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Sample records for expression test reduces

  1. Benefits of expressive writing in reducing test anxiety: A randomized controlled trial in Chinese samples.

    Science.gov (United States)

    Shen, Lujun; Yang, Lei; Zhang, Jing; Zhang, Meng

    2018-01-01

    To explore the effect of expressive writing of positive emotions on test anxiety among senior-high-school students. The Test Anxiety Scale (TAS) was used to assess the anxiety level of 200 senior-high-school students. Seventy-five students with high anxiety were recruited and divided randomly into experimental and control groups. Each day for 30 days, the experimental group engaged in 20 minutes of expressive writing of positive emotions, while the control group was asked to merely write down their daily events. A second test was given after the month-long experiment to analyze whether there had been a reduction in anxiety among the sample. Quantitative data was obtained from TAS scores. The NVivo10.0 software program was used to examine the frequency of particular word categories used in participants' writing manuscripts. Senior-high-school students indicated moderate to high test anxiety. There was a significant difference in post-test results (P 0.05). Students' writing manuscripts were mainly encoded on five code categories: cause, anxiety manifestation, positive emotion, insight and evaluation. There was a negative relation between positive emotion, insight codes and test anxiety. There were significant differences in the positive emotion, anxiety manifestation, and insight code categories between the first 10 days' manuscripts and the last 10 days' ones. Long-term expressive writing of positive emotions appears to help reduce test anxiety by using insight and positive emotion words for Chinese students. Efficient and effective intervention programs to ease test anxiety can be designed based on this study.

  2. Benefits of expressive writing in reducing test anxiety: A randomized controlled trial in Chinese samples.

    Directory of Open Access Journals (Sweden)

    Lujun Shen

    Full Text Available To explore the effect of expressive writing of positive emotions on test anxiety among senior-high-school students.The Test Anxiety Scale (TAS was used to assess the anxiety level of 200 senior-high-school students. Seventy-five students with high anxiety were recruited and divided randomly into experimental and control groups. Each day for 30 days, the experimental group engaged in 20 minutes of expressive writing of positive emotions, while the control group was asked to merely write down their daily events. A second test was given after the month-long experiment to analyze whether there had been a reduction in anxiety among the sample. Quantitative data was obtained from TAS scores. The NVivo10.0 software program was used to examine the frequency of particular word categories used in participants' writing manuscripts.Senior-high-school students indicated moderate to high test anxiety. There was a significant difference in post-test results (P 0.05. Students' writing manuscripts were mainly encoded on five code categories: cause, anxiety manifestation, positive emotion, insight and evaluation. There was a negative relation between positive emotion, insight codes and test anxiety. There were significant differences in the positive emotion, anxiety manifestation, and insight code categories between the first 10 days' manuscripts and the last 10 days' ones.Long-term expressive writing of positive emotions appears to help reduce test anxiety by using insight and positive emotion words for Chinese students. Efficient and effective intervention programs to ease test anxiety can be designed based on this study.

  3. Benefits of expressive writing in reducing test anxiety: A randomized controlled trial in Chinese samples

    Science.gov (United States)

    Zhang, Jing; Zhang, Meng

    2018-01-01

    Purpose To explore the effect of expressive writing of positive emotions on test anxiety among senior-high-school students. Methods The Test Anxiety Scale (TAS) was used to assess the anxiety level of 200 senior-high-school students. Seventy-five students with high anxiety were recruited and divided randomly into experimental and control groups. Each day for 30 days, the experimental group engaged in 20 minutes of expressive writing of positive emotions, while the control group was asked to merely write down their daily events. A second test was given after the month-long experiment to analyze whether there had been a reduction in anxiety among the sample. Quantitative data was obtained from TAS scores. The NVivo10.0 software program was used to examine the frequency of particular word categories used in participants’ writing manuscripts. Results Senior-high-school students indicated moderate to high test anxiety. There was a significant difference in post-test results (P 0.05). Students’ writing manuscripts were mainly encoded on five code categories: cause, anxiety manifestation, positive emotion, insight and evaluation. There was a negative relation between positive emotion, insight codes and test anxiety. There were significant differences in the positive emotion, anxiety manifestation, and insight code categories between the first 10 days’ manuscripts and the last 10 days’ ones. Conclusions Long-term expressive writing of positive emotions appears to help reduce test anxiety by using insight and positive emotion words for Chinese students. Efficient and effective intervention programs to ease test anxiety can be designed based on this study. PMID:29401473

  4. Emotional facial expressions reduce neural adaptation to face identity.

    Science.gov (United States)

    Gerlicher, Anna M V; van Loon, Anouk M; Scholte, H Steven; Lamme, Victor A F; van der Leij, Andries R

    2014-05-01

    In human social interactions, facial emotional expressions are a crucial source of information. Repeatedly presented information typically leads to an adaptation of neural responses. However, processing seems sustained with emotional facial expressions. Therefore, we tested whether sustained processing of emotional expressions, especially threat-related expressions, would attenuate neural adaptation. Neutral and emotional expressions (happy, mixed and fearful) of same and different identity were presented at 3 Hz. We used electroencephalography to record the evoked steady-state visual potentials (ssVEP) and tested to what extent the ssVEP amplitude adapts to the same when compared with different face identities. We found adaptation to the identity of a neutral face. However, for emotional faces, adaptation was reduced, decreasing linearly with negative valence, with the least adaptation to fearful expressions. This short and straightforward method may prove to be a valuable new tool in the study of emotional processing.

  5. Developmental Hypothyroidism Reduces the Expression of ...

    Science.gov (United States)

    Disruption of thyroid hormone (TH) is a known effect of environmental contaminants. Neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been implicated in brain dysfunction resulting from severe developmental TH insufficiency. Neurotrophins are also implicated in activity-dependent plasticity, a process critical for appropriate use-dependent connectivity in the developing brain and for memory formation in the adult. This study examined activity-induced expression of neurotrophin gene products in the hippocampus using the long-term potentiation (LTP) after developmental hypothyroidism induced by propylthiouracil (PTU). Pregnant rats were exposed to PTU (0 or I0ppm) via the drinking water from early gestation to weaning. Adult male offspring were anesthetized with urethane and implanted with electrodes in the dentate gyrus (00) and perforant path (PP). LTP was induced by PP stimulation and responses from 00 were monitored at 15m intervals until sacrifice of the animals 5 h later. The 00 was dissected from the stimulated and nonstimulated hemispheres for rtPCR analysis of the neurotrophins Bdnf, Ngf, Ntf3 and related genes Egrl, Arc, Klf9. We found no PTU-induced difference in basal levels of expression of any of these genes in the nonstimulated 00. LTP increased expression of Bdnf, Ngf, Arc and Klj9 in the control DG, and reduced expression of Ntf3. LTP in DG from PTU animals failed to increase expression of Bdnf,

  6. Ice load reducer for dams : laboratory tests

    Energy Technology Data Exchange (ETDEWEB)

    Lupien, R.; Cote, A.; Robert, A. [Institut de Recherche d' Hydro-Quebec, Varennes, PQ (Canada)

    2009-07-01

    Many studies have focused on measuring static ice loads on various hydraulic structures in Canada. This paper discussed a Hydro-Quebec research project whose main purpose was to harmonize the ice thrust value in load combinations for use in general hydraulic works or for specific cases. The objectives of the project were to obtain a better understanding of existing data and to characterize sites and their influence on ice thrust; study the structural mechanisms involved in the generation of ice thrust, their consequences on the structural behaviour of ice and the natural mitigating circumstances that may be offered by ice properties or site operating procedures; and examine the relevance of developing an ice load reducer for works that might not fit the harmonized design value. The paper presented the main research goals and ice load reducer goals, with particular focus on the four pipe samples that were planned, built and tested. The experimental program involved checking the pipe shape behaviour in terms of flexibility-stiffness; maximum deformations; maximum load reduction; permanent deformations; and, ability to shape recovering. The testing also involved examining the strength versus strain rate; creep versus strain rate; and creep capacity under biaxial state of tension and compression. It was concluded that the two phenomena involved in generation of ice thrust, notably thermal expansion and water level changes, had very low strain rates. 8 refs., 2 tabs., 16 figs.

  7. Combined approach to reduced duration integrated leakage rate testing

    International Nuclear Information System (INIS)

    Galanti, P.J.

    1987-01-01

    Even though primary reactor containment allowable leakage rates are expressed in weight percent per day of contained air, engineers have been attempting to define acceptable methods to test in < 24 h as long as these tests have been performed. The reasons to reduce testing duration are obvious, because time not generating electricity is time not generating revenue for the utilities. The latest proposed revision to 10CFR50 Appendix J, concerning integrated leakage rate testing (ILRTs), was supplemented with a draft regulatory guide proposing yet another method. This paper proposes a method that includes elements of currently accepted concepts for short duration testing with a standard statistical check for criteria acceptance. Following presentation of the method, several cases are presented showing the results of these combined criteria

  8. Reduced Ang2 expression in aging endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Hohensinner, P.J., E-mail: philipp.hohensinner@meduniwien.ac.at [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ebenbauer, B. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Kaun, C.; Maurer, G. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Huber, K. [Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); 3rd Medical Department, Wilhelminenhospital, Vienna (Austria); Sigmund Freud University, Medical Faculty, Vienna (Austria); Wojta, J. [Department of Internal Medicine II, Medical University of Vienna, Vienna (Austria); Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna (Austria); Core Facilities, Medical University of Vienna, Vienna (Austria)

    2016-06-03

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  9. Reduced Ang2 expression in aging endothelial cells

    International Nuclear Information System (INIS)

    Hohensinner, P.J.; Ebenbauer, B.; Kaun, C.; Maurer, G.; Huber, K.; Wojta, J.

    2016-01-01

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. -- Highlights: •Endothelial cells display signs of aging before reaching proliferative senescence. •Aging endothelial cells express more angiopoietin 1 and less angiopoietin 2 than young endothelial cells. •Migratory capacity is reduced in aging endothelial cells.

  10. Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence.

    Science.gov (United States)

    Bernstein, Harris; Prasad, Anil; Holubec, Hana; Bernstein, Carol; Payne, Claire M; Ramsey, Lois; Dvorakova, Katerina; Wilson, Megan; Warneke, James A; Garewal, Harinder

    2006-06-01

    Pms2 protein is a component of the DNA mismatch repair complex responsible both for post-replication correction of DNA nucleotide mispairs and for early steps in apoptosis. Germline mutations in DNA mismatch repair genes give rise to hereditary non-polyposis colon cancer, which accounts for about 4% of colon cancers. However, little is known about the expression of mismatch repair proteins in relation to sporadic colon cancer, which accounts for the great majority of colon cancers. Multiple samples were taken from the non-neoplastic flat mucosa of colon resections from patients with no colonic neoplasia, a tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome-stained epoxy sections using morphologic criteria. Samples from patients without colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the base of crypts, while samples from 2 of the 3 colons with a tubulovillous adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2 expression. Samples from patients with an adenocarcinoma that had reduced Pms2 expression also exhibited reduced apoptosis capability in nearby tissue samples, evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced Pms2 expression in the colonic mucosa may be an early step in progression to colon cancer. This reduction may cause decreased mismatch repair, increased genetic instability, and/or reduced apoptotic capability. Immunohistochemical determination of reduced Pms2 expression, upon further testing, may prove to be a promising early biomarker of risk of progression to malignancy.

  11. Reduced Ang2 expression in aging endothelial cells.

    Science.gov (United States)

    Hohensinner, P J; Ebenbauer, B; Kaun, C; Maurer, G; Huber, K; Wojta, J

    2016-06-03

    Aging endothelial cells are characterized by increased cell size, reduced telomere length and increased expression of proinflammatory cytokines. In addition, we describe here that aging reduces the migratory distance of endothelial cells. Furthermore, we observe an increase of the quiescence protein Ang1 and a decrease of the endothelial activation protein Ang2 upon aging. Supplementing Ang2 to aged endothelial cells restored their migratory capacity. We conclude that aging shifts the balance of the Ang1/Ang2 network favouring a quiescent state. Activation of endothelial cells in aging might be necessary to enhance wound healing capacities. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Expressive Writing as a Brief Intervention for Reducing Drinking Intentions

    OpenAIRE

    Young, Chelsie M.; Rodriguez, Lindsey M.; Neighbors, Clayton

    2013-01-01

    The present study examined the effectiveness of expressive writing in reducing drinking behavior. We expected that students prompted to write about negative drinking experiences would show greater decreases in future drinking intentions compared to the neutral and the positive writing conditions. We also expected that decreases in drinking intentions following the writing prompts might differ based on current drinking and AUDIT scores. Participants included 200 (76% female) undergraduates who...

  13. New EPA Guidance for Testing Pesticides Will Reduce Animal Testing

    Science.gov (United States)

    EPA is issuing guidance for requesting waivers of acute dermal toxicity testing requirements for pesticide formulations, which will lead to fewer animal tests for acute dermal toxicity for pesticides.

  14. Inheritance and expression of reduced culm number character in rice

    International Nuclear Information System (INIS)

    Takamure, I.; Kinoshita, T.

    1985-01-01

    A mutant with a reduced culm number was found in M 2 population of AC-3 (a strain regenerated from A-5 Akamuro by another culture) after gamma-ray irradiation of dry seeds. In F2 population of the crossing between the mutant line, N-133 and the original strain, A-5, it was demonstrated that a single recessive gene, rcn is responsible for the reduced culm number type. A pleiotropic effect showing dwarfness was expressed although the seed fertility was unaffected. In the linkage analysis, it was found that rcn was linked with the genes belonging to the first linkage group such as wx (glutinous endosperm) and C (Chromogen for anthocyanin) in the order of wx-C-rcn. In addition, rcn was epistatic to the dwarf genes, d-2 (ebisu dwarf), d-3, d-4, d-5 (triplicate genes for bunketsu waito) and d-10 (toyohikari-bunwai). As for the relation with d-6 (ebisumochi dwarf), a non-parental dwarf type with a reduced culm number and shorter lower (below the second) internodes occurred as a double recessive genotype. The character expression of the mutant gene, rcn was remarkably affected. by the temperature conditlons during the growth period. Plant height and culm number of the mutant recovered to nearly normal when grown in a plastic house with the application of nitrogen. Since the plant height and culm number were retarded by the treatment with cold water (15°C), it was demonstrated that the gene expression was conditioned by the low temperature

  15. Erythropoietin reduces the expression of myostatin in mdx dystrophic mice

    Energy Technology Data Exchange (ETDEWEB)

    Feder, D.; Rugollini, M.; Santomauro, A. Jr; Oliveira, L.P.; Lioi, V.P. [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Santos, R. dos; Ferreira, L.G.; Nunes, M.T.; Carvalho, M.H. [Universidade de São Paulo, Instituto de Ciências Biomédicas, São Paulo, SP (Brazil); Delgado, P.O.; Carvalho, A.A.S. [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Fonseca, F.L.A. [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Universidade Federal de São Paulo, Ambientais e Farmacêuticas, Instituto de Ciências Químicas, Diadema, SP (Brazil)

    2014-09-05

    Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO=0.60±0.11, control=1.07±0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-β1 (rhEPO=0.95±0.14, control=1.05±0.16) and TNF-α (rhEPO=0.73±0.20, control=1.01±0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.

  16. Erythropoietin reduces the expression of myostatin in mdx dystrophic mice

    International Nuclear Information System (INIS)

    Feder, D.; Rugollini, M.; Santomauro, A. Jr; Oliveira, L.P.; Lioi, V.P.; Santos, R. dos; Ferreira, L.G.; Nunes, M.T.; Carvalho, M.H.; Delgado, P.O.; Carvalho, A.A.S.; Fonseca, F.L.A.

    2014-01-01

    Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. In this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO=0.60±0.11, control=1.07±0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-β1 (rhEPO=0.95±0.14, control=1.05±0.16) and TNF-α (rhEPO=0.73±0.20, control=1.01±0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle

  17. RNAi reduces expression and intracellular retention of mutant cartilage oligomeric matrix protein.

    Directory of Open Access Journals (Sweden)

    Karen L Posey

    2010-04-01

    Full Text Available Mutations in cartilage oligomeric matrix protein (COMP, a large extracellular glycoprotein expressed in musculoskeletal tissues, cause two skeletal dysplasias, pseudoachondroplasia and multiple epiphyseal dysplasia. These mutations lead to massive intracellular retention of COMP, chondrocyte death and loss of growth plate chondrocytes that are necessary for linear growth. In contrast, COMP null mice have only minor growth plate abnormalities, normal growth and longevity. This suggests that reducing mutant and wild-type COMP expression in chondrocytes may prevent the toxic cellular phenotype causing the skeletal dysplasias. We tested this hypothesis using RNA interference to reduce steady state levels of COMP mRNA. A panel of shRNAs directed against COMP was tested. One shRNA (3B reduced endogenous and recombinant COMP mRNA dramatically, regardless of expression levels. The activity of the shRNA against COMP mRNA was maintained for up to 10 weeks. We also demonstrate that this treatment reduced ER stress. Moreover, we show that reducing steady state levels of COMP mRNA alleviates intracellular retention of other extracellular matrix proteins associated with the pseudoachondroplasia cellular pathology. These findings are a proof of principle and the foundation for the development of a therapeutic intervention based on reduction of COMP expression.

  18. Reduced Interference from Memory Testing: A Postretrieval Monitoring Account

    Science.gov (United States)

    Pierce, Benton H.; Gallo, David A.; McCain, Jason L.

    2017-01-01

    Initial learning can interfere with subsequent learning (proactive interference [PI]), but recent work indicates initial testing can reduce PI. Here, we tested 2 alternative hypotheses of this effect: Does testing reduce PI by constraining retrieval to the target list, or by facilitating a postretrieval monitoring process? Participants first…

  19. Expressive writing as a brief intervention for reducing drinking intentions.

    Science.gov (United States)

    Young, Chelsie M; Rodriguez, Lindsey M; Neighbors, Clayton

    2013-12-01

    The present study examined the effectiveness of expressive writing in reducing drinking behavior. We expected that students prompted to write about negative drinking experiences would show greater decreases in future drinking intentions compared to the neutral and the positive writing conditions. We also expected that decreases in drinking intentions following the writing prompts might differ based on current drinking and AUDIT scores. Participants included 200 (76% female) undergraduates who completed measures of their current drinking behavior. They were then randomly assigned to either write about: a time when they had a lot to drink that was a good time (Positive); a time when they had a lot to drink that was a bad time (Negative); or their first day of college (Neutral), followed by measures assessing intended drinking over the next three months. Results revealed that participants intended to drink significantly fewer drinks per week and engage in marginally fewer heavy drinking occasions after writing about a negative drinking occasion when compared to control. Interactions provided mixed findings suggesting that writing about a positive event was associated with higher drinking intentions for heavier drinkers. Writing about a negative event was associated with higher intentions among heavier drinkers, but lower intentions among those with higher AUDIT scores. This research builds on previous expressive writing interventions by applying this technique to undergraduate drinkers. Preliminary results provide some support for this innovative strategy but also suggest the need for further refinement, especially with heavier drinkers. © 2013.

  20. Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

    Directory of Open Access Journals (Sweden)

    BA Walter

    2016-07-01

    Full Text Available The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4 ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease.

  1. Chronic sleep deprivation markedly reduces coagulation factor VII expression

    Science.gov (United States)

    Pinotti, Mirko; Bertolucci, Cristiano; Frigato, Elena; Branchini, Alessio; Cavallari, Nicola; Baba, Kenkichi; Contreras-Alcantara, Susana; Ehlen, J. Christopher; Bernardi, Francesco; Paul, Ketema N.; Tosini, Gianluca

    2010-01-01

    Chronic sleep loss, a common feature of human life in industrialized countries, is associated to cardiovascular disorders. Variations in functional parameters of coagulation might contribute to explain this relationship. By exploiting the mouse model and a specifically designed protocol, we demonstrated that seven days of partial sleep deprivation significantly decreases (−30.5%) the thrombin generation potential in plasma evaluated upon extrinsic (TF/FVIIa pathway) but not intrinsic activation of coagulation. This variation was consistent with a decrease (−49.8%) in the plasma activity levels of factor VII (FVII), the crucial physiologicalal trigger of coagulation, which was even more pronounced at the liver mRNA level (−85.7%). The recovery in normal sleep conditions for three days completely restored thrombin generation and FVII activity in plasma. For the first time, we demonstrate that chronic sleep deprivation on its own reduces, in a reversible manner, the FVII expression levels, thus influencing the TF/FVIIa activation pathway efficiency. PMID:20418241

  2. Decoding Facial Expressions: A New Test with Decoding Norms.

    Science.gov (United States)

    Leathers, Dale G.; Emigh, Ted H.

    1980-01-01

    Describes the development and testing of a new facial meaning sensitivity test designed to determine how specialized are the meanings that can be decoded from facial expressions. Demonstrates the use of the test to measure a receiver's current level of skill in decoding facial expressions. (JMF)

  3. Hypertonic saline impedes tumor cell-endothelial cell interaction by reducing adhesion molecule and laminin expression.

    LENUS (Irish Health Repository)

    Shields, Conor J

    2012-02-03

    BACKGROUND: Hypertonic saline infusion dampens inflammatory responses and suppresses neutrophil-endothelial interaction by reducing adhesion molecule expression. This study tested the hypothesis that hypertonic saline attenuates tumor cell adhesion to the endothelium through a similar mechanism. METHODS: Human colon cancer cells (LS174T) were transfected with green fluorescent protein and exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6 under hypertonic and isotonic conditions for 1 and 4 hours. Confluent human umbilical vein endothelial cells were similarly exposed. Cellular apoptosis and expression of adhesion molecules and laminin were measured by flow cytometry. Tumor cell adhesion to endothelium and laminin was assessed with fluorescence microscopy. Data are represented as mean +\\/- standard error of mean, and an ANOVA test was performed to gauge statistical significance, with P <.05 considered significant. RESULTS: Hypertonic exposure significantly reduced tumor cell adhesion despite the presence of the perioperative cell stressors (42 +\\/- 2.9 vs 172.5 +\\/- 12.4, P <.05), attenuated tumor cell beta-1 integrin (14.43 vs 23.84, P <.05), and endothelial cell laminin expression (22.78 +\\/- 2.2 vs 33.74 +\\/- 2.4, P <.05), but did not significantly alter cell viability. CONCLUSION: Hypertonic saline significantly attenuates tumor cell adhesion to endothelium by inhibiting adhesion molecule and laminin expression. This may halt the metastatic behavior of tumor cells shed at surgery.

  4. Reduced enrichment for research and test reactors: Proceedings

    International Nuclear Information System (INIS)

    1993-07-01

    The 15th annual Reduced Enrichment for Research and Test Reactors (RERTR) international meeting was organized by Ris oe National Laboratory in cooperation with the International Atomic Energy Agency and Argonne National Laboratory. The topics of the meeting were the following: National Programs, Fuel Fabrication, Licensing Aspects, States of Conversion, Fuel Testing, and Fuel Cycle. Individual papers have been cataloged separately

  5. Reduced enrichment for research and test reactors: Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    1993-07-01

    The 15th annual Reduced Enrichment for Research and Test Reactors (RERTR) international meeting was organized by Ris{o} National Laboratory in cooperation with the International Atomic Energy Agency and Argonne National Laboratory. The topics of the meeting were the following: National Programs, Fuel Fabrication, Licensing Aspects, States of Conversion, Fuel Testing, and Fuel Cycle. Individual papers have been cataloged separately.

  6. Testosterone regulates granzyme K expression in rat testes

    Directory of Open Access Journals (Sweden)

    Dutta Dibyendu

    2017-10-01

    Full Text Available Objective. Testosterone depletion induces increased germ cell apoptosis in testes. However, limited studies exist on genes that regulate the germ cell apoptosis. Granzymes (GZM are serine proteases that induce apoptosis in various tissues. Multiple granzymes, including GZMA, GZMB and GZMN, are present in testes. Th us, we investigated which granzyme may be testosterone responsive and possibly may have a role in germ cell apoptosis aft er testosterone depletion. Methods. Ethylene dimethane sulfonate (EDS, a toxicant that selectively ablates the Leydig cells, was injected into rats to withdraw the testosterone. The testosterone depletion effects after 7 days post-EDS were verified by replacing the testosterone exogenously into EDS-treated rats. Serum or testicular testosterone was measured by radioimmunoassay. Using qPCR, mRNAs of granzyme variants in testes were quantified. The germ cell apoptosis was identified by TUNEL assay and the localization of GZMK was by immunohistochemistry. Results. EDS treatment eliminated the Leydig cells and depleted serum and testicular testosterone. At 7 days post-EDS, testis weights were reduced 18% with increased germ cell apoptosis plus elevation GZMK expression. GZMK was not associated with TUNEL-positive cells, but was localized to stripped cytoplasm of spermatids. In addition, apoptotic round spermatids were observed in the caput epididymis. Conclusions. GZMK expression in testes is testosterone dependent. GZMK is located adjacent to germ cells in seminiferous tubules and the presence of apoptotic round spermatids in the epididymis suggest its role in the degradation of microtubules in ectoplasmic specializations. Thus, overexpression of GZMK may indirectly regulate germ cell apoptosis by premature release of round spermatids from seminiferous tubule lumen.

  7. Reducing unnecessary lab testing in the ICU with artificial intelligence.

    Science.gov (United States)

    Cismondi, F; Celi, L A; Fialho, A S; Vieira, S M; Reti, S R; Sousa, J M C; Finkelstein, S N

    2013-05-01

    To reduce unnecessary lab testing by predicting when a proposed future lab test is likely to contribute information gain and thereby influence clinical management in patients with gastrointestinal bleeding. Recent studies have demonstrated that frequent laboratory testing does not necessarily relate to better outcomes. Data preprocessing, feature selection, and classification were performed and an artificial intelligence tool, fuzzy modeling, was used to identify lab tests that do not contribute an information gain. There were 11 input variables in total. Ten of these were derived from bedside monitor trends heart rate, oxygen saturation, respiratory rate, temperature, blood pressure, and urine collections, as well as infusion products and transfusions. The final input variable was a previous value from one of the eight lab tests being predicted: calcium, PTT, hematocrit, fibrinogen, lactate, platelets, INR and hemoglobin. The outcome for each test was a binary framework defining whether a test result contributed information gain or not. Predictive modeling was applied to recognize unnecessary lab tests in a real world ICU database extract comprising 746 patients with gastrointestinal bleeding. Classification accuracy of necessary and unnecessary lab tests of greater than 80% was achieved for all eight lab tests. Sensitivity and specificity were satisfactory for all the outcomes. An average reduction of 50% of the lab tests was obtained. This is an improvement from previously reported similar studies with average performance 37% by [1-3]. Reducing frequent lab testing and the potential clinical and financial implications are an important issue in intensive care. In this work we present an artificial intelligence method to predict the benefit of proposed future laboratory tests. Using ICU data from 746 patients with gastrointestinal bleeding, and eleven measurements, we demonstrate high accuracy in predicting the likely information to be gained from proposed future

  8. Reducing unnecessary lab testing in the ICU with artificial intelligence

    Science.gov (United States)

    Cismondi, F.; Celi, L.A.; Fialho, A.S.; Vieira, S.M.; Reti, S.R.; Sousa, J.M.C.; Finkelstein, S.N.

    2017-01-01

    Objectives To reduce unnecessary lab testing by predicting when a proposed future lab test is likely to contribute information gain and thereby influence clinical management in patients with gastrointestinal bleeding. Recent studies have demonstrated that frequent laboratory testing does not necessarily relate to better outcomes. Design Data preprocessing, feature selection, and classification were performed and an artificial intelligence tool, fuzzy modeling, was used to identify lab tests that do not contribute an information gain. There were 11 input variables in total. Ten of these were derived from bedside monitor trends heart rate, oxygen saturation, respiratory rate, temperature, blood pressure, and urine collections, as well as infusion products and transfusions. The final input variable was a previous value from one of the eight lab tests being predicted: calcium, PTT, hematocrit, fibrinogen, lactate, platelets, INR and hemoglobin. The outcome for each test was a binary framework defining whether a test result contributed information gain or not. Patients Predictive modeling was applied to recognize unnecessary lab tests in a real world ICU database extract comprising 746 patients with gastrointestinal bleeding. Main results Classification accuracy of necessary and unnecessary lab tests of greater than 80% was achieved for all eight lab tests. Sensitivity and specificity were satisfactory for all the outcomes. An average reduction of 50% of the lab tests was obtained. This is an improvement from previously reported similar studies with average performance 37% by [1–3]. Conclusions Reducing frequent lab testing and the potential clinical and financial implications are an important issue in intensive care. In this work we present an artificial intelligence method to predict the benefit of proposed future laboratory tests. Using ICU data from 746 patients with gastrointestinal bleeding, and eleven measurements, we demonstrate high accuracy in predicting the

  9. Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression.

    Science.gov (United States)

    Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J; Miyamoto, Hiroshi

    2014-08-01

    To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P=.026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (Pcancer-specific survival of MI tumors (P=.067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P=.034). GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. Copyright© by the American Society for Clinical Pathology.

  10. Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Ploug, Thorkil; Størling, Joachim

    2014-01-01

    Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design. In t...... accumulation and attenuates peripheral insulin resistance in obese mice........ In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo......Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design...

  11. Efficacy test of a toothpaste in reducing extrinsic dental stain

    Science.gov (United States)

    Agustanti, A.; Ramadhani, S. A.; Adiatman, M.; Rahardjo, A.; Callea, M.; Yavuz, I.; Maharani, D. A.

    2017-08-01

    This clinical trial compared the external dental stain reduction achieved by tested toothpaste versus placebo in adult patients. In this double-blind, parallel, randomised clinical trial, 45 female volunteers with a mean age of 20 years old were included. All study subjects front teeth were topically applicated with Silver Diamine Fluoride (SDF) to create external dental stains. Subjects were randomized into test (n=22) and control (n=23) groups. Toothpastes were used for two days to analyse the effects of removing external stains on the labial surfaces of all anterior teeth. VITA Easyshade Advance 4.0 was used to measure dental extrinsic stains changes. The analysis showed statistically significant efficacy of the tested toothpaste in reducing external dental stain caused by SDF, comparing to the placebo toothpaste, after one and two days of usage. The tested toothpaste was effective in reducing dental stain.

  12. Saccharomyces cerevisiae expressing bacteriophage endolysins reduce Lactobacillus contamination during fermentation

    Science.gov (United States)

    One of the challenges facing the fuel ethanol industry is the management of bacterial contamination during fermentation. Lactobacillus species are the predominant contaminants that decrease the profitability of biofuel production by reducing ethanol yields and causing “stuck” fermentations, which i...

  13. Satellite Vibration Testing: Angle optimisation method to Reduce Overtesting

    Science.gov (United States)

    Knight, Charly; Remedia, Marcello; Aglietti, Guglielmo S.; Richardson, Guy

    2018-06-01

    Spacecraft overtesting is a long running problem, and the main focus of most attempts to reduce it has been to adjust the base vibration input (i.e. notching). Instead this paper examines testing alternatives for secondary structures (equipment) coupled to the main structure (satellite) when they are tested separately. Even if the vibration source is applied along one of the orthogonal axes at the base of the coupled system (satellite plus equipment), the dynamics of the system and potentially the interface configuration mean the vibration at the interface may not occur all along one axis much less the corresponding orthogonal axis of the base excitation. This paper proposes an alternative testing methodology in which the testing of a piece of equipment occurs at an offset angle. This Angle Optimisation method may have multiple tests but each with an altered input direction allowing for the best match between all specified equipment system responses with coupled system tests. An optimisation process that compares the calculated equipment RMS values for a range of inputs with the maximum coupled system RMS values, and is used to find the optimal testing configuration for the given parameters. A case study was performed to find the best testing angles to match the acceleration responses of the centre of mass and sum of interface forces for all three axes, as well as the von Mises stress for an element by a fastening point. The angle optimisation method resulted in RMS values and PSD responses that were much closer to the coupled system when compared with traditional testing. The optimum testing configuration resulted in an overall average error significantly smaller than the traditional method. Crucially, this case study shows that the optimum test campaign could be a single equipment level test opposed to the traditional three orthogonal direction tests.

  14. Innovative approaches to reduce animal testing : replace whenever possible, reduce through refinement and mechanistic understanding

    NARCIS (Netherlands)

    Ravenzwaay, van B.

    2013-01-01

    'Many of the in vitro toxicological studies have not been sufficiently validated to determine their applicability domain, even less have gained regulatory acceptance. Major advantage of in vitro testing today is the early identification of significant hazards in compound development and reduced and

  15. Reduced Insulin Receptor Expression Enhances Proximal Tubule Gluconeogenesis.

    Science.gov (United States)

    Pandey, Gaurav; Shankar, Kripa; Makhija, Ekta; Gaikwad, Anil; Ecelbarger, Carolyn; Mandhani, Anil; Srivastava, Aneesh; Tiwari, Swasti

    2017-02-01

    Reduced insulin receptor protein levels have been reported in the kidney cortex from diabetic humans and animals. We recently reported that, targeted deletion of insulin receptor (IR) from proximal tubules (PT) resulted in hyperglycemia in non-obese mice. To elucidate the mechanism, we examined human proximal tubule cells (hPTC) and C57BL/6 mice fed with high-fat diet (HFD, 60% fat for 20 weeks). Immunoblotting revealed a significantly lower protein level of IR in HFD compare to normal chow diet (NCD). Furthermore, a blunted rise in p-AKT 308 levels in the kidney cortex of HFD mice was observed in response to acute insulin (0.75 IU/kg body weight, i.p) relative to NCD n = 8/group, P gluconeogenesis. Transcript levels of the gluconeogenic enzyme PEPCK were significantly increased in cAMP/DEXA-stimulated hPTC cells (n = 3, P gluconeogenesis and PEPCK induction was significantly attenuated in IR (siRNA) silenced hPTC (n = 3, P gluconeogenesis. Thus reduced insulin signaling of the proximal tubule may contribute to hyperglycemia in the metabolic syndrome via elevated gluconeogenesis. J. Cell. Biochem. 118: 276-285, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Thermosyphon Flooding in Reduced Gravity Environments Test Results

    Science.gov (United States)

    Gibson, Marc A.; Jaworske, Donald A.; Sanzi, Jim; Ljubanovic, Damir

    2013-01-01

    The condenser flooding phenomenon associated with gravity aided two-phase thermosyphons was studied using parabolic flights to obtain the desired reduced gravity environment (RGE). The experiment was designed and built to test a total of twelve titanium water thermosyphons in multiple gravity environments with the goal of developing a model that would accurately explain the correlation between gravitational forces and the maximum axial heat transfer limit associated with condenser flooding. Results from laboratory testing and parabolic flights are included in this report as part I of a two part series. The data analysis and correlations are included in a follow on paper.

  17. Instrumented impact testing machine with reduced specimen oscillation effects

    International Nuclear Information System (INIS)

    Rintamaa, R.; Rahka, K.; Wallin, K.

    1984-07-01

    Owing to small and inexpensive specimens the Charpy impact test is widely used in quality control and alloy development. Limitations in power reactor survellance capsules it is also widely used for safety analysis purposes. Instrumenting the tup and computerizing data acquisition, makes dynamic fracture mechanics data measurement possible and convenient. However, the dynamic effects (inertia forces, specimen oscillations) in the impact test cause inaccuracies in the recorded load-time diagram and hence diminish the reliability of the calculated dynamic fracture mechanics parameters. To decrease inaccuracies a new pendulum type of instrumented impact test apparatus has been developed and constructed in the Metals Laboratory of the Technical Research Centre of Finland. This tester is based on a new principle involving inverted test geometry. The purpose of the geometry inversion is to reduce inertia load and specimen oscillation effects. Further, the new impact tester has some other novel features: e.g. the available initia impact energy is about double compared to the conventional standard (300 J) impact tester allowing the use of larger (10 x 20 x 110 mm) bend specimens than normal Charpy specimens. Also, the rotation asix in the three point bending is nearly stationary making COD-measurements possible. An experimental test series is described in which the inertia effects and specimen oscillations are compared in the conventional and new impact tester utilizing Charpy V-notch specimens. Comparison of the two test geometries is also made with the aid of an analytical model using finite element method (FEM) analysis. (author)

  18. Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

    International Nuclear Information System (INIS)

    Salem, Tamer Z.; Zhang, Fengrui; Thiem, Suzanne M.

    2013-01-01

    Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

  19. Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Salem, Tamer Z. [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbial Molecular Biology, AGERI, Agricultural Research Center, Giza 12619 (Egypt); Division of Biomedical Sciences, Zewail University, Zewail City of Science and Technology, Giza 12588 (Egypt); Zhang, Fengrui [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Thiem, Suzanne M., E-mail: smthiem@msu.edu [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States)

    2013-01-20

    Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

  20. Reduced enrichment for research and test reactors: Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    1993-08-01

    November 9--10, 1978, marked the first of what has become an annual event--the International Meeting on Reduced Enrichment for Research and Test Reactors (RERTR). The meeting brought together for the first time many people who became major program participants in later years. This first meeting emphasized fuel development, and it established the basis for all later meetings. Believing that the proceedings of this first meeting are important as a historical record of the beginning of the international RERTR effort. This report provides presentations and discussions of this original meeting. Individual papers have been cataloged separately.

  1. Reduced enrichment for research and test reactors: Proceedings

    International Nuclear Information System (INIS)

    1993-08-01

    November 9--10, 1978, marked the first of what has become an annual event--the International Meeting on Reduced Enrichment for Research and Test Reactors (RERTR). The meeting brought together for the first time many people who became major program participants in later years. This first meeting emphasized fuel development, and it established the basis for all later meetings. Believing that the proceedings of this first meeting are important as a historical record of the beginning of the international RERTR effort. This report provides presentations and discussions of this original meeting. Individual papers have been cataloged separately

  2. ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence

    Directory of Open Access Journals (Sweden)

    Riggins Gregory J

    2011-01-01

    Full Text Available Abstract Background Mounting evidence has indicated that ABI3 (ABI family member 3 function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown. Methods The present study investigated ABI3 expression in a large panel of benign and malignant thyroid tumors and explored a correlation between the expression of ABI3 and its potential partner ABI3-binding protein (ABI3BP. We next explored the biological effects of ABI3 ectopic expression in thyroid and colon carcinoma cell lines, in which its expression was reduced or absent. Results We not only observed that ABI3 expression is reduced or lost in most carcinomas but also that there is a positive correlation between ABI3 and ABI3BP expression. Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression. Conclusions Our result links ABI3 to the pathogenesis and progression of some cancers and suggests that ABI3 or its pathway might have interest as therapeutic target. These results also suggest that the pathways through which ABI3 works should be further characterized.

  3. Reduced enrichment for research and test reactors: Proceedings

    International Nuclear Information System (INIS)

    1988-05-01

    The international effort to develop new research reactor fuel materials and designs based on the use of low-enriched uranium, instead of highly-enriched uranium, has made much progress during the eight years since its inception. To foster direct communication and exchange of ideas among the specialist in this area, the Reduced Enrichment Research and Test Reactor (RERTR) Program, at the Argonne National Laboratory, sponsored this meeting as the ninth of a series which began in 1978. All previous meetings of this series are listed on the facing page. The focus of this meeting was on the LEU fuel demonstration which was in progress at the Oak Ridge Research (ORR) reactor, not far from where the meeting was held. The visit to the ORR, where a silicide LEU fuel with 4.8 g A/cm 3 was by then in routine use, illustrated how far work has progressed

  4. Reduced enrichment for research and test reactors: Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    1988-05-01

    The international effort to develop new research reactor fuel materials and designs based on the use of low-enriched uranium, instead of highly-enriched uranium, has made much progress during the eight years since its inception. To foster direct communication and exchange of ideas among the specialist in this area, the Reduced Enrichment Research and Test Reactor (RERTR) Program, at the Argonne National Laboratory, sponsored this meeting as the ninth of a series which began in 1978. All previous meetings of this series are listed on the facing page. The focus of this meeting was on the LEU fuel demonstration which was in progress at the Oak Ridge Research (ORR) reactor, not far from where the meeting was held. The visit to the ORR, where a silicide LEU fuel with 4.8 g A/cm/sup 3/ was by then in routine use, illustrated how far work has progressed.

  5. The RERTR [Reduced Enrichment Research and Test Reactor] program:

    International Nuclear Information System (INIS)

    Travelli, A.

    1987-01-01

    The progress of the Reduced Enrichment Research and Test Reactor (RERTR) program is described. After a brief summary of the results which the RERTR program, in collaboration with its many international partners, had achieved by the end of 1986, the activities, results and new developments which ocurred in 1987 are reviewed. Irradiation of the second miniplate series, concentrating on U 3 Si 2 -Al and U 3 Si-Al fuels was completed and postirradiation examinations were performed on many of its miniplates. The whole-core ORR demonstration with U 3 Si 2 -Al fuel at 4.8 g U/cm 3 was completed at the end of March with excellent results and with 29 elements estimated to have reached at least 40 % average burnup. Good progress was made in the area of LEU usage for the production of fission 99 Mo, and in the coordination of safety evaluations related to LEU conversions of U.S. university reactors. Planned activities include testing and demonstrating advanced fuels intended to allow use of reduced enrichment uranium in very-high-performance reactors. Two candidate fuels are U 3 Si-Al with 19.75 % enrichment and U 3 Si 2 -Al with 45 % enrichment. Demonstration of these fuels will include irradiation of full-size elements and, possibly, a full-core demonstration. Achievement of the final program goals is still projected for 1990. This progress could not have been possible without the close international cooperation which has existed from the beginning, and which is essential to the ultimate success of the RERTR program. (Author)

  6. Application of glycine reduces arsenic accumulation and toxicity in Oryza sativa L. by reducing the expression of silicon transporter genes.

    Science.gov (United States)

    Kumar Dubey, Arvind; Kumar, Navin; Ranjan, Ruma; Gautam, Ambedkar; Pande, Veena; Sanyal, Indraneel; Mallick, Shekhar

    2018-02-01

    The present study was intended to investigate the role of amino acid glycine in detoxification of As in Oryza sativa L. The growth parameters such as, shoot length and fresh weight were decreased during As(III) and As(V) toxicity. However, the application of glycine recovered the growth parameters against As stress. The application of glycine reduced the As accumulation in all the treatments, and it was more effective against As(III) treatment and reduced the accumulation by 68% in root and 71% in shoot. Similarly, the translocation of As from root to shoot, was higher against As(III) and As(V) treatments, whereas, reduced upon glycine application. The translocation of Fe and Na was also affected by As, which was lower under As(III) and As(V) treatments. However, the application of glycine significantly enhanced the translocation of Fe and Na in the shoot. Besides, the expression of lower silicon transporters i.e. Lsi-1 and Lsi-2 was observed to be significantly suppressed in the root with the application of glycine against As treatment. Similarly, the expression of three GRX and two GST gene isoforms were found to be significantly increased with glycine application. Simultaneously, the activities of antioxidant enzymes i.e. l-arginine dependent NOS, SOD, NTR and GRX were found to be significantly enhanced in the presence of glycine. Increased activities of antioxidant enzymes coincided with the decreased level of TBARS and H 2 O 2 in rice seedlings. Overall, the results suggested that the application of glycine reduces As accumulation through suppressing the gene expression of lower silicon transporters and ameliorates As toxicity by enhancing antioxidants defense mechanism in rice seedlings. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation.

    Science.gov (United States)

    Nagarajan, Raman P; Hogart, Amber R; Gwye, Ynnez; Martin, Michelle R; LaSalle, Janine M

    2006-01-01

    Mutations in MECP2, encoding methyl CpG binding protein 2 (MeCP2), cause most cases of Rett syndrome (RTT), an X-linked neurodevelopmental disorder. Both RTT and autism are "pervasive developmental disorders" and share a loss of social, cognitive and language skills and a gain in repetitive stereotyped behavior, following apparently normal perinatal development. Although MECP2 coding mutations are a rare cause of autism, MeCP2 expression defects were previously found in autism brain. To further study the role of MeCP2 in autism spectrum disorders (ASDs), we determined the frequency of MeCP2 expression defects in brain samples from autism and other ASDs. We also tested the hypotheses that MECP2 promoter mutations or aberrant promoter methylation correlate with reduced expression in cases of idiopathic autism. MeCP2 immunofluorescence in autism and other neurodevelopmental disorders was quantified by laser scanning cytometry and compared with control postmortem cerebral cortex samples on a large tissue microarray. A significant reduction in MeCP2 expression compared to age-matched controls was found in 11/14 autism (79%), 9/9 RTT (100%), 4/4 Angelman syndrome (100%), 3/4 Prader-Willi syndrome (75%), 3/5 Down syndrome (60%), and 2/2 attention deficit hyperactivity disorder (100%) frontal cortex samples. One autism female was heterozygous for a rare MECP2 promoter variant that correlated with reduced MeCP2 expression. A more frequent occurrence was significantly increased MECP2 promoter methylation in autism male frontal cortex compared to controls. Furthermore, percent promoter methylation of MECP2 significantly correlated with reduced MeCP2 protein expression. These results suggest that both genetic and epigenetic defects lead to reduced MeCP2 expression and may be important in the complex etiology of autism.

  8. Reduced expression of p27 is a novel mechanism of docetaxel resistance in breast cancer cells

    International Nuclear Information System (INIS)

    Brown, Iain; Shalli, Kawan; McDonald, Sarah L; Moir, Susan E; Hutcheon, Andrew W; Heys, Steven D; Schofield, Andrew C

    2004-01-01

    Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. However, apoptosis and cell cycle regulation are key mechanisms by which most chemotherapeutic agents exert their cytotoxic effects. We created two docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) and performed cDNA microarray analysis to identify candidate genes associated with docetaxel resistance. Gene expression changes were validated at the RNA and protein levels by reverse transcription PCR and western analysis, respectively. Gene expression cDNA microarray analysis demonstrated reduced p27 expression in docetaxel-resistant breast cancer cells. Although p27 mRNA expression was found to be reduced only in MCF-7 docetaxel-resistant sublines (2.47-fold), reduced expression of p27 protein was noted in both MCF-7 and MDA-MB-231 docetaxel-resistant breast cancer cells (2.83-fold and 3.80-fold, respectively). This study demonstrates that reduced expression of p27 is associated with acquired resistance to docetaxel in breast cancer cells. An understanding of the genes that are involved in resistance to chemotherapy may allow further development in modulating drug resistance, and may permit selection of those patients who are most likely to benefit from such therapies

  9. Inhibition of STAT3 phosphorylation by sulforaphane reduces adhesion molecule expression in vascular endothelial cell.

    Science.gov (United States)

    Cho, Young S; Kim, Chan H; Ha, Tae S; Ahn, Hee Y

    2015-11-18

    Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS-mediated increase in ICAM-1 and VCAM-1 expression, (P < 0.01) in HUVEC. Sulforaphane also prevented the LPS-mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P < 0.01). Stattic, a STAT3 inhibitor, reduced the LPS-induced expression of ICAM-1 and VCAM-1, and STAT3 phosphorylation (P < 0.01). STAT3 small interfering RNA treatment reduced the LPS-induced expression of ICAM-1, VCAM-1, and STAT3 (P < 0.01). Sulforaphane reduced LPS-mediated THP-1 monocyte adhesion to HUVEC (P < 0.01). In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, and this effect was prevented by sulforaphane. These data provide insight into the mechanism through which sulforaphane partly reduces the expression of ICAM-1 and VCAM-1 on the vascular wall by inhibiting STAT3 phosphorylation.

  10. Increased NY-ESO-1 Expression and Reduced Infiltrating CD3+ T Cells in Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Mara Giavina-Bianchi

    2015-01-01

    Full Text Available NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79, rarely in in situ melanoma (1/10 and not in benign nevi (0/20. Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P=0.007 and inversely correlated with superficial spreading melanoma (P<0.02. NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P=0.017. When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P=0.010 or as isolated cells (P=0.002 than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.

  11. Retinoic acid reduces human neuroblastoma cell migration and invasiveness: effects on DCX, LIS1, neurofilaments-68 and vimentin expression

    International Nuclear Information System (INIS)

    Messi, Elio; Florian, Maria C; Caccia, Claudio; Zanisi, Mariarosa; Maggi, Roberto

    2008-01-01

    Neuroblastoma is a severe pediatric tumor, histologically characterised by a variety of cellular phenotypes. One of the pharmacological approaches to neuroblastoma is the treatment with retinoic acid. The mechanism of action of retinoic acid is still unclear, and the development of resistance to this differentiating agent is a great therapy problem. Doublecortin, a microtubule-associated protein involved in neuronal migration, has recently been proposed as a molecular marker for the detection of minimal residual disease in human neuroblastoma. Nevertheless, no information is available on the expression of doublecortin in the different cell-types composing human neuroblastoma, its correlation with neuroblastoma cell motility and invasiveness, and the possible modulations exerted by retinoic acid treatment. We analysed by immunofluorescence and by Western blot analysis the presence of doublecortin, lissencephaly-1 (another protein involved in neuronal migration) and of two intermediate filaments proteins, vimentin and neurofilament-68, in SK-N-SH human neuroblastoma cell line both in control conditions and under retinoic acid treatment. Migration and cell invasiveness studies were performed by wound scratch test and a modified microchemotaxis assay, respectively. Doublecortin is expressed in two cell subtypes considered to be the more aggressive and that show high migration capability and invasiveness. Vimentin expression is excluded by these cells, while lissencephaly-1 and neurofilaments-68 are immunodetected in all the cell subtypes of the SK-N-SH cell line. Treatment with retinoic acid reduces cell migration and invasiveness, down regulates doublecortin and lissencephaly-1 expression and up regulates neurofilament-68 expression. However, some cells that escape from retinoic acid action maintain migration capability and invasiveness and express doublecortin. a) Doublecortin is expressed in human neuroblastoma cells that show high motility and invasiveness; b

  12. Differential expression of growth factors in irradiated mouse testes

    International Nuclear Information System (INIS)

    Mauduit, Claire; Siah, Ahmed; Foch, Marie; Chapet, Olivier; Clippe, Sebastien; Gerard, Jean-Pierre; Benahmed, Mohamed

    2001-01-01

    Purpose: By using as an experimental model the male mouse gonad, which contains both radiosensitive (germ) and radioresistant (somatic) cells, we have studied the growth factor (and/or receptor) expression of transforming growth factor-β receptor (TGFβ RI), stem cell factor (SCF), c-kit, Fas-L, Fas, tumor necrosis factor receptor (TNF R55), and leukemia inhibiting factor receptor (LIF-R) after local irradiation. Methods and Materials: Adult male mice were locally irradiated on the testes. Induction of apoptosis in the different testicular cell types following X-ray radiation was identified by the TdT-mediated dUTP Nick End Labeling (TUNEL) approach. Growth factor expression was evidenced by semiquantitative RT-PCR and Western blot analyses. Results: Apoptosis, identified through the TUNEL approach, occurred in radiosensitive testicular (premeotic) germ cells with the following kinetics: the number of apoptotic cells increased after 24 h (p<0.001) and was maximal 48 h after a 2-Gy ionizing radiation (p<0.001). Apoptotic cells were no longer observed 72 h after a 2-Gy irradiation. The number of apoptotic cells increased with the dose of irradiation (1-4 Gy). In the seminiferous tubules, the growth factor expression in premeiotic radiosensitive germ cells was modulated by irradiation. Indeed Fas, c-kit, and LIF-R expression, which occurs in (radiosensitive) germ cells, decreased 24 h after a 2-Gy irradiation, and the maximal decrease was observed with a 4-Gy irradiation. The decrease in Stra8 expression occurred earlier, at 4 h after a 2-Gy irradiation. In addition, a significant (p<0.03) decrease in Stra8 mRNA levels was observed at the lowest dose used (0.5 Gy, 48 h). Moreover, concerning a growth factor receptor, such as TGFβ RI, which is expressed both in radiosensitive and radioresistant cells, we observed a differential expression depending on the cell radiosensitivity after irradiation. Indeed, TGFβ RI expression was increased after irradiation in

  13. Reduced expression levels of PTEN are associated with decreased sensitivity of HCC827 cells to icotinib.

    Science.gov (United States)

    Zhai, Yang; Zhang, Yanjun; Nan, Kejun; Liang, Xuan

    2017-05-01

    The clinical resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been linked to EGFR T790M resistance mutations or MET amplifications. Additional mechanisms underlying EGFR-TKI drug resistance remain unclear. The present study demonstrated that icotinib significantly inhibited the proliferation and increased the apoptosis rate of HCC827 cells; the cellular mRNA and protein expression levels of phosphatase and tensin homolog (PTEN) were also significantly downregulated. To investigate the effect of PTEN expression levels on the sensitivity of HCC827 cells to icotinib, PTEN expression was silenced using a PTEN-specific small interfering RNA. The current study identified that the downregulation of PTEN expression levels may promote cellular proliferation in addition to decreasing the apoptosis of HCC827 cells, and may reduce the sensitivity of HCC827 cells to icotinib. These results suggested that reduced PTEN expression levels were associated with the decreased sensitivity of HCC827 cells to icotinib. Furthermore, PTEN expression levels may be a useful marker for predicting icotinib resistance and elucidating the resistance mechanisms underlying EGFR-mutated NSCLC.

  14. GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury.

    Science.gov (United States)

    Duann, Pu; Lianos, Elias A

    2009-09-01

    Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-beta1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury.

  15. Experiences of the REACH testing proposals system to reduce animal testing.

    Science.gov (United States)

    Taylor, Katy; Stengel, Wolfgang; Casalegno, Carlotta; Andrew, David

    2014-01-01

    In order to reduce animal testing, companies registering chemical substances under the EU REACH legislation must propose rather than conduct certain tests on animals. Third parties can submit 'scientifically valid information' relevant to these proposals to the Agency responsible, the European Chemicals Agency (ECHA), who are obliged to take the information into account. The European Coalition to End Animal Experiments (ECEAE) provided comments on nearly half of the 817 proposals for vertebrate tests on 480 substances published for comment for the first REACH deadline (between 1 August 2009 and 31 July 2012). The paper summarises the response by registrants and the Agency to third party comments and highlights issues with the use of read across, in vitro tests, QSAR and weight of evidence approaches. Use of existing data and evidence that testing is legally or scientifically unjustified remain the most successful comments for third parties to submit. There is a worrying conservatism within the Agency regarding the acceptance of alternative approaches and examples of where registrants have also failed to maximise opportunities to avoid testing.

  16. Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients

    Directory of Open Access Journals (Sweden)

    Coco Claudio

    2012-09-01

    Full Text Available Abstract Background Expression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG complex, have been previously reported to be altered in colorectal cancers. Methods Expression levels of CD133 and α-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated. Results Scattered cells positive for CD133 were rarely detected at the bases of the crypts in normal colonic mucosa while in cancer cells the median percentage of positive cells was 5% (range 0–80. A significant correlation was observed with pT parameter and tumor stage but not with tumor grade and N status. Recurrence and death from disease were significantly more frequent in CD133-high expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (p = 0.002 and overall (p = 0.008 survival. Expression of α-DG was reduced in a significant fraction of tumors but low α-DG staining did not correlate with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in α-DG-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor tumors for both disease-free (p = 0.02 and overall (p = 0.02 survival. Increased expression of CD133, but not loss of α-DG, confirmed to be an independent prognostic parameters at a multivariate analysis associated with an increased risk of recurrence (RR = 2.4; p = 0.002 and death (RR = 2.3; p = 0.003. Conclusions Loss of α-DG and increased CD133 expression are frequent events in human colon cancer and evaluation of CD133 expression could help to identify high-risk colon cancer patients.

  17. An Acceptance-Based Psychoeducation Intervention to Reduce Expressed Emotion in Relatives of Bipolar Patients

    Science.gov (United States)

    Eisner, Lori R.; Johnson, Sheri L.

    2008-01-01

    Expressed emotion (EE) is a robust predictor of outcome in bipolar disorder. Despite decades of research, interventions to reduce EE levels have had only modest effects. This study used an expanded model of EE to develop an intervention. Research has demonstrated a strong link between attributions and EE in families of patients with psychiatric…

  18. Zinc oxide nanoparticle reduced biofilm formation and antigen 43 expressions in uropathogenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Ali Shakerimoghaddam

    2017-04-01

    Full Text Available Objective(s: This study aimed to investigate the effect of zinc oxide nanoparticles (ZnO-np on biofilm formation and expression of the flu gene in uropathogenic Escherichia coli (UPEC strains. Materials and Methods: Minimum inhibitory concentration (MIC of ZnO-np was determined by agar dilution method. The effect of MIC and sub-MIC concentrations of ZnO-np on biofilm formation were determined by microtiter plate assay. The expression level of the flu gene was assessed by Real-Time PCR assay. Results: MIC and sub-MIC ZnO-np concentrations reduced biofilm formation by 50% and 33.4%, respectively. Sub-MIC ZnO-np concentration significantly reduced the flu gene expression in the UPEC isolates (P

  19. Treatability Test Plan for an In Situ Biostimulation Reducing Barrier

    Energy Technology Data Exchange (ETDEWEB)

    Truex, Michael J.; Vermeul, Vince R.; Long, Philip E.; Brockman, Fred J.; Oostrom, Mart; Hubbard, Susan; Borden, Robert C.; Fruchter, Jonathan S.

    2007-07-21

    This treatability test plan supports a new, integrated strategy to accelerate cleanup of chromium in the Hanford 100 Areas. This plan includes performing a field-scale treatability test for bioreduction of chromate, nitrate, and dissolved oxygen. In addition to remediating a portion of the plume and demonstrating reduction of electron acceptors in the plume, the data from this test will be valuable for designing a full-scale bioremediation system to apply at this and other chromium plumes at Hanford.

  20. Angiotensin II Reduces Food Intake by Altering Orexigenic Neuropeptide Expression in the Mouse Hypothalamus

    Science.gov (United States)

    Yoshida, Tadashi; Semprun-Prieto, Laura; Wainford, Richard D.; Sukhanov, Sergiy; Kapusta, Daniel R.

    2012-01-01

    Angiotensin II (Ang II), which is elevated in many chronic disease states such as end-stage renal disease and congestive heart failure, induces cachexia and skeletal muscle wasting by increasing muscle protein breakdown and reducing food intake. Neurohormonal mechanisms that mediate Ang II-induced appetite suppression are unknown. Consequently, we examined the effect of Ang II on expression of genes regulating appetite. Systemic Ang II (1 μg/kg · min) infusion in FVB mice rapidly reduced hypothalamic expression of neuropeptide Y (Npy) and orexin and decreased food intake at 6 h compared with sham-infused controls but did not change peripheral leptin, ghrelin, adiponectin, glucagon-like peptide, peptide YY, or cholecystokinin levels. These effects were completely blocked by the Ang II type I receptor antagonist candesartan or deletion of Ang II type 1a receptor. Ang II markedly reduced phosphorylation of AMP-activated protein kinase (AMPK), an enzyme that is known to regulate Npy expression. Intracerebroventricular Ang II infusion (50 ng/kg · min) caused a reduction of food intake, and Ang II dose dependently reduced Npy and orexin expression in the hypothalamus cultured ex vivo. The reduction of Npy and orexin in hypothalamic cultures was completely prevented by candesartan or the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside. Thus, Ang II type 1a receptor-dependent Ang II signaling reduces food intake by suppressing the hypothalamic expression of Npy and orexin, likely via AMPK dephosphorylation. These findings have major implications for understanding mechanisms of cachexia in chronic disease states such as congestive heart failure and end-stage renal disease, in which the renin-angiotensin system is activated. PMID:22234465

  1. In vitro vaccine potency testing: a proposal for reducing animal use for requalification testing.

    Science.gov (United States)

    Brown, K; Stokes, W

    2012-01-01

    This paper proposes a program under which the use of animals for requalification of in vitro potency tests could be eliminated. Standard References (USDA/CVB nomenclature) would be developed, characterized, stored and monitored by selected reference laboratories worldwide. These laboratories would employ scientists skilled in protein and glycoprotein chemistry and equipped with state-of-the-art instruments for required analyses. After Standard References are established, the reference laboratories would provide them to the animal health industry as "gold standards". Companies would then establish and validate a correlation between the Standard Reference and the company Master Reference (USDA/CVB nomenclature) using an internal in vitro assay. After this correlation is established, the company could use the Standard References for qualifying, monitoring and requalifying company Master References without the use of animals. Such a program would eliminate the need for animals for requalification of Master References and the need for each company to develop and validate a battery of Master Reference Monitoring assays. It would also provide advantages in terms of reduced costs and reduced time for requalification testing. As such it would provide a strong incentive for companies to develop and use in vitro assays for potency testing.

  2. Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Baldry, Mara; Nielsen, Anita; Bojer, Martin S.

    2016-01-01

    Staphylococcus aureus is a serious human pathogen and antibiotic resistant, community-associated strains, such as the methicillin resistant S. aureus (MRSA) strain USA300, continue to spread. To avoid resistance, anti-virulence therapy has been proposed where toxicity is targeted rather than...... viability. Previously we have shown that norlichexanthone, a small non-reduced tricyclic polyketide produced by fungi and lichens, reduces expression of hla encoding α-hemolysin as well as the regulatory RNAIII of the agr quorum sensing system in S. aureus 8325-4. The aim of the present study was to further...... SaeRS system. Our data show that norlichexanthone treatment reduces expression of key virulence factors in CA-MRSA strain USA300 via AgrA binding and represses biofilm formation....

  3. Norlichexanthone Reduces Virulence Gene Expression and Biofilm Formation in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Baldry, Mara; Nielsen, Anita; Bojer, Martin S.

    2016-01-01

    characterise the mode of action of norlichexanthone and its effect on biofilm formation. We find that norlichexanthone reduces expression of both hla and RNAIII also in strain USA300. Structurally, norlichexanthone resembles ω-hydroxyemodin that recently was shown to bind the agr two component response......-hydroxyemodin however, norlichexanthone reduces staphylococcal biofilm formation. Transcriptomic analysis revealed that genes regulated by the SaeRS two-component system are repressed by norlichexanthone when compared to untreated cells, an effect that was mitigated in strain Newman carrying a partially constitutive...... SaeRS system. Our data show that norlichexanthone treatment reduces expression of key virulence factors in CA-MRSA strain USA300 via AgrA binding and represses biofilm formation....

  4. Treatability Test Plan for an In Situ Biostimulation Reducing Barrier

    Energy Technology Data Exchange (ETDEWEB)

    Truex, Michael J.; Vermeul, Vince R.; Long, Philip E.; Brockman, Fred J.; Oostrom, Mart; Hubbard, Susan; Borden, Robert C.; Fruchter, Jonathan S.

    2007-10-26

    This treatability test plan supports a new, integrated strategy to accelerate cleanup of chromium in the 100 Areas at the Hanford Site. This plan includes performing a field-scale treatability test for bioreduction of chromate, nitrate, and dissolved oxygen. In addition to remediating a portion of the plume and demonstrating reduction of electron acceptors in the plume, the data from this test will be valuable for designing a full-scale bioremediation system to apply at this and other chromium plumes at the Hanford Site.

  5. A Complex Interaction Between Reduced Reelin Expression and Prenatal Organophosphate Exposure Alters Neuronal Cell Morphology

    Directory of Open Access Journals (Sweden)

    Brian R. Mullen

    2016-06-01

    Full Text Available Genetic and environmental factors are both likely to contribute to neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and major depressive disorders. Prior studies from our laboratory and others have demonstrated that the combinatorial effect of two factors—reduced expression of reelin protein and prenatal exposure to the organophosphate pesticide chlorpyrifos oxon—gives rise to acute biochemical effects and to morphological and behavioral phenotypes in adolescent and young adult mice. In the current study, we examine the consequences of these factors on reelin protein expression and neuronal cell morphology in adult mice. While the cell populations that express reelin in the adult brain appear unchanged in location and distribution, the levels of full length and cleaved reelin protein show persistent reductions following prenatal exposure to chlorpyrifos oxon. Cell positioning and organization in the hippocampus and cerebellum are largely normal in animals with either reduced reelin expression or prenatal exposure to chlorpyrifos oxon, but cellular complexity and dendritic spine organization is altered, with a skewed distribution of immature dendritic spines in adult animals. Paradoxically, combinatorial exposure to both factors appears to generate a rescue of the dendritic spine phenotypes, similar to the mitigation of behavioral and morphological changes observed in our prior study. Together, our observations support an interaction between reelin expression and chlorpyrifos oxon exposure that is not simply additive, suggesting a complex interplay between genetic and environmental factors in regulating brain morphology.

  6. Reduced seed germination in Arabidopsis over-expressing SWI/SNF2 ATPase genes.

    Science.gov (United States)

    Leeggangers, Hendrika A C F; Folta, Adam; Muras, Aleksandra; Nap, Jan-Peter; Mlynarova, Ludmila

    2015-02-01

    In the life of flowering plants, seed germination is a critical step to ensure survival into the next generation. Generally the seed prior to germination has been in a dormant state with a low rate of metabolism. In the transition from a dormant seed to a germinating seed, various epigenetic mechanisms play a regulatory role. Here, we demonstrate that the over-expression of chromatin remodeling ATPase genes (AtCHR12 or AtCHR23) reduced the frequency of seed germination in Arabidopsis thaliana up to 30% relative to the wild-type seeds. On the other hand, single loss-of-function mutations of the two genes did not affect seed germination. The reduction of germination in over-expressing mutants was more pronounced in stress conditions (salt or high temperature), showing the impact of the environment. Reduced germinations upon over-expression coincided with increased transcript levels of seed maturation genes and with reduced degradation of their mRNAs stored in dry seeds. Our results indicate that repression of AtCHR12/23 gene expression in germinating wild-type Arabidopsis seeds is required for full germination. This establishes a functional link between chromatin modifiers and regulatory networks towards seed maturation and germination. © 2014 Scandinavian Plant Physiology Society.

  7. Cryomdoule Test Stand Reduced-Magnetic Support Design at Fermilab

    Energy Technology Data Exchange (ETDEWEB)

    McGee, Mike [Fermilab; Chandrasekaran, Saravan Kumar [Fermilab; Crawford, Anthony [Fermilab; Harms, Elvin [Fermilab; Leibfritz, Jerry [Fermilab; Wu, Genfa [Fermilab

    2016-06-01

    In a partnership with SLAC National Accelerator Laboratory (SLAC) and Jefferson Lab, Fermilab will assemble and test 17 of the 35 total 1.3 GHz cryomodules for the Linac Coherent Light Source II (LCLS-II) Project. These devices will be tested at Fermilab's Cryomodule Test Facility (CMTF) within the Cryomodule Test Stand (CMTS-1) cave. The problem of magnetic pollution became one of major issues during design stage of the LCLS-II cryomodule as the average quality factor of the accelerating cavities is specified to be 2.7 x 10¹⁰. One of the possible ways to mitigate the effect of stray magnetic fields and to keep it below the goal of 5 mGauss involves the application of low permeable materials. Initial permeability and magnetic measurement studies regarding the use of 316L stainless steel material indicated that cold work (machining) and heat affected zones from welding would be acceptable.

  8. Phenobarbital reduces blood glucose and gluconeogenesis through down-regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression in rats.

    Science.gov (United States)

    Oda, Hiroaki; Okuda, Yuji; Yoshida, Yukiko; Kimura, Noriko; Kakinuma, Atsushi

    2015-10-23

    The regulatory mechanism of phosphoenolpyruvate carboykinase (GTP) (EC 4.1.1.32) (PEPCK) gene expression and gluconeogenesis by phenobarbital (PB), which is known to induce drug-metabolizing enzymes, was investigated. Higher level of PEPCK mRNA was observed in spherical rat primary hepatocytes on EHS-gel than monolayer hepatocytes on TIC (type I collagen). We found that PB directly suppressed PEPCK gene expression in spherical hepatocytes on EHS-gel, but not in those on TIC. PB strongly suppressed cAMP-dependent induction of PEPCK gene expression. Tyrosine aminotransferase (TAT), another gluconeogenic enzyme, was induced by cAMP, but not suppressed by PB. Chronic administration of PB reduced hepatic PEPCK mRNA in streptozotocin-induced diabetic and nondiabetic rats, and PB reduced blood glucose level in diabetic rats. Increased TAT mRNA in diabetic rats was not suppressed by PB. These results indicated that PB-dependent reduction is specific to PEPCK. From pyrvate challenge test, PB suppressed the increased gluconeogenesis in diabetic rats. PEPCK gene promoter activity was suppressed by PB in HepG2 cells. In conclusion, we found that spherical hepatocytes cultured on EHS-gel are capable to respond to PB to suppress PEPCK gene expression. Moreover, our results indicate that hypoglycemic action of PB result from transcriptional repression of PEPCK gene and subsequent suppression of gluconeogenesis. Copyright © 2015. Published by Elsevier Inc.

  9. Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

    Directory of Open Access Journals (Sweden)

    José Jaime Herrera-Pérez

    2013-01-01

    Full Text Available In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT expression associated with low testosterone (T levels. The objectives of this study were to establish (1 if brain SERT expression is reduced by aging and (2 if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population.

  10. Generalized reduced rank tests using the singular value decomposition

    NARCIS (Netherlands)

    Kleibergen, F.R.; Paap, R.

    2002-01-01

    We propose a novel statistic to test the rank of a matrix. The rank statistic overcomes deficiencies of existing rank statistics, like: necessity of a Kronecker covariance matrix for the canonical correlation rank statistic of Anderson (1951), sensitivity to the ordering of the variables for the LDU

  11. Generalized Reduced Rank Tests using the Singular Value Decomposition

    NARCIS (Netherlands)

    F.R. Kleibergen (Frank); R. Paap (Richard)

    2003-01-01

    textabstractWe propose a novel statistic to test the rank of a matrix. The rank statistic overcomes deficiencies of existing rank statistics, like: necessity of a Kronecker covariance matrix for the canonical correlation rank statistic of Anderson (1951), sensitivity to the ordering of the variables

  12. Histone deacetylase inhibition reduces cardiac Connexin43 expression and gap junction communication

    Directory of Open Access Journals (Sweden)

    Qin eXu

    2013-04-01

    Full Text Available Histone deactylase (HDAC inhibitors are being investigated as novel therapies for cancer, inflammation, neurodegeneration, and heart failure. The effects of HDAC inhibitors on the functional expression of cardiac gap junctions (GJ are essentially unknown. The purpose of this study was to determine the effects of trichostatin A (TSA and vorinostat (VOR on functional GJ expression in ventricular cardiomyocytes. The effects of HDAC inhibition on connexin43 (Cx43 expression and functional GJ assembly were examined in primary cultured neonatal mouse ventricular myocytes. TSA and VOR reduced Cx43 mRNA, protein expression, and immunolocalized Cx43 GJ plaque area within ventricular myocyte monolayer cultures in a dose-dependent manner. Chromatin-immunoprecipitation experiments revealed altered protein interactions with the Cx43 promoter. VOR also altered the phosphorylation state of several key regulatory Cx43 phospho-serine sites. Patch clamp analysis revealed reduced electrical coupling between isolated ventricular myocyte pairs, altered transjunctional voltage-dependent inactivation kinetics, and steady state junctional conductance inactivation and recovery relationships. Single GJ channel conductance was reduced to 54 pS only by maximum inhibitory doses of TSA (>= 100 nM. These two hydroxamate pan-HDAC inhibitors exert multiple levels of regulation on ventricular GJ communication by altering Cx43 expression, GJ area, post-translational modifications (e.g. phosphorylation, acetylation, gating, and channel conductance. Although a 50% downregulation of Cx43 GJ communication alone may not be sufficient to slow ventricular conduction or induce arrhythmias, the development of class-selective HDAC inhibitors may help avoid the potential negative cardiovascular effects of pan-HDACI.

  13. Elimination of Kalrn Expression in POMC Cells Reduces Anxiety-Like Behavior and Contextual Fear Learning

    Science.gov (United States)

    Mandela, Prashant; Yan, Yan; LaRese, Taylor; Eipper, Betty A.; Mains, Richard E.

    2014-01-01

    Kalirin, a Rho GDP/GTP exchange factor for Rac1 and RhoG, is known to play an essential role in the formation and maintenance of excitatory synapses and in the secretion of neuropeptides. Mice unable to express any of the isoforms of Kalrn in cells that produce POMC at any time during development (POMC cells) exhibited reduced anxiety-like behavior and reduced acquisition of passive avoidance behavior, along with sex-specific alteration in the corticosterone response to restraint stress. Strikingly, lack of Kalrn expression in POMC cells closely mimicked the effects of global Kalrn knockout on anxiety-like behavior and passive avoidance conditioning without causing the other deficits noted in Kalrn knockout mice. Our data suggest that deficits in excitatory inputs onto POMC neurons are responsible for the behavioral phenotypes observed. PMID:25014196

  14. Elimination of Kalrn expression in POMC cells reduces anxiety-like behavior and contextual fear learning.

    Science.gov (United States)

    Mandela, Prashant; Yan, Yan; LaRese, Taylor; Eipper, Betty A; Mains, Richard E

    2014-07-01

    Kalirin, a Rho GDP/GTP exchange factor for Rac1 and RhoG, is known to play an essential role in the formation and maintenance of excitatory synapses and in the secretion of neuropeptides. Mice unable to express any of the isoforms of Kalrn in cells that produce POMC at any time during development (POMC cells) exhibited reduced anxiety-like behavior and reduced acquisition of passive avoidance behavior, along with sex-specific alteration in the corticosterone response to restraint stress. Strikingly, lack of Kalrn expression in POMC cells closely mimicked the effects of global Kalrn knockout on anxiety-like behavior and passive avoidance conditioning without causing the other deficits noted in Kalrn knockout mice. Our data suggest that deficits in excitatory inputs onto POMC neurons are responsible for the behavioral phenotypes observed. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Benzylglucosinolate Derived Isothiocyanate from Tropaeolum majus Reduces Gluconeogenic Gene and Protein Expression in Human Cells.

    Directory of Open Access Journals (Sweden)

    Valentina Guzmán-Pérez

    Full Text Available Nasturtium (Tropaeolum majus L. contains high concentrations of benzylglcosinolate. We found that a hydrolysis product of benzyl glucosinolate-the benzyl isothiocyanate (BITC-modulates the intracellular localization of the transcription factor Forkhead box O 1 (FOXO1. FoxO transcription factors can antagonize insulin effects and trigger a variety of cellular processes involved in tumor suppression, longevity, development and metabolism. The current study evaluated the ability of BITC-extracted as intact glucosinolate from nasturtium and hydrolyzed with myrosinase-to modulate i the insulin-signaling pathway, ii the intracellular localization of FOXO1 and, iii the expression of proteins involved in gluconeogenesis, antioxidant response and detoxification. Stably transfected human osteosarcoma cells (U-2 OS with constitutive expression of FOXO1 protein labeled with GFP (green fluorescent protein were used to evaluate the effect of BITC on FOXO1. Human hepatoma HepG2 cell cultures were selected to evaluate the effect on gluconeogenic, antioxidant and detoxification genes and protein expression. BITC reduced the phosphorylation of protein kinase B (AKT/PKB and FOXO1; promoted FOXO1 translocation from cytoplasm into the nucleus antagonizing the insulin effect; was able to down-regulate the gene and protein expression of gluconeogenic enzymes; and induced the gene expression of antioxidant and detoxification enzymes. Knockdown analyses with specific siRNAs showed that the expression of gluconeogenic genes was dependent on nuclear factor (erythroid derived-like2 (NRF2 and independent of FOXO1, AKT and NAD-dependent deacetylase sirtuin-1 (SIRT1. The current study provides evidence that BITC might have a role in type 2 diabetes T2D by reducing hepatic glucose production and increasing antioxidant resistance.

  16. How to reduce errors in applying impairment tests

    OpenAIRE

    Petersen, Christian; Plenborg, Thomas

    2007-01-01

    Fair value accounting has become predominant in accounting as a vast number of IAS/IFRS standards are based on fair value accounting, including IAS 36 Impairment of assets. Fair value accounting for goodwill is technically challenging, since market prices are not observable. Thus, valuation technologies must be applied in order to test goodwill for impairment. While prior research on goodwill has concentrated on either the (dis)advantages for each accounting procedure for goodwill or exami...

  17. Testing a flexible method to reduce false monsoon onsets.

    Directory of Open Access Journals (Sweden)

    Mathew Alexander Stiller-Reeve

    Full Text Available To generate information about the monsoon onset and withdrawal we have to choose a monsoon definition and apply it to data. One problem that arises is that false monsoon onsets can hamper our analysis, which is often alleviated by smoothing the data in time or space. Another problem is that local communities or stakeholder groups may define the monsoon differently. We therefore aim to develop a technique that reduces false onsets for high-resolution gridded data, while also being flexible for different requirements that can be tailored to particular end-users. In this study, we explain how we developed our technique and demonstrate how it successfully reduces false onsets and withdrawals. The presented results yield improved information about the monsoon length and its interannual variability. Due to this improvement, we are able to extract information from higher resolution data sets. This implies that we can potentially get a more detailed picture of local climate variations that can be used in more local climate application projects such as community-based adaptations.

  18. Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder

    Science.gov (United States)

    Bychkov, ER; Ahmed, MR; Gurevich, VV; Benovic, JL; Gurevich, EV

    2011-01-01

    Alterations of multiple G protein-mediated signaling pathways are detected in schizophrenia. G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting powerful influence on receptor functions. Modifications of arrestin and/or GRKs expression may contribute to schizophrenia pathology. Cortical expression of arrestins and GRKs was measured postmortem in control and subjects with schizophrenia or schizoaffective disorder. Additionally, arrestin/GRK expression was determined in elderly patients with schizophrenia and age-matched control. Patients with schizophrenia, but not schizoaffective disorder, displayed reduced concentration of arrestin and GRK mRNAs and GRK3 protein. Arrestins and GRK significantly decreased with age. In elderly patients, GRK6 was reduced, with other GRKs and arrestins unchanged. Reduced cortical concentration of GRKs in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder. PMID:21784156

  19. Histone deacetylase inhibitors reduce the number of herpes simplex virus-1 genomes initiating expression in individual cells

    Directory of Open Access Journals (Sweden)

    Lev Shapira

    2016-12-01

    Full Text Available Although many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1 fluorescence-expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s. Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA, Suberohydroxamic Acid (SBX, Valporic Acid (VPA and Suberoylanilide Hydoxamic Acid (SAHA. We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the gene expression from the viral genomes. Different cell types (HFF, Vero and U2OS, which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (PML and ATRX, which may explain the lower number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in

  20. Psoriatic T cells reduce epidermal turnover time and affect cell proliferation contributed from differential gene expression.

    Science.gov (United States)

    Li, Junqin; Li, Xinhua; Hou, Ruixia; Liu, Ruifeng; Zhao, Xincheng; Dong, Feng; Wang, Chunfang; Yin, Guohua; Zhang, Kaiming

    2015-09-01

    Psoriasis is mediated primarily by T cells, which reduce epidermal turnover time and affect keratinocyte proliferation. We aimed to identify differentially expressed genes (DEG) in T cells from normal, five pairs of monozygotic twins concordant or discordant for psoriasis, to determine whether these DEG may account for the influence to epidermal turnover time and keratinocyte proliferation. The impact of T cells on keratinocyte proliferation and epidermal turnover time were investigated separately by immunohistochemistry and cultured with (3) H-TdR. mRNA expression patterns were investigated by RNA sequencing and verified by real-time reverse transcription polymerase chain reaction. After co-culture with psoriatic T cells, the expression of Ki-67, c-Myc and p53 increased, while expression of Bcl-2 and epidermal turnover time decreased. There were 14 DEG which were found to participate in the regulation of cell proliferation or differentiation. Psoriatic T cells exhibited the ability to decrease epidermal turnover time and affect keratinocyte proliferation because of the differential expression of PPIL1, HSPH1, SENP3, NUP54, FABP5, PLEKHG3, SLC9A9 and CHCHD4. © 2015 Japanese Dermatological Association.

  1. Intracerebroventricular C75 decreases meal frequency and reduces AgRP gene expression in rats.

    Science.gov (United States)

    Aja, Susan; Bi, Sheng; Knipp, Susan B; McFadden, Jill M; Ronnett, Gabriele V; Kuhajda, Francis P; Moran, Timothy H

    2006-07-01

    3-Carboxy-4-alkyl-2-methylenebutyrolactone (C75), an inhibitor of fatty acid synthase and stimulator of carnitine palmitoyltransferase-1, reduces food intake and body weight in rodents when given systemically or centrally. Intracellular molecular mechanisms involving changes in cellular energy status are proposed to initiate the feeding and body weight reductions. However, effectors that lie downstream of these initial steps are not yet fully identified. Present experiments characterize the time courses of hypophagia and weight loss after single injections of C75 into the lateral cerebroventicle in rats and go on to identify specific meal pattern changes and coinciding alterations in gene expression for feeding-related hypothalamic neuropeptides. C75 reduced chow intake and body weight dose dependently. Although the principal effects occurred on the first day, weight losses relative to vehicle control were maintained over multiple days. C75 did not affect generalized locomotor activity. C75 began to reduce feeding after a 6-h delay. The hypophagia was due primarily to decreased meal number during 6-12 h without a significant effect on meal size, suggesting that central C75 reduced the drive to initiate meals. C75 prevented the anticipated hypophagia-induced increases in mRNA for AgRP in the arcuate nucleus at 22 h and at 6 h when C75 begins to suppress feeding. Overall, the data suggest that gene expression changes leading to altered melanocortin signaling are important for the hypophagic response to intracerebroventricular C75.

  2. Reducing uncertainty in geostatistical description with well testing pressure data

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, A.C.; He, Nanqun [Univ. of Tulsa, OK (United States); Oliver, D.S. [Chevron Petroleum Technology Company, La Habra, CA (United States)

    1997-08-01

    Geostatistics has proven to be an effective tool for generating realizations of reservoir properties conditioned to static data, e.g., core and log data and geologic knowledge. Due to the lack of closely spaced data in the lateral directions, there will be significant variability in reservoir descriptions generated by geostatistical simulation, i.e., significant uncertainty in the reservoir descriptions. In past work, we have presented procedures based on inverse problem theory for generating reservoir descriptions (rock property fields) conditioned to pressure data and geostatistical information represented as prior means for log-permeability and porosity and variograms. Although we have shown that the incorporation of pressure data reduces the uncertainty below the level contained in the geostatistical model based only on static information (the prior model), our previous results assumed did not explicitly account for uncertainties in the prior means and the parameters defining the variogram model. In this work, we investigate how pressure data can help detect errors in the prior means. If errors in the prior means are large and are not taken into account, realizations conditioned to pressure data represent incorrect samples of the a posteriori probability density function for the rock property fields, whereas, if the uncertainty in the prior mean is incorporated properly into the model, one obtains realistic realizations of the rock property fields.

  3. Recombinant myostatin reduces highly expressed microRNAs in differentiating C2C12 cells

    Directory of Open Access Journals (Sweden)

    Zachary A. Graham

    2017-03-01

    Full Text Available Myostatin is small glycopeptide that is produced and secreted by skeletal muscle. It is a potent negative regulator of muscle growth that has been associated with conditions of frailty. In C2C12 cells, myostatin limits cell differentiation. Myostatin acts through activin receptor IIB, activin receptor-like kinase (ALK and Smad transcription factors. microRNAs (miRNA are short, 22 base pair nucleotides that bind to the 3′ UTR of target mRNA to repress translation or reduce mRNA stability. In the present study, expression in differentiating C2C12 cells of the myomiRs miR-1 and 133a were down-regulated following treatment with 1 µg of recombinant myostatin at 1 d post-induction of differentiation while all myomiRs (miR-1, 133a/b and 206 were upregulated by SB431542, a potent ALK4/5/7 inhibitor which reduces Smad2 signaling, at 1 d and all, with the exception of miR-206, were upregulated by SB431542 at 3 d. The expression of the muscle-enriched miR-486 was greater following treatment with SB431542 but not altered by myostatin. Other highly expressed miRNAs in skeletal muscle, miR-23a/b and 145, were altered only at 1 d post-induction of differentiation. miR-27b responded differently to treatments at 1 d, where it was upregulated, as compared to 3 d, where it was downregulated. Neither myostatin nor SB431542 altered cell size or cell morphology. The data indicate that myostatin represses myomiR expression in differentiating C2C12 cells and that inhibition of Smad signaling with SB431542 can result in large changes in highly expressed miRNAs in differentiating myoblasts.

  4. Expression of a bacterial 3-dehydroshikimate dehydratase reduces lignin content and improves biomass saccharification efficiency.

    Science.gov (United States)

    Eudes, Aymerick; Sathitsuksanoh, Noppadon; Baidoo, Edward E K; George, Anthe; Liang, Yan; Yang, Fan; Singh, Seema; Keasling, Jay D; Simmons, Blake A; Loqué, Dominique

    2015-12-01

    Lignin confers recalcitrance to plant biomass used as feedstocks in agro-processing industries or as source of renewable sugars for the production of bioproducts. The metabolic steps for the synthesis of lignin building blocks belong to the shikimate and phenylpropanoid pathways. Genetic engineering efforts to reduce lignin content typically employ gene knockout or gene silencing techniques to constitutively repress one of these metabolic pathways. Recently, new strategies have emerged offering better spatiotemporal control of lignin deposition, including the expression of enzymes that interfere with the normal process for cell wall lignification. In this study, we report that expression of a 3-dehydroshikimate dehydratase (QsuB from Corynebacterium glutamicum) reduces lignin deposition in Arabidopsis cell walls. QsuB was targeted to the plastids to convert 3-dehydroshikimate - an intermediate of the shikimate pathway - into protocatechuate. Compared to wild-type plants, lines expressing QsuB contain higher amounts of protocatechuate, p-coumarate, p-coumaraldehyde and p-coumaryl alcohol, and lower amounts of coniferaldehyde, coniferyl alcohol, sinapaldehyde and sinapyl alcohol. 2D-NMR spectroscopy and pyrolysis-gas chromatography/mass spectrometry (pyro-GC/MS) reveal an increase of p-hydroxyphenyl units and a reduction of guaiacyl units in the lignin of QsuB lines. Size-exclusion chromatography indicates a lower degree of lignin polymerization in the transgenic lines. Therefore, our data show that the expression of QsuB primarily affects the lignin biosynthetic pathway. Finally, biomass from these lines exhibits more than a twofold improvement in saccharification efficiency. We conclude that the expression of QsuB in plants, in combination with specific promoters, is a promising gain-of-function strategy for spatiotemporal reduction of lignin in plant biomass. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The

  5. Candida krusei and Candida glabrata reduce the filamentation of Candida albicans by downregulating expression of HWP1 gene.

    Science.gov (United States)

    de Barros, Patrícia Pimentel; Freire, Fernanda; Rossoni, Rodnei Dennis; Junqueira, Juliana Campos; Jorge, Antonio Olavo Cardoso

    2017-07-01

    Pathogenicity of Candida albicans is associated with its capacity switch from yeast-like to hyphal growth. The hyphal form is capable to penetrate the epithelial surfaces and to damage the host tissues. Therefore, many investigations have focused on mechanisms that control the morphological transitions of C. albicans. Recently, certain studies have showed that non-albicans Candida species can reduce the capacity of C. albicans to form biofilms and to develop candidiasis in animal models. Then, the objective of this study was to evaluate the effects of Candida krusei and Candida glabrata on the morphogenesis of C. albicans. Firstly, the capacity of reference and clinical strains of C. albicans in forming hyphae was tested in vitro. After that, the expression of HWP1 (hyphal wall protein 1) gene was determined by quantitative real-time PCR (polymerase chain reaction) assay. For both reference and clinical strains, a significant inhibition of the hyphae formation was observed when C. albicans was incubated in the presence of C. krusei or C. glabrata compared to the control group composed only by C. albicans. In addition, the culture mixed of C. albicans-C. krusei or C. albicans-C. glabrata reduced significantly the expression of HWP1 gene of C. albicans in relation to single cultures of this specie. In both filamentation and gene expression assays, C. krusei showed the higher inhibitory activity on the morphogenesis of C. albicans compared to C. glabrata. C. krusei and C. glabrata are capable to reduce the filamentation of C. albicans and consequently decrease the expression of the HWP1 gene.

  6. Phaleria macrocarpa reduces glomerular growth factor expression in alloxan-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Evy Sulistyoningrum

    2013-08-01

    Full Text Available Background Diabetic nephropathy (DN is the most serious complication of diabetes, causing end-stage renal disease throughout the world. Recent studies have reported a direct role of vascular endothelial growth factor (VEGF and transforming growth factor-â (TGF-â in DN pathogenesis. VEGF and TGF-â are expressed early in glomeruli in response to hyperglycemia. Active substances of Phaleria macrocarpa (PM pericarp are known to have nephroprotective effects. This study aimed to evaluate the effects of Phaleria macrocarpa (Scheff. Boerl pericarp extract on VEGF and TGF-â expression in alloxan-induced diabetic rats. Methods An experimental study was conducted on twenty five male albino (Sprague Dawley rats divided into five groups (of five each: normal control; diabetic; diabetic + metformin 100 mg/kgBW; diabetic + methanolic PM extract 250 mg/kgBW; and diabetic + aqueous PM extract 250 mg/kgBW. Diabetes was induced by alloxan monohydrate 150 mg/BW intraperitoneally. Treatment was given for 3 weeks. VEGF and TGF-â expression analysis was performed by means of immunohistochemical technique. Differences between groups were assessed by one-way ANOVA. Results VEGF expression in the PM extract group was significantly lower than that in the diabetic group and even metformin group (p<0.01. TGF-â expression in methanolic PM extract group was significantly lower than in diabetic and metformin group (p<0.01, but aqueous PM extract group only showed significancy when compared with diabetic group (p< 0.01. Conclusions Phaleria macrocarpa pericarp extract reduces glomerular expression of TGF-â and VEGF in alloxan-induced diabetic rats.

  7. Reduced TH expression and α-synuclein accumulation contribute towards nigrostriatal dysfunction in experimental hepatic encephalopathy.

    Science.gov (United States)

    Suárez, Isabel; Bodega, Guillermo; Rubio, Miguel; Fernández, Benjamín

    2017-01-01

    The present work examines α-synuclein expression in the nigrostriatal system of a rat chronic hepatic encephalopathy model induced by portacaval anastomosis (PCA). There is evidence that dopaminergic dysfunction in disease conditions is strongly associated with such expression. Possible relationships among dopaminergic neurons, astroglial cells and α-synuclein expression were sought. Brain tissue samples from rats at 1 and 6 months post-PCA, and controls, were analysed immunohistochemically using antibodies against tyrosine hydroxylase (TH), α-synuclein, glial fibrillary acidic protein (GFAP) and ubiquitin (Ub). In the control rats, TH immunoreactivity was detected in the neuronal cell bodies and processes in the substantia nigra pars compacta (SNc). A dense TH-positive network of neurons was also seen in the striatum. In the PCA-exposed rats, however, a reduction in TH-positive neurons was seen at both 1 and 6 months in the SNc, as well as a reduction in TH-positive fibres in the striatum. This was coincident with the appearance of α-synuclein-immunoreactive neurons in the SNc; some of the TH-positive neurons also showed α-synuclein immunoreactivity. In addition, α-synuclein accumulation was seen in the SNc and striatum at both 1 and 6 months post-PCA, whereas α-synuclein was only mildly expressed in the nigrostriatal pathway of the controls. Astrogliosis was also seen following PCA, as revealed by increased GFAP expression from 1 month to 6 months post-PCA in both the SN and striatum. The astroglial activation level in the SN paralleled the reduced neuronal expression of TH throughout PCA exposure. α-synuclein accumulation following PCA may induce dopaminergic dysfunction via the downregulation of TH, as well as astroglial activation.

  8. Reduced myelin basic protein and actin-related gene expression in visual cortex in schizophrenia.

    Science.gov (United States)

    Matthews, Paul R; Eastwood, Sharon L; Harrison, Paul J

    2012-01-01

    Most brain gene expression studies of schizophrenia have been conducted in the frontal cortex or hippocampus. The extent to which alterations occur in other cortical regions is not well established. We investigated primary visual cortex (Brodmann area 17) from the Stanley Neuropathology Consortium collection of tissue from 60 subjects with schizophrenia, bipolar disorder, major depression, or controls. We first carried out a preliminary array screen of pooled RNA, and then used RT-PCR to quantify five mRNAs which the array identified as differentially expressed in schizophrenia (myelin basic protein [MBP], myelin-oligodendrocyte glycoprotein [MOG], β-actin [ACTB], thymosin β-10 [TB10], and superior cervical ganglion-10 [SCG10]). Reduced mRNA levels were confirmed by RT-PCR for MBP, ACTB and TB10. The MBP reduction was limited to transcripts containing exon 2. ACTB and TB10 mRNAs were also decreased in bipolar disorder. None of the transcripts were altered in subjects with major depression. Reduced MBP mRNA in schizophrenia replicates findings in other brain regions and is consistent with oligodendrocyte involvement in the disorder. The decreases in expression of ACTB, and the actin-binding protein gene TB10, suggest changes in cytoskeletal organisation. The findings confirm that the primary visual cortex shows molecular alterations in schizophrenia and extend the evidence for a widespread, rather than focal, cortical pathophysiology.

  9. Expression of Arabidopsis hexokinase in citrus guard cells controls stomatal aperture and reduces transpiration

    Directory of Open Access Journals (Sweden)

    Nitsan eLugassi

    2015-12-01

    Full Text Available Hexokinase (HXK is a sugar-phosphorylating enzyme involved in sugar-sensing. It has recently been shown that HXK in guard cells mediates stomatal closure and coordinates photosynthesis with transpiration in the annual species tomato and Arabidopsis. To examine the role of HXK in the control of the stomatal movement of perennial plants, we generated citrus plants that express Arabidopsis HXK1 (AtHXK1 under KST1, a guard cell-specific promoter. The expression of KST1 in the guard cells of citrus plants has been verified using GFP as a reporter gene. The expression of AtHXK1 in the guard cells of citrus reduced stomatal conductance and transpiration with no negative effect on the rate of photosynthesis, leading to increased water-use efficiency. The effects of light intensity and humidity on stomatal behavior were examined in rooted leaves of the citrus plants. The optimal intensity of photosynthetically active radiation and lower humidity enhanced stomatal closure of AtHXK1-expressing leaves, supporting the role of sugar in the regulation of citrus stomata. These results suggest that HXK coordinates photosynthesis and transpiration and stimulates stomatal closure not only in annual species, but also in perennial species.

  10. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    International Nuclear Information System (INIS)

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-01-01

    Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  11. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  12. Expression of Arabidopsis Hexokinase in Citrus Guard Cells Controls Stomatal Aperture and Reduces Transpiration.

    Science.gov (United States)

    Lugassi, Nitsan; Kelly, Gilor; Fidel, Lena; Yaniv, Yossi; Attia, Ziv; Levi, Asher; Alchanatis, Victor; Moshelion, Menachem; Raveh, Eran; Carmi, Nir; Granot, David

    2015-01-01

    Hexokinase (HXK) is a sugar-phosphorylating enzyme involved in sugar-sensing. It has recently been shown that HXK in guard cells mediates stomatal closure and coordinates photosynthesis with transpiration in the annual species tomato and Arabidopsis. To examine the role of HXK in the control of the stomatal movement of perennial plants, we generated citrus plants that express Arabidopsis HXK1 (AtHXK1) under KST1, a guard cell-specific promoter. The expression of KST1 in the guard cells of citrus plants has been verified using GFP as a reporter gene. The expression of AtHXK1 in the guard cells of citrus reduced stomatal conductance and transpiration with no negative effect on the rate of photosynthesis, leading to increased water-use efficiency. The effects of light intensity and humidity on stomatal behavior were examined in rooted leaves of the citrus plants. The optimal intensity of photosynthetically active radiation and lower humidity enhanced stomatal closure of AtHXK1-expressing leaves, supporting the role of sugar in the regulation of citrus stomata. These results suggest that HXK coordinates photosynthesis and transpiration and stimulates stomatal closure not only in annual species, but also in perennial species.

  13. Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals.

    Science.gov (United States)

    Moussaieff, Arieh; Gross, Moshe; Nesher, Elimelech; Tikhonov, Tatiana; Yadid, Gal; Pinhasov, Albert

    2012-12-01

    Incensole acetate (IA), a constituent of Boswellia resin ('frankincense'), was previously demonstrated to exhibit an antidepressive-like effect in the Forced Swim Test (FST) in mice following single dose administration (50 mg/kg). Here, we show that acute administration of considerably lower dose (10 mg/kg) IA to selectively bred mice, showing prominent submissive behavior, exerted significant antidepressant-like effects in the FST. Furthermore, chronic administration of 1 or 5 mg/kg per day of IA for three consecutive weeks dose- and time-dependently reduced the submissiveness of the mice in the Dominant-Submissive Relationship test, developed to screen the chronic effect of antidepressants. This behavioral effect was concomitant to reduced serum corticosterone levels, dose-dependent down-regulation of corticotropin releasing factor and up-regulation of brain derived neurotrophic factor transcripts IV and VI expression in the hippocampus. These data suggest that IA modulates the hypothalamic-pituitary-adrenal (HPA) axis and influences hippocampal gene expression, leading to beneficial behavioral effects supporting its potential as a novel treatment of depressive-like disorders.

  14. Reduced Variance of Gene Expression at Numerous Loci in a Population of Chickens Selected for High Feather Pecking

    DEFF Research Database (Denmark)

    Hughes, A L; Buitenhuis, A J

    2010-01-01

    among populations with respect to mean expression scores, but numerous transcripts showed reduced variance in expression scores in the high FP population in comparison to control and low FP populations. The reduction in variance in the high FP population generally involved transcripts whose expression...

  15. Nuclear protein import is reduced in cells expressing nuclear envelopathy-causing lamin A mutants

    International Nuclear Information System (INIS)

    Busch, Albert; Kiel, Tilman; Heupel, Wolfgang-M.; Wehnert, Manfred; Huebner, Stefan

    2009-01-01

    Lamins, which form the nuclear lamina, not only constitute an important determinant of nuclear architecture, but additionally play essential roles in many nuclear functions. Mutations in A-type lamins cause a wide range of human genetic disorders (laminopathies). The importance of lamin A (LaA) in the spatial arrangement of nuclear pore complexes (NPCs) prompted us to study the role of LaA mutants in nuclear protein transport. Two mutants, causing prenatal skin disease restrictive dermopathy (RD) and the premature aging disease Hutchinson Gilford progeria syndrome, were used for expression in HeLa cells to investigate their impact on the subcellular localization of NPC-associated proteins and nuclear protein import. Furthermore, dynamics of the LaA mutants within the nuclear lamina were studied. We observed affected localization of NPC-associated proteins, diminished lamina dynamics for both LaA mutants and reduced nuclear import of representative cargo molecules. Intriguingly, both LaA mutants displayed similar effects on nuclear morphology and functions, despite their differences in disease severity. Reduced nuclear protein import was also seen in RD fibroblasts and impaired lamina dynamics for the nucleoporin Nup153. Our data thus represent the first study of a direct link between LaA mutant expression and reduced nuclear protein import.

  16. Melatonin reduces the expression of chemokines in rat with trinitrobenzene sulfonic acid-induced colitis

    International Nuclear Information System (INIS)

    Li, Jun H.; Zhou, W.; Liu, K.; Li, Hong X.; Wang, L.

    2008-01-01

    Objective was to investigate the effect of melatonin on the colon inflammatory injury of rats with colitis and determine whether this effect is associated with inhibition of chemoattractant molecules interleukins (IL-8) and monocyte chemoattractant protein (MCP)-1.The study was designed and implemented in JingMen No.1 People's Hospital, HuBei Province, from May 2006 to April 2007. It involved 72 animals divided into 6 groups of 12 each: normal group, model group, 5-aminosalisalicylic acid group, and melatonin group (dose of 2.5, 5.0 and 10.0mg/kg). Rat colitis model was established by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enema. Interleukin-8 and MCP-1 proteins in colon tissue were examined by immunohistochemistry and western blot. The messenger-RNA expressions of chemokines were determined by reverse transcription polymerase chain reaction analysis. Trinitrobenzene sulfonic acid enema resulted in pronounced pathological changes of colonic mucosa in model rats, which were in accordance with the significantly elevated Myeloperoxidase activity. Expressions of chemokines were up-regulated in colitis. Melatonin treatment reduced colonic lesions and improved colitis symptom, and decreased the protein and mRNA expressions of IL-8 and MCP-1 significantly in colon tissues of rats with colitis. Chemokines IL-8 and MCP-1 are elevated in mucosal tissues in colitis and play an important role in the perpetuation of tissue destructive inflammatory process; melatonin reduces colonic inflammatory injury of rats colitis through down-regulating the expressions of chemokines. Melatonin can be considered as a novel therapeutic alternative for the treatment of inflammatory bowel disease. (author)

  17. Testing of Baker Flo-XS Pipeline Drag-Reducing Additive. Compilation of Tests and Results

    National Research Council Canada - National Science Library

    Guiliano, John

    2000-01-01

    ... 0.8 ppm for errors in injection). Through a CRADA with Buckeye Pipeline Inc, thermal stability testing of the additive was completed. Additionally, low temperature testing, additive/additive compatibility testing and specification testing of additized fuel was also completed. Material compatibility testing was also taken into consideration.

  18. Reduced angiogenic factor expression in intrauterine fetal growth restriction using semiquantitative immunohistochemistry and digital image analysis.

    Science.gov (United States)

    Alahakoon, Thushari I; Zhang, Weiyi; Arbuckle, Susan; Zhang, Kewei; Lee, Vincent

    2018-05-01

    To localize, quantify and compare angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), as well as their receptors fms-like tyrosine kinase receptor (Flt-1) and kinase insert domain receptor (KDR) in the placentas of normal pregnancy and complications of preeclampsia (PE), intrauterine fetal growth restriction (IUGR) and PE + IUGR. In a prospective cross-sectional case-control study, 30 pregnant women between 24-40 weeks of gestation, were recruited into four clinical groups. Representative placental samples were stained for VEGF, PlGF, Flt-1 and KDR. Analysis was performed using semiquantitative methods and digital image analysis. The overall VEGF and Flt-1 were strongly expressed and did not show any conclusive difference in the expression between study groups. PlGF and KDR were significantly reduced in expression in the placentas from pregnancies complicated by IUGR compared with normal and preeclamptic pregnancies. The lack of PlGF and KDR may be a cause for the development of IUGR and may explain the loss of vasculature and villous architecture in IUGR. Automated digital image analysis software is a viable alternative method to the manual reading of placental immunohistochemical staining. © 2018 Japan Society of Obstetrics and Gynecology.

  19. Atorvastatin reduces lipopolysaccharide-induced expression of cyclooxygenase-2 in human pulmonary epithelial cells

    Directory of Open Access Journals (Sweden)

    Chen Ping

    2005-04-01

    Full Text Available Abstract Objective To explore the effects of atorvastatin on expression of cyclooxygenase-2 (COX-2 in human pulmonary epithelial cells (A549. Methods A549 cells were incubated in DMEM medium containing lipopolysaccharide (LPS in the presence or absence of atorvastatin. After incubation, the medium was collected and the amount of prostaglandin E2 (PGE2 was measured by enzyme-linked immunosorbent assay (ELISA. The cells were harvested, and COX-2 mRNA and protein were analyzed by RT-PCR and western-blot respectively. Results LPS increased the expression of COX-2 mRNA and production of PGE2 in a dose- and time-dependent manner in A549. Induction of COX-2 mRNA and protein by LPS were inhibited by atorvastatin in a dose-dependent manner. Atorvastatin also significantly decreased LPS-induced production of PGE2. There was a positive correlation between reduced of COX-2 mRNA and decreased of PGE2 (r = 0.947, P Conclusion Atorvastatin down-regulates LPS-induced expression of the COX-2 and consequently inhibits production of PGE2 in cultured A549 cells.

  20. Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia

    Science.gov (United States)

    Kim, Jae Hwan; Lee, Yong Woo; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

    2010-01-01

    Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of -arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood–brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limitting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia. PMID:20029450

  1. Naringenin Inhibits Adipogenesis and Reduces Insulin Sensitivity and Adiponectin Expression in Adipocytes

    Directory of Open Access Journals (Sweden)

    Allison J. Richard

    2013-01-01

    Full Text Available Adipose tissue development and function are widely studied to examine the relationship between obesity and the metabolic syndrome. It is well documented that the inability of adipose tissue to properly increase its lipid storage capacity during the obese state can lead to metabolic dysfunction. In a blind screen of 425 botanicals, we identified naringenin as an inhibitor of adipocyte differentiation. Naringenin is one of the most abundant citrus flavonoids, and recent studies have demonstrated antihyperlipidemic capabilities. These studies have largely focused on the effects of naringenin on the liver. Our biochemical studies clearly demonstrate that naringenin inhibits adipogenesis and impairs mature fat cell function. Naringenin specifically inhibited adipogenesis in a dose-dependent fashion as judged by examining lipid accumulation and induction of adipocyte marker protein expression. In mature 3T3-L1 adipocytes, naringenin reduced the ability of insulin to induce IRS-1 tyrosine phosphorylation and substantially inhibited insulin-stimulated glucose uptake in a dose-dependent manner and over a time frame of 1.5 to 24 hours. Exposure to naringenin also inhibited adiponectin protein expression in mature murine and human adipocytes. Our studies have revealed that naringenin may have a negative impact on adipocyte-related diseases by limiting differentiation of preadipocytes, by significantly inducing insulin resistance, and by decreasing adiponectin expression in mature fat cells.

  2. Reduced Sympathetic Innervation in Endometriosis is Associated to Semaphorin 3C and 3F Expression.

    Science.gov (United States)

    Scheerer, Claudia; Frangini, Sergio; Chiantera, Vito; Mechsner, Sylvia

    2017-09-01

    Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic innervation and the expression of the specific semaphorins and receptors possibly involved in the neuroimmunomodulation in endometriosis. Our studies revealed an affected innervation and a significant increase of semaphorins and their receptors in peritoneal endometriotic tissue. Thereby, the expression of the receptors was identified on the membrane of noradrenergic nerve fibers and vessels. Macrophages and activated fibroblasts were found in higher density levels and additionally express semaphorins in peritoneal endometriotic tissue. Inflammation leads to an increased release of immune cells, which secrete a variety of inflammatory factors capable of affecting innervation. Therefore, our data suggests that the chronic inflammatory condition in endometriosis might contribute to the increase of semaphorins, which could possibly affect the innervation in peritoneal endometriosis.

  3. Campylobacter jejuni cocultured with epithelial cells reduces surface capsular polysaccharide expression.

    LENUS (Irish Health Repository)

    Corcionivoschi, N

    2012-02-01

    The host cell environment can alter bacterial pathogenicity. We employed a combination of cellular and molecular techniques to study the expression of Campylobacter jejuni polysaccharides cocultured with HCT-8 epithelial cells. After two passages, the amount of membrane-bound high-molecular-weight polysaccharide was considerably reduced. Microarray profiling confirmed significant downregulation of capsular polysaccharide (CPS) locus genes. Experiments using conditioned media showed that sugar depletion occurred only when the bacterial and epithelial cells were cocultured. CPS depletion occurred when C. jejuni organisms were exposed to conditioned media from a different C. jejuni strain but not when exposed to conditioned media from other bacterial species. Proteinase K or heat treatment of conditioned media under coculture conditions abrogated the effect on the sugars, as did formaldehyde fixation and cycloheximide treatment of host cells or chloramphenicol treatment of the bacteria. However, sugar depletion was not affected in flagellar export (fliQ) and quorum-sensing (luxS) gene mutants. Passaged C. jejuni showed reduced invasiveness and increased serum sensitivity in vitro. C. jejuni alters its surface polysaccharides when cocultured with epithelial cells, suggesting the existence of a cross talk mechanism that modulates CPS expression during infection.

  4. Deafness and permanently reduced potassium channel gene expression and function in hypothyroid Pit1dw mutants

    Science.gov (United States)

    Mustapha, Mirna; Fang, Qing; Gong, Tzy-Wen; Dolan, David F.; Raphael, Yehoash; Camper, Sally A.; Duncan, R. Keith

    2012-01-01

    The absence of thyroid hormone (TH) during late gestation and early infancy can cause irreparable deafness in both humans and rodents. A variety of rodent models have been utilized in an effort to identify the underlying molecular mechanism. Here, we characterize a mouse model of secondary hypothyroidism, pituitary transcription factor 1 (Pit1dw), which has profound, congenital deafness that is rescued by oral TH replacement. These mutants have tectorial membrane abnormalities, including a prominent Hensen's stripe, elevated β-tectorin composition, and disrupted striated-sheet matrix. They lack distortion product otoacoustic emissions and cochlear microphonic responses, and exhibit reduced endocochlear potentials, suggesting defects in outer hair cell function and potassium recycling. Auditory system and hair cell physiology, histology and anatomy studies reveal novel defects of hormone deficiency related to deafness: (1) permanently impaired expression of KCNJ10 in the stria vascularis of Pit1dw mice, which likely contributes to the reduced endocochlear potential, (2) significant outer hair cell loss in the mutants, which may result from cellular stress induced by the lower KCNQ4 expression and current levels in Pit1dw mutant outer hair cells and (3) sensory and strial cell deterioration, which may have implications for thyroid hormone dysregulation in age related hearing impairment. In summary, we suggest that these defects in outer hair cell and strial cell function are important contributors to the hearing impairment in Pit1dw mice. PMID:19176829

  5. Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia.

    Science.gov (United States)

    Tischkowitz, M D; Morgan, N V; Grimwade, D; Eddy, C; Ball, S; Vorechovsky, I; Langabeer, S; Stöger, R; Hodgson, S V; Mathew, C G

    2004-03-01

    Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder caused by mutations in one of seven known genes (FANCA,C,D2,E,F,G and BRCA2). Mutations in the FANCA gene are the most prevalent, accounting for two-thirds of FA cases. Affected individuals have greatly increased risks of acute myeloid leukemia (AML). This raises the question as to whether inherited or acquired mutations in FA genes might be involved in the development of sporadic AML. Quantitative fluorescent PCR was used to screen archival DNA from sporadic AML cases for FANCA deletions, which account for 40% of FANCA mutations in FA homozygotes. Four heterozygous deletions were found in 101 samples screened, which is 35-fold higher than the expected population frequency for germline FANCA deletions (PFANCA in the AML samples with FANCA deletions did not detect mutations in the second allele and there was no evidence of epigenetic silencing by hypermethylation. However, real-time quantitative PCR analysis in these samples showed reduced expression of FANCA compared to nondeleted AML samples and to controls. These findings suggest that gene deletions and reduced expression of FANCA may be involved in the promotion of genetic instability in a subset of cases of sporadic AML.

  6. Chemical Inhibition of Kynureninase Reduces Pseudomonas aeruginosa Quorum Sensing and Virulence Factor Expression.

    Science.gov (United States)

    Kasper, Stephen H; Bonocora, Richard P; Wade, Joseph T; Musah, Rabi Ann; Cady, Nathaniel C

    2016-04-15

    The opportunistic pathogen Pseudomonas aeruginosa utilizes multiple quorum sensing (QS) pathways to coordinate an arsenal of virulence factors. We previously identified several cysteine-based compounds inspired by natural products from the plant Petiveria alliacea which are capable of antagonizing multiple QS circuits as well as reducing P. aeruginosa biofilm formation. To understand the global effects of such compounds on virulence factor production and elucidate their mechanism of action, RNA-seq transcriptomic analysis was performed on P. aeruginosa PAO1 exposed to S-phenyl-l-cysteine sulfoxide, the most potent inhibitor from the prior study. Exposure to this inhibitor down-regulated expression of several QS-regulated virulence operons (e.g., phenazine biosynthesis, type VI secretion systems). Interestingly, many genes that were differentially regulated pertain to the related metabolic pathways that yield precursors of pyochelin, tricarboxylic acid cycle intermediates, phenazines, and Pseudomonas quinolone signal (PQS). Activation of the MexT-regulon was also indicated, including the multidrug efflux pump encoded by mexEF-oprN, which has previously been shown to inhibit QS and pathogenicity. Deeper investigation of the metabolites involved in these systems revealed that S-phenyl-l-cysteine sulfoxide has structural similarity to kynurenine, a precursor of anthranilate, which is critical for P. aeruginosa virulence. By supplementing exogenous anthranilate, the QS-inhibitory effect was reversed. Finally, it was shown that S-phenyl-l-cysteine sulfoxide competitively inhibits P. aeruginosa kynureninase (KynU) activity in vitro and reduces PQS production in vivo. The kynurenine pathway has been implicated in P. aeruginosa QS and virulence factor expression; however, this is the first study to show that targeted inhibition of KynU affects P. aeruginosa gene expression and QS, suggesting a potential antivirulence strategy.

  7. An Anacardiaceae preparation reduces the expression of inflammation-related genes in murine macrophages.

    Science.gov (United States)

    Leiro, J; García, D; Arranz, J A; Delgado, R; Sanmartín, M L; Orallo, F

    2004-08-01

    This study investigated the effects of an aqueous extract of the stem bark of Mangifera indica L. (Anacardiaceae; Vimang), which contains a defined mixture of components including polyphenols (principally mangiferin, MA), triterpenes, phytosteroids, fatty acids and microelements, on expression of inflammation mediators in inflammatory murine macrophages after stimulation in vitro with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). In vitro treatment with Vimang at 4 microg/ml reduced levels of NOS-2 mRNA and NOS-2, while treatment at 40 microg/ml also reduced levels of COX-2 mRNA, COX-2, and prostaglandin E2 (PGE2). Results suggested that MA is involved in these effects. In vitro treatment with Vimang at 40 microg/ml also inhibited mRNA levels of the proinflammatory cytokines interleukin 1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha) and colony-stimulating factor (GM-CSF), but did not affect mRNA levels of IL-6 or tumor growth factor-beta (TGF-beta). Extracellular release of TNF-alpha by inflammatory macrophages was inhibited by in vitro treatment with Vimang at the same concentrations that showed inhibition of TNF-alpha mRNA levels. The inhibition of TNF-alpha production appears to be at least partially attributable to MA. Vimang at 4 microg/ml decreased mRNA levels of nuclear factor-kappaB (NF-kappaB) but did not affect expression of the NF-kappaB inhibitor (IkappaB). These data indicate that the potent anti-inflammatory effects of Vimang are due to selective modulation of the expression of inflammation-related genes, leading to attenuation of macrophage activation.

  8. Subchronic nandrolone administration reduces cardiac oxidative markers during restraint stress by modulating protein expression patterns.

    Science.gov (United States)

    Pergolizzi, Barbara; Carriero, Vitina; Abbadessa, Giuliana; Penna, Claudia; Berchialla, Paola; De Francia, Silvia; Bracco, Enrico; Racca, Silvia

    2017-10-01

    Nandrolone decanoate (ND), an anabolic-androgenic steroid prohibited in collegiate and professional sports, is associated with detrimental cardiovascular effects through redox-dependent mechanisms. We previously observed that high-dose short-term ND administration (15 mg/kg for 2 weeks) did not induce left heart ventricular hypertrophy and, paradoxically, improved postischemic response, whereas chronic ND treatment (5 mg/kg twice a week for 10 weeks) significantly reduced the cardioprotective effect of postconditioning, with an increase in infarct size and a decrease in cardiac performance. We wanted to determine whether short-term ND administration could affect the oxidative redox status in animals exposed to acute restraint stress. Our hypothesis was that, depending on treatment schedule, ND may have a double-edged sword effect. Measurement of malondialdehyde and 4-hydroxynonenal, two oxidative stress markers, in rat plasma and left heart ventricular tissue, revealed that the levels of both markers were increased in animals exposed to restraint stress, whereas no increase in marker levels was noted in animals pretreated with ND, indicating a possible protective action of ND against stress-induced oxidative damage. Furthermore, isolation and identification of proteins extracted from the left heart ventricular tissue samples of rats pretreated or not with ND and exposed to acute stress showed a prevalent expression of enzymes involved in amino acid synthesis and energy metabolism. Among other proteins, peroxiredoxin 6 and alpha B-crystallin, both involved in the oxidative stress response, were predominantly expressed in the left heart ventricular tissues of the ND-pretreated rats. In conclusion, ND seems to reduce oxidative stress by inducing the expression of antioxidant proteins in the hearts of restraint-stressed animals, thus contributing to amelioration of postischemic heart performance.

  9. Tailgate test kit for determining appropriate sediment reducing chemicals and dose rates : final report.

    Science.gov (United States)

    2017-07-01

    This study develops a Tailgate Test Kit to be used in the field to test flocculants for reducing turbidity in construction stormwater discharge. Turbidity of stormwater runoff at construction sites varies depending on which site soils are exposed to ...

  10. Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons.

    Science.gov (United States)

    Hasan, Wohaib; Smith, Peter G

    2014-04-01

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain

    Directory of Open Access Journals (Sweden)

    Mignot Emmanuel

    2007-05-01

    Full Text Available Abstract Background Narcolepsy causes dramatic behavioral alterations in both humans and dogs, with excessive sleepiness and cataplexy triggered by emotional stimuli. Deficiencies in the hypocretin system are well established as the origin of the condition; both from studies in humans who lack the hypocretin ligand (HCRT and in dogs with a mutation in hypocretin receptor 2 (HCRTR2. However, little is known about molecular alterations downstream of the hypocretin signals. Results By using microarray technology we have screened the expression of 29760 genes in the brains of Doberman dogs with a heritable form of narcolepsy (homozygous for the canarc-1 [HCRTR-2-2] mutation, and their unaffected heterozygous siblings. We identified two neuropeptide precursor molecules, Tachykinin precursor 1 (TAC1 and Proenkephalin (PENK, that together with Suppressor of cytokine signaling 2 (SOCS2, showed reduced expression in narcoleptic brains. The difference was particularly pronounced in the amygdala, where mRNA levels of PENK were 6.2 fold lower in narcoleptic dogs than in heterozygous siblings, and TAC1 and SOCS2 showed 4.4 fold and 2.8 fold decrease in expression, respectively. The results obtained from microarray experiments were confirmed by real-time RT-PCR. Interestingly, it was previously shown that a single dose of amphetamine-like stimulants able to increase wakefulness in the dogs, also produce an increase in the expression of both TAC1 and PENK in mice. Conclusion These results suggest that TAC1, PENK and SOCS2 might be intimately connected with the excessive daytime sleepiness not only in dogs, but also in other species, possibly including humans.

  12. Anticancer Drug 2-Methoxyestradiol Protects against Renal Ischemia/Reperfusion Injury by Reducing Inflammatory Cytokines Expression

    Directory of Open Access Journals (Sweden)

    Ying-Yin Chen

    2014-01-01

    -A-treated RMC and NRK52E cells. Conclusions. 2ME2 reduces renal I/R injury in mice because it inhibits the expression of ROS and proinflammatory cytokines and induces antiapoptotic proteins.

  13. Spexin peptide is expressed in human endocrine and epithelial tissues and reduced after glucose load in type 2 diabetes.

    Science.gov (United States)

    Gu, Liping; Ma, Yuhang; Gu, Mingyu; Zhang, Ying; Yan, Shuai; Li, Na; Wang, Yufan; Ding, Xiaoying; Yin, Jiajing; Fan, Nengguang; Peng, Yongde

    2015-09-01

    Spexin mRNA and protein are widely expressed in rat tissues and associate with weight loss in rodents of diet-induced obesity. Its location in endocrine and epithelial cells has also been suggested. Spexin is a novel peptide that involves weight loss in rodents of diet-induced obesity. Therefore, we aimed to examine its expression in human tissues and test whether spexin could have a role in glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). The expression of the spexin gene and immunoreactivity in the adrenal gland, skin, stomach, small intestine, liver, thyroid, pancreatic islets, visceral fat, lung, colon, and kidney was higher than that in the muscle and connective tissue. Immunoreactive serum spexin levels were reduced in T2DM patients and correlated with fasting blood glucose (FBG, r=-0.686, Pepithelial tissues, indicating that spexin may be involved in physiological functions of endocrine and in several other tissues. Circulating spexin levels are low in T2DM patients and negatively related to blood glucose and lipids suggesting that the peptide may play a role in glucose and lipid metabolism in T2DM. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Advanced Gas Cooled Reactor Materials Program. Reducing helium impurity depletion in HTGR materials testing

    International Nuclear Information System (INIS)

    Baldwin, D.H.

    1984-08-01

    Moisture depletion in HTGR materials testing rigs has been empirically studied in the GE High Temperature Reactor Materials Testing Laboratory (HTRMTL). Tests have shown that increased helium flow rates and reduction in reactive (oxidizable) surface area are effective means of reducing depletion. Further, a portion of the depletion has been shown to be due to the presence of free C released by the dissociation of CH 4 . This depletion component can be reduced by reducing the helium residence time (increasing the helium flow rate) or by reducing the CH 4 concentration in the test gas. Equipment modifications to reduce depletion have been developed, tested, and in most cases implemented in the HTRMTL to date. These include increasing the Helium Loop No. 1 pumping capacity, conversion of metallic retorts and radiation shields to alumina, isolation of thermocouple probes from the test gas by alumina thermowells, and substitution of non-reactive Mo-TZM for reactive metallic structural components

  15. BEAT: A Web-Based Boolean Expression Fault-Based Test Case Generation Tool

    Science.gov (United States)

    Chen, T. Y.; Grant, D. D.; Lau, M. F.; Ng, S. P.; Vasa, V. R.

    2006-01-01

    BEAT is a Web-based system that generates fault-based test cases from Boolean expressions. It is based on the integration of our several fault-based test case selection strategies. The generated test cases are considered to be fault-based, because they are aiming at the detection of particular faults. For example, when the Boolean expression is in…

  16. Mindfulness-Based Stress Reduction training reduces loneliness and pro-inflammatory gene expression in older adults: a small randomized controlled trial.

    Science.gov (United States)

    Creswell, J David; Irwin, Michael R; Burklund, Lisa J; Lieberman, Matthew D; Arevalo, Jesusa M G; Ma, Jeffrey; Breen, Elizabeth Crabb; Cole, Steven W

    2012-10-01

    Lonely older adults have increased expression of pro-inflammatory genes as well as increased risk for morbidity and mortality. Previous behavioral treatments have attempted to reduce loneliness and its concomitant health risks, but have had limited success. The present study tested whether the 8-week Mindfulness-Based Stress Reduction (MBSR) program (compared to a Wait-List control group) reduces loneliness and downregulates loneliness-related pro-inflammatory gene expression in older adults (N = 40). Consistent with study predictions, mixed effect linear models indicated that the MBSR program reduced loneliness, compared to small increases in loneliness in the control group (treatment condition × time interaction: F(1,35) = 7.86, p = .008). Moreover, at baseline, there was an association between reported loneliness and upregulated pro-inflammatory NF-κB-related gene expression in circulating leukocytes, and MBSR downregulated this NF-κB-associated gene expression profile at post-treatment. Finally, there was a trend for MBSR to reduce C Reactive Protein (treatment condition × time interaction: (F(1,33) = 3.39, p = .075). This work provides an initial indication that MBSR may be a novel treatment approach for reducing loneliness and related pro-inflammatory gene expression in older adults. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Effectiveness of Structured Psychodrama and Systematic Desensitization in Reducing Test Anxiety.

    Science.gov (United States)

    Kipper, David A.; Giladi, Daniel

    1978-01-01

    Students with examination anxiety took part in study of effectiveness of two kinds of treatment, structured psychodrama and systematic desensitization, in reducing test anxiety. Results showed that subjects in both treatment groups significantly reduced test-anxiety scores. Structured psychodrama is as effective as systematic desensitization in…

  18. Maillard reaction products enriched food extract reduce the expression of myofibroblast phenotype markers.

    Science.gov (United States)

    Ruhs, Stefanie; Nass, Norbert; Somoza, Veronika; Friess, Ulrich; Schinzel, Reinhard; Silber, Rolf-Edgar; Simm, Andreas

    2007-04-01

    Advanced glycation end products (AGE) are associated with a wide range of degenerative diseases. The present investigation aimed at analysing the influence of AGE containing nutritional extracts on cardiac fibroblasts (CFs) as the major cell type responsible for cardiac fibrosis. Mice CFs were treated with bread crust extract (BCE) which contained significant amounts of a variety of AGE modifications. BCE treatment with up to 30 mg/mL did not impair cell viability. Furthermore, BCE induced a moderate elevation of reactive oxygen species (ROS) production and activation of redox sensitive pathways like the p42/44(MAPK), p38(MAPK) and NF-kappaB but did not alter Akt kinase phosphorylation. Expression of smooth muscle alpha-actin and tropomyosin-1, which represent markers for myofibroblast differentiation, was reduced after bread crust treatment. These data suggest a putative antifibrotic effect of melanoidin-rich food.

  19. Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

    Science.gov (United States)

    Rosa, Damiana D; Grześkowiak, Łukasz M; Ferreira, Célia L L F; Fonseca, Ana Carolina M; Reis, Sandra A; Dias, Mariana M; Siqueira, Nathane P; Silva, Leticia L; Neves, Clóvis A; Oliveira, Leandro L; Machado, Alessandra B F; Peluzio, Maria do Carmo G

    2016-08-10

    There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1β) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

  20. Mucuna pruriens reduces inducible nitric oxide synthase expression in Parkinsonian mice model.

    Science.gov (United States)

    Yadav, Satyndra Kumar; Rai, Sachchida Nand; Singh, Surya Pratap

    2017-03-01

    Parkinson's disease is one of the most common neurodegenerative disease found in aged peoples. Plentiful studies are being conducted to find a suitable and effective cure for this disease giving special impetus on use of herbal plants. The study aimed at investigating the effect of ethanolic extract of Mucuna pruriens (Mp) on level of nitric oxide (NO) in paraquat (PQ) induced Parkinson's disease (PD) mouse model and its subsequent contribution to lipid peroxidation. Twenty four Swiss albino mice were divided into three groups; Control, PQ and PQ+Mp. PQ doses were given intraperitoneally, twice in a week and oral dose of ethanolic extract of Mp seed was given for 9 weeks. Nitrite content and lipid peroxidation was measured in all treated groups along with respective controls. RNA was isolated from the nigrostriatal tissue of control and the treated mice and was reverse transcribed into cDNA. PCR was performed to amplify iNOS mRNA and western blot analysis was performed to check its protein level. We had also perfused the mice in all treated group and performed Tyrosine hydroxylase (TH) and iNOS immunoreactivity in substantia nigra region of mice brain. PQ-treatment increased nitrite content, expression of iNOS and lipid peroxidation compared to respective controls. Mp treatment resulted in a significant attenuation of iNOS expression, nitrite content and lipid peroxidation demonstrating that it reduces nitric oxide in PQ-induced Parkinson's disease. Interestingly; we also observed that mRNA, protein expression and immunoreactivity of iNOS was significantly decreased after Mp treatment and TH immunoreactivity was significantly improved after the treatment of Mp. Our results demonstrated that Mp protects the dopaminergic neurons from the NO injury in substantia nigra. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Reduced expression of PARK2 in manganese-exposed smelting workers.

    Science.gov (United States)

    Fan, Ximin; Luo, Ying; Fan, Qiyuan; Zheng, Wei

    2017-09-01

    Manganese (Mn) is widely used in modern industries. Occupational exposure to Mn is known to cause clinical syndromes similar, but not identical to, Parkinson's disease. This human cohort study was designed to investigate if workers exposed to Mn altered the PARK2 gene expression, leading to Mn-induced neurotoxicity. Workers (n=26) occupationally exposed to Mn were recruited from a Mn-iron (Fe) alloy smelter, and control workers (n=20) without Mn-exposure were from an Fe smelter from Zunyi City in China. Subjects were matched with socioeconomic status and background for environmental factors. Metal concentrations were determined by atomic absorption spectrophotometry (AAS). Total RNA from the blood samples was isolated and analyzed by RT-PCR to quantify PARK2. The data showed that Mn concentrations in plasma, red blood cell (RBC) and saliva, and the cumulative Mn-exposure were about 2.2, 2.0, 1.7 and 3.0 fold higher, respectively, in Mn-exposed workers than those in control subjects (pworkers was significantly decreased by 42% as compared to controls (p<0.01). Linear regression analysis further established that the expression of PARK2 mRNA was inversely correlated with Mn levels in plasma, RBC and saliva, as well as the cumulative Mn exposure (p<0.01). Taken together, it seems likely that Mn exposure among smelters may lead to a reduced expression of PARK2, which may partly explain the Mn-induced Parkinsonian disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Statins reduce the expressions of Tim-3 on NK cells and NKT cells in atherosclerosis.

    Science.gov (United States)

    Zhang, Na; Zhang, Min; Liu, Ru-Tao; Zhang, Peng; Yang, Chun-Lin; Yue, Long-Tao; Li, Heng; Li, Yong-Kang; Duan, Rui-Sheng

    2018-02-15

    3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have an immuno-regulatory effect in addition to lowing-lipids. Accumulated evidence showed that the expressions of T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) on natural killer (NK) cells increased in atherosclerotic patients and animal models. In this study, 14 patients treated with rosuvastatin and 12 patients with atorvastatin for more than 3 months were included and 20 patients without statins treatment as control. Both statins treatment reduced the expressions of Tim-3 on NK cells and their subtypes, natural killer T (NKT) cells and CD3 + T cells, and increased the proportions of NKT cells among peripheral blood mononuclear cells, accompanied by the decreased levels of total cholesterol, low density lipoprotein, and increased ratios of high density lipoprotein to cholesterol. These may contribute to the functions of statins in the treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Eugenol reduces the expression of virulence-related exoproteins in Staphylococcus aureus.

    Science.gov (United States)

    Qiu, Jiazhang; Feng, Haihua; Lu, Jing; Xiang, Hua; Wang, Dacheng; Dong, Jing; Wang, Jianfeng; Wang, Xiaoliang; Liu, Juxiong; Deng, Xuming

    2010-09-01

    Eugenol, an essential oil component in plants, has been demonstrated to possess activity against both gram-positive and gram-negative bacteria. This study examined the influence that subinhibitory concentrations of eugenol may have on the expression of the major exotoxins produced by Staphylococcus aureus. The results from a tumor necrosis factor (TNF) release assay and a hemolysin assay indicated that S. aureus cultured with graded subinhibitory concentrations of eugenol (16 to 128 microg/ml) dose dependently decreased the TNF-inducing and hemolytic activities of culture supernatants. Western blot analysis showed that eugenol significantly reduced the production of staphylococcal enterotoxin A (SEA), SEB, and toxic shock syndrome toxin 1 (the key exotoxins to induce TNF release), as well as the expression of alpha-hemolysin (the major hemolysin to cause hemolysis). In addition, this suppression was also evaluated at the transcriptional level via real-time reverse transcription (RT)-PCR analysis. The transcriptional analysis indicated that 128 microg/ml of eugenol remarkably repressed the transcription of the S. aureus sea, seb, tst, and hla genes. According to these results, eugenol has the potential to be rationally applied on food products as a novel food antimicrobial agent both to inhibit the growth of bacteria and to suppress the production of exotoxins by S. aureus.

  4. Loss of arylformamidase with reduced thymidine kinase expression leads to impaired glucose tolerance

    Directory of Open Access Journals (Sweden)

    Alison J. Hugill

    2015-11-01

    Full Text Available Tryptophan metabolites have been linked in observational studies with type 2 diabetes, cognitive disorders, inflammation and immune system regulation. A rate-limiting enzyme in tryptophan conversion is arylformamidase (Afmid, and a double knockout of this gene and thymidine kinase (Tk has been reported to cause renal failure and abnormal immune system regulation. In order to further investigate possible links between abnormal tryptophan catabolism and diabetes and to examine the effect of single Afmid knockout, we have carried out metabolic phenotyping of an exon 2 Afmid gene knockout. These mice exhibit impaired glucose tolerance, although their insulin sensitivity is unchanged in comparison to wild-type animals. This phenotype results from a defect in glucose stimulated insulin secretion and these mice show reduced islet mass with age. No evidence of a renal phenotype was found, suggesting that this published phenotype resulted from loss of Tk expression in the double knockout. However, despite specifically removing only exon 2 of Afmid in our experiments we also observed some reduction of Tk expression, possibly due to a regulatory element in this region. In summary, our findings support a link between abnormal tryptophan metabolism and diabetes and highlight beta cell function for further mechanistic analysis.

  5. Reduced proliferation and osteocalcin expression in osteoblasts of male idiopathic osteoporosis.

    Science.gov (United States)

    Ruiz-Gaspà, Sílvia; Blanch-Rubió, Josep; Ciria-Recasens, Manuel; Monfort, Jordi; Tío, Laura; Garcia-Giralt, Natàlia; Nogués, Xavier; Monllau, Joan C; Carbonell-Abelló, Jordi; Pérez-Edo, Lluis

    2010-03-01

    Osteoporosis is characterized by low bone mineral density (BMD), resulting in increasing susceptibility to bone fractures. In men, it has been related to some diseases and toxic habits, but in some instances the cause of the primary--or idiopathic--osteoporosis is not apparent. In a previous study, our group compared histomorphometric measurements in cortical and cancellous bones from male idiopathic osteoporosis (MIO) patients to those of control subjects and found reduced bone formation without major differences in bone resorption. To confirm these results, this study analyzed the etiology of this pathology, examining the osteoblast behavior in vitro. We compared two parameters of osteoblast activity in MIO patients and controls: osteoblastic proliferation and gene expression of COL1A1 and osteocalcin, in basal conditions and with vitamin D(3) added. All these experiments were performed from a first-passage osteoblastic culture, obtained from osteoblasts that had migrated from the transiliac explants to the plate. The results suggested that the MIO osteoblast has a slower proliferation rate and decreased expression of genes related to matrix formation, probably due to a lesser or slower response to some stimulus. We concluded that, contrary to female osteoporosis, in which loss of BMD is predominantly due to increased resorption, low BMD in MIO seems to be due to an osteoblastic defect.

  6. Selected lactic acid-producing bacterial isolates with the capacity to reduce Salmonella translocation and virulence gene expression in chickens.

    Directory of Open Access Journals (Sweden)

    Xiaojian Yang

    Full Text Available BACKGROUND: Probiotics have been used to control Salmonella colonization/infection in chickens. Yet the mechanisms of probiotic effects are not fully understood. This study has characterized our previously-selected lactic acid-producing bacterial (LAB isolates for controlling Salmonella infection in chickens, particularly the mechanism underlying the control. METHODOLOGY/PRINCIPAL FINDINGS: In vitro studies were conducted to characterize 14 LAB isolates for their tolerance to low pH (2.0 and high bile salt (0.3-1.5% and susceptibility to antibiotics. Three chicken infection trials were subsequently carried out to evaluate four of the isolates for reducing the burden of Salmonella enterica serovar Typhimurium in the broiler cecum. Chicks were gavaged with LAB cultures (10(6-7 CFU/chick or phosphate-buffered saline (PBS at 1 day of age followed by Salmonella challenge (10(4 CFU/chick next day. Samples of cecal digesta, spleen, and liver were examined for Salmonella counts on days 1, 3, or 4 post-challenge. Salmonella in the cecum from Trial 3 was also assessed for the expression of ten virulence genes located in its pathogenicity island-1 (SPI-1. These genes play a role in Salmonella intestinal invasion. Tested LAB isolates (individuals or mixed cultures were unable to lower Salmonella burden in the chicken cecum, but able to attenuate Salmonella infection in the spleen and liver. The LAB treatments also reduced almost all SPI-1 virulence gene expression (9 out of 10 in the chicken cecum, particularly at the low dose. In vitro treatment with the extracellular culture fluid from a LAB culture also down-regulated most SPI-1 virulence gene expression. CONCLUSIONS/SIGNIFICANCE: The possible correlation between attenuation of Salmonella infection in the chicken spleen and liver and reduction of Salmonella SPI-1 virulence gene expression in the chicken cecum by LAB isolates is a new observation. Suppression of Salmonella virulence gene expression in

  7. Expression of PML tumor suppressor in A 431 cells reduces cellular growth by inhibiting the epidermal growth factor receptor expression

    International Nuclear Information System (INIS)

    Vallian, S.; Chang, K.S.

    2004-01-01

    Our previous studies showed that the promyelocytic leukemia, PML, protein functions as a cellular and growth suppressor. Transient expression of PML was also found to repress the activity of the epidermal growth factor receptor gene promoter. In this study we have examined the effects of PML on A431 cells, which express a high level of + protein. The PML gene was introduced into the cells using the adenovirus-mediated gene transfer system. Western blot analysis on the extracts from the cells expressing PML showed a significant repression in the expression of the epidermal growth factor receptor protein. The cells were examined for growth and DNA synthesis. The data showed a marked reduction in both growth and DNA synthesis rate in the cells expressing PML compared with the control cells. Furthermore, in comparison with the controls, the cells expressing PML were found to be more in G1 phase, fewer in S and about the same number in the G2/M phase. This data clearly demonstrated that the repression of epidermal growth factor receptor expression in A 431 cells by PML was associated with inhibition of cell growth and alteration of the cell cycle distribution, suggesting a novel mechanism for the known growth inhibitory effects of PML

  8. A powerful nonparametric method for detecting differentially co-expressed genes: distance correlation screening and edge-count test.

    Science.gov (United States)

    Zhang, Qingyang

    2018-05-16

    Differential co-expression analysis, as a complement of differential expression analysis, offers significant insights into the changes in molecular mechanism of different phenotypes. A prevailing approach to detecting differentially co-expressed genes is to compare Pearson's correlation coefficients in two phenotypes. However, due to the limitations of Pearson's correlation measure, this approach lacks the power to detect nonlinear changes in gene co-expression which is common in gene regulatory networks. In this work, a new nonparametric procedure is proposed to search differentially co-expressed gene pairs in different phenotypes from large-scale data. Our computational pipeline consisted of two main steps, a screening step and a testing step. The screening step is to reduce the search space by filtering out all the independent gene pairs using distance correlation measure. In the testing step, we compare the gene co-expression patterns in different phenotypes by a recently developed edge-count test. Both steps are distribution-free and targeting nonlinear relations. We illustrate the promise of the new approach by analyzing the Cancer Genome Atlas data and the METABRIC data for breast cancer subtypes. Compared with some existing methods, the new method is more powerful in detecting nonlinear type of differential co-expressions. The distance correlation screening can greatly improve computational efficiency, facilitating its application to large data sets.

  9. MECHANICAL VIBRATION INHIBITS OSTEOCLAST FORMATION BY REDUCING DC-STAMP RECEPTOR EXPRESSION IN OSTEOCLAST PRECURSOR CELLS

    Science.gov (United States)

    Kulkarni, R.N.; Voglewede, P.A.; Liu, D.

    2014-01-01

    It is well known that physical inactivity leads to loss of muscle mass, but it also causes bone loss. Mechanistically, osteoclastogenesis and bone resorption have recently been shown to be regulated by vibration. However, the underlying mechanism behind the inhibition of osteoclast formation is yet unknown. Therefore, we investigated whether mechanical vibration of osteoclast precursor cells affects osteoclast formation by the involvement of fusion-related molecules such as dendritic cell-specific transmembrane protein (DC-STAMP), and P2X7 receptor (P2X7R). RAW264.7 (a murine osteoclastic-like cell line) cells were treated with 20 ng/ml receptor activator of NF-κB ligand (RANKL). For 3 consecutive days, the cells were subjected to 1 hour of mechanical vibration with 20 µm displacement at a frequency of 4 Hz and compared to the control cells that were treated under the same condition but without the vibration. After 5 days of culture, osteoclast formation was determined. Gene expression of DC-STAMP and P2X7R by RAW264.7 cells were determined after 1 hour mechanical vibration, while protein production of the DC-STAMP was determined after 6 hours of post incubation after vibration. As a result, mechanical vibration of RAW264.7 cells inhibited the formation of osteoclasts. Vibration down-regulated DC-STAMP gene expression by 1.6-fold in the presence of RANKL and by 1.4-fold in the absence of RANKL. Additionally, DC-STAMP protein production was also down-regulated by 1.4-fold in the presence of RANKL and by 1.2-fold in the absence of RANKL in RAW264.7 cells in response to mechanical vibration. However, vibration did not affect P2X7R gene expression. Mouse anti-DC-STAMP antibody inhibited osteoclast formation in the absence of vibration. Our results suggest that mechanical vibration of osteoclast precursor cells reduce DC-STAMP expression in osteoclast precursor cells leading to the inhibition of osteoclast formation. PMID:23994170

  10. Mechanical vibration inhibits osteoclast formation by reducing DC-STAMP receptor expression in osteoclast precursor cells.

    Science.gov (United States)

    Kulkarni, Rishikesh N; Voglewede, Philip A; Liu, Dawei

    2013-12-01

    It is well known that physical inactivity leads to loss of muscle mass, but it also causes bone loss. Mechanistically, osteoclastogenesis and bone resorption have recently been shown to be regulated by vibration. However, the underlying mechanism behind the inhibition of osteoclast formation is yet unknown. Therefore, we investigated whether mechanical vibration of osteoclast precursor cells affects osteoclast formation by the involvement of fusion-related molecules such as dendritic cell-specific transmembrane protein (DC-STAMP) and P2X7 receptor (P2X7R). RAW264.7 (a murine osteoclastic-like cell line) cells were treated with 20ng/ml receptor activator of NF-κB ligand (RANKL). For 3 consecutive days, the cells were subjected to 1h of mechanical vibration with 20μm displacement at a frequency of 4Hz and compared to the control cells that were treated under the same condition but without the vibration. After 5days of culture, osteoclast formation was determined. Gene expression of DC-STAMP and P2X7R by RAW264.7 cells was determined after 1h of mechanical vibration, while protein production of the DC-STAMP was determined after 6h of postincubation after vibration. As a result, mechanical vibration of RAW264.7 cells inhibited the formation of osteoclasts. Vibration down-regulated DC-STAMP gene expression by 1.6-fold in the presence of RANKL and by 1.4-fold in the absence of RANKL. Additionally, DC-STAMP protein production was also down-regulated by 1.4-fold in the presence of RANKL and by 1.2-fold in the absence of RANKL in RAW264.7 cells in response to mechanical vibration. However, vibration did not affect P2X7R gene expression. Mouse anti-DC-STAMP antibody inhibited osteoclast formation in the absence of vibration. Our results suggest that mechanical vibration of osteoclast precursor cells reduces DC-STAMP expression in osteoclast precursor cells leading to the inhibition of osteoclast formation. © 2013 Elsevier Inc. All rights reserved.

  11. Involvement of aberrant DNA methylation on reduced expression of lysophosphatidic acid receptor-1 gene in rat tumor cell lines

    International Nuclear Information System (INIS)

    Tsujiuchi, Toshifumi; Shimizu, Kyoko; Onishi, Mariko; Sugata, Eriko; Fujii, Hiromasa; Mori, Toshio; Honoki, Kanya; Fukushima, Nobuyuki

    2006-01-01

    Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation, migration, and protects cells from apoptosis. It interacts with specific G protein-coupled transmembrane receptors. Recently, it has been reported that alterations of LPA receptor expression might be important in the malignant transformation of tumor cells. Therefore, to assess an involvement of DNA methylation in reduced expression of the LPA receptor-1 (lpa1) gene, we investigated the expression of the lpa1 gene and its DNA methylation patterns in rat tumor cell lines. Both rat brain-derived neuroblastoma B103 and liver-derived hepatoma RH7777 cells used in this study indicated no expression of lpa1. For the analysis of methylation status, bisulfite sequencing was performed with B103 and RH7777 cells, comparing with other lpa1 expressed cells and normal tissues of brain and liver. The lpa1 expressed cells and tissues were all unmethylated in this region of lpa1. In contrast, both B103 and RH7777 cells were highly methylated, correlating with reduced expression of the lpa1. Treatment with 5-aza 2'-deoxycytidine induced expression of lpa1 gene in B103 and RH7777 cells after 24 h. In RH7777 cells treated with 5-aza 2'-deoxycytidine, stress fiber formation was also observed in response to LPA in RH7777 cells, but not in untreated RH7777 cells. These results suggest that aberrant DNA methylation of the lpa1 gene may be involved in its reduced expression in rat tumor cells

  12. Reducing test-data volume and test-power simultaneously in LFSR reseeding-based compression environment

    Energy Technology Data Exchange (ETDEWEB)

    Wang Weizheng; Kuang Jishun; You Zhiqiang; Liu Peng, E-mail: jshkuang@163.com [College of Information Science and Engineering, Hunan University, Changsha 410082 (China)

    2011-07-15

    This paper presents a new test scheme based on scan block encoding in a linear feedback shift register (LFSR) reseeding-based compression environment. Meanwhile, our paper also introduces a novel algorithm of scan-block clustering. The main contribution of this paper is a flexible test-application framework that achieves significant reductions in switching activity during scan shift and the number of specified bits that need to be generated via LFSR reseeding. Thus, it can significantly reduce the test power and test data volume. Experimental results using Mintest test set on the larger ISCAS'89 benchmarks show that the proposed method reduces the switching activity significantly by 72%-94% and provides a best possible test compression of 74%-94% with little hardware overhead. (semiconductor integrated circuits)

  13. Anethole potentiates dodecanol's fungicidal activity by reducing PDR5 expression in budding yeast.

    Science.gov (United States)

    Fujita, Ken-Ichi; Ishikura, Takayuki; Jono, Yui; Yamaguchi, Yoshihiro; Ogita, Akira; Kubo, Isao; Tanaka, Toshio

    2017-02-01

    trans-Anethole (anethole), a major component of anise oil, has a broad antimicrobial spectrum and a weaker antimicrobial potency than other available antibiotics. When combined with polygodial, nagilactone E, and n-dodecanol, anethole has been shown to exhibit synergistic antifungal activity against a budding yeast, Saccharomyces cerevisiae, and a human opportunistic pathogenic yeast, Candida albicans. However, the mechanism underlying this synergistic effect of anethole has not been characterized. We studied this mechanism using dodecanol-treated S. cerevisiae cells and focusing on genes related to multidrug efflux. Although dodecanol transiently reduced the number of colony forming units, this recovered to levels similar to those of untreated cells with continued incubation beyond 24h. Reverse transcription polymerase chain reaction analysis revealed overexpression of an ATP-binding cassette (ABC) transporter gene, PDR5, in addition to a slight increase in PDR11, PDR12, and PDR15 transcriptions in dodecanol-treated cells. In the presence of anethole, these effects were attenuated and the fungicidal activity of dodecanol was extended. Dodecanol showed longer lasting fungicidal activity against a Δpdr5. In addition, Δpdr3 and Δlge1, lack transcription factors of PDR5 and PDR3, were partly and completely susceptible to dodecanol, respectively. Furthermore, combination of anethole with fluconazole was also found to exhibit synergy on C. albicans. These results indicated that although anethole reduced the transcription of several transporters, PDR5 expression was particularly relevant to dodecanol efflux. Anethole is expected to be a promising candidate drug for the inhibition of efflux by reducing the transcription of several ABC transporters. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Optimising parallel R correlation matrix calculations on gene expression data using MapReduce.

    Science.gov (United States)

    Wang, Shicai; Pandis, Ioannis; Johnson, David; Emam, Ibrahim; Guitton, Florian; Oehmichen, Axel; Guo, Yike

    2014-11-05

    High-throughput molecular profiling data has been used to improve clinical decision making by stratifying subjects based on their molecular profiles. Unsupervised clustering algorithms can be used for stratification purposes. However, the current speed of the clustering algorithms cannot meet the requirement of large-scale molecular data due to poor performance of the correlation matrix calculation. With high-throughput sequencing technologies promising to produce even larger datasets per subject, we expect the performance of the state-of-the-art statistical algorithms to be further impacted unless efforts towards optimisation are carried out. MapReduce is a widely used high performance parallel framework that can solve the problem. In this paper, we evaluate the current parallel modes for correlation calculation methods and introduce an efficient data distribution and parallel calculation algorithm based on MapReduce to optimise the correlation calculation. We studied the performance of our algorithm using two gene expression benchmarks. In the micro-benchmark, our implementation using MapReduce, based on the R package RHIPE, demonstrates a 3.26-5.83 fold increase compared to the default Snowfall and 1.56-1.64 fold increase compared to the basic RHIPE in the Euclidean, Pearson and Spearman correlations. Though vanilla R and the optimised Snowfall outperforms our optimised RHIPE in the micro-benchmark, they do not scale well with the macro-benchmark. In the macro-benchmark the optimised RHIPE performs 2.03-16.56 times faster than vanilla R. Benefiting from the 3.30-5.13 times faster data preparation, the optimised RHIPE performs 1.22-1.71 times faster than the optimised Snowfall. Both the optimised RHIPE and the optimised Snowfall successfully performs the Kendall correlation with TCGA dataset within 7 hours. Both of them conduct more than 30 times faster than the estimated vanilla R. The performance evaluation found that the new MapReduce algorithm and its

  15. Facial expression coding in children and adolescents with autism: Reduced adaptability but intact norm-based coding.

    Science.gov (United States)

    Rhodes, Gillian; Burton, Nichola; Jeffery, Linda; Read, Ainsley; Taylor, Libby; Ewing, Louise

    2018-05-01

    Individuals with autism spectrum disorder (ASD) can have difficulty recognizing emotional expressions. Here, we asked whether the underlying perceptual coding of expression is disrupted. Typical individuals code expression relative to a perceptual (average) norm that is continuously updated by experience. This adaptability of face-coding mechanisms has been linked to performance on various face tasks. We used an adaptation aftereffect paradigm to characterize expression coding in children and adolescents with autism. We asked whether face expression coding is less adaptable in autism and whether there is any fundamental disruption of norm-based coding. If expression coding is norm-based, then the face aftereffects should increase with adaptor expression strength (distance from the average expression). We observed this pattern in both autistic and typically developing participants, suggesting that norm-based coding is fundamentally intact in autism. Critically, however, expression aftereffects were reduced in the autism group, indicating that expression-coding mechanisms are less readily tuned by experience. Reduced adaptability has also been reported for coding of face identity and gaze direction. Thus, there appears to be a pervasive lack of adaptability in face-coding mechanisms in autism, which could contribute to face processing and broader social difficulties in the disorder. © 2017 The British Psychological Society.

  16. Difficulties Using Standardized Tests to Identify the Receptive Expressive Gap in Bilingual Children's Vocabularies.

    Science.gov (United States)

    Gibson, Todd A; Oller, D Kimbrough; Jarmulowicz, Linda

    2018-03-01

    Receptive standardized vocabulary scores have been found to be much higher than expressive standardized vocabulary scores in children with Spanish as L1, learning L2 (English) in school (Gibson et al., 2012). Here we present evidence suggesting the receptive-expressive gap may be harder to evaluate than previously thought because widely-used standardized tests may not offer comparable normed scores. Furthermore monolingual Spanish-speaking children tested in Mexico and monolingual English-speaking children in the US showed other, yet different statistically significant discrepancies between receptive and expressive scores. Results suggest comparisons across widely used standardized tests in attempts to assess a receptive-expressive gap are precarious.

  17. Everolimus immunosuppression reduces the serum expression of fibrosis markers in liver transplant recipients.

    Science.gov (United States)

    Fernández-Yunquera, Ainhoa; Ripoll, Cristina; Bañares, Rafael; Puerto, Marta; Rincón, Diego; Yepes, Ismael; Catalina, Vega; Salcedo, Magdalena

    2014-06-24

    To evaluate the expression of serum fibrosis markers in liver transplantation (LT) recipients on everolimus monotherapy compared to patients on an anti-calcineurin regimen. This cross-sectional case-control study included LT patients on everolimus monotherapy (cases) (E) (n = 30) and matched controls on an anti-calcineurin regimen (calcineurin inhibitors, CNI), paired by etiology of liver disease and time since LT (n = 30). Clinical characteristics, blood tests and elastography were collected. Serum levels of transforming growth factor-β (TGF-β), angiopoietin-1, tumor necrosis factor (TNF), platelet derived growth factor, amino-terminal propeptide of type III procollagen (PIIINP), hyaluronic acid (HA), VCM-1 (ng/mL), interleukin (IL)-10, interferon-inducible protein 10 (IP-10), vascular endothelial growth factor and hepatocyte growth factor (HGF) (pg/mL) were determined by enzyme-linked immunosorbent assay. Expression of these markers between E and CNI was compared. Stratified analysis was done according to factors that may influence liver fibrosis. Variables are described with medians (interquartillic range) or percentages. A total of 60 patients [age: 59 (49-64), hepatitis C virus (HCV): n = 21 (35%), time from LT: 73 mo (16-105)] were included. Patients had been on everolimus for a median of 15 mo. No differences in inflammatory activity, APRI test or liver elastography were found between the groups. No significant differences were observed between the groups in serum levels of PIIINP, metalloproteinase type = 1, angiopoietin, HGF, IP-10, TNF-α, IL-10 and vascular cell adhesion molecule. Patients on E had a lower expression of TGF-β [E: 12.7 (3.7-133.6), CNI: 152.5 (14.4-333.2), P = 0.009] and HA [E: 702.89 (329.4-838.2), CNI: 1513.6 (691.9-1951.4), P = 0.001] than those on CNI. This difference was maintained in the stratified analysis when recipient age is more than 50 years (TFG-β1: P = 0.06; HA: P = 0.005), in patients without active neoplasia (TFG-β1

  18. Aberrant Methylation and Reduced Expression of LHX9 in Malignant Gliomas of Childhood

    Directory of Open Access Journals (Sweden)

    Valentina Vladimirova

    2009-07-01

    Full Text Available High-grade gliomas (HGGs of childhood represent approximately 7% of pediatric brain tumors. They are highly invasive tumors and respond poorly to conventional treatments in contrast to pilocytic astrocytomas, which usually are well demarcated and frequently can be cured by surgery. The molecular events for this clinical relevant finding are only partially understood. In the current study, to identify aberrantly methylated genes that may be involved in the tumorigenesis of pediatric HGGs, we performed a microarray-based differential methylation hybridization approach and found frequent hypermethylation of the LHX9 (human Lim-homebox 9 gene encoding a transcription factor involved in brain development. Bisulfite genomic sequencing and combined bisulfite restriction analysis showed that HGGs were frequently methylated at two CpG-rich LHX9 regions in comparison to benign, nondiffuse pilocytic astrocytomas and normal brain tissues. The LHX9 hypermethylation was associated with reduced messenger RNA expression in pediatric HGG samples and corresponding cell lines. This epigenetic modification was reversible by pharmacological inhibition (5-aza-2′-deoxycytidine, and reexpression of LHX9 transcript was induced in pediatric glioma cell lines. Exogenous expression of LHX9 in glioma cell lines did not directly affect cell proliferation and apoptosis but specifically inhibited glioma cell migration and invasion in vitro, suggesting a possible implication of LHX9 in the migratory phenotype of HGGs. Our results demonstrate that the LHX9 gene is frequently silenced in pediatric malignant astrocytomas by hypermethylation and that this epigenetic alteration is involved in glioma cell migration and invasiveness.

  19. 76 FR 69595 - Application of Third Party Testing Requirements; Reducing Third Party Testing Burdens

    Science.gov (United States)

    2011-11-08

    ... material change in the product's design or manufacturing process, including the sourcing of component parts...)) defines a ``children's product,'' in relevant part, as a consumer product designed or intended primarily... testing by a third party) be designed to show the similarity between the products? Also, sampling...

  20. Reduced expression of ZDHHC2 is associated with lymph node metastasis and poor prognosis in gastric adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Shu-Mei Yan

    Full Text Available BACKGROUND: Zinc finger, DHHC-type containing 2 (ZDHHC2, originally named as reduced expression associated with metastasis protein (REAM, has been proposed as a putative tumor/metastasis suppressor gene and is often aberrantly decreased in human cancers. However ZDHHC2 expression pattern and its clinical significance have not yet been investigated in gastric adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative Real-Time PCR (qRT-PCR and immunostaining were performed to detect ZDHHC2 expression in gastric adenocarcinoma, and then the correlation between ZDHHC2 expression and clinicpathologic parameters, and patient survival was analyzed. Compared to the adjacent normal tissues, ZDHHC2 expression was significantly reduced in gastric tumor tissues as shown by qRT-PCR and immunostaining. Low expression of ZDHHC2 was observed in 44.7% (211/472 of gastric adenocarcinoma patients, and was associated significantly with lymph node metastasis (p<0.001 and histological grade (p<0.001. Multivariate Cox regression analysis indicated that ZDHHC2 expression had a significant, independent predictive value for survival of gastric cancer patients (HR = 0.627, p = 0.001. CONCLUSIONS/SIGNIFICANCE: Our data suggest that reduced ZDHHC2 expression is associated with lymph node metastasis and independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.

  1. Reduced FOXO1 expression accelerates skin wound healing and attenuates scarring.

    Science.gov (United States)

    Mori, Ryoichi; Tanaka, Katsuya; de Kerckhove, Maiko; Okamoto, Momoko; Kashiyama, Kazuya; Tanaka, Katsumi; Kim, Sangeun; Kawata, Takuya; Komatsu, Toshimitsu; Park, Seongjoon; Ikematsu, Kazuya; Hirano, Akiyoshi; Martin, Paul; Shimokawa, Isao

    2014-09-01

    The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1(+/-) mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a(-/-) mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1(+/-) mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. HYDROXYCHLOROQUINE REDUCES BINDING OF ANTIPHOSPHOLIPID ANTIBODIES TO SYNCYTIOTROPHOBLASTS AND RESTORES ANNEXIN A5 EXPRESSION

    Science.gov (United States)

    Wu, Xiao-Xuan; Guller, Seth; Rand, Jacob H.

    2011-01-01

    Objectives Antibody-mediated disruption of the annexin A5 (AnxA5) anticoagulant shield has been posited to be a thrombogenic mechanism in the antiphospholipid syndrome. We recently showed that the antimalarial drug, hydroxychloroquine, dissociates antiphospholipid immune complexes and restores AnxA5 binding to planar phospholipid bilayer. Using quantitative immunoassays, we demonstrated similar effects on BeWo trophoblasts. We therefore investigated the effects of the drug on localization of AnxA5 in primary cultures of human placental syncytiotrophoblasts (SCTs). Study Laser confocal microscopy with computer-based morphometric analysis was used to localize AnxA5 and antiphospholipid antibodies on SCTs exposed to polyclonal and monoclonal antiphospholipid and control IgGs. Results Hydroxychloroquine reversed the effects of the antiphospholipid antibodies on the SCTs by markedly reducing IgG binding and restoring AnxA5 expression. Conclusions These results provide the first morphologic evidence for this effect of hydroxychloroquine on human placental SCTs and support the possibility of novel treatments that target antiphospholipid antibody binding. PMID:21871597

  3. NASA Lewis Stirling SPRE testing and analysis with reduced number of cooler tubes

    International Nuclear Information System (INIS)

    Wong, W.A.; Cairelli, J.E.; Swec, D.M.; Doeberling, T.J.; Lakatos, T.F.; Madi, F.J.

    1994-01-01

    Free-piston Stirling power converters are a candidate for high capacity space power applications. The Space Power Research Engine (SPRE), a free-piston Stirling engine coupled with a linear alternator, is being tested at the NASA Lewis Research Center in support of the Civil Space Technology Initiative. The SPRE is used as a test bed for evaluating converter modifications which have the potential to improve converter performance and for validating computer code predictions. Reducing the number of cooler tubes on the SPRE has been identified as a modification with the potential to significantly improve power and efficiency. This paper describes experimental tests designed to investigate the effects of reducing the number of cooler tubes on converter power, efficiency and dynamics. Presented are test results from the converter operating with a reduced number of cooler tubes and comparisons between this data and both baseline test data and computer code predictions

  4. Nifedipine treatment reduces resting calcium concentration, oxidative and apoptotic gene expression, and improves muscle function in dystrophic mdx mice.

    Directory of Open Access Journals (Sweden)

    Francisco Altamirano

    Full Text Available Duchenne Muscular Dystrophy (DMD is a recessive X-linked genetic disease, caused by mutations in the gene encoding dystrophin. DMD is characterized in humans and in mdx mice by a severe and progressive destruction of muscle fibers, inflammation, oxidative/nitrosative stress, and cell death. In mdx muscle fibers, we have shown that basal ATP release is increased and that extracellular ATP stimulation is pro-apoptotic. In normal fibers, depolarization-induced ATP release is blocked by nifedipine, leading us to study the potential therapeutic effect of nifedipine in mdx muscles and its relation with extracellular ATP signaling. Acute exposure to nifedipine (10 µM decreased [Ca(2+]r, NF-κB activity and iNOS expression in mdx myotubes. In addition, 6-week-old mdx mice were treated with daily intraperitoneal injections of nifedipine, 1 mg/Kg for 1 week. This treatment lowered the [Ca(2+]r measured in vivo in the mdx vastus lateralis. We demonstrated that extracellular ATP levels were higher in adult mdx flexor digitorum brevis (FDB fibers and can be significantly reduced after 1 week of treatment with nifedipine. Interestingly, acute treatment of mdx FDB fibers with apyrase, an enzyme that completely degrades extracellular ATP to AMP, reduced [Ca(2+]r to a similar extent as was seen in FDB fibers after 1-week of nifedipine treatment. Moreover, we demonstrated that nifedipine treatment reduced mRNA levels of pro-oxidative/nitrosative (iNOS and gp91(phox/p47(phox NOX2 subunits and pro-apoptotic (Bax genes in mdx diaphragm muscles and lowered serum creatine kinase (CK levels. In addition, nifedipine treatment increased muscle strength assessed by the inverted grip-hanging test and exercise tolerance measured with forced swimming test in mdx mice. We hypothesize that nifedipine reduces basal ATP release, thereby decreasing purinergic receptor activation, which in turn reduces [Ca(2+]r in mdx skeletal muscle cells. The results in this work open new

  5. Safety testing of GM-rice expressing PHA-E lectin using a new animal test design

    DEFF Research Database (Denmark)

    Poulsen, Morten; Schrøder, Malene; Wilcks, Andrea

    2007-01-01

    The 90-day animal study is the core study for the safety assessment of genetically modified foods in the SAFOTEST project. The model compound tested in the 90-day study was a rice variety expressing the kidney bean Phaseolus vulgaris lectin agglutinin E-form (PHA-E lectin). Female Wistar rats were...... safety testing of genetically modified foods....

  6. Optimizing human semen cryopreservation by reducing test vial volume and repetitive test vial sampling

    DEFF Research Database (Denmark)

    Jensen, Christian F S; Ohl, Dana A; Parker, Walter R

    2015-01-01

    OBJECTIVE: To investigate optimal test vial (TV) volume, utility and reliability of TVs, intermediate temperature exposure (-88°C to -93°C) before cryostorage, cryostorage in nitrogen vapor (VN2) and liquid nitrogen (LN2), and long-term stability of VN2 cryostorage of human semen. DESIGN......: Prospective clinical laboratory study. SETTING: University assisted reproductive technology (ART) laboratory. PATIENT(S): A total of 594 patients undergoing semen analysis and cryopreservation. INTERVENTION(S): Semen analysis, cryopreservation with different intermediate steps and in different volumes (50......-1,000 μL), and long-term storage in LN2 or VN2. MAIN OUTCOME MEASURE(S): Optimal TV volume, prediction of cryosurvival (CS) in ART procedure vials (ARTVs) with pre-freeze semen parameters and TV CS, post-thaw motility after two- or three-step semen cryopreservation and cryostorage in VN2 and LN2. RESULT...

  7. A reduced transcriptome approach to assess environmental toxicants using zebrafish embryo tests

    Science.gov (United States)

    This paper reports on the pilot testing of a new bioassay platform that monitors expression of 1600 genes in zebrafish embryos exposed to either single chemicals or complex water samples. The method provides a more cost effective, high throughput means to broadly evaluate the pot...

  8. A Test to Express Diagnostic Cohesion of Football Team

    OpenAIRE

    Alexandra O. Savinkina

    2017-01-01

    We proposed to assess the cohesion of a football team by its subject-goal and subject-value unity according to the A.V. Petrovsky theory. Goal unity was measured by the degree of compliance of the priority targets for various players in the team. Values were estimated by the coincidence of the ideas about a perfect football player. On the basis of the provisional diagnosis of the six teams, we had made the lists of goals and values. The tests were piloted on 35 football teams. The results all...

  9. Comparison of Anxiety Management Training and Desensitization in Reducing Test and Other Anxieties.

    Science.gov (United States)

    Deffenbacher, Jerry L.; Shelton, John L.

    1978-01-01

    Effects of systematic desensitization and anxiety management training in reducing test anxiety and generalizing to other anxieties were compared. Both desensitization and anxiety management training produced significant reduction of text anxiety, but by follow-up, anxiety management training produced significantly more test-anxiety reduction on…

  10. The Facial Expression Action Stimulus Test. A test battery for the assessment of face memory, face and object perception, configuration processing and facial expression recognition

    Directory of Open Access Journals (Sweden)

    Beatrice eDe Gelder

    2015-10-01

    Full Text Available There are many ways to assess face perception skills. In this study, we describe a novel task battery FEAST (Facial Expression Action Stimulus Test developed to test recognition of identity and expressions of human faces as well as stimulus control categories. The FEAST consists of a neutral and emotional face memory task, a face and object identity matching task, a face and house part-to-whole matching task, and a human and animal facial expression matching task. The identity and part-to-whole matching tasks contain both upright and inverted conditions. The results provide reference data of a healthy sample of controls in two age groups for future users of the FEAST.

  11. CPT1α over-expression increases long-chain fatty acid oxidation and reduces cell viability with incremental palmitic acid concentration in 293T cells

    International Nuclear Information System (INIS)

    Jambor de Sousa, Ulrike L.; Koss, Michael D.; Fillies, Marion; Gahl, Anja; Scheeder, Martin R.L.; Cardoso, M. Cristina; Leonhardt, Heinrich; Geary, Nori; Langhans, Wolfgang; Leonhardt, Monika

    2005-01-01

    To test the cellular response to an increased fatty acid oxidation, we generated a vector for an inducible expression of the rate-limiting enzyme carnitine palmitoyl-transferase 1α (CPT1α). Human embryonic 293T kidney cells were transiently transfected and expression of the CPT1α transgene in the tet-on vector was activated with doxycycline. Fatty acid oxidation was measured by determining the conversion of supplemented, synthetic cis-10-heptadecenoic acid (C17:1n-7) to C15:ln-7. CPT1α over-expression increased mitochondrial long-chain fatty acid oxidation about 6-fold. Addition of palmitic acid (PA) decreased viability of CPT1α over-expressing cells in a concentration-dependent manner. Both, PA and CPT1α over-expression increased cell death. Interestingly, PA reduced total cell number only in cells over-expressing CPT1α, suggesting an effect on cell proliferation that requires PA translocation across the mitochondrial inner membrane. This inducible expression system should be well suited to study the roles of CPT1 and fatty acid oxidation in lipotoxicity and metabolism in vivo

  12. Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice.

    Science.gov (United States)

    Vincent, Jessica; Adura, Carolina; Gao, Pu; Luz, Antonio; Lama, Lodoe; Asano, Yasutomi; Okamoto, Rei; Imaeda, Toshihiro; Aida, Jumpei; Rothamel, Katherine; Gogakos, Tasos; Steinberg, Joshua; Reasoner, Seth; Aso, Kazuyoshi; Tuschl, Thomas; Patel, Dinshaw J; Glickman, J Fraser; Ascano, Manuel

    2017-09-29

    Cyclic GMP-AMP synthase is essential for innate immunity against infection and cellular damage, serving as a sensor of DNA from pathogens or mislocalized self-DNA. Upon binding double-stranded DNA, cyclic GMP-AMP synthase synthesizes a cyclic dinucleotide that initiates an inflammatory cellular response. Mouse studies that recapitulate causative mutations in the autoimmune disease Aicardi-Goutières syndrome demonstrate that ablating the cyclic GMP-AMP synthase gene abolishes the deleterious phenotype. Here, we report the discovery of a class of cyclic GMP-AMP synthase inhibitors identified by a high-throughput screen. These compounds possess defined structure-activity relationships and we present crystal structures of cyclic GMP-AMP synthase, double-stranded DNA, and inhibitors within the enzymatic active site. We find that a chemically improved member, RU.521, is active and selective in cellular assays of cyclic GMP-AMP synthase-mediated signaling and reduces constitutive expression of interferon in macrophages from a mouse model of Aicardi-Goutières syndrome. RU.521 will be useful toward understanding the biological roles of cyclic GMP-AMP synthase and can serve as a molecular scaffold for development of future autoimmune therapies.Upon DNA binding cyclic GMP-AMP synthase (cGAS) produces a cyclic dinucleotide, which leads to the upregulation of inflammatory genes. Here the authors develop small molecule cGAS inhibitors, functionally characterize them and present the inhibitor and DNA bound cGAS crystal structures, which will facilitate drug development.

  13. Kalanchoe blossfeldiana plants expressing the Arabidopsis etr1-1 allele show reduced ethylene sensitivity.

    Science.gov (United States)

    Sanikhani, Mohsen; Mibus, Heiko; Stummann, Bjarne M; Serek, Margrethe

    2008-04-01

    Transgenic Kalanchoe blossfeldiana Poelln. with reduced ethylene sensitivity in flowers was obtained by Agrobacterium tumefaciens-mediated transformation using the plasmid pBEO210 containing the mutant ethylene receptor gene etr1-1 from Arabidopsis thaliana under the control of the flower-specific fbp1-promoter from Petunia. Three ethylene-resistent T0 lines, 300, 324 and 331, were selected and analyzed for postharvest-performance and morphological characteristics. Line 324 was found to be infertile and only slightly less ethylene-sensitive than control-plants, but lines 300 and 331 had significantly increased ethylene-resistance and were fertile. These two lines were analyzed for copy-number of the etr1-1 gene by Southern blotting and were crossed with the ethylene-sensitive cultivar 'Celine' to create T1 progeny. Line 300 contains two T-DNA copies per nucleus, one of which is rearranged, and these are unlinked according to segregation data from the crossing to 'Celine' and PCR-analysis of progeny plants. For control plants all flowers were closed after 2 days at 2 microl l(-1 )ethylene, but for line 300 only 33% were closed after 10 days. Line 331 contains three T-DNA copies per nucleus and is more sensitive to ethylene than line 300. In the line 300 the etr1-1 gene was found by RT-PCR to be expressed in petals and stamens but not in carpels and sepals. Both lines 300 and 331, and their progeny, appear morphologically and physiologically identical to control plants except for the higher ethylene resistance. Line 300 and its progeny with only one T-DNA copy have very low ethylene sensitivity and may be useful in future breeding.

  14. Feeding the developing brain: Juvenile rats fed diet rich in prebiotics and bioactive milk fractions exhibit reduced anxiety-related behavior and modified gene expression in emotion circuits.

    Science.gov (United States)

    Mika, Agnieszka; Gaffney, Michelle; Roller, Rachel; Hills, Abigail; Bouchet, Courtney A; Hulen, Kristina A; Thompson, Robert S; Chichlowski, Maciej; Berg, Brian M; Fleshner, Monika

    2018-01-30

    Early life nutrition is critical for brain development. Dietary prebiotics and bioactive milk fractions support brain development by increasing plasticity and altering activity in brain regions important for cognition and emotion regulation, perhaps through the gut-microbiome-brain axis. Here we examined the impact of a diet containing prebiotics, lactoferrin, and milk fat globule membrane (test diet) on beneficial gut bacteria, basal gene expression for activity and plasticity markers within brain circuits important for cognition and anxiety, and anxiety-related behavior in the open field. Juvenile male F344 rats were fed the test diet or a calorically matched control diet beginning postnatal day 24. After 4 weeks on diets, rats were sacrificed and brains were removed. Test diet significantly increased mRNA expression for cfos, brain derived neurotropic factor, and the GluN1 subunit of the NMDA receptor in the prefrontal cortex and reduced cfos mRNA within the amygdala. Diet-induced increases in fecal Lactobacillus spp., measured using selective bacterial culture, positively correlated with altered gene expression for cfos and serotonin receptors within multiple brain regions. In a separate cohort of juvenile rats, 4 weeks of the test diet increased time spent in the center of the open field, a behavior indicative of reduced anxiety. These data demonstrate that early life diets containing prebiotics and bioactive milk fractions can adaptively alter genes in neural circuits underlying emotion regulation and decrease anxiety-related behavior. Copyright © 2018. Published by Elsevier B.V.

  15. Reduced expression of bax in small cell lung cancer cells is not sufficient to induce cisplatin-resistance

    Directory of Open Access Journals (Sweden)

    Biagosch J

    2010-10-01

    Full Text Available Abstract Resistance to cisplatin in the course of chemotherapy contributes to the poor prognosis of small cell lung cancer (SCLC. B cell lymphoma-2 is the founding member of a large family of proteins that either promote or inhibit apoptosis. We aimed at investigating if the pro-apoptotic members Bad, Bax, Bim and Bid are involved in cisplatin-resistance. Cisplatin-resistance in the SCLC cell line H1339 was induced by repetitive exposure to cisplatin. Protein expression was quantified by Western Blot and immuno-fluorescence analysis. Protein expression was altered using siRNA interference. Four "cycles" of 0.5 μg/ml cisplatin led to partial cisplatin-resistance in H1339 cells. The expression of Bad, Bim and Bid was comparable in naïve and resistant cells while the expression of Bax was reduced in the resistant clone. But, reducing Bax expression in naïve cells did not lead to altered cisplatin sensitivity neither in H1339 nor in H187 SCLC cells. We conclude that the reduced Bax expression after exposure to cisplatin is not sufficient to induce cis-platin-resistance in SCLC cells.

  16. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Chihiro Moriya

    2016-01-01

    Full Text Available We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD or a 60% high-fat diet (HFD with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects.

  17. Irradiation of rat brain reduces P-glycoprotein expression and function

    NARCIS (Netherlands)

    Bart, J.; Nagengast, W. B.; Coppes, R. P.; Wegman, T. D.; van der Graaf, W. T. A.; Groen, H. J. M.; Vaalburg, W.; de Vries, E. G. E.; Hendrikse, N. H.

    2007-01-01

    The blood - brain barrier ( BBB) hampers delivery of several drugs including chemotherapeutics to the brain. The drug efflux pump P- glycoprotein ( P- gp), expressed on brain capillary endothelial cells, is part of the BBB. P- gp expression on capillary endothelium decreases 5 days after brain

  18. Budget impact analysis of gene expression tests to aid therapy decisions for breast cancer patients in Germany.

    Science.gov (United States)

    Lux, M P; Nabieva, N; Hildebrandt, T; Rebscher, H; Kümmel, S; Blohmer, J-U; Schrauder, M G

    2018-02-01

    Many women with early-stage, hormone receptor-positive breast cancer may not benefit from adjuvant chemotherapy. Gene expression tests can reduce chemotherapy over- and undertreatment by providing prognostic information on the likelihood of recurrence and, with Oncotype DX, predictive information on chemotherapy benefit. These tests are currently not reimbursed by German healthcare payers. An analysis was conducted to evaluate the budget impact of gene expression tests in Germany. Costs of gene expression tests and medical and non-medical costs associated with treatment were assessed from healthcare payer and societal perspectives. Costs were estimated from data collected at a university hospital and were combined with decision impact data for Oncotype DX, MammaPrint, Prosigna and EndoPredict (EPclin). Changes in chemotherapy use and budget impact were evaluated over 1 year for 20,000 women. Chemotherapy was associated with substantial annual costs of EUR 19,003 and EUR 84,412 per therapy from the healthcare payer and societal perspective, respectively. Compared with standard care, only Oncotype DX was associated with cost savings to healthcare payers and society (EUR 5.9 million and EUR 253 million, respectively). Scenario analysis showed that both women at high clinical but low genomic risk and low clinical but high genomic risk were important contributors to costs. Oncotype DX was the only gene expression test that was estimated to reduce costs versus standard care in Germany. The reimbursement of Oncotype DX testing in standard clinical practice in Germany should be considered. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Thymine DNA Glycosylase (TDG) is involved in the pathogenesis of intestinal tumors with reduced APC expression.

    Science.gov (United States)

    Xu, Jinfei; Cortellino, Salvatore; Tricarico, Rossella; Chang, Wen-Chi; Scher, Gabrielle; Devarajan, Karthik; Slifker, Michael; Moore, Robert; Bassi, Maria Rosaria; Caretti, Elena; Clapper, Margie; Cooper, Harry; Bellacosa, Alfonso

    2017-10-27

    Thymine DNA Glycosylase (TDG) is a base excision repair enzyme that acts as a thymine and uracil DNA N-glycosylase on G:T and G:U mismatches, thus protecting CpG sites in the genome from mutagenesis by deamination. In addition, TDG has an epigenomic function by removing the novel cytosine derivatives 5-formylcytosine and 5-carboxylcytosine (5caC) generated by Ten-Eleven Translocation (TET) enzymes during active DNA demethylation. We and others previously reported that TDG is essential for mammalian development. However, its involvement in tumor formation is unknown. To study the role of TDG in tumorigenesis, we analyzed the effects of its inactivation in a well-characterized model of tumor predisposition, the Apc Min mouse strain. Mice bearing a conditional Tdg flox allele were crossed with Fabpl ::Cre transgenic mice, in the context of the Apc Min mutation, in order to inactivate Tdg in the small intestinal and colonic epithelium. We observed an approximately 2-fold increase in the number of small intestinal adenomas in the test Tdg -mutant Apc Min mice in comparison to control genotypes (p=0.0001). This increase occurred in female mice, and is similar to the known increase in intestinal adenoma formation due to oophorectomy. In the human colorectal cancer (CRC) TCGA database, the subset of patients with TDG and APC expression in the lowest quartile exhibits an excess of female cases. We conclude that TDG inactivation plays a role in intestinal tumorigenesis initiated by mutation/underexpression of APC . Our results also indicate that TDG may be involved in sex-specific protection from CRC.

  20. Feedback enhances the positive effects and reduces the negative effects of multiple-choice testing.

    Science.gov (United States)

    Butler, Andrew C; Roediger, Henry L

    2008-04-01

    Multiple-choice tests are used frequently in higher education without much consideration of the impact this form of assessment has on learning. Multiple-choice testing enhances retention of the material tested (the testing effect); however, unlike other tests, multiple-choice can also be detrimental because it exposes students to misinformation in the form of lures. The selection of lures can lead students to acquire false knowledge (Roediger & Marsh, 2005). The present research investigated whether feedback could be used to boost the positive effects and reduce the negative effects of multiple-choice testing. Subjects studied passages and then received a multiple-choice test with immediate feedback, delayed feedback, or no feedback. In comparison with the no-feedback condition, both immediate and delayed feedback increased the proportion of correct responses and reduced the proportion of intrusions (i.e., lure responses from the initial multiple-choice test) on a delayed cued recall test. Educators should provide feedback when using multiple-choice tests.

  1. Optimal testing input sets for reduced diagnosis time of nuclear power plant digital electronic circuits

    International Nuclear Information System (INIS)

    Kim, D.S.; Seong, P.H.

    1994-01-01

    This paper describes the optimal testing input sets required for the fault diagnosis of the nuclear power plant digital electronic circuits. With the complicated systems such as very large scale integration (VLSI), nuclear power plant (NPP), and aircraft, testing is the major factor of the maintenance of the system. Particularly, diagnosis time grows quickly with the complexity of the component. In this research, for reduce diagnosis time the authors derived the optimal testing sets that are the minimal testing sets required for detecting the failure and for locating of the failed component. For reduced diagnosis time, the technique presented by Hayes fits best for the approach to testing sets generation among many conventional methods. However, this method has the following disadvantages: (a) it considers only the simple network (b) it concerns only whether the system is in failed state or not and does not provide the way to locate the failed component. Therefore the authors have derived the optimal testing input sets that resolve these problems by Hayes while preserving its advantages. When they applied the optimal testing sets to the automatic fault diagnosis system (AFDS) which incorporates the advanced fault diagnosis method of artificial intelligence technique, they found that the fault diagnosis using the optimal testing sets makes testing the digital electronic circuits much faster than that using exhaustive testing input sets; when they applied them to test the Universal (UV) Card which is a nuclear power plant digital input/output solid state protection system card, they reduced the testing time up to about 100 times

  2. Sugar and hexokinase suppress expression of PIP aquaporins and reduce leaf hydraulics that preserves leaf water potential.

    Science.gov (United States)

    Kelly, Gilor; Sade, Nir; Doron-Faigenboim, Adi; Lerner, Stephen; Shatil-Cohen, Arava; Yeselson, Yelena; Egbaria, Aiman; Kottapalli, Jayaram; Schaffer, Arthur A; Moshelion, Menachem; Granot, David

    2017-07-01

    Sugars affect central aspects of plant physiology, including photosynthesis, stomatal behavior and the loss of water through the stomata. Yet, the potential effects of sugars on plant aquaporins (AQPs) and water conductance have not been examined. We used database and transcriptional analyses, as well as cellular and whole-plant functional techniques to examine the link between sugar-related genes and AQPs. Database analyses revealed a high level of correlation between the expression of AQPs and that of sugar-related genes, including the Arabidopsis hexokinases 1 (AtHXK1). Increased expression of AtHXK1, as well as the addition of its primary substrate, glucose (Glc), repressed the expression of 10 AQPs from the plasma membrane-intrinsic proteins (PIP) subfamily (PIP-AQPs) and induced the expression of two stress-related PIP-AQPs. The osmotic water permeability of mesophyll protoplasts of AtHXK1-expressing plants and the leaf hydraulic conductance of those plants were significantly reduced, in line with the decreased expression of PIP-AQPs. Conversely, hxk1 mutants demonstrated a higher level of hydraulic conductance, with increased water potential in their leaves. In addition, the presence of Glc reduced leaf water potential, as compared with an osmotic control, indicating that Glc reduces the movement of water from the xylem into the mesophyll. The production of sugars entails a significant loss of water and these results suggest that sugars and AtHXK1 affect the expression of AQP genes and reduce leaf water conductance, to coordinate sugar levels with the loss of water through transpiration. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  3. Reduced methylation of the thromboxane synthase gene is correlated with its increased vascular expression in preeclampsia.

    Science.gov (United States)

    Mousa, Ahmad A; Strauss, Jerome F; Walsh, Scott W

    2012-06-01

    Preeclampsia is characterized by increased thromboxane and decreased prostacyclin levels, which predate symptoms, and can explain some of the clinical manifestations of preeclampsia, including hypertension and thrombosis. In this study, we examined DNA methylation of the promoter region of the thromboxane synthase gene (TBXAS1) and the expression of thromboxane synthase in systemic blood vessels of normal pregnant and preeclamptic women. Thromboxane synthase is responsible for the synthesis of thromboxane A(2), a potent vasoconstrictor and activator of platelets. We also examined the effect of experimentally induced DNA hypomethylation on the expression of thromboxane synthase in a neutrophil-like cell line (HL-60 cells) and in cultured vascular smooth muscle and endothelial cells. We found that DNA methylation of the TBXAS1 promoter was decreased and thromboxane synthase expression was increased in omental arteries of preeclamptic women as compared with normal pregnant women. Increased thromboxane synthase expression was observed in vascular smooth muscles cells, endothelial cells, and infiltrating neutrophils. Experimentally induced DNA hypomethylation only increased expression of thromboxane synthase in the neutrophil-like cell line, whereas tumor necrosis factor-α, a neutrophil product, increased its expression in cultured vascular smooth muscle cells. Our study suggests that epigenetic mechanisms and release of tumor necrosis factor-α by infiltrating neutrophils could contribute to the increased expression of thromboxane synthase in maternal systemic blood vessels, contributing to the hypertension and coagulation abnormalities associated with preeclampsia.

  4. Visual determinants of reduced performance on the Stroop color-word test in normal aging individuals.

    Science.gov (United States)

    van Boxtel, M P; ten Tusscher, M P; Metsemakers, J F; Willems, B; Jolles, J

    2001-10-01

    It is unknown to what extent the performance on the Stroop color-word test is affected by reduced visual function in older individuals. We tested the impact of common deficiencies in visual function (reduced distant and close acuity, reduced contrast sensitivity, and color weakness) on Stroop performance among 821 normal individuals aged 53 and older. After adjustment for age, sex, and educational level, low contrast sensitivity was associated with more time needed on card I (word naming), red/green color weakness with slower card 2 performance (color naming), and reduced distant acuity with slower performance on card 3 (interference). Half of the age-related variance in speed performance was shared with visual function. The actual impact of reduced visual function may be underestimated in this study when some of this age-related variance in Stroop performance is mediated by visual function decrements. It is suggested that reduced visual function has differential effects on Stroop performance which need to be accounted for when the Stroop test is used both in research and in clinical settings. Stroop performance measured from older individuals with unknown visual status should be interpreted with caution.

  5. Effects of Reducing the Cognitive Load of Mathematics Test Items on Student Performance

    Directory of Open Access Journals (Sweden)

    Susan C. Gillmor

    2015-01-01

    Full Text Available This study explores a new item-writing framework for improving the validity of math assessment items. The authors transfer insights from Cognitive Load Theory (CLT, traditionally used in instructional design, to educational measurement. Fifteen, multiple-choice math assessment items were modified using research-based strategies for reducing extraneous cognitive load. An experimental design with 222 middle-school students tested the effects of the reduced cognitive load items on student performance and anxiety. Significant findings confirm the main research hypothesis that reducing the cognitive load of math assessment items improves student performance. Three load-reducing item modifications are identified as particularly effective for reducing item difficulty: signalling important information, aesthetic item organization, and removing extraneous content. Load reduction was not shown to impact student anxiety. Implications for classroom assessment and future research are discussed.

  6. Ovarian hormone deprivation reduces oxytocin expression in Paraventricular Nucleus preautonomic neurons and correlates with baroreflex impairment in rats

    Directory of Open Access Journals (Sweden)

    Vitor Ulisses De Melo

    2016-10-01

    Full Text Available The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN. Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation.

  7. Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

    Directory of Open Access Journals (Sweden)

    Ma Jianjun

    2008-10-01

    Full Text Available Abstract Background NDRG2 (N-Myc downstream-regulated gene 2 was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. Methods In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40 and carcinomas (n = 35, along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. Results The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Conclusion Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.

  8. Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

    International Nuclear Information System (INIS)

    Zhao, Huadong; Chen, Suning; Lin, Wei; Shi, Hai; Ma, Jianjun; Liu, Xinping; Ma, Qingjiu; Yao, Libo; Zhang, Jian; Lu, Jianguo; He, Xianli; Chen, Changsheng; Li, Xiaojun; Gong, Li; Bao, Guoqiang; Fu, Qiang

    2008-01-01

    NDRG2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40) and carcinomas (n = 35), along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma

  9. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical & Analytical Sciences, University of the West of England, Faculty of Health and Applied Sciences, University of the West of England, Frenchay, Bristol BS16 1QY (United Kingdom); Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos [School of Cellular & Molecular Medicine, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD (United Kingdom)

    2015-09-17

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  10. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    David Qualtrough

    2015-09-01

    Full Text Available Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  11. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    Qualtrough, David; Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos

    2015-01-01

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer

  12. Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression.

    Science.gov (United States)

    DeSmet, Marsha L; Fleet, James C

    2017-10-01

    High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH) 2 D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH) 2 D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene. Young Adult Mouse Colon (YAMC) and Rat Intestinal Epithelial (RIE) cell lines with stable expression of mutant H-RAS had suppressed 1,25(OH) 2 D-mediated induction of CYP24A1 mRNA. The RAS effects were associated with lower Vitamin D receptor (VDR) mRNA and protein levels in YAMC and RIE cells and they could be partially reversed by VDR overexpression. RAS-mediated suppression of VDR levels was not due to either reduced VDR mRNA stability or increased VDR gene methylation. However, chromatin accessibility to the VDR gene at the proximal promoter (-300bp), an enhancer region at -6kb, and an enhancer region located in exon 3 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). These data show that constitutively active RAS signaling suppresses 1,25(OH) 2 D-mediated gene transcription in colon epithelial cells by reducing VDR gene transcription but the mechanism for this suppression is not yet known. These data suggest that cancers with RAS-activating mutations may be less responsive to vitamin D mediated treatment or chemoprevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    Energy Technology Data Exchange (ETDEWEB)

    Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

    2003-09-01

    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

  14. Antisense to the glucocorticoid receptor in hippocampal dentate gyrus reduces immobility in forced swim test

    NARCIS (Netherlands)

    Korte, S.M.; de Kloet, E.R.; Buwalda, B; Bouman, S.D.; Bohus, B

    1996-01-01

    Immobility time of rats in the forced swim test was reduced after bilateral infusion of an 18-mer antisense phosphorothioate oligodeoxynucleotide targeted to the glucocorticoid receptor mRNA into the dentate gyrus of the hippocampus. Vehicle-, sense- and scrambled sequence-treated animals spent

  15. How to save costs by reducing unnecessary testing: Lean thinking in clinical practice

    NARCIS (Netherlands)

    Vegting, I.L.; van Beneden, M.; Kramer, M.H.H.; Thijs, A.; Kostense, P.J.; Nanayakkara, P.W.B.

    2012-01-01

    Background: The burden of health care expenditure on national budgets has increased dramatically over the past decade. A pilot study in our hospital demonstrated that many unnecessary diagnostic tests were performed routinely. The aim of this study was to reduce the costs of unnecessary diagnostic

  16. Tuberculin skin testing in patients with HIV infection: limited benefit of reduced cutoff values

    NARCIS (Netherlands)

    Cobelens, Frank G.; Egwaga, Saidi M.; van Ginkel, Tessa; Muwinge, Hemed; Matee, Mecky I.; Borgdorff, Martien W.

    2006-01-01

    BACKGROUND: When determining eligibility for isoniazid preventive therapy of human immunodeficiency virus (HIV)-infected patients, the cutoff value of the tuberculin skin test (TST) is often reduced from an induration of 10 mm in diameter to one of 5 mm in diameter to compensate for loss of

  17. Comparison of Three Methods of Reducing Test Anxiety: Systematic Desensitization, Implosive Therapy, and Study Counseling

    Science.gov (United States)

    Cornish, Richard D.; Dilley, Josiah S.

    1973-01-01

    Systematic desensitization, implosive therapy, and study counseling have all been effective in reducing test anxiety. In addition, systematic desensitization has been compared to study counseling for effectiveness. This study compares all three methods and suggests that systematic desentization is more effective than the others, and that implosive…

  18. Rex3 (reduced in expression 3) as a new tumor marker in mouse hepatocarcinogenesis

    International Nuclear Information System (INIS)

    Braeuning, Albert; Jaworski, Maike; Schwarz, Michael; Koehle, Christoph

    2006-01-01

    In a previous microarray expression analysis, Rex3, a gene formerly not linked to tumor formation, was found to be highly overexpressed in both Ctnnb1-(β-Catenin) and Ha-ras-mutated mouse liver tumors. Subsequent analyses by in situ hybridization and real-time PCR confirmed a general liver tumor-specific overexpression of the gene (up to 400-fold). To investigate the role of Rex3 in liver tumors, hepatoma cells were transfected with FLAG- and Myc-tagged Rex3 expression vectors. Rex3 was shown to be exclusively localized to the cytoplasm, as determined by fluorescence microscopy and Western blotting. However, forced overexpression of Rex3 did not significantly affect proliferation or stress-induced apoptosis of transfected mouse hepatoma cells. Rex3 mRNA was determined in primary hepatocytes in culture by real-time PCR. In primary mouse hepatocytes, expression of Rex3 increased while cells dedifferentiated in culture. This effect was abolished when hepatocytes were maintained in a differentiated state. Furthermore, expression of Rex3 decreased in mouse liver with age of mice and the expression profile was highly correlated to that of the tumor markers α-fetoprotein and H19. The findings suggest a role of Rex3 as a marker for hepatocyte differentiation/dedifferentiation processes and tumor formation

  19. Reduced expression of exocytotic proteins caused by anti-cholinesterase pesticides in Brachionus calyciflorus (Rotifera: Monogononta

    Directory of Open Access Journals (Sweden)

    IA Pérez-Legaspi

    Full Text Available AbstractThe organophosphate and carbamate pesticides methyl-parathion and carbaryl have a common action mechanism: they inhibit acetylcholinesterase enzyme by blocking the transmission of nerve impulses. However, they can alter the expression of exocytotic membrane proteins (SNARE, by modifying release of neurotransmitters and other substances. This study evaluated the adverse effects of the pesticides methyl-parathion and carbaryl on expression of SNARE proteins: Syntaxin-1, Syntaxin-4 and SNAP-23 in freshwater rotifer Brachionus calyciflorus. Protein expression of these three proteins was analyzed before and after exposure to these two pesticides by Western Blot. The expression of Syntaxin-1, Syntaxin-4 and SNAP-23 proteins in B. calyciflorussignificantly decreases with increasing concentration of either pesticides. This suggests that organophosphates and carbamates have adverse effects on expression of membrane proteins of exocytosis by altering the recognition, docking and fusion of presynaptic and vesicular membranes involved in exocytosis of neurotransmitters. Our results demonstrate that the neurotoxic effect of anticholinesterase pesticides influences the interaction of syntaxins and SNAP-25 and the proper assembly of the SNARE complex.

  20. Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation.

    Science.gov (United States)

    Arnardottir, Erna S; Nikonova, Elena V; Shockley, Keith R; Podtelezhnikov, Alexei A; Anafi, Ron C; Tanis, Keith Q; Maislin, Greg; Stone, David J; Renger, John J; Winrow, Christopher J; Pack, Allan I

    2014-10-01

    To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation. Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 h of continuous wakefulness and subsequent recovery sleep, for a total of 19 time-points per subject, with every 2-h psychomotor vigilance task (PVT) assessment when awake. Sleep laboratory. Fourteen subjects who were previously identified as behaviorally resistant (n = 7) or sensitive (n = 7) to sleep deprivation by PVT. Thirty-eight hours of continuous wakefulness. We found 4,481 unique genes with a significant 24-h diurnal rhythm during a normal sleep-wake cycle in blood (false discovery rate [FDR] sleep. After accounting for circadian effects, two genes (SREBF1 and CPT1A, both involved in lipid metabolism) exhibited small, but significant, linear changes in expression with the duration of sleep deprivation (FDR sleep deprivation was a reduction in the amplitude of the diurnal rhythm of expression of normally cycling probe sets. This reduction was noticeably higher in behaviorally resistant subjects than sensitive subjects, at any given P value. Furthermore, blood cell type enrichment analysis showed that the expression pattern difference between sensitive and resistant subjects is mainly found in cells of myeloid origin, such as monocytes. Individual differences in behavioral effects of sleep deprivation are associated with differences in diurnal amplitude of gene expression for genes that show circadian rhythmicity. © 2014 Associated Professional Sleep Societies, LLC.

  1. Characterization of test specimens produced in reduced size for X-ray microtomography (µ-CT tests

    Directory of Open Access Journals (Sweden)

    E. E. BERNARDES

    Full Text Available Abstract The need to use reduced sample sizes, in order to attain improved spatial resolution in (µ-CT tests applied in Portland cement composites, makes researchers perform the fractionation of materials to obtain samples with dimensions compatible with the capacity of the scanning equipment, which might cause alterations in the microstructure under analysis. Therefore, a test specimen (TS with dimensions compatible with the scanning capacity of a microtomography system that operates with an X-ray tube and voltage ranging from 20 to 100 kV was proposed. Axial compression strength tests were made and their total porosity was assessed by an apparent density and solid fraction density ratio, which were obtained by means of mercury and helium pycnometry and µ-CT technique, respectively. The adoption of that TS has shown to be viable for providing a sample with a higher level of representation.

  2. mRNA-binding protein TIA-1 reduces cytokine expression in human endometrial stromal cells and is down-regulated in ectopic endometrium.

    Science.gov (United States)

    Karalok, Hakan Mete; Aydin, Ebru; Saglam, Ozlen; Torun, Aysenur; Guzeloglu-Kayisli, Ozlem; Lalioti, Maria D; Kristiansson, Helena; Duke, Cindy M P; Choe, Gina; Flannery, Clare; Kallen, Caleb B; Seli, Emre

    2014-12-01

    Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3'-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF-α, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL-6 or TNF-α expression in these cells. We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-α increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-α expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-α expression. Endometrial

  3. Finding differentially expressed genes in high dimensional data: Rank based test statistic via a distance measure.

    Science.gov (United States)

    Mathur, Sunil; Sadana, Ajit

    2015-12-01

    We present a rank-based test statistic for the identification of differentially expressed genes using a distance measure. The proposed test statistic is highly robust against extreme values and does not assume the distribution of parent population. Simulation studies show that the proposed test is more powerful than some of the commonly used methods, such as paired t-test, Wilcoxon signed rank test, and significance analysis of microarray (SAM) under certain non-normal distributions. The asymptotic distribution of the test statistic, and the p-value function are discussed. The application of proposed method is shown using a real-life data set. © The Author(s) 2011.

  4. Seismic tests on a reduced scale mock-up of a reprocessing plant cooling pond

    International Nuclear Information System (INIS)

    Queval, J.C.; Gantenbein, F.; Lebelle, M.

    1995-01-01

    In conjunction with COGEMA and SGN, CEA has launched an important research program to validate the reprocessing plant cooling pond calculation mainly for the effect of the racks on the fluid-pond interaction. The paper presents the tests performed on a reduced scale mock-up (scale 1/5). The tests are composed by: -random excitations at very low excitation level to measure the natural frequencies, especially the first sloshing mode frequency; -sinusoidal tests to measure the damping; -seismic tests performed with 3 different time reduction scales (1, 1/5, 1/√5) and 3 different synthetic accelerograms. Two types of simplified model with added masses and finite element model were developed. Comparisons of measured and calculated pressure fields against the panels will be presented. The measured frequencies, obtained during tests, are in good agreement with Housner's results. (authors). 2 refs., 4 figs., 5 tabs

  5. γ-Oryzanol reduces adhesion molecule expression in vascular endothelial cells via suppression of nuclear factor-κB activation.

    Science.gov (United States)

    Sakai, Satoshi; Murata, Takahisa; Tsubosaka, Yoshiki; Ushio, Hideki; Hori, Masatoshi; Ozaki, Hiroshi

    2012-04-04

    γ-Oryzanol (γ-ORZ) is a mixture of phytosteryl ferulates purified from rice bran oil. In this study, we examined whether γ-ORZ represents a suppressive effect on the lipopolysaccharide (LPS)-induced adhesion molecule expression on vascular endothelium. Treatment with LPS elevated the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in bovine aortic endothelial cells (BAECs). Pretreatment with γ-ORZ dose-dependently decreased the LPS-mediated expression of these genes. Western blotting also revealed that pretreatment with γ-ORZ dose-dependently inhibited LPS-induced VCAM-1 expression in human umbilical vein endothelial cells. Consistently, pretreatment with γ-ORZ dose-dependently reduced LPS-induced U937 monocyte adhesion to BAECs. In immunofluorescence, LPS caused nuclear factor-κB (NF-κB) nuclear translocation in 40% of BAECs, which indicates NF-κB activation. Pretreatment with γ-ORZ, as well as its components (cycloartenyl ferulate, ferulic acid, or cycloartenol), dose-dependently inhibited LPS-mediated NF-κB activation. Collectively, our results suggested that γ-ORZ reduced LPS-mediated adhesion molecule expression through NF-κB inhibition in vascular endothelium.

  6. HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.

    Science.gov (United States)

    Schloss, Jennifer; Ali, Riyasat; Racine, Jeremy J; Chapman, Harold D; Serreze, David V; DiLorenzo, Teresa P

    2018-04-09

    Type 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing β cells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with impaired immunological tolerance to insulin and increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared with littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, confirming that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, it will facilitate the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells, which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage by CD8 T cells, demonstrating that some TCR Vβ families have a preference for particular class I MHC alleles. Copyright © 2018 by The American Association of Immunologists, Inc.

  7. Evaluation of the performance of the reduced local lymph node assay for skin sensitization testing.

    Science.gov (United States)

    Ezendam, Janine; Muller, Andre; Hakkert, Betty C; van Loveren, Henk

    2013-06-01

    The local lymph node assay (LLNA) is the preferred method for classification of sensitizers within REACH. To reduce the number of mice for the identification of sensitizers the reduced LLNA was proposed, which uses only the high dose group of the LLNA. To evaluate the performance of this method for classification, LLNA data from REACH registrations were used and classification based on all dose groups was compared to classification based on the high dose group. We confirmed previous examinations of the reduced LLNA showing that this method is less sensitive compared to the LLNA. The reduced LLNA misclassified 3.3% of the sensitizers identified in the LLNA and misclassification occurred in all potency classes and that there was no clear association with irritant properties. It is therefore not possible to predict beforehand which substances might be misclassified. Another limitation of the reduced LLNA is that skin sensitizing potency cannot be assessed. For these reasons, it is not recommended to use the reduced LLNA as a stand-alone assay for skin sensitization testing within REACH. In the future, the reduced LLNA might be of added value in a weight of evidence approach to confirm negative results obtained with non-animal approaches. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Reduced Expression of HLA-DR on Monocytes During Severe Respiratory Syncytial Virus Infections

    NARCIS (Netherlands)

    Ahout, I.M.L.; Jans, J.; Haroutiounian, L.; Simonetti, E.R.; Gaast-de Jongh, C.E. van der; Diavatopoulos, D.A.; Jonge, M.I. de; Groot, R. de; Ferwerda, G.

    2016-01-01

    BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants with a wide spectrum of disease severity. Besides environmental and genetic factors, it is thought that the innate immune system plays a pivotal role. The aim of this study was to investigate the expression

  9. SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala

    Science.gov (United States)

    Sinai, Laleh; Duffy, Steven; Roder, John C.

    2010-01-01

    The Src protein tyrosine kinase plays a central role in the regulation of N-methyl-d-aspartate receptor (NMDAR) activity by regulating NMDAR subunit 2B (NR2B) surface expression. In the amygdala, NMDA-dependent synaptic plasticity resulting from convergent somatosensory and auditory inputs contributes to emotional memory; however, the role of Src…

  10. The Careful Puppet Master: Reducing risk and fortifying acceptance testing with Jenkins CI

    Science.gov (United States)

    Smith, Jason A.; Richman, Gabriel; DeStefano, John; Pryor, James; Rao, Tejas; Strecker-Kellogg, William; Wong, Tony

    2015-12-01

    Centralized configuration management, including the use of automation tools such as Puppet, can greatly increase provisioning speed and efficiency when configuring new systems or making changes to existing systems, reduce duplication of work, and improve automated processes. However, centralized management also brings with it a level of inherent risk: a single change in just one file can quickly be pushed out to thousands of computers and, if that change is not properly and thoroughly tested and contains an error, could result in catastrophic damage to many services, potentially bringing an entire computer facility offline. Change management procedures can—and should—be formalized in order to prevent such accidents. However, like the configuration management process itself, if such procedures are not automated, they can be difficult to enforce strictly. Therefore, to reduce the risk of merging potentially harmful changes into our production Puppet environment, we have created an automated testing system, which includes the Jenkins CI tool, to manage our Puppet testing process. This system includes the proposed changes and runs Puppet on a pool of dozens of RedHat Enterprise Virtualization (RHEV) virtual machines (VMs) that replicate most of our important production services for the purpose of testing. This paper describes our automated test system and how it hooks into our production approval process for automatic acceptance testing. All pending changes that have been pushed to production must pass this validation process before they can be approved and merged into production.

  11. Design and test of aircraft engine isolators for reduced interior noise

    Science.gov (United States)

    Unruh, J. F.; Scheidt, D. C.

    1982-01-01

    Improved engine vibration isolation was proposed to be the most weight and cost efficient retrofit structure-borne noise control measure for single engine general aviation aircraft. A study was carried out the objectives: (1) to develop an engine isolator design specification for reduced interior noise transmission, (2) select/design candidate isolators to meet a 15 dB noise reduction design goal, and (3) carry out a proof of concept evaluation test. Analytical model of the engine, vibration isolators and engine mount structure were coupled to an empirical model of the fuselage for noise transmission evaluation. The model was used to develop engine isolator dynamic properties design specification for reduced noise transmission. Candidate isolators ere chosen from available product literature and retrofit to a test aircraft. A laboratory based test procedure was then developed to simulate engine induced noise transmission in the aircraft for a proof of concept evaluation test. Three candidate isolator configurations were evaluated for reduced structure-borne noise transmission relative to the original equipment isolators.

  12. Opportunities and strategies to further reduce animal use for Leptospira vaccine potency testing.

    Science.gov (United States)

    Walker, A; Srinivas, G B

    2013-09-01

    Hamsters are routinely infected with virulent Leptospira for two purposes in the regulation of biologics: the performance of Codified potency tests and maintenance of challenge culture for the Codified potency tests. Options for reducing animal use in these processes were explored in a plenary lecture at the "International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the Way Forward" held at the Center for Veterinary Biologics in September 2012. The use of validated in vitro potency assays such as those developed by the U.S. Department of Agriculture for Leptospira (L.) canicola, Leptospira grippotyphosa, Leptospira pomona, and Leptospira icterohaemorrhagiae rather than the Codified hamster vaccination-challenge assay was encouraged. Alternatives such as reduced animal numbers in the hamster vaccination-challenge testing were considered for problematic situations. Specifically, the merits of sharing challenge controls, reducing group sizes, and eliminating animals for concurrent challenge dose titration were assessed. Options for maintaining virulent, stable cultures without serial passage through hamsters or with decreased hamster use were also discussed. The maintenance of virulent Leptospira without the use of live animals is especially difficult since a reliable means to maintain virulence after multiple in vitro passages has not yet been identified. Published by Elsevier Ltd.

  13. Proceedings of the 1988 International Meeting on Reduced Enrichment for Research and Test Reactors

    Energy Technology Data Exchange (ETDEWEB)

    1993-07-01

    The international effort to develop and implement new research reactor fuels utilizing low-enriched uranium, instead of highly- enriched uranium, continues to make solid progress. This effort is the cornerstone of a widely shared policy aimed at reducing, and possibly eliminating, international traffic in highly-enriched uranium and the nuclear weapon proliferation concerns associated with this traffic. To foster direct communication and exchange of ideas among the specialists in this area, the Reduced Enrichment Research and Test Reactor (RERTR) Program, at Argonne National Laboratory, sponsored this meeting as the eleventh of a series which began 1978. Individual papers presented at the meeting have been cataloged separately.

  14. Proceedings of the 1988 International Meeting on Reduced Enrichment for Research and Test Reactors

    International Nuclear Information System (INIS)

    1993-07-01

    The international effort to develop and implement new research reactor fuels utilizing low-enriched uranium, instead of highly- enriched uranium, continues to make solid progress. This effort is the cornerstone of a widely shared policy aimed at reducing, and possibly eliminating, international traffic in highly-enriched uranium and the nuclear weapon proliferation concerns associated with this traffic. To foster direct communication and exchange of ideas among the specialists in this area, the Reduced Enrichment Research and Test Reactor (RERTR) Program, at Argonne National Laboratory, sponsored this meeting as the eleventh of a series which began 1978. Individual papers presented at the meeting have been cataloged separately

  15. High expression of testes-specific protease 50 is associated with poor prognosis in colorectal carcinoma.

    Directory of Open Access Journals (Sweden)

    Lei Zheng

    Full Text Available BACKGROUND: Testes-specific protease 50 (TSP50 is normally expressed in testes and abnormally expressed in breast cancer, but whether TSP50 is expressed in colorectal carcinoma (CRC and its clinical significance is unclear. We aimed to detect TSP50 expression in CRC, correlate it with clinicopathological factors, and assess its potential diagnostic and prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: TSP50 mRNAs and proteins were detected in 7 CRC cell lines and 8 CRC specimens via RT-PCR and Western blot analysis. Immunohistochemical analysis of TSP50, p53 and carcinoembryonic antigen (CEA with tissue microarrays composed of 95 CRCs, 20 colorectal adenomas and 20 normal colorectal tissues were carried out and correlated with clinicopathological characteristics and disease-specific survival for CRC patients. There was no significant correlation between the expression levels of TSP50 and p53 (P = 0.751 or CEA (P = 0.663. Abundant expression of TSP50 protein was found in CRCs (68.4% while it was poorly expressed in colorectal adenomas and normal tissues (P<0.0001. Thus, CRCs can be distinguished from them with high specificity (92.5% and positive predictive value (PPV, 95.6%. The survival of CRC patients with high TSP50 expression was significantly shorter than that of the patients with low TSP50 expression (P = 0.010, specifically in patients who had early-stage tumors (stage I and II; P = 0.004. Multivariate Cox regression analysis indicated that high TSP50 expression was a statistically significant independent risk factor (hazard ratio  = 2.205, 95% CI = 1.214-4.004, P = 0.009. CONCLUSION: Our data demonstrate that TSP50 is a potential effective indicator of poor survival for CRC patients, especially for those with early-stage tumors.

  16. Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration.

    Science.gov (United States)

    Hatazawa, Yukino; Ono, Yusuke; Hirose, Yuma; Kanai, Sayaka; Fujii, Nobuharu L; Machida, Shuichi; Nishino, Ichizo; Shimizu, Takahiko; Okano, Masaki; Kamei, Yasutomi; Ogawa, Yoshihiro

    2018-03-01

    DNA methylation is an epigenetic mechanism regulating gene expression. In this study, we observed that DNA methyltransferase 3a (Dnmt3a) expression is decreased after muscle atrophy. We made skeletal muscle-specific Dnmt3a-knockout (Dnmt3a-KO) mice. The regeneration capacity after muscle injury was markedly decreased in Dnmt3a-KO mice. Diminished mRNA and protein expression of Dnmt3a were observed in skeletal muscles as well as in satellite cells, which are important for muscle regeneration, in Dnmt3a-KO mice. Dnmt3a-KO satellite cell showed smaller in size (length/area), suggesting suppressed myotube differentiation. Microarray analysis of satellite cells showed that expression of growth differentiation factor 5 (Gdf5) mRNA was markedly increased in Dnmt3a-KO mice. The DNA methylation level of the Gdf5 promoter was markedly decreased in Dnmt3a-KO satellite cells. In addition, DNA methylation inhibitor azacytidine treatment increased Gdf5 expression in wild-type satellite cells, suggesting Gdf5 expression is regulated by DNA methylation. Also, we observed increased inhibitor of differentiation (a target of Gdf5) mRNA expression in Dnmt3a-KO satellite cells. Thus, Dnmt3a appears to regulate satellite cell differentiation via DNA methylation. This mechanism may play a role in the decreased regeneration capacity during atrophy such as in aged sarcopenia.-Hatazawa, Y., Ono, Y., Hirose, Y., Kanai, S., Fujii, N. L., Machida, S., Nishino, I., Shimizu, T., Okano, M., Kamei, Y., Ogawa, Y. Reduced Dnmt3a increases Gdf5 expression with suppressed satellite cell differentiation and impaired skeletal muscle regeneration.

  17. Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease.

    Science.gov (United States)

    Santos, Rodrigo Ribeiro; Torres, Karen C; Lima, Giselle S; Fiamoncini, Carolina M; Mapa, Filipe C; Pereira, Patricia A; Rezende, Vitor B; Martins, Luiza C; Bicalho, Maria A; Moraes, Edgar N; Reis, Helton J; Teixeira, Antonio L; Romano-Silva, Marco A

    2014-01-03

    Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia. © 2013 Elsevier Inc. All rights reserved.

  18. β-Conglycinin Reduces the Tight Junction Occludin and ZO-1 Expression in IPEC-J2

    Directory of Open Access Journals (Sweden)

    Yuan Zhao

    2014-01-01

    Full Text Available Soybean allergy presents a health threat to humans and animals. The mechanism by which food/feed allergen β-conglycinin injures the intestinal barrier has not been well understood. In this study, the changes of epithelial permeability, integrity, metabolic activity, the tight junction (TJ distribution and expression induced by β-conglycinin were evaluated using IPEC-J2 model. The results showed a significant decrease of trans-epithelial electrical resistance (TEER (p < 0.001 and metabolic activity (p < 0.001 and a remarkable increase of alkaline phosphatase (AP activity (p < 0.001 in a dose-dependent manner. The expression levels of tight junction occludin and ZO-1 were decreased (p < 0.05. The reduced fluorescence of targets and change of cellular morphology were recorded. The tight junction occludin and ZO-1 mRNA expression linearly declined with increasing β-conglycinin (p < 0.001.

  19. Reducing patient identification errors related to glucose point-of-care testing

    Directory of Open Access Journals (Sweden)

    Gaurav Alreja

    2011-01-01

    Full Text Available Background: Patient identification (ID errors in point-of-care testing (POCT can cause test results to be transferred to the wrong patient′s chart or prevent results from being transmitted and reported. Despite the implementation of patient barcoding and ongoing operator training at our institution, patient ID errors still occur with glucose POCT. The aim of this study was to develop a solution to reduce identification errors with POCT. Materials and Methods: Glucose POCT was performed by approximately 2,400 clinical operators throughout our health system. Patients are identified by scanning in wristband barcodes or by manual data entry using portable glucose meters. Meters are docked to upload data to a database server which then transmits data to any medical record matching the financial number of the test result. With a new model, meters connect to an interface manager where the patient ID (a nine-digit account number is checked against patient registration data from admission, discharge, and transfer (ADT feeds and only matched results are transferred to the patient′s electronic medical record. With the new process, the patient ID is checked prior to testing, and testing is prevented until ID errors are resolved. Results: When averaged over a period of a month, ID errors were reduced to 3 errors/month (0.015% in comparison with 61.5 errors/month (0.319% before implementing the new meters. Conclusion: Patient ID errors may occur with glucose POCT despite patient barcoding. The verification of patient identification should ideally take place at the bedside before testing occurs so that the errors can be addressed in real time. The introduction of an ADT feed directly to glucose meters reduced patient ID errors in POCT.

  20. Testes and brain gene expression in precocious male and adult maturing Atlantic salmon (Salmo salar

    Directory of Open Access Journals (Sweden)

    Houeix Benoit

    2010-03-01

    Full Text Available Abstract Background The male Atlantic salmon generally matures in fresh water upon returning after one or several years at sea. Some fast-growing male parr develop an alternative life strategy where they sexually mature before migrating to the oceans. These so called 'precocious' parr or 'sneakers' can successfully fertilise adult female eggs and so perpetuate their line. We have used a custom-built cDNA microarray to investigate gene expression changes occurring in the salmon gonad and brain associated with precocious maturation. The microarray has been populated with genes selected specifically for involvement in sexual maturation (precocious and adult and in the parr-smolt transformation. Results Immature and mature parr collected from a hatchery-reared stock in January were significantly different in weight, length and condition factor. Changes in brain expression were small - never more than 2-fold on the microarray, and down-regulation of genes was much more pronounced than up-regulation. Significantly changing genes included isotocin, vasotocin, cathepsin D, anamorsin and apolipoprotein E. Much greater changes in expression were seen in the testes. Among those genes in the testis with the most significant changes in expression were anti-Mullerian hormone, collagen 1A, and zinc finger protein (Zic1, which were down-regulated in precocity and apolipoproteins E and C-1, lipoprotein lipase and anti-leukoproteinase precursor which were up-regulated in precocity. Expression changes of several genes were confirmed in individual fish by quantitative PCR and several genes (anti-Mullerian hormone, collagen 1A, beta-globin and guanine nucleotide binding protein (G protein beta polypeptide 2-like 1 (GNB2L1 were also examined in adult maturing testes. Down-regulation of anti-Mullerian hormone was judged to be greater than 160-fold for precocious males and greater than 230-fold for November adult testes in comparison to July testes by this method. For

  1. Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Stavri, Simona; Trusca, Violeta G.; Simionescu, Maya; Gafencu, Anca V., E-mail: anca.gafencu@icbp.ro

    2015-05-29

    The atheroprotective role of macrophage-derived apolipoprotein E (apoE) is well known. Our previous reports demonstrated that inflammatory stress down-regulates apoE expression in macrophages, aggravating atherogenesis. Metformin, extensively used as an anti-diabetic drug, has also anti-inflammatory properties, and thus confers vascular protection. In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress. The results showed that metformin slightly increases the apoE expression only at high doses (5–10 mM). Low doses of metformin (1–3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages. Our experiments demonstrated that LPS-induced NF-κB binds to the macrophage-specific distal regulatory element of apoE gene, namely to the multienhancer 2 (ME.2) and its 5′-deletion fragments. The NF-κB binding on ME.2 and apoE promoter has a down-regulatory effect. In addition, data revealed that metformin impairs NF-κB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress. The positive effect of metformin in the inflammatory states, its clinical safety and low cost, make this drug a potential adjuvant in the therapeutic strategies for atherosclerosis. - Highlights: • High doses of metformin slightly increase apoE expression in macrophages. • Low doses of metformin up-regulate apoE gene in endotoxin-stressed macrophages. • Metformin reduces the negative effect of LPS on apoE expression by NF-κB inhibition.

  2. Osteoblast CFTR inactivation reduces differentiation and osteoprotegerin expression in a mouse model of cystic fibrosis-related bone disease.

    Directory of Open Access Journals (Sweden)

    Michael S Stalvey

    Full Text Available Low bone mass and increased fracture risk are recognized complications of cystic fibrosis (CF. CF-related bone disease (CFBD is characterized by uncoupled bone turnover--impaired osteoblastic bone formation and enhanced osteoclastic bone resorption. Intestinal malabsorption, vitamin D deficiency and inflammatory cytokines contribute to CFBD. However, epidemiological investigations and animal models also support a direct causal link between inactivation of skeletal cystic fibrosis transmembrane regulator (CFTR, the gene that when mutated causes CF, and CFBD. The objective of this study was to examine the direct actions of CFTR on bone. Expression analyses revealed that CFTR mRNA and protein were expressed in murine osteoblasts, but not in osteoclasts. Functional studies were then performed to investigate the direct actions of CFTR on osteoblasts using a CFTR knockout (Cftr-/- mouse model. In the murine calvarial organ culture assay, Cftr-/- calvariae displayed significantly less bone formation and osteoblast numbers than calvariae harvested from wildtype (Cftr+/+ littermates. CFTR inactivation also reduced alkaline phosphatase expression in cultured murine calvarial osteoblasts. Although CFTR was not expressed in murine osteoclasts, significantly more osteoclasts formed in Cftr-/- compared to Cftr+/+ bone marrow cultures. Indirect regulation of osteoclastogenesis by the osteoblast through RANK/RANKL/OPG signaling was next examined. Although no difference in receptor activator of NF-κB ligand (Rankl mRNA was detected, significantly less osteoprotegerin (Opg was expressed in Cftr-/- compared to Cftr+/+ osteoblasts. Together, the Rankl:Opg ratio was significantly higher in Cftr-/- murine calvarial osteoblasts contributing to a higher osteoclastogenesis potential. The combined findings of reduced osteoblast differentiation and lower Opg expression suggested a possible defect in canonical Wnt signaling. In fact, Wnt3a and PTH-stimulated canonical Wnt

  3. Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages

    International Nuclear Information System (INIS)

    Stavri, Simona; Trusca, Violeta G.; Simionescu, Maya; Gafencu, Anca V.

    2015-01-01

    The atheroprotective role of macrophage-derived apolipoprotein E (apoE) is well known. Our previous reports demonstrated that inflammatory stress down-regulates apoE expression in macrophages, aggravating atherogenesis. Metformin, extensively used as an anti-diabetic drug, has also anti-inflammatory properties, and thus confers vascular protection. In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress. The results showed that metformin slightly increases the apoE expression only at high doses (5–10 mM). Low doses of metformin (1–3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages. Our experiments demonstrated that LPS-induced NF-κB binds to the macrophage-specific distal regulatory element of apoE gene, namely to the multienhancer 2 (ME.2) and its 5′-deletion fragments. The NF-κB binding on ME.2 and apoE promoter has a down-regulatory effect. In addition, data revealed that metformin impairs NF-κB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress. The positive effect of metformin in the inflammatory states, its clinical safety and low cost, make this drug a potential adjuvant in the therapeutic strategies for atherosclerosis. - Highlights: • High doses of metformin slightly increase apoE expression in macrophages. • Low doses of metformin up-regulate apoE gene in endotoxin-stressed macrophages. • Metformin reduces the negative effect of LPS on apoE expression by NF-κB inhibition

  4. Assisted Reproduction Causes Reduced Fetal Growth Associated with Downregulation of Paternally Expressed Imprinted Genes That Enhance Fetal Growth in Mice.

    Science.gov (United States)

    Li, Bo; Chen, Shuqiang; Tang, Na; Xiao, Xifeng; Huang, Jianlei; Jiang, Feng; Huang, Xiuying; Sun, Fangzhen; Wang, Xiaohong

    2016-02-01

    Alteration of intrauterine growth trajectory is linked to metabolic diseases in adulthood. In mammalian and, specifically, human species, pregnancies through assisted reproductive technology (ART) are associated with changes in intrauterine growth trajectory. However, it is still unclear how ART alters intrauterine growth trajectory, especially reduced fetal growth in early to midgestation. In this study, using a mouse model, it was found that ART procedures reduce fetal and placental growth at Embryonic Day 10.5. Furthermore, ART leads to decreased methylation levels at H19, KvDMR1, and Snrpn imprinting control regions in the placentae, instead of fetuses. Furthermore, in the placenta, ART downregulated a majority of parentally expressed imprinted genes, which enhance fetal growth, whereas it upregulated a majority of maternally expressed genes which repress fetal growth. Additionally, the expression of genes that regulate placental development was also affected by ART. ART also downregulated a majority of placental nutrient transporters. Disruption of genomic imprinting and abnormal expression of developmentally and functionally relevant genes in placenta may influence the placental development and function, which affect fetal growth and reprogramming. © 2016 by the Society for the Study of Reproduction, Inc.

  5. Gibberellic acid alleviates cadmium toxicity by reducing nitric oxide accumulation and expression of IRT1 in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Zhu, Xiao Fang; Jiang, Tao; Wang, Zhi Wei; Lei, Gui Jie; Shi, Yuan Zhi; Li, Gui Xin; Zheng, Shao Jian

    2012-01-01

    Highlights: ► Cd reduces endogenous GA levels in Arabidopsis. ► GA exogenous applied decreases Cd accumulation in plant. ► GA suppresses the Cd-induced accumulation of NO. ► Decreased NO level downregulates the expression of IRT1. ► Suppressed IRT1 expression reduces Cd transport across plasma membrane. - Abstract: Gibberellic acid (GA) is involved in not only plant growth and development but also plant responses to abiotic stresses. Here it was found that treating the plants with GA concentrations from 0.1 to 5 μM for 24 h had no obvious effect on root elongation in the absence of cadmium (Cd), whereas in the presence of Cd 2+ , GA at 5 μM improved root growth, reduced Cd content and lipid peroxidation in the roots, indicating that GA can partially alleviate Cd toxicity. Cd 2+ increased nitric oxide (NO) accumulation in the roots, but GA remarkably reduced it, and suppressed the up-regulation of the expression of IRT1. In contrary, the beneficial effect of GA on alleviating Cd toxicity was not observed in an IRT1 knock-out mutant irt1, suggesting the involvement of IRT1 in Cd 2+ absorption. Furthermore, the GA-induced reduction of NO and Cd content can also be partially reversed by the application of a NO donor (S-nitrosoglutathione [GSNO]). Taken all these together, the results showed that GA-alleviated Cd toxicity is mediated through the reduction of the Cd-dependent NO accumulation and expression of Cd 2+ uptake related gene-IRT1 in Arabidopsis.

  6. Gibberellic acid alleviates cadmium toxicity by reducing nitric oxide accumulation and expression of IRT1 in Arabidopsis thaliana

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Xiao Fang [State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Jiang, Tao [Key Laboratory of Conservation Biology for Endangered Wildlife of the Ministry of Education, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Wang, Zhi Wei [State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Lei, Gui Jie [Key Laboratory of Conservation Biology for Endangered Wildlife of the Ministry of Education, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Shi, Yuan Zhi [The Key Laboratory of Tea Chemical Engineering, Ministry of Agriculture, Yunqi Road 1, Hangzhou 310008 (China); Li, Gui Xin, E-mail: guixinli@zju.edu.cn [College of Agronomy and Biotechnology, Zhejiang University, Hangzhou 310058 (China); Zheng, Shao Jian [State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Key Laboratory of Conservation Biology for Endangered Wildlife of the Ministry of Education, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China)

    2012-11-15

    Highlights: Black-Right-Pointing-Pointer Cd reduces endogenous GA levels in Arabidopsis. Black-Right-Pointing-Pointer GA exogenous applied decreases Cd accumulation in plant. Black-Right-Pointing-Pointer GA suppresses the Cd-induced accumulation of NO. Black-Right-Pointing-Pointer Decreased NO level downregulates the expression of IRT1. Black-Right-Pointing-Pointer Suppressed IRT1 expression reduces Cd transport across plasma membrane. - Abstract: Gibberellic acid (GA) is involved in not only plant growth and development but also plant responses to abiotic stresses. Here it was found that treating the plants with GA concentrations from 0.1 to 5 {mu}M for 24 h had no obvious effect on root elongation in the absence of cadmium (Cd), whereas in the presence of Cd{sup 2+}, GA at 5 {mu}M improved root growth, reduced Cd content and lipid peroxidation in the roots, indicating that GA can partially alleviate Cd toxicity. Cd{sup 2+} increased nitric oxide (NO) accumulation in the roots, but GA remarkably reduced it, and suppressed the up-regulation of the expression of IRT1. In contrary, the beneficial effect of GA on alleviating Cd toxicity was not observed in an IRT1 knock-out mutant irt1, suggesting the involvement of IRT1 in Cd{sup 2+} absorption. Furthermore, the GA-induced reduction of NO and Cd content can also be partially reversed by the application of a NO donor (S-nitrosoglutathione [GSNO]). Taken all these together, the results showed that GA-alleviated Cd toxicity is mediated through the reduction of the Cd-dependent NO accumulation and expression of Cd{sup 2+} uptake related gene-IRT1 in Arabidopsis.

  7. A computational environment for creating and testing reduced chemical kinetic mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, C.J.; Swensen, D.A.; Harding, T.V.; Cremer, M.A.; Bockelie, M.J. [Reaction Engineering International, Salt Lake City, UT (USA)

    2002-02-01

    This paper describes software called computer assisted reduced mechanism problem solving environment (CARM-PSE) that gives the engineer the ability to rapidly set up, run and examine large numbers of problems comparing detailed and reduced (approximate) chemistry. CARM-PSE integrates the automatic chemical mechanism reduction code CARM and the codes that simulate perfectly stirred reactors and plug flow reactors into a user-friendly computational environment. CARM-PSE gives the combustion engineer the ability to easily test chemical approximations over many hundreds of combinations of inputs in a multidimensional parameter space. The demonstration problems compare detailed and reduced chemical kinetic calculations for methane-air combustion, including nitrogen oxide formation, in a stirred reactor and selective non-catalytic reduction of NOx, in coal combustion flue gas.

  8. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption

    OpenAIRE

    Atar Herziger; Amel Benzerga; Jana Berkessel; Niken L. Dinartika; Matija Franklin; Kamilla K. Steinnes; Felicia Sundström

    2017-01-01

    Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing soc...

  9. Generation of transgenic cattle expressing human β-defensin 3 as an approach to reducing susceptibility to Mycobacterium bovis infection.

    Science.gov (United States)

    Su, Feng; Wang, Yongsheng; Liu, Guanghui; Ru, Kun; Liu, Xin; Yu, Yuan; Liu, Jun; Wu, Yongyan; Quan, Fusheng; Guo, Zekun; Zhang, Yong

    2016-03-01

    Bovine tuberculosis results from infection with Mycobacterium bovis, a member of the Mycobacterium tuberculosis family. Worldwide, M. bovis infections result in economic losses in the livestock industry; cattle production is especially hard-hit by this disease. Generating M. bovis-resistant cattle may potentially mitigate the impact of this disease by reducing M. bovis infections. In this study, we used transgenic somatic cell nuclear transfer to generate cattle expressing the gene encoding human β-defensin 3 (HBD3), which confers resistance to mycobacteria in vitro. We first generated alveolar epithelial cells expressing HBD3 under the control of the bovine MUC1 promoter, and confirmed that these cells secreted HBD3 and possessed anti-mycobacterial capacity. We then generated and identified transgenic cattle by somatic cell nuclear transfer. The cleavage and blastocyst formation rates of genetically modified embryos provided evidence that monoclonal transgenic bovine fetal fibroblast cells have an integral reprogramming ability that is similar to that of normal cells. Five genetically modified cows were generated, and their anti-mycobacterial capacities were evaluated. Alveolar epithelial cells and macrophages from these cattle expressed higher levels of HBD3 protein compared with non-transgenic cells and possessed effective anti-mycobacterial capacity. These results suggest that the overall risk of M. bovis infection in transgenic cattle is efficiently reduced, and support the development of genetically modified animals as an effective tool to reduce M. bovis infection. © 2016 Federation of European Biochemical Societies.

  10. Abrogation of epithelial BMP2 and BMP4 causes Amelogenesis Imperfecta by reducing MMP20 and KLK4 expression.

    Science.gov (United States)

    Xie, Xiaohua; Liu, Chao; Zhang, Hua; Jani, Priyam H; Lu, Yongbo; Wang, Xiaofang; Zhang, Bin; Qin, Chunlin

    2016-05-05

    Amelogenesis Imperfecta (AI) can be caused by the deficiencies of enamel matrix proteins, molecules responsible for the transportation and secretion of enamel matrix components, and proteases processing enamel matrix proteins. In the present study, we discovered the double deletion of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic protein 4 (Bmp4) in the dental epithelium by K14-cre resulted in hypoplastic enamel and reduced density in X-ray radiography as well as shortened enamel rods under scanning electron microscopy. Such enamel phenotype was consistent with the diagnosis of hypoplastic amelogenesis imperfecta. Histological and molecular analyses revealed that the removal of matrix proteins in the mutant enamel was drastically delayed, which was coincided with the greatly reduced expression of matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4). Although the expression of multiple enamel matrix proteins was down-regulated in the mutant ameloblasts, the cleavage of ameloblastin was drastically impaired. Therefore, we attributed the AI primarily to the reduction of MMP20 and KLK4. Further investigation found that BMP/Smad4 signaling pathway was down-regulated in the K14-cre;Bmp2(f/f);Bmp4(f/f)ameloblasts, suggesting that the reduced MMP20 and KLK4 expression may be due to the attenuated epithelial BMP/Smad4 signaling.

  11. Reduced DICER1 Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Properties and Resistance to Apoptotic Stimuli.

    Science.gov (United States)

    Alsaleh, Ghada; Nehmar, Ramzi; Blüml, Stephan; Schleiss, Cédric; Ostermann, Eleonore; Dillenseger, Jean-Philippe; Sayeh, Amira; Choquet, Philippe; Dembele, Doulaye; Francois, Antoine; Salmon, Jean-Hugues; Paul, Nicodème; Schabbauer, Gernot; Bierry, Guillaume; Meyer, Alain; Gottenberg, Jacques-Eric; Haas, Gabrielle; Pfeffer, Sebastien; Vallat, Laurent; Sibilia, Jean; Bahram, Seiamak; Georgel, Philippe

    2016-08-01

    While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ). The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme-linked immunosorbent assay. We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli. The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses. © 2016, American College of Rheumatology.

  12. Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity

    Directory of Open Access Journals (Sweden)

    Peter W. Lindinger

    2015-09-01

    Full Text Available Obesity is associated with impaired mitochondrial function. This study compares mitochondrial protein expression in omental fat in obese and non-obese humans. Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass-spectrometry, 128 proteins with potentially different abundances in patient groups were identified, 62 of the 128 proteins are mainly localized in the mitochondria. Further quantification of 12 of these 62 proteins by immune dot blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin being inversely associated with BMI, and mitofilin being inversely correlated with gender.

  13. Reduced gene expression levels after chronic exposure to high concentrations of air pollutants

    Czech Academy of Sciences Publication Activity Database

    Rössner ml., Pavel; Tulupová, Elena; Rössnerová, Andrea; Líbalová, Helena; Hoňková, Kateřina; Gmuender, H.; Pastorková, Anna; Švecová, Vlasta; Topinka, Jan; Šrám, Radim

    2015-01-01

    Roč. 780, oct (2015), s. 60-70 ISSN 0027-5107 R&D Projects: GA MŽP(CZ) SP/1B3/8/08; GA MŠk(CZ) LO1508; GA ČR GA13-13458S; GA MŠk 2B08005 Institutional support: RVO:68378041 Keywords : chronic exposure * air pollution * gene expression profiles * human health * particulate matter * polycyclic aromatic hydrocarbons Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.581, year: 2015

  14. Important mitochondrial proteins in human omental adipose tissue show reduced expression in obesity.

    Science.gov (United States)

    Lindinger, Peter W; Christe, Martine; Eberle, Alex N; Kern, Beatrice; Peterli, Ralph; Peters, Thomas; Jayawardene, Kamburapola J I; Fearnley, Ian M; Walker, John E

    2015-09-01

    Obesity is associated with impaired mitochondrial function. This study compares mitochondrial protein expression in omental fat in obese and non-obese humans. Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass-spectrometry, 128 proteins with potentially different abundances in patient groups were identified, 62 of the 128 proteins are mainly localized in the mitochondria. Further quantification of 12 of these 62 proteins by immune dot blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin being inversely associated with BMI, and mitofilin being inversely correlated with gender.

  15. Reduced expression of ASS is closely related to clinicopathological features and post-resectional survival of hepatocellular carcinoma.

    Science.gov (United States)

    Yang, Hua; Lin, Ming; Xiong, Fu Xia; Yang, Yu; Nie, Xiu; Zhou, Rou Li

    2010-01-01

    Argininosuccinate synthetase (ASS) has previously been proven to be reductively expressed in hepatocellular carcinoma (HCC) and various types of HCC cell lines. Arginine, the product of ASS, has been used as a target in HCC by recombinant human arginase or arginine deiminase, which is now in the phase II clinical trial stage. This study aimed to present the levels of ASS expression in HCCs and its correlation with clinicopathological features and prognosis of HCC patients. Immunohistochemical detection of ASS was performed on samples from 71 patients with HCC. Positive staining was found in 21 HCCs, with a score of 2, as well as in normal liver tissues. Reduced ASS staining was found in 70.4% (50/71) of HCC tissues, including 21 with a score of 0 and 29 with a score of 1. The staining score in cancer tissues was significantly associated with gender, background liver, histopathological differentiation, recurrence, TNM staging and portal vein invasion (PASS expression had significantly poorer overall and disease-free survival (PASS was reductively or negatively expressed in a large portion of HCC, and that ASS levels in HCCs correlated inversely with prognosis. In conclusion, a high expression of ASS may be a novel marker of poor prognosis of patients presenting with HCC.

  16. Matrix attachment regions (MARs) enhance transformation frequencies and reduce variance of transgene expression in barley

    DEFF Research Database (Denmark)

    Petersen, K.; Leah, R.; Knudsen, S.

    2002-01-01

    -MAR from petunia revealed that only the P1-MAR had specific binding affinity for barley nuclear matrices. The barley transformation frequency with the uidA reporter gene was increased 2-fold when the gene was flanked with either the P1-MAR or TBS-MAR, while the gene copy number was strongly reduced...

  17. A new efficient statistical test for detecting variability in the gene expression data.

    Science.gov (United States)

    Mathur, Sunil; Dolo, Samuel

    2008-08-01

    DNA microarray technology allows researchers to monitor the expressions of thousands of genes under different conditions. The detection of differential gene expression under two different conditions is very important in microarray studies. Microarray experiments are multi-step procedures and each step is a potential source of variance. This makes the measurement of variability difficult because approach based on gene-by-gene estimation of variance will have few degrees of freedom. It is highly possible that the assumption of equal variance for all the expression levels may not hold. Also, the assumption of normality of gene expressions may not hold. Thus it is essential to have a statistical procedure which is not based on the normality assumption and also it can detect genes with differential variance efficiently. The detection of differential gene expression variance will allow us to identify experimental variables that affect different biological processes and accuracy of DNA microarray measurements.In this article, a new nonparametric test for scale is developed based on the arctangent of the ratio of two expression levels. Most of the tests available in literature require the assumption of normal distribution, which makes them inapplicable in many situations, and it is also hard to verify the suitability of the normal distribution assumption for the given data set. The proposed test does not require the assumption of the distribution for the underlying population and hence makes it more practical and widely applicable. The asymptotic relative efficiency is calculated under different distributions, which show that the proposed test is very powerful when the assumption of normality breaks down. Monte Carlo simulation studies are performed to compare the power of the proposed test with some of the existing procedures. It is found that the proposed test is more powerful than commonly used tests under almost all the distributions considered in the study. A

  18. Phenotypical expression of reduced mobility during limb ontogeny in frogs: the knee-joint case

    Directory of Open Access Journals (Sweden)

    Maria Laura Ponssa

    2016-02-01

    Full Text Available Movement is one of the most important epigenetic factors for normal development of the musculoskeletal system, particularly during genesis and joint development. Studies regarding alterations to embryonic mobility, performed on anurans, chickens and mammals, report important phenotypical similarities as a result of the reduction or absence of this stimulus. The precise stage of development at which the stimulus modification generates phenotypic modifications however, is yet to be determined. In this work we explore whether the developmental effects of abnormal mobility can appear at any time during development or whether they begin to express themselves in particular phases of tadpole ontogeny. We conducted five experiments that showed that morphological abnormalities are not visible until Stages 40–42. Morphology in earlier stages remains normal, probably due to the fact that the bones/muscles/tendons have not yet developed and therefore are not affected by immobilization. These results suggest the existence of a specific period of phenotypical expression in which normal limb movement is necessary for the correct development of the joint tissue framework.

  19. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression

    International Nuclear Information System (INIS)

    Pinton, Philippe; Nougayrede, Jean-Philippe; Del Rio, Juan-Carlos; Moreno, Carolina; Marin, Daniela E.; Ferrier, Laurent; Bracarense, Ana-Paula; Kolf-Clauw, Martine; Oswald, Isabelle P.

    2009-01-01

    'The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health.

  20. Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression.

    Science.gov (United States)

    Hinds, Terry D; Peck, Bailey; Shek, Evan; Stroup, Steven; Hinson, Jennifer; Arthur, Susan; Marino, Joseph S

    2016-02-11

    Unlike the glucocorticoid receptor α (GRα), GR β (GRβ) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C₂C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C₂C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

  1. Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression

    Directory of Open Access Journals (Sweden)

    Terry D. Hinds

    2016-02-01

    Full Text Available Unlike the glucocorticoid receptor α (GRα, GR β (GRβ has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx and muscle ring finger 1 (MuRF1 response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

  2. Reduced Enrichment for Research and Test Reactors. Proceedings of the XIV international meeting

    Energy Technology Data Exchange (ETDEWEB)

    Suripto, Asmedi; Hastowo, Hudi; Hersubeno, J B [eds.

    1995-07-01

    Apart from the progress of the Reduced Enrichment Research and Test Reactor (RERTR) Program the national programs of Indonesia, Japan and China were presented. The major events, findings, and activities of 1991 are reviewed with a brief summary of the results which the RERTR Program had achieved by the end of 1990 in collaboration with its many international partners. The RERTR program, has concentrated its efforts on technology transfer and implementation activities consistent with the guidance received from the Department of Energy at the end of 1990. A number of presentations were devoted to development of new fuel uranium silicide fuel elements, fuel irradiation testing and reactor core conversions from highly enriched (HEU) to slightly enriched uranium (LEU). Calculations and measurements of converted reactor core parameters were shown related to safety test and analysis. Fuel cycle issue were discussed as well. One should note that a significant number of papers were devoted to Indonesian GA SIWABESSY reactor core conversion and related topics.

  3. Testing increases suggestibility for narrative-based misinformation but reduces suggestibility for question-based misinformation.

    Science.gov (United States)

    LaPaglia, Jessica A; Chan, Jason C K

    2013-01-01

    A number of recent studies have found that recalling details of an event following its occurrence can increase people's suggestibility to later presented misinformation. However, several other studies have reported the opposite result, whereby earlier retrieval can reduce subsequent eyewitness suggestibility. In the present study, we investigated whether differences in the way misinformation is presented can modulate the effects of testing on suggestibility. Participants watched a video of a robbery and some were questioned about the event immediately afterwards. Later, participants were exposed to misinformation in a narrative (Experiment 1) or in questions (Experiment 2). Consistent with previous studies, we found that testing increased suggestibility when misinformation was presented via a narrative. Remarkably, when misinformation was presented in questions, testing decreased suggestibility. Copyright © 2013 John Wiley & Sons, Ltd.

  4. Reduced Enrichment for Research and Test Reactors. Proceedings of the XIV international meeting

    International Nuclear Information System (INIS)

    Suripto, Asmedi; Hastowo, Hudi; Hersubeno, J.B.

    1995-01-01

    Apart from the progress of the Reduced Enrichment Research and Test Reactor (RERTR) Program the national programs of Indonesia, Japan and China were presented. The major events, findings, and activities of 1991 are reviewed with a brief summary of the results which the RERTR Program had achieved by the end of 1990 in collaboration with its many international partners. The RERTR program, has concentrated its efforts on technology transfer and implementation activities consistent with the guidance received from the Department of Energy at the end of 1990. A number of presentations were devoted to development of new fuel uranium silicide fuel elements, fuel irradiation testing and reactor core conversions from highly enriched (HEU) to slightly enriched uranium (LEU). Calculations and measurements of converted reactor core parameters were shown related to safety test and analysis. Fuel cycle issue were discussed as well. One should note that a significant number of papers were devoted to Indonesian GA SIWABESSY reactor core conversion and related topics

  5. A unique laboratory test rig reduces the need for offshore tests to combat calcium naphthenate deposition in oilfield process equipment.

    Energy Technology Data Exchange (ETDEWEB)

    Mediaas, Heidi; Grande, Knut; Hustad, Britt-Marie; Hoevik, Kim Reidar; Kummernes, Hege; Nergaard, Bjoern; Vindstad, Jens Emil

    2006-03-15

    Producing and refining high-TAN crude oils introduces a number of challenges, among which calcium naphthenate deposition in process facilities is the most serious production issue. Until recently, the only option for studying chemicals and process parameters in order to prevent naphthenate deposition has been field tests. Statoil has now developed a small scale pilot plant where these experiments can be performed in the laboratory at Statoil's Research and Technology Center in Trondheim, Norway. The results from the pilot plant are in full agreement with the extensive naphthenate experience obtained from almost 9 years operation of the Heidrun oilfield. The design and operational procedures for this test facility are based on the recent discovery by Statoil and ConocoPhillips of the ARN acid. The ARN acid is a prerequisite for calcium naphthenate deposition. The new continuous flow pilot plant, the Naphthenate Rig, is used to develop new environmental friendly naphthenate inhibitors and to optimize process operating conditions. Since it operates on real crudes the need for field tests in qualifying new naphthenate inhibitors is reduced. To the best of our knowledge, the rig is the first of its kind in the world. (Author)

  6. GSMA: Gene Set Matrix Analysis, An Automated Method for Rapid Hypothesis Testing of Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Chris Cheadle

    2007-01-01

    Full Text Available Background: Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. The assignment of functional information to these complex patterns remains a challenging task in effectively interpreting data and correlating results from across experiments, projects and laboratories. Methods which allow the rapid and robust evaluation of multiple functional hypotheses increase the power of individual researchers to data mine gene expression data more efficiently.Results: We have developed (gene set matrix analysis GSMA as a useful method for the rapid testing of group-wise up- or downregulation of gene expression simultaneously for multiple lists of genes (gene sets against entire distributions of gene expression changes (datasets for single or multiple experiments. The utility of GSMA lies in its flexibility to rapidly poll gene sets related by known biological function or as designated solely by the end-user against large numbers of datasets simultaneously.Conclusions: GSMA provides a simple and straightforward method for hypothesis testing in which genes are tested by groups across multiple datasets for patterns of expression enrichment.

  7. Autism: reduced connectivity between cortical areas involved in face expression, theory of mind, and the sense of self.

    Science.gov (United States)

    Cheng, Wei; Rolls, Edmund T; Gu, Huaguang; Zhang, Jie; Feng, Jianfeng

    2015-05-01

    Whole-brain voxel-based unbiased resting state functional connectivity was analysed in 418 subjects with autism and 509 matched typically developing individuals. We identified a key system in the middle temporal gyrus/superior temporal sulcus region that has reduced cortical functional connectivity (and increased with the medial thalamus), which is implicated in face expression processing involved in social behaviour. This system has reduced functional connectivity with the ventromedial prefrontal cortex, which is implicated in emotion and social communication. The middle temporal gyrus system is also implicated in theory of mind processing. We also identified in autism a second key system in the precuneus/superior parietal lobule region with reduced functional connectivity, which is implicated in spatial functions including of oneself, and of the spatial environment. It is proposed that these two types of functionality, face expression-related, and of one's self and the environment, are important components of the computations involved in theory of mind, whether of oneself or of others, and that reduced connectivity within and between these regions may make a major contribution to the symptoms of autism. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  8. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption

    Directory of Open Access Journals (Sweden)

    Atar Herziger

    2017-06-01

    Full Text Available Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing social media trend (Minimalism in an empirical research design. The project will test (a whether the Minimalism trend could benefit consumers interested in reducing their consumption, and (b whether self-transcendence (i.e., biospheric and self-enhancement (i.e., egoistic and hedonic values and goals have a similar impact in promoting voluntary simplicity. A one-week intervention program will test the efficacy of watching user-generated voluntary simplicity videos in reducing non-essential consumption. Each of the two intervention conditions will present participants with similar tutorial videos on consumption reduction (e.g., decluttering, donating, while priming the relevant values and goals (self-transcendence or self-enhancement. These interventions will be compared to a control condition, involving no user-generated content. Participants will undergo baseline and post-intervention evaluations of: voluntary simplicity attitudes and behaviors, buying and shopping behaviors, values and goals in reducing consumption, and life satisfaction. Experience sampling will monitor affective state during the intervention. We provide a detailed stepwise procedure, materials, and equipment necessary for executing this intervention. The outlined research design is expected to contribute to the limited literature on voluntary simplicity, online behavioral change interventions, and the use of social marketing principles in consumer interventions.

  9. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption

    Science.gov (United States)

    Herziger, Atar; Benzerga, Amel; Berkessel, Jana; Dinartika, Niken L.; Franklin, Matija; Steinnes, Kamilla K.; Sundström, Felicia

    2017-01-01

    Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing social media trend (Minimalism) in an empirical research design. The project will test (a) whether the Minimalism trend could benefit consumers interested in reducing their consumption, and (b) whether self-transcendence (i.e., biospheric) and self-enhancement (i.e., egoistic and hedonic) values and goals have a similar impact in promoting voluntary simplicity. A one-week intervention program will test the efficacy of watching user-generated voluntary simplicity videos in reducing non-essential consumption. Each of the two intervention conditions will present participants with similar tutorial videos on consumption reduction (e.g., decluttering, donating), while priming the relevant values and goals (self-transcendence or self-enhancement). These interventions will be compared to a control condition, involving no user-generated content. Participants will undergo baseline and post-intervention evaluations of: voluntary simplicity attitudes and behaviors, buying and shopping behaviors, values and goals in reducing consumption, and life satisfaction. Experience sampling will monitor affective state during the intervention. We provide a detailed stepwise procedure, materials, and equipment necessary for executing this intervention. The outlined research design is expected to contribute to the limited literature on voluntary simplicity, online behavioral change interventions, and the use of social marketing principles in consumer interventions. PMID:28649220

  10. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption.

    Science.gov (United States)

    Herziger, Atar; Benzerga, Amel; Berkessel, Jana; Dinartika, Niken L; Franklin, Matija; Steinnes, Kamilla K; Sundström, Felicia

    2017-01-01

    Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing social media trend (Minimalism) in an empirical research design. The project will test (a) whether the Minimalism trend could benefit consumers interested in reducing their consumption, and (b) whether self-transcendence (i.e., biospheric) and self-enhancement (i.e., egoistic and hedonic) values and goals have a similar impact in promoting voluntary simplicity. A one-week intervention program will test the efficacy of watching user-generated voluntary simplicity videos in reducing non-essential consumption. Each of the two intervention conditions will present participants with similar tutorial videos on consumption reduction (e.g., decluttering, donating), while priming the relevant values and goals (self-transcendence or self-enhancement). These interventions will be compared to a control condition, involving no user-generated content. Participants will undergo baseline and post-intervention evaluations of: voluntary simplicity attitudes and behaviors, buying and shopping behaviors, values and goals in reducing consumption, and life satisfaction. Experience sampling will monitor affective state during the intervention. We provide a detailed stepwise procedure, materials, and equipment necessary for executing this intervention. The outlined research design is expected to contribute to the limited literature on voluntary simplicity, online behavioral change interventions, and the use of social marketing principles in consumer interventions.

  11. Case Management Reduces Length of Stay, Charges, and Testing in Emergency Department Frequent Users

    Directory of Open Access Journals (Sweden)

    Jameel Sughair

    2018-02-01

    Full Text Available Introduction: Case management is an effective, short-term means to reduce emergency department (ED visits in frequent users of the ED. This study sought to determine the effectiveness of case management on frequent ED users, in terms of reducing ED and hospital length of stay (LOS, accrued costs, and utilization of diagnostic tests. Methods: The study consisted of a retrospective chart review of ED and inpatient visits in our hospital’s ED case management program, comparing patient visits made in the one year prior to enrollment in the program, to the visits made in the one year after enrollment in the program. We examined the LOS, use of diagnostic testing, and monetary charges incurred by these patients one year prior and one year after enrollment into case management. Results: The study consisted of 158 patients in case management. Comparing the one year prior to enrollment to the one year after enrollment, ED visits decreased by 49%, inpatient admissions decreased by 39%, the use of computed tomography imaging decreased 41%, the use of ultrasound imaging decreased 52%, and the use of radiographs decreased 38%. LOS in the ED and for inpatient admissions decreased by 39%, reducing total LOS for these patients by 178 days. ED and hospital charges incurred by these patients decreased by 5.8 million dollars, a 41% reduction. All differences were statistically significant. Conclusion: Case management for frequent users of the ED is an effective method to reduce patient visits, the use of diagnostic testing, length of stay, and cost within our institution.

  12. Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

    Science.gov (United States)

    Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun

    2017-12-01

    Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Triple negative breast cancers have a reduced expression of DNA repair genes.

    Directory of Open Access Journals (Sweden)

    Enilze Ribeiro

    Full Text Available DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia in paraffin embedded samples of triple negative breast cancer (TNBC compared to luminal A breast cancer (LABC. Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.

  14. Preterm Birth Reduces Nutrient Absorption With Limited Effect on Immune Gene Expression and Gut Colonization in Pigs

    DEFF Research Database (Denmark)

    Østergaard, Mette V; Cilieborg, Malene S.; Skovgaard, Kerstin

    2015-01-01

    The primary risk factors for necrotizing enterocolitis (NEC) are preterm birth, enteral feeding, and gut colonization. It is unclear whether feeding and colonization induce excessive expression of immune genes that lead to NEC. Using a pig model, we hypothesized that reduced gestational age would...... upregulate immune-related genes and cause bacterial imbalance after birth. Preterm (85%-92% gestation, n = 53) and near-term (95%-99% gestation, n = 69) pigs were delivered by cesarean section and euthanized at birth or after 2 days of infant formula or bovine colostrum feeding. At birth, preterm delivery...... reduced 5 of 30 intestinal genes related to nutrient absorption and innate immunity, relative to near-term pigs, whereas 2 genes were upregulated. Preterm birth also reduced ex vivo intestinal glucose and leucine uptake (40%-50%), but failed to increase cytokine secretions from intestinal explants...

  15. From guidelines to hospital practice: reducing inappropriate ordering of thyroid hormone and antibody tests.

    Science.gov (United States)

    Toubert, M E; Chevret, S; Cassinat, B; Schlageter, M H; Beressi, J P; Rain, J D

    2000-06-01

    Because of major technical improvements and conscious care about cost effectiveness, limiting the inadequate use of thyroid biological tests appears to be a major issue. To (i) estimate the ordering prevalence of each thyroid test, (ii) assess the prevalence of relevant thyroid tests, and (iii) evaluate the impact of expressing justification for tests during a 2-month intervention period on these prevalences. During a prospective 2-month survey (June-July 1997), all the request forms were divided into four groups of prescription: (1) investigation of thyroid function, (2) taking drugs affecting the thyroid, (3) monitoring of nodule and cancer, and (4) investigation of thyroid autoimmunity. Their appropriateness was thus determined according to consensus in our hospital and previously published recommendations. Results were compared with those of retrospective similar 2-month periods in 1996 and 1998. Combinations of thyroid function tests and thyroid antibodies were analyzed during the 1996, 1997 and 1998 periods. The overall estimated rate of appropriate ordering between 1996 and 1997 increased from 42.5% to 72.4% (P<10(-4)), with a significant improvement in each group of main diagnosis referral, except in group 3 where suitability was always over 85%. However, in group 4, appropriateness remained low (36%). Combinations of thyroid tests revealed an increase in single TSH order forms and single autoantibodies to thyroperoxidase (TPOAb) ones, while TSH+free thyroxine+free tri-iodothyronine and TPOAb+ autoantibodies to thyroglobulin ones decreased significantly. Interestingly, all these changes were maintained 1 year later (June-July 1998) even though physicians were not aware of this new study. Persistent change in medical practice was thus assessed.

  16. GENE EXPRESSION IN THE TESTES OF NORMOSPERMIC VERSUS TERATOSPERMIC DOMESTIC CATS USING HUMAN CDNA MICROARRAY ANALYSES

    Science.gov (United States)

    GENE EXPRESSION IN THE TESTES OF NORMOSPERMIC VERSUS TERATOSPERMIC DOMESTIC CATS USING HUMAN cDNA MICROARRAY ANALYSESB.S. Pukazhenthi1, J. C. Rockett2, M. Ouyang3, D.J. Dix2, J.G. Howard1, P. Georgopoulos4, W.J. J. Welsh3 and D. E. Wildt11Department of Reproductiv...

  17. High-throughput testing of terpenoid biosynthesis candidate genes using transient expression in Nicotiana benthamiana

    DEFF Research Database (Denmark)

    Bach, Søren Spanner; Bassard, Jean-Étienne André; Andersen-Ranberg, Johan

    2014-01-01

    To respond to the rapidly growing number of genes putatively involved in terpenoid metabolism, a robust high-throughput platform for functional testing is needed. An in planta expression system offers several advantages such as the capacity to produce correctly folded and active enzymes localized...

  18. Identification of reduced-order model for an aeroelastic system from flutter test data

    Directory of Open Access Journals (Sweden)

    Wei Tang

    2017-02-01

    Full Text Available Recently, flutter active control using linear parameter varying (LPV framework has attracted a lot of attention. LPV control synthesis usually generates controllers that are at least of the same order as the aeroelastic models. Therefore, the reduced-order model is required by synthesis for avoidance of large computation cost and high-order controller. This paper proposes a new procedure for generation of accurate reduced-order linear time-invariant (LTI models by using system identification from flutter testing data. The proposed approach is in two steps. The well-known poly-reference least squares complex frequency (p-LSCF algorithm is firstly employed for modal parameter identification from frequency response measurement. After parameter identification, the dominant physical modes are determined by clear stabilization diagrams and clustering technique. In the second step, with prior knowledge of physical poles, the improved frequency-domain maximum likelihood (ML estimator is presented for building accurate reduced-order model. Before ML estimation, an improved subspace identification considering the poles constraint is also proposed for initializing the iterative procedure. Finally, the performance of the proposed procedure is validated by real flight flutter test data.

  19. Immunization of Mice with Lactobacillus casei Expressing a Beta-Intimin Fragment Reduces Intestinal Colonization by Citrobacter rodentium ▿ †

    OpenAIRE

    Ferreira, P. C. D.; da Silva, J. B.; Piazza, R. M. F.; Eckmann, L.; Ho, P. L.; Oliveira, M. L. S.

    2011-01-01

    Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in children from developing countries. Intimate adhesion of the bacteria to intestinal cells occurs via binding of the adhesin intimin to the TIR receptor exposed on cell surfaces. Here, Lactobacillus casei expressing a fragment of β-intimin (L. casei-Intcv) was tested as mucosal vaccines in mice against intestinal colonization with the murine pathogen Citrobacter rodentium. Oral or sublingual immunization of C57BL/6 mice ...

  20. Cloning of transgenic tobacco BY-2 cells; an efficient method to analyse and reduce high natural heterogeneity of transgene expression.

    Science.gov (United States)

    Nocarova, Eva; Fischer, Lukas

    2009-04-22

    Phenotypic characterization of transgenic cell lines, frequently used in plant biology studies, is complicated because transgene expression in individual cells is often heterogeneous and unstable. To identify the sources and to reduce this heterogeneity, we transformed tobacco (Nicotiana tabacum L.) BY-2 cells with a gene encoding green fluorescent protein (GFP) using Agrobacterium tumefaciens, and then introduced a simple cloning procedure to generate cell lines derived from the individual transformed cells. Expression of the transgene was monitored by analysing GFP fluorescence in the cloned lines and also in lines obtained directly after transformation. The majority ( approximately 90%) of suspension culture lines derived from calli that were obtained directly from transformation consisted of cells with various levels of GFP fluorescence. In contrast, nearly 50% of lines generated by cloning cells from the primary heterogeneous suspensions consisted of cells with homogenous GFP fluorescence. The rest of the lines exhibited "permanent heterogeneity" that could not be resolved by cloning. The extent of fluorescence heterogeneity often varied, even among genetically identical clones derived from the primary transformed lines. In contrast, the offspring of subsequent cloning of the cloned lines was uniform, showing GFP fluorescence intensity and heterogeneity that corresponded to the original clone. The results demonstrate that, besides genetic heterogeneity detected in some lines, the primary lines often contained a mixture of epigenetically different cells that could be separated by cloning. This indicates that a single integration event frequently results in various heritable expression patterns, which are probably accidental and become stabilized in the offspring of the primary transformed cells early after the integration event. Because heterogeneity in transgene expression has proven to be a serious problem, it is highly advisable to use transgenes tagged with

  1. A novel thromboxane A2 receptor N42S variant results in reduced surface expression and platelet dysfunction.

    Science.gov (United States)

    Nisar, Shaista P; Lordkipanidzé, Marie; Jones, Matthew L; Dawood, Ban; Murden, Sherina; Cunningham, Margaret R; Mumford, Andrew D; Wilde, Jonathan T; Watson, Steve P; Mundell, Stuart J; Lowe, Gillian C

    2014-05-05

    A small number of thromboxane receptor variants have been described in patients with a bleeding history that result in platelet dysfunction. We have identified a patient with a history of significant bleeding, who expresses a novel heterozygous thromboxane receptor variant that predicts an asparagine to serine substitution (N42S). This asparagine is conserved across all class A GPCRs, suggesting a vital role for receptor structure and function.We investigated the functional consequences of the TP receptor heterozygous N42S substitution by performing platelet function studies on platelet-rich plasma taken from the patient and healthy controls. We investigated the N42S mutation by expressing the wild-type (WT) and mutant receptor in human embryonic kidney (HEK) cells. Aggregation studies showed an ablation of arachidonic acid responses in the patient, whilst there was right-ward shift of the U46619 concentration response curve (CRC). Thromboxane generation was unaffected. Calcium mobilisation studies in cells lines showed a rightward shift of the U46619 CRC in N42S-expressing cells compared to WT. Radioligand binding studies revealed a reduction in BMax in platelets taken from the patient and in N42S-expressing cells, whilst cell studies confirmed poor surface expression. We have identified a novel thromboxane receptor variant, N42S, which results in platelet dysfunction due to reduced surface expression. It is associated with a significant bleeding history in the patient in whom it was identified. This is the first description of a naturally occurring variant that results in the substitution of this highly conserved residue and confirms the importance of this residue for correct GPCR function.

  2. Susceptibility to virus-cell fusion at the plasma membrane is reduced through expression of HIV gp41 cytoplasmic domains

    International Nuclear Information System (INIS)

    Malinowsky, Katharina; Luksza, Julia; Dittmar, Matthias T.

    2008-01-01

    The cytoplasmic tail of the HIV transmembrane protein plays an important role in viral infection. In this study we analyzed the role of retroviral cytoplasmic tails in modulating the cytoskeleton and interfering with virus-cell fusion. HeLaP4 cells expressing different HIV cytoplasmic tail constructs showed reduced acetylated tubulin levels whereas the cytoplasmic tail of MLV did not alter microtubule stability indicating a unique function for the lentiviral cytoplasmic tail. The effect on tubulin is mediated through the membrane proximal region of the HIV cytoplasmic tail and was independent of membrane localization. Site-directed mutagenesis identified three motifs in the HIV-2 cytoplasmic tail required to effect the reduction in acetylated tubulin. Both the YxxΦ domain and amino acids 21 to 45 of the HIV-2 cytoplasmic tail need to be present to change the level of acetylated tubulin in transfected cells. T-cells stably expressing one HIV-2 cytoplasmic tail derived construct showed also a reduction in acetylated tubulin thus confirming the importance of this effect not only for HeLaP4 and 293T cells. Challenge experiments using transiently transfected HeLaP4 cells and T cells stably expressing an HIV cytoplasmic tail construct revealed both reduced virus-cell fusion and replication of HIV-1 NL4.3 compared to control cells. In the virus-cell fusion assay only virions pseudotyped with either HIV or MLV envelopes showed reduced fusion efficiency, whereas VSV-G pseudotyped virions where not affected by the expression of HIV derived cytoplasmic tail constructs, indicating that fusion at the plasma but not endosomal membrane is affected. Overexpression of human histone-deacetylase 6 (HDAC6) and constitutively active RhoA resulted in a reduction of acetylated tubulin and reduced virus-cell fusion as significant as that observed following expression of HIV cytoplasmic tail constructs. Inhibition of HDAC6 showed a strong increase in acetylated tubulin and increase of

  3. Fluoride exposure changed the structure and the expressions of Y chromosome related genes in testes of mice.

    Science.gov (United States)

    Cao, Jinling; Chen, Yan; Chen, Jianjie; Yan, Hanghang; Li, Meiyan; Wang, Jundong

    2016-10-01

    It is known that during spermatogenesis, pluripotent germ cells differentiate to become efficient delivery vehicles to the oocyte of paternal DNA, and the process is easily damaged by external poison. In this study, the effects of fluoride on the body weight, fluoride content in femur, testosterone levels in serum and testis, sperm quality, and the expressions of Y chromosome microdeletion genes and protein levels were examined in testes of Kunming male mice treated with different concentrations of 0, 25, 50, 100 mg/L of NaF in drinking water for 11 weeks, respectively. The results showed that compared with the control group, fluoride contents in three treatment groups were significantly increased and the structure of testes was seriously injured. The testosterone contents and the sperm count were decreased. Sperm malformation ratio was distinctly elevated. The expressions of Sly and HSF2 mRNA were markedly reduced in 100 mg/L NaF group and Ssty2 mRNA expression was dramatically decreased in 50 and 100 mg/L NaF groups. Meanwhile, the protein levels of Ssty2 and Sly were significantly reduced in 50 and 100 mg/L NaF groups and HSF2 protein levels were significantly decreased in 100 mg/L NaF group. These studies indicated that fluoride had toxic effects on male reproductive system by reducing the testosterone and sperm count, and increasing the sperm malformation ratio, supported by the damage of testicular structure, as a consequence of depressed HSF2 level, which resulted in the down-regulation of Ssty2 and Sly mRNA and protein. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Arctigenin reduces blood pressure by modulation of nitric oxide synthase and NADPH oxidase expression in spontaneously hypertensive rats.

    Science.gov (United States)

    Liu, Ying; Wang, Guoyuan; Yang, Mingguang; Chen, Haining; zhao, Yan; Yang, Shucai; Sun, Changhao

    2015-12-25

    Arctigenin is a bioactive constituent from dried seeds of Arctium lappa L., which was traditionally used as medicine. Arctigenin exhibits various bioactivities, but its effects on blood pressure regulation are still not widely studied. In this study, we investigated antihypertensive effects of arctigenin by long-term treatment in spontaneously hypertensive rats (SHRs). Arctigenin (50 mg/kg) or vehicle was administered to SHRs or Wistar rats as negative control by oral gavage once a day for total 8 weeks. Nifedipine (3 mg/kg) was used as a positive drug control. After treatment, hemodynamic and physical parameters, vascular reactivity in aorta, the concentration of plasma arctigenin and serum thromboxane B2, NO release and vascular p-eNOS, p-Akt, caveolin-1 protein expression, and vascular superoxide anion generation and p47phox protein expression were detected and analyzed. The results showed that arctigenin significantly reduced systolic blood pressure and ameliorated endothelial dysfunction of SHRs. Arctigenin reduced the levels of thromboxane B2 in plasma and superoxide anion in thoracic aorta of SHRs. Furthermore, arctigenin increased the NO production by enhancing the phosphorylation of Akt and eNOS (Ser 1177), and inhibiting the expression of NADPH oxidase in thoracic aorta of SHRs. Our data suggested that antihypertensive mechanisms of arctigenin were associated with enhanced eNOS phosphorylation and decreased NADPH oxidase-mediated superoxide anion generation. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Boron toxicity tolerance in barley through reduced expression of the multifunctional aquaporin HvNIP2;1.

    Science.gov (United States)

    Schnurbusch, Thorsten; Hayes, Julie; Hrmova, Maria; Baumann, Ute; Ramesh, Sunita A; Tyerman, Stephen D; Langridge, Peter; Sutton, Tim

    2010-08-01

    Boron (B) toxicity is a significant limitation to cereal crop production in a number of regions worldwide. Here we describe the cloning of a gene from barley (Hordeum vulgare), underlying the chromosome 6H B toxicity tolerance quantitative trait locus. It is the second B toxicity tolerance gene identified in barley. Previously, we identified the gene Bot1 that functions as an efflux transporter in B toxicity-tolerant barley to move B out of the plant. The gene identified in this work encodes HvNIP2;1, an aquaporin from the nodulin-26-like intrinsic protein (NIP) subfamily that was recently described as a silicon influx transporter in barley and rice (Oryza sativa). Here we show that a rice mutant for this gene also shows reduced B accumulation in leaf blades compared to wild type and that the mutant protein alters growth of yeast (Saccharomyces cerevisiae) under high B. HvNIP2;1 facilitates significant transport of B when expressed in Xenopus oocytes compared to controls and to another NIP (NOD26), and also in yeast plasma membranes that appear to have relatively high B permeability. We propose that tolerance to high soil B is mediated by reduced expression of HvNIP2;1 to limit B uptake, as well as by increased expression of Bot1 to remove B from roots and sensitive tissues. Together with Bot1, the multifunctional aquaporin HvNIP2;1 is an important determinant of B toxicity tolerance in barley.

  6. Chlorella vulgaris reduces the impact of stress on hypothalamic-pituitary-adrenal axis and brain c-fos expression.

    Science.gov (United States)

    Souza Queiroz, Julia; Marín Blasco, Ignacio; Gagliano, Humberto; Daviu, Nuria; Gómez Román, Almudena; Belda, Xavier; Carrasco, Javier; Rocha, Michelle C; Palermo Neto, João; Armario, Antonio

    2016-03-01

    Predominantly emotional stressors activate a wide range of brain areas, as revealed by the expression of immediate early genes, such as c-fos. Chlorella vulgaris (CV) is considered a biological response modifier, as demonstrated by its protective activities against infections, tumors and stress. We evaluated the effect of acute pretreatment with CV on the peripheral and central responses to forced swimming stress in adult male rats. Pretreatment with CV produced a significant reduction of stress-related hypothalamic-pituitary-adrenal activation, demonstrated by decreased corticotrophin releasing factor gene expression in the hypothalamic paraventricular nucleus (PVN) and lower ACTH response. Hyperglycemia induced by the stressor was similarly reduced. This attenuated neuroendocrine response to stress occurred in parallel with a diminished c-fos expression in most evaluated areas, including the PVN. The data presented in this study reinforce the usefulness of CV to diminish the impact of stressors, by reducing the HPA response. Although our results suggest a central effect of CV, further studies are necessary to understand the precise mechanisms underpinning this effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Reducing and Sustaining Duplicate Medical Record Creation by Usability Testing and System Redesign.

    Science.gov (United States)

    Khunlertkit, Adjhaporn; Dorissaint, Leonard; Chen, Allen; Paine, Lori; Pronovost, Peter J

    2017-10-25

    Duplicate medical record creation is a common and consequential health care systems error often caused by poor search system usability and inappropriate user training. We conducted two phases of scenario-based usability testing with patient registrars working in areas at risk of generating duplicate medical records. Phase 1 evaluated the existing search system, which led to system redesigns. Phase 2 tested the redesigned system to mitigate potential errors before health system-wide implementation. To evaluate system effectiveness, we compared the monthly potential duplicate medical record rates for preimplementation and postimplementation months. The existing system could not effectively handle a misspelling, which led to failed search and duplicate medical record creation. Using the existing system, 96% of registrars found commonly spelled patient names whereas only 69% successfully found complicated names. Registrars lacked knowledge and usage of a phonetic matching function to assist in misspelling. The new system consistently captured the correct patient regardless of misspelling, but search returned more potential matches, resulting in, on average, 4 seconds longer to select common names. Potential monthly duplicate medical record rate reduced by 38%, from 4% to 2.3% after implementation of the new system, and has sustained at an average of 2.5% for 2 years. Usability testing was an effective method to reveal problems and aid system redesign to deliver a more user friendly system, hence reducing the potential for medical record duplication. Greater standards for usability would ensure that these improvements can be realized before rather than after exposing patients to risks.

  8. Cortisol response to the Trier Social Stress Test in obese and reduced obese individuals.

    Science.gov (United States)

    Therrien, Fanny; Drapeau, Vicky; Lalonde, Josée; Lupien, Sonia J; Beaulieu, Serge; Doré, Jean; Tremblay, Angelo; Richard, Denis

    2010-05-01

    Impact of body weight loss, body fat distribution and the nutritional status on the cortisol response to the Trier Social Stress Test (TSST) was investigated in this study. Fifty-one men (17 non-obese, 20 abdominally obese and 14 reduced obese) and 28 women (12 non-obese, 10 peripherally obese and 6 reduced obese) were subjected to the TSST in fed and fasted states. The TSST response was determined using salivary cortisol measurements. The nutritional status (being fed or fasted) had no effect on the cortisol levels during and following the TSST. Reduced obese men exhibited lower cortisol levels than non-obese men. Cortisol levels in obese men were not different from those of non-obese and reduced obese subjects. In women, there was no significant difference between groups. These finding suggest that weight status in men influences cortisol reactivity to a psychological stress and the different responses seen among genders could be linked to the different fat distributions that characterize men and women. Copyright 2010 Elsevier B.V. All rights reserved.

  9. Reduced HRAS G12V-Driven Tumorigenesis of Cell Lines Expressing KRAS C118S.

    Directory of Open Access Journals (Sweden)

    Lu Huang

    Full Text Available In many different human cancers, one of the HRAS, NRAS, or KRAS genes in the RAS family of small GTPases acquires an oncogenic mutation that renders the encoded protein constitutively GTP-bound and thereby active, which is well established to promote tumorigenesis. In addition to oncogenic mutations, accumulating evidence suggests that the wild-type isoforms may also be activated and contribute to oncogenic RAS-driven tumorigenesis. In this regard, redox-dependent reactions with cysteine 118 (C118 have been found to promote activation of wild-type HRAS and NRAS. We sought to determine if this residue is also important for the activation of wild-type KRAS and promotion of tumorigenesis. Thus, we mutated C118 to serine (C118S in wild-type KRAS to block redox-dependent reactions at this site. We now report that this mutation reduced the level of GTP-bound KRAS and impaired RAS signaling stimulated by the growth factor EGF. With regards to tumorigenesis, we also report that oncogenic HRAS-transformed human cells in which endogenous KRAS was knocked down and replaced with KRASC118S exhibited reduced xenograft tumor growth, as did oncogenic HRAS-transformed KrasC118S/C118S murine cells in which the C118S mutation was knocked into the endogenous Kras gene. Taken together, these data suggest a role for redox-dependent activation of wild-type KRAS through C118 in oncogenic HRAS-driven tumorigenesis.

  10. Status of the RERTR [Reduced Enrichment Research and Test Reactor] program in Argentina

    International Nuclear Information System (INIS)

    Giorsetti, D.R.

    1987-01-01

    The Argentine Atomic Energy Commission started in 1978 the Reduced Enrichment Research and Test Reactors in the field of reactor engineering; engineering, development and manufacturing of fuel elements and research reactors operators. This program was initiated with the conviction that it would contribute to the international efforts to reduce risks of nuclear weapons proliferation owing to an uncontrolled use of highly enriched uranium. It was intended to convert RA-3 reactor to make possible its operation with low enriched fuel (LEU), instead of high enriched fuel (HEU) and to develop manufacturing techniques for said LEU. Afterwards, this program was adapted to assist other countries in reactors conversion, development of the corresponding fuel elements and supply of fuel elements to other countries. (Author)

  11. Determination of kinetic constants from tests of reducibility and their application for modelling in metallurgy

    International Nuclear Information System (INIS)

    Pustejovska, P.; Silvie, B.

    2013-01-01

    The paper analyses details for renewal of the research in blast furnace process within Research Centre ENET at VSB - Technical University of Ostrava. A newly established laboratory for reducibility testing is an impuls to overcome the former limits and renew a research in its coherence after years. The paper deals with the possibilities of optimization of blast furnace operation. In the introduction, it sums up different approaches how to model blast furnace operation. It discusses the variety of optimal operation for different kinds of iron making technologies. It evaluates reduction course and reducing gas consumption in the stack of reduction aggregate. In the experimental, it creates kinetics model of blast furnace operating using Matlab mathematical library. It determines kinetic and heat limits of carbon consumption for different process conditions. (author)

  12. Intrapartum synthetic oxytocin reduce the expression of primitive reflexes associated with breastfeeding.

    Science.gov (United States)

    Marín Gabriel, Miguel A; Olza Fernández, Ibone; Malalana Martínez, Ana M; González Armengod, Carmen; Costarelli, Valeria; Millán Santos, Isabel; Fernández-Cañadas Morillo, Aurora; Pérez Riveiro, Pilar; López Sánchez, Francisco; García Murillo, Lourdes

    2015-05-01

    Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. A cohort prospective study was conducted at a tertiary hospital. Mother-infant dyads who received intrapartum oxytocin (n=53) were compared with mother-infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent.

  13. A preoperative cotininury test for abdominoplasty reduces peri-operative complications.

    Science.gov (United States)

    Delaunay, F; Coquerel-Beghin, D; Magalon, G; Cohen, S R; Casanova, D; Niddam, J; Milliez, P-Y; Peillon, C; Delpierre, V; Auquit-Auckbur, I

    2018-05-16

    Smoking induces complications in plastic surgery, in particular wound healing delays. Despite a 4-weeks' abstinence asking before and after surgery, some patients denied or hid their consumption. The aim of this study was to evaluate the effectiveness of a cotininury detection test in terms of improvement in outcomes after an abdominoplasty. This retrospective cohort study included patients who underwent an abdominoplasty with umbilical transposition and lipoaspiration. Current smokers were asked to stop smoking 4 weeks before and after surgery. After 2013, we performed a preoperative cotininury test for patients having abdominoplasty, with a cancellation of surgery in case of positive result. We analyzed the test's effectiveness on delayed healing and on other complications. Two hundred and thirty-five patients were included; 80 were tested and 21,3% had a positive test. There was significantly less delayed healing in the "screening" group than in the "no screening": 20,3% versus 41,5% (P=0,002). Alike, complications were significantly less frequent in the "screening" group than in the "no screening": 18,1% versus 42,3% (P<0,001). The routine use of the cotininury test in preoperative abdominoplasties significantly reduces risk of delayed healing and other serious complications. It is an objective test, which is simple, quick and non-invasive. Smoking cessation must be at least 4 weeks before and after the surgery. Following medical advice to cease smoking by the surgeon and anesthetist, referral to an appropriate tobacco-addiction specialist clinic may be helpful for the patient who has difficulty stopping smoking. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. 'Fluorescent Cell Chip' for immunotoxicity testing: Development of the c-fos expression reporter cell lines

    International Nuclear Information System (INIS)

    Trzaska, Dominika; Zembek, Patrycja; Olszewski, Maciej; Adamczewska, Violetta; Ulleras, Erik; Dastych, JarosIaw

    2005-01-01

    The Fluorescent Cell Chip for in vitro immunotoxicity testing employs cell lines derived from lymphocytes, mast cells, and monocytes-macrophages transfected with various EGFP cytokine reporter gene constructs. While cytokine expression is a valid endpoint for in vitro immunotoxicity screening, additional marker for the immediate-early response gene expression level could be of interest for further development and refinement of the Fluorescent Cell Chip. We have used BW.5147.3 murine thymoma transfected with c-fos reporter constructs to obtain reporter cell lines expressing ECFP under the control of murine c-fos promoter. These cells upon serum withdrawal and readdition and incubation with heavy metal compounds showed paralleled induction of c-Fos expression as evidenced by Real-Time PCR and ECFP fluorescence as evidenced by computer-supported fluorescence microscopy. In conclusion, we developed fluorescent reporter cell lines that could be employed in a simple and time-efficient screening assay for possible action of chemicals on c-Fos expression in lymphocytes. The evaluation of usefulness of these cells for the Fluorescent Cell Chip-based detection of immunotoxicity will require additional testing with a larger number of chemicals

  15. High-risk human papillomavirus E7 expression reduces cell-surface MHC class I molecules and increases susceptibility to natural killer cells

    DEFF Research Database (Denmark)

    Bottley, G; Watherston, O G; Hiew, Y-L

    2007-01-01

    a role for E7 in tumour immune evasion. We show that knockdown of E7 expression in HPV16- and HPV18-transformed cervical carcinoma cells by RNA interference increased expression of major histocompatibility complex (MHC) class I at the cell surface and reduced susceptibility of these cells to natural...... killer (NK) cells. Tetracycline-regulated induction of HPV16 E7 resulted in reduced expression of cell surface MHC class I molecules and increased NK cell killing. Our results suggest that, for HPV-associated malignancies, reduced MHC class I expression is the result of an active immune evasion strategy...

  16. Progress of the RERTR [Reduced Enrichment Research and Test Reactor] Program in 1989

    International Nuclear Information System (INIS)

    Travelli, A.

    1989-01-01

    The progress of the Reduced Enrichment Research and Test Reactor (RERTR) Program is described. After a brief summary of the results which the RERTR Program, in collaboration with its many international partners, had achieved by the end of 1988, the major events, findings, and activities of 1989 are reviewed. The scope of the RERTR Program activities was curtailed, in 1989, by an unexpected legislative restriction which limited the ability of the Arms Control and Disarmament Agency to adequately fund the program. Nevertheless, the thrust of the major planned program activities was maintained, and meaningful results were obtained in several areas of great significance for future work. 15 refs., 12 figs

  17. CONCENTRATION OF HARMFUL SUBSTANCES REDUCING IN SURFACE LAYER OF ATMOSPHERE AT RHEOSTAT LOCOMOTIVE TESTS

    Directory of Open Access Journals (Sweden)

    E. A. Bondar

    2010-06-01

    Full Text Available It is shown that at present an acceptable way of reducing the concentration of harmful substances in the surface layer of the atmosphere at rheostat tests of locomotives is their dispersion in a large volume of air. Channels, installed above an exhaust pipe of diesel locomotive with a break at the gas flow, work as ejectors. We have solved jointly the equation of aerodynamic characteristics of the ejector device and the equation of diffusion of gases; as a result the calculated dependence for determining the necessary height of ejector device has been obtained.

  18. Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms

    DEFF Research Database (Denmark)

    Kristensen, D.M.; Nielsen, J.E.; Skakkebaek, N.E.

    2008-01-01

    NANOG and OCT-3/4, UTF-1 and REX-1 are expressed throughout human testes development. The expression pattern indicated that UTF-1 plays a possible role in spermatogonial self-renewal, whereas expression of REX-1 in meiotic cells from both testes and ovary indicate a role in meiosis. UFT-1 and REX-1...... and REX-1 during human gonadal development and in TGCT. METHODS: Expression of UTF-1 and REX-1 was studied in 52 specimens from human gonadal development and in 86 samples from TGCT. RESULTS: UTF-1 and REX-1 were expressed throughout male gonadal development. In the mature testis, UTF-1 was expressed...

  19. Reduced H3K27me3 expression in Merkel cell polyoma virus-positive tumors.

    Science.gov (United States)

    Busam, Klaus J; Pulitzer, Melissa P; Coit, Daniel C; Arcila, Maria; Leng, Danielle; Jungbluth, Achim A; Wiesner, Thomas

    2017-06-01

    Merkel cell carcinoma is a primary cutaneous neuroendocrine carcinoma, which once metastatic is difficult to treat. Recent mutation analyses of Merkel cell carcinoma revealed a low number of mutations in Merkel cell polyomavirus-associated tumors, and a high number of mutations in virus-negative combined squamous cell and neuroendocrine carcinomas of chronically sun-damaged skin. We speculated that the paucity of mutations in virus-positive Merkel cell carcinoma may reflect a pathomechanism that depends on derangements of chromatin without alterations in the DNA sequence (epigenetic dysregulation). One central epigenetic regulator is the Polycomb repressive complex 2 (PRC2), which silences genomic regions by trimethylating (me3) lysine (K) 27 of histone H3, and thereby establishes the histone mark H3K27me3. Recent experimental research data demonstrated that PRC2 loss in mice skin results in the formation of Merkel cells. Prompted by these findings, we explored a possible contribution of PRC2 loss in human Merkel cell carcinoma. We examined the immunohistochemical expression of H3K27me3 in 35 Merkel cell carcinomas with pure histological features (22 primary and 13 metastatic lesions) and in 5 combined squamous and neuroendocrine carcinomas of the skin. We found a strong reduction of H3K27me3 staining in tumors with pure histologic features and virus-positive Merkel cell carcinomas. Combined neuroendocrine carcinomas had no or only minimal loss of H3K27me3 labeling. Our findings suggest that a PRC2-mediated epigenetic deregulation may play a role in the pathogenesis of virus-positive Merkel cell carcinomas and in tumors with pure histologic features.

  20. Deletion of Nhlh2 results in a defective torpor response and reduced Beta adrenergic receptor expression in adipose tissue.

    Directory of Open Access Journals (Sweden)

    Umesh D Wankhade

    2010-08-01

    Full Text Available Mice with a targeted deletion of the basic helix-loop-helix transcription factor, Nescient Helix-Loop-Helix 2 (Nhlh2, display adult-onset obesity with significant increases in their fat depots, abnormal responses to cold exposure, and reduced spontaneous physical activity levels. These phenotypes, accompanied by the hypothalamic expression of Nhlh2, make the Nhlh2 knockout (N2KO mouse a useful model to study the role of central nervous system (CNS control on peripheral tissue such as adipose tissue.Differences in body temperature and serum analysis of leptin were performed in fasted and ad lib fed wild-type (WT and N2KO mice. Histological analysis of white (WAT and brown adipose tissue (BAT was performed. Gene and protein level expression of inflammatory and metabolic markers were compared between the two genotypes.We report significant differences in serum leptin levels and body temperature in N2KO mice compared with WT mice exposed to a 24-hour fast, suggestive of a defect in both white (WAT and brown adipose tissue (BAT function. As compared to WT mice, N2KO mice showed increased serum IL-6 protein and WAT IL-6 mRNA levels. This was accompanied by slight elevations of mRNA for several macrophage markers, including expression of macrophage specific protein F4/80 in adipose, suggestive of macrophage infiltration of WAT in the mutant animals. The mRNAs for beta3-adrenergic receptors (beta3-AR, beta2-AR and uncoupling proteins were significantly reduced in WAT and BAT from N2KO mice compared with WT mice.These studies implicate Nhlh2 in the central control of WAT and BAT function, with lack of Nhlh2 leading to adipose inflammation and altered gene expression, impaired leptin response to fasting, all suggestive of a deficient torpor response in mutant animals.

  1. PDE4 inhibition reduces neointima formation and inhibits VCAM-1 expression and histone methylation in an Epac-dependent manner.

    Science.gov (United States)

    Lehrke, Michael; Kahles, Florian; Makowska, Anna; Tilstam, Pathricia V; Diebold, Sebastian; Marx, Judith; Stöhr, Robert; Hess, Katharina; Endorf, Elizabeth B; Bruemmer, Dennis; Marx, Nikolaus; Findeisen, Hannes M

    2015-04-01

    Phosphodiesterase 4 (PDE4) activity mediates cAMP-dependent smooth muscle cell (SMC) activation following vascular injury. In this study we have investigated the effects of specific PDE4 inhibition with roflumilast on SMC proliferation and inflammatory activation in vitro and neointima formation following guide wire-induced injury of the femoral artery in mice in vivo. In vitro, roflumilast did not affect SMC proliferation, but diminished TNF-α induced expression of the vascular cell adhesion molecule 1 (VCAM-1). Specific activation of the cAMP effector Epac, but not PKA activation mimicked the effects of roflumilast on VCAM-1 expression. Consistently, the reduction of VCAM-1 expression was rescued following inhibition of Epac. TNF-α induced NFκB p65 translocation and VCAM-1 promoter activity were not altered by roflumilast in SMCs. However, roflumilast treatment and Epac activation repressed the induction of the activating epigenetic histone mark H3K4me2 at the VCAM-1 promoter, while PKA activation showed no effect. Furthermore, HDAC inhibition blocked the inhibitory effect of roflumilast on VCAM-1 expression. Both, roflumilast and Epac activation reduced monocyte adhesion to SMCs in vitro. Finally, roflumilast treatment attenuated femoral artery intima-media ratio by more than 50% after 4weeks. In summary, PDE4 inhibition regulates VCAM-1 through a novel Epac-dependent mechanism, which involves regulatory epigenetic components and reduces neointima formation following vascular injury. PDE4 inhibition and Epac activation might represent novel approaches for the treatment of vascular diseases, including atherosclerosis and in-stent restenosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Genomic testing interacts with reproductive surplus in reducing genetic lag and increasing economic net return

    DEFF Research Database (Denmark)

    Hjortø, Line; Ettema, Jehan Frans; Kargo, Morten

    2015-01-01

    Until now, genomic information has mainly been used to improve the accuracy of genomic breeding values for breeding animals at a population level. However, we hypothesize that the use of information from genotyped females also opens up the possibility of reducing genetic lag in a dairy herd......, especially if genomic tests are used in combination with sexed semen or a high management level for reproductive performance, because both factors provide the opportunity for generating a reproductive surplus in the herd. In this study, sexed semen is used in combination with beef semen to produce high......-value crossbred beef calves. Thus, on average there is no surplus of and selection among replacement heifers whether to go into the herd or to be sold. In this situation, the selection opportunities arise when deciding which cows to inseminate with sexed semen, conventional semen, or beef semen. We tested...

  3. Performance and durability tests of smart icephobic coatings to reduce ice adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Janjua, Zaid A.; Turnbull, Barbara [Faculty of Engineering, University of Nottingham (United Kingdom); Choy, Kwang-Leong; Pandis, Christos [Institute for Materials Discovery, University College London (UCL) (United Kingdom); Liu, Junpeng; Hou, Xianghui; Choi, Kwing-So [Faculty of Engineering, University of Nottingham (United Kingdom)

    2017-06-15

    Highlights: • Repeated ice adhesion and removal occurs on nanocoatings. • Icephobicity of nanocoatings reduces with each test cycle. • Adhesion strength linked to contact angle hysteresis in Gaussian fit. • Icephobicity not linked to hydrophobicity. - Abstract: The accretion of ice can cause damage in applications ranging from power lines and shipping decks, to wind turbines and rail infrastructure. In particular on aircraft, it can change aerodynamic characteristics, greatly affecting the flight safety. Commercial aircraft are therefore required to be equipped with de-icing devices, such as heating mats over the wings. The application of icephobic coatings near the leading edge of a wing can in theory reduce the high power requirements of heating mats, which melt ice that forms there. Such coatings are effective in preventing the accretion of runback ice, formed from airborne supercooled droplets, or the water that the heating mats generate as it is sheared back over the wing's upper surface. However, the durability and the practicality of applying them over a large wing surface have been prohibitive factors in deploying this technology so far. Here, we evaluated the ice adhesion strength of four non-conductive coatings and seven thermally conductive coatings by shearing ice samples from coated plates by spinning them in a centrifuge device. The durability of the coating performance was also assessed by repeating the tests, each time regrowing ice samples on the previously-used coatings. Contact angle parameters of each coating were tested for each test to determine influence on ice adhesion strength. The results indicate that contact angle hysteresis is a crucial parameter in determining icephobicity of a coating and hydrophobicity is not necessarily linked to icephobicity.

  4. Reduced Utilization of Selenium by Naked Mole Rats Due to a Specific Defect in GPx1 Expression*

    Science.gov (United States)

    Kasaikina, Marina V.; Lobanov, Alexei V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E.; Turanov, Anton A.; Finney, Lydia; Vogt, Stefan; Park, Thomas J.; Miller, Richard A.; Hatfield, Dolph L.; Gladyshev, Vadim N.

    2011-01-01

    Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower in MR liver and kidney than in mouse tissues. In addition, metabolic labeling of MR cells with 75Se revealed a loss of the abundant glutathione peroxidase 1 (GPx1) band, whereas other selenoproteins were preserved. To characterize the MR selenoproteome, we sequenced its liver transcriptome. Gene reconstruction revealed standard selenoprotein sequences except for GPx1, which had an early stop codon, and SelP, which had low selenocysteine content. When expressed in HEK 293 cells, MR GPx1 was present in low levels, and its expression could be rescued neither by removing the early stop codon nor by replacing its SECIS element. In addition, GPx1 mRNA was present in lower levels in MR liver than in mouse liver. To determine if GPx1 deficiency could account for the reduced selenium content, we analyzed GPx1 knock-out mice and found reduced selenium levels in their livers and kidneys. Thus, MR is characterized by the reduced utilization of selenium due to a specific defect in GPx1 expression. PMID:21372135

  5. Anti-ceramidase LCL385 acutely reduces BCL-2 expression in the hippocampus but is not associated with an increase of learned helplessness in rats.

    Science.gov (United States)

    Nahas, Ziad; Jiang, Yan; Zeidan, Youssef H; Bielawska, Alicja; Szulc, Zdzislaw; Devane, Lindsay; Kalivas, Peter; Hannun, Yusuf A

    2009-01-30

    Evidence from in situ studies supports the role of anti-apoptotic factors in the antidepressant responses of certain psychotropics. The availability of anti-ceramidase pro-apoptocic compound (LCL385) provides an opportunity to test in vivo the relation between hippocampal apopotosis and learned helplessness. 40 Sprague-Dawley male rodents underwent an FST after a treatment with LCL385, desipramine (DMI), or placebo (SAL) over 3 days. Behavioral responses, including immobility, swimming and climbing were counted during the 6min test. Western blot labeling was used to detect anti-apoptosis in hippocampus. DMI alone was associated with reduced immobility and increased climbing whereas LCL385 alone showed a decrease in Bcl-2/beta-actin ratio. Direct modulation of Bcl-2 expression in the hippocampus is not associated with learned helplessness in stressed rats. Three-day administration of DMI and LCL385 show divergent effects on behavioral and anti-apoptotic measures.

  6. Comparison of small n statistical tests of differential expression applied to microarrays

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    Lee Anna Y

    2009-02-01

    Full Text Available Abstract Background DNA microarrays provide data for genome wide patterns of expression between observation classes. Microarray studies often have small samples sizes, however, due to cost constraints or specimen availability. This can lead to poor random error estimates and inaccurate statistical tests of differential expression. We compare the performance of the standard t-test, fold change, and four small n statistical test methods designed to circumvent these problems. We report results of various normalization methods for empirical microarray data and of various random error models for simulated data. Results Three Empirical Bayes methods (CyberT, BRB, and limma t-statistics were the most effective statistical tests across simulated and both 2-colour cDNA and Affymetrix experimental data. The CyberT regularized t-statistic in particular was able to maintain expected false positive rates with simulated data showing high variances at low gene intensities, although at the cost of low true positive rates. The Local Pooled Error (LPE test introduced a bias that lowered false positive rates below theoretically expected values and had lower power relative to the top performers. The standard two-sample t-test and fold change were also found to be sub-optimal for detecting differentially expressed genes. The generalized log transformation was shown to be beneficial in improving results with certain data sets, in particular high variance cDNA data. Conclusion Pre-processing of data influences performance and the proper combination of pre-processing and statistical testing is necessary for obtaining the best results. All three Empirical Bayes methods assessed in our study are good choices for statistical tests for small n microarray studies for both Affymetrix and cDNA data. Choice of method for a particular study will depend on software and normalization preferences.

  7. Experimental results of the SMART ECC injection performance with reduced scale of test facility

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Young Il; Cho, Seok; Ko, Yung Joo; Shin, Yong Cheol; Kwon, Tae Soon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-05-15

    SMART pressurized water reactor type is different from the existing integral NSSS commercial pressurized water reactor system which is equipped with the main features. In addition, RCS piping is removed and the feature of the SBLOCA is a major design break accident. SWAT (SMART ECC Water Asymmetric Two-phase choking test facility) test facility is to simulate the 2 inch SBLOCA of the SMART using with reduced scale. The Test was performed to produce experimental data for the validation of the TASS/SMR-S thermal hydraulic analysis code, and to investigate the related thermal hydraulic phenomena in the down-comer region during the 2 inch SBLOCA of the safety inject line. The particular phenomena for the observation are ECC bypass and multi-dimensional flow characteristics to verify the effectiveness and performance of the safety injection system. In this paper, the corresponding steady state test conditions, including initial and boundary conditions along with major measuring parameters, and related experimental results were described

  8. Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis

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    Dohnert MB

    2012-03-01

    Full Text Available Marcelo B Dohnert1,2, Mirelli Venâncio1, Jonathann C Possato1, Rodrigo C Zeferino1, Luciana H Dohnert2, Alexandra I Zugno1, Cláudio T De Souza1, Marcos MS Paula1, Thais F Luciano11Postgraduation Program in Health Sciences, Programa de Pós-graduação em Ciências da Saúde PPGCS, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, 2Department of Physiotherapy, Universidade Luterana do Brasil, Torres, Rio Grande do Sul, BrazilIntroduction: Tendinitis affects a substantial number of people in several occupations involving repetitive work or direct trauma. Iontophoresis is a therapeutic alternative used in the treatment of injury during the inflammatory phase. In recent years, gold nanoparticles (GNP have been studied due to their therapeutic anti-inflammatory capacity and as an alternative to the transport of several proteins. Purpose: This study evaluates the therapeutic effects of iontophoresis using GNPs and diclofenac diethylammonium on inflammatory parameters in rats challenged with traumatic tendinitis.Methods: Wistar rats were divided in three treatment groups (n = 15: (1 iontophoresis + diclofenac diethylammonium; (2 iontophoresis + GNP; and (3 iontophoresis + diclofenac diethylammonium + GNP. External control was formed by challenged tendons without treatment (n = 15. Iontophoresis was administered using 0.3 mA direct current on 1.5 cm² electrodes. Results: The levels of both inflammatory cytokines were significantly higher in untreated challenged rats, when compared with the control (5.398 ± 234 for interleukin 1 beta and 6.411 ± 432 for tumor necrosis factor alpha, which confirms the occurrence of an inflammatory stage in injury (P < 0.05. A significant decrease was observed in expression of cytokines interleukin 1 beta in the three treatment groups, in comparison with untreated challenged tendons, although, in the group treated with diclofenac and GNP, results were similar to the control (1.732 ± 239 (P < 0

  9. Thymol reduces oxidative stress, aortic intimal thickening, and inflammation-related gene expression in hyperlipidemic rabbits

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    Ya-Mei Yu

    2016-07-01

    Full Text Available Atherosclerosis plays a key role in the development of cardiovascular diseases, and is often associated with oxidative stress and local inflammation. Thymol, a major polyphenolic compound in thyme, exhibits antioxidant and anti-inflammatory properties. In this study, we measured the in vitro antioxidant activity of thymol, and investigated the effect of thymol on high-fat-diet-induced hyperlipidemia and atherosclerosis. New Zealand white rabbits were fed with regular chow, high-fat and high-cholesterol diet (HC, T3, or T6 (HC with thymol supplementation at 3 mg/kg/d or 6 mg/kg/d, respectively for 8 weeks. Aortic intimal thickening, serum lipid parameters, multiple inflammatory markers, proinflammatory cytokines, and atherosclerosis-associated indicators were significantly increased in the HC group but decreased upon thymol supplementation. In summary, thymol exhibits antioxidant activity, and may suppress the progression of high-fat-diet-induced hyperlipidemia and atherosclerosis by reducing aortic intimal lipid lesion, lowering serum lipids and oxidative stress, and alleviating inflammation-related responses.

  10. Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

    Science.gov (United States)

    Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

    2013-11-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice. © 2013.

  11. Reduced RAN expression and disrupted transport between cytoplasm and nucleus; a key event in Alzheimer's disease pathophysiology.

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    Diego Mastroeni

    Full Text Available Transcription of DNA is essential for cell maintenance and survival; inappropriate localization of proteins that are involved in transcription would be catastrophic. In Alzheimer's disease brains, and in vitro studies, we have found qualitative and quantitative deficits in transport into the nucleus of DNA methyltransferase 1 (DNMT1 and RNA polymerase II (RNA pol II, accompanied by their abnormal sequestration in the cytoplasm. RAN (RAs-related Nuclear protein knockdown, by siRNA and oligomeric Aβ42 treatment in neurons, replicate human data which indicate that transport disruption in AD may be mechanistically linked to reduced expression of RAN, a pivotal molecule in nucleocytoplasmic transport. In vitro studies also indicate a significant role for oligomeric Aβ42 in the observed phenomena. We propose a model in which reduced transcription regulators in the nucleus and their increased presence in the cytoplasm may lead to many of the cellular manifestations of Alzheimer's disease.

  12. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

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    Roberto Furlanetto Jr

    2017-02-01

    Full Text Available Objective: We studied the effect of resistance exercise (RE on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF. Material and methods : Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams were randomly allocated into five groups: control group (CT-Sham; n = 6; group with rheumatoid arthritis (RA; n = 6; group with rheumatoid arthritis subjected to RE (RAEX; n = 6; ovariectomy group with rheumatoid arthritis (RAOV; n = 6; and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6. After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results : The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV, but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions : LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1. However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF.

  13. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    International Nuclear Information System (INIS)

    Theunissen, P.T.; Robinson, J.F.; Pennings, J.L.A.; Herwijnen, M.H. van; Kleinjans, J.C.S.; Piersma, A.H.

    2012-01-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  14. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    Energy Technology Data Exchange (ETDEWEB)

    Theunissen, P.T., E-mail: Peter.Theunissen@rivm.nl [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Robinson, J.F. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Pennings, J.L.A. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Herwijnen, M.H. van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Kleinjans, J.C.S. [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Piersma, A.H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Institute for Risk Assessment Sciences, Faculty of Veterinary Sciences, Utrecht University, Utrecht (Netherlands)

    2012-08-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  15. Reduced expression of Nogo-A leads to motivational deficits in rats

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    Thomas eEnkel

    2014-01-01

    Full Text Available Nogo-A is an important neurite growth-regulatory protein in the adult and developing nervous system. Mice lacking Nogo-A, or rats with neuronal Nogo-A deficiency, exhibit behavioral abnormalities such as impaired short-term memory, decreased prepulse inhibition and behavioral inflexibility. In the current study we extended the behavioral profile of the Nogo-A deficient rat line with respect to reward sensitivity and motivation and determined the concentrations of the monoamines dopamine and serotonin in the prefrontal cortex, dorsal striatum and nucleus accumbens. Using a limited access consumption task, we found similar intake of a sweet condensed milk solution following ad libitum or restricted feeding in wild-type and Nogo-A deficient rats, indicating normal reward sensitivity and translation of hunger into feeding behavior. When tested for motivation in a spontaneous progressive ratio task, Nogo-A rats exhibited lower break points and tended to have lower ‘highest completed ratios’. Further, under extinction conditions responding ceased substantially earlier in these rats. Finally, in the prefrontal cortex we found increased tissue levels of serotonin, while dopamine was unaltered. Dopamine and serotonin levels were also unaltered in the dorsal striatum and the nucleus accumbens. In summary, these results suggest a role for Nogo-A regulated processes in motivated behavior and related neurochemistry. The behavioral pattern observed resembles aspects of the negative symptomatology of schizophrenia.

  16. Branched-chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein-expressing mice

    Science.gov (United States)

    Korenaga, Masaaki; Nishina, Sohji; Korenaga, Keiko; Tomiyama, Yasuyuki; Yoshioka, Naoko; Hara, Yuichi; Sasaki, Yusuke; Shimonaka, Yasushi; Hino, Keisuke

    2015-01-01

    Background & Aims Branched-chain amino acids (BCAA) reduce the incidence of hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the mechanisms that underlie these effects remain unknown. Previously, we reported that oxidative stress in male transgenic mice that expressed hepatitis C virus polyprotein (HCVTgM) caused hepatic iron accumulation by reducing hepcidin transcription, thereby leading to HCC development. This study investigated whether long-term treatment with BCAA reduced hepatic iron accumulation and oxidative stress in iron-overloaded HCVTgM and in patients with HCV-related advanced fibrosis. Methods Male HCVTgM were fed an excess-iron diet that comprised either casein or 3.0% BCAA, or a control diet, for 6 months. Results For HCVTgM, BCAA supplementation increased the serum hepcidin-25 levels and antioxidant status [ratio of biological antioxidant potential (BAP) relative to derivatives of reactive oxygen metabolites (dROM)], decreased the hepatic iron contents, attenuated reactive oxygen species generation, and restored mitochondrial superoxide dismutase expression and mitochondrial complex I activity in the liver compared with mice fed the control diet. After 48 weeks of BCAA supplementation in patients with HCV-related advanced fibrosis, BAP/dROM and serum hepcidin-25 increased and serum ferritin decreased compared with the pretreatment levels. Conclusions BCAA supplementation reduced oxidative stress by restoring mitochondrial function and improved iron metabolism by increasing hepcidin-25 in both iron-overloaded HCVTgM and patients with HCV-related advanced fibrosis. These activities of BCAA may partially account for their inhibitory effects on HCC development in cirrhosis patients. PMID:25156780

  17. Gene expression-based biological test for major depressive disorder: an advanced study

    Directory of Open Access Journals (Sweden)

    Watanabe S

    2017-02-01

    Full Text Available Shin-ya Watanabe,1 Shusuke Numata,1 Jun-ichi Iga,2 Makoto Kinoshita,1 Hidehiro Umehara,1 Kazuo Ishii,3 Tetsuro Ohmori1 1Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 2Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, 3Department of Applied Biological Science, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan Purpose: Recently, we could distinguished patients with major depressive disorder (MDD from nonpsychiatric controls with high accuracy using a panel of five gene expression markers (ARHGAP24, HDAC5, PDGFC, PRNP, and SLC6A4 in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder.Patients and methods: We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR, and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls. Subsequently, a linear discriminant function was developed for use in discriminating between patients with MDD and without MDD.Results: This expression panel was able to segregate patients with MDD from those without MDD with a sensitivity and specificity of 64% and 67.9%, respectively.Conclusion: Further research to identify MDD-specific markers is needed to improve the performance of this biological test. Keywords: depressive disorder, biomarker, gene expression, schizophrenia, bipolar disorder

  18. Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans.

    Science.gov (United States)

    Winchester, Wendy J; Gore, Katrina; Glatt, Sophie; Petit, Wendy; Gardiner, Jennifer C; Conlon, Kelly; Postlethwaite, Michael; Saintot, Pierre-Philippe; Roberts, Sonia; Gosset, James R; Matsuura, Tomomi; Andrews, Mark D; Glossop, Paul A; Palmer, Michael J; Clear, Nicola; Collins, Susie; Beaumont, Kevin; Reynolds, David S

    2014-11-01

    The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  19. Reducing cytoplasmic polyamine oxidase activity in Arabidopsis increases salt and drought tolerance by reducing reactive oxygen species production and increasing defense gene expression

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    G.H.M. eSagor

    2016-02-01

    Full Text Available The link between polyamine oxidases (PAOs, which function in polyamine catabolism, and stress responses remains elusive. Here, we address this issue using Arabidopsis pao mutants in which the expression of the five PAO genes is knocked-out or knocked-down. As the five single pao mutants and wild type (WT showed similar response to salt stress, we tried to generate the mutants that have either the cytoplasmic PAO pathway (pao1 pao5 or the peroxisomal PAO pathway (pao2 pao3 pao4 silenced. However, the latter triple mutant was not obtained. Thus, in this study, we used two double mutants, pao1 pao5 and pao2 pao4. Of interest, pao1 pao5 mutant was NaCl- and drought-tolerant, whereas pao2 pao4 showed similar sensitivity to those stresses as WT. To reveal the underlying mechanism of salt tolerance, further analyses were performed. Na uptake of the mutant (pao1 pao5 decreased to 75% of WT. PAO activity of the mutant was reduced to 62% of WT. The content of reactive oxygen species (ROS such as hydrogen peroxide, a reaction product of PAO action, and superoxide anion in the mutant became 81% and 72% of the levels in WT upon salt treatment. The mutant contained 2.8-fold higher thermospermine compared to WT. Moreover, the mutant induced the genes of salt overly sensitive-, abscisic acid (ABA-dependent- and ABA-independent- pathways more strongly than WT upon salt treatment. The results suggest that the Arabidopsis plant silencing cytoplasmic PAOs shows salinity tolerance by reducing ROS production and strongly inducing subsets of stress-responsive genes under stress conditions.

  20. Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.

    Science.gov (United States)

    Hedenqvist, Patricia; Trbakovic, Amela; Thor, Andreas; Ley, Cecilia; Ekman, Stina; Jensen-Waern, Marianne

    2016-08-01

    In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10×10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II.

    Science.gov (United States)

    Doublier, Sophie; Salvidio, Gennaro; Lupia, Enrico; Ruotsalainen, Vesa; Verzola, Daniela; Deferrari, Giacomo; Camussi, Giovanni

    2003-04-01

    We studied the distribution of nephrin in renal biopsies from 17 patients with diabetes and nephrotic syndrome (7 type 1 and 10 type 2 diabetes), 6 patients with diabetes and microalbuminuria (1 type 1 and 5 type 2 diabetes), and 10 normal subjects. Nephrin expression was semiquantitatively evaluated by measuring immunofluorescence intensity by digital image analysis. We found an extensive reduction of nephrin staining in both type 1 (67 +/- 9%; P < 0.001) and type 2 (65 +/- 10%; P < 0.001) diabetic patients with diabetes and nephrotic syndrome when compared with control subjects. The pattern of staining shifted from punctate/linear distribution to granular. In patients with microalbuminuria, the staining pattern of nephrin also showed granular distribution and reduction intensity of 69% in the patient with type 1 diabetes and of 62 +/- 4% (P < 0.001) in the patients with type 2 diabetes. In vitro studies on human cultured podocytes demonstrated that glycated albumin and angiotensin II reduced nephrin expression. Glycated albumin inhibited nephrin synthesis through the engagement of receptor for advanced glycation end products, whereas angiotensin II acted on cytoskeleton redistribution, inducing the shedding of nephrin. This study indicates that the alteration in nephrin expression is an early event in proteinuric patients with diabetes and suggests that glycated albumin and angiotensin II contribute to nephrin downregulation.

  2. Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2.

    Directory of Open Access Journals (Sweden)

    David Ramonet

    2011-04-01

    Full Text Available Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene cause late-onset, autosomal dominant familial Parkinson's disease (PD and also contribute to idiopathic PD. LRRK2 mutations represent the most common cause of PD with clinical and neurochemical features that are largely indistinguishable from idiopathic disease. Currently, transgenic mice expressing wild-type or disease-causing mutants of LRRK2 have failed to produce overt neurodegeneration, although abnormalities in nigrostriatal dopaminergic neurotransmission have been observed. Here, we describe the development and characterization of transgenic mice expressing human LRRK2 bearing the familial PD mutations, R1441C and G2019S. Our study demonstrates that expression of G2019S mutant LRRK2 induces the degeneration of nigrostriatal pathway dopaminergic neurons in an age-dependent manner. In addition, we observe autophagic and mitochondrial abnormalities in the brains of aged G2019S LRRK2 mice and markedly reduced neurite complexity of cultured dopaminergic neurons. These new LRRK2 transgenic mice will provide important tools for understanding the mechanism(s through which familial mutations precipitate neuronal degeneration and PD.

  3. Glutamate reduces glucose utilization while concomitantly enhancing AQP9 and MCT2 expression in cultured rat hippocampal neurons

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    Fabio eTescarollo

    2014-08-01

    Full Text Available The excitatory neurotransmitter glutamate has been reported to have a major impact on brain energy metabolism. Using primary cultures of rat hippocampal neurons, we observed that glutamate reduces glucose utilization in this cell type, suggesting alteration in mitochondrial oxidative metabolism. The aquaglyceroporin AQP9 and the monocarboxylate transporter MCT2, two transporters for oxidative energy substrates, appear to be present in mitochondria of these neurons. Moreover, they not only co-localize but they interact with each other as they were found to co-immunoprecipitate from hippocampal neuron homogenates. Exposure of cultured hippocampal neurons to glutamate 100 µM for 1 hour led to enhanced expression of both AQP9 and MCT2 at the protein level without any significant change at the mRNA level. In parallel, a similar increase in the protein expression of LDHA was evidenced without an effect on the mRNA level. These data suggest that glutamate exerts an influence on neuronal energy metabolism likely through a regulation of the expression of some key mitochondrial proteins.

  4. Electrochemical Testing of Gas Tungsten Arc Welded and Reduced Pressure Electron Beam Welded Alloy 22

    International Nuclear Information System (INIS)

    Day, S D; Wong, F G; Gordon, S R; Wong, L L; Rebak, R B

    2006-01-01

    Alloy 22 (N06022) is the material selected for the fabrication of the outer shell of the nuclear waste containers for the Yucca Mountain high-level nuclear waste repository site. A key technical issue in the waste package program has been the integrity of the container weld joints. The currently selected welding process for fabricating and sealing the containers is the traditional gas tungsten arc welding (GTAW) or TIG method. An appealing faster alternative technique is reduced pressure electron beam (RPEB) welding. It was of interest to compare the corrosion properties of specimens prepared using both types of welding techniques. Standard electrochemical tests were carried on GTAW and RPEB welds as well as on base metal (non-welded) to determine their relative corrosion behavior in simulated concentrated water (SCW) at 90 C (alkaline), 1 M HCl at 60 C (acidic) and 1 M NaCl at 90 C (neutral) solutions. Results show that for all practical purposes, the three tested materials had the same electrochemical behavior in the three tested electrolytes

  5. Electrochemical Testing of Gas Tungsten ARC Welded and Reduced Pressure Electron Beam Welded Alloy 22

    International Nuclear Information System (INIS)

    S. Daniel Day; Frank M.G. Wong; Steven R. Gordon; Lana L. Wong; Raul B. Rebak

    2006-01-01

    Alloy 22 (N06022) is the material selected for the fabrication of the outer shell of the nuclear waste containers for the Yucca Mountain high-level nuclear waste repository site. A key technical issue in the waste package program has been the integrity of the container weld joints. The currently selected welding process for fabricating and sealing the containers is the traditional gas tungsten arc welding (GTAW) or TIC method. An appealing faster alternative technique is reduced pressure electron beam (RPEB) welding. It was of interest to compare the corrosion properties of specimens prepared using both types of welding techniques. Standard electrochemical tests were carried on GTAW and RPEB welds as well as on base metal (non-welded) to determine their relative corrosion behavior in simulated concentrated water (SCW) at 90 C (alkaline), 1 M HCI at 60 C (acidic) and 1 M NaCl at 90 C (neutral) solutions. Results show that for all practical purposes, the three tested materials had the same electrochemical behavior in the three tested electrolytes

  6. Liver Growth Factor (LGF Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich’s Ataxia Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Lucía Calatrava-Ferreras

    2016-12-01

    Full Text Available Friedreich’s ataxia (FA is a severe disorder with autosomal recessive inheritance that is caused by the abnormal expansion of GAA repeat in intron 1 of FRDA gen. This alteration leads to a partial silencing of frataxin transcription, causing a multisystem disorder disease that includes neurological and non-neurological damage. Recent studies have proven the effectiveness of neurotrophic factors in a number of neurodegenerative diseases. Therefore, we intend to determine if liver growth factor (LGF, which has a demonstrated antioxidant and neuroprotective capability, could be a useful therapy for FA. To investigate the potential therapeutic activity of LGF we used transgenic mice of the FXNtm1MknTg (FXNYG8Pook strain. In these mice, intraperitoneal administration of LGF (1.6 μg/mouse exerted a neuroprotective effect on neurons of the lumbar spinal cord and improved cardiac hypertrophy. Both events could be the consequence of the increment in frataxin expression induced by LGF in spinal cord (1.34-fold and heart (1.2-fold. LGF also upregulated by 2.6-fold mitochondrial chain complex IV expression in spinal cord, while in skeletal muscle it reduced the relation oxidized glutathione/reduced glutathione. Since LGF partially restores motor coordination, we propose LGF as a novel factor that may be useful in the treatment of FA.

  7. Stable Toll-Like Receptor 10 Knockdown in THP-1 Cells Reduces TLR-Ligand-Induced Proinflammatory Cytokine Expression

    Directory of Open Access Journals (Sweden)

    Hai Van Le

    2016-06-01

    Full Text Available Toll-like receptor 10 (TLR10 is the only orphan receptor whose natural ligand and function are unknown among the 10 human TLRs. In this study, to test whether TLR10 recognizes some known TLR ligands, we established a stable TLR10 knockdown human monocytic cell line THP-1 using TLR10 short hairpin RNA lentiviral particle and puromycin selection. Among 60 TLR10 knockdown clones that were derived from each single transduced cell, six clones were randomly selected, and then one of those clones, named E7, was chosen for the functional study. E7 exhibited approximately 50% inhibition of TLR10 mRNA and protein expression. Of all the TLRs, only the expression of TLR10 changed significantly in this cell line. Additionally, phorbol 12-myristate 13-acetate-induced macrophage differentiation of TLR10 knockdown cells was not affected in the knockdown cells. When exposed to TLR ligands, such as synthetic diacylated lipoprotein (FSL-1, lipopolysaccharide (LPS, and flagellin, significant induction of proinflammatory cytokine gene expression including Interleukin-8 (IL-8, Interleukin-1 beta (IL-1β, Tumor necrosis factor-alpha (TNF-α and Chemokine (C–C Motif Ligand 20 (CCL20 expression, was found in the control THP-1 cells, whereas the TLR10 knockdown cells exhibited a significant reduction in the expression of IL-8, IL-1β, and CCL20. TNF-α was the only cytokine for which the expression did not decrease in the TLR10 knockdown cells from that measured in the control cells. Analysis of putative binding sites for transcription factors using a binding-site-prediction program revealed that the TNF-α promoter does not have putative binding sites for AP-1 or c-Jun, comprising a major transcription factor along with NF-κB for TLR signaling. Our results suggest that TLR10 is involved in the recognition of FSL-1, LPS, and flagellin and TLR-ligand-induced expression of TNF-α does not depend on TLR10.

  8. Stable Toll-Like Receptor 10 Knockdown in THP-1 Cells Reduces TLR-Ligand-Induced Proinflammatory Cytokine Expression.

    Science.gov (United States)

    Le, Hai Van; Kim, Jae Young

    2016-06-01

    Toll-like receptor 10 (TLR10) is the only orphan receptor whose natural ligand and function are unknown among the 10 human TLRs. In this study, to test whether TLR10 recognizes some known TLR ligands, we established a stable TLR10 knockdown human monocytic cell line THP-1 using TLR10 short hairpin RNA lentiviral particle and puromycin selection. Among 60 TLR10 knockdown clones that were derived from each single transduced cell, six clones were randomly selected, and then one of those clones, named E7, was chosen for the functional study. E7 exhibited approximately 50% inhibition of TLR10 mRNA and protein expression. Of all the TLRs, only the expression of TLR10 changed significantly in this cell line. Additionally, phorbol 12-myristate 13-acetate-induced macrophage differentiation of TLR10 knockdown cells was not affected in the knockdown cells. When exposed to TLR ligands, such as synthetic diacylated lipoprotein (FSL-1), lipopolysaccharide (LPS), and flagellin, significant induction of proinflammatory cytokine gene expression including Interleukin-8 (IL-8), Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha (TNF-α) and Chemokine (C-C Motif) Ligand 20 (CCL20) expression, was found in the control THP-1 cells, whereas the TLR10 knockdown cells exhibited a significant reduction in the expression of IL-8, IL-1β, and CCL20. TNF-α was the only cytokine for which the expression did not decrease in the TLR10 knockdown cells from that measured in the control cells. Analysis of putative binding sites for transcription factors using a binding-site-prediction program revealed that the TNF-α promoter does not have putative binding sites for AP-1 or c-Jun, comprising a major transcription factor along with NF-κB for TLR signaling. Our results suggest that TLR10 is involved in the recognition of FSL-1, LPS, and flagellin and TLR-ligand-induced expression of TNF-α does not depend on TLR10.

  9. Reduced expression of Jak-1 and Tyk-2 proteins leads to interferon resistance in Hepatitis C virus replicon

    Directory of Open Access Journals (Sweden)

    Luftig Ronald

    2007-09-01

    Full Text Available Abstract Background Alpha interferon in combination with ribavirin is the standard therapy for hepatitis C virus infection. Unfortunately, a significant number of patients fail to eradicate their infection with this regimen. The mechanisms of IFN-resistance are unclear. The aim of this study was to determine the contribution of host cell factors to the mechanisms of interferon resistance using replicon cell lines. Results HCV replicons with high and low activation of the IFN-promoter were cultured for a prolonged period of time in the presence of interferon-alpha (IFN-alpha2b. Stable replicon cell lines with resistant phenotype were isolated and characterized by their ability to continue viral replication in the presence of IFN-alpha. Interferon resistant cell colonies developed only in replicons having lower activation of the IFN promoter and no resistant colonies arose from replicons that exhibit higher activation of the IFN promoter. Individual cell clones were isolated and nine IFN resistant cell lines were established. HCV RNA and protein levels in these cells were not altered by IFN- alpha2b. Reduced signaling and IFN-resistant phenotype was found in all Huh-7 cell lines even after eliminating HCV, suggesting that cellular factors are involved. Resistant phenotype in the replicons is not due to lack of interferon receptor expression. All the cell lines show defect in the JAK-STAT signaling and phosphorylation of STAT 1 and STAT 2 proteins were strongly inhibited due to reduced expression of Tyk2 and Jak-1 protein. Conclusion This in vitro study provides evidence that altered expression of the Jak-Stat signaling proteins can cause IFN resistance using HCV replicon cell clones.

  10. Boron Toxicity Tolerance in Barley through Reduced Expression of the Multifunctional Aquaporin HvNIP2;11[W

    Science.gov (United States)

    Schnurbusch, Thorsten; Hayes, Julie; Hrmova, Maria; Baumann, Ute; Ramesh, Sunita A.; Tyerman, Stephen D.; Langridge, Peter; Sutton, Tim

    2010-01-01

    Boron (B) toxicity is a significant limitation to cereal crop production in a number of regions worldwide. Here we describe the cloning of a gene from barley (Hordeum vulgare), underlying the chromosome 6H B toxicity tolerance quantitative trait locus. It is the second B toxicity tolerance gene identified in barley. Previously, we identified the gene Bot1 that functions as an efflux transporter in B toxicity-tolerant barley to move B out of the plant. The gene identified in this work encodes HvNIP2;1, an aquaporin from the nodulin-26-like intrinsic protein (NIP) subfamily that was recently described as a silicon influx transporter in barley and rice (Oryza sativa). Here we show that a rice mutant for this gene also shows reduced B accumulation in leaf blades compared to wild type and that the mutant protein alters growth of yeast (Saccharomyces cerevisiae) under high B. HvNIP2;1 facilitates significant transport of B when expressed in Xenopus oocytes compared to controls and to another NIP (NOD26), and also in yeast plasma membranes that appear to have relatively high B permeability. We propose that tolerance to high soil B is mediated by reduced expression of HvNIP2;1 to limit B uptake, as well as by increased expression of Bot1 to remove B from roots and sensitive tissues. Together with Bot1, the multifunctional aquaporin HvNIP2;1 is an important determinant of B toxicity tolerance in barley. PMID:20581256

  11. Earthquake forecasting test for Kanto district to reduce vulnerability of urban mega earthquake disasters

    Science.gov (United States)

    Yokoi, S.; Tsuruoka, H.; Nanjo, K.; Hirata, N.

    2012-12-01

    Collaboratory for the Study of Earthquake Predictability (CSEP) is a global project on earthquake predictability research. The final goal of this project is to search for the intrinsic predictability of the earthquake rupture process through forecast testing experiments. The Earthquake Research Institute, the University of Tokyo joined CSEP and started the Japanese testing center called as CSEP-Japan. This testing center provides an open access to researchers contributing earthquake forecast models applied to Japan. Now more than 100 earthquake forecast models were submitted on the prospective experiment. The models are separated into 4 testing classes (1 day, 3 months, 1 year and 3 years) and 3 testing regions covering an area of Japan including sea area, Japanese mainland and Kanto district. We evaluate the performance of the models in the official suite of tests defined by CSEP. The total number of experiments was implemented for approximately 300 rounds. These results provide new knowledge concerning statistical forecasting models. We started a study for constructing a 3-dimensional earthquake forecasting model for Kanto district in Japan based on CSEP experiments under the Special Project for Reducing Vulnerability for Urban Mega Earthquake Disasters. Because seismicity of the area ranges from shallower part to a depth of 80 km due to subducting Philippine Sea plate and Pacific plate, we need to study effect of depth distribution. We will develop models for forecasting based on the results of 2-D modeling. We defined the 3D - forecasting area in the Kanto region with test classes of 1 day, 3 months, 1 year and 3 years, and magnitudes from 4.0 to 9.0 as in CSEP-Japan. In the first step of the study, we will install RI10K model (Nanjo, 2011) and the HISTETAS models (Ogata, 2011) to know if those models have good performance as in the 3 months 2-D CSEP-Japan experiments in the Kanto region before the 2011 Tohoku event (Yokoi et al., in preparation). We use CSEP

  12. Expression

    Directory of Open Access Journals (Sweden)

    Wang-Xia Wang

    2014-02-01

    Full Text Available The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs, sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively. In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS. In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs. Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

  13. Reduced brain-derived neurotrophic factor expression in cortex and hippocampus involved in the learning and memory deficit in molarless SAMP8 mice

    Institute of Scientific and Technical Information of China (English)

    JIANG Qing-song; LIANG Zi-liang; WU Min-Jie; FENG Lin; LIU Li-li; ZHANG Jian-jun

    2011-01-01

    Background The molarless condition has been reported to compromise learning and memory functions. However, it remains unclear how the molarless condition directly affects the central nervous system, and the functional consequences on the brain cortex and hippocampus have not been described in detail. The aim of this study was to find the molecular mechanism related with learning and memory deficit after a bilateral molarless condition having been surgically induced in senescence-accelerated mice/prone8 (SAMP8) mice, which may ultimately provide an experimental basis for clinical prevention of senile dementia.Methods Mice were either sham-operated or subjected to complete molar removal. The animals' body weights were monitored every day. Learning ability and memory were measured in a water maze test at the end of the 1 st, 2nd, and 3rd months after surgery. As soon as significantly prolonged escape latency in the molarless group was detected, the locomotor activity was examined in an open field test. Subsequently, the animals were decapitated and the cortex and hippocampus were dissected for Western blotting to measure the expression levels of brain-derived neurotrophic factor (BDNF) and the tropomyosin related kinase B (TrkB), the high affinity receptor of BDNF.Results Slightly lower weights were consistently observed in the molarless group, but there was no significant difference in weights between the two groups (P>0.05). Compared with the sham group, the molarless group exhibited lengthened escape latency in the water maze test three months after surgery, whereas no difference in locomotor activity was observed. Meanwhile, in the cortex and hippocampus, BDNF levels were significantly decreased in the molarless group (P<0.05); but the expression of its receptor, TrkB, was not significantly affected.Conclusion These results suggested that the molarless condition impaired learning and memory abilities in SAMP8mice three months after teeth extraction, and this

  14. TestMeEast: a campaign to increase HIV testing in hospitals and to reduce late diagnosis.

    Science.gov (United States)

    Bath, R; O'Connell, R; Lascar, M; Ferrand, R; Strachan, S; Matin, N; Bassnet, I; Orkin, C

    2016-01-01

    Late diagnosis occurs in almost half of those diagnosed in the UK (HIV Prevention England, 2013. Retrieved June 22, 2014, from HIV Prevention England: http://www.hivpreventionengland.org.uk/Campaigns-Current/National-HIV-Testing-Week ). Testing occurs mainly in sexual health and antenatal clinics despite recommendations to test more broadly [Ellis, S., & Curtis, H. (2012). HIV diagnoses and missed opportunities. Results of the British HIV association (BHIVA) National Audit 2010. Clinical Medicine, 12(5), 430-434]. We report the findings of an HIV-testing week campaign to offer testing to those who have blood tests as part of routine care within outpatient clinics and emergency departments of six London hospitals. The campaign target was to test 500 patients a day during the 2013 National HIV Testing Week (NHTW). Clinic staff and medical students were trained to offer routine HIV testing. Linkage to care was arranged for those who tested HIV-positive. During NHTW we tested 2402 of the planned 2500 test target. 2402/4317 (55.6% 95% CI 54.1-57.1%) of those who had routine blood tests were tested for HIV. There were eight HIV-positive tests; three were new diagnoses (all linked to care). The campaign hashtag #TestMeEast achieved a total Twitter "reach" of 238, 860 and the campaign had widespread news coverage. Our campaign showed that staff and students could be trained and mobilised to do thousands of routine HIV tests during a campaign.

  15. Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain.

    Science.gov (United States)

    Lewis, Jo E; Brameld, John M; Hill, Phil; Cocco, Cristina; Noli, Barbara; Ferri, Gian-Luca; Barrett, Perry; Ebling, Francis J P; Jethwa, Preeti H

    2017-01-01

    VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well

  16. Development of Reduced Activation Ferritic-Martensitic Steels and fabrication technologies for Indian test blanket module

    Energy Technology Data Exchange (ETDEWEB)

    Raj, Baldev [Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Jayakumar, T., E-mail: tjk@igcar.gov.in [Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India)

    2011-10-01

    For the development of Reduced Activation Ferritic-Martensitic Steel (RAFMS), for the Indian Test Blanket Module for ITER, a 3-phase programme has been adopted. The first phase consists of melting and detailed characterization of a laboratory scale heat conforming to Eurofer 97 composition, to demonstrate the capability of the Indian industry for producing fusion grade steel. In the second phase which is currently in progress, the chemical composition will be optimized with respect to tungsten and tantalum for better combination of mechanical properties. Characterization of the optimized commercial scale India-specific RAFM steel will be carried out in the third phase. The first phase of the programme has been successfully completed and the tensile, impact and creep properties are comparable with Eurofer 97. Laser and electron beam welding parameters have been optimized and welding consumables were developed for Narrow Gap - Gas Tungsten Arc welding and for laser-hybrid welding.

  17. Technical issues of reduced activation ferritic/martensitic steels for fabrication of ITER test blanket modules

    International Nuclear Information System (INIS)

    Tanigawa, H.; Hirose, T.; Shiba, K.; Kasada, R.; Wakai, E.; Serizawa, H.; Kawahito, Y.; Jitsukawa, S.; Kimura, A.; Kohno, Y.; Kohyama, A.; Katayama, S.; Mori, H.; Nishimoto, K.; Klueh, R.L.; Sokolov, M.A.; Stoller, R.E.; Zinkle, S.J.

    2008-01-01

    Reduced activation ferritic/martensitic steels (RAFMs) are recognized as the primary candidate structural materials for fusion blanket systems. The RAFM F82H was developed in Japan with emphasis on high-temperature properties and weldability. Extensive irradiation studies have conducted on F82H, and it has the most extensive available database of irradiated and unirradiated properties of all RAFMs. The objective of this paper is to review the R and D status of F82H and to identify the key technical issues for the fabrication of an ITER test blanket module (TBM) suggested from the recent research achievements in Japan. This work clarified that the primary issues with F82H involve welding techniques and the mechanical properties of weld joints. This is the result of the distinctive nature of the joint caused by the phase transformation that occurs in the weld joint during cooling, and its impact on the design of a TBM will be discussed

  18. The RERTR [Reduced Enrichment Research and Test Reactor] Program: Progress and plans

    International Nuclear Information System (INIS)

    Travelli, A.

    1987-01-01

    The progress of the Reduced Enrichment Research and Test Reactor (RERTR) Program is described. After a brief summary of the results which the RERTR Program, in collaboration with its many international partners, had achieved by the end of 1986, the activities, results, and new developments which occurred in 1987 are reviewed. Irradiation of the second miniplate series, concentrating on U 3 Si 2 -Al and U 3 Si-Al fuels, was completed and postirradiation examinations were performed on many of its miniplates. The whole-core ORR demonstration with U 3 Si 2 -Al fuel at 4.8 g U/cm 3 was completed at the end of March with excellent results and with 29 elements estimated to have reached at least 40% average burnup. Good progress was made in the area of LEU usage for the production of fission 99 Mo, and in the coordination of safety evaluations related to LEU conversions of US university reactors. Planned activities include testing and demonstrating advanced fuels intended to allow use of reduced enrichment uranium in very-high-performance reactors. Two candidate fuels are U 3 Si-Al with 19.75% enrichment and U 3 Si 2 -Al with 45% enrichment. Demonstration of these fuels will include irradiation of full-size elements and, possibly, a full-core demonstration. Achievement of the final program goals is still projected for 1990. This progress could not have been possible without the close international cooperation which has existed from the beginning, and which is essential to the ultimate success of the RERTR Program

  19. Usability Testing of the BRANCH Smartphone App Designed to Reduce Harmful Drinking in Young Adults.

    Science.gov (United States)

    Milward, Joanna; Deluca, Paolo; Drummond, Colin; Watson, Rod; Dunne, Jacklyn; Kimergård, Andreas

    2017-08-08

    Electronic screening and brief intervention (eSBI) apps demonstrate potential to reduce harmful drinking. However, low user engagement rates with eSBI reduce overall effectiveness of interventions. As "Digital Natives," young adults have high expectations of app quality. Ensuring that the design, content, and functionality of an eSBI app are acceptable to young adults is an integral stage to the development process. The objective of this study was to identify usability barriers and enablers for an app, BRANCH, targeting harmful drinking in young adults. The BRANCH app contains a drinking diary, alcohol reduction goal setting functions, normative drinking feedback, and information on risks and advice for cutting down. The app includes a social feature personalized to motivate cutting down and to promote engagement with a point-based system for usage. Three focus groups were conducted with 20 users who had tested the app for 1 week. A detailed thematic analysis was undertaken. The first theme, "Functionality" referred to how users wanted an easy-to-use interface, with minimum required user-input. Poor functionality was considered a major usability barrier. The second theme, "Design" described how an aesthetic with minimum text, clearly distinguishable tabs and buttons and appealing infographics was integral to the level of usability. The final theme, "Content" described how participants wanted all aspects of the app to be automatically personalized to them, as well as providing them with opportunities to personalize the app themselves, with increased options for social connectivity. There are high demands for apps such as BRANCH that target skilled technology users including young adults. Key areas to optimize eSBI app development that emerged from testing BRANCH with representative users include high-quality functionality, appealing aesthetics, and improved personalization. ©Joanna Milward, Paolo Deluca, Colin Drummond, Rod Watson, Jacklyn Dunne, Andreas Kimerg

  20. Proceedings of the 1990 International Meeting on Reduced Enrichment for Research and Test Reactors

    Energy Technology Data Exchange (ETDEWEB)

    1993-07-01

    The global effort to reduce, and possibly, eliminate the international traffic in highly-enriched uranium caused by its use in research reactors requires extensive cooperation and free exchange of information among all participants. To foster this free exchange of information, the Reduced Enrichment Research and Test Reactor (RERTR) Program, at Argonne National Laboratory, sponsored this meeting as the thirteenth of a series which began in 1978. The common effort brought together, past, a large number of specialists from many countries. On hundred twenty-three participants from 26 countries, including scientists, reactor operators, and personnel from commercial fuel suppliers, research centers, and government organizations, convened in Newport, Rhode Island to discuss their results, their activities, and their plans relative to converting research reactors to low-enriched fuels. As more and more reactors convert to the use of low-enriched uranium, the emphasis of our effort has begun to shift from research and development to tasks more directly related to implementation of the new fuels and technologies that have been developed, and to refinements of those fuels and technologies. It is appropriate, for this reason, that the emphasis of this meeting was placed on safety and on conversion experiences. This individual papers in this report have been cataloged separately.

  1. Proceedings of the 1990 International Meeting on Reduced Enrichment for Research and Test Reactors

    International Nuclear Information System (INIS)

    1993-07-01

    The global effort to reduce, and possibly, eliminate the international traffic in highly-enriched uranium caused by its use in research reactors requires extensive cooperation and free exchange of information among all participants. To foster this free exchange of information, the Reduced Enrichment Research and Test Reactor (RERTR) Program, at Argonne National Laboratory, sponsored this meeting as the thirteenth of a series which began in 1978. The common effort brought together, past, a large number of specialists from many countries. On hundred twenty-three participants from 26 countries, including scientists, reactor operators, and personnel from commercial fuel suppliers, research centers, and government organizations, convened in Newport, Rhode Island to discuss their results, their activities, and their plans relative to converting research reactors to low-enriched fuels. As more and more reactors convert to the use of low-enriched uranium, the emphasis of our effort has begun to shift from research and development to tasks more directly related to implementation of the new fuels and technologies that have been developed, and to refinements of those fuels and technologies. It is appropriate, for this reason, that the emphasis of this meeting was placed on safety and on conversion experiences. This individual papers in this report have been cataloged separately

  2. Exposure to aged crumb rubber reduces survival time during a stress test in earthworms (Eisenia fetida).

    Science.gov (United States)

    Pochron, Sharon; Nikakis, Jacqueline; Illuzzi, Kyra; Baatz, Andrea; Demirciyan, Loriana; Dhillon, Amritjot; Gaylor, Thomas; Manganaro, Alexa; Maritato, Nicholas; Moawad, Michael; Singh, Rajwinder; Tucker, Clara; Vaughan, Daniel

    2018-04-01

    Solid waste management struggles with the sustainable disposal of used tires. One solution involves shredding used tires into crumb rubber and using the material as infill for artificial turf. However, crumb rubber contains hydrocarbons, organic compounds, and heavy metals, and it travels into the environment. Earthworms living in soil contaminated with virgin crumb rubber gained 14% less body weight than did earthworms living in uncontaminated soil, but the impact of aged crumb rubber on the earthworms is unknown. Since many athletic fields contain aged crumb rubber, we compared the body weight, survivorship, and longevity in heat and light stress for earthworms living in clean topsoil to those living in topsoil contaminated with aged crumb rubber. We also characterized levels of metals, nutrients, and micronutrients of both soil treatments and compared those to published values for soil contaminated with virgin crumb rubber. Consistent with earlier research, we found that contaminated soil did not inhibit microbial respiration rates. Aged crumb rubber, like new crumb rubber, had high levels of zinc. However, while exposure to aged crumb rubber did not reduce earthworm body weight as did exposure to new crumb rubber, exposure to aged crumb rubber reduced earthworm survival time during a stress test by a statistically significant 38 min (16.2%) relative to the survival time for worms that had lived in clean soil. Aged crumb rubber and new crumb rubber appear to pose similar toxic risks to earthworms. This study suggests an environmental cost associated with the current tire-recycling solution.

  3. Testing Mediators of Reduced Drinking for Veterans in Alcohol Care Management.

    Science.gov (United States)

    Moskal, Dezarie; Maisto, Stephen A; Possemato, Kyle; Lynch, Kevin G; Oslin, David W

    2018-03-26

    Alcohol Care Management (ACM) is a manualized treatment provided by behavioral health providers working in a primary care team aimed at increasing patients' treatment engagement and decreasing their alcohol use. Research has shown that ACM is effective in reducing alcohol consumption; however, the mechanisms of ACM are unknown. Therefore, the purpose of this study is to examine the mechanisms of change in ACM in the context of a randomized clinical trial evaluating the effectiveness of ACM. This study performed secondary data analysis of existing data from a larger study that involved a sample of U.S. veterans (N = 163) who met criteria for current alcohol dependence. Upon enrollment into the study, participants were randomized to receive either ACM or standard care. ACM was delivered in-person or by telephone within the primary care clinic and focused on the use of oral naltrexone and manualized psychosocial support. According to theory, we hypothesized several ACM treatment components that would mediate alcohol consumption outcomes: engagement in addiction treatment, reduced craving, and increased readiness to change. Parallel mediation models were performed by the PROCESS macro Model 4 in SPSS to test study hypotheses. The institutional review boards at each of the participating facilities approved all study procedures before data collection. As hypothesized, results showed that treatment engagement mediated the relation between treatment and both measures of alcohol consumption outcomes, the percentage of alcohol abstinent days, and the percentage of heavy drinking days. Neither craving nor readiness to change mediated the treatment effect on either alcohol consumption outcome. Findings suggest that ACM may be effective in changing drinking patterns partially due to an increase in treatment engagement. Future research may benefit from evaluating the specific factors that underlie increased treatment engagement. The current study provides evidence that alcohol

  4. GPER mediated estradiol reduces miR-148a to promote HLA-G expression in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Sifeng, E-mail: taosifeng@aliyun.com; He, Haifei; Chen, Qiang; Yue, Wenjie

    2014-08-15

    Highlights: • E2 induces the level of miR-148a in MCF-7 and MDA-MB-231 cells. • GPER mediates the E2-induced increase of miR-148a in MCF-7 and MDA-MB-231 cells. • E2-GPER regulates the expression of HLA-G by miR-148a. - Abstract: Breast cancer is the most common malignant diseases in women. miR-148a plays an important role in regulation of cancer cell proliferation and cancer invasion and down-regulation of miR-148a has been reported in both estrogen receptor (ER) positive and triple-negative (TN) breast cancer. However, the regulation mechanism of miR-148a is unclear. The role of estrogen signaling, a signaling pathway is important in development and progression of breast cancer. Therefore, we speculated that E2 may regulate miR-148a through G-protein-coupled estrogen receptor-1 (GPER). To test our hypothesis, we checked the effects of E2 on miR-148a expression in ER positive breast cancer cell MCF-7 and TN cancer cell MDA-MB-231. Then we used GPER inhibitor G15 to investigate whether GPER is involved in regulation of E2 on miR-148a. Furthermore, we analyzed whether E2 affects the expression of HLA-G, which is a miR-148a target gene through GPER. The results showed that E2 induces the level of miR-148a in MCF-7 and MDA-MB-231 cells, GPER mediates the E2-induced increase in miR-148a expression in MCF-7 and MDA-MB-231 cells and E2-GPER regulates the expression of HLA-G by miR-148a. In conclusion, our findings offer important new insights into the ability of estrogenic GPER signaling to trigger HLA-G expression through inhibiting miR-148a that supports immune evasion in breast cancer.

  5. Connexin 43 expression in human and mouse testes with impaired spermatogenesis

    Directory of Open Access Journals (Sweden)

    M Kotula-Balak

    2009-08-01

    Full Text Available Connexin 43 (Cx43 belongs to a family of proteins that form gap junction channels. The aim of this study was to examine the expression of Cx43 in the testis of a patient with Klinefelter’s syndrome and of mice with the mosaic mutation and a partial deletion in the long arm of the Y chromosome. These genetic disorders are characterized by the presence of numerous degenerated seminiferous tubules and impaired spermatogenesis. In mouse testes, the expression and presence of Cx43 were detected by means of immunohistochemistry and Western blot analysis, respectively. In testes of Klinefelter’s patient only immunoexpression of Cx43 was detected. Regardless of the species Cx43 protein was ubiquitously distributed in testes of reproductively normal males, whereas in those with testicular disorders either a weak intensity of staining or no staining within the seminiferous tubules was observed. Moderate to strong or very strong staining was confined to the interstitial tissue. In an immunoblot analysis of testicular homogenates Cx43 appeared as one major band of approximately 43 kDa. Our study adds three more examples of pathological gonads in which the absence or apparent decrease of Cx43 expression within the seminiferous tubules was found. A positive correlation between severe spermatogenic impairment and loss of Cx43 immunoreactivity observed in this study supports previous data that gap junctions play a crucial role in spermatogenesis. Strong Cx43 expression detected mostly in the interstitial tissue of the Klinefelter’s patient may presumably be of importance in sustaining Leydig cell metabolic activity. However, the role of gap junction communication in the control of Leydig cell function seems to be more complex than originally thought.

  6. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2

    Directory of Open Access Journals (Sweden)

    Quadros Edward V

    2009-05-01

    Full Text Available Abstract Background Recent evidence suggests that several human cancers are capable of uncoupling of mitochondrial ATP generation in the presence of intact tricarboxylic acid (TCA enzymes. The goal of the current study was to test the hypothesis that ketone bodies can inhibit cell growth in aggressive cancers and that expression of uncoupling protein 2 is a contributing factor. The proposed mechanism involves inhibition of glycolytic ATP production via a Randle-like cycle while increased uncoupling renders cancers unable to produce compensatory ATP from respiration. Methods Seven aggressive human cancer cell lines, and three control fibroblast lines were grown in vitro in either 10 mM glucose medium (GM, or in glucose plus 10 mM acetoacetate [G+AcA]. The cells were assayed for cell growth, ATP production and expression of UCP2. Results There was a high correlation of cell growth with ATP concentration (r = 0.948 in a continuum across all cell lines. Controls demonstrated normal cell growth and ATP with the lowest density of mitochondrial UCP2 staining while all cancer lines demonstrated proportionally inhibited growth and ATP, and over-expression of UCP2 (p Conclusion Seven human cancer cell lines grown in glucose plus acetoacetate medium showed tightly coupled reduction of growth and ATP concentration. The findings were not observed in control fibroblasts. The observed over-expression of UCP2 in cancer lines, but not in controls, provides a plausible molecular mechanism by which acetoacetate spares normal cells but suppresses growth in cancer lines. The results bear on the hypothesized potential for ketogenic diets as therapeutic strategies.

  7. The bio-complex "reaction pattern in vertebrate cells" reduces cytokine-induced cellular adhesion molecule mRNA expression in human endothelial cells by attenuation of NF-kappaB translocation.

    Science.gov (United States)

    Rönnau, Cindy; Liebermann, Herbert E H; Helbig, Franz; Staudt, Alexander; Felix, Stephan B; Ewert, Ralf; Landsberger, Martin

    2009-02-28

    The bio-complex "reaction pattern in vertebrate cells" (RiV) is mainly represented by characteristic exosome-like particles--probably as reaction products of cells to specific stress. The transcription factor NF-kappaB plays a central role in inflammation. We tested the hypothesis that RiV particle preparations (RiV-PP) reduce cellular adhesion molecule (CAM) expression (ICAM-1, VCAM-1, E-selectin) by the attenuation of NF-kappaB translocation in human umbilical vein endothelial cells (HUVEC). After 4 hours, pre-incubation of HUVEC with RiV-PP before stimulation with TNF-alpha significantly reduced ICAM-1 (65.5+/-10.3%) and VCAM-1 (71.1+/-12.3%) mRNA expression compared to TNF-alpha-treated cells (100%, n=7). ICAM-1 surface expression was significantly albeit marginally reduced in RiV/TNF-alpha- treated cells (92.0+/-5.6%, n=4). No significant effect was observed on VCAM-1 surface expression. In RiV/TNF-alpha-treated cells (n=4), NF-kappaB subunits p50 (85.7+/-4.1%) and p65 (85.0+/-1.8%) nuclear translocation was significantly reduced. RiV-PP may exert an anti-inflammatory effect in HUVEC by reducing CAM mRNA expression via attenuation of p50 and p65 translocation.

  8. Pain elicited by the Cold Pressor Test: A gender-comparative FACS coding study of spontaneous, faked and inhibited expressions.

    OpenAIRE

    Gil, Luisa; De Sousa, Cristina; Baunninger-Huber, Eva; Schiestl, Cathrin; Toussaint, Kyra; Gruber, Verena; Oliveira, Armando Monica; Duarte, Ana Catarina

    2012-01-01

    Evolutionary theories of pain have conjectured a better ability of males to control their facial expressions of pain, and of females to express and communicate emotions through the face. The present study involved 24 participants (12 men; 12 women). Pain was induced via the Cold Pressor Test (CPT), and three expressive contexts (spontaneous, faked an inhibited) were created through instructions. Elicited pain expressions were FACS coded and frequency, indices were derived for the observed Act...

  9. Incubation of ethanol reinstatement depends on test conditions and how ethanol consumption is reduced

    Science.gov (United States)

    Ginsburg, Brett C.; Lamb, R. J.

    2015-01-01

    In reinstatement studies (a common preclinical procedure for studying relapse), incubation occurs (longer abstinence periods result in more responding). This finding is discordant with the clinical literature. Identifying determinants of incubation could aid in interpreting reinstatement and identifying processes involved in relapse. Reinstated responding was examined in rats trained to respond for ethanol and food under a multiple concurrent schedule (Component 1: ethanol FR5, food FR150; Component 2: ethanol FR5, food FR5–alternating across the 30-min session). Ethanol consumption was then reduced for 1 or 16 sessions either by suspending training (rats remained in home cage) or by providing alternative reinforcement (only Component 2 stimuli and contingencies were presented throughout the session). In the next session, stimuli associated with Component 1 were presented and responses recorded but ethanol and food were never delivered. Two test conditions were studied: fixed-ratio completion either produced ethanol- or food-associated stimuli (signaled) or had no programmed consequence (unsignaled). Incubation of ethanol responding was observed only after suspended training during signaled test sessions. Incubation of food responding was also observed after suspended training. These results are most consistent with incubation resulting from a degradation of feedback functions limiting extinction responding, rather than an increased motivation. PMID:25595114

  10. SALL4 expression in gonocytes and spermatogonial clones of postnatal mouse testes.

    Directory of Open Access Journals (Sweden)

    Kathrin Gassei

    Full Text Available The spermatogenic lineage is established after birth when gonocytes migrate to the basement membrane of seminiferous tubules and give rise to spermatogonial stem cells (SSC. In adults, SSCs reside within the population of undifferentiated spermatogonia (A(undiff that expands clonally from single cells (A(single to form pairs (A(paired and chains of 4, 8 and 16 A(aligned spermatogonia. Although stem cell activity is thought to reside in the population of A(single spermatogonia, new research suggests that clone size alone does not define the stem cell pool. The mechanisms that regulate self-renewal and differentiation fate decisions are poorly understood due to limited availability of experimental tools that distinguish the products of those fate decisions. The pluripotency factor SALL4 (sal-like protein 4 is implicated in stem cell maintenance and patterning in many organs during embryonic development, but expression becomes restricted to the gonads after birth. We analyzed the expression of SALL4 in the mouse testis during the first weeks after birth and in adult seminiferous tubules. In newborn mice, the isoform SALL4B is expressed in quiescent gonocytes at postnatal day 0 (PND0 and SALL4A is upregulated at PND7 when gonocytes have colonized the basement membrane and given rise to spermatogonia. During steady-state spermatogenesis in adult testes, SALL4 expression overlapped substantially with PLZF and LIN28 in A(single, A(paired and A(aligned spermatogonia and therefore appears to be a marker of undifferentiated spermatogonia in mice. In contrast, co-expression of SALL4 with GFRα1 and cKIT identified distinct subpopulations of A(undiff in all clone sizes that might provide clues about SSC regulation. Collectively, these results indicate that 1 SALL4 isoforms are differentially expressed at the initiation of spermatogenesis, 2 SALL4 is expressed in undifferentiated spermatogonia in adult testes and 3 SALL4 co-staining with GFRα1 and c

  11. Design of Hydraulic Bushing and Vehicle Testing for Reducing the Judder Vibration

    Directory of Open Access Journals (Sweden)

    Kim Youngman

    2018-01-01

    Full Text Available Generally, judder vibration is a low-frequency vibration phenomenon caused by a braking force imbalance that occurs when a vehicle is lightly decelerated within a range of 0.1 to 0.2g at a speed of 120 to 60 km/h. This comes from the change in the brake disk thickness (DTV, which is mainly caused by the side run-out (SRO and thermal deformation. The adoption of hydro-bushing in the low arm G bushings of the vehicle front suspension has been done in order to provide great damping in a particular frequency range (<20Hz in order to prevent this judder vibration from being transmitted to the body. The hydro bushing was formulated using a lumped parameter model. The fluid passage between the two chambers was modelled as a nonlinear element such as an orifice, and its important parameters (resistance, compliance were measured using a simplified experimental setup. The main design parameters are the ratio of the cross-sectional area of the chamber to the fluid passage, the length of the fluid passage, etc., and their optimal design is such that the loss angle is greater than 45 ° in the target frequency range of 10 to 20 Hz. The hydro bushing designed for reducing the judder vibration was prepared for the actual vehicle application test and applied to the actual vehicle test. In this study, the proposed hydro bushing was applied to the G bushing of the low arm of the front suspension system of the vehicle. The loss angle of the manufactured hydro bushing was measured using acceleration signals before and after passing through the bushing. The actual vehicle test was performed on the noise dynamometer for the performance analysis of the judder vibration reduction.

  12. The U.S. reduced enrichment research and test reactor (RERTR) program

    International Nuclear Information System (INIS)

    Travelli, A.

    1993-01-01

    Research and test reactors are widely deployed to study the irradiation behavior of materials of interest in nuclear engineering, to produce radioisotopes for medicine, industry, and agriculture, and as a basic research and teaching tool. In order to maximize neutron flux per unit power and/or to minimize capital costs and fuel cycle costs, most of these reactors were de- signed to utilize uranium with very high enrichment (in the 70% to 95% range). Research reactor fuels with such high uranium enrichment cause a potential risk of nuclear weapons proliferation. Over 140 research and test reactors of significant power (between 10 kW and 250 MW) are in operation with very highly enriched uranium in more than 35 countries, with total power in excess of 1,700 MW. The overall annual fuel requirement of these reactors corresponds to approximately 1,200 kg of 235 U. This highly strategic material is normally exported from the United States, converted to metal form, shipped to a fuel fabricator, and then shipped to the reactor site in finished fuel element form. At the reactor site the fuel is first stored, then irradiated, stored again, and eventually shipped back to the United States for reprocessing. The whole cycle takes approximately four years to complete, bringing the total required fuel inventory to approximately 5,000 kg of 235 U. The resulting international trade in highly-enriched uranium may involve several countries in the process of refueling a single reactor and creates a considerable concern that the highly-enriched uranium may be diverted for non-peaceful purposes while in fabrication, transport, or storage, particularly when it is in the unirradiated form. The proliferation resistance of nuclear fuels used in research and test reactors can be considerably improved by reducing their uranium enrichment to a value less than 20%, but significantly greater than natural to avoid excessive plutonium production

  13. Decentral gene expression analysis: analytical validation of the Endopredict genomic multianalyte breast cancer prognosis test

    Directory of Open Access Journals (Sweden)

    Kronenwett Ralf

    2012-10-01

    Full Text Available Abstract Background EndoPredict (EP is a clinically validated multianalyte gene expression test to predict distant metastasis in ER-positive, HER2-negative breast cancer treated with endocrine therapy alone. The test is based on the combined analysis of 12 genes in formalin-fixed, paraffin-embedded (FFPE tissue by reverse transcription-quantitative real-time PCR (RT-qPCR. Recently, it was shown that EP is feasible for reliable decentralized assessment of gene expression. The aim of this study was the analytical validation of the performance characteristics of the assay and its verification in a molecular-pathological routine laboratory. Methods Gene expression values to calculate the EP score were assayed by one-step RT-qPCR using RNA from FFPE tumor tissue. Limit of blank, limit of detection, linear range, and PCR efficiency were assessed for each of the 12 PCR assays using serial samples dilutions. Different breast cancer samples were used to evaluate RNA input range, precision and inter-laboratory variability. Results PCR assays were linear up to Cq values between 35.1 and 37.2. Amplification efficiencies ranged from 75% to 101%. The RNA input range without considerable change of the EP score was between 0.16 and 18.5 ng/μl. Analysis of precision (variation of day, day time, instrument, operator, reagent lots resulted in a total noise (standard deviation of 0.16 EP score units on a scale from 0 to 15. The major part of the total noise (SD 0.14 was caused by the replicate-to-replicate noise of the PCR assays (repeatability and was not associated with different operating conditions (reproducibility. Performance characteristics established in the manufacturer’s laboratory were verified in a routine molecular pathology laboratory. Comparison of 10 tumor samples analyzed in two different laboratories showed a Pearson coefficient of 0.995 and a mean deviation of 0.15 score units. Conclusions The EP test showed reproducible performance

  14. Decentral gene expression analysis: analytical validation of the Endopredict genomic multianalyte breast cancer prognosis test

    International Nuclear Information System (INIS)

    Kronenwett, Ralf; Brase, Jan C; Weber, Karsten E; Fisch, Karin; Müller, Berit M; Schmidt, Marcus; Filipits, Martin; Dubsky, Peter; Petry, Christoph; Dietel, Manfred; Denkert, Carsten; Bohmann, Kerstin; Prinzler, Judith; Sinn, Bruno V; Haufe, Franziska; Roth, Claudia; Averdick, Manuela; Ropers, Tanja; Windbergs, Claudia

    2012-01-01

    EndoPredict (EP) is a clinically validated multianalyte gene expression test to predict distant metastasis in ER-positive, HER2-negative breast cancer treated with endocrine therapy alone. The test is based on the combined analysis of 12 genes in formalin-fixed, paraffin-embedded (FFPE) tissue by reverse transcription-quantitative real-time PCR (RT-qPCR). Recently, it was shown that EP is feasible for reliable decentralized assessment of gene expression. The aim of this study was the analytical validation of the performance characteristics of the assay and its verification in a molecular-pathological routine laboratory. Gene expression values to calculate the EP score were assayed by one-step RT-qPCR using RNA from FFPE tumor tissue. Limit of blank, limit of detection, linear range, and PCR efficiency were assessed for each of the 12 PCR assays using serial samples dilutions. Different breast cancer samples were used to evaluate RNA input range, precision and inter-laboratory variability. PCR assays were linear up to C q values between 35.1 and 37.2. Amplification efficiencies ranged from 75% to 101%. The RNA input range without considerable change of the EP score was between 0.16 and 18.5 ng/μl. Analysis of precision (variation of day, day time, instrument, operator, reagent lots) resulted in a total noise (standard deviation) of 0.16 EP score units on a scale from 0 to 15. The major part of the total noise (SD 0.14) was caused by the replicate-to-replicate noise of the PCR assays (repeatability) and was not associated with different operating conditions (reproducibility). Performance characteristics established in the manufacturer’s laboratory were verified in a routine molecular pathology laboratory. Comparison of 10 tumor samples analyzed in two different laboratories showed a Pearson coefficient of 0.995 and a mean deviation of 0.15 score units. The EP test showed reproducible performance characteristics with good precision and negligible laboratory

  15. More powerful significant testing for time course gene expression data using functional principal component analysis approaches.

    Science.gov (United States)

    Wu, Shuang; Wu, Hulin

    2013-01-16

    One of the fundamental problems in time course gene expression data analysis is to identify genes associated with a biological process or a particular stimulus of interest, like a treatment or virus infection. Most of the existing methods for this problem are designed for data with longitudinal replicates. But in reality, many time course gene experiments have no replicates or only have a small number of independent replicates. We focus on the case without replicates and propose a new method for identifying differentially expressed genes by incorporating the functional principal component analysis (FPCA) into a hypothesis testing framework. The data-driven eigenfunctions allow a flexible and parsimonious representation of time course gene expression trajectories, leaving more degrees of freedom for the inference compared to that using a prespecified basis. Moreover, the information of all genes is borrowed for individual gene inferences. The proposed approach turns out to be more powerful in identifying time course differentially expressed genes compared to the existing methods. The improved performance is demonstrated through simulation studies and a real data application to the Saccharomyces cerevisiae cell cycle data.

  16. Testing the psychometric properties of a Chinese version of the level of expressed emotion scale.

    Science.gov (United States)

    Chien, Wai Tong; Chan, Zenobia Chung-Yee; Chan, Sally Wai-Chi

    2014-01-01

    This study tested the psychometric properties of a Chinese version of the level of expressed emotion scale in Hong Kong Chinese patients with severe mental illness and their family caregivers. First, the semantic equivalence with the original English version and test-retest reliability at 2-week interval of the Chinese version was examined. After that, the reproducibility, construct validity, and internal consistency of the Chinese version were tested. The Chinese version indicated good semantic equivalence with the English version (kappa values = 0.76-0.95 and ICC = 0.81-0.92), test-retest reliability (r = 0.89-0.95, P Chinese version had substantial loadings on one of the four factors identified (intrusiveness/hostility, attitude towards patient, tolerance, and emotional involvement), accounting for 71.8% of the total variance of expressed emotion. In confirmatory factor analysis, the identified four-factor model showed the best fit based on all fit indices (χ (2)/df = 1.93, P = 0.75; AGFI = 0.96; TLI = 1.02; RMSEA = 0.031; WRMR = 0.78) to the collected data. The four-factor Chinese version also indicated a good concurrent validity with significant correlations with family functioning (r = -0.54) and family burden (r = 0.49) and a satisfactory reproducibility over six months (intraclass correlation coefficient of 0.90). The mean scores of the overall and subscale of the Chinese version in patients with unipolar disorder were higher than in other illness groups (schizophrenia, psychotic disorders, and bipolar disorder; P Chinese version demonstrates sound psychometric properties to measure families' expressed emotion in Chinese patients with severe mental illness, which are found varied across countries.

  17. Testing the Psychometric Properties of a Chinese Version of the Level of Expressed Emotion Scale

    Directory of Open Access Journals (Sweden)

    Wai Tong Chien

    2014-01-01

    Full Text Available This study tested the psychometric properties of a Chinese version of the level of expressed emotion scale in Hong Kong Chinese patients with severe mental illness and their family caregivers. First, the semantic equivalence with the original English version and test-retest reliability at 2-week interval of the Chinese version was examined. After that, the reproducibility, construct validity, and internal consistency of the Chinese version were tested. The Chinese version indicated good semantic equivalence with the English version (kappa values = 0.76–0.95 and ICC = 0.81–0.92, test-retest reliability (r = 0.89–0.95, P<0.01, and internal consistency (Cronbach’s α = 0.86–0.92. Among 262 patients with severe mental illness and their caregivers, the 50-item Chinese version had substantial loadings on one of the four factors identified (intrusiveness/hostility, attitude towards patient, tolerance, and emotional involvement, accounting for 71.8% of the total variance of expressed emotion. In confirmatory factor analysis, the identified four-factor model showed the best fit based on all fit indices (χ2/df = 1.93, P=0.75; AGFI = 0.96; TLI = 1.02; RMSEA = 0.031; WRMR = 0.78 to the collected data. The four-factor Chinese version also indicated a good concurrent validity with significant correlations with family functioning (r = −0.54 and family burden (r = 0.49 and a satisfactory reproducibility over six months (intraclass correlation coefficient of 0.90. The mean scores of the overall and subscale of the Chinese version in patients with unipolar disorder were higher than in other illness groups (schizophrenia, psychotic disorders, and bipolar disorder; P<0.01. The Chinese version demonstrates sound psychometric properties to measure families’ expressed emotion in Chinese patients with severe mental illness, which are found varied across countries.

  18. The Expression of Markers for Intratubular Germ Cell Neoplasia in Normal Infantile Testes

    Directory of Open Access Journals (Sweden)

    Kolja Kvist

    2018-06-01

    Full Text Available BackgroundPositive immunohistochemical expression of testicular cancer markers is often reported beyond 12 months of age in cryptorchid testes, which is assumed to indicate delayed maturation of the fetal germ cells, or neoplastic changes. These findings allowed for questions as to the extent of positive reaction in normal testes. The aim of the study was to clarify the expression of these markers in a normal material up to 2 years.MethodsTesticular material from 69 boys aged 1–690 days, who died of causes with no association of testicular pathology. Histology sections were incubated with primary antibodies including anti-placental-like alkaline phosphatase (PLAP, anti-C-Kit, anti-D2–40, and anti-Oct3/4. The mean germ cell number per tubular transverse section (G/T was calculated based on the G/T of both testes of every boy.ResultsThe mean G/T declined through the 690 days. PLAP appeared stably expressed throughout the ages studied. The likelihood of a positive reaction for C-Kit waned with increasing age within the study period. Positive staining for D2–40 and Oct3/4 was demonstrated up to 6 and 9 months respectively.ConclusionUp to 1 or 2 years of age, normal infantile testes contain germ cells positive for the immunohistochemical markers commonly utilized to aid in the detection of testicular cancer. This finding supports the concept of germ cells undergoing a continuous maturational process in a heterogeneous fashion, and that this process is not complete by 2 years of age.

  19. Reducing Retroactive Interference through the Use of Different Encoding Techniques: An Exploration of Pre-Test/Post-Test Analyses

    Science.gov (United States)

    Cumming, John M.; De Miranda, Michael A.

    2012-01-01

    Retroactive interference (RI) in list learning occurs when the learning of a second list of words interferes with the recall of the first learned list. Having the lists be thematically different can reduce retroactive interference within list learning; however, this study demonstrates how RI can be reduced when the lists contain similar words.…

  20. Forced expression of stabilized c-Fos in dendritic cells reduces cytokine production and immune responses in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ryoko; Suzuki, Mayu; Sakaguchi, Ryota; Hasegawa, Eiichi; Kimura, Akihiro; Shichita, Takashi; Sekiya, Takashi [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency, CREST, Chiyoda-ku 102-0075 (Japan); Shiraishi, Hiroshi [Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga (Japan); Shimoda, Kouji [Department of Laboratory Animal Center, Keio University School of Medicine, Tokyo (Japan); Yoshimura, Akihiko, E-mail: yoshimura@a6.keio.jp [Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582 (Japan); Japan Science and Technology Agency, CREST, Chiyoda-ku 102-0075 (Japan)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos produced less inflammatory cytokines. Black-Right-Pointing-Pointer Dendritic cells expressing stabilized c-Fos activated T cells less efficiently. Black-Right-Pointing-Pointer Transgenic mice expressing stabilized c-Fos were resistant to EAE model. -- Abstract: Intracellular cyclic adenosine monophosphate (cAMP) suppresses innate immunity by inhibiting proinflammatory cytokine production by monocytic cells. We have shown that the transcription factor c-Fos is responsible for cAMP-mediated suppression of inflammatory cytokine production, and that c-Fos protein is stabilized by IKK{beta}-mediated phosphorylation. We found that S308 is one of the major phosphorylation sites, and that the S308D mutation prolongs c-Fos halflife. To investigate the role of stabilized c-Fos protein in dendritic cells (DCs) in vivo, we generated CD11c-promoter-deriven c-FosS308D transgenic mice. As expected, bone marrow-derived DCs (BMDCs) from these Tg mice produced smaller amounts of inflammatory cytokines, including TNF-{alpha}, IL-12, and IL-23, but higher levels of IL-10, in response to LPS, than those from wild-type (Wt) mice. When T cells were co-cultured with BMDCs from Tg mice, production of Th1 and Th17 cytokines was reduced, although T cell proliferation was not affected. Tg mice demonstrated more resistance to experimental autoimmune encephalomyelitis (EAE) than did Wt mice. These data suggest that c-Fos in DCs plays a suppressive role in certain innate and adaptive immune responses.

  1. Incongruence Between Observers’ and Observed Facial Muscle Activation Reduces Recognition of Emotional Facial Expressions From Video Stimuli

    Directory of Open Access Journals (Sweden)

    Tanja S. H. Wingenbach

    2018-06-01

    Full Text Available According to embodied cognition accounts, viewing others’ facial emotion can elicit the respective emotion representation in observers which entails simulations of sensory, motor, and contextual experiences. In line with that, published research found viewing others’ facial emotion to elicit automatic matched facial muscle activation, which was further found to facilitate emotion recognition. Perhaps making congruent facial muscle activity explicit produces an even greater recognition advantage. If there is conflicting sensory information, i.e., incongruent facial muscle activity, this might impede recognition. The effects of actively manipulating facial muscle activity on facial emotion recognition from videos were investigated across three experimental conditions: (a explicit imitation of viewed facial emotional expressions (stimulus-congruent condition, (b pen-holding with the lips (stimulus-incongruent condition, and (c passive viewing (control condition. It was hypothesised that (1 experimental condition (a and (b result in greater facial muscle activity than (c, (2 experimental condition (a increases emotion recognition accuracy from others’ faces compared to (c, (3 experimental condition (b lowers recognition accuracy for expressions with a salient facial feature in the lower, but not the upper face area, compared to (c. Participants (42 males, 42 females underwent a facial emotion recognition experiment (ADFES-BIV while electromyography (EMG was recorded from five facial muscle sites. The experimental conditions’ order was counter-balanced. Pen-holding caused stimulus-incongruent facial muscle activity for expressions with facial feature saliency in the lower face region, which reduced recognition of lower face region emotions. Explicit imitation caused stimulus-congruent facial muscle activity without modulating recognition. Methodological implications are discussed.

  2. Neonatal Gene Therapy for Hemophilia B by a Novel Adenovirus Vector Showing Reduced Leaky Expression of Viral Genes.

    Science.gov (United States)

    Iizuka, Shunsuke; Sakurai, Fuminori; Tachibana, Masashi; Ohashi, Kazuo; Mizuguchi, Hiroyuki

    2017-09-15

    Gene therapy during neonatal and infant stages is a promising approach for hemophilia B, a congenital disorder caused by deficiency of blood coagulation factor IX (FIX). An adenovirus (Ad) vector has high potential for use in neonatal or infant gene therapy for hemophilia B due to its superior transduction properties; however, leaky expression of Ad genes often reduces the transduction efficiencies by Ad protein-mediated tissue damage. Here, we used a novel Ad vector, Ad-E4-122aT, which exhibits a reduction in the leaky expression of Ad genes in liver, in gene therapy studies for neonatal hemophilia B mice. Ad-E4-122aT exhibited significantly higher transduction efficiencies than a conventional Ad vector in neonatal mice. In neonatal hemophilia B mice, a single neonatal injection of Ad-E4-122aT expressing human FIX (hFIX) (Ad-E4-122aT-AHAFIX) maintained more than 6% of the normal plasma hFIX activity levels for approximately 100 days. Sequential administration of Ad-E4-122aT-AHAFIX resulted in more than 100% of the plasma hFIX activity levels for more than 100 days and rescued the bleeding phenotypes of hemophilia B mice. In addition, immunotolerance to hFIX was induced by Ad-E4-122aT-AHAFIX administration in neonatal hemophilia B mice. These results indicated that Ad-E4-122aT is a promising gene delivery vector for neonatal or infant gene therapy for hemophilia B.

  3. Incongruence Between Observers' and Observed Facial Muscle Activation Reduces Recognition of Emotional Facial Expressions From Video Stimuli.

    Science.gov (United States)

    Wingenbach, Tanja S H; Brosnan, Mark; Pfaltz, Monique C; Plichta, Michael M; Ashwin, Chris

    2018-01-01

    According to embodied cognition accounts, viewing others' facial emotion can elicit the respective emotion representation in observers which entails simulations of sensory, motor, and contextual experiences. In line with that, published research found viewing others' facial emotion to elicit automatic matched facial muscle activation, which was further found to facilitate emotion recognition. Perhaps making congruent facial muscle activity explicit produces an even greater recognition advantage. If there is conflicting sensory information, i.e., incongruent facial muscle activity, this might impede recognition. The effects of actively manipulating facial muscle activity on facial emotion recognition from videos were investigated across three experimental conditions: (a) explicit imitation of viewed facial emotional expressions (stimulus-congruent condition), (b) pen-holding with the lips (stimulus-incongruent condition), and (c) passive viewing (control condition). It was hypothesised that (1) experimental condition (a) and (b) result in greater facial muscle activity than (c), (2) experimental condition (a) increases emotion recognition accuracy from others' faces compared to (c), (3) experimental condition (b) lowers recognition accuracy for expressions with a salient facial feature in the lower, but not the upper face area, compared to (c). Participants (42 males, 42 females) underwent a facial emotion recognition experiment (ADFES-BIV) while electromyography (EMG) was recorded from five facial muscle sites. The experimental conditions' order was counter-balanced. Pen-holding caused stimulus-incongruent facial muscle activity for expressions with facial feature saliency in the lower face region, which reduced recognition of lower face region emotions. Explicit imitation caused stimulus-congruent facial muscle activity without modulating recognition. Methodological implications are discussed.

  4. Incongruence Between Observers’ and Observed Facial Muscle Activation Reduces Recognition of Emotional Facial Expressions From Video Stimuli

    Science.gov (United States)

    Wingenbach, Tanja S. H.; Brosnan, Mark; Pfaltz, Monique C.; Plichta, Michael M.; Ashwin, Chris

    2018-01-01

    According to embodied cognition accounts, viewing others’ facial emotion can elicit the respective emotion representation in observers which entails simulations of sensory, motor, and contextual experiences. In line with that, published research found viewing others’ facial emotion to elicit automatic matched facial muscle activation, which was further found to facilitate emotion recognition. Perhaps making congruent facial muscle activity explicit produces an even greater recognition advantage. If there is conflicting sensory information, i.e., incongruent facial muscle activity, this might impede recognition. The effects of actively manipulating facial muscle activity on facial emotion recognition from videos were investigated across three experimental conditions: (a) explicit imitation of viewed facial emotional expressions (stimulus-congruent condition), (b) pen-holding with the lips (stimulus-incongruent condition), and (c) passive viewing (control condition). It was hypothesised that (1) experimental condition (a) and (b) result in greater facial muscle activity than (c), (2) experimental condition (a) increases emotion recognition accuracy from others’ faces compared to (c), (3) experimental condition (b) lowers recognition accuracy for expressions with a salient facial feature in the lower, but not the upper face area, compared to (c). Participants (42 males, 42 females) underwent a facial emotion recognition experiment (ADFES-BIV) while electromyography (EMG) was recorded from five facial muscle sites. The experimental conditions’ order was counter-balanced. Pen-holding caused stimulus-incongruent facial muscle activity for expressions with facial feature saliency in the lower face region, which reduced recognition of lower face region emotions. Explicit imitation caused stimulus-congruent facial muscle activity without modulating recognition. Methodological implications are discussed. PMID:29928240

  5. Calcimimetic R568 inhibits tetrodotoxin-sensitive colonic electrolyte secretion and reduces c-fos expression in myenteric neurons.

    Science.gov (United States)

    Sun, Xiangrong; Tang, Lieqi; Winesett, Steven; Chang, Wenhan; Cheng, Sam Xianjun

    2018-02-01

    Calcium-sensing receptor (CaSR) is expressed on neurons of both submucosal and myenteric plexuses of the enteric nervous system (ENS) and the CaSR agonist R568 inhibited Cl - secretion in intestine. The purpose of this study was to localize the primary site of action of R568 in the ENS and to explore how CaSR regulates secretion through the ENS. Two preparations of rat proximal and distal colon were used. The full-thickness preparation contained both the submucosal and myenteric plexuses, whereas for the "stripped" preparation the myenteric plexus with the muscle layers was removed. Both preparations were mounted onto Ussing chambers and Cl - secretory responses were compared by measuring changes in short circuit current (I sc ). Two tissue-specific CaSR knockouts (i.e., neuron-specific vs. enterocyte-specific) were generated to compare the effect of R568 on expression of c-fos protein in myenteric neurons by immunocytochemistry. In full-thickness colons, tetrodotoxin (TTX) inhibited I sc , both in proximal and distal colons. A nearly identical inhibition was produced by R568. However, in stripped preparations, while the effect of TTX on I sc largely remained, the effect of R568 was nearly completely eliminated. In keeping with this, R568 reduced c-fos protein expression only in myenteric neurons of wild type mice and mutant mice that contained CaSR in neurons (i.e., villin Cre/Casr flox/flox mice), but not in myenteric neurons of nestin Cre/Casr flox/flox mice in which neuronal cell CaSR was eliminated. These results indicate that R568 exerts its anti-secretory effects predominantly via CaSR-mediated inhibition of neuronal activity in the myenteric plexus. Published by Elsevier Inc.

  6. Reduced expression of dermcidin, a peptide active against propionibacterium acnes, in sweat of patients with acne vulgaris.

    Science.gov (United States)

    Nakano, Toshiaki; Yoshino, Takashi; Fujimura, Takao; Arai, Satoru; Mukuno, Akira; Sato, Naoya; Katsuoka, Kensei

    2015-09-01

    Dermcidin (DCD), an antimicrobial peptide with a broad spectrum of activity against bacteria such as Propionibacterum acnes, is expressed constitutively in sweat in the absence of stimulation due to injury or inflammation. The aim of this study was to determine the relationship between DCD expression and acne vulgaris associated with P. acnes. The antimicrobial activity of recombinant full-length DCD (50 μg/ml) was 97% against Escherichia coli and 100% against Staphylococcus aureus. Antimicrobial activity against P. acnes ranged from 68% at 50 μg/ml DCD to 83% at 270 μg/ml DCD. DCD concentration in sweat from patients with acne vulgaris (median 9.8 μg/ml, range 6.9-95.3 μg/ml) was significantly lower than in healthy subjects (median 136.7 μg/ml, range 45.4-201.6 μg/ml) (p = 0.001). DCD demonstrated concentration-dependent, but partial, microbicidal activity against P. acnes. These results suggest that reduced DCD concentration in sweat in patients with inflammatory acne may permit proliferation of P. acnes in pilosebaceous units, resulting in progression of inflammatory acne.

  7. Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit.

    Directory of Open Access Journals (Sweden)

    Luisa Diomede

    Full Text Available The presence of amyloid aggregates of the 42 amino acid peptide of amyloid beta (Aβ42 in the brain is the characteristic feature of Alzheimer's disease (AD. Amyloid beta (Aβ deposition is also found in muscle fibers of individuals affected by inclusion body myositis (sIBM, a rare muscular degenerative disease affecting people over 50. Both conditions are presently lacking an effective therapeutic treatment. There is increasing evidence to suggest that natural polyphenols may prevent the formation of toxic amyloid aggregates; this applies also to oleuropein aglycone (OLE, the most abundant polyphenol in extra virgin olive oil, previously shown to hinder amylin and Aβ aggregation. Here we evaluated the ability of OLE to interfere with Aβ proteotoxicity in vivo by using the transgenic CL2006 and CL4176 strains of Caenorhabditis elegans, simplified models of AD and of sIBM, which express human Aβ in the cytoplasm of body wall muscle cells. OLE-fed CL2006 worms displayed reduced Aβ plaque deposition, less abundant toxic Aβ oligomers, remarkably decreased paralysis and increased lifespan with respect to untreated animals. A protective effect was also observed in CL4176 worms but only when OLE was administered before the induction of the Aβ transgene expression. These effects were specific, dose-related, and not mediated by the known polyphenolic anti-oxidant activity, suggesting that, in this model organism, OLE interferes with the Aβ aggregation skipping the appearance of toxic species, as already shown in vitro for Aβ42.

  8. Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression.

    Directory of Open Access Journals (Sweden)

    Pin-Shern Chen

    Full Text Available BACKGROUND: Diosgenin, a steroidal saponin obtained from fenugreek (Trigonella foenum graecum, was found to exert anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis in a variety of tumor cells. However, the effect of diosgenin on cancer metastasis remains unclear. The aim of the study is to examine the effect of diosgenin on migration and invasion in human prostate cancer PC-3 cells. METHODS AND PRINCIPAL FINDINGS: Diosgenin inhibited proliferation of PC-3 cells in a dose-dependent manner. When treated with non-toxic doses of diosgenin, cell migration and invasion were markedly suppressed by in vitro wound healing assay and Boyden chamber invasion assay, respectively. Furthermore, diosgenin reduced the activities of matrix metalloproteinase-2 (MMP-2 and MMP-9 by gelatin zymography assay. The mRNA level of MMP-2, -9, -7 and extracellular inducer of matrix metalloproteinase (EMMPRIN were also suppressed while tissue inhibitor of metalloproteinase-2 (TIMP-2 was increased by diosgenin. In addition, diosgenin abolished the expression of vascular endothelial growth factor (VEGF in PC-3 cells and tube formation of endothelial cells. Our immunoblotting assays indicated that diosgenin potently suppressed the phosphorylation of phosphatidylinositide-3 kinase (PI3K, Akt, extracellular signal regulating kinase (ERK and c-Jun N-terminal kinase (JNK. In addition, diosgenin significantly decreased the nuclear level of nuclear factor kappa B (NF-κB, suggesting that diosgenin inhibited NF-κB activity. CONCLUSION/SIGNIFICANCE: The results suggested that diosgenin inhibited migration and invasion of PC-3 cells by reducing MMPs expression. It also inhibited ERK, JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for diosgenin in anti-metastatic therapy.

  9. Cell wall composition and digestibility alterations in Brachypodium distachyon achieved through reduced expression of the UDP-arabinopyranose mutase

    Science.gov (United States)

    Rancour, David M.; Hatfield, Ronald D.; Marita, Jane M.; Rohr, Nicholas A.; Schmitz, Robert J.

    2015-01-01

    Nucleotide-activated sugars are essential substrates for plant cell-wall carbohydrate-polymer biosynthesis. The most prevalent grass cell wall (CW) sugars are glucose (Glc), xylose (Xyl), and arabinose (Ara). These sugars are biosynthetically related via the UDP–sugar interconversion pathway. We sought to target and generate UDP–sugar interconversion pathway transgenic Brachypodium distachyon lines resulting in CW carbohydrate composition changes with improved digestibility and normal plant stature. Both RNAi-mediated gene-suppression and constitutive gene-expression approaches were performed. CWs from 336 T0 transgenic plants with normal appearance were screened for complete carbohydrate composition. RNAi mutants of BdRGP1, a UDP-arabinopyranose mutase, resulted in large alterations in CW carbohydrate composition with significant decreases in CW Ara content but with minimal change in plant stature. Five independent RNAi-RGP1 T1 plant lines were used for in-depth analysis of plant CWs. Real-time PCR analysis indicated that gene expression levels for BdRGP1, BdRGP2, and BdRGP3 were reduced in RNAi-RGP1 plants to 15–20% of controls. CW Ara content was reduced by 23–51% of control levels. No alterations in CW Xyl and Glc content were observed. Corresponding decreases in CW ferulic acid (FA) and ferulic acid-dimers (FA-dimers) were observed. Additionally, CW p-coumarates (pCA) were decreased. We demonstrate the CW pCA decrease corresponds to Ara-coupled pCA. Xylanase-mediated digestibility of RNAi-RGP1 Brachypodium CWs resulted in a near twofold increase of released total carbohydrate. However, cellulolytic hydrolysis of CW material was inhibited in leaves of RNAi-RGP1 mutants. Our results indicate that targeted manipulation of UDP–sugar biosynthesis can result in biomass with substantially altered compositions and highlights the complex effect CW composition has on digestibility. PMID:26136761

  10. Mao-to Prolongs the Survival of and Reduces TNF-α Expression in Mice with Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Zhu Shijie

    2010-01-01

    Full Text Available Goal of this study was to evaluate effects of Mao-to on development of myocarditis induced by encephalomyocarditis (EMC virus in mice. Mice were randomly divided into five groups. Group N included uninfected controls (n = 18, while group A, B and C underwent intraperitoneal injection of EMC virus. Group A was administered oral saline from day 0 to day 4. Group B was administered oral Mao-to (500 mg−1 kg−1 day−1 from day 0 to day 4. Group C was administered Mao-to from day 2 to day 6. Group D was administered Mao-to from day 5 to day 10. Treated mice were followed for survival rates during 2 weeks after infection. Body weight (BW and organ weights including heart (HW, lungs, thymus and spleen were examined on days 4, 6 and 14. Survival rate of group C (36.4% was significantly improved compared with group A, B or D (0% of each, P < 0.05. HW and HW/BW ratio in group C was significantly (P < 0.05 lower than those in group A, B or D. Viral titers of hearts were significantly different among groups A, B and C. Cardiac expression in tumor necrosis factor-α (TNF-α was significantly reduced in group C in comparison with group A, B or D on day 6 by immunohistochemical study. Administration of Mao-to starting on day 2 improves mortality resulting from viral myocarditis in mice with reduced expression of cardiac TNF-α. These findings suggest that timing of Mao-to is crucial for preventing cardiac damage in mice with viral myocarditis.

  11. Test battery for measuring the perception and recognition of facial expressions of emotion

    Science.gov (United States)

    Wilhelm, Oliver; Hildebrandt, Andrea; Manske, Karsten; Schacht, Annekathrin; Sommer, Werner

    2014-01-01

    Despite the importance of perceiving and recognizing facial expressions in everyday life, there is no comprehensive test battery for the multivariate assessment of these abilities. As a first step toward such a compilation, we present 16 tasks that measure the perception and recognition of facial emotion expressions, and data illustrating each task's difficulty and reliability. The scoring of these tasks focuses on either the speed or accuracy of performance. A sample of 269 healthy young adults completed all tasks. In general, accuracy and reaction time measures for emotion-general scores showed acceptable and high estimates of internal consistency and factor reliability. Emotion-specific scores yielded lower reliabilities, yet high enough to encourage further studies with such measures. Analyses of task difficulty revealed that all tasks are suitable for measuring emotion perception and emotion recognition related abilities in normal populations. PMID:24860528

  12. The RERTR [Reduced Enrichment Research and Test Reactor] program: A progress report

    International Nuclear Information System (INIS)

    Travelli, A.

    1986-11-01

    The progress of the Reduced Enrichment Research and Test Reactor (RERTR) Program is described. After a brief summary of the results which the RERTR Program, in collaboration with its many international partners, had achieved by the end of 1985, the activities, results, and new developments which occurred in 1986 are reviewed. The second miniplate series, concentrating on U 3 Si 2 -Al and U 3 Si-Al fuels, was expanded and its irradiation continued. Postirradiation examinations of several of these miniplates and of six previously irradiated U 3 Si 2 -Al full-size elements were completed with excellent results. The whole-core ORR demonstration with U 3 Si 2 -Al fuel at 4.8 g U/cm 3 is well under way and due for completion before the end of 1987. DOE removed an important barrier to conversions by announcing that the new LEU fuels will be accepted for reprocessing. New DOE prices for enrichment and reprocessing services were calculated to have minimal effect on HEU reactors, and to reduce by about 8 to 10% the total fuel cycle costs of LEU reactors. New program activities include preliminary feasibility studies of LEU use in DOE reactors, evaluation of the feasibility to use LEU targets for the production of fission-product 99 Mo, and responsibility for coordinating safety evaluations related to LEU conversions of US university reactors, as required by NRC. Achievement of the final program goals is projected for 1990. This progress could not have been achieved without close international cooperation, whose continuation and intensification are essential to the achievement of the ultimate goals of the RERTR Program

  13. Pattern of c-Fos expression induced by tail suspension test in the mouse brain

    Directory of Open Access Journals (Sweden)

    Kentaro Hiraoka

    2017-06-01

    Full Text Available The tail suspension test (TST has been widely used as a screening assay for antidepressant drugs. However, the neural substrates underlying the stress response and antidepressant-like effect during the TST remain largely unknown despite the prevalence of this test. In the present study, we used immunohistochemistry to examine alterations in c-Fos expression as a measure of neuronal activity in the mouse brain after acute administration of the antidepressant drugs nortriptyline or escitalopram (or saline as a control with or without a subsequent TST session. We found that without the TST session, nortriptyline administration enhanced the density of c-Fos-immunoreactive cells in regions of the central extended amygdala, paraventricular hypothalamic nucleus, and relevant regions of the brain stem, whereas escitalopram did not change c-Fos expression in any region. Following the TST in the absence of antidepressant drugs, we observed a significant increase in c-Fos-positive cell density in a number of brain regions within the limbic telencephalon, hypothalamus, and brain stem. We detected a statistically significant interaction using an analysis of variance between the main effects of the drug and stress response in four regions: the infralimbic cortex, lateral septal nucleus (intermediate part, ventrolateral preoptic nucleus, and solitary nucleus. Following the TST, escitalopram but not nortriptyline increased c-Fos-positive cell density in the infralimbic cortex and ventrolateral preoptic nucleus, whereas nortriptyline but not escitalopram increased c-Fos expression in the solitary nucleus. Both antidepressants significantly increased c-Fos expression in the lateral septal nucleus (intermediate part. The present results indicate that neuronal activity increases in septo-hypothalamic regions and related structures, especially the lateral septal nucleus, following administration of drugs producing an antidepressant-like effect in mice subjected to

  14. Exercise preconditioning reduces brain damage and inhibits TNF-alpha receptor expression after hypoxia/reoxygenation: an in vivo and in vitro study.

    Science.gov (United States)

    Ding, Yun-Hong; Mrizek, Michael; Lai, Qin; Wu, Yimin; Reyes, Raul; Li, Jie; Davis, William W; Ding, Yuchuan

    2006-11-01

    Exercise reduces ischemia and reperfusion injury in rat stroke models. We investigated whether gradual increases in tumor necrosis factor-alpha (TNF-alpha) reported during exercise down-regulates expression of TNF-alpha receptors I and II (TNFRI and II) in stroke, leading to reduced brain damage. Adult male Sprague Dawley rats were subjected to 30 minutes of exercise on a treadmill each day for 3 weeks. Then, stroke was induced by a 2-hour middle cerebral artery (MCA) occlusion using an intra-luminal filament. Expressions of TNFRI and II mRNA in the brain were detected using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Protein expressions of TNFRI and II were determined by enzyme-linked immunoabsorbant assay (ELISA) in serum and brain homogenates. Spatial distribution of TNF-alpha receptors in brain regions was determined with immunocytochemistry. In human umbilical vein endothelial cells (HUVEC), we addressed the causal effect of TNF-alpha pretreatment on TNF I and II expression using ELISA and real-time PCR. In exercised rats after stroke, brain infarct was significantly (p<0.01) reduced in the entire MCA supplied regions, associated with a mild expression of TNFRI and II mRNA and protein. The TNF-alpha receptors were restricted to the ischemic core. In contrast, a robust expression of TNFRI and II molecules was found in non-exercised rats subjected to similar ischemia/reperfusion insults. An in vitro study revealed a causal link between TNF-alpha pretreatment and reduced cellular expression of TNF-alpha receptors under hypoxic/reoxygenated conditions. Our results suggest that reduced-brain damage in ischemic rats after exercise preconditioning may be attributable to the reduced expression of TNF-alpha receptors. Chronically increased TNF-alpha expression was also found to reduce TNFI and II responding to acute ischemia/reperfusion insult.

  15. Nondestructive Semistatic Testing Methodology for Assessing Fish Textural Characteristics via Closed-Form Mathematical Expressions

    Directory of Open Access Journals (Sweden)

    D. Dimogianopoulos

    2017-01-01

    Full Text Available This paper presents a novel methodology based on semistatic nondestructive testing of fish for the analytical computation of its textural characteristics via closed-form mathematical expressions. The novelty is that, unlike alternatives, explicit values for both stiffness and viscoelastic textural attributes may be computed, even if fish of different size/weight are tested. Furthermore, the testing procedure may be adapted to the specifications (sampling rate and accuracy of the available equipment. The experimental testing involves a fish placed on the pan of a digital weigh scale, which is subsequently tested with a ramp-like load profile in a custom-made installation. The ramp slope is (to some extent adjustable according to the specification (sampling rate and accuracy of the equipment. The scale’s reaction to fish loading, namely, the reactive force, is collected throughout time and is shown to depend on the fish textural attributes according to a closed-form mathematical formula. The latter is subsequently used along with collected data in order to compute these attributes rapidly and effectively. Four whole raw sea bass (Dicentrarchus labrax of various sizes and textures were tested. Changes in texture, related to different viscoelastic characteristics among the four fish, were correctly detected and quantified using the proposed methodology.

  16. Expression of nerve growth factor and its receptor, tyrosine kinase receptor A, in rooster testes.

    Science.gov (United States)

    Ma, Wei; Wang, Chunqiang; Su, Yuhong; Tian, Yumin; Zhu, Hongyan

    2015-10-01

    Nerve growth factor (NGF), which is required for the survival and differentiation of the nervous system, is also thought to play an important role in the development of mammalian reproductive tissues. To explore the function of NGF in the male reproductive system of non-mammalian animals, we determined the presence of NGF and its receptor, tyrosine kinase receptor A (TrkA), in rooster testes and investigated the regulation of NGF and TrkA expression by follicle-stimulating hormone (FSH). The mRNA and protein levels of NGF and TrkA in 6-week-old rooster testes were lower than those in 12-, 16- or 20-week age groups; levels were highest in the 16-week group. Immunohistochemistry showed that NGF and TrkA were both detected in spermatogonia, spermatocytes and spermatids. NGF immunoreactivity was observed in Leydig cells and strong TrkA signals were present in Sertoli cells. Meanwhile, FSH increased TrkA transcript levels in rooster testes in a dose-dependent manner. We present novel evidence for the developmental and FSH-regulated expression of the NGF/TrkA system, and our findings suggest that the NGF/TrkA system may play a prominent role in chicken spermatogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

    Science.gov (United States)

    Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

    2013-02-01

    Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop. © 2012 John Wiley & Sons A/S.

  18. Validation of differential gene expression algorithms: Application comparing fold-change estimation to hypothesis testing

    Directory of Open Access Journals (Sweden)

    Bickel David R

    2010-01-01

    performance. The posterior predictive assessment corroborates these findings. Conclusions Algorithms for detecting differential gene expression may be compared by estimating each algorithm's error in predicting expression ratios, whether such ratios are defined across microarray channels or between two independent groups. According to two distinct estimators of prediction error, algorithms using hierarchical models outperform the other algorithms of the study. The fact that fold-change shrinkage performed as well as conventional model selection criteria calls for investigating algorithms that combine the strengths of significance testing and fold-change estimation.

  19. Aging Reduces an ERRalpha-Directed Mitochondrial Glutaminase Expression Suppressing Glutamine Anaplerosis and Osteogenic Differentiation of Mesenchymal Stem Cells.

    Science.gov (United States)

    Huang, Tongling; Liu, Renzhong; Fu, Xuekun; Yao, Dongsheng; Yang, Meng; Liu, Qingli; Lu, William W; Wu, Chuanyue; Guan, Min

    2017-02-01

    Aging deteriorates osteogenic capacity of mesenchymal stem/stromal cells (MSCs), contributing to imbalanced bone remodeling and osteoporosis. Glutaminase (Gls) catabolizes glutamine into glutamate at the first step of mitochondrial glutamine (Gln)-dependent anaplerosis which is essential for MSCs upon osteogenic differentiation. Estrogen-related receptor α (ERRα) regulates genes required for mitochondrial function. Here, we found that ERRα and Gls are upregulated by osteogenic induction in human MSCs (hMSCs). In contrast, osteogenic differentiation capacity and glutamine consumption of MSCs, as well as ERRα, Gls and osteogenic marker genes are significantly reduced with age. We demonstrated that ERRα binds to response elements on Gls promoter and affects glutamine anaplerosis through transcriptional induction of Gls. Conversely, mTOR inhibitor rapamycin, ERRα inverse agonist compound 29 or Gls inhibitor BPTES leads to reduced Gln anaplerosis and deteriorated osteogenic differentiation of hMSCs. Importantly, overexpression of ERRα or Gls restored impairment by these inhibitors. Finally, we proved that compensated ERRα or Gls expression indeed potentiated Gln anaplerosis and osteogenic capability of elderly mice MSCs in vitro. Together, we establish that Gls is a novel ERRα target gene and ERRα/Gls signaling pathway plays an important role in osteogenic differentiation of MSCs, providing new sights into novel regenerative therapeutics development. Our findings suggest that restoring age-related mitochondrial Gln-dependent anaplerosis may be beneficial for degenerative bone disorders such as osteoporosis. Stem Cells 2017;35:411-424. © 2016 AlphaMed Press.

  20. Does a Negative Triple Test Reduce the Rate of Negative Appendectomy in Adults?

    Directory of Open Access Journals (Sweden)

    Mahmoud F. Sakr

    2012-08-01

    Results: Sixty-seven patients (65.9% were female and 35 (34.1% were male. Their ages ranged between 16 and 49 years (mean 27.5 years. Most patients (87.3% had their symptoms for 12-36 hours before hospital admission. The mean values for TLC, NP, and CRP were 7,573/ and micro;L, 54.53%, and 0.61 mg/L, respectively. Of the 102 patients with NTT, 101 (99% proved not to have appendiceal inflammation (NPV=99%. Only 39 patients were operated upon, of whom 38 (97.4% had a normal appendix, and the remaining 63 patients were either discharged (n=47 or referred to other specialties (n=16. There were significantly more women (76.3%, 29/38 with negative appendectomy than men (24.7%, 9/38 (X2= 21.1, p=0.0001. Gynecological causes were the most common (60.5%, 23/38 and in 11 cases, the exact etiology could not be identified. Conclusions: From the data presented, it may be concluded that TLC, NP and CRP blood levels (triple test should be measured upon hospital admission of adult patients with clinically suspected acute appendicitis. If used judiciously, they may spare the group of patients with an NTT an unnecessary surgical operation, hence markedly reducing the NAR with its potential risks. [Arch Clin Exp Surg 2012; 1(4.000: 229-236

  1. Randomized test of an implementation intention-based tool to reduce stress-induced eating.

    Science.gov (United States)

    O'Connor, Daryl B; Armitage, Christopher J; Ferguson, Eamonn

    2015-06-01

    Stress may indirectly contribute to disease (e.g. cardiovascular disease, cancer) by producing deleterious changes to diet. The purpose of this study was to test the effectiveness of a stress management support (SMS) tool to reduce stress-related unhealthy snacking and to promote stress-related healthy snacking. Participants were randomized to complete a SMS tool with instruction to link stressful situations with healthy snack alternatives (experimental) or a SMS tool without a linking instruction (control). On-line daily reports of stressors and snacking were completed for 7 days. Daily stressors were associated with unhealthy snack consumption in the control condition but not in the experimental condition. Participants highly motivated towards healthy eating consumed a greater number of healthy snacks in the experimental condition on stressful days compared to participants in the experimental condition with low and mean levels of motivation. This tool is an effective, theory driven, intervention that helps to protect against stress-induced high-calorie snack consumption.

  2. A premature demise for RERTR [Reduced Enrichment for Research and Test Reactors programme]?

    International Nuclear Information System (INIS)

    Rydell, R.J.

    1990-01-01

    A common commitment from France, Belgium, Germany and the US to eliminate highly enriched uranium from their research reactors is needed to help guard against this material falling into the wrong hands. In the US, an essential part of this commitment would be rekindling the weakened Reduced Enrichment for Research and Test Reactors programme (RERTR). This is an American initiative to develop low-enrichment uranium fuel for research reactors that have previously required weapons-usable material. Underway since 1978 at Argonne National Laboratory, RERTR has achieved some impressive results: the development of higher density, low enriched fuels that are suitable for use at over 90% of the world's research reactors; a net reduction of US exports of highly enriched uranium (HEU) from the annual 700kg levels in the late 1970s to a 1990 level of just over 100kg; the encouragement of international scientific co-operation aimed at developing new fuels and facilitating the conversion of existing reactors to these fuels. However, in recent years, the US commitment to RERTR has been declining -budgets have fallen and advanced fuel development work has terminated. (author)

  3. Reducing health impacts of biomass burning for cooking. The need for cookstove performance testing

    Energy Technology Data Exchange (ETDEWEB)

    Abeliotis, K. [Department of Home Economics and Ecology, Harokopio University, Athens (Greece); Pakula, C. [Institute of Agricultural Engineering, Section Household and Appliance Technology, Rheinische Friedrich-Wilhelms University, Bonn (Germany)

    2013-08-15

    Biomass is a renewable energy source that is routinely used for cooking in the developing world, especially in rural areas. The World Health Organization estimates that about 2.5 billion people globally rely on biomass, such as wood, agricultural waste and animal dung to meet their energy needs for cooking utilising traditional low-efficiency cookstoves. However, certain human health risks are associated with the inhalation of off-gases resulting from the indoor use of biomass for cooking, especially for women and children who spend more of their time at home. On the other hand, use of energy-efficient cookstoves is considered to reduce those risks. Thus, qualitative and quantitative measurements of cookstove performance are necessary in order to make different stoves and different cooking processes comparable. The aim of this paper is the presentation of the current situation regarding biomass use for cooking with emphasis placed on the developing world, the brief of the adverse health impacts of biomass burning based on the review of literature, the presentation of the merits of improved efficiency cookstoves and to highlight the need for stove performance tests. The demand of different types of biomass is not likely to change in the near future in the developing world since biomass is readily available and cheap. Thus, the efforts to improve household air quality must concentrate on improving cookstoves efficiency and ventilation of the flue gases outdoors. Programmes for the improvement of the cookstoves efficiency in the developing world should be part of the development agenda.

  4. Proceedings of the international meeting on development, fabrication and application of reduced enrichment fuels for research and test reactors

    International Nuclear Information System (INIS)

    1983-08-01

    Separate abstracts were prepared for each of the papers presented in the following areas: (1) Reduced Enrichment Fuels for Research and Test Reactors (RERTR) Program Status; (2) Fuel Development; (3) Fuel Demonstrations; (4) General Topics; and (5) Specific Reactor Applications

  5. Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor

    Directory of Open Access Journals (Sweden)

    Zhang WW

    2017-10-01

    Full Text Available Wei-Wei Zhang,1,2 Feng Bai,1 Jin Wang,1 Rong-Hua Zheng,1 Li-Wang Yang,1 Erskine A James,3 Zhi-Qing Zhao1,4 1Department of Physiology, Shanxi Medical University, 2Department of Anesthesiology, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, China; 3Department of Internal Medicine, Navicent Health, Macon, 4Department of Basic Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USA Abstract: Angiotensin II (Ang II is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC. In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p<0.05 and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, which were accompanied by reduced levels of transforming growth factor beta 1 and Smad2/3. Collagen I synthesis was inhibited and collagen-rich fibrosis was attenuated. Relative to the TAC group, cardiac systolic function was preserved, as shown by increased left ventricular systolic pressure (204±51 vs 110±19

  6. Short-term visual deprivation reduces interference effects of task-irrelevant facial expressions on affective prosody judgments

    Directory of Open Access Journals (Sweden)

    Ineke eFengler

    2015-04-01

    Full Text Available Several studies have suggested that neuroplasticity can be triggered by short-term visual deprivation in healthy adults. Specifically, these studies have provided evidence that visual deprivation reversibly affects basic perceptual abilities. The present study investigated the long-lasting effects of short-term visual deprivation on emotion perception. To this aim, we visually deprived a group of young healthy adults, age-matched with a group of non-deprived controls, for 3 hours and tested them before and after visual deprivation (i.e., after 8 h on average and at 4 week follow-up on an audio-visual (i.e., faces and voices emotion discrimination task. To observe changes at the level of basic perceptual skills, we additionally employed a simple audio-visual (i.e., tone bursts and light flashes discrimination task and two unimodal (one auditory and one visual perceptual threshold measures. During the 3 h period, both groups performed a series of auditory tasks. To exclude the possibility that changes in emotion discrimination may emerge as a consequence of the exposure to auditory stimulation during the 3 h stay in the dark, we visually deprived an additional group of age-matched participants who concurrently performed unrelated (i.e., tactile tasks to the later tested abilities. The two visually deprived groups showed enhanced affective prosodic discrimination abilities in the context of incongruent facial expressions following the period of visual deprivation; this effect was partially maintained until follow-up. By contrast, no changes were observed in affective facial expression discrimination and in the basic perception tasks in any group. These findings suggest that short-term visual deprivation per se triggers a reweighting of visual and auditory emotional cues, which seem to possibly prevail for longer durations.

  7. Mobile Phone Intervention to Reduce Youth Suicide in Rural Communities: Field Test.

    Science.gov (United States)

    Pisani, Anthony R; Wyman, Peter A; Gurditta, Kunali; Schmeelk-Cone, Karen; Anderson, Carolyn L; Judd, Emily

    2018-05-31

    Suicide is a leading cause of death among 10- to 19-year-olds in the United States, with 5% to 8% attempting suicide each year. Suicide risk rises significantly during early adolescence and is higher in rural and underserved communities. School-based universal prevention programs offer a promising way of reducing suicide by providing strategies for emotion regulation and encouraging help-seeking behaviors and youth-adult connectedness. However, such programs frequently run into difficulties in trying to engage a broad range of students. Text messaging is a dominant medium of communication among youths, and studies show both efficacy and uptake in text messaging interventions aimed at adolescents. Text-based interventions may, thus, offer a means for school-based universal prevention programs to engage adolescents who would otherwise be difficult to reach. We field tested Text4Strength, an automated, interactive text messaging intervention that seeks to reach a broad range of early adolescents in rural communities. Text4Strength extends Sources of Strength, a peer-led school suicide prevention program, by encouraging emotion regulation, help-seeking behaviors, and youth-adult connectedness in adolescents. The study tested the appeal and feasibility of Text4Strength and its potential to extend universal school-based suicide prevention. We field tested Text4Strength with 42 ninth-grade students. Over 9 weeks, students received 28 interactive message sequences across 9 categories (Sources of Strength introduction, positive friend, mentors, family support, healthy activities, generosity, spirituality, medical access, and emotion regulation strategies). The message sequences included games, requests for advice, questions about students' own experiences, and peer testimonial videos. We measured baseline mental health characteristics, frequency of replies, completion of sequences and video viewing, appeal to students, and their perception of having benefited from the

  8. A better state-of-mind: deep breathing reduces state anxiety and enhances test performance through regulating test cognitions in children.

    Science.gov (United States)

    Khng, Kiat Hui

    2017-11-01

    A pre-test/post-test, intervention-versus-control experimental design was used to examine the effects, mechanisms and moderators of deep breathing on state anxiety and test performance in 122 Primary 5 students. Taking deep breaths before a timed math test significantly reduced self-reported feelings of anxiety and improved test performance. There was a statistical trend towards greater effectiveness in reducing state anxiety for boys compared to girls, and in enhancing test performance for students with higher autonomic reactivity in test-like situations. The latter moderation was significant when comparing high-versus-low autonomic reactivity groups. Mediation analyses suggest that deep breathing reduces state anxiety in test-like situations, creating a better state-of-mind by enhancing the regulation of adaptive-maladaptive thoughts during the test, allowing for better performance. The quick and simple technique can be easily learnt and effectively applied by most children to immediately alleviate some of the adverse effects of test anxiety on psychological well-being and academic performance.

  9. Peptide-Conjugated Nanoparticles Reduce Positive Co-stimulatory Expression and T Cell Activity to Induce Tolerance.

    Science.gov (United States)

    Kuo, Robert; Saito, Eiji; Miller, Stephen D; Shea, Lonnie D

    2017-07-05

    Targeted approaches to treat autoimmune diseases would improve upon current therapies that broadly suppress the immune system and lead to detrimental side effects. Antigen-specific tolerance was induced using poly(lactide-co-glycolide) nanoparticles conjugated with disease-relevant antigen to treat a model of multiple sclerosis. Increasing the nanoparticle dose and amount of conjugated antigen both resulted in more durable immune tolerance. To identify active tolerance mechanisms, we investigated downstream cellular and molecular events following nanoparticle internalization by antigen-presenting cells. The initial cell response to nanoparticles indicated suppression of inflammatory signaling pathways. Direct and functional measurement of surface MHC-restricted antigen showed positive correlation with both increasing particle dose from 1 to 100 μg/mL and increasing peptide conjugation by 2-fold. Co-stimulatory analysis of cells expressing MHC-restricted antigen revealed most significant decreases in positive co-stimulatory molecules (CD86, CD80, and CD40) following high doses of nanoparticles with higher peptide conjugation, whereas expression of a negative co-stimulatory molecule (PD-L1) remained high. T cells isolated from mice immunized against myelin proteolipid protein (PLP 139-151 ) were co-cultured with antigen-presenting cells administered PLP 139-151 -conjugated nanoparticles, which resulted in reduced T cell proliferation, increased T cell apoptosis, and a stronger anti-inflammatory response. These findings indicate several potential mechanisms used by peptide-conjugated nanoparticles to induce antigen-specific tolerance. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  10. Developmental Vitamin D (DVD) Deficiency Reduces Nurr1 and TH Expression in Post-mitotic Dopamine Neurons in Rat Mesencephalon.

    Science.gov (United States)

    Luan, Wei; Hammond, Luke Alexander; Cotter, Edmund; Osborne, Geoffrey William; Alexander, Suzanne Adele; Nink, Virginia; Cui, Xiaoying; Eyles, Darryl Walter

    2018-03-01

    Developmental vitamin D (DVD) deficiency has been proposed as an important risk factor for schizophrenia. Our previous study using Sprague Dawley rats found that DVD deficiency disrupted the ontogeny of mesencephalic dopamine neurons by decreasing the mRNA level of a crucial differentiation factor of dopamine cells, the nuclear receptor related 1 protein (Nurr1). However, it remains unknown whether this reflects a reduction in dopamine cell number or in Nurr1 expression. It is also unclear if any particular subset of developing dopamine neurons in the mesencephalon is selectively affected. In this study, we employed state-of-the-art spinning disk confocal microscopy optimized for the imaging of tissue sections and 3D segmentation to assess post-mitotic dopamine cells on a single-cell basis in the rat mesencephalon at embryonic day 15. Our results showed that DVD deficiency did not alter the number, morphology, or positioning of post-mitotic dopamine cells. However, the ratio of Nurr1+TH+ cells in the substantia nigra pars compacta (SNc) compared with the ventral tegmental area (VTA) was increased in DVD-deficient embryos. In addition, the expression of Nurr1 in immature dopamine cells and mature dopamine neurons in the VTA was decreased in DVD-deficient group. Tyrosine hydroxylase was selectively reduced in SNc of DVD-deficient mesencephalon. We conclude that DVD deficiency induced early alterations in mesencephalic dopamine development may in part explain the abnormal dopamine-related behaviors found in this model. Our findings may have broader implications for how certain environmental risk factors for schizophrenia may shape the ontogeny of dopaminergic systems and by inference increase the risk of schizophrenia.

  11. Proceedings of the 1978 international meeting on reduced enrichment for research and test reactors

    Energy Technology Data Exchange (ETDEWEB)

    Travelli, A [Argonne National Laboratory, Argonne, IL (United States)

    1993-08-01

    November 9-10, 1978, marked the first of what has become an annual event - the International Meeting on Reduced Enrichment for Research and Test Reactors (RERTR). The RERTR Program had been started only three months earlier, and the meeting brought together for the first time many people who became major program participants in later years. This first meeting emphasized fuel development, and while it established the basis for all later meetings, it was unique in several respects. It was a time of feeling each other out, and of sharing new ideas, concerns, and hopes. In the absence of an established precedent, a number of participants came with written papers while others made only verbal presentations. Informality added spice and special importance to the discussions at the end of each presentation and, especially, to the panel discussion at the end of the meeting. An important achievement was a consensus on near-, medium-, and long-term density goals for the various fuels. This consensus resulted in a list written on the blackboard at the end of the panel discussion, and reproduced on page 216, which outlined the goals of each fabricator. Luckily, both presentations and discussions were recorded on audio tape. These recordings were transcribed and used to complete the informal presentations and to append the discussions at the end of each presentation. Considerable effort was expended in clearing the transcribed papers and key discussions with the participants. A few issues could not be resolved quickly, and in the frantic rush of those early years, these proceedings were set aside. Believing that the proceedings of this first meeting are important as a historical record of the beginning of the international RERTR effort, we have recently dusted off the manuscript and finished our editing job.

  12. Proceedings of the 1978 international meeting on reduced enrichment for research and test reactors

    International Nuclear Information System (INIS)

    Travelli, A.

    1993-08-01

    November 9-10, 1978, marked the first of what has become an annual event - the International Meeting on Reduced Enrichment for Research and Test Reactors (RERTR). The RERTR Program had been started only three months earlier, and the meeting brought together for the first time many people who became major program participants in later years. This first meeting emphasized fuel development, and while it established the basis for all later meetings, it was unique in several respects. It was a time of feeling each other out, and of sharing new ideas, concerns, and hopes. In the absence of an established precedent, a number of participants came with written papers while others made only verbal presentations. Informality added spice and special importance to the discussions at the end of each presentation and, especially, to the panel discussion at the end of the meeting. An important achievement was a consensus on near-, medium-, and long-term density goals for the various fuels. This consensus resulted in a list written on the blackboard at the end of the panel discussion, and reproduced on page 216, which outlined the goals of each fabricator. Luckily, both presentations and discussions were recorded on audio tape. These recordings were transcribed and used to complete the informal presentations and to append the discussions at the end of each presentation. Considerable effort was expended in clearing the transcribed papers and key discussions with the participants. A few issues could not be resolved quickly, and in the frantic rush of those early years, these proceedings were set aside. Believing that the proceedings of this first meeting are important as a historical record of the beginning of the international RERTR effort, we have recently dusted off the manuscript and finished our editing job

  13. The Bodily Expressive Action Stimulus Test (BEAST). Construction and Validation of a Stimulus Basis for Measuring Perception of Whole Body Expression of Emotions.

    Science.gov (United States)

    de Gelder, Beatrice; Van den Stock, Jan

    2011-01-01

    Whole body expressions are among the main visual stimulus categories that are naturally associated with faces and the neuroscientific investigation of how body expressions are processed has entered the research agenda this last decade. Here we describe the stimulus set of whole body expressions termed bodily expressive action stimulus test (BEAST), and we provide validation data for use of these materials by the community of emotion researchers. The database was composed of 254 whole body expressions from 46 actors expressing 4 emotions (anger, fear, happiness, and sadness). In all pictures the face of the actor was blurred and participants were asked to categorize the emotions expressed in the stimuli in a four alternative-forced-choice task. The results show that all emotions are well recognized, with sadness being the easiest, followed by fear, whereas happiness was the most difficult. The BEAST appears a valuable addition to currently available tools for assessing recognition of affective signals. It can be used in explicit recognition tasks as well as in matching tasks and in implicit tasks, combined either with facial expressions, with affective prosody, or presented with affective pictures as context in healthy subjects as well as in clinical populations.

  14. Farewell to the Earth and the Moon -ESA's Mars Express successfully tests its instruments

    Science.gov (United States)

    2003-07-01

    The routine check-outs of Mars Express's instruments and of the Beagle-2 lander, performed during the last weeks, have been very successful. "As in all space missions little problems have arisen, but they have been carefully evaluated and solved. Mars Express continues on its way to Mars performing beautifully", comments Chicarro. The views of the Earth/Moon system were taken on 3 July 2003 by Mars Express's High Resolution Stereo Camera (HRSC), when the spacecraft was 8 million kilometres from Earth. The image taken shows true colours; the Pacific Ocean appears in blue, and the clouds near the Equator and in mid to northern latitudes in white to light grey. The image was processed by the Instrument Team at the Institute of Planetary Research of DLR, Berlin (Germany). It was built by combining a super resolution black and white HRSC snap-shot image of the Earth and the Moon with colour information obtained by the blue, green, and red sensors of the instrument. “The pictures and the information provided by the data prove the camera is working very well. They provide a good indication of what to expect once the spacecraft is in its orbit around Mars, at altitudes of only 250-300 kilometres: very high resolution images with brilliant true colour and in 3D,” says the Principal Investigator of the HRSC, Gerhard Neukum, of the Freie Universität of Berlin (Germany). This camera will be able to distinguish details of up to 2 metres on the Martian surface. Another striking demonstration of Mars Express's instruments high performance are the data taken by the OMEGA spectrometer. Once at Mars, this instrument will provide the best map of the molecular and mineralogical composition of the whole planet, with 5% of the planetary surface in high resolution. Minerals and other compounds such as water will be charted as never before. As the Red Planet is still too far away, the OMEGA team devised an ingenious test for their instrument: to detect the Earth’s surface

  15. Cultural and Gender Differences in Experiences and Expression of Test Anxiety among Chinese, Finnish, and Swedish Grade 3 Pupils

    Science.gov (United States)

    Nyroos, Mikaela; Korhonen, Johan; Peng, Aihui; Linnanmäki, Karin; Svens-Liavåg, Camilla; Bagger, Anette; Sjöberg, Gunnar

    2015-01-01

    While test anxiety has been studied extensively, little consideration has been given to the cultural impacts of children's experiences and expressions of test anxiety. The aim of this work was to examine whether variance in test anxiety scores can be predicted based on gender and cultural setting. Three hundred and ninety-eight pupils in Grade 3…

  16. EXPRESS

    International Nuclear Information System (INIS)

    Ancelin, C.; Le, P.; DeSaint-Quentin, S.; Villatte, N.

    1987-01-01

    This paper presents EXPRESS, an expert system developed for the automation of reliability studies. The first part consists in the description of the method for static thermohydraulic systems. In this step, the authors define the knowledge representation based on the two inference engines - ALOUETTE and LCR developed by EDF. They explain all the process to construct a fault tree from a topological and functional description of the system. Numerous examples are exhibited in illustration of the method. This is followed by the lessons derived from the studies performed on some safety systems of the PALUEL nuclear plant. The development of the same approach for electric power systems is described, insisting on the difference resulting from the sequential nature of these systems. Finally, they show the main advantages identified during the studies

  17. Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models

    Directory of Open Access Journals (Sweden)

    Kung PJ

    2014-10-01

    Full Text Available Pin-Jui Kung,1,* Yu-Chen Tao,1,* Ho-Chiang Hsu,1 Wan-Ling Chen,1 Te-Hsien Lin,1 Donala Janreddy,2 Ching-Fa Yao,2 Kuo-Hsuan Chang,3 Jung-Yaw Lin,1 Ming-Tsan Su,1 Chung-Hsin Wu,1 Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li1 1Department of Life Science, 2Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan; 3Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: In spinocerebellar ataxia type 17 (SCA17, the expansion of a translated CAG repeat in the TATA box binding protein (TBP gene results in a long polyglutamine (polyQ tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment. Keywords: spinocerebellar ataxia type 17, TATA box binding protein, polyQ aggregation, indole and derivative, therapeutics

  18. Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits.

    Science.gov (United States)

    Rossignoli, Matheus Teixeira; Lopes-Aguiar, Cleiton; Ruggiero, Rafael Naime; Do Val da Silva, Raquel Araujo; Bueno-Junior, Lezio Soares; Kandratavicius, Ludmyla; Peixoto-Santos, José Eduardo; Crippa, José Alexandre; Cecilio Hallak, Jaime Eduardo; Zuardi, Antonio Waldo; Szawka, Raphael Escorsim; Anselmo-Franci, Janete; Leite, João Pereira; Romcy-Pereira, Rodrigo Neves

    2017-05-14

    The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has implications for the treatment of post-traumatic stress disorders. Cannabidiol (CBD), the major non-psychotomimetic phytocannabinoid of the Cannabis sativa plant, is known to modulate contextual fear memory acquisition in rodents. However, it is still not clear how CBD interferes with PFC-dependent processes during post-training memory consolidation. Here, we tested whether intra-PFC infusions of CBD immediately after or 5h following contextual fear conditioning was able to interfere with memory consolidation. Neurochemical and cellular correlates of the CBD treatment were evaluated by the quantification of extracellular levels of dopamine (DA), serotonin, and their metabolites in the PFC and by measuring the cellular expression of activity-dependent transcription factors in cortical and limbic regions. Our results indicate that bilateral intra-PFC CBD infusion impaired contextual fear memory consolidation when applied 5h after conditioning, but had no effect when applied immediately after it. This effect was associated with a reduction in DA turnover in the PFC following retrieval 5days after training. We also observed that post-conditioning infusion of CBD reduced c-fos and zif-268 protein expression in the hippocampus, PFC, and thalamus. Our findings support that CBD interferes with contextual fear memory consolidation by reducing PFC influence on cortico-limbic circuits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Immunization of mice with Lactobacillus casei expressing a beta-intimin fragment reduces intestinal colonization by Citrobacter rodentium.

    Science.gov (United States)

    Ferreira, P C D; da Silva, J B; Piazza, R M F; Eckmann, L; Ho, P L; Oliveira, M L S

    2011-11-01

    Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in children from developing countries. Intimate adhesion of the bacteria to intestinal cells occurs via binding of the adhesin intimin to the TIR receptor exposed on cell surfaces. Here, Lactobacillus casei expressing a fragment of β-intimin (L. casei-Int(cv)) was tested as mucosal vaccines in mice against intestinal colonization with the murine pathogen Citrobacter rodentium. Oral or sublingual immunization of C57BL/6 mice with L. casei-Int(cv) induced anti-Int(cv) IgA in feces but no IgG in sera. Conversely, anti-Int(cv) IgG was induced in the sera of mice after sublingual immunization with purified Int(cv). All vaccines were able to decrease C. rodentium recovery from feces. However, this reduction was more evident and sustained over time in mice immunized with L. casei-Int(cv) by the sublingual route. These mice also displayed an increase in interleukin 6 (IL-6) and gamma interferon (IFN-γ) secretion by spleen cells 10 days after infection. Additionally, oral or sublingual immunization of C3H/HePas mice, which are highly susceptible to C. rodentium infection, with L. casei-Int(cv) induced anti-Int(cv) antibodies and significantly increased survival after challenge. Immunohistological analysis of colon sections revealed that C. rodentium was located in deep fractions of the tissue from C3H/HePas mice immunized with L. casei whereas superficial staining was observed in colon sections from mice immunized with L. casei-Int(cv.) The results indicate that vaccines composed of L. casei expressing intimin may represent a promising approach and that the C3H/HePas infection model with C. rodentium can be used to evaluate potential vaccines against EPEC.

  20. Immunization of Mice with Lactobacillus casei Expressing a Beta-Intimin Fragment Reduces Intestinal Colonization by Citrobacter rodentium ▿ †

    Science.gov (United States)

    Ferreira, P. C. D.; da Silva, J. B.; Piazza, R. M. F.; Eckmann, L.; Ho, P. L.; Oliveira, M. L. S.

    2011-01-01

    Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in children from developing countries. Intimate adhesion of the bacteria to intestinal cells occurs via binding of the adhesin intimin to the TIR receptor exposed on cell surfaces. Here, Lactobacillus casei expressing a fragment of β-intimin (L. casei-Intcv) was tested as mucosal vaccines in mice against intestinal colonization with the murine pathogen Citrobacter rodentium. Oral or sublingual immunization of C57BL/6 mice with L. casei-Intcv induced anti-Intcv IgA in feces but no IgG in sera. Conversely, anti-Intcv IgG was induced in the sera of mice after sublingual immunization with purified Intcv. All vaccines were able to decrease C. rodentium recovery from feces. However, this reduction was more evident and sustained over time in mice immunized with L. casei-Intcv by the sublingual route. These mice also displayed an increase in interleukin 6 (IL-6) and gamma interferon (IFN-γ) secretion by spleen cells 10 days after infection. Additionally, oral or sublingual immunization of C3H/HePas mice, which are highly susceptible to C. rodentium infection, with L. casei-Intcv induced anti-Intcv antibodies and significantly increased survival after challenge. Immunohistological analysis of colon sections revealed that C. rodentium was located in deep fractions of the tissue from C3H/HePas mice immunized with L. casei whereas superficial staining was observed in colon sections from mice immunized with L. casei-Intcv. The results indicate that vaccines composed of L. casei expressing intimin may represent a promising approach and that the C3H/HePas infection model with C. rodentium can be used to evaluate potential vaccines against EPEC. PMID:21900533

  1. Reduced Clostridium difficile Tests and Laboratory-Identified Events With a Computerized Clinical Decision Support Tool and Financial Incentive.

    Science.gov (United States)

    Madden, Gregory R; German Mesner, Ian; Cox, Heather L; Mathers, Amy J; Lyman, Jason A; Sifri, Costi D; Enfield, Kyle B

    2018-06-01

    We hypothesized that a computerized clinical decision support tool for Clostridium difficile testing would reduce unnecessary inpatient tests, resulting in fewer laboratory-identified events. Census-adjusted interrupted time-series analyses demonstrated significant reductions of 41% fewer tests and 31% fewer hospital-onset C. difficile infection laboratory-identified events following this intervention.Infect Control Hosp Epidemiol 2018;39:737-740.

  2. Low PIP4K2B expression in human breast tumors correlates with reduced patient survival: A role for PIP4K2B in the regulation of E-cadherin expression.

    Science.gov (United States)

    Keune, Willem-Jan; Sims, Andrew H; Jones, David R; Bultsma, Yvette; Lynch, James T; Jirström, Karin; Landberg, Goran; Divecha, Nullin

    2013-12-01

    Phosphatidylinositol-5-phosphate (PtdIns5P) 4-kinase β (PIP4K2B) directly regulates the levels of two important phosphoinositide second messengers, PtdIns5P and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P2]. PIP4K2B has been linked to the regulation of gene transcription, to TP53 and AKT activation, and to the regulation of cellular reactive oxygen accumulation. However, its role in human tumor development and on patient survival is not known. Here, we have interrogated the expression of PIP4K2B in a cohort (489) of patients with breast tumor using immunohistochemical staining and by a meta-analysis of gene expression profiles from 2,999 breast tumors, both with associated clinical outcome data. Low PIP4K2B expression was associated with increased tumor size, high Nottingham histological grade, Ki67 expression, and distant metastasis, whereas high PIP4K2B expression strongly associated with ERBB2 expression. Kaplan-Meier curves showed that both high and low PIP4K2B expression correlated with poorer patient survival compared with intermediate expression. In normal (MCF10A) and tumor (MCF7) breast epithelial cell lines, mimicking low PIP4K2B expression, using short hairpin RNA interference-mediated knockdown, led to a decrease in the transcription and expression of the tumor suppressor protein E-cadherin (CDH1). In MCF10A cells, knockdown of PIP4K2B enhanced TGF-β-induced epithelial to mesenchymal transition (EMT), a process required during the development of metastasis. Analysis of gene expression datasets confirmed the association between low PIP4K2B and low CDH1expression. Decreased CDH1 expression and enhancement of TGF-β-induced EMT by reduced PIP4K2B expression might, in part, explain the association between low PIP4K2B expression and poor patient survival.

  3. Integrated Vibration and Acceleration Testing to Reduce Payload Mass, Cost and Mission Risk, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose to develop a capability to provide integrated acceleration, vibration, and shock testing using a state-of-the-art centrifuge, allowing for the test of...

  4. Lactococcus lactis NCC 2287 Alleviates Food Allergic Manifestations in Sensitized Mice by Reducing IL-13 Expression Specifically in the Ileum

    Directory of Open Access Journals (Sweden)

    Adrian W. Zuercher

    2012-01-01

    Full Text Available Objective. Utilizing a food allergy murine model, we have investigated the intrinsic antiallergic potential of the Lactococcus lactis NCC 2287 strain. Methods. BALB/c mice were sensitized at weekly intervals with ovalbumin (OVA plus cholera toxin (CT by the oral route for 7 weeks. In this model, an oral challenge with a high dose of OVA at the end of the sensitization period leads to clinical symptoms. Lactococcus lactis NCC 2287 was given to mice via the drinking water during sensitization (prevention phase or after sensitization (management phase. Results. Lactococcus lactis NCC 2287 administration to sensitized mice strikingly reduced allergic manifestations in the management phase upon challenge, when compared to control mice. No preventive effect was observed with the strain. Lactococcus lactis NCC 2287 significantly decreased relative expression levels of the Th-2 cytokine, IL-13, and associated chemokines CCL11 (eotaxin-1 and CCL17 (TARC in the ileum. No effect was observed in the jejunum. Conclusion/Significance. These results taken together designate Lactococcus lactis NCC 2287 as a candidate probiotic strain appropriate in the management of allergic symptoms.

  5. Decreased SAP expression in T cells from patients with SLE contributes to early signaling abnormalities and reduced IL-2 production

    Science.gov (United States)

    Karampetsou, Maria P.; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C.; Tsokos, George C.

    2016-01-01

    T cells from patients with systemic lupus erythematosus (SLE) display a number of functions including increased early signaling events following engagement of the T cell receptor (TCR). Signaling lymphocytic activation molecule family (SLAMF) cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating immune response. Here we present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and 3 men with SLE independently of disease activity. In SLE T cells the SAP protein is also subject to increased degradation by a caspase-3. Forced expression of SAP in SLE T cells simultaneously heightened IL-2 production, calcium (Ca2+) responses and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR antibodies, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID:27183584

  6. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression.

    Science.gov (United States)

    Peeters, Janneke G C; Vervoort, Stephin J; Tan, Sander C; Mijnheer, Gerdien; de Roock, Sytze; Vastert, Sebastiaan J; Nieuwenhuis, Edward E S; van Wijk, Femke; Prakken, Berent J; Creyghton, Menno P; Coffer, Paul J; Mokry, Michal; van Loosdregt, Jorg

    2015-09-29

    The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA) is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4(+) memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression

    Directory of Open Access Journals (Sweden)

    Janneke G.C. Peeters

    2015-09-01

    Full Text Available The underlying molecular mechanisms for many autoimmune diseases are poorly understood. Juvenile idiopathic arthritis (JIA is an exceptionally well-suited model for studying autoimmune diseases due to its early onset and the possibility to analyze cells derived from the site of inflammation. Epigenetic profiling, utilizing primary JIA patient-derived cells, can contribute to the understanding of autoimmune diseases. With H3K27ac chromatin immunoprecipitation, we identified a disease-specific, inflammation-associated, typical enhancer and super-enhancer signature in JIA patient synovial-fluid-derived CD4+ memory/effector T cells. RNA sequencing of autoinflammatory site-derived patient T cells revealed that BET inhibition, utilizing JQ1, inhibited immune-related super-enhancers and preferentially reduced disease-associated gene expression, including cytokine-related processes. Altogether, these results demonstrate the potential use of enhancer profiling to identify disease mediators and provide evidence for BET inhibition as a possible therapeutic approach for the treatment of autoimmune diseases.

  8. Use of predefined biochemical admission profiles does not reduce the number of tests or total cost

    DEFF Research Database (Denmark)

    Pareek, Manan; Haidl, Felix; Folkestad, Lars

    2014-01-01

    The objective of this pilot study was to evaluate whether the use of predefined biochemical profiles as an alternative to individually ordered blood tests by the treating physicians resulted in fewer tests or a lower total cost.......The objective of this pilot study was to evaluate whether the use of predefined biochemical profiles as an alternative to individually ordered blood tests by the treating physicians resulted in fewer tests or a lower total cost....

  9. Randomised controlled trial of routine individual feedback to improve rationality and reduce numbers of test requests.

    Science.gov (United States)

    Winkens, R A; Pop, P; Bugter-Maessen, A M; Grol, R P; Kester, A D; Beusmans, G H; Knottnerus, J A

    1995-02-25

    Feedback can be described as a way to provide information on doctors' performance to enable changes in future behaviour. Feedback is used with the aim of changing test-ordering behaviour. It can lead to reductions in test usage and cost savings. It is not sufficiently clear, however, whether feedback leads to more appropriate test use. Since 1985, the Diagnostic Coordinating Center Maastricht has been giving feedback on diagnostic tests as a routine health care activity to all family doctors in its region. Both quantity and quality of requests are discussed. In a randomised, controlled trial over 2.5 years, discussion of tests not included previously was added to the existing routine feedback. One group of family doctors (n = 39) received feedback on test-group A (electrocardiography, endoscopy, cervical smears, and allergy tests), the other (n = 40) on test-group B (radiographic and ultrasonographic tests). Thus, each group of doctors acted as a control group for the other. Changes in volume and rationality of requests were analysed. The number of requests decreased during the trial (p = 0.036). Request numbers decreased particularly for test-group A (p = 0.04). The proportion of requests that were non-rational decreased more in the intervention than in the control groups (p = 0.009). Rationality improved predominantly for test-group B (p = 0.043). Thus, routine feedback can change the quantity and quality of requests.

  10. Stable isotope labeling of glycoprotein expressed in silkworms using immunoglobulin G as a test molecule

    Energy Technology Data Exchange (ETDEWEB)

    Yagi, Hirokazu [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan); Nakamura, Masatoshi [National Institute of Agrobiological Sciences, Genetic Resources Conservation Research Unit, Genetic Resources Center (Japan); Yokoyama, Jun [Taiyo Nippon Sanso Corporation, Tsukuba Laboratories (Japan); Zhang, Ying; Yamaguchi, Takumi [National Institutes of Natural Sciences, Institute for Molecular Science and Okazaki Institute for Integrative Bioscience (Japan); Kondo, Sachiko [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan); Kobayashi, Jun [Yamaguchi University, Department of Biological and Environmental Sciences, Faculty of Agriculture (Japan); Kato, Tatsuya; Park, Enoch Y. [Shizuoka University, Laboratory of Biotechnology, Research Institute of Green Science and Technology (Japan); Nakazawa, Shiori [Nagoya University, Sugashima Marine Biological Laboratory, Graduate School of Science (Japan); Hashii, Noritaka; Kawasaki, Nana [National Institute of Health Sciences, Division of Biological Chemistry and Biologicals (Japan); Kato, Koichi, E-mail: kkato@phar.nagoya-cu.ac.jp [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan)

    2015-06-15

    Silkworms serve as promising bioreactors for the production of recombinant proteins, including glycoproteins and membrane proteins, for structural and functional protein analyses. However, lack of methodology for stable isotope labeling has been a major deterrent to using this expression system for nuclear magnetic resonance (NMR) structural biology. Here we developed a metabolic isotope labeling technique using commercially available silkworm larvae. The fifth instar larvae were infected with baculoviruses for co-expression of recombinant human immunoglobulin G (IgG) as a test molecule, with calnexin as a chaperone. They were subsequently reared on an artificial diet containing {sup 15}N-labeled yeast crude protein extract. We harvested 0.1 mg of IgG from larva with a {sup 15}N-enrichment ratio of approximately 80 %. This allowed us to compare NMR spectral data of the Fc fragment cleaved from the silkworm-produced IgG with those of an authentic Fc glycoprotein derived from mammalian cells. Therefore, we successfully demonstrated that our method enables production of isotopically labeled glycoproteins for NMR studies.

  11. Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.

    Science.gov (United States)

    Reeve, Richard; Cox, Sarah; Smitsaart, Eliana; Beascoechea, Claudia Perez; Haas, Bernd; Maradei, Eduardo; Haydon, Daniel T; Barnett, Paul

    2011-07-26

    The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Reduce, Reuse, Recycle: The Longitudinal Value of Local Cut Scores Using State Test Data

    Science.gov (United States)

    Nelson, Peter M.; Van Norman, Ethan R.; VanDerHeyden, Amanda

    2017-01-01

    We used existing reading (n = 1,498) and math (n = 2,260) data to evaluate state test scores for screening middle school students. In Phase 1, state test data were used to create a research-derived cut score that was optimal for predicting state test performance the following year. In Phase 2, those cut scores were applied with future cohorts.…

  13. Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.

    LENUS (Irish Health Repository)

    Frodl, T

    2012-01-01

    Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and\\/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.

  14. Internalized homophobia and reduced HIV testing among men who have sex with men in China.

    Science.gov (United States)

    Pyun, Thomas; Santos, Glenn-Milo; Arreola, Sonya; Do, Tri; Hebert, Pato; Beck, Jack; Makofane, Keletso; Wilson, Patrick A; Ayala, George

    2014-03-01

    Although previous research has examined barriers and facilitators of HIV testing among men who have sex with men (MSM) in China, few studies have focused on social factors, including homophobia and internalized homophobia. This study utilized data from a global online survey to determine correlates of HIV testing as part of a subanalysis focused on Chinese MSM. Controlling for age, HIV knowledge, number of sexual partners, and other covariates, ever having tested for HIV was significantly correlated with lower internalized homophobia. This study suggests that stigma associated with sexual orientation may serve as a barrier to participation in HIV testing and other health-promoting behaviors.

  15. Reduced Capacity in a Dichotic Memory Test for Adult Patients with ADHD

    Science.gov (United States)

    Dige, Niels; Maahr, Eija; Backenroth-Ohsako, Gunnel

    2010-01-01

    Objective: To evaluate whether a dichotic memory test would reveal deficits in short-term working-memory recall and long-term memory recall in a group of adult patients with ADHD. Methods: A dichotic memory test with ipsilateral backward speech distraction in an adult ADHD group (n = 69) and a control group (n = 66) is used to compare performance…

  16. Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.

    Science.gov (United States)

    McDermott, Carmel M; Liu, Dan; Ade, Catherine; Schrader, Laura A

    2015-02-01

    Females experience depression, posttraumatic stress disorder (PTSD), and anxiety disorders at approximately twice the rate of males, but the mechanisms underlying this difference remain undefined. The effect of sex hormones on neural substrates presents a possible mechanism. We investigated the effect of ovariectomy at two ages, before puberty and in adulthood, and 17β-estradiol (E2) replacement administered chronically in drinking water on anxiety level, fear memory formation, and extinction. Based on previous studies, we hypothesized that estradiol replacement would impair fear memory formation and enhance extinction rate. Females, age 4 weeks and 10 weeks, were divided randomly into 4 groups; sham surgery, OVX, OVX+low E2 (200nM), and OVX+high E2 (1000nM). Chronic treatment with high levels of E2 significantly increased anxiety levels measured in the elevated plus maze. In both age groups, high levels of E2 significantly increased contextual fear memory but had no effect on cued fear memory. In addition, high E2 decreased the rate of extinction in both ages. Finally, catechol-O-methyltransferase (COMT) is important for regulation of catecholamine levels, which play a role in fear memory formation and extinction. COMT expression in the hippocampus was significantly reduced by high E2 replacement, implying increased catecholamine levels in the hippocampus of high E2 mice. These results suggest that estradiol enhanced fear memory formation, and inhibited fear memory extinction, possibly stabilizing the fear memory in female mice. This study has implications for a neurobiological mechanism for PTSD and anxiety disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. CX4945 suppresses the growth of castration-resistant prostate cancer cells by reducing AR-V7 expression.

    Science.gov (United States)

    Deng, Chuangzhong; Chen, Jieping; Guo, Shengjie; Wang, Yanjun; Zhou, Qianghua; Li, Zaishang; Yang, Xingping; Yu, Xingsu; Zhang, Zhenfeng; Zhou, Fangjian; Han, Hui; Yao, Kai

    2017-08-01

    The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay. Protein and mRNA levels of full-length AR (AR-FL) and AR-V7 were determined by qPCR and western blot, respectively. The nuclear translocation of p50 and p65 was assessed to reflect the activity of the NF-κB pathway. CX4945 reduced the proliferation of CRPC cells in a dose-dependent and time-dependent manner. AR-V7 rather than AR-FL was downregulated by CX4945 in both the mRNA and protein level. Furthermore, CX4945 could restore the sensitivity of CRPC cells to bicalutamide. The analysis of possible mechanisms demonstrated that the inhibition of CK2 diminished the phosphorylation of p65 at ser529 and thus attenuated the activity of the NF-κB pathway. The inhibition of CK2 by CX4945 can repress the viability of CRPC cells and restore their sensitivity to anti-androgen therapy by suppressing AR-V7. This finding presents a potential option for the treatment of prostate cancer, especially CRPC.

  18. Effective and specific in planta RNAi in cyst nematodes: expression interference of four parasitism genes reduces parasitic success.

    Science.gov (United States)

    Sindhu, Anoop S; Maier, Tom R; Mitchum, Melissa G; Hussey, Richard S; Davis, Eric L; Baum, Thomas J

    2009-01-01

    Cyst nematodes are highly evolved sedentary plant endoparasites that use parasitism proteins injected through the stylet into host tissues to successfully parasitize plants. These secretory proteins likely are essential for parasitism as they are involved in a variety of parasitic events leading to the establishment of specialized feeding cells required by the nematode to obtain nourishment. With the advent of RNA interference (RNAi) technology and the demonstration of host-induced gene silencing in parasites, a new strategy to control pests and pathogens has become available, particularly in root-knot nematodes. Plant host-induced silencing of cyst nematode genes so far has had only limited success but similarly should disrupt the parasitic cycle and render the host plant resistant. Additional in planta RNAi data for cyst nematodes are being provided by targeting four parasitism genes through host-induced RNAi gene silencing in transgenic Arabidopsis thaliana, which is a host for the sugar beet cyst nematode Heterodera schachtii. Here it is reported that mRNA abundances of targeted nematode genes were specifically reduced in nematodes feeding on plants expressing corresponding RNAi constructs. Furthermore, this host-induced RNAi of all four nematode parasitism genes led to a reduction in the number of mature nematode females. Although no complete resistance was observed, the reduction of developing females ranged from 23% to 64% in different RNAi lines. These observations demonstrate the relevance of the targeted parasitism genes during the nematode life cycle and, potentially more importantly, suggest that a viable level of resistance in crop plants may be accomplished in the future using this technology against cyst nematodes.

  19. Validating a test to assess early childhood learners’ ability to perceive, express and appreciate emotions

    Directory of Open Access Journals (Sweden)

    Jose Miguel Mestre Navas

    2011-10-01

    Full Text Available Emotional Education, regardless of the school level, has an important mission in the goal of any educational project: socialising younger generations. However, it is also important to assess implemented programs by means of a valid, reliable measure of the progression of children’s’ cognitive and emotional development. Using a sample of 138 early childhood learners (aged from 3 to 6 this paper tested an instrument for assessing the ability to perceive, appreciate and express emotions (as defined by Mayer & Salovey’s model, 1997; 2007. Also, external criteria were developed by teachers on several issues related to children’s social and personal adaptation (school rules, achievement, impulsiveness, social acceptance of peers and hostility. Findings suggest that children from 3 to 6 years who obtain best scores in the perception and assessment of basic emotions are considered by their teachers to better adjust to school rules, to better control impulses, to achieve better academic performance and to be less problematic. It is also important to note that the study is at its initial stages and presents some limitations, as certain important variables such as personality and verbal ability are not controlled. Nevertheless, it should be pointed out that children showed great enthusiasm in taking the test.

  20. Home-based voluntary HIV counselling and testing found highly acceptable and to reduce inequalities

    Directory of Open Access Journals (Sweden)

    Michelo Charles

    2010-06-01

    Full Text Available Abstract Background Low uptake of voluntary HIV counselling and testing (VCT in sub-Saharan Africa is raising acceptability concerns which might be associated with ways by which it is offered. We investigated the acceptability of home-based delivery of counselling and HIV testing in urban and rural populations in Zambia where VCT has been offered mostly from local clinics. Methods A population-based HIV survey was conducted in selected communities in 2003 (n = 5035. All participants stating willingness to be HIV tested were offered VCT at home and all counselling was conducted in the participants' homes. In the urban area post-test counselling and giving of results were done the following day whereas in rural areas this could take 1-3 weeks. Results Of those who indicated willingness to be HIV tested, 76.1% (95%CI 74.9-77.2 were counselled and received the test result. Overall, there was an increase in the proportion ever HIV tested from 18% before provision of home-based VCT to 38% after. The highest increase was in rural areas; among young rural men aged 15-24 years up from 14% to 42% vs. for urban men from 17% to 37%. Test rates by educational attainment changed from being positively associated to be evenly distributed after home-based VCT. Conclusions A high uptake was achieved by delivering HIV counselling and testing at home. The highest uptakes were seen in rural areas, in young people and groups with low educational attainment, resulting in substantial reductions in existing inequalities in accessing VCT services.

  1. Low-Cost, Class D Testing of Spacecraft Photovoltaic Systems Can Reduce Risk

    Science.gov (United States)

    Forgione, Joshua B.; Kojima, Gilbert K.; Hanel, Robert; Mallinson, Mark V.

    2014-01-01

    The end-to-end verification of a spacecraft photovoltaic power generation system requires light! Specifically, the standard practice for doing so is the Large Area Pulsed Solar Simulation (LAPSS). A LAPSS test can characterize a photovoltaic system's efficiency via its response to rapidly applied impulses of simulated sunlight. However, a Class D program on a constrained budget and schedule may not have the resources to ship an entire satellite for a LAPSS test alone. Such was the case with the Lunar Atmospheric and Dust Environment Explorer (LADEE) program, which was also averse to the risk of hardware damage during shipment. When the Electrical Power System (EPS) team was denied a spacecraft-level LAPSS test, the lack of an end-to-end power generation test elevated to a project-level technical risk. The team pulled together very limited resources to not only eliminate the risk, but build a process to monitor the health of the system through mission operations. We discuss a process for performing a low-cost, end-to-end test of the LADEE photovoltaic system. The approach combines system-level functional test, panel-level performance results, and periodic inspection (and repair) up until launch. Following launch, mission operations tools are utilized to assess system performance based on a scant amount of data. The process starts in manufacturing at the subcontractor. The panel manufacturer provides functional test and LAPSS data on each individual panel. We apply an initial assumption that the per-panel performance is sufficient to meet the power generation requirements. The manufacturer's data is also carried as the performance allocation for each panel during EPS system modeling and initial mission operations. During integration and test, a high-power, professional theater lamp system provides simulated sunlight to each panel on the spacecraft, thereby permitting a true end-to-end system test. A passing test results in a step response to nearly full-rated current

  2. EPA Releases Draft Policy to Reduce Animal Testing for Skin Sensitization

    Science.gov (United States)

    The document, Draft Interim Science Policy: Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing, describes the science behind the non-animal alternatives that can now be used to identify skin sensitization.

  3. STRATEGIES TO REDUCE OR REPLACE THE USE OF ANIMALS IN THE ENDOCRINE SCREENING AND TESTING PROGRAM.

    Science.gov (United States)

    Abstract: The US Environmental Protection Agency (EPA) is developing a screening and testing program for endocrine disrupting chemicals (EDCs) to detect alterations of hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen and thyroid hormone synthesis and androgen (AR...

  4. Reducing test anxiety and improving academic self-esteem in high school and college students with learning disabilities.

    Science.gov (United States)

    Wachelka, D; Katz, R C

    1999-09-01

    Test anxiety seems like a benign problem to some people, but it can be potentially serious when it leads to high levels of distress and academic failure in otherwise capable students. Because test anxiety is common in older students with learning disabilities (LD), it is surprising that little research has been done on ways to reduce the distress these students experience in test situations. In this study, we used a randomized pretest-posttest control group design to examine the effectiveness of a cognitive-behavioral treatment for reducing test anxiety and improving academic self-esteem in a cohort (N = 27) of high school and college students with learning disabilities (LD). All of the students participated voluntarily. They were enrolled in classes for students with learning problems. Before the study began, they complained of test anxiety and showed an elevated score on the Test Anxiety Inventory (TAI). Eleven students (85%) completed the 8-week long treatment, which consisted of progressive muscle relaxation, guided imagery, self-instruction training, as well as training in study and test-taking skills. Results showed significant improvement in the treated group which was not evident in an untreated control group (N = 16). Compared to the control group, the treated group showed significant reductions in test anxiety on the TAI, as well as improvement in study skills and academic self-esteem as measured by the Survey of Study Habits and Attitudes, and the school scale of the Coopersmith Self-Esteem Inventory. These results extend the generality of similar studies on reducing test anxiety and improving academic self-esteem in younger students. They also suggest that relief from test anxiety can be expected fairly quickly when cognitive-behavioral methods are used. Additional implications and methodological limitations of the study are discussed.

  5. Potential impact of the MR spectroscopic cancer blood test on reducing the need for lung biopsy

    International Nuclear Information System (INIS)

    Simon, M.; Fossel, E.T.

    1989-01-01

    Lung biopsies are generally performed to identify or rule out malignancy. A clinical presumption of lung malignancy without biopsy proof may result in unjustified surgery. The authors sought to test the value of the MR cancer blood test (CBT) recently described. They obtained prebiopsy blood samples (2 mL) from 65 patients undergoing lung biopsy for radiologically identified lesions. The CBT was performed blinded, and the result was then compared with the pathologic diagnosis obtained from biopsy. Results are presented

  6. Testing whether reduced cognitive performance in burnout can be reversed by a motivational intervention

    NARCIS (Netherlands)

    Dam, A. van; Keijsers, G.P.J.; Eling, P.A.T.M.; Becker, E.S.

    2011-01-01

    It has been suggested that the motivation to spend effort is decreased in burnout patients, resulting in reduced cognitive performance. A question that remains is whether this decreased motivation can be reversed by motivational interventions. We investigated this by examining the effect of a

  7. Improving Papanicolaou test quality and reducing medical errors by using Toyota production system methods.

    Science.gov (United States)

    Raab, Stephen S; Andrew-Jaja, Carey; Condel, Jennifer L; Dabbs, David J

    2006-01-01

    The objective of the study was to determine whether the Toyota production system process improves Papanicolaou test quality and patient safety. An 8-month nonconcurrent cohort study that included 464 case and 639 control women who had a Papanicolaou test was performed. Office workflow was redesigned using Toyota production system methods by introducing a 1-by-1 continuous flow process. We measured the frequency of Papanicolaou tests without a transformation zone component, follow-up and Bethesda System diagnostic frequency of atypical squamous cells of undetermined significance, and diagnostic error frequency. After the intervention, the percentage of Papanicolaou tests lacking a transformation zone component decreased from 9.9% to 4.7% (P = .001). The percentage of Papanicolaou tests with a diagnosis of atypical squamous cells of undetermined significance decreased from 7.8% to 3.9% (P = .007). The frequency of error per correlating cytologic-histologic specimen pair decreased from 9.52% to 7.84%. The introduction of the Toyota production system process resulted in improved Papanicolaou test quality.

  8. Hypnotherapy and Test Anxiety: Two Cognitive-Behavioral Constructs. The Effects of Hypnosis in Reducing Test Anxiety and Improving Academic Achievement in College Students.

    Science.gov (United States)

    Sapp, Marty

    A two-group randomized multivariate analysis of covariance (MANCOVA) was used to investigate the effects of cognitive-behavioral hypnosis in reducing test anxiety and improving academic performance in comparison to a Hawthorne control group. Subjects were enrolled in a rigorous introductory psychology course which covered an entire text in one…

  9. Why do fearful facial expressions elicit behavioral approach? Evidence from a combined approach-avoidance implicit association test.

    Science.gov (United States)

    Hammer, Jennifer L; Marsh, Abigail A

    2015-04-01

    Despite communicating a "negative" emotion, fearful facial expressions predominantly elicit behavioral approach from perceivers. It has been hypothesized that this seemingly paradoxical effect may occur due to fearful expressions' resemblance to vulnerable, infantile faces. However, this hypothesis has not yet been tested. We used a combined approach-avoidance/implicit association test (IAT) to test this hypothesis. Participants completed an approach-avoidance lever task during which they responded to fearful and angry facial expressions as well as neutral infant and adult faces presented in an IAT format. Results demonstrated an implicit association between fearful facial expressions and infant faces and showed that both fearful expressions and infant faces primarily elicit behavioral approach. The dominance of approach responses to both fearful expressions and infant faces decreased as a function of psychopathic personality traits. Results suggest that the prosocial responses to fearful expressions observed in most individuals may stem from their associations with infantile faces. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  10. [Neratinib + Valproate] exposure permanently reduces ERBB1 and RAS expression in 4T1 mammary tumors and enhances M1 macrophage infiltration.

    Science.gov (United States)

    Booth, Laurence; Roberts, Jane L; Rais, Rumeesa; Kirkwood, John; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Poklepovic, Andrew; Dent, Paul

    2018-01-19

    The irreversible ERBB1/2/4 inhibitor neratinib has been shown in vitro to rapidly reduce the expression of ERBB1/2/4 and RAS proteins via autophagic/lysosomal degradation. We have recently demonstrated that neratinib and valproate interact to suppress the growth of 4T1 mammary tumors but had not defined whether the [neratinib + valproate] drug combination, in a mouse, had altered the biology of the 4T1 cells. Exposure of 4T1 mammary tumors to [neratinib + valproate] for three days resulted, two weeks later, in tumors that expressed less ERBB1, K-RAS, N-RAS, indoleamine-pyrrole 2,3-dioxygenase (IDO-1), ornithine decarboxylase (ODC) and had increased Class I MHCA expression. Tumors previously exposed to [neratinib + valproate] grew more slowly than those exposed to vehicle control and contained more CD8+ cells and activated NK cells. M1 but not M2 macrophage infiltration was significantly enhanced by the drug combination. In vitro exposure of 4T1 tumor cells to [neratinib + valproate] variably reduced the expression of histone deacetylases 1-11. In vivo , prior exposure of tumors to [neratinib + valproate] permanently reduced the expression of HDACs 1-3, 6 and 10. Combined knock down of HDACs 1/2/3 or of 3/10 rapidly reduced the expression IDO-1, and ODC and increased the expression of MHCA. H&E staining of normal tissues at animal nadir revealed no obvious cyto-architectural differences between control and drug-treated animals. We conclude that [neratinib + valproate] evolves 4T1 tumors to grow more slowly and to be more sensitive to checkpoint immunotherapy antibodies.

  11. Expressed parental concern regarding childhood stuttering and the Test of Childhood Stuttering.

    Science.gov (United States)

    Tumanova, Victoria; Choi, Dahye; Conture, Edward G; Walden, Tedra A

    The purpose of the present study was to determine whether the Test of Childhood Stuttering observational rating scales (TOCS; Gillam et al., 2009) (1) differed between parents who did versus did not express concern (independent from the TOCS) about their child's speech fluency; (2) correlated with children's frequency of stuttering measured during a child-examiner conversation; and (3) correlated with the length and complexity of children's utterances, as indexed by mean length of utterance (MLU). Participants were 183 young children ages 3:0-5:11. Ninety-one had parents who reported concern about their child's stuttering (65 boys, 26 girls) and 92 had parents who reported no such concern (50 boys, 42 girls). Participants' conversational speech during a child-examiner conversation was analyzed for (a) frequency of occurrence of stuttered and non-stuttered disfluencies, and (b) MLU. Besides expressing concern or lack thereof about their child's speech fluency, parents completed the TOCS observational rating scales documenting how often they observe different disfluency types in speech of their children, as well as disfluency-related consequences. There were three main findings. First, parents who expressed concern (independently from the TOCS) about their child's stuttering reported significantly higher scores on the TOCS Speech Fluency and Disfluency-Related Consequences rating scales. Second, children whose parents rated them higher on the TOCS Speech Fluency rating scale produced more stuttered disfluencies during a child-examiner conversation. Third, children with higher scores on the TOCS Disfluency-Related Consequences rating scale had shorter MLU during child-examiner conversation, across age and level of language ability. Findings support the use of the TOCS observational rating scales as one documentable, objective means to determine parental perception of and concern about their child's stuttering. Findings also support the notion that parents are

  12. Reducing duplicate testing: a comparison of two clinical decision support tools.

    Science.gov (United States)

    Procop, Gary W; Keating, Catherine; Stagno, Paul; Kottke-Marchant, Kandice; Partin, Mary; Tuttle, Robert; Wyllie, Robert

    2015-05-01

    Unnecessary duplicate laboratory testing is common and costly. Systems-based means to avert unnecessary testing should be investigated and employed. We compared the effectiveness and cost savings associated with two clinical decision support tools to stop duplicate testing. The Hard Stop required telephone contact with the laboratory and justification to have the duplicate test performed, whereas the Smart Alert allowed the provider to bypass the alert at the point of order entry without justification. The Hard Stop alert was significantly more effective than the Smart Alert (92.3% vs 42.6%, respectively; P < .0001). The cost savings realized per alert activation was $16.08/alert for the Hard Stop alert vs $3.52/alert for the Smart Alert. Structural and process changes that require laboratory contact and justification for duplicate testing are more effective than interventions that allow providers to bypass alerts without justification at point of computerized physician order entry. Copyright© by the American Society for Clinical Pathology.

  13. Maternal Pre-Gravid Obesity Changes Gene Expression Profiles Towards Greater Inflammation and Reduced Insulin Sensitivity in Umbilical Cord

    Science.gov (United States)

    Thakali, Keshari M.; Saben, Jessica; Faske, Jennifer B.; Lindsey, Forrest; Gomez-Acevedo, Horacio; Lowery, Curtis L.; Badger, Thomas M.; Andres, Aline; Shankar, Kartik

    2014-01-01

    Background Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC). Methods UCs from 12 lean (pre-gravid BMI obese (OW/OB, pre-gravid BMI ≥25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays (Affymetrix). Metabolic parameters were assayed in mother’s plasma and cord blood. Results Although offspring birth weight and adiposity (at 2-wk) did not differ between groups, expression of 232 transcripts was affected in UC from OW/OB compared to those of lean mothers. GSEA analysis revealed an up-regulation of genes related to metabolism, stimulus and defense response and inhibitory to insulin signaling in the OW/OB group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from OW/OB moms, while endothelin receptor B, KFL10, PEG3 and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST and SOCS1 were positively correlated (pmaternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life. PMID:24819376

  14. Reducing Test Anxiety among 12th Grade Students: Iraqi Kurdistan Region/Soran City as an Example

    Science.gov (United States)

    Faqe, Chiayee Khorshid; Moheddin, Kurdistan Rafiq; Kakamad, Karwan Kakabra

    2016-01-01

    This study aims at reducing test anxiety among twelfth grade students at Soran city high schools. Throughout the study both quantitative and qualitative methods used to collect data. The participants were 450 twelfth grade students in five schools at Soran City-Kurdistan region of Iraq. Non-random purposive sampling because the students needed…

  15. Proceedings of the international meeting on reduced enrichment for research and test reactors

    International Nuclear Information System (INIS)

    Tsuchihashi, Keichiro

    1984-05-01

    The purpose of the Meeting was to exchange and discuss the most up-to-date information on the progress of various programs related to research and test reactor core conversion from high enriched uranium to lower enriched uranium. The papers presented during the Meeting were divided into 9 sessions and one round able discussion which concluded the Meeting. The Sessions were: Program, Fuel Development, Fuel Fabrication, Irradiation testing, Safety Analysis, Special Reactor Conversion, Reactor Design, Critical Experiments, and Reprocessing and Spent Fuel Storage. Thus, topics of this Meeting were of a very wide range that was expected to result in information exchange valuable for all the participants in the RERTR program

  16. Proceedings of the international meeting on reduced enrichment for research and test reactors

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchihashi, Keichiro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1984-05-01

    The purpose of the Meeting was to exchange and discuss the most up-to-date information on the progress of various programs related to research and test reactor core conversion from high enriched uranium to lower enriched uranium. The papers presented during the Meeting were divided into 9 sessions and one round able discussion which concluded the Meeting. The Sessions were: Program, Fuel Development, Fuel Fabrication, Irradiation testing, Safety Analysis, Special Reactor Conversion, Reactor Design, Critical Experiments, and Reprocessing and Spent Fuel Storage. Thus, topics of this Meeting were of a very wide range that was expected to result in information exchange valuable for all the participants in the RERTR program.

  17. Altered Expression of the Malate-Permeable Anion Channel OsALMT4 Reduces the Growth of Rice Under Low Radiance

    Directory of Open Access Journals (Sweden)

    Jie Liu

    2018-05-01

    Full Text Available We examined the function of OsALMT4 in rice (Oryza sativa L. which is a member of the aluminum-activated malate transporter family. Previous studies showed that OsALMT4 localizes to the plasma membrane and that expression in transgenic rice lines results in a constitutive release of malate from the roots. Here, we show that OsALMT4 is expressed widely in roots, shoots, flowers, and grain but not guard cells. Expression was also affected by ionic and osmotic stress, light and to the hormones ABA, IAA, and salicylic acid. Malate efflux from the transgenic plants over-expressing OsALMT4 was inhibited by niflumate and salicylic acid. Growth of transgenic lines with either increased OsALMT4 expression or reduced expression was measured in different environments. Light intensity caused significant differences in growth between the transgenic lines and controls. When day-time light was reduced from 700 to 300 μmol m-2s-1 independent transgenic lines with either increased or decreased OsALMT4 expression accumulated less biomass compared to their null controls. This response was not associated with differences in photosynthetic capacity, stomatal conductance or sugar concentrations in tissues. We propose that by disrupting malate fluxes across the plasma membrane carbon partitioning and perhaps signaling are affected which compromises growth under low light. We conclude that OsALMT4 is expressed widely in rice and facilitates malate efflux from different cell types. Altering OsALMT4 expression compromises growth in low-light environments.

  18. Increasing preload volume with water reduces rated appetite but not food intake in healthy men even with minimum delay between preload and test meal.

    Science.gov (United States)

    Gray, Richard W; French, Stephen J; Robinson, Tristan M; Yeomans, Martin R

    2003-02-01

    The role of gastric volume in the short-term control of eating in humans remains unclear, with some studies reporting that food volume alone can reduce appetite but others finding no such effect. A recent study in our laboratory, found effects of preload volume on subjective appetite (hunger, fullness) but not intake, and found effects of preload energy on intake but not appetite. That study used an interval of 30 min between serving preloads and the test meal, and the present study attempted to maximise the effects of the volume manipulation by removing the delay between the preload and test meal. We administered four soup-based preloads varying in volume (150 and 450 ml) using water, and energy density (1.4 and 4.2 kJ/ml) using maltodextrin, producing three energy levels (209, 629, 629 and 1886 kJ; repeated measures). These were followed immediately by an unlimited hot pasta lunch, during which food weight was monitored continuously by computer. Increasing soup volume at constant energy (629 kJ) reduced appetite ratings, but not intake. In contrast, increasing soup energy at constant volume (450 ml) reduced intake, without affecting appetite. The discrepancies between our results and other reported studies suggest that volume is more influential when intakes are large, or that there may be a threshold concentration for nutrients in the GI tract before volume alone is tangibly expressed in subsequent eating.

  19. Behavioural testing based breeding policy reduces the prevalence of fear and aggression related behaviour in Rottweilers

    NARCIS (Netherlands)

    Borg, van der Joanne A.M.; Graat, Lisette; Beerda, Bonne

    2017-01-01

    Behavioural testing allows to exclude dogs that are fearful and aggressive from the breeding population, but relatively little is known about the effectiveness of such strategies in practice. From 2001 till 2009 parent purebred Dutch Rottweilers had to pass the Socially Acceptable Behaviour

  20. Proceedings of the 1984 international meeting on Reduced Enrichment for Research and Test Reactors. Base technology

    International Nuclear Information System (INIS)

    1985-07-01

    More than 40 papers were presented at this RERTR Meeting during the following sessions: Status of RERTR programs and licensing procedures; LEU fuel element development; fuel fabrication and testing; economics; mixed reactor cores; and applications, i.e. neutronics and thermal hydraulics design of upgraded reactors, with new LEU fuel, fuel cycle studies, feasibility and safety analyses

  1. Proceedings of the 1984 international meeting on Reduced Enrichment for Research and Test Reactors. Base technology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1985-07-01

    More than 40 papers were presented at this RERTR Meeting during the following sessions: Status of RERTR programs and licensing procedures; LEU fuel element development; fuel fabrication and testing; economics; mixed reactor cores; and applications, i.e. neutronics and thermal hydraulics design of upgraded reactors, with new LEU fuel, fuel cycle studies, feasibility and safety analyses.

  2. Opening address at the international meeting on reduced enrichment for research and test reactors

    International Nuclear Information System (INIS)

    Kazuo Sato

    1984-01-01

    The purpose of the Meeting was to exchange and discuss the most up-to-date information on the progress of variuos programs related to research and test reactor core conversion from high enriched uranium to lower enriched uranium. More detailed status of the RERTR program in Japan, as the host country is covered in this presentation

  3. The effectiveness of psychoeducation and systematic desensitization to reduce test anxiety among first-year pharmacy students.

    Science.gov (United States)

    Rajiah, Kingston; Saravanan, Coumaravelou

    2014-11-15

    To analyze the effect of psychological intervention on reducing performance anxiety and the consequences of the intervention on first-year pharmacy students. In this experimental study, 236 first-year undergraduate pharmacy students from a private university in Malaysia were approached between weeks 5 and 7 of their first semester to participate in the study. The completed responses for the Westside Test Anxiety Scale (WTAS), the Kessler Perceived Distress Scale (PDS), and the Academic Motivation Scale (AMS) were received from 225 students. Out of 225 students, 42 exhibited moderate to high test anxiety according to the WTAS (score ranging from 30 to 39) and were randomly placed into either an experiment group (n=21) or a waiting list control group (n=21). The prevalence of test anxiety among pharmacy students in this study was lower compared to other university students in previous studies. The present study's anxiety management of psychoeducation and systematic education for test anxiety reduced lack of motivation and psychological distress and improved grade point average (GPA). Psychological intervention helped significantly reduce scores of test anxiety, psychological distress, and lack of motivation, and it helped improve students' GPA.

  4. Reduced STMN1 expression induced by RNA interference inhibits the bioactivity of pancreatic cancer cell line Panc-1.

    Science.gov (United States)

    Li, J; Hu, G H; Kong, F J; Wu, K M; He, B; Song, K; Sun, W J

    2014-01-01

    Increased expression of STMN1 has been observed in many tumor forms, but its expression and potential biological role in pancreatic cancer is still unknown. In this study, we demonstrated that STMN1 was expressed to a large extent in pancreatic cancer tissues and cell lines as compared to normal pancreatic tissues. Suppression of STMN1 expression via transfection with STMN1-specific siRNA could not only significantly inhibit the proliferation, migration and invasion ability of Panc-1 cells, but also enhance the apoptosis of Panc-1 cells. In addition, downregulation of STMN1 obviously enhanced the acetylation level of α-tubulin. All these results indicated that STMN1 plays an important role in pancreatic cancer development, and might serve as a potential therapeutic target for pancreatic cancer.

  5. Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducing Npc1l1 expression

    Directory of Open Access Journals (Sweden)

    Takuya Kikuchi

    2016-11-01

    Conclusion: Intestinal CREBH regulates dietary cholesterol flow from the small intestine by controlling the expression of multiple intestinal transporters. We propose that intestinal CREBH could be a therapeutic target for hypercholesterolemia.

  6. TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters

    International Nuclear Information System (INIS)

    Schneiderman, Rosa S; Shmueli, Esther; Kirson, Eilon D; Palti, Yoram

    2010-01-01

    Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields - TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin. Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line Emt R1 ; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs. TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells. The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors

  7. Pokemon reduces Bcl-2 expression through NF-κ Bp65: A possible mechanism of hepatocellular carcinoma.

    Science.gov (United States)

    Zhao, Xinkai; Ning, Qiaoming; Sun, Xiaoning; Tian, De'an

    2011-06-01

    To investigate the relationship among Pokemon, NF-κ B p65 and Bcl-2 in hepatoma cells. HCC cell HepG2, SMMC7721 and human fetal liver cell line LO2 cells were used, and expression of Pokemon, NF-κ B p65 and Bcl-2 in three cells were detected by real-time PCR and western blot. Then siRNA of Pokemon was applied to inhibit the expression of Pokemon and NF-κ B p65 and apoptotic rate was determined by flow cytometric analysis. Expressions of Pokemon, NF-κ B p65 and Bcl-2 in human hepatoma cell HepG2, SMMC7721 expression were significantly higher than those in human embryonic stem cells LO2. siRNA of Pokemon inhibited the expression of Pokemon, NF-κ B p65 and Bcl-2 in liver cancer cells, and significantly increased apoptosis of liver cells. While siRNA of NF-κ B p65 inhibited the expression of NF-κ B p65 and Bcl-2, but Pokemon expression in hepatoma cells had no significant change. The proto-oncogene Pokemon can inhibit P14ARF by specific transcription regulation of cell cycle and can induce tumors. In addition, Pokemon can regulate NF-κ B p65 through the expression of apoptosis repressor, and promote the development of liver cancer. It suggests signal network in the liver include the regulation of new non-classical NF-κ B regulatory pathway. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  8. POD-1/Tcf21 overexpression reduces endogenous SF-1 and StAR expression in rat adrenal cells

    Directory of Open Access Journals (Sweden)

    M. M. França

    2015-12-01

    Full Text Available During gonad and adrenal development, the POD-1/capsulin/TCF21transcription factor negatively regulates SF-1/NR5A1expression, with higher SF-1 levels being associated with increased adrenal cell proliferation and tumorigenesis. In adrenocortical tumor cells, POD-1 binds to the SF-1 E-box promoter region, decreasing SF-1 expression. However, the modulation of SF-1 expression by POD-1 has not previously been described in normal adrenal cells. Here, we analyzed the basal expression of Pod-1 and Sf-1 in primary cultures of glomerulosa (G and fasciculata/reticularis (F/R cells isolated from male Sprague-Dawley rats, and investigated whether POD-1 overexpression modulates the expression of endogenous Sf-1 and its target genes in these cells. POD-1 overexpression, following the transfection of pCMVMycPod-1, significantly decreased the endogenous levels of Sf-1 mRNA and protein in F/R cells, but not in G cells, and also decreased the expression of the SF-1 target StAR in F/R cells. In G cells overexpressing POD-1, no modulation of the expression of SF-1 targets, StAR and CYP11B2, was observed. Our data showing that G and F/R cells respond differently to ectopic POD-1 expression emphasize the functional differences between the outer and inner zones of the adrenal cortex, and support the hypothesis that SF-1 is regulated by POD-1/Tcf21 in normal adrenocortical cells lacking the alterations in cellular physiology found in tumor cells.

  9. PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

    International Nuclear Information System (INIS)

    Ghorai, Atanu; Sarma, Asitikantha; Chowdhury, Priyanka; Ghosh, Utpal

    2016-01-01

    Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was

  10. Nppa and Nppb act redundantly during zebrafish cardiac development to confine AVC marker expression and reduce cardiac jelly volume.

    Science.gov (United States)

    Grassini, Daniela R; Lagendijk, Anne K; De Angelis, Jessica E; Da Silva, Jason; Jeanes, Angela; Zettler, Nicole; Bower, Neil I; Hogan, Benjamin M; Smith, Kelly A

    2018-05-11

    Atrial natriuretic peptide ( nppa/anf ) and brain natriuretic peptide ( nppb/bnp ) form a gene cluster with expression in the chambers of the developing heart. Despite restricted expression, a function in cardiac development has not been demonstrated by mutant analysis. This is attributed to functional redundancy however their genomic location in cis has impeded formal analysis. Using genome-editing, we generated mutants for nppa and nppb and found single mutants indistinguishable from wildtype whereas nppa / nppb double mutants display heart morphogenesis defects and pericardial oedema. Analysis of atrioventricular canal (AVC) markers show expansion of bmp4 , tbx2b, has2 and versican expression into the atrium of double mutants. This expanded expression correlates with increased extracellular matrix in the atrium. Using a biosensor for Hyaluronic acid to measure the cardiac jelly (cardiac extracellular matrix), we confirm cardiac jelly expansion in nppa / nppb double mutants. Finally, bmp4 knockdown rescues the expansion of has2 expression and cardiac jelly in double mutants. This definitively shows that nppa and nppb function redundantly during cardiac development to restrict gene expression to the AVC, preventing excessive cardiac jelly synthesis in the atrial chamber. © 2018. Published by The Company of Biologists Ltd.

  11. Developing a new generation of breast cancer clinical gene expression tests.

    Science.gov (United States)

    Kos, Zuzana; Nielsen, Torsten O

    2014-07-07

    When treatment decisions are based purely on clinicopathological factors, many women with estrogen receptor-positive/human epidermal growth factor receptor 2-negative cancers are overtreated. Gene expression profiles are valuable clinical tools that stratify the recurrence risk to identify patients most likely to benefit from adjuvant systemic therapies. Building upon greater understanding of tumor biology and more rigorous approaches to validation (including independent studies with a high level of evidence), several second-generation multigene tests have been developed. In the previous issue, Martin and colleagues report the third clinical validation study for EndoPredict, a distributed assay to assess risk of distant recurrences in estrogen receptor-positive/human epidermal growth factor receptor 2-negative women. The authors confirm the assay's independent prognostic value in premenopausal and postmenopausal, node-positive women treated with contemporary chemotherapy followed by endocrine therapy. EndoPredict did not, however, predict benefit from adding paclitaxel. Predictive signatures for selecting among chemotherapy regimens remain an area needing further development.

  12. Reducing tilt-to-length coupling for the LISA test mass interferometer

    Science.gov (United States)

    Tröbs, M.; Schuster, S.; Lieser, M.; Zwetz, M.; Chwalla, M.; Danzmann, K.; Fernández Barránco, G.; Fitzsimons, E. D.; Gerberding, O.; Heinzel, G.; Killow, C. J.; Perreur-Lloyd, M.; Robertson, D. I.; Schwarze, T. S.; Wanner, G.; Ward, H.

    2018-05-01

    Objects sensed by laser interferometers are usually not stable in position or orientation. This angular instability can lead to a coupling of angular tilt to apparent longitudinal displacement—tilt-to-length coupling (TTL). In LISA this is a potential noise source for both the test mass interferometer and the long-arm interferometer. We have experimentally investigated TTL coupling in a setup representative for the LISA test mass interferometer and used this system to characterise two different imaging systems (a two-lens design and a four-lens design) both designed to minimise TTL coupling. We show that both imaging systems meet the LISA requirement of  ±25 μm rad‑1 for interfering beams with relative angles of up to  ±300 μrad. Furthermore, we found a dependency of the TTL coupling on beam properties such as the waist size and location, which we characterised both theoretically and experimentally.

  13. Design and Test of Semi-Active Vibration-Reducing System for Lathe

    Directory of Open Access Journals (Sweden)

    Hongsheng Hu

    2014-09-01

    Full Text Available In this paper, its theory design, analysis and test system of semi-active vibration controlling system used for precision machine have been done. Firstly, lathe bed and spindle entity were modeled by using UG software; Then modes of the machine bed and the key components of spindle were obtained by using ANSYS software; Finally, harmonic response analysis of lathe spindle under complex load was acquired, which provided a basis of MR damper’s structure optimization design for a certain type of precision machine. In order to prove its effectives, a prototype semi-active vibration controlling lathe with MR damper was developed. Tests have been done, and comparison results between passive vibration isolation equipment and semi-active vibration controlling equipment proved its good performances of MR damper.

  14. Production and Test of 352 MHZ Niobum-Sputtered Reduced-$\\beta$ Cavities

    CERN Document Server

    Benvenuti, Cristoforo; Calatroni, Sergio; Chiaveri, Enrico; Tückmantel, Joachim

    1997-01-01

    Three types of 352 MHz single-cell cavities foreseen for different particle speeds (v/c=0.8, 0.625 and 0.48) have been designed and built with the niobium sputtered on copper technique. We report on the results of the cold tests at 4.5 and 2.5 K and the actual status of the data analysis.

  15. The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes.

    Science.gov (United States)

    Katzenberger, Rebeccah J; Rach, Elizabeth A; Anderson, Ashley K; Ohler, Uwe; Wassarman, David A

    2012-01-01

    To investigate the importance of core promoter elements for tissue-specific transcription of RNA polymerase II genes, we examined testis-specific transcription in Drosophila melanogaster. Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE). The TCE functions in the 5' untranslated region of Mst(3)CGP mRNAs to repress translation, and it also functions in a heterologous gene to regulate transcription. We found that among genes with focused initiation patterns, the TCE is significantly enriched in core promoters of genes that are specifically expressed in testes but not in core promoters of genes that are specifically expressed in other tissues. The TCE is variably located in core promoters and is conserved in melanogaster subgroup species, but conservation dramatically drops in more distant species. In transgenic flies, short (300-400 bp) genomic regions containing a TCE directed testis-specific transcription of a reporter gene. Mutation of the TCE significantly reduced but did not abolish reporter gene transcription indicating that the TCE is important but not essential for transcription activation. Finally, mutation of testis-specific TFIID (tTFIID) subunits significantly reduced the transcription of a subset of endogenous TCE-containing but not TCE-lacking genes, suggesting that tTFIID activity is limited to TCE-containing genes but that tTFIID is not an obligatory regulator of TCE-containing genes. Thus, the TCE is a core promoter element in a subset of genes that are specifically expressed in testes. Furthermore, the TCE regulates transcription in the context of short genomic regions, from variable locations in the core promoter, and both dependently and independently of tTFIID. These findings set the stage for determining the mechanism by which the TCE regulates testis-specific transcription and understanding the

  16. Ganoderma lucidum Polysaccharides Reduce Lipopolysaccharide-Induced Interleukin-1β Expression in Cultured Smooth Muscle Cells and in Thoracic Aortas in Mice

    Directory of Open Access Journals (Sweden)

    Chan-Jung Liang

    2014-01-01

    Full Text Available The expression of inflammatory cytokines on vascular walls is a critical event in vascular diseases and inflammation. The aim of the present study was to examine the effects of an extract of Ganoderma lucidum (Reishi polysaccharides (EORPs, which is effective against immunological disorders, on interleukin- (IL- 1β expression by human aortic smooth muscle cells (HASMCs and the underlying mechanism. The lipopolysaccharide- (LPS- induced IL-1β expression was significantly reduced when HASMCs were pretreated with EORP by Western blot and immunofluorescent staining. Pretreatment with 10 μg/mL EORP decreased LPS-induced ERK, p38, JNK, and Akt phosphorylation. But the increase in IL-1β expression with LPS treatment was only inhibited by pretreatment with the ERK1/2 inhibitor, while the JNK and p38 inhibitors had no effect. In addition, EORP reduced the phosphorylation and nuclear translocation of nuclear factor- (NF- κB p65 in LPS-treated HASMCs. Furthermore, in vivo, IL-1β expression was strongly expressed in thoracic aortas in LPS-treated mice. Oral administration of EORP decreased IL-1β expression. The level of IL-1β expression in LPS-treated or in LPS/EORP-treated group was very low and was similar to that of the saline-treated group in toll-like receptor 4-deficient (TLR4−/− mice. These findings suggest that EORP has the anti-inflammatory property and could prove useful in the prevention of vascular diseases and inflammatory responses.

  17. Mechanical unloading reduces microtubule actin crosslinking factor 1 expression to inhibit β-catenin signaling and osteoblast proliferation.

    Science.gov (United States)

    Yin, Chong; Zhang, Yan; Hu, Lifang; Tian, Ye; Chen, Zhihao; Li, Dijie; Zhao, Fan; Su, Peihong; Ma, Xiaoli; Zhang, Ge; Miao, Zhiping; Wang, Liping; Qian, Airong; Xian, Cory J

    2018-07-01

    Mechanical unloading was considered a major threat to bone homeostasis, and has been shown to decrease osteoblast proliferation although the underlying mechanism is unclear. Microtubule actin crosslinking factor 1 (MACF1) is a cytoskeletal protein that regulates cellular processes and Wnt/β-catenin pathway, an essential signaling pathway for osteoblasts. However, the relationship between MACF1 expression and mechanical unloading, and the function and the associated mechanisms of MACF1 in regulating osteoblast proliferation are unclear. This study investigated effects of mechanical unloading on MACF1 expression levels in cultured MC3T3-E1 osteoblastic cells and in femurs of mice with hind limb unloading; and it also examined the role and potential action mechanisms of MACF1 in osteoblast proliferation in MACF1-knockdown, overexpressed or control MC3T3-E1 cells treated with or without the mechanical unloading condition. Results showed that the mechanical unloading condition inhibited osteoblast proliferation and MACF1 expression in MC3T3-E1 osteoblastic cells and mouse femurs. MACF1 knockdown decreased osteoblast proliferation, while MACF1 overexpression increased it. The inhibitory effect of mechanical unloading on osteoblast proliferation also changed with MACF1 expression levels. Furthermore, MACF1 was found to enhance β-catenin expression and activity, and mechanical unloading decreased β-catenin expression through MACF1. Moreover, β-catenin was found an important regulator of osteoblast proliferation, as its preservation by treatment with its agonist lithium attenuated the inhibitory effects of MACF1-knockdown or mechanical unloading on osteoblast proliferation. Taken together, mechanical unloading decreases MACF1 expression, and MACF1 up-regulates osteoblast proliferation through enhancing β-catenin signaling. This study has thus provided a mechanism for mechanical unloading-induced inhibited osteoblast proliferation. © 2017 Wiley Periodicals, Inc.

  18. Nurturing the Continuum of HIV Testing, Treatment and Prevention Matrix Cascade in Reducing HIV Transmission.

    Science.gov (United States)

    Yah, Clarence S

    2017-11-01

    Despite the shift in antiretroviral therapy (ARVs) eligibility cascade from CD4 ≤ 200 to CD4 ≤ 350 to CD4 ≤ 500 mm 3 , HIV related morbidity and mortality continue to escalate annually, as do HIV infections. The new paradigm of treatment for all HIV positives individual irrespective of CD4 count may significantly reduce HIV and related illnesses. The author assumes that all HIV infected partners should be eligible for HIV treatment and care, irrespective of CD4 count. A second assumption is that high risk HIV negative partners have free access to continuum of HIV pre-exposure prophylaxis (PrEP), post exposure prophylaxis (PEP) and other prevention packages. A literature review search was used to extract evidence-based ARVs-HIV treatment and prevention interventions among HIV positives and high risk partners respectively. Only articles published in English and indexed in journal nuclei were used for the study. The information was used to nurture understanding of HIV treatment and prevention approaches as well as HIV incidence multiplier effect among HIV serodiscordant partners. The imputed HIV incident reference was assumed at 1.2 per 100 person-years (2). This was based on the imputation that retention in care, adherence and other predetermined factors are functions of an effective health care delivery system. The model showed a reduced HIV transmission from 1.2 per 100 person-years to 1.032 per 100 person-years in 6 months. The average threshold period of HIV suppressed partners on ARVs to an undetectable level. The combined multiplier protective-effect probability of transmitting HIV from HIV positive partners on ARVs-suppressed viremic load to HIV negative partners on PrEP/PEP-prevention was detected at 86. The model showed a significant reduction in HIV incidence. Placing serodiscordant sexual partners in HIV treatment and prevention plays a significant role in reducing and controlling HIV infection. Therefore, the policy of enrolling all HIV positives

  19. Testing climate-smart irrigation strategies to reduce methane emissions from rice fields

    Science.gov (United States)

    Runkle, B.; Suvocarev, K.; Reba, M. L.

    2017-12-01

    Approximately 11% of the global 308 Tg CH4 anthropogenic emissions are currently attributed to rice cultivation. In this study, the impact of water conservation practices on rice field CH4 emissions was evaluated in Arkansas, the leading state in US rice cultivation. While conserving water, the Alternate Wetting and Drying (AWD) irrigation practice can also reduce CH4 emissions through the deliberate, periodic introduction of aerobic conditions. Seasonal CH4emissions from a pair of adjacent, production-sized rice fields were estimated and compared during the 2015 to 2017 growing seasons using the eddy covariance method on each field. The fields were alternately treated with continuous flood (CF) and AWD irrigation. In 2015, the seasonal cumulative carbon losses by CH4 emission were 30.3 ± 6.3 and 141.9 ± 8.6 kg CH4-C ha-1 for the AWD and CF treatments, respectively. Data from 2016 and 2017 will be analyzed and shown within this presentation; an initial view demonstrates consistent findings to 2015. When accounting for differences in field conditions and soils, the AWD practice is attributable to a 36-51% reduction in seasonal emissions. The substantial decrease in CH4 emissions by AWD supports previous chamber-based research and offers strong evidence for the efficacy of AWD in reducing CH4 emissions in Arkansas rice production. The AWD practice has enabled the sale of credits for carbon offsets trading and this new market could encourage CH4 emissions reductions on a national scale. These eddy covariance towers are being placed into a regional perspective including crop and forest land in the three states comprising the Mississippi Delta: Arkansas, Mississippi, and Louisiana.

  20. On the Reduced Testing of a Primitive Element in ${\\\\mathbb Z}_n^\\\\times$

    OpenAIRE

    Suzuki, Hideo; スズキ, ヒデオ; Hideo, Suzuki

    2015-01-01

    The primitive roots in ${\\mathbb Z}_n^\\times$ are defined and exist iff $n = 2, 4, p^{\\alpha}, 2p^{\\alpha}$. Knuth gave the definition of the primitive roots in ${\\mathbb Z}_{p^\\alpha}^\\times$, and showed the necessary and sufficient condition for testing a primitive root in ${\\mathbb Z}_{p^\\alpha}^\\times$. In this paper we define the primitive elements in ${\\mathbb Z}_n^\\times$, which is a generalization of primitive roots, as elements that take the maximum multiplicative order.And we give t...

  1. Results and Lessons Learned from Performance Testing of Humans in Spacesuits in Simulated Reduced Gravity

    Science.gov (United States)

    Chappell, Steven P.; Norcross, Jason R.; Gernhardt, Michael L.

    2009-01-01

    NASA's Constellation Program has plans to return to the Moon within the next 10 years. Although reaching the Moon during the Apollo Program was a remarkable human engineering achievement, fewer than 20 extravehicular activities (EVAs) were performed. Current projections indicate that the next lunar exploration program will require thousands of EVAs, which will require spacesuits that are better optimized for human performance. Limited mobility and dexterity, and the position of the center of gravity (CG) are a few of many features of the Apollo suit that required significant crew compensation to accomplish the objectives. Development of a new EVA suit system will ideally result in performance close to or better than that in shirtsleeves at 1 G, i.e., in "a suit that is a pleasure to work in, one that you would want to go out and explore in on your day off." Unlike the Shuttle program, in which only a fraction of the crew perform EVA, the Constellation program will require that all crewmembers be able to perform EVA. As a result, suits must be built to accommodate and optimize performance for a larger range of crew anthropometry, strength, and endurance. To address these concerns, NASA has begun a series of tests to better understand the factors affecting human performance and how to utilize various lunar gravity simulation environments available for testing.

  2. Building on a solid foundation: SAR and QSAR as a fundamental strategy to reduce animal testing.

    Science.gov (United States)

    Sullivan, K M; Manuppello, J R; Willett, C E

    2014-01-01

    The development of more efficient, ethical, and effective means of assessing the effects of chemicals on human health and the environment was a lifetime goal of Gilman Veith. His work has provided the foundation for the use of chemical structure for informing toxicological assessment by regulatory agencies the world over. Veith's scientific work influenced the early development of the SAR models in use today at the US Environmental Protection Agency. He was the driving force behind the Organisation for Economic Co-operation and Development QSAR Toolbox. Veith was one of a few early pioneers whose vision led to the linkage of chemical structure and biological activity as a means of predicting adverse apical outcomes (known as a mode of action, or an adverse outcome pathway approach), and he understood at an early stage the power that could be harnessed when combining computational and mechanistic biological approaches as a means of avoiding animal testing. Through the International QSAR Foundation he organized like-minded experts to develop non-animal methods and frameworks for the assessment of chemical hazard and risk for the benefit of public and environmental health. Avoiding animal testing was Gil's passion, and his work helped to initiate the paradigm shift in toxicology that is now rendering this feasible.

  3. [Testing reliability and validity of reduced substitutes for leadership scales(rd-SLS)].

    Science.gov (United States)

    Kim, Jeong-Hee

    2005-10-01

    This paper was conducted to test the reliability and validity of rd-SLS, developed by Podsakoff, et al. (1993) which measured 'substitutes for leadership'. The subjects were 345 nurses in 5 general hospitals. Cronbach's and the Guttman split-half coefficient were used to test the reliability of rd-SLS. Factor analysis, and the correlations of the rv-SLS and SLS with rd-SLS were used for convergent and discriminant validity. Cronbach's data was 0.76 and the Guttman split-half coefficient was 0.52. Twelve factors evolved by factor analysis, which explained 70.4% of the total variance. This result was similar to previous study results. However, 'Indifference toward organizational rewards'-related items were classified two factors. It was not clear t hat the rd-SLS consisted of 13 concepts(factors). The correlations of the rv-SLS and SLS with the rd-SLS were 0.93 and 0.87 respectively. The rd-SLS showed a moderate degree of validity and reliability. Thus, it is recommended to use the rd-SLS in general nursing organizations for screening for leadership substitutes. In addition, it is necessary to clarify the concept of organizational rewards. In a further study, the factor structure of the rd-SLS may be considered.

  4. Reduced miR-433 expression is associated with advanced stages and early relapse of colorectal cancer and restored miR-433 expression suppresses the migration, invasion and proliferation of tumor cells in vitro and in nude mice.

    Science.gov (United States)

    Zhang, Jian; Zhang, Lei; Zhang, Tong; Dong, Xin-Min; Zhu, Yu; Chen, Long-Hua

    2018-05-01

    The expression of microRNA (miR-433) is altered in various types of human cancer. The present study analyzed the prognostic and biological value of miR-433 expression in colorectal cancer using reverse transcription-quantitative polymerase chain reaction in 125 colorectal tissue specimens (including a test cohort of 40 cases of paired colorectal cancer and adjacent normal mucosae and a confirmation cohort of 85 cases of stage I-III colorectal cancer). In vitro and nude mouse xenograft experiments were subsequently used to assess the effects of miR-433 expression on the regulation of colorectal cancer cell proliferation, adhesion, migration, and invasion. The data indicated that miR-433 expression was significantly downregulated in colorectal cancer tissues in the test and confirmation patient cohorts and that low miR-433 expression was associated with advanced tumor stage and early relapse. Furthermore, the restoration of miR-433 expression was able to significantly inhibit the proliferation of tumor cells by inducing G1-S cell cycle arrest, suppressing cyclinD1 and CDK4 expression, and markedly inhibited the migratory and invasive capacities of tumor cells in vitro . The restoration of miR-433 expression or liposome-based delivery of miR-433 mimics suppressed the growth of colorectal cancer cell xenografts in nude mice. In conclusion, miR-433 may be a putative tumor suppressor in colorectal cancer, and the detection of low miR-433 expression will be investigated in further studies as a putative biomarker for the detection of early relapse in patients with colorectal cancer.

  5. Lemon Odor Reduces Stress-induced Neuronal Activation in the Emotion Expression System: An Animal Model Study

    Science.gov (United States)

    Sanada, Kazue; Sugimoto, Koji; Shutoh, Fumihiro; Hisano, Setsuji

    Perception of particular sensory stimuli from the surroundings can influence emotion in individuals. In an uncomfortable situation, humans protect themselves from some aversive stimulus by acutely evoking a stress response. Animal model studies have contributed to an understanding of neuronal mechanisms underlying the stress response in humans. To study a possible anti-stressful effect of lemon odor, an excitation of neurons secreting corticotropin-releasing hormone (CRH) as a primary factor of the hypothalamic-pituitary-adrenal axis (HPA) was analyzed in animal model experiments, in which rats are restrained in the presence or absence of the odor. The effect was evaluated by measuring expression of c-Fos (an excited neuron marker) in the hypothalamic paraventricular nucleus (PVN), a key structure of the HPA in the brain. We prepared 3 animal groups: Groups S, L and I. Groups S and L were restrained for 30 minutes while being blown by air and being exposed to the lemon odor, respectively. Group I was intact without any treatment. Two hours later of the onset of experiments, brains of all groups were sampled and processed for microscopic examination. Brain sections were processed for c-Fos immunostaining and/or in situ hybridization for CRH. In Group S but not in Group I, c-Fos expression was found in the PVN. A combined in situ hybridization-immunohistochemical dual labeling revealed that CRH mRNA-expressing neurons express c-Fos. In computer-assisted automatic counting, the incidence of c-Fos-expressing neurons in the entire PVN was statistically lower in Group L than in Group S. Detailed analysis of PVN subregions demonstrated that c-Fos-expressing neurons are fewer in Group L than in Group S in the dorsal part of the medial parvocellular subregion. These results may suggest that lemon odor attenuates the restraint stress-induced neuronal activation including CRH neurons, presumably mimicking an aspect of stress responses in humans.

  6. High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression

    Directory of Open Access Journals (Sweden)

    Bjartell Anders

    2011-09-01

    Full Text Available Abstract Background High expression of the RNA-binding protein RBM3 has previously been found to be associated with good prognosis in breast cancer, ovarian cancer, malignant melanoma and colorectal cancer. The aim of this study was to examine the prognostic impact of immunohistochemical RBM3 expression in prostate cancer. Findings Immunohistochemical RBM3 expression was examined in a tissue microarray with malignant and benign prostatic specimens from 88 patients treated with radical prostatectomy for localized disease. While rarely expressed in benign prostate gland epithelium, RBM3 was found to be up-regulated in prostate intraepithelial neoplasia and present in various fractions and intensities in invasive prostate cancer. High nuclear RBM3 expression was significantly associated with a prolonged time to biochemical recurrence (BCR (HR 0.56, 95% CI: 0.34-0.93, p = 0.024 and clinical progression (HR 0.09, 95% CI: 0.01-0.71, p = 0.021. These associations remained significant in multivariate analysis, adjusted for preoperative PSA level in blood, pathological Gleason score and presence or absence of extracapsular extension, seminal vesicle invasion and positive surgical margin (HR 0.41, 95% CI: 0.19-0.89, p = 0.024 for BCR and HR 0.06, 95% CI: 0.01-0.50, p = 0.009 for clinical progression. Conclusion Our results demonstrate that high nuclear expression of RBM3 in prostate cancer is associated with a prolonged time to disease progression and, thus, a potential biomarker of favourable prognosis. The value of RBM3 for prognostication, treatment stratification and follow-up of prostate cancer patients should be further validated in larger studies.

  7. Fabrication and testing of a device capable of reducing the incidence of ventricular shunt promoted metastasis.

    Science.gov (United States)

    Halperin, E C; Samulski, T; Oakes, W J; Friedman, H S

    1996-01-01

    Some malignant brain tumors shed cells into the cerebrospinal fluid (CSF). These tumors may implant throughout the neuroaxis via the CSF. With the placement of a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt, tumor cells free-floating in the CSF may be carried through the shunt to the remainder of the body. Mechanical filtration devices to prevent this are not reliable. We report the development of a new device capable of reducing the incidence of shunt promoted metastasis. The device exposes the draining CSF, as it passes through a baffle system, to a localized high-intensity radiation field adequately shielded from surrounding normal tissue. The prototype consists of geometrically fixed iodine-125 (125I) sources. The device accommodates the maximum CSF flow rate of 500 ml/24 hours. Radiation exposure to clonogenic cells occurs as they transit through the baffle system. Since the volume of the prototype device is 14 ml, a tumor cell floating through the device will be exposed to radiation for 40 minutes. Utilizing the human medulloblastoma cell line D425 MED, a limiting dilution clonogenic assay was performed. Suspensions of tumor cells in liquid medium were pumped through the device at the maximum anticipated CSF production rate of 0.35 ml/min. After the cells, with their tissue culture medium, were received from the device, a series of nine 5-fold dilutions were prepared from the suspensions which initially contained 10(6) tumor cell/ml. Plates were then incubated and growth was demonstrated by visual scoring of colonies of more than 20 cells. Limiting dilution data analysis was performed. Radiation surveys of the fully loaded (approximately 1.8 Ci) 125I prototype were conducted. A well calibrator was used to measure the activity of the fully loaded device. When the device was loaded with 125I seeds providing a dose of 364-479 cGy the probability of clonogen survival was 0.033. Radiation exposure levels at the exterior surface of the shielded device

  8. Reduced expression of the polymeric immunoglobulin receptor in pancreatic and periampullary adenocarcinoma signifies tumour progression and poor prognosis.

    Directory of Open Access Journals (Sweden)

    Richard Fristedt

    Full Text Available The polymeric immunoglobulin receptor (pIgR is a key component of the mucosal immune system that mediates epithelial transcytosis of immunoglobulins. High pIgR expression has been reported to correlate with a less aggressive tumour phenotype and an improved prognosis in several human cancer types. Here, we examined the expression and prognostic significance of pIgR in pancreatic and periampullary adenocarcinoma. The study cohort encompasses a consecutive series of 175 patients surgically treated with pancreaticoduodenectomy for pancreatic and periampullary adenocarcinoma in Malmö and Lund University Hospitals, Sweden, between 2001-2011. Tissue microarrays were constructed from primary tumours (n = 175 and paired lymph node metastases (n = 105. A multiplied score was calculated from the fraction and intensity of pIgR staining. Classification and regression tree analysis was used to select the prognostic cut-off. Unadjusted and adjusted hazard ratios (HR for death and recurrence within 5 years were calculated. pIgR expression could be evaluated in 172/175 (98.3% primary tumours and in 96/105 (91.4% lymph node metastases. pIgR expression was significantly down-regulated in lymph node metastases as compared with primary tumours (p = 0.018. Low pIgR expression was significantly associated with poor differentiation grade (p < 0.001, perineural growth (p = 0.027, lymphatic invasion (p = 0.016, vascular invasion (p = 0.033 and infiltration of the peripancreatic fat (p = 0.039. In the entire cohort, low pIgR expression was significantly associated with an impaired 5-year survival (HR = 2.99, 95% confidence interval (CI 1.71-5.25 and early recurrence (HR = 2.89, 95% CI 1.67-4.98. This association remained significant for survival after adjustment for conventional clinicopathological factors, tumour origin and adjuvant treatment (HR = 1.98, 95% CI 1.10-3.57. These results demonstrate, for the first time, that high tumour-specific pIgR expression signifies

  9. The development and testing of reduced enrichment fuels for Canadian research reactors

    International Nuclear Information System (INIS)

    Wood, J.C.; Foo, M.T.; Berthiaume, L.C.

    1983-01-01

    Fuel rods of uranium silicide dispersed in aluminum and clad in aluminum have been developed and tested in the laboratory and in-reactor. The properties of the dispersion fuel materials proved satisfactory with regard to thermal conductivity, aqueous corrosion resistance, strength and ductility, and thermal stability below 473 K. A vacancy condensation model is proposed to account for the thermally-induced swelling that occurs above 473 K by virtue of the chemical reactions that occur between the dispersed silicide fuel particles and the aluminum matrix. The in-reactor fuel core swelling was less than % after irradiation at high powers 76-131 kW/m) to a high terminal burnup (79.2 at% of U-235 atoms). (author)

  10. Ectopic Expression of Xylella fastidiosa rpfF Conferring Production of Diffusible Signal Factor in Transgenic Tobacco and Citrus Alters Pathogen Behavior and Reduces Disease Severity.

    Science.gov (United States)

    Caserta, R; Souza-Neto, R R; Takita, M A; Lindow, S E; De Souza, A A

    2017-11-01

    The pathogenicity of Xylella fastidiosa is associated with its ability to colonize the xylem of host plants. Expression of genes contributing to xylem colonization are suppressed, while those necessary for insect vector acquisition are increased with increasing concentrations of diffusible signal factor (DSF), whose production is dependent on RpfF. We previously demonstrated that transgenic citrus plants ectopically expressing rpfF from a citrus strain of X. fastidiosa subsp. pauca exhibited less susceptibility to Xanthomonas citri subsp. citri, another pathogen whose virulence is modulated by DSF accumulation. Here, we demonstrate that ectopic expression of rpfF in both transgenic tobacco and sweet orange also confers a reduction in disease severity incited by X. fastidiosa and reduces its colonization of those plants. Decreased disease severity in the transgenic plants was generally associated with increased expression of genes conferring adhesiveness to the pathogen and decreased expression of genes necessary for active motility, accounting for the reduced population sizes achieved in the plants, apparently by limiting pathogen dispersal through the plant. Plant-derived DSF signal molecules in a host plant can, therefore, be exploited to interfere with more than one pathogen whose virulence is controlled by DSF signaling.

  11. Elimination of contaminating cap genes in AAV vector virions reduces immune responses and improves transgene expression in a canine gene therapy model.

    Science.gov (United States)

    Wang, Z; Halbert, C L; Lee, D; Butts, T; Tapscott, S J; Storb, R; Miller, A D

    2014-04-01

    Animal and human gene therapy studies utilizing AAV vectors have shown that immune responses to AAV capsid proteins can severely limit transgene expression. The main source of capsid antigen is that associated with the AAV vectors, which can be reduced by stringent vector purification. A second source of AAV capsid proteins is that expressed from cap genes aberrantly packaged into AAV virions during vector production. This antigen source can be eliminated by the use of a cap gene that is too large to be incorporated into an AAV capsid, such as a cap gene containing a large intron (captron gene). Here, we investigated the effects of elimination of cap gene transfer and of vector purification by CsCl gradient centrifugation on AAV vector immunogenicity and expression following intramuscular injection in dogs. We found that both approaches reduced vector immunogenicity and that combining the two produced the lowest immune responses and highest transgene expression. This combined approach enabled the use of a relatively mild immunosuppressive regimen to promote robust micro-dystrophin gene expression in Duchenne muscular dystrophy-affected dogs. Our study shows the importance of minimizing AAV cap gene impurities and indicates that this improvement in AAV vector production may benefit human applications.

  12. Long-term diet-induced hypertension in rats is associated with reduced expression and function of small artery SKCa, IKCa, and Kir2.1 channels

    DEFF Research Database (Denmark)

    Gradel, Anna Katrina Jógvansdóttir; Salomonsson, Max; Sørensen, Charlotte Mehlin

    2018-01-01

    in long-term diet-induced hypertension in rats. Hypothesis: A 28-week diet rich in fat, fructose, or both, will lead to changes in K+ transporter expression and function, which is associated with increased blood pressure and decreased arterial function. Methods and Results: Male Sprague Dawley rats......RNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries. BW was increased in the High Fat and High Fat/Fruc groups, and SBP was increased in the High Fat/Fruc group. mRNA expression of SKCa, IKCa, and Kir2.1 K+ channels were reduced in the High Fat/Fruc group. Reduced EDH......-type relaxation to acetylcholine was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all experimental diet groups. Conclusions: Reduced expression and function of SKCa, IKCa and Kir2.1 channels is associated with elevated blood pressure in rats fed...

  13. Can expressions of anger enhance creativity? A test of the emotions as social information (EASI) model

    NARCIS (Netherlands)

    van Kleef, Gerben A.; Anastasopoulou, Christina; Nijstad, Bernard A.

    We investigated whether expressions of anger can enhance creative performance. Building on the emotions as social information (EASI) model (Van Kleef, 2009), we predicted that the interpersonal effects of anger expressions on creativity depend on the target's epistemic motivation (EM) the desire to

  14. Can expressions of anger enhance creativity? A test of the emotions as social information (EASI) model

    NARCIS (Netherlands)

    van Kleef, G.A.; Anastasopoulou, C.; Nijstad, B.A.

    2010-01-01

    We investigated whether expressions of anger can enhance creative performance. Building on the emotions as social information (EASI) model (Van Kleef, 2009), we predicted that the interpersonal effects of anger expressions on creativity depend on the target's epistemic motivation (EM)—the desire to

  15. Stereotypes of emotional expressiveness of northerners and southerners: a cross-cultural test of Montesquieu's hypotheses.

    Science.gov (United States)

    Pennebaker, J W; Rimé, B; Blankenship, V E

    1996-02-01

    Montesquieu argued that residents of warmer climates are more emotionally expressive than those living in cooler ones. More than 2,900 college students from 26 countries completed a brief questionnaire assessing the degree to which they considered Northerners and Southerners within their own countries to be emotionally expressive. In addition, individuals rated themselves on their own degree of expressiveness. In partial confirmation of Montesquieu's hypothesis, it was found that large within-country North-South stereotypes exist. Especially in Old World countries, Northerners are viewed as less emotionally expressive than Southerners. Regression and other analyses revealed that self-ratings of expressiveness were, in fact, related to being from the South and to warmer mean temperatures. Several possible explanations for these effects are discussed.

  16. 5-HTTLPR Expression Outside the Skin: An Experimental Test of the Emotional Reactivity Hypothesis in Children.

    Science.gov (United States)

    Weeland, Joyce; Slagt, Meike; Brummelman, Eddie; Matthys, Walter; de Castro, Bram Orobio; Overbeek, Geertjan

    2015-01-01

    There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the 5-HTTLPR polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity -the intensity of an individual's response to other's emotions- has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G×E). Compared to children homozygous for the L-allele (LL-genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors. However, the association between 5-HTTLPR and emotional reactivity in children has not yet been empirically tested. Therefore, the goal of this study was to test this association in a large-scale experiment. Children (N = 521, 52.5% boys, Mage = 9.72 years) were genotyped and randomly assigned to happy, angry or neutral dynamic facial expressions and vocalizations. Motor and affective emotional reactivity were assessed through children's self-reported negative and positive affect (n = 460) and facial electromyography activity (i.e., fEMG: the zygomaticus or "smile" muscle and the corrugator or "frown" muscle, n = 403). Parents reported on their negative and positive parenting behaviors. Children mimicked and experienced the emotion they were exposed to. However, neither motor reactivity nor affective reactivity to these emotions depended on children's 5-HTTLPR genotype: SS/SL-genotypes did not manifest any stronger response to emotional stimuli than LL-genotypes. This finding remained the same when taking the broader family environment into account, controlling for kinship, age, gender and genetic ancestry, and when including a tri-allelic factor. We found no evidence for an association between the 5-HTTLPR polymorphism and children's emotional

  17. Reduced function of the serotonin transporter is associated with decreased expression of BDNF in rodents as well as in humans.

    NARCIS (Netherlands)

    Molteni, R.; Cattaneo, A.; Calabrese, F.; Macchi, F.; Olivier, J.D.A.; Racagni, G.; Ellenbroek, A.A.; Gennarelli, M.; Riva, M.A.

    2010-01-01

    In order to identify the molecular mechanisms that may contribute to the enhanced susceptibility to depression under serotonin transporter (SERT) dysfunction, we analyzed the expression of brain-derived neurotrophic factor (BDNF), a key player in neuronal plasticity, which is implicated in the

  18. The reducing agent Dithiothreitol (DTT) increases expression of c-myc and c- fos protooncogenes in human cells

    DEFF Research Database (Denmark)

    Skouv, J.; Sørensen, Ilona Kryspin; Frandsen, H.

    1995-01-01

    The objective of the present study was to assess the possible tumour promoting activity of the food mutagen 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), by studying its influence on the expression of three genes considered to be of relevance in the tumour promotion step...

  19. Neurosteroids reduce social isolation-induced behavioral deficits: a proposed link with neurosteroid-mediated upregulation of BDNF expression

    Directory of Open Access Journals (Sweden)

    Mauricio Schüler Nin

    2011-11-01

    Full Text Available The pharmacological action of SSRI antidepressants may include a normalization of the decreased brain levels of neurosteroids such as that of the progesterone metabolite allopregnanolone and that of the brain-derived neurotrophic factor (BDNF, which are decreased in patients with depression and PTSD. Allopregnanolone and BDNF decrease in these patients is associated with behavioral symptom severity. Antidepressant treatment upregulates both allopregnanolone levels and the expression of BDNF in a manner that significantly correlates with improved symptomatology, which suggests that neurosteroid biosynthesis and BDNF expression may be interrelated. Preclinical studies using the socially isolated mouse as an animal model of behavioral deficits that resemble some of the symptoms observed in PTSD patients have shown that fluoxetine and derivatives improve anxiety-like behavior, fear responses, and aggressive behavior by elevating the corticolimbic levels of allopregnanolone and BDNF mRNA expression. These actions appeared to be independent and more selective from the action of these drugs on 5-HT reuptake inhibition.Hence, this review addresses the hypothesis that in PTSD or depressed patients brain allopregnanolone levels and BDNF expression upregulation may be part of the mechanisms involved in the beneficial actions of antidepressants or other selective brain steroidogenic stimulant (SBSS molecules.

  20. Reduced Recognition of Dynamic Facial Emotional Expressions and Emotion-Specific Response Bias in Children with an Autism Spectrum Disorder

    Science.gov (United States)

    Evers, Kris; Steyaert, Jean; Noens, Ilse; Wagemans, Johan

    2015-01-01

    Emotion labelling was evaluated in two matched samples of 6-14-year old children with and without an autism spectrum disorder (ASD; N = 45 and N = 50, resp.), using six dynamic facial expressions. The Emotion Recognition Task proved to be valuable demonstrating subtle emotion recognition difficulties in ASD, as we showed a general poorer emotion…

  1. Reduced E-Cadherin and Aberrant β-Catenin Expression are Associated With Advanced Disease in Signet-Ring Cell Carcinomas.

    Science.gov (United States)

    Ma, Yihong R; Ren, Zhiyong; Conner, Michael G; Siegal, Gene P; Wei, Shi

    2017-07-01

    Signet-ring cell carcinomas (SRCCs) tend to present at higher stages and thus are generally associated with a worse prognosis. It has been postulated that a deficiency of E-cadherin may be causal in the pathogenesis of SRCC in animal models. In this study, we systemically analyzed the expression of E-cadherin and β-catenin, a key component of the cadherin complex, in 137 consecutive SRCCs of various organ systems to explore the significance of these molecules in the pathogenesis and progression of SRCCs. Seventy-six percent of SRCCs showed loss or reduced E-cadherin expression. Aberrant β-catenin expression, defined as loss of membranous expression and nuclear/cytoplasmic subcellular localization, was observed in 60% of these cases, with the altered β-catenin expression observed most commonly in the breast (93%) and least in the lung (38%) primaries. Further, the aberrant β-catenin was significantly associated with pathologic nodal stage (P=0.002) and clinical stage (P=0.02). Our findings demonstrated that reduced membranous E-cadherin and aberrant β-catenin expression were frequent events in SRCCs of various organs, and that the altered β-catenin expression was significantly associated with advanced disease. The observations further support the importance of these molecules in the pathogenesis of SRCCs, and indicate the fundamental role of the Wnt/β-catenin signaling pathway in the progression of these tumors. Further investigations of the downstream molecules in this cascade may provide potential novel therapeutic targets for this aggressive tumor type.

  2. Ruxolitinib synergizes with DMF to kill via BIM+BAD-induced mitochondrial dysfunction and via reduced SOD2/TRX expression and ROS.

    Science.gov (United States)

    Tavallai, Mehrad; Booth, Laurence; Roberts, Jane L; McGuire, William P; Poklepovic, Andrew; Dent, Paul

    2016-04-05

    We determined whether the myelofibrosis drug ruxolitinib, an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could interact with the multiple sclerosis drug dimethyl-fumarate (DMF) to kill tumor cells; studies used the in vivo active form of the drug, mono-methyl fumarate (MMF). Ruxolitinib interacted with MMF to kill brain, breast, lung and ovarian cancer cells, and enhanced the lethality of standard of care therapies such as paclitaxel and temozolomide. MMF also interacted with other FDA approved drugs to kill tumor cells including Celebrex® and Gilenya®. The combination of [ruxolitinib + MMF] inactivated ERK1/2, AKT, STAT3 and STAT5; reduced expression of MCL-1, BCL-XL, SOD2 and TRX; increased BIM expression; decreased BAD S112 S136 phosphorylation; and enhanced pro-caspase 3 cleavage. Expression of activated forms of STAT3, MEK1 or AKT each significantly reduced drug combination lethality; prevented BAD S112 S136 dephosphorylation and decreased BIM expression; and preserved TRX, SOD2, MCL-1 and BCL-XL expression. The drug combination increased the levels of reactive oxygen species in cells, and over-expression of TRX or SOD2 prevented drug combination tumor cell killing. Over-expression of BCL-XL or knock down of BAX, BIM, BAD or apoptosis inducing factor (AIF) protected tumor cells. The drug combination increased AIF : HSP70 co-localization in the cytosol but this event did not prevent AIF : eIF3A association in the nucleus.

  3. A Novel Platelet Activating Factor Receptor Antagonist Reduces Cell Infiltration and Expression of Inflammatory Mediators in Mice Exposed to Desiccating Conditions after PRK

    Directory of Open Access Journals (Sweden)

    Salomon Esquenazi

    2009-01-01

    Results. Confocal microscopy showed an increased number of reflective structures in the corneal epithelium after PRK and exposure to DE in eyes treated with vehicle as compared to eyes treated with LAU-0901. Significant decrease of COX-2 and Arginase I expression and reduced alpha SMA cells was observed after PRK and exposure to DE in eyes treated with LAU-0901. Discussion: Exposure of mice to a DE after PRK increases the epithelial turnover rate. PAF is involved in the inflammatory cell infiltration and expression of inflammatory cytokines that follow PRK under DE.

  4. Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs.

    Science.gov (United States)

    Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Di Nardo, Giovanna; Gilardi, Gianfranco

    2012-12-01

    In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing the requirement for both the P450 reductase and the expensive cofactor NADPH. In this work, P450 2C20 from Macaca fascicularis, homologue of the human P450 2C8 has been taken as a model system to develop such an alternative in vitro method by two different approaches. In the first approach called "molecular Lego", a soluble self-sufficient chimera was generated by fusing the P450 2C20 domain with the reductase domain of cytochrome P450 BM3 from Bacillus megaterium (P450 2C20/BMR). In the second approach, the need for the redox partner and also NADPH were both obviated by the direct immobilization of the P450 2C20 on glassy carbon and gold electrodes. Both systems were then compared to those obtained from the reconstituted P450 2C20 monooxygenase in presence of the human P450 reductase and NADPH using paclitaxel and amodiaquine, two typical drug substrates of the human P450 2C8. The K(M) values calculated for the 2C20 and 2C20/BMR in solution and for 2C20 immobilized on electrodes modified with gold nanoparticles were 1.9 ± 0.2, 5.9 ± 2.3, 3.0 ± 0.5 μM for paclitaxel and 1.2 ± 0.2, 1.6±0.2 and 1.4 ± 0.2 μM for amodiaquine, respectively. The data obtained not only show that the engineering of M. fascicularis did not affect its catalytic properties but also are consistent with K(M) values measured for the microsomal human P450 2C8 and therefore show the feasibility of developing alternative in vitro animal tests. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Daily online testing in large classes: boosting college performance while reducing achievement gaps.

    Directory of Open Access Journals (Sweden)

    James W Pennebaker

    Full Text Available An in-class computer-based system, that included daily online testing, was introduced to two large university classes. We examined subsequent improvements in academic performance and reductions in the achievement gaps between lower- and upper-middle class students in academic performance. Students (N = 901 brought laptop computers to classes and took daily quizzes that provided immediate and personalized feedback. Student performance was compared with the same data for traditional classes taught previously by the same instructors (N = 935. Exam performance was approximately half a letter grade above previous semesters, based on comparisons of identical questions asked from earlier years. Students in the experimental classes performed better in other classes, both in the semester they took the course and in subsequent semester classes. The new system resulted in a 50% reduction in the achievement gap as measured by grades among students of different social classes. These findings suggest that frequent consequential quizzing should be used routinely in large lecture courses to improve performance in class and in other concurrent and subsequent courses.

  6. Effects of the pesticide methoxychlor on gene expression in the liver and testes of the male largemouth bass (Micropterus salmoides)

    Science.gov (United States)

    Blum, Jason L.; Nyagode, Beatrice A.; James, Margaret O.; Denslow, Nancy D.

    2010-01-01

    The organochlorine pesticide methoxychlor (MXC) is an environmental estrogen known to stimulate the expression of the egg-yolk protein, vitellogenin (Vtg) in fish species. To begin to understand the underlying mechanisms for how MXC exerts its deleterious effects on the endocrine system, male largemouth bass (Micropterus salmoides) were treated with 2.5, 10, or 25 mg/kg MXC and compared to fish pair-treated with 1 mg/kg 17β-estradiol (E2), and vehicle control. Fish were sacrificed 24, 48, or 72 h following treatment. The liver and testes were then assayed for changes in expression of the three bass estrogen receptors (ERs α, βa, and βb) in tissues, as well as Vtg and cytochrome P450 (CYP) 3A isoform 68 in the liver and steroidogenic acute regulatory protein (StAR) in the testes. In the liver, significant increases in gene expression were seen for each of the genes measured by 24 h and each returned to the level of the vehicle by 72 h. Total testosterone 6β-hydroxylase activity, reflective of CYP3A activity, was also increased by 24 h for all of the exposures. In the testes, ERα was unaffected by any treatment, ERβa was upregulated only by MXC, peaking at 24 h for the 2.5 and 10 mg/kg MXC and at 48 h for the 25 mg/kg MXC treatment. By 72 h, the MXC effects had disappeared, while E2 significantly decreased the expression of ERβa mRNA. ERβb expression in the testes was stimulated by all concentrations of MXC by 24 h and the effect remained up to 72 h, whereas E2 had no effect. Finally, StAR expression was found to also be decreased by E2 and all MXC treatments. However, the effect on StAR expression by E2 occurred within 24 h, while the effect by all concentrations of MXC was not seen until 72 h after treatment. The stimulatory effects of E2 and 25 mg/kg MXC on the expression of the ERs in the liver were opposite to the responses seen in the testes, suggesting an inverted relationship between these two tissue types. These results provide a possible mechanism

  7. Pre-exposure to food temptation reduces subsequent consumption: A test of the procedure with a South-African sample.

    Science.gov (United States)

    Duh, Helen Inseng; Grubliauskiene, Aiste; Dewitte, Siegfried

    2016-01-01

    It has been suggested that the consumption of unhealthy Westernized diet in a context of poverty and resultant food insecurity may have contributed to South-Africa's status of the third fattest country in the World. Considering that a number of South-Africans are reported to have experienced, or are still experiencing food insecurity, procedures which have been shown to reduce the consumption of unhealthy food in higher income countries may be ineffective in South-Africa. We thus tested the robustness of the so called pre-exposure procedure in South-Africa. We also tested the moderating role of childhood poverty in the pre-exposure procedure. With the pre-exposure procedure, a respondent is exposed to a tempting unhealthy food (e.g. candy) in a context that is designed such that eating the food interferes with a task goal. The typical result is that this procedure spills over and reduces consumption of similar tempting food later on. An experimental study conducted in a South-African laboratory showed that the pre-exposure effect is robust even with a sample, where food insecurity prevails. Childhood poverty did not moderate the effect. This study proves that behavioral procedures aimed at reducing the consumption of unhealthy food would be valuable in less rich non-Western countries. Further testing of the robustness of the pre-exposure effect is however recommended in other poorer food insecure countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Deletion of the B-B' and C-C' regions of inverted terminal repeats reduces rAAV productivity but increases transgene expression.

    Science.gov (United States)

    Zhou, Qingzhang; Tian, Wenhong; Liu, Chunguo; Lian, Zhonghui; Dong, Xiaoyan; Wu, Xiaobing

    2017-07-14

    Inverted terminal repeats (ITRs) of the adeno-associated virus (AAV) are essential for rescue, replication, packaging, and integration of the viral genome. While ITR mutations have been identified in previous reports, we designed a new truncated ITR lacking the B-B' and C-C' regions named as ITRΔBC and investigated its effects on viral genome replication, packaging, and expression of recombinant AAV (rAAV). The packaging ability was compared between ITRΔBC rAAV and wild-type (wt) ITR rAAV. Our results showed the productivity of ITRΔBC rAAV was reduced 4-fold, which is consistent with the 8-fold decrease in the replication of viral genomic DNA of ITRΔBC rAAV compared with wt ITR rAAV. Surprisingly, transgene expression was significantly higher for ITRΔBC rAAV. A preliminary exploration of the underlying mechanisms was carried out by inhibiting and degrading the ataxia telangiectasia mutated (ATM) protein and the Mre11 complex (MRN), respectively, since the rAAV expression was inhibited by the ATM and/or MRN through cis interaction or binding with wt ITRs. We demonstrated that the inhibitory effects were weakened on ITRΔBC rAAV expression. This study suggests deletion in ITR can affect the transgene expression of AAV, which provides a new way to improve the AAV expression through ITRs modification.

  9. Welcome address to the 26th international meeting on Reduced Enrichment for Research and Test Reactors

    International Nuclear Information System (INIS)

    Sokolov, Y.

    2005-01-01

    While the IAEA has been a vigorous supporter of the RERTR programme since its inception. RERTR and the related fresh and spent fuel return efforts have gained new momentum with the launching of the Global Threat Reduction Initiative (GTRI) by U.S. Energy Secretary Abraham here in Vienna on May 25, 2004. All of the activities to be be discussed are included within the framework of the GTRI. The international programmes to qualify high density, LEU, dispersion fuels based on U-Mo alloys have run into unexpected technical difficulties that will delay qualification. A number of the presentations address the problems that have been encountered. At the same time, it is encouraging that the international resolve to reduce and eventually eliminate HEU in international commerce appears to have strengthened. In the past year, fresh HEU at research reactors in different countries have been returned to the country of origin. In all these examples, the return of the fresh fuel was accompanied by plans for conversion of existing reactors or design of new reactors to use LEU, as well as for the repatriation of spent research reactor fuel. The IAEA, particularly the Department of Technical Cooperation and my Department of Nuclear Energy has played an important role in implementing these fresh fuel return activities. In addition, several of the reactor conversion projects will be carried out under the auspices of IAEA technical cooperation projects and with important involvement of the Department of Nuclear Energy. The IAEA has also supported the repatriation of spent fuel to the country of original enrichment. The U.S. spent fuel acceptance programme has been operating for more than eight years, and was originally scheduled to terminate in 2006. Important announcements concerning the extension of the U.S. programme are expected. At the same time, the IAEA has been working hard with the U.S. and Russia to initiate the Russian research reactor spent fuel return programme. We are

  10. DEVELOPMENTAL HYPOTHYROIDISM REDUCES PARVALBUMIN EXPRESSION IN GABAERGIC NEURONS OF CORTEX AND HIPPOCAMPUS: IMMUNOHISTOCHEMICAL FINDINGS AND FUNCTIONAL CORRELATES.

    Science.gov (United States)

    GABAergic interneurons comprise the bulk of local inhibitory neuronal circuitry in cortex and hippocampus and a subpopulation of these interneurons contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe hypothyroidism reduced PV immunoreact...

  11. Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms

    DEFF Research Database (Denmark)

    Kristensen, David M; Nielsen, John E; Skakkebaek, Niels E

    2008-01-01

    UTF-1 and REX-1/ZFP42 are transcription factors involved in pluripotency. Because of phenotypic similarities between pluripotent embryonic stem cells and testicular germ cell tumours (TGCT) and the derivation of pluripotent cells from testes, we investigated the expression of UTF-1 and REX-1 during...... human gonadal development and in TGCT....

  12. Design and Validation of a Photographic Expressive Persian Grammar Test for Children Aged 4-6 Years

    Science.gov (United States)

    Haresabadi, Fatemeh; Ebadi, Abbas; Shirazi, Tahereh Sima; Dastjerdi Kazemi, Mehdi

    2016-01-01

    Syntax has a high importance among linguistic parameters, and syntax-related problems are the most common in language disorders. Therefore, the present study aimed to design a Photographic Expressive Persian Grammar Test for Iranian children in the age group of 4-6 years and to determine its validity and reliability. First, the target…

  13. Problem-Solving Test: The Role of a Micro-RNA in the Regulation of "fos" Gene Expression

    Science.gov (United States)

    Szeberenyi, Jozsef

    2009-01-01

    The "fos" proto-oncogene codes for a component of the AP1 transcription factor, an important regulator of gene expression and cell proliferation. Dysregulation of AP1 function may lead to the malignant transformation of the cell. The present test describes an experiment in which the role of a micro-RNA (miR-7b) in the regulation of "fos" gene…

  14. Reduced expression of argininosuccinate synthetase 1 has a negative prognostic impact in patients with pancreatic ductal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Qingqing Liu

    Full Text Available Argininosuccinate synthetase 1 (ASS1, the rate-limiting enzyme for arginine biosynthesis, is expressed in many types of human malignancies. Recent studies showed that ASS1 may have tumor suppressor function and that ASS1 deficiency is associated with clinical aggressiveness in nasopharyngeal carcinoma, myxofibrosarcomas and bladder cancer. The goal of this study was to evaluate the prognostic impact of ASS1 expression in patients with pancreatic ductal adenocarcinoma (PDAC. Our study included two independent cohorts: untreated cohort, which was comprised of 135 patients with PDAC who underwent pancreatoduodenectomy (PD without pre-operative neoadjuvant therapy, and treated cohort, which was comprised of 122 patients with PDAC who have completed neoadjuvant therapy and PD. The expression level of ASS1 was evaluated by immunohistochemistry and the results were correlated with clinicopathologic parameters and survival using SPSS statistics. Our study showed that 12% of PDAC in untreated cohort and 15% of PDAC in treated cohort has low expression of ASS1 (ASS1-low. ASS1-low was associated with higher recurrence (p = 0.045, shorter disease-free survival (DFS, 4.8 ± 1.6 months vs 15.3 ± 2.2 months, p = 0.001 and shorter overall survival (OS, 14.6 ± 6.4 months vs 26.5 ± 3.5 months, p = 0.005 in untreated cohort and shorter OS in treated cohort compared to ASS1-high tumors. In multivariate analysis, ASS1-low (HR: 0.45, 95% CI: 0.26-0.79, p = 0.005 was an independent prognostic factor for DFS in untreated cohort and an independent prognostic factor for OS (HR: 0.56, 95% CI: 0.32-0.97, p = 0.04 in treated cohort. Our results provide supporting evidence for future clinical trial using arginine deprivation agents either alone or in combination with conventional chemotherapy in treating pancreatic cancer.

  15. Rht18 Semidwarfism in Wheat Is Due to Increased GA 2-oxidaseA9 Expression and Reduced GA Content

    Czech Academy of Sciences Publication Activity Database

    Ford, B. A.; Foo, E.; Sharwood, R.; Karafiátová, Miroslava; Vrána, Jan; MacMillan, C.; Nichols, D. S.; Steuernagel, B.; Uauy, C.; Doležel, Jaroslav; Chandler, M.; Spielmeyer, W.

    2018-01-01

    Roč. 177, č. 1 (2018), s. 168-180 ISSN 0032-0889 R&D Projects: GA MŠk(CZ) LO1204; GA ČR GBP501/12/G090 Institutional support: RVO:61389030 Keywords : green-revolution * gibberellin biosynthesis * ectopic expression * common wheat * gene * rice * barley * mutant * chromosomes Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 6.456, year: 2016

  16. P02.04MICRORNA-MEDIATED DOWN-REGULATION OF NKG2D LIGAND EXPRESSION REDUCES GLIOMA CELL IMMUNOGENICITY

    Science.gov (United States)

    Codo, P.; Weller, M.; Meister, G.; Szabo, E.; Steinle, A.; Wolter, M.; Reifenberger, G.; Roth, P.

    2014-01-01

    Glioblastoma is a primary brain tumor with a dismal prognosis despite comprehensive therapeutic regimens. It is characterized by diffuse infiltration of the surrounding healthy brain tissue, well-adapted to hypoxic conditions and regarded as paradigmatic for tumor-associated immunosuppression. One of the major activating receptors of natural killer (NK) cells is NKG2D. It binds to at least 8 ligands (NKG2DL) which are induced after malignant transformation and cellular stress. Regulation of NKG2DL expression may be affected by endogenous RNA molecules known as microRNA (miRNA). Here, we aimed at characterizing the role of miRNA in the control of NKG2DL expression in glioma cells. We selected 6 miRNA that were described or predicted to target NKG2DL. Three of the miRNA candidates, miR-20a, miR-93 and miR-106b, were expressed in glioma cell lines and were also detected in glioblastoma tissue specimens. Silencing of these miRNA with locked nucleic acid (LNA) molecules resulted in an up-regulation of NKG2DL cell surface levels which translated into increased sensitivity to immune cell killing. This effect was reversed by neutralizing NKG2D antibodies, confirming that enhanced immune cell lysis upon miRNA silencing was mediated through the NKG2D system. We conclude that the expression of several miRNA may contribute to the immune escape of glioma cells at the level of the NKG2D system. Therapeutic targeting of miRNA that regulate NKG2DL levels may therefore represent a promising approach to allow for more potent immune responses against glioblastoma.

  17. Diminished humoral responses against and reduced gene expression levels of human endogenous retrovirus-K (HERV-K) in psoriasis.

    Science.gov (United States)

    Gupta, Rashmi; Michaud, Henri-Alexandre; Zeng, Xue; Debbaneh, Maya; Arron, Sarah T; Jones, R Brad; Ormsby, Christopher E; Nixon, Douglas F; Liao, Wilson

    2014-09-16

    Psoriasis is a multifactorial, chronic disease of skin affecting 2-3% of the world's population. Genetic studies of psoriasis have identified a number of susceptibility genes that are involved in anti-viral immunity. Furthermore, physiological studies have also found an increase in anti-viral proteins in psoriatic skin. These findings suggest the presence of an anti-viral state in psoriatic skin. However, the triggers for this anti-viral cascade and its consequences for host immunity are not known. Endogenous retroviruses have previously been described in many autoimmune diseases including psoriasis. In the present study we examined the humoral immune response against human endogenous retrovirus-K (HERV-K) proteins and the cutaneous expression levels of multiple HERV-K genes in psoriasis patients and healthy controls. In psoriatic sera we observed a significant decrease in IgM response against three HERV-K proteins: Env surface unit (SU), Env transmembrane protein (TM), and Gag capsid (CA) in comparison to sera obtained from blood bank healthy controls. A decrease in IgG response was also observed against CA. Furthermore, using quantitative RT-PCR we observed a decrease in the expression of HERV-K Env, Gag, Pol and Rec as well as ERV-9 genes in lesional psoriatic skin as compared to healthy skin. Together, our results suggest that the pro-inflammatory, anti-viral state in psoriasis is associated with diminished expression of HERV-K gene transcripts and a concomitant decrease in humoral responses to HERV-K. Our results indicate that a simple model where continuous, minimally changing HERV-K expression serves as an antigenic trigger in psoriasis might not be correct and further studies are needed to decipher the possible relationship between psoriasis and HERVs.

  18. Differential expression of IGFBPs in Laron syndrome-derived lymphoblastoid cell lines: Potential correlation with reduced cancer incidence.

    Science.gov (United States)

    Somri, Lina; Sarfstein, Rive; Lapkina-Gendler, Lena; Nagaraj, Karthik; Laron, Zvi; Bach, Leon A; Werner, Haim

    2018-04-01

    Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is a growth disorder that results from mutation of the GH-receptor (GHR) gene leading to congenital insulin-like growth factor-1 (IGF-1) deficiency. Recent epidemiological studies have shown that LS patients are protected from cancer development. Genome-wide profiling identified genes and signaling pathways that are differentially represented in LS patients, and that may contribute to cancer protection. The present study was aimed at evaluating the hypothesis that IGF binding proteins (IGFBPs) are differentially expressed in LS, most probably as a result of low circulating levels of IGF-1. Furthermore, we postulated that IGFBPs might be differentially regulated by oxidative stress in this condition and, therefore, may contribute to cancer evasion. Our results show that IGFBP-3, which is predominantly protective, was highly expressed in LS-derived lymphoblastoid cells in comparison to control cells from the same ethnic group. On the other hand, levels of IGFBP-2, -4, -5, and -6 were diminished in LS patients, as demonstrated by RQ-PCR, Western immunoblots and confocal immunofluorescence. In addition, our data provide evidence for a pattern of IGFBP response to H 2 O 2 treatment that might be associated with distinct expression of apoptosis markers (BCL2, pro-caspase-9, pro-caspase-3) in LS. In summary, differential expression of specific IGFBPs in LS might be correlated with cellular mechanisms underlying cancer protection and, probably, additional phenotypes due to congenital IGF-1 deficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene.

    Directory of Open Access Journals (Sweden)

    Rebecca L Skalsky

    Full Text Available Glioblastoma is a highly aggressive malignant tumor involving glial cells in the human brain. We used high-throughput sequencing to comprehensively profile the small RNAs expressed in glioblastoma and non-tumor brain tissues. MicroRNAs (miRNAs made up the large majority of small RNAs, and we identified over 400 different cellular pre-miRNAs. No known viral miRNAs were detected in any of the samples analyzed. Cluster analysis revealed several miRNAs that were significantly down-regulated in glioblastomas, including miR-128, miR-124, miR-7, miR-139, miR-95, and miR-873. Post-transcriptional editing was observed for several miRNAs, including the miR-376 family, miR-411, miR-381, and miR-379. Using the deep sequencing information, we designed a lentiviral vector expressing a cell suicide gene, the herpes simplex virus thymidine kinase (HSV-TK gene, under the regulation of a miRNA, miR-128, that was found to be enriched in non-tumor brain tissue yet down-regulated in glioblastomas, Glioblastoma cells transduced with this vector were selectively killed when cultured in the presence of ganciclovir. Using an in vitro model to recapitulate expression of brain-enriched miRNAs, we demonstrated that neuronally differentiated SH-SY5Y cells transduced with the miRNA-regulated HSV-TK vector are protected from killing by expression of endogenous miR-128. Together, these results provide an in-depth analysis of miRNA dysregulation in glioblastoma and demonstrate the potential utility of these data in the design of miRNA-regulated therapies for the treatment of brain cancers.

  20. Polyphenol-Rich Extract from Propolis Reduces the Expression and Activity of Streptococcus mutans Glucosyltransferases at Subinhibitory Concentrations

    Directory of Open Access Journals (Sweden)

    Jorge Jesús Veloz

    2016-01-01

    Full Text Available Tooth decay is an infectious disease, whose main causative agent identified is Streptococcus mutans (S. mutans. Diverse treatments have been used to eradicate this microorganism, including propolis. To date, it has been shown that polyphenols from Chilean propolis inhibit S. mutans growth and biofilm formation. However, the molecular mechanisms underlying this process are unclear. In the present study, we