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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

    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

  2. High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma.

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    Firdaus S Dhabhar

    Full Text Available In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED, 3 times/week, 10-weeks. The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome, and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th, cytolytic (CTL, and regulatory (Treg T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden, increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression, lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity, and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis. These results suggest that the deleterious effects of high trait anxiety

  3. Duchenne muscular dystrophy models show their age

    OpenAIRE

    Chamberlain, Jeffrey S.

    2010-01-01

    The lack of appropriate animal models has hampered efforts to develop therapies for Duchenne muscular dystrophy (DMD). A new mouse model lacking both dystrophin and telomerase (Sacco et al., 2010) closely mimics the pathological progression of human DMD and shows that muscle stem cell activity is a key determinant of disease severity.

  4. Rats with decreased brain cholecystokinin levels show increased responsiveness to peripheral electrical stimulation-induced analgesia.

    Science.gov (United States)

    Zhang, L X; Li, X L; Wang, L; Han, J S

    1997-01-16

    Using the P77PMC strain of rat, which is genetically prone to audiogenic seizures, and also has decreased levels of cholecystokinin (CCK), we examined the analgesic response to peripheral electrical stimulation, which is, in part, opiate-mediated. A number of studies have suggested that CCK may function as an antagonist to endogenous opiate effects. Therefore, we hypothesized that the P77PMC animals would show an enhanced analgesic response based on their decreased CCK levels producing a diminished endogenous opiate antagonism. We found that the analgesic effect on tail flick latency produced by 100 Hz peripheral electrical stimulation was more potent and longer lasting in P77PMC rats than in control rats. Moreover, the potency of the stimulation-produced analgesia correlated with the vulnerability to audiogenic seizures in these rats. We were able to block the peripheral electrical stimulation-induced analgesia (PSIA) using a cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay showed that the content of CCK-8 in cerebral cortex, hippocampus and periaqueductal gray was much lower in P77PMC rat than in controls. These results suggest that low CCK-8 content in the central nervous system of the P77PMC rats may be related to the high analgesic response to peripheral electrical stimulation, and further support the notion that CCK may be endogenous opiate antagonist.

  5. 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

  6. Ob/ob mouse livers show decreased oxidative phosphorylation efficiencies and anaerobic capacities after cold ischemia.

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    Michael J J Chu

    Full Text Available BACKGROUND: Hepatic steatosis is a major risk factor for graft failure in liver transplantation. Hepatic steatosis shows a greater negative influence on graft function following prolonged cold ischaemia. As the impact of steatosis on hepatocyte metabolism during extended cold ischaemia is not well-described, we compared markers of metabolic capacity and mitochondrial function in steatotic and lean livers following clinically relevant durations of cold preservation. METHODS: Livers from 10-week old leptin-deficient obese (ob/ob, n = 9 and lean C57 mice (n = 9 were preserved in ice-cold University of Wisconsin solution. Liver mitochondrial function was then assessed using high resolution respirometry after 1.5, 3, 5, 8, 12, 16 and 24 hours of storage. Metabolic marker enzymes for anaerobiosis and mitochondrial mass were also measured in conjunction with non-bicarbonate tissue pH buffering capacity. RESULTS: Ob/ob and lean mice livers showed severe (>60% macrovesicular and mild (<30% microvesicular steatosis on Oil Red O staining, respectively. Ob/ob livers had lower baseline enzymatic complex I activity but similar adenosine triphosphate (ATP levels compared to lean livers. During cold storage, the respiratory control ratio and complex I-fueled phosphorylation deteriorated approximately twice as fast in ob/ob livers compared to lean livers. Ob/ob livers also demonstrated decreased ATP production capacities at all time-points analyzed compared to lean livers. Ob/ob liver baseline lactate dehydrogenase activities and intrinsic non-bicarbonate buffering capacities were depressed by 60% and 40%, respectively compared to lean livers. CONCLUSIONS: Steatotic livers have impaired baseline aerobic and anaerobic capacities compared to lean livers, and mitochondrial function indices decrease particularly from after 5 hours of cold preservation. These data provide a mechanistic basis for the clinical recommendation of shorter cold storage durations in

  7. Fascicles and the interfascicular matrix show decreased fatigue life with ageing in energy storing tendons.

    Science.gov (United States)

    Thorpe, Chavaunne T; Riley, Graham P; Birch, Helen L; Clegg, Peter D; Screen, Hazel R C

    2017-07-01

    Tendon is composed of rope-like fascicles bound together by interfascicular matrix (IFM). The IFM is critical for the function of energy storing tendons, facilitating sliding between fascicles to allow these tendons to cyclically stretch and recoil. This capacity is required to a lesser degree in positional tendons. We have previously demonstrated that both fascicles and IFM in energy storing tendons have superior fatigue resistance compared with positional tendons, but the effect of ageing on the fatigue properties of these different tendon subunits has not been determined. Energy storing tendons become more injury-prone with ageing, indicating reduced fatigue resistance, hence we tested the hypothesis that the decline in fatigue life with ageing in energy storing tendons would be more pronounced in the IFM than in fascicles. We further hypothesised that tendon subunit fatigue resistance would not alter with ageing in positional tendons. Fascicles and IFM from young and old energy storing and positional tendons were subjected to cyclic fatigue testing until failure, and mechanical properties were calculated. The results show that both IFM and fascicles from the SDFT exhibit a similar magnitude of reduced fatigue life with ageing. By contrast, the fatigue life of positional tendon subunits was unaffected by ageing. The age-related decline in fatigue life of tendon subunits in energy storing tendons is likely to contribute to the increased risk of injury in aged tendons. Full understanding of the mechanisms resulting in this reduced fatigue life will aid in the development of treatments and interventions to prevent age-related tendinopathy. Understanding the effect of ageing on tendon-structure function relationships is crucial for the development of effective preventative measures and treatments for age-related tendon injury. In this study, we demonstrate for the first time that the fatigue resistance of the interfascicular matrix decreases with ageing in energy

  8. A single-nucleotide polymorphism of human neuropeptide s gene originated from Europe shows decreased bioactivity.

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    Cheng Deng

    Full Text Available Using accumulating SNP (Single-Nucleotide Polymorphism data, we performed a genome-wide search for polypeptide hormone ligands showing changes in the mature regions to elucidate genotype/phenotype diversity among various human populations. Neuropeptide S (NPS, a brain peptide hormone highly conserved in vertebrates, has diverse physiological effects on anxiety, fear, hyperactivity, food intake, and sleeping time through its cognate receptor-NPSR. Here, we report a SNP rs4751440 (L(6-NPS causing non-synonymous substitution on the 6(th position (V to L of the NPS mature peptide region. L(6-NPS has a higher allele frequency in Europeans than other populations and probably originated from European ancestors ~25,000 yrs ago based on haplotype analysis and Approximate Bayesian Computation. Functional analyses indicate that L(6-NPS exhibits a significant lower bioactivity than the wild type NPS, with ~20-fold higher EC50 values in the stimulation of NPSR. Additional evolutionary and mutagenesis studies further demonstrate the importance of the valine residue in the 6(th position for NPS functions. Given the known physiological roles of NPS receptor in inflammatory bowel diseases, asthma pathogenesis, macrophage immune responses, and brain functions, our study provides the basis to elucidate NPS evolution and signaling diversity among human populations.

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

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

    2013-05-01

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

  10. 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.

  11. Time dependent patient no-show predictive modelling development.

    Science.gov (United States)

    Huang, Yu-Li; Hanauer, David A

    2016-05-09

    Purpose - The purpose of this paper is to develop evident-based predictive no-show models considering patients' each past appointment status, a time-dependent component, as an independent predictor to improve predictability. Design/methodology/approach - A ten-year retrospective data set was extracted from a pediatric clinic. It consisted of 7,291 distinct patients who had at least two visits along with their appointment characteristics, patient demographics, and insurance information. Logistic regression was adopted to develop no-show models using two-thirds of the data for training and the remaining data for validation. The no-show threshold was then determined based on minimizing the misclassification of show/no-show assignments. There were a total of 26 predictive model developed based on the number of available past appointments. Simulation was employed to test the effective of each model on costs of patient wait time, physician idle time, and overtime. Findings - The results demonstrated the misclassification rate and the area under the curve of the receiver operating characteristic gradually improved as more appointment history was included until around the 20th predictive model. The overbooking method with no-show predictive models suggested incorporating up to the 16th model and outperformed other overbooking methods by as much as 9.4 per cent in the cost per patient while allowing two additional patients in a clinic day. Research limitations/implications - The challenge now is to actually implement the no-show predictive model systematically to further demonstrate its robustness and simplicity in various scheduling systems. Originality/value - This paper provides examples of how to build the no-show predictive models with time-dependent components to improve the overbooking policy. Accurately identifying scheduled patients' show/no-show status allows clinics to proactively schedule patients to reduce the negative impact of patient no-shows.

  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. Model of optical response of marine aerosols to Forbush decreases

    DEFF Research Database (Denmark)

    Bondo, Torsten; Enghoff, Martin Andreas Bødker; Svensmark, Henrik

    2010-01-01

    In order to elucidate the effect of galactic cosmic rays on cloud formation, we investigate the optical response of marine aerosols to Forbush decreases - abrupt decreases in galactic cosmic rays - by means of modeling. We vary the nucleation rate of new aerosols, in a sectional coagulation...

  15. Model shows future cut in U.S. ozone levels

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    A joint U.S. auto-oil industry research program says modeling shows that changing gasoline composition can reduce ozone levels for Los Angeles in 2010 and for New York City and Dallas-Fort Worth in 2005. The air quality modeling was based on vehicle emissions research data released late last year (OGJ, Dec. 24, 1990, p. 20). The effort is sponsored by the big three auto manufacturers and 14 oil companies. Sponsors the cars and small trucks account for about one third of ozone generated in the three cities studied but by 2005-10 will account for only 5-9%

  16. Swedish and American studies show that initiatives to decrease maternal obesity could play a key role in reducing preterm birth.

    Science.gov (United States)

    Gould, Jeffrey B; Mayo, Jonathan; Shaw, Gary M; Stevenson, David K

    2014-06-01

    Maternal obesity is a major source of preventable perinatal morbidity, but studies of the relationship between obesity and preterm birth have been inconsistent. This review looks at two major studies covering just under 3.5 million births, from California, USA, and Sweden. Inconsistent findings in previous studies appear to stem from the complex relationship between obesity and preterm birth. Initiatives to decrease maternal obesity represent an important strategy in reducing preterm birth. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  17. Ataxia telangiectasia derived iPS cells show preserved x-ray sensitivity and decreased chromosomal instability

    OpenAIRE

    Fukawatase, Yoshihiro; Toyoda, Masashi; Okamura, Kohji; Nakamura, Ken-ichi; Nakabayashi, Kazuhiko; Takada, Shuji; Yamazaki-Inoue, Mayu; Masuda, Akira; Nasu, Michiyo; Hata, Kenichiro; Hanaoka, Kazunori; Higuchi, Akon; Takubo, Kaiyo; Umezawa, Akihiro

    2014-01-01

    Ataxia telangiectasia is a neurodegenerative inherited disease with chromosomal instability and hypersensitivity to ionizing radiation. iPS cells lacking ATM (AT-iPS cells) exhibited hypersensitivity to X-ray irradiation, one of the characteristics of the disease. While parental ataxia telangiectasia cells exhibited significant chromosomal abnormalities, AT-iPS cells did not show any chromosomal instability in vitro for at least 80 passages (560 days). Whole exome analysis also showed a compa...

  18. Hip Fractures: What Information Does the Evidence Show That Patients and Families Need to Decrease 30-Day Readmission?

    Science.gov (United States)

    Gardner, Kristin OʼMara

    2015-01-01

    The current bundled payment reimbursement from the Centers for Medicare & Medicaid Services will not cover the additional cost of hospital readmission for the same diagnosis, and patients with hip fractures have one of the highest cost-saving opportunities when compared with other admission reasons. Common reasons for readmission to the hospital after hip fracture include pneumonia, dehydration, and mobility issues. The learning modalities including visual, aural, read/write, and kinesthetic were used to make recommendations on how the education can be incorporated into the instruction of patients with hip fractures and their families. These learning techniques can be used to develop education to decrease possibility of 30-day readmission after hip fracture. Nurses must focus their education to meet the needs of each individual patient, adapting to different types of adult learners to increase the health literacy of patients with hip fractures and their families.

  19. 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.

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

    Science.gov (United States)

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

    2003-08-01

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

  2. 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.

  3. 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

  4. Showing that the race model inequality is not violated

    DEFF Research Database (Denmark)

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

    2012-01-01

    important being race models and coactivation models. Redundancy gains consistent with the race model have an upper limit, however, which is given by the well-known race model inequality (Miller, 1982). A number of statistical tests have been proposed for testing the race model inequality in single...... participants and groups of participants. All of these tests use the race model as the null hypothesis, and rejection of the null hypothesis is considered evidence in favor of coactivation. We introduce a statistical test in which the race model prediction is the alternative hypothesis. This test controls...

  5. 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...

  6. Gene therapy decreases seizures in a model of Incontinentia pigmenti.

    Science.gov (United States)

    Dogbevia, Godwin K; Töllner, Kathrin; Körbelin, Jakob; Bröer, Sonja; Ridder, Dirk A; Grasshoff, Hanna; Brandt, Claudia; Wenzel, Jan; Straub, Beate K; Trepel, Martin; Löscher, Wolfgang; Schwaninger, Markus

    2017-07-01

    Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. In a mouse model of IP, we administered a single intravenous dose of the adeno-associated virus (AAV) vector, AAV-BR1-CAG-NEMO, delivering the Nemo gene to the brain endothelium. Spontaneous epileptic seizures and the integrity of the blood-brain barrier (BBB) were monitored. The endothelium-targeted gene therapy improved the integrity of the BBB. In parallel, it reduced the incidence of seizures and delayed their occurrence. Neonate mice intravenously injected with the AAV-BR1-CAG-NEMO vector developed no hepatocellular carcinoma or other major adverse effects 11 months after vector injection, demonstrating that the vector has a favorable safety profile. The data show that the BBB is a target of antiepileptic treatment and, more specifically, provide evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in IP. Ann Neurol 2017;82:93-104. © 2017 American Neurological Association.

  7. Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

    Science.gov (United States)

    Stohn, J Patrizia; Martinez, M Elena; Hernandez, Arturo

    2016-12-01

    Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Direct Covalent Grafting of Phytate to Titanium Surfaces through Ti-O-P Bonding Shows Bone Stimulating Surface Properties and Decreased Bacterial Adhesion.

    Science.gov (United States)

    Córdoba, Alba; Hierro-Oliva, Margarita; Pacha-Olivenza, Miguel Ángel; Fernández-Calderón, María Coronada; Perelló, Joan; Isern, Bernat; González-Martín, María Luisa; Monjo, Marta; Ramis, Joana M

    2016-05-11

    Myo-inositol hexaphosphate, also called phytic acid or phytate (IP6), is a natural molecule abundant in vegetable seeds and legumes. Among other functions, IP6 inhibits bone resorption. It is adsorbed on the surface of hydroxyapatite, inhibiting its dissolution and decreasing the progressive loss of bone mass. We present here a method to directly functionalize Ti surfaces covalently with IP6, without using a cross-linker molecule, through the reaction of the phosphate groups of IP6 with the TiO2 layer of Ti substrates. The grafting reaction consisted of an immersion in an IP6 solution to allow the physisorption of the molecules onto the substrate, followed by a heating step to obtain its chemisorption, in an adaptation of the T-Bag method. The reaction was highly dependent on the IP6 solution pH, only achieving a covalent Ti-O-P bond at pH 0. We evaluated two acidic pretreatments of the Ti surface, to increase its hydroxylic content, HNO3 30% and HF 0.2%. The structure of the coated surfaces was characterized by X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and ellipsometry. The stability of the IP6 coating after three months of storage and after sterilization with γ-irradiation was also determined. Then, we evaluated the biological effect of Ti-IP6 surfaces in vitro on MC3T3-E1 osteoblastic cells, showing an osteogenic effect. Finally, the effect of the surfaces on the adhesion and biofilm viability of oral microorganisms S. mutans and S. sanguinis was also studied, and we found that Ti-IP6 surfaces decreased the adhesion of S. sanguinis. A surface that actively improves osseointegration while decreasing the bacterial adhesion could be suitable for use in bone implants.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-12

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  11. Projected 21st century decrease in marine productivity: a multi-model analysis

    Directory of Open Access Journals (Sweden)

    M. Steinacher

    2010-03-01

    Full Text Available Changes in marine net primary productivity (PP and export of particulate organic carbon (EP are projected over the 21st century with four global coupled carbon cycle-climate models. These include representations of marine ecosystems and the carbon cycle of different structure and complexity. All four models show a decrease in global mean PP and EP between 2 and 20% by 2100 relative to preindustrial conditions, for the SRES A2 emission scenario. Two different regimes for productivity changes are consistently identified in all models. The first chain of mechanisms is dominant in the low- and mid-latitude ocean and in the North Atlantic: reduced input of macro-nutrients into the euphotic zone related to enhanced stratification, reduced mixed layer depth, and slowed circulation causes a decrease in macro-nutrient concentrations and in PP and EP. The second regime is projected for parts of the Southern Ocean: an alleviation of light and/or temperature limitation leads to an increase in PP and EP as productivity is fueled by a sustained nutrient input. A region of disagreement among the models is the Arctic, where three models project an increase in PP while one model projects a decrease. Projected changes in seasonal and interannual variability are modest in most regions. Regional model skill metrics are proposed to generate multi-model mean fields that show an improved skill in representing observation-based estimates compared to a simple multi-model average. Model results are compared to recent productivity projections with three different algorithms, usually applied to infer net primary production from satellite observations.

  12. Decreasing Kd uncertainties through the application of thermodynamic sorption models

    International Nuclear Information System (INIS)

    Domènech, Cristina; García, David; Pękala, Marek

    2015-01-01

    Radionuclide retardation processes during transport are expected to play an important role in the safety assessment of subsurface disposal facilities for radioactive waste. The linear distribution coefficient (K d ) is often used to represent radionuclide retention, because analytical solutions to the classic advection–diffusion-retardation equation under simple boundary conditions are readily obtainable, and because numerical implementation of this approach is relatively straightforward. For these reasons, the K d approach lends itself to probabilistic calculations required by Performance Assessment (PA) calculations. However, it is widely recognised that K d values derived from laboratory experiments generally have a narrow field of validity, and that the uncertainty of the K d outside this field increases significantly. Mechanistic multicomponent geochemical simulators can be used to calculate K d values under a wide range of conditions. This approach is powerful and flexible, but requires expert knowledge on the part of the user. The work presented in this paper aims to develop a simplified approach of estimating K d values whose level of accuracy would be comparable with those obtained by fully-fledged geochemical simulators. The proposed approach consists of deriving simplified algebraic expressions by combining relevant mass action equations. This approach was applied to three distinct geochemical systems involving surface complexation and ion-exchange processes. Within bounds imposed by model simplifications, the presented approach allows radionuclide K d values to be estimated as a function of key system-controlling parameters, such as the pH and mineralogy. This approach could be used by PA professionals to assess the impact of key geochemical parameters on the variability of radionuclide K d values. Moreover, the presented approach could be relatively easily implemented in existing codes to represent the influence of temporal and spatial changes in

  13. 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.

  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. Spared pre-irradiated area in pustular lesions induced by icotinib showing decreased expressions of CD1a+ langerhans cells and FGFR2

    International Nuclear Information System (INIS)

    Zhao Qiong; Wang Yi Na; Wang Bo

    2013-01-01

    Icotinib hydrochloride, a novel inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved by the State Food and Drug Administration for the treatment of advanced non-small-cell lung cancer. Up to date, cutaneous response to icotinib is largely unknown. Here we report an uncommon lesional phenomenon in a 56-year-old Chinese male with non-small-cell lung cancer, who received icotinib as a second-line treatment. Characteristic papulopustular rash on the chest and back was observed 4 days later. Interestingly, the rash completely spares a pre-irradiated area. The immunohistochemical study in the lesional skin area and spared skin area revealed a significant decrease in CD1a + Langerhans cells, Ki-67 as well as FGFR2 in the spared area than in the lesional area. Thus, the present case indicated that loss of the basal layer of proliferative cells and antigen-presenting cells (Langerhans cell), as well as the down-regulation of FGFR2 signaling in the pre-irradiated skin area, may join forces in inhibiting icotinib-associated cutaneous reactions. To our knowledge, this is the first report of both lesional area and lesion-spared area in a Chinese male receiving treatment with a new epidermal growth factor receptor-tyrosine kinase inhibitor (icotinib). The immunohistochemical reactions described here also provide new insight into the pathogenesis of epidermal growth factor receptor-tyrosine kinase inhibitor-related skin toxicities, and the role that other tyrosine kinase receptors (including FGFR) played in non-small-cell lung cancer. (author)

  16. Spared pre-irradiated area in pustular lesions induced by icotinib showing decreased expressions of CD1a+ langerhans cells and FGFR2.

    Science.gov (United States)

    Zhao, Qiong; Wang, Yi Na; Wang, Bo

    2013-02-01

    Icotinib hydrochloride, a novel inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved by the State Food and Drug Administration for the treatment of advanced non-small-cell lung cancer. Up to date, cutaneous response to icotinib is largely unknown. Here we report an uncommon lesional phenomenon in a 56-year-old Chinese male with non-small-cell lung cancer, who received icotinib as a second-line treatment. Characteristic papulopustular rash on the chest and back was observed 4 days later. Interestingly, the rash completely spares a pre-irradiated area. The immunohistochemical study in the lesional skin area and spared skin area revealed a significant decrease in CD1a(+) Langerhans cells, Ki-67 as well as FGFR2 in the spared area than in the lesional area. Thus, the present case indicated that loss of the basal layer of proliferative cells and antigen-presenting cells (Langerhans cell), as well as the down-regulation of FGFR2 signaling in the pre-irradiated skin area, may join forces in inhibiting icotinib-associated cutaneous reactions. To our knowledge, this is the first report of both lesional area and lesion-spared area in a Chinese male receiving treatment with a new epidermal growth factor receptor-tyrosine kinase inhibitor (icotinib). The immunohistochemical reactions described here also provide new insight into the pathogenesis of epidermal growth factor receptor-tyrosine kinase inhibitor-related skin toxicities, and the role that other tyrosine kinase receptors (including FGFR) played in non-small-cell lung cancer.

  17. 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.

  18. Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss.

    Directory of Open Access Journals (Sweden)

    Mathilde Doyard

    Full Text Available Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe-/- male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe-/- animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe-/- mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski's fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis.

  19. An Analytical Diffusion–Expansion Model for Forbush Decreases Caused by Flux Ropes

    Science.gov (United States)

    Dumbović, Mateja; Heber, Bernd; Vršnak, Bojan; Temmer, Manuela; Kirin, Anamarija

    2018-06-01

    We present an analytical diffusion–expansion Forbush decrease (FD) model ForbMod, which is based on the widely used approach of an initially empty, closed magnetic structure (i.e., flux rope) that fills up slowly with particles by perpendicular diffusion. The model is restricted to explaining only the depression caused by the magnetic structure of the interplanetary coronal mass ejection (ICME). We use remote CME observations and a 3D reconstruction method (the graduated cylindrical shell method) to constrain initial boundary conditions of the FD model and take into account CME evolutionary properties by incorporating flux rope expansion. Several flux rope expansion modes are considered, which can lead to different FD characteristics. In general, the model is qualitatively in agreement with observations, whereas quantitative agreement depends on the diffusion coefficient and the expansion properties (interplay of the diffusion and expansion). A case study was performed to explain the FD observed on 2014 May 30. The observed FD was fitted quite well by ForbMod for all expansion modes using only the diffusion coefficient as a free parameter, where the diffusion parameter was found to correspond to an expected range of values. Our study shows that, in general, the model is able to explain the global properties of an FD caused by a flux rope and can thus be used to help understand the underlying physics in case studies.

  20. Analysis of an inventory model for both linearly decreasing demand and holding cost

    Science.gov (United States)

    Malik, A. K.; Singh, Parth Raj; Tomar, Ajay; Kumar, Satish; Yadav, S. K.

    2016-03-01

    This study proposes the analysis of an inventory model for linearly decreasing demand and holding cost for non-instantaneous deteriorating items. The inventory model focuses on commodities having linearly decreasing demand without shortages. The holding cost doesn't remain uniform with time due to any form of variation in the time value of money. Here we consider that the holding cost decreases with respect to time. The optimal time interval for the total profit and the optimal order quantity are determined. The developed inventory model is pointed up through a numerical example. It also includes the sensitivity analysis.

  1. Spatial occupancy models applied to atlas data show Southern Ground Hornbills strongly depend on protected areas.

    Science.gov (United States)

    Broms, Kristin M; Johnson, Devin S; Altwegg, Res; Conquest, Loveday L

    2014-03-01

    Determining the range of a species and exploring species--habitat associations are central questions in ecology and can be answered by analyzing presence--absence data. Often, both the sampling of sites and the desired area of inference involve neighboring sites; thus, positive spatial autocorrelation between these sites is expected. Using survey data for the Southern Ground Hornbill (Bucorvus leadbeateri) from the Southern African Bird Atlas Project, we compared advantages and disadvantages of three increasingly complex models for species occupancy: an occupancy model that accounted for nondetection but assumed all sites were independent, and two spatial occupancy models that accounted for both nondetection and spatial autocorrelation. We modeled the spatial autocorrelation with an intrinsic conditional autoregressive (ICAR) model and with a restricted spatial regression (RSR) model. Both spatial models can readily be applied to any other gridded, presence--absence data set using a newly introduced R package. The RSR model provided the best inference and was able to capture small-scale variation that the other models did not. It showed that ground hornbills are strongly dependent on protected areas in the north of their South African range, but less so further south. The ICAR models did not capture any spatial autocorrelation in the data, and they took an order, of magnitude longer than the RSR models to run. Thus, the RSR occupancy model appears to be an attractive choice for modeling occurrences at large spatial domains, while accounting for imperfect detection and spatial autocorrelation.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Would Outsourcing Increase or Decrease Wage Inequality? Two Models, Two Answers

    OpenAIRE

    Wenli Cheng; Dingsheng Zhang

    2005-01-01

    This paper develops two models to study the impact of outsourcing on wage inequality between skilled and unskilled labor in the developed country and the developing country. The first model assumes symmetric production technologies in both countries, and predicts that outsourcing will increase wage inequality in the developed country, but decrease wage inequality in the developing country. The second model assumes asymmetric technologies in the production of the intermediate good and predicts...

  7. 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

  8. A low free-parameter stochastic model of daily Forbush decrease indices

    Science.gov (United States)

    Patra, Sankar Narayan; Bhattacharya, Gautam; Panja, Subhash Chandra; Ghosh, Koushik

    2014-01-01

    Forbush decrease is a rapid decrease in the observed galactic cosmic ray intensity pattern occurring after a coronal mass ejection. In the present paper we have analyzed the daily Forbush decrease indices from January, 1967 to December, 2003 generated in IZMIRAN, Russia. First the entire indices have been smoothened and next we have made an attempt to fit a suitable stochastic model for the present time series by means of a necessary number of process parameters. The study reveals that the present time series is governed by a stationary autoregressive process of order 2 with a trace of white noise. Under the consideration of the present model we have shown that chaos is not expected in the present time series which opens up the possibility of validation of its forecasting (both short-term and long-term) as well as its multi-periodic behavior.

  9. 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.

  10. Model of the synthesis of trisporic acid in Mucorales showing bistability.

    Science.gov (United States)

    Werner, S; Schroeter, A; Schimek, C; Vlaic, S; Wöstemeyer, J; Schuster, S

    2012-12-01

    An important substance in the signalling between individuals of Mucor-like fungi is trisporic acid (TA). This compound, together with some of its precursors, serves as a pheromone in mating between (+)- and (-)-mating types. Moreover, intermediates of the TA pathway are exchanged between the two mating partners. Based on differential equations, mathematical models of the synthesis pathways of TA in the two mating types of an idealised Mucor-fungus are here presented. These models include the positive feedback of TA on its own synthesis. The authors compare three sub-models in view of bistability, robustness and the reversibility of transitions. The proposed modelling study showed that, in a system where intermediates are exchanged, a reversible transition between the two stable steady states occurs, whereas an exchange of the end product leads to an irreversible transition. The reversible transition is physiologically favoured, because the high-production state of TA must come to an end eventually. Moreover, the exchange of intermediates and TA is compared with the 3-way handshake widely used by computers linked in a network.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  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. 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.

  19. Failure of CMIP5 climate models in simulating post-1950 decreasing trend of Indian monsoon

    Science.gov (United States)

    Saha, Anamitra; Ghosh, Subimal; Sahana, A. S.; Rao, E. P.

    2014-10-01

    Impacts of climate change on Indian Summer Monsoon Rainfall (ISMR) and the growing population pose a major threat to water and food security in India. Adapting to such changes needs reliable projections of ISMR by general circulation models. Here we find that, majority of new generation climate models from Coupled Model Intercomparison Project phase5 (CMIP5) fail to simulate the post-1950 decreasing trend of ISMR. The weakening of monsoon is associated with the warming of Southern Indian Ocean and strengthening of cyclonic formation in the tropical western Pacific Ocean. We also find that these large-scale changes are not captured by CMIP5 models, with few exceptions, which is the reason of this failure. Proper representation of these highlighted geophysical processes in next generation models may improve the reliability of ISMR projections. Our results also alert the water resource planners to evaluate the CMIP5 models before using them for adaptation strategies.

  20. 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

    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...... the absorption of phenolic acids. The difference between the artery and the vein for all phenolic acids was small, indicating that the release of phenolic acids in the large intestine was not sufficient to create a porto-arterial concentration difference. Although, the porto-arterial difference was small...... consumed. Benzoic acid derivatives showed low concentration in the plasma (phenolic acids, likely because it is an intermediate in the phenolic acid metabolism...

  1. 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.

  2. Rubber particle proteins, HbREF and HbSRPP, show different interactions with model membranes.

    Science.gov (United States)

    Berthelot, Karine; Lecomte, Sophie; Estevez, Yannick; Zhendre, Vanessa; Henry, Sarah; Thévenot, Julie; Dufourc, Erick J; Alves, Isabel D; Peruch, Frédéric

    2014-01-01

    The biomembrane surrounding rubber particles from the hevea latex is well known for its content of numerous allergen proteins. HbREF (Hevb1) and HbSRPP (Hevb3) are major components, linked on rubber particles, and they have been shown to be involved in rubber synthesis or quality (mass regulation), but their exact function is still to be determined. In this study we highlighted the different modes of interactions of both recombinant proteins with various membrane models (lipid monolayers, liposomes or supported bilayers, and multilamellar vesicles) to mimic the latex particle membrane. We combined various biophysical methods (polarization-modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS)/ellipsometry, attenuated-total reflectance Fourier-transform infrared (ATR-FTIR), solid-state nuclear magnetic resonance (NMR), plasmon waveguide resonance (PWR), fluorescence spectroscopy) to elucidate their interactions. Small rubber particle protein (SRPP) shows less affinity than rubber elongation factor (REF) for the membranes but displays a kind of "covering" effect on the lipid headgroups without disturbing the membrane integrity. Its structure is conserved in the presence of lipids. Contrarily, REF demonstrates higher membrane affinity with changes in its aggregation properties, the amyloid nature of REF, which we previously reported, is not favored in the presence of lipids. REF binds and inserts into membranes. The membrane integrity is highly perturbed, and we suspect that REF is even able to remove lipids from the membrane leading to the formation of mixed micelles. These two homologous proteins show affinity to all membrane models tested but neatly differ in their interacting features. This could imply differential roles on the surface of rubber particles. © 2013.

  3. Ab Initio Modeling Of Friction Reducing Agents Shows Quantum Mechanical Interactions Can Have Macroscopic Manifestation.

    Science.gov (United States)

    Hernández Velázquez, J D; Barroso-Flores, J; Gama Goicochea, A

    2016-11-23

    Two of the most commonly encountered friction-reducing agents used in plastic sheet production are the amides known as erucamide and behenamide, which despite being almost identical chemically, lead to markedly different values of the friction coefficient. To understand the origin of this contrasting behavior, in this work we model brushes made of these two types of linear-chain molecules using quantum mechanical numerical simulations under the density functional theory at the B97D/6-31G(d,p) level of theory. Four chains of erucamide and behenamide were linked to a 2 × 10 zigzag graphene sheet and optimized both in vacuum and in continuous solvent using the SMD implicit solvation model. We find that erucamide chains tend to remain closer together through π-π stacking interactions arising from the double bonds located at C13-C14, a feature behenamide lacks, and thus a more spread configuration is obtained with the latter. It is argued that this arrangement of the erucamide chains is responsible for the lower friction coefficient of erucamide brushes, compared with behenamide brushes, which is a macroscopic consequence of cooperative quantum mechanical interactions. While only quantum level interactions are modeled here, we show that behenamide chains are more spread out in the brush than erucamide chains as a consequence of those interactions. The spread-out configuration allows more solvent particles to penetrate the brush, leading in turn to more friction, in agreement with macroscopic measurements and mesoscale simulations of the friction coefficient reported in the literature.

  4. Decrease of Staphylococcus aureus Virulence by Helcococcus kunzii in a Caenorhabditis elegans Model.

    Science.gov (United States)

    Ngba Essebe, Christelle; Visvikis, Orane; Fines-Guyon, Marguerite; Vergne, Anne; Cattoir, Vincent; Lecoustumier, Alain; Lemichez, Emmanuel; Sotto, Albert; Lavigne, Jean-Philippe; Dunyach-Remy, Catherine

    2017-01-01

    Social bacterial interactions are considered essential in numerous infectious diseases, particularly in wounds. Foot ulcers are a common complication in diabetic patients and these ulcers become frequently infected. This infection is usually polymicrobial promoting cell-to-cell communications. Staphylococcus aureus is the most prevalent pathogen isolated. Its association with Helcococcus kunzii , commensal Gram-positive cocci, is frequently described. The aim of this study was to assess the impact of co-infection on virulence of both H. kunzii and S. aureus strains in a Caenorhabditis elegans model. To study the host response, qRT-PCRs targeting host defense genes were performed. We observed that H. kunzii strains harbored a very low (LT50: 5.7 days ± 0.4) or an absence of virulence (LT50: 6.9 days ± 0.5). In contrast, S. aureus strains (LT50: 2.9 days ± 0.4) were significantly more virulent than all H. kunzii ( P aureus strains were associated, H. kunzii significantly reduced the virulence of the S. aureus strain in nematodes (LT50 between 4.4 and 5.2 days; P aureus led to a strong induction of defense genes ( lys-5, sodh-1 , and cyp-37B1 ) while H. kunzii did not. No statistical difference of host response genes expression was observed when C. elegans were infected with either S. aureus alone or with S. aureus + H. kunzii . Moreover, two well-characterized virulence factors ( hla and agr ) present in S. aureus were down-regulated when S. aureus were co-infected with H. kunzii . This study showed that H. kunzii decreased the virulence of S. aureus without modifying directly the host defense response. Factor(s) produced by this bacterium modulating the staphylococci virulence must be investigated.

  5. Obesity decreases the oxidant stress induced by tobacco smoke in a rat model.

    Science.gov (United States)

    Montaño, Martha; Pérez-Ramos, J; Esquivel, A; Rivera-Rosales, R; González-Avila, G; Becerril, C; Checa, M; Ramos, C

    2016-09-01

    Obesity and emphysema are associated with low-grade systemic inflammation and oxidant stress. Assuming that the oxidant stress induced by emphysema would be decreased by obesity, we analyzed the oxidant/antioxidant state in a rat model combining both diseases simultaneously. Obesity was induced using sucrose, while emphysema by exposure to tobacco smoke. End-points evaluated were: body weight, abdominal fat, plasma dyslipidemia and malondialdehyde (MDA), insulin and glucose AUC, activities of Mn-superoxide dismutase (Mn-SOD), glutathione reductase (GR), glutathione transferase (GST) and glutathione peroxidase (GPx); lung MnSOD and 3-nitrotyrosine (3-NT) immunostaining, and expression of αV and β6 integrin subunits. In rats with obesity, the body weight, abdominal fat, plasma triglyceride levels, glucose AUC, insulin levels, GST activity, and αV and β6 integrin expressions were amplified. The rats with emphysema had lower values of body weight, abdominal fat, plasma insulin, triglycerides and glucose AUC but higher values of plasma MDA, GPx activity, and the lung expression of the αV and β6 integrins. The combination of obesity and emphysema compared to either condition alone led to diminished body weight, abdominal fat, plasma insulin MDA levels, GPx and GST activities, and αV and β6 integrin expressions; these parameters were all previously increased by obesity. Immunostaining for MnSOD augmented in all experimental groups, but the staining for 3-NT only increased in rats treated with tobacco alone or combined with sucrose. Results showed that obesity reduces oxidant stress and integrin expression, increasing antioxidant enzyme activities; these changes seem to partly contribute to a protective mechanism of obesity against emphysema development.

  6. Vortexlet models of flapping flexible wings show tuning for force production and control

    International Nuclear Information System (INIS)

    Mountcastle, A M; Daniel, T L

    2010-01-01

    Insect wings are compliant structures that experience deformations during flight. Such deformations have recently been shown to substantially affect induced flows, with appreciable consequences to flight forces. However, there are open questions related to the aerodynamic mechanisms underlying the performance benefits of wing deformation, as well as the extent to which such deformations are determined by the boundary conditions governing wing actuation together with mechanical properties of the wing itself. Here we explore aerodynamic performance parameters of compliant wings under periodic oscillations, subject to changes in phase between wing elevation and pitch, and magnitude and spatial pattern of wing flexural stiffness. We use a combination of computational structural mechanics models and a 2D computational fluid dynamics approach to ask how aerodynamic force production and control potential are affected by pitch/elevation phase and variations in wing flexural stiffness. Our results show that lift and thrust forces are highly sensitive to flexural stiffness distributions, with performance optima that lie in different phase regions. These results suggest a control strategy for both flying animals and engineering applications of micro-air vehicles.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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 Institutional support: RVO:86652079 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 Subject RIV: GC - Agronomy OBOR OECD: Agronomy, plant breeding and plant protection Impact factor: 2.571, year: 2016

  14. Xiao-Qing-Long-Tang shows preventive effect of asthma in an allergic asthma mouse model through neurotrophin regulation

    Science.gov (United States)

    2013-01-01

    Background This study investigates the effect of Xiao-Qing-Long-Tang (XQLT) on neurotrophin in an established mouse model of Dermatophagoides pteronyssinus (Der p)-induced acute allergic asthma and in a LA4 cell line model of lung adenoma. The effects of XQLT on the regulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), airway hyper-responsiveness (AHR) and immunoglobulin E were measured. Methods LA4 cells were stimulated with 100 μg/ml Der p 24 h and the supernatant was collected for ELISA analysis. Der p-stimulated LA4 cells with either XQLT pre-treatment or XQLT co-treatment were used to evaluate the XQLT effect on neurotrophin. Balb/c mice were sensitized on days 0 and 7 with a base-tail injection of 50 μg Dermatophagoides pteronyssinus (Der p) that was emulsified in 50 μl incomplete Freund’s adjuvant (IFA). On day 14, mice received an intra-tracheal challenge of 50 μl Der p (2 mg/ml). XQLT (1g/Kg) was administered orally to mice either on days 2, 4, 6, 8, 10 and 12 as a preventive strategy or on day 15 as a therapeutic strategy. Results XQLT inhibited expression of those NGF, BDNF and thymus-and activation-regulated cytokine (TARC) in LA4 cells that were subjected to a Der p allergen. Both preventive and therapeutic treatments with XQLT in mice reduced AHR. Preventive treatment with XQLT markedly decreased NGF in broncho-alveolar lavage fluids (BALF) and BDNF in serum, whereas therapeutic treatment reduced only serum BDNF level. The reduced NGF levels corresponded to a decrease in AHR by XQLT treatment. Reduced BALF NGF and TARC and serum BDNF levels may have been responsible for decreased eosinophil infiltration into lung tissue. Immunohistochemistry showed that p75NTR and TrkA levels were reduced in the lungs of mice under both XQLT treatment protocols, and this reduction may have been correlated with the prevention of the asthmatic reaction by XQLT. Conclusion XQLT alleviated allergic inflammation including AHR, Ig

  15. Models of alien species richness show moderate predictive accuracy and poor transferability

    Directory of Open Access Journals (Sweden)

    César Capinha

    2018-06-01

    Full Text Available Robust predictions of alien species richness are useful to assess global biodiversity change. Nevertheless, the capacity to predict spatial patterns of alien species richness remains largely unassessed. Using 22 data sets of alien species richness from diverse taxonomic groups and covering various parts of the world, we evaluated whether different statistical models were able to provide useful predictions of absolute and relative alien species richness, as a function of explanatory variables representing geographical, environmental and socio-economic factors. Five state-of-the-art count data modelling techniques were used and compared: Poisson and negative binomial generalised linear models (GLMs, multivariate adaptive regression splines (MARS, random forests (RF and boosted regression trees (BRT. We found that predictions of absolute alien species richness had a low to moderate accuracy in the region where the models were developed and a consistently poor accuracy in new regions. Predictions of relative richness performed in a superior manner in both geographical settings, but still were not good. Flexible tree ensembles-type techniques (RF and BRT were shown to be significantly better in modelling alien species richness than parametric linear models (such as GLM, despite the latter being more commonly applied for this purpose. Importantly, the poor spatial transferability of models also warrants caution in assuming the generality of the relationships they identify, e.g. by applying projections under future scenario conditions. Ultimately, our results strongly suggest that predictability of spatial variation in richness of alien species richness is limited. The somewhat more robust ability to rank regions according to the number of aliens they have (i.e. relative richness, suggests that models of aliens species richness may be useful for prioritising and comparing regions, but not for predicting exact species numbers.

  16. ISO-66, a novel inhibitor of macrophage migration, shows efficacy in melanoma and colon cancer models.

    Science.gov (United States)

    Ioannou, Kyriaki; Cheng, Kai Fan; Crichlow, Gregg V; Birmpilis, Anastasios I; Lolis, Elias J; Tsitsilonis, Ourania E; Al-Abed, Yousef

    2014-10-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, whereas prolonged administration of ISO-66 in mice with established syngeneic melanoma or colon cancer was non-toxic and resulted in a significant decrease in tumor burden. Subsequent ex vivo analysis of mouse splenocytes revealed that the observed decrease in tumor growth rates was likely mediated by the selective in vivo expansion of antitumor-reactive effector cells induced by ISO-66. Compared to other MIF-inactivating strategies employed in vivo, the anticancer activity of ISO-66 is demonstrated to be of equal or better efficacy. Our findings suggest that targeting MIF, via highly specific and stable compounds, such as ISO-66, may be effective for cancer treatment and stimulation of anticancer immune responses.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. ZVI Addition in Continuous Anaerobic Digestion Systems Dramatically Decreases P Recovery Potential: Dynamic Modelling

    DEFF Research Database (Denmark)

    Puyol, D.; Flores Alsina, Xavier; Segura, Y.

    2017-01-01

    The objective of this study is to show the preliminary results of a (dynamic) mathematical model describing the effects of zero valent iron (ZVI) addition during the anaerobic digestion of waste activated sludge from wastewater treatment systems. A modified version of the Anaerobic Digestion Model...... No. 1 (ADM1) upgraded with an improved physico-chemical description, ZVI corrosion, propionate uptake enhancement and multiple mineral precipitation is used as a modelling platform. The proposed approach is tested against two case studies which correspond to two lab scale anaerobic digesters (AD2, AD....... Simulations demonstrate that the model is capable to satisfactorily reproduce the dynamics of hydrolysis, acetogenesis, acidogenesis, nutrient release, pH and methanogenesis in the control anaerobic digester (AD1). This study also evidences the enhancement of methane production by the influence of ZVI...

  3. 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...

  4. 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.

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

    Science.gov (United States)

    Nash, Evelyn E; Peters, Brian M; Lilly, Elizabeth A; Noverr, Mairi C; Fidel, Paul L

    2016-01-01

    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.

  6. Hyperglycemia decreases expression of 14-3-3 proteins in an animal model of stroke.

    Science.gov (United States)

    Jeon, Seong-Jun; Sung, Jin-Hee; Koh, Phil-Ok

    2016-07-28

    Diabetes is a severe metabolic disorder and a major risk factor for stroke. Stroke severity is worse in patients with diabetes compared to the non-diabetic population. The 14-3-3 proteins are a family of conserved acidic proteins that are ubiquitously expressed in cells and tissues. These proteins are involved in many cellular processes including metabolic pathways, signal transduction, protein trafficking, protein synthesis, and cell cycle control. This study investigated 14-3-3 proteins expression in the cerebral cortex of animals with diabetes, cerebral ischemic injury and a combination of both diabetes and cerebral ischemic injury. Diabetes was induced by intraperitoneal injection of streptozotocin (40mg/kg) in adult male rats. After 4 weeks of treatment, middle cerebral artery occlusion (MCAO) was performed for the induction of focal cerebral ischemia and cerebral cortex tissue was collected 24h after MCAO. We confirmed that diabetes increases infarct volume following MCAO compared to non-diabetic animals. In diabetic animals with MCAO injury, reduction of 14-3-3 β/α, 14-3-3 ζ/δ, 14-3-3 γ, and 14-3-3 ε isoforms was detected. The expression of these proteins was significantly decreased in diabetic animals with MCAO injury compared to diabetic-only and MCAO-only animals. Moreover, Western blot analysis ascertained the decreased expression of 14-3-3 family proteins in diabetic animals with MCAO injury, including β/α, ζ/δ, γ, ε, τ, and η isoforms. These results show the changes of 14-3-3 proteins expression in streptozotocin-induced diabetic animals with MCAO injury. Thus, these findings suggest that decreases in 14-3-3 proteins might be involved in the regulation of 14-3-3 proteins under the presence of diabetes following MCAO. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Model of the multipolar engine with decreased cogging torque by asymmetrical distribution of the magnets

    Science.gov (United States)

    Goryca, Zbigniew; Paduszyński, Kamil; Pakosz, Artur

    2018-03-01

    This paper presents the results of field calculations of cogging torque for a 12-pole torque motor with an 18-slot stator. A constant angular velocity magnet and the same size gap between n-1 magnets were assumed. In these conditions, the effect of change of the n-th gap between magnets on the cogging torque was tested. Due to considerable length of the machine the calculations were performed using a 2D model. The n-th gap for which the cogging torque assumed the lowest value was evaluated. The cogging torque of the machine with symmetrical magnetic circuit (the same size of gap between magnets) was compared to the one of the asymmetrical machine. With proper choice of asymmetry, the cogging torque for the machine decreased by four times.

  8. 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.

  9. 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.

  10. 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.

  11. Distraction sneakers decrease the expected level of aggression within groups: a game-theoretic model.

    Science.gov (United States)

    Dubois, Frédérique; Giraldeau, Luc-Alain; Hamilton, Ian M; Grant, James W A; Lefebvre, Louis

    2004-08-01

    Hawk-dove games have been extensively used to predict the conditions under which group-living animals should defend their resources against potential usurpers. Typically, game-theoretic models on aggression consider that resource defense may entail energetic and injury costs. However, intruders may also take advantage of owners who are busy fighting to sneak access to unguarded resources, imposing thereby an additional cost on the use of the escalated hawk strategy. In this article we modify the two-strategy hawk-dove game into a three-strategy hawk-dove-sneaker game that incorporates a distraction-sneaking tactic, allowing us to explore its consequences on the expected level of aggression within groups. Our model predicts a lower proportion of hawks and hence lower frequencies of aggressive interactions within groups than do previous two-strategy hawk-dove games. The extent to which distraction sneakers decrease the frequency of aggression within groups, however, depends on whether they search only for opportunities to join resources uncovered by other group members or for both unchallenged resources and opportunities to usurp.

  12. 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

  13. 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.

  14. Decreasing mitochondrial fission alleviates hepatic steatosis in a murine model of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Galloway, Chad A; Lee, Hakjoo; Brookes, Paul S; Yoon, Yisang

    2014-09-15

    Mitochondria produce the majority of cellular ATP through oxidative phosphorylation, and their capacity to do so is influenced by many factors. Mitochondrial morphology is recently suggested as an important contributor in controlling mitochondrial bioenergetics. Mitochondria divide and fuse continuously, which is affected by environmental factors, including metabolic alterations. Underscoring its bioenergetic influence, altered mitochondrial morphology is reported in tissues of patients and in animal models of metabolic dysfunction. In this study, we found that mitochondrial fission plays a vital role in the progression of nonalcoholic fatty liver disease (NAFLD). The development of hepatic steatosis, oxidative/nitrative stress, and hepatic tissue damage, induced by a high-fat diet, were alleviated in genetically manipulated mice suppressing mitochondrial fission. The alleviation of steatosis was recapitulated in primary hepatocytes with the inhibition of mitochondrial fission. Mechanistically, our study indicates that fission inhibition enhances proton leak under conditions of free fatty acid incubation, implicating bioenergetic change through manipulating mitochondrial fission. Taken together, our results suggest a mechanistic role for mitochondrial fission in the etiology of NAFLD. The efficacy of decreasing mitochondrial fission in the suppression of NAFLD suggests that mitochondrial fission represents a novel target for therapeutic treatment of NAFLD. Copyright © 2014 the American Physiological Society.

  15. 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...

  16. 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

  17. Assessment of wastewater treatment facility compliance with decreasing ammonia discharge limits using a regression tree model.

    Science.gov (United States)

    Suchetana, Bihu; Rajagopalan, Balaji; Silverstein, JoAnn

    2017-11-15

    A regression tree-based diagnostic approach is developed to evaluate factors affecting US wastewater treatment plant compliance with ammonia discharge permit limits using Discharge Monthly Report (DMR) data from a sample of 106 municipal treatment plants for the period of 2004-2008. Predictor variables used to fit the regression tree are selected using random forests, and consist of the previous month's effluent ammonia, influent flow rates and plant capacity utilization. The tree models are first used to evaluate compliance with existing ammonia discharge standards at each facility and then applied assuming more stringent discharge limits, under consideration in many states. The model predicts that the ability to meet both current and future limits depends primarily on the previous month's treatment performance. With more stringent discharge limits predicted ammonia concentration relative to the discharge limit, increases. In-sample validation shows that the regression trees can provide a median classification accuracy of >70%. The regression tree model is validated using ammonia discharge data from an operating wastewater treatment plant and is able to accurately predict the observed ammonia discharge category approximately 80% of the time, indicating that the regression tree model can be applied to predict compliance for individual treatment plants providing practical guidance for utilities and regulators with an interest in controlling ammonia discharges. The proposed methodology is also used to demonstrate how to delineate reliable sources of demand and supply in a point source-to-point source nutrient credit trading scheme, as well as how planners and decision makers can set reasonable discharge limits in future. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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.

  19. Dispersed oil decreases the ability of a model fish (Dicentrarchus labrax) to cope with hydrostatic pressure.

    Science.gov (United States)

    Dussauze, Matthieu; Pichavant-Rafini, Karine; Belhomme, Marc; Buzzacott, Peter; Privat, Killian; Le Floch, Stéphane; Lemaire, Philippe; Theron, Michaël

    2017-01-01

    Data on the biological impact of oil dispersion in deep-sea environment are scarce. Hence, the aim of this study was to evaluate the potential interest of a pressure challenge as a new experimental approach for the assessment of consequences of chemically dispersed oil, followed by a high hydrostatic pressure challenge. This work was conducted on a model fish: juvenile Dicentrarchus labrax. Seabass were exposed for 48 h to dispersant alone (nominal concentration (NC) = 4 mg L -1 ), mechanically dispersed oil (NC = 80 mg L -1 ), two chemically dispersed types of oil (NC = 50 and 80 mg L -1 with a dispersant/oil ratio of 1/20), or kept in clean seawater. Fish were then exposed for 30 min at a simulated depth of 1350 m, corresponding to pressure of 136 absolute atmospheres (ATA). The probability of fish exhibiting normal activity after the pressure challenge significantly increased from 0.40 to 0.55 when they were exposed to the dispersant but decreased to 0.26 and 0.11 in the case of chemical dispersion of oil (at 50 and 80 mg L -1 , respectively). The chemical dispersion at 80 mg L -1 also induced an increase in probability of death after the pressure challenge (from 0.08 to 0.26). This study clearly demonstrates the ability of a pressure challenge test to give evidence of the effects of a contaminant on the capacity of fish to face hydrostatic pressure. It opens new perspectives on the analysis of the biological impact of chemical dispersion of oil at depth, especially on marine species performing vertical migrations.

  20. 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

  1. 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.

  2. Daily ingestion of the probiotic Lactobacillus paracasei ST11 decreases Vaccinia virus dissemination and lethality in a mouse model.

    Science.gov (United States)

    Dos Santos Pereira Andrade, A C; Lima, M Teixeira; Oliveira, G Pereira; Calixto, R Silva; de Sales E Souza, É Lorenna; da Glória de Souza, D; de Almeida Leite, C M; Ferreira, J M Siqueira; Kroon, E G; de Oliveira, D Bretas; Dos Santos Martins, F; Abrahão, J S

    2017-02-07

    Vaccinia virus (VACV) is an important pathogen. Although studies have shown relationships between probiotics and viruses, the effect of probiotics on VACV infection is unknown. Therefore, this work aims to investigate the probiotics effects on VACV infection. Mice were divided into four groups, two non-infected groups, one receiving the probiotic, the other one not receiving it, and two groups infected intranasally with VACV Western Reserve (VACV-WR) receiving or not receiving the probiotic. Viral titres in organs and cytokine production in the lungs were analysed. Lung samples were also subjected to histological analysis. The intake of probiotic results in reduction in viral spread with a significant decrease of VACV titer on lung, liver and brain of treated group. In addition,treatment with the probiotic results in attenuated mice lung inflammation showing fewer lesions on histological findings and decreased lethality in mice infected with VACV. The ingestion of Lactobacillus paracasei ST11 (LPST11) after VACV infection resulted in 2/9 animal lethality compared with 4/9 in the VACV group. This is the first study on probiotics and VACV interactions, providing not only information about this interaction, but also proposing a model for future studies involving probiotics and other poxvirus.

  3. 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

  4. OKN-007 decreases free radical levels in a preclinical F98 rat glioma model.

    Science.gov (United States)

    Coutinho de Souza, Patricia; Smith, Nataliya; Atolagbe, Oluwatomisin; Ziegler, Jadith; Njoku, Charity; Lerner, Megan; Ehrenshaft, Marilyn; Mason, Ronald P; Meek, Bill; Plafker, Scott M; Saunders, Debra; Mamedova, Nadezda; Towner, Rheal A

    2015-10-01

    Free radicals are associated with glioma tumors. Here, we report on the ability of an anticancer nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)] to decrease free radical levels in F98 rat gliomas using combined molecular magnetic resonance imaging (mMRI) and immunospin-trapping (IST) methodologies. Free radicals are trapped with the spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), to form DMPO macromolecule radical adducts, and then further tagged by immunospin trapping by an antibody against DMPO adducts. In this study, we combined mMRI with a biotin-Gd-DTPA-albumin-based contrast agent for signal detection with the specificity of an antibody for DMPO nitrone adducts (anti-DMPO probe), to detect in vivo free radicals in OKN-007-treated rat F98 gliomas. OKN-007 was found to significantly decrease (P free radical levels detected with an anti-DMPO probe in treated animals compared to untreated rats. Immunoelectron microscopy was used with gold-labeled antibiotin to detect the anti-DMPO probe within the plasma membrane of F98 tumor cells from rats administered anti-DMPO in vivo. OKN-007 was also found to decrease nuclear factor erythroid 2-related factor 2, inducible nitric oxide synthase, 3-nitrotyrosine, and malondialdehyde in ex vivo F98 glioma tissues via immunohistochemistry, as well as decrease 3-nitrotyrosine and malondialdehyde adducts in vitro in F98 cells via ELISA. The results indicate that OKN-007 effectively decreases free radicals associated with glioma tumor growth. Furthermore, this method can potentially be applied toward other types of cancers for the in vivo detection of macromolecular free radicals and the assessment of antioxidants. Copyright © 2015. Published by Elsevier Inc.

  5. 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

  6. 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

  7. Aerobic Exercise Decreases Lung Inflammation by IgE Decrement in an OVA Mice Model.

    Science.gov (United States)

    Camargo Hizume-Kunzler, Deborah; Greiffo, Flavia R; Fortkamp, Bárbara; Ribeiro Freitas, Gabriel; Keller Nascimento, Juliana; Regina Bruggemann, Thayse; Melo Avila, Leonardo; Perini, Adenir; Bobinski, Franciane; Duarte Silva, Morgana; Rocha Lapa, Fernanda; Paula Vieira, Rodolfo; Vargas Horewicz, Verônica; Soares Dos Santos, Adair Roberto; Cattelan Bonorino, Kelly

    2017-06-01

    Aerobic exercise (AE) reduces lung function decline and risk of exacerbations in asthmatic patients. However, the inflammatory lung response involved in exercise during the sensitization remains unclear. Therefore, we evaluated the effects of exercise for 2 weeks in an experimental model of sensitization and single ovalbumin-challenge. Mice were divided into 4 groups: mice non-sensitized and not submitted to exercise (Sedentary, n=10); mice non-sensitized and submitted to exercise (Exercise, n=10); mice sensitized and exposed to ovalbumin (OVA, n=10); and mice sensitized, submitted to exercise and exposed to OVA (OVA+Exercise, n=10). 24 h after the OVA/saline exposure, we counted inflammatory cells from bronchoalveolar fluid (BALF), lung levels of total IgE, IL-4, IL-5, IL-10 and IL-1ra, measurements of OVA-specific IgG1 and IgE, and VEGF and NOS-2 expression via western blotting. AE reduced cell counts from BALF in the OVA group (p<0.05), total IgE, IL-4 and IL-5 lung levels and OVA-specific IgE and IgG1 titers (p<0.05). There was an increase of NOS-2 expression, IL-10 and IL-1ra lung levels in the OVA groups (p<0.05). Our results showed that AE attenuated the acute lung inflammation, suggesting immunomodulatory properties on the sensitization process in the early phases of antigen presentation in asthma. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Clearing the air: Alberta a model of success in decreasing venting, flaring

    International Nuclear Information System (INIS)

    Harrison, L.

    2004-01-01

    An historical review of flaring and venting in the Alberta oilfields is presented. The story begins with gas production in the Turner Valley, Alberta in 1931, Western Canada's first, largest and most productive source of oil and naphtha until the discovery of Leduc in 1947. Gas production at Turner Valley reached 500 mmcf per day, of which about 486 mmcf was flared. Through the efforts of the Alberta Energy and Utilities Board (EUB) and its predecessors venting and flaring was drastically cut, to the point where in 2003 the World Bank Group, an agency of the United Nations, approached the EUB to present the Alberta flaring and venting reduction model to developing countries. Accordingly, a Flaring Workshop was held at Calgary in October 2003, attended by delegates from Algeria, Angola, Cameroon, Indonesia and Nigeria. The article also details the EUB's requirements for upstream flaring in Alberta, as laid down in 'Guide 60'. The draft Guide was released in January 2003, the final draft is targeted for February 2004. In brief, the Guide requires operators, by means of a 'decision tree analysis' method which is described in the Guide, to evaluate whether it is possible to reduce or eliminate flaring and venting; it also requires operators to evaluate economic feasibility, and to determine the feasibility of conserving as much gas as possible. New developments in the field of sensors, controls and optical flow meters are also reviewed. An appended statistical summary of gas flaring trends in selected countries, compiled by the World Bank in 2000 shows Nigeria, Iran, Russia, Algeria and Mexico as the countries with the highest volumes of flaring. To give an indication of the volume of gas wasted through flaring, it is reliably estimated that the amount of gas flared in 2000 by African countries alone, could have fuelled power plants to generate sufficient electric power to meet fully half of the continent's needs for electric power. 1 tab., 2 figs

  9. Hybrid liposomes showing enhanced accumulation in tumors as theranostic agents in the orthotopic graft model mouse of colorectal cancer.

    Science.gov (United States)

    Okumura, Masaki; Ichihara, Hideaki; Matsumoto, Yoko

    2018-11-01

    Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in a buffer solution. This study aimed to elucidate the therapeutic effects and ability of HLs to detect (diagnosis) cancer in an orthotopic graft mouse model of colorectal cancer with HCT116 cells for the use of HLs as theranostic agents. In the absence of a chemotherapeutic drug, HLs exhibited therapeutic effects by inhibiting the growth of HCT116 colorectal cancer cells in vitro, possibly through an increase in apoptosis. Intravenously administered HLs also caused a remarkable reduction in the relative cecum weight in an orthotopic graft mouse model of colorectal cancer. A decrease in tumor size in the cecal sections was confirmed by histological analysis using HE staining. TUNEL staining indicated an induction of apoptosis in HCT116 cells in the orthotopic graft mouse model of colorectal cancer. For the detection (diagnosis) of colorectal cancer by HLs, the accumulation of HLs encapsulating a fluorescent probe (ICG) was observed in HCT116 cells in the in vivo colorectal cancer model following intravenous administration. These data indicate that HLs can accumulate in tumor cells in the cecum of the orthotopic graft mouse model of colorectal cancer for a prolonged period of time, and inhibit the growth of HCT116 cells.

  10. Modeling Patient No-Show History and Predicting Future Outpatient Appointment Behavior in the Veterans Health Administration.

    Science.gov (United States)

    Goffman, Rachel M; Harris, Shannon L; May, Jerrold H; Milicevic, Aleksandra S; Monte, Robert J; Myaskovsky, Larissa; Rodriguez, Keri L; Tjader, Youxu C; Vargas, Dominic L

    2017-05-01

    Missed appointments reduce the efficiency of the health care system and negatively impact access to care for all patients. Identifying patients at risk for missing an appointment could help health care systems and providers better target interventions to reduce patient no-shows. Our aim was to develop and test a predictive model that identifies patients that have a high probability of missing their outpatient appointments. Demographic information, appointment characteristics, and attendance history were drawn from the existing data sets from four Veterans Affairs health care facilities within six separate service areas. Past attendance behavior was modeled using an empirical Markov model based on up to 10 previous appointments. Using logistic regression, we developed 24 unique predictive models. We implemented the models and tested an intervention strategy using live reminder calls placed 24, 48, and 72 hours ahead of time. The pilot study targeted 1,754 high-risk patients, whose probability of missing an appointment was predicted to be at least 0.2. Our results indicate that three variables were consistently related to a patient's no-show probability in all 24 models: past attendance behavior, the age of the appointment, and having multiple appointments scheduled on that day. After the intervention was implemented, the no-show rate in the pilot group was reduced from the expected value of 35% to 12.16% (p value < 0.0001). The predictive model accurately identified patients who were more likely to miss their appointments. Applying the model in practice enables clinics to apply more intensive intervention measures to high-risk patients. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

  11. 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.

  12. 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

  13. 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.

  14. 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

    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...

  15. Individual Diet Modeling Shows How to Balance the Diet of French Adults with or without Excessive Free Sugar Intakes.

    Science.gov (United States)

    Lluch, Anne; Maillot, Matthieu; Gazan, Rozenn; Vieux, Florent; Delaere, Fabien; Vaudaine, Sarah; Darmon, Nicole

    2017-02-20

    Dietary changes needed to achieve nutritional adequacy for 33 nutrients were determined for 1719 adults from a representative French national dietary survey. For each individual, an iso-energy nutritionally adequate diet was generated using diet modeling, staying as close as possible to the observed diet. The French food composition table was completed with free sugar (FS) content. Results were analyzed separately for individuals with FS intakes in their observed diets ≤10% or >10% of their energy intake (named below FS-ACCEPTABLE and FS-EXCESS, respectively). The FS-EXCESS group represented 41% of the total population (average energy intake of 14.2% from FS). Compared with FS-ACCEPTABLE individuals, FS-EXCESS individuals had diets of lower nutritional quality and consumed more energy (2192 vs. 2123 kcal/day), particularly during snacking occasions (258 vs. 131 kcal/day) (all p -values diets were significant increases in fresh fruits, starchy foods, water, hot beverages and plain yogurts; and significant decreases in mixed dishes/sandwiches, meat/eggs/fish and cheese. For FS-EXCESS individuals only, the optimization process significantly increased vegetables and significantly decreased sugar-sweetened beverages, sweet products and fruit juices. The diets of French adults with excessive intakes of FS are of lower nutritional quality, but can be optimized via specific dietary changes.

  16. Maple Syrup Decreases TDP-43 Proteotoxicity in a Caenorhabditis elegans Model of Amyotrophic Lateral Sclerosis (ALS).

    Science.gov (United States)

    Aaron, Catherine; Beaudry, Gabrielle; Parker, J Alex; Therrien, Martine

    2016-05-04

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing death of the motor neurons. Proteotoxicity caused by TDP-43 protein is an important aspect of ALS pathogenesis, with TDP-43 being the main constituent of the aggregates found in patients. We have previously tested the effect of different sugars on the proteotoxicity caused by the expression of mutant TDP-43 in Caenorhabditis elegans. Here we tested maple syrup, a natural compound containing many active molecules including sugars and phenols, for neuroprotective activity. Maple syrup decreased several age-dependent phenotypes caused by the expression of TDP-43(A315T) in C. elegans motor neurons and requires the FOXO transcription factor DAF-16 to be effective.

  17. Treatment with escitalopram but not desipramine decreases escape latency times in a learned helplessness model using juvenile rats.

    Science.gov (United States)

    Reed, Abbey L; Anderson, Jeffrey C; Bylund, David B; Petty, Frederick; El Refaey, Hesham; Happe, H Kevin

    2009-08-01

    The pharmacological treatment of depression in children and adolescents is different from that of adults due to the lack of efficacy of certain antidepressants in the pediatric age group. Our current understanding of why these differences occur is very limited. To develop more effective treatments, a juvenile animal model of depression was tested to validate it as a possible model to specifically study pediatric depression. Procedures for use with juvenile rats at postnatal day (PND) 21 and 28 were adapted from the adult learned helplessness model in which, 24 h after exposure to inescapable stress, animals are unable to remove themselves from an easily escapable stressor. Rats were treated for 7 days with either the selective serotonin reuptake inhibitor escitalopram at 10 mg/kg or the tricyclic antidepressant desipramine at 3, 10, or 15 mg/kg to determine if treatment could decrease escape latency times. Escitalopram treatment was effective at decreasing escape latency times in all ages tested. Desipramine treatment did not decrease escape latency times for PND 21 rats, but did decrease times for PND 28 and adult animals. The learned helplessness model with PND 21 rats predicts the efficacy of escitalopram and the lack of efficacy of desipramine seen in the treatment of pediatric depression. These findings suggest that the use of PND 21 rats in a modified learned helplessness procedure may be a valuable model of human pediatric depression that can predict pediatric antidepressant efficacy and be used to study antidepressant mechanisms involved in pediatric depression.

  18. Experimental results showing the internal three-component velocity field and outlet temperature contours for a model gas turbine combustor

    CSIR Research Space (South Africa)

    Meyers, BC

    2011-09-01

    Full Text Available by the American Institute of Aeronautics and Astronautics Inc. All rights reserved ISABE-2011-1129 EXPERIMENTAL RESULTS SHOWING THE INTERNAL THREE-COMPONENT VELOCITY FIELD AND OUTLET TEMPERATURE CONTOURS FOR A MODEL GAS TURBINE COMBUSTOR BC Meyers*, GC... identifier c Position identifier F Fuel i Index L (Combustor) Liner OP Orifice plate Introduction There are often inconsistencies when comparing experimental and Computational Fluid Dynamics (CFD) simulations for gas turbine combustors [1...

  19. Decreasing Damaging Effects of Stress-Bound Situations: Toward a New Model of Leadership Under Stress

    Science.gov (United States)

    1990-07-01

    Economia 5001 Eisenhower Avenue Travessa Estevio Pinto Alexandria, VA 22333-5600 Lisboa, Portugal 8a. NAME OF FUNDING/SPONSORING 8b. OFFICE SYMBOL 9...should be contingent upon the particular organizational pattern and culture . To test a possible model, a quasi-experimental study trained 18 instructors...cohesion, the particular organizational pattern and the culture related to it. (Pereira and Jesuino, 1987, final report). An important shortcoming of the

  20. Pasteurization of breastmilk decreases the rate of postnatally acquired cytomegalovirus infections, but shows a nonsignificant trend to an increased rate of necrotizing enterocolitis in very preterm infants--a preliminary study.

    Science.gov (United States)

    Stock, Katharina; Griesmaier, Elke; Brunner, Barbara; Neubauer, Vera; Kiechl-Kohlendorfer, Ursula; Trawöger, Rudolf

    2015-03-01

    This study assessed whether feeding preterm infants unpasteurized breastmilk (1) decreases the rate of late-onset sepsis and necrotizing enterocolitis and (2) increases the rate of postnatally acquired cytomegalovirus infections. Between January 2008 and July 2013, preterm infants below 32 completed weeks of gestational age admitted to the neonatal intensive care unit of Innsbruck Medical University (Innsbruck, Austria) (n=344) were eligible for the study. Of those, 323 fed breastmilk were retrospectively enrolled in the study. Two groups were formed, with 164 infants being fed unpasteurized and 159 infants being fed pasteurized breastmilk. There was no significant difference in the rate of late-onset sepsis or necrotizing enterocolitis between the unpasteurized and pasteurized breastmilk groups (late-onset sepsis, 15.9% versus 15.1% [p=0.486]; necrotizing enterocolitis, 2.4% versus 4.4% [p=0.254]). The number of infants diagnosed with postnatally acquired cytomegalovirus infection was significantly higher in the unpasteurized group (39.3%) compared with the pasteurized group (4.2%) (p=0.008). Feeding preterm infants unpasteurized breastmilk increases the rate of postnatally acquired cytomegalovirus infections. However, we also demonstrate a nonsignificant trend to a decreased rate of necrotizing enterocolitis in the unpasteurized group, which needs to be confirmed in larger studies.

  1. 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

  2. Food pattern modeling shows that the 2010 Dietary Guidelines for sodium and potassium cannot be met simultaneously

    Science.gov (United States)

    Maillot, Matthieu; Monsivais, Pablo; Drewnowski, Adam

    2013-01-01

    The 2010 US Dietary Guidelines recommended limiting intake of sodium to 1500 mg/d for people older than 50 years, African Americans, and those suffering from chronic disease. The guidelines recommended that all other people consume less than 2300 mg sodium and 4700 mg of potassium per day. The theoretical feasibility of meeting the sodium and potassium guidelines while simultaneously maintaining nutritional adequacy of the diet was tested using food pattern modeling based on linear programming. Dietary data from the National Health and Nutrition Examination Survey 2001-2002 were used to create optimized food patterns for 6 age-sex groups. Linear programming models determined the boundary conditions for the potassium and sodium content of the modeled food patterns that would also be compatible with other nutrient goals. Linear programming models also sought to determine the amounts of sodium and potassium that both would be consistent with the ratio of Na to K of 0.49 and would cause the least deviation from the existing food habits. The 6 sets of food patterns were created before and after an across-the-board 10% reduction in sodium content of all foods in the Food and Nutrition Database for Dietary Studies. Modeling analyses showed that the 2010 Dietary Guidelines for sodium were incompatible with potassium guidelines and with nutritionally adequate diets, even after reducing the sodium content of all US foods by 10%. Feasibility studies should precede or accompany the issuing of dietary guidelines to the public. PMID:23507224

  3. 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.

  4. 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

  5. Exogenous galanin attenuates spatial memory impairment and decreases hippocampal β-amyloid levels in rat model of Alzheimer's disease.

    Science.gov (United States)

    Li, Lei; Yu, Liling; Kong, Qingxia

    2013-11-01

    One of the major pathological characteristics of Alzheimer's disease (AD) is the presence of enhanced deposits of beta-amyloid peptide (Aβ). The neuropeptide galanin (GAL) and its receptors are overexpressed in degenerating brain regions in AD. The functional consequences of galaninergic systems plasticity in AD are unclear. The objective of the present study was to investigate whether exogenous galanin could attenuate spatial memory impairment and hippocampal Aβ aggregation in rat model of AD. The effects of Aβ, galanin, galanin receptor 1 agonist M617 and galanin receptor 2 agonist AR-M1896 on spatial memory were tested by Morris water maze. The effects of Aβ, galanin, M617 and AR-M1896 on hippocampal Aβ protein expression were evaluated by western blot assay. The expression of galanin, galanin receptors 1 and 2 in rats' hippocampus were detected by real time PCR and western blot assay. The results showed that (1) Galanin administration was effective in improving the spatial memory and decreasing hippocampal Aβ levels after intracerebroventricular injection of Aβ; (2) AR-M1896 rather than M617 could imitate these effects of galanin; (3) GAL and GALR2 mRNA and protein levels increased significantly in hippocampus after Aβ administration, while GALR1 mRNA and protein levels did not change; (4) GAL, AR-M1896 and M617 administration did not show significant effect on GAL, GalR1 and GalR2 mRNA and protein levels in hippocampus after Aβ administration. These results implied that galanin receptor 2, but not receptor 1 was involved in the protective effects against spatial memory impairment and hippocampal Aβ aggregation.

  6. 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.

  7. 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

  8. Electroacupuncture decreases the progression of ovarian hyperstimulation syndrome in a rat model.

    Science.gov (United States)

    Chen, Li; Sun, Hai-Xiang; Xia, You-Bing; Sui, Liu-Cai; Zhou, Ji; Huang, Xuan; Zhou, Jing-Wei; Shao, Yi-Dan; Shen, Tao; Sun, Qin; Liang, Yuan-Jiao; Yao, Bing

    2016-05-01

    This study aimed to elucidate the effect of electroacupuncture treatment on preventing early ovarian hyperstimulation syndrome (OHSS) and the potential mechanisms involved using an induced rat model. The ovarian response was examined by measuring ovary weight, vascular permeability, levels of inflammation (interleukin-6), tumour necrosis factor alpha, chemokine ligand 2 (also known as monocyte chemoactic protein 1), vascular endothelial growth factor and hormone concentrations (oestradiol, progesterone, testosterone and prolactin). Sprague-Dawley female rats underwent ovarian stimulation to induce OHSS. Hyperstimulated rats received consecutive electroacupuncture treatment from 3 days before the beginning of pregnant mare serum gonadotrophin treatment or the time point of pregnant mare serum gonadotrophin treatment respectively, and last until 3 days after HCG administration. Electroacupuncture treatment reduced ovary weight and vascular permeability in hyperstimulated rats. Electroacupuncture treatment also reduced the levels of serum steroid hormones (progesterone and testosterone), inflammatory cytokines (interleukin-6, tumour necrosis factor alpha and monocyte chemotactic protein 1 and vascular endothelial growth factor in hyperstimulated rats. The results indicate that electroacupuncture can modulate endocrine hormone secretion and affect the secretion of inflammatory cytokines and vascular endothelial growth factor, and thus prevent the progress of OHSS. Electroacupuncture may provide a simple and effective method for the prevention and treatment of OHSS. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Decreasing maternal myostatin programs adult offspring bone strength in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Oestreich, Arin K; Kamp, William M; McCray, Marcus G; Carleton, Stephanie M; Karasseva, Natalia; Lenz, Kristin L; Jeong, Youngjae; Daghlas, Salah A; Yao, Xiaomei; Wang, Yong; Pfeiffer, Ferris M; Ellersieck, Mark R; Schulz, Laura C; Phillips, Charlotte L

    2016-11-22

    During fetal development, the uterine environment can have effects on offspring bone architecture and integrity that persist into adulthood; however, the biochemical and molecular mechanisms remain unknown. Myostatin is a negative regulator of muscle mass. Parental myostatin deficiency (Mstn tm1Sjl/+ ) increases muscle mass in wild-type offspring, suggesting an intrauterine programming effect. Here, we hypothesized that Mstn tm1Sjl/+ dams would also confer increased bone strength. In wild-type offspring, maternal myostatin deficiency altered fetal growth and calvarial collagen content of newborn mice and conferred a lasting impact on bone geometry and biomechanical integrity of offspring at 4 mo of age, the age of peak bone mass. Second, we sought to apply maternal myostatin deficiency to a mouse model with osteogenesis imperfecta (Col1a2 oim ), a heritable connective tissue disorder caused by abnormalities in the structure and/or synthesis of type I collagen. Femora of male Col1a2 oim/+ offspring from natural mating of Mstn tm1Sjl/+ dams to Col1a2 oim/+ sires had a 15% increase in torsional ultimate strength, a 29% increase in tensile strength, and a 24% increase in energy to failure compared with age, sex, and genotype-matched offspring from natural mating of Col1a2 oim/+ dams to Col1a2 oim/+ sires. Finally, increased bone biomechanical strength of Col1a2 oim/+ offspring that had been transferred into Mstn tm1Sjl/+ dams as blastocysts demonstrated that the effects of maternal myostatin deficiency were conferred by the postimplantation environment. Thus, targeting the gestational environment, and specifically prenatal myostatin pathways, provides a potential therapeutic window and an approach for treating osteogenesis imperfecta.

  10. Does model fit decrease the uncertainty of the data in comparison with a general non-model least squares fit?

    International Nuclear Information System (INIS)

    Pronyaev, V.G.

    2003-01-01

    The information entropy is taken as a measure of knowledge about the object and the reduced univariante variance as a common measure of uncertainty. Covariances in the model versus non-model least square fits are discussed

  11. 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

  12. Proteasomes remain intact, but show early focal alteration in their composition in a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; Agar, Jeffrey N; Hong, Yu; Taylor, David M; Minotti, Sandra; Figlewicz, Denise A; Durham, Heather D

    2008-06-01

    In amyotrophic lateral sclerosis caused by mutations in Cu/Zn-superoxide dismutase (SOD1), altered solubility and aggregation of the mutant protein implicates failure of pathways for detecting and catabolizing misfolded proteins. Our previous studies demonstrated early reduction of proteasome-mediated proteolytic activity in lumbar spinal cord of SOD1(G93A) transgenic mice, tissue particularly vulnerable to disease. The purpose of this study was to identify any underlying abnormalities in proteasomal structure. In lumbar spinal cord of pre-symptomatic mice [postnatal day 45 (P45) and P75], normal levels of structural 20S alpha subunits were incorporated into 20S/26S proteasomes; however, proteasomal complexes separated by native gel electrophoresis showed decreased immunoreactivity with antibodies to beta3, a structural subunit of the 20S proteasome core, and beta5, the subunit with chymotrypsin-like activity. This occurred prior to increase in beta5i immunoproteasomal subunit. mRNA levels were maintained and no association of mutant SOD1 with proteasomes was identified, implicating post-transcriptional mechanisms. mRNAs also were maintained in laser captured motor neurons at a later stage of disease (P100) in which multiple 20S proteins are reduced relative to the surrounding neuropil. Increase in detergent-insoluble, ubiquitinated proteins at P75 provided further evidence of stress on mechanisms of protein quality control in multiple cell types prior to significant motor neuron death.

  13. 68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model.

    Science.gov (United States)

    Liu, Fei; Zhu, Hua; Yu, Jiangyuan; Han, Xuedi; Xie, Qinghua; Liu, Teli; Xia, Chuanqin; Li, Nan; Yang, Zhi

    2017-06-01

    Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68 Ga/ 177 Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68 Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68 Ga/ 177 Lu for 68 Ga/ 177 Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177 Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68 Ga-DOTA-TATE or 177 Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68 Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68 Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

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

    Science.gov (United States)

    Manfré, Giuseppe; Clemensson, Erik K H; Kyriakou, Elisavet I; Clemensson, Laura E; van der Harst, Johanneke E; Homberg, Judith R; Nguyen, Huu Phuc

    2017-01-01

    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.

  15. Appetite - decreased

    Science.gov (United States)

    Loss of appetite; Decreased appetite; Anorexia ... Any illness can reduce appetite. If the illness is treatable, the appetite should return when the condition is cured. Loss of appetite can cause weight ...

  16. Lixisenatide, a drug developed to treat type 2 diabetes, shows neuroprotective effects in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    McClean, Paula L; Hölscher, Christian

    2014-11-01

    Type 2 diabetes is a risk factor for developing Alzheimer's disease (AD). In the brains of AD patients, insulin signalling is desensitised. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates insulin signalling, and analogues such as liraglutide are on the market as treatments for type 2 diabetes. We have previously shown that liraglutide showed neuroprotective effects in the APPswe/PS1ΔE9 mouse model of AD. Here, we test the GLP-1 receptor agonist lixisenatide in the same mouse model and compare the effects to liraglutide. After ten weeks of daily i.p. injections with liraglutide (2.5 or 25 nmol/kg) or lixisenatide (1 or 10 nmol/kg) or saline of APP/PS1 mice at an age when amyloid plaques had already formed, performance in an object recognition task was improved in APP/PS1 mice by both drugs at all doses tested. When analysing synaptic plasticity in the hippocampus, LTP was strongly increased in APP/PS1 mice by either drug. Lixisenatide (1 nmol/kg) was most effective. The reduction of synapse numbers seen in APP/PS1 mice was prevented by the drugs. The amyloid plaque load and dense-core Congo red positive plaque load in the cortex was reduced by both drugs at all doses. The chronic inflammation response (microglial activation) was also reduced by all treatments. The results demonstrate that the GLP-1 receptor agonists liraglutide and lixisenatide which are on the market as treatments for type 2 diabetes show promise as potential drug treatments of AD. Lixisenatide was equally effective at a lower dose compared to liraglutide in some of the parameters measured. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Novel AAV-based rat model of forebrain synucleinopathy shows extensive pathologies and progressive loss of cholinergic interneurons.

    Directory of Open Access Journals (Sweden)

    Patrick Aldrin-Kirk

    Full Text Available Synucleinopathies, characterized by intracellular aggregation of α-synuclein protein, share a number of features in pathology and disease progression. However, the vulnerable cell population differs significantly between the disorders, despite being caused by the same protein. While the vulnerability of dopamine cells in the substantia nigra to α-synuclein over-expression, and its link to Parkinson's disease, is well studied, animal models recapitulating the cortical degeneration in dementia with Lewy-bodies (DLB are much less mature. The aim of this study was to develop a first rat model of widespread progressive synucleinopathy throughout the forebrain using adeno-associated viral (AAV vector mediated gene delivery. Through bilateral injection of an AAV6 vector expressing human wild-type α-synuclein into the forebrain of neonatal rats, we were able to achieve widespread, robust α-synuclein expression with preferential expression in the frontal cortex. These animals displayed a progressive emergence of hyper-locomotion and dysregulated response to the dopaminergic agonist apomorphine. The animals receiving the α-synuclein vector displayed significant α-synuclein pathology including intra-cellular inclusion bodies, axonal pathology and elevated levels of phosphorylated α-synuclein, accompanied by significant loss of cortical neurons and a progressive reduction in both cortical and striatal ChAT positive interneurons. Furthermore, we found evidence of α-synuclein sequestered by IBA-1 positive microglia, which was coupled with a distinct change in morphology. In areas of most prominent pathology, the total α-synuclein levels were increased to, on average, two-fold, which is similar to the levels observed in patients with SNCA gene triplication, associated with cortical Lewy body pathology. This study provides a novel rat model of progressive cortical synucleinopathy, showing for the first time that cholinergic interneurons are vulnerable

  18. In vitro and in vivo models of cerebral ischemia show discrepancy in therapeutic effects of M2 macrophages.

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    Virginie Desestret

    Full Text Available THE INFLAMMATORY RESPONSE FOLLOWING ISCHEMIC STROKE IS DOMINATED BY INNATE IMMUNE CELLS: resident microglia and blood-derived macrophages. The ambivalent role of these cells in stroke outcome might be explained in part by the acquisition of distinct functional phenotypes: classically (M1 and alternatively activated (M2 macrophages. To shed light on the crosstalk between hypoxic neurons and macrophages, an in vitro model was set up in which bone marrow-derived macrophages were co-cultured with hippocampal slices subjected to oxygen and glucose deprivation. The results showed that macrophages provided potent protection against neuron cell loss through a paracrine mechanism, and that they expressed M2-type alternative polarization. These findings raised the possibility of using bone marrow-derived M2 macrophages in cellular therapy for stroke. Therefore, 2 million M2 macrophages (or vehicle were intravenously administered during the subacute stage of ischemia (D4 in a model of transient middle cerebral artery occlusion. Functional neuroscores and magnetic resonance imaging endpoints (infarct volumes, blood-brain barrier integrity, phagocytic activity assessed by iron oxide uptake were longitudinally monitored for 2 weeks. This cell-based treatment did not significantly improve any outcome measure compared with vehicle, suggesting that this strategy is not relevant to stroke therapy.

  19. Image-based multiscale mechanical modeling shows the importance of structural heterogeneity in the human lumbar facet capsular ligament.

    Science.gov (United States)

    Zarei, Vahhab; Liu, Chao J; Claeson, Amy A; Akkin, Taner; Barocas, Victor H

    2017-08-01

    The lumbar facet capsular ligament (FCL) primarily consists of aligned type I collagen fibers that are mainly oriented across the joint. The aim of this study was to characterize and incorporate in-plane local fiber structure into a multiscale finite element model to predict the mechanical response of the FCL during in vitro mechanical tests, accounting for the heterogeneity in different scales. Characterization was accomplished by using entire-domain polarization-sensitive optical coherence tomography to measure the fiber structure of cadaveric lumbar FCLs ([Formula: see text]). Our imaging results showed that fibers in the lumbar FCL have a highly heterogeneous distribution and are neither isotropic nor completely aligned. The averaged fiber orientation was [Formula: see text] ([Formula: see text] in the inferior region and [Formula: see text] in the middle and superior regions), with respect to lateral-medial direction (superior-medial to inferior-lateral). These imaging data were used to construct heterogeneous structural models, which were then used to predict experimental gross force-strain behavior and the strain distribution during equibiaxial and strip biaxial tests. For equibiaxial loading, the structural model fit the experimental data well but underestimated the lateral-medial forces by [Formula: see text]16% on average. We also observed pronounced heterogeneity in the strain field, with stretch ratios for different elements along the lateral-medial axis of sample typically ranging from about 0.95 to 1.25 during a 12% strip biaxial stretch in the lateral-medial direction. This work highlights the multiscale structural and mechanical heterogeneity of the lumbar FCL, which is significant both in terms of injury prediction and microstructural constituents' (e.g., neurons) behavior.

  20. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Xi; Feng, Xueshang [SIGMA Weather Group, State Key Laboratory of Space Weather, National Space Science Center, Chinese Academy of Sciences, Beijing 100190 (China); Potgieter, Marius S. [Centre for Space Research, North-West University, Potchefstroom 2520 (South Africa); Zhang, Ming [Department of Physics and Space Sciences, Florida Institute of Technology, 150 West University Boulevard, Melbourne, FL 32901 (United States)

    2017-04-10

    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.

  2. Inhibitory effects on bone resorption in postmenopausal osteoporosis model mice by delivery of serum calcium decreasing factor (caldecrin) gene

    International Nuclear Information System (INIS)

    Oi, Michi; Kido, Seisui; Hasegawa, Hiroya; Fujimoto, Kengo; Tomomura, Mineko; Kanegae, Haruhide; Suda, Naoto; Tomomura, Akito

    2011-01-01

    Osteoporosis is a common condition in which decrease in the bone volume and strength occurs due to increased bone resorption. Caldecrin is a serine protease, with a molecular weight of 28kDa, and it is the causative factor of hypocalcemia frequently seen in acute pancreatitis. Recent reports have shown that caldecrin also acts to inhibit both differentiation of the osteoclasts and function of the mature osteoclasts. In this study, the osteoporosis model mice were used and bilateral ovariectomy was conducted in these mice. Effect of bone absorption was estimated after introducing genetically the pCaldecrin-IRES-hrGFP expressing vector into the femoral muscle by use of the hemagglutinating virus of Japan (HVJ)-liposomes. After the bilateral ovariectomy, serum calcium levels were raised and the bone mass of the femur was decreased. However, in the genetically introduced groups of the model mice, serum calcium levels were significantly lowered. Concomitantly, significant increase in bone density, trabecular width and number of trabecular was observed. Moreover, based on the histological findings, inhibition of bone resorption in the caldecrin-introduced osteoporosis model mice was confirmed. The present study indicates that caldecrin can be expected to become a novel cure for osteoporosis. (author)

  3. The Small Heat Shock Protein α-Crystallin B Shows Neuroprotective Properties in a Glaucoma Animal Model

    Directory of Open Access Journals (Sweden)

    Fabian Anders

    2017-11-01

    Full Text Available Glaucoma is a neurodegenerative disease that leads to irreversible retinal ganglion cell (RGC loss and is one of the main causes of blindness worldwide. The pathogenesis of glaucoma remains unclear, and novel approaches for neuroprotective treatments are urgently needed. Previous studies have revealed significant down-regulation of α-crystallin B as an initial reaction to elevated intraocular pressure (IOP, followed by a clear but delayed up-regulation, suggesting that this small heat-shock protein plays a pathophysiological role in the disease. This study analyzed the neuroprotective effect of α-crystallin B in an experimental animal model of glaucoma. Significant IOP elevation induced by episcleral vein cauterization resulted in a considerable impairment of the RGCs and the retinal nerve fiber layer. An intravitreal injection of α-crystallin B at the time of the IOP increase was able to rescue the RGCs, as measured in a functional photopic electroretinogram, retinal nerve fiber layer thickness, and RGC counts. Mass-spectrometry-based proteomics and antibody-microarray measurements indicated that a α-crystallin injection distinctly up-regulated all of the subclasses (α, β, and γ of the crystallin protein family. The creation of an interactive protein network revealed clear correlations between individual proteins, which showed a regulatory shift resulting from the crystallin injection. The neuroprotective properties of α-crystallin B further demonstrate the potential importance of crystallin proteins in developing therapeutic options for glaucoma.

  4. Fourier transform infrared imaging showing reduced unsaturated lipid content in the hippocampus of a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Leskovjan, Andreana C; Kretlow, Ariane; Miller, Lisa M

    2010-04-01

    Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer's disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier transform infrared imaging (FTIRI) to visualize the unsaturated lipid content in specific regions of the hippocampus in the PSAPP mouse model of AD as a function of plaque formation. Specifically, the unsaturated lipid content was imaged using the olefinic =CH stretching mode at 3012 cm(-1). The axonal, dendritic, and somatic layers of the hippocampus were examined in the mice at 13, 24, 40, and 56 weeks old. Results showed that lipid unsaturation in the axonal layer was significantly increased with normal aging in control (CNT) mice (p avoiding progression of the disease.

  5. 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.

  6. ALLOPURINOL DOES NOT DECREASE BLOOD PRESSURE OR PREVENT THE DEVELOPMENT OF HYPERTENSION IN THE DOCA-SALT RAT MODEL

    Science.gov (United States)

    Szasz, Theodora; Linder, A. Elizabeth; Davis, Robert P.; Burnett, Robert; Fink, Gregory D.; Watts, Stephanie W.

    2010-01-01

    Reactive oxygen species (ROS) play an important role in the pathogenesis of hypertension, disease in which ROS levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a ROS-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on BP have yielded controversial results. We hypothesized that XO inhibition would decrease BP or attenuate the development of DOCA-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg/day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by HPLC measurements of XO metabolites in urine, serum and tissues demonstrating decrease in products, increase in substrates and detection of the active metabolite of allopurinol, oxypurinol. We monitored BP continuously via radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension, regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model. PMID:20881613

  7. Allopurinol does not decrease blood pressure or prevent the development of hypertension in the deoxycorticosterone acetate-salt rat model.

    Science.gov (United States)

    Szasz, Theodora; Linder, A Elizabeth; Davis, Robert P; Burnett, Robert; Fink, Gregory D; Watts, Stephanie W

    2010-12-01

    Reactive oxygen species play an important role in the pathogenesis of hypertension, disease in which reactive oxygen species levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a reactive oxygen species-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on blood pressure have yielded controversial results. We hypothesized that XO inhibition would decrease blood pressure or attenuate the development of deoxycorticosterone acetate (DOCA)-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg per day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by high-performance liquid chromatography measurements of XO metabolites in urine, serum, and tissues demonstrating a decrease in products, increase in substrates, and detection of the active metabolite of allopurinol, oxypurinol. We monitored blood pressure continuously through radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model.

  8. Decreased prothrombotic effects of pegylated recombinant human megakaryocyte growth and development factor in thrombocytopenic state in a rat thrombosis model.

    Science.gov (United States)

    Nishiyama, U; Kuwaki, T; Akahori, H; Kato, T; Ikeda, Y; Miyazaki, H

    2005-02-01

    Previous in vitro studies demonstrated that thrombopoietin (TPO) acts on platelets to activate a variety of intracellular signaling pathways and to enhance platelet sensitivity to multiple agonists. Little is known, however, about whether TPO exerts prothrombotic effects in vivo. The aim of this study was to examine the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a pegylated N-terminal domain of human TPO, in a rat model of venous thrombosis. A microthrombus was photochemically induced on the vessel wall of a mesenteric venule, but the vessel was not occluded by it. A single intravenous injection of PEG-rHuMGDF (3 microg kg(-1)) after the thrombus generation into normal rats enhanced the thrombus size, resulting in transient thrombotic occlusion in the majority of rats. Stimulatory effects on thrombus growth were also observed following administration of glycosylated recombinant human full-length TPO (6 microg kg(-1)). In rats rendered thrombocytopenic by total body irradiation, however, PEG-rHuMGDF, even at 300 microg kg(-1), did not induce a significant increase in thrombus size or thrombotic occlusion. Platelets from thrombocytopenic rats had decreased surface levels of c-Mpl and decreased sensitivity to PEG-rHuMGDF in an in vitro aggregation response. Thus, decreased prothrombotic effects of PEG-rHuMGDF in thrombocytopenic rats might be the result not only of low platelet counts but also of decreased platelet reactivity to PEG-rHuMGDF. These results indicate that PEG-rHuMGDF has little effect on venous thrombus formation in thrombocytopenic states associated with high endogenous TPO levels.

  9. 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.

  10. Yi-gan san restores behavioral alterations and a decrease of brain glutathione level in a mouse model of schizophrenia.

    Science.gov (United States)

    Makinodan, Manabu; Yamauchi, Takahira; Tatsumi, Kouko; Okuda, Hiroaki; Noriyama, Yoshinobu; Sadamatsu, Miyuki; Kishimoto, Toshifumi; Wanaka, Akio

    2009-01-01

    The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

  11. Yi-Gan San Restores Behavioral Alterations and a Decrease of Brain Glutathione Level in a Mouse Model of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Manabu Makinodan M.D.

    2009-01-01

    Full Text Available The traditional Chinese herbal medicine yi-gan san has been used to cure neuropsychological disorders. Schizophrenia can be one of the target diseases of yi-gan san. We aimed at evaluating the possible use of yi-gan san in improving the schizophrenic symptoms of an animal model. Yi-gan san or distilled water was administered to mice born from pregnant mice injected with polyinosinic-polycytidilic acid or phosphate buffered saline. The former is a model of schizophrenia based on the epidemiological data that maternal infection leads to psychotic disorders including schizophrenia in the offspring. Prepulse inhibition and sensitivity to methamphetamine in open field tests were analyzed and the total glutathione content of whole brains was measured. Yi-gan san reversed the decrease in prepulse inhibition, hypersensitivity to methamphetamine and cognitive deficits found in the model mice to the level of control mice. Total glutathione content in whole brains was reduced in the model mice but was restored to normal levels by yi-gan san treatment. These results suggest that yi-gan san may have ameliorating effects on the pathological symptoms of schizophrenia.

  12. Omigapil treatment decreases fibrosis and improves respiratory rate in dy(2J mouse model of congenital muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Qing Yu

    Full Text Available Congenital muscular dystrophy is a distinct group of diseases presenting with weakness in infancy or childhood and no current therapy. One form, MDC1A, is the result of laminin alpha-2 deficiency and results in significant weakness, respiratory insufficiency and early death. Modification of apoptosis is one potential pathway for therapy in these patients.dy(2J mice were treated with vehicle, 0.1 mg/kg or 1 mg/kg of omigapil daily via oral gavage over 17.5 weeks. Untreated age matched BL6 mice were used as controls. Functional, behavioral and histological measurements were collected.dy(2J mice treated with omigapil showed improved respiratory rates compared to vehicle treated dy(2J mice (396 to 402 vs. 371 breaths per minute, p<0.03 and similar to control mice. There were no statistical differences in normalized forelimb grip strength between dy(2J and controls at baseline or after 17.5 weeks and no significant differences seen among the dy(2J treatment groups. At 30-33 weeks of age, dy(2J mice treated with 0.1 mg/kg omigapil showed significantly more movement time and less rest time compared to vehicle treated. dy(2J mice showed normal cardiac systolic function throughout the trial. dy(2J mice had significantly lower hindlimb maximal (p<0.001 and specific force (p<0.002 compared to the control group at the end of the trial. There were no statistically significant differences in maximal or specific force among treatments. dy(2J mice treated with 0.1 mg/kg/day omigapil showed decreased percent fibrosis in both gastrocnemius (p<0.03 and diaphragm (p<0.001 compared to vehicle, and in diaphragm (p<0.013 when compared to 1 mg/kg/day omigapil treated mice. Omigapil treated dy(2J mice demonstrated decreased apoptosis.Omigapil therapy (0.1 mg/kg improved respiratory rate and decreased skeletal and respiratory muscle fibrosis in dy(2J mice. These results support a putative role for the use of omigapil in laminin deficient congenital muscular dystrophy

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models.

    Science.gov (United States)

    Brito, Marlon V; de Oliveira, Cleide; Salu, Bruno R; Andrade, Sonia A; Malloy, Paula M D; Sato, Ana C; Vicente, Cristina P; Sampaio, Misako U; Maffei, Francisco H A; Oliva, Maria Luiza V

    2014-05-01

    The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Chronic Stress Decreases Basal Levels of Memory-Related Signaling Molecules in Area CA1 of At-Risk (Subclinical) Model of Alzheimer's Disease.

    Science.gov (United States)

    Alkadhi, Karim A; Tran, Trinh T

    2015-08-01

    An important factor that may affect the severity and time of onset of Alzheimer's disease (AD) is chronic stress. Epidemiological studies report that chronically stressed individuals are at an increased risk for developing AD. The purpose of this study was to reveal whether chronic psychosocial stress could hasten the appearance of AD symptoms including changes in basal levels of cognition-related signaling molecules in subjects who are at risk for the disease. We investigated the effect of chronic psychosocial stress on basal levels of memory-related signaling molecules in area CA1 of subclinical rat model of AD. The subclinical symptomless rat model of AD was induced by osmotic pump continuous intracerebroventricular (ICV) infusion of 160 pmol/day Aβ1-42 for 14 days. Rats were chronically stressed using the psychosocial stress intruder model. Western blot analysis of basal protein levels of important signaling molecules in hippocampal area CA1 showed no significant difference between the subclinical AD rat model and control rat. Following six weeks of psychosocial stress, molecular analysis showed that subclinical animals subjected to stress have significantly reduced basal levels of p-CaMKII and decreased p-CaMKII/t-CaMKII ratio as well as decreased basal levels of p-CREB, total CREB, and BDNF. The present results suggest that these changes in basal levels of signaling molecules may be responsible for impaired learning, memory, and LTP in this rat model, which support the proposition that chronic stress may accelerate the emergence of AD in susceptible individuals.

  19. 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...

  20. 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.

  1. A Mouse Model of Hyperproliferative Human Epithelium Validated by Keratin Profiling Shows an Aberrant Cytoskeletal Response to Injury

    Directory of Open Access Journals (Sweden)

    Samal Zhussupbekova

    2016-07-01

    Full Text Available A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7 demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.

  2. 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.

  3. Daily Supplementation of D-ribose Shows No Therapeutic Benefits in the MHC-I Transgenic Mouse Model of Inflammatory Myositis

    Science.gov (United States)

    Coley, William; Rayavarapu, Sree; van der Meulen, Jack H.; Duba, Ayyappa S.; Nagaraju, Kanneboyina

    2013-01-01

    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. PMID:23785461

  4. 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.

  5. A network model shows the importance of coupled processes in the microbial N cycle in the Cape Fear River Estuary

    Science.gov (United States)

    Hines, David E.; Lisa, Jessica A.; Song, Bongkeun; Tobias, Craig R.; Borrett, Stuart R.

    2012-06-01

    Estuaries serve important ecological and economic functions including habitat provision and the removal of nutrients. Eutrophication can overwhelm the nutrient removal capacity of estuaries and poses a widely recognized threat to the health and function of these ecosystems. Denitrification and anaerobic ammonium oxidation (anammox) are microbial processes responsible for the removal of fixed nitrogen and diminish the effects of eutrophication. Both of these microbial removal processes can be influenced by direct inputs of dissolved inorganic nitrogen substrates or supported by microbial interactions with other nitrogen transforming pathways such as nitrification and dissimilatory nitrate reduction to ammonium (DNRA). The coupling of nitrogen removal pathways to other transformation pathways facilitates the removal of some forms of inorganic nitrogen; however, differentiating between direct and coupled nitrogen removal is difficult. Network modeling provides a tool to examine interactions among microbial nitrogen cycling processes and to determine the within-system history of nitrogen involved in denitrification and anammox. To examine the coupling of nitrogen cycling processes, we built a nitrogen budget mass balance network model in two adjacent 1 cm3 sections of bottom water and sediment in the oligohaline portion of the Cape Fear River Estuary, NC, USA. Pathway, flow, and environ ecological network analyses were conducted to characterize the organization of nitrogen flow in the estuary and to estimate the coupling of nitrification to denitrification and of nitrification and DNRA to anammox. Centrality analysis indicated NH4+ is the most important form of nitrogen involved in removal processes. The model analysis further suggested that direct denitrification and coupled nitrification-denitrification had similar contributions to nitrogen removal while direct anammox was dominant to coupled forms of anammox. Finally, results also indicated that partial

  6. 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

  7. Earth system model simulations show different feedback strengths of the terrestrial carbon cycle under glacial and interglacial conditions

    Directory of Open Access Journals (Sweden)

    M. Adloff

    2018-04-01

    Full Text Available In simulations with the MPI Earth System Model, we study the feedback between the terrestrial carbon cycle and atmospheric CO2 concentrations under ice age and interglacial conditions. We find different sensitivities of terrestrial carbon storage to rising CO2 concentrations in the two settings. This result is obtained by comparing the transient response of the terrestrial carbon cycle to a fast and strong atmospheric CO2 concentration increase (roughly 900 ppm in Coupled Climate Carbon Cycle Model Intercomparison Project (C4MIP-type simulations starting from climates representing the Last Glacial Maximum (LGM and pre-industrial times (PI. In this set-up we disentangle terrestrial contributions to the feedback from the carbon-concentration effect, acting biogeochemically via enhanced photosynthetic productivity when CO2 concentrations increase, and the carbon–climate effect, which affects the carbon cycle via greenhouse warming. We find that the carbon-concentration effect is larger under LGM than PI conditions because photosynthetic productivity is more sensitive when starting from the lower, glacial CO2 concentration and CO2 fertilization saturates later. This leads to a larger productivity increase in the LGM experiment. Concerning the carbon–climate effect, it is the PI experiment in which land carbon responds more sensitively to the warming under rising CO2 because at the already initially higher temperatures, tropical plant productivity deteriorates more strongly and extratropical carbon is respired more effectively. Consequently, land carbon losses increase faster in the PI than in the LGM case. Separating the carbon–climate and carbon-concentration effects, we find that they are almost additive for our model set-up; i.e. their synergy is small in the global sum of carbon changes. Together, the two effects result in an overall strength of the terrestrial carbon cycle feedback that is almost twice as large in the LGM experiment

  8. Earth system model simulations show different feedback strengths of the terrestrial carbon cycle under glacial and interglacial conditions

    Science.gov (United States)

    Adloff, Markus; Reick, Christian H.; Claussen, Martin

    2018-04-01

    In simulations with the MPI Earth System Model, we study the feedback between the terrestrial carbon cycle and atmospheric CO2 concentrations under ice age and interglacial conditions. We find different sensitivities of terrestrial carbon storage to rising CO2 concentrations in the two settings. This result is obtained by comparing the transient response of the terrestrial carbon cycle to a fast and strong atmospheric CO2 concentration increase (roughly 900 ppm) in Coupled Climate Carbon Cycle Model Intercomparison Project (C4MIP)-type simulations starting from climates representing the Last Glacial Maximum (LGM) and pre-industrial times (PI). In this set-up we disentangle terrestrial contributions to the feedback from the carbon-concentration effect, acting biogeochemically via enhanced photosynthetic productivity when CO2 concentrations increase, and the carbon-climate effect, which affects the carbon cycle via greenhouse warming. We find that the carbon-concentration effect is larger under LGM than PI conditions because photosynthetic productivity is more sensitive when starting from the lower, glacial CO2 concentration and CO2 fertilization saturates later. This leads to a larger productivity increase in the LGM experiment. Concerning the carbon-climate effect, it is the PI experiment in which land carbon responds more sensitively to the warming under rising CO2 because at the already initially higher temperatures, tropical plant productivity deteriorates more strongly and extratropical carbon is respired more effectively. Consequently, land carbon losses increase faster in the PI than in the LGM case. Separating the carbon-climate and carbon-concentration effects, we find that they are almost additive for our model set-up; i.e. their synergy is small in the global sum of carbon changes. Together, the two effects result in an overall strength of the terrestrial carbon cycle feedback that is almost twice as large in the LGM experiment as in the PI experiment

  9. Actinobacteria from Termite Mounds Show Antiviral Activity against Bovine Viral Diarrhea Virus, a Surrogate Model for Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Marina Aiello Padilla

    2015-01-01

    Full Text Available Extracts from termite-associated bacteria were evaluated for in vitro antiviral activity against bovine viral diarrhea virus (BVDV. Two bacterial strains were identified as active, with percentages of inhibition (IP equal to 98%. Both strains were subjected to functional analysis via the addition of virus and extract at different time points in cell culture; the results showed that they were effective as posttreatments. Moreover, we performed MTT colorimetric assays to identify the CC50, IC50, and SI values of these strains, and strain CDPA27 was considered the most promising. In parallel, the isolates were identified as Streptomyces through 16S rRNA gene sequencing analysis. Specifically, CDPA27 was identified as S. chartreusis. The CDPA27 extract was fractionated on a C18-E SPE cartridge, and the fractions were reevaluated. A 100% methanol fraction was identified to contain the compound(s responsible for antiviral activity, which had an SI of 262.41. GC-MS analysis showed that this activity was likely associated with the compound(s that had a peak retention time of 5 min. Taken together, the results of the present study provide new information for antiviral research using natural sources, demonstrate the antiviral potential of Streptomyces chartreusis compounds isolated from termite mounds against BVDV, and lay the foundation for further studies on the treatment of HCV infection.

  10. 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.

  11. Modelled seasonal influenza mortality shows marked differences in risk by age, sex, ethnicity and socioeconomic position in New Zealand.

    Science.gov (United States)

    Khieu, Trang Q T; Pierse, Nevil; Telfar-Barnard, Lucy Frances; Zhang, Jane; Huang, Q Sue; Baker, Michael G

    2017-09-01

    Influenza is responsible for a large number of deaths which can only be estimated using modelling methods. Such methods have rarely been applied to describe the major socio-demographic characteristics of this disease burden. We used quasi Poisson regression models with weekly counts of deaths and isolates of influenza A, B and respiratory syncytial virus for the period 1994 to 2008. The estimated average mortality rate was 13.5 per 100,000 people which was 1.8% of all deaths in New Zealand. Influenza mortality differed markedly by age, sex, ethnicity and socioeconomic position. Relatively vulnerable groups were males aged 65-79 years (Rate ratio (RR) = 1.9, 95% CI: 1.9, 1.9 compared with females), Māori (RR = 3.6, 95% CI: 3.6, 3.7 compared with European/Others aged 65-79 years), Pacific (RR = 2.4, 95% CI: 2.4, 2.4 compared with European/Others aged 65-79 years) and those living in the most deprived areas (RR = 1.8, 95% CI: 1.3, 2.4) for New Zealand Deprivation (NZDep) 9&10 (the most deprived) compared with NZDep 1&2 (the least deprived). These results support targeting influenza vaccination and other interventions to the most vulnerable groups, in particular Māori and Pacific people and men aged 65-79 years and those living in the most deprived areas. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  12. Andrographis Paniculata shows anti-nociceptive effects in an animal model of sensory hypersensitivity associated with migraine.

    Science.gov (United States)

    Greco, Rosaria; Siani, Francesca; Demartini, Chiara; Zanaboni, Annamaria; Nappi, Giuseppe; Davinelli, Sergio; Scapagnini, Giovanni; Tassorelli, Cristina

    2016-01-01

    Administration of nitroglycerin (NTG) to rats induces a hyperalgesic condition and neuronal activation of central structures involved in migraine pain. In order to identify therapeutic strategies for migraine pain, we evaluated the anti-nociceptive activity of Andrographis Paniculata (AP), a herbaceous plant, in the hyperalgesia induced by NTG administration in the formalin test. We also analyzed mRNA expression of cytokines in specific brain areas after AP treatment. Male Sprague-Dawley rats were pre-treated with AP extract 30 minutes before NTG or vehicle injection. The data show that AP extract significantly reduced NTG-induced hyperalgesia in phase II of the test, 4 hours after NTG injection. In addition, AP extract reduced IL-6 mRNA expression in the medulla and mesencephalon and also mRNA levels of TNFalpha in the mesencephalic region. These findings suggest that AP extract may be a potential therapeutic approach in the treatment of general pain, and possibly of migraine.

  13. 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.

  14. An inducible transgenic mouse model for immune mediated hepatitis showing clearance of antigen expressing hepatocytes by CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Marcin Cebula

    Full Text Available The liver has the ability to prime immune responses against neo antigens provided upon infections. However, T cell immunity in liver is uniquely modulated by the complex tolerogenic property of this organ that has to also cope with foreign agents such as endotoxins or food antigens. In this respect, the nature of intrahepatic T cell responses remains to be fully characterized. To gain deeper insight into the mechanisms that regulate the CD8+ T cell responses in the liver, we established a novel OVA_X_CreER(T2 mouse model. Upon tamoxifen administration OVA antigen expression is observed in a fraction of hepatocytes, resulting in a mosaic expression pattern. To elucidate the cross-talk of CD8+ T cells with antigen-expressing hepatocytes, we adoptively transferred K(b/OVA257-264-specific OT-I T cells to OVA_X_CreER(T2 mice or generated triple transgenic OVA_X CreER(T2_X_OT-I mice. OT-I T cells become activated in OVA_X_CreER(T2 mice and induce an acute and transient hepatitis accompanied by liver damage. In OVA_X_CreER(T2_X_OT-I mice, OVA induction triggers an OT-I T cell mediated, fulminant hepatitis resulting in 50% mortality. Surviving mice manifest a long lasting hepatitis, and recover after 9 weeks. In these experimental settings, recovery from hepatitis correlates with a complete loss of OVA expression indicating efficient clearance of the antigen-expressing hepatocytes. Moreover, a relapse of hepatitis can be induced upon re-induction of cured OVA_X_CreER(T2_X_OT-I mice indicating absence of tolerogenic mechanisms. This pathogen-free, conditional mouse model has the advantage of tamoxifen inducible tissue specific antigen expression that reflects the heterogeneity of viral antigen expression and enables the study of intrahepatic immune responses to both de novo and persistent antigen. It allows following the course of intrahepatic immune responses: initiation, the acute phase and antigen clearance.

  15. Landscape evolution models using the stream power incision model show unrealistic behavior when m ∕ n equals 0.5

    Directory of Open Access Journals (Sweden)

    J. S. Kwang

    2017-12-01

    Full Text Available Landscape evolution models often utilize the stream power incision model to simulate river incision: E = KAmSn, where E is the vertical incision rate, K is the erodibility constant, A is the upstream drainage area, S is the channel gradient, and m and n are exponents. This simple but useful law has been employed with an imposed rock uplift rate to gain insight into steady-state landscapes. The most common choice of exponents satisfies m ∕ n = 0.5. Yet all models have limitations. Here, we show that when hillslope diffusion (which operates only on small scales is neglected, the choice m ∕ n = 0.5 yields a curiously unrealistic result: the predicted landscape is invariant to horizontal stretching. That is, the steady-state landscape for a 10 km2 horizontal domain can be stretched so that it is identical to the corresponding landscape for a 1000 km2 domain.

  16. Growth Modeling of the Maternal Cytokine Milieu throughout Normal Pregnancy: Macrophage-Derived Chemokine Decreases as Inflammation/Counterregulation Increases

    Directory of Open Access Journals (Sweden)

    Shernan G. Holtan

    2015-01-01

    Full Text Available Several recent studies have shown differences in the maternal immune milieu at different phases of pregnancy, but most studies have been cross-sectional or of relatively few time points. Levels of 42 cytokines were determined using a multiplex bead-based assay on archived serum from a cohort of pregnant women N=16 at median of 18 time points tested, from the first trimester through to parturition, per woman. Unconditional growth modeling was then used to determine time-dependent changes in levels of these cytokines. Macrophage-derived chemokine (MDC, aka CCL22 decreases as pregnancy progresses. IL-1β, IL-6, IL-8, IL-12p70, IL-13, IL-15, IP-10, and FLT3-ligand increase as a function of gestational weeks, and IFNα2, IL-1ra, IL-3, IL-9, IL-12p40, and soluble CD40 ligand increase as a function of trimester. As pregnancy normally progresses, a maternal shift away from a type 2-biased immune response and toward an inflammatory/counterregulatory response is observed.

  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. 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.

  19. An orally available, small-molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model.

    Science.gov (United States)

    Krumm, Stefanie A; Yan, Dan; Hovingh, Elise S; Evers, Taylor J; Enkirch, Theresa; Reddy, G Prabhakar; Sun, Aiming; Saindane, Manohar T; Arrendale, Richard F; Painter, George; Liotta, Dennis C; Natchus, Michael G; von Messling, Veronika; Plemper, Richard K

    2014-04-16

    Measles virus is a highly infectious morbillivirus responsible for major morbidity and mortality in unvaccinated humans. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral RNA polymerase. Prophylactic oral treatment of ferrets infected intranasally with a lethal CDV dose reduced viremia and prolonged survival. Ferrets infected with the same dose of virus that received post-infection treatment at the onset of viremia showed low-grade viral loads, remained asymptomatic, and recovered from infection, whereas control animals succumbed to the disease. Animals that recovered also mounted a robust immune response and were protected against rechallenge with a lethal CDV dose. Drug-resistant viral recombinants were generated and found to be attenuated and transmission-impaired compared to the genetic parent virus. These findings may pioneer a path toward an effective morbillivirus therapy that could aid measles eradication by synergizing with vaccination to close gaps in herd immunity due to vaccine refusal.

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

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    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.

  1. Long-Term Field Data and Climate-Habitat Models Show That Orangutan Persistence Depends on Effective Forest Management and Greenhouse Gas Mitigation

    Science.gov (United States)

    Gregory, Stephen D.; Brook, Barry W.; Goossens, Benoît; Ancrenaz, Marc; Alfred, Raymond; Ambu, Laurentius N.; Fordham, Damien A.

    2012-01-01

    Background Southeast Asian deforestation rates are among the world’s highest and threaten to drive many forest-dependent species to extinction. Climate change is expected to interact with deforestation to amplify this risk. Here we examine whether regional incentives for sustainable forest management will be effective in improving threatened mammal conservation, in isolation and when combined with global climate change mitigation. Methodology/Principal Findings Using a long time-series of orangutan nest counts for Sabah (2000–10), Malaysian Borneo, we evaluated the effect of sustainable forest management and climate change scenarios, and their interaction, on orangutan spatial abundance patterns. By linking dynamic land-cover and downscaled global climate model projections, we determine the relative influence of these factors on orangutan spatial abundance and use the resulting statistical models to identify habitat crucial for their long-term conservation. We show that land-cover change the degradation of primary forest had the greatest influence on orangutan population size. Anticipated climate change was predicted to cause reductions in abundance in currently occupied populations due to decreased habitat suitability, but also to promote population growth in western Sabah by increasing the suitability of presently unoccupied regions. Conclusions/Significance We find strong quantitative support for the Sabah government’s proposal to implement sustainable forest management in all its forest reserves during the current decade; failure to do so could result in a 40 to 80 per cent regional decline in orangutan abundance by 2100. The Sabah orangutan is just one (albeit iconic) example of a forest-dependent species that stands to benefit from sustainable forest management, which promotes conservation of existing forests. PMID:22970145

  2. 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.

  3. 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

  4. 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.

  5. Recombinant nAG (a Salamander-Derived Protein Decreases the Formation of Hypertrophic Scarring in the Rabbit Ear Model

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    Mohammad M. Al-Qattan

    2014-01-01

    Full Text Available nAG (newt-Anterrior Gradient protein is the key mediator of regrowth of amputated limbs in salamanders. In a previous work in our lab, a new nAG gene (suitable for humans was designed and cloned. The cloned vector was transfected into primary human fibroblasts. The expression of nAG in human primary fibroblasts was found to suppress collagen expression. The current study shows that local injection of recombinant nAG reduces scar hypertrophy in the rabbit ear model. This is associated with lower scar elevation index (SEI, lower levels of collagen I & III, higher levels of MMP1, and a higher degree of scar maturation in experimental wounds compared to controls.

  6. Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Calon, Frédéric; Lim, Giselle P; Morihara, Takashi; Yang, Fusheng; Ubeda, Oliver; Salem, Norman; Frautschy, Sally A; Cole, Greg M

    2005-08-01

    Epidemiological data indicate that low n-3 polyunsaturated fatty acids (PFA) intake is a readily manipulated dietary risk factor for Alzheimer's disease (AD). Studies in animals confirm the deleterious effect of n-3 PFA depletion on cognition and on dendritic scaffold proteins. Here, we show that in transgenic mice overexpressing the human AD gene APPswe (Tg2576), safflower oil-induced n-3 PFA deficiency caused a decrease in N-methyl-D-aspartate (NMDA) receptor subunits, NR2A and NR2B, in the cortex and hippocampus with no loss of the presynaptic markers, synaptophysin and synaptosomal-associated protein 25 (SNAP-25). n-3 PFA depletion also decreased the NR1 subunit in the hippocampus and Ca2+/calmodulin-dependent protein kinase (CaMKII) in the cortex of Tg2576 mice. These effects of dietary n-3 PFA deficiency were greatly amplified in Tg2576 mice compared to nontransgenic mice. Loss of the NR2B receptor subunit was not explained by changes in mRNA expression, but correlated with p85alpha phosphatidylinositol 3-kinase levels. Most interestingly, n-3 PFA deficiency dramatically increased levels of protein fragments, corresponding to caspase/calpain-cleaved fodrin and gelsolin in Tg2576 mice. This effect was minimal in nontransgenic mice suggesting that n-3 PFA depletion potentiated caspase activation in the Tg2576 mouse model of AD. Dietary supplementation with docosahexaenoic acid (DHA; 22 : 6n-3) partly protected from NMDA receptor subunit loss and accumulation of fodrin and gelsolin fragments but fully prevented CaMKII decrease. The marked effect of dietary n-3 PFA on NMDA receptors and caspase/calpain activation in the cortex of an animal model of AD provide new insights into how dietary essential fatty acids may influence cognition and AD risk.

  7. 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

  8. Prospects of an alternative treatment against Trypanosoma cruzi based on abietic acid derivatives show promising results in Balb/c mouse model.

    Science.gov (United States)

    Olmo, F; Guardia, J J; Marin, C; Messouri, I; Rosales, M J; Urbanová, K; Chayboun, I; Chahboun, R; Alvarez-Manzaneda, E J; Sánchez-Moreno, M

    2015-01-07

    Chagas disease, caused by the protozoa parasite Trypanosoma cruzi, is an example of extended parasitaemia with unmet medical needs. Current treatments based on old-featured benznidazole (Bz) and nifurtimox are expensive and do not fulfil the criteria of effectiveness, and a lack of toxicity devoid to modern drugs. In this work, a group of abietic acid derivatives that are chemically stable and well characterised were introduced as candidates for the treatment of Chagas disease. In vitro and in vivo assays were performed in order to test the effectiveness of these compounds. Finally, those which showed the best activity underwent additional studies in order to elucidate the possible mechanism of action. In vitro results indicated that some compounds have low toxicity (i.e. >150 μM, against Vero cell) combined with high efficacy (i.e. <20 μM) against some forms of T. cruzi. Further in vivo studies on mice models confirmed the expectations of improvements in infected mice. In vivo tests on the acute phase gave parasitaemia inhibition values higher those of Bz, and a remarkable decrease in the reactivation of parasitaemia was found in the chronic phase after immunosuppression of the mice treated with one of the compounds. The morphological alterations found in treated parasites with our derivatives confirmed extensive damage; energetic metabolism disturbances were also registered by (1)H NMR. The demonstrated in vivo activity and low toxicity, together with the use of affordable starting products and the lack of synthetic complexity, put these abietic acid derivatives in a remarkable position toward the development of an anti-Chagasic agent. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Enteral intestinal alkaline phosphatase administration in newborns decreases iNOS expression in a neonatal necrotizing enterocolitis rat model.

    Science.gov (United States)

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

    2013-01-01

    To determine if intestinal alkaline phosphatase (IAP) decreases intestinal injury resulting from experimentally induced necrotizing enterocolitis (NEC). We hypothesized that IAP administration prevents the initial development of NEC related intestinal inflammation. Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day 1 of life. Pre-term pups were exposed to intermittent hypoxia and formula containing LPS to induce NEC. Select NEC pups were given 40, 4 or 0.4 units/kg of bovine IAP (NEC+IAP40u, IAP4u or IAP0.4u) enterally, once daily. Ileal sections were evaluated by real-time PCR (qRT-PCR) for IAP, iNOS, IL-1β, IL-6, and TNF-α mRNA and immunofluorescence for 3-nitrotyrosine (3-NT). Experimentally induced NEC decreased IAP mRNA expression by 66% (p ≤ 0.001). IAP supplementation increased IAP mRNA expression to control. Supplemental enteral IAP decreased nitrosative stress as measured by iNOS mRNA expression and 3-NT staining in the NEC stressed pups (p ≤ 0.01), as well as decreased intestinal TNF-α mRNA expression. In addition, IAP decreased LSP translocation into the serum in the treated pups. We conclude that enterally administered IAP prevents NEC-related intestinal injury and inflammation. Enteral IAP may prove a useful strategy in the prevention of NEC in preterm neonates. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Photothermal Therapy Using Gold Nanorods and Near-Infrared Light in a Murine Melanoma Model Increases Survival and Decreases Tumor Volume

    Directory of Open Access Journals (Sweden)

    Mary K. Popp

    2014-01-01

    Full Text Available Photothermal therapy (PTT treatments have shown strong potential in treating tumors through their ability to target destructive heat preferentially to tumor regions. In this paper we demonstrate that PTT in a murine melanoma model using gold nanorods (GNRs and near-infrared (NIR light decreases tumor volume and increases animal survival to an extent that is comparable to the current generation of melanoma drugs. GNRs, in particular, have shown a strong ability to reach ablative temperatures quickly in tumors when exposed to NIR light. The current research tests the efficacy of GNRs PTT in a difficult and fast growing murine melanoma model using a NIR light-emitting diode (LED light source. LED light sources in the NIR spectrum could provide a safer and more practical approach to photothermal therapy than lasers. We also show that the LED light source can effectively and quickly heat in vitro and in vivo models to ablative temperatures when combined with GNRs. We anticipate that this approach could have significant implications for human cancer therapy.

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

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    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.

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

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    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.

  15. 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.

  16. Show and Tell: Video Modeling and Instruction Without Feedback Improves Performance but Is Not Sufficient for Retention of a Complex Voice Motor Skill.

    Science.gov (United States)

    Look, Clarisse; McCabe, Patricia; Heard, Robert; Madill, Catherine J

    2018-02-02

    Modeling and instruction are frequent components of both traditional and technology-assisted voice therapy. This study investigated the value of video modeling and instruction in the early acquisition and short-term retention of a complex voice task without external feedback. Thirty participants were randomized to two conditions and trained to produce a vocal siren over 40 trials. One group received a model and verbal instructions, the other group received a model only. Sirens were analyzed for phonation time, vocal intensity, cepstral peak prominence, peak-to-peak time, and root-mean-square error at five time points. The model and instruction group showed significant improvement on more outcome measures than the model-only group. There was an interaction effect for vocal intensity, which showed that instructions facilitated greater improvement when they were first introduced. However, neither group reproduced the model's siren performance across all parameters or retained the skill 1 day later. Providing verbal instruction with a model appears more beneficial than providing a model only in the prepractice phase of acquiring a complex voice skill. Improved performance was observed; however, the higher level of performance was not retained after 40 trials in both conditions. Other prepractice variables may need to be considered. Findings have implications for traditional and technology-assisted voice therapy. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

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

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    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.

  18. Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression.

    Science.gov (United States)

    Xiang, Wei; Tian, Canhui; Peng, Shunli; Zhou, Liang; Pan, Suyue; Deng, Zhen

    2017-11-04

    The let-7 family of microRNAs (miRNAs) plays an important role on endothelial cell function. However, there have been few studies on their role under ischemic conditions. In this study, we demonstrate that let-7i, belonging to the let-7 family, rescues human brain microvascular endothelial cells (HBMECs) in an oxygen-glucose deprivation (OGD) model. Our data show that the expression of let-7 family miRNAs was downregulated after OGD. Overexpression of let-7i significantly alleviated cell death and improved survival of OGD-treated HBMECs. Let-7i also protected permeability in an in vitro blood brain barrier (BBB) model. Further, let-7i downregulated the expression of toll-like receptor 4 (TLR4), an inflammation trigger. Moreover, overexpression of let-7i decreased matrix metallopeptidase 9 (MMP9) and inducible nitric oxide synthase (iNOS) expression under OGD. Upon silencing TLR4 expression in HBMECs, the anti-inflammatory effect of let-7i was abolished. Our research suggests that let-7i promotes OGD-induced inflammation via downregulating TLR4 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Raghav, Anil; Lotekar, Ajay [University Department of Physics, University of Mumbai, Vidyanagari, Santacruz (E), Mumbai-400098 (India); Bhaskar, Ankush; Vichare, Geeta; Yadav, Virendra, E-mail: raghavanil1984@gmail.com, E-mail: ankushbhaskar@gmail.com, E-mail: ablotekar@gmail.com, E-mail: vicharegeeta@gmail.com, E-mail: virendray.iig@gmail.com [Indian Institute of Geomagnetism, Plot 5, Sector 18, New Panvel, Navi Mumbai-410218 (India)

    2014-10-01

    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.

  1. Modelling decreased food chain accumulation of HOCs due to strong sorption to carbonaceous materials and metabolic transformation

    NARCIS (Netherlands)

    Moermond, C.T.A.; Traas, T.P.; Roessink, I.; Veltman, K.; Hendriks, A.J.; Koelmans, A.A.

    2007-01-01

    The predictive power of bioaccumulation models may be limited when they do not account for strong sorption of organic contaminants to carbonaceous materials (CM) such as black carbon, and when they do not include metabolic transformation. We tested a food web accumulation model, including sorption

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

    Science.gov (United States)

    Zeng, Lingling; Yang, Yang; Hu, Yujuan; Sun, Yu; Du, Zhengde; Xie, Zhen; Zhou, Tao; Kong, Weijia

    2014-01-01

    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.

  3. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    Science.gov (United States)

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    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......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...

  5. Cost-effectiveness of milk powder fortified with potassium to decrease blood pressure and prevent cardiovascular events among the adult population in China: a Markov model.

    Science.gov (United States)

    Dainelli, Livia; Xu, Tingting; Li, Min; Zimmermann, Diane; Fang, Hai; Wu, Yangfeng; Detzel, Patrick

    2017-09-25

    To model the long-term cost-effectiveness of consuming milk powder fortified with potassium to decrease systolic blood pressure (SBP) and prevent cardiovascular events. A best case scenario analysis using a Markov model was conducted. 8.67% of 50-79 year olds who regularly consume milk in China, including individuals with and without a prior diagnosis of hypertension. The model simulated the potential impact of a daily intake of two servings of milk powder fortified with potassium (+700 mg/day) vs the consumption of a milk powder without potassium fortification, assuming a market price equal to 0.99 international dollars (intl$; the consumption of a milk powder without potassium fortification, assuming a market price equal to intl$0.99 for the latter and to intl$1.12 for the first (+13.13%). Both deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the results. Estimates of the incidence of cardiovascular events and subsequent mortality in China were derived from the literature as well as the effect of increasing potassium intake on blood pressure. The incremental cost-effectiveness ratio (ICER) was used to determine the cost-effectiveness of a milk powder fortified with potassium taking into consideration the direct medical costs associated with the cardiovascular events, loss of working days and health utilities impact. With an ICER equal to int$4711.56 per QALY (quality-adjusted life year) in the best case scenario and assuming 100% compliance, the daily consumption of a milk powder fortified with potassium shown to be a cost-effective approach to decrease SBP and reduce cardiovascular events in China. Healthcare savings due to prevention would amount to intl$8.41 billion. Sensitivity analyses showed the robustness of the results. Together with other preventive interventions, the consumption of a milk powder fortified with potassium could represent a cost-effective strategy to attenuate the rapid rise in

  6. Bio-Spectroscopic Imaging Provides Evidence of Hippocampal Zn Deficiency and Decreased Lipid Unsaturation in an Accelerated Ageing Mouse Model.

    Science.gov (United States)

    Fimognari, Nicholas; Hollings, Ashley; Lam, Virginie; Tidy, Rebecca J; Kewish, Cameron M; Albrecht, Matthew A; Takechi, Ryu; Mamo, John C L; Hackett, Mark J

    2018-06-14

    Western society is facing a health epidemic due to the increasing incidence of dementia in ageing populations, and there are still few effective diagnostic methods, minimal treatment options, and no cure. Ageing is the greatest risk factor for memory loss that occurs during the natural ageing process, as well as being the greatest risk factor for neurodegenerative disease such as Alzheimer's disease. Therefore, greater understanding of the biochemical pathways that drive a healthy ageing brain towards dementia (pathological ageing or Alzheimer's disease), is required to accelerate the development of improved diagnostics and therapies. Unfortunately, many animal models of dementia model chronic amyloid precursor protein over-expression, which although highly relevant to mechanisms of amyloidosis and familial Alzheimer's disease, does not model well dementia during the natural ageing process. A promising animal model reported to model mechanisms of accelerated natural ageing and memory impairments, is the senescence accelerated murine prone strain 8 (SAMP8), which has been adopted by many research group to study the biochemical transitions that occur during brain ageing. A limitation to traditional methods of biochemical characterisation is that many important biochemical and elemental markers (lipid saturation, lactate, transition metals) cannot be imaged at meso- or micro-spatial resolution. Therefore, in this investigation we report the first multi-modal biospectroscopic characterisation of the SAMP8 model, and have identified important biochemical and elemental alterations, and co-localisations, between 4 month old SAMP8 mice and the relevant control (SAMR1) mice. Specifically, we demonstrate direct evidence of altered metabolism and disturbed lipid homeostasis within corpus callosum white matter, in addition to localised hippocampal metal deficiencies, in the accelerated ageing phenotype. Such findings have important implication for future research aimed at

  7. 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

  8. Decrease in heart rate after longitudinal participation in the Groningen Active Living Model (GALM) recreational sports programme

    NARCIS (Netherlands)

    de Jong, Johan; Lemmink, Koen; Scherder, Erik; Stewart, Roy; King, Abby; Stevens, Martin

    2009-01-01

    The aim of this study was to investigate changes in heart rate during submaximal exercise as an index of cardiovascular function in older adults participating in the Groningen Active Living Model recreational sports programme who were sedentary or underactive at baseline. A repeated measurement

  9. 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.

  10. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in preclinical models.

    Science.gov (United States)

    Paulsen, Daniela; Urban, Andreas; Knorr, Andreas; Hirth-Dietrich, Claudia; Siegling, Angela; Volk, Hans-Dieter; Mercer, Andrew A; Limmer, Andreas; Schumak, Beatrix; Knolle, Percy; Ruebsamen-Schaeff, Helga; Weber, Olaf

    2013-01-01

    Inactivated orf virus (iORFV), strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV) and hepatitis B virus (HBV). Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

  11. Inactivated ORF virus shows antifibrotic activity and inhibits human hepatitis B virus (HBV and hepatitis C virus (HCV replication in preclinical models.

    Directory of Open Access Journals (Sweden)

    Daniela Paulsen

    Full Text Available Inactivated orf virus (iORFV, strain D1701, is a potent immune modulator in various animal species. We recently demonstrated that iORFV induces strong antiviral activity in animal models of acute and chronic viral infections. In addition, we found D1701-mediated antifibrotic effects in different rat models of liver fibrosis. In the present study, we compare iORFV derived from two different strains of ORFV, D1701 and NZ2, respectively, with respect to their antifibrotic potential as well as their potential to induce an antiviral response controlling infections with the hepatotropic pathogens hepatitis C virus (HCV and hepatitis B virus (HBV. Both strains of ORFV showed anti-viral activity against HCV in vitro and against HBV in a transgenic mouse model without signs of necro-inflammation in vivo. Our experiments suggest that the absence of liver damage is potentially mediated by iORFV-induced downregulation of antigen cross-presentation in liver sinus endothelial cells. Furthermore, both strains showed significant anti-fibrotic activity in rat models of liver fibrosis. iORFV strain NZ2 appeared more potent compared to strain D1701 with respect to both its antiviral and antifibrotic activity on the basis of dosages estimated by titration of active virus. These results show a potential therapeutic approach against two important human liver pathogens HBV and HCV that independently addresses concomitant liver fibrosis. Further studies are required to characterize the details of the mechanisms involved in this novel therapeutic principle.

  12. Clinical ethics residency for nurses: an education model to decrease moral distress and strengthen nurse retention in acute care.

    Science.gov (United States)

    Grace, Pamela J; Robinson, Ellen M; Jurchak, Martha; Zollfrank, Angelika A; Lee, Susan M

    2014-12-01

    The experience of unaddressed moral distress can lead to nurse attrition and/or distancing from patients, compromising patient care. Nurses who are confident in their ethical decision making abilities and moral agency have the antidote to moral distress for themselves and their colleagues and can act as local or institutional ethics resources. We describe a grant-funded model education program designed to increase ethics competence throughout the institution.

  13. 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 with a conce......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...... 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...

  14. 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.

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

    Science.gov (United States)

    Olmo, Francisco; Urbanová, Kristína; Rosales, Maria Jose; Martín-Escolano, Ruben; Sánchez-Moreno, Manuel; Marín, Clotilde

    2015-12-01

    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 (1)H 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.

  16. 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

  17. 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

  18. Interdisciplinary Care Model Independently Decreases Use of Critical Care Services After Corrective Surgery for Adult Degenerative Scoliosis.

    Science.gov (United States)

    Adogwa, Owoicho; Elsamadicy, Aladine A; Sergesketter, Amanda R; Ongele, Michael; Vuong, Victoria; Khalid, Syed; Moreno, Jessica; Cheng, Joseph; Karikari, Isaac O; Bagley, Carlos A

    2018-03-01

    Interdisciplinary management of elderly patients requiring spine surgery has been shown to improve short- and long-term outcomes. The aim of this study was to determine whether an interdisciplinary team approach mitigates use of intensive care unit (ICU) resources. A unique comanagement model for elderly patients undergoing lumbar fusion surgery was implemented at a major academic medical center. The Peri-operative Optimization of Senior Health Program (POSH) was launched with the aim of improving outcomes in elderly patients (>65 years old) undergoing complex lumbar spine surgery. In this model, a geriatrician evaluates elderly patients preoperatively, comanages daily throughout hospital course, and coordinates multidisciplinary rehabilitation, along with the neurosurgical team. We retrospectively reviewed the first 100 cases after the initiation of the POSH protocol and compared them with the immediately preceding 25 cases to assess the rates of ICU transfer and independent predictors of ICU admission. A total of 125 patients undergoing lumbar decompression and fusion surgery were enrolled in this pilot program. Baseline characteristics and intraoperative variables, as well as number of fusion levels and duration of surgery, were similar between both cohorts. There was a significant difference in the use of ICU services (ICU admission rates) between both cohorts, with the non-POSH cohort having a 3-fold increase compared with the POSH cohort (P < 0.0001). In a multivariate analysis, lack of an interdisciplinary comanagement team approach was an independent predictor for ICU transfers in elderly patients undergoing corrective surgery (odds ratio 8.51, 95% confidence interval 2.972-24.37, P < 0.0001). Our study suggests that an interdisciplinary comanagement model between geriatrics and neurosurgery is independently associated with reduced use of critical care services. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model.

    Science.gov (United States)

    Swift, Brenna E; Williams, Brent A; Kosaka, Yoko; Wang, Xing-Hua; Medin, Jeffrey A; Viswanathan, Sowmya; Martinez-Lopez, Joaquin; Keating, Armand

    2012-07-01

    Novel therapies capable of targeting drug resistant clonogenic MM cells are required for more effective treatment of multiple myeloma. This study investigates the cytotoxicity of natural killer cell lines against bulk and clonogenic multiple myeloma and evaluates the tumor burden after NK cell therapy in a bioluminescent xenograft mouse model. The cytotoxicity of natural killer cell lines was evaluated against bulk multiple myeloma cell lines using chromium release and flow cytometry cytotoxicity assays. Selected activating receptors on natural killer cells were blocked to determine their role in multiple myeloma recognition. Growth inhibition of clonogenic multiple myeloma cells was assessed in a methylcellulose clonogenic assay in combination with secondary replating to evaluate the self-renewal of residual progenitors after natural killer cell treatment. A bioluminescent mouse model was developed using the human U266 cell line transduced to express green fluorescent protein and luciferase (U266eGFPluc) to monitor disease progression in vivo and assess bone marrow engraftment after intravenous NK-92 cell therapy. Three multiple myeloma cell lines were sensitive to NK-92 and KHYG-1 cytotoxicity mediated by NKp30, NKp46, NKG2D and DNAM-1 activating receptors. NK-92 and KHYG-1 demonstrated 2- to 3-fold greater inhibition of clonogenic multiple myeloma growth, compared with killing of the bulk tumor population. In addition, the residual colonies after treatment formed significantly fewer colonies compared to the control in a secondary replating for a cumulative clonogenic inhibition of 89-99% at the 20:1 effector to target ratio. Multiple myeloma tumor burden was reduced by NK-92 in a xenograft mouse model as measured by bioluminescence imaging and reduction in bone marrow engraftment of U266eGFPluc cells by flow cytometry. This study demonstrates that NK-92 and KHYG-1 are capable of killing clonogenic and bulk multiple myeloma cells. In addition, multiple myeloma

  20. Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP).

    Science.gov (United States)

    Karami, Masoume; Bathaie, S Zahra; Tiraihi, Taqi; Habibi-Rezaei, Mehran; Arabkheradmand, Jalil; Faghihzadeh, Soghrat

    2013-12-15

    Various approaches have been offered to alleviate chronic pain resulting from spinal cord injuries (SCIs). Application of herbs and natural products, with potentially lower adverse effects, to cure diseases has been recommended in both traditional and modern medicines. Here, the effect of crocin on chronic pain induced by spinal cord contusion was investigated in an animal model. Female Wistar rats were randomly divided into five groups (5 rats in each); three groups were contused at the L1 level. One group was treated with crocin (150mg/kg) two weeks after spinal cord injury; the second group, control, was treated with vehicle only; and the third group was treated with ketoprofen. Two normal groups were also considered with or without crocin treatment. The mechanical behavioral test, the locomotor recovery test and the thermal behavioral test were applied weekly to evaluate the injury and recovery of rats. Significant improvements (plocomotor recovery tests were seen in the rats treated with crocin. Thermal behavioral test did not show any significant changes due to crocin treatment. Plasma concentration of calcitonin-gene related peptide (CGRP) changed from 780.2±2.3 to 1140.3±4.5pg/ml due to SCI and reached 789.1±2.7pg/ml after crocin treatment. These changes were significant at the level of p<0.05. The present study shows the beneficial effects of crocin treatment on chronic pain induced by SCI, through decreasing CGRP as an important mediator of inflammation and pain. Copyright © 2013 Elsevier GmbH. All rights reserved.

  1. 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.

  2. Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

    Science.gov (United States)

    Vilaplana, Cristina; Marzo, Elena; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanesa; Cardona, Pere-Joan

    2013-07-15

    C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

  3. 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.

  4. 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

  5. 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.

  6. Controlled reperfusion decreased reperfusion induced oxidative stress and evoked inflammatory response in experimental aortic-clamping animal model.

    Science.gov (United States)

    Jancsó, G; Arató, E; Hardi, P; Nagy, T; Pintér, Ö; Fazekas, G; Gasz, B; Takacs, I; Menyhei, G; Kollar, L; Sínay, L

    2016-09-12

    Revascularization after long term aortic ischaemia in vascular surgery induces reperfusion injury accompanied with oxidative stress and inflammatory responses. The hypothesis of this study was that the aortic occlusion followed by controlled reperfusion (CR) can reduce the ischaemia-reperfusion injury, the systemic and local inflammatory response induced by oxidative stress.Animal model was used. animals underwent a 4-hour infrarenal aortic occlusion followed by continuous reperfusion. Treated group: animals were treated with CR: after a 4-hour infrarenal aortic occlusion we made CR for 30 minutes with the crystalloid reperfusion solution (blood: crystalloid solution ratio 1:1) on pressure 60 Hgmm. Blood samples were collected different times. The developing oxidative stress was detected by the plasma levels of malondialdehyde, reduced glutathion, thiol groups and superoxide dismutase. The inflammatory response was measured by phorbol myristate acetate-induced leukocyte reactive oxygen species production and detection of change in myeloperoxidase levels. The animals were anaesthetized one week after terminating ligation and biopsy was taken from quadriceps muscle and large parenchymal organs.CR significantly reduced the postischaemic oxydative stress and inflammatory responses in early reperfusion period. Pathophysiological results: The rate of affected muscle fibers by degeneration was significantly higher in the untreated animal group. The infiltration of leukocytes in muscle and parenchymal tissues was significantly lower in the treatedgroup.CR can improve outcome after acute lower-limb ischaemia. The results confirm that CR might be also a potential therapeutic approach in vascular surgery against reperfusion injury in acute limb ischaemia. Supported by OTKA K108596.

  7. 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.

  8. A novel life cycle modeling system for Ebola virus shows a genome length-dependent role of VP24 in virus infectivity.

    Science.gov (United States)

    Watt, Ari; Moukambi, Felicien; Banadyga, Logan; Groseth, Allison; Callison, Julie; Herwig, Astrid; Ebihara, Hideki; Feldmann, Heinz; Hoenen, Thomas

    2014-09-01

    Work with infectious Ebola viruses is restricted to biosafety level 4 (BSL4) laboratories, presenting a significant barrier for studying these viruses. Life cycle modeling systems, including minigenome systems and transcription- and replication-competent virus-like particle (trVLP) systems, allow modeling of the virus life cycle under BSL2 conditions; however, all current systems model only certain aspects of the virus life cycle, rely on plasmid-based viral protein expression, and have been used to model only single infectious cycles. We have developed a novel life cycle modeling system allowing continuous passaging of infectious trVLPs containing a tetracistronic minigenome that encodes a reporter and the viral proteins VP40, VP24, and GP1,2. This system is ideally suited for studying morphogenesis, budding, and entry, in addition to genome replication and transcription. Importantly, the specific infectivity of trVLPs in this system was ∼ 500-fold higher than that in previous systems. Using this system for functional studies of VP24, we showed that, contrary to previous reports, VP24 only very modestly inhibits genome replication and transcription when expressed in a regulated fashion, which we confirmed using infectious Ebola viruses. Interestingly, we also discovered a genome length-dependent effect of VP24 on particle infectivity, which was previously undetected due to the short length of monocistronic minigenomes and which is due at least partially to a previously unknown function of VP24 in RNA packaging. Based on our findings, we propose a model for the function of VP24 that reconciles all currently available data regarding the role of VP24 in nucleocapsid assembly as well as genome replication and transcription. Ebola viruses cause severe hemorrhagic fevers in humans, with no countermeasures currently being available, and must be studied in maximum-containment laboratories. Only a few of these laboratories exist worldwide, limiting our ability to study

  9. 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.

  10. Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation.

    Science.gov (United States)

    Cordes, Henrik; Thiel, Christoph; Baier, Vanessa; Blank, Lars M; Kuepfer, Lars

    2018-01-01

    Drug-induced perturbations of the endogenous metabolic network are a potential root cause of cellular toxicity. A mechanistic understanding of such unwanted side effects during drug therapy is therefore vital for patient safety. The comprehensive assessment of such drug-induced injuries requires the simultaneous consideration of both drug exposure at the whole-body and resulting biochemical responses at the cellular level. We here present a computational multi-scale workflow that combines whole-body physiologically based pharmacokinetic (PBPK) models and organ-specific genome-scale metabolic network (GSMN) models through shared reactions of the xenobiotic metabolism. The applicability of the proposed workflow is illustrated for isoniazid, a first-line antibacterial agent against Mycobacterium tuberculosis , which is known to cause idiosyncratic drug-induced liver injuries (DILI). We combined GSMN models of a human liver with N-acetyl transferase 2 (NAT2)-phenotype-specific PBPK models of isoniazid. The combined PBPK-GSMN models quantitatively describe isoniazid pharmacokinetics, as well as intracellular responses, and changes in the exometabolome in a human liver following isoniazid administration. Notably, intracellular and extracellular responses identified with the PBPK-GSMN models are in line with experimental and clinical findings. Moreover, the drug-induced metabolic perturbations are distributed and attenuated in the metabolic network in a phenotype-dependent manner. Our simulation results show that a simultaneous consideration of both drug pharmacokinetics at the whole-body and metabolism at the cellular level is mandatory to explain drug-induced injuries at the patient level. The proposed workflow extends our mechanistic understanding of the biochemistry underlying adverse events and may be used to prevent drug-induced injuries in the future.

  11. 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.

  12. 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.

  13. Climate Envelope Modeling and Dispersal Simulations Show Little Risk of Range Extension of the Shipworm, Teredo navalis (L.), in the Baltic Sea

    Science.gov (United States)

    Appelqvist, Christin; Al-Hamdani, Zyad K.; Jonsson, Per R.; Havenhand, Jon N.

    2015-01-01

    The shipworm, Teredo navalis, is absent from most of the Baltic Sea. In the last 20 years, increased frequency of T. navalis has been reported along the southern Baltic Sea coasts of Denmark, Germany, and Sweden, indicating possible range-extensions into previously unoccupied areas. We evaluated the effects of historical and projected near-future changes in salinity, temperature, and oxygen on the risk of spread of T. navalis in the Baltic. Specifically, we developed a simple, GIS-based, mechanistic climate envelope model to predict the spatial distribution of favourable conditions for adult reproduction and larval metamorphosis of T. navalis, based on published environmental tolerances to these factors. In addition, we used a high-resolution three-dimensional hydrographic model to simulate the probability of spread of T. navalis larvae within the study area. Climate envelope modeling showed that projected near-future climate change is not likely to change the overall distribution of T. navalis in the region, but will prolong the breeding season and increase the risk of shipworm establishment at the margins of the current range. Dispersal simulations indicated that the majority of larvae were philopatric, but those that spread over a wider area typically spread to areas unfavourable for their survival. Overall, therefore, we found no substantive evidence for climate-change related shifts in the distribution of T. navalis in the Baltic Sea, and no evidence for increased risk of spread in the near-future. PMID:25768305

  14. Climate envelope modeling and dispersal simulations show little risk of range extension of the Shipworm, Teredo navalis (L., in the Baltic sea.

    Directory of Open Access Journals (Sweden)

    Christin Appelqvist

    Full Text Available The shipworm, Teredo navalis, is absent from most of the Baltic Sea. In the last 20 years, increased frequency of T. navalis has been reported along the southern Baltic Sea coasts of Denmark, Germany, and Sweden, indicating possible range-extensions into previously unoccupied areas. We evaluated the effects of historical and projected near-future changes in salinity, temperature, and oxygen on the risk of spread of T. navalis in the Baltic. Specifically, we developed a simple, GIS-based, mechanistic climate envelope model to predict the spatial distribution of favourable conditions for adult reproduction and larval metamorphosis of T. navalis, based on published environmental tolerances to these factors. In addition, we used a high-resolution three-dimensional hydrographic model to simulate the probability of spread of T. navalis larvae within the study area. Climate envelope modeling showed that projected near-future climate change is not likely to change the overall distribution of T. navalis in the region, but will prolong the breeding season and increase the risk of shipworm establishment at the margins of the current range. Dispersal simulations indicated that the majority of larvae were philopatric, but those that spread over a wider area typically spread to areas unfavourable for their survival. Overall, therefore, we found no substantive evidence for climate-change related shifts in the distribution of T. navalis in the Baltic Sea, and no evidence for increased risk of spread in the near-future.

  15. Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model.

    Science.gov (United States)

    Ponce-Lopez, Teresa; Liy-Salmeron, Gustavo; Hong, Enrique; Meneses, Alfredo

    2011-12-02

    Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of

  16. 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

  17. Showing Value (Editorial

    Directory of Open Access Journals (Sweden)

    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!

  18. 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...

  19. Modeling Glaucoma: Retinal Ganglion Cells Generated from Induced Pluripotent Stem Cells of Patients with SIX6 Risk Allele Show Developmental Abnormalities.

    Science.gov (United States)

    Teotia, Pooja; Van Hook, Matthew J; Wichman, Christopher S; Allingham, R Rand; Hauser, Michael A; Ahmad, Iqbal

    2017-11-01

    Glaucoma represents a group of multifactorial diseases with a unifying pathology of progressive retinal ganglion cell (RGC) degeneration, causing irreversible vision loss. To test the hypothesis that RGCs are intrinsically vulnerable in glaucoma, we have developed an in vitro model using the SIX6 risk allele carrying glaucoma patient-specific induced pluripotent stem cells (iPSCs) for generating functional RGCs. Here, we demonstrate that the efficiency of RGC generation by SIX6 risk allele iPSCs is significantly lower than iPSCs-derived from healthy, age- and sex-matched controls. The decrease in the number of RGC generation is accompanied by repressed developmental expression of RGC regulatory genes. The SIX6 risk allele RGCs display short and simple neurites, reduced expression of guidance molecules, and immature electrophysiological signature. In addition, these cells have higher expression of glaucoma-associated genes, CDKN2A and CDKN2B, suggesting an early onset of the disease phenotype. Consistent with the developmental abnormalities, the SIX6 risk allele RGCs display global dysregulation of genes which map on developmentally relevant biological processes for RGC differentiation and signaling pathways such as mammalian target of rapamycin that integrate diverse functions for differentiation, metabolism, and survival. The results suggest that SIX6 influences different stages of RGC differentiation and their survival; therefore, alteration in SIX6 function due to the risk allele may lead to cellular and molecular abnormalities. These abnormalities, if carried into adulthood, may make RGCs vulnerable in glaucoma. Stem Cells 2017;35:2239-2252. © 2017 AlphaMed Press.

  20. Corpos sob controle: Um estudo de caso sobre a relação entre corpo e signo no reality show estadunidense America’s Next Top Model

    Directory of Open Access Journals (Sweden)

    Júnior Ratts

    2015-08-01

    Full Text Available Este trabalho tem como objetivo analisar as potencialidades corporais do individuo contemporâneo em sua luta diária pela conquista da individualidade e do reconhecimento coletivo. Para tanto, a pesquisa toma como objeto o reality show estadunidense America’s Next Top Model a fim de tentar compreender melhor, a partir das experiências das candidatas do programa, como se estabelecem as relações táticas e estratégicas entre o sujeito e o mundo e de que forma as expectativas e consequências geradas por esses “embates cotidianos” com a realidade e com o Outro chegam ao corpo, transformando-o numa “arma” e num produto sociocultural

  1. 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

  2. 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.

  3. 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.

  4. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma.

    Science.gov (United States)

    Patwardhan, Parag P; Ivy, Kathryn S; Musi, Elgilda; de Stanchina, Elisa; Schwartz, Gary K

    2016-01-26

    Sarcomas are rare but highly aggressive mesenchymal tumors with a median survival of 10-18 months for metastatic disease. Mutation and/or overexpression of many receptor tyrosine kinases (RTKs) including c-Met, PDGFR, c-Kit and IGF1-R drive defective signaling pathways in sarcomas. MGCD516 (Sitravatinib) is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth. In the present study, we evaluated the efficacy of MGCD516 both in vitro and in mouse xenograft models in vivo. MGCD516 treatment resulted in significant blockade of phosphorylation of potential driver RTKs and induced potent anti-proliferative effects in vitro. Furthermore, MGCD516 treatment of tumor xenografts in vivo resulted in significant suppression of tumor growth. Efficacy of MGCD516 was superior to imatinib and crizotinib, two other well-studied multi-kinase inhibitors with overlapping target specificities, both in vitro and in vivo. This is the first report describing MGCD516 as a potent multi-kinase inhibitor in different models of sarcoma, superior to imatinib and crizotinib. Results from this study showing blockade of multiple driver signaling pathways provides a rationale for further clinical development of MGCD516 for the treatment of patients with soft-tissue sarcoma.

  5. 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.

  6. Bifactor Models Show a Superior Model Fit: Examination of the Factorial Validity of Parent-Reported and Self-Reported Symptoms of Attention-Deficit/Hyperactivity Disorders in Children and Adolescents.

    Science.gov (United States)

    Rodenacker, Klaas; Hautmann, Christopher; Görtz-Dorten, Anja; Döpfner, Manfred

    2016-01-01

    Various studies have demonstrated that bifactor models yield better solutions than models with correlated factors. However, the kind of bifactor model that is most appropriate is yet to be examined. The current study is the first to test bifactor models across the full age range (11-18 years) of adolescents using self-reports, and the first to test bifactor models with German subjects and German questionnaires. The study sample included children and adolescents aged between 6 and 18 years recruited from a German clinical sample (n = 1,081) and a German community sample (n = 642). To examine the factorial validity, we compared unidimensional, correlated factors and higher-order and bifactor models and further tested a modified incomplete bifactor model for measurement invariance. Bifactor models displayed superior model fit statistics compared to correlated factor models or second-order models. However, a more parsimonious incomplete bifactor model with only 2 specific factors (inattention and impulsivity) showed a good model fit and a better factor structure than the other bifactor models. Scalar measurement invariance was given in most group comparisons. An incomplete bifactor model would suggest that the specific inattention and impulsivity factors represent entities separable from the general attention-deficit/hyperactivity disorder construct and might, therefore, give way to a new approach to subtyping of children beyond and above attention-deficit/hyperactivity disorder. © 2016 S. Karger AG, Basel.

  7. Sodium phenylbutyrate reverses lysosomal dysfunction and decreases amyloid-β42 in an in vitro-model of inclusion-body myositis.

    Science.gov (United States)

    Nogalska, Anna; D'Agostino, Carla; Engel, W King; Askanas, Valerie

    2014-05-01

    Sporadic inclusion-body myositis (s-IBM) is a severe, progressive muscle disease for which there is no enduring treatment. Pathologically characteristic are vacuolated muscle fibers having: accumulations of multi-protein aggregates, including amyloid-β(Aβ) 42 and its toxic oligomers; increased γ-secretase activity; and impaired autophagy. Cultured human muscle fibers with experimentally-impaired autophagy recapitulate some of the s-IBM muscle abnormalities, including vacuolization and decreased activity of lysosomal enzymes, accompanied by increased Aβ42, Aβ42 oligomers, and increased γ-secretase activity. Sodium phenylbutyrate (NaPB) is an orally bioavailable small molecule approved by the FDA for treatment of urea-cycle disorders. Here we describe that NaPB treatment reverses lysosomal dysfunction in an in vitro model of inclusion-body myositis, involving cultured human muscle fibers. NaPB treatment improved lysosomal activity, decreased Aβ42 and its oligomers, decreased γ-secretase activity, and virtually prevented muscle-fiber vacuolization. Accordingly, NaPB might be considered a potential treatment of s-IBM patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Studies Using an in Vitro Model Show Evidence of Involvement of Epithelial-Mesenchymal Transition of Human Endometrial Epithelial Cells in Human Embryo Implantation*

    Science.gov (United States)

    Uchida, Hiroshi; Maruyama, Tetsuo; Nishikawa-Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori

    2012-01-01

    Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin. PMID:22174415

  9. Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

    Science.gov (United States)

    Schimunek, Lukas; Serve, Rafael; Teuben, Michel P. J.; Störmann, Philipp; Auner, Birgit; Woschek, Mathias; Pfeifer, Roman; Horst, Klemens; Simon, Tim-P.; Kalbitz, Miriam; Sturm, Ramona; Pape, Hans-C.; Hildebrand, Frank; Marzi, Ingo

    2017-01-01

    In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased

  10. 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

  11. 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

  12. A novel mouse model carrying a human cytoplasmic dynein mutation shows motor behavior deficits consistent with Charcot-Marie-Tooth type 2O disease.

    Science.gov (United States)

    Sabblah, Thywill T; Nandini, Swaran; Ledray, Aaron P; Pasos, Julio; Calderon, Jami L Conley; Love, Rachal; King, Linda E; King, Stephen J

    2018-01-29

    Charcot-Marie-Tooth disease (CMT) is a peripheral neuromuscular disorder in which axonal degeneration causes progressive loss of motor and sensory nerve function. The loss of motor nerve function leads to distal muscle weakness and atrophy, resulting in gait problems and difficulties with walking, running, and balance. A mutation in the cytoplasmic dynein heavy chain (DHC) gene was discovered to cause an autosomal dominant form of the disease designated Charcot-Marie-Tooth type 2 O disease (CMT2O) in 2011. The mutation is a single amino acid change of histidine into arginine at amino acid 306 (H306R) in DHC. In order to understand the onset and progression of CMT2, we generated a knock-in mouse carrying the corresponding CMT2O mutation (H304R/+). We examined H304R/+ mouse cohorts in a 12-month longitudinal study of grip strength, tail suspension, and rotarod assays. H304R/+ mice displayed distal muscle weakness and loss of motor coordination phenotypes consistent with those of individuals with CMT2. Analysis of the gastrocnemius of H304R/+ male mice showed prominent defects in neuromuscular junction (NMJ) morphology including reduced size, branching, and complexity. Based on these results, the H304R/+ mouse will be an important model for uncovering functions of dynein in complex organisms, especially related to CMT onset and progression.

  13. Exploring the Interactions of the Dietary Plant Flavonoids Fisetin and Naringenin with G-Quadruplex and Duplex DNA, Showing Contrasting Binding Behavior: Spectroscopic and Molecular Modeling Approaches.

    Science.gov (United States)

    Bhattacharjee, Snehasish; Chakraborty, Sandipan; Sengupta, Pradeep K; Bhowmik, Sudipta

    2016-09-01

    Guanine-rich sequences have the propensity to fold into a four-stranded DNA structure known as a G-quadruplex (G4). G4 forming sequences are abundant in the promoter region of several oncogenes and become a key target for anticancer drug binding. Here we have studied the interactions of two structurally similar dietary plant flavonoids fisetin and naringenin with G4 as well as double stranded (duplex) DNA by using different spectroscopic and modeling techniques. Our study demonstrates the differential binding ability of the two flavonoids with G4 and duplex DNA. Fisetin more strongly interacts with parallel G4 structure than duplex DNA, whereas naringenin shows stronger binding affinity to duplex rather than G4 DNA. Molecular docking results also corroborate our spectroscopic results, and it was found that both of the ligands are stacked externally in the G4 DNA structure. C-ring planarity of the flavonoid structure appears to be a crucial factor for preferential G4 DNA recognition of flavonoids. The goal of this study is to explore the critical effects of small differences in the structure of closely similar chemical classes of such small molecules (flavonoids) which lead to the contrasting binding properties with the two different forms of DNA. The resulting insights may be expected to facilitate the designing of the highly selective G4 DNA binders based on flavonoid scaffolds.

  14. Talking with TV shows

    DEFF Research Database (Denmark)

    Sandvik, Kjetil; Laursen, Ditte

    2014-01-01

    User interaction with radio and television programmes is not a new thing. However, with new cross-media production concepts such as X Factor and Voice, this is changing dramatically. The second-screen logic of these productions encourages viewers, along with TV’s traditional one-way communication...... mode, to communicate on interactive (dialogue-enabling) devices such as laptops, smartphones and tablets. Using the TV show Voice as our example, this article shows how the technological and situational set-up of the production invites viewers to engage in new ways of interaction and communication...

  15. 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)

  16. Obesity in show cats.

    Science.gov (United States)

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  17. Honored Teacher Shows Commitment.

    Science.gov (United States)

    Ratte, Kathy

    1987-01-01

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

  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. The energy show

    International Nuclear Information System (INIS)

    1988-01-01

    The Energy Show is a new look at the problems of world energy, where our supplies come from, now and in the future. The programme looks at how we need energy to maintain our standards of living. Energy supply is shown as the complicated set of problems it is - that Fossil Fuels are both raw materials and energy sources, that some 'alternatives' so readily suggested as practical options are in reality a long way from being effective. (author)

  20. Tyrosine kinase inhibitors show different anti-brain metastases efficacy in NSCLC: A direct comparative analysis of icotinib, gefitinib, and erlotinib in a nude mouse model.

    Science.gov (United States)

    Tan, Jianlong; Li, Min; Zhong, Wen; Hu, Chengping; Gu, Qihua; Xie, Yali

    2017-11-17

    Brain metastasis is an increasing problem in non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs), including gefitinib, erlotinib, and icotinib, are reported to be effective in patients with brain metastases. However, direct comparative studies of the pharmacokinetics and efficacy of these three drugs in treating brain metastases are lacking. In the present investigation, we found that gefitinib penetrated the blood-tumor barrier and was distributed to brain metastases more effectively than erlotinib or icotinib in a nude mouse model. The 1-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 9.82±1.03%, 4.83±0.25%, and 2.62±0.21%, respectively. The 2-h ratio of brain metastases to plasma concentration for gefitinib, erlotinib, and icotinib was 15.11±2.00%, 5.73±1.31%, and 2.69±0.31%, respectively. Gefitinib exhibited the strongest antitumor activity ( p gefitinib vs. erlotinib =0.005; p gefitinib vs. icotinib =0.002). Notably, erlotinib exhibited a better treatment efficacy than icotinib ( p =0.037). Consistently, immunohistochemical data showed that TKIs differentially inhibit the proliferation of metastatical tumor cells. Gefitinib and erlotinib markedly inhibited the proliferation of tumor cells, while there were more ki-67-positive tumor cells in the icotinib group. Additionally, gefitinib inhibited the phosphorylation of EGFR better than the other drugs, whereas pEGFR expression levels in erlotinib groups were lower than levels in the icotinib group ( p gefitinib vs. erlotinib =0.995; p gefitinib vs. icotinib =0.028; p erlotinib vs. icotinib =0.042).Altogether, our findings suggest that gefitinib and erlotinib can inhibit the growth of PC-9-luc brain tumors. Gefitinib demonstrated better antitumor activity and penetration rate in brain metastases than erlotinib or icotinib.

  1. 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.

  2. Inhibition of the Decrease of Volatile Esters and Terpenes During Storage of Wines and a Model Wine Medium by Wine Phenolic Extracts

    Directory of Open Access Journals (Sweden)

    Ioannis Lambropoulos

    2007-01-01

    Full Text Available The effect of red wine phenolic extracts on the stability of wine volatile esters and terpenes was examined. Muscat (white and Xinomavro (red wines were enriched with each extract at 120 or 200 mg/L, and stored in open bottles at 20 °C for 3 and 2.5 days, respectively. Moreover, a model wine medium containing isoamyl acetate, ethyl hexanoate and linalool was enriched with each extract at 100 mg/L, and stored in sealed bottles at 20 °C for 45–90 days. All samples were analysed for volatiles using SPME along with GC-MS analysis. Phenolic composition of wine extracts was determined using HPLC-DAD. No effect on the concentration of any volatiles was observed as a result of the addition of each extract in each wine or the model medium. A wine extract rich in phenolic acids and another one rich in anthocyanins and flavanols inhibited the decrease of volatile esters and terpenes in one or both wines and the model medium. Among them were several important for the aroma of wine such as ethyl acetate, isoamyl acetate, ethyl hexanoate, ethyl octanoate, ethyl decanoate and linalool. The results presented here indicate that wine phenolic acids, and anthocyanins or flavanols may be taken into account as potent inhibitors of the disappearance of volatile esters and terpenes in wines.

  3. 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.

  4. Increased cystic fibrosis transmembrane conductance regulators expression and decreased epithelial sodium channel alpha subunits expression in early abortion: findings from a mouse model and clinical cases of abortion.

    Directory of Open Access Journals (Sweden)

    Min Zhou

    Full Text Available The status of the maternal endometrium is vital in regulating humoral homeostasis and for ensuring embryo implantation. Cystic fibrosis transmembrane conductance regulators (CFTR and epithelial sodium channel alpha subunits (ENaC-α play an important role in female reproduction by maintaining humoral and cell homeostasis. However, it is not clear whether the expression levels of CFTR and ENaC-α in the decidual component during early pregnancy are related with early miscarriage. CBA×DBA/2 mouse mating has been widely accepted as a classical model of early miscarriage. The abortion rate associated with this mating was 33.33% in our study. The decidua of abortion-prone CBA female mice (DBA/2 mated had higher CFTR mRNA and protein expression and lower ENaC-α mRNA and protein expression, compared to normal pregnant CBA mice (BLAB/C mated. Furthermore, increased CFTR expression and decreased ENaC-α expression were observed in the uterine tissue from women with early miscarriage, as compared to those with successful pregnancy. In conclusion, increased CFTR expression and decreased ENaC-α expression in the decidua of early abortion may relate with failure of early pregnancy.

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

    Science.gov (United States)

    Tan, Xiao; Gong, Zaiwu; Huang, Minji; Wang, Zhou-Jing

    2017-02-14

    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. Heat Shock Protein 90 Inhibitor Decreases Collagen Synthesis of Keloid Fibroblasts and Attenuates the Extracellular Matrix on the Keloid Spheroid Model.

    Science.gov (United States)

    Lee, Won Jai; Lee, Ju Hee; Ahn, Hyo Min; Song, Seung Yong; Kim, Yong Oock; Lew, Dae Hyun; Yun, Chae-Ok

    2015-09-01

    The 90-kDa heat-shock protein (heat-shock protein 90) is an abundant cytosolic chaperone, and inhibition of heat-shock protein 90 by 17-allylamino-17-demethoxygeldanamycin (17-AAG) compromises transforming growth factor (TGF)-β-mediated transcriptional responses by enhancing TGF-β receptor I and II degradation, thus preventing Smad2/3 activation. In this study, the authors evaluated whether heat-shock protein 90 regulates TGF-β signaling in the pathogenesis and treatment of keloids. Keloid fibroblasts were treated with 17-AAG (10 μM), and mRNA levels of collagen types I and III were determined by real-time reverse- transcriptase polymerase chain reaction. Also, secreted TGF-β1 was assessed by enzyme-linked immunosorbent assay. The effect of 17-AAG on protein levels of Smad2/3 complex was determined by Western blot analysis. In addition, in 17-AAG-treated keloid spheroids, the collagen deposition and expression of major extracellular matrix proteins were investigated by means of Masson trichrome staining and immunohistochemistry. The authors found that heat-shock protein 90 is overexpressed in human keloid tissue compared with adjacent normal tissue, and 17-AAG decreased mRNA levels of type I collagen, secreted TGF-ß1, and Smad2/3 complex protein expression in keloid fibroblasts. Masson trichrome staining revealed that collagen deposition was decreased in 17-AAG-treated keloid spheroids, and immunohistochemical analysis showed that expression of collagen types I and III, elastin, and fibronectin was markedly decreased in 17-AAG-treated keloid spheroids. These results suggest that the antifibrotic action of heat-shock protein 90 inhibitors such as 17-AAG may have therapeutic effects on keloids.

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

    Science.gov (United States)

    Shaaban, Zahra; Jafarzadeh Shirazi, Mohammad Reza; Nooranizadeh, Mohammad Hossein; Tamadon, Amin; Rahmanifar, Farhad; Ahmadloo, Somayeh; Ramezani, Amin; Zamiri, Mohammad Javad; Razeghian Jahromi, Iman; Sabet Sarvestani, Fatemeh; Hosseinabadi, Omid Koohi

    2018-01-01

    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. PMID:29334206

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  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. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  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...

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

    Science.gov (United States)

    Galvão, Lívia C.C.; Rosalen, Pedro L.; Rivera-Ramos, Isamar; Franco, Gilson C.N.; Kajfasz, Jessica K; Abranches, Jacqueline; Bueno-Silva, Bruno; Koo, Hyun; Lemos, José A.

    2016-01-01

    SUMMARY 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 (ΔspxA1 and ΔspxA1ΔspxA2) 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 ΔspxA2 strain showed increased production of glucans from sucrose, without affecting the total amount of bacteria within biofilms when compared to 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 ΔspxA2 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 the essentiality of animal models in the characterization of bacterial traits implicated in virulence. PMID:27037617

  20. 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.

  1. Isogenic Human iPSC Parkinson’s Model Shows Nitrosative Stress-Induced Dysfunction in MEF2-PGC1α Transcription

    OpenAIRE

    Ryan, Scott D.; Dolatabadi, Nima; Chan, Shing Fai; Zhang, Xiaofei; Akhtar, Mohd Waseem; Parker, James; Soldner, Frank; Sunico, Carmen R.; Nagar, Saumya; Talantova, Maria; Lee, Brian; Lopez, Kevin; Nutter, Anthony; Shan, Bing; Molokanova, Elena

    2013-01-01

    Parkinson’s disease (PD) is characterized by loss of A9 dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). An association has been reported between PD and exposure to mitochondrial toxins, including environmental pesticides paraquat, maneb, and rotenone. Here, using a robust, patient-derived stem cell model of PD allowing comparison of A53T α-synuclein (α-syn) mutant cells and isogenic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations in A...

  2. 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.

  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. 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.

  5. 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

  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. 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.

  8. A novel transgenic mouse model of growth plate dysplasia reveals that decreased chondrocyte proliferation due to chronic ER stress is a key factor in reduced bone growth

    Directory of Open Access Journals (Sweden)

    Benedetta Gualeni

    2013-11-01

    Disease mechanisms leading to different forms of chondrodysplasia include extracellular matrix (ECM alterations and intracellular stress resulting in abnormal changes to chondrocyte proliferation and survival. Delineating the relative contribution of these two disease mechanisms is a major challenge in understanding disease pathophysiology in genetic skeletal diseases and a prerequisite for developing effective therapies. To determine the influence of intracellular stress and changes in chondrocyte phenotype to the development of chondrodysplasia, we targeted the expression of the G2320R mutant form of thyroglobulin to the endoplasmic reticulum (ER of resting and proliferating chondrocytes. Previous studies on this mutant protein have shown that it induces intracellular aggregates and causes cell stress and death in the thyroid gland. The expression and retention of this exogenous mutant protein in resting and proliferating chondrocytes resulted in a chronic cell stress response, growth plate dysplasia and reduced bone growth, without inducing any alterations to the architecture and organization of the cartilage ECM. More significantly, the decreased bone growth seemed to be the direct result of reduced chondrocyte proliferation in the proliferative zone of growth plates in transgenic mice, without transcriptional activation of a classical unfolded protein response (UPR or apoptosis. Overall, these data show that mutant protein retention in the ER of resting and proliferative zone chondrocytes is sufficient to cause disrupted bone growth. The specific disease pathways triggered by mutant protein retention do not necessarily involve a prototypic UPR, but all pathways impact upon chondrocyte proliferation in the cartilage growth plate.

  9. 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.

  10. 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.

  11. Novel H7N9 influenza virus shows low infectious dose, high growth rate, and efficient contact transmission in the guinea pig model.

    Science.gov (United States)

    Gabbard, Jon D; Dlugolenski, Daniel; Van Riel, Debby; Marshall, Nicolle; Galloway, Summer E; Howerth, Elizabeth W; Campbell, Patricia J; Jones, Cheryl; Johnson, Scott; Byrd-Leotis, Lauren; Steinhauer, David A; Kuiken, Thijs; Tompkins, S Mark; Tripp, Ralph; Lowen, Anice C; Steel, John

    2014-02-01

    The zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals. We report here that, in the guinea pig model, a human isolate of novel H7N9 influenza virus, A/Anhui/1/2013 (An/13), is highly dissimilar to an H7N1 avian isolate and instead behaves similarly to a human seasonal strain in several respects. An/13 was found to have a low 50% infectious dose, grow to high titers in the upper respiratory tract, and transmit efficiently among cocaged guinea pigs. The pH of fusion of the hemagglutinin (HA) and the binding of virus to fixed guinea pig tissues were also examined. The An/13 HA displayed a relatively elevated pH of fusion characteristic of many avian strains, and An/13 resembled avian viruses in terms of attachment to tissues. One important difference was seen between An/13 and both the H3N2 human and the H7N1 avian viruses: when inoculated intranasally at a high dose, only the An/13 virus led to productive infection of the lower respiratory tract of guinea pigs. In sum, An/13 was found to retain fusion and attachment properties of an avian influenza virus but displayed robust growth and contact transmission in the guinea pig model atypical of avian strains and indicative of mammalian adaptation.

  12. Novel H7N9 Influenza Virus Shows Low Infectious Dose, High Growth Rate, and Efficient Contact Transmission in the Guinea Pig Model

    Science.gov (United States)

    Gabbard, Jon D.; Dlugolenski, Daniel; Van Riel, Debby; Marshall, Nicolle; Galloway, Summer E.; Howerth, Elizabeth W.; Campbell, Patricia J.; Jones, Cheryl; Johnson, Scott; Byrd-Leotis, Lauren; Steinhauer, David A.; Kuiken, Thijs; Tompkins, S. Mark; Tripp, Ralph; Lowen, Anice C.

    2014-01-01

    The zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals. We report here that, in the guinea pig model, a human isolate of novel H7N9 influenza virus, A/Anhui/1/2013 (An/13), is highly dissimilar to an H7N1 avian isolate and instead behaves similarly to a human seasonal strain in several respects. An/13 was found to have a low 50% infectious dose, grow to high titers in the upper respiratory tract, and transmit efficiently among cocaged guinea pigs. The pH of fusion of the hemagglutinin (HA) and the binding of virus to fixed guinea pig tissues were also examined. The An/13 HA displayed a relatively elevated pH of fusion characteristic of many avian strains, and An/13 resembled avian viruses in terms of attachment to tissues. One important difference was seen between An/13 and both the H3N2 human and the H7N1 avian viruses: when inoculated intranasally at a high dose, only the An/13 virus led to productive infection of the lower respiratory tract of guinea pigs. In sum, An/13 was found to retain fusion and attachment properties of an avian influenza virus but displayed robust growth and contact transmission in the guinea pig model atypical of avian strains and indicative of mammalian adaptation. PMID:24227867

  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.

    Science.gov (United States)

    Fine, Daniel H; Markowitz, Kenneth; Fairlie, Karen; Tischio-Bereski, Debbie; Ferrandiz, Javier; Godboley, Dipti; Furgang, David; Gunsolley, John; Best, Al

    2014-01-01

    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. 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.

  15. 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.

  16. 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...

  17. 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....

  18. Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model.

    Science.gov (United States)

    Inoue, Ken; Naito, Yuji; Takagi, Tomohisa; Hayashi, Natsuko; Hirai, Yasuko; Mizushima, Katsura; Horie, Ryusuke; Fukumoto, Kohei; Yamada, Shinya; Harusato, Akihito; Hirata, Ikuhiro; Omatsu, Tatsushi; Yoshida, Naohisa; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Handa, Osamu; Konishi, Hideyuki; Wakabayashi, Naoki; Yagi, Nobuaki; Ichikawa, Hiroshi; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-01-01

    Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor β1 (TGF-β1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-β1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

  19. Increased stress reactivity is associated with cognitive deficits and decreased hippocampal brain-derived neurotrophic factor in a mouse model of affective disorders.

    Science.gov (United States)

    Knapman, A; Heinzmann, J-M; Hellweg, R; Holsboer, F; Landgraf, R; Touma, C

    2010-07-01

    Cognitive deficits are a common feature of major depression (MD), with largely unknown biological underpinnings. In addition to the affective and cognitive symptoms of MD, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly observed in these patients. Increased plasma glucocorticoid levels are known to render the hippocampus susceptible to neuronal damage. This structure is important for learning and memory, creating a potential link between HPA axis dysregulation and cognitive deficits in depression. In order to further elucidate how altered stress responsiveness may contribute to the etiology of MD, three mouse lines with high (HR), intermediate (IR), or low (LR) stress reactivity were generated by selective breeding. The aim of the present study was to investigate whether increased stress reactivity is associated with deficits in hippocampus-dependent memory tests. To this end, we subjected mice from the HR, IR, and LR breeding lines to tests of recognition memory, spatial memory, and depression-like behavior. In addition, measurements of brain-derived neurotrophic factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our results demonstrate that HR mice exhibit hippocampus-dependent memory deficits along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress reactivity mouse lines are a promising animal model of the cognitive deficits in MD with the unique feature of a genetic predisposition for an altered HPA axis reactivity, which provides the opportunity to explore the progression of the symptoms of MD, predisposing genetic factors as well as new treatment strategies. Copyright 2009 Elsevier Ltd. All rights reserved.

  20. 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.

  1. 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.

  2. 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

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

    Science.gov (United States)

    Vermeiren, Joan; Van den Abbeele, Pieter; Laukens, Debby; Vigsnaes, Louise Kristine; De Vos, Martine; Boon, Nico; Van de Wiele, Tom

    2012-03-01

    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 of Roseburia spp. were lower in the mucosal fractions of the UC samples. qPCR analysis for butyryl-CoA:acetate CoA transferase, responsible for butyrate production, displayed a lower abundance in both the luminal and mucosal fractions of the UC samples. The M-SHIME model revealed depletion in butyrate producing microbial communities not restricted to the luminal but also in the mucosal samples from UC patients compared to HV. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  4. 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.)

  5. 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.

  6. 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...

  7. 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- ...

  8. 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.

  9. 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.

  10. 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.

  11. Technologies for Decreasing Mining Losses

    Science.gov (United States)

    Valgma, Ingo; Väizene, Vivika; Kolats, Margit; Saarnak, Martin

    2013-12-01

    In case of stratified deposits like oil shale deposit in Estonia, mining losses depend on mining technologies. Current research focuses on extraction and separation possibilities of mineral resources. Selective mining, selective crushing and separation tests have been performed, showing possibilities of decreasing mining losses. Rock crushing and screening process simulations were used for optimizing rock fractions. In addition mine backfilling, fine separation, and optimized drilling and blasting have been analyzed. All tested methods show potential and depend on mineral usage. Usage in addition depends on the utilization technology. The questions like stability of the material flow and influences of the quality fluctuations to the final yield are raised.

  12. 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

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

    OpenAIRE

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

    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 ...

  14. The Adnectin CT-322 is a novel VEGF receptor 2 inhibitor that decreases tumor burden in an orthotopic mouse model of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Miller Andrew F

    2008-11-01

    Full Text Available Abstract Background Pancreatic cancer continues to have a 5-year survival of less than 5%. Therefore, more effective therapies are necessary to improve prognosis in this disease. Angiogenesis is required for tumor growth, and subsequently, mediators of angiogenesis are attractive targets for therapy. Vascular endothelial growth factor (VEGF is a well-characterized mediator of tumor angiogenesis that functions primarily by binding and activating VEGF receptor 2 (VEGFR2. In this study, we evaluate the use of CT-322, a novel biologic (Adnectin. This small protein is based on a human fibronectin domain and has beneficial properties in that it is fully human, stable, and is produced in bacteria. CT-322 binds to and inhibits activation of VEGFR2. Methods The efficacy of CT-322 was evaluated in vivo using two orthotopic pancreatic tumor models. The first model was a human tumor xenograft where MiaPaCa-2 cells were injected into the tail of the pancreas of nude mice. The second model was a syngeneic tumor using Pan02 cells injected into pancreas of C57BL/6J mice. In both models, therapy was initiated once primary tumors were established. Mice bearing MiaPaCa-2 tumors were treated with vehicle or CT-322 alone. Gemcitabine alone or in combination with CT-322 was added to the treatment regimen of mice bearing Pan02 tumors. Therapy was given twice a week for six weeks, after which the animals were sacrificed and evaluated (grossly and histologically for primary and metastatic tumor burden. Primary tumors were also evaluated by immunohistochemistry for the level of apoptosis (TUNEL, microvessel density (MECA-32, and VEGF-activated blood vessels (Gv39M. Results Treatment with CT-322 was effective at preventing pancreatic tumor growth and metastasis in orthotopic xenograft and syngeneic models of pancreatic cancer. Additionally, CT-322 treatment increased apoptosis, reduced microvessel density and reduced the number of VEGF-activated blood vessels in tumors

  15. Passive immunization targeting the N-terminal projection domain of tau decreases tau pathology and improves cognition in a transgenic mouse model of Alzheimer disease and tauopathies.

    Science.gov (United States)

    Dai, Chun-ling; Chen, Xia; Kazim, Syed Faraz; Liu, Fei; Gong, Cheng-Xin; Grundke-Iqbal, Inge; Iqbal, Khalid

    2015-04-01

    Intraneuronal accumulation of abnormally hyperphosphorylated tau in the brain is a histopathological hallmark of Alzheimer's disease and a family of related neurodegenerative disorders collectively called tauopathies. At present there is no effective treatment available for these progressive neurodegenerative diseases which are clinically characterized by dementia in mid to old-age. Here we report the treatment of 14-17-months-old 3xTg-AD mice with tau antibodies 43D (tau 6-18) and 77E9 (tau 184-195) to the N-terminal projection domain of tau or mouse IgG as a control by intraperitoneal injection once a week for 4 weeks, and the effects of the passive immunization on reduction of hyperphosphorylated tau, Aβ accumulation and cognitive performance in these animals. We found that treatment with tau antibodies 43D and 77E9 reduced total tau level, decreased tau hyperphosphorylated at Ser199, Ser202/Thr205 (AT8), Thr205, Ser262/356 (12E8), and Ser396/404 (PHF-1) sites, and a trend to reduce Aβ pathology. Most importantly, targeting N-terminal tau especially by 43D (tau 6-18) improved reference memory in the Morris water maze task in 3xTg-AD mice. We did not observe any abnormality in general physical characteristics of the treated animals with either of the two antibodies during the course of this study. Taken together, our studies demonstrate for the first time (1) that passive immunization targeting normal tau can effectively clear the hyperphosphorylated protein and possibly reduce Aβ pathology from the brain and (2) that targeting N-terminal projection domain of tau containing amino acid 6-18 is especially beneficial. Thus, targeting selective epitopes of N-terminal domain of tau may present a novel effective therapeutic opportunity for Alzheimer disease and other tauopathies.

  16. Genetic myostatin decrease in the golden retriever muscular dystrophy model does not significantly affect the ubiquitin proteasome system despite enhancing the severity of disease.

    Science.gov (United States)

    Cotten, Steven W; Kornegay, Joe N; Bogan, Daniel J; Wadosky, Kristine M; Patterson, Cam; Willis, Monte S

    2013-01-01

    Recent studies suggest that inhibiting the protein myostatin, a negative regulator of skeletal muscle mass, may improve outcomes in patients with Duchenne muscular dystrophy by enhancing muscle mass. When the dystrophin-deficient golden retriever muscular dystrophy (GRMD) dog was bred with whippets having a heterozygous mutation for the myostatin gene, affected GRMD dogs with decreased myostatin (GRippets) demonstrated an accelerated physical decline compared to related affected GRMD dogs with full myostatin. To examine the role of the ubiquitin proteasome and calpain systems in this accelerated decline, we determined the expression of the muscle ubiquitin ligases MuRF1, Atrogin-1, RNF25, RNF11, and CHIP: the proteasome subunits PSMA6, PSMB4, and PSME1: and calpain 1/2 by real time PCR in the cranial sartorius and vastus lateralis muscles in control, affected GRMD, and GRippet dogs. While individual affected GRMD and GRippet dogs contributed to an increased variability seen in ubiquitin ligase expression, neither group was significantly different from the control group. The affected GRMD dogs demonstrated significant increases in caspase-like and trypsin-like activity in the cranial sartorius; however, all three proteasome activities in the GRippet muscles did not differ from controls. Increased variability in calpain 1 and calpain 2 expression and activity in the affected GRMD and GRippet groups were identified, but no statistical differences from the control group were seen. These studies suggest a role of myostatin in the disease progression of GRMD, which does not significantly involve key components of the ubiquitin proteasome and calpain systems involved in the protein quality control of sarcomere and other structural skeletal muscle proteins.

  17. 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

    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...... of Roseburia spp. were lower in the mucosal fractions of the UC samples. qPCR analysis for butyryl-CoA:acetate CoA transferase, responsible for butyrate production, displayed a lower abundance in both the luminal and mucosal fractions of the UC samples. The M-SHIME model revealed depletion in butyrate...

  18. Administration of recombinant interleukin-11 improves the hemodynamic functions and decreases third space fluid loss in a porcine model of hemorrhagic shock and resuscitation.

    Science.gov (United States)

    Honma, Kaneatsu; Koles, Nancy L; Alam, Hasan B; Rhee, Peter; Rollwagen, Florence M; Olsen, Cara; Keith, James C; Pollack, Matthew

    2005-06-01

    We have previously demonstrated that the administration of recombinant human interleukin-11 (rhIL-11) during resuscitation improves the blood pressure in a rodent model of hemorrhagic shock. The purpose of this study was to determine whether the effects of rhIL-11 could be reproduced in a large animal model and to elucidate the impact of rhIL-11 administration on the intravascular volume status and the degree of third space fluid loss after resuscitation. A 40% blood volume hemorrhage was induced in swine (n = 45, weight of 25-35 kg) followed by a 1-h shock period and resuscitation with 0.9% sodium chloride (three times the shed blood volume). The animals were randomized to receive sham hemorrhage (group I, sham); sham hemorrhage and 50 microg/kg rhIL-11 (group II, sham + IL-11); no drug (group III, saline); or 50 microg/kg rhIL-11 (group IV, IL-11). Blood and urine samples were obtained and analyzed at baseline, at the end of hemorrhaging, and thereafter once every hour. The pleural and peritoneal effusions were precisely quantified by using clinically accepted criteria. The mean arterial pressure (MAP) was higher postresuscitation (PR) in groups I, II, and IV (71.4 +/- 7.5 mmHg, 71.0 +/- 8.9 mmHg, and 72.9 +/- 12.3 mmHg, respectively) than in group III (59.9 +/- 10.9 mmHg), and the cardiac output of PR was higher in group IV (3.46 +/- 0.56 L/min) than in group III (2.99 +/- 0.62 L/min; P < 0.01). The difference in MAP between groups I and II became statistically significant at 40 min after rhIL-11 injection and such a difference persisted for 90 min. After resuscitation, the urine output was higher, and the urine specific gravity and third space fluid loss were lower in group IV (1434 +/- 325 mL and 1.0035, 82 +/- 21 mL) than in group III (958 +/- 390 mL and 1.0053, 125 +/- 32 mL; P < 0.05). In a porcine model of hemorrhagic shock, the administration of rhIL-11 at the start of resuscitation significantly improved the cardiac output and blood pressure. This

  19. Extract of Irish potatoes (Solanum tuberosum L.) decreases body weight gain and adiposity and improves glucose control in the mouse model of diet-induced obesity.

    Science.gov (United States)

    Kubow, Stan; Hobson, Luc; Iskandar, Michèle M; Sabally, Kebba; Donnelly, Danielle J; Agellon, Luis B

    2014-11-01

    Both sexes of mice were fed a high fat diet (HFD) for 10 weeks without and with polyphenolic-rich potato extracts (PRPE) of cultivars Onaway and Russet Burbank. PRPE attenuated weight gain in male and female mice by as much as 63.2%, which was associated mostly with a reduction in adiposity. Mice receiving PRPE showed enhanced capacity for blood glucose clearance. Sex differences regarding the impact of HFD and PRPE on plasma levels of insulin, ghrelin, leptin, gastric inhibitory peptide, and resistin were noted. PRPE may serve as part of a preventative dietary strategy against the development of obesity and type 2 diabetes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. 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

  1. Malaria morbidity and mortality in Ebola-affected countries caused by decreased health-care capacity, and the potential effect of mitigation strategies: a modelling analysis.

    Science.gov (United States)

    Walker, Patrick G T; White, Michael T; Griffin, Jamie T; Reynolds, Alison; Ferguson, Neil M; Ghani, Azra C

    2015-07-01

    The ongoing Ebola epidemic in parts of west Africa largely overwhelmed health-care systems in 2014, making adequate care for malaria impossible and threatening the gains in malaria control achieved over the past decade. We quantified this additional indirect burden of Ebola virus disease. We estimated the number of cases and deaths from malaria in Guinea, Liberia, and Sierra Leone from Demographic and Health Surveys data for malaria prevalence and coverage of malaria interventions before the Ebola outbreak. We then removed the effect of treatment and hospital care to estimate additional cases and deaths from malaria caused by reduced health-care capacity and potential disruption of delivery of insecticide-treated bednets. We modelled the potential effect of emergency mass drug administration in affected areas on malaria cases and health-care demand. If malaria care ceased as a result of the Ebola epidemic, untreated cases of malaria would have increased by 45% (95% credible interval 43-49) in Guinea, 88% (83-93) in Sierra Leone, and 140% (135-147) in Liberia in 2014. This increase is equivalent to 3·5 million (95% credible interval 2·6 million to 4·9 million) additional untreated cases, with 10,900 (5700-21,400) additional malaria-attributable deaths. Mass drug administration and distribution of insecticide-treated bednets timed to coincide with the 2015 malaria transmission season could largely mitigate the effect of Ebola virus disease on malaria. These findings suggest that untreated malaria cases as a result of reduced health-care capacity probably contributed substantially to the morbidity caused by the Ebola crisis. Mass drug administration can be an effective means to mitigate this burden and reduce the number of non-Ebola fever cases within health systems. UK Medical Research Council, UK Department for International Development, Bill & Melinda Gates Foundation. Copyright © 2015 Walker et al. Open Access article distributed under the terms of CC BY

  2. 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.

  3. 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

    OpenAIRE

    Lee, Young il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-01-01

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes 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 ...

  4. 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......-time bacteremia in Funen County, Denmark, during 2000-2008 (N = 7786). We reported mean and annual incidence rates (per 100,000 person-years), overall and by place of acquisition. Trends were estimated using a Poisson regression model. RESULTS: The overall incidence rate was 215.7, including 99.0 for community......-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 incidence rate of community-acquired bacteremia decreased by 25.6% from 119.0 to 93.8 (3.7% annually, p

  5. 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......, and the dynamic nature of the task in most games. We consider the game shows Card Sharks, Jeopardy!, Lingo, and finally Deal Or No Deal. We provide a detailed case study of the analyses of Deal Or No Deal, since it is suitable for inference about risk attitudes and has attracted considerable attention....

  6. 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)

  7. Reality show: um paradoxo nietzschiano

    Directory of Open Access Journals (Sweden)

    Ilana Feldman

    2011-01-01

    Full Text Available

    O fenômeno dos reality shows - e a subseqüente relação entre imagem e verdade - assenta-se sobre uma série de paradoxos. Tais paradoxos podem ser compreendidos à luz do pensamento do filósofo alemão Friedrich Nietzsche, que, através dos usos de formulações paradoxais, concebia a realidade como um mundo de pura aparência e a verdade como um acréscimo ficcional, como um efeito. A ficção é então tomada, na filosofia de Nietzsche, não em seu aspecto falsificante e desrealizador - como sempre pleiteou nossa tradição metafísica -, mas como condição necessária para que certa espécie de invenção possa operar como verdade. Sendo assim, a própria expressão reality show, através de sua formulação paradoxal, engendra explicitamente um mundo de pura aparência, em que a verdade, a parte reality da proposição, é da ordem do suplemento, daquilo que se acrescenta ficcionalmente - como um adjetivo - a show. O ornamento, nesse caso, passa a ocupar o lugar central, apontando para o efeito produzido: o efeito-de-verdade. Seguindo, então, o pensamento nietzschiano e sua atualização na contemporaneidade, investigaremos de que forma os televisivos “shows de realidade” operam paradoxalmente, em consonância com nossas paradoxais práticas culturais.

  8. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

    Directory of Open Access Journals (Sweden)

    Frentzel Stefan

    2010-06-01

    Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

  9. 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.

  10. 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.

  11. Decreased levels of active uPA and KLK8 assessed by [111 In]MICA-401 binding correlate with the seizure burden in an animal model of temporal lobe epilepsy.

    Science.gov (United States)

    Missault, Stephan; Peeters, Lore; Amhaoul, Halima; Thomae, David; Van Eetveldt, Annemie; Favier, Barbara; Thakur, Anagha; Van Soom, Jeroen; Pitkänen, Asla; Augustyns, Koen; Joossens, Jurgen; Staelens, Steven; Dedeurwaerdere, Stefanie

    2017-09-01

    Urokinase-type plasminogen activator (uPA) and kallikrein-related peptidase 8 (KLK8) are serine proteases that contribute to extracellular matrix (ECM) remodeling after brain injury. They can be labelled with the novel radiotracer [ 111 In]MICA-401. As the first step in exploring the applicability of [ 111 In]MICA-401 in tracing the mechanisms of postinjury ECM reorganization in vivo, we performed in vitro and ex vivo studies, assessing [ 111 In]MICA-401 distribution in the brain in two animal models: kainic acid-induced status epilepticus (KASE) and controlled cortical impact (CCI)-induced traumatic brain injury (TBI). In the KASE model, in vitro autoradiography with [ 111 In]MICA-401 was performed at 7 days and 12 weeks post-SE. To assess seizure burden, rats were monitored using video-electroencephalography (EEG) for 1 month before the 12-week time point. In the CCI model, in vitro autoradiography was performed at 4 days and ex vivo autoradiography at 7 days post-TBI. At 7 days post-SE, in vitro autoradiography revealed significantly decreased [ 111 In]MICA-401 binding in hippocampal CA3 subfield and extrahippocampal temporal lobe (ETL). In the chronic phase, when animals had developed spontaneous seizures, specific binding was decreased in CA3 and CA1/CA2 subfields of hippocampus, dentate gyrus, ETL, and parietal cortex. Of interest, KASE rats with the highest frequency of seizures had the lowest hippocampal [ 111 In]MICA-401 binding (r = -0.76, p ≤ 0.05). Similarly, at 4 days post-TBI, in vitro [ 111 In]MICA-401 binding was significantly decreased in medial and lateral perilesional cortex and ipsilateral dentate gyrus. Ex vivo autoradiography at 7 days post-TBI, however, revealed increased tracer uptake in perilesional cortex and hippocampus, which was likely related to tracer leakage due to blood-brain barrier (BBB) disruption. Strong association of reduced [ 111 In]MICA-401 binding with seizure burden in the KASE model suggests that analysis of reduced

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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…

  17. [Why is bread consumption decreasing?].

    Science.gov (United States)

    Rolland, M F; Chabert, C; Serville, Y

    1977-01-01

    In France bread plays a very special and ambivalent role among our foodstuffs because of the considerable drop in its consumption, its alleged harmful effects on our health and the respect in which it is traditionally held. More than half the 1 089 adults interviewed in this study say they have decreased their consumption of bread in the last 10 years. The reasons given vary according to age, body weight and urbanization level. The main reasons given for this restriction are the desire to prevent or reduce obesity, the decrease in physical activity, the general reduction in food consumption and the possibility of diversifying foods even further. Moreover, the decreasing appeal of bread in relation to other foods, as well as a modification in the structure of meals, in which bread becomes less useful to accompany other food, accentuate this loss of attraction. However, the respect for bread as part of the staple diet remains very acute as 95 p. 100 of those interviewed express a reluctance to throw bread away, more for cultural than economic reasons. Mechanization and urbanization having brought about a decrease in energy needs, the most common alimentary adaptation is general caloric restriction by which glucids, and especially bread, are curtailed.

  18. Distraction decreases prefrontal oxygenation: A NIRS study.

    Science.gov (United States)

    Ozawa, Sachiyo; Hiraki, Kazuo

    2017-04-01

    When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. 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.

  20. Magical thinking decreases across adulthood.

    Science.gov (United States)

    Brashier, Nadia M; Multhaup, Kristi S

    2017-12-01

    Magical thinking, or illogical causal reasoning such as superstitions, decreases across childhood, but almost no data speak to whether this developmental trajectory continues across the life span. In four experiments, magical thinking decreased across adulthood. This pattern replicated across two judgment domains and could not be explained by age-related differences in tolerance of ambiguity, domain-specific knowledge, or search for meaning. These data complement and extend findings that experience, accumulated over decades, guides older adults' judgments so that they match, or even exceed, young adults' performance. They also counter participants' expectations, and cultural sayings (e.g., "old wives' tales"), that suggest that older adults are especially superstitious. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Does fertility decrease household consumption?

    OpenAIRE

    Jungho Kim; Henriette Engelhardt; Alexia Fürnkranz-Prskawetz; Arnstein Aassve

    2009-01-01

    This paper presents an empirical analysis of the relationship between fertility and a direct measure of poverty for Indonesia, a country, which has experienced unprecedented economic growth and sharp fertility declines over recent decades. It focuses on illustrating the sensitivity of the effect of fertility on household consumption with respect to the equivalence scale by applying the propensity score matching method. The analysis suggests that a newborn child decreases household consumption...

  2. 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.

  3. Decreasing Fires in Mediterranean Europe.

    Science.gov (United States)

    Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

    2016-01-01

    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.

  4. INVENTORY DECISIONS WITH DECREASING PURCHASING COSTS

    OpenAIRE

    XIANGPEI HU; HUIMIN WANG; YUNZENG WANG

    2012-01-01

    Costs of many items drop systematically throughout their life-cycles, due to advances in technology and competition. Motivated by the management of service parts for some high-tech products, this paper studies inventory decisions for such items. In a periodic review setting with stochastic demand, we model the purchasing costs of successive periods as a stochastic and decreasing sequence. Unit selling price of the item is determined as some mark-up of the purchasing cost and, hence, will chan...

  5. Methodology of decreasing software complexity using ontology

    Science.gov (United States)

    DÄ browska-Kubik, Katarzyna

    2015-09-01

    In this paper a model of web application`s source code, based on the OSD ontology (Ontology for Software Development), is proposed. This model is applied to implementation and maintenance phase of software development process through the DevOntoCreator tool [5]. The aim of this solution is decreasing software complexity of that source code, using many different maintenance techniques, like creation of documentation, elimination dead code, cloned code or bugs, which were known before [1][2]. Due to this approach saving on software maintenance costs of web applications will be possible.

  6. Price of forest chips decreasing

    International Nuclear Information System (INIS)

    Hakkila, P.

    2001-01-01

    Use of forest chips was studied in 1999 in the national Puuenergia (Wood Energy) research program. Wood combusting heating plants were questioned about are the main reasons restricting the increment of the use of forest chips. Heating plants, which did not use forest chips at all or which used less than 250 m 3 (625 bulk- m 3 ) in 1999 were excluded. The main restrictions for additional use of forest chips were: too high price of forest chips; lack of suppliers and/or uncertainty of deliveries; technical problems of reception and processing of forest chips; insufficiency of boiler output especially in winter; and unsatisfactory quality of chips. The price of forest chips becomes relatively high because wood biomass used for production of forest chips has to be collected from wide area. Heavy equipment has to be used even though small fragments of wood are processed, which increases the price of chips. It is essential for forest chips that the costs can be pressed down because competition with fossil fuels, peat and industrial wood residues is hard. Low market price leads to the situation in which forest owner gets no price of the raw material, the entrepreneurs operate at the limit of profitability and renovation of machinery is difficult, and forest chips suppliers have to sell the chips at prime costs. Price of forest chips has decreased significantly during the past decade. Nominal price of forest chips is now lower than two decades ago. The real price of chips has decreased even more than the nominal price, 35% during the past decade and 20% during the last five years. Chips, made of small diameter wood, are expensive because the price includes the felling costs and harvesting is carried out at thinning lots. Price is especially high if chips are made of delimbed small diameter wood due to increased the work and reduced amount of chips. The price of logging residue chips is most profitable because cutting does not cause additional costs. Recovery of chips is

  7. 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…

  8. Noncommunicable Diseases: Three Decades Of Global Data Show A Mixture Of Increases And Decreases In Mortality Rates.

    Science.gov (United States)

    Ali, Mohammed K; Jaacks, Lindsay M; Kowalski, Alysse J; Siegel, Karen R; Ezzati, Majid

    2015-09-01

    Noncommunicable diseases are the leading health concerns of the modern era, accounting for two-thirds of global deaths, half of all disability, and rapidly growing costs. To provide a contemporary overview of the burdens caused by noncommunicable diseases, we compiled mortality data reported by authorities in forty-nine countries for atherosclerotic cardiovascular diseases; diabetes; chronic respiratory diseases; and lung, colon, breast, cervical, liver, and stomach cancers. From 1980 to 2012, on average across all countries, mortality for cardiovascular disease, stomach cancer, and cervical cancer declined, while mortality for diabetes, liver cancer, and female chronic respiratory disease and lung cancer increased. In contrast to the relatively steep cardiovascular and cancer mortality declines observed in high-income countries, mortality for cardiovascular disease and chronic respiratory disease was flat in most low- and middle-income countries, which also experienced increasing breast and colon cancer mortality. These divergent mortality patterns likely reflect differences in timing and magnitude of risk exposures, health care, and policies to counteract the diseases. Improving both the coverage and the accuracy of mortality documentation in populous low- and middle-income countries is a priority, as is the need to rigorously evaluate societal-level interventions. Furthermore, given the complex, chronic, and progressive nature of noncommunicable diseases, policies and programs to prevent and control them need to be multifaceted and long-term, as returns on investment accrue with time. Project HOPE—The People-to-People Health Foundation, Inc.

  9. 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

  10. 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

  11. Rigidity spectrum of Forbush decrease

    International Nuclear Information System (INIS)

    Sakakibara, S.; Munakata, K.; Nagashima, K.

    1985-01-01

    Using data from neutron monitors and muon telescopes at surface and underground stations, the average rigidity spectrum of Forbush decreases (Fds) during the period of 1978-1982 were obtained. Thirty eight Ed-events are classified into two groups, Hard Fd and Soft FD according to size of Fd at the Sakashita station. It is found that a spectral form of a fractional-power type (P to the-gamma sub 1 (P+P sub c) to the -gamma sub2) is more suitable than that of a power-exponential type or of a power type with an upper limiting rigidity. The best fitted spectrum of the fractional-power type is expressed by gamma sub1 = 0.37, gamma sub2 = 0.89 and P subc = 10 GV for Hard Fd and gamma sub1 = 0.77, gamma sub2 = 1.02 and P sub c - 14GV for Soft Fd

  12. Method of decreasing nuclear power

    International Nuclear Information System (INIS)

    Masuda, Hiromi

    1987-01-01

    Purpose: To easily attain the power decreasing in a HWLWR type reactor and improve the reactor safety. Method: The method is applied to a nuclear reactor in which the reactor reactivity is controlled by control rods and liquid posions dissolved in moderators. Means for forecasting the control rod operation amount required for the reactor power down and means for removing liquid poisons in the moderators are provided. The control rod operation amount required for the power down is forecast before the power down and the liquid poisons in the moderators are removed. Then, the control rods are inserted into a deep insertion position to reduce the reactor power. This invention can facilitate easy power down, as well as provide effects of improving the controllability in the usual operation and of avoiding abrupt power down which leads to an improved availability. (Kamimura, M.)

  13. Observed Decrease of North American Winter Temperature Variability

    Science.gov (United States)

    Rhines, A. N.; Tingley, M.; McKinnon, K. A.; Huybers, P. J.

    2015-12-01

    There is considerable interest in determining whether temperature variability has changed in recent decades. Model ensembles project that extratropical land temperature variance will detectably decrease by 2070. We use quantile regression of station observations to show that decreasing variability is already robustly detectable for North American winter during 1979--2014. Pointwise trends from GHCND stations are mapped into a continuous spatial field using thin-plate spline regression, resolving small-scales while providing uncertainties accounting for spatial covariance and varying station density. We find that variability of daily temperatures, as measured by the difference between the 95th and 5th percentiles, has decreased markedly in winter for both daily minima and maxima. Composites indicate that the reduced spread of winter temperatures primarily results from Arctic amplification decreasing the meridional temperature gradient. Greater observed warming in the 5th relative to the 95th percentile stems from asymmetric effects of advection during cold versus warm days; cold air advection is generally from northerly regions that have experienced greater warming than western or southwestern regions that are generally sourced during warm days.

  14. 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.

  15. Neer Award 2016: reduced muscle degeneration and decreased fatty infiltration after rotator cuff tear in a poly(ADP-ribose) polymerase 1 (PARP-1) knock-out mouse model.

    Science.gov (United States)

    Kuenzler, Michael B; Nuss, Katja; Karol, Agnieszka; Schär, Michael O; Hottiger, Michael; Raniga, Sumit; Kenkel, David; von Rechenberg, Brigitte; Zumstein, Matthias A

    2017-05-01

    Disturbed muscular architecture, atrophy, and fatty infiltration remain irreversible in chronic rotator cuff tears even after repair. Poly (adenosine 5'-diphosphate-ribose) polymerase 1 (PARP-1) is a key regulator of inflammation, apoptosis, muscle atrophy, muscle regeneration, and adipocyte development. We hypothesized that the absence of PARP-1 would lead to a reduction in damage to the muscle subsequent to combined tenotomy and neurectomy in a PARP-1 knockout (KO) mouse model. PARP-1 KO and wild-type C57BL/6 (WT group) mice were analyzed at 1, 6, and 12 weeks (total n = 84). In all mice, the supraspinatus and infraspinatus muscles of the left shoulder were detached and denervated. Macroscopic analysis, magnetic resonance imaging, gene expression analysis, immunohistochemistry, and histology were used to assess the differences in PARP-1 KO and WT mice. The muscles in the PARP-1 KO group had significantly less retraction, atrophy, and fatty infiltration after 12 weeks than in the WT group. Gene expression of inflammatory, apoptotic, adipogenic, and muscular atrophy genes was significantly decreased in PARP-1 KO mice in the first 6 weeks. Absence of PARP-1 leads to a reduction in muscular architectural damage, early inflammation, apoptosis, atrophy, and fatty infiltration after combined tenotomy and neurectomy of the rotator cuff muscle. Although the macroscopic reaction to injury is similar in the first 6 weeks, the ability of the muscles to regenerate was much greater in the PARP-1 KO group, leading to a near-normalization of the muscle after 12 weeks. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  16. Suppressing cAMP response element-binding protein transcription shortens the duration of status epilepticus and decreases the number of spontaneous seizures in the pilocarpine model of epilepsy.

    Science.gov (United States)

    Zhu, Xinjian; Dubey, Deepti; Bermudez, Camilo; Porter, Brenda E

    2015-12-01

    Current epilepsy therapies directed at altering the function of neurotransmitter receptors or ion channels, or release of synaptic vesicles fail to prevent seizures in approximately 30% of patients. A better understanding of the molecular mechanism underlying epilepsy is needed to provide new therapeutic targets. The activity of cyclic AMP (cAMP) response element-binding protein (CREB), a major transcription factor promoting CRE-mediated transcription, increases following a prolonged seizure called status epilepticus. It is also increased in the seizure focus of patients with medically intractable focal epilepsy. Herein we explored the effect of acute suppression of CREB activity on status epilepticus and spontaneous seizures in a chronic epilepsy model. Pilocarpine chemoconvulsant was used to induce status epilepticus. To suppress CREB activity, a transgenic mouse line expressing an inducible dominant negative mutant of CREB (CREB(IR) ) with a serine to alanine 133 substitution was used. Status epilepticus and spontaneous seizures of transgenic and wild-type mice were analyzed using video-electroencephalography (EEG) to assess the effect of CREB suppression on seizures. Our findings indicate that activation of CREB(IR) shortens the duration of status epilepticus. The frequency of spontaneous seizures decreased in mice with chronic epilepsy during CREB(IR) induction; however, the duration of the spontaneous seizures was unchanged. Of interest, we found significantly reduced levels of phospho-CREB Ser133 upon activation of CREB(IR) , supporting prior work suggesting that binding to the CRE site is important for CREB phosphorylation. Our results suggest that CRE transcription supports seizure activity both during status epilepticus and in spontaneous seizures. Thus, blocking of CRE transcription is a novel target for the treatment of epilepsy. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  17. 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.

  18. Did liberalising bar hours decrease traffic accidents?

    Science.gov (United States)

    Green, Colin P; Heywood, John S; Navarro, Maria

    2014-05-01

    Legal bar closing times in England and Wales have historically been early and uniform. Recent legislation liberalised closing times with the object of reducing social problems thought associated with drinking to "beat the clock." Indeed, using both difference in difference and synthetic control approaches we show that one consequence of this liberalisation was a decrease in traffic accidents. This decrease is heavily concentrated among younger drivers. Moreover, we provide evidence that the effect was most pronounced in the hours of the week directly affected by the liberalisation: late nights and early mornings on weekends. This evidence survives a series of robustness checks and suggests at least one socially positive consequence of extending bar hours. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. 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.

  20. Bacteriophages show promise as antimicrobial agents.

    Science.gov (United States)

    Alisky, J; Iczkowski, K; Rapoport, A; Troitsky, N

    1998-01-01

    The emergence of antibiotic-resistant bacteria has prompted interest in alternatives to conventional drugs. One possible option is to use bacteriophages (phage) as antimicrobial agents. We have conducted a literature review of all Medline citations from 1966-1996 that dealt with the therapeutic use of phage. There were 27 papers from Poland, the Soviet Union, Britain and the U.S.A. The Polish and Soviets administered phage orally, topically or systemically to treat a wide variety of antibiotic-resistant pathogens in both adults and children. Infections included suppurative wound infections, gastroenteritis, sepsis, osteomyelitis, dermatitis, empyemas and pneumonia; pathogens included Staphylococcus, Streptococcus, Klebsiella, Escherichia, Proteus, Pseudomonas, Shigella and Salmonella spp. Overall, the Polish and Soviets reported success rates of 80-95% for phage therapy, with rare, reversible gastrointestinal or allergic side effects. However, efficacy of phage was determined almost exclusively by qualitative clinical assessment of patients, and details of dosages and clinical criteria were very sketchy. There were also six British reports describing controlled trials of phage in animal models (mice, guinea pigs and livestock), measuring survival rates and other objective criteria. All of the British studies raised phage against specific pathogens then used to create experimental infections. Demonstrable efficacy against Escherichia, Acinetobacter, Pseudomonas and Staphylococcus spp. was noted in these model systems. Two U.S. papers dealt with improving the bioavailability of phage. Phage is sequestered in the spleen and removed from circulation. This can be overcome by serial passage of phage through mice to isolate mutants that resist sequestration. In conclusion, bacteriophages may show promise for treating antibiotic resistant pathogens. To facilitate further progress, directions for future research are discussed and a directory of authors from the reviewed

  1. The Alpha value decrease when the annual individual effective dose decreases?

    International Nuclear Information System (INIS)

    Sordi, Gian M.; Marchiusi, Thiago; Sousa, Jefferson de J.

    2008-01-01

    A recent IAEA publication tells that a few entities took different alpha values for maxima individual doses. Beyond to disregard the international agencies, that recommend only one alpha value for each country, the alpha values decreases when the individual doses decreases and the practice happens exactly the conversely as we will show in this paper. We will prove that the alpha value increase when the maximum individual doses decreases in a four different manner. The first one we call the theoretical conception and it is linked to the emergent of the ALARA policy and to the purpose that led to the 3/10 of the annual limits, for to decrease the individual doses as a first resort and a 1/10 as a last resort. The second prove will be based in a small mine example used in the ICRP publication number 55 concerning to the optimization and the quantitative decision-aiding techniques in radiological protection where we will determine the alpha value ranges in which each radiological protection options becomes the analytical solution. The third prove will be based in the determination of the optimized thickness example of a plane shielding for a radiation source exposed in the ICRP publication number 37. We will use, also, the numerical example provided there. Eventually, as four prove we will show that the alpha value dos not only increases with the maximum individual dose decrease, but also, with the shielding geometry. (author)

  2. 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.

  3. Lifestyle Decreases Risk Factors for Cardiovascular Diseases

    Science.gov (United States)

    Slavíček, Jaroslav; Kittnar, Otomar; Fraser, Gary E.; Medová, Eva; Konečná, Jana; Žižka, Robert; Dohnalová, Alena; Novák, Vladimír

    2009-01-01

    Summary The morbidity and mortality of the cardiovascular diseases is high in the developed countries. The lifestyle changes are capable to decrease it by 50%. The aim of the present study was to measure the parameters of some risk factors before and after a one-week NEW START rehabilitative retreat. 1,349 volunteers, 320 men, 1,029 woman, mean age 51±14.5 (SD) years participated in 30 rehabilitative retreats from 1999–2006 in the Czech Republic, using a low-fat, low-energy, lacto-ovo-vegetarian diet and exercise, in a stress-free environment. Body weight, height, BMI, blood pressure, heart rate, serum cholesterol and blood glucose were measured. Body weight decreased in 1,223 measured persons from 71.2±14.38 (SD) to 70.6±14.02 kg (pSeventh-day Adventists than in controls who never observed the diet and avail the lifestyle programs. The parameters were nonsignificantly changed one year after finishing the retreat in the sample of 68 persons showing the positive effect of retreats. Our results showed, that the intake of a low-fat, low-energy diet, over the course of one week in a stress-free environment, had positive impact on the risk factors of cardiovascular diseases. PMID:19256282

  4. Benazepril hydrochloride improves diabetic nephropathy and decreases proteinuria by decreasing ANGPTL-4 expression.

    Science.gov (United States)

    Xue, Lingyu; Feng, Xiaoqing; Wang, Chuanhai; Zhang, Xuebin; Sun, Wenqiang; Yu, Kebo

    2017-10-04

    This study aimed to investigate the effects of benazepril hydrochloride (BH) on proteinuria and ANGPTL-4 expression in a diabetic nephropathy (DN) rat model. A total of 72 Wistar male rats were randomly divided into three groups: normal control (NC), DN group and BH treatment (BH) groups. The DN model was induced by streptozotocin (STZ). Weight, glucose, proteinuria, biochemical indicators and the kidney weight index were examined at 8, 12 and 16 weeks. In addition, ANGPTL-4 protein and mRNA expressions were assessed by immunohistochemistry and qRT-PCR, respectively. Relationships between ANGPTL-4 and biochemical indicators were investigated using Spearman analysis. Weight was significantly lower but glucose levels were significantly higher in both the DN and BH groups than in the NC group (P Benazepril hydrochloride improves DN and decreases proteinuria by decreasing ANGPTL-4 expression.

  5. Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis.

    Directory of Open Access Journals (Sweden)

    Weiling Xu

    Full Text Available Asthma, a chronic inflammatory airway disease, is typified by high levels of TH2-cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma.

  6. Stop signals decrease choices for palatable foods through decreased food evaluation

    Science.gov (United States)

    Veling, Harm; Aarts, Henk; Stroebe, Wolfgang

    2013-01-01

    The present study explores whether presenting specific palatable foods in close temporal proximity of stop signals in a go/no-go task decreases subsequent evaluations of such foods among participants with a relatively high appetite. Furthermore, we tested whether any decreased evaluations could mediate subsequent food choice. Participants first received a go/no-go task in which palatable foods were consistently linked to go cues or no-go cues within participants. Next, evaluation of the palatable foods was measured as well as food choice. Replicating previous work, results show that among participants with a relatively high appetite palatable foods associated with no-go cues are less often chosen as snacks compared to when these foods are associated with go cues, whereas this manipulation did not affect participants with a relatively low appetite. Moreover, this effect was completely mediated by decreased evaluation of the palatable foods that had been associated with the no-go cues, whereas evaluation of the foods associated with go cues did not mediate this effect. Results further showed that the devaluation effect of foods associated with no-go cues was independent of the amount of pairings (4 vs. 12 vs. 24) with the no-go cues. The current findings suggest that decreased food evaluation is a mechanism that explains effects of stop signals on food choice. PMID:24324451

  7. Breastfeeding Is Associated with Decreased Childhood Maltreatment.

    Science.gov (United States)

    Kremer, Kristen P; Kremer, Theodore R

    Child maltreatment has serious implications for youth outcomes, yet its associations with early parenting practices are not fully understood. This study investigated whether breastfeeding practices are correlated with childhood maltreatment. Data were utilized from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative and longitudinal study of adolescents. The analytic sample comprised 4,159 adolescents. The outcome variables included four subtypes of childhood maltreatment (neglect, inadequate supervision, physical abuse, and sexual abuse). The primary independent variable was breastfeeding duration. Covariates of the child, mother, and household were included in analyses. Logistic regression models were employed to predict odds of maltreatment subtypes from breastfeeding duration and covariates. Compared with adolescents never breastfed, adolescents breastfed 9 months or longer had a reduced odds of having experienced neglect (odds ratio [OR] = 0.54; 95% confidence interval [CI] = 0.35-0.83) and sexual abuse (OR = 0.47; 95% CI = 0.24-0.93) after controlling for covariates. Breastfeeding duration is significantly associated with decreased childhood neglect and sexual abuse. Breastfeeding practices should be explored as a consideration among clinicians when assessing maltreatment risk. Further research should examine whether a causal relationship exists between breastfeeding and decreased maltreatment.

  8. 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.

  9. 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.

  10. Dual Component Removable Partial Denture shows improved ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-02-18

    Feb 18, 2009 ... 2Faculty of Dentistry, the University of Hong Kong, Hong Kong. 3Department of ... an example of poor oral condition caused mainly by periodontitis, and ... working model of the Dual Component Removable Partial Denture.

  11. UV Photography Shows Hidden Sun Damage

    Science.gov (United States)

    ... mcat1=de12", ]; for (var c = 0; c UV photography shows hidden sun damage A UV photograph gives ... developing skin cancer and prematurely aged skin. Normal photography UV photography 18 months of age: This boy's ...

  12. Educational Outreach: The Space Science Road Show

    Science.gov (United States)

    Cox, N. L. J.

    2002-01-01

    The poster presented will give an overview of a study towards a "Space Road Show". The topic of this show is space science. The target group is adolescents, aged 12 to 15, at Dutch high schools. The show and its accompanying experiments would be supported with suitable educational material. Science teachers at schools can decide for themselves if they want to use this material in advance, afterwards or not at all. The aims of this outreach effort are: to motivate students for space science and engineering, to help them understand the importance of (space) research, to give them a positive feeling about the possibilities offered by space and in the process give them useful knowledge on space basics. The show revolves around three main themes: applications, science and society. First the students will get some historical background on the importance of space/astronomy to civilization. Secondly they will learn more about novel uses of space. On the one hand they will learn of "Views on Earth" involving technologies like Remote Sensing (or Spying), Communication, Broadcasting, GPS and Telemedicine. On the other hand they will experience "Views on Space" illustrated by past, present and future space research missions, like the space exploration missions (Cassini/Huygens, Mars Express and Rosetta) and the astronomy missions (Soho and XMM). Meanwhile, the students will learn more about the technology of launchers and satellites needed to accomplish these space missions. Throughout the show and especially towards the end attention will be paid to the third theme "Why go to space"? Other reasons for people to get into space will be explored. An important question in this is the commercial (manned) exploration of space. Thus, the questions of benefit of space to society are integrated in the entire show. It raises some fundamental questions about the effects of space travel on our environment, poverty and other moral issues. The show attempts to connect scientific with

  13. 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...

  14. 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.

  15. 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…

  16. 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…

  17. 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.

  18. 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

  19. '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

  20. 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

  1. 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.

  2. The Presentation of Science in Everyday Life: The Science Show

    Science.gov (United States)

    Watermeyer, Richard

    2013-01-01

    This paper constitutes a case-study of the "science show" model of public engagement employed by a company of science communicators focused on the popularization of science, technology, engineering and mathematics (STEM) subject disciplines with learner constituencies. It examines the potential of the science show to foster the interest…

  3. α-Asarone Attenuates Cognitive Deficit in a Pilocarpine-Induced Status Epilepticus Rat Model via a Decrease in the Nuclear Factor-κB Activation and Reduction in Microglia Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Hui-juan Liu

    2017-12-01

    Full Text Available BackgroundTemporal lobe epilepsy (TLE is one of the most drug-resistant types of epilepsy with about 80% of TLE patients falling into this category. Increasing evidence suggests that neuroinflammation, which has a critical role in the epileptogenesis of TLE, is associated with microglial activation. Therefore, agents that act toward the alleviation in microglial activation and the attenuation of neuroinflammation are promising candidates to treat TLE. α-Asarone is a major active ingredient of the Acori Graminei Rhizoma used in Traditional Chinese Medicine, which has been used to improve various disease conditions including stroke and convulsions. In addition, an increasing number of studies suggested that α-asarone can attenuate microglia-mediated neuroinflammation. Thus, we hypothesized that α-asarone is a promising neuroprotective agent for the treatment of the TLE.MethodsThe present study evaluated the therapeutic effects of α-asarone on microglia-mediated neuroinflammation and neuroprotection in vitro and in vivo, using an untreated control group, a status epilepticus (SE-induced group, and an SE-induced α-asarone pretreated group. A pilocarpine-induced rat model of TLE was established to investigate the neuroprotective effects of α-asarone in vivo. For the in vitro study, lipopolysaccharide (LPS-stimulated primary cultured microglial cells were used.ResultsThe results indicated that the brain microglial activation in the rats of the SE rat model led to important learning and memory deficit. Preventive treatment with α-asarone restrained microglial activation and reduced learning and memory deficit. In the in vitro studies, α-asarone significantly suppressed proinflammatory cytokine production in primary cultured microglial cells and attenuated the LPS-stimulated neuroinflammatory responses. Our mechanistic study revealed that α-asarone inhibited inflammatory processes by regulation the transcription levels of kappa-B, by blocking

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Spontaneous entropy decrease and its statistical formula

    OpenAIRE

    Xing, Xiu-San

    2007-01-01

    Why can the world resist the law of entropy increase and produce self-organizing structure? Does the entropy of an isolated system always only increase and never decrease? Can be thermodymamic degradation and self-organizing evolution united? How to unite? In this paper starting out from nonequilibrium entropy evolution equation we proved that a new entropy decrease could spontaneously emerge in nonequilibrium system with internal attractive interaction. This new entropy decrease coexists wit...

  9. Myopes show increased susceptibility to nearwork aftereffects.

    Science.gov (United States)

    Ciuffreda, K J; Wallis, D M

    1998-09-01

    Some aspects of accommodation may be slightly abnormal (or different) in myopes, compared with accommodation in emmetropes and hyperopes. For example, the initial magnitude of accommodative adaptation in the dark after nearwork is greatest in myopes. However, the critical test is to assess this initial accommodative aftereffect and its subsequent decay in the light under more natural viewing conditions with blur-related visual feedback present, if a possible link between this phenomenon and clinical myopia is to be considered. Subjects consisted of adult late- (n = 11) and early-onset (n = 13) myopes, emmetropes (n = 11), and hyperopes (n = 9). The distance-refractive state was assessed objectively using an autorefractor immediately before and after a 10-minute binocular near task at 20 cm (5 diopters [D]). Group results showed that myopes were most susceptible to the nearwork aftereffect. It averaged 0.35 D in initial magnitude, with considerably faster posttask decay to baseline in the early-onset (35 seconds) versus late-onset (63 seconds) myopes. There was no myopic aftereffect in the remaining two refractive groups. The myopes showed particularly striking accommodatively related nearwork aftereffect susceptibility. As has been speculated and found by many others, transient pseudomyopia may cause or be a precursor to permanent myopia or myopic progression. Time-integrated increased retinal defocus causing axial elongation is proposed as a possible mechanism.

  10. Increasing spin-flips and decreasing cost: Perturbative corrections for external singles to the complete active space spin flip model for low-lying excited states and strong correlation

    International Nuclear Information System (INIS)

    Mayhall, Nicholas J.; Head-Gordon, Martin

    2014-01-01

    An approximation to the spin-flip extended configuration interaction singles method is developed using a second-order perturbation theory approach. In addition to providing significant efficiency advantages, the new framework is general for an arbitrary number of spin-flips, with the current implementation being applicable for up to around 4 spin-flips. Two new methods are introduced: one which is developed using non-degenerate perturbation theory, spin-flip complete active-space (SF-CAS(S)), and a second quasidegenerate perturbation theory method, SF-CAS(S) 1 . These two approaches take the SF-CAS wavefunction as the reference, and then perturbatively includes the effect of single excitations. For the quasidegenerate perturbation theory method, SF-CAS(S) 1 , the subscripted “1” in the acronym indicates that a truncated denominator expansion is used to obtain an energy-independent down-folded Hamiltonian. We also show how this can alternatively be formulated in terms of an extended Lagrangian, by introducing an orthonormality constraint on the first-order wavefunction. Several numerical examples are provided, which demonstrate the ability of SF-CAS(S) and SF-CAS(S) 1 to describe bond dissociations, singlet-triplet gaps of organic molecules, and exchange coupling parameters for binuclear transition metal complexes

  11. Can photobiomodulation associated with implantation of mesenchymal adipose-derived stem cells attenuate the expression of MMPs and decrease degradation of type II collagen in an experimental model of osteoarthritis?

    Science.gov (United States)

    Stancker, Tatiane Garcia; Vieira, Stella Souza; Serra, Andrey Jorge; do Nascimento Lima, Rafael; Dos Santos Feliciano, Regiane; Silva, José Antônio; Dos Santos, Solange Almeida; Dos Santos Vieira, Marcia Ataize; Simões, Maíra Cecília Brandão; Leal-Junior, Ernesto Cesar; de Tarso Camillo de Carvalho, Paulo

    2018-03-08

    This study aimed to determine whether photobiomodulation therapy (PBMT) could improve the bioavailability and chondroprotective benefits of mesenchymal stem cells injected into the knees of rats used as an experimental model of osteoarthritis (OA) as well as reduce the expression of matrix metalloproteinases (MMPs) and degradation of type II collagen (COL2-1) in the cartilage. Adipose-derived stem/stromal cells (ADSCs) were collected from three male Fischer 344 rats and characterized by flow cytometry. Fifty female Fischer 344 rats were distributed into five groups of 10 animals each. These groups were as follows: control, OA, OA PBMT, OA ADSC, and OA ADSC PBMT. OA was induced in the animals using a 4% papain solution. Animals from the OA ADSC and OA ADSC PBMT groups received an intra-articular injection of 10 × 10 6 ADSCs and were treated with PBMT by irradiation (wavelength: 808 nm, power: 50 mW, energy: 42 J, energy density: 71.2 J/cm 2 , spot size: 0.028). Euthanasia was performed 7 days after the first treatment. The use of PBMT alone and the injection of ADSCs resulted in downregulation of pro-inflammatory cytokines and MPs in cartilage compared to the OA group. PBMT and ADSCs caused upregulation of tissue inhibitors of MPs 1 and 2 and mRNA and protein expression of COL2-1 in cartilage compared to the OA group. The intra-articular injection of ADSCs and PBMT prevented joint degeneration resulting from COL2-1 degradation and modulated inflammation by downregulating cytokines and MMPs in the OA group.

  12. 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

  13. 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

  14. Sled Towing Acutely Decreases Acceleration Sprint Time.

    Science.gov (United States)

    Wong, Megan A; Dobbs, Ian J; Watkins, Casey M; Barillas, Saldiam R; Lin, Anne; Archer, David C; Lockie, Robert G; Coburn, Jared W; Brown, Lee E

    2017-11-01

    Wong, MA, Dobbs, IJ, Watkins, C, Barillas, SR, Lin, A, Archer, DC, Lockie, RG, Coburn, JW, and Brown, LE. Sled towing acutely decreases acceleration sprint time. J Strength Cond Res 31(11): 3046-3051, 2017-Sled towing is a common form of overload training in sports to develop muscular strength for sprinting. This type of training leads to acute and chronic outcomes. Acute training potentially leads to postactivation potentiation (PAP), which is when subsequent muscle performance is enhanced after a preload stimulus. The purpose of this study was to determine differences between rest intervals after sled towing on acute sprint speed. Twenty healthy recreationally trained men (age = 22.3 ± 2.4 years, height = 176.95 ± 5.46 cm, mass = 83.19 ± 11.31 kg) who were currently active in a field sport twice a week for the last 6 months volunteered to participate. A maximal 30-meter (m) baseline (BL) body mass (BM) sprint was performed (with splits at 5, 10, 20, and 30 m) followed by 5 visits where participants sprinted 30 m towing a sled at 30% BM then rested for 2, 4, 6, 8, or 12 minutes. They were instructed to stand still during rest times. After the rest interval, they performed a maximal 30-m post-test BM sprint. Analysis of variance (ANOVA) revealed that post sled tow BM sprint times (4.47 ± 0.21 seconds) were less than BL times (4.55 ± 0.18 seconds) on an individualized rest interval basis. A follow-up 2 × 4 ANOVA showed that this decrease occurred only in the acceleration phase over the first 5 m (BL = 1.13 ± 0.08 seconds vs. Best = 1.08 ± 0.08 seconds), which may be the result of PAP and the complex relationship between fatigue and potentiation relative to the intensity of the sled tow and the rest interval. Therefore, coaches should test their athletes on an individual basis to determine optimal rest time after a 30-m 30% BM sled tow to enhance acute sprint speed.

  15. Ancient bacteria show evidence of DNA repair

    DEFF Research Database (Denmark)

    Johnson, Sarah Stewart; Hebsgaard, Martin B; Christensen, Torben R

    2007-01-01

    -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...... geological timescales. There has been no direct evidence in ancient microbes for the most likely mechanism, active DNA repair, or for the metabolic activity necessary to sustain it. In this paper, we couple PCR and enzymatic treatment of DNA with direct respiration measurements to investigate long...... 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....

  16. 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.

  17. Use of biofuels in road transport decreases

    International Nuclear Information System (INIS)

    Segers, R.

    2011-01-01

    The use of biofuels decreased from 3.5 percent, for all gasoline and diesel used by road transport in 2009, to 2 percent in 2010. Particularly the use of biodiesel decreased, dropping from 3.5 to 1.5 percent. The use of biogasoline remained stable, catering for 3 percent of all gasoline use. [nl

  18. 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.

  19. 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

  20. Grazing disturbance increases transient but decreases persistent soil seed bank.

    Science.gov (United States)

    Ma, Miaojun; Walck, Jeffrey L; Ma, Zhen; Wang, Lipei; Du, Guozhen

    2018-04-30

    Very few studies have examined whether the impacts of grazing disturbance on soil seed banks occur directly or indirectly through aboveground vegetation and soil properties. The potential role of the seed bank in alpine wetland restoration is also unknown. We used SEM (structural equation modeling) to explore the direct effect of grazing disturbance on the seed bank and the indirect effect through aboveground vegetation and soil properties. We also studied the role of the seed bank on the restoration potential in wetlands with various grazing intensities: low (fenced, winter grazed only), medium (seasonally grazed), and high (whole-year grazed). For the seed bank, species richness and density per plot showed no difference among grazing intensities for each depth (0-5, 5-10, 10-15 cm) and for the whole depth (0-15 cm) in spring and summer. There was no direct effect of grazing disturbance on seed bank richness and density both in spring and summer, and also no indirect effect on the seed bank through its direct effect on vegetation richness and abundance. Grazing disturbance indirectly increased spring seed bank density but decreased summer seed bank density through its direct effect (negative correlation) on soil moisture and total nitrogen and its indirect effect on vegetation abundance. Species composition of the vegetation changed with grazing regime, but that of the seed bank did not. An increased trend of similarity between the seed bank and aboveground vegetation with increased grazing disturbance was found in the shallow depth and in the whole depth only in spring. Although there was almost no change in seed bank size with grazing intensities, grazing disturbance increased the quantity of transient seeds but decreased persistent seeds. Persistent seeds stored in the soil could play a crucial role in vegetation regeneration and in restoration of degraded wetland ecosystems. The seed bank should be an integral part of alpine wetland restoration programs.

  1. Soliton-effect generation of Raman pulses in optical fibers with slowly decreasing dispersion

    International Nuclear Information System (INIS)

    Wenhua Cao; Youwei Zhang

    1995-01-01

    We suggested that single-mode fibers with slowly decreasing dispersion (FSDD) should be used for the generation of tunable ultrashort RAman pulses. A mathematical model is obtained for the description of ultrafast stimulated Raman scattering in optical fibers with slowly decreasing dispersion. Numerical simulations show that, under identical pump conditions, Raman pulse generated from this kind of fiber is shorter with a higher peak power than that generated from conventional fibers. This means that the Raman threshold of fibers with slowly decreasing dispersion may be lower than that of conventional fibers. Given pump conditions, we found that the highest peak power and narrowest width of the Raman pulse correspond to an optimal decrement velocity of the fiber dispersion

  2. 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 ...

  3. Using a Nonaversive Procedure to Decrease Refusals.

    Science.gov (United States)

    Spooner, Fred; And Others

    1990-01-01

    A nonaversive technique was used to teach a severely handicapped woman to decrease her refusals. The technique employed precision teaching via precise daily measurement strategies, environmental analysis, and a focus on building appropriate behavior. (JDD)

  4. Autoimmune Response Confers Decreased Cardiac Function in ...

    African Journals Online (AJOL)

    inflammatory response; rather, autoimmune response would keep affecting decreased heart function in. RHD patients who ... untreated children. Nearly 30 - 45 % of the affected children could ..... Technology Department of Anhui Province (PR.

  5. Guilt decreasing marketing communication: an unexplored appeal

    OpenAIRE

    B. BUSACCA; SOSCIA I; PITRELLI E

    2007-01-01

    The phenomenon of guilt is relevant to a variety of consumption situations and practitioners around the world have continued to use it as a communication appeal. Marketing literature demonstrated that guilt as a distinct emotion can be aroused by advertising. Nevertheless, the capacity of advertising to decrease guilt was neglected by marketing scholars and the aim of this research is to assess the role of the guilt decreasing appeal in reducing anticipated guilt. Findings demonstrate the eff...

  6. Decreasing Multicollinearity: A Method for Models with Multiplicative Functions.

    Science.gov (United States)

    Smith, Kent W.; Sasaki, M. S.

    1979-01-01

    A method is proposed for overcoming the problem of multicollinearity in multiple regression equations where multiplicative independent terms are entered. The method is not a ridge regression solution. (JKS)

  7. 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...

  8. 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.

  9. Forbush decreases and particle acceleration in the outer heliosphere

    International Nuclear Information System (INIS)

    Van Allen, J.A.; Mihalov, J.D.

    1990-01-01

    Major solar flare activity in 1989 has provided examples of the local acceleration of protons at 28 AU (Pioneer 11) and of the propagation of Forbush decreases in galactic cosmic ray intensity to a heliocentric radial distance of 47 AU (Pioneer 10). The combination of these and previous data at lesser distances shows (a) that Forbush decreases propagate with essentially constant magnitude to (at least) 47 AU and with similar magnitude at widely different ecliptic longitudes and (b) that the times for recovery from such decreases become progressively greater as the radial distance increases, being of the order of months in the outer heliosphere. A phenomenological scheme for (b) is proposed and fresh support is given to the hypothesis that the solar cycle modulation of the galactic cosmic ray intensity is attributable primarily to overlapping Forbush decreases which are more frequent and of greater magnitude near times of maximum solar activity than at times of lesser activity

  10. 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...

  11. 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.

  12. Impact of Rice Paddy Areas Decrease on Local Climate over Taiwan

    Science.gov (United States)

    Lo, M. H.; Wen, W. H.; Chen, C. C.

    2014-12-01

    Agricultural irrigation practice is one of the important anthropogenic processes in the land surface modeling. Irrigation can decrease local surface temperature with alternating surface energy partitioning. Rice paddy is the major food crop in Asian monsoon region and rice is grown under flooded conditions during the growing season; hence, the rice paddy can be considered as an open water body, which has more impacts on the surface energy budget than other cropland does. In this study, we explore how the rice paddy area changes affect Taiwan's regional climate from both observational data and numerical modeling exercise. The Weather Research and Forecasting (WRF) model is utilized to explore impacts of rice paddy area changes on the regional climate, and energy and water budget changes. In addition, temperature datasets from six automatic weather stations in the northern Taiwan and two stations in the southern Taiwan are analyzed in this study to explore how the Daily Temperature Range (DTR) changes with the decreased rice paddy areas. Previous studies show that due to the urban heat island effect, aerosol direct and indirect effects, and global warming, the DTR has decreased in the past 4 decades observed from most of the weather stations around Taiwan. However, the declined rice paddy area may increase the DTR with higher Bowen ratio during the daytime. Preliminary results show that DTR is decreased in weather stations near the urban area, but increased in weather stations near fallow areas in the past 20 years. It shows that different land use changes may have opposite impacts on local and regional climate.

  13. Simulation of decreasing reactor power level with BWR simulator

    International Nuclear Information System (INIS)

    Suwoto; Zuhair; Rivai, Abu Khalid

    2002-01-01

    Study on characteristic of BWR using Desktop PC Based Simulator Program was analysed. This simulator is more efficient and cheaper for analyzing of characteristic and dynamic respond than full scope simulator for decreasing power level of BW. Dynamic responses of BWR reactor was investigated during the power level reduction from 100% FP (Full Power) which is 3926 MWth to 0% FP with 25% steps and 1 % FP/sec rate. The overall results for core flow rate, reactor steam flow, feed-water flow and turbine-generator power show tendency proportional to reduction of reactor power. This results show that reactor power control in BWR could be done by control of re-circulation flow that alter the density of water used as coolant and moderator. Decreasing the re-circulation flow rate will decrease void density which has negative reactivity and also affect the position of control rods

  14. Does Corruption Increase or Decrease Employment in Firms?

    OpenAIRE

    Beltrán, Arlette

    2015-01-01

    This article uses representative data for firms for Latin American firms and show that corruption decreases employment in firms. This result is robust to changes in specification and also consistent with the use of an instrumental variables approach. Corruption appears to negatively impact the growth and wealth in a country, not by introducing labour distortion in firms, but by keeping them small.

  15. 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

  16. 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

  17. 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.

  18. Decreased hedonic responsiveness following chronic mild stress is not secondary to loss of body weight.

    Science.gov (United States)

    Willner, P; Moreau, J L; Nielsen, C K; Papp, M; Sluzewska, A

    1996-07-01

    Chronic exposure to mild unpredictable stress (CMS) has previously been found to decrease hedonic responsiveness, as measured by the consumption of palatable sweet solutions or sensitivity to brain stimulation reward. These effects are reversed by chronic treatment with antidepressant drugs, and the CMS procedure has been proposed as a relatively valid animal model of depression. It has recently been suggested that the behavioural effects of CMS may be secondary to loss of body weight. This article collates data from five laboratories using the CMS procedure. Data are presented from seven studies using five different rat strains, as well as CD1 mice. Three-week exposure to CMS significantly decreased sucrose consumption by Lister hooded, PVG hooded, Wistar, and Wistar WU rats, and by CD1 mice, and sensitivity to brain stimulation reward in Ibm:Ro Ro rats. Weight loss in different experiments varied between 0 and 10%. Hedonic sensitivity relative to body weight (e.g., mg sucrose/g body weight) decreased significantly in all experiments. Animals maintained on a restricted feeding regime lost weight but did not show decreases in sucrose intake. It is concluded that decreased hedonic sensitivity following chronic mild stress cannot be attributed to loss of body weight.

  19. Decreased sound tolerance: hyperacusis, misophonia, diplacousis, and polyacousis.

    Science.gov (United States)

    Jastreboff, Pawel J; Jastreboff, Margaret M

    2015-01-01

    Definitions, potential mechanisms, and treatments for decreased sound tolerance, hyperacusis, misophonia, and diplacousis are presented with an emphasis on the associated physiologic and neurophysiological processes and principles. A distinction is made between subjects who experience these conditions versus patients who suffer from them. The role of the limbic and autonomic nervous systems and other brain systems involved in cases of bothersome decreased sound tolerance is stressed. The neurophysiological model of tinnitus is outlined with respect to how it may contribute to our understanding of these phenomena and their treatment. © 2015 Elsevier B.V. All rights reserved.

  20. Show Horse Welfare: Horse Show Competitors' Understanding, Awareness, and Perceptions of Equine Welfare.

    Science.gov (United States)

    Voigt, Melissa A; Hiney, Kristina; Richardson, Jennifer C; Waite, Karen; Borron, Abigail; Brady, Colleen M

    2016-01-01

    The purpose of this study was to gain a better understanding of stock-type horse show competitors' understanding of welfare and level of concern for stock-type show horses' welfare. Data were collected through an online questionnaire that included questions relating to (a) interest and general understanding of horse welfare, (b) welfare concerns of the horse show industry and specifically the stock-type horse show industry, (c) decision-making influences, and (d) level of empathic characteristics. The majority of respondents indicated they agree or strongly agree that physical metrics should be a factor when assessing horse welfare, while fewer agreed that behavioral and mental metrics should be a factor. Respondent empathy levels were moderate to high and were positively correlated with the belief that mental and behavioral metrics should be a factor in assessing horse welfare. Respondents indicated the inhumane practices that most often occur at stock-type shows include excessive jerking on reins, excessive spurring, and induced excessive unnatural movement. Additionally, respondents indicated association rules, hired trainers, and hired riding instructors are the most influential regarding the decisions they make related to their horses' care and treatment.

  1. Accurate decisions in an uncertain world: collective cognition increases true positives while decreasing false positives.

    Science.gov (United States)

    Wolf, Max; Kurvers, Ralf H J M; Ward, Ashley J W; Krause, Stefan; Krause, Jens

    2013-04-07

    In a wide range of contexts, including predator avoidance, medical decision-making and security screening, decision accuracy is fundamentally constrained by the trade-off between true and false positives. Increased true positives are possible only at the cost of increased false positives; conversely, decreased false positives are associated with decreased true positives. We use an integrated theoretical and experimental approach to show that a group of decision-makers can overcome this basic limitation. Using a mathematical model, we show that a simple quorum decision rule enables individuals in groups to simultaneously increase true positives and decrease false positives. The results from a predator-detection experiment that we performed with humans are in line with these predictions: (i) after observing the choices of the other group members, individuals both increase true positives and decrease false positives, (ii) this effect gets stronger as group size increases, (iii) individuals use a quorum threshold set between the average true- and false-positive rates of the other group members, and (iv) individuals adjust their quorum adaptively to the performance of the group. Our results have broad implications for our understanding of the ecology and evolution of group-living animals and lend themselves for applications in the human domain such as the design of improved screening methods in medical, forensic, security and business applications.

  2. 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.

  3. 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.

  4. Best in show but not best shape: a photographic assessment of show dog body condition.

    Science.gov (United States)

    Such, Z R; German, A J

    2015-08-01

    Previous studies suggest that owners often wrongly perceive overweight dogs to be in normal condition. The body shape of dogs attending shows might influence owners' perceptions, with online images of overweight show winners having a negative effect. This was an observational in silico study of canine body condition. 14 obese-prone breeds and 14 matched non-obese-probe breeds were first selected, and one operator then used an online search engine to identify 40 images, per breed, of dogs that had appeared at a major national UK show (Crufts). After images were anonymised and coded, a second observer subjectively assessed body condition, in a single sitting, using a previously validated method. Of 1120 photographs initially identified, 960 were suitable for assessing body condition, with all unsuitable images being from longhaired breeds. None of the dogs (0 per cent) were underweight, 708 (74 per cent) were in ideal condition and 252 (26 per cent) were overweight. Pugs, basset hounds and Labrador retrievers were most likely to be overweight, while standard poodles, Rhodesian ridgebacks, Hungarian vizslas and Dobermanns were least likely to be overweight. Given the proportion of show dogs from some breeds that are overweight, breed standards should be redefined to be consistent with a dog in optimal body condition. British Veterinary Association.

  5. Decreased decorin expression in the tumor microenvironment

    International Nuclear Information System (INIS)

    Bozoky, Benedek; Savchenko, Andrii; Guven, Hayrettin; Ponten, Fredrik; Klein, George; Szekely, Laszlo

    2014-01-01

    Decorin is a small leucine-rich proteoglycan, synthesized and deposited by fibroblasts in the stroma where it binds to collagen I. It sequesters several growth factors and antagonizes numerous members of the receptor tyrosine kinase family. In experimental murine systems, it acted as a potent tumor suppressor. Examining the Human Protein Atlas online database of immunostained tissue samples we have surveyed decorin expression in silico in several different tumor types, comparing them with corresponding normal tissues. We found that decorin is abundantly secreted and deposited in normal connective tissue but its expression is consistently decreased in the tumor microenvironment. We developed a software to quantitate the difference in expression. The presence of two closely related proteoglycans in the newly formed tumor stroma indicated that the decreased decorin expression was not caused by the delay in proteoglycan deposition in the newly formed connective tissue surrounding the tumor

  6. Calming Meditation Increases Altruism, Decreases Parochialism

    OpenAIRE

    Frost, Karl

    2017-01-01

    It has been proposed that cultivating calm will increase altruism and decrease parochialism, where altruism is defined as self-sacrifice in support of others, regardless of group affiliation or identity, and parochialism is defined as prosocial self-sacrifice restricted to fellow members of a group. Such could be the case with a calming meditation practice. An alternate hypothesis, coming from the study of ritual, proposes that shared practices lead to bonding, increasing parochialism, but no...

  7. 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.

  8. 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

  9. A note on inverses of non-decreasing Lévy processes

    NARCIS (Netherlands)

    J.A. Ferreira

    2001-01-01

    textabstractWe show that, apart from deterministic processes, compound Poisson processes with exponential jumps are the only (shifted) non-decreasing Lévy processes whose inverses are also (shifted) non-decreasing Lévy processes.

  10. 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

  11. Do socioeconomic mortality differences decrease with rising age?

    Directory of Open Access Journals (Sweden)

    Rasmus Hoffmann

    2005-08-01

    Full Text Available The impact of SES on mortality is an established finding in mortality research. I examine, whether this impact decreases with age. Most research finds evidence for this decrease but it is unknown whether the decline is due to mortality selection. My data come from the US-HRS Study and includes 9376 persons aged 59+, which are followed over 8 years. The variables allow a time varying measurement of SES, health and behavior. Event-history-analysis is applied to analyze mortality differentials. My results show that socioeconomic mortality differences are stable across ages whereas they decline clearly with decreasing health. The first finding that health rather than age is the equalizer combined with the second finding of unequally distributed health leads to the conclusion that in old age, the impact of SES is transferred to health and is stable across ages.

  12. 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.

  13. Design and Analysis of LT Codes with Decreasing Ripple Size

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Popovski, Petar; Østergaard, Jan

    2012-01-01

    In this paper we propose a new design of LT codes, which decreases the amount of necessary overhead in comparison to existing designs. The design focuses on a parameter of the LT decoding process called the ripple size. This parameter was also a key element in the design proposed in the original...... work by Luby. Specifically, Luby argued that an LT code should provide a constant ripple size during decoding. In this work we show that the ripple size should decrease during decoding, in order to reduce the necessary overhead. Initially we motivate this claim by analytical results related...... to the redundancy within an LT code. We then propose a new design procedure, which can provide any desired achievable decreasing ripple size. The new design procedure is evaluated and compared to the current state of the art through simulations. This reveals a significant increase in performance with respect...

  14. Decreased Stress Levels in Nurses: A Benefit of Quiet Time.

    Science.gov (United States)

    Riemer, Heather C; Mates, Joanna; Ryan, Linda; Schleder, Bonnie J

    2015-09-01

    The benefits of quiet time, a therapeutic method of improving the health care environment, have been evaluated in patients, but only a few studies have examined the effects of quiet time on intensive care nurses. To evaluate the effects of implementing quiet time in a medical-surgical intensive care unit on levels of light, noise, and nurses' stress. Quiet time consisted of turning down the unit lights for a designated time. Levels of light, noise, and nurses' stress were measured. Nurses' stress levels were measured by using a 100-point visual analog scale; unit noise, by using a digital sound level meter (model 407736, Extech Instruments); and unit light, by using an illumination light meter (model 615, Huygen Corporation). Measurements were obtained 30 minutes before and 30 minutes, 1 hour, and 2 hours after implementation of quiet time. Analysis of variance and comparisons of means indicated that both light levels and nurses' stress levels were significantly decreased after quiet time (both P quiet time, but the decrease was not significant (P = .08). Use of quiet time resulted in decreased light levels and decreased stress levels among nurses. Quiet time is an easily performed energy-saving intervention to promote a healthy work environment. ©2015 American Association of Critical-Care Nurses.

  15. 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.

  16. SPP will decrease price of transport

    International Nuclear Information System (INIS)

    Janoska, J.

    2003-01-01

    Starting next year gas utility Slovensky plynarensky priemysel, a.s., Bratislava (SPP) will decrease the fees for transport of gas to its client from third parties. This decision should have a positive effect mainly on large industrial customers. The fact that SPP decided not to apply the approved ruling to its full extent was the result of negotiations with the regulator and the Ministry of Economy. SPP is not afraid it might lose customers. This decision only gives them a competitive advantage. (Author)

  17. 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.

  18. 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.

  19. 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.

  20. Phosphorus limitation and heat stress decrease calcification in Emiliania huxleyi

    Directory of Open Access Journals (Sweden)

    A. C. Gerecht

    2018-02-01

    Full Text Available 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. 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.

  2. Increasing survival time decreases the cost-effectiveness of using "test & treat'' to eliminate HIV epidemics.

    Science.gov (United States)

    Wagner, Bradley G; Coburn, Brian J; Blower, Sally

    2013-01-01

    Treating HIV-infected individuals reduces their viral load, consequently increasing their survival time and decreasing their infectivity. It has been proposed that universal testing and treatment (i.e., universal "test & treat'') could lead to HIV elimination and would be extremely cost-effective. It is now being debated whether to use a universal "test & treat'' approach in the "real-world'' as a prevention strategy to control HIV epidemics. However current modeling predictions of the impact, and cost-effectiveness, of universal `"est & treat'' strategies are based on an unrealistically short survival time for treated individuals. Here we use mathematical modeling and a longer, more realistic, survival time. We model the potential impact of a universal "test & treat'' strategy in South Africa. Our results show that increasing the length of the survival time on treatment, although beneficial to individuals, reduces the probability of eliminating HIV and decreases the cost-effectiveness of using universal "test & treat'' strategies. Therefore our results show that individual-level benefits and public health benefits will conflict when using "test &treat'' strategies to reduce HIV transmission.

  3. 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.

  4. 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...... 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...

  5. Optimization of hip joint replacement location to decrease maximum von Mi ses Stress

    International Nuclear Information System (INIS)

    Pourjamali, H.; Najarian, S.; Katoozian, H. R.

    2001-01-01

    Hip replacement is used for inoperable femur head injuries and femur fractures where internal fixation can not be used. This operation is one of the most common orthopedic operations that many research have been done about it. Among these we can mention implant and cement materials and composites optimization and also implant shape optimization. This study was designed to optimize artificial hip joint position (placement) to decrease maximal von mi sees stress. First, a model of femur and implant were made and then a computer program was written with the ability to change the position of implant through an acceptable range in the femur. In each of these positions, the program simulated femur and implant according to finite element method and made, applied forces were weight and muscle traction. Our findings show that a small deviation of the implant from femur bone center causes a considerable decrease in von mi sees stress that consequently results in longer maintenance of the implant

  6. Increased water deficit decreases Douglas fir growth throughout western US forests.

    Science.gov (United States)

    Restaino, Christina M; Peterson, David L; Littell, Jeremy

    2016-08-23

    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 represent distinct climate environments in the western United States, we show that increased temperature decreases growth via vapor pressure deficit (VPD) across all latitudes. Using 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.

  7. Decreasing trend in severe weather occurrence over China during the past 50 years

    Science.gov (United States)

    Zhang, Qinghong; Ni, Xiang; Zhang, Fuqing

    2017-04-01

    Understanding the trend of localized severe weather under the changing climate is of great significance but remains challenging which is at least partially due to the lack of persistent and homogeneous severe weather observations at climate scales while the detailed physical processes of severe weather cannot be resolved in global climate models. Based on continuous and coherent severe weather reports from over 500 manned stations, for the first time, this study shows a significant decreasing trend in severe weather occurrence across China during the past five decades. The total number of severe weather days that have either thunderstorm, hail and/or damaging wind decrease about 50% from 1961 to 2010. It is further shown that the reduction in severe weather occurrences correlates strongly with the weakening of East Asian summer monsoon which is the primary source of moisture and dynamic forcing conducive for warm-season severe weather over China.

  8. 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

  9. Structural change in developing countries: has it decreased gender inequality?

    OpenAIRE

    Michelle Rendall

    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...

  10. Decreased NAA in gray matter is correlated with decreased availability of acetate in white matter in postmortem multiple sclerosis cortex.

    Science.gov (United States)

    Li, S; Clements, R; Sulak, M; Gregory, R; Freeman, E; McDonough, J

    2013-11-01

    Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids.

  11. Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

    Science.gov (United States)

    Barfield, Whitney L; Uaesoontrachoon, Kitipong; Wu, Chung-Sheih; Lin, Stephen; Chen, Yue; Wang, Paul C; Kanaan, Yasmine; Bond, Vernon; Hoffman, Eric P

    2014-08-01

    A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients. © The Author 2014. Published by Oxford University Press.

  12. 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.

  13. 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

  14. The readability of scientific texts is decreasing over time

    Science.gov (United States)

    2017-01-01

    Clarity and accuracy of reporting are fundamental to the scientific process. Readability formulas can estimate how difficult a text is to read. Here, in a corpus consisting of 709,577 abstracts published between 1881 and 2015 from 123 scientific journals, we show that the readability of science is steadily decreasing. Our analyses show that this trend is indicative of a growing use of general scientific jargon. These results are concerning for scientists and for the wider public, as they impact both the reproducibility and accessibility of research findings. PMID:28873054

  15. 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

  16. 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.

  17. Trends in mortality decrease and economic growth

    NARCIS (Netherlands)

    Niu, G.; Melenberg, B.

    2014-01-01

    The vast literature on extrapolative stochastic mortality models focuses mainly on the extrapolation of past mortality trends and summarizes the trends by one or more latent factors. However, the interpretation of these trends is typically not very clear. On the other hand, explanation methods are

  18. 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.

  19. Ionizing radiation decreases human cancer mortality rates

    International Nuclear Information System (INIS)

    Luckey, T.D.

    1997-01-01

    Information from nine studies with exposed nuclear workers and military observers of atmospheric bomb explosions confirms the results from animal studies which showed that low doses of ionizing radiation are beneficial. The usual ''healthy worker effect'' was eliminated by using carefully selected control populations. The results from 13 million person-years show the cancer mortality rate of exposed persons is only 65.6% that of carefully selected unexposed controls. This overwhelming evidence makes it politically untenable and morally wrong to withhold public health benefits of low dose irradiation. Safe supplementation of ionizing radiation should become a public health service. (author)

  20. Troubleshooting at Reverse Osmosis performance decrease

    Energy Technology Data Exchange (ETDEWEB)

    Soons, Jan [KEMA (Netherlands)

    2011-07-01

    There are several causes for a decrease in Reverse Osmosis (RO) membrane performance each of which requiring actions to tackle the possible cause. Two of the main factors affecting the performance of the system are the feed quality (poor feed quality can lead to fouling of the membranes) and the operational conditions (including the maximum allowed pressure, minimum cleaning frequencies and types, recovery rate etc, which should be according to the design conditions). If necessary, pre-treatment will be applied in order to remove the fouling agents from the influent, reduce scaling (through the addition of anti-scalants) and for the protection of the membranes (for example, sodium metabisulphite addition for the removal of residual chlorine which can harm the membranes). Fouling is not strictly limited to the use of surface water as feed water, also relatively clean water sources will, over time, lead to organic and inorganic fouling when cleaning is not optimum. When fouling occurs, the TransMembrane Pressure (TMP) increases and more energy will be needed to produce the same amount of product water. Also, the cleaning rate will increase, reducing the production rate and increasing the chemical consumption and the produced waste streams. Furthermore, the quality of the effluent will decrease (lower rejection rates at higher pressures) and the lifetime of the membranes will decrease. Depending on the type of fouling different cleaning regimes will have to be applied: acidic treatment for inorganic fouling, the addition of bases against organic fouling. Therefore, it is very important to have a clear view of the type of fouling that is occurring, in order to apply the correct treatment methods. Another important aspect to be kept in mind is that the chemistry of the water - in the first place ruled by the feed water composition - can change during passage of the modules, in particular in cases where the RO system consists of two or more RO trains, and where the

  1. 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.

  2. Pumilio2-deficient mice show a predisposition for epilepsy

    Directory of Open Access Journals (Sweden)

    Philipp Follwaczny

    2017-11-01

    Full Text Available Epilepsy is a neurological disease that is caused by abnormal hypersynchronous activities of neuronal ensembles leading to recurrent and spontaneous seizures in human patients. Enhanced neuronal excitability and a high level of synchrony between neurons seem to trigger these spontaneous seizures. The molecular mechanisms, however, regarding the development of neuronal hyperexcitability and maintenance of epilepsy are still poorly understood. Here, we show that pumilio RNA-binding family member 2 (Pumilio2; Pum2 plays a role in the regulation of excitability in hippocampal neurons of weaned and 5-month-old male mice. Almost complete deficiency of Pum2 in adult Pum2 gene-trap mice (Pum2 GT causes misregulation of genes involved in neuronal excitability control. Interestingly, this finding is accompanied by the development of spontaneous epileptic seizures in Pum2 GT mice. Furthermore, we detect an age-dependent increase in Scn1a (Nav1.1 and Scn8a (Nav1.6 mRNA levels together with a decrease in Scn2a (Nav1.2 transcript levels in weaned Pum2 GT that is absent in older mice. Moreover, field recordings of CA1 pyramidal neurons show a tendency towards a reduced paired-pulse inhibition after stimulation of the Schaffer-collateral-commissural pathway in Pum2 GT mice, indicating a predisposition to the development of spontaneous seizures at later stages. With the onset of spontaneous seizures at the age of 5 months, we detect increased protein levels of Nav1.1 and Nav1.2 as well as decreased protein levels of Nav1.6 in those mice. In addition, GABA receptor subunit alpha-2 (Gabra2 mRNA levels are increased in weaned and adult mice. Furthermore, we observe an enhanced GABRA2 protein level in the dendritic field of the CA1 subregion in the Pum2 GT hippocampus. We conclude that altered expression levels of known epileptic risk factors such as Nav1.1, Nav1.2, Nav1.6 and GABRA2 result in enhanced seizure susceptibility and manifestation of epilepsy in the

  3. 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 ...

  4. Vinegar decreases allergenic response in lentil and egg food allergy.

    Science.gov (United States)

    Armentia, A; Dueñas-Laita, A; Pineda, F; Herrero, M; Martín, B

    2010-01-01

    Food allergy results from an atypical response of the mucosal immune system to orally consumed allergens. Antacid medication inhibits the digestion of dietary proteins and causes food allergy. A decrease of the gastric pH might enhance the function of digestion and reduce the risk of food allergy. To test a possible decrease in the allergenicity of powerful food allergens (egg, chicken, lentils) with the addition of vinegar during the cooking process. We included seven patients who suffered from anaphylaxis due to egg, chicken and lentils. We added vinegar to egg, chicken and lentil processed extracts used for skin prick tests (SPT) and compared the wheal areas obtained with the same extracts sources and the same way but without vinegar addition. Immunodetection was performed with the different processed extracts and patients' sera. Only one patient consented food challenge with vinegar-marinated-chicken. Wheal areas were significantly minor with the food extract with vinegar. Immunodetection showed a decrease of the response with vinegar processed extracts. Vinegar addition during the cooking process may decrease lentil and chicken allergenicity. Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

  5. Task-related signal decrease on functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Hara, Yoshie; Nakamura, Mitsugu; Tamaki, Norihiko; Tamura, Shogo; Kitamura, Junji

    2001-01-01

    An atypical pattern of signal change was identified on functional magnetic resonance (fMR) imaging in pathologic patients. Three normal volunteers and 34 patients with pathologic lesions near the primary motor cortex underwent fMR imaging with echo-planar imaging while performing a hand motor task. Signal intensities were evaluated with the z-score method, and the time course and changes of the signal intensity were calculated. Nine of the 34 patients with pathologic lesions displayed a significant task-related signal reduction in motor-related areas. They also presented a conventional task-related signal increase in other motor-related areas. The time courses of the increase and decrease were the inverse of each other. There was no significant difference between rates of signal increase and decrease. Our findings suggest that this atypical signal decrease is clinically significant, and that impaired vascular reactivity and altered oxygen metabolism could contribute to the task-related signal reduction. Brain areas showing such task-related signal decrease should be preserved at surgery. (author)

  6. Oxalic acid decreases calcium absorption in rats

    International Nuclear Information System (INIS)

    Weaver, C.M.; Martin, B.R.; Ebner, J.S.; Krueger, C.A.

    1987-01-01

    Calcium absorption from salts and foods intrinsically labeled with 45 Ca was determined in the rat model. Calcium bioavailability was nearly 10 times greater for low oxalate kale, CaCO 3 and CaCl 2 than from CaC 2 O 4 (calcium oxalate) and spinach (high in oxalates). Extrinsic and intrinsic labeling techniques gave a similar assessment of calcium bioavailability from kale but not from spinach

  7. Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.

    Science.gov (United States)

    Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André

    2015-11-01

    Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 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...

  9. 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.

  10. 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.

  11. Estrogen inhibits lysyl oxidase and decreases mechanical function in engineered ligaments.

    Science.gov (United States)

    Lee, Cassandra A; Lee-Barthel, Ann; Marquino, Louise; Sandoval, Natalie; Marcotte, George R; Baar, Keith

    2015-05-15

    Women are more likely to suffer an anterior cruciate ligament (ACL) rupture than men, and the incidence of ACL rupture in women rises with increasing estrogen levels. We used an engineered ligament model to determine how an acute rise in estrogen decreases the mechanical properties of ligaments. Using fibroblasts isolated from human ACLs from male or female donors, we engineered ligaments and determined that ligaments made from female ACL cells had more collagen and were equal in strength to those made from male ACL cells. We then treated engineered ligaments for 14 days with low (5 pg/ml), medium (50 pg/ml), or high (500 pg/ml) estrogen, corresponding to the range of in vivo serum estrogen concentrations and found that collagen within the grafts increased without a commensurate increase in mechanical strength. Mimicking the menstrual cycle, with 12 days of low estrogen followed by 2 days of physiologically high estrogen, resulted in a decrease in engineered ligament mechanical function with no change in the amount of collagen in the graft. The decrease in mechanical stiffness corresponded with a 61.7 and 76.9% decrease in the activity of collagen cross-linker lysyl oxidase with 24 and 48 h of high estrogen, respectively. Similarly, grafts treated with the lysyl oxidase inhibitor β-aminoproprionitrile (BAPN) for 24 h showed a significant decrease in ligament mechanical strength [control (CON) = 1.58 ± 0.06 N; BAPN = 1.06 ± 0.13 N] and stiffness (CON = 7.7 ± 0.46 MPa; BAPN = 6.1 ± 0.71 MPa) without changing overall collagen levels (CON = 396 ± 11.5 μg; BAPN = 382 ± 11.6 μg). Together, these data suggest that the rise in estrogen during the follicular phase decreases lysyl oxidase activity in our engineered ligament model and if this occurs in vivo may decrease the stiffness of ligaments and contribute to the elevated rate of ACL rupture in women. Copyright © 2015 the American Physiological Society.

  12. 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.

  13. Some human activities to decrease public radiation dose

    International Nuclear Information System (INIS)

    Pan Ziqiang; Guo Minqiang

    1994-01-01

    The necessity of studying the variations in radiation levels from the balance viewpoint is discussed. Some human activities may increase, while others may decrease, radiation dose to population. In 1988, China's investigation showed that travel by air caused a raise of population collective dose by 3.6 x 10 1 man·Sv, while travel by ship, train and vehicle lead to a drop of 5.36 x 10 2 man·Sv, and that dwellings of coal cinder brick decreased collective dose by 3.5 x 10 3 man·Sv, while buildings of reinforced concrete structure increased collective dose by 3.7 x 10 3 man·Sv. It is inadequate to only study those activities which may increase radiation levels

  14. 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

  15. Compliance With Recommended Food Saf