and selected extreme years were classified using two approaches describing their pattern. The expert diagnostic approach (EDA) combines two aspects of IRS patterns: location of the maximum yield (nine classes) and strength of the yield response with respect to climate (four classes), resulting in a total of 36 combined classes defined using criteria pre-specified by experts. The statistical diagnostic approach (SDA) groups IRSs by comparing their pattern and magnitude, without attempting to interpret these features. It applies a hierarchical clustering method, grouping response patterns using a distance metric that combines the spatial correlation and Euclidian distance between IRS pairs. The two approaches were used to investigate whether different patterns of yield response could be related to different properties of the crop models, specifically their genealogy, calibration and process description. Although no single model property across a large model ensemble was found to explain the integrated yield response to temperature and precipitation perturbations, the

  2. A physics-explicit model of bacterial conjugation shows the stabilizing role of the conjugative junction

    OpenAIRE

    Pastuszak, Jakub; Waclaw, Bartlomiej

    2017-01-01

    Conjugation is a process in which bacteria exchange DNA through a physical connection (conjugative junction) between mating cells. Despite its significance for processes such as the spread of antibiotic resistance, the role of physical forces in conjugation is poorly understood. Here we use computer models to show that the conjugative junction not only serves as a link to transfer the DNA but it also mechanically stabilises the mating pair which significantly increases the conjugation rate. W...

  3. Microarray profiling shows distinct differences between primary tumors and commonly used preclinical models in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wang, Weining; Iyer, N. Gopalakrishna; Tay, Hsien Ts’ung; Wu, Yonghui; Lim, Tony K. H.; Zheng, Lin; Song, In Chin; Kwoh, Chee Keong; Huynh, Hung; Tan, Patrick O. B.; Chow, Pierce K. H.

    2015-01-01

    Despite advances in therapeutics, outcomes for hepatocellular carcinoma (HCC) remain poor and there is an urgent need for efficacious systemic therapy. Unfortunately, drugs that are successful in preclinical studies often fail in the clinical setting, and we hypothesize that this is due to functional differences between primary tumors and commonly used preclinical models. In this study, we attempt to answer this question by comparing tumor morphology and gene expression profiles between primary tumors, xenografts and HCC cell lines. Hep G2 cell lines and tumor cells from patient tumor explants were subcutaneously (ectopically) injected into the flank and orthotopically into liver parenchyma of Mus Musculus SCID mice. The mice were euthanized after two weeks. RNA was extracted from the tumors, and gene expression profiling was performed using the Gene Chip Human Genome U133 Plus 2.0. Principal component analyses (PCA) and construction of dendrograms were conducted using Partek genomics suite. PCA showed that the commonly used HepG2 cell line model and its xenograft counterparts were vastly different from all fresh primary tumors. Expression profiles of primary tumors were also significantly divergent from their counterpart patient-derived xenograft (PDX) models, regardless of the site of implantation. Xenografts from the same primary tumors were more likely to cluster together regardless of site of implantation, although heat maps showed distinct differences in gene expression profiles between orthotopic and ectopic models. The data presented here challenges the utility of routinely used preclinical models. Models using HepG2 were vastly different from primary tumors and PDXs, suggesting that this is not clinically representative. Surprisingly, site of implantation (orthotopic versus ectopic) resulted in limited impact on gene expression profiles, and in both scenarios xenografts differed significantly from the original primary tumors, challenging the long

  4. Understanding decreases in land relative humidity with global warming: conceptual model and GCM simulations

    OpenAIRE

    Byrne, Michael P.; O'Gorman, Paul A.

    2016-01-01

    Climate models simulate a strong land-ocean contrast in the response of near-surface relative humidity to global warming: relative humidity tends to increase slightly over oceans but decrease substantially over land. Surface energy balance arguments have been used to understand the response over ocean but are difficult to apply over more complex land surfaces. Here, a conceptual box model is introduced, involving moisture transport between the land and ocean boundary layers and evapotranspira...

  5. Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and DifferentiationSummary

    Directory of Open Access Journals (Sweden)

    Richard J. von Furstenberg

    2017-11-01

    Full Text Available Background & Aims: Although cells comprising esophageal submucosal glands (ESMGs represent a potential progenitor cell niche, new models are needed to understand their capacity to proliferate and differentiate. By histologic appearance, ESMGs have been associated with both overlying normal squamous epithelium and columnar epithelium. Our aim was to assess ESMG proliferation and differentiation in a 3-dimensional culture model. Methods: We evaluated proliferation in human ESMGs from normal and diseased tissue by proliferating cell nuclear antigen immunohistochemistry. Next, we compared 5-ethynyl-2′-deoxyuridine labeling in porcine ESMGs in vivo before and after esophageal injury with a novel in vitro porcine organoid ESMG model. Microarray analysis of ESMGs in culture was compared with squamous epithelium and fresh ESMGs. Results: Marked proliferation was observed in human ESMGs of diseased tissue. This activated ESMG state was recapitulated after esophageal injury in an in vivo porcine model, ESMGs assumed a ductal appearance with increased proliferation compared with control. Isolated and cultured porcine ESMGs produced buds with actively cycling cells and passaged to form epidermal growth factor–dependent spheroids. These spheroids were highly proliferative and were passaged multiple times. Two phenotypes of spheroids were identified: solid squamous (P63+ and hollow/ductal (cytokeratin 7+. Microarray analysis showed spheroids to be distinct from parent ESMGs and enriched for columnar transcripts. Conclusions: Our results suggest that the activated ESMG state, seen in both human disease and our porcine model, may provide a source of cells to repopulate damaged epithelium in a normal manner (squamous or abnormally (columnar epithelium. This culture model will allow the evaluation of factors that drive ESMGs in the regeneration of injured epithelium. The raw microarray data have been uploaded to the National Center for

  6. Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation.

    Science.gov (United States)

    von Furstenberg, Richard J; Li, Joy; Stolarchuk, Christina; Feder, Rachel; Campbell, Alexa; Kruger, Leandi; Gonzalez, Liara M; Blikslager, Anthony T; Cardona, Diana M; McCall, Shannon J; Henning, Susan J; Garman, Katherine S

    2017-11-01

    Although cells comprising esophageal submucosal glands (ESMGs) represent a potential progenitor cell niche, new models are needed to understand their capacity to proliferate and differentiate. By histologic appearance, ESMGs have been associated with both overlying normal squamous epithelium and columnar epithelium. Our aim was to assess ESMG proliferation and differentiation in a 3-dimensional culture model. We evaluated proliferation in human ESMGs from normal and diseased tissue by proliferating cell nuclear antigen immunohistochemistry. Next, we compared 5-ethynyl-2'-deoxyuridine labeling in porcine ESMGs in vivo before and after esophageal injury with a novel in vitro porcine organoid ESMG model. Microarray analysis of ESMGs in culture was compared with squamous epithelium and fresh ESMGs. Marked proliferation was observed in human ESMGs of diseased tissue. This activated ESMG state was recapitulated after esophageal injury in an in vivo porcine model, ESMGs assumed a ductal appearance with increased proliferation compared with control. Isolated and cultured porcine ESMGs produced buds with actively cycling cells and passaged to form epidermal growth factor-dependent spheroids. These spheroids were highly proliferative and were passaged multiple times. Two phenotypes of spheroids were identified: solid squamous (P63+) and hollow/ductal (cytokeratin 7+). Microarray analysis showed spheroids to be distinct from parent ESMGs and enriched for columnar transcripts. Our results suggest that the activated ESMG state, seen in both human disease and our porcine model, may provide a source of cells to repopulate damaged epithelium in a normal manner (squamous) or abnormally (columnar epithelium). This culture model will allow the evaluation of factors that drive ESMGs in the regeneration of injured epithelium. The raw microarray data have been uploaded to the National Center for Biotechnology Information Gene Expression Omnibus (accession number: GSE100543).

  7. Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy.

    Directory of Open Access Journals (Sweden)

    Estefanía de Munck

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive motor neuron degenerative disease that has no effective treatment up to date. Drug discovery tasks have been hampered due to the lack of knowledge in its molecular etiology together with the limited animal models for research. Recently, a motor neuron disease animal model has been developed using β-N-methylamino-L-alanine (L-BMAA, a neurotoxic amino acid related to the appearing of ALS. In the present work, the neuroprotective role of VP2.51, a small heterocyclic GSK-3 inhibitor, is analysed in this novel murine model together with the analysis of autophagy. VP2.51 daily administration for two weeks, starting the first day after L-BMAA treatment, leads to total recovery of neurological symptoms and prevents the activation of autophagic processes in rats. These results show that the L-BMAA murine model can be used to test the efficacy of new drugs. In addition, the results confirm the therapeutic potential of GSK-3 inhibitors, and specially VP2.51, for the disease-modifying future treatment of motor neuron disorders like ALS.

  8. Human Commercial Models' Eye Colour Shows Negative Frequency-Dependent Selection.

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    Isabela Rodrigues Nogueira Forti

    Full Text Available In this study we investigated the eye colour of human commercial models registered in the UK (400 female and 400 male and Brazil (400 female and 400 male to test the hypothesis that model eye colour frequency was the result of negative frequency-dependent selection. The eye colours of the models were classified as: blue, brown or intermediate. Chi-square analyses of data for countries separated by sex showed that in the United Kingdom brown eyes and intermediate colours were significantly more frequent than expected in comparison to the general United Kingdom population (P<0.001. In Brazil, the most frequent eye colour brown was significantly less frequent than expected in comparison to the general Brazilian population. These results support the hypothesis that model eye colour is the result of negative frequency-dependent selection. This could be the result of people using eye colour as a marker of genetic diversity and finding rarer eye colours more attractive because of the potential advantage more genetically diverse offspring that could result from such a choice. Eye colour may be important because in comparison to many other physical traits (e.g., hair colour it is hard to modify, hide or disguise, and it is highly polymorphic.

  9. Human Commercial Models' Eye Colour Shows Negative Frequency-Dependent Selection.

    Science.gov (United States)

    Forti, Isabela Rodrigues Nogueira; Young, Robert John

    2016-01-01

    In this study we investigated the eye colour of human commercial models registered in the UK (400 female and 400 male) and Brazil (400 female and 400 male) to test the hypothesis that model eye colour frequency was the result of negative frequency-dependent selection. The eye colours of the models were classified as: blue, brown or intermediate. Chi-square analyses of data for countries separated by sex showed that in the United Kingdom brown eyes and intermediate colours were significantly more frequent than expected in comparison to the general United Kingdom population (PBrazilian population. These results support the hypothesis that model eye colour is the result of negative frequency-dependent selection. This could be the result of people using eye colour as a marker of genetic diversity and finding rarer eye colours more attractive because of the potential advantage more genetically diverse offspring that could result from such a choice. Eye colour may be important because in comparison to many other physical traits (e.g., hair colour) it is hard to modify, hide or disguise, and it is highly polymorphic.

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

    Science.gov (United States)

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

    2015-05-19

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

  11. MTO1-deficient mouse model mirrors the human phenotype showing complex I defect and cardiomyopathy.

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    Lore Becker

    Full Text Available Recently, mutations in the mitochondrial translation optimization factor 1 gene (MTO1 were identified as causative in children with hypertrophic cardiomyopathy, lactic acidosis and respiratory chain defect. Here, we describe an MTO1-deficient mouse model generated by gene trap mutagenesis that mirrors the human phenotype remarkably well. As in patients, the most prominent signs and symptoms were cardiovascular and included bradycardia and cardiomyopathy. In addition, the mutant mice showed a marked worsening of arrhythmias during induction and reversal of anaesthesia. The detailed morphological and biochemical workup of murine hearts indicated that the myocardial damage was due to complex I deficiency and mitochondrial dysfunction. In contrast, neurological examination was largely normal in Mto1-deficient mice. A translational consequence of this mouse model may be to caution against anaesthesia-related cardiac arrhythmias which may be fatal in patients.

  12. The RESET Mindset Model applied on decreasing antibiotic usage in dairy cattle in the Netherlands.

    Science.gov (United States)

    Lam, T J G M; Jansen, J; Wessels, R J

    2017-01-01

    Prudent use of antibiotics is important to prevent antibiotic resistance in humans and in animals. For this reason politicians demanded a decrease of total antibiotic use and of use of critically important antibiotics in animal husbandry in the Netherlands. In the dairy sector the use of antibiotics almost halved in the years 2009-2015, with a decrease of the use of critically important antibiotics to very low levels. To realize a sustainable decrease in antibiotic usage, the mindset towards the subject was considered crucial. Based on several models from social psychology, the RESET Mindset Model was used. This model contains the most important cues to change human behaviour, being Rules and regulations, Education and information, Social pressure, Economics, and Tools. To change behaviour of groups in order to reach a tipping point, it is of utmost importance to not choose among the different cues, but to use them all. In order to decrease antibiotic usage in dairy cattle in the Netherlands several actions, obliged as well as voluntary, were undertaken. An independent veterinary medicine authority was founded that became active for all animal sectors. In the dairy sector a national database on antibiotic usage called MediRund was developed, which made transparency and benchmarking on antibiotic usage at the national and the herd level possible. Several other activities are described, such as herd health and treatment plans, selective dry cow therapy, and the strong limitation on the use of critically important antibiotics. Antibiotic usage at the herd level, referred to as the 'antibiotic number', became an important and socially accepted herd level parameter. The actions undertaken worked through different cues, all part of the RESET Mindset Model. As such, different types of dairy farmers sensitive to different types of cues were motivated to change their behaviour. Antibiotic usage in dairy cattle in the Netherlands decreased significantly by intense

  13. Expression of hepatic lipid droplets is decreased in the nitrofen model of congenital diaphragmatic hernia.

    Science.gov (United States)

    Takahashi, Hiromizu; Kutasy, Balazs; Friedmacher, Florian; Takahashi, Toshiaki; Puri, Prem

    2016-02-01

    Prenatal mortality in newborn infants with congenital diaphragmatic hernia (CDH) has been attributed to increased amounts of liver hernia ion through the diaphragmatic defect. Antenatal studies in human and rodent fetus with CDH further demonstrated a contribution of the developing liver in the pathogenesis of CDH. The abnormal hepatic growth in experimental animal models, therefore, indicates a disruption of normal liver development in CDH. However, the underlying structural, histological and functional changes in the liver of animals with CDH remain unclear. We design this study to test the hypothesis that the morphological and cellular liver development is altered in the nitrogen-induced CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Livers and chest were harvested on D21 and divided into two groups: control (n = 8), nitrofen with CDH (CDH, n = 8). Haematoxylin-eosin (Straub et al. Histopathology 68:617-631, 2013) staining was performed to evaluate underlying morphological changes. Apoptosis was checked by using TUNEL staining and apoptotic cell number was counted on 16-16 slides in 25 fields by two independent viewers. Hepatic lipid droplet expressions were evaluated by hepatic adipose differentiation-related protein (ARDP) expression. Compared to controls markedly increased hypertrophy was seen in CDH group. Significantly increased apoptotic cell numbers were detected in CDH group compared to controls (5.1 ± 1.5 vs 2.1 ± 0.6) (p CDH group compared to controls. Immunohistochemistry showed markedly decreased hepatic ADRP immunoreactivity in CDH fetuses compared to controls. Our findings provide strong evidence of hepatic hypertrophy and increased cell apoptosis in the liver of nitrofen-induced CDH. These morphological changes may affect liver lipid droplet expression function.

  14. Visual modeling shows that avian host parents use multiple visual cues in rejecting parasitic eggs.

    Science.gov (United States)

    Spottiswoode, Claire N; Stevens, Martin

    2010-05-11

    One of the most striking outcomes of coevolution between species is egg mimicry by brood parasitic birds, resulting from rejection behavior by discriminating host parents. Yet, how exactly does a host detect a parasitic egg? Brood parasitism and egg rejection behavior provide a model system for exploring the relative importance of different visual cues used in a behavioral task. Although hosts are discriminating, we do not know exactly what cues they use, and to answer this it is crucial to account for the receiver's visual perception. Color, luminance ("perceived lightness") and pattern information have never been simultaneously quantified and experimentally tested through a bird's eye. The cuckoo finch Anomalospiza imberbis and its hosts show spectacular polymorphisms in egg appearance, providing a good opportunity for investigating visual discrimination owing to the large range of patterns and colors involved. Here we combine field experiments in Africa with modeling of avian color vision and pattern discrimination to identify the specific visual cues used by hosts in making rejection decisions. We found that disparity between host and foreign eggs in both color and several aspects of pattern (dispersion, principal marking size, and variability in marking size) were important predictors of rejection, especially color. These cues correspond exactly to the principal differences between host and parasitic eggs, showing that hosts use the most reliable available cues in making rejection decisions, and select for parasitic eggs that are increasingly mimetic in a range of visual attributes.

  15. Transchromosomic cell model of Down syndrome shows aberrant migration, adhesion and proteome response to extracellular matrix

    Directory of Open Access Journals (Sweden)

    Cotter Finbarr E

    2009-08-01

    Full Text Available Abstract Background Down syndrome (DS, caused by trisomy of human chromosome 21 (HSA21, is the most common genetic birth defect. Congenital heart defects (CHD are seen in 40% of DS children, and >50% of all atrioventricular canal defects in infancy are caused by trisomy 21, but the causative genes remain unknown. Results Here we show that aberrant adhesion and proliferation of DS cells can be reproduced using a transchromosomic model of DS (mouse fibroblasts bearing supernumerary HSA21. We also demonstrate a deacrease of cell migration in transchromosomic cells independently of their adhesion properties. We show that cell-autonomous proteome response to the presence of Collagen VI in extracellular matrix is strongly affected by trisomy 21. Conclusion This set of experiments establishes a new model system for genetic dissection of the specific HSA21 gene-overdose contributions to aberrant cell migration, adhesion, proliferation and specific proteome response to collagen VI, cellular phenotypes linked to the pathogenesis of CHD.

  16. Estimating carbon and showing impacts of drought using satellite data in regression-tree models

    Science.gov (United States)

    Boyte, Stephen; Wylie, Bruce K.; Howard, Danny; Dahal, Devendra; Gilmanov, Tagir G.

    2018-01-01

    Integrating spatially explicit biogeophysical and remotely sensed data into regression-tree models enables the spatial extrapolation of training data over large geographic spaces, allowing a better understanding of broad-scale ecosystem processes. The current study presents annual gross primary production (GPP) and annual ecosystem respiration (RE) for 2000–2013 in several short-statured vegetation types using carbon flux data from towers that are located strategically across the conterminous United States (CONUS). We calculate carbon fluxes (annual net ecosystem production [NEP]) for each year in our study period, which includes 2012 when drought and higher-than-normal temperatures influence vegetation productivity in large parts of the study area. We present and analyse carbon flux dynamics in the CONUS to better understand how drought affects GPP, RE, and NEP. Model accuracy metrics show strong correlation coefficients (r) (r ≥ 94%) between training and estimated data for both GPP and RE. Overall, average annual GPP, RE, and NEP are relatively constant throughout the study period except during 2012 when almost 60% less carbon is sequestered than normal. These results allow us to conclude that this modelling method effectively estimates carbon dynamics through time and allows the exploration of impacts of meteorological anomalies and vegetation types on carbon dynamics.

  17. Visualizing Three-dimensional Slab Geometries with ShowEarthModel

    Science.gov (United States)

    Chang, B.; Jadamec, M. A.; Fischer, K. M.; Kreylos, O.; Yikilmaz, M. B.

    2017-12-01

    Seismic data that characterize the morphology of modern subducted slabs on Earth suggest that a two-dimensional paradigm is no longer adequate to describe the subduction process. Here we demonstrate the effect of data exploration of three-dimensional (3D) global slab geometries with the open source program ShowEarthModel. ShowEarthModel was designed specifically to support data exploration, by focusing on interactivity and real-time response using the Vrui toolkit. Sixteen movies are presented that explore the 3D complexity of modern subduction zones on Earth. The first movie provides a guided tour through the Earth's major subduction zones, comparing the global slab geometry data sets of Gudmundsson and Sambridge (1998), Syracuse and Abers (2006), and Hayes et al. (2012). Fifteen regional movies explore the individual subduction zones and regions intersecting slabs, using the Hayes et al. (2012) slab geometry models where available and the Engdahl and Villasenor (2002) global earthquake data set. Viewing the subduction zones in this way provides an improved conceptualization of the 3D morphology within a given subduction zone as well as the 3D spatial relations between the intersecting slabs. This approach provides a powerful tool for rendering earth properties and broadening capabilities in both Earth Science research and education by allowing for whole earth visualization. The 3D characterization of global slab geometries is placed in the context of 3D slab-driven mantle flow and observations of shear wave splitting in subduction zones. These visualizations contribute to the paradigm shift from a 2D to 3D subduction framework by facilitating the conceptualization of the modern subduction system on Earth in 3D space.

  18. Metabolic remodeling agents show beneficial effects in the dystrophin-deficient mdx mouse model

    Directory of Open Access Journals (Sweden)

    Jahnke Vanessa E

    2012-08-01

    Full Text Available Abstract Background Duchenne muscular dystrophy is a genetic disease involving a severe muscle wasting that is characterized by cycles of muscle degeneration/regeneration and culminates in early death in affected boys. Mitochondria are presumed to be involved in the regulation of myoblast proliferation/differentiation; enhancing mitochondrial activity with exercise mimetics (AMPK and PPAR-delta agonists increases muscle function and inhibits muscle wasting in healthy mice. We therefore asked whether metabolic remodeling agents that increase mitochondrial activity would improve muscle function in mdx mice. Methods Twelve-week-old mdx mice were treated with two different metabolic remodeling agents (GW501516 and AICAR, separately or in combination, for 4 weeks. Extensive systematic behavioral, functional, histological, biochemical, and molecular tests were conducted to assess the drug(s' effects. Results We found a gain in body and muscle weight in all treated mice. Histologic examination showed a decrease in muscle inflammation and in the number of fibers with central nuclei and an increase in fibers with peripheral nuclei, with significantly fewer activated satellite cells and regenerating fibers. Together with an inhibition of FoXO1 signaling, these results indicated that the treatments reduced ongoing muscle damage. Conclusions The three treatments produced significant improvements in disease phenotype, including an increase in overall behavioral activity and significant gains in forelimb and hind limb strength. Our findings suggest that triggering mitochondrial activity with exercise mimetics improves muscle function in dystrophin-deficient mdx mice.

  19. Male Wistar rats show individual differences in an animal model of conformity.

    Science.gov (United States)

    Jolles, Jolle W; de Visser, Leonie; van den Bos, Ruud

    2011-09-01

    Conformity refers to the act of changing one's behaviour to match that of others. Recent studies in humans have shown that individual differences exist in conformity and that these differences are related to differences in neuronal activity. To understand the neuronal mechanisms in more detail, animal tests to assess conformity are needed. Here, we used a test of conformity in rats that has previously been evaluated in female, but not male, rats and assessed the nature of individual differences in conformity. Male Wistar rats were given the opportunity to learn that two diets differed in palatability. They were subsequently exposed to a demonstrator that had consumed the less palatable food. Thereafter, they were exposed to the same diets again. Just like female rats, male rats decreased their preference for the more palatable food after interaction with demonstrator rats that had eaten the less palatable food. Individual differences existed for this shift, which were only weakly related to an interaction between their own initial preference and the amount consumed by the demonstrator rat. The data show that this conformity test in rats is a promising tool to study the neurobiology of conformity.

  20. A zebrafish model of glucocorticoid resistance shows serotonergic modulation of the stress response

    Directory of Open Access Journals (Sweden)

    Brian eGriffiths

    2012-10-01

    Full Text Available One function of glucocorticoids is to restore homeostasis after an acute stress response by providing negative feedback to stress circuits in the brain. Loss of this negative feedback leads to elevated physiological stress and may contribute to depression, anxiety and post-traumatic stress disorder. We investigated the early, developmental effects of glucocorticoid signaling deficits on stress physiology and related behaviors using a mutant zebrafish, grs357, with non-functional glucocorticoid receptors. These mutants are morphologically inconspicuous and adult-viable. A previous study of adult grs357 mutants showed loss of glucocorticoid-mediated negative feedback and elevated physiological and behavioral stress markers. Already at five days post-fertilization, mutant larvae had elevated whole body cortisol, increased expression of pro-opiomelanocortin (POMC, the precursor of adrenocorticotropic hormone (ACTH, and failed to show normal suppression of stress markers after dexamethasone treatment. Mutant larvae had larger auditory-evoked startle responses compared to wildtype sibling controls (grwt, despite having lower spontaneous activity levels. Fluoxetine (Prozac treatment in mutants decreased startle responding and increased spontaneous activity, making them behaviorally similar to wildtype. This result mirrors known effects of selective serotonin reuptake inhibitors (SSRIs in modifying glucocorticoid signaling and alleviating stress disorders in human patients. Our results suggest that larval grs357 zebrafish can be used to study behavioral, physiological and molecular aspects of stress disorders. Most importantly, interactions between glucocorticoid and serotonin signaling appear to be highly conserved among vertebrates, suggesting deep homologies at the neural circuit level and opening up new avenues for research into psychiatric conditions.

  1. A Mechanical Model for Decrease in Coupling Prior to the 2011 M9 Tohoku Earthquake

    Science.gov (United States)

    Mavrommatis, A. P.; Segall, P.; Johnson, K. M.

    2016-12-01

    The degree to which faults are partitioned into distinct seismic and aseismic zones is a central question in earthquake physics. The conventional "asperity model" posits that faults are partitioned into stationary velocity-weakening (VW) patches (asperities) that are locked interseismically and velocity-strengthening (VS) regions that creep stably without accumulating stress. However, studies of GPS-derived deformation in northern Japan have showed that interseismic strain in the Tohoku region did not accumulate at a constant rate (as expected), but gradually decreased from 1996 and 2011 (e.g., Mavrommatis et al., GRL, 2014). This change in strain rate is consistent with locked asperities (corresponding to historical rupture zones) shrinking by 75% in area during this period. Here, we use physics-based simulations of earthquake cycles with dynamic weakening (e.g., Jiang and Lapusta, Science, 2016) to develop a physical model for shrinking asperities. We conduct two- and three-dimensional quasi-dynamic simulations including rate-and-state friction and thermal pressurization (TP). We consider circular asperities in which the innermost region is VW while the remaining fault is VS, and with efficient TP in the VW and part of the VS regions. Dynamic rupture begins in the VW region, but due to TP it propagates through the VS region. Shear stress during rapid slip is dropped to very low levels. During the interseismic period, shear stress in the VS region is gradually recovered to its state-steady value at the plate rate, at which point stable creep occurs. The creep front propagates inward, effectively eroding the locked asperity. The locked area shrinks roughly linearly in time through the VS region. Creep penetrates only a short distance into the VW patch before the next dynamic event nucleates. Locked asperities shrink more slowly at lower values of hydraulic diffusivity, higher nominal friction coefficient or background effective normal stress in the VS region, and

  2. Decrease of plasma platelet-activating factor acetylhydrolase activity in lipopolysaccharide induced mongolian gerbil sepsis model.

    Directory of Open Access Journals (Sweden)

    Junwei Yang

    Full Text Available Platelet-activating factor (PAF plays an important role in the pathogenesis of sepsis, and the level of plasma PAF acetylhydrolase (pPAF-AH, which inactivates PAF, decreases in sepsis patients except for the sepsis caused by severe leptospirosis. Usually, increase of pPAF-AH activity was observed in lipopolysaccharide (LPS-induced Syrian hamster and rat sepsis models, while contradictory effects were reported for mouse model in different studies. Here, we demonstrated the in vivo effects of LPS upon the change of pPAF-AH activity in C57BL/6 mice and Mongolian gerbils. After LPS-treatment, the clinical manifestations of Mongolian gerbil model were apparently similar to that of C57BL/6 mouse sepsis model. The pPAF-AH activity increased in C57BL/6 mice after LPS induction, but decreased in Mongolian gerbils, which was similar to that of the human sepsis. It thus suggests that among the LPS-induced rodent sepsis models, only Mongolian gerbil could be used for the study of pPAF-AH related to the pathogenesis of human sepsis. Proper application of this model might enable people to clarify the underline mechanism accounted for the contradictory results between the phase II and phase III clinical trials for the administration of recombinant human pPAF-AH in the sepsis therapy.

  3. Etoposide incorporated into camel milk phospholipids liposomes shows increased activity against fibrosarcoma in a mouse model.

    Science.gov (United States)

    Maswadeh, Hamzah M; Aljarbou, Ahmad N; Alorainy, Mohammed S; Alsharidah, Mansour S; Khan, Masood A

    2015-01-01

    Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS). Anticancer drug etoposide (ETP) was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP) and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes) and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes). The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.

  4. Etoposide Incorporated into Camel Milk Phospholipids Liposomes Shows Increased Activity against Fibrosarcoma in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Hamzah M. Maswadeh

    2015-01-01

    Full Text Available Phospholipids were isolated from camel milk and identified by using high performance liquid chromatography and gas chromatography-mass spectrometry (GC/MS. Anticancer drug etoposide (ETP was entrapped in liposomes, prepared from camel milk phospholipids, to determine its activity against fibrosarcoma in a murine model. Fibrosarcoma was induced in mice by injecting benzopyrene (BAP and tumor-bearing mice were treated with various formulations of etoposide, including etoposide entrapped camel milk phospholipids liposomes (ETP-Cam-liposomes and etoposide-loaded DPPC-liposomes (ETP-DPPC-liposomes. The tumor-bearing mice treated with ETP-Cam-liposomes showed slow progression of tumors and increased survival compared to free ETP or ETP-DPPC-liposomes. These results suggest that ETP-Cam-liposomes may prove to be a better drug delivery system for anticancer drugs.

  5. Phenolic Acids from Wheat Show Different Absorption Profiles in Plasma: A Model Experiment with Catheterized Pigs

    DEFF Research Database (Denmark)

    Nørskov, Natalja; Hedemann, Mette Skou; Theil, Peter Kappel

    2013-01-01

    consumed. Benzoic acid derivatives showed low concentration in the plasma (diets. The exception was p-hydroxybenzoic acid, with a plasma concentration (4 ± 0.4 μM), much higher than the other plant phenolic acids, likely because it is an intermediate in the phenolic acid metabolism......The concentration and absorption of the nine phenolic acids of wheat were measured in a model experiment with catheterized pigs fed whole grain wheat and wheat aleurone diets. Six pigs in a repeated crossover design were fitted with catheters in the portal vein and mesenteric artery to study....... It was concluded that plant phenolic acids undergo extensive interconversion in the colon and that their absorption profiles reflected their low bioavailability in the plant matrix....

  6. Cause Analysis Of Outpatient Visits Decreasing Based On Service Quality Gaps Model

    OpenAIRE

    Wulandari, Ratna Dwi; Halim, Christine Natalia

    2013-01-01

    In healthcare services, gap between quality service by provider and the expectation of consumer arefrequently found. This research was aimed to analyze why the number of outpatient visit in Usada HospitalSidoarjo gradually decreased. This research identified 7 kind of gap using service quality gaps model. This wascross-sectional study with descriptive approach. Interview using questionnaire had done to 100 outpatient, 13management official, and 18 Usada hospital€™s employees. The expected ser...

  7. Atovaquone Nanosuspensions Show Excellent Therapeutic Effect in a New Murine Model of Reactivated Toxoplasmosis

    Science.gov (United States)

    Schöler, Nadja; Krause, Karsten; Kayser, Oliver; Müller, Rainer H.; Borner, Klaus; Hahn, Helmut; Liesenfeld, Oliver

    2001-01-01

    Immunocompromised patients are at risk of developing toxoplasma encephalitis (TE). Standard therapy regimens (including sulfadiazine plus pyrimethamine) are hampered by severe side effects. While atovaquone has potent in vitro activity against Toxoplasma gondii, it is poorly absorbed after oral administration and shows poor therapeutic efficacy against TE. To overcome the low absorption of atovaquone, we prepared atovaquone nanosuspensions (ANSs) for intravenous (i.v.) administration. At concentrations higher than 1.0 μg/ml, ANS did not exert cytotoxicity and was as effective as free atovaquone (i.e., atovaquone suspended in medium) against T. gondii in freshly isolated peritoneal macrophages. In a new murine model of TE that closely mimics reactivated toxoplasmosis in immunocompromised hosts, using mice with a targeted mutation in the gene encoding the interferon consensus sequence binding protein, i.v.-administered ANS doses of 10.0 mg/kg of body weight protected the animals against development of TE and death. Atovaquone was detectable in the sera, brains, livers, and lungs of mice by high-performance liquid chromatography. Development of TE and mortality in mice treated with 1.0- or 0.1-mg/kg i.v. doses of ANS did not differ from that in mice treated orally with 100 mg of atovaquone/kg. In conclusion, i.v. ANSs may prove to be an effective treatment alternative for patients with TE. PMID:11353624

  8. New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies.

    Science.gov (United States)

    Doğan, İnci Selin; Saraç, Selma; Sari, Suat; Kart, Didem; Eşsiz Gökhan, Şebnem; Vural, İmran; Dalkara, Sevim

    2017-04-21

    Azole antifungals are potent inhibitors of fungal lanosterol 14α demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design, synthesis, and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 μg/mL against Candida albicans. Additionally, some of our compounds, such as 19 (MIC: 0.25 μg/mL), were potent against resistant C. glabrata, a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action, we performed computational analysis utilizing molecular docking and dynamics simulations on the C. albicans and C. glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Lymph Node Transplantation Decreases Swelling and Restores Immune Responses in a Transgenic Model of Lymphedema.

    Directory of Open Access Journals (Sweden)

    Jung-Ju Huang

    Full Text Available Secondary lymphedema is a common complication of cancer treatment and recent studies have demonstrated that lymph node transplantation (LNT can decrease swelling, as well as the incidence of infections. However, although these results are exciting, the mechanisms by which LNT improves these pathologic findings of lymphedema remain unknown. Using a transgenic mouse model of lymphedema, this study sought to analyze the effect of LNT on lymphatic regeneration and T cell-mediated immune responses.We used a mouse model in which the expression of the human diphtheria toxin receptor is driven by the FLT4 promoter to enable the local ablation of the lymphatic system through subdermal hindlimb diphtheria toxin injections. Popliteal lymph node dissection was subsequently performed after a two-week recovery period, followed by either orthotopic LNT or sham surgery after an additional two weeks. Hindlimb swelling, lymphatic vessel regeneration, immune cell trafficking, and T cell-mediated immune responses were analyzed 10 weeks later.LNT resulted in a marked decrease in hindlimb swelling, fibroadipose tissue deposition, and decreased accumulation of perilymphatic inflammatory cells, as compared to controls. In addition, LNT induced a marked lymphangiogenic response in both capillary and collecting lymphatic vessels. Interestingly, the resultant regenerated lymphatics were abnormal in appearance on lymphangiography, but LNT also led to a notable increase in dendritic cell trafficking from the periphery to the inguinal lymph nodes and improved adaptive immune responses.LNT decreases pathological changes of lymphedema and was shown to potently induce lymphangiogenesis. Lymphatic vessels induced by LNT were abnormal in appearance, but were functional and able to transport antigen-presenting cells. Animals treated with LNT have an increased ability to mount T cell-mediated immune responses when sensitized to antigens in the affected hindlimb.

  10. Lymph Node Transplantation Decreases Swelling and Restores Immune Responses in a Transgenic Model of Lymphedema.

    Science.gov (United States)

    Huang, Jung-Ju; Gardenier, Jason C; Hespe, Geoffrey E; García Nores, Gabriela D; Kataru, Raghu P; Ly, Catherine L; Martínez-Corral, Inés; Ortega, Sagrario; Mehrara, Babak J

    2016-01-01

    Secondary lymphedema is a common complication of cancer treatment and recent studies have demonstrated that lymph node transplantation (LNT) can decrease swelling, as well as the incidence of infections. However, although these results are exciting, the mechanisms by which LNT improves these pathologic findings of lymphedema remain unknown. Using a transgenic mouse model of lymphedema, this study sought to analyze the effect of LNT on lymphatic regeneration and T cell-mediated immune responses. We used a mouse model in which the expression of the human diphtheria toxin receptor is driven by the FLT4 promoter to enable the local ablation of the lymphatic system through subdermal hindlimb diphtheria toxin injections. Popliteal lymph node dissection was subsequently performed after a two-week recovery period, followed by either orthotopic LNT or sham surgery after an additional two weeks. Hindlimb swelling, lymphatic vessel regeneration, immune cell trafficking, and T cell-mediated immune responses were analyzed 10 weeks later. LNT resulted in a marked decrease in hindlimb swelling, fibroadipose tissue deposition, and decreased accumulation of perilymphatic inflammatory cells, as compared to controls. In addition, LNT induced a marked lymphangiogenic response in both capillary and collecting lymphatic vessels. Interestingly, the resultant regenerated lymphatics were abnormal in appearance on lymphangiography, but LNT also led to a notable increase in dendritic cell trafficking from the periphery to the inguinal lymph nodes and improved adaptive immune responses. LNT decreases pathological changes of lymphedema and was shown to potently induce lymphangiogenesis. Lymphatic vessels induced by LNT were abnormal in appearance, but were functional and able to transport antigen-presenting cells. Animals treated with LNT have an increased ability to mount T cell-mediated immune responses when sensitized to antigens in the affected hindlimb.

  11. Trans-nonachlor decreases miR-141-3p levels in human melanocytes in vitro promoting melanoma cell characteristics and shows a multigenerational impact on miR-8 levels in Drosophila.

    Science.gov (United States)

    Verrando, Patrick; Capovilla, Maria; Rahmani, Roger

    2016-08-10

    Epidemiological association studies have revealed a role for pesticides in cancer occurrence, while a growing number of reports have highlighted the deleterious epigenetic modifications that can be produced by environmental factors. However, epidemiological data currently lack molecular support to unravel the epigenetic impact of pesticides on carcinogenesis. Based on epidemiological studies of melanoma, our data show for the first time that trans-nonachlor (TNC), a component of the pesticide chlordane, modulates the microRNA miR-141-3p in human melanocytic cells in vitro, with effects on melanomagenesis parameters. TNC downregulates the level of miR-141-3p in normal melanocytes to levels found endogenously in several melanoma cell lines. Ectopic expression of either a synthetic miRNA mimic or inhibitor in human melanocytic cells revealed that TNC counteracts the inhibitory effects of miR-141-3p on melanoma cell anchorage-independent growth ability, their invasive potential, and expression of a multipotent, embryonic-like, aggressive cancer phenotype (termed vasculogenic mimicry), involving VE-Cadherin. In addition, the data suggest that miR-141-3p regulates vasculogenic mimicry through extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidyl inositol-3-kinase (PI3K). Notably, in the Drosophila animal model, TNC also decreased the level of miR-8, the sole miR-141-3p fly ortholog. Importantly, the downregulation of miR-8 levels induced by TNC in ancestors was transmitted through multigenerations, with a progressive reversion over time. Such a decrease in miR-8 levels translated to a loss-of-weight phenotype in offspring. Providing support to epidemiological data, these results altogether suggest that TNC may favor melanomagenesis by lowering the levels of miR-141-3p, thereby activating melanoma cell processes. Although any such conclusions in humans are yet to be determined, these experiments in Drosophila demonstrate that TNC can promote an epigenetic

  12. Showing a model's eye movements in examples does not improve learning of problem-solving tasks

    NARCIS (Netherlands)

    van Marlen, Tim; van Wermeskerken, Margot; Jarodzka, Halszka; van Gog, Tamara

    2016-01-01

    Eye movement modeling examples (EMME) are demonstrations of a computer-based task by a human model (e.g., a teacher), with the model's eye movements superimposed on the task to guide learners' attention. EMME have been shown to enhance learning of perceptual classification tasks; however, it is an

  13. Climate Modelling Shows Increased Risk to Eucalyptus sideroxylon on the Eastern Coast of Australia Compared to Eucalyptus albens.

    Science.gov (United States)

    Shabani, Farzin; Kumar, Lalit; Ahmadi, Mohsen

    2017-11-24

    Aim: To identify the extent and direction of range shift of Eucalyptus sideroxylon and E. albens in Australia by 2050 through an ensemble forecast of four species distribution models (SDMs). Each was generated using four global climate models (GCMs), under two representative concentration pathways (RCPs). Location: Australia. Methods : We used four SDMs of (i) generalized linear model, (ii) MaxEnt, (iii) random forest, and (iv) boosted regression tree to construct SDMs for species E. sideroxylon and E. albens under four GCMs including (a) MRI-CGCM3, (b) MIROC5, (c) HadGEM2-AO and (d) CCSM4, under two RCPs of 4.5 and 6.0. Here, the true skill statistic (TSS) index was used to assess the accuracy of each SDM. Results: Results showed that E. albens and E. sideroxylon will lose large areas of their current suitable range by 2050 and E. sideroxylon is projected to gain in eastern and southeastern Australia. Some areas were also projected to remain suitable for each species between now and 2050. Our modelling showed that E. sideroxylon will lose suitable habitat on the western side and will not gain any on the eastern side because this region is one the most heavily populated areas in the country, and the populated areas are moving westward. The predicted decrease in E. sideroxylon's distribution suggests that land managers should monitor its population closely, and evaluate whether it meets criteria for a protected legal status. Main conclusions: Both Eucalyptus sideroxylon and E. albens will be negatively affected by climate change and it is projected that E. sideroxylon will be at greater risk of losing habitat than E. albens .

  14. Climate Modelling Shows Increased Risk to Eucalyptus sideroxylon on the Eastern Coast of Australia Compared to Eucalyptus albens

    Directory of Open Access Journals (Sweden)

    Farzin Shabani

    2017-11-01

    Full Text Available Aim: To identify the extent and direction of range shift of Eucalyptus sideroxylon and E. albens in Australia by 2050 through an ensemble forecast of four species distribution models (SDMs. Each was generated using four global climate models (GCMs, under two representative concentration pathways (RCPs. Location: Australia. Methods: We used four SDMs of (i generalized linear model, (ii MaxEnt, (iii random forest, and (iv boosted regression tree to construct SDMs for species E. sideroxylon and E. albens under four GCMs including (a MRI-CGCM3, (b MIROC5, (c HadGEM2-AO and (d CCSM4, under two RCPs of 4.5 and 6.0. Here, the true skill statistic (TSS index was used to assess the accuracy of each SDM. Results: Results showed that E. albens and E. sideroxylon will lose large areas of their current suitable range by 2050 and E. sideroxylon is projected to gain in eastern and southeastern Australia. Some areas were also projected to remain suitable for each species between now and 2050. Our modelling showed that E. sideroxylon will lose suitable habitat on the western side and will not gain any on the eastern side because this region is one the most heavily populated areas in the country, and the populated areas are moving westward. The predicted decrease in E. sideroxylon’s distribution suggests that land managers should monitor its population closely, and evaluate whether it meets criteria for a protected legal status. Main conclusions: Both Eucalyptus sideroxylon and E. albens will be negatively affected by climate change and it is projected that E. sideroxylon will be at greater risk of losing habitat than E. albens.

  15. Silencing of the rotavirus NSP4 protein decreases the incidence of biliary atresia in murine model.

    Directory of Open Access Journals (Sweden)

    Jiexiong Feng

    Full Text Available Biliary atresia is a common disease in neonates which causes obstructive jaundice and progressive hepatic fibrosis. Our previous studies indicate that rotavirus infection is an initiator in the pathogenesis of experimental biliary atresia (BA through the induction of increased nuclear factor-kappaB and abnormal activation of the osteopontin inflammation pathway. In the setting of rotavirus infection, rotavirus nonstructural protein 4 (NSP4 serves as an important immunogen, viral protein 7 (VP7 is necessary in rotavirus maturity and viral protein 4 (VP4 is a virulence determiner. The purpose of the current study is to clarify the roles of NSP4, VP7 and VP4 in the pathogenesis of experimental BA. Primary cultured extrahepatic biliary epithelia were infected with Rotavirus (mmu18006. Small interfering RNA targeting NSP4, VP7 or VP4 was transfected before rotavirus infection both in vitro and in vivo. We analyzed the incidence of BA, morphological change, morphogenesis of viral particles and viral mRNA and protein expression. The in vitro experiments showed NSP4 silencing decreased the levels of VP7 and VP4, reduced viral particles and decreased cytopathic effect. NSP4-positive cells had strongly positive expression of integrin subunit α2. Silencing of VP7 or VP4 partially decreased epithelial injury. Animal experiments indicated after NSP4 silencing, mouse pups had lower incidence of BA than after VP7 or VP4 silencing. However, 33.3% of VP4-silenced pups (N = 6 suffered BA and 50% of pups (N = 6 suffered biliary injury after VP7 silencing. Hepatic injury was decreased after NSP4 or VP4 silencing. Neither VP4 nor VP7 were detected in the biliary ducts after NSP4. All together, NSP4 silencing down-regulates VP7 and VP4, resulting in decreased incidence of BA.

  16. Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

    Science.gov (United States)

    Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

    2017-05-01

    Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

  17. The Analytical Diffusion-Expansion Model for Forbush Decreases Caused by Flux Ropes

    Science.gov (United States)

    Dumbovic, M.; Temmer, M.

    2017-12-01

    Identification and tracking of interplanetary coronal mass ejections (ICMEs) throughout the heliosphere is a growingly important aspect of space weather research. One of the "signatures" of ICME passage is the corresponding Forbush decrease (FD), a short term decrease in the galactic cosmic ray flux. These depressions are observed at the surface of the Earth for over 50 years, by several spacecraft in interplanetary space in the past couple of decades, and recently also on Mars' surface with Curiosity rover. In order to use FDs as ICME signatures efficiently, it is important to model ICME interaction with energetic particles by taking into account ICME evolution and constraining the model with observational data. We present an analytical diffusion-expansion FD model ForbMod which is based on the widely used approach of the initially empty, closed magnetic structure (i.e. flux rope) which fills up slowly with particles by perpendicular diffusion. The model is restricted to explain only the depression caused by the magnetic structure of the ICME and not of the associated shock. We use remote CME observations and a 3D reconstruction method (the Graduated Cylindrical Shell method) to constrain initial and boundary conditions of the FD model and take into account CME evolutionary properties by incorporating flux rope expansion. Several options of flux rope expansion are regarded as the competing mechanism to diffusion which can lead to different FD characteristics. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 745782.

  18. Local and Remote Postconditioning Decrease Intestinal Injury in a Rabbit Ischemia/Reperfusion Model

    Directory of Open Access Journals (Sweden)

    Mu Yang

    2016-01-01

    Full Text Available Intestinal ischemia/reperfusion (I/R injury is a significant problem that is associated with high morbidity and mortality in critical settings. This injury may be ameliorated using postconditioning protocol. In our study, we created a rabbit intestinal I/R injury model to analyze the effects of local ischemia postconditioning (LIPo and remote ischemia postconditioning (RIPo on intestinal I/R injury. We concluded that LIPo affords protection in intestinal I/R injury in a comparable fashion with RIPo by decreasing oxidative stress, neutrophil activation, and apoptosis.

  19. Ischemic femoral head osteonecrosis in a piglet model causes three dimensional decrease in acetabular coverage.

    Science.gov (United States)

    Upasani, Vidyadhar V; Jeffords, Megan E; Farnsworth, Christine L; Padilla, David; Lopreiato, Nick; Aruwajoye, Olumide O; Kim, Harry K W

    2017-09-15

    Legg-Calve-Perthes disease (LCPD) is a childhood form of ischemic osteonecrosis marked by development of severe femoral head deformity and premature osteoarthritis. The pathogenesis of femoral head deformity has been studied extensively using a piglet model of ischemic osteonecrosis, however, accompanying acetabular changes have not been investigated. The purpose of this study was to determine if acetabular changes accompany femoral head deformity in a well-established piglet model of LCPD and to define the acetabular changes using three dimensional computed tomography (3-D CT) and modeling. Twenty-four piglets were surgically induced with ischemic osteonecrosis on the right side. The contralateral hip was used as control. At 8 weeks postoperative, pelvi were retrieved and imaged with CT. Custom software was used to measure acetabular morphologic parameters on 3-D CT images. Moderate to severe femoral head deformities were present in all animals. Acetabula with accompanying femoral head deformity had a significant decrease in acetabular version and tilt (p femoral head deformity following ischemic osteonecrosis produces specific and predictable changes to the shape of the acetabulum. Acetabular changes described in patients with LCPD were observed in the piglet model. This model may serve as a valuable tool to elucidate the relationship between femoral head and acetabular deformities. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  20. Classifying multi-model wheat yield impact response surfaces showing sensitivity to temperature and precipitation change

    NARCIS (Netherlands)

    Fronzek, Stefan; Pirttioja, Nina; Carter, Timothy R.; Bindi, Marco; Hoffmann, Holger; Palosuo, Taru; Ruiz-Ramos, Margarita; Tao, Fulu; Trnka, Miroslav; Acutis, Marco; Asseng, Senthold; Baranowski, Piotr; Basso, Bruno; Bodin, Per; Buis, Samuel; Cammarano, Davide; Deligios, Paola; Destain, Marie France; Dumont, Benjamin; Ewert, Frank; Ferrise, Roberto; François, Louis; Gaiser, Thomas; Hlavinka, Petr; Jacquemin, Ingrid; Kersebaum, Kurt Christian; Kollas, Chris; Krzyszczak, Jaromir; Lorite, Ignacio J.; Minet, Julien; Minguez, M.I.; Montesino, Manuel; Moriondo, Marco; Müller, Christoph; Nendel, Claas; Öztürk, Isik; Perego, Alessia; Rodríguez, Alfredo; Ruane, Alex C.; Ruget, Françoise; Sanna, Mattia; Semenov, Mikhail A.; Slawinski, Cezary; Stratonovitch, Pierre; Supit, Iwan; Waha, Katharina; Wang, Enli; Wu, Lianhai; Zhao, Zhigan; Rötter, Reimund P.

    2018-01-01

    Crop growth simulation models can differ greatly in their treatment of key processes and hence in their response to environmental conditions. Here, we used an ensemble of 26 process-based wheat models applied at sites across a European transect to compare their sensitivity to changes in

  1. Classifying multi-model wheat yield impact response surfaces showing sensitivity to temperature and precipitation change

    Czech Academy of Sciences Publication Activity Database

    Fronzek, S.; Pirttioja, N. K.; Carter, T. R.; Bindi, M.; Hoffmann, H.; Palosuo, T.; Ruiz-Ramos, M.; Tao, F.; Trnka, Miroslav; Acutis, M.; Asseng, S.; Baranowski, P.; Basso, B.; Bodin, P.; Buis, S.; Cammarano, D.; Deligios, P.; Destain, M. F.; Dumont, B.; Ewert, F.; Ferrise, R.; Francois, L.; Gaiser, T.; Hlavinka, Petr; Jacquemin, I.; Kersebaum, K. C.; Kollas, C.; Krzyszczak, J.; Lorite, I. J.; Minet, J.; Ines Minguez, M.; Montesino, M.; Moriondo, M.; Mueller, C.; Nendel, C.; Öztürk, I.; Perego, A.; Rodriguez, A.; Ruane, A. C.; Ruget, F.; Sanna, M.; Semenov, M. A.; Slawinski, C.; Stratonovitch, P.; Supit, I.; Waha, K.; Wang, E.; Wu, L.; Zhao, Z.; Rötter, R.

    2018-01-01

    Roč. 159, jan (2018), s. 209-224 ISSN 0308-521X Keywords : climate-change * crop models * probabilistic assessment * simulating impacts * british catchments * uncertainty * europe * productivity * calibration * adaptation * Classification * Climate change * Crop model * Ensemble * Sensitivity analysis * Wheat Impact factor: 2.571, year: 2016

  2. Predictive Modeling of Influenza Shows the Promise of Applied Evolutionary Biology.

    Science.gov (United States)

    Morris, Dylan H; Gostic, Katelyn M; Pompei, Simone; Bedford, Trevor; Łuksza, Marta; Neher, Richard A; Grenfell, Bryan T; Lässig, Michael; McCauley, John W

    2018-02-01

    Seasonal influenza is controlled through vaccination campaigns. Evolution of influenza virus antigens means that vaccines must be updated to match novel strains, and vaccine effectiveness depends on the ability of scientists to predict nearly a year in advance which influenza variants will dominate in upcoming seasons. In this review, we highlight a promising new surveillance tool: predictive models. Based on data-sharing and close collaboration between the World Health Organization and academic scientists, these models use surveillance data to make quantitative predictions regarding influenza evolution. Predictive models demonstrate the potential of applied evolutionary biology to improve public health and disease control. We review the state of influenza predictive modeling and discuss next steps and recommendations to ensure that these models deliver upon their considerable biomedical promise. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. An EMG-driven biomechanical model that accounts for the decrease in moment generation capacity during a dynamic fatigued condition.

    Science.gov (United States)

    Rao, Guillaume; Berton, Eric; Amarantini, David; Vigouroux, Laurent; Buchanan, Thomas S

    2010-07-01

    Although it is well known that fatigue can greatly reduce muscle forces, it is not generally included in biomechanical models. The aim of the present study was to develop an electromyographic-driven (EMG-driven) biomechanical model to estimate the contributions of flexor and extensor muscle groups to the net joint moment during a nonisokinetic functional movement (squat exercise) performed in nonfatigued and in fatigued conditions. A methodology that aims at balancing the decreased muscle moment production capacity following fatigue was developed. During an isometric fatigue session, a linear regression was created linking the decrease in force production capacity of the muscle (normalized force/EMG ratio) to the EMG mean frequency. Using the decrease in mean frequency estimated through wavelet transforms between dynamic squats performed before and after the fatigue session as input to the previous linear regression, a coefficient accounting for the presence of fatigue in the quadriceps group was computed. This coefficient was used to constrain the moment production capacity of the fatigued muscle group within an EMG-driven optimization model dedicated to estimate the contributions of the knee flexor and extensor muscle groups to the net joint moment. During squats, our results showed significant increases in the EMG amplitudes with fatigue (+23.27% in average) while the outputs of the EMG-driven model were similar. The modifications of the EMG amplitudes following fatigue were successfully taken into account while estimating the contributions of the flexor and extensor muscle groups to the net joint moment. These results demonstrated that the new procedure was able to estimate the decrease in moment production capacity of the fatigued muscle group.

  4. Meteorological conditions associated to high sublimation amounts in semiarid high-elevation Andes decrease the performance of empirical melt models

    Science.gov (United States)

    Ayala, Alvaro; Pellicciotti, Francesca; MacDonell, Shelley; McPhee, James; Burlando, Paolo

    2015-04-01

    Empirical melt (EM) models are often preferred to surface energy balance (SEB) models to calculate melt amounts of snow and ice in hydrological modelling of high-elevation catchments. The most common reasons to support this decision are that, in comparison to SEB models, EM models require lower levels of meteorological data, complexity and computational costs. However, EM models assume that melt can be characterized by means of a few index variables only, and their results strongly depend on the transferability in space and time of the calibrated empirical parameters. In addition, they are intrinsically limited in accounting for specific process components, the complexity of which cannot be easily reconciled with the empirical nature of the model. As an example of an EM model, in this study we use the Enhanced Temperature Index (ETI) model, which calculates melt amounts using air temperature and the shortwave radiation balance as index variables. We evaluate the performance of the ETI model on dry high-elevation sites where sublimation amounts - that are not explicitly accounted for the EM model - represent a relevant percentage of total ablation (1.1 to 8.7%). We analyse a data set of four Automatic Weather Stations (AWS), which were collected during the ablation season 2013-14, at elevations between 3466 and 4775 m asl, on the glaciers El Tapado, San Francisco, Bello and El Yeso, which are located in the semiarid Andes of central Chile. We complement our analysis using data from past studies in Juncal Norte Glacier (Chile) and Haut Glacier d'Arolla (Switzerland), during the ablation seasons 2008-09 and 2006, respectively. We use the results of a SEB model, applied to each study site, along the entire season, to calibrate the ETI model. The ETI model was not designed to calculate sublimation amounts, however, results show that their ability is low also to simulate melt amounts at sites where sublimation represents larger percentages of total ablation. In fact, we

  5. Metabolic modeling of energy balances in Mycoplasma hyopneumoniae shows that pyruvate addition increases growth rate.

    Science.gov (United States)

    Kamminga, Tjerko; Slagman, Simen-Jan; Bijlsma, Jetta J E; Martins Dos Santos, Vitor A P; Suarez-Diez, Maria; Schaap, Peter J

    2017-10-01

    Mycoplasma hyopneumoniae is cultured on large-scale to produce antigen for inactivated whole-cell vaccines against respiratory disease in pigs. However, the fastidious nutrient requirements of this minimal bacterium and the low growth rate make it challenging to reach sufficient biomass yield for antigen production. In this study, we sequenced the genome of M. hyopneumoniae strain 11 and constructed a high quality constraint-based genome-scale metabolic model of 284 chemical reactions and 298 metabolites. We validated the model with time-series data of duplicate fermentation cultures to aim for an integrated model describing the dynamic profiles measured in fermentations. The model predicted that 84% of cellular energy in a standard M. hyopneumoniae cultivation was used for non-growth associated maintenance and only 16% of cellular energy was used for growth and growth associated maintenance. Following a cycle of model-driven experimentation in dedicated fermentation experiments, we were able to increase the fraction of cellular energy used for growth through pyruvate addition to the medium. This increase in turn led to an increase in growth rate and a 2.3 times increase in the total biomass concentration reached after 3-4 days of fermentation, enhancing the productivity of the overall process. The model presented provides a solid basis to understand and further improve M. hyopneumoniae fermentation processes. Biotechnol. Bioeng. 2017;114: 2339-2347. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. The speed of memory errors shows the influence of misleading information: Testing the diffusion model and discrete-state models.

    Science.gov (United States)

    Starns, Jeffrey J; Dubé, Chad; Frelinger, Matthew E

    2018-05-01

    In this report, we evaluate single-item and forced-choice recognition memory for the same items and use the resulting accuracy and reaction time data to test the predictions of discrete-state and continuous models. For the single-item trials, participants saw a word and indicated whether or not it was studied on a previous list. The forced-choice trials had one studied and one non-studied word that both appeared in the earlier single-item trials and both received the same response. Thus, forced-choice trials always had one word with a previous correct response and one with a previous error. Participants were asked to select the studied word regardless of whether they previously called both words "studied" or "not studied." The diffusion model predicts that forced-choice accuracy should be lower when the word with a previous error had a fast versus a slow single-item RT, because fast errors are associated with more compelling misleading memory retrieval. The two-high-threshold (2HT) model does not share this prediction because all errors are guesses, so error RT is not related to memory strength. A low-threshold version of the discrete state approach predicts an effect similar to the diffusion model, because errors are a mixture of responses based on misleading retrieval and guesses, and the guesses should tend to be slower. Results showed that faster single-trial errors were associated with lower forced-choice accuracy, as predicted by the diffusion and low-threshold models. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Zebrafish (Danio rerio) as a model for the study of aging and exercise: physical ability and trainability decrease with age.

    Science.gov (United States)

    Gilbert, Matthew J H; Zerulla, Tanja C; Tierney, Keith B

    2014-02-01

    A rapidly aging global population has motivated the development and use of models for human aging. Studies on aging have shown parallels between zebrafish and humans at the internal organization level; however, few parallels have been studied at the whole-organism level. Furthermore, the effectiveness of exercise as a method to mitigate the effects of aging has not been studied in zebrafish. We investigated the effects of aging and intermittent exercise on swimming performance, kinematics and behavior. Young, middle-aged and old zebrafish (20-29, 36-48 and 60-71% of average lifespan, respectively) were exercised to exhaustion in endurance and sprint swimming tests once a week for four weeks. Both endurance and sprint performance decreased with increased age. Swimming performance improved with exercise training in young and middle-aged zebrafish, but not in old zebrafish. Tail-beat amplitude, which is akin to stride length in humans, increased for all age groups with training. Zebrafish turning frequency, which is an indicator of routine activity, decreased with age but showed no change with exercise. In sum, our results show that zebrafish exhibit a decline in whole-organism performance and trainability with age. These findings closely resemble the senescence-related declines in physical ability experienced by humans and mammalian aging models and therefore support the use of zebrafish as a model for human exercise and aging. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Modeling a Conventional Electroporation Pulse Train: Decreased Pore Number, Cumulative Calcium Transport and an Example of Electrosensitization.

    Science.gov (United States)

    Son, Reuben S; Gowrishankar, Thiruvallur R; Smith, Kyle C; Weaver, James C

    2016-03-01

    Pulse trains are widely used in electroporation (EP) for both general biomedical research and clinical applications such as nonthermal tumor ablation. Here we use a computational method based on a meshed transport network to investigate a cell system model's response to a train of identical, evenly spaced electric field pulses. We obtain an unexpected result: the number of membrane pores decreases during the application of twenty 1.0 kV/cm, 100 μs pulses, delivered at 1 Hz. This pulse train initially creates 13,000 membrane pores, but pore number decreases by a factor of 15 to about 830 pores throughout subsequent pulses. We conclude that pore number can greatly diminish during a train of identical pulses, with direct consequences for the transport of solutes across an electroporated membrane. Although application of additional pulses is generally intended to increase the effects of EP, we show that these pulses do not significantly enhance calcium delivery into the cell. Instead, calcium delivery can be significantly increased by varying inter-pulse intervals. We show that inserting a 300-s interruption midway in a widely used eight-pulse train (a protocol for electrosensitization) yields a ∼ twofold delivery increase. Overall, our modeling shows support for electrosensitization, in which multiple pulse protocols that maximize pore number over time can yield significant increase of transport of calcium compared to standard pulse trains.

  9. Simple solvable energy-landscape model that shows a thermodynamic phase transition and a glass transition.

    Science.gov (United States)

    Naumis, Gerardo G

    2012-06-01

    When a liquid melt is cooled, a glass or phase transition can be obtained depending on the cooling rate. Yet, this behavior has not been clearly captured in energy-landscape models. Here, a model is provided in which two key ingredients are considered in the landscape, metastable states and their multiplicity. Metastable states are considered as in two level system models. However, their multiplicity and topology allows a phase transition in the thermodynamic limit for slow cooling, while a transition to the glass is obtained for fast cooling. By solving the corresponding master equation, the minimal speed of cooling required to produce the glass is obtained as a function of the distribution of metastable states.

  10. Modeled hydrologic metrics show links between hydrology and the functional composition of stream assemblages.

    Science.gov (United States)

    Patrick, Christopher J; Yuan, Lester L

    2017-07-01

    Flow alteration is widespread in streams, but current understanding of the effects of differences in flow characteristics on stream biological communities is incomplete. We tested hypotheses about the effect of variation in hydrology on stream communities by using generalized additive models to relate watershed information to the values of different flow metrics at gauged sites. Flow models accounted for 54-80% of the spatial variation in flow metric values among gauged sites. We then used these models to predict flow metrics in 842 ungauged stream sites in the mid-Atlantic United States that were sampled for fish, macroinvertebrates, and environmental covariates. Fish and macroinvertebrate assemblages were characterized in terms of a suite of metrics that quantified aspects of community composition, diversity, and functional traits that were expected to be associated with differences in flow characteristics. We related modeled flow metrics to biological metrics in a series of stressor-response models. Our analyses identified both drying and base flow instability as explaining 30-50% of the observed variability in fish and invertebrate community composition. Variations in community composition were related to variations in the prevalence of dispersal traits in invertebrates and trophic guilds in fish. The results demonstrate that we can use statistical models to predict hydrologic conditions at bioassessment sites, which, in turn, we can use to estimate relationships between flow conditions and biological characteristics. This analysis provides an approach to quantify the effects of spatial variation in flow metrics using readily available biomonitoring data. © 2017 by the Ecological Society of America.

  11. Downscaling CMIP5 climate models shows increased tropical cyclone activity over the 21st century.

    Science.gov (United States)

    Emanuel, Kerry A

    2013-07-23

    A recently developed technique for simulating large [O(10(4))] numbers of tropical cyclones in climate states described by global gridded data is applied to simulations of historical and future climate states simulated by six Coupled Model Intercomparison Project 5 (CMIP5) global climate models. Tropical cyclones downscaled from the climate of the period 1950-2005 are compared with those of the 21st century in simulations that stipulate that the radiative forcing from greenhouse gases increases by over preindustrial values. In contrast to storms that appear explicitly in most global models, the frequency of downscaled tropical cyclones increases during the 21st century in most locations. The intensity of such storms, as measured by their maximum wind speeds, also increases, in agreement with previous results. Increases in tropical cyclone activity are most prominent in the western North Pacific, but are evident in other regions except for the southwestern Pacific. The increased frequency of events is consistent with increases in a genesis potential index based on monthly mean global model output. These results are compared and contrasted with other inferences concerning the effect of global warming on tropical cyclones.

  12. Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model.

    Directory of Open Access Journals (Sweden)

    Laure B Bindels

    Full Text Available The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl, characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay. These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle.

  13. Retinoic acid decreases the severity of Salmonella enterica serovar Typhimurium mediated gastroenteritis in a mouse model.

    Science.gov (United States)

    Sinha, Ritam; Howlader, Debaki Ranjan; Mukherjee, Priyadarshini; Rai, Sulabh; Nag, Dhrubajyoti; Koley, Hemanta

    2016-07-01

    Gastroenteritis is a global burden; it's the major cause of morbidity and mortality both in adults and children of developing countries. Salmonella is one of the leading causes of bacteria-mediated gastroenteritis and due to its increasing multidrug antibiotic resistance; Salmonella-mediated gastroenteritis is difficult to control. Retinoic acid, the biologically active agent of vitamin A has an anti-inflammatory effect on experimental colitis. In this study we have shown All trans retinoic acid (ATRA) treatment down regulates Salmonella-mediated colitis in a murine model. Macroscopic signs of inflammation such as decrease in body weight and cecum weight, shorter length of proximal colon and pathological score of colitis were observed less in ATRA treated mice than in a vehicle control group. ATRA treatment not only reduced pro-inflammatory cytokine responses, such as TNF-α, IL-6, IL-1β, IFN-γ and IL-17 production but also increased IL-10 response in the supernatant of intestinal tissue. Results also suggested that ATRA treatment enhances the number of FoxP3-expressing T regulatory cells in MLN and also decreases bacterial load in systemic organs. We concluded that ATRA treatment indeed reduces Salmonella Typhimurium-mediated gastroenteritis in mice, suggesting it could be an important part of an alternative therapeutic approach to combat the disease. Copyright © 2016 Elsevier GmbH. All rights reserved.

  14. Polygonum multiflorum Decreases Airway Allergic Symptoms in a Murine Model of Asthma.

    Science.gov (United States)

    Lee, Chen-Chen; Lee, Yueh-Lun; Wang, Chien-N; Tsai, Hsing-Chuan; Chiu, Chun-Lung; Liu, Leroy F; Lin, Hung-Yun; Wu, Reen

    2016-01-01

    The root of Polygonum multiflorum (also called He-Shou-Wu in Chinese) is a common herb and medicinal food in Asia used for its anti-aging properties. Our study investigated the therapeutic potential of an extract of the root of Polygonum multiflorum (PME) in allergic asthma by using a mouse model. Feeding of 0.5 and 1 mg/mouse PME inhibited ovalbumin (OVA)-induced allergic asthma symptoms, including airway inflammation, mucus production, and airway hyper-responsiveness (AHR), in a dose-dependent manner. To discern PME's mechanism of action, we examined the profile and cytokine production of inflammatory cells in bronchial alveolar lavage fluid (BALF). We found that eosinophils, the main inflammatory cell infiltrate in the lung of OVA-immunized mice, significantly decreased after PME treatment. Th2 cytokine levels, including interleukin (IL)-4, IL-5, IL-13, eotaxin, and the proinflammatory cytokine tumor necrosis factor (TNF)-[Formula: see text], decreased in PME-treated mice. Elevated mRNA expression of Th2 transcription factor GATA-3 in the lung tissue was also inhibited after oral feeding of PME in OVA-immunized mice. Thus, we conclude that PME produces anti-asthma activity through the inhibition of Th2 cell activation.

  15. The decrease of carbonation efficiency of CaO along calcination-carbonation cycles: Experiments and modelling

    Energy Technology Data Exchange (ETDEWEB)

    Bouquet, E.; Leyssens, G.; Schonnenbeck, C.; Gilot, P. [Laboratoire de Gestion des Risques et Environnement, Mulhouse (France)

    2009-05-15

    Successive calcination-carbonation cycles, using CaO as sorbent, have been performed either in a classical fixed bed reactor or using a thermogravimetric analyser. Significant differences in carbonation efficiencies were obtained, possibly due to different conditions prevailing for CaO sintering during the calcination stage. The effect of the presence of CO{sub 2} on sintering was confirmed. A simple model of the decay of the carbonation capacity along cycles based on the specific surface area of non-sintered micrograins of CaO is able to predict the decrease of the extent of conversion obtained after 40 carbonations along calcination-carbonation cycles. The asymptotic extent of conversion is obtained when all the micrograins present within a grain are sintered. A detailed model of the carbonation shows that the voids present between the micrograins are filled up by carbonate when a critical thickness of the carbonate layer around each micrograin reaches 43 nm. Then, carbonation becomes controlled by diffusion at the scale of the whole grain, with the CO{sub 2} diffusion coefficient decreasing (at 650 {sup o}C) from 2 x 10{sup -12} to 6.5 x 10{sup -14} m{sup 2}/s as carbonation proceeds from 50% conversion to 76% (first cycle). This scale change for diffusion is responsible for the drastic decrease of the carbonation rate after the voids between micrograins are filled up.

  16. Animal Models for Muscular Dystrophy Show Different Patterns of Sarcolemmal Disruption

    OpenAIRE

    Straub, Volker; Rafael, Jill A.; Chamberlain, Jeffrey S.; Campbell, Kevin P.

    1997-01-01

    Genetic defects in a number of components of the dystrophin–glycoprotein complex (DGC) lead to distinct forms of muscular dystrophy. However, little is known about how alterations in the DGC are manifested in the pathophysiology present in dystrophic muscle tissue. One hypothesis is that the DGC protects the sarcolemma from contraction-induced damage. Using tracer molecules, we compared sarcolemmal integrity in animal models for muscular dystrophy and in muscular dystrophy patient samples. Ev...

  17. The PROMETHEUS bundled payment experiment: slow start shows problems in implementing new payment models.

    Science.gov (United States)

    Hussey, Peter S; Ridgely, M Susan; Rosenthal, Meredith B

    2011-11-01

    Fee-for-service payment is blamed for many of the problems observed in the US health care system. One of the leading alternative payment models proposed in the Affordable Care Act of 2010 is bundled payment, which provides payment for all of the care a patient needs over the course of a defined clinical episode, instead of paying for each discrete service. We evaluated the initial "road test" of PROMETHEUS Payment, one of several bundled payment pilot projects. The project has faced substantial implementation challenges, and none of the three pilot sites had executed contracts or made bundled payments as of May 2011. The pilots have taken longer to set up than expected, primarily because of the complexity of the payment model and the fact that it builds on the existing fee-for-service payment system and other complexities of health care. Participants continue to see promise and value in the bundled payment model, but the pilot results suggest that the desired benefits of this and other payment reforms may take time and considerable effort to materialize.

  18. A Murine Model of Candida glabrata Vaginitis Shows No Evidence of an Inflammatory Immunopathogenic Response.

    Directory of Open Access Journals (Sweden)

    Evelyn E Nash

    Full Text Available Candida glabrata is the second most common organism isolated from women with vulvovaginal candidiasis (VVC, particularly in women with uncontrolled diabetes mellitus. However, mechanisms involved in the pathogenesis of C. glabrata-associated VVC are unknown and have not been studied at any depth in animal models. The objective of this study was to evaluate host responses to infection following efforts to optimize a murine model of C. glabrata VVC. For this, various designs were evaluated for consistent experimental vaginal colonization (i.e., type 1 and type 2 diabetic mice, exogenous estrogen, varying inocula, and co-infection with C. albicans. Upon model optimization, vaginal fungal burden and polymorphonuclear neutrophil (PMN recruitment were assessed longitudinally over 21 days post-inoculation, together with vaginal concentrations of IL-1β, S100A8 alarmin, lactate dehydrogenase (LDH, and in vivo biofilm formation. Consistent and sustained vaginal colonization with C. glabrata was achieved in estrogenized streptozotocin-induced type 1 diabetic mice. Vaginal PMN infiltration was consistently low, with IL-1β, S100A8, and LDH concentrations similar to uninoculated mice. Biofilm formation was not detected in vivo, and co-infection with C. albicans did not induce synergistic immunopathogenic effects. This data suggests that experimental vaginal colonization of C. glabrata is not associated with an inflammatory immunopathogenic response or biofilm formation.

  19. Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation

    DEFF Research Database (Denmark)

    Cremer, Signe Emilie; Zois, Nora Elisabeth; Moesgaard, S. G.

    2015-01-01

    surgically induced MR or sham-operation, resulting in three MR groups: control (CON, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). The gene expression levels of 5-HT1BR, 5-HT2AR, 5-HT2BR, SERT and TPH-1 were analysed using quantitative PCR (qPCR) in the mitral valve (MV), anterior papillary......-uptake transporter (SERT) in MMVD-affected valves, increased valvular 5-HT synthesis and decreased clearance have been suggested. It remains unknown how haemodynamic changes associated with mitral regurgitation (MR) affect 5-HT markers in the mitral valve, myocardium and circulation. Twenty-eight pigs underwent...... muscle (AP) and left ventricle (LV). MV 5-HT2BR was also analysed with immunohistochemistry (IHC) in relation to histological lesions and valvular myofibroblasts. All 5-HTR mRNAs were up-regulated in MV compared to AP and LV (P SERT and TPH-1 were up-regulated in AP and LV compared...

  20. Increasing and decreasing motor and cognitive output: a model of general action and inaction goals.

    Science.gov (United States)

    Albarracín, Dolores; Handley, Ian M; Noguchi, Kenji; McCulloch, Kathleen C; Li, Hong; Leeper, Joshua; Brown, Rick D; Earl, Allison; Hart, William P

    2008-09-01

    General action and inaction goals can influence the amount of motor or cognitive output irrespective of the type of behavior in question, with the same stimuli producing trivial and important motor and cognitive manifestations normally viewed as parts of different systems. A series of experiments examined the effects of instilling general action and inaction goals using word primes, such as "action" and "rest." The first 5 experiments showed that the same stimuli influenced motor output, such as doodling on a piece of paper and eating, as well as cognitive output, such as recall and problem solving. The last 2 experiments supported the prediction that these diverse effects can result from the instigation of general action and inaction goals. Specifically, these last 2 studies confirmed that participants were motivated to achieve active or inactive states and that attaining them decreased the effects of the primes on behavior.

  1. Application of an artificial neural network model to predict delayed decrease of serum creatinine in pediatric patients after kidney transplantation.

    Science.gov (United States)

    Santori, G; Fontana, I; Valente, U

    2007-01-01

    Artificial neural network, a computer-based technology that uses nonlinear statistics to recognize the relationship between input variables and an output variable, has been previously applied to outcome prediction in adult kidney recipients. In this study, we evaluated the effectiveness of a neural network model to predict a delayed decrease of serum creatinine in pediatric kidney recipients. The neural network was constructed with a training set of pediatric kidney recipients (n = 107) by using 20 input variables and assuming for the output variable, the time after 3 days to reach a serum creatinine level 50% below that before kidney transplantation. In the final model, the following input variables showing higher predictive values were retained: serum creatinine on day 1 post transplant, urine volume in the first 24 hours, diagnostic category, pretransplant dialysis mode, patient sex, donor sex, body weight on day 1 posttransplant, and patient age. The model was validated in a second set of patients (n = 41) by blinding the network for the output variable. The overall accuracies of the neural network for the training set, the validation set, and the whole patient cohort were 89.1%, 76.92%, and 87.14%, respectively. A comparative logistic regression analysis revealed only serum creatinine on day 1 posttransplant to be an independent predictor for the output variable (overall accuracy: 79.05%). The neural network showed sensitivity and specificity for the whole patient cohort to be 0.875 and 0.87, respectively, whereas using logistic regression sensitivity and specificity yields 0.37 and 0.94, respectively. This study proposes a neural network model that seemed to predict a delayed decrease in serum creatinine among pediatric kidney recipients. The availability of the source code may allow development of stand-alone neural networks to validate our model in prospective studies.

  2. Global thermal niche models of two European grasses show high invasion risks in Antarctica.

    Science.gov (United States)

    Pertierra, Luis R; Aragón, Pedro; Shaw, Justine D; Bergstrom, Dana M; Terauds, Aleks; Olalla-Tárraga, Miguel Ángel

    2017-07-01

    The two non-native grasses that have established long-term populations in Antarctica (Poa pratensis and Poa annua) were studied from a global multidimensional thermal niche perspective to address the biological invasion risk to Antarctica. These two species exhibit contrasting introduction histories and reproductive strategies and represent two referential case studies of biological invasion processes. We used a multistep process with a range of species distribution modelling techniques (ecological niche factor analysis, multidimensional envelopes, distance/entropy algorithms) together with a suite of thermoclimatic variables, to characterize the potential ranges of these species. Their native bioclimatic thermal envelopes in Eurasia, together with the different naturalized populations across continents, were compared next. The potential niche of P. pratensis was wider at the cold extremes; however, P. annua life history attributes enable it to be a more successful colonizer. We observe that particularly cold summers are a key aspect of the unique Antarctic environment. In consequence, ruderals such as P. annua can quickly expand under such harsh conditions, whereas the more stress-tolerant P. pratensis endures and persist through steady growth. Compiled data on human pressure at the Antarctic Peninsula allowed us to provide site-specific biosecurity risk indicators. We conclude that several areas across the region are vulnerable to invasions from these and other similar species. This can only be visualized in species distribution models (SDMs) when accounting for founder populations that reveal nonanalogous conditions. Results reinforce the need for strict management practices to minimize introductions. Furthermore, our novel set of temperature-based bioclimatic GIS layers for ice-free terrestrial Antarctica provide a mechanism for regional and global species distribution models to be built for other potentially invasive species. © 2017 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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.

  4. Progesterone treatment shows benefit in a pediatric model of moderate to severe bilateral brain injury.

    Directory of Open Access Journals (Sweden)

    Rastafa I Geddes

    Full Text Available Controlled cortical impact (CCI models in adult and aged Sprague-Dawley (SD rats have been used extensively to study medial prefrontal cortex (mPFC injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury.Twenty-eight-day old (PND 28 male Sprague Dawley rats received sham (n = 24 or CCI (n = 47 injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight or vehicle injections on post-injury days (PID 1-7, subjected to behavioral testing from PID 9-27, and analyzed for lesion size at PID 28.The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats.Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits.

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

    Directory of Open Access Journals (Sweden)

    Daniel Komnig

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

  6. Analyzing the effect of decreasing cytosolic triosephosphate isomerase on Solanum tuberosum hairy root cells using a kinetic-metabolic model.

    Science.gov (United States)

    Valancin, Alexandre; Srinivasan, Balasubrahmanyan; Rivoal, Jean; Jolicoeur, Mario

    2013-03-01

    A kinetic-metabolic model of Solanum tuberosum hairy roots is presented in the interest of understanding the effect on the plant cell metabolism of a 90% decrease in cytosolic triosephosphate isomerase (cTPI, EC 5.3.1.1) expression by antisense RNA. The model considers major metabolic pathways including glycolysis, pentose phosphate pathway, and TCA cycle, as well as anabolic reactions leading to lipids, nucleic acids, amino acids, and structural hexoses synthesis. Measurements were taken from shake flask cultures for six extracellular nutrients (sucrose, fructose, glucose, ammonia, nitrate, and inorganic phosphate) and 15 intracellular compounds including sugar phosphates (G6P, F6P, R5P, E4P) and organic acids (PYR, aKG, SUCC, FUM, MAL) and the six nutrients. From model simulations and experimental data it can be noted that plant cell metabolism redistributes metabolic fluxes to compensate for the cTPI decrease, leading to modifications in metabolites levels. Antisense roots showed increased exchanges between the pentose phosphate pathway and the glycolysis, an increased oxygen uptake and growth rate. Copyright © 2012 Wiley Periodicals, Inc.

  7. Sclerostin Antibody Reverses Bone Loss by Increasing Bone Formation and Decreasing Bone Resorption in a Rat Model of Male Osteoporosis.

    Science.gov (United States)

    Li, Xiaodong; Ominsky, Michael S; Villasenor, Kelly S; Niu, Qing-Tian; Asuncion, Frank J; Xia, Xuechun; Grisanti, Mario; Wronski, Thomas J; Simonet, W Scott; Ke, Hua Zhu

    2018-01-01

    Sclerostin antibody (Scl-Ab) restored bone mass and strength in the ovariectomized rat model of postmenopausal osteoporosis. Increased bone mineral density (BMD) and decreased skeletal fragility fracture risk have been reported in postmenopausal osteoporotic women receiving Scl-Ab. In males, loss of androgen leads to rapid decreases in BMD and an increased risk of fragility fractures. We hypothesized that Scl-Ab could reverse the loss of bone mass and strength caused by androgen ablation in the orchiectomized (ORX) rat model of male osteoporosis. We treated 9-month-old ORX Sprague Dawley rats (3 months after ORX) subcutaneously twice weekly with vehicle or Scl-Ab (5 or 25 mg/kg) for 6 weeks (n = 10 per group). Both doses of Scl-Ab fully reversed the BMD deficit in the lumbar spine and femur and tibia in ORX rats. Microcomputed tomography showed that the bone mass in the fifth lumbar vertebral body, femur diaphysis, and femoral neck were dose-dependently restored by Scl-Ab. The bone strength at these sites increased significantly with Scl-Ab to levels matching those of sham-operated controls and correlated positively with improvements in bone mineral content, demonstrating bone quality maintenance. Dynamic histomorphometry of the tibial diaphysis and second lumbar vertebral body demonstrated that Scl-Ab significantly increased bone formation on periosteal, endocortical, and trabecular surfaces and significantly decreased bone resorption on endocortical and trabecular surfaces. The effects of Scl-Ab on increasing bone formation and decreasing bone resorption led to restoration of bone mass and strength in androgen-deficient rats. These findings support the ongoing evaluation of Scl-Ab as a potential therapeutic agent for osteoporosis in men. Copyright © 2018 Endocrine Society.

  8. Voluntary Running Attenuates Memory Loss, Decreases Neuropathological Changes and Induces Neurogenesis in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Tapia-Rojas, Cheril; Aranguiz, Florencia; Varela-Nallar, Lorena; Inestrosa, Nibaldo C

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by loss of memory and cognitive abilities, and the appearance of amyloid plaques composed of the amyloid-β peptide (Aβ) and neurofibrillary tangles formed of tau protein. It has been suggested that exercise might ameliorate the disease; here, we evaluated the effect of voluntary running on several aspects of AD including amyloid deposition, tau phosphorylation, inflammatory reaction, neurogenesis and spatial memory in the double transgenic APPswe/PS1ΔE9 mouse model of AD. We report that voluntary wheel running for 10 weeks decreased Aβ burden, Thioflavin-S-positive plaques and Aβ oligomers in the hippocampus. In addition, runner APPswe/PS1ΔE9 mice showed fewer phosphorylated tau protein and decreased astrogliosis evidenced by lower staining of GFAP. Further, runner APPswe/PS1ΔE9 mice showed increased number of neurons in the hippocampus and exhibited increased cell proliferation and generation of cells positive for the immature neuronal protein doublecortin, indicating that running increased neurogenesis. Finally, runner APPswe/PS1ΔE9 mice showed improved spatial memory performance in the Morris water maze. Altogether, our findings indicate that in APPswe/PS1ΔE9 mice, voluntary running reduced all the neuropathological hallmarks of AD studied, reduced neuronal loss, increased hippocampal neurogenesis and reduced spatial memory loss. These findings support that voluntary exercise might have therapeutic value on AD. © 2015 International Society of Neuropathology.

  9. Modeling serotonin uptake in the lung shows endothelial transporters dominate over cleft permeation

    Science.gov (United States)

    Bassingthwaighte, James B.

    2013-01-01

    A four-region (capillary plasma, endothelium, interstitial fluid, cell) multipath model was configured to describe the kinetics of blood-tissue exchange for small solutes in the lung, accounting for regional flow heterogeneity, permeation of cell membranes and through interendothelial clefts, and intracellular reactions. Serotonin uptake data from the Multiple indicator dilution “bolus sweep” experiments of Rickaby and coworkers (Rickaby DA, Linehan JH, Bronikowski TA, Dawson CA. J Appl Physiol 51: 405–414, 1981; Rickaby DA, Dawson CA, and Linehan JH. J Appl Physiol 56: 1170–1177, 1984) and Malcorps et al. (Malcorps CM, Dawson CA, Linehan JH, Bronikowski TA, Rickaby DA, Herman AG, Will JA. J Appl Physiol 57: 720–730, 1984) were analyzed to distinguish facilitated transport into the endothelial cells (EC) and the inhibition of tracer transport by nontracer serotonin in the bolus of injectate from the free uninhibited permeation through the clefts into the interstitial fluid space. The permeability-surface area products (PS) for serotonin via the inter-EC clefts were ∼0.3 ml·g−1·min−1, low compared with the transporter-mediated maximum PS of 13 ml·g−1·min−1 (with Km = ∼0.3 μM and Vmax = ∼4 nmol·g−1·min−1). The estimates of serotonin PS values for EC transporters from their multiple data sets were similar and were influenced only modestly by accounting for the cleft permeability in parallel. The cleft PS estimates in these Ringer-perfused lungs are less than half of those for anesthetized dogs (Yipintsoi T. Circ Res 39: 523–531, 1976) with normal hematocrits, but are compatible with passive noncarrier-mediated transport observed later in the same laboratory (Dawson CA, Linehan JH, Rickaby DA, Bronikowski TA. Ann Biomed Eng 15: 217–227, 1987; Peeters FAM, Bronikowski TA, Dawson CA, Linehan JH, Bult H, Herman AG. J Appl Physiol 66: 2328–2337, 1989) The identification and quantitation of the cleft pathway conductance from these

  10. Decreased tonic inhibition in cerebellar granule cells causes motor dysfunction in a mouse model of Angelman syndrome.

    Science.gov (United States)

    Egawa, Kiyoshi; Kitagawa, Kyoko; Inoue, Koichi; Takayama, Masakazu; Takayama, Chitoshi; Saitoh, Shinji; Kishino, Tatsuya; Kitagawa, Masatoshi; Fukuda, Atsuo

    2012-12-05

    Angelman syndrome is a neurodevelopmental disorder caused by loss of function of the UBE3A gene encoding a ubiquitin E3 ligase. Motor dysfunction is a characteristic feature of Angelman syndrome, but neither the mechanisms of action nor effective therapeutic strategies have yet been elucidated. We report that tonic inhibition is specifically decreased in cerebellar granule cells of Ube3a-deficient mice, a model of Angelman syndrome. As a mechanism underlying this decrease in tonic inhibition, we show that Ube3a controls degradation of γ-aminobutyric acid (GABA) transporter 1 (GAT1) and that deficiency of Ube3a induces a surplus of GAT1 that results in a decrease in GABA concentrations in the extrasynaptic space. Administering low doses of 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridin-3-ol (THIP), a selective extrasynaptic GABA(A) receptor agonist, improves the abnormal firing properties of a population of Purkinje cells in cerebellar brain slices and reduces cerebellar ataxia in Ube3a-deficient mice in vivo. These results suggest that pharmacologically increasing tonic inhibition may be a useful strategy for alleviating motor dysfunction in Angelman syndrome.

  11. Hyperglycemia decreases preoxiredoxin-2 expression in a middle cerebral artery occlusion model.

    Science.gov (United States)

    Koh, Phil-Ok

    2017-06-01

    Diabetes is a major risk factor for stroke and is also associated with worsened outcomes following a stroke. Peroxiredoxin-2 exerts potent neuroprotective effects against oxidative stress. In the present study, we identified altered peroxiredoxin-2 expression in an ischemic stroke model under hyperglycemic conditions. Adult male rats were administrated streptozotocin (40 mg/kg) via intraperitoneal injection to induce diabetes. Middle cerebral artery occlusion (MCAO) was induced surgically 4 weeks after streptozotocin treatment and cerebral cortex tissues were isolated 24 hours after MCAO. Peroxiredoxin-2 expression was evaluated in the cerebral cortex of MCAO-operated animals using a proteomics approach, and was found to be decreased. In addition, the reduction in peroxiredoxin-2 levels was more severe in cerebral ischemia with diabetes compared to animals without diabetes. Reverse-transcriptase PCR and Western blot analyses confirmed the significantly reduced peroxiredoxin-2 expression in MCAO-operated animals under hyperglycemic conditions. It is an accepted fact that peroxiredoxin-2 has antioxidative activity against ischemic injury. Thus, the findings of this study suggest that a more severe reduction in peroxiredoxin-2 under hyperglycemic conditions leads to worsened brain damage during cerebral ischemia with diabetes.

  12. The RESET Mindset Model applied on decreasing antibiotic usage in dairy cattle in the Netherlands

    OpenAIRE

    Lam, T. J. G. M.; Wessels, R. J.; Jansen, Jolanda

    2017-01-01

    BACKGROUND: Prudent use of antibiotics is important to prevent antibiotic resistance in humans and in animals. For this reason politicians demanded a decrease of total antibiotic use and of use of critically important antibiotics in animal husbandry in the Netherlands. In the dairy sector the use of antibiotics almost halved in the years 2009-2015, with a decrease of the use of critically important antibiotics to very low levels. THEORY OF BEHAVIOUR CHANGE: To realize a sustainable decrease i...

  13. Magnesium sulfate treatment reverses seizure susceptibility and decreases neuroinflammation in a rat model of severe preeclampsia.

    Directory of Open Access Journals (Sweden)

    Abbie Chapman Johnson

    Full Text Available Eclampsia, defined as unexplained seizure in a woman with preeclampsia, is a life-threatening complication of pregnancy with unclear etiology. Magnesium sulfate (MgSO4 is the leading eclamptic seizure prophylactic, yet its mechanism of action remains unclear. Here, we hypothesized severe preeclampsia is a state of increased seizure susceptibility due to blood-brain barrier (BBB disruption and neuroinflammation that lowers seizure threshold. Further, MgSO4 decreases seizure susceptibility by protecting the BBB and preventing neuroinflammation. To model severe preeclampsia, placental ischemia (reduced uteroplacental perfusion pressure; RUPP was combined with a high cholesterol diet (HC to cause maternal endothelial dysfunction. RUPP+HC rats developed symptoms associated with severe preeclampsia, including hypertension, oxidative stress, endothelial dysfunction and fetal and placental growth restriction. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ; mg/kg required to elicit seizure in RUPP + HC ± MgSO4 and compared to normal pregnant controls (n = 6/group; gestational day 20. RUPP+HC rats were more sensitive to PTZ with seizure threshold being ∼ 65% lower vs. control (12.4 ± 1.7 vs. 36.7 ± 3.9 mg/kg PTZ; p<0.05 that was reversed by MgSO4 (45.7 ± 8.7 mg/kg PTZ; p<0.05 vs. RUPP+HC. BBB permeability to sodium fluorescein, measured in-vivo (n = 5-7/group, was increased in RUPP+HC vs. control rats, with more tracer passing into the brain (15.9 ± 1.0 vs. 12.2 ± 0.3 counts/gram ×1000; p<0.05 and was unaffected by MgSO4 (15.6 ± 1.0 counts/gram ×1000; p<0.05 vs. controls. In addition, RUPP+HC rats were in a state of neuroinflammation, indicated by 35 ± 2% of microglia being active compared to 9 ± 2% in normal pregnancy (p<0.01; n = 3-8/group. MgSO4 treatment reversed neuroinflammation, reducing microglial activation to 6 ± 2% (p<0.01 vs. RUPP+HC. Overall, RUPP+HC rats were in a state of augmented

  14. 14 Days of supplementation with blueberry extract shows anti-atherogenic properties and improves oxidative parameters in hypercholesterolemic rats model.

    Science.gov (United States)

    Ströher, Deise Jaqueline; Escobar Piccoli, Jacqueline da Costa; Güllich, Angélica Aparecida da Costa; Pilar, Bruna Cocco; Coelho, Ritiéle Pinto; Bruno, Jamila Benvegnú; Faoro, Debora; Manfredini, Vanusa

    2015-01-01

    The effects of supplementation with blueberry (BE) extract (Vaccinium ashei Reade) for 14 consecutive days on biochemical, hematological, histopathological and oxidative parameters in hypercholesterolemic rats were investigated. After supplementation with lyophilized extract of BE, the levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides were decreased. Histopathological analysis showed significant decrease (p < 0.05) of aortic lesions in hypercholesterolemic rats. Oxidative parameters showed significant reductions (p < 0.05) in oxidative damage to lipids and proteins and an increase in activities of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase. The BE extract showed an important cardioprotective effect by the improvements in the serum lipid profile, antioxidant system, particularly in reducing oxidative stress associated with hypercholesterolemia and anti-atherogenic effect in rats.

  15. KEEFEKTIFAN MODEL SHOW NOT TELL DAN MIND MAP PADA PEMBELAJARAN MENULIS TEKS EKSPOSISI BERDASARKAN MINAT PESERTA DIDIK KELAS X SMK

    Directory of Open Access Journals (Sweden)

    Wiwit Lili Sokhipah

    2015-03-01

    Full Text Available Tujuan penelitian ini adalah (1 menentukan keefektifan penggunaan model show not tell pada pembelajaran keterampilan menulis teks eksposisi berdasarkan minat peserta didik SMK Kelas X, (2 menentukan keefektifan penggunaan model mind map pada pembelajaran keterampilan menulis teks eksposisi berdasarkan minat peserta didik SMK kelas X, (3 menentukan keefektifan interaksi show not tell dan mind map pada pembelajaran keterampilan menulis teks eksposisi berdasarkan minat peserta didik SMK kelas X. Penelitian ini adalah quasi experimental design (pretes-postes control group design. Dalam desain ini terdapat dua kelompok eksperimen yakni penerapan model show not tell dalam pembelajaran keterampilan menulis teks eksposisipeserta didik dengan minat tinggi dan penerapan model mind map dalam pembelajaran keterampilan menulis teks eksposisi  peserta didik dengan minat rendah. Hasil penelitian adalah (1 model show not tell efektif digunakan  dalam membelajarkan menulis teks eksposisi bagi peserta didik yang memiliki minat tinggi, (2 model mind map efektif digunakan dalam membelajarkan menulis teks eksposisi bagi peserta didik yang memiliki minat rendah, dan (3 model show not tell lebih efektif digunakan dalam membelajarkan menulis teks eksposisi bagi peserta didik yang memiliki minat tinggi, sedangkan model mind map efektif digunakan dalam membelajarkan teks eksposisi pagi peserta didik yang memiliki minat rendah.

  16. Paeoniflorin improves cardiac function and decreases adverse postinfarction left ventricular remodeling in a rat model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Chen H

    2018-04-01

    Full Text Available Hengwen Chen,* Yan Dong,* Xuanhui He, Jun Li, Jie Wang Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China *These authors contributed equally to this work Background: Paeoniflorin (PF is the active component of Paeonia lactiflora Pall. or Paeonia veitchii Lynch. This study was, therefore, aimed to evaluate the improvement and mechanism of the PF on ventricular remodeling in rats with acute myocardial infarction (AMI. Materials and methods: In this study, AMI model was established by ligating the anterior descending coronary artery in Wistar rats. After 4 weeks gavage of PF, the apparent signs and the left ventricle weight index of Wistar rats were observed. The left ventricular ejection fraction (LVEF was evaluated by Doppler ultrasonography. Changes in cardiac morphology were observed by pathologic examination, and apoptosis was observed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, enzyme-linked immunosorbent assay was used to detect the expression of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6 interleukin-10 (IL-10 and brain natriuretic peptide (BNP. Immunohistochemistry and Western blot method were applied to detect Caspase-3 and Caspase-9. Results: Compared with the model control, the survival conditions of rats in all treatment groups were generally improved after PF treatment. LVEF was significantly increased, and both left ventricular end-diastolic inner diameter and left ventricular end-systolic inner diameter were significantly reduced. Moreover, pathologic examination showed that the myocardium degeneration of the rats treated with PF was decreased, including neater arrangement, more complete myofilament, more uniform gap and less interstitial collagen fibers. Furthermore, the mitochondrial structure of cardiomyocytes was significantly improved. The ultrastructure was clear, and the arrangement of myofilament was more regular. Also, the expression of

  17. PA-X protein decreases replication and pathogenicity of swine influenza virus in cultured cells and mouse models.

    Science.gov (United States)

    Gong, Xiao-Qian; Sun, Ying-Feng; Ruan, Bao-Yang; Liu, Xiao-Min; Wang, Qi; Yang, Hai-Ming; Wang, Shuai-Yong; Zhang, Peng; Wang, Xiu-Hui; Shan, Tong-Ling; Tong, Wu; Zhou, Yan-Jun; Li, Guo-Xin; Zheng, Hao; Tong, Guang-Zhi; Yu, Hai

    2017-06-01

    Swine influenza viruses have been circulating in pigs throughout world and might be potential threats to human health. PA-X protein is a newly discovered protein produced from the PA gene by ribosomal frameshifting and the effects of PA-X on the 1918 H1N1, the pandemic 2009 H1N1, the highly pathogenic avian H5N1 and the avian H9N2 influenza viruses have been reported. However, the role of PA-X in the pathogenesis of swine influenza virus is still unknown. In this study, we rescued the H1N1 wild-type (WT) classical swine influenza virus (A/Swine/Guangdong/1/2011 (H1N1)) and H1N1 PA-X deficient virus containing mutations at the frameshift motif, and compared their replication properties and pathogenicity of swine influenza virus in vitro and in vivo. Our results show that the expression of PA-X inhibits virus replication and polymerase activity in cultured cells and decreases virulence in mouse models. Therefore, our study demonstrates that PA-X protein acts as a negative virulence regulator for classical H1N1 swine influenza virus and decreases virulence by inhibiting viral replication and polymerase activity, deepening our understanding of the pathogenesis of swine influenza virus. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Cystatin C deficiency suppresses tumor growth in a breast cancer model through decreased proliferation of tumor cells.

    Science.gov (United States)

    Završnik, Janja; Butinar, Miha; Prebanda, Mojca Trstenjak; Krajnc, Aleksander; Vidmar, Robert; Fonović, Marko; Grubb, Anders; Turk, Vito; Turk, Boris; Vasiljeva, Olga

    2017-09-26

    Cysteine cathepsins are proteases that, in addition to their important physiological functions, have been associated with multiple pathologies, including cancer. Cystatin C (CstC) is a major endogenous inhibitor that regulates the extracellular activity of cysteine cathepsins. We investigated the role of cystatin C in mammary cancer using CstC knockout mice and a mouse model of breast cancer induced by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium. We showed that the ablation of CstC reduced the rate of mammary tumor growth. Notably, a decrease in the proliferation of CstC knockout PyMT tumor cells was demonstrated ex vivo and in vitro , indicating a role for this protease inhibitor in signaling pathways that control cell proliferation. An increase in phosphorylated p-38 was observed in CstC knockout tumors, suggesting a novel function for cystatin C in cancer development, independent of the TGF-β pathway. Moreover, proteomic analysis of the CstC wild-type and knockout PyMT primary cell secretomes revealed a decrease in the levels of 14-3-3 proteins in the secretome of knock-out cells, suggesting a novel link between cysteine cathepsins, cystatin C and 14-3-3 proteins in tumorigenesis, calling for further investigations.

  19. Decrease of serum adenine nucleotide hydrolysis in an irritant contact dermatitis mice model: potential P2X7R involvement.

    Science.gov (United States)

    Zanin, R F; da Silva, G L; Erig, T; Sperotto, N D M; Leite, C E; Coutinho-Silva, R; Batastini, A M O; Morrone, Fernanda Bueno

    2015-06-01

    Extracellular adenosine 5'-triphosphate (ATP) has significant effects on a variety of pathological conditions and it is the main physiological agonist of P2X7 purinergic receptor (P2X7R). It is known that ATP acting via purinergic receptors plays a relevant role on skin inflammation, and P2X7R is required to neutrophil recruitment in a mice model of irritant contact dermatitis (ICD).The present study investigated the effects of chemical irritant croton oil (CrO) upon ATP, ADP, and AMP hydrolysis in mice blood serum, and the potential involvement of P2X7R. The topical application CrO induced a decrease on soluble ATP/ADPase activities (~50 %), and the treatment with the selective P2X7R antagonist, A438079, reversed these effects to control level. Furthermore, we showed that CrO decreased cellular viability (52.6 % ± 3.9) in relation to the control and caused necrosis in keratinocytes (PI positive cells). The necrosis induced by CrO was prevented by the pre-treatment with the selective P2X7R antagonist A438079. The results presented herein suggest that CrO exerts an inhibitory effect on the activity of ATPDase in mouse serum, reinforcing the idea that ICD has a pathogenic mechanism dependent of CD39. Furthermore, it is tempting to suggest that P2X7R may act as a controller of the extracellular levels of ATP.

  20. A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models.

    Science.gov (United States)

    Britti, Domenico; Crupi, Rosalia; Impellizzeri, Daniela; Gugliandolo, Enrico; Fusco, Roberta; Schievano, Carlo; Morittu, Valeria Maria; Evangelista, Maurizio; Di Paola, Rosanna; Cuzzocrea, Salvatore

    2017-08-02

    Osteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment is to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose important challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous levels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute conditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat models of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as benchmark. PEA-Q decreased inflammatory and hyperalgesic responses induced by carrageenan injection, as shown by: (i) paw oedema reduction, (ii) decreased severity in histological inflammatory score, (iii) reduced activity of myeloperoxidase, i.e., a marker of inflammatory cell infiltration, and (iv) decreased thermal hyperalgesia. Overall PEA-Q showed superior effects compared to meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i) reduced mechanical allodynia and improved locomotor function, (ii) protected cartilage against MIA-induced histological damage, and (iii) counteracted the increased serum concentration of tumor necrosis factor alpha, interleukin 1 beta, metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects was comparable to, or even greater than, those of meloxicam. The present

  1. The RESET Mindset Model applied on decreasing antibiotic usage in dairy cattle in the Netherlands

    NARCIS (Netherlands)

    Lam, T. J. G. M.; Wessels, R. J.; Jansen, Jolanda

    2017-01-01

    BACKGROUND: Prudent use of antibiotics is important to prevent antibiotic resistance in humans and in animals. For this reason politicians demanded a decrease of total antibiotic use and of use of critically important antibiotics in animal husbandry in the Netherlands. In the dairy sector the use of

  2. Plot showing ATLAS limits on Standard Model Higgs production in the mass range 110-150 GeV

    CERN Multimedia

    ATLAS Collaboration

    2011-01-01

    The combined upper limit on the Standard Model Higgs boson production cross section divided by the Standard Model expectation as a function of mH is indicated by the solid line. This is a 95% CL limit using the CLs method in in the low mass range. The dotted line shows the median expected limit in the absence of a signal and the green and yellow bands reflect the corresponding 68% and 95% expected

  3. Plot showing ATLAS limits on Standard Model Higgs production in the mass range 100-600 GeV

    CERN Multimedia

    ATLAS Collaboration

    2011-01-01

    The combined upper limit on the Standard Model Higgs boson production cross section divided by the Standard Model expectation as a function of mH is indicated by the solid line. This is a 95% CL limit using the CLs method in the entire mass range. The dotted line shows the median expected limit in the absence of a signal and the green and yellow bands reflect the corresponding 68% and 95% expected

  4. Decreased Libido

    Science.gov (United States)

    ... causes decreased libido? Decreased libido often accompanies other sexual disorders. Although most men with erectile dysfunction do not complain of decreased libido, after time, persistent failure with erections and sexual performance can lead to reduced sex drive in ...

  5. Influence of Turmeric Rhizome Powder diets on decreasing oxidative stress caused by heat stress inbroiler model

    Directory of Open Access Journals (Sweden)

    Seyyed Javad Hosseini-Vashan

    2012-08-01

    Full Text Available Background and Aim: Production of reactive oxygen species (ROS increases during oxidative stress conditions, which stimulates diabetes, inflammatory reactions, rheumatism and anemia. Some antioxidant properties of turmeric rhizome powder (TRP were revealed by previous researchers. The present study was conducted to evaluate the influence of TRP on decreasing effects of oxidative stress resulted from heat stress in broiler chickens.   Materials and Methods: In this experimental study, two-hundred-sixty-four 1-day-old broilers were divided into 3 dietary treatments. The dietary treatments involved 0(control, 0.4 and 0.8% turmeric rhizome powder (cases. In order to create oxidative stress, the ambient temperature was daily raised from 21 to 33oc for 5 hours (11a.m-4p.m throughout the 28th-42nd days. Blood lipids, Glutathione peroxidase (GPx ,superoxide dismutase (SOD, and Tiobarbituric acid reaction score (TBARS were determined at the end of the experiment.   Results: The results revealed that total cholesterol and triglyceride were not affected. The 0.4 TRP diet decreased blood LDL (46.7±3.01 compared to basal group (52.0±2.17. HDL increased in broilers fed 0.8% TRP (74.0 ± 3.87 compared to chickens with basal diet (63.7± 2.98. Enzyme activity of GPx improved in broilers fed TRP diets (225.9± 11.52 as compared to chickens with basal diet(183.1± 8.52 however, the TRP diet did not affect enzyme activity of SOD (P > 0.05. The TBARS index decreased in broilers fed TRP (0.76 ± 0.0052 in basal vs.0.49 ± 0.0032 in 0.8% TRP.   Conclusion: The major bioactive component of TRP is Curcumin that can improve the antioxidant properties under oxidative stress and high ambient temperature.

  6. Decreased Temporomandibular Joint Range of Motion in a Model of Early Osteoarthritis in the Rabbit

    Science.gov (United States)

    Henderson, Sarah E.; Tudares, Mauro A.; Tashman, Scott; Almarza, Alejandro J.

    2015-01-01

    Purpose Analysis of mandibular biomechanics could help with understanding the mechanisms of temporomandibular joint (TMJ) disorders (TMJDs), such as osteoarthritis (TMJ-OA), by investigating the effects of injury or disease on TMJ movement. The objective of the present study was to determine the functional kinematic implications of mild TMJ-OA degeneration caused by altered occlusion from unilateral splints in the rabbit. Materials and Methods Altered occlusion of the TMJ was mechanically induced in rabbits by way of a unilateral molar dental splint (n = 3). TMJ motion was assessed using 3-dimensional (3D) skeletal kinematics twice, once before and once after 6 weeks of splint placement with the splints removed, after allowing 3 days of recovery. The relative motion of the condyle to the fossa and the distance between the incisors were tracked. Results An overall decrease in the range of joint movement was observed at the incisors and in the joint space between the condyle and fossa. The incisor movement decreased from 7.0 ± 0.5 mm to 6.2 ± 0.5 mm right to left, from 5.5 ± 2.2 mm to 4.6 ± 0.8 mm anterior to posterior, and from 13.3 ± 1.8 mm to 11.6 ± 1.4 mm superior to inferior (P < .05). The total magnitude of the maximum distance between the points on the condyle and fossa decreased from 3.6 ± 0.8 mm to 3.1 ± 0.6 mm for the working condyle and 2.8 ± 0.4 mm to 2.5 ± 0.4 mm for the balancing condyle (P < .05). The largest decreases were seen in the anteroposterior direction for both condyles. Conclusion Determining the changes in condylar movement might lead to a better understanding of the early predictors in the development of TMJ-OA and determining when the symptoms become a chronic, irreversible problem. PMID:25889371

  7. Omentopexy improves vascularization and decreases stricture formation of esophageal anastomoses in a dog model.

    Science.gov (United States)

    Hayari, Lili; Hershko, Dan D; Shoshani, Hadas; Maor, Ron; Mordecovich, Daniel; Shoshani, Gideon

    2004-04-01

    Anastomotic strictures are common after primary esophageal anastomosis in pediatric patients. Recent studies provided evidence that omentopexy may improve vascularization of gastroesophageal anastomoses and decrease the rate of stricture-related complications. The effect of omentopexy on primary esophago-esophageal anastomosis, however, is unknown. The aim of the current study was to examine the role of omentopexy on the healing process of primary midesopageal anastomoses. Six dogs were operated on. A 5-cm portion of the midesophagus was resected, and continuity was restored by end-to-end anastomosis. In 3 dogs, an omental pedicle was placed around the anastomotic region. Eating patterns were recorded and functional swallowing was evaluated by fluoroscopic studies. Eight weeks after the operations, the experimental animals were killed and anastomotic lumen diameters and vascularization of the anastomotic sites were evaluated by radiographic studies and histologic examination, respectively. Two dogs in the omentopexy group were able to resume regular feeding, whereas none of the dogs in the control group were able to tolerate solid food intake. Fluoroscopic studies found preserved motility patterns of the esophagus in the omentoesophagopexy group, while prestenotic dilatation and delayed food clearance through the anastomosis were observed in the control group. Histologically, neovascularization was observed at the anastomotic site in the omentoesophagopexy group in contrast to the marked degree of fibrosis displayed in the control group. Omentopexy may improve vascularization and decrease stricture formation after primary esophagoesophageal anastomosis.

  8. A Markov chain approach to modelling charge exchange processes of an ion beam in monotonically increasing or decreasing potentials

    International Nuclear Information System (INIS)

    Shrier, O; Khachan, J; Bosi, S

    2006-01-01

    A Markov chain method is presented as an alternative approach to Monte Carlo simulations of charge exchange collisions by an energetic hydrogen ion beam with a cold background hydrogen gas. This method was used to determine the average energy of the resulting energetic neutrals along the path of the beam. A comparison with Monte Carlo modelling showed a good agreement but with the advantage that it required much less computing time and produced no numerical noise. In particular, the Markov chain method works well for monotonically increasing or decreasing electrostatic potentials. Finally, a good agreement is obtained with experimental results from Doppler shift spectroscopy on energetic beams from a hollow cathode discharge. In particular, the average energy of ions that undergo charge exchange reaches a plateau that can be well below the full energy that might be expected from the applied voltage bias, depending on the background gas pressure. For example, pressures of ∼20 mTorr limit the ion energy to ∼20% of the applied voltage

  9. Corresponding decrease in neuronal markers signals progressive parvalbumin neuron loss in MAM schizophrenia model.

    Science.gov (United States)

    Gill, Kathryn M; Grace, Anthony A

    2014-10-01

    Alteration in normal hippocampal (HPC) function attributed to reduced parvalbumin (PV) expression has been consistently reported in schizophrenia patients and in animal models of schizophrenia. However, it is unclear whether there is an overall loss of interneurons as opposed to a reduction in activity-dependent PV content. Co-expression of PV and the constitutively expressed substance P (SP)-receptor protein has been utilized in other models to ascertain the degree of cell survival, as opposed to reduction in activity-dependent PV content, in the HPC. The present study measured the co-expression of PV and SP-receptors in the dentate and dorsal and ventral CA3 subregions of the HPC in the methylazoymethanol acetate (MAM) rat neurodevelopmental model of schizophrenia. In addition, these changes were compared at the post-natal day 27 (PND27) and post-natal day 240 (PND > 240) time points. Brains from PND27 and PND > 240 MAM (n = 8) and saline (SAL, n = 8) treated offspring were immunohistochemically processed for the co-expression of PV and SP-receptors. The dorsal dentate, dorsal CA3 and ventral CA3 subregions of PND27 and PND > 240 MAM rats demonstrated significant reductions in PV but not SP-receptor expression, signifying a loss of PV-content. In contrast, in the ventral dentate the co-expression of PV and SP-receptors was significantly reduced only in PND > 240 MAM animals, suggesting a reduction in cell number. While MAM-induced reduction of PV content occurs in CA3 of dorsal and ventral HPC, the most substantial loss of interneuron number is localized to the ventral dentate of PND > 240 animals. The disparate loss of PV in HPC subregions likely impacts intra-HPC network activity in MAM rats.

  10. NEW SOLUTION AND ITS IMPACT ON INCREASING, DECREASING AND BATHTUB SHAPED FAILURE RATE MODEL

    Directory of Open Access Journals (Sweden)

    Mahmudul Alam

    2009-01-01

    Full Text Available The maximum likelihood equations of IDB distribution can’t be solved analytically. Solutions of the MLE equations can be obtained numerically. But the problem is to detect the initial value of the parameters to solve the nonlinear MLE equations. A technique is developed for formulating the initial value of the parameter to solve the MLE equations of IDB distribution. Considering all the facts, though IDB distribution is not suitable for graduating mortality data but the model can graduate mortality data of Bangladesh in the age range of 0-8 very well.

  11. Targeting CYP450 modulation to decrease the risk of induced cataract in the experimental model

    Directory of Open Access Journals (Sweden)

    Patel D

    2010-01-01

    Full Text Available Background: Diabetes is one of the major causes of cataract. Some drugs prescribed for the treatment of diabetes are the modulators of CYP450, which may alter the risk of cataract. Objective: To study the effect of CYP450 modulation in galactosemic cataract. Materials and Methods: Male Sprague-Dawley suckling rats were allotted to four groups (n = 6, as follows: Group 1: Normal control, Group 2: Galactose control, Group 3: CYP450 inhibitor pretreated and Group 4: CYP450 inducer pretreated. Cataract was induced in animals of all groups except group 1 by feeding them galactose (50%, 21 days after parturition. From the eighteenth day of life, CYP450 inhibitor (nifedipine; 8.1 mg/kg and CYP450 inducer (pioglitazone; 3.8 mg/kg were given orally to groups 3 and 4, respectively. The maturation pattern of the cataract was observed by an operating microscope, every third day. Biochemical changes in the lenses of all groups, for example, CYP450 activity expressed as ΅M NADPH oxidized / unit time, alterations in the levels of total proteins, soluble proteins, and reduced glutathione (GSH following the induction of cataract, were estimated. Results: The microscopic examination of the lenses indicated that CYP450 inhibitor pre-treatment delayed (fourteenth day the occurrence of cataract, while CYP450 inducer pretreatment demonstrated an early (ninth day cataract as compared to galactose control rats (twelfth day. A significant decrease and increase in CYP450 activity was observed with the CYP450 inhibitor and inducer pre-treatment, respectively. There was no alteration in the GSH level, but a significant increase in total and soluble protein was found in groups 3 and 4 as compared to group 2. Conclusion: CYP450 may have a role in the initiation of cataract without any effect on the maturation pattern, as revealed by the delayed occurrence of cataract with the CYP450 inhibitor and an early onset of cataract with the CYP450 inducer.

  12. Human mast cells decrease SLPI levels in type II – like alveolar cell model, in vitro

    Directory of Open Access Journals (Sweden)

    Nyström Max

    2003-08-01

    Full Text Available Abstract Background Mast cells are known to accumulate at sites of inflammation and upon activation to release their granule content, e.g. histamine, cytokines and proteases. The secretory leukocyte protease inhibitor (SLPI is produced in the respiratory mucous and plays a role in regulating the activity of the proteases. Result We have used the HMC-1 cell line as a model for human mast cells to investigate their effect on SLPI expression and its levels in cell co-culture experiments, in vitro. In comparison with controls, we found a significant reduction in SLPI levels (by 2.35-fold, p Conclusion These results indicate that SLPI-producing cells may assist mast cell migration and that the regulation of SLPI release and/or consumption by mast cells requires interaction between these cell types. Therefore, a "local relationship" between mast cells and airway epithelial cells might be an important step in the inflammatory response.

  13. Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts' Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model.

    Science.gov (United States)

    Serena, Elena; Zatti, Susi; Zoso, Alice; Lo Verso, Francesca; Tedesco, F Saverio; Cossu, Giulio; Elvassore, Nicola

    2016-12-01

    : Restoration of the protein dystrophin on muscle membrane is the goal of many research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of ongoing preclinical and clinical trials suggest that partial restoration of dystrophin might be sufficient to significantly reduce muscle damage. Different myogenic progenitors are candidates for cell therapy of muscular dystrophies, but only satellite cells and pericytes have already entered clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from DMD patients, using a microengineered model. We designed an ad hoc experimental strategy to miniaturize on a chip the standard process of muscle regeneration independent of variables such as inflammation and fibrosis. It is based on the coculture, at different ratios, of human dystrophin-positive myogenic progenitors and dystrophin-negative myoblasts in a substrate with muscle-like physiological stiffness and cell micropatterns. Results showed that both healthy myoblasts and mesoangioblasts restored dystrophin expression in DMD myotubes. However, mesoangioblasts showed unexpected efficiency with respect to myoblasts in dystrophin production in terms of the amount of protein produced (40% vs. 15%) and length of the dystrophin membrane domain (210-240 µm vs. 40-70 µm). These results show that our microscaled in vitro model of human DMD skeletal muscle validated previous in vivo preclinical work and may be used to predict efficacy of new methods aimed at enhancing dystrophin accumulation and distribution before they are tested in vivo, reducing time, costs, and variability of clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of human mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from

  14. Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts’ Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model

    Science.gov (United States)

    Serena, Elena; Zatti, Susi; Zoso, Alice; Lo Verso, Francesca; Tedesco, F. Saverio; Cossu, Giulio

    2016-01-01

    Restoration of the protein dystrophin on muscle membrane is the goal of many research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of ongoing preclinical and clinical trials suggest that partial restoration of dystrophin might be sufficient to significantly reduce muscle damage. Different myogenic progenitors are candidates for cell therapy of muscular dystrophies, but only satellite cells and pericytes have already entered clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from DMD patients, using a microengineered model. We designed an ad hoc experimental strategy to miniaturize on a chip the standard process of muscle regeneration independent of variables such as inflammation and fibrosis. It is based on the coculture, at different ratios, of human dystrophin-positive myogenic progenitors and dystrophin-negative myoblasts in a substrate with muscle-like physiological stiffness and cell micropatterns. Results showed that both healthy myoblasts and mesoangioblasts restored dystrophin expression in DMD myotubes. However, mesoangioblasts showed unexpected efficiency with respect to myoblasts in dystrophin production in terms of the amount of protein produced (40% vs. 15%) and length of the dystrophin membrane domain (210–240 µm vs. 40–70 µm). These results show that our microscaled in vitro model of human DMD skeletal muscle validated previous in vivo preclinical work and may be used to predict efficacy of new methods aimed at enhancing dystrophin accumulation and distribution before they are tested in vivo, reducing time, costs, and variability of clinical experimentation. Significance This study aimed to provide in vitro quantitative evidence of the ability of human mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes

  15. Alpha-1 antitrypsin protein and gene therapies decrease autoimmunity and delay arthritis development in mouse model

    Directory of Open Access Journals (Sweden)

    Atkinson Mark A

    2011-02-01

    Full Text Available Abstract Background Alpha-1 antitrypsin (AAT is a multi-functional protein that has anti-inflammatory and tissue protective properties. We previously reported that human AAT (hAAT gene therapy prevented autoimmune diabetes in non-obese diabetic (NOD mice and suppressed arthritis development in combination with doxycycline in mice. In the present study we investigated the feasibility of hAAT monotherapy for the treatment of chronic arthritis in collagen-induced arthritis (CIA, a mouse model of rheumatoid arthritis (RA. Methods DBA/1 mice were immunized with bovine type II collagen (bCII to induce arthritis. These mice were pretreated either with hAAT protein or with recombinant adeno-associated virus vector expressing hAAT (rAAV-hAAT. Control groups received saline injections. Arthritis development was evaluated by prevalence of arthritis and arthritic index. Serum levels of B-cell activating factor of the TNF-α family (BAFF, antibodies against both bovine (bCII and mouse collagen II (mCII were tested by ELISA. Results Human AAT protein therapy as well as recombinant adeno-associated virus (rAAV8-mediated hAAT gene therapy significantly delayed onset and ameliorated disease development of arthritis in CIA mouse model. Importantly, hAAT therapies significantly reduced serum levels of BAFF and autoantibodies against bCII and mCII, suggesting that the effects are mediated via B-cells, at least partially. Conclusion These results present a new drug for arthritis therapy. Human AAT protein and gene therapies are able to ameliorate and delay arthritis development and reduce autoimmunity, indicating promising potential of these therapies as a new treatment strategy for RA.

  16. Regression model analysis of the decreasing trend of cesium-137 concentration in the atmosphere since the Fukushima accident.

    Science.gov (United States)

    Kitayama, Kyo; Ohse, Kenji; Shima, Nagayoshi; Kawatsu, Kencho; Tsukada, Hirofumi

    2016-11-01

    The decreasing trend of the atmospheric 137 Cs concentration in two cities in Fukushima prefecture was analyzed by a regression model to clarify the relation between the parameter of the decrease in the model and the trend and to compare the trend with that after the Chernobyl accident. The 137 Cs particle concentration measurements were conducted in urban Fukushima and rural Date sites from September 2012 to June 2015. The 137 Cs particle concentrations were separated in two groups: particles of more than 1.1 μm aerodynamic diameters (coarse particles) and particles with aerodynamic diameter lower than 1.1 μm (fine particles). The averages of the measured concentrations were 0.1 mBq m -3 in Fukushima and Date sites. The measured concentrations were applied in the regression model which decomposed them into two components: trend and seasonal variation. The trend concentration included the parameters for the constant and the exponential decrease. The parameter for the constant was slightly different between the Fukushima and Date sites. The parameter for the exponential decrease was similar for all the cases, and much higher than the value of the physical radioactive decay except for the concentration in the fine particles at the Date site. The annual decreasing rates of the 137 Cs concentration evaluated by the trend concentration ranged from 44 to 53% y -1 with average and standard deviation of 49 ± 8% y -1 for all the cases in 2013. In the other years, the decreasing rates also varied slightly for all cases. These indicated that the decreasing trend of the 137 Cs concentration was nearly unchanged for the location and ground contamination level in the three years after the accident. The 137 Cs activity per aerosol particle mass also decreased with the same trend as the 137 Cs concentration in the atmosphere. The results indicated that the decreasing trend of the atmospheric 137 Cs concentration was related with the reduction of the 137 Cs concentration

  17. Decreased aortic smooth muscle contraction in a rat model of multibacterial sepsis.

    Science.gov (United States)

    Wang, Changhua; Mansard, Arnaud; Giummelly, Philippe; Atkinson, Jeffrey

    2004-12-01

    We investigated whether blockade of the smooth muscle cell (SMC) inducible nitric oxide synthase (iNOS)-soluble guanylyl cyclase (sGC) vasodilator pathway would restore the fall in vasoreactivity produced by sepsis following cecal ligation and perforation (CLP) in rats. Contraction of adjacent aortic rings paired for the presence or absence of endothelial cells (EC) was recorded following high [K(+)](e) (40 mm) or norepinephrine (NE, 10(-8) to 10(-5) m) in the presence of the nitric oxide synthase inhibitor (NOS), N(G)-nitro-l-arginine methyl ester (l-NAME, 0.3 mm) or the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 5 mum). In EC-denuded rings, sepsis halved SMC contraction induced by high [K(+)](e) or NE; neither l-NAME nor ODQ produced an increase in NE E(max) or high [K(+)](e)-evoked contraction. In conclusion, SMC contractility is globally reduced in CLP; this reduction does not appear to be explained by induction of SMC NOS in this CLP model.

  18. Plectasin shows intracellular activity against Staphylococcus aureus in human THP-1 monocytes and in a mouse peritonitis model

    DEFF Research Database (Denmark)

    Brinch, Karoline Sidelmann; Sandberg, Anne; Baudoux, Pierre

    2009-01-01

    Antimicrobial therapy of infections with Staphylococcus aureus can pose a challenge due to slow response to therapy and recurrence of infection. These treatment difficulties can partly be explained by intracellular survival of staphylococci, which is why the intracellular activity...... was maintained (maximal relative efficacy [E(max)], 1.0- to 1.3-log reduction in CFU) even though efficacy was inferior to that of extracellular killing (E(max), >4.5-log CFU reduction). Animal studies included a novel use of the mouse peritonitis model, exploiting extra- and intracellular differentiation assays...... concentration. These findings stress the importance of performing studies of extra- and intracellular activity since these features cannot be predicted from traditional MIC and killing kinetic studies. Application of both the THP-1 and the mouse peritonitis models showed that the in vitro results were similar...

  19. Coadministration of doxorubicin and etoposide loaded in camel milk phospholipids liposomes showed increased antitumor activity in a murine model

    Directory of Open Access Journals (Sweden)

    Maswadeh HM

    2015-04-01

    Full Text Available Hamzah M Maswadeh,1 Ahmed N Aljarbou,1 Mohammed S Alorainy,2 Arshad H Rahmani,3 Masood A Khan3 1Department of Pharmaceutics, College of Pharmacy, 2Department of Pharmacology and Therapeutics, College of Medicine, 3College of Applied Medical Sciences, Qassim University, Buraydah, Kingdom of Saudi Arabia Abstract: Small unilamellar vesicles from camel milk phospholipids (CML mixture or from 1,2 dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC were prepared, and anticancer drugs doxorubicin (Dox or etoposide (ETP were loaded. Liposomal formulations were used against fibrosarcoma in a murine model. Results showed a very high percentage of Dox encapsulation (~98% in liposomes (Lip prepared from CML-Lip or DPPC-Lip, whereas the percentage of encapsulations of ETP was on the lower side, 22% of CML-Lip and 18% for DPPC-Lip. Differential scanning calorimetry curves show that Dox enhances the lamellar formation in CML-Lip, whereas ETP enhances the nonlamellar formation. Differential scanning calorimetry curves also showed that the presence of Dox and ETP together into DPPC-Lip produced the interdigitation effect. The in vivo anticancer activity of liposomal formulations of Dox or ETP or a combination of both was assessed against benzopyrene (BAP-induced fibrosarcoma in a murine model. Tumor-bearing mice treated with a combination of Dox and ETP loaded into CML-Lip showed increased survival and reduced tumor growth compared to other groups, including the combination of Dox and ETP in DPPC-Lip. Fibrosarcoma-bearing mice treated with a combination of free (Dox + ETP showed much higher tumor growth compared to those groups treated with CML-Lip-(Dox + ETP or DPPC-Lip-(Dox + ETP. Immunohistochemical study was also performed to show the expression of tumor-suppressor PTEN, and it was found that the tumor tissues from the group of mice treated with a combination of free (Dox + ETP showed greater loss of cytoplasmic PTEN than tumor tissues obtained from the

  20. Connecting with The Biggest Loser: an extended model of parasocial interaction and identification in health-related reality TV shows.

    Science.gov (United States)

    Tian, Yan; Yoo, Jina H

    2015-01-01

    This study investigates audience responses to health-related reality TV shows in the setting of The Biggest Loser. It conceptualizes a model for audience members' parasocial interaction and identification with cast members and explores antecedents and outcomes of parasocial interaction and identification. Data analysis suggests the following direct relationships: (1) audience members' exposure to the show is positively associated with parasocial interaction, which in turn is positively associated with identification, (2) parasocial interaction is positively associated with exercise self-efficacy, whereas identification is negatively associated with exercise self-efficacy, and (3) exercise self-efficacy is positively associated with exercise behavior. Indirect effects of parasocial interaction and identification on exercise self-efficacy and exercise behavior are also significant. We discuss the theoretical and practical implications of these findings.

  1. Pancreatic Response to Gold Nanoparticles Includes Decrease of Oxidative Stress and Inflammation In Autistic Diabetic Model

    Directory of Open Access Journals (Sweden)

    Manar E. Selim

    2015-01-01

    Full Text Available Background: Gold nanoparticles (AuNPs have a wide range of applications in various fields. This study provides an understanding of the modulatory effects of AuNPs on an antioxidant system in male Wistar diabetic rats with autism spectrum disorder (ASD. Normal littermates fed by control mothers were injected with citrate buffer alone and served as normal, untreated controls controlin this study. Diabetes mellitus (DM was induced by administering a single intraperitoneal injection of streptozotocin (STZ (100 mg/kg to the pups of (ND diabetic group, which had been fasted overnight. Autistic pups from mothers that had received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception were randomly divided into 2 groups (n 2 7/group as follow; administering single intraperitoneal injection of streptozotocin (STZ ( (100 mg/kg to the overnight fasted autistic pups of (AD autistic diabetic group. The treatment was started on the 5th day after STZ injection with the same dose as in group II and it was considered as 1st day of treatment with gold nanoparticles for 7 days to each rat of (group IV treated autistic diabetic group(TAD at a dosage of 2.5 mg/kg. b. wt. Results: At this dose of administration AuNPs, the activities of hepatic superoxide dismutase (SOD, glutathione peroxidase (GPx, and catalase were greater in group TAD compared with the control group (P 0.05 in the liver of autistic diabetic AuNPs -supplemented rats, whereas reduced glutathione was markedly higher than in control rats, especially after administration of AuNPs. Moreover, the kidney functions in addition to the fat profile scoring supported the protective potential of that dose of AuNPs. The beta cells revealed euchromatic nuclei with no evidence of separation of nuclear membrane. Conclusions: Our results showed that AuNPs improved many of the oxidative stress parameters (SOD, GPx and, CAT, plasma antioxidant capacity (ORAC and lipid profile

  2. Restless led syndrome model Drosophila melanogaster show successful olfactory learning and 1-day retention of the acquired memory

    Directory of Open Access Journals (Sweden)

    Mika F. Asaba

    2013-09-01

    Full Text Available Restless Legs Syndrome (RLS is a prevalent but poorly understood disorder that ischaracterized by uncontrollable movements during sleep, resulting in sleep disturbance.Olfactory memory in Drosophila melanogaster has proven to be a useful tool for the study ofcognitive deficits caused by sleep disturbances, such as those seen in RLS. A recently generatedDrosophila model of RLS exhibited disturbed sleep patterns similar to those seen in humans withRLS. This research seeks to improve understanding of the relationship between cognitivefunctioning and sleep disturbances in a new model for RLS. Here, we tested learning andmemory in wild type and dBTBD9 mutant flies by Pavlovian olfactory conditioning, duringwhich a shock was paired with one of two odors. Flies were then placed in a T-maze with oneodor on either side, and successful associative learning was recorded when the flies chose theside with the unpaired odor. We hypothesized that due to disrupted sleep patterns, dBTBD9mutant flies would be unable to learn the shock-odor association. However, the current studyreports that the recently generated Drosophila model of RLS shows successful olfactorylearning, despite disturbed sleep patterns, with learning performance levels matching or betterthan wild type flies.

  3. The BACHD Rat Model of Huntington Disease Shows Specific Deficits in a Test Battery of Motor Function

    Directory of Open Access Journals (Sweden)

    Giuseppe Manfré

    2017-11-01

    Full Text Available Rationale: Huntington disease (HD is a progressive neurodegenerative disorder characterized by motor, cognitive and neuropsychiatric symptoms. HD is usually diagnosed by the appearance of motor deficits, resulting in skilled hand use disruption, gait abnormality, muscle wasting and choreatic movements. The BACHD transgenic rat model for HD represents a well-established transgenic rodent model of HD, offering the prospect of an in-depth characterization of the motor phenotype.Objective: The present study aims to characterize different aspects of motor function in BACHD rats, combining classical paradigms with novel high-throughput behavioral phenotyping.Methods: Wild-type (WT and transgenic animals were tested longitudinally from 2 to 12 months of age. To measure fine motor control, rats were challenged with the pasta handling test and the pellet reaching test. To evaluate gross motor function, animals were assessed by using the holding bar and the grip strength tests. Spontaneous locomotor activity and circadian rhythmicity were assessed in an automated home-cage environment, namely the PhenoTyper. We then integrated existing classical methodologies to test motor function with automated home-cage assessment of motor performance.Results: BACHD rats showed strong impairment in muscle endurance at 2 months of age. Altered circadian rhythmicity and locomotor activity were observed in transgenic animals. On the other hand, reaching behavior, forepaw dexterity and muscle strength were unaffected.Conclusions: The BACHD rat model exhibits certain features of HD patients, like muscle weakness and changes in circadian behavior. We have observed modest but clear-cut deficits in distinct motor phenotypes, thus confirming the validity of this transgenic rat model for treatment and drug discovery purposes.

  4. Network models of TEM β-lactamase mutations coevolving under antibiotic selection show modular structure and anticipate evolutionary trajectories.

    Science.gov (United States)

    Guthrie, Violeta Beleva; Allen, Jennifer; Camps, Manel; Karchin, Rachel

    2011-09-01

    Understanding how novel functions evolve (genetic adaptation) is a critical goal of evolutionary biology. Among asexual organisms, genetic adaptation involves multiple mutations that frequently interact in a non-linear fashion (epistasis). Non-linear interactions pose a formidable challenge for the computational prediction of mutation effects. Here we use the recent evolution of β-lactamase under antibiotic selection as a model for genetic adaptation. We build a network of coevolving residues (possible functional interactions), in which nodes are mutant residue positions and links represent two positions found mutated together in the same sequence. Most often these pairs occur in the setting of more complex mutants. Focusing on extended-spectrum resistant sequences, we use network-theoretical tools to identify triple mutant trajectories of likely special significance for adaptation. We extrapolate evolutionary paths (n = 3) that increase resistance and that are longer than the units used to build the network (n = 2). These paths consist of a limited number of residue positions and are enriched for known triple mutant combinations that increase cefotaxime resistance. We find that the pairs of residues used to build the network frequently decrease resistance compared to their corresponding singlets. This is a surprising result, given that their coevolution suggests a selective advantage. Thus, β-lactamase adaptation is highly epistatic. Our method can identify triplets that increase resistance despite the underlying rugged fitness landscape and has the unique ability to make predictions by placing each mutant residue position in its functional context. Our approach requires only sequence information, sufficient genetic diversity, and discrete selective pressures. Thus, it can be used to analyze recent evolutionary events, where coevolution analysis methods that use phylogeny or statistical coupling are not possible. Improving our ability to assess

  5. BO-1055, a novel DNA cross-linking agent with remarkable low myelotoxicity shows potent activity in sarcoma models.

    Science.gov (United States)

    Ambati, Srikanth R; Shieh, Jae-Hung; Pera, Benet; Lopes, Eloisi Caldas; Chaudhry, Anisha; Wong, Elissa W P; Saxena, Ashish; Su, Tsann-Long; Moore, Malcolm A S

    2016-07-12

    DNA damaging agents cause rapid shrinkage of tumors and form the basis of chemotherapy for sarcomas despite significant toxicities. Drugs having superior efficacy and wider therapeutic windows are needed to improve patient outcomes. We used cell proliferation and apoptosis assays in sarcoma cell lines and benign cells; γ-H2AX expression, comet assay, immunoblot analyses and drug combination studies in vitro and in patient derived xenograft (PDX) models. BO-1055 caused apoptosis and cell death in a concentration and time dependent manner in sarcoma cell lines. BO-1055 had potent activity (submicromolar IC50) against Ewing sarcoma and rhabdomyosarcoma, intermediate activity in DSRCT (IC50 = 2-3μM) and very weak activity in osteosarcoma (IC50 >10μM) cell lines. BO-1055 exhibited a wide therapeutic window compared to other DNA damaging drugs. BO-1055 induced more DNA double strand breaks and γH2AX expression in cancer cells compared to benign cells. BO-1055 showed inhibition of tumor growth in A673 xenografts and caused tumor regression in cyclophosphamide resistant patient-derived Ewing sarcoma xenografts and A204 xenografts. Combination of BO-1055 and irinotecan demonstrated synergism in Ewing sarcoma PDX models. Potent activity on sarcoma cells and its relative lack of toxicity presents a strong rationale for further development of BO-1055 as a therapeutic agent.

  6. Demographical history and palaeodistribution modelling show range shift towards Amazon Basin for a Neotropical tree species in the LGM.

    Science.gov (United States)

    Vitorino, Luciana Cristina; Lima-Ribeiro, Matheus S; Terribile, Levi Carina; Collevatti, Rosane G

    2016-10-13

    We studied the phylogeography and demographical history of Tabebuia serratifolia (Bignoniaceae) to understand the disjunct geographical distribution of South American seasonally dry tropical forests (SDTFs). We specifically tested if the multiple and isolated patches of SDTFs are current climatic relicts of a widespread and continuously distributed dry forest during the last glacial maximum (LGM), the so called South American dry forest refugia hypothesis, using ecological niche modelling (ENM) and statistical phylogeography. We sampled 235 individuals of T. serratifolia in 17 populations in Brazil and analysed the polymorphisms at three intergenic chloroplast regions and ITS nuclear ribosomal DNA. Coalescent analyses showed a demographical expansion at the last c. 130 ka (thousand years before present). Simulations and ENM also showed that the current spatial pattern of genetic diversity is most likely due to a scenario of range expansion and range shift towards the Amazon Basin during the colder and arid climatic conditions associated with the LGM, matching the expected for the South American dry forest refugia hypothesis, although contrasting to the Pleistocene Arc hypothesis. Populations in more stable areas or with higher suitability through time showed higher genetic diversity. Postglacial range shift towards the Southeast and Atlantic coast may have led to spatial genome assortment due to leading edge colonization as the species tracks suitable environments, leading to lower genetic diversity in populations at higher distance from the distribution centroid at 21 ka. Haplotype sharing or common ancestry among populations from Caatinga in Northeast Brazil, Atlantic Forest in Southeast and Cerrado biome and ENM evince the past connection among these biomes.

  7. A Numerical Study of Forbush Decreases with a 3D Cosmic-Ray Modulation Model Based on an SDE Approach

    International Nuclear Information System (INIS)

    Luo, Xi; Feng, Xueshang; Potgieter, Marius S.; Zhang, Ming

    2017-01-01

    Based on the reduced diffusion mechanism for producing Forbush decreases (Fds) in the heliosphere, we constructed a three-dimensional (3D) diffusion barrier, and by incorporating it into a stochastic differential equation (SDE) based time-dependent, cosmic-ray transport model, a 3D numerical model for simulating Fds is built and applied to a period of relatively quiet solar activity. This SDE model generally corroborates previous Fd simulations concerning the effects of the solar magnetic polarity, the tilt angle of the heliospheric current sheet (HCS), and cosmic-ray particle energy. Because the modulation processes in this 3D model are multi-directional, the barrier’s geometrical features affect the intensity profiles of Fds differently. We find that both the latitudinal and longitudinal extent of the barrier have relatively fewer effects on these profiles than its radial extent and the level of decreased diffusion inside the disturbance. We find, with the 3D approach, that the HCS rotational motion causes the relative location from the observation point to the HCS to vary, so that a periodic pattern appears in the cosmic-ray intensity at the observing location. Correspondingly, the magnitude and recovery time of an Fd change, and the recovering intensity profile contains oscillation as well. Investigating the Fd magnitude variation with heliocentric radial distance, we find that the magnitude decreases overall and, additionally, that the Fd magnitude exhibits an oscillating pattern as the radial distance increases, which coincides well with the wavy profile of the HCS under quiet solar modulation conditions.

  8. Decrease of d -wave pairing strength in spite of the persistence of magnetic excitations in the overdoped Hubbard model

    International Nuclear Information System (INIS)

    Huang, Edwin W.; Scalapino, Douglas J.; Maier, Thomas A.; Moritz, Brian; Devereaux, Thomas P.

    2017-01-01

    Evidence for the presence of high-energy magnetic excitations in overdoped La 2–x Sr x CuO 4 (LSCO) has raised questions regarding the role of spin fluctuations in the pairing mechanism. If they remain present in overdoped LSCO, why does T c decrease in this doping regime? Here, using results for the dynamic spin susceptibility Imχ(q,ω) obtained from a determinantal quantum Monte Carlo calculation for the Hubbard model, we address this question. We find that while high-energy magnetic excitations persist in the overdoped regime, they lack the momentum to scatter pairs between the antinodal regions. Finally, it is the decrease in the spectral weight at large momentum transfer, not observed by resonant inelastic x-ray scattering, which leads to a reduction in the d-wave spin-fluctuation pairing strength.

  9. Dynamic Properties of the Solow Model with Increasing or Decreasing Population and Time-to-Build Technology

    Directory of Open Access Journals (Sweden)

    Luca Guerrini

    2013-01-01

    Full Text Available We introduce a time-to-build technology in a Solow model with nonconstant population. Our analysis shows that the population dynamics may be a source of stability switches and Hopf bifurcations. The analytical results are obtained using the recent technique introduced by Beretta and Kuang (2002 in the studying of delayed differential equations with delay-dependent coefficients in characteristic equation. Numerical simulations are performed in order to illustrate the main dynamic features of the model.

  10. A new formulation of cannabidiol in cream shows therapeutic effects in a mouse model of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Giacoppo, Sabrina; Galuppo, Maria; Pollastro, Federica; Grassi, Gianpaolo; Bramanti, Placido; Mazzon, Emanuela

    2015-10-21

    The present study was designed to investigate the efficacy of a new formulation of alone, purified cannabidiol (CBD) (>98 %), the main non-psychotropic cannabinoid of Cannabis sativa, as a topical treatment in an experimental model of autoimmune encephalomyelitis (EAE), the most commonly used model for multiple sclerosis (MS). Particularly, we evaluated whether administration of a topical 1 % CBD-cream, given at the time of symptomatic disease onset, could affect the EAE progression and if this treatment could also recover paralysis of hind limbs, qualifying topical-CBD for the symptomatic treatment of MS. In order to have a preparation of 1 % of CBD-cream, pure CBD have been solubilized in propylene glycoland basic dense cream O/A. EAE was induced by immunization with myelin oligodendroglial glycoprotein peptide (MOG35-55) in C57BL/6 mice. After EAE onset, mice were allocated into several experimental groups (Naïve, EAE, EAE-1 % CBD-cream, EAE-vehicle cream, CTRL-1 % CBD-cream, CTRL-vehicle cream). Mice were observed daily for signs of EAE and weight loss. At the sacrifice of the animals, which occurred at the 28(th) day from EAE-induction, spinal cord and spleen tissues were collected in order to perform histological evaluation, immunohistochemistry and western blotting analysis. Achieved results surprisingly show that daily treatment with topical 1 % CBD-cream may exert neuroprotective effects against EAE, diminishing clinical disease score (mean of 5.0 in EAE mice vs 1.5 in EAE + CBD-cream), by recovering of paralysis of hind limbs and by ameliorating histological score typical of disease (lymphocytic infiltration and demyelination) in spinal cord tissues. Also, 1 % CBD-cream is able to counteract the EAE-induced damage reducing release of CD4 and CD8α T cells (spleen tissue localization was quantified about 10,69 % and 35,96 % of positive staining respectively in EAE mice) and expression of the main pro-inflammatory cytokines as well as several other

  11. The Ras antagonist, farnesylthiosalicylic acid (FTS, decreases fibrosis and improves muscle strength in dy/dy mouse model of muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Yoram Nevo

    Full Text Available The Ras superfamily of guanosine-triphosphate (GTP-binding proteins regulates a diverse spectrum of intracellular processes involved in inflammation and fibrosis. Farnesythiosalicylic acid (FTS is a unique and potent Ras inhibitor which decreased inflammation and fibrosis in experimentally induced liver cirrhosis and ameliorated inflammatory processes in systemic lupus erythematosus, neuritis and nephritis animal models. FTS effect on Ras expression and activity, muscle strength and fibrosis was evaluated in the dy(2J/dy(2J mouse model of merosin deficient congenital muscular dystrophy. The dy(2J/dy(2J mice had significantly increased RAS expression and activity compared with the wild type mice. FTS treatment significantly decreased RAS expression and activity. In addition, phosphorylation of ERK, a Ras downstream protein, was significantly decreased following FTS treatment in the dy(2J/dy(2J mice. Clinically, FTS treated mice showed significant improvement in hind limb muscle strength measured by electronic grip strength meter. Significant reduction of fibrosis was demonstrated in the treated group by quantitative Sirius Red staining and lower muscle collagen content. FTS effect was associated with significantly inhibition of both MMP-2 and MMP-9 activities. We conclude that active RAS inhibition by FTS was associated with attenuated fibrosis and improved muscle strength in the dy(2J/dy(2J mouse model of congenital muscular dystrophy.

  12. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life.

    Science.gov (United States)

    Guedj, Jeremie; Dahari, Harel; Rong, Libin; Sansone, Natasha D; Nettles, Richard E; Cotler, Scott J; Layden, Thomas J; Uprichard, Susan L; Perelson, Alan S

    2013-03-05

    The nonstructural 5A (NS5A) protein is a target for drug development against hepatitis C virus (HCV). Interestingly, the NS5A inhibitor daclatasvir (BMS-790052) caused a decrease in serum HCV RNA levels by about two orders of magnitude within 6 h of administration. However, NS5A has no known enzymatic functions, making it difficult to understand daclatasvir's mode of action (MOA) and to estimate its antiviral effectiveness. Modeling viral kinetics during therapy has provided important insights into the MOA and effectiveness of a variety of anti-HCV agents. Here, we show that understanding the effects of daclatasvir in vivo requires a multiscale model that incorporates drug effects on the HCV intracellular lifecycle, and we validated this approach with in vitro HCV infection experiments. The model predicts that daclatasvir efficiently blocks two distinct stages of the viral lifecycle, namely viral RNA synthesis and virion assembly/secretion with mean effectiveness of 99% and 99.8%, respectively, and yields a more precise estimate of the serum HCV half-life, 45 min, i.e., around four times shorter than previous estimates. Intracellular HCV RNA in HCV-infected cells treated with daclatasvir and the HCV polymerase inhibitor NM107 showed a similar pattern of decline. However, daclatasvir treatment led to an immediate and rapid decline of extracellular HCV titers compared to a delayed (6-9 h) and slower decline with NM107, confirming an effect of daclatasvir on both viral replication and assembly/secretion. The multiscale modeling approach, validated with in vitro kinetic experiments, brings a unique conceptual framework for understanding the mechanism of action of a variety of agents in development for the treatment of HCV.

  13. Use of the Reamer/Irrigator/Aspirator Decreases Carotid and Cranial Embolic Events in a Canine Model.

    Science.gov (United States)

    Miller, Anna N; Deal, Dwight; Green, James; Houle, Timothy; Brown, William; Thore, Clara; Stump, David; Webb, Lawrence X

    2016-04-20

    Approximately 2 million patients in the United States annually undergo total joint arthroplasty with reaming and placement of intramedullary nails, resulting in extravasation of bone marrow and fat into the circulatory system and potentially causing fat embolism syndrome. Acute and chronic changes in mental status documented after these procedures may be related to embolic events. The Reamer/Irrigator/Aspirator (RIA) device has been shown to decrease intramedullary pressure during reaming. We hypothesized that the use of the RIA in a canine model would reduce the number of microemboli detected in the carotid artery and brain compared with nailing either with or without reaming. Twenty-four large canines underwent unreamed nailing (UR), sequentially reamed nailing (SR), or RIA-reamed nailing (RIA) of bilateral femora (eight dogs per group). During reaming and nailing, the number and size of microemboli transiting the carotid artery were recorded. After euthanasia, the brain was harvested for immunostaining and measurement of microinfarction volumes. Total embolic load passing through the carotid artery was 0.049 cc (UR), 0.045 cc (SR), and 0.013 cc (RIA). The number and size of microemboli in the UR and SR groups were similar; however, the RIA group had significantly fewer larger-sized (>200-μm) emboli (p = 0.03). Pathologic examination of the brain confirmed particulate emboli, and histologic analyses demonstrated upregulation of stress-related proteins in all groups, with fewer emboli and less evidence of stress for RIA reaming. RIA reaming decreased microemboli compared with traditional reaming and unreamed nailing, suggesting that intramedullary pressure and heat are important variables. The documented embolic events and brain stress may help to explain subtle neurobehavioral symptoms commonly seen in patients after undergoing long-bone reaming procedures. RIA reaming decreased cranial embolic events and may have an ameliorating effect on postoperative

  14. Hyaluronic acid decreases IL-6 and IL-8 secretion and permeability in an inflammatory model of interstitial cystitis.

    Science.gov (United States)

    Rooney, Peadar; Srivastava, Akshay; Watson, Luke; Quinlan, Leo R; Pandit, Abhay

    2015-06-01

    Hyaluronic acid (HA) has received a lot of attention recently as a biomaterial with applications in wound healing, drug delivery, vascular repair and cell and/or gene delivery. Interstitial cystitis (IC) is characterised by an increase in the permeability of the bladder wall urothelium due to loss of the glycosaminoglycan (GAG) layer. The degradation of the urothelium leads to chronic pain and urinary dysfunction. The aetiology of the degradation of the GAG layer in this instance is currently unknown. At a clinical level, GAG replacement therapy using a HA solution is currently utilised as a treatment for IC. However, there is a significant lack of data on the mechanism of action of HA in IC. The current study investigates the mechanistic effect of clinically relevant HA treatment on an in vitro model of IC using urothelial cells, examining cytokine secretion, GAG secretion and trans-epithelial permeability. This study demonstrates that HA can significantly decrease induced cytokine secretion (4-5 fold increase), increase sulphated GAG production (2-fold increase) and without altering tight junction expression, decrease trans-epithelial permeability, suggesting that the HA pathway is a clinical target and potential treatment vector. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  15. Decreased exploratory activity in a mouse model of 15q duplication syndrome; implications for disturbance of serotonin signaling.

    Directory of Open Access Journals (Sweden)

    Kota Tamada

    Full Text Available Autism spectrum disorders (ASDs have garnered significant attention as an important grouping of developmental brain disorders. Recent genomic studies have revealed that inherited or de novo copy number variations (CNVs are significantly involved in the pathophysiology of ASDs. In a previous report from our laboratory, we generated mice with CNVs as a model of ASDs, with a duplicated mouse chromosome 7C that is orthologous to human chromosome 15q11-13. Behavioral analyses revealed paternally duplicated (patDp/+ mice displayed abnormal behaviors resembling the symptoms of ASDs. In the present study, we extended these findings by performing various behavioral tests with C57BL/6J patDp/+ mice, and comprehensively measuring brain monoamine levels with ex vivo high performance liquid chromatography. Compared with wild-type controls, patDp/+ mice exhibited decreased locomotor and exploratory activities in the open field test, Y-maze test, and fear-conditioning test. Furthermore, their decreased activity levels overcame increased appetite induced by 24 hours of food deprivation in the novelty suppressed feeding test. Serotonin levels in several brain regions of adult patDp/+ mice were lower than those of wild-type control, with no concurrent changes in brain levels of dopamine or norepinephrine. Moreover, analysis of monoamines in postnatal developmental stages demonstrated reduced brain levels of serotonin in young patDp/+ mice. These findings suggest that a disrupted brain serotonergic system, especially during postnatal development, may generate the phenotypes of patDp/+ mice.

  16. Intraperitoneal curcumin decreased lung, renal and heart injury in abdominal aorta ischemia/reperfusion model in rat.

    Science.gov (United States)

    Aydin, Mehmet Salih; Caliskan, Ahmet; Kocarslan, Aydemir; Kocarslan, Sezen; Yildiz, Ali; Günay, Samil; Savik, Emin; Hazar, Abdussemet; Yalcin, Funda

    2014-01-01

    Previous studies have demonstrated that curcumin (CUR) has protective effects against ischemia reperfusion injury to various organs. We aimed to determine whether CUR has favorable effects on tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Thirty rats were divided into three groups as sham, control and treatment (CUR) group. Control and CUR groups underwent abdominal aorta ischemia for 60 min followed by a 120 min period of reperfusion. In the CUR group, CUR was given 5 min before reperfusion at a dose of 200 mg/kg via an intraperitoneal route. Total antioxidant capacity (TAC), total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured, and lung, renal and heart tissue histopathology were evaluated with light microscopy. TOS and OSI activity in blood samples were statistically decreased in sham and CUR groups compared to the control group (p OSI). Renal, lung, heart injury scores of sham and CUR groups were statistically decreased compared to control group (p model. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  17. A conceptual model for worksite intelligent physical exercise training - IPET - intervention for decreasing life style health risk indicators among employees

    DEFF Research Database (Denmark)

    Sjøgaard, Gisela; Justesen, Just Bendix; Murray, Mike

    2014-01-01

    BACKGROUND: Health promotion at the work site in terms of physical activity has proven positive effects but optimization of relevant exercise training protocols and implementation for high adherence are still scanty.Methods/design: The aim of this paper is to present a study protocol...... indicators, 2) Improve muscle strength and decrease musculoskeletal disorders, 3) Succeed in regular adherence to worksite and leisure physical activity training, and 3) Reduce sickness absence and productivity losses (presenteeism) in office workers. The present RCT study enrolled almost 400 employees...... with a conceptual model for planning the optimal individually tailored physical exercise training for each worker based on individual health check, existing guidelines and state of the art sports science training recommendations in the broad categories of cardiorespiratory fitness, muscle strength in specific body...

  18. Polysaccharides from the Medicinal Mushroom Cordyceps taii Show Antioxidant and Immunoenhancing Activities in a D-Galactose-Induced Aging Mouse Model

    Directory of Open Access Journals (Sweden)

    Jian-Hui Xiao

    2012-01-01

    Full Text Available Cordyceps taii, an edible medicinal mushroom native to south China, is recognized as an unparalleled resource of healthy foods and drug discovery. In the present study, the antioxidant pharmacological properties of C. taii were systematically investigated. In vitro assays revealed the scavenging activities of the aqueous extract and polysaccharides of C. taii against various free radicals, that is, 1,1-diphenyl-2-picrylhydrazyl radical, hydroxyl radical, and superoxide anion radical. The EC50 values for superoxide anion-free radical ranged from 2.04 mg/mL to 2.49 mg/mL, which was at least 2.6-fold stronger than that of antioxidant thiourea. The polysaccharides also significantly enhanced the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase and markedly decreased the malondialdehyde production of lipid peroxidation in a D-galactose-induced aging mouse model. Interestingly, the immune function of the administration group was significantly boosted compared with the D-galactose-induced aging model group. Therefore, the C. taii polysaccharides possessed potent antioxidant activity closely associated with immune function enhancement and free radical scavenging. These findings suggest that the polysaccharides are a promising source of natural antioxidants and antiaging drugs. Consequently, a preliminary chemical investigation was performed using gas chromatography-mass spectroscopy and revealed that the polysaccharides studied were mainly composed of glucose, mannose, and galactose. Fourier-transform infrared spectra also showed characteristic polysaccharide absorption bands.

  19. Characterization of chronic constriction of the saphenous nerve, a model of neuropathic pain in mice showing rapid molecular and electrophysiological changes.

    Science.gov (United States)

    Walczak, Jean-Sébastien; Pichette, Vincent; Leblond, François; Desbiens, Karine; Beaulieu, Pierre

    2006-05-15

    Neuropathic pain is one of the most inextricable problems encountered in clinics, because few facts are known about its etiology. Nerve injury often leads to allodynia and hyperalgesia, which are symptoms of neuropathic pain. The aim of this study was to understand some molecular and electrophysiological mechanisms of neuropathic pain after chronic constriction of the saphenous nerve (CCS) in mice. After surgery, CCS mice displayed significant allodynia and hyperalgesia, which were sensitive to acute systemic injection of morphine (4 mg/kg), gabapentin (50 mg/kg), amitriptyline (10 mg/kg), and the cannabinoid agonist WIN 55,212-2 (5 mg/kg). These behavioral changes were accompanied after surgery by an increase of c-Fos expression and by an overexpression of mu-opioid and cannabinoid CB1 and CB2 receptors in the spinal cord and the dorsal hind paw skin. In combination with the skin-nerve preparation, this model showed a decrease in functional receptive fields downstream to the injury and the apparition of A-fiber ectopic discharges. In conclusion, CCS injury induced behavioral, molecular, and electrophysiological rearrangements that might help us in better understanding the peripheral mechanisms of neuropathic pain. This model takes advantage of the possible use in the future of genetically modified mice and of an exclusively sensory nerve for a comprehensive study of peripheral mechanisms of neuropathic pain. Copyright 2006 Wiley-Liss, Inc.

  20. A water-soluble extract from Cucurbita moschata shows anti-obesity effects by controlling lipid metabolism in a high fat diet-induced obesity mouse model.

    Science.gov (United States)

    Choi, Hyounjeong; Eo, Haekwan; Park, Kyoungcheol; Jin, Mirim; Park, Eun-Jin; Kim, Seon-Hee; Park, Jeong Euy; Kim, Sunyoung

    2007-08-03

    During the screening of a variety of plant sources for their anti-obesity activity, it was found that a water-soluble extract, named PG105, prepared from stem parts of Cucurbita moschata, contains potent anti-obesity activities in a high fat diet-induced obesity mouse model. In this animal model, increases in body weight and fat storage were suppressed by 8-week oral administration of PG105 at 500 mg/kg, while the overall amount of food intake was not affected. Furthermore, PG105 protected the development of fatty liver and increased the hepatic beta-oxidation activity. Results from blood analysis showed that the levels of triglyceride and cholesterol were significantly lowered by PG105 administration, and also that the level of leptin was reduced, while that of adiponectin was increased. To understand the underlying mechanism at the molecular level, the effects of PG105 were examined on the expression of the genes involved in lipid metabolism by Northern blot analysis. In the liver of PG105-treated mice, the mRNA level of lipogenic genes such as SREBP-1c and SCD-1 was decreased, while that of lipolytic genes such as PPARalpha, ACO-1, CPT-1, and UCP-2 was modestly increased. Our data suggest that PG105 may have great potential as a novel anti-obesity agent in that both inhibition of lipid synthesis and acceleration of fatty acid breakdown are induced by this reagent.

  1. CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of infantile spasms.

    Science.gov (United States)

    Briggs, Stephen W; Mowrey, Wenzhu; Hall, Charles B; Galanopoulou, Aristea S

    2014-01-01

    Infantile spasms (IS) have poor outcomes and limited treatment options, including vigabatrin, a γ-aminobutyric acid (GABA) aminotransferase inactivator. Vigabatrin has been associated with retinal toxicity. A high affinity vigabatrin analogue (CPP-115; Catalyst Pharmaceutical Partners, Inc., Coral Gables, FL, U.S.A.) has shown lower risk of retinal toxicity. Here, we test the efficacy of CPP-115 in reducing spasms and its tolerability in the multiple-hit rat model of IS, in which daily vigabatrin reduced spasms for only one day, but was not well tolerated. Male rats were treated with the protocol of the multiple-hit model of IS on postnatal day 3 (PN3). Using a randomized, blinded, vehicle-controlled, dose-response study design, CPP-115 (0.1, 1, or 5 mg/kg intraperitoneally [i.p.]) or vehicle was given daily (PN4-12) or as a single injection (PN7) after spasm onset. Intermittent video- or video-electroencephalography (EEG) monitoring was done. Secondary end points included the following: daily weights, survival, performance on open field activity, surface righting time, and negative geotaxis (PN3-20), horizontal bar (PN13-20), and Barnes maze (PN16-19). Statistics used a linear mixed model of raw or normalized log-transformed data, taking into account the repeated observations on each animal. The lower CPP-115 doses (0.1-1 mg/kg/day, PN4-12) reduced spasms between PN6 and 7 without increasing mortality. CPP-115 at 5 mg/kg/day (PN4-12) reduced spasms earlier (PN5), but was eventually lethal. A single CPP-115 injection (1 mg/kg, i.p.) decreased electroclinical spasms acutely but transiently. CPP-115 transiently improved the probability to >50% reduction of spasms, but did not accelerate spasm cessation. CPP-115 did not alter neurodevelopmental outcomes or visuospatial learning. We provide proof-of-concept evidence that CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of IS at considerably lower and better tolerated doses than vigabatrin

  2. Bioavailability of particulate metal to zebra mussels: Biodynamic modelling shows that assimilation efficiencies are site-specific

    Energy Technology Data Exchange (ETDEWEB)

    Bourgeault, Adeline, E-mail: bourgeault@ensil.unilim.fr [Cemagref, Unite de Recherche Hydrosystemes et Bioprocedes, 1 rue Pierre-Gilles de Gennes, 92761 Antony (France); FIRE, FR-3020, 4 place Jussieu, 75005 Paris (France); Gourlay-France, Catherine, E-mail: catherine.gourlay@cemagref.fr [Cemagref, Unite de Recherche Hydrosystemes et Bioprocedes, 1 rue Pierre-Gilles de Gennes, 92761 Antony (France); FIRE, FR-3020, 4 place Jussieu, 75005 Paris (France); Priadi, Cindy, E-mail: cindy.priadi@eng.ui.ac.id [LSCE/IPSL CEA-CNRS-UVSQ, Avenue de la Terrasse, 91198 Gif-sur-Yvette (France); Ayrault, Sophie, E-mail: Sophie.Ayrault@lsce.ipsl.fr [LSCE/IPSL CEA-CNRS-UVSQ, Avenue de la Terrasse, 91198 Gif-sur-Yvette (France); Tusseau-Vuillemin, Marie-Helene, E-mail: Marie-helene.tusseau@ifremer.fr [IFREMER Technopolis 40, 155 rue Jean-Jacques Rousseau, 92138 Issy-Les-Moulineaux (France)

    2011-12-15

    This study investigates the ability of the biodynamic model to predict the trophic bioaccumulation of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni) and zinc (Zn) in a freshwater bivalve. Zebra mussels were transplanted to three sites along the Seine River (France) and collected monthly for 11 months. Measurements of the metal body burdens in mussels were compared with the predictions from the biodynamic model. The exchangeable fraction of metal particles did not account for the bioavailability of particulate metals, since it did not capture the differences between sites. The assimilation efficiency (AE) parameter is necessary to take into account biotic factors influencing particulate metal bioavailability. The biodynamic model, applied with AEs from the literature, overestimated the measured concentrations in zebra mussels, the extent of overestimation being site-specific. Therefore, an original methodology was proposed for in situ AE measurements for each site and metal. - Highlights: > Exchangeable fraction of metal particles did not account for the bioavailability of particulate metals. > Need for site-specific biodynamic parameters. > Field-determined AE provide a good fit between the biodynamic model predictions and bioaccumulation measurements. - The interpretation of metal bioaccumulation in transplanted zebra mussels with biodynamic modelling highlights the need for site-specific assimilation efficiencies of particulate metals.

  3. Bioavailability of particulate metal to zebra mussels: biodynamic modelling shows that assimilation efficiencies are site-specific.

    Science.gov (United States)

    Bourgeault, Adeline; Gourlay-Francé, Catherine; Priadi, Cindy; Ayrault, Sophie; Tusseau-Vuillemin, Marie-Hélène

    2011-12-01

    This study investigates the ability of the biodynamic model to predict the trophic bioaccumulation of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni) and zinc (Zn) in a freshwater bivalve. Zebra mussels were transplanted to three sites along the Seine River (France) and collected monthly for 11 months. Measurements of the metal body burdens in mussels were compared with the predictions from the biodynamic model. The exchangeable fraction of metal particles did not account for the bioavailability of particulate metals, since it did not capture the differences between sites. The assimilation efficiency (AE) parameter is necessary to take into account biotic factors influencing particulate metal bioavailability. The biodynamic model, applied with AEs from the literature, overestimated the measured concentrations in zebra mussels, the extent of overestimation being site-specific. Therefore, an original methodology was proposed for in situ AE measurements for each site and metal. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model

    DEFF Research Database (Denmark)

    Kempf, Stefan J; Metaxas, Athanasios; Ibáñez-Vea, María

    2016-01-01

    The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology.We used the double APPswe/PS1ΔE9 mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosyl...

  5. Oxidative stress, serotonergic changes and decreased ultrasonic vocalizations in a mouse model of Smith-Lemli-Opitz syndrome.

    Science.gov (United States)

    Sharif, N F; Korade, Z; Porter, N A; Harrison, F E

    2017-07-01

    Smith-Lemli-Opitz syndrome is an inherited monogenic disorder in which mutations to the 7-dehydrocholesterol (7-DHC) reductase (Dhcr7) gene lead to deficits in cholesterol synthesis. As a result, many patients suffer from gross physiological and neurological deficits. The purpose of this study was to identify a potential abnormal behavioral phenotype in a compound mutant mouse model for Smith-Lemli-Opitz disease (Dhcr7 Δ3 -5/ T93M ) to further validate the model and to provide potential targets for future therapeutic interventions. We also sought to identify some of the underlying changes in brain function that may be responsible for behavioral differences among groups. The Dhcr7 compound mutant mice were smaller than their single mutant littermates. Both single and compound heterozygous mice made fewer ultrasonic vocalizations when separated from the dam, which may suggest a communication deficit in these animals. Striking increases of the highly oxidizable 7-DHC were observed in the compound mutant mice. 7-Dehydrocholesterol is the precursor to cholesterol and builds up because of decreased function of the mutated Dhcr7 enzyme. Additionally, several differences were noted in the serotonergic system including increased expression of the serotonin transporter and increased uptake of serotonin by isolated synaptosomes. We propose that changes to the oxidative environment during development can have a significant impact on the development of serotonergic function and that this contributes to behavioral differences observed in the mutant mice. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  6. Advanced imaging techniques show progressive arthropathy following experimentally induced knee bleeding in a factor VIII-/- rat model

    DEFF Research Database (Denmark)

    Sorensen, K. R.; Roepstorff, K.; Petersen, M.

    2015-01-01

    Background: Joint pathology is most commonly assessed by radiogra-phy, but ultrasonography (US) is increasingly recognized for its acces-sibility, safety and ability to show soft tissue changes, the earliestindicators of haemophilic arthropathy (HA). US, however, lacks theability to visualize...

  7. Automated home cage assessment shows behavioral changes in a transgenic mouse model of spinocerebellar ataxia type 17.

    Science.gov (United States)

    Portal, Esteban; Riess, Olaf; Nguyen, Huu Phuc

    2013-08-01

    Spinocerebellar Ataxia type 17 (SCA17) is an autosomal dominantly inherited, neurodegenerative disease characterized by ataxia, involuntary movements, and dementia. A novel SCA17 mouse model having a 71 polyglutamine repeat expansion in the TATA-binding protein (TBP) has shown age related motor deficit using a classic motor test, yet concomitant weight increase might be a confounding factor for this measurement. In this study we used an automated home cage system to test several motor readouts for this same model to confirm pathological behavior results and evaluate benefits of automated home cage in behavior phenotyping. Our results confirm motor deficits in the Tbp/Q71 mice and present previously unrecognized behavioral characteristics obtained from the automated home cage, indicating its use for high-throughput screening and testing, e.g. of therapeutic compounds. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. BO-1055, a novel DNA cross-linking agent with remarkable low myelotoxicity shows potent activity in sarcoma models

    OpenAIRE

    Ambati, Srikanth R.; Shieh, Jae-Hung; Pera, Benet; Lopes, Eloisi Caldas; Chaudhry, Anisha; Wong, Elissa W.P.; Saxena, Ashish; Su, Tsann-Long; Moore, Malcolm A.S.

    2016-01-01

    DNA damaging agents cause rapid shrinkage of tumors and form the basis of chemotherapy for sarcomas despite significant toxicities. Drugs having superior efficacy and wider therapeutic windows are needed to improve patient outcomes. We used cell proliferation and apoptosis assays in sarcoma cell lines and benign cells; ?-H2AX expression, comet assay, immunoblot analyses and drug combination studies in vitro and in patient derived xenograft (PDX) models. BO-1055 caused apoptosis and cell death...

  9. Betting on change: Tenet deal with Vanguard shows it's primed to try ACO effort, new payment model.

    Science.gov (United States)

    Kutscher, Beth

    2013-07-01

    Tenet Healthcare Corp.'s acquisition of Vanguard Health Systems is a sign the investor-owned chain is willing to take a chance on alternative payment models such as accountable care organizations. There's no certainty that ACOs will deliver the improvements on quality or cost savings, but Vanguard Vice Chairman Keith Pitts, left, says his system's Pioneer ACO in Detroit has already achieved some cost savings.

  10. Restless led syndrome model Drosophila melanogaster show successful olfactory learning and 1-day retention of the acquired memory

    OpenAIRE

    Mika F. Asaba; Adrian A. Bates; Hoa M. Dao; Mika J. Maeda

    2013-01-01

    Restless Legs Syndrome (RLS) is a prevalent but poorly understood disorder that ischaracterized by uncontrollable movements during sleep, resulting in sleep disturbance.Olfactory memory in Drosophila melanogaster has proven to be a useful tool for the study ofcognitive deficits caused by sleep disturbances, such as those seen in RLS. A recently generatedDrosophila model of RLS exhibited disturbed sleep patterns similar to those seen in humans withRLS. This research seeks to improve understand...

  11. Tribal implementation of a patient-centred medical home model in Alaska accompanied by decreased hospital use

    Directory of Open Access Journals (Sweden)

    Janet M. Johnston

    2013-08-01

    Full Text Available Background. Between 1995 and 1998, tribally owned Southcentral Foundation (SCF incrementally assumed responsibility from the Indian Health Service (IHS for primary care services on the Alaska Native Medical Center (ANMC campus in Anchorage, Alaska. In 1999, SCF began implementing components of a Patient-Centered Medical Home (PCMH model to improve access and continuity of care. Objective. To evaluate hospitalisation trends before, during and after PCMH implementation. Design. Time series analysis of aggregated medical record data. Methods. Regression analysis with correlated errors was used to estimate trends over time for the percent of customer-owners hospitalised overall and for specific conditions during 4 time periods (March 1996–July 1999: SCF assumes responsibility for primary care; August 1999–July 2000: PCMH implementation starts; August 2000–April 2005: early post-PCMH implementation; May 2005–December 2009: later post-PCMH implementation. Analysis was restricted to individuals residing in Southcentral Alaska and receiving health care at ANMC. Results. The percent of SCF customer-owners hospitalised per month for any reason was steady before and during PCMH implementation, declined steadily immediately following implementation and subsequently stabilised. The percent hospitalised per month for unintentional injury or poisoning also declined during and after the PCMH implementation. Among adult asthma patients, the percent hospitalised annually for asthma declined prior to and during implementation and remained lower thereafter. The percent of heart failure patients hospitalised annually for heart failure remained relatively constant throughout the study period while the percent of hypertension patients hospitalised for hypertension shifted higher between 1999 and 2002 compared to earlier and later years. Conclusion. Implementation of PCMH at SCF was accompanied by decreases in the percent of customer-owners hospitalised monthly

  12. Daily supplementation of D-ribose shows no therapeutic benefits in the MHC-I transgenic mouse model of inflammatory myositis.

    Directory of Open Access Journals (Sweden)

    William Coley

    Full Text Available BACKGROUND: Current treatments for idiopathic inflammatory myopathies (collectively called myositis focus on the suppression of an autoimmune inflammatory response within the skeletal muscle. However, it has been observed that there is a poor correlation between the successful suppression of muscle inflammation and an improvement in muscle function. Some evidence in the literature suggests that metabolic abnormalities in the skeletal muscle underlie the weakness that continues despite successful immunosuppression. We have previously shown that decreased expression of a purine nucleotide cycle enzyme, adenosine monophosphate deaminase (AMPD1, leads to muscle weakness in a mouse model of myositis and may provide a mechanistic basis for muscle weakness. One of the downstream metabolites of this pathway, D-ribose, has been reported to alleviate symptoms of myalgia in patients with a congenital loss of AMPD1. Therefore, we hypothesized that supplementing exogenous D-ribose would improve muscle function in the mouse model of myositis. We treated normal and myositis mice with daily doses of D-ribose (4 mg/kg over a 6-week time period and assessed its effects using a battery of behavioral, functional, histological and molecular measures. RESULTS: Treatment with D-ribose was found to have no statistically significant effects on body weight, grip strength, open field behavioral activity, maximal and specific forces of EDL, soleus muscles, or histological features. Histological and gene expression analysis indicated that muscle tissues remained inflamed despite treatment. Gene expression analysis also suggested that low levels of the ribokinase enzyme in the skeletal muscle might prevent skeletal muscle tissue from effectively utilizing D-ribose. CONCLUSIONS: Treatment with daily oral doses of D-ribose showed no significant effect on either disease progression or muscle function in the mouse model of myositis.

  13. Decreased DNA Methylation in the Shati/Nat8l Promoter in Both Patients with Schizophrenia and a Methamphetamine-Induced Murine Model of Schizophrenia-Like Phenotype.

    Directory of Open Access Journals (Sweden)

    Kyosuke Uno

    Full Text Available The number of patients with schizophrenia has increased over the past decade. Previously, many studies have been performed to establish its diagnostic criteria, prophylactic methods, and effective therapies. In this study, we analyzed whether the ratios of DNA methylation in CpG islands of the Shati/Nat8l is decreased in model mice of schizophrenia-like phenotype using genomic DNA collected from brain regions and peripheral blood, since the mouse model of schizophrenia-like phenotype, mice treated repeatedly with methamphetamine showed increase of Shati/Nat8l mRNA expression in our previous experiment. The ratios of Shati/Nat8l CpG island methylation were significantly decreased in both the nucleus accumbens and the peripheral blood of model mice compared with those of control mice. We also investigated Shati/Nat8l methylation in the blood of patients with schizophrenia. We found that Shati/Nat8l CpG island methylation ratios were lower in the patients with schizophrenia than in the healthy controls, which is consistent with our findings in the mice model. To our knowledge, this is the first study to show similar alterations in methylation status of a particular genomic DNA site in both the brain and peripheral blood of mice. Furthermore, the same phenomenon was observed in corresponding human genomic sequences of the DNA extracted from the peripheral blood of patients with schizophrenia. Based on our findings, DNA methylation profiles of the CpG island of Shati/Nat8l might be a diagnostic biomarker of schizophrenia.

  14. CP-809,101, a selective 5-HT2C agonist, shows activity in animal models of antipsychotic activity.

    Science.gov (United States)

    Siuciak, Judith A; Chapin, Douglas S; McCarthy, Sheryl A; Guanowsky, Victor; Brown, Janice; Chiang, Phoebe; Marala, Ravi; Patterson, Terrell; Seymour, Patricia A; Swick, Andrew; Iredale, Philip A

    2007-02-01

    CP-809,101 is a potent, functionally selective 5-HT(2C) agonist that displays approximately 100% efficacy in vitro. The aim of the present studies was to assess the efficacy of a selective 5-HT(2C) agonist in animal models predictive of antipsychotic-like efficacy and side-effect liability. Similar to currently available antipsychotic drugs, CP-809,101 dose-dependently inhibited conditioned avoidance responding (CAR, ED(50)=4.8 mg/kg, sc). The efficacy of CP-809,101 in CAR was completely antagonized by the concurrent administration of the 5-HT(2C) receptor antagonist, SB-224,282. CP-809,101 antagonized both PCP- and d-amphetamine-induced hyperactivity with ED(50) values of 2.4 and 2.9 mg/kg (sc), respectively and also reversed an apomorphine induced-deficit in prepulse inhibition. At doses up to 56 mg/kg, CP-809,101 did not produce catalepsy. Thus, the present results demonstrate that the 5-HT(2C) agonist, CP-809,101, has a pharmacological profile similar to that of the atypical antipsychotics with low extrapyramidal symptom liability. CP-809,101 was inactive in two animal models of antidepressant-like activity, the forced swim test and learned helplessness. However, CP-809,101 was active in novel object recognition, an animal model of cognitive function. These data suggest that 5-HT(2C) agonists may be a novel approach in the treatment of psychosis as well as for the improvement of cognitive dysfunction associated with schizophrenia.

  15. Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model.

    Science.gov (United States)

    Squitieri, Ferdinando; Di Pardo, Alba; Favellato, Mariagrazia; Amico, Enrico; Maglione, Vittorio; Frati, Luigi

    2015-11-01

    Huntington disease (HD) is a neurodegenerative disorder for which new treatments are urgently needed. Pridopidine is a new dopaminergic stabilizer, recently developed for the treatment of motor symptoms associated with HD. The therapeutic effect of pridopidine in patients with HD has been determined in two double-blind randomized clinical trials, however, whether pridopidine exerts neuroprotection remains to be addressed. The main goal of this study was to define the potential neuroprotective effect of pridopidine, in HD in vivo and in vitro models, thus providing evidence that might support a potential disease-modifying action of the drug and possibly clarifying other aspects of pridopidine mode-of-action. Our data corroborated the hypothesis of neuroprotective action of pridopidine in HD experimental models. Administration of pridopidine protected cells from apoptosis, and resulted in highly improved motor performance in R6/2 mice. The anti-apoptotic effect observed in the in vitro system highlighted neuroprotective properties of the drug, and advanced the idea of sigma-1-receptor as an additional molecular target implicated in the mechanism of action of pridopidine. Coherent with protective effects, pridopidine-mediated beneficial effects in R6/2 mice were associated with an increased expression of pro-survival and neurostimulatory molecules, such as brain derived neurotrophic factor and DARPP32, and with a reduction in the size of mHtt aggregates in striatal tissues. Taken together, these findings support the theory of pridopidine as molecule with disease-modifying properties in HD and advance the idea of a valuable therapeutic strategy for effectively treating the disease. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. Performance modeling and valuation of snow-covered PV systems: examination of a simplified approach to decrease forecasting error.

    Science.gov (United States)

    Bosman, Lisa B; Darling, Seth B

    2018-03-22

    The advent of modern solar energy technologies can improve the costs of energy consumption on a global, national, and regional level, ultimately spanning stakeholders from governmental entities to utility companies, corporations, and residential homeowners. For those stakeholders experiencing the four seasons, accurately accounting for snow-related energy losses is important for effectively predicting photovoltaic performance energy generation and valuation. This paper provides an examination of a new, simplified approach to decrease snow-related forecasting error, in comparison to current solar energy performance models. A new method is proposed to allow model designers, and ultimately users, the opportunity to better understand the return on investment for solar energy systems located in snowy environments. The new method is validated using two different sets of solar energy systems located near Green Bay, WI, USA: a 3.0-kW micro inverter system and a 13.2-kW central inverter system. Both systems were unobstructed, facing south, and set at a tilt of 26.56°. Data were collected beginning in May 2014 (micro inverter system) and October 2014 (central inverter system), through January 2018. In comparison to reference industry standard solar energy prediction applications (PVWatts and PVsyst), the new method results in lower mean absolute percent errors per kilowatt hour of 0.039 and 0.055%, respectively, for the micro inverter system and central inverter system. The statistical analysis provides support for incorporating this new method into freely available, online, up-to-date prediction applications, such as PVWatts and PVsyst.

  17. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.

    Science.gov (United States)

    Ramonell, Kimberly M; Zhang, Wenxiao; Hadley, Annette; Chen, Ching-Wen; Fay, Katherine T; Lyons, John D; Klingensmith, Nathan J; McConnell, Kevin W; Coopersmith, Craig M; Ford, Mandy L

    2017-01-01

    Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.

  18. Early arthritis induces disturbances at bone nanostructural level reflected in decreased tissue hardness in an animal model of arthritis.

    Science.gov (United States)

    Vidal, Bruno; Cascão, Rita; Finnilä, Mikko A J; Lopes, Inês P; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena; Fonseca, João E

    2018-01-01

    Arthritis induces joint erosions and skeletal bone fragility. The main goal of this work was to analyze the early arthritis induced events at bone architecture and mechanical properties at tissue level. Eighty-eight Wistar rats were randomly housed in experimental groups, as follows: adjuvant induced arthritis (AIA) (N = 47) and a control healthy group (N = 41). Rats were monitored during 22 days for the inflammatory score, ankle perimeter and body weight and sacrificed at different time points (11 and 22 days post disease induction). Bone samples were collected for histology, micro computed tomography (micro-CT), 3-point bending and nanoindentation. Blood samples were also collected for bone turnover markers and systemic cytokine quantification. At bone tissue level, measured by nanoindentation, there was a reduction of hardness in the arthritic group, associated with an increase of the ratio of bone concentric to parallel lamellae and of the area of the osteocyte lacuna. In addition, increased bone turnover and changes in the microstructure and mechanical properties were observed in arthritic animals, since the early phase of arthritis, when compared with healthy controls. We have shown in an AIA rat model that arthritis induces very early changes at bone turnover, structural degradation and mechanical weakness. Bone tissue level is also affected since the early phase of arthritis, characterized by decreased tissue hardness associated with changes in bone lamella organization and osteocyte lacuna surface. These observations highlight the pertinence of immediate control of inflammation in the initial stages of arthritis.

  19. Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis.

    Science.gov (United States)

    Bassi, E; Liberman, M; Martinatti, M K; Bortolotto, L A; Laurindo, F R M

    2014-02-01

    Vascular calcification decreases compliance and increases morbidity. Mechanisms of this process are unclear. The role of oxidative stress and effects of antioxidants have been poorly explored. We investigated effects of the antioxidants lipoic acid (LA) and tempol in a model of atherosclerosis associated with elastocalcinosis. Male New Zealand white rabbits (2.5-3.0 kg) were fed regular chow (controls) or a 0.5% cholesterol (chol) diet+104 IU/day vitamin D2 (vitD) for 12 weeks, and assigned to treatment with water (vehicle, n=20), 0.12 mmol·kg-1·day-1 LA (n=11) or 0.1 mmol·kg-1·day-1 tempol (n=15). Chol+vitD-fed rabbits developed atherosclerotic plaques associated with expansive remodeling, elastic fiber disruption, medial calcification, and increased aortic stiffness. Histologically, LA prevented medial calcification by ∼60% and aortic stiffening by ∼60%. LA also preserved responsiveness to constrictor agents, while intima-media thickening was increased. In contrast to LA, tempol was associated with increased plaque collagen content, medial calcification and aortic stiffness, and produced differential changes in vasoactive responses in the chol+vitD group. Both LA and tempol prevented superoxide signals with chol+vitD. However, only LA prevented hydrogen peroxide-related signals with chol+vitD, while tempol enhanced them. These data suggest that LA, opposite to tempol, can minimize calcification and compliance loss in elastocalcionosis by inhibition of hydrogen peroxide generation.

  20. CXCR4 blockade decreases CD4+ T cell exhaustion and improves survival in a murine model of polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Kimberly M Ramonell

    Full Text Available Sepsis is a dysregulated systemic response to infection involving many inflammatory pathways and the induction of counter-regulatory anti-inflammatory processes that results in a state of immune incompetence and can lead to multi-organ failure. CXCR4 is a chemokine receptor that, following ligation by CXCL12, directs cells to bone marrow niches and also plays an important role in T cell cosignaling and formation of the immunological synapse. Here, we investigated the expression and function of CXCR4 in a murine model of polymicrobial sepsis. Results indicate that CXCR4 is selectively upregulated on naïve CD4+ and CD8+ T cells and CD4+ central memory T cells following the induction of sepsis, and that CXCR4 antagonism resulted in a significant decrease in sepsis-induced mortality. We probed the mechanistic basis for these findings and found that CXCR4 antagonism significantly increased the number of peripheral CD4+ and CD8+ T cells following sepsis. Moreover, mice treated with the CXCR4 antagonist contained fewer PD-1+ LAG-3+ 2B4+ cells, suggesting that blockade of CXCR4 mitigates CD4+ T cell exhaustion during sepsis. Taken together, these results characterize CXCR4 as an important pathway that modulates immune dysfunction and mortality following sepsis, which may hold promise as a target for future therapeutic intervention in septic patients.

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

    Science.gov (United States)

    Sturgeon, Craig; Lan, Jinggang; Fasano, Alessio

    2017-06-01

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

  2. Photodynamic therapy using chloro-aluminum phthalocyanine decreases inflammatory response in an experimental rat periodontal disease model.

    Science.gov (United States)

    de Moraes, Maiara; Vasconcelos, Roseane Carvalho; Longo, João Paulo Figueiró; Muehlmann, Luis Alexandre; de Azevedo, Ricardo Bentes; de Araújo Júnior, Raimundo Fernandes; Araujo, Aurigena Antunes; de Lisboa Lopes Costa, Antonio

    2017-02-01

    Emerging evidence suggests that photodynamic therapy (PDT) can exhibit immunomodulatory activity. The purpose of the present study was to analyse cytokine profiles after application of PDT in gingival tissues of rats with ligature-induced periodontal disease (PD). Periodontal disease was induced through the introduction of a cotton thread around the first left mandibular molar, while the right side molars did not receive ligatures. After 7days of PD evolution, ligatures were removed from the left side, and the animals were randomically divided into the following treatment groups: I, rats without treatment; II, rats received chloro-aluminum phthalocyanine (AlClPc); III, rats received low-level laser alone; and IV, rats received AlClPc associated with low-level laser (PDT). The animals were killed 7days after the treatments, and the mandibles were histologically processed to assess morphological and immunohistochemical profile, while gingival tissues were removed for quantification of tumor necrosis factor (TNF)-α, interleukin (IL-)1β and IL-10 expression (by ELISA). Histomorphological analysis of periodontal tissues demonstrated that PDT-treated animals show tissue necrosis, as well as lower TNF- α expression, compared to ligatured animals treated with AlClPc alone. It was concluded that PDT using AlClPc entrapped in a lipid nanoemulsion may be useful in therapies, because of immunomodulatory effects that decreased the inflammatory response and cause tissue destruction. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Decreasing DOC trends in soil solution along the hillslopes at two IM sites in southern Sweden--geochemical modeling of organic matter solubility during acidification recovery.

    Science.gov (United States)

    Löfgren, Stefan; Gustafsson, Jon Petter; Bringmark, Lage

    2010-12-01

    Numerous studies report increased concentrations of dissolved organic carbon (DOC) during the last two decades in boreal lakes and streams in Europe and North America. Recently, a hypothesis was presented on how various spatial and temporal factors affect the DOC dynamics. It was concluded that declining sulphur deposition and thereby increased DOC solubility, is the most important driver for the long-term DOC concentration trends in surface waters. If this recovery hypothesis is correct, the DOC levels should increase both in the soil solution as well as in the surrounding surface waters as soil pH rises and the ionic strength declines due to the reduced input of SO(4)(2-) ions. In this project a geochemical model was set up to calculate the net humic charge and DOC solubility trends in soils during the period 1996-2007 at two integrated monitoring sites in southern Sweden, showing clear signs of acidification recovery. The Stockholm Humic Model was used to investigate whether the observed DOC solubility is related to the humic charge and to examine how pH and ionic strength influence it. Soil water data from recharge and discharge areas, covering both podzols and riparian soils, were used. The model exercise showed that the increased net charge following the pH increase was in many cases counteracted by a decreased ionic strength, which acted to decrease the net charge and hence the DOC solubility. Thus, the recovery from acidification does not necessarily have to generate increasing DOC trends in soil solution. Depending on changes in pH, ionic strength and soil Al pools, the trends might be positive, negative or indifferent. Due to the high hydraulic connectivity with the streams, the explanations to the DOC trends in surface waters should be searched for in discharge areas and peat lands. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Amniotic fluid stem cells with low γ-interferon response showed behavioral improvement in Parkinsonism rat model.

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chang

    Full Text Available Amniotic fluid stem cells (AFSCs are multipotent stem cells that may be used in transplantation medicine. In this study, AFSCs established from amniocentesis were characterized on the basis of surface marker expression and differentiation potential. To further investigate the properties of AFSCs for translational applications, we examined the cell surface expression of human leukocyte antigens (HLA of these cells and estimated the therapeutic effect of AFSCs in parkinsonian rats. The expression profiles of HLA-II and transcription factors were compared between AFSCs and bone marrow-derived mesenchymal stem cells (BMMSCs following treatment with γ-IFN. We found that stimulation of AFSCs with γ-IFN prompted only a slight increase in the expression of HLA-Ia and HLA-E, and the rare HLA-II expression could also be observed in most AFSCs samples. Consequently, the expression of CIITA and RFX5 was weakly induced by γ-IFN stimulation of AFSCs compared to that of BMMSCs. In the transplantation test, Sprague Dawley rats with 6-hydroxydopamine lesioning of the substantia nigra were used as a parkinsonian-animal model. Following the negative γ-IFN response AFSCs injection, apomorphine-induced rotation was reduced by 75% in AFSCs engrafted parkinsonian rats but was increased by 53% in the control group after 12-weeks post-transplantation. The implanted AFSCs were viable, and were able to migrate into the brain's circuitry and express specific proteins of dopamine neurons, such as tyrosine hydroxylase and dopamine transporter. In conclusion, the relative insensitivity AFSCs to γ-IFN implies that AFSCs might have immune-tolerance in γ-IFN inflammatory conditions. Furthermore, the effective improvement of AFSCs transplantation for apomorphine-induced rotation paves the way for the clinical application in parkinsonian therapy.

  5. Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions.

    Science.gov (United States)

    Masum, Md Abdul; Ichii, Osamu; Elewa, Yaser Hosny Ali; Nakamura, Teppei; Kon, Yasuhiro

    2017-09-04

    The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34 + glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34 + tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34 + glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. From the analysis of mouse models, we identified inverse pathological correlations between the number of

  6. Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis

    Directory of Open Access Journals (Sweden)

    E. Bassi

    2014-02-01

    Full Text Available Vascular calcification decreases compliance and increases morbidity. Mechanisms of this process are unclear. The role of oxidative stress and effects of antioxidants have been poorly explored. We investigated effects of the antioxidants lipoic acid (LA and tempol in a model of atherosclerosis associated with elastocalcinosis. Male New Zealand white rabbits (2.5-3.0 kg were fed regular chow (controls or a 0.5% cholesterol (chol diet+104 IU/day vitamin D2 (vitD for 12 weeks, and assigned to treatment with water (vehicle, n=20, 0.12 mmol·kg-1·day-1 LA (n=11 or 0.1 mmol·kg-1·day-1 tempol (n=15. Chol+vitD-fed rabbits developed atherosclerotic plaques associated with expansive remodeling, elastic fiber disruption, medial calcification, and increased aortic stiffness. Histologically, LA prevented medial calcification by ∼60% and aortic stiffening by ∼60%. LA also preserved responsiveness to constrictor agents, while intima-media thickening was increased. In contrast to LA, tempol was associated with increased plaque collagen content, medial calcification and aortic stiffness, and produced differential changes in vasoactive responses in the chol+vitD group. Both LA and tempol prevented superoxide signals with chol+vitD. However, only LA prevented hydrogen peroxide-related signals with chol+vitD, while tempol enhanced them. These data suggest that LA, opposite to tempol, can minimize calcification and compliance loss in elastocalcionosis by inhibition of hydrogen peroxide generation.

  7. Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model.

    Science.gov (United States)

    Rentea, Rebecca M; Liedel, Jennifer L; Fredrich, Katherine; Welak, Scott R; Pritchard, Kirkwood A; Oldham, Keith T; Simpson, Pippa M; Gourlay, David M

    2012-10-01

    Supplementation of intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, decreases the severity of necrotizing enterocolitis (NEC)-associated intestinal injury and permeability. We hypothesized that IAP administration is protective in a dose-dependent manner of the inflammatory response in a neonatal rat model. Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day of life 3. Control pups were vaginally delivered and dam fed. Preterm pups were delivered via cesarean section and exposed to intermittent hypoxia and formula feeds containing lipopolysaccharide (NEC) with and without IAP. Three different standardized doses were administered to a group of pups treated with 40, 4, and 0.4U/kg of bovine IAP (NEC+IAP40, IAP4, or IAP0.4U). Reverse transcription-real-time polymerase chain reaction (RT-PCR) for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α on liver and lung tissues and serum cytokine analysis for interleukin (IL)-1β, IL-6, IL-10, and TNF-α were performed. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests, expressed as mean±standard error of the mean and P≤0.05 considered significant. Levels of cytokines IL-1β, IL-6, and TNF-α increased significantly in NEC versus control, returning to control levels with increasing doses of supplemental enteral IAP. Hepatic and pulmonary TNF-α and iNOS messenger ribonucleic acid expressions increased in NEC, and the remaining elevated despite IAP supplementation. Proinflammatory cytokine expression is increased systemically with intestinal NEC injury. Administration of IAP significantly reduces systemic proinflammatory cytokine expression in a dose-dependent manner. Early supplemental enteral IAP may reduce NEC-related injury and be useful for reducing effects caused by a proinflammatory cascade. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...... and have decreasing relative risk premium. We finally introduce the notion of partial risk neutral preferences on binary lotteries and show that partial risk neutrality is equivalent to preferences with decreasing relative risk premium...

  9. Accounting for the Decreasing Denitrification Potential of Aquifers in Travel-Time Based Reactive-Transport Models of Nitrate

    Science.gov (United States)

    Cirpka, O. A.; Loschko, M.; Wöhling, T.; Rudolph, D. L.

    2017-12-01

    Excess nitrate concentrations pose a threat to drinking-water production from groundwater in all regions of intensive agriculture worldwide. Natural organic matter, pyrite, and other reduced constituents of the aquifer matrix can be oxidized by aerobic and denitrifying bacteria, leading to self-cleaning of groundwater. Various studies have shown that the heterogeneity of both hydraulic and chemical aquifer properties influence the reactive behavior. Since the exact spatial distributions of these properties are not known, predictions on the temporal evolution of nitrate should be probabilistic. However, the computational effort of pde-based, spatially explicit multi-component reactive-transport simulations are so high that multiple model runs become impossible. Conversely, simplistic models that treat denitrification as first-order decay process miss important controls on denitrification. We have proposed a Lagrangian framework of nonlinear reactive transport, in which the electron-donor supply by the aquifer matrix is parameterized by a relative reactivity, that is the reaction rate relative to a standard reaction rate for identical solute concentrations (Loschko et al., 2016). We could show that reactive transport simplifies to solving a single ordinary dfferential equation in terms of the cumulative relative reactivity for a given combination of inflow concentrations. Simulating 3-D flow and reactive transport are computationally so inexpensive that Monte Carlo simulation become feasible. The original scheme did not consider a change of the relative reactivity over time, implying that the electron-donor pool in the matrix is infinite. We have modified the scheme to address the consumption of the reducing aquifer constituents upon the reactions. We also analyzed how a minimally complex model of aerobic respiration and denitrification could look like. With the revised scheme, we performed Monte Carlo simulations in 3-D domains, confirming that the uncertainty in

  10. The Effect of Educational Intervention based on BASNEF Model on Decreasing the Cesarean Section Rate among Pregnant Women in Khomain Country.

    Science.gov (United States)

    Arefi, Zohreh; Hekamatpou, Davod; Orouji, Mohammad Ali; Shaahmadi, Zahra; Khushemehri, Giti; Shaahmadi, Faramarz

    2015-09-01

    Over the past two decades, the incidence of cesarean section in most countries has increased. Cesarean section increases the risk of death and complications in the mother and fetus. Educational interventions based on behavior change models can play an important role in reduce the rate of cesarean section. The aim of our study is investigation the effect of educational intervention based on BASNEF Model on decreasing of cesarean section rate among pregnant women in Khomain County, from June to November 2013. In this interventional study, 140 nulliparous women who were in their last trimester of pregnancy were randomly allocated to case and control groups. Data gathering instrument was a questionnaire based on BASNEF framework. Data were analyzed by SPSS 14 software. The scores of knowledge, attitudes, subjective norms, and enabling factors in the intervention group than the control group showed a significant difference (p cesarean section. By Chi-square test showed that the difference in the type of delivery between the two groups was statistically significant (p cesarean section.

  11. A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects.

    Science.gov (United States)

    Suggs, Jennifer A; Melkani, Girish C; Glasheen, Bernadette M; Detor, Mia M; Melkani, Anju; Marsan, Nathan P; Swank, Douglas M; Bernstein, Sanford I

    2017-06-01

    Individuals with inclusion body myopathy type 3 (IBM3) display congenital joint contractures with early-onset muscle weakness that becomes more severe in adulthood. The disease arises from an autosomal dominant point mutation causing an E706K substitution in myosin heavy chain type IIa. We have previously expressed the corresponding myosin mutation (E701K) in homozygous Drosophila indirect flight muscles and recapitulated the myofibrillar degeneration and inclusion bodies observed in the human disease. We have also found that purified E701K myosin has dramatically reduced actin-sliding velocity and ATPase levels. Since IBM3 is a dominant condition, we now examine the disease state in heterozygote Drosophila in order to gain a mechanistic understanding of E701K pathogenicity. Myosin ATPase activities in heterozygotes suggest that approximately equimolar levels of myosin accumulate from each allele. In vitro actin sliding velocity rates for myosin isolated from the heterozygotes were lower than the control, but higher than for the pure mutant isoform. Although sarcomeric ultrastructure was nearly wild type in young adults, mechanical analysis of skinned indirect flight muscle fibers revealed a 59% decrease in maximum oscillatory power generation and an approximately 20% reduction in the frequency at which maximum power was produced. Rate constant analyses suggest a decrease in the rate of myosin attachment to actin, with myosin spending decreased time in the strongly bound state. These mechanical alterations result in a one-third decrease in wing beat frequency and marginal flight ability. With aging, muscle ultrastructure and function progressively declined. Aged myofibrils showed Z-line streaming, consistent with the human heterozygote phenotype. Based upon the mechanical studies, we hypothesize that the mutation decreases the probability of the power stroke occurring and/or alters the degree of movement of the myosin lever arm, resulting in decreased in vitro

  12. A Drosophila model of dominant inclusion body myopathy type 3 shows diminished myosin kinetics that reduce muscle power and yield myofibrillar defects

    Directory of Open Access Journals (Sweden)

    Jennifer A. Suggs

    2017-06-01

    Full Text Available Individuals with inclusion body myopathy type 3 (IBM3 display congenital joint contractures with early-onset muscle weakness that becomes more severe in adulthood. The disease arises from an autosomal dominant point mutation causing an E706K substitution in myosin heavy chain type IIa. We have previously expressed the corresponding myosin mutation (E701K in homozygous Drosophila indirect flight muscles and recapitulated the myofibrillar degeneration and inclusion bodies observed in the human disease. We have also found that purified E701K myosin has dramatically reduced actin-sliding velocity and ATPase levels. Since IBM3 is a dominant condition, we now examine the disease state in heterozygote Drosophila in order to gain a mechanistic understanding of E701K pathogenicity. Myosin ATPase activities in heterozygotes suggest that approximately equimolar levels of myosin accumulate from each allele. In vitro actin sliding velocity rates for myosin isolated from the heterozygotes were lower than the control, but higher than for the pure mutant isoform. Although sarcomeric ultrastructure was nearly wild type in young adults, mechanical analysis of skinned indirect flight muscle fibers revealed a 59% decrease in maximum oscillatory power generation and an approximately 20% reduction in the frequency at which maximum power was produced. Rate constant analyses suggest a decrease in the rate of myosin attachment to actin, with myosin spending decreased time in the strongly bound state. These mechanical alterations result in a one-third decrease in wing beat frequency and marginal flight ability. With aging, muscle ultrastructure and function progressively declined. Aged myofibrils showed Z-line streaming, consistent with the human heterozygote phenotype. Based upon the mechanical studies, we hypothesize that the mutation decreases the probability of the power stroke occurring and/or alters the degree of movement of the myosin lever arm, resulting in

  13. An exponential growth model with decreasing r captures bottom-up effects on the population growth of Aphis glycines Matsumura (Hemiptera: Aphididae)

    NARCIS (Netherlands)

    Costamagna, A.C.; Werf, van der W.; Bianchi, F.J.J.A.; Landis, D.A.

    2007-01-01

    1 There is ample evidence that the life history and population dynamics of aphids are closely linked to plant phenology. Based on life table studies, it has been proposed that the growth of aphid populations could be modeled with an exponential growth model, with r decreasing linearly with time.

  14. Techniques for managing behaviour in pediatric dentistry: comparative study of live modelling and tell-show-do based on children's heart rates during treatment.

    Science.gov (United States)

    Farhat-McHayleh, Nada; Harfouche, Alice; Souaid, Philippe

    2009-05-01

    Tell-show-do is the most popular technique for managing children"s behaviour in dentists" offices. Live modelling is used less frequently, despite the satisfactory results obtained in studies conducted during the 1980s. The purpose of this study was to compare the effects of these 2 techniques on children"s heart rates during dental treatments, heart rate being the simplest biological parameter to measure and an increase in heart rate being the most common physiologic indicator of anxiety and fear. For this randomized, controlled, parallel-group single-centre clinical trial, children 5 to 9 years of age presenting for the first time to the Saint Joseph University dental care centre in Beirut, Lebanon, were divided into 3 groups: those in groups A and B were prepared for dental treatment by means of live modelling, the mother serving as the model for children in group A and the father as the model for children in group B. The children in group C were prepared by a pediatric dentist using the tell-show-do method. Each child"s heart rate was monitored during treatment, which consisted of an oral examination and cleaning. A total of 155 children met the study criteria and participated in the study. Children who received live modelling with the mother as model had lower heart rates than those who received live modelling with the father as model and those who were prepared by the tell-show-do method (p pediatric dentistry.

  15. QUALITY OF NURSING WORK LIFE IMPROVEMENT MODEL TO DECREASE NURSE INTENTION TO QUIT IN PREMIER SURABAYA HOSPITAL

    Directory of Open Access Journals (Sweden)

    Jany Prihastuty

    2017-04-01

    Full Text Available Introduction: Quality of Nursing Work Life (QNWL is a thing that needs attention by human resource management approach. The purpose of this research was to provide develop model to increase QNWL in order to lower nurse’s intention to quit the Premier Hospital Surabaya. Methods: Design used in the structure was explanatory research. The independent variables was Internal factors (Individual factors, social and environment conceptual factors, operational factors, administrative factors where as the dependent variable from this study was intention to quit, and moderator variables QNWL random sampling technique. Total sample was 160 nurses, taken according to inclusion criteria. The research was conducted in Premier Hospital Surabaya from October 2012 - July 2013. Data were collected by using structured questionnaire. Data were then analyzed by using multiple linear regression test with level of significance of ≤ 0.05. Result: The results showed, QNWL was influenced by relationships inter-professional part of variabel social and environment conceptual factors, supervision monitoring part of variabel operational factors, career development part of variabel administrative factors. Intention to quit influenced by relationships between nurses, inter-departmental and inter-professional part of variabel social and environment conceptual factors and salaries and benefits part of variabel administrative factors with significant value p = 0.005. Discussion: It can be concluded good inter-professional relation, supervision monitoring, and good career development affected QNWL. Good relationships between nurses, inter-departmental and inter- professional led to lower intention to quit. Low salary and benefits led nurse’s intention to quit getting stronger.

  16. Purinergic 2Y1 receptor stimulation decreases cerebral edema and reactive gliosis in a traumatic brain injury model.

    Science.gov (United States)

    Talley Watts, Lora; Sprague, Shane; Zheng, Wei; Garling, R Justin; Jimenez, David; Digicaylioglu, Murat; Lechleiter, James

    2013-01-01

    Traumatic brain injury (TBI) is the leading cause of death and disability in children and young adults. Neuroprotective agents that may promote repair or counteract damage after injury do not currently exist. We recently reported that stimulation of the purinergic receptor subtype P2Y(1)R using 2-methylthioladenosine 5' diphosphate (2MeSADP) significantly reduced cytotoxic edema induced by photothrombosis. Here, we tested whether P2Y(1)R stimulation was neuroprotective after TBI. A controlled closed head injury model was established for mice using a pneumatic impact device. Brains were harvested at 1, 3, or 7 days post-injury and assayed for morphological changes by immunocytochemistry, Western blot analysis, and wet/dry weight. Cerebral edema and expression of both aquaporin type 4 and glial fibrillary acidic protein were increased at all time points examined. Immunocytochemical measurements in both cortical and hippocampal slices also revealed significant neuronal swelling and reactive gliosis. Treatment of mice with 2MeSADP (100 μM) or MRS2365 (100 μM) 30 min after trauma significantly reduced all post-injury symptoms of TBI including edema, neuronal swelling, reactive gliosis, and AQ4 expression. The neuroprotective effect was lost in IP(3)R2-/- mice treated with 2MeSADP. Immunocytochemical labeling of brain slices confirmed that P2Y(1)R expression was defined to cortical and hippocampal astrocytes, but not neurons. Taken together, the data show that stimulation of astrocytic P2Y(1)Rs significantly reduces brain injury after acute trauma and is mediated by the IP(3)-signaling pathway. We suggest that enhancing astrocyte mitochondrial metabolism offers a promising neuroprotective strategy for a broad range of brain injuries.

  17. Platelet autologous growth factors decrease the osteochondral regeneration capability of a collagen-hydroxyapatite scaffold in a sheep model

    Directory of Open Access Journals (Sweden)

    Giavaresi Gianluca

    2010-09-01

    Full Text Available Abstract Background Current research aims to develop innovative approaches to improve chondral and osteochondral regeneration. The objective of this study was to investigate the regenerative potential of platelet-rich plasma (PRP to enhance the repair process of a collagen-hydroxyapatite scaffold in osteochondral defects in a sheep model. Methods PRP was added to a new, multi-layer gradient, nanocomposite scaffold that was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. Twenty-four osteochondral lesions were created in sheep femoral condyles. The animals were randomised to three treatment groups: scaffold, scaffold loaded with autologous PRP, and empty defect (control. The animals were sacrificed and evaluated six months after surgery. Results Gross evaluation and histology of the specimens showed good integration of the chondral surface in both treatment groups. Significantly better bone regeneration and cartilage surface reconstruction were observed in the group treated with the scaffold alone. Incomplete bone regeneration and irregular cartilage surface integration were observed in the group treated with the scaffold where PRP was added. In the control group, no bone and cartilage defect healing occurred; defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. Conclusions The hydroxyapatite-collagen scaffold enhanced osteochondral lesion repair, but the combination with platelet growth factors did not have an additive effect; on the contrary, PRP administration had a negative effect on the results obtained by disturbing the regenerative process. In the scaffold + PRP group, highly amorphous cartilaginous repair tissue and poorly spatially organised underlying bone tissue were found.

  18. MicroRNA-155 Deficiency Leads to Decreased Atherosclerosis, Increased White Adipose Tissue Obesity, and Non-alcoholic Fatty Liver Disease: A NOVEL MOUSE MODEL OF OBESITY PARADOX.

    Science.gov (United States)

    Virtue, Anthony; Johnson, Candice; Lopez-Pastraña, Jahaira; Shao, Ying; Fu, Hangfei; Li, Xinyuan; Li, Ya-Feng; Yin, Ying; Mai, Jietang; Rizzo, Victor; Tordoff, Michael; Bagi, Zsolt; Shan, Huimin; Jiang, Xiaohua; Wang, Hong; Yang, Xiao-Feng

    2017-01-27

    Obesity paradox (OP) describes a widely observed clinical finding of improved cardiovascular fitness and survival in some overweight or obese patients. The molecular mechanisms underlying OP remain enigmatic partly due to a lack of animal models mirroring OP in patients. Using apolipoprotein E knock-out (apoE -/- ) mice on a high fat (HF) diet as an atherosclerotic obesity model, we demonstrated 1) microRNA-155 (miRNA-155, miR-155) is significantly up-regulated in the aortas of apoE -/- mice, and miR-155 deficiency in apoE -/- mice inhibits atherosclerosis; 2) apoE -/- /miR-155 -/- (double knock-out (DKO)) mice show HF diet-induced obesity, adipocyte hypertrophy, and present with non-alcoholic fatty liver disease; 3) DKO mice demonstrate HF diet-induced elevations of plasma leptin, resistin, fed-state and fasting insulin and increased expression of adipogenic transcription factors but lack glucose intolerance and insulin resistance. Our results are the first to present an OP model using DKO mice with features of decreased atherosclerosis, increased obesity, and non-alcoholic fatty liver disease. Our findings suggest the mechanistic role of reduced miR-155 expression in OP and present a new OP working model based on a single miRNA deficiency in diet-induced obese atherogenic mice. Furthermore, our results serve as a breakthrough in understanding the potential mechanism underlying OP and provide a new biomarker and novel therapeutic target for OP-related metabolic diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Quantitative understanding of Forbush decrease drivers based on shock-only and CME-only models using global signature of February 14, 1978 event

    International Nuclear Information System (INIS)

    Raghav, Anil; Lotekar, Ajay; Bhaskar, Ankush; Vichare, Geeta; Yadav, Virendra

    2014-01-01

    We have studied the Forbush decrease (FD) event that occurred on February 14, 1978 using 43 neutron monitor observatories to understand the global signature of FD. We have studied rigidity dependence of shock amplitude and total FD amplitude. We have found almost the same power law index for both shock phase amplitude and total FD amplitude. Local time variation of shock phase amplitude and maximum depression time of FD have been investigated which indicate possible effect of shock/CME orientation. We have analyzed rigidity dependence of time constants of two phase recovery. Time constants of slow component of recovery phase show rigidity dependence and imply possible effect of diffusion. Solar wind speed was observed to be well correlated with slow component of FD recovery phase. This indicates solar wind speed as possible driver of recovery phase. To investigate the contribution of interplanetary drivers, shock and CME in FD, we have used shock-only and CME-only models. We have applied these models separately to shock phase and main phase amplitudes respectively. This confirms presently accepted physical scenario that the first step of FD is due to propagating shock barrier and second step is due to flux rope of CME/magnetic cloud

  20. Intake of Moringa oleifera Leaf Extract Decreases IL-1 and TNF-α Levels in Dyslipidemic Wistar Rat Model

    Directory of Open Access Journals (Sweden)

    Sri Wahyuni

    2017-05-01

    Full Text Available Changes in consumption behavior to instant food cause various health problems, such as obesity, dislipidemia, and atherosclerosis. A study was conducted to investigate Moringa oleifera extract as an anti-inflammation product that decreases the levels of biochemical markers IL-1 and TNF-a. This experiment was done with randomized pre- and posttest control-group design, employing 40 Wistar rats separated into five groups: control group 0% M. oleifera leaf extract (P0, treatment group 1 with 10% M. oleifera leaf extract (P1, treatment group 2 with 15% M. oleifera leaf extract (P2, treatment group 3 with 20% M. oleifera leaf extract (P3, and treatment group 4 with 25% M. oleifera leaf extract (P4. This research observed that intake of 20% M. oleifera leaf extract results in the highest significant decrease of 15.42% of IL-1 level (134.64 ± 1.98 to 113.87 ± 4.30 pg/mL and decrease of 45.63% of TNF-α level (28.62 ± 1.25 to 15.56 ± 7.20 pg/mL. Therefore, it can be concluded that intake of M. oleifera leaf extract by Wistar rat has anti-inflammatory effects on chronic dyslipidemia through decrease of IL-1 and TNF-α levels and histopathology profile. Further research is required to determine whether the application of M. oleifera leaf extract (daun kelor in humans will have similar anti-inflammation effects.

  1. Experimental and Finite Element Modeling of Near-Threshold Fatigue Crack Growth for the K-Decreasing Test Method

    Science.gov (United States)

    Smith, Stephen W.; Seshadri, Banavara R.; Newman, John A.

    2015-01-01

    The experimental methods to determine near-threshold fatigue crack growth rate data are prescribed in ASTM standard E647. To produce near-threshold data at a constant stress ratio (R), the applied stress-intensity factor (K) is decreased as the crack grows based on a specified K-gradient. Consequently, as the fatigue crack growth rate threshold is approached and the crack tip opening displacement decreases, remote crack wake contact may occur due to the plastically deformed crack wake surfaces and shield the growing crack tip resulting in a reduced crack tip driving force and non-representative crack growth rate data. If such data are used to life a component, the evaluation could yield highly non-conservative predictions. Although this anomalous behavior has been shown to be affected by K-gradient, starting K level, residual stresses, environmental assisted cracking, specimen geometry, and material type, the specifications within the standard to avoid this effect are limited to a maximum fatigue crack growth rate and a suggestion for the K-gradient value. This paper provides parallel experimental and computational simulations for the K-decreasing method for two materials (an aluminum alloy, AA 2024-T3 and a titanium alloy, Ti 6-2-2-2-2) to aid in establishing clear understanding of appropriate testing requirements. These simulations investigate the effect of K-gradient, the maximum value of stress-intensity factor applied, and material type. A material independent term is developed to guide in the selection of appropriate test conditions for most engineering alloys. With the use of such a term, near-threshold fatigue crack growth rate tests can be performed at accelerated rates, near-threshold data can be acquired in days instead of weeks without having to establish testing criteria through trial and error, and these data can be acquired for most engineering materials, even those that are produced in relatively small product forms.

  2. Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Weiner, H L; Lemere, C A; Maron, R

    2000-01-01

    Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease-implicated ......Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease......-implicated proteins can induce antigen-specific anti-inflammatory immune responses in mucosal lymphoid tissue which then act systemically. We hypothesized that chronic mucosal administration of Abeta peptide might induce an anti-inflammatory process in AD brain tissue that could beneficially affect...... Abeta plaque burden and Abeta42 levels in mice treated intranasally with Abeta peptide versus controls treated with myelin basic protein or left untreated. This lower Abeta burden was associated with decreased local microglial and astrocytic activation, decreased neuritic dystrophy, serum anti...

  3. Decrease in paracellular permeability and chemosensitivity to doxorubicin by claudin-1 in spheroid culture models of human lung adenocarcinoma A549 cells.

    Science.gov (United States)

    Akizuki, Risa; Maruhashi, Ryohei; Eguchi, Hiroaki; Kitabatake, Kazuki; Tsukimoto, Mitsutoshi; Furuta, Takumi; Matsunaga, Toshiyuki; Endo, Satoshi; Ikari, Akira

    2018-03-07

    Chemotherapy resistance is a major problem in the treatment of cancer, but the underlying mechanisms are not fully understood. We found that the expression levels of claudin-1 (CLDN1) and 3, tight junctional proteins, are upregulated in cisplatin (CDDP)-resistant human lung adenocarcinoma A549 (A549R) cells. A549R cells showed cross-resistance to doxorubicin (DXR). Here, the expression mechanism and function of CLDN1 and 3 were examined. CLDN1 and 3 were mainly localized at tight junctions concomitant with zonula occludens (ZO)-1, a scaffolding protein, in A549 and A549R cells. The phosphorylation levels of Src, MEK, ERK, c-Fos, and Akt in A549R cells were higher than those in A549 cells. The expression levels of CLDN1 and 3 were decreased by LY-294002, a phosphoinositide 3-kinase (PI3K) inhibitor, and BAY 11-7082, an NF-κB inhibitor. The overexpression of CLDN1 and 3 decreased the paracellular permeability of DXR in A549 cells. Hypoxia levels in A549R and CLDN1-overexpressing cells (CLDN1/A549) were greater than those in A549, mock/A549, and CLDN3/A549 cells in a spheroid culture model. In contrast, accumulation in the region inside the spheroids and the toxicity of DXR in A549R and CLDN1/A549 cells were lower than those in other cells. Furthermore, the accumulation and toxicity of DXR were rescued by CLDN1 siRNA in A549R cells. We suggest that CLDN1 is upregulated by CDDP resistance through activation of a PI3K/Akt/NF-κB pathway, resulting in the inhibition of penetration of anticancer drugs into the inner area of spheroids. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Evolutionary Modeling Predicts a Decrease in Postcopulatory Sperm Viability as a Response to Increasing Levels of Sperm Competition

    NARCIS (Netherlands)

    Engqvist, Leif

    Sperm competition has been found to have a strong influence on the evolution of many male and female reproductive traits. Theoretical models have shown that, with increasing levels of sperm competition, males are predicted to increase ejaculate investment, and there is ample empirical evidence

  5. A Policy Model for Use of Aversive and Deprivation Procedures to Decrease Problem Behaviors of Students in Special Education.

    Science.gov (United States)

    Braaten, Sheldon

    1991-01-01

    A draft policy developed by the Minneapolis (Minnesota) public schools concerning the use of aversive or deprivation procedures with students who are handicapped is presented. The policy model covers such elements as response to prior interventions; written treatment plan; informed consent; supervision; maintenance and retention of records;…

  6. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...... relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky...

  7. Rikkunshito, a Japanese Kampo Medicine, Ameliorates Decreased Feeding Behavior via Ghrelin and Serotonin 2B Receptor Signaling in a Novelty Stress Murine Model

    Directory of Open Access Journals (Sweden)

    Chihiro Yamada

    2013-01-01

    Full Text Available We investigated the effects of rikkunshito (RKT, a ghrelin signal enhancer, on the decrease in food intake after exposure to novelty stress in mice. RKT administration (500 mg/kg, per os improved the decrease in 6 h cumulative food intake. In control mice, the plasma acylated ghrelin levels significantly increased by 24 h fasting. In contrast, the acylated ghrelin levels did not increase by fasting in mice exposed to the novelty stress. RKT administration to the novelty stress mice showed a significant increase in the acylated ghrelin levels compared with that in the distilled-water-treated control mice. Food intake after administering serotonin 2B (5-HT2B receptor antagonists was evaluated to clarify the role of 5-HT2B receptor activation in the decrease in feeding behavior after novelty stress. SB215505 and SB204741, 5-HT2B receptor antagonists, significantly improved the decrease in food intake after exposure to novelty stress. A component of RKT, isoliquiritigenin, prevented the decrease in 6 h cumulative food intake. Isoliquiritigenin showed 5-HT2B receptor antagonistic activity in vitro. In conclusion, the results suggested that RKT improves the decrease in food intake after novelty stress probably via 5-HT2B receptor antagonism of isoliquiritigenin contained in RKT.

  8. Rikkunshito, a Japanese kampo medicine, ameliorates decreased feeding behavior via ghrelin and serotonin 2B receptor signaling in a novelty stress murine model.

    Science.gov (United States)

    Yamada, Chihiro; Saegusa, Yayoi; Nakagawa, Koji; Ohnishi, Shunsuke; Muto, Shuichi; Nahata, Miwa; Sadakane, Chiharu; Hattori, Tomohisa; Sakamoto, Naoya; Takeda, Hiroshi

    2013-01-01

    We investigated the effects of rikkunshito (RKT), a ghrelin signal enhancer, on the decrease in food intake after exposure to novelty stress in mice. RKT administration (500 mg/kg, per os) improved the decrease in 6 h cumulative food intake. In control mice, the plasma acylated ghrelin levels significantly increased by 24 h fasting. In contrast, the acylated ghrelin levels did not increase by fasting in mice exposed to the novelty stress. RKT administration to the novelty stress mice showed a significant increase in the acylated ghrelin levels compared with that in the distilled-water-treated control mice. Food intake after administering serotonin 2B (5-HT(2B)) receptor antagonists was evaluated to clarify the role of 5-HT(2B) receptor activation in the decrease in feeding behavior after novelty stress. SB215505 and SB204741, 5-HT(2B) receptor antagonists, significantly improved the decrease in food intake after exposure to novelty stress. A component of RKT, isoliquiritigenin, prevented the decrease in 6 h cumulative food intake. Isoliquiritigenin showed 5-HT(2B) receptor antagonistic activity in vitro. In conclusion, the results suggested that RKT improves the decrease in food intake after novelty stress probably via 5-HT(2B) receptor antagonism of isoliquiritigenin contained in RKT.

  9. The effect of an instructional program based on health belief model in decreasing cesarean rate among primiparous pregnant mothers.

    Science.gov (United States)

    Hassani, Laleh; Aghamolaei, Teamur; Ghanbarnejad, Amin; Dadipoor, Sakineh

    2016-01-01

    Although cesarean section has saved many mothers' and infants' lives, the problem is in its increasing prevalence. According to recent statistics, the current rate of cesarean in Iran is in fact 3-4 times as more than the standard rate defined by WHO. Therefore, the present study is aimed to estimate the effect of an instructional program based on health belief model on reducing cesarean rate among primiparous pregnant women. In this semi-experimental research, 60 primiparous women who had visited Bandar Abbas Healthcare Centers were selected as the subjects. They were in their 26-30(th) week of pregnancy. They were selected in a multi-stage cluster sampling method (a combination of clustering and simple randomization), and were divided into two groups, subjects and control group. The data were gathered using a valid and reliable questionnaire. The instructional intervention was done after the completion of the pretest questionnaire based on the sub-constructs of the health belief model in six instructional sessions. 1 month after the intervention, posttest questionnaires were completed by the subjects in both groups. The data were analyzed using descriptive statistics, standard deviation, independent t-test, and paired t-test. The significance level was set at health belief model can significantly influence pregnant women's awareness, intention, and choice of delivery type.

  10. Spatial Heterodyne Observations of Water (SHOW) vapour in the upper troposphere and lower stratosphere from a high altitude aircraft: Modelling and sensitivity analysis

    Science.gov (United States)

    Langille, J. A.; Letros, D.; Zawada, D.; Bourassa, A.; Degenstein, D.; Solheim, B.

    2018-04-01

    A spatial heterodyne spectrometer (SHS) has been developed to measure the vertical distribution of water vapour in the upper troposphere and the lower stratosphere with a high vertical resolution (∼500 m). The Spatial Heterodyne Observations of Water (SHOW) instrument combines an imaging system with a monolithic field-widened SHS to observe limb scattered sunlight in a vibrational band of water (1363 nm-1366 nm). The instrument has been optimized for observations from NASA's ER-2 aircraft as a proof-of-concept for a future low earth orbit satellite deployment. A robust model has been developed to simulate SHOW ER-2 limb measurements and retrievals. This paper presents the simulation of the SHOW ER-2 limb measurements along a hypothetical flight track and examines the sensitivity of the measurement and retrieval approach. Water vapour fields from an Environment and Climate Change Canada forecast model are used to represent realistic spatial variability along the flight path. High spectral resolution limb scattered radiances are simulated using the SASKTRAN radiative transfer model. It is shown that the SHOW instrument onboard the ER-2 is capable of resolving the water vapour variability in the UTLS from approximately 12 km - 18 km with ±1 ppm accuracy. Vertical resolutions between 500 m and 1 km are feasible. The along track sampling capability of the instrument is also discussed.

  11. Fixed-Angle, Posteriorly Connected Anterior Cage Reconstruction Improves Stiffness and Decreases Cancellous Subsidence in a Spondylectomy Model.

    Science.gov (United States)

    Colman, Matthew W; Guss, Andrew; Bachus, Kent N; Spiker, W Ryan; Lawrence, Brandon D; Brodke, Darrel S

    2016-05-01

    An idealized biomechanical model. The aim of this study was to evaluate the biomechanical properties of a construct designed to minimize intervertebral cage subsidence and maximize stiffness. Reconstruction after vertebral resection typically involves posterior segmental fixation and anterior interbody support. However, poor bone density, adjuvant radiation, or the oncologic need for endplate resection make interbody device subsidence and resultant instrumentation failure a significant concern. An idealized thoracolumbar spondylectomy reconstruction model was constructed using titanium segmental instrumentation and Delrin plastic. In vivo mechanical stress was simulated on a custom multi-axis spine simulator. Rigid body position in space was measured using an optical motion-capture system. Cancellous subsidence was modeled using a 1 cm thick wafer of number 3 closed-cell Sawbones foam at one endplate. Ten foam specimens were tested in a control state consisting of posterior segmental fixation with a free interbody cage. Ten additional foam specimens were tested in the test state, with the Delrin interbody cage "connected" to the posterior rods using two additional pedicle screws placed into the cage. Foam indentation was quantified using a precision digital surface-mapping device, and subsidence volume calculated using geometric integration. The control group exhibited significantly greater foam indentation after cycling, with a mean subsidence volume of 1906 mm [95% confidence interval (95% CI) 1810-2001] than the connected cage group subsidence volume of 977 mm (95% CI 928-1026 mm; P subsidence compared with a traditional unconnected cage. N/A.

  12. Complex cells decrease errors for the Müller-Lyer illusion in a model of the visual ventral stream

    Directory of Open Access Journals (Sweden)

    Astrid eZeman

    2014-09-01

    Full Text Available To improve robustness in object recognition, many artificial visual systems imitate the way in which the human visual cortex encodes object information as a hierarchical set of features. These systems are usually evaluated in terms of their ability to accurately categorize well-defined, unambiguous objects and scenes. In the real world, however, not all objects and scenes are presented clearly, with well-defined labels and interpretations. Visual illusions demonstrate a disparity between perception and objective reality, allowing psychophysicists to methodically manipulate stimuli and study our interpretation of the environment. One prominent effect, the Müller-Lyer illusion, is demonstrated when the perceived length of a line is contracted (or expanded by the addition of arrowheads (or arrow-tails to its ends. HMAX, a benchmark object recognition system, consistently produces a bias when classifying Müller-Lyer images. HMAX is a hierarchical, artificial neural network that imitates the ‘simple’ and ‘complex’ cell layers found in the visual ventral stream. In this study, we perform two experiments to explore the Müller-Lyer illusion in HMAX, asking: 1 How do simple versus complex cell operations within HMAX affect illusory bias and precision? 2 How does varying the position of the figures in the input image affect classification using HMAX? In our first experiment, we assessed classification after traversing each layer of HMAX and found that in general, kernel operations performed by simple cells increase bias and uncertainty while max-pooling operations executed by complex cells decrease bias and uncertainty. In our second experiment, we increased variation in the positions of figures in the input that reduced bias and uncertainty in HMAX. Our findings suggest that the Müller-Lyer illusion is exacerbated by the vulnerability of simple cell operations to positional fluctuations, but ameliorated by the robustness of complex cell

  13. Traditional graft preparation decreases physiologic responses, diminishes viscoelasticity, and reduces cellular viability of the conduit: a porcine saphenous vein model

    Science.gov (United States)

    Wise, Eric S.; Hocking, Kyle M.; Luo, Weifeng; Feldman, Daniel L.; Song, Jun; Komalavilas, Padmini; Cheung-Flynn, Joyce; Brophy, Colleen M.

    2016-01-01

    Traditional methods of intraoperative human saphenous vein (SV) preparation for use as bypass grafts can be deleterious to the conduit. The purpose of this study was to characterize acute graft preparation injury, and to mitigate this harm via an improved preparation technique. Porcine saphenous veins were surgically harvested (unprepared controls, UnP) and prepared using the traditional (TraP) and improved preparations (ImP). The TraP used unregulated radial distension, marking with a surgical skin marker and preservation in heparinized normal saline. ImP used pressure-regulated distension, brilliant blue FCF-based pen marking and preservation in heparinized Plasma-Lyte A. Rings from each preparation were suspended on a muscle bath for characterization of physiologic responses to vasoactive agents and viscoelasticity. Cellular viability was assessed using the methyl thiazolyl tetrazolium (MTT) assay and the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay for apoptosis. Contractile responses to potassium chloride (110 mM) and phenylephrine (10 μM), and endothelial -dependent and -independent vasodilatory responses to carbachol (0.5 μM) and sodium nitroprusside (1 μM), respectively, were decreased in TraP tissues compared to both UnP and ImP tissues (P ≤ .05). TraP tissues demonstrated diminished viscoelasticity relative to UnP and ImP tissues (P ≤ .05), and reduced cellular viability relative to UnP control (P ≤ .01) by the MTT assay. On TUNEL assay, TraP tissues demonstrated a greater degree of apoptosis relative to UnP and ImP tissues (P ≤ .01). In conclusion, an improved preparation technique prevents vascular graft smooth muscle and endothelial injury observed in tissues prepared using a traditional approach. PMID:27216870

  14. Complex cells decrease errors for the Müller-Lyer illusion in a model of the visual ventral stream.

    Science.gov (United States)

    Zeman, Astrid; Obst, Oliver; Brooks, Kevin R

    2014-01-01

    To improve robustness in object recognition, many artificial visual systems imitate the way in which the human visual cortex encodes object information as a hierarchical set of features. These systems are usually evaluated in terms of their ability to accurately categorize well-defined, unambiguous objects and scenes. In the real world, however, not all objects and scenes are presented clearly, with well-defined labels and interpretations. Visual illusions demonstrate a disparity between perception and objective reality, allowing psychophysicists to methodically manipulate stimuli and study our interpretation of the environment. One prominent effect, the Müller-Lyer illusion, is demonstrated when the perceived length of a line is contracted (or expanded) by the addition of arrowheads (or arrow-tails) to its ends. HMAX, a benchmark object recognition system, consistently produces a bias when classifying Müller-Lyer images. HMAX is a hierarchical, artificial neural network that imitates the "simple" and "complex" cell layers found in the visual ventral stream. In this study, we perform two experiments to explore the Müller-Lyer illusion in HMAX, asking: (1) How do simple vs. complex cell operations within HMAX affect illusory bias and precision? (2) How does varying the position of the figures in the input image affect classification using HMAX? In our first experiment, we assessed classification after traversing each layer of HMAX and found that in general, kernel operations performed by simple cells increase bias and uncertainty while max-pooling operations executed by complex cells decrease bias and uncertainty. In our second experiment, we increased variation in the positions of figures in the input images that reduced bias and uncertainty in HMAX. Our findings suggest that the Müller-Lyer illusion is exacerbated by the vulnerability of simple cell operations to positional fluctuations, but ameliorated by the robustness of complex cell responses to such

  15. Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson's Disease Model in Mice.

    Science.gov (United States)

    Mani, Sugumar; Sekar, Sathiya; Barathidasan, Rajamani; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Sevanan, Murugan; Chidambaram, Saravana Babu; Essa, Musthafa Mohamed; Guillemin, Gilles J; Sakharkar, Meena Kishore

    2018-02-09

    The present study was designed to ascertain the role of naringenin (NGN), a citrus fruit flavanone, against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced α-synuclein (SYN) pathology and neuroinflammation in a mouse model. NGN was administered to C57BL/6J mice once a day for 5 consecutive days prior to the MPTP intoxication. On day 5, 40-50 min after the NGN or vehicle administration, MPTP was injected in two divided doses (2× 40 mg/kg, i.p. at 16 h apart). The animals were observed for motor functions 48 h after the first MPTP injection. The animals were then euthanized, the brains collected to analyze SYN pathology, cytokines, and oxidative stress levels in the substantia nigra region. The NGN significantly downregulated SYN and upregulated dopamine transporter (DAT) and tyrosine hydroxylase (TH) protein expressions. It also downregulated tumor necrosis factor-α (TNFα) and interleukin 1β (IL1β) mRNA expressions and improved superoxide dismutase levels. It also reduced glutathione levels when compared to vehicle-treated PD animals. The upregulation of TH corroborates to an increase in dopamine, DOPAC, and homovanillic acid turnover and motor functions with NGN treatment. To summarize, NGN, a dietary flavone, has the potential to counteract MPTP-induced dopaminergic degeneration by regulating SYN pathology, neuroinflammation, and oxidative stress. This warrants the investigation of NGN's potential effects in a genetic model of PD.

  16. Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

    Directory of Open Access Journals (Sweden)

    Lingling Zeng

    Full Text Available Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal. We showed that malondialdehyde (MDA levels were increased and manganese superoxide dismutase (SOD2 activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

  17. A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

    Science.gov (United States)

    Kelsey, Thomas W; Li, Lucy Q; Mitchell, Rod T; Whelan, Ashley; Anderson, Richard A; Wallace, W Hamish B

    2014-01-01

    The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5-97.5 percentile)] at 15.4 (7.2-31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile)] to 13.0 (6.6-25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.

  18. Mask leak increases and minute ventilation decreases when chest compressions are added to bag ventilation in a neonatal manikin model.

    Science.gov (United States)

    Tracy, Mark B; Shah, Dharmesh; Hinder, Murray; Klimek, Jan; Marceau, James; Wright, Audrey

    2014-05-01

    To determine changes in respiratory mechanics when chest compressions are added to mask ventilation, as recommended by the International Liaison Committee on Resuscitation (ILCOR) guidelines for newborn infants. Using a Laerdal Advanced Life Support leak-free baby manikin and a 240-mL self-inflating bag, 58 neonatal staff members were randomly paired to provide mask ventilation, followed by mask ventilation with chest compressions with a 1:3 ratio, for two minutes each. A Florian respiratory function monitor was used to measure respiratory mechanics, including mask leak. The addition of chest compressions to mask ventilation led to a significant reduction in inflation rate, from 63.9 to 32.9 breaths per minute (p mask leak of 6.8% (p mask ventilation, in accordance with the ILCOR guidelines, in a manikin model is associated with a significant reduction in delivered ventilation and increase in mask leak. If similar findings occur in human infants needing an escalation in resuscitation, there is a potential risk of either delay in recovery or inadequate response to resuscitation. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  19. Methamphetamine decreases CD4 T cell frequency and alters pro-inflammatory cytokine production in a model of drug abuse

    Science.gov (United States)

    Mata, Mariana M.; Napier, T. Celeste; Graves, Steven M.; Mahmood, Fareeha; Raeisi, Shohreh; Baum, Linda L.

    2015-01-01

    The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the comorbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n = 18) or be given saline (control; n = 16) for 14 days. One day after the last self-administration session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γand TNF-α, and frequencies of CD4+, CD8+, CD200+ and CD11b/c+ lymphocytes in the spleen. Rats that self-administer methamphetamine had a lower frequency of CD4+ T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4+ T cells. Methamphetamine using rats had a higher frequency of CD8+ T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Or data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why African American men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection. PMID:25678251

  20. Methamphetamine decreases CD4 T cell frequency and alters pro-inflammatory cytokine production in a model of drug abuse.

    Science.gov (United States)

    Mata, Mariana M; Napier, T Celeste; Graves, Steven M; Mahmood, Fareeha; Raeisi, Shohreh; Baum, Linda L

    2015-04-05

    The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the co-morbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n=18) or be given saline (control; n=16) for 14 days. One day after the last operant session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γ and TNF-α, and frequencies of CD4(+), CD8(+), CD200(+) and CD11b/c(+) lymphocytes in the spleen. Rats that self-administered methamphetamine had a lower frequency of CD4(+) T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4(+) T cells. Methamphetamine using rats had a higher frequency of CD8(+) T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Our data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Phosphatidylcholine 36:1 concentration decreases along with demyelination in the cuprizone animal model and post-mortem of multiple sclerosis brain tissue.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Hildebrand, Kayla D; Nyamoya, Stella D; Amor, Sandra; Bazinet, Richard P; Kipp, Markus

    2018-03-25

    Multiple sclerosis (MS) is a demyelinating and inflammatory disease. Myelin is enriched in lipids, and more specifically, oleic acid. The goal of this study was to evaluate the concentration of oleic acid following demyelination and remyelination in the cuprizone model, test if these changes occurred in specific lipid species, and whether differences in the cuprizone model correlate with changes observed in post-mortem human brains. Eight-week-old C57Bl/6 mice were fed a 0.2% cuprizone diet for 5 weeks and some animals allowed to recover for 11 days. Demyelination, inflammation, and lipid concentrations were measured in the corpus callosum. Standard fatty acid techniques and liquid chromatography combined with tandem mass spectrometry were performed to measure concentrations of fatty acids in total brain lipids and a panel of lipid species within the phosphatidylcholine (PC). Similar measurements were conducted in post-mortem brain tissues of MS patients and were compared to healthy controls. Five weeks of cuprizone administration resulted in demyelination followed by significant remyelination after 11 days of recovery. Compared to control, oleic acid was decreased after 5 weeks of cuprizone treatment and increased during the recovery phase. This decrease in oleic acid was associated with a specific decrease in the PC 36:1 pool. Similar results were observed in human post-mortem brains. Decreases in myelin content in the cuprizone model was accompanied with decreases in oleic acid concentration and is associated with PC 36:1 suggesting that specific lipids could be a potential biomarker for myelin degeneration. The biological relevance of oleic acid for disease progression remains to be verified. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Decreased intracellular [Ca2+ ] coincides with reduced expression of Dhprα1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis.

    Science.gov (United States)

    Wang, Meng-Meng; Hao, Li-Ying; Guo, Feng; Zhong, Bin; Zhong, Xiao-Mei; Yuan, Jing; Hao, Yi-Fei; Zhao, Shuang; Sun, Xue-Fei; Lei, Ming; Jiao, Guang-Yu

    2017-12-01

    Sepsis can cause decreased diaphragmatic contractility. Intracellular calcium as a second messenger is central to diaphragmatic contractility. However, changes in intracellular calcium concentration ([Ca 2+ ]) and the distribution and co-localization of relevant calcium channels [dihydropyridine receptors, (DHPRα1s) and ryanodine receptors (RyR1)] remain unclear during sepsis. In this study we investigated the effect of changed intracellular [Ca 2+ ] and expression and distribution of DHPRα1s and RyR1 on diaphragm function during sepsis. We measured diaphragm contractility and isolated diaphragm muscle cells in a rat model of sepsis. The distribution and co-localization of DHPRα1s and RyR1 were determined using immunohistochemistry and immunofluorescence, whereas intracellular [Ca 2+ ] was measured by confocal microscopy and fluorescence spectrophotometry. Septic rat diaphragm contractility, expression of DHPRα1s and RyR1, and intracellular [Ca 2+ ] were significantly decreased in the rat sepsis model compared with controls. Decreased intracellular [Ca 2+ ] coincides with diaphragmatic contractility and decreased expression of DHPRα1s and RyR1 in sepsis. Muscle Nerve 56: 1128-1136, 2017. © 2017 Wiley Periodicals, Inc.

  3. An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase

    Directory of Open Access Journals (Sweden)

    Francisco Olmo

    2015-12-01

    Full Text Available In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz, two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by 1H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.

  4. A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.

    Directory of Open Access Journals (Sweden)

    Sandhya Boyapalle

    Full Text Available Human immunodeficiency virus (HIV types 1 and 2 (HIV-1 and HIV-2 are the etiologic agents of AIDS. Most HIV-1 infected individuals worldwide are women, who acquire HIV infections during sexual contact. Blocking HIV mucosal transmission and local spread in the female lower genital tract is important in preventing infection and ultimately eliminating the pandemic. Microbicides work by destroying the microbes or preventing them from establishing an infection. Thus, a number of different types of microbicides are under investigation, however, the lack of their solubility and bioavailability, and toxicity has been major hurdles. Herein, we report the development of multifunctional chitosan-lipid nanocomplexes that can effectively deliver plasmids encoding siRNA(s as microbicides without adverse effects and provide significant protection against HIV in both in vitro and in vivo models. Chitosan or chitosan-lipid (chlipid was complexed with a cocktail of plasmids encoding HIV-1-specific siRNAs (psiRNAs and evaluated for their efficacy in HEK-293 cells, PBMCs derived from nonhuman primates, 3-dimensional human vaginal ectocervical tissue (3D-VEC model and also in non-human primate model. Moreover, prophylactic administration of the chlipid to deliver a psiRNA cocktail intravaginally with a cream formulation in a non-human primate model showed substantial reduction of SHIV (simian/human immunodeficiency virus SF162 viral titers. Taken together, these studies demonstrate the potential of chlipid-siRNA nanocomplexes as a potential genetic microbicide against HIV infections.

  5. Decreased surface expression of the δ subunit of the GABAA receptor contributes to reduced tonic inhibition in dentate granule cells in a mouse model of fragile X syndrome.

    Science.gov (United States)

    Zhang, Nianhui; Peng, Zechun; Tong, Xiaoping; Lindemeyer, A Kerstin; Cetina, Yliana; Huang, Christine S; Olsen, Richard W; Otis, Thomas S; Houser, Carolyn R

    2017-11-01

    While numerous changes in the GABA system have been identified in models of Fragile X Syndrome (FXS), alterations in subunits of the GABA A receptors (GABA A Rs) that mediate tonic inhibition are particularly intriguing. Considering the key role of tonic inhibition in controlling neuronal excitability, reduced tonic inhibition could contribute to FXS-associated disorders such as hyperactivity, hypersensitivity, and increased seizure susceptibility. The current study has focused on the expression and function of the δ subunit of the GABA A R, a major subunit involved in tonic inhibition, in granule cells of the dentate gyrus in the Fmr1 knockout (KO) mouse model of FXS. Electrophysiological studies of dentate granule cells revealed a marked, nearly four-fold, decrease in tonic inhibition in the Fmr1 KO mice, as well as reduced effects of two δ subunit-preferring pharmacological agents, THIP and DS2, supporting the suggestion that δ subunit-containing GABA A Rs are compromised in the Fmr1 KO mice. Immunohistochemistry demonstrated a small but statistically significant decrease in δ subunit labeling in the molecular layer of the dentate gyrus in Fmr1 KO mice compared to wildtype (WT) littermates. The discrepancy between the large deficits in GABA-mediated tonic inhibition in granule cells in the Fmr1 KO mice and only modest reductions in immunolabeling of the δ subunit led to studies of surface expression of the δ subunit. Cross-linking experiments followed by Western blot analysis demonstrated a small, non-significant decrease in total δ subunit protein in the hippocampus of Fmr1 KO mice, but a four-fold decrease in surface expression of the δ subunit in these mice. No significant changes were observed in total or surface expression of the α4 subunit protein, a major partner of the δ subunit in the forebrain. Postembedding immunogold labeling for the δ subunit demonstrated a large, three-fold, decrease in the number of symmetric synapses with

  6. Synthesis, Modelling, and Anticonvulsant Studies of New Quinazolines Showing Three Highly Active Compounds with Low Toxicity and High Affinity to the GABA-A Receptor

    Directory of Open Access Journals (Sweden)

    Mohamed F. Zayed

    2017-01-01

    Full Text Available Some novel fluorinated quinazolines (5a–j were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR, mass spectrometry (MS spectra, 1H nuclear magnetic resonance (NMR, 13C-NMR, and elemental analysis (CHN. The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ test and maximal electroshock (MES-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds 5b, 5c, and 5d showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization.

  7. Site-directed mutagenesis and molecular modelling studies show the role of Asp82 and cysteines in rat acylase 1, a member of the M20 family

    International Nuclear Information System (INIS)

    Herga, Sameh; Brutus, Alexandre; Vitale, Rosa Maria; Miche, Helene; Perrier, Josette; Puigserver, Antoine; Scaloni, Andrea; Giardina, Thierry

    2005-01-01

    Acylase 1 from rat kidney catalyzes the hydrolysis of acyl-amino acids. Sequence alignment has shown that this enzyme belongs to the metalloprotein family M20. Site-directed mutagenesis experiments led to the identification of one functionally important amino acid residue located near one of the zinc coordinating residues, which play a critical role in the enzymatic activity. The D82N- and D82E-substituted forms showed no significant activity and very low activity, respectively, along with a loss of zinc coordination. Molecular modelling investigations indicated a putative role of D82 in ensuring a proper protonation of catalytic histidine. In addition, none of the five cysteine residues present in the rat kidney acylase 1 sequence seemed involved in the catalytic process: the loss of activity induced by the C294A substitution was probably due to a conformational change in the 3D structure

  8. Analysis of the Fgfr2C342Y mouse model shows condensation defects due to misregulation of Sox9 expression in prechondrocytic mesenchyme

    Directory of Open Access Journals (Sweden)

    Emma Peskett

    2017-02-01

    Full Text Available Syndromic craniosynostosis caused by mutations in FGFR2 is characterised by developmental pathology in both endochondral and membranous skeletogenesis. Detailed phenotypic characterisation of features in the membranous calvarium, the endochondral cranial base and other structures in the axial and appendicular skeleton has not been performed at embryonic stages. We investigated bone development in the Crouzon mouse model (Fgfr2C342Y at pre- and post-ossification stages to improve understanding of the underlying pathogenesis. Phenotypic analysis was performed by whole-mount skeletal staining (Alcian Blue/Alizarin Red and histological staining of sections of CD1 wild-type (WT, Fgfr2C342Y/+ heterozygous (HET and Fgfr2C342Y/C342Y homozygous (HOM mouse embryos from embryonic day (E12.5-E17.5 stages. Gene expression (Sox9, Shh, Fgf10 and Runx2 was studied by in situ hybridisation and protein expression (COL2A1 by immunohistochemistry. Our analysis has identified severely decreased osteogenesis in parts of the craniofacial skeleton together with increased chondrogenesis in parts of the endochondral and cartilaginous skeleton in HOM embryos. The Sox9 expression domain in tracheal and basi-cranial chondrocytic precursors at E13.5 in HOM embryos is increased and expanded, correlating with the phenotypic observations which suggest FGFR2 signalling regulates Sox9 expression. Combined with abnormal staining of type II collagen in pre-chondrocytic mesenchyme, this is indicative of a mesenchymal condensation defect. An expanded spectrum of phenotypic features observed in the Fgfr2C342Y/C342Y mouse embryo paves the way towards better understanding the clinical attributes of human Crouzon–Pfeiffer syndrome. FGFR2 mutation results in impaired skeletogenesis; however, our findings suggest that many phenotypic aberrations stem from a primary failure of pre-chondrogenic/osteogenic mesenchymal condensation and link FGFR2 to SOX9, a principal regulator of

  9. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

    Science.gov (United States)

    Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

    2017-01-01

    The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

  10. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

    Directory of Open Access Journals (Sweden)

    Erik Karl Håkan Clemensson

    Full Text Available The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

  11. Show them the money? The role of pay, managerial need support, and justice in a self-determination theory model of intrinsic work motivation.

    Science.gov (United States)

    Olafsen, Anja H; Halvari, Hallgeir; Forest, Jacques; Deci, Edward L

    2015-08-01

    The link between money and motivation has been a debated topic for decades, especially in work organizations. However, field studies investigating the amount of pay in relation to employee motivation is lacking and there have been calls for empirical studies addressing compensation systems and motivation in the work domain. The purpose of this study was to examine outcomes associated with the amount of pay, and perceived distributive and procedural justice regarding pay in relation to those for perceived managerial need support. Participants were 166 bank employees who also reported on their basic psychological need satisfaction and intrinsic work motivation. SEM-analyses tested a self-determination theory (SDT) model, with satisfaction of the competence and autonomy needs as an intervening variable. The primary findings were that amount of pay and employees' perceived distributive justice regarding their pay were unrelated to employees' need satisfaction and intrinsic work motivation, but procedural justice regarding pay did affect these variables. However, managerial need support was the most important factor for promoting need satisfaction and intrinsic work motivation both directly, indirectly, and as a moderator in the model. Hence, the results of the present organizational field study support earlier laboratory experiments within the SDT framework showing that monetary rewards did not enhance intrinsic motivation. This seems to have profound implications for organizations concerned about motivating their employees. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  12. Showing Value (Editorial

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    Denise Koufogiannakis

    2009-06-01

    librarians on student achievement. Todd notes, “If we do not show value, we will not have a future. Evidence-based practice is not about the survival of school librarians, it’s about the survival of our students” (40. In this issue we feature school libraries and their connection to evidence based practice. Former Editor-in-Chief, Lindsay Glynn, began putting the wheels in motion for this feature almost a year ago. She invited Carol Gordon and Ross Todd to act as guest editors of the section, drawing upon their contacts and previous work in this field. The result is an issue with five feature articles exploring different aspects of the connection between school libraries and evidence based practice, from the theoretical to the practical. In addition, there is a thought-provoking Commentary by David Loertscher, asking whether we need the evolutionary model of evidence based practice, or something more revolutionary!In addition to the Feature section, we have a well-rounded issue with articles on the topics of library human resources, and the development of a scholars’ portal. As well, there are a record 10 evidence summaries and our educational EBL101 column. I hope there is something for everyone in this issue of EBLIP – enjoy, and see you soon in Stockholm!

  13. Show-Bix &

    DEFF Research Database (Denmark)

    2014-01-01

    The anti-reenactment 'Show-Bix &' consists of 5 dias projectors, a dial phone, quintophonic sound, and interactive elements. A responsive interface will enable the Dias projectors to show copies of original dias slides from the Show-Bix piece ”March på Stedet”, 265 images in total. The copies are...

  14. Inhalation of coriander volatile oil increased anxiolytic-antidepressant-like behaviors and decreased oxidative status in beta-amyloid (1-42) rat model of Alzheimer's disease.

    Science.gov (United States)

    Cioanca, Oana; Hritcu, Lucian; Mihasan, Marius; Trifan, Adriana; Hancianu, Monica

    2014-05-28

    The present study analyzed the possible anxiolytic, antidepressant and antioxidant proprieties of inhaled coriander volatile oil extracted from Coriandrum sativum var. microcarpum in beta-amyloid (1-42) rat model of Alzheimer's disease. The anxiolytic- and antidepressant-like effects of inhaled coriander volatile oil were studied by means of in vivo (elevated plus-maze and forced swimming tests) approaches. Also, the antioxidant activity in the hippocampus was assessed using catalase specific activity and the total content of the reduced glutathione. The beta-amyloid (1-42)-treated rats exhibited the following: decrease of the locomotor activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming and immobility times within forced swimming test. Exposure to coriander volatile oil significantly improved these parameters, suggesting anxiolytic- and antidepressant-like effects. Moreover, coriander volatile oil decreased catalase activity and increased glutathione level in the hippocampus. Our results suggest that multiple exposures to coriander volatile oil can be useful as a mean to counteract anxiety, depression and oxidative stress in Alzheimer's disease conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia

    Science.gov (United States)

    Dominguez, Jessica A.; Xie, Yan; Dunne, W. Michael; Yoseph, Benyam P.; Burd, Eileen M.; Coopersmith, Craig M.; Davidson, Nicholas O.

    2012-01-01

    Background The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the “motor” of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO), which exhibit a block in chylomicron assembly together with lipid malabsorption. Methodology/Principal Findings Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%) dying compared to 5/17 (29%) control mice (p<0.05). This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL) levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice. Conclusions/Significance These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by

  16. Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia.

    Directory of Open Access Journals (Sweden)

    Jessica A Dominguez

    Full Text Available The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the "motor" of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO, which exhibit a block in chylomicron assembly together with lipid malabsorption.Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0% dying compared to 5/17 (29% control mice (p<0.05. This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice.These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by metabolic and physiological adaptations in both intestinal and

  17. Development of a novel pink-eyed dilution mouse model showing progressive darkening of the eyes and coat hair with aging.

    Science.gov (United States)

    Ishikawa, Akira; Sugiyama, Makoto; Hondo, Eiichi; Kinoshita, Keiji; Yamagishi, Yuki

    2015-01-01

    Oca2(p-cas) (oculocutaneous albinism II; pink-eyed dilution castaneus) is a coat color mutant gene on mouse chromosome 7 that arose spontaneously in wild Mus musculus castaneus mice. Mice homozygous for Oca2(p-cas) usually exhibit pink eyes and gray coat hair on the non-agouti genetic background, and this ordinary phenotype remains unchanged throughout life. During breeding of a mixed strain carrying this gene on the C57BL/6J background, we discovered a novel spontaneous mutation that causes darkening of the eyes and coat hair with aging. In this study, we developed a novel mouse model showing this unique phenotype. Gross observations revealed that the pink eyes and gray coat hair of the novel mutant young mice became progressively darker in color by approximately 3 months after birth. Light and transmission-electron microscopic observations revealed a marked increase in melanin pigmentation of coat hair shafts and choroid of the eye in the novel mice compared to that in the ordinary mice. Sequence analysis of Oca2(p-cas) revealed a 4.1-kb deletion involving exons 15 and 16 of its wild-type gene. However, there was no sequence difference between the two types of mutant mice. Mating experiments suggested that the novel mutant phenotype was not inherited in a simple fashion, due to incomplete penetrance. The novel spontaneous mutant mouse is the first example of progressive hair darkening animals and is an essential animal model for understanding of the regulation mechanisms of melanin biosynthesis with aging.

  18. Assessing a five factor model of PTSD: is dysphoric arousal a unique PTSD construct showing differential relationships with anxiety and depression?

    Science.gov (United States)

    Armour, Cherie; Elhai, Jon D; Richardson, Don; Ractliffe, Kendra; Wang, Li; Elklit, Ask

    2012-03-01

    Posttraumatic stress disorder's (PTSD) latent structure has been widely debated. To date, two four-factor models (Numbing and Dysphoria) have received the majority of factor analytic support. Recently, Elhai et al. (2011) proposed and supported a revised (five-factor) Dysphoric Arousal model. Data were gathered from two separate samples; War veterans and Primary Care medical patients. The three models were compared and the resultant factors of the Dysphoric Arousal model were validated against external constructs of depression and anxiety. The Dysphoric Arousal model provided significantly better fit than the Numbing and Dysphoria models across both samples. When differentiating between factors, the current results support the idea that Dysphoric Arousal can be differentiated from Anxious Arousal but not from Emotional Numbing when correlated with depression. In conclusion, the Dysphoria model may be a more parsimonious representation of PTSD's latent structure in these trauma populations despite superior fit of the Dysphoric Arousal model. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH).

    Science.gov (United States)

    Cortez-Pinto, Helena; Borralho, Paula; Machado, Jorge; Lopes, Maria T; Gato, Inês V; Santos, António M; Guerreiro, António S

    2016-01-01

    Gut microbiota may play a role in non-alcoholic steatohepatitis (NASH). Previous studies showed that prebiotics and probiotics might halt the progression of steatohepatitis. To clarify the potential effect of Synbiotic 2000 ® Forte (Synb) in preventing or ameliorating diet induced steatohepatitis, particularly in fibrosis progression and how this intervention correlates with gut microbiota composition and endotoxinemia. Twenty-seven C57BL/6 mice were divided into three groups: chow diet (CD, n = 7); high-fat choline deficient diet (HFCD, n = 10) and HFCD diet supplemented with Synbiotic 2000 ® Forte (four probiotic strains and four prebiotics mixture) (HFCD + Synb, n = 10). At 6 and 18 weeks, blood samples (lipopolysaccharides assay - LPS), cecal feaces (gut microbiota) and liver tissue (histology) were collected for analysis. Both HCFD diet mice developed steatohepatitis with ballooning at 6 and 18 weeks, opposite to CD. Comparison of histological scores in HFCD and HFCD + Synb, at 6 and 18 weeks showed no significant difference regarding steatosis, inflammation, or ballooning. Evaluating fibrosis with Sirius Red, and degree of smooth-muscle cell activation, HFCD mice had significantly more fibrosis; addition of Synb significantly reduced fibrosis at 6 weeks and 18 weeks. Serum endotoxin levels were similarly increased in HFCD and HFCD + Synb at week 6; however at week 18 HFCD + Synb had significantly lower endotoxin levels than HFCD. Gut microbiota of HFCD vs CD, showed no significant differences regarding the phyla Firmicutes and Bacteroidetes , either at 6 or 18 weeks; Proteobacteria increased at 6 week (3.3) and 18 week (7.5), while the addition of Synb resulted in a decrease at week 18 (-3.90). Fusobacteria markedly increase at week 18 (10.0), but less so with the addition of Synb (5.2). Synbiotic 2000 ® Forte is able to modulate the mouse gut microbiota reducing the degree of fibrosis while simultaneously decreasing endotoxemia.

  20. Mechanical ventilation with high tidal volumes attenuates myocardial dysfunction by decreasing cardiac edema in a rat model of LPS-induced peritonitis

    Directory of Open Access Journals (Sweden)

    Smeding Lonneke

    2012-03-01

    Full Text Available Abstract Background Injurious mechanical ventilation (MV may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We investigated the effects of MV with injuriously high tidal volumes on the myocardium in an animal model of sepsis. Methods Normal rats and intraperitoneal (i.p. lipopolysaccharide (LPS-treated rats were ventilated with low (6 ml/kg and high (19 ml/kg tidal volumes (Vt under general anesthesia. Non-ventilated animals served as controls. Mean arterial pressure (MAP, central venous pressure (CVP, cardiac output (CO and pulmonary plateau pressure (Pplat were measured. Ex vivo myocardial function was measured in isolated Langendorff-perfused hearts. Cardiac expression of endothelial vascular cell adhesion molecule (VCAM-1 and edema were measured to evaluate endothelial inflammation and leakage. Results MAP decreased after LPS-treatment and Vt-dependently, both independent of each other and with interaction. MV Vt-dependently increased CVP and Pplat and decreased CO. LPS-induced peritonitis decreased myocardial function ex vivo but MV attenuated systolic dysfunction Vt-dependently. Cardiac endothelial VCAM-1 expression was increased by LPS treatment independent of MV. Cardiac edema was lowered Vt-dependently by MV, particularly after LPS, and correlated inversely with systolic myocardial function parameters ex vivo. Conclusion MV attenuated LPS-induced systolic myocardial dysfunction in a Vt-dependent manner. This was associated with a reduction in cardiac edema following a lower transmural coronary venous outflow pressure during LPS-induced coronary inflammation.

  1. Renal Denervation Decreases Susceptibility to Arrhythmogenic Cardiac Alternans and Ventricular Arrhythmia in a Rat Model of Post-Myocardial Infarction Heart Failure

    Directory of Open Access Journals (Sweden)

    Sheng-Nan Chang, MD

    2017-04-01

    Full Text Available Summary: Several studies have shown the beneficial effect of renal denervation (RDN in the treatment of ventricular arrhythmia, especially in the setting of heart failure (HF. However, the underlying mechanism of antiarrhythmic effect of RDN is unknown. Arrhythmogenic cardiac alternans, particularly spatially discordant repolarization alternans, characterized by simultaneous prolongation and shortening of action potential duration (APD in different myocardial regions, is central to the genesis of ventricular fibrillation in HF. Whether RDN decreases the susceptibility to arrhythmogenic cardiac alternans in HF has never been addressed before. The authors used a rat model of post-myocardial infarction HF and dual voltage-calcium optical mapping to investigate whether RDN could attenuate arrhythmogenic cardiac alternans that predisposes to ventricular arrhythmias, as well as the hemodynamic effect of RDN in HF. The HF rats had increased body weights, dilated hearts, and lower blood pressure. The HF rats also had longer ventricular APDs and a delay in the decay of the calcium transient, typical electrophysiological features of human HF. Susceptibility to calcium transient alternans, APD alternans, and spatially discordant APD alternans was increased in the HF hearts. RDN significantly attenuated a delay in the decay of the calcium transient, calcium transient and APD alternans, and importantly, the discordant APD alternans, and thereby decreased the incidence of induced ventricular arrhythmia in HF. RDN did not further decrease blood pressure in HF rats. In conclusion, RDN improves calcium cycling and prevents spatially discordant APD alternans and ventricular arrhythmia in HF. RDN does not aggravate hemodynamics in HF. Key Words: alternans, arrhythmia mechanism, heart failure, renal denervation

  2. Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition.

    Science.gov (United States)

    Chen, C L; Chou, K J; Fang, H C; Hsu, C Y; Huang, W C; Huang, C W; Huang, C K; Chen, H Y; Lee, P T

    2015-12-02

    Pathophysiological changes associated with chronic kidney disease impair angiogenic processes and increase renal fibrosis. Progenitor-like cells derived from adult kidney have been previously used to promote regeneration in acute kidney injury, even though it remained unclear whether the cells could be beneficial in chronic kidney disease (CKD). In this study, we established a CKD model by five-sixths nephrectomy and mouse kidney progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks after establishing CKD. We examined the impact of MKPCs on the progression of renal fibrosis and the potential of MKPCs to preserve the angiogenic process and prevent endothelial mesenchymal transition in vivo and in vitro. Our results demonstrate that the MKPCs delayed interstitial fibrosis and the progression of glomerular sclerosis and ameliorated the decline of kidney function. At 17 weeks, the treated mice exhibited lower blood pressures, higher hematocrit levels, and larger kidney sizes than the control mice. In addition, the MKPC treatment prolonged the survival of the mice with chronic kidney injuries. We observed a decreased recruitment of macrophages and myofibroblasts in the interstitium and the increased tubular proliferation. Notably, MKPC both decreased the level of vascular rarefaction and prevented endothelial mesenchymal transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and prevented TGF-β-induced EndoMT through downregulation of phosphorylated Smad 3 in vitro. MKPCs may be a beneficial treatment for kidney diseases characterized by progressive renal fibrosis. The enhanced preservation of angiogenic processes following MKPC injections may be associated with decreased fibrosis in the remnant kidney. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell

  3. Talk Show Science.

    Science.gov (United States)

    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)

  4. Decrease in parvalbumin-expressing neurons in the hippocampus and increased phencyclidine-induced locomotor activity in the rat methylazoxymethanol (MAM) model of schizophrenia.

    Science.gov (United States)

    Penschuck, Silke; Flagstad, Peter; Didriksen, Michael; Leist, Marcel; Michael-Titus, Adina T

    2006-01-01

    Treatment of rats with methylazoxymethanol (MAM) on gestational day (GD)17 disrupts corticolimbic development in the offspring (MAM-GD17 rats) and leads to abnormalities in adult MAM-GD17 rats resembling those described in schizophrenic patients. The underlying changes in specific cortical and limbic cell populations remain to be characterised. In schizophrenia, decreases in inhibitory gamma-aminobutyric acid (GABA)-containing interneurons that express the calcium-binding protein parvalbumin have been reported in the prefrontal cortex and hippocampus. In this study we analysed the expression of parvalbumin (PV), calretinin (CR) and calbindin (CB) in the prefrontal cortex and hippocampus of MAM-GD17 rats. Exposure in utero to MAM led to a significant decrease in the number of neurons expressing PV in the hippocampus, but not the prefrontal cortex. Neurons expressing CR or CB were not affected in either structure. The neurochemical changes in MAM-GD17 rats were accompagnied by increased hyperlocomotion after administration of phencyclidine (PCP), analogous to the hypersensitivity of schizophrenic patients to PCP. Therefore, the developmental MAM-GD17 model reproduces key neurochemical and behavioural features that reflect cortical and subcortical dysfunction in schizophrenia, and could be a useful tool in the development of new antipsychotic drugs.

  5. Selecting Cooking Methods to Decrease Persistent Organic Pollutant Concentrations in Food of Animal Origin Using a Consensus Decision-Making Model

    Directory of Open Access Journals (Sweden)

    Xiao Tan

    2017-02-01

    Full Text Available Persistent organic pollutants (POPs pose serious threats to human health. Increasing attention has been paid to POPs to protect the environment and prevent disease. Humans are exposed to POPs through diet (the major route, inhaling air and dust and skin contact. POPs are very lipophilic and hydrophobic, meaning that they accumulate in fatty tissues in animals and can biomagnify. Humans can therefore be exposed to relatively high POP concentrations in food of animal origin. Cooking animal products can decrease the POP contents, and different cooking methods achieve different reduction rates. Here, a consensus decision-making model with interval preference relations is used to prioritize cooking methods for specific animal products in terms of reducing POP concentrations. Two consistency mathematical expressions (I-consistency and I I -consistency are defined, then the ideal interval preference relations are determined for the cooking methods with respect to different social choice principles. The objective is to minimize disparities between individual judgments and the ideal consensus judgment. Consistency is used as a constraint to determine the rationality of the consistency definitions. A numerical example indicated that baking is the best cooking method for decreasing POP concentrations in grass carp. The I-consistency results were more acceptable than the I I -consistency results.

  6. Decreased Expression of Arginine-Phenylalanine-Amide-Related Peptide-3 Gene in Dorsomedial Hypothalamic Nucleus of Constant Light Exposure Model of Polycystic Ovarian Syndrome

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    Zahra Shaaban

    2018-01-01

    Full Text Available Background An abnormality in pulse amplitude and frequency of gonadotropin releasing hormone (GnRH secretion is the most characteristics of polycystic ovarian syndrome (PCOS. On the other hand, arginine-phenylalanine-amide (RFamide-related peptide-3 (RFRP3 inhibits the secretion of GnRH in mammalian hypothalamus. The current study performed in order to investigate the expression of RFRP3 mRNA in the dorsomedial hypothalamic nucleus (DMH after the induction of PCOS in a rat model of constant light exposure, and the possible role of parity on occurrence of PCOS. Materials and Methods In the experimental study, female nulliparous (n=12 and primiparous (n=12 rats were randomly subdivided into control and PCOS subgroups (n=6. PCOS were induced by 90 days exposure to constant light. After 90 days, blood, brain, and ovaries were sampled. Serum levels of follicle stimulating hormone (FSH, luteinizing hormone (LH, and testosterone were evaluated. In addition, six adult female ovariectomized rats as a control of real-time polymerase chain reaction (PCR tests were prepared and in the DMH of all rats, the relative mRNA expression of RFRP3 was assessed. Results Histological evaluation of ovaries represented the polycystic features. In addition, serum concentrations of testosterone in the PCOS subgroups were more than the controls (P<0.05. Furthermore, the relative expression of RFRP3 mRNA in PCOS subgroups was lower than the controls (P<0.05. Conclusion Constant light model of the PCOS-induced rats decreased the gene expression of RFRP3 in the DMH that suggests the decrease of RFRP3 may reduce its inhibitory effect on GnRH during the PCOS pathogenesis. This effect was stronger in the nulliparous rats than the primiparous.

  7. Physics Reality Show

    Science.gov (United States)

    Erukhimova, Tatiana

    The attention span of K-12 students is very short; they are used to digesting information in short snippets through social media and TV. To get the students interested in physics, we created the Physics Reality Show: a series of staged short videos with duration no longer than a few minutes. Each video explains and illustrates one physics concept or law through a fast-paced sequence of physics demonstrations and experiments. The cast consists entirely of physics undergraduate students with artistic abilities and substantial experience in showing physics demonstrations at current outreach events run by the department: Physics Shows and Physics & Engineering Festival. Undergraduate students are of almost the same age as their high-school audience. They are in the best position to connect with kids and convey their fascination with physics. The PI and other faculty members who are involved in the outreach advise and coach the cast. They help students in staging the episodes and choosing the most exciting and relevant demonstrations. Supported by the APS mini-outreach Grant.

  8. Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

    Directory of Open Access Journals (Sweden)

    Patricia Ferrer

    Full Text Available Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S3"-(HO-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50 of 6 µM for Plasmodium falciparum in contrast to the IC(50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

  9. Chronic Cigarette Smoking Impairs Erectile Function through Increased Oxidative Stress and Apoptosis, Decreased nNOS, Endothelial and Smooth Muscle Contents in a Rat Model.

    Directory of Open Access Journals (Sweden)

    Yun-Ching Huang

    Full Text Available Cigarette use is an independent risk factor for the development of erectile dysfunction (ED. While the association between chronic smoking and ED is well established, the fundamental mechanism(s of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS for 4 weeks (n = 10, 12 weeks (n = 10, and 24 weeks (n = 10. At the 24-week time point all rats were assessed with intracavernous pressure (ICP during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS. Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED.

  10. Not a "reality" show.

    Science.gov (United States)

    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.

  11. Epidemiology of dengue fever: A model with temporary cross-immunity and possible secondary infection shows bifurcations and chaotic behaviour in wide parameter regions.

    NARCIS (Netherlands)

    Aguilar, M.; Kooi, B.W.; Stollenwerk, N.

    2008-01-01

    Basic models suitable to explain the epidemiology of dengue fever have previously shown the possibility of deterministically chaotic attractors, which might explain the observed fluctuations found in empiric outbreak data. However, the region of bifurcations and chaos require strong enhanced

  12. Availability of a pediatric trauma center in a disaster surge decreases triage time of the pediatric surge population: a population kinetics model

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    Grikscheit Tracy C

    2011-10-01

    Full Text Available Abstract Background The concept of disaster surge has arisen in recent years to describe the phenomenon of severely increased demands on healthcare systems resulting from catastrophic mass casualty events (MCEs such as natural disasters and terrorist attacks. The major challenge in dealing with a disaster surge is the efficient triage and utilization of the healthcare resources appropriate to the magnitude and character of the affected population in terms of its demographics and the types of injuries that have been sustained. Results In this paper a deterministic population kinetics model is used to predict the effect of the availability of a pediatric trauma center (PTC upon the response to an arbitrary disaster surge as a function of the rates of pediatric patients' admission to adult and pediatric centers and the corresponding discharge rates of these centers. We find that adding a hypothetical pediatric trauma center to the response documented in an historical example (the Israeli Defense Forces field hospital that responded to the Haiti earthquake of 2010 would have allowed for a significant increase in the overall rate of admission of the pediatric surge cohort. This would have reduced the time to treatment in this example by approximately half. The time needed to completely treat all children affected by the disaster would have decreased by slightly more than a third, with the caveat that the PTC would have to have been approximately as fast as the adult center in discharging its patients. Lastly, if disaster death rates from other events reported in the literature are included in the model, availability of a PTC would result in a relative mortality risk reduction of 37%. Conclusions Our model provides a mathematical justification for aggressive inclusion of PTCs in planning for disasters by public health agencies.

  13. Preventative topical diclofenac treatment differentially decreases tumor burden in male and female Skh-1 mice in a model of UVB-induced cutaneous squamous cell carcinoma

    Science.gov (United States)

    Oberyszyn, Tatiana M.

    2013-01-01

    Ultraviolet B (UVB) light is the major environmental carcinogen contributing to non-melanoma skin cancer (NMSC) development. There are over 3.5 million NMSC diagnoses in two million patients annually, with men having a 3-fold greater incidence of squamous cell carcinoma (SCC) compared with women. Chronic inflammation has been linked to tumorigenesis, with a key role for the cyclooxygenase-2 (COX-2) enzyme. Diclofenac, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, currently is prescribed to patients as a short-term therapeutic agent to induce SCC precursor lesion regression. However, its efficacy as a preventative agent in patients without evidence of precursor lesions but with significant UVB-induced cutaneous damage has not been explored. We previously demonstrated in a murine model of UVB-induced skin carcinogenesis that when exposed to equivalent UVB doses, male mice had lower levels of inflammation but developed increased tumor multiplicity, burden and grade compared with female mice. Because of the discrepancy in the degree of inflammation between male and female skin, we sought to determine if topical treatment of previously damaged skin with an anti-inflammatory COX-2 inhibitor would decrease tumor burden and if it would be equally effective in the sexes. Our results demonstrated that despite observed sex differences in the inflammatory response, prolonged topical diclofenac treatment of chronically UVB-damaged skin effectively reduced tumor multiplicity in both sexes. Unexpectedly, tumor burden was significantly decreased only in male mice. Our data suggest a new therapeutic use for currently available topical diclofenac as a preventative intervention for patients predisposed to cutaneous SCC development before lesions appear. PMID:23125227

  14. Background, design and conceptual model of the cluster randomized multiple-component workplace study: FRamed Intervention to Decrease Occupational Muscle pain - "FRIDOM"

    Directory of Open Access Journals (Sweden)

    Jeanette Reffstrup Christensen

    2016-10-01

    Full Text Available Abstract Background Several RCT studies have aimed to reduce either musculoskeletal disorders, sickness presenteeism, sickness absenteeism or a combination of these among females with high physical work demands. These studies have provided evidence that workplace health promotion (WHP interventions are effective, but long-term effects are still uncertain. These studies either lack to succeed in maintaining intervention effects or lack to document if effects are maintained past a one-year period. This paper describes the background, design and conceptual model of the FRIDOM (FRamed Intervention to Decrease Occupational Muscle pain WHP program among health care workers. A job group characterized by having high physical work demands, musculoskeletal disorders, high sickness presenteeism - and absenteeism. Methods FRIDOM aimed to reduce neck and shoulder pain. Secondary aims were to decrease sickness presenteeism, sickness absenteeism and lifestyle-diseases such as other musculoskeletal disorders as well as metabolic-, and cardiovascular disorders – and to maintain participation to regular physical exercise training, after a one year intervention period. The entire concept was tailored to a population of female health care workers. This was done through a multi-component intervention including 1 intelligent physical exercise training (IPET, dietary advice and weight loss (DAW and cognitive behavioural training (CBT. Discussion The FRIDOM program has the potential to provide evidence-based knowledge of the pain reducing effect of a multi component WHP among a female group of employees with a high prevalence of musculoskeletal disorders and in a long term perspective evaluate the effects on sickness presenteeism and absenteeism as well as risk of life-style diseases. Trial registration NCT02843269 , 06.27.2016 - retrospectively registered.

  15. Background, design and conceptual model of the cluster randomized multiple-component workplace study: FRamed Intervention to Decrease Occupational Muscle pain - "FRIDOM".

    Science.gov (United States)

    Christensen, Jeanette Reffstrup; Bredahl, Thomas Viskum Gjelstrup; Hadrévi, Jenny; Sjøgaard, Gisela; Søgaard, Karen

    2016-10-24

    Several RCT studies have aimed to reduce either musculoskeletal disorders, sickness presenteeism, sickness absenteeism or a combination of these among females with high physical work demands. These studies have provided evidence that workplace health promotion (WHP) interventions are effective, but long-term effects are still uncertain. These studies either lack to succeed in maintaining intervention effects or lack to document if effects are maintained past a one-year period. This paper describes the background, design and conceptual model of the FRIDOM (FRamed Intervention to Decrease Occupational Muscle pain) WHP program among health care workers. A job group characterized by having high physical work demands, musculoskeletal disorders, high sickness presenteeism - and absenteeism. FRIDOM aimed to reduce neck and shoulder pain. Secondary aims were to decrease sickness presenteeism, sickness absenteeism and lifestyle-diseases such as other musculoskeletal disorders as well as metabolic-, and cardiovascular disorders - and to maintain participation to regular physical exercise training, after a one year intervention period. The entire concept was tailored to a population of female health care workers. This was done through a multi-component intervention including 1) intelligent physical exercise training (IPET), dietary advice and weight loss (DAW) and cognitive behavioural training (CBT). The FRIDOM program has the potential to provide evidence-based knowledge of the pain reducing effect of a multi component WHP among a female group of employees with a high prevalence of musculoskeletal disorders and in a long term perspective evaluate the effects on sickness presenteeism and absenteeism as well as risk of life-style diseases. NCT02843269 , 06.27.2016 - retrospectively registered.

  16. SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's disease.

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    Michal Mielcarek

    Full Text Available Huntington's disease (HD is a progressive neurological disorder for which there are no disease-modifying treatments. Transcriptional dysregulation is a major molecular feature of HD, which significantly contributes to disease progression. Therefore, the development of histone deacetylase (HDAC inhibitors as therapeutics for HD has been energetically pursued. Suberoylanilide hydroxamic acid (SAHA - a class I HDAC as well an HDAC6 inhibitor, improved motor impairment in the R6/2 mouse model of HD. Recently it has been found that SAHA can also promote the degradation of HDAC4 and possibly other class IIa HDACs at the protein level in various cancer cell lines. To elucidate whether SAHA is a potent modifier of HDAC protein levels in vivo, we performed two independent mouse trials. Both WT and R6/2 mice were chronically treated with SAHA and vehicle. We found that prolonged SAHA treatment causes the degradation of HDAC4 in cortex and brain stem, but not hippocampus, without affecting its transcript levels in vivo. Similarly, SAHA also decreased HDAC2 levels without modifying the expression of its mRNA. Consistent with our previous data, SAHA treatment diminishes Hdac7 transcript levels in both wild type and R6/2 brains and unexpectedly was found to decrease Hdac11 in R6/2 but not wild type. We investigated the effects of SAHA administration on well-characterised molecular readouts of disease progression. We found that SAHA reduces SDS-insoluble aggregate load in the cortex and brain stem but not in the hippocampus of the R6/2 brains, and that this was accompanied by restoration of Bdnf cortical transcript levels.

  17. Fas-deficient mice have impaired alveolar neutrophil recruitment and decreased expression of anti-KC autoantibody:KC complexes in a model of acute lung injury

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    Gil Sucheol

    2012-10-01

    Full Text Available Abstract Background Exposure to mechanical ventilation enhances lung injury in response to various stimuli, such as bacterial endotoxin (LPS. The Fas/FasL system is a receptor ligand system that has dual pro-apoptotic and pro-inflammatory functions and has been implicated in the pathogenesis of lung injury. In this study we test the hypothesis that a functioning Fas/FasL system is required for the development of lung injury in mechanically ventilated mice. Methods C57BL/6 (B6 and Fas-deficient lpr mice were exposed to either intra-tracheal PBS followed by spontaneous breathing or intra-tracheal LPS followed by four hours mechanical ventilation with tidal volumes of 10 mL/kg, respiratory rate of 150 breaths per minute, inspired oxygen 0.21 and positive end expiratory pressure (PEEP of 3 cm of water. Results Compared with the B6 mice, the lpr mice showed attenuation of the neutrophilic response as measured by decreased numbers of BAL neutrophils and lung myeloperoxidase activity. Interestingly, the B6 and lpr mice had similar concentrations of pro-inflammatory cytokines, including CXCL1 (KC, and similar measurements of permeability and apoptosis. However, the B6 mice showed greater deposition of anti-KC:KC immune complexes in the lungs, as compared with the lpr mice. Conclusions We conclude that a functioning Fas/FasL system is required for full neutrophilic response to LPS in mechanically ventilated mice.

  18. Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline.

    Directory of Open Access Journals (Sweden)

    Liliana B Menalled

    2010-03-01

    Full Text Available Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington's disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition.

  19. A Combination of Coffee Compounds Shows Insulin-Sensitizing and Hepatoprotective Effects in a Rat Model of Diet-Induced Metabolic Syndrome

    DEFF Research Database (Denmark)

    Shokouh, Pedram; Jeppesen, Per Bendix; Hermansen, Kjeld

    2017-01-01

    control, but improved fed hyperinsulinemia (mean difference = 30.80 mU/L, p = 0.044) and homeostatic model assessment-insulin resistance (HOMA-IR) (mean difference = 15.29, p = 0.033), and plasma adiponectin levels (mean difference = -0.99 µg/mL, p = 0.048). The impact of nutraceuticals on post...

  20. Models of Plankton Community Changes during a Warm Water Anomaly in Arctic Waters Show Altered Trophic Pathways with Minimal Changes in Carbon Export

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    Maria Vernet

    2017-05-01

    Full Text Available Carbon flow through pelagic food webs is an expression of the composition, biomass and activity of phytoplankton as primary producers. In the near future, severe environmental changes in the Arctic Ocean are expected to lead to modifications of phytoplankton communities. Here, we used a combination of linear inverse modeling and ecological network analysis to study changes in food webs before, during, and after an anomalous warm water event in the eastern Fram Strait of the West Spitsbergen Current (WSC that resulted in a shift from diatoms to flagellates during the summer (June–July. The model predicts substantial differences in the pathways of carbon flow in diatom- vs. Phaeocystis/nanoflagellate-dominated phytoplankton communities, but relatively small differences in carbon export. The model suggests a change in the zooplankton community and activity through increasing microzooplankton abundance and the switching of meso- and macrozooplankton feeding from strict herbivory to omnivory, detritivory and coprophagy. When small cells and flagellates dominated, the phytoplankton carbon pathway through the food web was longer and the microbial loop more active. Furthermore, one step was added in the flow from phytoplankton to mesozooplankton, and phytoplankton carbon to higher trophic levels is available via detritus or microzooplankton. Model results highlight how specific changes in phytoplankton community composition, as expected in a climate change scenario, do not necessarily lead to a reduction in carbon export.

  1. Cross-biome transplants of plant litter show decomposition models extend to a broader climatic range but lose predictability at the decadal time scale

    Science.gov (United States)

    William S. Currie; Mark E. Harmon; Ingrid C. Burke; Stephen C. Hart; William J. Parton; Whendee L. Silver

    2009-01-01

    We analyzed results from 10-year long field incubations of foliar and fine root litter from the Long-term lntersite Decomposition Experiment Team (LIDET) study. We tested whether a variety of climate and litter quality variables could be used to develop regression models of decomposition parameters across wide ranges in litter quality and climate and whether these...

  2. Inactivation of the spxA1 or spxA2 gene of Streptococcus mutans decreases virulence in the rat caries model.

    Science.gov (United States)

    Galvão, L C C; Rosalen, P L; Rivera-Ramos, I; Franco, G C N; Kajfasz, J K; Abranches, J; Bueno-Silva, B; Koo, H; Lemos, J A

    2017-04-01

    In oral biofilms, the major environmental challenges encountered by Streptococcus mutans are acid and oxidative stresses. Previously, we showed that the transcriptional regulators SpxA1 and SpxA2 are involved in general stress survival of S. mutans with SpxA1 playing a primary role in activation of antioxidant and detoxification strategies whereas SpxA2 serves as a back up activator of oxidative stress genes. We have also found that spxA1 mutant strains (∆spxA1 and ∆spxA1∆spxA2) are outcompeted by peroxigenic oral streptococci in vitro and have impaired abilities to colonize the teeth of rats fed a highly cariogenic diet. Here, we show that the Spx proteins can also exert regulatory roles in the expression of additional virulence attributes of S. mutans. Competence activation is significantly impaired in Δspx strains and the production of mutacin IV and V is virtually abolished in ΔspxA1 strains. Unexpectedly, the ∆spxA2 strain showed increased production of glucans from sucrose, without affecting the total amount of bacteria within biofilms when compared with the parent strain. By using the rat caries model, we showed that the capacity of the ΔspxA1 and ΔspxA2 strains to cause caries on smooth tooth surfaces is significantly impaired. The ∆spxA2 strain also formed fewer lesions on sulcal surfaces. This report reveals that global regulation via Spx contributes to the cariogenic potential of S. mutans and highlights that animal models are essential in the characterization of bacterial traits implicated in virulence. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation.

    Science.gov (United States)

    Jun, Ji Hye; Choi, Jong Ho; Bae, Si Hyun; Oh, Seh Hoon; Kim, Gi Jin

    2016-09-01

    Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

  4. Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation

    Directory of Open Access Journals (Sweden)

    Ji Hye Jun

    2016-09-01

    Full Text Available Background/Aims Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL. Methods The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs treated with lithocholic acid (LCA and siRNA-CRP. Results The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. Conclusion CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

  5. Oral administration of Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 suppresses inflammation by decreasing interleukin-6 responses in a murine model of atopic dermatitis.

    Science.gov (United States)

    Kano, Hiroshi; Kita, Junko; Makino, Seiya; Ikegami, Shuji; Itoh, Hiroyuki

    2013-06-01

    The oral intake of Lactobacillus spp. can provide beneficial effects to the host by modulating the immune response. Atopic dermatitis (AD) is an allergic inflammatory disease mediated by various immune responses. In this study, we examined the effect of a Lactobacillus strain, Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1), on AD development in a murine model of AD that was developed by the topical application of mite antigen in NC/Nga mice. The oral intake of heat-killed OLL1073R-1 cells inhibited both the development of dermatitis and the elevation of an acute inflammation marker, serum amyloid A. Another bacterial strain, Lactobacillus rhamnosus OLL2984, exerted no inhibitory effects on dermatitis. The oral intake of heat-killed OLL1073R-1 cells also attenuated secretion of IL-6 from lymph node cells in response to mite antigen and reduced IL-6 levels in inflamed tissues, such as auricles. Production of IFN-γ or IL-4 was not influenced by OLL1073R-1 intake. We also found that inhibition of IL-6 signaling by gp130-Fc (a fusion protein consisting of the extracellular portion of glycoprotein 130 fused to the Fc region of human IgG1) markedly decreased the severity of dermatitis in NC/Nga mice. Moreover, secretion of IL-6 by lymph node cells was augmented in NC/Nga mice compared with that in BALB/c mice. These results indicate that IL-6 plays an essential role in the development of dermatitis in the NC/Nga mouse model of AD, and that OLL1073R-1 inhibits dermatitis, at least in part, by suppressing the IL-6 response. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  6. A conceptual model for worksite intelligent physical exercise training--IPET--intervention for decreasing life style health risk indicators among employees: a randomized controlled trial.

    Science.gov (United States)

    Sjøgaard, Gisela; Justesen, Just Bendix; Murray, Mike; Dalager, Tina; Søgaard, Karen

    2014-06-26

    Health promotion at the work site in terms of physical activity has proven positive effects but optimization of relevant exercise training protocols and implementation for high adherence are still scanty. The aim of this paper is to present a study protocol with a conceptual model for planning the optimal individually tailored physical exercise training for each worker based on individual health check, existing guidelines and state of the art sports science training recommendations in the broad categories of cardiorespiratory fitness, muscle strength in specific body parts, and functional training including balance training. The hypotheses of this research are that individually tailored worksite-based intelligent physical exercise training, IPET, among workers with inactive job categories will: 1) Improve cardiorespiratory fitness and/or individual health risk indicators, 2) Improve muscle strength and decrease musculoskeletal disorders, 3) Succeed in regular adherence to worksite and leisure physical activity training, and 3) Reduce sickness absence and productivity losses (presenteeism) in office workers. The present RCT study enrolled almost 400 employees with sedentary jobs in the private as well as public sectors. The training interventions last 2 years with measures at baseline as well as one and two years follow-up. If proven effective, the intelligent physical exercise training scheduled as well as the information for its practical implementation can provide meaningful scientifically based information for public health policy. ClinicalTrials.gov, number: NCT01366950.

  7. A conceptual model for worksite intelligent physical exercise training - IPET - intervention for decreasing life style health risk indicators among employees: a randomized controlled trial

    Science.gov (United States)

    2014-01-01

    Background Health promotion at the work site in terms of physical activity has proven positive effects but optimization of relevant exercise training protocols and implementation for high adherence are still scanty. Methods/Design The aim of this paper is to present a study protocol with a conceptual model for planning the optimal individually tailored physical exercise training for each worker based on individual health check, existing guidelines and state of the art sports science training recommendations in the broad categories of cardiorespiratory fitness, muscle strength in specific body parts, and functional training including balance training. The hypotheses of this research are that individually tailored worksite-based intelligent physical exercise training, IPET, among workers with inactive job categories will: 1) Improve cardiorespiratory fitness and/or individual health risk indicators, 2) Improve muscle strength and decrease musculoskeletal disorders, 3) Succeed in regular adherence to worksite and leisure physical activity training, and 3) Reduce sickness absence and productivity losses (presenteeism) in office workers. The present RCT study enrolled almost 400 employees with sedentary jobs in the private as well as public sectors. The training interventions last 2 years with measures at baseline as well as one and two years follow-up. Discussion If proven effective, the intelligent physical exercise training scheduled as well as the information for its practical implementation can provide meaningful scientifically based information for public health policy. Trial Registration ClinicalTrials.gov, number: NCT01366950. PMID:24964869

  8. Methanolic extract of Piper nigrum fruits improves memory impairment by decreasing brain oxidative stress in amyloid beta(1-42) rat model of Alzheimer's disease.

    Science.gov (United States)

    Hritcu, Lucian; Noumedem, Jaurès A; Cioanca, Oana; Hancianu, Monica; Kuete, Victor; Mihasan, Marius

    2014-04-01

    The present study analyzed the possible memory-enhancing and antioxidant proprieties of the methanolic extract of Piper nigrum L. fruits (50 and 100 mg/kg, orally, for 21 days) in amyloid beta(1-42) rat model of Alzheimer's disease. The memory-enhancing effects of the plant extract were studied by means of in vivo (Y-maze and radial arm-maze tasks) approaches. Also, the antioxidant activity in the hippocampus was assessed using superoxide dismutase-, catalase-, glutathione peroxidase-specific activities and the total content of reduced glutathione, malondialdehyde, and protein carbonyl levels. The amyloid beta(1-42)-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory and reference memory errors within radial arm-maze task. Administration of the plant extract significantly improved memory performance and exhibited antioxidant potential. Our results suggest that the plant extract ameliorates amyloid beta(1-42)-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.

  9. Gastrointestinal Simulation Model TWIN-SHIME Shows Differences between Human Urolithin-Metabotypes in Gut Microbiota Composition, Pomegranate Polyphenol Metabolism, and Transport along the Intestinal Tract.

    Science.gov (United States)

    García-Villalba, Rocío; Vissenaekens, Hanne; Pitart, Judit; Romo-Vaquero, María; Espín, Juan C; Grootaert, Charlotte; Selma, María V; Raes, Katleen; Smagghe, Guy; Possemiers, Sam; Van Camp, John; Tomas-Barberan, Francisco A

    2017-07-12

    A TWIN-SHIME system was used to compare the metabolism of pomegranate polyphenols by the gut microbiota from two individuals with different urolithin metabotypes. Gut microbiota, ellagitannin metabolism, short-chain fatty acids (SCFA), transport of metabolites, and phase II metabolism using Caco-2 cells were explored. The simulation reproduced the in vivo metabolic profiles for each metabotype. The study shows for the first time that microbial composition, metabolism of ellagitannins, and SCFA differ between metabotypes and along the large intestine. The assay also showed that pomegranate phenolics preserved intestinal cell integrity. Pomegranate polyphenols enhanced urolithin and propionate production, as well as Akkermansia and Gordonibacter prevalence with the highest effect in the descending colon. The system provides an insight into the mechanisms of pomegranate polyphenol gut microbiota metabolism and absorption through intestinal cells. The results obtained by the combined SHIME/Caco-2 cell system are consistent with previous human and animal studies and show that although urolithin metabolites are present along the gastrointestinal tract due to enterohepatic circulation, they are predominantly produced in the distal colon region.

  10. Comparison of G protein sequences of South African street rabies viruses showing distinct progression of the disease in a mouse model of experimental rabies.

    Science.gov (United States)

    Seo, Wonhyo; Servat, Alexandre; Cliquet, Florence; Akinbowale, Jenkins; Prehaud, Christophe; Lafon, Monique; Sabeta, Claude

    Rabies is a fatal zoonotic disease and infections generally lead to a fatal encephalomyelitis in both humans and animals. In South Africa, domestic (dogs) and the wildlife (yellow mongoose) host species maintain the canid and mongoose rabies variants respectively. In this study, pathogenicity differences of South African canid and mongoose rabies viruses were investigated in a murine model, by assessing the progression of clinical signs and survivorship. Comparison of glycoprotein gene sequences revealed amino acid differences that may underpin the observed pathogenicity differences. Cumulatively, our results suggest that the canid rabies virus may be more neurovirulent in mice than the mongoose rabies variant. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  11. A Combination of Coffee Compounds Shows Insulin-Sensitizing and Hepatoprotective Effects in a Rat Model of Diet-Induced Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Pedram Shokouh

    2017-12-01

    Full Text Available Since coffee may help to prevent the development of metabolic syndrome (MetS, we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. In this study, 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high-fructose diet with or without a mixture of caffeic acid (30 mg/day, trigonelline (20 mg/day, and cafestol (1 mg/day for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control, but improved fed hyperinsulinemia (mean difference = 30.80 mU/L, p = 0.044 and homeostatic model assessment-insulin resistance (HOMA-IR (mean difference = 15.29, p = 0.033, and plasma adiponectin levels (mean difference = −0.99 µg/mL, p = 0.048. The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating (mean difference = 4.75 U/L, p = 0.014 and intrahepatocellular alanine transaminase activity was assessed by hyperpolarized-13C nuclear magnetic resonance NMR spectroscopy and found to be reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future.

  12. Transcriptomic Analysis of Lung Tissue from Cigarette Smoke-Induced Emphysema Murine Models and Human Chronic Obstructive Pulmonary Disease Show Shared and Distinct Pathways.

    Science.gov (United States)

    Yun, Jeong H; Morrow, Jarrett; Owen, Caroline A; Qiu, Weiliang; Glass, Kimberly; Lao, Taotao; Jiang, Zhiqiang; Perrella, Mark A; Silverman, Edwin K; Zhou, Xiaobo; Hersh, Craig P

    2017-07-01

    Although cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD), the underlying molecular mechanisms for the significant variability in developing COPD in response to CS are incompletely understood. We performed lung gene expression profiling of two different wild-type murine strains (C57BL/6 and NZW/LacJ) and two genetic models with mutations in COPD genome-wide association study genes (HHIP and FAM13A) after 6 months of chronic CS exposure and compared the results to human COPD lung tissues. We identified gene expression patterns that correlate with severity of emphysema in murine and human lungs. Xenobiotic metabolism and nuclear erythroid 2-related factor 2-mediated oxidative stress response were commonly regulated molecular response patterns in C57BL/6, Hhip +/- , and Fam13a -/- murine strains exposed chronically to CS. The CS-resistant Fam13a -/- mouse and NZW/LacJ strain revealed gene expression response pattern differences. The Fam13a -/- strain diverged in gene expression compared with C57BL/6 control only after CS exposure. However, the NZW/LacJ strain had a unique baseline expression pattern, enriched for nuclear erythroid 2-related factor 2-mediated oxidative stress response and xenobiotic metabolism, and converged to a gene expression pattern similar to the more susceptible wild-type C57BL/6 after CS exposure. These results suggest that distinct molecular pathways may account for resistance to emphysema. Surprisingly, there were few genes commonly modulated in mice and humans. Our study suggests that gene expression responses to CS may be largely species and model dependent, yet shared pathways could provide biologically significant insights underlying individual susceptibility to CS.

  13. Macrophage inflammatory protein-1α shows predictive value as a risk marker for subjects and sites vulnerable to bone loss in a longitudinal model of aggressive periodontitis.

    Directory of Open Access Journals (Sweden)

    Daniel H Fine

    Full Text Available Improved diagnostics remains a fundamental goal of biomedical research. This study was designed to assess cytokine biomarkers that could predict bone loss (BL in localized aggressive periodontitis. 2,058 adolescents were screened. Two groups of 50 periodontally healthy adolescents were enrolled in the longitudinal study. One group had Aggregatibacter actinomycetemcomitans (Aa, the putative pathogen, while the matched cohort did not. Cytokine levels were assessed in saliva and gingival crevicular fluid (GCF. Participants were sampled, examined, and radiographed every 6 months for 2-3 years. Disease was defined as radiographic evidence of BL. Saliva and GCF was collected at each visit, frozen, and then tested retrospectively after detection of BL. Sixteen subjects with Aa developed BL. Saliva from Aa-positive and Aa-negative healthy subjects was compared to subjects who developed BL. GCF was collected from 16 subjects with BL and from another 38 subjects who remained healthy. GCF from BL sites in the 16 subjects was compared to healthy sites in these same subjects and to healthy sites in subjects who remained healthy. Results showed that cytokines in saliva associated with acute inflammation were elevated in subjects who developed BL (i.e., MIP-1α MIP-1β IL-α, IL-1β and IL-8; p<0.01. MIP-1α was elevated 13-fold, 6 months prior to BL. When MIP-1α levels were set at 40 pg/ml, 98% of healthy sites were below that level (Specificity; whereas, 93% of sites with BL were higher (Sensitivity, with comparable Predictive Values of 98%; p<0.0001; 95% C.I. = 42.5-52.7. MIP-1α consistently showed elevated levels as a biomarker for BL in both saliva and GCF, 6 months prior to BL. MIP-1α continues to demonstrate its strong candidacy as a diagnostic biomarker for both subject and site vulnerability to BL.

  14. Decreased colonization of fecal Clostridium coccoides/Eubacterium rectale species from ulcerative colitis patients in an in vitro dynamic gut model with mucin environment

    DEFF Research Database (Denmark)

    Vermeiren, Joan; Van den Abbeele, Pieter; Laukens, Debby

    2012-01-01

    The mucus layer in the colon, acting as a barrier to prevent invasion of pathogens, is thinner and discontinuous in patients with ulcerative colitis (UC). A recent developed in vitro dynamic gut model, the M-SHIME, was used to compare long-term colonization of the mucin layer by the microbiota from...... six healthy volunteers (HV) and six UC patients and thus distinguish the mucin adhered from the luminal microbiota. Although under the same nutritional conditions, short-chain fatty acid production by the luminal communities from UC patients showed a tendency toward a lower butyrate production. A more...... in-depth community analysis of those microbial groups known to produce butyrate revealed that the diversity of the Clostridium coccoides/Eubacterium rectale and Clostridium leptum group, and counts of Faecalibacterium prausnitzii were lower in the luminal fractions of the UC samples. Counts...

  15. Decrease in endogenous brain allopregnanolone induces autism spectrum disorder (ASD)-like behavior in mice: A novel animal model of ASD.

    Science.gov (United States)

    Ebihara, Ken; Fujiwara, Hironori; Awale, Suresh; Dibwe, Dya Fita; Araki, Ryota; Yabe, Takeshi; Matsumoto, Kinzo

    2017-09-15

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder with core symptoms of social impairments and restrictive repetitive behaviors. Recent evidence has implicated a dysfunction in the GABAergic system in the pathophysiology of ASD. We investigated the role of endogenous allopregnanolone (ALLO), a neurosteroidal positive allosteric modulator of GABA A receptors, in the regulation of ASD-like behavior in male mice using SKF105111 (SKF), an inhibitor of type I and type II 5α-reductase, a rate-limiting enzyme of ALLO biosynthesis. SKF impaired sociability-related performance, as analyzed by three different tests; i.e., the 3-chamber test and social interaction in the open field and resident-intruder tests, without affecting olfactory function elucidated by the buried food test. SKF also induced repetitive grooming behavior without affecting anxiety-like behavior. SKF had no effect on short-term spatial working memory or long-term fear memory, but enhanced latent learning ability in male mice. SKF-induced ASD-like behavior in male mice was abolished by the systemic administration of ALLO (1mg/kg, i.p.) and methylphenidate (MPH: 2.5mg/kg, i.p.), a dopamine transporter inhibitor. The effects of SKF on brain ALLO contents in male mice were reversed by ALLO, but not MPH. On the other hand, SKF failed to induce ASD-like behavior or a decline in brain ALLO contents in female mice. These results suggest that ALLO regulates episodes of ASD-like behavior by positively modulating the function of GABA A receptors linked to the dopaminergic system. Moreover, a sex-dependently induced decrease in brain ALLO contents may provide an animal model to study the main features of ASD. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate, Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy

    Directory of Open Access Journals (Sweden)

    Karima Schwab

    2018-01-01

    Full Text Available α-Synuclein (α-Syn aggregation is a pathological feature of synucleinopathies, neurodegenerative disorders that include Parkinson’s disease (PD. We have tested whether N,N,N′,N′-tetramethyl-10H-phenothiazine-3,7-diaminium bis(hydromethanesulfonate (leuco-methylthioninium bis(hydromethanesulfonate; LMTM, a tau aggregation inhibitor, affects α-Syn aggregation in vitro and in vivo. Both cellular and transgenic models in which the expression of full-length human α-Syn (h-α-Syn fused with a signal sequence peptide to promote α-Syn aggregation were used. Aggregated α-Syn was observed following differentiation of N1E-115 neuroblastoma cells transfected with h-α-Syn. The appearance of aggregated α-Syn was inhibited by LMTM, with an EC50 of 1.1 μM, with minimal effect on h-α-Syn mRNA levels being observed. Two independent lines of mice (L58 and L62 transgenic for the same fusion protein accumulated neuronal h-α-Syn that, with aging, developed into fibrillary inclusions characterized by both resistance to proteinase K (PK-cleavage and their ability to bind thiazin red. There was a significant decrease in α-Syn-positive neurons in multiple brain regions following oral treatment of male and female mice with LMTM administered daily for 6 weeks at 5 and 15 mg MT/kg. The early aggregates of α-Syn and the late-stage fibrillar inclusions were both susceptible to inhibition by LMTM, a treatment that also resulted in the rescue of movement and anxiety-related traits in these mice. The results suggest that LMTM may provide a potential disease modification therapy in PD and other synucleinopathies through the inhibition of α-Syn aggregation.

  17. Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

    Science.gov (United States)

    Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

    2017-09-01

    Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

  18. Measuring performance at trade shows

    DEFF Research Database (Denmark)

    Hansen, Kåre

    2004-01-01

    Trade shows is an increasingly important marketing activity to many companies, but current measures of trade show performance do not adequately capture dimensions important to exhibitors. Based on the marketing literature's outcome and behavior-based control system taxonomy, a model is built...... that captures a outcome-based sales dimension and four behavior-based dimensions (i.e. information-gathering, relationship building, image building, and motivation activities). A 16-item instrument is developed for assessing exhibitors perceptions of their trade show performance. The paper presents evidence...... of the scale's reliability, factor structure, and validity on the basis of analyzing data from independent samples of exhibitors at the international trade shows SIAL (Paris) and ANUGA (Cologne); and it concludes with a discussion of potential managerial applications and implications for future research. New...

  19. LRRTM1-deficient mice show a rare phenotype of avoiding small enclosures—A tentative mouse model for claustrophobia-like behaviour

    Science.gov (United States)

    Laakso, T.; Lauren, J.; Strittmatter, S.M.; Airaksinen, M.S.

    2013-01-01

    The LRRTM family proteins have been shown to act as synaptogenic cell adhesion molecules via interaction with presynaptic neurexins and are associated with neuropsychiatric disorders. LRRTM1-knockout mice have subtle morphological deficits in excitatory hippocampal synapses and were suggested to have impaired cognitive function. Here we report that LRRTM1-knockout mice exhibit an extraordinary phenotype of avoiding small enclosures. In the light–dark box, the knockout mice escape to dark through a standard opening as quickly as wild-type littermates but avoid escaping through a small doorway. While all wild-type mice spontaneously enter a small tube, most knockout mice do not. This apparent aversion to enter narrow space may explain other abnormalities such as increased time in open arms in the elevated plus maze and less visits through a tunnel in the IntelliCage. Moreover, LRRTM1-knockout mice show increased social interaction, reduced nest building and MK801-induced locomotion, and slower swim speed but normal water maze learning. Since LRRTM1 is predominantly expressed in thalamus, hippocampus and limbic cortex, specific synaptic defects in those areas presumably cause these behavioural abnormalities. PMID:23089646

  20. LRRTM1-deficient mice show a rare phenotype of avoiding small enclosures--a tentative mouse model for claustrophobia-like behaviour.

    Science.gov (United States)

    Voikar, V; Kulesskaya, N; Laakso, T; Lauren, J; Strittmatter, S M; Airaksinen, M S

    2013-02-01

    The LRRTM family proteins have been shown to act as synaptogenic cell adhesion molecules via interaction with presynaptic neurexins and are associated with neuropsychiatric disorders. LRRTM1-knockout mice have subtle morphological deficits in excitatory hippocampal synapses and were suggested to have impaired cognitive function. Here we report that LRRTM1-knockout mice exhibit an extraordinary phenotype of avoiding small enclosures. In the light-dark box, the knockout mice escape to dark through a standard opening as quickly as wild-type littermates but avoid escaping through a small doorway. While all wild-type mice spontaneously enter a small tube, most knockout mice do not. This apparent aversion to enter narrow space may explain other abnormalities such as increased time in open arms in the elevated plus maze and less visits through a tunnel in the IntelliCage. Moreover, LRRTM1-knockout mice show increased social interaction, reduced nest building and MK801-induced locomotion, and slower swim speed but normal water maze learning. Since LRRTM1 is predominantly expressed in thalamus, hippocampus and limbic cortex, specific synaptic defects in those areas presumably cause these behavioural abnormalities. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Program impact pathway analysis of a social franchise model shows potential to improve infant and young child feeding practices in Vietnam.

    Science.gov (United States)

    Nguyen, Phuong H; Menon, Purnima; Keithly, Sarah C; Kim, Sunny S; Hajeebhoy, Nemat; Tran, Lan M; Ruel, Marie T; Rawat, Rahul

    2014-10-01

    By mapping the mechanisms through which interventions are expected to achieve impact, program impact pathway (PIP) analysis lays out the theoretical causal links between program activities, outcomes, and impacts. This study examines the pathways through which the Alive & Thrive (A&T) social franchise model is intended to improve infant and young child feeding (IYCF) practices in Vietnam. Mixed methods were used, including qualitative interviews with franchise management board members (n = 12), surveys with health providers (n = 120), counseling observations (n = 160), and household surveys (n = 2045). Six PIP components were assessed: 1) franchise management, 2) training and IYCF knowledge of health providers, 3) service delivery, 4) program exposure and utilization, 5) maternal behavioral determinants (knowledge, beliefs, and intentions) toward optimal IYCF practices, and 6) IYCF practices. Data were collected from A&T-intensive areas (A&T-I; mass media + social franchise) and A&T-nonintensive areas (A&T-NI; mass media only) by using a cluster-randomized controlled trial design. Data from 2013 were compared with baseline where similar measures were available. Results indicate that mechanisms are in place for effective management of the franchise system, despite challenges to routine monitoring. A&T training was associated with increased capacity of providers, resulting in higher-quality IYCF counseling (greater technical knowledge and communication skills during counseling) in A&T-I areas. Franchise utilization increased from 10% in 2012 to 45% in 2013 but fell below the expected frequency of 9-15 contacts per mother-child dyad. Improvements in breastfeeding knowledge, beliefs, intentions, and practices were greater among mothers in A&T-I areas than among those in A&T-NI areas. In conclusion, there are many positive changes along the impact pathway of the franchise services, but challenges in utilization and demand creation should be addressed to achieve the full

  2. Progesterone treatment shows greater protection in brain vs. retina in a rat model of middle cerebral artery occlusion: Progesterone receptor levels may play an important role.

    Science.gov (United States)

    Allen, Rachael S; Sayeed, Iqbal; Oumarbaeva, Yuliya; Morrison, Katherine C; Choi, Paul H; Pardue, Machelle T; Stein, Donald G

    2016-11-22

    To determine whether inflammation increases in retina as it does in brain following middle cerebral artery occlusion (MCAO), and whether the neurosteroid progesterone, shown to have protective effects in both retina and brain after MCAO, reduces inflammation in retina as well as brain. MCAO rats treated systemically with progesterone or vehicle were compared with shams. Protein levels of cytosolic NF-κB, nuclear NF-κB, phosphorylated NF-κB, IL-6, TNF-α, CD11b, progesterone receptor A and B, and pregnane X receptor were assessed in retinas and brains at 24 and 48 h using western blots. Following MCAO, significant increases were observed in the following inflammatory markers: pNF-κB and CD11b at 24 h in both brain and retina, nuclear NF-κB at 24 h in brain and 48 h in retina, and TNF-α at 24 h in brain.Progesterone treatment in MCAO animals significantly attenuated levels of the following markers in brain: pNF-κB, nuclear NF-κB, IL-6, TNF-α, and CD11b, with significantly increased levels of cytosolic NF-κB. Retinas from progesterone-treated animals showed significantly reduced levels of nuclear NF-κB and IL-6 and increased levels of cytosolic NF-κB, with a trend for reduction in other markers. Post-MCAO, progesterone receptors A and B were upregulated in brain and downregulated in retina. Inflammatory markers increased in both brain and retina after MCAO, with greater increases observed in brain. Progesterone treatment reduced inflammation, with more dramatic reductions observed in brain than retina. This differential effect may be due to differences in the response of progesterone receptors in brain and retina after injury.

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

    Science.gov (United States)

    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.

    2015-01-01

    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. PMID:25217574

  4. Decreasing serial cost sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2009-01-01

    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...... rule was provided by Moulin and Shenker (J Econ Theory 64:178-201, 1994). This paper gives an axiomatic characterization of the decreasing serial rule....

  5. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...... of the increasing serial rule was provided by Moulin and Shenker [Journal of Economic Theory 64 (1994) 178]. This paper gives an axiomatic characterization of the decreasing serial rule...

  6. Effect of Petiveria alliacea Leaves Extract in Decreasing Serum Level of Blood Glucose Level Through Activation of AMPK-α1 in Diabetes Mellitus Rat Models

    Directory of Open Access Journals (Sweden)

    Arifa Mustika

    2017-03-01

    Full Text Available Singawalang (Petiveria alliaceae is a medicinal herb that is used traditionally as folk medicine for various diseases. The plant has been used as an antidiabetic agent in Indonesian society. Until now, the effect and mechanism of action of Petiveria alliaceae as antidiabetic agent is not clear. The aim of the study was to determine the effect of Petiveria alliaceae to blood glucose level and to identify expression of AMPK-α1 in rat liver. The research was experimental study with randomized and was conducted at Laboratory Pharmacology and Therapy, and Laboratory Patology Anatomy, Faculty of Medicine, Universitas Airlangga, on April until August 2015. Twenty five male rats were injected by Streptozotocin to create diabetic rat models and randomly divided into 5 groups. The group 1, 2 and 3 are treatment groups that were given the ethanol extract of Petiveria alliaceae at dose 90 mg/kgbw, 180 mg/kgbw, and 360 mg/kgbw, orally, once daily for fourteen days. The fourth group is a negative control who were given distilled water and the fifth group is a positive control who were given metformin at dose 150 mg/kgbw. On the 15th day, blood glucose level were measured by glucometer and the rats were sacrificed to collect the liver. Expression of AMPK-α1 were assessed by immunohistochemistry. Data were analyzed by ANAVA and Wilcoxon (α=0,05. The results have been showed that there were significant differences in glucose blood level between negative control with the group were given the extract at dose 90 mg/kgbw, 360 mg/kgbw and positive control, between dose 180 mg/kgbw with dose 360 mg/kgbw and positive control. A significant differences of expression of AMPK-α1 showed between dose 180 mg/kgbw with dose 360 mg/kgbw and positive control. The conclusion of this study was the extract ethanol of Singawalang leaves reduce blood glucose level in diabetes mellitus rat models through increase in the expression of AMPK-α1.

  7. Tokyo Motor Show 2003; Tokyo Motor Show 2003

    Energy Technology Data Exchange (ETDEWEB)

    Joly, E.

    2004-01-01

    The text which follows present the different techniques exposed during the 37. Tokyo Motor Show. The report points out the great tendencies of developments of the Japanese automobile industry. The hybrid electric-powered vehicles or those equipped with fuel cells have been highlighted by the Japanese manufacturers which allow considerable budgets in the research of less polluting vehicles. The exposed models, although being all different according to the manufacturer, use always a hybrid system: fuel cell/battery. The manufacturers have stressed too on the intelligent systems for navigation and safety as well as on the design and comfort. (O.M.)

  8. Calbindins decreased after space flight.

    Science.gov (United States)

    Sergeev, I N; Rhoten, W B; Carney, M D

    1996-12-01

    Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins

  9. Decreasing asthma morbidity

    African Journals Online (AJOL)

    1994-12-12

    Dec 12, 1994 ... Apart from the optimal use of drugs, various supplementary methods have been tested to decrease asthma morbidity, usually in patients from reiatively affluent socio-economic backgrounds. A study of additional measures taken in a group of moderate to severe adult asthmatics from very poor socio- ...

  10. The flinders sensitive line rats, a genetic model of depression, show abnormal serotonin receptor mRNA expression in the brain that is reversed by 17beta-estradiol.

    Science.gov (United States)

    Osterlund, M K; Overstreet, D H; Hurd, Y L

    1999-12-10

    The possible link between estrogen and serotonin (5-HT) in depression was investigated using a genetic animal model of depression, the Flinders Sensitive Line (FSL) rats, in comparison to control Flinders Resistant Line rats. The mRNA levels of the estrogen receptor (ER) alpha and beta subtypes and the 5-HT(1A) and 5-HT(2A) receptors were analyzed in several limbic-related areas of ovariectomized FSL and FRL rats treated with 17beta-estradiol (0.15 microg/g) or vehicle. The FSL animals were shown to express significantly lower levels of the 5-HT(2A) receptor transcripts in the perirhinal cortex, piriform cortex, and medial anterodorsal amygdala and higher levels in the CA 2-3 region of the hippocampus. The only significant difference between the rat lines in ER mRNA expression was found in the medial posterodorsal amygdala, where the FSL rats showed lower ERalpha expression levels. Overall, estradiol treatment increased 5-HT(2A) and decreased 5-HT(1A) receptor mRNA levels in several of the examined regions of both lines. Thus, in many areas, estradiol was found to regulate the 5-HT receptor mRNA expression in the opposite direction to the alterations found in the FSL rats. These findings further support the implication of 5-HT receptors, in particular the 5-HT(2A) subtype, in the etiology of affective disorders. Moreover, the ability of estradiol to regulate the expression of the 5-HT(1A) and 5-HT(2A) receptor genes might account for the reported influence of gonadal hormones in mood and depression.

  11. Direct measurements show decreasing methane emissions from natural gas local distribution systems in the United States.

    Science.gov (United States)

    Lamb, Brian K; Edburg, Steven L; Ferrara, Thomas W; Howard, Touché; Harrison, Matthew R; Kolb, Charles E; Townsend-Small, Amy; Dyck, Wesley; Possolo, Antonio; Whetstone, James R

    2015-04-21

    Fugitive losses from natural gas distribution systems are a significant source of anthropogenic methane. Here, we report on a national sampling program to measure methane emissions from 13 urban distribution systems across the U.S. Emission factors were derived from direct measurements at 230 underground pipeline leaks and 229 metering and regulating facilities using stratified random sampling. When these new emission factors are combined with estimates for customer meters, maintenance, and upsets, and current pipeline miles and numbers of facilities, the total estimate is 393 Gg/yr with a 95% upper confidence limit of 854 Gg/yr (0.10% to 0.22% of the methane delivered nationwide). This fraction includes emissions from city gates to the customer meter, but does not include other urban sources or those downstream of customer meters. The upper confidence limit accounts for the skewed distribution of measurements, where a few large emitters accounted for most of the emissions. This emission estimate is 36% to 70% less than the 2011 EPA inventory, (based largely on 1990s emission data), and reflects significant upgrades at metering and regulating stations, improvements in leak detection and maintenance activities, as well as potential effects from differences in methodologies between the two studies.

  12. Anxious women do not show the expected decrease in cardiovascular stress responsiveness as pregnancy advances.

    Science.gov (United States)

    Braeken, M A K A; Jones, A; Otte, R A; Widjaja, D; Van Huffel, S; Monsieur, G J Y J; van Oirschot, C M; Van den Bergh, B R H

    2015-10-01

    Altered stress responsiveness is a risk factor for mental and physical illness. In non-pregnant populations, it is well-known that anxiety can alter the physiological regulation of stress reactivity. Characterization of corresponding risks for pregnant women and their offspring requires greater understanding of how stress reactivity and recovery are influenced by pregnancy and women's anxiety feelings. In the current study, women were presented repeatedly with mental arithmetic stress tasks in the first and third pregnancy trimester and reported their trait anxiety using the state trait anxiety inventory. Cardiovascular stress reactivity in late pregnancy was lower than reactivity in the first pregnancy trimester (heart rate (HR): t(197)=4.98, pprogression. Although this is a limitation, the clear differences between anxious and non-anxious pregnant women are important, regardless of the extent to which differing habituation between the groups is responsible. Less dampened stress reactivity through pregnancy may pose long-term risks for anxious women and their offspring. Follow-up studies are required to determine these risks. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Anxious women do not show the expected decrease in cardiovascular stress responsiveness as pregnancy advances

    NARCIS (Netherlands)

    Braeken, M A K A; Jones, A; Otte, R A; Widjaja, D; Van Huffel, S; Monsieur, G J Y J; van Oirschot, C M; Van den Bergh, B R H

    2015-01-01

    Altered stress responsiveness is a risk factor for mental and physical illness. In non-pregnant populations, it is well-known that anxiety can alter the physiological regulation of stress reactivity. Characterization of corresponding risks for pregnant women and their offspring requires greater

  14. Project WIN Evaluation Shows Decreased Violence and Improved Conflict Resolution Skills for Middle School Students

    Science.gov (United States)

    Roberts, Laura; Yeomans, Peter; Ferro-Almeida, Susan

    2007-01-01

    We believe the problems of school violence are linked to competition and bullying in school culture. We also believe that by fostering more cooperation and more compassion in school culture, we can reduce school violence. One of the ways to develop school culture is to implement conflict resolution training. In the current study, we introduced…

  15. Commentary on “Inhibition of interleukin-1beta decreases aneurysm formation and progression in a novel model of thoracic aortic aneurysms”

    Directory of Open Access Journals (Sweden)

    Yonghua Bi

    2015-09-01

    Full Text Available Aortic aneurysm is a silent but life-threatening disease, whose pathogenesis remains poorly understood. Aneurysm models have been induced in small animals to study its pathogenesis, Johnston WF et al. successfully induced a novel model of thoracic aortic aneurysms (TAA by periadventitial application of elastase in mice. We comment on this model according to our experiment. We hypothesize that endogenous MMPs, especially MMP2, play a vital role in complex repair process of aneurysmal wall, which should be a key target in the investigation and treatment of aortic aneurysms.

  16. Decreased reactivation of a herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) mutant using the in vivo mouse UV-B model of induced reactivation

    Science.gov (United States)

    BenMohamed, Lbachir; Osorio, Nelson; Srivastava, Ruchi; Khan, Arif A.; Simpson, Jennifer L.; Wechsler, Steven L.

    2015-01-01

    Blinding ocular herpetic disease in humans is due to herpes simplex virus type 1 (HSV-1) reactivations from latency, rather than to primary acute infection. The cellular and molecular mechanisms that control the HSV-1 latency-reactivation cycle remain to be fully elucidated. The aim of this study was to determine if reactivation of the HSV-1 latency associated transcript (LAT) deletion mutant (dLAT2903) was impaired in this model, as it is in the rabbit model of induced and spontaneous reactivation and in the explant TG induced reactivation model in mice. The eyes of mice latently infected with wild type HSV-1 strain McKrae (LAT(+) virus) or dLAT2903 (LAT(−) virus) were irradiated with UV-B and reactivation was determined. We found that compared to LAT(−) virus, LAT(+) virus reactivated at a higher rate as determined by shedding of virus in tears on days 3 to 7 after UV-B treatment. Thus, the UV-B induced reactivation model of HSV-1 appears to be a useful small animal model for studying the mechanisms involved in how LAT enhances the HSV-1 reactivation phenotype. The utility of the model for investigating the immune evasion mechanisms regulating the HSV-1 latency/reactivation cycle and for testing the protective efficacy of candidate therapeutic vaccines and drugs are discussed. PMID:26002839

  17. Decreased number of acetylcholine receptors is the mechanism that alters the time course of muscle relaxants in myasthenia gravis : a study in a rat model

    NARCIS (Netherlands)

    De Haes, A; Proost, JH; De Baets, MH; Stassen, MHW; Houwertjes, MC; Wierda, JMKH

    Background: In myasthenic patients, the time course of action of non-depolarizing neuromuscular blocking agents is prolonged and the sensitivity is increased. We used our antegrade perfused rat peroneal nerve anterior tibialis muscle model to investigate if this altered time course of effect and

  18. 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.

    Science.gov (United States)

    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.

  19. Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Koo, Jung-Hoon; Kang, Eun-Bum; Oh, Yoo-Sung; Yang, Dae-Seung; Cho, Joon-Yong

    2017-02-01

    Accumulation of amyloid-β (Aβ) correlates significantly with progressive cognitive deficits, a main symptom of Alzheimer's disease (AD). Although treadmill exercise reduces Aβ levels, the molecular mechanisms underlying the effects are not fully understood. We hypothesize that treadmill exercise decreases Aβ production and alleviates cognitive deficits by activating the non-amyloidogenic pathway via SIRT-1 signaling. Treadmill exercise improved cognitive deficits and alleviated neurotoxicity. Most importantly, treadmill exercise increased SIRT-1 level, which subsequently resulted in increased ADAM-10 level by down-regulation of ROCK-1 and upregulation of RARβ, ultimately facilitating the non-amyloidogenic pathway. Treadmill exercise-induced activation in SIRT-1 level also elevated PGC-1α level and reduced BACE-1 and C-99 level, resulting in inhibition of the amyloidogenic pathway. Treadmill exercise may thus inhibit Aβ production via upregulation of SIRT-1, which biases amyloid precursor protein processing toward the non-amyloidogenic pathway. This study provides novel and valuable insight into the molecular mechanisms possibly by which treadmill exercise reduces Aβ production. Copyright © 2016. Published by Elsevier Inc.

  20. Decreased Axon Caliber Underlies Loss of Fiber Tract Integrity, Disproportional Reductions in White Matter Volume, and Microcephaly in Angelman Syndrome Model Mice.

    Science.gov (United States)

    Judson, Matthew C; Burette, Alain C; Thaxton, Courtney L; Pribisko, Alaine L; Shen, Mark D; Rumple, Ashley M; Del Cid, Wilmer A; Paniagua, Beatriz; Styner, Martin; Weinberg, Richard J; Philpot, Benjamin D

    2017-08-02

    Angelman syndrome (AS) is a debilitating neurodevelopmental disorder caused by loss of function of the maternally inherited UBE3A allele. It is currently unclear how the consequences of this genetic insult unfold to impair neurodevelopment. We reasoned that by elucidating the basis of microcephaly in AS, a highly penetrant syndromic feature with early postnatal onset, we would gain new insights into the mechanisms by which maternal UBE3A loss derails neurotypical brain growth and function. Detailed anatomical analysis of both male and female maternal Ube3a -null mice reveals that microcephaly in the AS mouse model is primarily driven by deficits in the growth of white matter tracts, which by adulthood are characterized by densely packed axons of disproportionately small caliber. Our results implicate impaired axon growth in the pathogenesis of AS and identify noninvasive structural neuroimaging as a potentially valuable tool for gauging therapeutic efficacy in the disorder. SIGNIFICANCE STATEMENT People who maternally inherit a deletion or nonfunctional copy of the UBE3A gene develop Angelman syndrome (AS), a severe neurodevelopmental disorder. To better understand how loss of maternal UBE3A function derails brain development, we analyzed brain structure in a maternal Ube3a knock-out mouse model of AS. We report that the volume of white matter (WM) is disproportionately reduced in AS mice, indicating that deficits in WM development are a major factor underlying impaired brain growth and microcephaly in the disorder. Notably, we find that axons within the WM pathways of AS model mice are abnormally small in caliber. This defect is associated with slowed nerve conduction, which could contribute to behavioral deficits in AS, including motor dysfunction. Copyright © 2017 the authors 0270-6474/17/377347-15$15.00/0.

  1. Theoretical modeling of the urinary supersaturation of calcium salts in healthy individuals and kidney stone patients: Precursors, speciation and therapeutic protocols for decreasing its value

    Science.gov (United States)

    Rodgers, Allen L.; Allie-Hamdulay, Shameez; Jackson, Graham E.; Durbach, Ian

    2013-11-01

    BackgroundSupersaturation (SS) of urinary salts has been extensively invoked for assessing the risk of renal stone formation, but precursors have often been ignored. Our objectives were to establish by computer modeling, which urinary components are essential for calculating reliable SS values, to investigate whether unique equilibrium processes occur in the urine of stone formers (SF) which might account for their higher SS levels relative to healthy controls (N), to determine the relative efficacies of three different, widely-used protocols for lowering urinary SS of calcium salts and to examine the influence of precursors.

  2. Cerebral Oedema, Blood-Brain Barrier Breakdown and the Decrease in Na(+),K(+)-ATPase Activity in the Cerebral Cortex and Hippocampus are Prevented by Dexamethasone in an Animal Model of Maple Syrup Urine Disease.

    Science.gov (United States)

    Rosa, Luciana; Galant, Leticia S; Dall'Igna, Dhébora M; Kolling, Janaina; Siebert, Cassiana; Schuck, Patrícia F; Ferreira, Gustavo C; Wyse, Angela T S; Dal-Pizzol, Felipe; Scaini, Giselli; Streck, Emilio L

    2016-08-01

    Maple syrup urine disease (MSUD) is a rare metabolic disorder associated with acute and chronic brain dysfunction. This condition has been shown to lead to macroscopic cerebral alterations that are visible on imaging studies. Cerebral oedema is widely considered to be detrimental for MSUD patients; however, the mechanisms involved are still poorly understood. Therefore, we investigated whether acute administration of branched-chain amino acids (BCAA) causes cerebral oedema, modifies the Na(+),K(+)-ATPase activity, affects the permeability of the blood-brain barrier (BBB) and alters the levels of cytokines in the hippocampus and cerebral cortex of 10-day-old rats. Additionally, we investigated the influence of concomitant administration of dexamethasone on the alterations caused by BCAA. Our results showed that the animals submitted to the model of MSUD exhibited an increase in the brain water content, both in the cerebral cortex and in the hippocampus. By investigating the mechanism of cerebral oedema, we discovered an association between H-BCAA and the Na(+),K(+)-ATPase activity and the permeability of the BBB to small molecules. Moreover, the H-BCAA administration increases Il-1β, IL-6 and TNF-α levels in the hippocampus and cerebral cortex, whereas IL-10 levels were decreased in the hippocampus. Interestingly, we showed that the administration of dexamethasone successfully reduced cerebral oedema, preventing the inhibition of Na(+),K(+)-ATPase activity, BBB breakdown and the increase in the cytokines levels. In conclusion, these findings suggest that dexamethasone can improve the acute cerebral oedema and brain injury associated with high levels of BCAA, either through a direct effect on brain capillary Na(+),K(+)-ATPase or through a generalized effect on the permeability of the BBB to all compounds.

  3. Fasudil, a clinically safe ROCK inhibitor, decreases disease burden in a Cbl/Cbl-b deficiency-driven murine model of myeloproliferative disorders.

    Science.gov (United States)

    William, Basem M; An, Wei; Feng, Dan; Nadeau, Scott; Mohapatra, Bhopal C; Storck, Matthew A; Band, Vimla; Band, Hamid

    2016-05-01

    Mutations in Cbl or Cbl-b gene occur in 10% of myeloproliferative disorder (MPD) patients and are associated with poor prognosis. Hematopoietic Cbl/Cbl-b double knockout (DKO) leads to a disease in mice phenotypically similar to human MPDs. The aim of this study was to evaluate the anti-MPD activity of a clinically safe drug, Fasudil, identified in an in vitro kinase inhibitor as an inhibitor of proliferation of DKO mouse hematopoietic stem/progenitor cells (HSPCs). Fasudil exhibited relatively selective anti-proliferative activity against Cbl/Cbl-b DKO vs. control murine bone marrow HSPCs. We established a mouse model with uniform time of MPD onset by transplanting Cbl/Cbl-b DKO HSPCs into busulfan-conditioned NOD/SCID/gamma chain-deficient mice. Four weeks post-transplant, mice were treated with 100 mg/kg fasudil (13 mice) or water (control, 8 mice) daily by oral gavage, followed by blood cell count every 2 weeks. By 2 weeks of treatment, total white cell and monocyte counts were significantly lower in mice treated with fasudil. We observed a trend towards improved survival in fasudil-treated mice that did not reach statistical significance. Notably, prolonged survival beyond 27 weeks was observed in two fasudil-treated mice, nearly twice the 16-week average life-span in the Cbl/Cbl-b DKO MPD model. Our results suggest a therapeutic potential for fasudil, a clinically safe drug with promising results in vascular diseases, in the treatment of MPDs or other mutant Cbl-driven myeloid disorders.

  4. Combination of vatalanib and a 20-HETE synthesis inhibitor results in decreased tumor growth in an animal model of human glioma

    Directory of Open Access Journals (Sweden)

    Shankar A

    2016-03-01

    different treatment groups: vehicle, vatalanib (oral treatment 50 mg/kg/d, HET0016 (intraperitoneal treatment 10 mg/kg/d, and combined (vatalanib and HET0016. Following scheduled treatments, all animals underwent magnetic resonance imaging on day 22, followed by euthanasia. Brain specimens were equally divided for immunohistochemistry and protein array analysis.Results: Our results demonstrated a trend that HET0016, alone or in combination with vatalanib, is capable of controlling the tumor growth compared with that of vatalanib alone, indicating attenuation of the unwanted effect of vatalanib. When both vatalanib and HET0016 were administered together on the day of the tumor implantation (0–21 days treatment, tumor volume, tumor blood volume, permeability, extravascular and extracellular space volume, tumor cell proliferation, and cell migration were decreased compared with that of the vehicle-treated group. Conclusion: HET0016 is capable of controlling tumor growth and migration, but these effects are dependent on the timing of drug administration. The addition of HET0016 to vatalanib may attenuate the unwanted effect of vatalanib.Keywords: magnetic resonance imaging, glioblastoma, antiangiogenic treatments, HET0016, vascular parameters, protein array

  5. Peripheral injections of melanin-concentrating hormone receptor 1 antagonist S38151 decrease food intake and body weight in rodent obesity models

    Directory of Open Access Journals (Sweden)

    Odile eDella-Zuana

    2012-12-01

    Full Text Available The compound S38151 is a nanomolar antagonist that acts at the melanin-concentrating hormone receptor 1 (MCH1. S38151 is more stable than its purely peptide counterpart, essentially because of the blockade of its N-terminus. Therefore, , its action on various models of obesity was studied. Acute intracerebroventricular (i.c.v. administration of S38151 in wild-type rats counteracted the effect of the stable precursor of melanin-concentrating hormone (MCH, NEI-MCH, in a dose-dependent manner (from 0.5 to 50 nmol/kg. In genetically obese Zucker fa/fa rats, daily i.c.v. administration of S38151 induced dose-dependent (5, 10, and 20 nmol/kg inhibition of food intake, water intake, and body weight gain, as well as increased motility (maximal effect observed at 20 nmol/kg. In Zucker fa/fa rats, intraperitoneal injection of S38151 (30 mg/kg induced complete inhibition of food consumption within 1 h. Daily intraperitoneal injection of S38151 (10 and 30 mg/kg into genetically obese ob/ob mice or diet-induced obese mice is able to limit body weight gain. Furthermore, S38151 administration (10 and 30 mg/kg does not affect food intake, water intake, or body weight gain in MCHR1-deleted mice, demonstrating that its effects are linked to its interaction with MCH1. These results validate MCH1 as a target of interest in obesity. S38151 cannot progress to the clinical phase because it is still too poorly stable in vivo.

  6. Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition.

    Directory of Open Access Journals (Sweden)

    Stuart J Smith

    Full Text Available INTRODUCTION: Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS. METHODS: CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and comparison with a cohort of 53 pediatric high grade gliomas conducted by genome wide gene expression and microRNA arrays, coupled with immunohistochemistry, ex vivo magnetic resonance spectroscopy and drug sensitivity evaluation using the histone deacetylase inhibitor, Vorinostat. RESULTS: Macroscopic RCCS aggregates recapitulated the heterogeneous morphology of brain tumors with a distinct proliferating rim, necrotic core and oxygen tension gradient. Gene expression and microRNA analyses revealed significant differences with 3D expression intermediate to 2D cultures and primary brain tumors. Metabolic profiling revealed differential profiles, with an increase in tumor specific metabolites in 3D. To evaluate the potential of the RCCS as a drug testing tool, we determined the efficacy of Vorinostat against aggregates of U87 and KNS42 glioblastoma cells. Both lines demonstrated markedly reduced sensitivity when assaying in 3D culture conditions compared to classical 2D drug screen approaches. CONCLUSIONS: Our comprehensive characterization demonstrates that 3D RCCS culture of high grade brain tumor cells has profound effects on the genetic, epigenetic and metabolic profiles of cultured cells, with these cells residing as an intermediate phenotype between that of 2D cultures and primary tumors. There is a discrepancy between 2D culture and tumor molecular profiles, and RCCS partially re-capitulates tissue specific features, allowing drug testing in a more relevant ex vivo system.

  7. Neonatal handling enduringly decreases anxiety and stress responses and reduces hippocampus and amygdala volume in a genetic model of differential anxiety: Behavioral-volumetric associations in the Roman rat strains.

    Science.gov (United States)

    Río-Álamos, Cristóbal; Oliveras, Ignasi; Piludu, Maria Antonietta; Gerbolés, Cristina; Cañete, Toni; Blázquez, Gloria; Lope-Piedrafita, Silvia; Martínez-Membrives, Esther; Torrubia, Rafael; Tobeña, Adolf; Fernández-Teruel, Alberto

    2017-02-01

    The hippocampus and amygdala have been proposed as key neural structures related to anxiety. A more active hippocampus/amygdala system has been related to greater anxious responses in situations involving conflict/novelty. The Roman Low- (RLA) and High-avoidance (RHA) rat lines/strains constitute a genetic model of differential anxiety. Relative to RHA rats, RLA rats exhibit enhanced anxiety/fearfulness, augmented hippocampal/amygdala c-Fos expression following exposure to novelty/conflict, increased hippocampal neuronal density and higher endocrine responses to stress. Neonatal handling (NH) is an environmental treatment with long-lasting anxiety/stress-reducing effects in rodents. Since hippocampus and amygdala volume are supposed to be related to anxiety/fear, we hypothesized a greater volume of both areas in RLA than in RHA rats, as well as that NH treatment would reduce anxiety and the volume of both structures, in particular in the RLA strain. Adult untreated and NH-treated RHA and RLA rats were tested for anxiety, sensorimotor gating (PPI), stress-induced corticosterone and prolactin responses, two-way active avoidance acquisition and in vivo 7 T 1H-Magnetic resonance image. As expected, untreated RLA rats showed higher anxiety and post-stress hormone responses, as well as greater hippocampus and amygdala volumes than untreated RHA rats. NH decreased anxiety/stress responses, especially in RLA rats, and significantly reduced hippocampus and amygdala volumes in this strain. Dorsal striatum volume was not different between the strains nor it was affected by NH. Finally, there were positive associations (as shown by correlations, factor analysis and multiple regression) between anxiety and PPI and hippocampus/amygdala volumes. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  8. Risk Aversion in Game Shows

    DEFF Research Database (Denmark)

    Andersen, Steffen; Harrison, Glenn W.; Lau, Morten I.

    2008-01-01

    We review the use of behavior from television game shows to infer risk attitudes. These shows provide evidence when contestants are making decisions over very large stakes, and in a replicated, structured way. Inferences are generally confounded by the subjective assessment of skill in some games...

  9. Decreased Expression of the Early Mitotic Gene, CHFR, Contributes to the Acquisition of Breast Cancer Phenotypes

    National Research Council Canada - National Science Library

    Privette, Lisa M

    2008-01-01

    .... As previously reported, nearly 40% of breast cancer show decreased CHFR expression compared to normal cells and tissues and the loss of CHFR expression by RNAi in cell culture models leads to the acquisition of several tumorigenic phenotypes...

  10. Mastery Learning and the Decreasing Variability Hypothesis.

    Science.gov (United States)

    Livingston, Jennifer A.; Gentile, J. Ronald

    1996-01-01

    This report results from studies that tested two variations of Bloom's decreasing variability hypothesis using performance on successive units of achievement in four graduate classrooms that used mastery learning procedures. Data do not support the decreasing variability hypothesis; rather, they show no change over time. (SM)

  11. An NR2B-Dependent Decrease in the Expression of trkB Receptors Precedes the Disappearance of Dopaminergic Cells in Substantia Nigra in a Rat Model of Presymptomatic Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Eduardo Riquelme

    2012-01-01

    Full Text Available Compensatory changes occurring during presymptomatic stages of Parkinson's disease (PD would explain that the clinical symptoms of the disease appear late, when the degenerative process is quite advanced. Several data support the proposition that brain-derived neurotrophic factor (BDNF could play a role in these plastic changes. In the present study, we evaluated the expression of the specific BDNF receptor, trkB, in a rat model of presymptomatic PD generated by intrastriatal injection of the neurotoxin 6-OHDA. Immunohistochemical studies revealed a decrease in trkB expression in SN pars compacta (SNc seven days after 6-OHDA injection. At this time point, no change in the number of tyrosine hydroxylase (TH immunoreactive (TH-IR cells is detected, although a decrease is evident 14 days after neurotoxin injection. The decrease in TH-positive cells and trkB expression in SNc was significantly prevented by systemic administration of Ifenprodil, a specific antagonist of NR2B-containing NMDA receptors. Therefore, an NR2B-NMDA receptor-dependent decrease in trkB expression precedes the disappearance of TH-IR cells in SNc in response to 6-OHDA injection. These results support the idea that a functional coupling between NMDA receptors and BDNF/trkB signalling may be important for the maintenance of the dopaminergic phenotype in SNc during presymptomatic stages of PD.

  12. Corticosteroids decrease glomerular angiotensin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Douglas, J.G.

    1987-03-01

    Angiotensin II (ANG II) receptors of glomerular mesangial cells are regulated in vivo by changes in Na balance, effects that are presumed to be secondary to changes in circulating ANG II. However, since changes in ANG II were accompanied by parallel changes in plasma aldosterone in all models tested, it is possible that aldosterone may have also participated in the modulation of glomerular ANG II receptors. To test this hypothesis, short-term aldosterone infusions within the physiological range were employed to favor actions that would be mediated through a high-affinity mineralocorticoid receptor. The glucocorticoid, dexamethasone, was also tested to determine the mineralocorticoid specificity of the response. Two infusion rates were associated with a decrease in glomerular /sup 125/I ANG II receptor density of 33 and 45%, respectively. Serum potassium and urinary Na/K ratio were lower in the aldosterone group. Spironolactone abolished the effect of aldosterone consistent with an action mediated through a specific mineralocorticoid receptor. These studies support the hypothesis that corticosteroids modulate glomerular ANG II receptors and validate the complexity of glomerular receptor modulation. The downregulation observed would be expected to diminish the ability of ANG II to influence glomerular hemodynamics in models such as mineralocorticoid and glucocorticoid-induced hypertension.

  13. Create a Polarized Light Show.

    Science.gov (United States)

    Conrad, William H.

    1992-01-01

    Presents a lesson that introduces students to polarized light using a problem-solving approach. After illustrating the concept using a slinky and poster board with a vertical slot, students solve the problem of creating a polarized light show using Polya's problem-solving methods. (MDH)

  14. Producing Talent and Variety Shows.

    Science.gov (United States)

    Szabo, Chuck

    1995-01-01

    Identifies key aspects of producing talent shows and outlines helpful hints for avoiding pitfalls and ensuring a smooth production. Presents suggestions concerning publicity, scheduling, and support personnel. Describes types of acts along with special needs and problems specific to each act. Includes a list of resources. (MJP)

  15. Electro-acupuncture decreases 5-HT, CGRP and increases NPY in the brain-gut axis in two rat models of Diarrhea-predominant irritable bowel syndrome(D-IBS).

    Science.gov (United States)

    Sun, Jianhua; Wu, Xiaoliang; Meng, Yunfang; Cheng, Jie; Ning, Houxu; Peng, Yongjun; Pei, Lixia; Zhang, Wei

    2015-09-29

    To examine whether electro-acupuncture (EA) could decrease 5-hydroxytryptamine (5-HT) and calcitonin gene-related peptide (CGRP), and increase neuro-peptide Y (NPY) in the brain-gut axis (BGA) in D-IBS using rat models. Rats were randomly exposed to unpredictable chronic stress for 3 weeks followed by 1-hour acute restraint stress (CAS) after 7 days of rest, or daily gavage of Senna decoction (6 g/kg) plus chronic restraint stress (for a duration of 2 h, starting from 1 h prior to the gavage) for 2 weeks (ISC). The content of 5-HT, CGRP and NPY in the distal colon, spinal cord, hypothalamus was examined at the end of the treatment. 1. The two rat models exhibited similar characteristics, e.g., increased number of fecal pellets expelled in 1 h, decreased sacchar-intake, decreased CRD, elevated 5-HT, CGRP content and decreased NPY in the distal colon, spinal cord, hypothalamus (P vs. that in healthy control rats). 2. A series of equations was developed based on correlation regression analysis. The analysis results demonstrated that 5-HT mediates the changes in hypothalamus, spinal cord and colon. 5-HT and CGRP in spinal cord was closely correlated with general behavior evaluation and other transmitters in BGA. 1. In comparison to 5-HT, CGRP and NPY (particularly in the spinal cord) had closer relationship with the D-IBS symptoms induced by either stress factors or Senna decotion. 2. EA treatment could restore the brain-gut axis to balanced levels.

  16. Complete Comparison Display (CCD) evaluation of ethanol extracts of Centella asiatica and Withania somnifera shows that they can non-synergistically ameliorate biochemical and behavioural damages in MPTP induced Parkinson's model of mice

    Science.gov (United States)

    Bhatnagar, Maheep; Goel, Ishan; Roy, Tathagato; Khurana, Sukant

    2017-01-01

    Parkinson’s disease remains as one of the most common debilitating neurodegenerative disorders. With the hopes of finding agents that can cure or reduce the pace of progression of the disease, we studied two traditional medicinal plants: Centella asiatica and Withania somnifera that have been explored in some recent studies. In agreement with the previous work on ethanol extracts of these two plants in mice model, we saw an improvement in oxidative stress profile as well as behavioral performance in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinson-like symptoms in Balb/c mice. Given the known potential of both the herbal extracts in improving Parkinson-like symptoms, we expected the combination of the two to show better results than either of the two but surprisingly there was no additivity in either oxidative stress or behavioural recovery. In fact, in some assays, the combination performed worse than either of the two individual constituents. This effect of mixtures highlights the need of testing mixtures in supplements market using enthomedicine. The necessity of comparing multiple groups in this study to get most information from the experiments motivated us to design a ladder-like visualization to show comparison with different groups that we call complete comparison display (CCD). In summary, we show the potential of Centella asiatica and Withania somnifera to ameliorate Parkinson’s disorder. PMID:28510600

  17. Complete Comparison Display (CCD evaluation of ethanol extracts of Centella asiatica and Withania somnifera shows that they can non-synergistically ameliorate biochemical and behavioural damages in MPTP induced Parkinson's model of mice.

    Directory of Open Access Journals (Sweden)

    Maheep Bhatnagar

    Full Text Available Parkinson's disease remains as one of the most common debilitating neurodegenerative disorders. With the hopes of finding agents that can cure or reduce the pace of progression of the disease, we studied two traditional medicinal plants: Centella asiatica and Withania somnifera that have been explored in some recent studies. In agreement with the previous work on ethanol extracts of these two plants in mice model, we saw an improvement in oxidative stress profile as well as behavioral performance in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP induced Parkinson-like symptoms in Balb/c mice. Given the known potential of both the herbal extracts in improving Parkinson-like symptoms, we expected the combination of the two to show better results than either of the two but surprisingly there was no additivity in either oxidative stress or behavioural recovery. In fact, in some assays, the combination performed worse than either of the two individual constituents. This effect of mixtures highlights the need of testing mixtures in supplements market using enthomedicine. The necessity of comparing multiple groups in this study to get most information from the experiments motivated us to design a ladder-like visualization to show comparison with different groups that we call complete comparison display (CCD. In summary, we show the potential of Centella asiatica and Withania somnifera to ameliorate Parkinson's disorder.

  18. Complete Comparison Display (CCD) evaluation of ethanol extracts of Centella asiatica and Withania somnifera shows that they can non-synergistically ameliorate biochemical and behavioural damages in MPTP induced Parkinson's model of mice.

    Science.gov (United States)

    Bhatnagar, Maheep; Goel, Ishan; Roy, Tathagato; Shukla, Sunil Dutt; Khurana, Sukant

    2017-01-01

    Parkinson's disease remains as one of the most common debilitating neurodegenerative disorders. With the hopes of finding agents that can cure or reduce the pace of progression of the disease, we studied two traditional medicinal plants: Centella asiatica and Withania somnifera that have been explored in some recent studies. In agreement with the previous work on ethanol extracts of these two plants in mice model, we saw an improvement in oxidative stress profile as well as behavioral performance in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinson-like symptoms in Balb/c mice. Given the known potential of both the herbal extracts in improving Parkinson-like symptoms, we expected the combination of the two to show better results than either of the two but surprisingly there was no additivity in either oxidative stress or behavioural recovery. In fact, in some assays, the combination performed worse than either of the two individual constituents. This effect of mixtures highlights the need of testing mixtures in supplements market using enthomedicine. The necessity of comparing multiple groups in this study to get most information from the experiments motivated us to design a ladder-like visualization to show comparison with different groups that we call complete comparison display (CCD). In summary, we show the potential of Centella asiatica and Withania somnifera to ameliorate Parkinson's disorder.

  19. "Medicine show." Alice in Doctorland.

    Science.gov (United States)

    1987-01-01

    This is an excerpt from the script of a 1939 play provided to the Institute of Social Medicine and Community Health by the Library of Congress Federal Theater Project Collection at George Mason University Library, Fairfax, Virginia, pages 2-1-8 thru 2-1-14. The Federal Theatre Project (FTP) was part of the New Deal program for the arts 1935-1939. Funded by the Works Progress Administration (WPA) its goal was to employ theater professionals from the relief rolls. A number of FTP plays deal with aspects of medicine and public health. Pageants, puppet shows and documentary plays celebrated progress in medical science while examining social controversies in medical services and the public health movement. "Medicine Show" sharply contrasts technological wonders with social backwardness. The play was rehearsed by the FTP but never opened because funding ended. A revised version ran on Broadway in 1940. The preceding comments are adapted from an excellent, well-illustrated review of five of these plays by Barabara Melosh: "The New Deal's Federal Theatre Project," Medical Heritage, Vol. 2, No. 1 (Jan/Feb 1986), pp. 36-47.

  20. A Teacher-Focused Intervention to Decrease PE Students' Amotivation by Increasing Need Satisfaction and Decreasing Need Frustration.

    Science.gov (United States)

    Cheon, Sung Hyeon; Reeve, Johnmarshall; Song, Yong-Gwan

    2016-06-01

    Intervention-induced gains in need satisfaction decrease PE students' amotivation. The present study adopted a dual-process model to test whether an intervention could also decrease need frustration and hence provide a second supplemental source to further decrease students' PE amotivation. Using an experimental, longitudinal research design, 19 experienced PE teachers (9 experimental, 10 control) and their 1,017 students participated in an intervention program to help teachers become both more autonomy supportive and less controlling. Multilevel repeated measures analyses showed that students of teachers in the experimental group reported greater T2, T3, and T4 perceived autonomy support, need satisfaction, and engagement and lesser T2, T3, and T4 perceived teacher control, need frustration, and amotivation than did students of teachers in the control group. Multilevel structural equation modeling analyses confirmed the hypothesized dual-process model in which both intervention-induced increases in need satisfaction and intervention-induced decreases need frustration decreased students' end-of-semester amotivation. We discuss the theoretical and practical implications of this new finding on the dual antecedents of diminished amotivation.

  1. Combined MRI and ³¹P-MRS investigations of the ACTA1(H40Y mouse model of nemaline myopathy show impaired muscle function and altered energy metabolism.

    Directory of Open Access Journals (Sweden)

    Charlotte Gineste

    Full Text Available Nemaline myopathy (NM is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle α-actin gene (ACTA1 account for ∼25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear. Additionally, recent Magnetic Resonance Imaging (MRI studies reported a progressive fatty infiltration of skeletal muscle with a specific muscle involvement in patients with ACTA1 mutations. We investigated strictly noninvasively the gastrocnemius muscle function of a mouse model carrying a mutation in the ACTA1 gene (H40Y. Skeletal muscle anatomy (hindlimb muscles and fat volumes and energy metabolism were studied using MRI and (31Phosphorus magnetic resonance spectroscopy. Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (from 1-150 Hz and a fatigue protocol (80 stimuli at 40 Hz. H40Y mice showed a reduction of both absolute (-40% and specific (-25% maximal force production as compared to controls. Interestingly, muscle weakness was associated with an improved resistance to fatigue (+40% and an increased energy cost. On the contrary, the force frequency relationship was not modified in H40Y mice and the extent of fatty infiltration was minor and not different from the WT group. We concluded that the H40Y mouse model does not reproduce human MRI findings but shows a severe muscle weakness which might be related to an alteration of intrinsic muscular properties. The increased energy cost in H40Y mice might be related to either an impaired mitochondrial function or an alteration at the cross-bridges level. Overall, we provided a unique set of anatomic, metabolic and functional biomarkers that might be relevant for monitoring the progression of NM disease but also for assessing the efficacy of potential therapeutic interventions at a preclinical level.

  2. The Ts65Dn mouse model of Down syndrome shows reduced expression of the Bcl-X(L) antiapoptotic protein in the hippocampus not accompanied by changes in molecular or cellular markers of cell death.

    Science.gov (United States)

    Rueda, Noemí; Flórez, Jesús; Martínez-Cué, Carmen

    2011-11-01

    The Ts65Dn (TS) mouse, the most widely used model of Down syndrome (DS), has a partial trisomy of a segment of chromosome 16 that is homologous to the distal part of human chromosome 21. This mouse shares many phenotypic characteristics with people with DS including neuromorphological, neurochemical, and cognitive disturbances. Both TS and DS brains show earlier aging and neurodegeneration. Since fibroblast cultures from TS mice and human DS hippocampal regions show increased apoptotic cell death it has been suggested that alterations in cerebral apoptosis might be implicated in the cognitive deficits found in TS mice and in people with DS. In the present study we have evaluated brain expression levels of several proapoptotic and antiapoptotic proteins from the mitochondrial (Bcl-2, Bcl-X(L), Bax and Bad) and the extrinsic (Fas-R and Fas-L) apoptotic pathways as well as the final executioner caspase-3, in the cortex and hippocampus of TS mice. No significant alterations in the expression levels of the proapoptotic Bad and Bax or the antiapoptotic Bcl-2 proteins in the cortex or hippocampus were found in TS mice. However, TS mice showed downregulation of Bcl-X(L) in the hippocampus. In the extrinsic pathway we found unchanged levels of Fas-L in both structures and also in the expression levels of Fas-R in the hippocampus. Although Bcl-X(L) downregulation suggests that the hippocampus of TS mice is less protected against programmed cell death, we did not find any evidence for increased apoptosis in TS mice since neither TUNEL-positive cells nor active caspase-3 expression were found in cortex or hippocampus of TS or CO mice. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. ADX71943 and ADX71441, novel positive allosteric modulators of the GABABreceptor with distinct central/peripheral profiles, show efficacy in the monosodium iodoacetate model of chronic osteoarthritis pain in the rat.

    Science.gov (United States)

    Kalinichev, Mikhail; Donovan-Rodriguez, Tansy; Girard, Françoise; Haddouk, Hasnaá; Royer-Urios, Isabelle; Schneider, Manfred; Bate, Simon T; Marker, Cheryl; Pomonis, James D; Poli, Sonia

    2017-01-15

    We tested novel positive allosteric modulators (PAMs) of the γ-aminobutyric acid receptor B (GABA B ), ADX71943 and ADX71441in the monosodium iodoacetate model of chronic osteoarthritis pain in rats with the objective to delineate the role of peripheral versus central GABA B receptor populations in modulation of chronic pain. Anesthetized Sprague-Dawley rats received an injection of monosodium iodoacetate into the knee and were tested for hyperalgesia starting post-MIA day 14. Effects of compounds on ipsilateral joint compression threshold were evaluated on post-MIA day 14 (after acute treatment), as well as after repeated, daily treatment on days 21 and 28 (ADX71943 only) and were compared to those of celecoxib (30mg/kg, p.o.). The PAMs were also tested in the rat rotarod test for potential muscle-relaxant effects. Acutely, ADX71943 (1-30mg/kg, p.o.), the peripherally restricted PAM, resulted in similar increases in pain threshold across the doses on day 14, while showing reduced efficacy on day 21 and no efficacy on day 28. A clear reduction in the efficacy of celecoxib across testing was also noted in this experiment. Acutely ADX71441 (0.3-15mg/kg, p.o.), the central-peripheral PAM, resulted in over 2-fold increases in pain threshold at 15mg/kg (but not at lower doses) on day 14, while causing more modest effects on day 21. Celecoxib increased pain threshold after both acute and daily treatment, showing overall similar efficacy. Thus, early, presumably more inflammatory phase of osteoarthritis pain in more sensitive to GABA B PAMs with peripherally restricted profile, while later, presumably more neuropathic phase is more sensitive to PAMs with central-peripheral profile. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Recent decrease in typhoon destructive potential and global warming implications

    Science.gov (United States)

    Lin, I.-I.; Chan, Johnny C. L.

    2015-05-01

    Typhoons (tropical cyclones) severely impact the half-billion population of the Asian Pacific. Intriguingly, during the recent decade, typhoon destructive potential (Power Dissipation Index, PDI) has decreased considerably (by ~35%). This decrease, paradoxically, has occurred despite the increase in typhoon intensity and ocean warming. Using the method proposed by Emanuel (in 2007), we show that the stronger negative contributions from typhoon frequency and duration, decrease to cancel the positive contribution from the increasing intensity, controlling the PDI. Examining the typhoons' environmental conditions, we find that although the ocean condition became more favourable (warming) in the recent decade, the atmospheric condition `worsened' at the same time. The `worsened' atmospheric condition appears to effectively overpower the `better' ocean conditions to suppress PDI. This stronger negative contribution from reduced typhoon frequency over the increased intensity is also present under the global warming scenario, based on analysis of the simulated typhoon data from high-resolution modelling.

  5. Recent decrease in typhoon destructive potential and global warming implications

    Science.gov (United States)

    Lin, I-I; Chan, Johnny C.L.

    2015-01-01

    Typhoons (tropical cyclones) severely impact the half-billion population of the Asian Pacific. Intriguingly, during the recent decade, typhoon destructive potential (Power Dissipation Index, PDI) has decreased considerably (by ∼35%). This decrease, paradoxically, has occurred despite the increase in typhoon intensity and ocean warming. Using the method proposed by Emanuel (in 2007), we show that the stronger negative contributions from typhoon frequency and duration, decrease to cancel the positive contribution from the increasing intensity, controlling the PDI. Examining the typhoons' environmental conditions, we find that although the ocean condition became more favourable (warming) in the recent decade, the atmospheric condition ‘worsened' at the same time. The ‘worsened' atmospheric condition appears to effectively overpower the ‘better' ocean conditions to suppress PDI. This stronger negative contribution from reduced typhoon frequency over the increased intensity is also present under the global warming scenario, based on analysis of the simulated typhoon data from high-resolution modelling. PMID:25990561

  6. Tilapia show immunization response against Ich

    Science.gov (United States)

    This study compares the immune response of Nile tilapia and red tilapia against parasite Ichthyophthirius multifiliis (Ich) using a cohabitation challenge model. Both Nile and red tilapia showed strong immune response post immunization with live Ich theronts by IP injection or immersion. Blood serum...

  7. A Mixture of Functionally Oligoclonal Humanized Monoclonal Antibodies That Neutralize Clostridium difficile TcdA and TcdB with High Levels of In Vitro Potency Shows In Vivo Protection in a Hamster Infection Model

    Science.gov (United States)

    Davies, Nicola L.; Compson, Joanne E.; MacKenzie, Brendon; O'Dowd, Victoria L.; Oxbrow, Amanda K. F.; Heads, James T.; Turner, Alison; Sarkar, Kaushik; Dugdale, Sarah L.; Jairaj, Mark; Christodoulou, Louis; Knight, David E. O.; Cross, Amanda S.; Hervé, Karine J. M.; Tyson, Kerry L.; Hailu, Hanna; Doyle, Carl B.; Ellis, Mark; Kriek, Marco; Cox, Matthew; Page, Matthew J. T.; Moore, Adrian R.; Lightwood, Daniel J.

    2013-01-01

    Clostridium difficile infections are a major cause of antibiotic-associated diarrhea in hospital and care facility patients. In spite of the availability of effective antibiotic treatments, C. difficile infection (CDI) is still a major cause of patient suffering, death, and substantial health care costs. Clostridium difficile exerts its major pathological effects through the actions of two protein exotoxins, TcdA and TcdB, which bind to and disrupt gut tissue. Antibiotics target the infecting bacteria but not the exotoxins. Administering neutralizing antibodies against TcdA and TcdB to patients receiving antibiotic treatment might modulate the effects of the exotoxins directly. We have developed a mixture of three humanized IgG1 monoclonal antibodies (MAbs) which neutralize TcdA and TcdB to address three clinical needs: reduction of the severity and duration of diarrhea, reduction of death rates, and reduction of the rate of recurrence. The UCB MAb mixture showed higher potency in a variety of in vitro binding and neutralization assays (∼10-fold improvements), higher levels of protection in a hamster model of CDI (82% versus 18% at 28 days), and higher valencies of toxin binding (12 versus 2 for TcdA and 3 versus 2 for TcdB) than other agents in clinical development. Comparisons of the MAb properties also offered some insight into the potential relative importance of TcdA and TcdB in the disease process. PMID:23324518

  8. A Family-Centered Feeding Intervention to Promote Food Acceptance and Decrease Challenging Behaviors in Children With ASD: Report of Follow-Up Data on a Train-the-Trainer Model Using EAT-UP.

    Science.gov (United States)

    Muldoon, Deirdre; Cosbey, Joanna

    2018-02-06

    This research note outlines the usefulness of Easing Anxiety Together with Understanding and Perseverance (EAT-UP), a train-the-trainer, family-centered feeding intervention, for promoting food acceptance of children with autism spectrum disorder (ASD). This report is a follow-up on a pilot study (n = 4) of the EAT-UP intervention previously completed by the same authors. Participants were 3 families of children with ASD receiving services from an outpatient department of a larger rehabilitation hospital in the northeastern United States. Three professionals working with the families were also recruited and trained by the first author, a speech-language pathologist experienced with the EAT-UP method. Initial assessment was followed by a baseline period for each participant. An individual mealtime plan was drafted for each family. Data on acceptance of less preferred food and the presence of challenging mealtime behaviors were recorded using direct observation and pre-, mid-, and postintervention measures and questionnaires. All children demonstrated increased food acceptance and dietary diversity and decreased challenging behaviors. Caregivers reported decreases in the frequency of problem behaviors and in the number of problem mealtime behaviors. Measures of procedural fidelity increased from 50% to 100% for registered behavior technicians and parents over the course of the EAT-UP intervention period. EAT-UP is an effective model for training professionals who work with families of children with ASD and challenging mealtime behavior. Implications for interprofessional practice and research are discussed.

  9. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.

    Science.gov (United States)

    Lee, Young Il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-08-15

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precede the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.

    Science.gov (United States)

    Desale, Swapnil S; Raja, Srikumar M; Kim, Jong Oh; Mohapatra, Bhopal; Soni, Kruti S; Luan, Haitao; Williams, Stetson H; Bielecki, Timothy A; Feng, Dan; Storck, Matthew; Band, Vimla; Cohen, Samuel M; Band, Hamid; Bronich, Tatiana K

    2015-06-28

    ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full

  11. Airplane radiation dose decrease during a strong Forbush decrease

    Czech Academy of Sciences Publication Activity Database

    Spurný, František; Kudela, K.; Dachev, T.

    2004-01-01

    Roč. 2, S05001 (2004), s. 1-4 ISSN 1542-7390 Grant - others:EC project(XE) FIGM-CT2000-00068 Institutional research plan: CEZ:AV0Z1048901 Keywords : airplane dose * Forbush decrease * cosmic rays Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

  12. Decreasing incidence rates of bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Stig Lønberg; Pedersen, C; Jensen, T G

    2014-01-01

    BACKGROUND: Numerous studies have shown that the incidence rate of bacteremia has been increasing over time. However, few studies have distinguished between community-acquired, healthcare-associated and nosocomial bacteremia. METHODS: We conducted a population-based study among adults with first......-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p ...) and the incidence rate of nosocomial bacteremia decreased by 28.9% from 82.2 to 56.0 (4.2% annually, p

  13. Elevated plasma homocysteine in association with decreased ...

    African Journals Online (AJOL)

    Conclusion: This study showed a significant increase in plasma tHcy coexisting with a decrease in plasma vitamin B12 TC, LDLC and HDLC, in depressed patients. Increased plasma homocysteine could be a sensitive indicator of plasma B vitamin deficiency. Keywords: Cholesterol; Depression; Homocysteine; Tryptophan; ...

  14. Aggregate Unemployment Decreases Individual Returns to Education

    Science.gov (United States)

    Ammermueller, Andreas; Kuckulenz, Anja; Zwick, Thomas

    2009-01-01

    Aggregate unemployment may affect individual returns to education through qualification-specific responses in participation and wage bargaining. This paper shows that an increase in regional unemployment by 1% decreases returns to education by 0.005 percentage points. This implies that higher skilled employees are better sheltered from labour…

  15. Decreased oxygen permeability of EVOH through molecular interactions

    Directory of Open Access Journals (Sweden)

    Zs. Peter

    2014-10-01

    Full Text Available Poly(ethylene-co-vinyl alcohol of 48 mol% ethylene content was modified with N,N'-bis(2,2,6,6-tetramethyl-4-piperidyl-isophthalamide (Nylostab SEED to decrease the oxygen permeability of the polymer. The additive was added in a wide concentration range from 0 to 10 wt%. The structure and properties of the polymer were characterized with various methods including differential scanning calorimetry, X-ray diffraction, mechanical testing, optical measurements and oxygen permeation. Interactions were estimated by molecular modeling and infrared spectroscopy. The results showed that oxygen permeation decreased considerably when the additive was added at less than 2.0 wt% concentration. The decrease resulted from the interaction of the hydroxyl groups of the polymer and the amide groups of the additive. The dissolution of the additive in the polymer led to decreased crystallinity, but also to decreased mobility of amorphous molecules. Stiffness and strength, but also deformability increased as a result. Above 2 wt% the additive forms a separate phase leading to the deterioration of properties. The success of the approach represents a novel way to control oxygen permeation in EVOH and in other polymers with similar functional groups capable of strong interactions.

  16. Forbush decreases registered onboard aircraft

    Czech Academy of Sciences Publication Activity Database

    Spurný, František; Kudela, K.; Dachev, T.

    2005-01-01

    Roč. 36, č. 9 (2005), s. 1634-1637 ISSN 0273-1177 Institutional research plan: CEZ:AV0Z10480505 Keywords : Forbush decrease * aircraft exposure * Si-detector Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 0.706, year: 2005

  17. Iron supplementation decreases severity of allergic inflammation in murine lung.

    Directory of Open Access Journals (Sweden)

    Laura P Hale

    Full Text Available The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans.

  18. Varicose veins show enhanced chemokine expression.

    Science.gov (United States)

    Solá, L del Rio; Aceves, M; Dueñas, A I; González-Fajardo, J A; Vaquero, C; Crespo, M Sanchez; García-Rodríguez, C

    2009-11-01

    Leucocyte infiltration in the wall of varicose veins has been reported previously. This study was designed to investigate the expression of pro-inflammatory cytokines and chemokines in control and in patients with varicose veins and to test the effect of treating varicose vein patients with acetylsalicylic acid (ASA) on cytokine expression prior to removal of varices. Sections of vein were removed during operation from both patient groups, and ribonuclease protection assays (RPAs) were performed to assess the expression of chemokines. Group I included non-varicose saphenous veins from healthy patients undergoing amputation for trauma. Varicose veins were obtained from patients with primary varicose undergoing surgical treatment who received no drug (group II) or treatment with 300 mg day(-1) of ASA for 15 days before surgery (group III). Non-varicose veins constitutively expressed low levels of monocyte-chemoattractant protein (MCP-1) and interleukin (IL)-8 mRNA. Varicose veins had a distinct chemokine expression pattern, since significant up-regulation of MCP-1 and IL-8 and a marked expression of IP-10, RANTES, MIP-1alpha and MIP-1beta mRNA were detected. Removal of the endothelium did not alter this pattern. Varicose veins obtained from patients treated with ASA showed a consistent decrease in chemokine expression, although it did not reach statistical significance. Varicose veins showed increased expression of several chemokines compared to control veins. A non-significant reduction of activation was observed following treatment with ASA for 15 days.

  19. Decreasing Fires in Mediterranean Europe.

    Directory of Open Access Journals (Sweden)

    Marco Turco

    Full Text Available Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value. These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011 and a mixed trend in Portugal (1980-2011. Similar overall results were found for the annual number of fires (NF, which globally decreased by about 12600 in the study period (about -59%, except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  20. Fault Zone Permeability Decrease Following Large Earthquakes in a Hydrothermal System

    Science.gov (United States)

    Shi, Zheming; Zhang, Shouchuan; Yan, Rui; Wang, Guangcai

    2018-02-01

    Seismic wave shaking-induced permeability enhancement in the shallow crust has been widely observed. Permeability decrease, however, is seldom reported. In this study, we document coseismic discharge and temperature decrease in a hot spring following the 1996 Lijiang Mw 7.0 and the 2004 Mw 9.0 earthquakes in the Balazhang geothermal field. We use three different models to constrain the permeability change and the mechanism of coseismic discharge decrease, and we use an end-member mixing model for the coseismic temperature change. Our results show that the earthquake-induced permeability decrease in the fault zone reduced the recharge from deep hot water, which may be the mechanism that explains the coseismic discharge and temperature responses. The changes in the hot spring response reflect the dynamic changes in the hydrothermal system; in the future, the earthquake-induced permeability decrease should be considered when discussing controls on permeability.

  1. Hemodilution causes decreased compliance in puppies.

    Science.gov (United States)

    Mavroudis, C; Ebert, P A

    1978-09-01

    Cardiopulmonary bypass and hemodilution in the newborn have been associated with increased myocardial edema, which may be due to immature connective tissue formation. Five adult and four puppy dogs were placed on bypass while compliance and ventricular function (intraventricular balloon) were measured during normohemoconcentration (NH) (hematocrit 45.1, osmolality 307) and hemodilution with normal saline (hematocrit 24.7, osmolality 307). Compared with NH, the adult group showed no change in compliance or function after 90 min of hemodilution. The puppy group showed a marked decrease in compliance with hemodilution compared to NH (P sensitive to edema formation than the adult during hemodilution and that filling pressures do not necessarily reflect ventricular performance during the early post-perfusion period when compliance is decreased.

  2. A Population Pharmacokinetic Modeling Approach Shows that Serum Penicillin G Concentrations Are Below Inhibitory Concentrations by Two Weeks after Benzathine Penicillin G Injection in the Majority of Young Adults

    Science.gov (United States)

    2014-11-01

    a proposed protective threshold against group A Streptococcus pyogenes (GAS). The final population model included linear absorption into a central...the prevention and treatment of group A Streptococcus pyogenes (GAS) infections. This minimum threshold differs among authorities but is usually set...liter is the suggested minimum protective concentration of penicillin G against group A streptococcus . Note that the majority of measured concen- trations

  3. Bilateral quinolinic acid-induced lipid peroxidation, decreased striatal monoamine levels and neurobehavioral deficits are ameliorated by GIP receptor agonist D-Ala2GIP in rat model of Huntington's disease.

    Science.gov (United States)

    Verma, Mahip K; Goel, Rajan; Nandakumar, Krishnadas; Nemmani, Kumar V S

    2018-03-22

    Huntington's disease (HD) is an inherited complex progressive neurodegenerative disorder with an established etiopathology linked to neuronal oxidative stress and corticostriatal excitotoxicity. Present study explores the effects of glucose-dependent insulinotropic polypeptide (GIP) receptor agonist on the neurobehavioral sequelae of quinolinic acid-induced phenotype of Huntington's disease in rats. Bilateral administration of quinolinic acid (300 nmol/4 μl) to the rat striatum led to characteristic deficits in, locomotor activity, motor coordination, neuromuscular coordination and short-term episodic memory. Therapeutic treatment for 14 days with a stable and brain penetrating GIP receptor agonist, D-Ala 2 GIP (100 nmol/kg, i.p.), attenuated the neurobehavioral deficits due to quinolinic acid (QA) administration. Protective actions of D-Ala 2 GIP were sensitive to blockade with a GIP receptor antagonist, (Pro 3 )GIP (50 nmol/kg, i.p.), indicating specific involvement of GIP receptor signaling pathway. Stimulation of GIP receptor with D-Ala 2 GIP attenuated lipid peroxidation, evidenced by reduced levels of brain malondialdehyde (MDA), and restoration of reduced glutathione (GSH) levels in brain. Quinolinic acid administration led to significant loss of striatal monoamines, e.g., norepinephrine, epinephrine, serotonin, dopamine, and metabolites, 3,4-Dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-Hydroxyindoleacetic acid (5-HIAA). D-Ala 2 GIP attenuated the QA-induced depletion of striatal monoamines, without affecting the monoamine degradation pathways. Thus, observed effects with D-Ala 2 GIP in the QA-induced Huntington's disease model could be attributable to reduction in lipid peroxidation, restoration of endogenous antioxidants and decreased striatal monoamine levels. These findings together suggest that stimulation of GIP receptor signaling pathway in brain could be a potential therapeutic strategy in the symptomatic management of

  4. Glial cell-derived neurotrophic factor alleviates sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nicotinic acetylcholine receptors in an experimental rat model of neuromyopathy.

    Science.gov (United States)

    Wang, Xin; Min, Su; Xie, Fei; Yang, Jun; Li, Liang; Chen, Jingyuan

    2018-02-05

    Sepsis-induced neuromuscular dysfunction results from up-regulation of the expression of γ- and α7-nicotinic acetylcholine receptors (nAChR). Although glial cell derived neurotrophic factor (GDNF) has been implicated in repairing and supporting neurons, little is known about the effects of GDNF on demyelination of nerves in sepsis. In this study, we tested the hypothesis that GDNF could alleviate sepsis-induced neuromuscular dysfunction by decreasing the expression of γ- and α7-nAChR in an experimental rat model of neuromyopathy. Rats were randomly divided into a sham group and a sepsis group. Levels of inflammatory factors, muscle function, and nicotinic acetylcholine receptors were tested in rats after cecal ligation and puncture (CLP). At 24 h after CLP, GDNF was injected around the sciatic nerve of sepsis rats, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining was used to detect the expression of nAChRs. GDNF and its downstream effector (Erk1/2 and GFR-α), neuregulin-1 (NRG-1) and γ- and α7-nAChR were measured using Western blot analysis. The expression of GDNF reached a minimum at 24 h after CLP. Compared with the sham group, the release of cytokines and the expression of γ- and α7-nAChR were significantly increased in the sepsis group. The administration of GDNF significantly alleviated sepsis-induced neuromuscular dysfunction, as well as reducing the expression of γ- and α7-nAChR. In addition, the expression of Erk1/2, GFR-α, NRG-1 were significantly increased after GDNF treatment. GDNF administration may improve patient outcomes by reducing the demyelination of nerves and the expression of γ- and α7-nAChR. Copyright © 2018. Published by Elsevier Inc.

  5. Projections of increased and decreased dengue incidence under climate change.

    Science.gov (United States)

    Williams, C R; Mincham, G; Faddy, H; Viennet, E; Ritchie, S A; Harley, D

    2016-10-01

    Dengue is the world's most prevalent mosquito-borne disease, with more than 200 million people each year becoming infected. We used a mechanistic virus transmission model to determine whether climate warming would change dengue transmission in Australia. Using two climate models each with two carbon emission scenarios, we calculated future dengue epidemic potential for the period 2046-2064. Using the ECHAM5 model, decreased dengue transmission was predicted under the A2 carbon emission scenario, whereas some increases are likely under the B1 scenario. Dengue epidemic potential may decrease under climate warming due to mosquito breeding sites becoming drier and mosquito survivorship declining. These results contradict most previous studies that use correlative models to show increased dengue transmission under climate warming. Dengue epidemiology is determined by a complex interplay between climatic, human host, and pathogen factors. It is therefore naive to assume a simple relationship between climate and incidence, and incorrect to state that climate warming will uniformly increase dengue transmission, although in general the health impacts of climate change will be negative.

  6. Children with ADHD Symptoms Show Decreased Activity in Ventral Striatum during the Anticipation of Reward, Irrespective of ADHD Diagnosis

    Science.gov (United States)

    van Hulst, Branko M.; de Zeeuw, Patrick; Bos, Dienke J.; Rijks, Yvonne; Neggers, Sebastiaan F. W.; Durston, Sarah

    2017-01-01

    Background: Changes in reward processing are thought to be involved in the etiology of attention-deficit/hyperactivity disorder (ADHD), as well as other developmental disorders. In addition, different forms of therapy for ADHD rely on reinforcement principles. As such, improved understanding of reward processing in ADHD could eventually lead to…

  7. Children with ADHD symptoms show decreased activity in ventral striatum during the anticipation of reward, irrespective of ADHD diagnosis

    NARCIS (Netherlands)

    van Hulst, Branko M.; de Zeeuw, Patrick; Bos, Dienke J.; Rijks, Yvonne; Neggers, Sebastiaan F W; Durston, Sarah

    2017-01-01

    Background: Changes in reward processing are thought to be involved in the etiology of attention-deficit/hyperactivity disorder (ADHD), as well as other developmental disorders. In addition, different forms of therapy for ADHD rely on reinforcement principles. As such, improved understanding of

  8. Nogo-A-deficient Transgenic Rats Show Deficits in Higher Cognitive Functions, Decreased Anxiety, and Altered Circadian Activity Patterns

    Czech Academy of Sciences Publication Activity Database

    Petrásek, Tomáš; Prokopová, Iva; Sládek, Martin; Weissová, Kamila; Vojtěchová, Iveta; Bahník, Štěpán; Zemanová, Anna; Schönig, K.; Berger, S.; Tews, B.; Bartsch, D.; Schwab, M. E.; Sumová, Alena; Stuchlík, Aleš

    2014-01-01

    Roč. 8, Mar 18 (2014), s. 90 ISSN 1662-5153 R&D Projects: GA MZd(CZ) NT13386 Grant - others:Rada Programu interní podpory projektů mezinárodní spolupráce AV ČR(CZ) M200111204; Univerzita Karlova(CZ) 365911 Institutional support: RVO:67985823 Keywords : behavior * Nogo-A * circadian system * learning * memory Subject RIV: FH - Neurology Impact factor: 3.270, year: 2014

  9. Hyperhomocysteinemia decreases bone blood flow

    Directory of Open Access Journals (Sweden)

    Neetu T

    2011-01-01

    Full Text Available Neetu Tyagi*, Thomas P Vacek*, John T Fleming, Jonathan C Vacek, Suresh C TyagiDepartment of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY, USA *These authors have equal authorshipAbstract: Elevated plasma levels of homocysteine (Hcy, known as hyperhomocysteinemia (HHcy, are associated with osteoporosis. A decrease in bone blood flow is a potential cause of compromised bone mechanical properties. Therefore, we hypothesized that HHcy decreases bone blood flow and biomechanical properties. To test this hypothesis, male Sprague–Dawley rats were treated with Hcy (0.67 g/L in drinking water for 8 weeks. Age-matched rats served as controls. At the end of the treatment period, the rats were anesthetized. Blood samples were collected from experimental or control rats. Biochemical turnover markers (body weight, Hcy, vitamin B12, and folate were measured. Systolic blood pressure was measured from the right carotid artery. Tibia blood flow was measured by laser Doppler flow probe. The results indicated that Hcy levels were significantly higher in the Hcy-treated group than in control rats, whereas vitamin B12 levels were lower in the Hcy-treated group compared with control rats. There was no significant difference in folate concentration and blood pressure in Hcy-treated versus control rats. The tibial blood flow index of the control group was significantly higher (0.78 ± 0.09 flow unit compared with the Hcy-treated group (0.51 ± 0.09. The tibial mass was 1.1 ± 0.1 g in the control group and 0.9 ± 0.1 in the Hcy-treated group. The tibia bone density was unchanged in Hcy-treated rats. These results suggest that Hcy causes a reduction in bone blood flow, which contributes to compromised bone biomechanical properties.Keywords: homocysteine, tibia, bone density

  10. Decreasing trend of groundwater in Turkey

    Science.gov (United States)

    Sarachi, S.; Moghim, S.; Famiglietti, J. S.

    2010-12-01

    In these days the increasing demand for water has created problems for availability of its resources. Some recent issues like population growth, global warming and inefficient methods of water consumption, generated the need to find sources of water other than surface water such as ground water. Excess using of groundwater in most parts of the world causes depletion of ground water in those areas. Scientists are trying to find efficient means to quantify these trends. GRACE (Gravity Recovery and Climate Experiment) including two satellites launched in March 2002, is making measurements of the Earth's gravity field which is used to display the change of storage of the water on the Earth. GRACE makes it possible to find the trend of the change of storage all over the world.It can show specific areas in the world that have dramatic decreasing trend of water storage. One of these regions that have been considered in this study is Turkey in western Asia, as one of the countries deeply affected by global warming. Turkey is identified as one of the first places where desertification will start in Europe, according to estimates by the UN Environment Program (UNEP). Turkey has 25 underground water tables and they had a decrease in level of 27 meters in the past 25 years (Turkey water report 2009). In this paper the change of the ground water is evaluated by applying the GRACE storage anomalies and the mass conservation equation that concludes the reduction trend in groundwater. The results clarify that decreasing trend of groundwater is more noticeable during recent years, particularly since 2006. Our results show that in recent years the average decrease in ground water level is 2.5 cm per year and the maximum decrease occurred in May 2007 with the value of about 7.9 cm. KEY WORDS: water resources; Ground water; Turkey; GRACE

  11. Peginterferon Beta-1a Shows Antitumor Activity as a Single Agent and Enhances Efficacy of Standard of Care Cancer Therapeutics in Human Melanoma, Breast, Renal, and Colon Xenograft Models.

    Science.gov (United States)

    Boccia, Antonio; Virata, Cyrus; Lindner, Daniel; English, Nicki; Pathan, Nuzhat; Brickelmaier, Margot; Hu, Xiao; Gardner, Jennifer L; Peng, Liaomin; Wang, Xinzhong; Zhang, Xiamei; Yang, Lu; Perron, Keli; Yco, Grace; Kelly, Rebecca; Gamez, James; Scripps, Thomas; Bennett, Donald; Joseph, Ingrid B; Baker, Darren P

    2017-01-01

    Because of its tumor-suppressive effect, interferon-based therapy has been used for the treatment of melanoma. However, limited data are available regarding the antitumor effects of pegylated interferons, either alone or in combination with approved anticancer drugs. We report that treatment of human WM-266-4 melanoma cells with peginterferon beta-1a induced apoptotic markers. Additionally, peginterferon beta-1a significantly inhibited the growth of human SK-MEL-1, A-375, and WM-266-4 melanoma xenografts established in immunocompromised mice. Peginterferon beta-1a regressed large, established WM-266-4 xenografts in nude mice. Treatment of SK-MEL-1 tumor-bearing mice with a combination of peginterferon beta-1a and the MEK inhibitor PD325901 ((R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide) significantly improved tumor growth inhibition compared with either agent alone. Examination of the antitumor activity of peginterferon beta-1a in combination with approved anticancer drugs in breast and renal carcinomas revealed improved antitumor activity in these preclinical xenograft models, as did the combination of peginterferon beta-1a and bevacizumab in a colon carcinoma xenograft model.

  12. Infection of Atlantic salmon with Moritella viscosus compared to a mechanical tissue injury model in rainbow trout show similar expression patterns of cytokine genes and may be related to triggering of the same signaling pathways

    DEFF Research Database (Denmark)

    Physical damage of tissue and multiple kinds of infections are found to cause inflammatory reactions in mammals. Regardless of the difference between non-pathogenic induced tissue damage and a bacterial infection, many of the same pathways and genes are triggered. To determine if the same...... phenomenon occurs in salmonid fishes, Atlantic salmon (Salmo salar) were infected with the bacteria Moritella viscosus, the causative agent of winter ulcer. The clinical signs showing visible, punctual lesions in the skin make this pathogen unique in order to study local inflammation. Muscle tissue...... mykiss) were subjected to controlled tissue disruption applying sterile needles to skin and muscle tissue to one side of the fish. Samples were taken 4, 8, 24 hours and 7 days post injury from both the injured side and non injured site, internal control. From both studies, the samples were subject...

  13. Decrease in effective electron mobility in the channel of a metal-oxide-semiconductor transistor as the gate length is decreased

    International Nuclear Information System (INIS)

    Frantsuzov, A. A.; Boyarkina, N. I.; Popov, V. P.

    2008-01-01

    Effective electron mobility μ eff in channels of metal-oxide-semiconductor transistors with a gate length L in the range of 3.8 to 0.34 μm was measured; the transistors were formed on wafers of the silicon-oninsulator type. It was found that μ eff decreases as L is decreased. It is shown that this decrease can be accounted for by the effect of series resistances of the source and drain only if it is assumed that there is a rapid increase in these resistances as the gate voltage is decreased. This assumption is difficult to substantiate. A more realistic model is suggested; this model accounts for the observed decrease in μ eff as L is decreased. The model implies that zones with a mobility lower than that in the middle part of the channel originate at the edges of the gate. An analysis shows that, in this case, the plot of the dependence of 1/μ eff on 1/L should be linear, which is exactly what is observed experimentally. The use of this plot makes it possible to determine both the electron mobility μ 0 in the middle part of the channel and the quantity A that characterizes the zones with lowered mobility at the gate’s edges.

  14. Physical activity decreases diverticular complications

    Science.gov (United States)

    Strate, Lisa L.; Liu, Yan L.; Aldoori, Walid H.; Giovannucci, Edward L.

    2011-01-01

    Objectives Little is known about the effect of physical activity on diverticular complications. This study examined prospectively the association between physical activity and diverticular bleeding and diverticulitis. Methods We studied 47,230 US males in the Health Professionals Follow-up Study cohort who were aged 40–75 years and free of diverticular disease, gastrointestinal cancer and inflammatory bowel disease at baseline in 1986. Men reporting newly diagnosed diverticular disease on biennial follow-up questionnaires were sent supplemental questionnaires outlining details of diagnosis and treatment. Physical activity was assessed every 2 years. Men recorded the average time per week spent in 8 recreational activities, and flights of stairs climbed per day. Cox proportional hazards regression was used to calculate relative risks. Results During 18 years of follow-up, 800 cases of diverticulitis, and 383 cases of diverticular bleeding were identified. Total cumulative physical activity was associated with a decreased risk of diverticulitis and diverticular bleeding. After adjustment for potential confounders, the relative risk (RR) for men in the highest quintile of total activity (≥57.4 Metabolic Equivalent (MET h/wk) was 0.75 (95% CI 0.58–0.95) for diverticulitis, and 0.54 (95% CI, 0.38–0.77) for bleeding when compared to men in the lowest quintile (≤8.2 MET h/wk). Vigorous activity was inversely related to diverticulitis (multivariable RR 0.66, 95% CI, 0.51–0.86), and bleeding (multivariable RR 0.61, 95% CI, 0.41 – 0.90) in a high vs. low comparison, whereas non-vigorous activity was not. These results were similar for recent (simple updated) and baseline activity. Conclusions Data from this large prospective cohort suggest that physical activity lowers the risk of diverticulitis and diverticular bleeding. Vigorous activity appears to account for this association. PMID:19367267

  15. Are urban noise pollution levels decreasing?

    Science.gov (United States)

    Arana, M

    2010-04-01

    The majority of acoustic impact studies developed over the last 50 years have used a similar acoustic parameter (L(eq), L(dn)) but the noise mapping methodology has been very uneven. The selection of the measurement points, the measurement periods, or the evaluation indices have not followed a unique criterion. Therefore, it is not possible to compare the sound pollution levels between different cities from those studies, at least in a rigorous sense. Even more, different studies carried out in the same city by different researchers during different years and using different methodologies are not conclusive whether the acoustic pollution increases or decreases. The present paper shows results, with statistical significance, about the evolution of the acoustic pollution obtained for two Spanish cities, Pamplona and Madrid. In both cases, it can be concluded that noise pollution decreases over time (P<0.01).

  16. Induction of T regulatory cells by the superagonistic anti-CD28 antibody D665 leads to decreased pathogenic IgG autoantibodies against desmoglein 3 in a HLA-transgenic mouse model of pemphigus vulgaris.

    Science.gov (United States)

    Schmidt, Thomas; Willenborg, Sebastian; Hünig, Thomas; Deeg, Cornelia A; Sonderstrup, Grete; Hertl, Michael; Eming, Rüdiger

    2016-04-01

    Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune disease of the skin and mucous membranes. Its pathogenesis is based on IgG autoantibodies that target the desmosomal cadherins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1) and induce intra-epidermal loss of adhesion. Although the PV pathogenesis is well-understood, therapeutic options are still limited to immunosuppressive drugs, particularly corticosteroids, which are associated with significant side effects. Dsg3-reactive T regulatory cells (Treg) have been previously identified in PV and healthy carriers of PV-associated HLA class II alleles. Ex vivo, Dsg3-specific Treg cells down-regulated the activation of pathogenic Dsg3-specific T-helper (Th) 2 cells. In this study, in a HLA-DRB1*04:02 transgenic mouse model of PV, peripheral Treg cells were modulated by the use of Treg-depleting or expanding monoclonal antibodies, respectively. Our findings show that, in vivo, although not statistically significant, Treg cells exert a clear down-regulatory effect on the Dsg3-driven T-cell response and, accordingly, the formation of Dsg3-specific IgG antibodies. These observations confirm the powerful immune regulatory functions of Treg cells and identify Treg cells as potential therapeutic modulators in PV. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Aerosol influence on the recent decadal decrease in tropical cyclone activity over the western North Pacific

    Science.gov (United States)

    Takahashi, C.; Watanabe, M.; Mori, M.

    2017-12-01

    Over the past two decades, the number of Tropical cyclone (TCs) has decreased markedly in the southeastern part of the western North Pacific (WNP) as a component of the interdecadal variation. This decrease has partially been explained by an internal low-frequency variability of sea surface temperature in the Pacific, but influences of external forcing remain unclear. We show that past changes in sulphate aerosol emissions significantly contributed to the resent observed decreasing trends in TC genesis frequency in the southeastern WNP, using multiple simulations by a global climate model. This mechanism and near-future projection of WNP TC genesis frequency will be presented.

  18. Obesity Decreases Perioperative Tissue Oxygenation

    Science.gov (United States)

    Kabon, Barbara; Nagele, Angelika; Reddy, Dayakar; Eagon, Chris; Fleshman, James W.; Sessler, Daniel I.; Kurz, Andrea

    2005-01-01

    Background: Obesity is an important risk factor for surgical site infections. The incidence of surgical wound infections is directly related to tissue perfusion and oxygenation. Fat tissue mass expands without a concomitant increase in blood flow per cell, which might result in a relative hypoperfusion with decreased tissue oxygenation. Consequently, we tested the hypotheses that perioperative tissue oxygen tension is reduced in obese surgical patients. Furthermore, we compared the effect of supplemental oxygen administration on tissue oxygenation in obese and non-obese patients. Methods: Forty-six patients undergoing major abdominal surgery were assigned to one of two groups according to their body mass index (BMI): BMI < 30 kg/m2 (non-obese) and BMI ≥ 30 kg/m2 (obese). Intraoperative oxygen administration was adjusted to arterial oxygen tensions of ≈150 mmHg and ≈300 mmHg in random order. Anesthesia technique and perioperative fluid management were standardized. Subcutaneous tissue oxygen tension was measured with a polarographic electrode positioned within a subcutaneous tonometer in the lateral upper arm during surgery, in the recovery room, and on the first postoperative day. Postoperative tissue oxygen was also measured adjacent to the wound. Data were compared with unpaired two tailed t-tests and Wilcoxon rank-sum tests; P < 0.05 was considered statistically significant. Results: Intraoperative subcutaneous tissue oxygen tension was significantly less in the obese patients at baseline (36 vs. 57 mmHg, P = 0.002) and with supplemental oxygen administration (47 vs. 76 mmHg, P = 0.014). Immediate postoperative tissue oxygen tension was also significantly less in subcutaneous tissue of the upper arm (43 vs. 54 mmHg, P = 0.011) as well as near the incision (42 vs. 62 mmHg, P = 0.012) in obese patients. In contrast, tissue oxygen tension was comparable in each group on the first postoperative morning. Conclusion: Wound and tissue hypoxia were common in obese

  19. Decreased Emotional Perception in Obesity.

    Science.gov (United States)

    Giel, Katrin Elisabeth; Hartmann, Armin; Zeeck, Almut; Jux, Anna; Vuck, Alexander; Gierthmuehlen, Petra C Guess; Wetzler-Burmeister, Edda; Sandholz, Angelika; Marjanovic, Goran; Joos, Andreas

    2016-07-01

    There is hardly any empirical evidence on emotion processing by controlled studies in obesity. Participants rated their emotions in response to visual emotional stimuli from the International Affective Picture System. Study 1 compared obese women with normal-weight controls and women with eating disorders. Study 2 compared obese men with normal-weight controls. Obese women had reduced emotional intensity scores for all basic emotions and the mixed emotion sadness-fear. Obese men had reduced scores for all emotions except happiness and disgust; anger showed a trend towards significance. The results were mainly based on ratings from non-depressed obese individuals. Obese men and women scored significantly lower on most basic and mixed emotions. Non-depressed obese subjects seem particularly affected. These new findings must be validated by further study, and longitudinal evaluation after weight loss, e.g. by bariatric surgery, will be of interest. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

  20. Decreasing luminescence lifetime of evaporating phosphorescent droplets

    Science.gov (United States)

    van der Voort, D. D.; Dam, N. J.; Sweep, A. M.; Kunnen, R. P. J.; van Heijst, G. J. F.; Clercx, H. J. H.; van de Water, W.

    2016-12-01

    Laser-induced phosphorescence has been used extensively to study spray dynamics. It is important to understand the influence of droplet evaporation in the interpretation of such measurements, as it increases luminescence quenching. By suspending a single evaporating n-heptane droplet in an acoustic levitator, the properties of lanthanide-complex europium-thenoyltrifluoroacetone-trioctylphosphine oxide (Eu-TTA-TOPO) phosphorescence are determined through high-speed imaging. A decrease was found in the measured phosphorescence decay coefficient (780 → 200 μs) with decreasing droplet volumes (10-9 → 10-11 m3) corresponding to increasing concentrations (10-4 → 10-2 M). This decrease continues up to the point of shell-formation at supersaturated concentrations. The diminished luminescence is shown not to be attributable to triplet-triplet annihilation, quenching between excited triplet-state molecules. Instead, the pure exponential decays found in the measurements show that a non-phosphorescent quencher, such as free TTA/TOPO, can be attributable to this decay. The concentration dependence of the phosphorescence lifetime can therefore be used as a diagnostic of evaporation in sprays.

  1. Salt as a mitigation option for decreasing nitrogen leaching losses from grazed pastures.

    Science.gov (United States)

    Ledgard, Stewart F; Welten, Brendon; Betteridge, Keith

    2015-12-01

    The main source of nitrogen (N) leaching from grazed pastures is animal urine with a high N deposition rate (i.e. per urine patch), particularly between late summer and early winter. Salt is a potential mitigation option as a diuretic to induce greater drinking-water intake, increase urination frequency, decrease urine N concentration and urine N deposition rate, and thereby potentially decrease N leaching. This hypothesis was tested in three phases: a cattle metabolism stall study to examine effects of salt supplementation rate on water consumption, urination frequency and urine N concentration; a grazing trial to assess effects of salt (150 g per heifer per day) on urination frequency; and a lysimeter study on effects of urine N rate on N leaching. Salt supplementation increased cattle water intake. Urination frequency increased by up to 69%, with a similar decrease in urine N deposition rate and no change in individual urination volume. Under field grazing, sensors showed increased urination frequency by 17%. Lysimeter studies showed a proportionally greater decrease in N leaching with decreased urine N rate. Modelling revealed that this could decrease per-hectare N leaching by 10-22%. Salt supplementation increases cattle water intake and urination frequency, resulting in a lower urine N deposition rate and proportionally greater decrease in urine N leaching. Strategic salt supplementation in autumn/early winter with feed is a practical mitigation option to decrease N leaching in grazed pastures. © 2015 Society of Chemical Industry.

  2. Significant Aerosol Influence on the Recent Decadal Decrease in Tropical Cyclone Activity Over the Western North Pacific

    Science.gov (United States)

    Takahashi, Chiharu; Watanabe, Masahiro; Mori, Masato

    2017-09-01

    Over the past two decades, the number of tropical cyclones (TCs) has decreased markedly in the southeastern part of the western North Pacific (WNP) as a component of the interdecadal variation. This decrease has partially been explained by an internal low-frequency variability of sea surface temperature (SST) in the Pacific, but influences of external forcing remain unclear. Here we show that past changes in sulfate aerosol emissions contributed approximately 60% of the observed decreasing trends in TC genesis frequency in the southeastern WNP for 1992-2011, using multiple simulations by a global climate model. This decrease was mainly attributed to the increased vertical wind shear and decreased low-level vorticity, associated with a trans-basin multidecadal SST change driven by aerosol forcing. The near-future projection shows that the aerosol forcing still has some potential influence on decadal TC change, but the projected decreasing frequency is mainly due to increasing greenhouse gases forcing.

  3. Dispersal-Based Microbial Community Assembly Decreases Biogeochemical Function

    Energy Technology Data Exchange (ETDEWEB)

    Graham, Emily B.; Stegen, James C.

    2017-11-01

    Much research has focused on improving ecosystem models by incorporating microbial regulation of biogeochemistry. However, models still struggle to predict biogeochemical function in future scenarios linked to accelerating global environmental change. Ecological mechanisms may influence the relationship between microbial communities and biogeochemistry, and here, we show that stochastic dispersal processes (e.g., wind-driven or hydrologic transport) can suppress biogeochemical function. Microbial communities are assembled by deterministic (e.g., selection) and stochastic (e.g., dispersal) processes, and the balance of these two processes is hypothesized to influence how microbial communities correspond to biogeochemical function. We explore the theoretical basis for this hypothesis and use ecological simulation models to demonstrate potential influences of assembly processes on ecosystem function. We assemble ‘receiving’ communities under different levels of dispersal from a source community (selection-only, moderate dispersal, and homogenizing dispersal). We then calculate the degree to which assembled individuals are adapted to their environment and relate the level of adaptation to biogeochemical function. We also use ecological null models to further link assembly the level of deterministic assembly to function. We find that dispersal can decrease biogeochemical function by increasing the proportion of maladapted taxa, outweighing selection. The niche breadth of taxa is also a key determinant of biogeochemical function, suggesting a tradeoff between the function of generalist and specialist species. Together, our results highlight the importance of considering ecological assembly processes to reduce uncertainty in predictions of biogeochemical cycles under future environmental scenarios.

  4. Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

    Directory of Open Access Journals (Sweden)

    Dexter L. Lee

    2011-01-01

    Full Text Available Peroxisome proliferator-activated receptor-alpha (PPAR-α activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6. Fenofibrate also induces cytochrome P450 4A (CYP4A and increases 20-hydroxyeicosatetraenoic acid (20-HETE production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2, while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically. Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23 and soluble expoxide hydrolase (sEH expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.

  5. Lymphedema treatment decreases pain intensity in lipedema.

    Science.gov (United States)

    Szolnoky, G; Varga, E; Varga, M; Tuczai, M; Dósa-Rácz, E; Kemény, L

    2011-12-01

    Lipedema is a disproportional obesity featuring light pressure-induced or spontaneous pain. On the basis of our clinical observations, lymphedema therapy, as practiced in our clinic, reduces the perception of pain beyond leg volume reduction. We therefore aimed to measure pain intensity prior and subsequent to treatment. 38 women with lipedema were enrolled in the study with 19 patients undergoing treatment and 19 serving as the control group using exclusively moisturizers. Treatment consisted of once daily manual lymph drainage (MLD), intermittent pneumatic compression (IPC), and multilayered short-stretch bandaging performed throughout a 5-day-course. Pain was evaluated with a 10-item questionnaire, a pain rating scale (PRS), and the Wong-Baker Faces scale. Treatment resulted in a significant reduction of pain with a decrease in mean scores of all three measures. In the control group, only PRS showed significant decrease. Our study results indicate that this treatment regimen not only reduces leg volume and capillary fragility, but also improves pain intensity in patients with lipedema.

  6. Statins Decrease Oxidative Stress and ICD Therapies

    Directory of Open Access Journals (Sweden)

    Heather L. Bloom

    2010-01-01

    Full Text Available Recent studies demonstrate that statins decrease ventricular arrhythmias in internal cardioverter defibrillator (ICD patients. The mechanism is unknown, but evidence links increased inflammatory and oxidative states with increased arrhythmias. We hypothesized that statin use decreases oxidation. Methods. 304 subjects with ICDs were surveyed for ventricular arrhythmia. Blood was analyzed for derivatives of reactive oxygen species (DROMs and interleukin-6 (IL-6. Results. Subjects included 252 (83% men, 58% on statins, 20% had ventricular arrhythmias. Average age was 63 years and ejection fraction (EF 20%. ICD implant duration was 29 ± 27 months. Use of statins correlated with lower ICD events (r=0.12, P=.02. Subjects on statins had lower hsCRP (5.2 versus 6.3; P=.05 and DROM levels (373 versus 397; P=.03. Other factors, including IL-6 and EF did not differ between statin and nonstatin use, nor did beta-blocker or antiarrhythmic use. Multivariate cross-correlation analysis demonstrated that DROMs, statins, IL-6 and EF were strongly associated with ICD events. Multivariate regression shows DROMs to be the dominant predictor. Conclusion. ICD event rate correlates with DROMs, a measure of lipid peroxides. Use of statins is associated with reduced DROMs and fewer ICD events, suggesting that statins exert their effect through reducing oxidation.

  7. Late-night talk show v USA

    OpenAIRE

    Halamásek, Šimon

    2013-01-01

    This thesis focuses on the history of talk show in USA with emphasis on its specific form, which is late-night talk show. The first chapter focuses on the creation of new television networks and the overall state of american broadcasting during the first era of the television talk show format. The thesis briefly describes radio broadcasting which served not only as an important source of inspiration for television but also as a starting platform for most talk show hosts. Next chapter theoreti...

  8. Acculturation, Cultivation, and Daytime TV Talk Shows.

    Science.gov (United States)

    Woo, Hyung-Jin; Dominick, Joseph R.

    2003-01-01

    Explores the cultivation phenomenon among international college students in the United States by examining the connection between levels of acculturation, daytime TV talk show viewing, and beliefs about social reality. Finds that students who scored low on acculturation and watched a great deal of daytime talk shows had a more negative perception…

  9. Effects of Talk Show Viewing on Adolescents.

    Science.gov (United States)

    Davis, Stacy; Mares, Marie-Louise

    1998-01-01

    Investigates the effects of talk-show viewing on high-school students' social-reality beliefs. Supports the hypothesis that viewers overestimate the frequency of deviant behaviors; does not find support for the hypothesis that viewers become desensitized to the suffering of others; and finds that talk-show viewing was positively related, among…

  10. An intervention to decrease cancer fatalism among rural elders.

    Science.gov (United States)

    Powe, B D; Weinrich, S

    1999-04-01

    To evaluate the effectiveness of a video intervention in decreasing cancer fatalism, increasing knowledge of colorectal cancer, and increasing participation in fecal-occult blood testing (FOBT). Repeated measures, pretest/post-test. Senior citizen centers in a rural southern state. Individuals were selected and assigned to the study group based on the center they attended. Centers were selected and assigned randomly to an intervention (n = 42) or control (n = 28) group. The age of the participants ranged from 52-92 years (X = 75). Pretest measures included the Powe Fatalism inventory, the Colorectal Cancer Knowledge Questionnaire, and the Demographic Data Questionnaire. The intervention group viewed the Medical University of South Carolina's video Telling the Story ... To Live is God's Will, and the control group viewed the American Cancer Society (ACS) video Colorectal Cancer: The Cancer No One Talks About. Hemoccult II kits were distributed to both groups at no cost. Post-test data were collected using the Powe Fatalism Inventory and the Colorectal Cancer Knowledge Questionnaire. Cancer fatalism, knowledge of colorectal cancer, and participation in FOBT. People who viewed the intervention video had a greater decrease in cancer fatalism scores and a greater increase in knowledge of colorectal cancer scores than the control group. Both groups had greater than 60% participation in FOBT. Telling the Story ... To Live is God's Will is an effective, self-contained, cost-effective intervention to decrease cancer fatalism and increase knowledge of colorectal cancer. The video was as effective as the ACS video on colorectal cancer in increasing participation in FOBT among rural elders. But, because Telling the Story ... To Live is God's Will also decreases cancer fatalism and increases knowledge, the potential exists for the increased screening behaviors to be maintained over time. Showing the video in waiting areas of community health centers to facilitate the discussion

  11. Career development at London Vet Show.

    Science.gov (United States)

    2016-09-03

    Are you considering a career change? Perhaps you want help to develop within your current role? Either way, you will find a relevant session in the BVA Career Development stream at the London Vet Show in November. British Veterinary Association.

  12. On the predictability of extremes: does the butterfly effect ever decrease?

    Science.gov (United States)

    Sterk, Alef; Stephenson, David; Holland, Mark; Mylne, Ken

    2016-04-01

    We investigate whether predictability always decreases for more extreme events. Predictability is measured by the Mean Squared Error (MSE), which is estimated from the difference of pairs of ensemble forecasts, conditioned on one of the forecast variables (the "pseudo-observation") exceeding a threshold. Using an exchangeable linear regression model for pairs of forecast variables, we show that the MSE can be decomposed into the sum of three terms: a threshold-independent constant, a mean term that always increases with threshold, and a variance term that can either increase, decrease, or stay constant with threshold. Using the Generalised Pareto Distribution to model wind speed excesses over a threshold, we show that MSE always increases with threshold at sufficiently high threshold. However, MSE can be a decreasing function of threshold at lower thresholds but only if the forecasts have finite upper bounds. The methodology is illustrated by application to daily wind speed forecasts for London made using the 24 member Met Office Global and Regional Ensemble Prediction System from 1 January 2009 to 31 May 2011. For this example, the mean term increases faster than the variance term decreases with increasing threshold, and so predictability decreases for more extreme events.

  13. Anti-vascular endothelial growth factor treatment decreases bladder pain in cyclophosphamide cystitis: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network animal model study.

    Science.gov (United States)

    Lai, H Henry; Shen, Baixin; Vijairania, Pooja; Zhang, Xiaowei; Vogt, Sherri K; Gereau, Robert W

    2017-10-01

    To investigate whether treatment with anti-vascular endothelial growth factor (VEGF)-neutralizing antibodies can reduce pain and voiding dysfunction in the cyclophosphamide (CYP) cystitis model of bladder pain in mice. Adult female mice received anti-VEGF-neutralizing antibodies (10 mg/kg i.p. B20-4.1.1 VEGF mAb) or saline (control) pre-treatment, followed by CYP (150 mg/kg i.p.) to induce acute cystitis. Pelvic nociceptive responses were assessed by applying von Frey filaments to the pelvic area. Spontaneous micturition was assessed using the void spot assay. Systemic anti-VEGF-neutralizing antibody treatment significantly reduced the pelvic nociceptive response to CYP cystitis compared with control (saline). In the anti-VEGF pre-treatment group, there was a significant increase in pelvic hypersensitivity, measured by the area under the curve (AUC) using von Frey filaments at 5 h post-CYP administration (P = 0.004); however, by 48 h and 96 h post-CYP administration, pelvic hypersensitivity had reduced by 54% and 47%, respectively, compared with the 5 h post-CYP administration time point, and were no longer significantly different from baseline (P = 0.22 and 0.17, respectively). There was no difference in urinary frequency and mean voided volume between the two pre-treatment groups. Systemic blockade of VEGF signalling with anti-VEGF-neutralizing antibodies was effective in reducing pelvic/bladder pain in the CYP cystitis model of bladder pain. Our data support the further investigation of the use of anti-VEGF antibodies to manage bladder pain or visceral pain. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  14. Near infra-red photoimmunotherapy with anti-CEA-IR700 results in extensive tumor lysis and a significant decrease in tumor burden in orthotopic mouse models of pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Ali A Maawy

    Full Text Available Photoimmunotherapy (PIT of cancer utilizes tumor-specific monoclonal antibodies conjugated to a photosensitizer phthalocyanine dye IR700 which becomes cytotoxic upon irradiation with near infrared light. In this study, we aimed to evaluate the efficacy of PIT on human pancreatic cancer cells in vitro and in vivo in an orthotopic nude mouse model. The binding capacity of anti-CEA antibody to BxPC-3 human pancreatic cancer cells was determined by FACS analysis. An in vitro cytotoxicity assay was used to determine cell death following treatment with PIT. For in vivo determination of PIT efficacy, nude mice were orthotopically implanted with BxPC-3 pancreatic tumors expressing green fluorescent protein (GFP. After tumor engraftment, the mice were divided into two groups: (1 treatment with anti-CEA-IR700 + 690 nm laser and (2 treatment with 690 nm laser only. Anti-CEA-IR700 (100 μg was administered to group (1 via tail vein injection 24 hours prior to therapy. Tumors were then surgically exposed and treated with phototherapy at an intensity of 150 mW/cm2 for 30 minutes. Whole body imaging was done subsequently for 5 weeks using an OV-100 small animal imaging system. Anti-CEA-IR700 antibody bound to the BxPC3 cells to a high degree as shown by FACS analysis. Anti-CEA-IR700 caused extensive cancer cell killing after light activation compared to control cells in cytotoxicity assays. In the orthotopic models of pancreatic cancer, the anti-CEA-IR700 group had significantly smaller tumors than the control after 5 weeks (p<0.001. There was no significant difference in the body weights of mice in the anti-CEA-IR700 and control groups indicating that PIT was well tolerated by the mice.

  15. Online Italian fandoms of American TV shows

    Directory of Open Access Journals (Sweden)

    Eleonora Benecchi

    2015-06-01

    Full Text Available The Internet has changed media fandom in two main ways: it helps fans connect with each other despite physical distance, leading to the formation of international fan communities; and it helps fans connect with the creators of the TV show, deepening the relationship between TV producers and international fandoms. To assess whether Italian fan communities active online are indeed part of transnational online communities and whether the Internet has actually altered their relationship with the creators of the original text they are devoted to, qualitative analysis and narrative interviews of 26 Italian fans of American TV shows were conducted to explore the fan-producer relationship. Results indicated that the online Italian fans surveyed preferred to stay local, rather than using geography-leveling online tools. Further, the sampled Italian fans' relationships with the show runners were mediated or even absent.

  16. 2008 LHC Open Days Physics: the show

    CERN Multimedia

    2008-01-01

    A host of events and activities await visitors to the LHC Open Days on 5 and 6 April. A highlight will be the physics shows funded by the European Physical Society (EPS), which are set to surprise and challenge children and adults alike! School children use their experience of riding a bicycle to understand how planets move around the sun (Copyright : Circus Naturally) Participating in the Circus Naturally show could leave a strange taste in your mouth! (Copyright : Circus Naturally) The Rino Foundation’s experiments with liquid nitrogen can be pretty exciting! (Copyright: The Rino Foundation)What does a bicycle have in common with the solar system? Have you ever tried to weigh air or visualise sound? Ever heard of a vacuum bazooka? If you want to discover the answers to these questions and more then come to the Physics Shows taking place at the CERN O...

  17. CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Piekarz Andrew D

    2012-07-01

    Full Text Available Abstract Background The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2 to bind to N-type voltage-activated calcium channels (CaV2.2 [Brittain et al. Nature Medicine 17:822–829 (2011]. Results and discussion Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K that bound with greater affinity to Ca2+ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP release compared to vehicle control. Conclusions Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3. Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against a particular subset of voltage-gated calcium channels resulting in a multipharmacology of

  18. A Talk Show from the Past.

    Science.gov (United States)

    Gallagher, Arlene F.

    1991-01-01

    Describes a two-day activity in which elementary students examine voting rights, the right to assemble, and women's suffrage. Explains the game, "Assemble, Reassemble," and a student-produced talk show with five students playing the roles of leaders of the women's suffrage movement. Profiles Elizabeth Cady Stanton, Lucretia Mott, Susan…

  19. See you at London Vet Show.

    Science.gov (United States)

    2016-11-05

    London Vet Show is fast approaching: it takes place from November 17 to 18 and is being held at ExCeL London for the first time. Zoe Davies, marketing manager, highlights some of what BVA is offering at the event. British Veterinary Association.

  20. Show Them You Really Want the Job

    Science.gov (United States)

    Perlmutter, David D.

    2012-01-01

    Showing that one really "wants" the job entails more than just really wanting the job. An interview is part Broadway casting call, part intellectual dating game, part personality test, and part, well, job interview. When there are 300 applicants for a position, many of them will "fit" the required (and even the preferred) skills listed in the job…

  1. Identification of genes showing differential expression profile

    Indian Academy of Sciences (India)

    Suppression subtractive hybridization was used to identify genes showing differential expression profile associated withgrowth rate in skeletal muscle tissue of Landrace weanling pig. Two subtracted cDNA populations were generated from mus-culus longissimus muscle tissues of selected pigs with extreme expected ...

  2. Mike Pentz showing visitors around CESAR

    CERN Multimedia

    CERN PhotoLab

    1964-01-01

    Mike Pentz, leader of the CESAR Group, shows visitors around the 2 MeV electron storage ring. Here they are in the vault of the injector (a 2 MV van de Graaff generator), next to the 2 beam lines, one leading to the ring, the other to the spectrometer.

  3. Identification of genes showing differential expression profile ...

    Indian Academy of Sciences (India)

    Abstract. Suppression subtractive hybridization was used to identify genes showing differential expression profile associated with growth rate in skeletal muscle tissue of Landrace weanling pig. Two subtracted cDNA populations were generated from mus- culus longissimus muscle tissues of selected pigs with extreme ...

  4. Laser entertainment and light shows in education

    Science.gov (United States)

    Sabaratnam, Andrew T.; Symons, Charles

    2002-05-01

    Laser shows and beam effects have been a source of entertainment since its first public performance May 9, 1969, at Mills College in Oakland, California. Since 1997, the Photonics Center, NgeeAnn Polytechnic, Singapore, has been using laser shows as a teaching tool. Students are able to exhibit their creative skills and learn at the same time how lasers are used in the entertainment industry. Students will acquire a number of skills including handling three- phase power supply, operation of cooling system, and laser alignment. Students also acquire an appreciation of the arts, learning about shapes and contours as they develop graphics for the shows. After holography, laser show animation provides a combination of the arts and technology. This paper aims to briefly describe how a krypton-argon laser, galvanometer scanners, a polychromatic acousto-optic modulator and related electronics are put together to develop a laser projector. The paper also describes how students are trained to make their own laser animation and beam effects with music, and at the same time have an appreciation of the operation of a Class IV laser and the handling of optical components.

  5. The Last Great American Picture Show

    NARCIS (Netherlands)

    Elsaesser, Thomas; King, Noel; Horwath, Alexander

    2004-01-01

    The Last Great American Picture Show brings together essays by scholars and writers who chart the changing evaluations of the American cinema of the 1970s, sometimes referred to as the decade of the lost generation, but now more and more recognized as the first New Hollywood, without which the

  6. The British Show in Australia, 1985

    Directory of Open Access Journals (Sweden)

    Anthony Bond

    2016-07-01

    Full Text Available In 1984–85, The British Show, an exhibition largely made up of New British Sculpture, was curated for Australia and New Zealand. This essay discusses the context and effects of the exhibition on art in Australia. It also seeks to define the sources of originality and innovation of the artists included.

  7. Identification of genes showing differential expression profile ...

    Indian Academy of Sciences (India)

    Suppression subtractive hybridization was used to identify genes showing differential expression profile associated withgrowth rate in skeletal muscle tissue of Landrace weanling pig. Two subtracted cDNA populations were generated from mus-culus longissimus muscle tissues of selected pigs with extreme expected ...

  8. 'Show me the money': energy projects financing

    International Nuclear Information System (INIS)

    Ball, C.

    2006-01-01

    This paper describes the business and business model of Corpfinance International (CFI). CFI consists of three businesses: structured financing, private equity/corporate finance advisory and securitization. Furthermore, CFI is the lender of record acting on behalf of and based on strong relationship with various Life Insurance Companies, Pension Funds and International Banks. CFI has in-house expertise in support of its lending advisory and investing activities

  9. High-frequency parameters of magnetic films showing magnetization dispersion

    International Nuclear Information System (INIS)

    Sidorenkov, V.V.; Zimin, A.B.; Kornev, Yu.V.

    1988-01-01

    Magnetization dispersion leads to skewed resonance curves shifted towards higher magnetizing fields, together with considerable reduction in the resonant absorption, while the FMR line width is considerably increased. These effects increase considerably with frequency, in contrast to films showing magnetic-anisotropy dispersion, where they decrease. It is concluded that there may be anomalies in the frequency dependence of the resonance parameters for polycrystalline magnetic films

  10. Computer Slide Shows: A Trap for Bad Teaching

    Science.gov (United States)

    Klemm, W. R.

    2007-01-01

    Slide shows presented with software such as PowerPoint or WordPerfect Presentations can trap instructors into bad teaching practices. Research on memory suggests that slide-show instruction can actually be less effective than traditional lecturing when the teacher uses a blackboard or overhead projector. The author proposes a model of classroom…

  11. La mujer, en los talk shows

    Directory of Open Access Journals (Sweden)

    Antrop. José Gamboa Cetina

    2001-01-01

    Full Text Available Dentro de los medios de comunicación, uno de los que más ha impactado a la población latinoamericana ha sido la televisión, y en la barra programática de las televisoras ha surgido un tipo de programas denominados talk shows. En los últimos meses, la sociedad mexicana ha vivido el "boom" de los talk shows, que en poco tiempo han saturado la barra de la programación vespertina de las dos principales empresas televisivas de la república mexicana. Este fenómeno puede estudiarse desde diversas perspectivas. Sin embargo, por motivos de espacio, en esta ocasión analizaremos su impacto en las mujeres, desde diferentes dimensiones.

  12. Glucocorticoids decrease Treg cell numbers in lungs of allergic mice.

    Science.gov (United States)

    Olsen, P C; Kitoko, J Z; Ferreira, T P; de-Azevedo, C T; Arantes, A C; Martins, Μ A

    2015-01-15

    Glucocorticoids have been the hallmark anti-inflammatory drug used to treat asthma. It has been shown that glucocorticoids ameliorate asthma by increasing numbers and activity of Tregs, in contrast recent data show that glucocorticoid might have an opposite effect on Treg cells from normal mice. Since Tregs are target cells that act on the resolution of asthma, the aim of this study was to elucidate the effect of glucocorticoid treatment on lung Tregs in mouse models of asthma. Allergen challenged mice were treated with either oral dexamethasone or nebulized budesonide. Broncoalveolar lavage and airway hyperresponsiveness were evaluated after allergenic challenge. Lung, thymic and lymph node cells were phenotyped on Treg through flow cytometry. Lung cytokine secretion was detected by ELISA. Although dexamethasone inhibited airway inflammation and hyperresponsiveness, improving resolution, we have found that both dexamethasone and budesonide induce a reduction of Treg numbers on lungs and lymphoid organs of allergen challenged mice. The reduction of lung Treg levels was independent of mice strain or type of allergen challenge. Our study also indicates that both glucocorticoids do not increase Treg activity through production of IL-10. Glucocorticoid systemic or localized treatment induced thymic atrophy. Taken together, our results demonstrate that glucocorticoids decrease Treg numbers and activity in different asthma mouse models, probably by reducing thymic production of T cells. Therefore, it is possible that glucocorticoids do not have beneficial effects on lung populations of Treg cells from asthmatic patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Hyper-arousal decreases human visual thresholds.

    Directory of Open Access Journals (Sweden)

    Adam J Woods

    Full Text Available Arousal has long been known to influence behavior and serves as an underlying component of cognition and consciousness. However, the consequences of hyper-arousal for visual perception remain unclear. The present study evaluates the impact of hyper-arousal on two aspects of visual sensitivity: visual stereoacuity and contrast thresholds. Sixty-eight participants participated in two experiments. Thirty-four participants were randomly divided into two groups in each experiment: Arousal Stimulation or Sham Control. The Arousal Stimulation group underwent a 50-second cold pressor stimulation (immersing the foot in 0-2° C water, a technique known to increase arousal. In contrast, the Sham Control group immersed their foot in room temperature water. Stereoacuity thresholds (Experiment 1 and contrast thresholds (Experiment 2 were measured before and after stimulation. The Arousal Stimulation groups demonstrated significantly lower stereoacuity and contrast thresholds following cold pressor stimulation, whereas the Sham Control groups showed no difference in thresholds. These results provide the first evidence that hyper-arousal from sensory stimulation can lower visual thresholds. Hyper-arousal's ability to decrease visual thresholds has important implications for survival, sports, and everyday life.

  14. COGNITIVE THERAPY DECREASE THE LEVEL OF DEPRESSION

    Directory of Open Access Journals (Sweden)

    Ah. Yusuf

    2017-07-01

    Full Text Available Introduction: Aging is a natural process in individuals. Most of the elderly have problems in dealing with this natural process. Lost of occupation, friends and loneliness may result in depression in this age group. Cognitive therapy changes pessimistic idea, unrealistic hopes and excessive self evaluation may result and justify depression. Cognitive therapy may help elderly to recognize the problem in life, to develop positive objective of life and to create more positive personality. The aimed of this study was to analyze the effect of cognitive therapy to reduce the level of depression. Method: This study was used a pre experimental pre post test design. Sample were 10 elderly people who met to the inclusion criteria. The independent variable was cognitive therapy and dependent variable was the level of depression in elderly. Data were collected by using Geriatric Depression Scale (GDS 15, then analyzed by using Wilcoxon Signed Rank Test with significance levelα≤0.05. Result: The result showed that cognitive therapy has an effect on reducing depression with significance level p=0.005. Discussion: It can be concluded that cognitive therapy was effective in reducing depression level in elderly. Further studies are recommended to analyze the effect of cognitive therapy on decreasing anxiety in elderly by measuring cathecolamin.

  15. Decreased lymphocyte dopamine transporter in romantic lovers.

    Science.gov (United States)

    Marazziti, Donatella; Baroni, Stefano; Giannaccini, Gino; Piccinni, Armando; Mucci, Federico; Catena-Dell'Osso, Mario; Rutigliano, Grazia; Massimetti, Gabriele; Dell'Osso, Liliana

    2017-06-01

    The role of dopamine (DA) in romantic love is suggested by different evidence and is supported by the findings of some brain imaging studies. The DA transporter (DAT) is a key structure in regulating the concentration of the neurotransmitter in the synaptic cleft. Given the presence of DAT in blood cells, the present study aimed to explore it in resting lymphocytes of 30 healthy subjects of both sexes in the early stage of romantic love (no longer than 6 months), as compared with 30 subjects involved in a long-lasting relationship. All subjects had no physical or psychiatric illness. The DAT was measured by means of the [3H]-WIN 35,428 binding and the [3H]-DA reuptake to resting lymphocytes membranes. Romantic love was assessed by a specific questionnaire developed by us. The results showed that the subjects in the early phase of romantic love had a global alteration of the lymphocyte DAT involving both a decreased number of proteins (Bmax) and a reduced functionality (Vmax). Taken together, these findings would indicate the presence of increased levels of DA in romantic love that, if paralleled by similar concentrations in the brain, would explain some peculiar features of this human feeling.

  16. Reality, ficción o show

    Directory of Open Access Journals (Sweden)

    Sandra Ruíz Moreno

    2002-01-01

    Full Text Available Para tener un punto de vista claro y objetivo frente a la polémica establecida en torno al programa “Protagonistas de novela” y la tendiente proliferación de los reality show en las parrillas de programación de la televisión colombiana, se realizó un análisis de texto y contenido de dicho programa, intentando definirlo desde sus posibilidades de realidad, ficción y show. Las unidades de análisis y el estudio de su tratamiento arrojaron un alto contenido que gira en torno a las emociones del ser humano relacionadas con la convivencia, tratadas a manera de show y con algunos aportes textuales de ficción, pero sin su elemento mediador básico, el actor, quitándole toda la posibilidad de tener un tratamiento con la profundidad, distancia y ética que requieren los temas de esta índole. El resultado es un formato que sólo busca altos índices de sintonía y que pertenece más a la denominada televisión “trash”, que a una búsqueda de realidad del hombre y mucho menos de sociedad.

  17. Monoamine oxidase A (MAO A) inhibitors decrease glioma progression

    Science.gov (United States)

    Vaikari, Vijaya Pooja; Kota, Rajesh; Chen, Kevin; Yeh, Tzu-Shao; Jhaveri, Niyati; Groshen, Susan L.; Olenyuk, Bogdan Z.; Chen, Thomas C.; Hofman, Florence M.; Shih, Jean C.

    2016-01-01

    Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug-resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis. PMID:26871599

  18. Hepatitis C Virus Core Protein Decreases Lipid Droplet Turnover

    Science.gov (United States)

    Harris, Charles; Herker, Eva; Farese, Robert V.; Ott, Melanie

    2011-01-01

    Steatosis is a frequent complication of hepatitis C virus infection. In mice, this condition is recapitulated by the expression of a single viral protein, the nucleocapsid core. Core localizes to the surface of lipid droplets (LDs) in infected liver cells through a process dependent on host diacylglycerol acyltransferase 1 (DGAT1), an enzyme that synthesizes triglycerides in the endoplasmic reticulum. Whether DGAT1 also plays a role in core-induced steatosis is uncertain. Here, we show that mouse embryonic fibroblasts isolated from DGAT1−/− mice are protected from core-induced steatosis, as are livers of DGAT1−/− mice expressing core, demonstrating that the steatosis is DGAT1-dependent. Surprisingly, core expression did not increase DGAT1 activity or triglyceride synthesis, thus excluding the possibility that core activates DGAT1 to cause steatosis. Instead, we find that DGAT1-dependent localization of core to LDs is a prerequisite for the steatogenic properties of the core. Using biochemical and immunofluorescence microscopy techniques, we show that the turnover of lipids in core-coated droplets is decreased, providing a physiological mechanism for core-induced steatosis. Our results support a bipartite model in which core first requires DGAT1 to gain access to LDs, and then LD-localized core interferes with triglyceride turnover, thus stabilizing lipid droplets and leading to steatosis. PMID:21984835

  19. Vitamin E decreases bone mass by stimulating osteoclast fusion.

    Science.gov (United States)

    Fujita, Koji; Iwasaki, Makiko; Ochi, Hiroki; Fukuda, Toru; Ma, Chengshan; Miyamoto, Takeshi; Takitani, Kimitaka; Negishi-Koga, Takako; Sunamura, Satoko; Kodama, Tatsuhiko; Takayanagi, Hiroshi; Tamai, Hiroshi; Kato, Shigeaki; Arai, Hiroyuki; Shinomiya, Kenichi; Itoh, Hiroshi; Okawa, Atsushi; Takeda, Shu

    2012-03-04

    Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells that are formed by mononuclear preosteoclast fusion. Fat-soluble vitamins such as vitamin D are pivotal in maintaining skeletal integrity. However, the role of vitamin E in bone remodeling is unknown. Here, we show that mice deficient in α-tocopherol transfer protein (Ttpa(-/-) mice), a mouse model of genetic vitamin E deficiency, have high bone mass as a result of a decrease in bone resorption. Cell-based assays indicated that α-tocopherol stimulated osteoclast fusion, independent of its antioxidant capacity, by inducing the expression of dendritic-cell-specific transmembrane protein, an essential molecule for osteoclast fusion, through activation of mitogen-activated protein kinase 14 (p38) and microphthalmia-associated transcription factor, as well as its direct recruitment to the Tm7sf4 (a gene encoding DC-STAMP) promoter. Indeed, the bone abnormality seen in Ttpa(-/-) mice was rescued by a Tm7sf4 transgene. Moreover, wild-type mice or rats fed an α-tocopherol-supplemented diet, which contains a comparable amount of α-tocopherol to supplements consumed by many people, lost bone mass. These results show that serum vitamin E is a determinant of bone mass through its regulation of osteoclast fusion.

  20. Curcumin Shows Antiviral Properties against Norovirus.

    Science.gov (United States)

    Yang, Minji; Lee, GilJae; Si, Jiyeon; Lee, Sung-Joon; You, Hyun Ju; Ko, GwangPyo

    2016-10-20

    Phytochemicals provide environmentally friendly and relatively inexpensive natural products, which could potentially benefit public health by controlling human norovirus (HuNoV) infection. In this study, 18 different phytochemicals were evaluated for antiviral effects against norovirus using murine norovirus (MNV) as a model for norovirus biology. Among these phytochemicals, curcumin (CCM) was the most potent anti-noroviral phytochemical, followed by resveratrol (RVT). In a cell culture infection model, exposure to CCM or RVT for 3 days reduced infectivity of norovirus by 91% and 80%, respectively. To confirm the antiviral capability of CCM, we further evaluated its antiviral efficacy at various doses (0.25, 0.5, 0.75, 1, and 2 mg/mL) and durations (short-term: 10, 30, 60, and 120 min; long-term: 1, 3, 7, and 14 days). The anti-noroviral effect of CCM was verified to occur in a dose-dependent manner. Additionally, we evaluated the inhibitory effect of each phytochemical on the replication of HuNoV using a HuNoV replicon-bearing cell line (HG23). Neither CCM nor RVT had a strong inhibitory effect on HuNoV replication, which suggests that their antiviral mechanism may involve viral entry or other life cycle stages rather than the replication of viral RNA. Our results demonstrated that CCM may be a promising candidate for development as an anti-noroviral agent to prevent outbreaks of foodborne illness.

  1. Bladder sensory desensitization decreases urinary urgency

    Directory of Open Access Journals (Sweden)

    Avelino António

    2007-06-01

    Full Text Available Abstract Background Bladder desensitization has been investigated as an alternative treatment for refractory detrusor overactivity. Most open and controlled clinical trials conducted with intravesical RTX showed that desensitization delays the appearance of involuntary detrusor contractions during bladder filling and decreases the number of episodes of urgency incontinence. Urgency is being recognised as the fundamental symptom of overactive bladder (OAB, a symptomatic complex which recent epidemiological studies have shown to affect more than 10% of the Western population. As anti-muscarinic drugs, the first line treatment for OAB, are far from being able to fully control urgency, the opportunity to test other therapeutic approaches is created. The present work was, therefore, designed as an exploratory investigation to evaluate the effect of bladder desensitization on urinary urgency. Methods Twenty-three OAB patients with refractory urgency entered, after given informed consent, a 30 days run-in period in which medications influencing the bladder function were interrupted. At the end of this period patients filled a seven-day voiding chart where they scored, using a 0–4 scale, the bladder sensations felt before each voiding. Then, patients were instilled with 100 ml of 10% ethanol in saline (vehicle solution and 30 days later a second seven-day voiding chart was collected. Finally, patients were instilled with 100 ml of 50 nM RTX in 10% ethanol in saline. At 1 and 3 months additional voiding charts were collected. At the end of the vehicle and 3 months period patients were asked to give their subjective impression about the outcome of the treatment and about the willingness to repeat the previous instillation. Results At the end of the run-in period the mean number of episodes of urgency per week was 71 ± 12 (mean ± SEM. After vehicle instillation, the mean number of episodes of urgency was 56 ± 11, but only 4 patients (17% considered

  2. Microbiological and environmental issues in show caves.

    Science.gov (United States)

    Saiz-Jimenez, Cesareo

    2012-07-01

    Cultural tourism expanded in the last half of the twentieth century, and the interest of visitors has come to include caves containing archaeological remains. Some show caves attracted mass tourism, and economical interests prevailed over conservation, which led to a deterioration of the subterranean environment and the rock art. The presence and the role of microorganisms in caves is a topic that is often ignored in cave management. Knowledge of the colonisation patterns, the dispersion mechanisms, and the effect on human health and, when present, over rock art paintings of these microorganisms is of the utmost importance. In this review the most recent advances in the study of microorganisms in caves are presented, together with the environmental implications of the findings.

  3. Ancient bacteria show evidence of DNA repair

    DEFF Research Database (Denmark)

    Johnson, Sarah Stewart; Hebsgaard, Martin B; Christensen, Torben R

    2007-01-01

    Recent claims of cultivable ancient bacteria within sealed environments highlight our limited understanding of the mechanisms behind long-term cell survival. It remains unclear how dormancy, a favored explanation for extended cellular persistence, can cope with spontaneous genomic decay over......-term survival of bacteria sealed in frozen conditions for up to one million years. Our results show evidence of bacterial survival in samples up to half a million years in age, making this the oldest independently authenticated DNA to date obtained from viable cells. Additionally, we find strong evidence...... that this long-term survival is closely tied to cellular metabolic activity and DNA repair that over time proves to be superior to dormancy as a mechanism in sustaining bacteria viability....

  4. Decreased oxidized glutathione with aerosolized cyclosporine delivery.

    Science.gov (United States)

    Katz, A; Coran, A G; Oldham, K T; Guice, K S

    1993-06-01

    Cyclosporine immunosuppression remains vital for successful lung transplantation. Cyclosporine also functions as a membrane active biological response modifier and has been noted to have a variable effect on ischemia-reperfusion (I/R) injury in various tissues. Glutathione plays an important role in the endogenous antioxidant defense system; plasma oxidized glutathione (GSSG) levels are useful as a sensitive indicator of in vivo oxidant stress and I/R injury. Lung transplantation results in ischemia, followed by a period of reperfusion, potentially producing functional injury. This study was designed to evaluate the effect of cyclosporine on oxygen radical generation in a model of single-lung transplantation. Single-lung transplantation was performed in 12 mongrel puppies, with animals assigned to receive either intravenous or aerosolized cyclosporine. Arterial blood and bronchoalveolar lavage fluid (BALF) samples were obtained to determine GSSG levels via a spectrophotometric technique. Samples were obtained both prior to and following the revascularization of the transplanted lung. Whole blood and tissue cyclosporine levels were determined via an high-performance liquid chromatography technique 3 hr following the completion of the transplant. Aerosolized cyclosporine administration resulted in greatly decreased arterial plasma and BALF GSSG levels, whole blood cyclosporine levels, and equivalent tissue cyclosporine levels when compared to intravenous cyclosporine delivery. These findings support the hypothesis that the transplanted lung is a source of GSSG production and release into plasma. Additionally, these findings suggest that cyclosporine may have a direct antioxidant effect on pulmonary tissue, with this activity occurring at the epithelial surface, an area susceptible to oxidant injury.

  5. Plant species descriptions show signs of disease.

    Science.gov (United States)

    Hood, Michael E; Antonovics, Janis

    2003-11-07

    It is well known that diseases can greatly influence the morphology of plants, but often the incidence of disease is either too rare or the symptoms too obvious for the 'abnormalities' to cause confusion in systematics. However, we have recently come across several misinterpretations of disease-induced traits that may have been perpetuated into modern species inventories. Anther-smut disease (caused by the fungus Microbotryum violaceum) is common in many members of the Caryophyllaceae and related plant families. This disease causes anthers of infected plants to be filled with dark-violet fungal spores rather than pollen. Otherwise, their vegetative morphology is within the normal range of healthy plants. Here, we present the results of a herbarium survey showing that a number of type specimens (on which the species name and original description are based) in the genus Silene from Asia are diseased with anther smut. The primary visible disease symptom, namely the dark-violet anthers, is incorporated into the original species descriptions and some of these descriptions have persisted unchanged into modern floras. This raises the question of whether diseased type specimens have erroneously been given unique species names.

  6. NASA GIBS Use in Live Planetarium Shows

    Science.gov (United States)

    Emmart, C. B.

    2015-12-01

    The American Museum of Natural History's Hayden Planetarium was rebuilt in year 2000 as an immersive theater for scientific data visualization to show the universe in context to our planet. Specific astrophysical movie productions provide the main daily programming, but interactive control software, developed at AMNH allows immersive presentation within a data aggregation of astronomical catalogs called the Digital Universe 3D Atlas. Since 2006, WMS globe browsing capabilities have been built into a software development collaboration with Sweden's Linkoping University (LiU). The resulting Uniview software, now a product of the company SCISS, is operated by about fifty planetariums around that world with ability to network amongst the sites for global presentations. Public presentation of NASA GIBS has allowed authoritative narratives to be presented within the range of data available in context to other sources such as Science on a Sphere, NASA Earth Observatory and Google Earth KML resources. Specifically, the NOAA supported World Views Network conducted a series of presentations across the US that focused on local ecological issues that could then be expanded in the course of presentation to national and global scales of examination. NASA support of for GIBS resources in an easy access multi scale streaming format like WMS has tremendously enabled particularly facile presentations of global monitoring like never before. Global networking of theaters for distributed presentations broadens out the potential for impact of this medium. Archiving and refinement of these presentations has already begun to inform new types of documentary productions that examine pertinent, global interdependency topics.

  7. Geoscience is Important? Show Me Why

    Science.gov (United States)

    Boland, M. A.

    2017-12-01

    "The public" is not homogenous and no single message or form of messaging will connect the entire public with the geosciences. One approach to promoting trust in, and engagement with, the geosciences is to identify specific sectors of the public and then develop interactions and communication products that are immediately relevant to that sector's interests. If the content and delivery are appropriate, this approach empowers people to connect with the geosciences on their own terms and to understand the relevance of the geosciences to their own situation. Federal policy makers are a distinct and influential subgroup of the general public. In preparation for the 2016 presidential election, the American Geosciences Institute (AGI) in collaboration with its 51 member societies prepared Geoscience for America's Critical Needs: Invitation to a National Dialogue, a document that identified major geoscience policy issues that should be addressed in a national policy platform. Following the election, AGI worked with eight other geoscience societies to develop Geoscience Policy Recommendations for the New Administration and the 115th Congress, which outlines specific policy actions to address national issues. State and local decision makers are another important subgroup of the public. AGI has developed online content, factsheets, and case studies with different levels of technical complexity so people can explore societally-relevant geoscience topics at their level of technical proficiency. A related webinar series is attracting a growing worldwide audience from many employment sectors. Partnering with government agencies and other scientific and professional societies has increased the visibility and credibility of these information products with our target audience. Surveys and other feedback show that these products are raising awareness of the geosciences and helping to build reciprocal relationships between geoscientists and decision makers. The core message of all

  8. Intraperitoneal inflammation decreases endometriosis in a mouse model

    OpenAIRE

    Nowak, N.M.; Fischer, O.M.; Gust, T.C.; Fuhrmann, U.; Habenicht, U.-F.; Schmidt, A.

    2008-01-01

    BACKGROUND The role of the immune system in the pathogenesis of endometriosis remains elusive. It has been shown that patients have an altered peritoneal environment with increased levels of inflammatory cytokines, activated macrophages and reduced clearance of retrogradely transported endometrial fragments. However, it is not known if this unique inflammatory situation is cause or consequence of endometriosis. This study investigates the impact of a pre-existing peritoneal inflammation on en...

  9. Showing shape with texture: two directions seem better than one

    Science.gov (United States)

    Kim, Sunghee; Hagh-Shenas, Haleh; Interrante, Victoria

    2003-06-01

    Studies have shown that observers' judgment of surface orientation and curvature is affected by the presence of surface texture pattern. However, the question of designing a texture pattern that does not hide the surace information nor does convey a misrepresentation of the surface remains unsolved. The answer to this question has important potential imapct across a wide range of visualization application. Molecular modeling and radiation therapy are among the many fields that are in need of accurately visualizing their data and could benefit from such methods. Over the past several years we have carried out a series of experiments to investigate the impact of various texture pattern characteristics on shape perception. In this paper we report the result of our most recent study. The task in this study was adjusting surface attitude probes under three different texture conditions and a control condition in which no texture was present. We later compare the performances of the subjects. The three texture conditions were: a doubly oriented texture in which approximately evenly spaced lines followed both of the principal directions, a singly oriented texture in which lines followed only the first principal direction, and a singly oriented line integral convolution. Over a series of 200 trials (4 texture conditions, 10 surface probe locations * five repeated measures) a total of five naive participants were asked to adjust a circular probe. The probes were randomly located on an arbitrary curved surface and its perpendicular extension appeared to be oriented in the direction of the surface normal. An analysis of the results showed that the performance was best in the two directional texture condition. Performances were further decreased in one directional and no texture conditions (in that order). The paper is organized as follows. In Section 1 we briefly describe the motivation for our work. In Section 2 we describe our experimental methods, including a brief summary

  10. Can Diuretics Decrease Your Potassium Level?

    Science.gov (United States)

    ... of low potassium? Can diuretics decrease your potassium level? Answers from Sheldon G. Sheps, M.D. Yes, ... your urine. This can lead to low potassium levels in your blood (hypokalemia). Signs and symptoms of ...

  11. CAN CHILD-CARE SUPPORT POLICIES HALT DECREASING FERTILITY?

    Directory of Open Access Journals (Sweden)

    Masaya Yasuoka

    2013-04-01

    Full Text Available Some earlier papers examine whether child allowances can raise fertility or not in an endogenous fertility model with a defined contribution pension system. They derive that a child allowance can raise fertility. This paper is aimed at deriving the level of child allowances or education subsidies to make the pension system sustainable. A child allowance can raise fertility instantaneously. However, in the long run, fertility might continue decreasing and the pension system might not be sustainable if less child allowance is provided. In a defined benefit system, tax burdens for pension benefits are heavy in an aging society with fewer children. A heavy tax burden reduces the household income and then decreases fertility. Therefore, child allowances must be provided to halt decreasing fertility in the long run. Nevertheless, given parametric conditions, education subsidy of more than a certain level can not halt the decrease of fertility in the long run.

  12. A Novel Method to Decrease Micro-residual Stresses of Fibrous Composites by Adding Carbon Nanotube

    Directory of Open Access Journals (Sweden)

    M. M. Shokrieh

    2013-12-01

    Full Text Available In this research, a novel method to decrease micro-residual stresses of fibrous composites by adding carbon nanotubes (CNTs is proposed in detail. The negative coefficient of thermal expansion and the high young’s modulus of CNTs can be utilized to counterbalance the process induced residual stresses in composites. To this end, first, the effects of adding CNTs to the matrix of fibrous composites in reducing the coefficient of thermal expansion (CTE and increasing of young’s modulus of matrix are studied theoretically. Then, a three phase micromechanical model (the energy method is used to model the effect of CNT in reducing the residual stresses of fibrous composites. The results show that by addition of CNTs, enhancements in properties of matrix are obtained and lead to decrease in micro-residual stresses of matrix and fiber up to 72%.

  13. Mice lacking neuropeptide Y show increased sensitivity to cocaine

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Woldbye, David Paul Drucker

    2012-01-01

    There is increasing data implicating neuropeptide Y (NPY) in the neurobiology of addiction. This study explored the possible role of NPY in cocaine-induced behavior using NPY knockout mice. The transgenic mice showed a hypersensitive response to cocaine in three animal models of cocaine addiction...

  14. Power decreases trust in social exchange.

    Science.gov (United States)

    Schilke, Oliver; Reimann, Martin; Cook, Karen S

    2015-10-20

    How does lacking vs. possessing power in a social exchange affect people's trust in their exchange partner? An answer to this question has broad implications for a number of exchange settings in which dependence plays an important role. Here, we report on a series of experiments in which we manipulated participants' power position in terms of structural dependence and observed their trust perceptions and behaviors. Over a variety of different experimental paradigms and measures, we find that more powerful actors place less trust in others than less powerful actors do. Our results contradict predictions by rational actor models, which assume that low-power individuals are able to anticipate that a more powerful exchange partner will place little value on the relationship with them, thus tends to behave opportunistically, and consequently cannot be trusted. Conversely, our results support predictions by motivated cognition theory, which posits that low-power individuals want their exchange partner to be trustworthy and then act according to that desire. Mediation analyses show that, consistent with the motivated cognition account, having low power increases individuals' hope and, in turn, their perceptions of their exchange partners' benevolence, which ultimately leads them to trust.

  15. Freshwater pearl mussels show plasticity of responses to different predation risks but also show consistent individual differences in responsiveness.

    Science.gov (United States)

    Wilson, Conor D; Arnott, Gareth; Elwood, Robert W

    2012-03-01

    Animals often show behavioural plasticity with respect to predation risk but also show behavioural syndromes in terms of consistency of responses to different stimuli. We examine these features in the freshwater pearl mussel. These bivalves often aggregate presumably to reduce predation risk to each individual. Predation risk, however, will be higher in the presence of predator cues. Here we use dimming light, vibration and touch as novel stimuli to examine the trade-off between motivation to feed and motivation to avoid predation. We present two experiments that each use three sequential novel stimuli to cause the mussels to close their valves and hence cease feeding. We find that mussels within a group showed shorter closure times than solitary mussels, consistent with decreased vulnerability to predation in group-living individuals. Mussels exposed to the odour of a predatory crayfish showed longer closures than control mussels, highlighting the predator assessment abilities of this species. However, individuals showed significant consistency in their closure responses across the trial series, in line with behavioural syndrome theory. Our results show that bivalves trade-off feeding and predator avoidance according to predation risk but the degree to which this is achieved is constrained by behavioural consistency. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Snacking on Television: A Content Analysis of Adolescents' Favorite Shows.

    Science.gov (United States)

    Eisenberg, Marla E; Larson, Nicole I; Gollust, Sarah E; Neumark-Sztainer, Dianne

    2016-05-19

    Snacking is a complex behavior that may be influenced by entertainment media. Research suggests that snacking and unhealthy foods are commonly shown in programming that targets young audiences, but shows selected for study have been limited. We conducted a content analysis on shows that were named as favorites by adolescents to characterize portrayals of snacking on popular television. A diverse sample of 2,130 adolescents (mean age, 14.3 y) listed 3 favorite television shows in a 2010 school-based survey. Three episodes each of the 25 most popular shows were coded for food-related content, including healthfulness, portion size, screen time use, setting, and social context. We also analyzed the characteristics of characters involved in eating incidents, the show type, and the show rating. We used χ(2) tests, binomial tests, and multilevel regression models to compare incidence of snacks versus meals, the characteristics of those involved, and snacking across show characteristics. Almost half of food incidents on television shows were snacks. Snacks were significantly more likely than meals to be "mostly unhealthy" (69.3% vs 22.6%, P Media awareness and literacy programs should include foods and snacking behaviors among the issues they address. More healthful portrayals of food and dietary intake in entertainment shows' content would create a healthier media environment for youth.

  17. GLOBAL DECREASES IN TOTAL OZONE DURING THE WINTER MONTHS

    OpenAIRE

    タカオ, トシノリ; Toshinori, TAKAO

    1990-01-01

    Global network of total ozone measurements by Dobson spectrophotometer shows ozone decrease in recent years. At midlatitudes of the Northern Hemisphere, ozone loss was significant during the winter months of 1983 and 1985. In some regions, there is a positive correlation between the annual mean of total ozone amounts and the solar cycle.

  18. Climate change leads to decreasing bird migration distances

    NARCIS (Netherlands)

    Visser, M.E.; Perdeck, A.C.; van Balen, J.H.; Both, C.

    2009-01-01

    Global climate change has led to warmer winters in NW Europe, shortening the distance between suitable overwintering areas and the breeding areas of many bird species. Here we show that winter recovery distances have decreased over the past seven decades, for birds ringed during the breeding season

  19. Climate change leads to decreasing bird migration distances

    NARCIS (Netherlands)

    Visser, Marcel E.; Perdeck, Albert C.; van Balen, Johan H.; Both, Christiaan

    Global climate change has led to warmer winters in NW Europe, shortening the distance between suitable overwintering areas and the breeding areas of many bird species. Here we show that winter recovery distances have decreased over the past seven decades, for birds ringed during the breeding season

  20. Decreased cell proliferation and higher oxidative stress in fibroblasts from Down Syndrome fetuses. Preliminary study.

    Science.gov (United States)

    Gimeno, Amparo; García-Giménez, José Luis; Audí, Laura; Toran, Nuria; Andaluz, Pilar; Dasí, Francisco; Viña, José; Pallardó, Federico V

    2014-01-01

    Down Syndrome is the most common chromosomal disease and is also known for its decreased incidence of solid tumors and its progeroid phenotype. Cellular and systemic oxidative stress has been considered as one of the Down Syndrome phenotype causes. We correlated, in a preliminary study, the fibroblast proliferation rate and different cell proliferation key regulators, like Rcan1 and the telomere length from Down Syndrome fetuses, with their oxidative stress profile and the Ribonucleic acid and protein expression of the main antioxidant enzymes together with their activity. Increased oxidized glutathione/glutathione ratio and high peroxide production were found in our cell model. These results correlated with a distorted antioxidant shield. The messenger RNA (SOD1) and protein levels of copper/zinc superoxide dismutase were increased together with a decreased mRNA expression and protein levels of glutathione peroxidase (GPx). As a consequence the [Cu/ZnSOD/(catalase+GPx)] activity ratio increases which explains the oxidative stress generated in the cell model. In addition, the expression of thioredoxin 1 and glutaredoxin 1 is decreased. The results obtained show a decreased antioxidant phenotype that correlates with increased levels of Regulator of calcineurin 1 and attrition of telomeres, both related to oxidative stress and cell cycle impairment. Our preliminary results may explain the proneness to a progeroid phenotype. © 2013.

  1. Machine-Learning-Based No Show Prediction in Outpatient Visits

    Directory of Open Access Journals (Sweden)

    Carlos Elvira

    2018-03-01

    Full Text Available A recurring problem in healthcare is the high percentage of patients who miss their appointment, be it a consultation or a hospital test. The present study seeks patient’s behavioural patterns that allow predicting the probability of no- shows. We explore the convenience of using Big Data Machine Learning models to accomplish this task. To begin with, a predictive model based only on variables associated with the target appointment is built. Then the model is improved by considering the patient’s history of appointments. In both cases, the Gradient Boosting algorithm was the predictor of choice. Our numerical results are considered promising given the small amount of information available. However, there seems to be plenty of room to improve the model if we manage to collect additional data for both patients and appointments.

  2. Decreasing prevalence of social drinkers in Australia.

    Science.gov (United States)

    Callinan, Sarah; Pennay, Amy; Livingston, Michael

    2017-04-01

    There has been a recent decrease in population level alcohol consumption in Australia, particularly in young people. Whether this is due to increasing abstinence or a shift in the way people think about alcohol is not known. The aim of this study is to investigate trends in self-identification of drinker types in Australia from 2001 to 2013 in light of shifting patterns of alcohol consumption in Australia. Five waves of the National Drug Strategy Household Survey from 2001 to 2013 (N=118,416) were used to assess trends in self-identification as a drinker type (non-, ex-, occasional, light, social, heavy and binge drinker). Consumption patterns and demographics of the self-identified groups were also examined. The pattern of self-identification has mostly remained steady over time. The two exceptions to this are a decrease in identification as a social drinker (28% to 22%) and a corresponding increase in identification as a non-drinker (from 19% to 27%). There are few changes over time in the demographic make-up of, or consumption patterns in, the social drinker category with the exception of those over 50, who continue to identify as social drinkers at the same rate. The recent increase in abstinence in Australia seems to be matched by a corresponding decrease in self-identified social drinkers, particularly among those under 50. This indicates that the decrease in consumption is not occurring in those most likely to experience harms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Elevated plasma homocysteine in association with decreased ...

    African Journals Online (AJOL)

    Objective: Increased plasma homocysteine, decreased vitamin B12 and folic acid levels have been implicated in depressive mood. Plasma homocystine, vitamin B12, folic acid tryptophan, lipids and lipoproteins were determined in depressed patients and ... toxic to neurons and blood vessels and can induce DNA strand.

  4. DECREASE IN NUMBERS OF THE EASTERN ROCKHOPPER ...

    African Journals Online (AJOL)

    The number of eastern rockhopper penguins Eudyptes chrysocome filholi breeding at subantarctic Marion Island decreased from about 173 000 pairs in 1994/95 to about 67 000 pairs in 2001/02. During 1994/95–2002/03 pairs fledged on average 0.40 chicks per year, an amount thought insufficient to balance mortality of ...

  5. Decreasing cloud cover drives the recent mass loss on the Greenland Ice Sheet.

    Science.gov (United States)

    Hofer, Stefan; Tedstone, Andrew J; Fettweis, Xavier; Bamber, Jonathan L

    2017-06-01

    The Greenland Ice Sheet (GrIS) has been losing mass at an accelerating rate since the mid-1990s. This has been due to both increased ice discharge into the ocean and melting at the surface, with the latter being the dominant contribution. This change in state has been attributed to rising temperatures and a decrease in surface albedo. We show, using satellite data and climate model output, that the abrupt reduction in surface mass balance since about 1995 can be attributed largely to a coincident trend of decreasing summer cloud cover enhancing the melt-albedo feedback. Satellite observations show that, from 1995 to 2009, summer cloud cover decreased by 0.9 ± 0.3% per year. Model output indicates that the GrIS summer melt increases by 27 ± 13 gigatons (Gt) per percent reduction in summer cloud cover, principally because of the impact of increased shortwave radiation over the low albedo ablation zone. The observed reduction in cloud cover is strongly correlated with a state shift in the North Atlantic Oscillation promoting anticyclonic conditions in summer and suggests that the enhanced surface mass loss from the GrIS is driven by synoptic-scale changes in Arctic-wide atmospheric circulation.

  6. Decreased Muscle Strength and Quality in Diabetes-Related Dementia

    Directory of Open Access Journals (Sweden)

    Akito Tsugawa

    2017-12-01

    Full Text Available Background/Aims: Diabetes-related dementia (DrD, a dementia subgroup associated with specific diabetes mellitus (DM-related metabolic abnormalities, is clinically and pathophysiologically different from Alzheimer disease (AD and vascular dementia. We determined whether skeletal muscle strength, quality, and mass decrease in individuals with DrD. Methods: We evaluated grip and knee extension strength, muscle mass, and gait speed in 106 patients with probable AD and without type 2 DM (AD[–DM] group, 74 patients with probable AD and with DM (AD[+DM] group, and 36 patients with DrD (DrD group. Muscle quality was defined as the ratio of muscle strength to muscle mass. Results: Both female and male subjects with DrD showed significantly decreased muscle strength and quality in the upper extremities compared with the subjects with AD[–DM] or AD[+DM]. Female subjects with DrD showed significantly decreased muscle quality in the lower extremities compared with the subjects with AD[–DM]. Both female and male subjects with DrD had a significantly lower gait speed compared with the subjects with AD[–DM]. However, there were no significant differences in muscle mass and the prevalence of sarcopenia between the groups. Conclusion: Subjects with DrD showed decreased muscle strength and quality, but not muscle mass, and had a low gait speed.

  7. Decrease of 5-Hydroxymethylcytosine Is Associated with Progression of Hepatocellular Carcinoma through Downregulation of TET1

    Science.gov (United States)

    Chen, Xuejiao; Shen, Junjie; Shan, Juanjuan; Xu, Yanmin; Yang, Zhi; Wu, Lin; Xia, Feng; Bie, Ping; Cui, Youhong; Bian, Xiu-wu; Qian, Cheng

    2013-01-01

    DNA methylation is an important epigenetic modification and is frequently altered in cancer. Convert of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation (TET) family enzymes plays important biological functions in embryonic stem cells, development, aging and disease. Recent reports showed that level of 5 hmC was altered in various types of cancers. However, the change of 5 hmC level in hepatocellular carcinoma (HCC) and association with clinical outcome were not well defined. Here, we reported that level of 5 hmC was decreased in HCC tissues, as compared with non-tumor tissues. Clincopathological analysis showed the decreased level of 5 hmC in HCC was associated with tumor size, AFP level and poor overall survival. We also found that the decreased level of 5 hmC in non-tumor tissues was associated with tumor recurrence in the first year after surgical resection. In an animal model with carcinogen DEN-induced HCC, we found that the level of 5 hmC was gradually decreased in the livers during the period of induction. There was further reduction of 5 hmC in tumor tissues when tumors were developed. In contrast, level of 5 mC was increased in HCC tissues and the increased 5 mC level was associated with capsular invasion, vascular thrombosis, tumor recurrence and overall survival. Furthermore, our data showed that expression of TET1, but not TET2 and TET3, was downregulated in HCC. Taken together, our data indicated 5 hmC may be served as a prognostic marker for HCC and the decreased expression of TET1 is likely one of the mechanisms underlying 5 hmC loss in HCC. PMID:23671639

  8. Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1.

    Directory of Open Access Journals (Sweden)

    Chungang Liu

    Full Text Available DNA methylation is an important epigenetic modification and is frequently altered in cancer. Convert of 5-methylcytosine (5 mC to 5-hydroxymethylcytosine (5 hmC by ten-eleven translocation (TET family enzymes plays important biological functions in embryonic stem cells, development, aging and disease. Recent reports showed that level of 5 hmC was altered in various types of cancers. However, the change of 5 hmC level in hepatocellular carcinoma (HCC and association with clinical outcome were not well defined. Here, we reported that level of 5 hmC was decreased in HCC tissues, as compared with non-tumor tissues. Clincopathological analysis showed the decreased level of 5 hmC in HCC was associated with tumor size, AFP level and poor overall survival. We also found that the decreased level of 5 hmC in non-tumor tissues was associated with tumor recurrence in the first year after surgical resection. In an animal model with carcinogen DEN-induced HCC, we found that the level of 5 hmC was gradually decreased in the livers during the period of induction. There was further reduction of 5 hmC in tumor tissues when tumors were developed. In contrast, level of 5 mC was increased in HCC tissues and the increased 5 mC level was associated with capsular invasion, vascular thrombosis, tumor recurrence and overall survival. Furthermore, our data showed that expression of TET1, but not TET2 and TET3, was downregulated in HCC. Taken together, our data indicated 5 hmC may be served as a prognostic marker for HCC and the decreased expression of TET1 is likely one of the mechanisms underlying 5 hmC loss in HCC.

  9. Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1.

    Science.gov (United States)

    Liu, Chungang; Liu, Limei; Chen, Xuejiao; Shen, Junjie; Shan, Juanjuan; Xu, Yanmin; Yang, Zhi; Wu, Lin; Xia, Feng; Bie, Ping; Cui, Youhong; Bian, Xiu-wu; Qian, Cheng

    2013-01-01

    DNA methylation is an important epigenetic modification and is frequently altered in cancer. Convert of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation (TET) family enzymes plays important biological functions in embryonic stem cells, development, aging and disease. Recent reports showed that level of 5 hmC was altered in various types of cancers. However, the change of 5 hmC level in hepatocellular carcinoma (HCC) and association with clinical outcome were not well defined. Here, we reported that level of 5 hmC was decreased in HCC tissues, as compared with non-tumor tissues. Clincopathological analysis showed the decreased level of 5 hmC in HCC was associated with tumor size, AFP level and poor overall survival. We also found that the decreased level of 5 hmC in non-tumor tissues was associated with tumor recurrence in the first year after surgical resection. In an animal model with carcinogen DEN-induced HCC, we found that the level of 5 hmC was gradually decreased in the livers during the period of induction. There was further reduction of 5 hmC in tumor tissues when tumors were developed. In contrast, level of 5 mC was increased in HCC tissues and the increased 5 mC level was associated with capsular invasion, vascular thrombosis, tumor recurrence and overall survival. Furthermore, our data showed that expression of TET1, but not TET2 and TET3, was downregulated in HCC. Taken together, our data indicated 5 hmC may be served as a prognostic marker for HCC and the decreased expression of TET1 is likely one of the mechanisms underlying 5 hmC loss in HCC.

  10. Optical response of marine aerosols to Forbush Decreases

    DEFF Research Database (Denmark)

    Enghoff, Martin Andreas Bødker

    A tempting approach to investigate the link between cosmic rays and climate is to explore Forbush decreases - sudden drops in the amount of galactic cosmic rays reaching Earth, caused by large Coronal Mass Ejections from the sun. Due to the sudden nature of these events effects from other solar...... parameters, such as total irradiance or UV can be ruled out. There has previously been several papers using observations to gauge the impact of Forbush decreases on cloud cover, but with no definitive conclusion. In this study we model the response of the optical parameters of marine aerosols – precursors...... for cloud drops. We are specifically looking at the Angstrom exponent and the optical thickness. The goal is to elucidate the sensitivity of the type and magnitude of response in these parameters during a Forbush decrease, to changes in aerosol production, condensable gases, and primary aerosols....

  11. Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

    International Nuclear Information System (INIS)

    Mackey, W.C.; Connolly, R.J.; Callow, A.D.

    1984-01-01

    The influence of a single dose of aspirin (5.4-7.4 mg/kg) on platelet uptake on 4-mm Dacron interposition grafts was studied in a baboon model using gamma camera scanning for 111-Indium labeled platelets. In vitro assessment of platelet function after aspirin administration revealed that in the baboon, as in the human, aspirin abolished arachidonic acid-induced platelet aggregation, prolonged the lag time between exposure to collagen and aggregation, and decreased plasma thromboxane B2 levels. Aspirin also prolonged the template bleeding time. Scans for 111-Indium labeled platelets revealed that pretreatment with a single dose of aspirin decreased platelet uptake on 4-mm Dacron carotid interposition grafts. This decrease in platelet uptake was associated with a significant improvement in 2-hour graft patency and with a trend toward improved 2-week patency

  12. Decreased prefrontal cortical dopamine transmission in alcoholism.

    Science.gov (United States)

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

    2014-08-01

    Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

  13. Global mortality from storm surges is decreasing

    Science.gov (United States)

    Bouwer, Laurens M.; Jonkman, Sebastiaan N.

    2018-01-01

    Changes in society’s vulnerability to natural hazards are important to understand, as they determine current and future risks, and the need to improve protection. Very large impacts including high numbers of fatalities occur due to single storm surge flood events. Here, we report on impacts of global coastal storm surge events since the year 1900, based on a compilation of events and data on loss of life. We find that over the past, more than eight thousand people are killed and 1.5 million people are affected annually by storm surges. The occurrence of very substantial loss of life (>10 000 persons) from single events has however decreased over time. Moreover, there is a consistent decrease in event mortality, measured by the fraction of exposed people that are killed, for all global regions, except South East Asia. Average mortality for storm surges is slightly higher than for river floods, but lower than for flash floods. We also find that for the same coastal surge water level, mortality has decreased over time. This indicates that risk reduction efforts have been successful, but need to be continued with projected climate change, increased rates of sea-level rise and urbanisation in coastal zones.

  14. Decreasing radioactive cesium in lodged buckwheat grain after harvest

    Directory of Open Access Journals (Sweden)

    Katashi Kubo

    2016-01-01

    Full Text Available This study assessed soil contamination with high radioactive cesium (R–Cs concentration in buckwheat grains by lodging, and assessed the possibility of R–Cs reduction in grain through post-harvest preparation. Analysis of buckwheat grain produced in farmers’ fields and reports from farmers indicated that grain from fields that had lodging showed higher R–Cs than grain from fields with no lodging. A field experiment demonstrated that R–Cs in grain after threshing and winnowing (TW was about six times higher in lodged plants than in nonlodged plants. In lodged plants, R–Cs in grain was decreased to about one-fourth by polishing, and was decreased to about one-seventh by ultrasonic cleaning, compared with R–Cs in grain after TW. These results demonstrate that R–Cs of buckwheat grain of lodged plants can be decreased by removing soil from the grain surface by polishing and winnowing.

  15. Evolution of the French greenhouse gas emissions: an eyewash decrease

    International Nuclear Information System (INIS)

    Marignac, Y.

    2010-01-01

    As the French greenhouse emissions displayed a significant decrease in 2009, compared with the reference levels of 1990, the author shows that this decrease cannot be in fact attributed to the environment policy, and more particularly not to the measures adopted within the frame of the 'Grenelle de l'Environnement'. An examination of the statistics reveals that this decrease cannot be explained by a structural transformation of energy production or consumption, but essentially by the current economic crisis. Therefore, the energetic transition which is supposed to allow the emissions to be divided by 4 in 2050, is not actually under way. On the contrary, it appears that, in a context of globalization of economy, emissions produced to satisfy French needs tend to increase through their foreign relocation

  16. Acutely decreased thermoregulatory energy expenditure or decreased activity energy expenditure both acutely reduce food intake in mice.

    Directory of Open Access Journals (Sweden)

    Karl J Kaiyala

    Full Text Available Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1 increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2 exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21 °C to 28 °C rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40 ± 1% and dark cycle energy expenditure (15 ± 3% at normal ambient temperature (21 °C. Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65 ± 7%, thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14 ± 2% at 21 °C; 21 ± 4% at 28 °C, while food intake was reduced during the dark cycle (0.9 ± 0.1 g in mice housed at 28 °C, but during the light cycle (0.3 ± 0.1 g in mice housed at 21 °C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R(2 = 0.51, p<0.01. We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure.

  17. ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis.

    Directory of Open Access Journals (Sweden)

    Cecilia Riquelme

    Full Text Available Duchenne muscular dystrophy (DMD is the most common inherited neuromuscular disease and is characterized by absence of the cytoskeletal protein dystrophin, muscle wasting, and fibrosis. We previously demonstrated that systemic infusion or oral administration of angiotensin-(1-7 (Ang-(1-7, a peptide with opposing effects to angiotensin II, normalized skeletal muscle architecture, decreased local fibrosis, and improved muscle function in mdx mice, a dystrophic model for DMD. In this study, we investigated the presence, activity, and localization of ACE2, the enzyme responsible for Ang-(1-7 production, in wild type (wt and mdx skeletal muscle and in a model of induced chronic damage in wt mice. All dystrophic muscles studied showed higher ACE2 activity than wt muscle. Immunolocalization studies indicated that ACE2 was localized mainly at the sarcolemma and, to a lesser extent, associated with interstitial cells. Similar results were observed in the model of chronic damage in the tibialis anterior (TA muscle. Furthermore, we evaluated the effect of ACE2 overexpression in mdx TA muscle using an adenovirus containing human ACE2 sequence and showed that expression of ACE2 reduced the fibrosis associated with TA dystrophic muscles. Moreover, we observed fewer inflammatory cells infiltrating the mdx muscle. Finally, mdx gastrocnemius muscles from mice infused with Ang-(1-7, which decreases fibrosis, contain less ACE2 associated with the muscle. This is the first evidence supporting ACE2 as an important therapeutic target to improve the dystrophic skeletal muscle phenotype.

  18. Music decreases aortic stiffness and wave reflections.

    Science.gov (United States)

    Vlachopoulos, Charalambos; Aggelakas, Angelos; Ioakeimidis, Nikolaos; Xaplanteris, Panagiotis; Terentes-Printzios, Dimitrios; Abdelrasoul, Mahmoud; Lazaros, George; Tousoulis, Dimitris

    2015-05-01

    Music has been related to cardiovascular health and used as adjunct therapy in patients with cardiovascular disease. Aortic stiffness and wave reflections are predictors of cardiovascular risk. We investigated the short-term effect of classical and rock music on arterial stiffness and wave reflections. Twenty healthy individuals (22.5±2.5 years) were studied on three different occasions and listened to a 30-min music track compilation (classical, rock, or no music for the sham procedure). Both classical and rock music resulted in a decrease of carotid-femoral pulse wave velocity (PWV) immediately after the end of music listening (all pclassical or rock music in a more sustained way (nadir by 6.0% and 5.8%, respectively, at time zero post-music listening, all pmusic preference was taken into consideration, both classical and rock music had a more potent effect on PWV in classical aficionados (by 0.20 m/s, p=0.003 and 0.13 m/s, p=0.015, respectively), whereas there was no effect in rock aficionados (all p=NS). Regarding wave reflections, classical music led to a more potent response in classical aficionados (AIx decrease by 9.45%), whereas rock led to a more potent response to rock aficionados (by 10.7%, all pMusic, both classical and rock, decreases aortic stiffness and wave reflections. Effect on aortic stiffness lasts for as long as music is listened to, while classical music has a sustained effect on wave reflections. These findings may have important implications, extending the spectrum of lifestyle modifications that can ameliorate arterial function. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Decreasing Human Trafficking through Sex Work Decriminalization.

    Science.gov (United States)

    Albright, Erin; D'Adamo, Kate

    2017-01-01

    In order to decrease human trafficking, health care workers should support the full decriminalization of prostitution. Similar to trafficking in other forms of labor, preventing trafficking in the sex trade requires addressing the different forms of marginalization that create vulnerable communities. By removing punitive laws that prevent reporting of exploitation and abuse, decriminalization allows sex workers to work more safely, thereby reducing marginalization and vulnerability. Decriminalization can also help destigmatize sex work and help resist political, social, and cultural marginalization of sex workers. © 2017 American Medical Association. All Rights Reserved.

  20. Phosphorus limitation and heat stress decrease calcification in Emiliania huxleyi

    Science.gov (United States)

    Gerecht, Andrea C.; Šupraha, Luka; Langer, Gerald; Henderiks, Jorijntje

    2018-02-01

    Calcifying haptophytes (coccolithophores) sequester carbon in the form of organic and inorganic cellular components (coccoliths). We examined the effect of phosphorus (P) limitation and heat stress on particulate organic and inorganic carbon (calcite) production in the coccolithophore Emiliania huxleyi. Both environmental stressors are related to rising CO2 levels and affect carbon production in marine microalgae, which in turn impacts biogeochemical cycling. Using semi-continuous cultures, we show that P limitation and heat stress decrease the calcification rate in E. huxleyi. However, using batch cultures, we show that different culturing approaches (batch versus semi-continuous) induce different physiologies. This affects the ratio of particulate inorganic (PIC) to organic carbon (POC) and complicates general predictions on the effect of P limitation on the PIC  /  POC ratio. We found heat stress to increase P requirements in E. huxleyi, possibly leading to lower standing stocks in a warmer ocean, especially if this is linked to lower nutrient input. In summary, the predicted rise in global temperature and resulting decrease in nutrient availability may decrease CO2 sequestration by E. huxleyi through lower overall carbon production. Additionally, the export of carbon may be diminished by a decrease in calcification and a weaker coccolith ballasting effect.

  1. Increased water deficit decreases Douglas fir growth throughout western US forests

    Science.gov (United States)

    Restaino, Christina M; Peterson, David L.; Littell, Jeremy

    2016-01-01

    Changes in tree growth rates can affect tree mortality and forest feedbacks to the global carbon cycle. As air temperature increases, evaporative demand also increases, increasing effective drought in forest ecosystems. Using a spatially comprehensive network of Douglas-fir (Pseudotsuga menziesii) chronologies from 122 locations that experience distinctly different climate in the western United States, we show that increased temperature decreases growth via vapor pressure deficit (VPD) across all latitudes. Under an ensemble of global circulation models, we project an increase in both the mean VPD associated with the lowest growth extremes and the probability of exceeding these VPD values. As temperature continues to increase in future decades, we can expect deficit-related stress to increase and consequently Douglas-fir growth to decrease throughout its US range.

  2. The use of combined radiation methods for decreasing the bacterial dissemination of enzyme preparations

    International Nuclear Information System (INIS)

    Samojlenko, I.I.; Fedotov, N.S.; Tumanyan, M.A.; Korolev, N.I.

    1984-01-01

    A study was made on possibility of using ionizing radiation in combination with alternative magnetic field (AMF) and heating for decreasing the bacterial dissemination of proteolytic enzymes. Papain, trypsin, chymotrypsin and amylorysin (the preparation possessing proteolytic and amylolytic activities) were subjected to gamma irradiation at 10-25 kGy dose range, the effect of AMF with 750 oe and heating at 50 deg during 60 min. Model tests conducted with the use of Escherichia Coli cells and Bacillus anthracoides spores showed that survival rate of bacteria irradiated in protective medium was lower in the case of combined magnetoradiation and thermoradiation effect. The use of 10 kGy dose of ionizing radiation in combination with treatment in alternative magnetic field or with heating provided the required decrease of dissemination of irradiated enzyme samples with complete conservation of proteolytic activity by them

  3. Serum Soluble Corin is Decreased in Stroke.

    Science.gov (United States)

    Peng, Hao; Zhu, Fangfang; Shi, Jijun; Han, Xiujie; Zhou, Dan; Liu, Yan; Zhi, Zhongwen; Zhang, Fuding; Shen, Yun; Ma, Juanjuan; Song, Yulin; Hu, Weidong

    2015-07-01

    Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls. Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively. Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke. © 2015 American Heart Association, Inc.

  4. Decrease in vibroactivity of gear drives

    Science.gov (United States)

    Dyundik, O. S.; Zgonnik, I. P.

    2018-01-01

    The analysis of technical and technological solutions to reduce the influence of dynamic intermating process to vibroactivity of a gear drive is carried out. The problem of a complete elimination has no solution due to a discrete way of power flow transformation by a gear drive. It is shown that a reduction of mesh stiffness is a controlled parameter in vibroactivity decrease. We have proposed to reduce the stiffness by means of a gear rim radial cut that provides small initial and stepwise variable stiffness of gearing. The technical solutions resulting in a smooth, dependent on a power flow running of stiffness by means of built-in control chain and usage of elastomeric materials are given. As a result, it is noted that the reduction of mesh stiffness at the same time leads to the increase in static deformation δ, and the dynamic load under intermating decreases. Elastomeric parameters’ variation t can provide the achievement of calculated mesh stiffness, depending on a variable power flow.

  5. Tomato Fruits Show Wide Phenomic Diversity but Fruit Developmental Genes Show Low Genomic Diversity.

    Directory of Open Access Journals (Sweden)

    Vijee Mohan

    Full Text Available Domestication of tomato has resulted in large diversity in fruit phenotypes. An intensive phenotyping of 127 tomato accessions from 20 countries revealed extensive morphological diversity in fruit traits. The diversity in fruit traits clustered the accessions into nine classes and identified certain promising lines having desirable traits pertaining to total soluble salts (TSS, carotenoids, ripening index, weight and shape. Factor analysis of the morphometric data from Tomato Analyzer showed that the fruit shape is a complex trait shared by several factors. The 100% variance between round and flat fruit shapes was explained by one discriminant function having a canonical correlation of 0.874 by stepwise discriminant analysis. A set of 10 genes (ACS2, COP1, CYC-B, RIN, MSH2, NAC-NOR, PHOT1, PHYA, PHYB and PSY1 involved in various plant developmental processes were screened for SNP polymorphism by EcoTILLING. The genetic diversity in these genes revealed a total of 36 non-synonymous and 18 synonymous changes leading to the identification of 28 haplotypes. The average frequency of polymorphism across the genes was 0.038/Kb. Significant negative Tajima'D statistic in two of the genes, ACS2 and PHOT1 indicated the presence of rare alleles in low frequency. Our study indicates that while there is low polymorphic diversity in the genes regulating plant development, the population shows wider phenotype diversity. Nonetheless, morphological and genetic diversity of the present collection can be further exploited as potential resources in future.

  6. Structural change in developing countries: has it decreased gender inequality?

    OpenAIRE

    Rendall, Michelle

    2012-01-01

    This paper examines the evolution of female labor market outcomes from 1987 to 2008 by assessing the role of changing labor demand requirements in four developing countries: Brazil, Mexico, India and Thailand. The results highlight the importance of structural change in reducing gender disparities by decreasing the labor demand for physical attributes. The results show that India, the country with the greatest physical labor requirements, exhibits the largest labor market gender inequality. I...

  7. Decreasing burned children's pain behavior: impacting the trauma of hydrotherapy.

    OpenAIRE

    Kelley, M L; Jarvie, G J; Middlebrook, J L; McNeer, M F; Drabman, R S

    1984-01-01

    We evaluated the effects of cartoon viewing with the use of a star feedback chart on two burned children's pain behavior during their physical therapy sessions. In addition, the degree to which the observational data corresponded with physical therapists' and mothers' ratings of the children's pain, fear, and cooperativeness was examined. Using a reversal single-subject design, the results showed that the children's pain behavior substantially decreased during experimental treatment sessions ...

  8. Decreasing barriers for nurse practitioner social entrepreneurship.

    Science.gov (United States)

    Sharp, Dayle B; Monsivais, Diane

    2014-10-01

    To describe difficulties associated with the business-related aspects of practice in role transition of rural nurse practitioners (NPs), and to give practice implications. This focused ethnographic study derived data from semi-structured interviews. Participants provided information about rural NP practice ownership and barriers. The sample consisted of 24 rural NPs living throughout the United States. The majority were 51-60 years of age (45%) and females (93%) who had been in rural practice for 1 to over 20 years. NP social entrepreneurs experience difficulties related to scope of practice, business skills, and role conflict. To decrease barriers for NP clinic ownership and management, NPs need to receive education related to financing a rural practice, legal/regulatory practices, strategic planning, leadership, and clinic management. ©2014 American Association of Nurse Practitioners.

  9. Decreasing Ambiguity of the Safety Culture Concept

    International Nuclear Information System (INIS)

    Inoue, Shiichiro; Hosoda, Satoshi; Suganuma, Takashi; Monta, Kazuo; Kameda, Akiyuki

    2001-01-01

    The status of the concept of ''safety culture'' is reviewed. It has not sufficiently taken root. One cause for this is the abstract nature of the concept. Organizations must become aware of the necessity of improving safety and have sufficient power to promote this. The culture of safety must be instilled in each employee, so that each of them will feel responsible for identifying weak points in plant safety. The authors devised a tool for a self-assessment of the safety culture. The tool will bring to light information divides, communication gaps, etc. Recognizing the vulnerabilities of the organization by themselves and discussing these weak points among them is the first step to decrease the ambiguity of the safety culture. The next step is to make these gaps known along with agreed-upon countermeasures. The concept of safety culture will be greatly clarified in this way and lead to safer nuclear power plants

  10. Decrease in prosaposin in spermatozoon is associated with polychlorinated biphenyl exposure.

    Science.gov (United States)

    Cai, Jia-Li; Sun, Ling-Bin; Guo, Zhi-Zhun; Jiang, Xiao-Ming; Zheng, Guan-Chao; Qiu, Hui-Ling; Sha, Ai-Guo; Wang, Chong-Gang; Ren, Jian-Zhi; Zuo, Zheng-Hong

    2015-01-01

    Polychlorinated biphenyls (PCBs) are a class of ubiquitous persistent organic pollutants and they have been associated with declining male fertility. In the present study, we aimed to determine the responsiveness of prosaposin (Psap) expression to PCB exposure. Male C57 mice were exposed to PCB mixture (Aroclor 1254) of environmental related doses by oral gavage. After exposure for 50 days, the expression of Psap was significantly decreased by PCB exposure in epididymides and epydidymal spermatozoa, but not in testis. The Psap abundance in sperm was decreased in a dose-dependent manner. Benchmark dose modeling revealed the 95% lower confidence limit on the benchmark dose (BMDL) and Benchmark Dose (BMD) for Psap reduction were 1.25 and 8.89 μg/kg Aroclor 1254, and for sperm motility reduction were 11.85 and 61.9 μg/kg Aroclor 1254. The depressed Psap level also showed a significant correlation (P<0.01, r=-0.531) with PCB accumulation in liver. In men with detectable PCB exposure in semen, Psap expression in sperm was significantly decreased whereas the semen parameters were unaffected. Linear regression showed that a negative association between total PCB level in seminal plasma and Psap level in ejaculated spermatozoa (P<0.05, r=-0.396). In conclusion, our data suggested that the abundance of Psap in sperm sample may be a sensitive endpoint to predict PCB exposure.

  11. Climate change decreases aquatic ecosystem productivity of Lake Tanganyika, Africa.

    Science.gov (United States)

    O'Reilly, Catherine M; Alin, Simone R; Plisnier, Pierre-Denis; Cohen, Andrew S; McKee, Brent A

    2003-08-14

    Although the effects of climate warming on the chemical and physical properties of lakes have been documented, biotic and ecosystem-scale responses to climate change have been only estimated or predicted by manipulations and models. Here we present evidence that climate warming is diminishing productivity in Lake Tanganyika, East Africa. This lake has historically supported a highly productive pelagic fishery that currently provides 25-40% of the animal protein supply for the populations of the surrounding countries. In parallel with regional warming patterns since the beginning of the twentieth century, a rise in surface-water temperature has increased the stability of the water column. A regional decrease in wind velocity has contributed to reduced mixing, decreasing deep-water nutrient upwelling and entrainment into surface waters. Carbon isotope records in sediment cores suggest that primary productivity may have decreased by about 20%, implying a roughly 30% decrease in fish yields. Our study provides evidence that the impact of regional effects of global climate change on aquatic ecosystem functions and services can be larger than that of local anthropogenic activity or overfishing.

  12. COLCHICINE DECREASES AIRWAY HYPERACTIVITY AFTER PHOSGENE EXPOSURE

    Science.gov (United States)

    Phosgene (COCl(2)) exposure affects an influx of inflammatory cells into the lung, which can be reduced in an animal model by pretreatment with colchicine. Inflammation in the respiratory tract can be associated with an increase in airway hyperreactivity. We tested the hypotheses...

  13. Polistes olivaceous decreases biotic surface colonization

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-15

    Dec 15, 2009 ... Polistes olivaceous on oral biotic surface (biofilm) model by means of pH response, population of oral bacteria and enamel .... Another 50 subjects used oral rinses of 0.9% normal saline to serve as a negative control and ... Bacterial count of S. mutans, S. sanguis and S. salivarus in each flow. Bacteria.

  14. Bayesian analysis of repairable systems showing a bounded failure intensity

    International Nuclear Information System (INIS)

    Guida, Maurizio; Pulcini, Gianpaolo

    2006-01-01

    The failure pattern of repairable mechanical equipment subject to deterioration phenomena sometimes shows a finite bound for the increasing failure intensity. A non-homogeneous Poisson process with bounded increasing failure intensity is then illustrated and its characteristics are discussed. A Bayesian procedure, based on prior information on model-free quantities, is developed in order to allow technical information on the failure process to be incorporated into the inferential procedure and to improve the inference accuracy. Posterior estimation of the model-free quantities and of other quantities of interest (such as the optimal replacement interval) is provided, as well as prediction on the waiting time to the next failure and on the number of failures in a future time interval is given. Finally, numerical examples are given to illustrate the proposed inferential procedure

  15. Measuring political polarization: Twitter shows the two sides of Venezuela

    Science.gov (United States)

    Morales, A. J.; Borondo, J.; Losada, J. C.; Benito, R. M.

    2015-03-01

    We say that a population is perfectly polarized when divided in two groups of the same size and opposite opinions. In this paper, we propose a methodology to study and measure the emergence of polarization from social interactions. We begin by proposing a model to estimate opinions in which a minority of influential individuals propagate their opinions through a social network. The result of the model is an opinion probability density function. Next, we propose an index to quantify the extent to which the resulting distribution is polarized. Finally, we apply the proposed methodology to a Twitter conversation about the late Venezuelan president, Hugo Chávez, finding a good agreement between our results and offline data. Hence, we show that our methodology can detect different degrees of polarization, depending on the structure of the network.

  16. A new and improved algorithm for the quantification of chromatin condensation from microscopic data shows decreased chromatin condensation in regenerating axolotl limb cells.

    Science.gov (United States)

    Sosnik, Julian; Vieira, Warren A; Webster, Kaitlyn A; Siegfried, Kellee R; McCusker, Catherine D

    2017-01-01

    The nuclear landscape plays an important role in the regulation of tissue and positional specific genes in embryonic and developing cells. Changes in this landscape can be dynamic, and are associated with the differentiation of cells during embryogenesis, and the de-differentiation of cells during induced pluripotent stem cell (iPSC) formation and in many cancers. However, tools to quantitatively characterize these changes are limited, especially in the in vivo context, where numerous tissue types are present and cells are arranged in multiple layers. Previous tools have been optimized for the monolayer nature of cultured cells. Therefore, we present a new algorithm to quantify the condensation of chromatin in two in vivo systems. We first developed this algorithm to quantify changes in chromatin compaction and validated it in differentiating spermatids in zebrafish testes. Our algorithm successfully detected the typical increase in chromatin compaction as these cells differentiate. We then employed the algorithm to quantify the changes that occur in amphibian limb cells as they participate in a regenerative response. We observed that the chromatin in the limb cells de-compacts as they contribute to the regenerating organ. We present this new tool as an open sourced software that can be readily accessed and optimized to quantify chromatin compaction in complex multi-layered samples.

  17. A new and improved algorithm for the quantification of chromatin condensation from microscopic data shows decreased chromatin condensation in regenerating axolotl limb cells.

    Directory of Open Access Journals (Sweden)

    Julian Sosnik

    Full Text Available The nuclear landscape plays an important role in the regulation of tissue and positional specific genes in embryonic and developing cells. Changes in this landscape can be dynamic, and are associated with the differentiation of cells during embryogenesis, and the de-differentiation of cells during induced pluripotent stem cell (iPSC formation and in many cancers. However, tools to quantitatively characterize these changes are limited, especially in the in vivo context, where numerous tissue types are present and cells are arranged in multiple layers. Previous tools have been optimized for the monolayer nature of cultured cells. Therefore, we present a new algorithm to quantify the condensation of chromatin in two in vivo systems. We first developed this algorithm to quantify changes in chromatin compaction and validated it in differentiating spermatids in zebrafish testes. Our algorithm successfully detected the typical increase in chromatin compaction as these cells differentiate. We then employed the algorithm to quantify the changes that occur in amphibian limb cells as they participate in a regenerative response. We observed that the chromatin in the limb cells de-compacts as they contribute to the regenerating organ. We present this new tool as an open sourced software that can be readily accessed and optimized to quantify chromatin compaction in complex multi-layered samples.

  18. Airline Overbooking Problem with Uncertain No-Shows

    Directory of Open Access Journals (Sweden)

    Chunxiao Zhang

    2014-01-01

    Full Text Available This paper considers an airline overbooking problem of a new single-leg flight with discount fare. Due to the absence of historical data of no-shows for a new flight, and various uncertain human behaviors or unexpected events which causes that a few passengers cannot board their aircraft on time, we fail to obtain the probability distribution of no-shows. In this case, the airlines have to invite some domain experts to provide belief degree of no-shows to estimate its distribution. However, human beings often overestimate unlikely events, which makes the variance of belief degree much greater than that of the frequency. If we still regard the belief degree as a subjective probability, the derived results will exceed our expectations. In order to deal with this uncertainty, the number of no-shows of new flight is assumed to be an uncertain variable in this paper. Given the chance constraint of social reputation, an overbooking model with discount fares is developed to maximize the profit rate based on uncertain programming theory. Finally, the analytic expression of the optimal booking limit is obtained through a numerical example, and the results of sensitivity analysis indicate that the optimal booking limit is affected by flight capacity, discount, confidence level, and parameters of the uncertainty distribution significantly.

  19. Calcium enhances cadmium tolerance and decreases cadmium ...

    African Journals Online (AJOL)

    We aimed at characterizing mechanisms controlling cadmium accumulation in lettuce, which is a food crop showing one of the highest capacities to accumulate this toxic compound. In this study, plants from three lettuce varieties were grown for eight days on media supplemented or not with cadmium (15 μM CdCl2) and ...

  20. Assessment of health impacts of decreased smoking prevalence in Copenhagen

    DEFF Research Database (Denmark)

    Holm, Astrid Ledgaard; Brønnum-Hansen, Henrik; Robinson, Kirstine Magtengaard

    2014-01-01

    Tobacco smoking is among the leading risk factors for chronic disease and early death in developed countries, including Denmark, where smoking causes 14% of the disease burden. In Denmark, many public health interventions, including smoking prevention, are undertaken by the municipalities......, but models to estimate potential health effects of local interventions are lacking. The aim of the current study was to model the effects of decreased smoking prevalence in Copenhagen, Denmark. Methods: The DYNAMO-HIA model was applied to the population of Copenhagen, by using health survey data and data......, and cessation and re-initiation rates among adults, which reduced the smoking prevalence to 4% by 2025, would have large beneficial effects on incidence and prevalence of smoking-related diseases and mortality. Health benefits could also be obtained through interventions targeting only cessation or re...

  1. El aumento de la expresión del ARNm de la enzima convertidora de angiotensina I homóloga (ECA-2 inducido por atorvastatina se asocia a menor fibrosis e hipertrofia ventricular izquierda en un modelo de cardiomiopatía diabética Atorvastatin induced increase in homologous angiotensin i converting enzyme (ACE2 mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Cristian Aguilar

    2011-06-01

    content assay and genetic expressions of ACE and ACE2 mRNA. Results. Myocardial hypertrophy index and collagen deposition were increased in diabetic rats, but not in the treated-diabetic rats, without producing changes in cholesterol levels. Myocardial ACE mRNA levels were increased while ACE2 mRNA levels were decreased in diabetic rats. Atorvastatin administration attenuated overexpression of ACE mRNA and overexpression of ACE-2 mRNA in diabetic rats. Conclusions. Our results indicate that atorvastatin, independently of its cholesterol-lowering capacity, lowers the ACE/ACE2 ratio to normal values and attenuates the development of adverse remodeling in the diabetic heart.

  2. Playing prosocial video games increases empathy and decreases schadenfreude.

    Science.gov (United States)

    Greitemeyer, Tobias; Osswald, Silvia; Brauer, Markus

    2010-12-01

    Past research provided abundant evidence that exposure to violent video games increases aggressive tendencies and decreases prosocial tendencies. In contrast, research on the effects of exposure to prosocial video games has been relatively sparse. The present research found support for the hypothesis that exposure to prosocial video games is positively related to prosocial affect and negatively related to antisocial affect. More specifically, two studies revealed that playing a prosocial (relative to a neutral) video game increased interpersonal empathy and decreased reported pleasure at another's misfortune (i.e., schadenfreude). These results lend further credence to the predictive validity of the General Learning Model (Buckley & Anderson, 2006) for the effects of media exposure on social tendencies.

  3. Decreased chewing activity during mouth breathing.

    Science.gov (United States)

    Hsu, H-Y; Yamaguchi, K

    2012-08-01

    This study examined the effect of mouth breathing on the strength and duration of vertical effect on the posterior teeth using related functional parameters during 3 min of gum chewing in 39 nasal breathers. A CO(2) sensor was placed over the mouth to detect expiratory airflow. When no airflow was detected from the mouth throughout the recording period, the subject was considered a nasal breather and enrolled in the study. Electromyographic (EMG) activity was recorded during 3 min of gum chewing. The protocol was repeated with the nostrils occluded. The strength of the vertical effect was obtained as integrated masseter muscle EMG activity, and the duration of vertical effect was also obtained as chewing stroke count, chewing cycle variation and EMG activity duration above baseline. Baseline activity was obtained from the isotonic EMG activity during jaw movement at 1.6 Hz without making tooth contact. The duration represented the percentage of the active period above baseline relative to the 3-min chewing period. Paired t-test and repeated analysis of variance were used to compare variables between nasal and mouth breathing. The integrated EMG activity and the duration of EMG activity above baseline, chewing stroke count and chewing cycle significantly decreased during mouth breathing compared with nasal breathing (Pbreathing was significantly greater than nasal breathing (Pbreathing reduces the vertical effect on the posterior teeth, which can affect the vertical position of posterior teeth negatively, leading to malocclusion. © 2012 Blackwell Publishing Ltd.

  4. Lower skin temperature decreases maximal cycling performance.

    Science.gov (United States)

    Imai, Daiki; Okazaki, Kazunobu; Matsumura, Shinya; Suzuki, Takashi; Miyazawa, Taiki; Suzuki, Akina; Takeda, Ryosuke; Hamamoto, Takeshi; Zako, Tetsuo; Kawabata, Takashi; Miyagawa, Toshiaki

    2011-12-01

    It is known that external cooling of body regions involved in exercise, prior to exercise, decreases anaerobic performance. However, there have been no studies reporting the effects of whole body skin surface cooling before exercise on maximal anaerobic capacity. In order to clarify the effects, we compared power output during the Wingate anaerobic test between preconditioning by exposure to temperature 10 degrees C and 25 degrees C. Eight healthy males carried out the Wingate test for 30 seconds, after pre-conditioning for 60 minutes using a perfusion suit with water at a temperature of 10 degrees C or 25 degrees C. We evaluated the peak power (PP) and peak power slope (PS) of the power output. Mean skin temperature (T(sk)) at 60 minutes of pre-conditioning in the 10 degrees C trial was significantly lower than in the 25 degrees C trial (p < 0.05). PP and also PS were significantly lower in the 10 degrees C trial than in the 25 degrees C trial. Changes (Δ) in PP between the 10 degrees C trial and the 25 degrees C trial were strongly correlated with ΔT(sk) and Δ in thigh and leg skin temperature (ΔT(thigh) and ΔT(leg), respectively), whereas ΔPS was strongly correlated with ΔT(sk), but not with ΔT(thigh) and ΔT(leg). Whole body skin surface cooling prior to exercise restricts anaerobic capacity, especially in the initial phase of exercise.

  5. Organophosphate pesticides induce morphological abnormalities and decrease locomotor activity and heart rate in Danio rerio and Xenopus laevis.

    Science.gov (United States)

    Watson, Fiona L; Schmidt, Hayden; Turman, Zackery K; Hole, Natalie; Garcia, Hena; Gregg, Jonathan; Tilghman, Joseph; Fradinger, Erica A

    2014-06-01

    Organophosphate pesticides (OPs), a class of acetylcholinesterase inhibitors, are used widely in agriculture to reduce insect populations. Because of the conservation of acetylcholinesterase between invertebrates and vertebrates, OPs also can adversely affect nontarget species, such as aquatic and terrestrial animals. This study used uniform conditions to analyze the morphological and physiological effects caused by developmental exposure to 3 commonly used OPs-chlorpyrifos, dichlorvos, and diazinon-on 2 aquatic vertebrate species, Danio rerio (zebrafish) and Xenopus laevis. Survival, locomotor activity, heart rate, and gross anatomical abnormalities, including kyphosis and edema, were observed over a 5-d period in response to OP concentrations ranging from 0 µM to 1000 µM. Both zebrafish and Xenopus showed decreased survival for all 3 OPs at higher concentrations. However, Xenopus showed higher mortality than zebrafish at lower chlorpyrifos and dichlorvos concentrations. Both models showed a dose-dependent decrease in heart rate and free-swimming larval activity in response to chlorpyrifos and dichlorvos. In addition, kyphosis and decreased spine length were prominent in Xenopus in response to 10 µM of chlorpyrifos and 0.1 µM dichlorvos. Although diazinon induced no effects on skeletal and cardiac motor activity in either species, it did induce cardiac edemas in zebrafish. Differences in the biological actions of OPs and their differential effects in these 2 vertebrate models demonstrate the importance of using common protocols and multiple models to evaluate the ecotoxicology of OPs. © 2014 SETAC.

  6. Task conflict in the Stroop task: When Stroop interference decreases as Stroop facilitation increases in a low task conflict context

    Directory of Open Access Journals (Sweden)

    Benjamin Andrew Parris

    2014-10-01

    Full Text Available In the present study participants completed two blocks of the Stroop task, one in which the Response-Stimulus Interval (RSI was 3500ms and one in which RSI was 200ms. It was expected that, in line with previous research, the shorter RSI would induce a low Task Conflict context by increasing focus on the colour identification goal in the Stroop task. Based on previous research showing the role of Task Conflict in the presence or absence Stroop facilitation, this was expected to lead to the novel finding of an increase in facilitation and simultaneous decrease in interference. Such a finding would be problematic for models of Stroop effects that predict these indices of performance should be affected in tandem. A crossover interaction is reported supporting these predictions. As predicted, the shorter RSI resulted in incongruent and congruent trial RTs decreasing relative to a static neutral baseline condition; hence interference decreased as facilitation increased. An explanatory model (expanding on the work of Goldfarb, Henik and colleagues is presented that: 1 Shows how under certain conditions the predictions from single mechanism models hold true (i.e. when Task conflict is held constant; 2 Shows how it is possible that interference can be affected by an experimental manipulation that leaves facilitation apparently untouched and; 3 Predicts that facilitation cannot be independently affected by an experimental manipulation.

  7. Structured learning of human interactions in TV shows.

    Science.gov (United States)

    Patron-Perez, Alonso; Marszalek, Marcin; Reid, Ian; Zisserman, Andrew

    2012-12-01

    The objective of this work is recognition and spatiotemporal localization of two-person interactions in video. Our approach is person-centric. As a first stage we track all upper bodies and heads in a video using a tracking-by-detection approach that combines detections with KLT tracking and clique partitioning, together with occlusion detection, to yield robust person tracks. We develop local descriptors of activity based on the head orientation (estimated using a set of pose-specific classifiers) and the local spatiotemporal region around them, together with global descriptors that encode the relative positions of people as a function of interaction type. Learning and inference on the model uses a structured output SVM which combines the local and global descriptors in a principled manner. Inference using the model yields information about which pairs of people are interacting, their interaction class, and their head orientation (which is also treated as a variable, enabling mistakes in the classifier to be corrected using global context). We show that inference can be carried out with polynomial complexity in the number of people, and describe an efficient algorithm for this. The method is evaluated on a new dataset comprising 300 video clips acquired from 23 different TV shows and on the benchmark UT--Interaction dataset.

  8. Thyroidectomy decreases snoring and sleep apnea symptoms.

    Science.gov (United States)

    Reiher, Alexandra E; Mazeh, Haggi; Schaefer, Sarah; Chen, Herbert; Sippel, Rebecca S

    2012-11-01

    Patients with goiter often complain of compressive symptoms, which may contribute to symptoms of obstructive sleep apnea (OSA). However, the impact of thyroid enlargement on these symptoms is not clear. Therefore, we sought to evaluate whether symptoms of sleep apnea resolved after thyroidectomy by using a validated questionnaire. The Berlin Questionnaire, a validated sleep apnea assessment tool, was provided to patients at a single academic institution before and after thyroidectomy. Patients who admitted to symptoms of snoring were asked to complete the questionnaire before and 8 weeks after surgery to assess for improvement in symptoms. The questionnaire uses 3 categories of questions to determine risk of sleep apnea. Two symptom categories must be positive for a patient to be considered high risk for sleep apnea. Forty-five patients completed both pre- and postoperative questionnaires. The average age of patients completing the questionnaire was 53±2 years, and 78% of patients were female. Average body mass index was 33.3±1.4 kg/m(2). Based on their preoperative questionnaire score, 71% of patients were considered to be high risk for OSA, and this decreased to 51% after surgery (p=0.002). Overall scores significantly improved after surgery (mean 2.0 vs. 1.6, psymptoms, gland weight at resection, presence of thyroiditis, or the largest dimension of the gland at resection. Thyroid surgery appears to significantly improve symptoms of OSA in patients who screened positive for symptoms before surgery. Evaluation of patients with OSA should include evaluation of thyroid disease, as symptoms of sleep apnea may improve with thyroidectomy.

  9. Decreasing post-succinylcholine myalgia in outpatients.

    Science.gov (United States)

    Melnick, B; Chalasani, J; Uy, N T; Phitayakorn, P; Mallett, S V; Rudy, T E

    1987-05-01

    The effectiveness of four pretreatment regimens in decreasing succinylcholine-induced myalgias was studied in healthy outpatients undergoing general anaesthesia for ambulatory surgery. Four hundred and forty adult females were randomly assigned to one of four pretreatment groups. Three hundred and ninety-five patients completed the study. One of the following pretreatments was given prior to injection of 1.5 mg X kg-1 of succinylcholine: normal saline IV three minutes and again immediately prior to succinylcholine; 0.06 mg X kg-1 d-tubo-curarine (dTc) IV three minutes prior and normal saline IV immediately prior; normal saline IV three minutes prior and 1.5 mg X kg-1 lidocaine IV immediately prior; 0.06 mg X kg-1 dTc IV three minutes prior and 1.5 mg X kg-1 lidocaine IV immediately prior. Fasciculations after injection of succinylcholine were observed and recorded. Patients were contacted by telephone 40-48 hours postoperatively and questioned about the presence of muscle pains. These pains, if present, were graded either mild or moderate to severe. The patients in the two dTc-containing groups exhibited less fasciculations than patients in the other two experimental groups. The dTc-lidocaine group had a lower incidence of moderate to severe fasciculations than in any of the other three groups. Patients in the dTc, lidocaine, and dTc-lidocaine experimental groups reported a higher incidence of absence of muscle pain and a lower incidence of moderate-severe pain than did patients in the saline group. The dTc-lidocaine group had more patients without myalgia and less patients with moderate to severe myalgias than any of the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Physics Outreach: Road Shows and World Year of Physics 2005

    Science.gov (United States)

    Micklavzina, Stanley

    2003-05-01

    The general public's awareness of science and physics is decreasing along with the number of physics students at universities on a global scale. One way to increase public and student interest while promoting the university's image is through science outreach activities. In February the APS sponsored a Physics Road Show Conference in Fort Collins Colorado where 55 attendees from around the country shared program information and exchanged ideas about different types of physics (and other science) outreach activities. Papers describing some of the programs can be found at the APS Forum on Education Spring 2003 newsletter: http://www.aps.org/units/fed/spring2003/index.html . The inspiration for the conference is the IUPAP's declaration making 2005 The World Year in Physics. In planning for 2005, the APS has initiated a communication avenue for discussion of ideas of how we bring physics to the public in 2005. If you would like to join in on the discussion visit http://listsvr.apsmsgs.org/cgi-bin/lyris.pl?enter=physicsontheroad . I will share highlights from the conference and ideas developing for 2005.

  11. Decreased Expression of DREAM Promotes the Degeneration of Retinal Neurons

    Science.gov (United States)

    Chintala, Shravan; Cheng, Mei; Zhang, Xiao

    2015-01-01

    The intrinsic mechanisms that promote the degeneration of retinal ganglion cells (RGCs) following the activation of N-Methyl-D-aspartic acid-type glutamate receptors (NMDARs) are unclear. In this study, we have investigated the role of downstream regulatory element antagonist modulator (DREAM) in NMDA-mediated degeneration of the retina. NMDA, phosphate-buffered saline (PBS), and MK801 were injected into the vitreous humor of C57BL/6 mice. At 12, 24, and 48 hours after injection, expression of DREAM in the retina was determined by immunohistochemistry, western blot analysis, and electrophoretic mobility-shift assay (EMSA). Apoptotic death of cells in the retina was determined by terminal deoxynucleotidyl transferace dUTP nick end labeling (TUNEL) assays. Degeneration of RGCs in cross sections and in whole mount retinas was determined by using antibodies against Tuj1 and Brn3a respectively. Degeneration of amacrine cells and bipolar cells was determined by using antibodies against calretinin and protein kinase C (PKC)-alpha respectively. DREAM was expressed constitutively in RGCs, amacrine cells, bipolar cells, as well as in the inner plexiform layer (IPL). NMDA promoted a progressive decrease in DREAM levels in all three cell types over time, and at 48 h after NMDA-treatment very low DREAM levels were evident in the IPL only. DREAM expression in retinal nuclear proteins was decreased progressively after NMDA-treatment, and correlated with its decreased binding to the c-fos-DRE oligonucleotides. A decrease in DREAM expression correlated significantly with apoptotic death of RGCs, amacrine cells and bipolar cells. Treatment of eyes with NMDA antagonist MK801, restored DREAM expression to almost normal levels in the retina, and significantly decreased NMDA-mediated apoptotic death of RGCs, amacrine cells, and bipolar cells. Results presented in this study show for the first time that down-regulation of DREAM promotes the degeneration of RGCs, amacrine cells, and

  12. Does improving Public Transport decrease Car Ownership? Evidence from the Copenhagen Metropolitan Area

    DEFF Research Database (Denmark)

    Mulalic, Ismir; Pilegaard, Ninette; Rouwendal, Jan

    Car ownership is lower in urban areas, which is probably related to the availability of better publict ransport. Better public transport thus may offer the possibility to relieve the many problems (congestion,health, and parking) associated with the presence of cars in urban areas. To investigate...... this issue, wedevelop and estimate a model for the simultaneous choice of a residential area and car ownership. Themodel is estimated on Danish register data for single-earner and dual-earners households in the greaterCopenhagen metropolitan area. We pay special attention to accessibility of the metro...... network whichoffers particularly high quality public transport. Simulations based on the estimated model show that forthe greater Copenhagen area a planned extension of the metro network decreases car ownership by 2-3%.Our results suggest also a substantial increase in the interest for living in areas...

  13. Architectures for Quantum Simulation Showing a Quantum Speedup

    Science.gov (United States)

    Bermejo-Vega, Juan; Hangleiter, Dominik; Schwarz, Martin; Raussendorf, Robert; Eisert, Jens

    2018-04-01

    One of the main aims in the field of quantum simulation is to achieve a quantum speedup, often referred to as "quantum computational supremacy," referring to the experimental realization of a quantum device that computationally outperforms classical computers. In this work, we show that one can devise versatile and feasible schemes of two-dimensional, dynamical, quantum simulators showing such a quantum speedup, building on intermediate problems involving nonadaptive, measurement-based, quantum computation. In each of the schemes, an initial product state is prepared, potentially involving an element of randomness as in disordered models, followed by a short-time evolution under a basic translationally invariant Hamiltonian with simple nearest-neighbor interactions and a mere sampling measurement in a fixed basis. The correctness of the final-state preparation in each scheme is fully efficiently certifiable. We discuss experimental necessities and possible physical architectures, inspired by platforms of cold atoms in optical lattices and a number of others, as well as specific assumptions that enter the complexity-theoretic arguments. This work shows that benchmark settings exhibiting a quantum speedup may require little control, in contrast to universal quantum computing. Thus, our proposal puts a convincing experimental demonstration of a quantum speedup within reach in the near term.

  14. Decreasing the stable trapping region during geomagnetic storm

    International Nuclear Information System (INIS)

    Mal'tsev, Yu.P.; Feshchenko, E.Yu.

    1998-01-01

    Within the frameworks of the magnetic field model, depending on the solar wind pressure, the B = B s (B s is the magnetic field in the undersolar point) contour behaviour in the equatorial plane is calculated. The boundary of stable trapping in the quiet time is at the distance of 10-11 R E by day and ∼ 7 R E by night. During strong storms this distance may be decreased up 4-5 R E . The calculation results coincide satisfactorily with satellite measurements

  15. Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

    Science.gov (United States)

    Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

  16. The Auckland Volcanic Field - a basaltic field showing random behavior?

    Science.gov (United States)

    Le Corvec, N.; Rowland, J. V.; Lindsay, J. M.

    2012-04-01

    Basaltic monogenetic volcanism is a worldwide phenomenon typically producing fields of volcanic centers that increase in number with time. The process of field growth is not constant but punctuated by single eruptions, flare-ups and hiatuses. The development of a volcanic field involves physical processes that occur in the mantle, where batches of basaltic magma originate, and within the intervening lithosphere through which magma is transferred to the surface. The spatial and temporal distribution of volcanic centers within such volcanic fields results from, and thus may provide insights to, these physical processes (e.g., magma production, tectonic controls), thereby aiding in our understanding of a volcanic field's future development. The Auckland Volcanic Field (AVF), which lies in the most populated area of New Zealand, comprises 50 volcanic centers and produced its last eruption ~600 years ago. A recent study has provided a relative chronology of the entire sequence of eruptions, which is here used together with the spatial distribution of volcanic centers to investigate the evolution of the field in time and space. Two methods were used: 1) the Poisson Nearest Neighbor (PNN) analysis which evaluates the spatial distribution of a natural population over the spatial distribution of a statistical random model, the Poisson model; and 2) the Voronoi analysis which evaluates the spatial characteristics of each volcanic center by dividing a region (i.e., the volcanic field) into a set of polygons. The results of the PNN analysis show that the temporal evolution of the spatial distribution of the volcanic centers within the AVF follows the Poisson model, therefore they cannot be used to extrapolate the future evolution of the volcanic field. The preliminary results of the Voronoi analysis show in combination with the geochemical signatures from some volcanic centers a possible zonation within the source region, and/or the magmas may be variably affected on their way

  17. Decreased retinal sensitivity in depressive disorder

    DEFF Research Database (Denmark)

    Berman, G.; Muttuvelu, D.; Berman, D.

    2018-01-01

    . The pupil light reflex was measured at inclusion and in the following summer using a binocular pupillometer. A protocol of low (1 lux) and high (400 lux) intensity red and blue lights was used to assess rod, cone and melanopsin-containing intrinsic photosensitive retinal ganglion cell input to the pupil...... reflex. RESULTS: The mean group pupil responses associated with a melanopsin-mediated sustained pupil response at 400 lux blue light were significantly reduced in the depressed subjects (N = 39) as compared to the healthy controls (N = 24) (P = 0.023). Across all groups, a reduction in number of daylight...... hours was significantly associated with a reduction in sustained pupil response (P = 0.007). All groups showed an equal effect of daylight hours on the melanopsin-mediated sustained pupil response. CONCLUSION: The melanopsin-mediated sustained pupil contraction to offset of high-intensity blue light...

  18. Modafinil decreases anxiety-like behaviour in zebrafish.

    Science.gov (United States)

    Johnson, Adrian; Hamilton, Trevor James

    2017-01-01

    Modafinil (2-((diphenylmethyl)sulfinyl)acetamide), a selective dopamine and norepinephrine transporter inhibitor, is most commonly prescribed for narcolepsy but has gained recent interest for treating a variety of disorders. Zebrafish ( Danio rerio) are becoming a model of choice for pharmacological and behavioural research. To investigate the behavioural effects of modafinil on anxiety, we administered doses of 0, 2, 20, and 200 mg/L for 30 minutes then tested zebrafish in the novel approach test. In this test, the fish was placed into a circular arena with a novel object in the center and motion-tracking software was used to quantify the time the fish spent in the outer area of the arena (thigmotaxis zone), middle third of the arena (transition zone) and center of the arena, as well as total distance traveled, immobility and meandering. Modafinil caused a decrease in time spent in the thigmotaxis zone and increased time spent in the transition zone across all doses. Modafinil did not significantly alter the time spent in the center zone (near the novel object), the distance moved, meandering, or the duration of time spent immobile. We also validated this test as a measure of anxiety with the administration of ethanol (1%) which decreased time spent in the thigmotaxis zone and increased time spent in the transition zone. These results suggest that modafinil decreases anxiety-like behaviour in zebrafish.

  19. Modafinil decreases anxiety-like behaviour in zebrafish

    Directory of Open Access Journals (Sweden)

    Adrian Johnson

    2017-02-01

    Full Text Available Modafinil (2-((diphenylmethylsulfinylacetamide, a selective dopamine and norepinephrine transporter inhibitor, is most commonly prescribed for narcolepsy but has gained recent interest for treating a variety of disorders. Zebrafish (Danio rerio are becoming a model of choice for pharmacological and behavioural research. To investigate the behavioural effects of modafinil on anxiety, we administered doses of 0, 2, 20, and 200 mg/L for 30 minutes then tested zebrafish in the novel approach test. In this test, the fish was placed into a circular arena with a novel object in the center and motion-tracking software was used to quantify the time the fish spent in the outer area of the arena (thigmotaxis zone, middle third of the arena (transition zone and center of the arena, as well as total distance traveled, immobility and meandering. Modafinil caused a decrease in time spent in the thigmotaxis zone and increased time spent in the transition zone across all doses. Modafinil did not significantly alter the time spent in the center zone (near the novel object, the distance moved, meandering, or the duration of time spent immobile. We also validated this test as a measure of anxiety with the administration of ethanol (1% which decreased time spent in the thigmotaxis zone and increased time spent in the transition zone. These results suggest that modafinil decreases anxiety-like behaviour in zebrafish.

  20. Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and decrease levels of N-acylethanolamines in hippocampus

    DEFF Research Database (Denmark)

    Hansen, Suzanne L; Nielsen, Ane H; Knudsen, Katrine E

    2009-01-01

    The ketogenic diet (KD) is used for the treatment of refractory epilepsy in children, however, the mechanism(s) remains largely unknown. Also, the antiepileptogenic potential in animal models of epilepsy has been poorly addressed. Activation of cannabinoid type-1 recepto