WorldWideScience

Sample records for differential regulatory effects

  1. IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1.

    Science.gov (United States)

    Neufert, Clemens; Becker, Christoph; Wirtz, Stefan; Fantini, Massimo C; Weigmann, Benno; Galle, Peter R; Neurath, Markus F

    2007-07-01

    IL-27 is an IL-12-related cytokine frequently present at sites of inflammation that can promote both anti- and pro-inflammatory immune responses. Here, we have analyzed the mechanisms how IL-27 may drive such divergent immune responses. While IL-27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in inhibiting the development of anti-inflammatory, inducible regulatory T cells (iTreg) was identified. In fact, IL-27 suppressed the development of adaptive, TGF-beta-induced Forkhead box transcription factor p3-positive (Foxp3(+)) Treg. Whereas the blockade of Th17 development was dependent on the transcription factor STAT1, the suppression of iTreg development was STAT1 independent, suggesting that IL-27 utilizes different signaling pathways to shape T cell-driven immune responses. Our data thus demonstrate that IL-27 controls the development of Th17 and iTreg cells via differential effects on STAT1.

  2. The regulatory landscape of osteogenic differentiation.

    Science.gov (United States)

    Håkelien, Anne-Mari; Bryne, Jan Christian; Harstad, Kristine G; Lorenz, Susanne; Paulsen, Jonas; Sun, Jinchang; Mikkelsen, Tarjei S; Myklebost, Ola; Meza-Zepeda, Leonardo A

    2014-10-01

    Differentiation of osteoblasts from mesenchymal stem cells (MSCs) is an integral part of bone development and homeostasis, and may when improperly regulated cause disease such as bone cancer or osteoporosis. Using unbiased high-throughput methods we here characterize the landscape of global changes in gene expression, histone modifications, and DNA methylation upon differentiation of human MSCs to the osteogenic lineage. Furthermore, we provide a first genome-wide characterization of DNA binding sites of the bone master regulatory transcription factor Runt-related transcription factor 2 (RUNX2) in human osteoblasts, revealing target genes associated with regulation of proliferation, migration, apoptosis, and with a significant overlap with p53 regulated genes. These findings expand on emerging evidence of a role for RUNX2 in cancer, including bone metastases, and the p53 regulatory network. We further demonstrate that RUNX2 binds to distant regulatory elements, promoters, and with high frequency to gene 3' ends. Finally, we identify TEAD2 and GTF2I as novel regulators of osteogenesis. © 2014 AlphaMed Press.

  3. A stochastic differential equation model for transcriptional regulatory networks

    Directory of Open Access Journals (Sweden)

    Quirk Michelle D

    2007-05-01

    Full Text Available Abstract Background This work explores the quantitative characteristics of the local transcriptional regulatory network based on the availability of time dependent gene expression data sets. The dynamics of the gene expression level are fitted via a stochastic differential equation model, yielding a set of specific regulators and their contribution. Results We show that a beta sigmoid function that keeps track of temporal parameters is a novel prototype of a regulatory function, with the effect of improving the performance of the profile prediction. The stochastic differential equation model follows well the dynamic of the gene expression levels. Conclusion When adapted to biological hypotheses and combined with a promoter analysis, the method proposed here leads to improved models of the transcriptional regulatory networks.

  4. Hypercholesterolemia Induces Differentiation of Regulatory T Cells in the Liver.

    Science.gov (United States)

    Mailer, Reiner K W; Gisterå, Anton; Polyzos, Konstantinos A; Ketelhuth, Daniel F J; Hansson, Göran K

    2017-05-26

    The liver is the central organ that responds to dietary cholesterol intake and facilitates the release and clearance of lipoprotein particles. Persistent hypercholesterolemia leads to immune responses against lipoprotein particles that drive atherosclerosis. However, the effect of hypercholesterolemia on hepatic T-cell differentiation remains unknown. To investigate hepatic T-cell subsets upon hypercholesterolemia. We observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg) cell population and increased the expression of transforming growth factor-β1 in the liver. Adoptive transfer experiments revealed that intrahepatically differentiated Treg cells relocated to the inflamed aorta in atherosclerosis-prone low-density lipoprotein receptor deficient (Ldlr(-/-)) mice. Moreover, hypercholesterolemia induced the differentiation of intrahepatic, but not intrasplenic, Th17 cells in wild-type mice, whereas the disrupted liver homeostasis in hypercholesterolemic Ldlr(-/-) mice led to intrahepatic Th1 cell differentiation and CD11b(+)CD11c(+) leukocyte accumulation. Our results elucidate a new mechanism that controls intrahepatic T-cell differentiation during atherosclerosis development and indicates that intrahepatically differentiated T cells contribute to the CD4(+) T-cell pool in the atherosclerotic aorta. © 2017 American Heart Association, Inc.

  5. Transcriptome sequencing from diverse human populations reveals differentiated regulatory architecture.

    Directory of Open Access Journals (Sweden)

    Alicia R Martin

    2014-08-01

    Full Text Available Large-scale sequencing efforts have documented extensive genetic variation within the human genome. However, our understanding of the origins, global distribution, and functional consequences of this variation is far from complete. While regulatory variation influencing gene expression has been studied within a handful of populations, the breadth of transcriptome differences across diverse human populations has not been systematically analyzed. To better understand the spectrum of gene expression variation, alternative splicing, and the population genetics of regulatory variation in humans, we have sequenced the genomes, exomes, and transcriptomes of EBV transformed lymphoblastoid cell lines derived from 45 individuals in the Human Genome Diversity Panel (HGDP. The populations sampled span the geographic breadth of human migration history and include Namibian San, Mbuti Pygmies of the Democratic Republic of Congo, Algerian Mozabites, Pathan of Pakistan, Cambodians of East Asia, Yakut of Siberia, and Mayans of Mexico. We discover that approximately 25.0% of the variation in gene expression found amongst individuals can be attributed to population differences. However, we find few genes that are systematically differentially expressed among populations. Of this population-specific variation, 75.5% is due to expression rather than splicing variability, and we find few genes with strong evidence for differential splicing across populations. Allelic expression analyses indicate that previously mapped common regulatory variants identified in eight populations from the International Haplotype Map Phase 3 project have similar effects in our seven sampled HGDP populations, suggesting that the cellular effects of common variants are shared across diverse populations. Together, these results provide a resource for studies analyzing functional differences across populations by estimating the degree of shared gene expression, alternative splicing, and

  6. Transcriptome sequencing from diverse human populations reveals differentiated regulatory architecture.

    Directory of Open Access Journals (Sweden)

    Alicia R Martin

    2014-08-01

    Full Text Available Large-scale sequencing efforts have documented extensive genetic variation within the human genome. However, our understanding of the origins, global distribution, and functional consequences of this variation is far from complete. While regulatory variation influencing gene expression has been studied within a handful of populations, the breadth of transcriptome differences across diverse human populations has not been systematically analyzed. To better understand the spectrum of gene expression variation, alternative splicing, and the population genetics of regulatory variation in humans, we have sequenced the genomes, exomes, and transcriptomes of EBV transformed lymphoblastoid cell lines derived from 45 individuals in the Human Genome Diversity Panel (HGDP. The populations sampled span the geographic breadth of human migration history and include Namibian San, Mbuti Pygmies of the Democratic Republic of Congo, Algerian Mozabites, Pathan of Pakistan, Cambodians of East Asia, Yakut of Siberia, and Mayans of Mexico. We discover that approximately 25.0% of the variation in gene expression found amongst individuals can be attributed to population differences. However, we find few genes that are systematically differentially expressed among populations. Of this population-specific variation, 75.5% is due to expression rather than splicing variability, and we find few genes with strong evidence for differential splicing across populations. Allelic expression analyses indicate that previously mapped common regulatory variants identified in eight populations from the International Haplotype Map Phase 3 project have similar effects in our seven sampled HGDP populations, suggesting that the cellular effects of common variants are shared across diverse populations. Together, these results provide a resource for studies analyzing functional differences across populations by estimating the degree of shared gene expression, alternative splicing, and

  7. Effects of a miR-31, Runx2, and Satb2 regulatory loop on the osteogenic differentiation of bone mesenchymal stem cells.

    Science.gov (United States)

    Deng, Yuan; Wu, Si; Zhou, Huifang; Bi, Xiaoping; Wang, Yefei; Hu, Yamin; Gu, Ping; Fan, Xianqun

    2013-08-15

    Recently, a cohort of miRNAs, including miR-31, was reported to be downregulated during osteogenic induction by miR microarray analysis. It remains unclear how changes in miR-31 expression collaborate with bone transcription factors to activate the biological pathways that regulate the differentiation of bone mesenchymal stem cells (BMSCs). Here the effects of miR-31, Runx2, and Satb2 on the osteogenic differentiation of BMSCs were investigated using mimics and inhibitors of miR-31, small interfering RNA for knockdown of Runx2 and plasmids for overexpression of Runx2. Our results showed that miR-31 expression decreased progressively in BMSC cultures during differentiation. Inhibition of miR-31 dramatically increased the alkaline phosphatase activity and mineralization in BMSC cultures. Additionally, miR-31 diminished the levels of the Satb2 protein without significantly affecting Satb2 mRNA levels, and Runx2 directly repressed miR-31 expression. Overexpression of miR-31 significantly reduced expression of the osteogenic transcription factors OPN, BSP, OSX, and OCN, but not Runx2. Furthermore, the high expression of miR-31 in BMSCs cultured in the proliferation medium repressed Satb2 protein levels, which may contribute to the maintenance of BMSCs in an undifferentiated state. In conclusion, our results suggest that a Runx2, Satb2, and miR-31 regulatory mechanism may play an important role in inducing BMSC osteogenic differentiation. The results of this study provide us with a better understanding of the molecular mechanisms that govern the BMSC fate.

  8. Differential Regulatory Analysis Based on Coexpression Network in Cancer Research

    Directory of Open Access Journals (Sweden)

    Junyi Li

    2016-01-01

    Full Text Available With rapid development of high-throughput techniques and accumulation of big transcriptomic data, plenty of computational methods and algorithms such as differential analysis and network analysis have been proposed to explore genome-wide gene expression characteristics. These efforts are aiming to transform underlying genomic information into valuable knowledges in biological and medical research fields. Recently, tremendous integrative research methods are dedicated to interpret the development and progress of neoplastic diseases, whereas differential regulatory analysis (DRA based on gene coexpression network (GCN increasingly plays a robust complement to regular differential expression analysis in revealing regulatory functions of cancer related genes such as evading growth suppressors and resisting cell death. Differential regulatory analysis based on GCN is prospective and shows its essential role in discovering the system properties of carcinogenesis features. Here we briefly review the paradigm of differential regulatory analysis based on GCN. We also focus on the applications of differential regulatory analysis based on GCN in cancer research and point out that DRA is necessary and extraordinary to reveal underlying molecular mechanism in large-scale carcinogenesis studies.

  9. Identifying gene regulatory network rewiring using latent differential graphical models.

    Science.gov (United States)

    Tian, Dechao; Gu, Quanquan; Ma, Jian

    2016-09-30

    Gene regulatory networks (GRNs) are highly dynamic among different tissue types. Identifying tissue-specific gene regulation is critically important to understand gene function in a particular cellular context. Graphical models have been used to estimate GRN from gene expression data to distinguish direct interactions from indirect associations. However, most existing methods estimate GRN for a specific cell/tissue type or in a tissue-naive way, or do not specifically focus on network rewiring between different tissues. Here, we describe a new method called Latent Differential Graphical Model (LDGM). The motivation of our method is to estimate the differential network between two tissue types directly without inferring the network for individual tissues, which has the advantage of utilizing much smaller sample size to achieve reliable differential network estimation. Our simulation results demonstrated that LDGM consistently outperforms other Gaussian graphical model based methods. We further evaluated LDGM by applying to the brain and blood gene expression data from the GTEx consortium. We also applied LDGM to identify network rewiring between cancer subtypes using the TCGA breast cancer samples. Our results suggest that LDGM is an effective method to infer differential network using high-throughput gene expression data to identify GRN dynamics among different cellular conditions.

  10. Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue.

    Science.gov (United States)

    Lacasa, D; Le Liepvre, X; Ferre, P; Dugail, I

    2001-04-13

    Fatty acid synthase (FAS), a nutritionally regulated lipogenic enzyme, is transcriptionally controlled by ADD1/SREBP1c (adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c), through insulin-mediated stimulation of ADD1/SREBP1c expression. Progesterone exerts lipogenic effects on adipocytes, and FAS is highly induced in breast tumor cell lines upon progesterone treatment. We show here that progesterone up-regulates ADD1/SREBP1c expression in the MCF7 breast cancer cell line and the primary cultured preadipocyte from rat parametrial adipose tissue. In MCF7, progesterone induced ADD1/SREBP1c and Metallothionein II (a well known progesterone-regulated gene) mRNAs, with comparable potency. In preadipocytes, progesterone increased ADD1/SREBP1c mRNA dose-dependently, but not SREBP1a or SREBP2. Run-on experiments demonstrated that progesterone action on ADD1/SREBP1c was primarily at the transcriptional level. The membrane-bound and mature nuclear forms of ADD1/SREBP1 protein accumulated in preadipocytes cultured with progesterone, and FAS induction could be abolished by adenovirus-mediated overexpression of a dominant negative form of ADD1/SREBP1 in these cells. Finally, in the presence of insulin, progesterone was unable to up-regulate ADD1/SREBP1c mRNA in preadipocytes, whereas its effect was restored after 24 h of insulin deprivation. Together these results demonstrate that ADD1/SREBP1c is controlled by progesterone, which, like insulin, acts by increasing ADD1/SREBP1c gene transcription. This provides a potential mechanism for the lipogenic actions of progesterone on adipose tissue.

  11. The effect of nutritional status and myogenic satellite cell age on turkey satellite cell proliferation, differentiation, and expression of myogenic transcriptional regulatory factors and heparan sulfate proteoglycans syndecan-4 and glypican-1.

    Science.gov (United States)

    Harthan, Laura B; McFarland, Douglas C; Velleman, Sandra G

    2014-01-01

    Posthatch satellite cell mitotic activity is a critical component of muscle development and growth. Satellite cells are myogenic stem cells that can be induced by nutrition to follow other cellular developmental pathways, and whose mitotic activity declines with age. The objective of the current study was to determine the effect of restricting protein synthesis on the proliferation and differentiation, expression of myogenic transcriptional regulatory factors myogenic determination factor 1, myogenin, and myogenic regulatory factor 4, and expression of the heparan sulfate proteoglycans syndecan-4 and glypican-1 in satellite cells isolated from 1-d-, 7-wk-, and 16-wk-old turkey pectoralis major muscle (1 d, 7 wk, and 16 wk cells, respectively) by using variable concentrations of Met and Cys. Four Met concentrations-30 (control), 7.5, 3, or 0 mg/L with 3.2 mg/L of Cys per 1 mg/L of Met-were used for culture of satellite cells to determine the effect of nutrition and age on satellite cell behavior during proliferation and differentiation. Proliferation was reduced by lower Met and Cys concentrations in all ages at 96 h of proliferation. Differentiation was increased in the 1 d Met-restricted cells, whereas the 7 wk cells treated with 3 mg/L of Met had decreased differentiation. Reduced Met and Cys levels from the control did not significantly affect the 16 wk cells at 72 h of differentiation. However, medium with no Met or Cys suppressed differentiation at all ages. The expression of myogenic determination factor 1, myogenin, myogenic regulatory factor 4, syndecan-4, and glypican-1 was differentially affected by age and Met or Cys treatment. These data demonstrate the age-specific manner in which turkey pectoralis major muscle satellite cells respond to nutritional availability and the importance of defining optimal nutrition to maximize satellite cell proliferation and differentiation for subsequent muscle mass accretion.

  12. An antisense oligodeoxynucleotide targeted against the type II sub. beta. regulatory subunit mRNA of protein kinase inhibits cAMP-induced differentiation in HL-60 leukemia cells without affecting phorbol ester effects

    Energy Technology Data Exchange (ETDEWEB)

    Tortora, G.; Clair, T.; Cho-Chung, Y.S. (National Institutes of Health, Bethesda, MD (USA))

    1990-01-01

    The type II{sub {beta}} regulatory subunit of cAMP-dependent protein kinase (RII{sub {beta}}) has been hypothesized to play an important role in the growth inhibition and differentiation induced by site-selective cAMP analogs in human cancer cells, but direct proof of this function has been lacking. To address this tissue, HL-60 human promyelocytic leukemia cells were exposed to RII{sub {beta}} antisense synthetic oligodeoxynucleotide, and the effects on cAMP-induced growth regulation were examined. Exposure of these cells to RII{sub {beta}} antisense oligodeoxynucleotide resulted in a decrease in cAMP analog-induced growth inhibition and differentiation without apparent effect on differentiation induced by phorbol esters. This loss in cAMP growth regulatory function correlated with a decrease in basal and induced levels of RII{sub {beta}} protein. Exposure to RII{sub {beta}} sense, RI{sub {alpha}} and RII{sub {alpha}} antisense, or irrelevant oligodeoxynucleotides had no such effect. These results show that the RII{sub {beta}} regulatory subunit of protein kinase plays a critical role in the cAMP-induced growth regulation of HL-60 leukemia cells.

  13. Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation

    Science.gov (United States)

    Goode, Debbie K.; Obier, Nadine; Vijayabaskar, M.S.; Lie-A-Ling, Michael; Lilly, Andrew J.; Hannah, Rebecca; Lichtinger, Monika; Batta, Kiran; Florkowska, Magdalena; Patel, Rahima; Challinor, Mairi; Wallace, Kirstie; Gilmour, Jane; Assi, Salam A.; Cauchy, Pierre; Hoogenkamp, Maarten; Westhead, David R.; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold; Bonifer, Constanze

    2016-01-01

    Summary Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development. PMID:26923725

  14. Effects of retinoic acid and hydrogen peroxide on sterol regulatory element-binding protein-1a activation during adipogenic differentiation of 3T3-L1 cells

    OpenAIRE

    Eldaim, Mabrouk A. Abd; Okamatsu-Ogura, Yuko; Terao, Akira; Kimura, Kazuhiro

    2010-01-01

    Both retinoic acid (RA) and oxidative stress (H2O2) increased transcription and cleavage of membrane-bound sterol regulatory element-binding protein (SREBP)-1, leading to enhanced transcription of fatty acid synthase (FAS) in hepatoma cells. On the other hand, RA and H2O2 decreased and increased lipogenesis in adipocytes, respectively, although roles of SREBP-1 activation in these effects remain to be elucidated. To elucidate its involvement, we examined the activation of SREBP...

  15. Differential network analysis reveals dysfunctional regulatory networks in gastric carcinogenesis.

    Science.gov (United States)

    Cao, Mu-Shui; Liu, Bing-Ya; Dai, Wen-Tao; Zhou, Wei-Xin; Li, Yi-Xue; Li, Yuan-Yuan

    2015-01-01

    Gastric Carcinoma is one of the most common cancers in the world. A large number of differentially expressed genes have been identified as being associated with gastric cancer progression, however, little is known about the underlying regulatory mechanisms. To address this problem, we developed a differential networking approach that is characterized by including a nascent methodology, differential coexpression analysis (DCEA), and two novel quantitative methods for differential regulation analysis. We first applied DCEA to a gene expression dataset of gastric normal mucosa, adenoma and carcinoma samples to identify gene interconnection changes during cancer progression, based on which we inferred normal, adenoma, and carcinoma-specific gene regulation networks by using linear regression model. It was observed that cancer genes and drug targets were enriched in each network. To investigate the dynamic changes of gene regulation during carcinogenesis, we then designed two quantitative methods to prioritize differentially regulated genes (DRGs) and gene pairs or links (DRLs) between adjacent stages. It was found that known cancer genes and drug targets are significantly higher ranked. The top 4% normal vs. adenoma DRGs (36 genes) and top 6% adenoma vs. carcinoma DRGs (56 genes) proved to be worthy of further investigation to explore their association with gastric cancer. Out of the 16 DRGs involved in two top-10 DRG lists of normal vs. adenoma and adenoma vs. carcinoma comparisons, 15 have been reported to be gastric cancer or cancer related. Based on our inferred differential networking information and known signaling pathways, we generated testable hypotheses on the roles of GATA6, ESRRG and their signaling pathways in gastric carcinogenesis. Compared with established approaches which build genome-scale GRNs, or sub-networks around differentially expressed genes, the present one proved to be better at enriching cancer genes and drug targets, and prioritizing

  16. Cpeb4-mediated translational regulatory circuitry controls terminal erythroid differentiation.

    Science.gov (United States)

    Hu, Wenqian; Yuan, Bingbing; Lodish, Harvey F

    2014-09-29

    While we have considerable understanding of the transcriptional networks controlling mammalian cell differentiation, our knowledge of posttranscriptional regulatory events is very limited. Using differentiation of primary erythroid cells as a model, we show that the sequence-specific mRNA-binding protein Cpeb4 is strongly induced by the erythroid-important transcription factors Gata1 and Tal1 and is essential for terminal erythropoiesis. By interacting with the translation initiation factor eIF3, Cpeb4 represses the translation of a large set of mRNAs, including its own mRNA. Thus, transcriptional induction and translational repression combine to form a negative feedback loop to control Cpeb4 protein levels within a specific range that is required for terminal erythropoiesis. Our study provides an example of how translational control is integrated with transcriptional regulation to precisely control gene expression during mammalian cell differentiation.

  17. Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation.

    Science.gov (United States)

    Ali, Niwa; Zirak, Bahar; Rodriguez, Robert Sanchez; Pauli, Mariela L; Truong, Hong-An; Lai, Kevin; Ahn, Richard; Corbin, Kaitlin; Lowe, Margaret M; Scharschmidt, Tiffany C; Taravati, Keyon; Tan, Madeleine R; Ricardo-Gonzalez, Roberto R; Nosbaum, Audrey; Bertolini, Marta; Liao, Wilson; Nestle, Frank O; Paus, Ralf; Cotsarelis, George; Abbas, Abul K; Rosenblum, Michael D

    2017-06-01

    The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of Tregs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Dissecting neural differentiation regulatory networks through epigenetic footprinting.

    Science.gov (United States)

    Ziller, Michael J; Edri, Reuven; Yaffe, Yakey; Donaghey, Julie; Pop, Ramona; Mallard, William; Issner, Robbyn; Gifford, Casey A; Goren, Alon; Xing, Jeffrey; Gu, Hongcang; Cacchiarelli, Davide; Tsankov, Alexander M; Epstein, Charles; Rinn, John L; Mikkelsen, Tarjei S; Kohlbacher, Oliver; Gnirke, Andreas; Bernstein, Bradley E; Elkabetz, Yechiel; Meissner, Alexander

    2015-02-19

    Models derived from human pluripotent stem cells that accurately recapitulate neural development in vitro and allow for the generation of specific neuronal subtypes are of major interest to the stem cell and biomedical community. Notch signalling, particularly through the Notch effector HES5, is a major pathway critical for the onset and maintenance of neural progenitor cells in the embryonic and adult nervous system. Here we report the transcriptional and epigenomic analysis of six consecutive neural progenitor cell stages derived from a HES5::eGFP reporter human embryonic stem cell line. Using this system, we aimed to model cell-fate decisions including specification, expansion and patterning during the ontogeny of cortical neural stem and progenitor cells. In order to dissect regulatory mechanisms that orchestrate the stage-specific differentiation process, we developed a computational framework to infer key regulators of each cell-state transition based on the progressive remodelling of the epigenetic landscape and then validated these through a pooled short hairpin RNA screen. We were also able to refine our previous observations on epigenetic priming at transcription factor binding sites and suggest here that they are mediated by combinations of core and stage-specific factors. Taken together, we demonstrate the utility of our system and outline a general framework, not limited to the context of the neural lineage, to dissect regulatory circuits of differentiation.

  19. Ribavirin exerts differential effects on functions of Cd4+ Th1, Th2, and regulatory T cell clones in hepatitis C.

    Directory of Open Access Journals (Sweden)

    Bettina Langhans

    Full Text Available Ribavirin improves outcomes of therapy in chronic hepatitis C but its mode of action has still remained unclear. Since ribavirin has been proposed to modulate the host's T cell responses, we studied its direct effects on CD4(+ T cell clones with diverse functional polarization which had been generated from patients with chronic hepatitis C. We analysed in vitro proliferation ([(3H] thymidine uptake and cytokine responses (IL-10, IFN-gamma at varying concentrations of ribavirin (0-10 µg/ml in 8, 9 and 7 CD4(+ TH1, TH2 and regulatory T cell (Treg clones, respectively. In co-culture experiments, we further determined effects of ribarivin on inhibition of TH1 and TH2 effector cells by Treg clones. All clones had been generated from peripheral blood of patients with chronic hepatitis C in the presence of HCV core protein. Ribavirin enhanced proliferation of T effector cells and increased production of IFN-gamma in TH1 clones, but had only little effect on IL-10 secretion in TH2 clones. However, ribavirin markedly inhibited IL-10 release in Treg clones in a dose dependent fashion. These Treg clones suppressed proliferation of T effector clones by their IL-10 secretion, and in co-culture assays ribavirin reversed Treg-mediated suppression of T effector cells. Our in vitro data suggest that--in addition to its immunostimulatory effects on TH1 cells--ribavirin can inhibit functions of HCV-specific Tregs and thus reverses Treg-mediated suppression of T effector cells in chronic hepatitis C.

  20. Differential regulation of native estrogen receptor-regulatory elements by estradiol, tamoxifen, and raloxifene.

    Science.gov (United States)

    Levy, Nitzan; Tatomer, Dierdre; Herber, Candice B; Zhao, Xiaoyue; Tang, Hui; Sargeant, Toby; Ball, Lonnele J; Summers, Jonathan; Speed, Terence P; Leitman, Dale C

    2008-02-01

    Estrogen receptors (ERs) regulate gene transcription by interacting with regulatory elements. Most information regarding how ER activates genes has come from studies using a small set of target genes or simple consensus sequences such as estrogen response element, activator protein 1, and Sp1 elements. However, these elements cannot explain the differences in gene regulation patterns and clinical effects observed with estradiol (E(2)) and selective estrogen receptor modulators. To obtain a greater understanding of how E(2) and selective estrogen receptor modulators differentially regulate genes, it is necessary to investigate their action on a more comprehensive set of native regulatory elements derived from ER target genes. Here we used chromatin immunoprecipitation-cloning and sequencing to isolate 173 regulatory elements associated with ERalpha. Most elements were found in the introns (38%) and regions greater than 10 kb upstream of the transcription initiation site (38%); 24% of the elements were found in the proximal promoter region (tamoxifen with ERalpha or ERbeta. Tamoxifen was more effective than raloxifene at activating the elements with ERalpha, whereas raloxifene was superior with ERbeta. Our findings demonstrate that E(2), tamoxifen, and raloxifene differentially regulate native ER-regulatory elements isolated by chromatin immunoprecipitation with ERalpha and ERbeta.

  1. Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo.

    Science.gov (United States)

    Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

    2016-10-01

    Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn's disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Effects of exposure to extremely low-frequency electromagnetic fields on the differentiation of Th17 T cells and regulatory T cells.

    Science.gov (United States)

    Lee, Yun-Jung; Hyung, Kyeong Eun; Yoo, Jong-Sun; Jang, Ye Won; Kim, Soo Jeong; Lee, Do Ik; Lee, Sang Joon; Park, So-Young; Jeong, Ji Hoon; Hwang, Kwang Woo

    2016-10-01

    The potential risks that electromagnetic fields (EMF) pose to human physiology have been debated for several decades, especially considering that EMF is almost omnipresent and some occupations involve regular exposure to particularly strong fields. In the present study, the effects of 60 Hz 0.3 mT EMF on CD4+ T cells were evaluated. Production of T cell related cytokines, IFN-γ and IL-2, was not altered in CD4+ T cells that were exposed to EMF, and cell proliferation was also unaffected. The expression of genes present in a subset of Th17 cells was upregulated following EMF exposure, and the production of effector cytokines of the IL-17A subset also increased. To determine signaling pathways that underlie these effects, phosphorylation of STAT3 and SMAD3, downstream molecules of cytokines critical for Th17 induction, was analyzed. Increased SMAD3 phosphorylation level in cells exposed to EMF, suggesting that SMAD3 may be at least in part causing the increased Th17 cell production. Differentiation of Treg, another CD4+ T cell subset induced by SMAD3 signaling, was also elevated following EMF exposure. These results suggest that 60 Hz 0.3 mT EMF exposure amplifies TGF-β signaling and increases the generation of specific T cell subsets.

  3. Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Hall John C

    2008-09-01

    Full Text Available Abstract Background The regulatory subunit of cAMP-dependent protein kinase (PKA exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I and type II (PKA-II. Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8. Results RIα transfected cells exhibit hyper-proliferative growth and RIIβ transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RIα, RIIβ, and parental OVCAR cells. Genes specifically up-regulated in RIα cells were highly enriched for pathways involved in cell growth while genes up-regulated in RIIβ cells were enriched for pathways involved in differentiation. A large group of genes (~3600 was regulated along an axis of proliferation/differentiation between RIα, parental, and RIIβ cells. RIα/wt and RIIβ/wt gene regulation was shown by two separate and distinct gene set analytical methods to be strongly cross-correlated with a generic model of cellular differentiation. Conclusion Overexpression of PKA regulatory subunits in an ovarian cancer cell line dramatically influences the cell phenotype. The proliferation phenotype is strongly correlated with recently identified clinical biomarkers predictive of poor prognosis in ovarian cancer suggesting a possible pivotal role for PKA regulation in disease progression.

  4. Modifier effects between regulatory and protein-coding variation.

    Directory of Open Access Journals (Sweden)

    Antigone S Dimas

    2008-10-01

    Full Text Available Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs. We predict that about 18% (1,502 out of 8,233 nsSNPs of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants.

  5. Modifier effects between regulatory and protein-coding variation.

    Science.gov (United States)

    Dimas, Antigone S; Stranger, Barbara E; Beazley, Claude; Finn, Robert D; Ingle, Catherine E; Forrest, Matthew S; Ritchie, Matthew E; Deloukas, Panos; Tavaré, Simon; Dermitzakis, Emmanouil T

    2008-10-01

    Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants.

  6. Differentiating the differential rotation effect.

    Science.gov (United States)

    Boyarskaya, Evgenia; Hecht, Heiko

    2012-07-01

    As an observer views a picture from different viewing angles, objects in the picture appear to maintain their orientation relative to the observer. For instance, the eyes of a portrait appear to follow the observer as he or she views the image from different angles. We have explored this rotation effect, often called the Mona Lisa effect. We report three experiments that used portrait photographs to test variations of the Mona Lisa effect. The first experiment introduced picture displacements relative to the observer in directions beyond the horizontal plane. The Mona Lisa effect remained robust for vertical and/or diagonal observer displacements. The experiment also included conditions in which the portrait had averted gaze directions. An interaction between picture position relative to the observer and gaze direction was found. The second experiment followed up on very pronounced individual differences, suggesting that the Mona Lisa effect is even stronger than it should be for half of all observers (over-rotators). These individual differences do not correlate with any of the standard personality dimensions (Big Five) or with spatial intelligence. In the third experiment, we extended the experiment to virtual 3D heads using the same gaze directions and picture displacements as for the 2D portrait faces. Besides the picture displacements relative to the observer, we also added observer displacements relative to the picture. 3D pictures showed the Mona Lisa effect, but to a smaller extent than did 2D pictures. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. A gene regulatory network for root epidermis cell differentiation in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Angela Bruex

    2012-01-01

    Full Text Available The root epidermis of Arabidopsis provides an exceptional model for studying the molecular basis of cell fate and differentiation. To obtain a systems-level view of root epidermal cell differentiation, we used a genome-wide transcriptome approach to define and organize a large set of genes into a transcriptional regulatory network. Using cell fate mutants that produce only one of the two epidermal cell types, together with fluorescence-activated cell-sorting to preferentially analyze the root epidermis transcriptome, we identified 1,582 genes differentially expressed in the root-hair or non-hair cell types, including a set of 208 "core" root epidermal genes. The organization of the core genes into a network was accomplished by using 17 distinct root epidermis mutants and 2 hormone treatments to perturb the system and assess the effects on each gene's transcript accumulation. In addition, temporal gene expression information from a developmental time series dataset and predicted gene associations derived from a Bayesian modeling approach were used to aid the positioning of genes within the network. Further, a detailed functional analysis of likely bHLH regulatory genes within the network, including MYC1, bHLH54, bHLH66, and bHLH82, showed that three distinct subfamilies of bHLH proteins participate in root epidermis development in a stage-specific manner. The integration of genetic, genomic, and computational analyses provides a new view of the composition, architecture, and logic of the root epidermal transcriptional network, and it demonstrates the utility of a comprehensive systems approach for dissecting a complex regulatory network.

  8. Pre-commercial procurement : regulatory effectiveness?

    NARCIS (Netherlands)

    Apostol, Anca Ramona

    2014-01-01

    Is public procurement of research and development (‘R&D’) services the key to European Union (‘EU’)’s sustainable welfare? Is it being regulated in accordance with economic prescripts for effectiveness? Is the regulatory and policy setting clear and comprehensive in order to stimulate a widespread u

  9. Analysis of regulatory network involved in mechanical induction of embryonic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Xinan Zhang

    Full Text Available Embryonic stem cells are conventionally differentiated by modulating specific growth factors in the cell culture media. Recently the effect of cellular mechanical microenvironment in inducing phenotype specific differentiation has attracted considerable attention. We have shown the possibility of inducing endoderm differentiation by culturing the stem cells on fibrin substrates of specific stiffness. Here, we analyze the regulatory network involved in such mechanically induced endoderm differentiation under two different experimental configurations of 2-dimensional and 3-dimensional culture, respectively. Mouse embryonic stem cells are differentiated on an array of substrates of varying mechanical properties and analyzed for relevant endoderm markers. The experimental data set is further analyzed for identification of co-regulated transcription factors across different substrate conditions using the technique of bi-clustering. Overlapped bi-clusters are identified following an optimization formulation, which is solved using an evolutionary algorithm. While typically such analysis is performed at the mean value of expression data across experimental repeats, the variability of stem cell systems reduces the confidence on such analysis of mean data. Bootstrapping technique is thus integrated with the bi-clustering algorithm to determine sets of robust bi-clusters, which is found to differ significantly from corresponding bi-clusters at the mean data value. Analysis of robust bi-clusters reveals an overall similar network interaction as has been reported for chemically induced endoderm or endodermal organs but with differences in patterning between 2-dimensional and 3-dimensional culture. Such analysis sheds light on the pathway of stem cell differentiation indicating the prospect of the two culture configurations for further maturation.

  10. Regulatory circuits controlling white versus brown adipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, Jacob B; Kristiansen, Karsten

    2006-01-01

    Adipose tissue is a major endocrine organ that exerts a profound influence on whole-body homoeostasis. Two types of adipose tissue exist in mammals: WAT (white adipose tissue) and BAT (brown adipose tissue). WAT stores energy and is the largest energy reserve in mammals, whereas BAT, expressing UCP......1 (uncoupling protein 1), can dissipate energy through adaptive thermogenesis. In rodents, ample evidence supports BAT as an organ counteracting obesity, whereas less is known about the presence and significance of BAT in humans. Despite the different functions of white and brown adipocytes......, knowledge of factors differentially influencing the formation of white and brown fat cells is sparse. Here we summarize recent progress in the molecular understanding of white versus brown adipocyte differentiation, including novel insights into transcriptional and signal transduction pathways. Since...

  11. Lin28b Regulates Fetal Regulatory T Cell Differentiation through Modulation of TGF-β Signaling.

    Science.gov (United States)

    Bronevetsky, Yelena; Burt, Trevor D; McCune, Joseph M

    2016-12-01

    Immune tolerance between the fetus and mother represents an active process by which the developing fetus must not mount immune responses to noninherited Ags on chimeric maternal cells that reside in fetal tissue. This is, in part, mediated by the suppressive influence of CD4(+)FOXP3(+)CD25(+) regulatory T cells (Tregs). Fetal secondary lymphoid organs have an increased frequency of Tregs and, as compared with adult T cells, fetal naive CD4(+) T cells exhibit a strong predisposition to differentiate into Tregs when stimulated. This effect is mediated by the TCR and TGF-β pathways, and fetal T cells show significantly increased Treg differentiation in response to anti-CD3 and TGF-β stimulation. Naive fetal T cells also exhibit increased signaling through the TGF-β pathway, with these cells demonstrating increased expression of the signaling mediators TGF-βRI, TGF-βRIII, and SMAD2, and higher levels of SMAD2/SMAD3 phosphorylation. Increased fetal Treg differentiation is mediated by the RNA-binding protein Lin28b, which is overexpressed in fetal T cells as compared with adult cells. When Lin28b expression is decreased in naive fetal T cells, they exhibit decreased Treg differentiation that is associated with decreased TGF-β signaling and lowered expression of TGF-βRI, TGF-βRIII, and SMAD2. Lin28b regulates the maturation of let-7 microRNAs, and these TGF-β signaling mediators are let-7 targets. We hypothesize that loss of Lin28b expression in fetal T cells leads to increased mature let-7, which causes decreased expression of TGF-βRI, TGF-βRIII, and SMAD2 proteins. A reduction in TGF-β signaling leads to reduced Treg numbers. Copyright © 2016 by The American Association of Immunologists, Inc.

  12. Regulatory effects of simvastatin on osteoblast proliferation, differentiation and connexin 43 expression%辛伐他汀对成骨细胞增殖分化及连接蛋白43表达的调控

    Institute of Scientific and Technical Information of China (English)

    王国亮; 蔡湘波; 李文壮; 罗胜明; 陈泽雁; 陈戈胜

    2014-01-01

    BACKGROUND:The effects and molecular mechanism of simvastatin on the proliferation and differentiation of osteoblasts remain unclear. Especial y, we do not know much about the effects of connexin 43. OBJECTIVE:To evaluate the effects of simvastatin on the proliferation and differentiation of osteoblasts and the regulatory effect of simvastatin on the expression of osteogenic genes and connexin 43. METHODS:Newborn Sprague-Dawley rats were chosen and the cranium digestion method was used to culture osteoblasts. The different concentrations of simvastatin (0.062 5, 0.125, 0.25, 0.5 and 1.0μmol/L) were used to deal with osteoblasts. The proliferative effect of simvastatin on osteoblasts was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The effect of simvastatin on osteoblast differentiation was measured with alkaline phosphatase activities. The mRNA and protein expression of osteogenic genes and connexin 43 were measured by real time quantitative RT-PCR and western blot assay. RESULTS AND CONCLUSION:There were no significant differences in absorbance values of simvastatin groups at 3 days (P>0.05). However, at 4 and 5 days, absorbance values were lower in the simvastatin groups than those in the control group (P  目的:探讨辛伐他汀对成骨细胞增殖分化及成骨基因和连接蛋白43表达的调控作用。  方法:选取新生SD大鼠,采用颅盖骨消化法培养成骨细胞。采用不同浓度辛伐他汀(0.0625,0.125,0.25,0.5和1.0μmol/L)处理成骨细胞,MTT检测辛伐他汀对成骨细胞增殖作用的影响;碱性磷酸酶活性检测辛伐他汀对成骨细胞分化作用的影响;实时定量RT-PCR和免疫印迹检测细胞成骨基因和间隙连接蛋白43 mRNA和蛋白的表达。  结果与结论:细胞培养第3天,辛伐他汀组各浓度组MTT吸光度值比较差异无显著性意义(P >0.05);但是培养第4天和第5天,辛伐他汀各浓度组MTT

  13. From System-Wide Differential Gene Expression to Perturbed Regulatory Factors: A Combinatorial Approach.

    Directory of Open Access Journals (Sweden)

    Gaurang Mahajan

    Full Text Available High-throughput experiments such as microarrays and deep sequencing provide large scale information on the pattern of gene expression, which undergoes extensive remodeling as the cell dynamically responds to varying environmental cues or has its function disrupted under pathological conditions. An important initial step in the systematic analysis and interpretation of genome-scale expression alteration involves identification of a set of perturbed transcriptional regulators whose differential activity can provide a proximate hypothesis to account for these transcriptomic changes. In the present work, we propose an unbiased and logically natural approach to transcription factor enrichment. It involves overlaying a list of experimentally determined differentially expressed genes on a background regulatory network coming from e.g. literature curation or computational motif scanning, and identifying that subset of regulators whose aggregated target set best discriminates between the altered and the unaffected genes. In other words, our methodology entails testing of all possible regulatory subnetworks, rather than just the target sets of individual regulators as is followed in most standard approaches. We have proposed an iterative search method to efficiently find such a combination, and benchmarked it on E. coli microarray and regulatory network data available in the public domain. Comparative analysis carried out on artificially generated differential expression profiles, as well as empirical factor overexpression data for M. tuberculosis, shows that our methodology provides marked improvement in accuracy of regulatory inference relative to the standard method that involves evaluating factor enrichment in an individual manner.

  14. From System-Wide Differential Gene Expression to Perturbed Regulatory Factors: A Combinatorial Approach.

    Science.gov (United States)

    Mahajan, Gaurang; Mande, Shekhar C

    2015-01-01

    High-throughput experiments such as microarrays and deep sequencing provide large scale information on the pattern of gene expression, which undergoes extensive remodeling as the cell dynamically responds to varying environmental cues or has its function disrupted under pathological conditions. An important initial step in the systematic analysis and interpretation of genome-scale expression alteration involves identification of a set of perturbed transcriptional regulators whose differential activity can provide a proximate hypothesis to account for these transcriptomic changes. In the present work, we propose an unbiased and logically natural approach to transcription factor enrichment. It involves overlaying a list of experimentally determined differentially expressed genes on a background regulatory network coming from e.g. literature curation or computational motif scanning, and identifying that subset of regulators whose aggregated target set best discriminates between the altered and the unaffected genes. In other words, our methodology entails testing of all possible regulatory subnetworks, rather than just the target sets of individual regulators as is followed in most standard approaches. We have proposed an iterative search method to efficiently find such a combination, and benchmarked it on E. coli microarray and regulatory network data available in the public domain. Comparative analysis carried out on artificially generated differential expression profiles, as well as empirical factor overexpression data for M. tuberculosis, shows that our methodology provides marked improvement in accuracy of regulatory inference relative to the standard method that involves evaluating factor enrichment in an individual manner.

  15. microRNA regulatory mechanism by which PLLA aligned nanofibers influence PC12 cell differentiation

    Science.gov (United States)

    Yu, Yadong; Lü, Xiaoying; Ding, Fei

    2015-08-01

    Objective. Aligned nanofibers (AFs) are regarded as promising biomaterials in nerve tissue engineering. However, a full understanding of the biocompatibility of AFs at the molecular level is still challenging. Therefore, the present study focused on identifying the microRNA (miRNA)-mediated regulatory mechanism by which poly-L-lactic acid (PLLA) AFs influence PC12 cell differentiation. Approach. Firstly, the effects of PLLA random nanofibers (RFs)/AFs and PLLA films (control) on the biological responses of PC12 cells that are associated with neuronal differentiation were examined. Then, SOLiD sequencing and cDNA microarray were employed to profile the expressions of miRNAs and mRNAs. The target genes of the misregulated miRNAs were predicted and compared with the mRNA profile data. Functions of the matched target genes (the intersection between the predicted target genes and the experimentally-determined, misregulated genes) were analyzed. Main results. The results revealed that neurites spread in various directions in control and RF groups. In the AF group, most neurites extended in parallel with each other. The glucose consumption and lactic acid production in the RF and AF groups were higher than those in the control group. Compared with the control group, 42 and 94 miRNAs were significantly dysregulated in the RF and AF groups, respectively. By comparing the predicted target genes with the mRNA profile data, five and 87 matched target genes were found in the RF and AF groups, respectively. Three of the matched target genes in the AF group were found to be associated with neuronal differentiation, whereas none had this association in the RF group. The PLLA AFs induced the dysregulation of miRNAs that regulate many biological functions, including axonal guidance, lipid metabolism and long-term potentiation. In particular, two miRNA-matched target gene-biological function modules associated with neuronal differentiation were identified as follows: (1) miR-23b, mi

  16. Role of cytokines in thymus- versus peripherally derived- regulatory T cell differentiation and function

    Directory of Open Access Journals (Sweden)

    jérémie david Goldstein

    2013-06-01

    Full Text Available CD4+CD25+Foxp3+ regulatory T cells (Tregs are essential players in the control of immune responses. Recently, accordingly to their origin, two main subsets of Tregs have been described: thymus-derived Tregs (tTregs and peripherally derived Tregs (pTregs. Numerous signaling pathways including the IL-2/STAT5 or the TGF-β/Smad3 pathways play a crucial role in segregating the two lineages. Here, we review some of the information existing on the distinct requirements of IL-2, TGF-β and TNF-α three major cytokines involved in tTreg and pTreg generation, homeostasis and function. Today it is clear that signaling via the IL-2Rβ chain (CD122 common to IL-2 and IL-15 is required for proper differentiation of tTregs and for tTreg and pTreg survival in the periphery. This notion has led to the development of promising therapeutic strategies based on low-dose IL-2 administration to boost the patients' own Treg compartment and dampen autoimmunity and inflammation. Also, solid evidence points to TGF-β as the master regulator of pTreg differentiation and homeostasis. However, therapeutic administration of TGF-β is difficult to implement due to toxicity and safety issues. Knowledge on the role of TNF-α on the biology of Tregs is fragmentary and inconsistent between mice and humans. Moreover, emerging results from the clinical use of TNF-α inhibitors indicate that part of their anti-inflammatory effect may be dependent on their action on Tregs. Given the profusion of clinical trials testing cytokine administration or blocking to modulate inflammatory diseases, a better knowledge of the effects of cytokines on tTregs and pTregs biology is necessary to improve the efficiency of these immunotherapies.

  17. Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling

    Science.gov (United States)

    Corral-Jara, Karla F.; Gómez-Leyva, Juan F.; Rosenstein, Yvonne; Jose-Abrego, Alexis; Roman, Sonia

    2016-01-01

    We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein, in vitro stimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor gene HAVCR1/TIM-1 was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1. PMID:27578921

  18. Schisandrin B inhibits Th1/Th17 differentiation and promotes regulatory T cell expansion in mouse lymphocytes.

    Science.gov (United States)

    Chen, Zhaoyang; Guo, Min; Song, Guohua; Gao, Jiping; Zhang, Yinhong; Jing, Zhijie; Liu, Tianfu; Dong, Chuan

    2016-06-01

    Schisandrin B (Sch-B), the most abundant active ingredient of the fruit of Schisandra chinensis, has been proposed to have antioxidant, anti-tumor and anti-inflammatory effects. The present study was undertaken to investigate the effect of Sch-B on differentiation of T helper cells (Th). Using mouse splenic lymphocytes stimulated with concanavalin A (Con A) in vitro and ex vivo as inflammation models, we found that Sch-B significantly inhibited secretion of Th1 and Th17 related cytokines, such as IFN-γ and IL-17. In addition, we found that Sch-B suppressed the differentiation of naive CD4+ T cells into Th1 and Th17 cells, while promoted their differentiation into the regulatory T cells (Treg) in vitro. We further found that Sch-B suppressed transcription of Th1-related T-box transcription factor, T-bet, and Th17-related transcription factor, retinoid related orphan receptor gamma t (RORγt), while enhanced transcription of Treg-related transcription factor forkhead box protein 3 (Foxp3) in naive CD4+ T cells under Th cell polarization conditions. Furthermore, the effect of Sch-B on the T cell differentiation was abrogated by heme oxygenase-1 (HO-1) inhibitor zinc protoporphyrin. Taken together, we conclude that Sch-B can modulate differentiation of naïve CD4+ T cells into specific lineages of effector cells, which may have potential benefits for treatment of autoimmune diseases.

  19. A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans.

    Science.gov (United States)

    Doitsidou, Maria; Flames, Nuria; Topalidou, Irini; Abe, Namiko; Felton, Terry; Remesal, Laura; Popovitchenko, Tatiana; Mann, Richard; Chalfie, Martin; Hobert, Oliver

    2013-06-15

    Terminal differentiation programs in the nervous system are encoded by cis-regulatory elements that control the expression of terminal features of individual neuron types. We decoded the regulatory information that controls the expression of five enzymes and transporters that define the terminal identity of all eight dopaminergic neurons in the nervous system of the Caenorhabditis elegans hermaphrodite. We show that the tightly coordinated, robust expression of these dopaminergic enzymes and transporters ("dopamine pathway") is ensured through a combinatorial cis-regulatory signature that is shared by all dopamine pathway genes. This signature is composed of an Ets domain-binding site, recognized by the previously described AST-1 Ets domain factor, and two distinct types of homeodomain-binding sites that act in a partially redundant manner. Through genetic screens, we identified the sole C. elegans Distalless/Dlx ortholog, ceh-43, as a factor that acts through one of the homeodomain sites to control both induction and maintenance of terminal dopaminergic fate. The second type of homeodomain site is a Pbx-type site, which is recognized in a partially redundant and neuron subtype-specific manner by two Pbx factors, ceh-20 and ceh-40, revealing novel roles of Pbx factors in the context of terminal neuron differentiation. Taken together, we revealed a specific regulatory signature and cognate, terminal selector-type transcription factors that define the entire dopaminergic nervous system of an animal. Dopaminergic neurons in the mouse olfactory bulb express a similar combinatorial transcription factor collective of Ets/Dlx/Pbx factors, suggesting deep phylogenetic conservation of dopaminergic regulatory programs.

  20. Regulatory mechanism of protein metabolic pathway during the differentiation process of chicken male germ cell.

    Science.gov (United States)

    Li, Dong; Zuo, Qisheng; Lian, Chao; Zhang, Lei; Shi, Qingqing; Zhang, Zhentao; Wang, Yingjie; Ahmed, Mahmoud F; Tang, Beibei; Xiao, Tianrong; Zhang, Yani; Li, Bichun

    2015-08-01

    We explored the regulatory mechanism of protein metabolism during the differentiation process of chicken male germ cells and provide a basis for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro. We sequenced the transcriptome of embryonic stem cells, primordial germ cells, and spermatogonial stem cells with RNA sequencing (RNA-Seq), bioinformatics analysis methods, and detection of the key genes by quantitative reverse transcription PCR (qRT-PCR). Finally, we found 16 amino acid metabolic pathways enriched in the biological metabolism during the differentiation process of embryonic stem cells to primordial germ cells and 15 amino acid metabolic pathways enriched in the differentiation stage of primordial germ cells to spermatogonial stem cells. We found three pathways, arginine-proline metabolic pathway, tyrosine metabolic pathway, and tryptophan metabolic pathway, significantly enriched in the whole differentiation process of embryonic stem cells to spermatogonial stem cells. Moreover, for these three pathways, we screened key genes such as NOS2, ADC, FAH, and IDO. qRT-PCR results showed that the expression trend of these genes were the same to RNA-Seq. Our findings showed that the three pathways and these key genes play an important role in the differentiation process of embryonic stem cells to male germ cells. These results provide basic information for improving the induction system of embryonic stem cell differentiation to male germ cells in vitro.

  1. NetDiff - Bayesian model selection for differential gene regulatory network inference.

    Science.gov (United States)

    Thorne, Thomas

    2016-12-16

    Differential networks allow us to better understand the changes in cellular processes that are exhibited in conditions of interest, identifying variations in gene regulation or protein interaction between, for example, cases and controls, or in response to external stimuli. Here we present a novel methodology for the inference of differential gene regulatory networks from gene expression microarray data. Specifically we apply a Bayesian model selection approach to compare models of conserved and varying network structure, and use Gaussian graphical models to represent the network structures. We apply a variational inference approach to the learning of Gaussian graphical models of gene regulatory networks, that enables us to perform Bayesian model selection that is significantly more computationally efficient than Markov Chain Monte Carlo approaches. Our method is demonstrated to be more robust than independent analysis of data from multiple conditions when applied to synthetic network data, generating fewer false positive predictions of differential edges. We demonstrate the utility of our approach on real world gene expression microarray data by applying it to existing data from amyotrophic lateral sclerosis cases with and without mutations in C9orf72, and controls, where we are able to identify differential network interactions for further investigation.

  2. Regulatory effects of fisetin on microglial activation.

    Science.gov (United States)

    Chuang, Jing-Yuan; Chang, Pei-Chun; Shen, Yi-Chun; Lin, Chingju; Tsai, Cheng-Fang; Chen, Jia-Hong; Yeh, Wei-Lan; Wu, Ling-Hsuan; Lin, Hsiao-Yun; Liu, Yu-Shu; Lu, Dah-Yuu

    2014-06-26

    Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin)-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase)-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

  3. Regulatory Effects of Fisetin on Microglial Activation

    Directory of Open Access Journals (Sweden)

    Jing-Yuan Chuang

    2014-06-01

    Full Text Available Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO production, and inducible nitric oxide synthase (iNOS expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

  4. A systems biology approach identifies a regulatory network in parotid acinar cell terminal differentiation.

    Directory of Open Access Journals (Sweden)

    Melissa A Metzler

    genetic switch involving transcription factors and microRNAs, and transition to an Xbp1 driven differentiation network. This proposed network suggests key regulatory interactions in parotid gland terminal differentiation.

  5. Overall Effects of China's Recent Macroeconomic Regulatory Policies

    Institute of Scientific and Technical Information of China (English)

    LiJianwei,; ZhuShida; DavidKelly

    2004-01-01

    China's economic regulatory policies in the last few years have played an important role in curbing the slide of its consistent growth drive. In terms of overall effects, the macroeconomic regulatory policies of each fiscal year have attained their targets. In some years, however,

  6. Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma.

    Science.gov (United States)

    Kudou, Michihiro; Shiozaki, Atsushi; Kosuga, Toshiyuki; Ichikawa, Daisuke; Konishi, Hirotaka; Morimura, Ryo; Komatsu, Shuhei; Ikoma, Hisashi; Fujiwara, Hitoshi; Okamoto, Kazuma; Hosogi, Shigekuni; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

    2016-01-01

    Background : Hypotonic shock induces cytocidal effects through cell rupture, and cancer therapy based on this mechanism has been clinically administered to hepatocellular carcinoma patients. We herein investigated the effectiveness of hypotonic shock combined with the inhibition of regulatory volume decrease as cancer therapy for hepatocellular carcinoma. Methods : Morphological changes in human hepatocellular carcinoma cell lines were observed under a differential interference contrast microscope connected to a high-speed digital video camera. Cell volume changes under hypotonic shock with or without chloride, potassium, or water channel blockers were observed using a high-resolution flow cytometer. In order to investigate cytocidal effects, the number of surviving cells was compared after exposure to hypotonic solution with and without each channel blocker (re-incubation experiment). Results : Video recordings showed that cells exposed to distilled water rapidly swelled and then ruptured. Cell volume measurements revealed regulatory volume decrease under mild hypotonic shock, whereas severe hypotonic shock increased the number of broken fragments as a result of cell rupture. Moreover, regulatory volume decrease was inhibited in cells treated with each channel blocker. Re-incubation experiments showed the cytocidal effects of hypotonic shock in cells exposed to hypotonic solution, and additional treatments with each channel blocker enhanced these effects. Conclusion : The inhibition of regulatory volume decrease with chloride, potassium, or water channel blockers may enhance the cytocidal effects of hypotonic shock in hepatocellular carcinoma. Hypotonic shock combined with the inhibition of regulatory volume decrease was a more effective therapy than hypotonic shock alone.

  7. Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Jing Liu

    2013-01-01

    Full Text Available Phenanthrene (Phe, a polycyclic aromatic hydrocarbon (PAH, is a major constituent of urban air pollution. There have been conflicting results regarding the role of other AhR ligands 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD and 6-formylindolo [3,2-b]carbazole (FICZ in modifying regulatory T cell populations (Treg or T helper (Th17 differentiation, and the effects of Phe have been understudied. We hypothesized that different chemical entities of PAH induce Treg to become either Th2 or Th17 effector T cells through epigenetic modification of FOXP3. To determine specific effects on T cell populations by phenanthrene, primary human Treg were treated with Phe, TCDD, or FICZ and assessed for function, gene expression, and phenotype. Methylation of CpG sites within the FOXP3 locus reduced FOXP3 expression, leading to impaired Treg function and conversion of Treg into a CD4+CD25lo Th2 phenotype in Phe-treated cells. Conversely, TCDD treatment led to epigenetic modification of IL-17A and conversion of Treg to Th17 T cells. These findings present a mechanism by which exposure to AhR-ligands mediates human T cell responses and begins to elucidate the relationship between environmental exposures, immune modulation, and initiation of human disease.

  8. Timing of in utero malaria exposure influences fetal CD4 T cell regulatory versus effector differentiation

    Directory of Open Access Journals (Sweden)

    Mary Prahl

    2016-10-01

    Full Text Available Abstract Background In malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses. Methods Using cord blood samples from a cohort of mother-infant pairs followed from early in pregnancy until delivery, flow cytometry analysis was completed to assess the relationship between pregnancy-associated malaria and fetal cord blood CD4 and dendritic cell phenotypes. Results Cord blood FoxP3+ Treg counts were higher in infants born to mothers with Plasmodium parasitaemia early in pregnancy (12–20 weeks of gestation; p = 0.048, but there was no association between Treg counts and the presence of parasites in the placenta at the time of delivery (by loop-mediated isothermal amplification (LAMP; p = 0.810. In contrast, higher frequencies of activated CD4 T cells (CD25+FoxP3−CD127+ were observed in the cord blood of neonates with active placental Plasmodium infection at the time of delivery (p = 0.035. This population exhibited evidence of effector memory differentiation, suggesting priming of effector T cells in utero. Lastly, myeloid dendritic cells were higher in the cord blood of infants with histopathologic evidence of placental malaria (p < 0.0001. Conclusion Together, these data indicate that in utero exposure to malaria drives expansion of both regulatory and effector T cells in the fetus, and that the timing of this exposure has a pivotal role in determining the polarization of the fetal immune response.

  9. Identification of Biomarker and Co-Regulatory Motifs in Lung Adenocarcinoma Based on Differential Interactions.

    Directory of Open Access Journals (Sweden)

    Ning Zhao

    Full Text Available Changes in intermolecular interactions (differential interactions may influence the progression of cancer. Specific genes and their regulatory networks may be more closely associated with cancer when taking their transcriptional and post-transcriptional levels and dynamic and static interactions into account simultaneously. In this paper, a differential interaction analysis was performed to detect lung adenocarcinoma-related genes. Furthermore, a miRNA-TF (transcription factor synergistic regulation network was constructed to identify three kinds of co-regulated motifs, namely, triplet, crosstalk and joint. Not only were the known cancer-related miRNAs and TFs (let-7, miR-15a, miR-17, TP53, ETS1, and so on were detected in the motifs, but also the miR-15, let-7 and miR-17 families showed a tendency to regulate the triplet, crosstalk and joint motifs, respectively. Moreover, several biological functions (i.e., cell cycle, signaling pathways and hemopoiesis associated with the three motifs were found to be frequently targeted by the drugs for lung adenocarcinoma. Specifically, the two 4-node motifs (crosstalk and joint based on co-expression and interaction had a closer relationship to lung adenocarcinoma, and so further research was performed on them. A 10-gene biomarker (UBC, SRC, SP1, MYC, STAT3, JUN, NR3C1, RB1, GRB2 and MAPK1 was selected from the joint motif, and a survival analysis indicated its significant association with survival. Among the ten genes, JUN, NR3C1 and GRB2 are our newly detected candidate lung adenocarcinoma-related genes. The genes, regulators and regulatory motifs detected in this work will provide potential drug targets and new strategies for individual therapy.

  10. A microfluidic platform reveals differential response of regulatory T cells to micropatterned costimulation arrays.

    Science.gov (United States)

    Lee, Joung-Hyun; Dustin, Michael L; Kam, Lance C

    2015-11-01

    T cells are key mediators of adaptive immunity. However, the overall immune response is often directed by minor subpopulations of this heterogeneous family of cells, owing to specificity of activation and amplification of functional response. Knowledge of differences in signaling and function between T cell subtypes is far from complete, but is clearly needed for understanding and ultimately leveraging this branch of the adaptive immune response. This report investigates differences in cell response to micropatterned surfaces by conventional and regulatory T cells. Specifically, the ability of cells to respond to the microscale geometry of TCR/CD3 and CD28 engagement is made possible using a magnetic-microfluidic device that overcomes limitations in imaging efficiency associated with conventional microscopy equipment. This device can be readily assembled onto micropatterned surfaces while maintaining the activity of proteins and other biomolecules necessary for such studies. In operation, a target population of cells is tagged using paramagnetic beads, and then trapped in a divergent magnetic field within the chamber. Following washing, the target cells are released to interact with a designated surface. Characterization of this system with mouse CD4(+) T cells demonstrated a 50-fold increase in target-to-background cell purity, with an 80% collection efficiency. Applying this approach to CD4(+)CD25(+) regulatory T cells, it is then demonstrated that these rare cells respond less selectively to micro-scale features of anti-CD3 antibodies than CD4(+)CD25(-) conventional T cells, revealing a difference in balance between TCR/CD3 and LFA-1-based adhesion. PKC-θ localized to the distal pole of regulatory T cells, away from the cell-substrate interface, suggests a mechanism for differential regulation of TCR/LFA-1-based adhesion. Moreover, specificity of cell adhesion to anti-CD3 features was dependent on the relative position of anti-CD28 signaling within the cell

  11. Regulatory fit effects on perceived fiscal exchange and tax compliance.

    Science.gov (United States)

    Leder, Susanne; Mannetti, Lucia; Hölzl, Erik; Kirchler, Erich

    2010-04-01

    Paying taxes can be considered a contribution to the welfare of a society. But even though tax payments are redistributed to citizens in the form of public goods and services, taxpayers often do not perceive many benefits from paying taxes. Information campaigns about the use of taxes for financing public goods and services could increase taxpayers' understanding of the importance of taxes, strengthen their perception of fiscal exchange and consequently also increase tax compliance. Two studies examined how fit between framing of information and taxpayers' regulatory focus affects perceived fiscal exchange and tax compliance. Taxpayers should perceive the exchange between tax payments and provision of public goods and services as higher if information framing suits their regulatory focus. Study 1 supported this hypothesis for induced regulatory focus. Study 2 replicated the findings for chronic regulatory focus and further demonstrated that regulatory fit also affects tax compliance. The results provide further evidence for findings from previous studies concerning regulatory fit effects on tax attitudes and extend these findings to a context with low tax morale.

  12. 环境内分泌干扰物对性分化和性发育的神经内分泌调控网络的影响%Effects of environmental endocrine disruptors on neuroendocrine regulatory networks related to sexual differentiation and sexual development:a review of recent studies

    Institute of Scientific and Technical Information of China (English)

    高连连; 蔡德培

    2012-01-01

    Environmental endocrine disrupters (EEDs) are pollutants of many exogenous chemical classes, which are ubiquitous and persistent in the environment and can interfere with the neuroendocrine systems,disturb body's natural steroidogenesis, secretion, and receptor binding,removal of other aspects, thus lead to abnormal development of the human bodies and their progenies. Neuroendocrine regulatory networks, especially the regulatory networks of the hypothalamus play vital roles in sexual differentiation and the process of puberty. When neuroendocrine homeostasis is disrupted by environmental endocrine chemicals, a variety of perturbations about sexual differentiation and sexual development can ensue,particularly when endocrine disruption occurs during critical developmental periods. Emerging evidences have shown that the brain can be the direct targets of EEDs. Among neuroendocrine regulatory networks, gonadotropin-releasing hormone (GnRH) neurons, the kisspeptin/GPR54 system, glial cells, and brain aromatase are significantly disrupted by EEDs. Besides, EEDs also have trans —generational effects. This article will provide an overview of the effect of environmental endocrine disruption on neuroendocrine regulatory networks related to sexual differentiation and sexual development.%环境内分泌干扰物(environmental endocrine disrupters,EEDs)是环境中存在的一大类外源性化合物,可干扰机体神经内分泌系统,影响体内天然激素的合成、释放及与受体结合、代谢等过程,进而导致机体及其子代异常发育.神经内分泌调控网络(尤其是下丘脑调控网络)在机体性分化、性发育中发挥关键作用.神经内分泌系统稳态的失衡可致一系列的异常发育,尤其是处于性发育关键时期的胚胎期与青春期.越来越多的研究表明,大脑是EEDs直接作用位点,神经内分泌调控网络中受EEDs显著干扰的主要有促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)

  13. Regulatory effects on the population dynamics and wave propagation in a cell lineage model.

    Science.gov (United States)

    Wang, Mao-Xiang; Ma, Yu-Qiang; Lai, Pik-Yin

    2016-03-21

    We consider the interplay of cell proliferation, cell differentiation (and de-differentiation), cell movement, and the effect of feedback regulations on the population and propagation dynamics of different cell types in a cell lineage model. Cells are assumed to secrete and respond to negative feedback molecules which act as a control on the cell lineage. The cell densities are described by coupled reaction-diffusion partial differential equations, and the propagating wave front solutions in one dimension are investigated analytically and by numerical solutions. In particular, wavefront propagation speeds are obtained analytically and verified by numerical solutions of the equations. The emphasis is on the effects of the feedback regulations on different stages in the cell lineage. It is found that when the progenitor cell is negatively regulated, the populations of the cell lineage are strongly down-regulated with the steady growth rate of the progenitor cell being driven to zero beyond a critical regulatory strength. An analytic expression for the critical regulation strength in terms of the model parameters is derived and verified by numerical solutions. On the other hand, if the inhibition is acting on the differentiated cells, the change in the population dynamics and wave propagation speed is small. In addition, it is found that only the propagating speed of the progenitor cells is affected by the regulation when the diffusion of the differentiated cells is large. In the presence of de-differentiation, the effect on down-regulating the progenitor population is weakened and there is no effect on the propagation speed due to regulation, suggesting that the effect of regulatory control is diminished by de-differentiation pathways.

  14. Cooperation goals, regulatory focus, and their combined effects on creativity

    NARCIS (Netherlands)

    Bittner, Jenny V.; Bruena, Mareen; Rietzschel, Eric F.

    2016-01-01

    This study examined the co-activation of cooperation versus competition goals with regulatory focus, and tested whether the combined effects on creativity are interactive or additive. An experiment with 192 adults showed two main effects, such that participants with a cooperation goal and a promotio

  15. Cooperation goals, regulatory focus, and their combined effects on creativity

    NARCIS (Netherlands)

    Bittner, Jenny V.; Bruena, Mareen; Rietzschel, Eric F.

    2016-01-01

    This study examined the co-activation of cooperation versus competition goals with regulatory focus, and tested whether the combined effects on creativity are interactive or additive. An experiment with 192 adults showed two main effects, such that participants with a cooperation goal and a

  16. Prediction of Cis-Regulatory Elements Controlling Genes Differentially Expressed by Retinal and Choroidal Vascular Endothelial Cells.

    Science.gov (United States)

    Choi, Dongseok; Appukuttan, Binoy; Binek, Sierra J; Planck, Stephen R; Stout, J Timothy; Rosenbaum, James T; Smith, Justine R

    2008-01-01

    Cultured endothelial cells of the human retina and choroid demonstrate distinct patterns of gene expression. We hypothesized that differential gene expression reflected differences in the interactions of transcription factors and respective cis-regulatory motifs(s) in these two emdothelial cell subpopulations, recognizing that motifs often exist as modules. We tested this hypothesis in silico by using TRANSFAC Professional and CisModule to identify cis-regulatory motifs and modules in genes that were differentially expressed by human retinal versus choroidal endothelial cells, as identified by analysis of a microarray data set. Motifs corresponding to eight transcription factors were significantly (p < 0.05) differentially abundant in genes that were relatively highly expressed in retinal (i.e., GCCR, HMGIY, HSF1, p53, VDR) or choroidal (i.e., E2F, YY1, ZF5) endothelial cells. Predicted cis-regulatory modules were quite different for these two groups of genes. Our findings raise the possibility of exploiting specific cis-regulatory motifs to target therapy at the ocular endothelial cells subtypes responsible for neovascular age-related macular degeneration or proliferative diabetic retinopathy.

  17. Reduction of regulatory risk: a network economic approach

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    Several definitions of regulatory risk are known from the literature. From the perspective of regulatory reform it is important to differentiate between the impact of a given regulatory scheme on the firm's risk exposure and the risk arising from discretionary behavior of regulatory agencies. Whereas the conse-quences of effective regulation in principle are known and accepted, excessive regulatory discretion may cause a strong need for regulatory reform. Regulatory reform focussing on the re...

  18. Regulatory Effects of Fisetin on Microglial Activation

    OpenAIRE

    Jing-Yuan Chuang; Pei-Chun Chang; Yi-Chun Shen; Chingju Lin; Cheng-Fang Tsai; Jia-Hong Chen; Wei-Lan Yeh; Ling-Hsuan Wu; Hsiao-Yun Lin; Yu-Shu Liu; Dah-Yuu Lu

    2014-01-01

    Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS...

  19. Regulatory Effects of Fisetin on Microglial Activation

    OpenAIRE

    Jing-Yuan Chuang; Pei-Chun Chang; Yi-Chun Shen; Chingju Lin; Cheng-Fang Tsai; Jia-Hong Chen; Wei-Lan Yeh; Ling-Hsuan Wu; Hsiao-Yun Lin; Yu-Shu Liu; Dah-Yuu Lu

    2014-01-01

    Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS...

  20. The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and nail differentiation.

    Science.gov (United States)

    Potter, Christopher S; Pruett, Nathanael D; Kern, Michael J; Baybo, Mary Ann; Godwin, Alan R; Potter, Kathleen A; Peterson, Ron L; Sundberg, John P; Awgulewitsch, Alexander

    2011-04-01

    Among the Hox genes, homeobox C13 (Hoxc13) has been shown to be essential for proper hair shaft differentiation, as Hoxc13 gene-targeted (Hoxc13(tm1Mrc)) mice completely lack external hair. Because of the remarkable overt phenotypic parallels to the Foxn1(nu) (nude) mutant mice, we sought to determine whether Hoxc13 and forkhead box N1 (Foxn1) might act in a common pathway of hair follicle (HF) differentiation. We show that the alopecia exhibited by both the Hoxc13(tm1Mrc) and Foxn1(nu) mice is because of strikingly similar defects in hair shaft differentiation and that both mutants suffer from a severe nail dystrophy. These phenotypic similarities are consistent with the extensive overlap between Hoxc13 and Foxn1 expression patterns in the HF and the nail matrix. Furthermore, DNA microarray analysis of skin from Hoxc13(tm1Mrc) mice identified Foxn1 as significantly downregulated along with numerous hair keratin genes. This Foxn1 downregulation apparently reflects the loss of direct transcriptional control by HOXC13 as indicated by our results obtained through co-transfection and chromatin immunoprecipitation (ChIP) assays. As presented in the discussion, these data support a regulatory model of keratinocyte differentiation in which HOXC13-dependent activation of Foxn1 is part of a regulatory cascade controlling the expression of terminal differentiation markers.

  1. Regulatory effect of porcine plasma protein hydrolysates on pasting and gelatinization action of corn starch.

    Science.gov (United States)

    Kong, Baohua; Niu, Haili; Sun, Fangda; Han, Jianchun; Liu, Qian

    2016-01-01

    The objective of this study was to investigate the regulatory effect of porcine plasma protein hydrolysates (PPPH) on the physicochemical, pasting, and gelatinization properties of corn starch (CS). The results showed that the solubility of CS markedly increased, whereas swelling power and gel penetration force decreased with increased PPPH concentration (Pgelatinization temperature as determined in differential scanning calorimetry (DSC) (Pgelatinization. Atomic force microscopy (AFM) images indicated that the blocklet sizes of gelatinized CS-PPPH mixtures were smaller and more uniform than native CS. The results proved that pasting and gelatinization abilities of CS can be effectively influenced by adding PPPH. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Expansion of myeloid-derived suppressor cells promotes differentiation of regulatory T cells in HIV-1+ individuals.

    Science.gov (United States)

    Wang, Ling; Zhao, Juan; Ren, Jun P; Wu, Xiao Y; Morrison, Zheng D; Elgazzar, Mohamed A; Ning, Shun B; Moorman, Jonathan P; Yao, Zhi Q

    2016-06-19

    Regulatory T cells (Tregs) contribute to HIV-1 disease progression by impairing antiviral immunity; however, the precise mechanisms responsible for the development of Tregs in the setting of HIV-1 infection are incompletely understood. In this study, we provide evidence that HIV-induced expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) promote the differentiation of Foxp3 Tregs. We measured MDSC induction and cytokine expression by flow cytometry and analyzed their functions by coculturing experiments. We observed a dramatic increase in M-MDSC frequencies in the peripheral blood of HIV-1 seropositive (HIV-1) individuals, even in those on antiretroviral therapy with undetectable viremia, when compared with healthy participants. We also observed increases in M-MDSCs after incubating healthy peripheral mononuclear cells (PBMCs) with HIV-1 proteins (gp120 or Tat) or Toll-like receptor 4 ligand lipopolysaccharides in vitro, an effect that could be abrogated in the presence of the phosphorylated signal transducer and activator of transcription 3 inhibitor, STA-21. Functional analyses indicated that M-MDSCs from HIV-1 individuals express higher levels of IL-10, tumor growth factor-β, IL-4 receptor α, p47, programmed death-ligand 1, and phosphorylated signal transducer and activator of transcription 3 - all of which are known mediators of myelopoiesis and immunosuppression. Importantly, incubation of healthy CD4 T cells with MDSCs derived from HIV-1 individuals significantly increased differentiation of Foxp3 Tregs. In addition, depletion of MDSCs from PBMCs of HIV-1 individuals led to a significant reduction of Foxp3 Tregs and increase of IFNγ production by CD4 T effector cells. These results suggest that HIV-induced MDSCs promote Treg cell development and inhibit T cell function - a hallmark of many chronic infectious diseases.

  3. Transcriptome analysis reveals regulatory networks underlying differential susceptibility to Botrytis cinerea in response to nitrogen availability in Solanum lycopersicum.

    Directory of Open Access Journals (Sweden)

    Andrea eVega

    2015-11-01

    Full Text Available Nitrogen (N is one of the main limiting nutrients for plant growth and crop yield. It is well documented that changes in nitrate availability, the main N source found in agricultural soils, influences a myriad of developmental programs and processes including the plant defense response. Indeed, many agronomical reports indicate that the plant N nutritional status influences their ability to respond effectively when challenged by different pathogens. However, the molecular mechanisms involved in N-modulation of plant susceptibility to pathogens are poorly characterized. In this work, we show that Solanum lycopersicum defense response to the necrotrophic fungus Botrytis cinerea is affected by plant N availability, with higher susceptibility in nitrate-limiting conditions. Global gene expression responses of tomato against B. cinerea under contrasting nitrate conditions reveals that plant primary metabolism is affected by the fungal infection regardless of N regimes. This result suggests that differential susceptibility to pathogen attack under contrasting N conditions is not only explained by a metabolic alteration. We used a systems biology approach to identify the transcriptional regulatory network implicated in plant response to the fungus infection under contrasting nitrate conditions. Interestingly, hub genes in this network are known key transcription factors involved in ethylene and jasmonic acid signaling. This result positions these hormones as key integrators of nitrate and defense against B. cinerea in tomato plants. Our results provide insights into potential crosstalk mechanisms between necrotrophic defense response and N status in plants.

  4. Emodin inhibits the differentiation and maturation of dendritic cells and increases the production of regulatory T cells.

    Science.gov (United States)

    Zhang, Wei; Li, Hong; Bu, Heqi; Chen, Hui; Tong, Hongfei; Liu, Dianlei; Guo, Hongchun; Lin, Sheng-Zhang

    2012-02-01

    The aim of this study was to characterize the effects of emodin on dendritic cells (DCs) and CD4⁺CD25⁺ regulatory T cells (Tregs). Myeloid DCs were prepared from peripheral blood mononuclear cells of healthy human donors and treated with emodin at different concentrations. The phenotype and T cell stimulatory capacity of these DCs were analyzed. The expression ratios of CD80 and CD83 in DCs in the presence of emodin (100 µg/ml) were significantly decreased compared with that in DCs without emodin treatment (Pincreased the number of Tregs, which expressed lower levels of human leukocyte antigen (HLA-DR), glucocorticoid-induced tumor necrosis factor receptor (GITR), and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) as compared to cells without emodin treatment. Our results suggest that emodin inhibits the differentiation and maturation of DCs and induces Tregs, which may be helpful for the modulation of the immune rejection after liver transplantation.

  5. Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance.

    Science.gov (United States)

    Lee, K J; Moon, J Y; Choi, H K; Kim, H O; Hur, G Y; Jung, K H; Lee, S Y; Kim, J H; Shin, C; Shim, J J; In, K H; Yoo, S H; Kang, K H; Lee, S Y

    2010-08-01

    Statins are potent inhibitors of hydroxyl-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, and have emerged as potential anti-cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)-10, transforming growth factor (TGF)-beta and indoleamine-2,3-dioxygenase (IDO) by tumours, which induce a regulatory T cell (T(reg)) response. In this study, we investigated the effect of simvastatin on the production of IL-10, TGF-beta and IDO production and the proliferation of T(regs) using several cancer cell lines, and Lewis lung cancer (3LL) cells-inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292). The production of the immune regulatory markers IL-10, TGF-beta in 3LL and NCI-H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin-treated mice groups. Therefore, while simvastatin had an anti-proliferative effect, it also exhibited immune tolerance-promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth.

  6. RNA sequencing of laser-capture microdissected compartments of the maize kernel identifies regulatory modules associated with endosperm cell differentiation.

    Science.gov (United States)

    Zhan, Junpeng; Thakare, Dhiraj; Ma, Chuang; Lloyd, Alan; Nixon, Neesha M; Arakaki, Angela M; Burnett, William J; Logan, Kyle O; Wang, Dongfang; Wang, Xiangfeng; Drews, Gary N; Yadegari, Ramin

    2015-03-01

    Endosperm is an absorptive structure that supports embryo development or seedling germination in angiosperms. The endosperm of cereals is a main source of food, feed, and industrial raw materials worldwide. However, the genetic networks that regulate endosperm cell differentiation remain largely unclear. As a first step toward characterizing these networks, we profiled the mRNAs in five major cell types of the differentiating endosperm and in the embryo and four maternal compartments of the maize (Zea mays) kernel. Comparisons of these mRNA populations revealed the diverged gene expression programs between filial and maternal compartments and an unexpected close correlation between embryo and the aleurone layer of endosperm. Gene coexpression network analysis identified coexpression modules associated with single or multiple kernel compartments including modules for the endosperm cell types, some of which showed enrichment of previously identified temporally activated and/or imprinted genes. Detailed analyses of a coexpression module highly correlated with the basal endosperm transfer layer (BETL) identified a regulatory module activated by MRP-1, a regulator of BETL differentiation and function. These results provide a high-resolution atlas of gene activity in the compartments of the maize kernel and help to uncover the regulatory modules associated with the differentiation of the major endosperm cell types. © 2015 American Society of Plant Biologists. All rights reserved.

  7. New transmembrane AMPA receptor regulatory protein isoform, gamma-7, differentially regulates AMPA receptors

    National Research Council Canada - National Science Library

    Kato, Akihiko S; Zhou, Wei; Milstein, Aaron D; Knierman, Mike D; Siuda, Edward R; Dotzlaf, Joe E; Yu, Hong; Hale, John E; Nisenbaum, Eric S; Nicoll, Roger A; Bredt, David S

    2007-01-01

    AMPA-type glutamate receptors (GluRs) mediate most excitatory signaling in the brain and are composed of GluR principal subunits and transmembrane AMPA receptor regulatory protein (TARP) auxiliary subunits...

  8. Stem cell regulatory gene expression in human adult dental pulp and periodontal ligament cells undergoing odontogenic/osteogenic differentiation.

    Science.gov (United States)

    Liu, Lu; Ling, Junqi; Wei, Xi; Wu, Liping; Xiao, Yin

    2009-10-01

    During development and regeneration, odontogenesis and osteogenesis are initiated by a cascade of signals driven by several master regulatory genes. In this study, we investigated the differential expression of 84 stem cell-related genes in dental pulp cells (DPCs) and periodontal ligament cells (PDLCs) undergoing odontogenic/osteogenic differentiation. Our results showed that, although there was considerable overlap, certain genes had more differential expression in PDLCs than in DPCs. CCND2, DLL1, and MME were the major upregulated genes in both PDLCs and DPCs, whereas KRT15 was the only gene significantly downregulated in PDLCs and DPCs in both odontogenic and osteogenic differentiation. Interestingly, a large number of regulatory genes in odontogenic and osteogenic differentiation interact or crosstalk via Notch, Wnt, transforming growth factor beta (TGF-beta)/bone morphogenic protein (BMP), and cadherin signaling pathways, such as the regulation of APC, DLL1, CCND2, BMP2, and CDH1. Using a rat dental pulp and periodontal defect model, the expression and distribution of both BMP2 and CDH1 have been verified for their spatial localization in dental pulp and periodontal tissue regeneration. This study has generated an overview of stem cell-related gene expression in DPCs and PDLCs during odontogenic/osteogenic differentiation and revealed that these genes may interact through the Notch, Wnt, TGF-beta/BMP, and cadherin signaling pathways to play a crucial role in determining the fate of dental derived cell and dental tissue regeneration. These findings provided a new insight into the molecular mechanisms of the dental tissue mineralization and regeneration.

  9. Targeting of de novo DNA methylation throughout the Oct-4 gene regulatory region in differentiating embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Rodoniki Athanasiadou

    Full Text Available Differentiation of embryonic stem (ES cells is accompanied by silencing of the Oct-4 gene and de novo DNA methylation of its regulatory region. Previous studies have focused on the requirements for promoter region methylation. We therefore undertook to analyse the progression of DNA methylation of the approximately 2000 base pair regulatory region of Oct-4 in ES cells that are wildtype or deficient for key proteins. We find that de novo methylation is initially seeded at two discrete sites, the proximal enhancer and distal promoter, spreading later to neighboring regions, including the remainder of the promoter. De novo methyltransferases Dnmt3a and Dnmt3b cooperate in the initial targeted stage of de novo methylation. Efficient completion of the pattern requires Dnmt3a and Dnmt1, but not Dnmt3b. Methylation of the Oct-4 promoter depends on the histone H3 lysine 9 methyltransferase G9a, as shown previously, but CpG methylation throughout most of the regulatory region accumulates even in the absence of G9a. Analysis of the Oct-4 regulatory domain as a whole has allowed us to detect targeted de novo methylation and to refine our understanding the roles of key protein components in this process.

  10. The Histone H2B Monoubiquitination Regulatory Pathway Is Required for Differentiation of Multipotent Stem Cells

    DEFF Research Database (Denmark)

    Karpiuk, Oleksandra; Najafova, Zeynab; Kramer, Frank;

    2012-01-01

    Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly und...

  11. Food safety regulatory systems in Europe and China:A study of how co-regulation can improve regulatory effectiveness

    Institute of Scientific and Technical Information of China (English)

    Kevin Chen; WANG Xin-xin; SONG Hai-ying

    2015-01-01

    Food safety has received a great deal of attention in both developed and developing countries in recent years. In China, the numerous food scandals and scares that have struck over the past decade have spurred signiifcant food safety regulatory reform, which has been increasingly oriented towards the public-private partnership model adopted by the Europe Union’s (EU) food safety regulatory system. This paper analyzes the development of both the EU’s and China’s food safety regu-latory systems, identiifes the current chalenges for China and additionaly considers the role of public-private partnership. The success of co-regulation in the food regulatory system would bring signiifcant beneifts and opportunities for China. Finaly, this paper recommends additional measures like training and grants to improve the private’s sector effectiveness in co-regulating China’s food safety issues.

  12. MicroRNA-29b/Tet1 regulatory axis epigenetically modulates mesendoderm differentiation in mouse embryonic stem cells

    Science.gov (United States)

    Tu, Jiajie; Ng, Shuk Han; Shui Luk, Alfred Chun; Liao, Jinyue; Jiang, Xiaohua; Feng, Bo; Lun Mak, Kingston King; Rennert, Owen M.; Chan, Wai-Yee; Lee, Tin-Lap

    2015-01-01

    Ten eleven translocation (Tet) family-mediated DNA oxidation on 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) represents a novel epigenetic modification that regulates dynamic gene expression during embryonic stem cells (ESCs) differentiation. Through the role of Tet on 5hmC regulation in stem cell development is relatively defined, how the Tet family is regulated and impacts on ESCs lineage development remains elusive. In this study, we show non-coding RNA regulation on Tet family may contribute to epigenetic regulation during ESCs differentiation, which is suggested by microRNA-29b (miR-29b) binding sites on the Tet1 3′ untranslated region (3′ UTR). We demonstrate miR-29b increases sharply after embyoid body (EB) formation, which causes Tet1 repression and reduction of cellular 5hmC level during ESCs differentiation. Importantly, we show this miR-29b/Tet1 regulatory axis promotes the mesendoderm lineage formation both in vitro and in vivo by inducing the Nodal signaling pathway and repressing the key target of the active demethylation pathway, Tdg. Taken together, our findings underscore the contribution of small non-coding RNA mediated regulation on DNA demethylation dynamics and the differential expressions of key mesendoderm regulators during ESCs lineage specification. MiR-29b could potentially be applied to enrich production of mesoderm and endoderm derivatives and be further differentiated into desired organ-specific cells. PMID:26130713

  13. The PLETHORA gene regulatory network guides growth and cell differentiation in Arabidopsis roots

    OpenAIRE

    Santuari, L.; Heidstra, R.

    2016-01-01

    Organ formation in animals and plants relies on precise control of cell state transitions to turn stem cell daughters into fully differentiated cells. In plants, cells cannot rearrange due to shared cell walls. Thus, differentiation progression and the accompanying cell expansion must be tightly coordinated across tissues. PLETHORA (PLT) transcription factor gradients are unique in their ability to guide the progression of cell differentiation at different positions in the growing Arabidopsis...

  14. Dimethyl sulfoxide inhibits spontaneous diabetes and autoimmune recurrence in non-obese diabetic mice by inducing differentiation of regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Gu-Jiun [Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC (China); Sytwu, Huey-Kang [Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC (China); Yu, Jyh-Cherng [Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Chen, Yuan-Wu [School of Dentistry, National Defense Medical Center, Taipei, Taiwan, ROC (China); Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Kuo, Yu-Liang [Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC (China); School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC (China); Yu, Chiao-Chi [Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC (China); Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Chang, Hao-Ming; Chan, De-Chuan [Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Huang, Shing-Hwa, E-mail: h610129@gmail.com [Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC (China); Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China)

    2015-01-15

    Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells. - Highlights: • We report a therapeutic potential of DMSO in autoimmune diabetes. • DMSO exhibits an immune modulatory effect. • DMSO treatment increases regulatory T cell differentiation. • The increase in STAT5 signaling pathway explains the effect of DMSO in Tregs.

  15. Tyrosol exhibits negative regulatory effects on LPS response and endotoxemia.

    Science.gov (United States)

    Lu, Jing; Huang, Guoren; Wang, Zhenning; Zhuang, Shuang; Xu, Linli; Song, Bocui; Xiong, Ying; Guan, Shuang

    2013-12-01

    Tyrosol, a phenolic compound, was isolated from wine, olive oil and other plant-derived products. In the present study, we first investigated the negative regulatory effects of tyrosol on cytokine production by lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro, and the results showed that tyrosol reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) secretion. This inspired us to further study the effects of tyrosol in vivo. Tyrosol significantly attenuated TNF-α, IL-1β and IL-6 production in serum from mice challenged with LPS, and consistent with the results in vitro. In the murine model of endotoxemia, mice were treated with tyrosol prior to or after LPS challenge. The results showed that tyrosol significantly increased mice survival. We further investigated signal transduction ways to determine how tyrosol works. The data revealed that tyrosol shocked LPS-induced mitogen activated protein kinases (MAPKs) and nuclear transcription factor-κB (NF-κB) signal transduction pathways in RAW 264.7 macrophages. These observations indicated that tyrosol exerted negative regulatory effects on LPS response in vitro and in vivo through suppressing NF-κB and p38/ERK MAPK signaling pathways.

  16. The PLETHORA Gene Regulatory Network Guides Growth and Cell Differentiation in Arabidopsis Roots

    NARCIS (Netherlands)

    Santuari, Luca; Sanchez-Perez, Gabino F.; Luijten, Marijn; Rutjens, Bas; Terpstra, Inez; Berke, Lidija; Gorte, Maartje; Prasad, Kalika; Bao, Dongping; Timmermans-Hereijgers, Johanna L.P.M.; Maeo, Kenichiro; Nakamura, Kenzo; Shimotohno, Akie; Pencik, Ales; Novak, Ondrej; Ljung, Karin; Heesch, Van Sebastiaan; Bruijn, De Ewart; Cuppen, Edwin; Willemsen, Viola; Mähönen, Ari Pekka; Lukowitz, Wolfgang; Snel, Berend; Ridder, De Dick; Scheres, Ben; Heidstra, Renze

    2016-01-01

    Organ formation in animals and plants relies on precise control of cell state transitions to turn stem cell daughters into fully differentiated cells. In plants, cells cannot rearrange due to shared cell walls. Thus, differentiation progression and the accompanying cell expansion must be tightly

  17. The PLETHORA gene regulatory network guides growth and cell differentiation in Arabidopsis roots

    NARCIS (Netherlands)

    Santuari, L.; Heidstra, R.

    2016-01-01

    Organ formation in animals and plants relies on precise control of cell state transitions to turn stem cell daughters into fully differentiated cells. In plants, cells cannot rearrange due to shared cell walls. Thus, differentiation progression and the accompanying cell expansion must be tightly

  18. The differential susceptibility to media effects model

    NARCIS (Netherlands)

    Valkenburg, P.M.; Peter, J.

    2013-01-01

    In this theoretical article, we introduce the Differential Susceptibility to Media Effects Model (DSMM), a new, integrative model to improve our understanding of media effects. The DSMM organizes, integrates, and extends the insights developed in earlier microlevel media-effects theories. It

  19. The differential susceptibility to media effects model

    NARCIS (Netherlands)

    Valkenburg, P.M.; Peter, J.

    2013-01-01

    In this theoretical article, we introduce the Differential Susceptibility to Media Effects Model (DSMM), a new, integrative model to improve our understanding of media effects. The DSMM organizes, integrates, and extends the insights developed in earlier microlevel media-effects theories. It disting

  20. The differential susceptibility to media effects model

    NARCIS (Netherlands)

    Valkenburg, P.M.; Peter, J.

    2013-01-01

    In this theoretical article, we introduce the Differential Susceptibility to Media Effects Model (DSMM), a new, integrative model to improve our understanding of media effects. The DSMM organizes, integrates, and extends the insights developed in earlier microlevel media-effects theories. It disting

  1. Collagen scaffold microenvironments modulate cell lineage commitment for differentiation of bone marrow cells into regulatory dendritic cells

    Science.gov (United States)

    Fang, Yongxiang; Wang, Bin; Zhao, Yannan; Xiao, Zhifeng; Li, Jing; Cui, Yi; Han, Sufang; Wei, Jianshu; Chen, Bing; Han, Jin; Meng, Qingyuan; Hou, Xianglin; Luo, Jianxun; Dai, Jianwu; Jing, Zhizhong

    2017-01-01

    The microenvironment plays a pivotal role for cell survival and functional regulation, and directs the cell fate determination. The biological functions of DCs have been extensively investigated to date. However, the influences of the microenvironment on the differentiation of bone marrow cells (BMCs) into dendritic cells (DCs) are not well defined. Here, we established a 3D collagen scaffold microenvironment to investigate whether such 3D collagen scaffolds could provide a favourable niche for BMCs to differentiate into specialised DCs. We found that BMCs embedded in the 3D collagen scaffold differentiated into a distinct subset of DC, exhibiting high expression of CD11b and low expression of CD11c, co-stimulator (CD40, CD80, CD83, and CD86) and MHC-II molecules compared to those grown in 2D culture. DCs cultured in the 3D collagen scaffold possessed weak antigen uptake ability and inhibited T-cell proliferation in vitro; in addition, they exhibited potent immunoregulatory function to alleviate allo-delay type hypersensitivity when transferred in vivo. Thus, DCs differentiated in the 3D collagen scaffold were defined as regulatory DCs, indicating that collagen scaffold microenvironments probably play an important role in modulating the lineage commitment of DCs and therefore might be applied as a promising tool for generation of specialised DCs. PMID:28169322

  2. Differential roles of regulatory light chain and myosin binding protein-C phosphorylations in the modulation of cardiac force development

    Energy Technology Data Exchange (ETDEWEB)

    Colson, Brett A.; Locher, Matthew R.; Bekyarova, Tanya; Patel, Jitandrakumar R.; Fitzsimons, Daniel P.; Irving, Thomas C.; Moss, Richard L. (IIT); (UW-MED)

    2010-05-25

    Phosphorylation of myosin regulatory light chain (RLC) by myosin light chain kinase (MLCK) and myosin binding protein-C (cMyBP-C) by protein kinase A (PKA) independently accelerate the kinetics of force development in ventricular myocardium. However, while MLCK treatment has been shown to increase the Ca{sup 2+} sensitivity of force (pCa{sub 50}), PKA treatment has been shown to decrease pCa{sub 50}, presumably due to cardiac troponin I phosphorylation. Further, MLCK treatment increases Ca{sup 2+}-independent force and maximum Ca{sup 2+}-activated force, whereas PKA treatment has no effect on either force. To investigate the structural basis underlying the kinase-specific differential effects on steady-state force, we used synchrotron low-angle X-ray diffraction to compare equatorial intensity ratios (I{sub 1,1}/I{sub 1,0}) to assess the proximity of myosin cross-bridge mass relative to actin and to compare lattice spacings (d{sub 1,0}) to assess the inter-thick filament spacing in skinned myocardium following treatment with either MLCK or PKA. As we showed previously, PKA phosphorylation of cMyBP-C increases I{sub 1,1}/I{sub 1,0} and, as hypothesized, treatment with MLCK also increased I{sub 1,1}/I{sub 1,0}, which can explain the accelerated rates of force development during activation. Importantly, interfilament spacing was reduced by {approx}2 nm ({Delta} 3.5%) with MLCK treatment, but did not change with PKA treatment. Thus, RLC or cMyBP-C phosphorylation increases the proximity of cross-bridges to actin, but only RLC phosphorylation affects lattice spacing, which suggests that RLC and cMyBP-C modulate the kinetics of force development by similar structural mechanisms; however, the effect of RLC phosphorylation to increase the Ca{sup 2+} sensitivity of force is mediated by a distinct mechanism, most probably involving changes in interfilament spacing.

  3. Potential effects of environmental regulatory procedures on geothermal development

    Energy Technology Data Exchange (ETDEWEB)

    Beeland, G.V.; Boies, D.B.

    1981-01-01

    The potential effects of several types of applicable environmental regulatory procedures on geothermal development were assessed, and particular problem areas were identified. The possible impact of procedures adopted pursuant to the following Federal statutes were analyzed: Clean Air Act; Clean Water Act; Safe Drinking Water Act; and Resource Conservation and Recovery Act. State regulations applicable, or potentially applicable, to geothermal facilities were also reviewed to determine: permit information requirements; pre-permit air or water quality monitoring requirements; effect of mandated time frames for permit approval; and potential for exemption of small facilities. The regulations of the following states were covered in the review: Alaska; Arizona; California; Colorado; Hawaii; Idaho; Montana; Nevada; New Mexico; Oregon; Utah; Washington; and Wyoming. (MHR)

  4. Targeting CD28, CTLA-4 and PD-L1 costimulation differentially controls immune synapses and function of human regulatory and conventional T-cells.

    Directory of Open Access Journals (Sweden)

    Nahzli Dilek

    Full Text Available CD28, CTLA-4 and PD-L1, the three identified ligands for CD80/86, are pivotal positive and negative costimulatory molecules that, among other functions, control T cell motility and formation of immune synapse between T cells and antigen-presenting cells (APCs. What remains incompletely understood is how CD28 leads to the activation of effector T cells (Teff but inhibition of suppression by regulatory T cells (Tregs, while CTLA-4 and PD-L1 inhibit Teff function but are crucial for the suppressive function of Tregs. Using alloreactive human T cells and blocking antibodies, we show here by live cell dynamic microscopy that CD28, CTLA-4, and PD-L1 differentially control velocity, motility and immune synapse formation in activated Teff versus Tregs. Selectively antagonizing CD28 costimulation increased Treg dwell time with APCs and induced calcium mobilization which translated in increased Treg suppressive activity, in contrast with the dampening effect on Teff responses. The increase in Treg suppressive activity after CD28 blockade was also confirmed with polyclonal Tregs. Whereas CTLA-4 played a critical role in Teff by reversing TCR-induced STOP signals, it failed to affect motility in Tregs but was essential for formation of the Treg immune synapse. Furthermore, we identified a novel role for PD-L1-CD80 interactions in suppressing motility specifically in Tregs. Thus, our findings reveal that the three identified ligands of CD80/86, CD28, CTLA-4 and PD-L1, differentially control immune synapse formation and function of the human Teff and Treg cells analyzed here. Individually targeting CD28, CTLA-4 and PD-L1 might therefore represent a valuable therapeutic strategy to treat immune disorders where effector and regulatory T cell functions need to be differentially targeted.

  5. The PLETHORA Gene Regulatory Network Guides Growth and Cell Differentiation in Arabidopsis Roots.

    Science.gov (United States)

    Santuari, Luca; Sanchez-Perez, Gabino F; Luijten, Marijn; Rutjens, Bas; Terpstra, Inez; Berke, Lidija; Gorte, Maartje; Prasad, Kalika; Bao, Dongping; Timmermans-Hereijgers, Johanna L P M; Maeo, Kenichiro; Nakamura, Kenzo; Shimotohno, Akie; Pencik, Ales; Novak, Ondrej; Ljung, Karin; van Heesch, Sebastiaan; de Bruijn, Ewart; Cuppen, Edwin; Willemsen, Viola; Mähönen, Ari Pekka; Lukowitz, Wolfgang; Snel, Berend; de Ridder, Dick; Scheres, Ben; Heidstra, Renze

    2016-12-01

    Organ formation in animals and plants relies on precise control of cell state transitions to turn stem cell daughters into fully differentiated cells. In plants, cells cannot rearrange due to shared cell walls. Thus, differentiation progression and the accompanying cell expansion must be tightly coordinated across tissues. PLETHORA (PLT) transcription factor gradients are unique in their ability to guide the progression of cell differentiation at different positions in the growing Arabidopsis thaliana root, which contrasts with well-described transcription factor gradients in animals specifying distinct cell fates within an essentially static context. To understand the output of the PLT gradient, we studied the gene set transcriptionally controlled by PLTs. Our work reveals how the PLT gradient can regulate cell state by region-specific induction of cell proliferation genes and repression of differentiation. Moreover, PLT targets include major patterning genes and autoregulatory feedback components, enforcing their role as master regulators of organ development. © 2016 American Society of Plant Biologists. All rights reserved.

  6. Differential effects of lenalidomide during plasma cell differentiation

    Science.gov (United States)

    Jourdan, Michel; Cren, Maïlys; Schafer, Peter; Robert, Nicolas; Duperray, Christophe; Vincent, Laure; Ceballos, Patrice; Cartron, Guillaume; Rossi, Jean-François; Moreaux, Jérôme; Chopra, Rajesh; Klein, Bernard

    2016-01-01

    Thalidomide, lenalidomide and pomalidomide have greatly improved the outcome of patients with multiple myeloma. However, their effects on plasma cells, the healthy counterpart of myeloma cells, are unknown. Here, we investigated lenalidomide effects on normal human plasma cell generation using an in vitro model. Lenalidomide inhibited the generation of pre-plasmablasts and early plasma cells, while it moderately affected plasmablast production. It also reduced the expression level of Ikaros, Aiolos, and IRF4 transcription factors, in plasmablasts and early plasma cells. This suggests that their differential sensitivity to lenalidomide is not due to a difference in Ikaros or Aiolos degradation. Lenalidomide also inhibited long-lived plasma cell generation, but did not impair their long-term survival once generated. This last observation is in agreement with the finding that lenalidomide treatment for 3-18 months did not affect the bone marrow healthy plasma cell count in allografted patients with multiple myeloma. Our findings should prompt to investigate whether lenalidomide resistance in patients with multiple myeloma could be associated with the emergence of malignant plasmablasts or long-lived plasma cells that are less sensitive to lenalidomide. PMID:27057635

  7. Differential effects of lenalidomide during plasma cell differentiation.

    Science.gov (United States)

    Jourdan, Michel; Cren, Maïlys; Schafer, Peter; Robert, Nicolas; Duperray, Christophe; Vincent, Laure; Ceballos, Patrice; Cartron, Guillaume; Rossi, Jean-François; Moreaux, Jérôme; Chopra, Rajesh; Klein, Bernard

    2016-05-10

    Thalidomide, lenalidomide and pomalidomide have greatly improved the outcome of patients with multiple myeloma. However, their effects on plasma cells, the healthy counterpart of myeloma cells, are unknown. Here, we investigated lenalidomide effects on normal human plasma cell generation using an in vitro model. Lenalidomide inhibited the generation of pre-plasmablasts and early plasma cells, while it moderately affected plasmablast production. It also reduced the expression level of Ikaros, Aiolos, and IRF4 transcription factors, in plasmablasts and early plasma cells. This suggests that their differential sensitivity to lenalidomide is not due to a difference in Ikaros or Aiolos degradation. Lenalidomide also inhibited long-lived plasma cell generation, but did not impair their long-term survival once generated. This last observation is in agreement with the finding that lenalidomide treatment for 3-18 months did not affect the bone marrow healthy plasma cell count in allografted patients with multiple myeloma. Our findings should prompt to investigate whether lenalidomide resistance in patients with multiple myeloma could be associated with the emergence of malignant plasmablasts or long-lived plasma cells that are less sensitive to lenalidomide.

  8. Distinct regulatory functions of calpain 1 and 2 during neural stem cell self-renewal and differentiation.

    Directory of Open Access Journals (Sweden)

    Daniela M Santos

    Full Text Available Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP. Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation.

  9. Regulatory constraints in the generation and differentiation of IgE-expressing B cells.

    Science.gov (United States)

    Yang, Zhiyong; Robinson, Marcus J; Allen, Christopher D C

    2014-06-01

    B cells expressing antibodies of the immunoglobulin E (IgE) isotype are rare, yet are heavily implicated in the pathogenesis of allergies and asthma. This review discusses recent methodological advances that permit sensitive probing of IgE-expressing (IgE(+)) B cells in vivo and have accordingly clarified the basic behavior and fate of IgE(+) B cells during immune responses in mouse models. IgE antibody secreting plasma cells can arise from extrafollicular foci, germinal centers, and memory B cells. However, compared to B cells expressing other isotypes, IgE(+) B cells are susceptible to multiple additional regulatory constraints that restrict the size of the IgE(+) B cell pool at each stage, coordinately limiting the overall magnitude, affinity, and duration of the IgE antibody response.

  10. Regulatory framework for access to safe, effective quality medicines

    NARCIS (Netherlands)

    Rägo, Lembit; Sillo, Hiiti; 't Hoen, Ellen; Zweygarth, Monika

    2014-01-01

    Medicines of uncertain quality, safety and efficacy can be worse than no treatment at all. It is the responsibility of national medicines regulatory authorities to protect patients from harm. Yet, there are great disparities in regulatory capacity globally, preventing large populations from accessin

  11. Moderating effect of regulatory focus on burnout and exercise behavior.

    Science.gov (United States)

    Liang, Huai-Liang; Kao, Yueh-Tzu; Lin, Cheng-Chen

    2013-12-01

    Applying Higgins' regulatory focus, which assumes that people pursue goals using means that match their self-regulatory motivation, the authors examined whether individual's promotion- or prevention-focused motivations in work would decrease participation in physical activity. Participants were 197 employees (163 men, 34 women, M age = 39 yr.) in five different Taiwanese manufacturing firms. They responded to Copenhagen Burnout Inventory, the Regulatory Focus Questionnaire, and Exercise Behavior at two different times, 8-10 weeks apart. Promotion-oriented regulatory focus significantly moderated the relationship between burnout and exercise, but prevention-oriented focus did not. BMI, blood pressure, cholesterol, and work hours contributed small but significant amounts of variance. A prevention focus was associated with more time for physical activity, even when participants were tired, supporting regulatory focus theory.

  12. The function of a regulatory gene,scrX related to differentiation in Streptomyces coelicolor

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A new gene, scrX from Streptomyces coelicolor was cloned and sequenced. It consists of 660 base pair, encoding a peptide of 220 amino acids. There are three rare codons in scrX which are AAA, AAA and ATA. scrX gene may be a typical differentiation regulator which was strictly controlled at translational level. The comparison of amino acids also revealed that ScrX belonged to Ic1R family which acted in transcriptional regulation of prokaryote. Studies on gene function by gene disruption and complementation indicated that scrX may play a positive regulation role in spore formation of Streptomyces coelicolor.

  13. Cell differentiation within a yeast colony: metabolic and regulatory parallels with a tumor-affected organism.

    Science.gov (United States)

    Cáp, Michal; Stěpánek, Luděk; Harant, Karel; Váchová, Libuše; Palková, Zdena

    2012-05-25

    Nutrient sensing and metabolic reprogramming are crucial for metazoan cell aging and tumor growth. Here, we identify metabolic and regulatory parallels between a layered, multicellular yeast colony and a tumor-affected organism. During development, a yeast colony stratifies into U and L cells occupying the upper and lower colony regions, respectively. U cells activate a unique metabolism controlled by the glutamine-induced TOR pathway, amino acid-sensing systems (SPS and Gcn4p) and signaling from mitochondria with lowered respiration. These systems jointly modulate U cell physiology, which adapts to nutrient limitations and utilize the nutrients released from L cells. Stress-resistant U cells share metabolic pathways and other similar characteristics with tumor cells, including the ability to proliferate. L cells behave similarly to stressed and starving cells, which activate degradative mechanisms to provide nutrients to U cells. Our data suggest a nutrient flow between both cell types, resembling the Cori cycle and glutamine-NH(4)(+) shuttle between tumor and healthy metazoan cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Differential expression of smooth muscle regulatory proteins in the uterosacral ligaments of women with uterine prolapse.

    Science.gov (United States)

    Takacs, Peter; Gualtieri, Marc; Nassiri, Mehdi; Candiotti, Keith; Fornoni, Alessia; Medina, Carlos A

    2010-06-01

    To compare smooth muscle regulatory protein expression in the uterosacral ligament (USL) of women with and without uterine prolapse. USLs ligament were sampled in women with (n = 9) or without (n = 9) uterine prolapse. Caldesmon, smooth muscle actin (SMA), myosin heavy chain, and zinc finger protein messenger RNA expression was assessed by quantitative real-time polymerase chain reaction. Immunohistochemistry and digital image analysis were used to determine protein expression. Caldesmon messenger RNA expression and the ratio of caldesmon-SMA messenger RNA expression was significantly increased in the USL from women with uterine prolapse compared with women without prolapse (caldesmon mean +/- standard deviation messenger RNA, 0.81 +/- 0.46 vs 0.39 +/- 0.16; P = .01 and caldesmon-SMA messenger RNA ratio, mean +/- standard deviation, 0.11 +/- 0.04 vs 0.07 +/- 0.02; P = .01). In addition, the ratio of caldesmon-SMA staining was significantly increased in women with uterine prolapse compared with women without prolapse (mean +/- standard deviation, 0.44 +/- 0.28 vs 0.28 +/- 0.16; P = .03). Uterine prolapse is associated with an increased ratio of caldesmon-SMA actin expression. Copyright 2010 Mosby, Inc. All rights reserved.

  15. The function of a regulatory gene, scrX related to differentiation in Streptomyces coelicolor

    Institute of Scientific and Technical Information of China (English)

    杨海花; 田宇清; 贾君永; 谭华荣

    2000-01-01

    A new gene, scrX from Streptomyces coelicolor was cloned and sequenced. It consists of 660 base pair, encoding a peptide of 220 amino acids. There are three rare codons in scrX which are AAA, AAA and ATA. scrXgene may be a typical differentiation regulator which was strictly controlled at translational level. The comparison of amino acids also revealed that ScrX belonged to Id R family which acted in transcriptional regulation of prokaryote. Studies on gene function by gene disruption and complementation indicated that scrX may play a positive regulation role in spore formation of Streptomyces coelicolor.A new gene, scrX from Streptomyces coelicolor was cloned and sequenced. It consists of 660 base pair, encoding a peptide of 220 amino acids. There are three rare codons in scrX which are AAA, AAA and ATA. scrXgene may be a typical differentiation regulator which was strictly controlled at translational level. The comparison of amino acids also revealed that ScrX belonged to Id R family which acted in tra

  16. The differential impact of academic self-regulatory methods on academic achievement among university students with and without learning disabilities.

    Science.gov (United States)

    Ruban, Lilia M; McCoach, D Betsy; McGuire, Joan M; Reis, Sally M

    2003-01-01

    Although research on academic self-regulation has proliferated in recent years, no studies have investigated the question of whether the perceived usefulness and the use of standard self-regulated learning strategies and compensation strategies provide a differential prediction of academic achievement for university students with and without learning disabilities (LD). We developed and tested a model explaining interrelationships among self-regulatory variables and grade point average (GPA) using structural equation modeling and multiple group analysis for students with LD (n = 53) and without LD (n = 421). Data were gathered using a new instrument, the Learning Strategies and Study Skills survey. The results of this study indicate that students with LD differed significantly from students without LD in the relationships between their motivation for and use of standard self-regulated learning strategies and compensation strategies, which in turn provided a differential explanation of academic achievement for students with and without LD. These paths of influence and idiosyncrasies of academic self-regulation among students with LD were interpreted in terms of social cognitive theory, metacognitive theory, and research conducted in the LD field.

  17. T-bet regulates differentiation of forkhead box protein 3+ regulatory T cells in programmed cell death-1-deficient mice

    Science.gov (United States)

    Tahara, M; Kondo, Y; Yokosawa, M; Tsuboi, H; Takahashi, S; Shibayama, S; Matsumoto, I; Sumida, T

    2015-01-01

    Programmed cell death-1 (PD-1) plays an important role in peripheral T cell tolerance, but whether or not it affects the differentiation of helper T cell subsets remains elusive. Here we describe the importance of PD-1 in the control of T helper type 1 (Th1) cell activation and development of forkhead box protein 3 (FoxP3+) regulatory T cells (Tregs). PD-1-deficient T cell-specific T-bet transgenic (P/T) mice showed growth retardation, and the majority died within 10 weeks. P/T mice showed T-bet over-expression, increased interferon (IFN)-γ production by CD4+ T cells and significantly low FoxP3+ Treg cell percentage. P/T mice developed systemic inflammation, which was probably induced by augmented Th1 response and low FoxP3+ Treg count. The study identified a unique, previously undescribed role for PD-1 in Th1 and Treg differentiation, with potential implication in the development of Th1 cell-targeted therapy. PMID:25219397

  18. The effect of dehydroleucodine in adipocyte differentiation.

    Science.gov (United States)

    Galvis, Adriana; Marcano, Adriana; Stefancin, Chad; Villaverde, Nicole; Priestap, Horacio A; Tonn, Carlos E; Lopez, Luis A; Barbieri, Manuel A

    2011-12-05

    Dehydroleucodine (DhL) is a sesquiterpene lactone of the guaianolide group with gastric cytoprotective activity. Recent studies have also demonstrated that DhL inhibits the proliferation of vascular smooth muscle cells. In this study we examined the effect of DhL in the differentiation of 3T3-L1 preadipocytes. The addition of DhL significantly inhibited the differentiation of 3T3-L1 preadipocytes along with a significant decrease in the accumulation of lipid content by a dramatic downregulation of the expression of adipogenic-specific transcriptional factors PPARγ and C-EBPα. However, phosphorylation of AMPKα, Erk1/2 and Akt1 was not inhibited by DhL treatment. Interestingly, we also found that 11,13-dihydrodehydroleucodine, a derivative of DhL with inactivated α-methylene-γ-lactone function, also inhibited the differentiation of 3T3-L1 preadipocytes. Taken together, these data suggest that DhL has an important inhibitory effect in cellular pathways regulating adipocyte differentiation by modulating the PPARγ expression, which is known to play a pivotal role during adipogenesis. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. 1,25(OH)2D3 induces regulatory T cell differentiation by influencing the VDR/PLC-γ1/TGF-β1/pathway.

    Science.gov (United States)

    Zhou, Qiang; Qin, Shengying; Zhang, Jinyan; Zhon, Lin; Pen, Zhihai; Xing, Tonghai

    2017-09-16

    Vitamin D has been recommended as an immune modulator in recent years, in addition to regulating calcium-phosphorous-bone metabolism. Clinical studies on organ transplantation found that vitamin D sufficiency patients were less likely to develop acute cellular rejection within one year after transplantation compared to those with vitamin D deficiency. Thus, a high percentage of regulatory T cells might play a key role in preventing acute cellular rejection (ACR). In this report, we studied the specific effects of 1,25(OH)2D3 on human T cell diff ;erentiation, and determined the potential molecule mechanism behind. Results showed that 1,25(OH)2D3 induced the differentiation of T-regulatory cells (Treg cells), while inhibiting Th17 cell proliferation. In addition, 1,25(OH)2D3 promoted secretion of the anti-inflammatory cytokine, transforming Growth Factor beta1 (TGF-β1) but suppressed pro-inflammatory cytokines such as interleukin-17 (IL-17). Phospholipase C gamma 1 (PLC-γ1) is an indispensable signaling protein downstream of the classical TCR signaling pathway and was shown to play a crucial role in T cell activation, while Naive T cells expressed less PLC-γ1. Here we showed that Vitamin D could significantly upregulate PLC-γ1 expression, which then induced expression of TGF-β1. In summary, 1,25(OH)2D3 indirectly modulates the differentiation of Treg/Th17 cells by aff ;ecting the VDR/PLC-γ1/TGF-β1pathway. These results indicate that administration 1,25(OH)2D3 supplements may be a beneficial treatment for organ transplantation recipients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Does regulatory fit lead to more effective health communication? A systematic review.

    Science.gov (United States)

    Ludolph, Ramona; Schulz, Peter J

    2015-03-01

    Many of today's threats to public health arise from people's lifestyle. Hence, the public's compliance with advice given for health promotion and disease prevention has to be enhanced. Much research traces back the efficacy of health promotion messages to message qualities, while other work focuses on recipient qualities. Regulatory focus theory posits inter-individual differences in motivational orientation, namely a promotion or prevention focus, and offers a unique chance to look at message and recipient variables at the same time (Higgins, 1997). Whereas a promotion-focused individual tries to achieve desired end-states, someone with a prevention focus is rather vigilant. If individuals' goal pursuit strategies match their regulatory orientation, they experience regulatory fit, which increases the perceived persuasiveness of health messages (Higgins, 2000). Such a match can be evoked by particularly framed messages that highlight a person's regulatory orientation. Thus, the assumption of regulatory fit goes beyond the concept of gain- and loss-framing. To assess whether regulatory fit contributes to the effectiveness of health communication, a systematic review was conducted. An extensive systematic search led to the inclusion of 30 studies, for which data were extracted and quality appraised. Findings were summarized using narrative synthesis. Most studies (n = 23) were conducted in the USA and assessed the effects of regulatory fit on behavioral intention (n = 21). Nineteen experiments used samples of university students, and the health context chosen most often was a healthy diet (n = 7). Sixteen experiments manipulated regulatory orientation whereas chronic regulatory focus was measured ten times. The majority of studies confirmed that regulatory fit enhanced the effectiveness of health messages, which did not vary much across different health domains or outcomes. Regulatory fit is a promising approach for tailoring health messages as the synergy effects of

  1. A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity.

    Directory of Open Access Journals (Sweden)

    Mariana Esther Martinez-Sanchez

    2015-06-01

    Full Text Available CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes versus extrinsic (produced by other cells components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells. This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-β and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular

  2. A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity

    Science.gov (United States)

    Martinez-Sanchez, Mariana Esther; Mendoza, Luis; Villarreal, Carlos; Alvarez-Buylla, Elena R.

    2015-01-01

    CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes) versus extrinsic (produced by other cells) components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells). This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-β and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular regulatory core

  3. Promoting effect of lactoferrin on barrier function and epithelial differentiation of human keratinocytes.

    Science.gov (United States)

    Uchida, Ryo; Aoki, Reiji; Aoki-Yoshida, Ayako; Tajima, Atsushi; Takayama, Yoshiharu

    2017-02-01

    The purpose of this study was to elucidate the effects of bovine lactoferrin on keratinocyte differentiation and barrier function. Addition of bovine lactoferrin to differentiating HaCaT human keratinocytes led to increased transepithelial electrical resistance (TER), a marker of epithelial barrier function. This elevation was followed by upregulation of two differentiation markers, involucrin and filaggrin. The expression level of sterol regulatory element-binding protein-1 was also enhanced by bovine lactoferrin. The lactoferrin-induced upregulation of involucrin and filaggrin expression were confirmed in normal human epidermal keratinocytes (NHEK). Treatment with SB203580, a p38 mitogen-activated protein kinase (MAPK) α inhibitor, impaired the upregulation of involucrin and filaggrin expression in response to lactoferrin. The elevation of p38 MAPK phosphorylation was further enhanced by lactoferrin in the initial stage of differentiation of HaCaT keratinocytes. The findings suggest that bovine lactoferrin promotes epithelial differentiation by a p38-MAPK-dependent mechanism.

  4. A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration.

    Directory of Open Access Journals (Sweden)

    Benjamin L King

    Full Text Available Although regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues. In order to identify a genetic signature that accompanies blastema formation, we employ next-generation sequencing to identify shared, differentially regulated mRNAs and noncoding RNAs in three different, highly regenerative animal systems: zebrafish caudal fins, bichir pectoral fins and axolotl forelimbs.These studies identified a core group of 5 microRNAs (miRNAs that were commonly upregulated and 5 miRNAs that were commonly downregulated, as well as 4 novel tRNAs fragments with sequences conserved with humans. To understand the potential function of these miRNAs, we built a network of 1,550 commonly differentially expressed mRNAs that had functional relationships to 11 orthologous blastema-associated genes. As miR-21 was the most highly upregulated and most highly expressed miRNA in all three models, we validated the expression of known target genes, including the tumor suppressor, pdcd4, and TGFβ receptor subunit, tgfbr2 and novel putative target genes such as the anti-apoptotic factor, bcl2l13, Choline kinase alpha, chka and the regulator of G-protein signaling, rgs5.Our extensive analysis of RNA-seq transcriptome profiling studies in three regenerative animal models, that diverged in evolution ~420 million years ago, reveals a common miRNA-regulated genetic network of blastema genes. These comparative studies extend our current understanding of limb/appendage regeneration by identifying previously unassociated blastema genes and the extensive regulation by miRNAs, which could serve as a foundation for future

  5. A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration

    Science.gov (United States)

    King, Benjamin L.; Yin, Viravuth P.

    2016-01-01

    Background Although regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues. In order to identify a genetic signature that accompanies blastema formation, we employ next-generation sequencing to identify shared, differentially regulated mRNAs and noncoding RNAs in three different, highly regenerative animal systems: zebrafish caudal fins, bichir pectoral fins and axolotl forelimbs. Results These studies identified a core group of 5 microRNAs (miRNAs) that were commonly upregulated and 5 miRNAs that were commonly downregulated, as well as 4 novel tRNAs fragments with sequences conserved with humans. To understand the potential function of these miRNAs, we built a network of 1,550 commonly differentially expressed mRNAs that had functional relationships to 11 orthologous blastema-associated genes. As miR-21 was the most highly upregulated and most highly expressed miRNA in all three models, we validated the expression of known target genes, including the tumor suppressor, pdcd4, and TGFβ receptor subunit, tgfbr2 and novel putative target genes such as the anti-apoptotic factor, bcl2l13, Choline kinase alpha, chka and the regulator of G-protein signaling, rgs5. Conclusions Our extensive analysis of RNA-seq transcriptome profiling studies in three regenerative animal models, that diverged in evolution ~420 million years ago, reveals a common miRNA-regulated genetic network of blastema genes. These comparative studies extend our current understanding of limb/appendage regeneration by identifying previously unassociated blastema genes and the extensive regulation by miRNAs, which could serve as a foundation

  6. Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy.

    Science.gov (United States)

    Yu, Xinlei; Long, Yun Chau; Shen, Han-Ming

    2015-01-01

    Autophagy is an evolutionarily conserved and exquisitely regulated self-eating cellular process with important biological functions. Phosphatidylinositol 3-kinases (PtdIns3Ks) and phosphoinositide 3-kinases (PI3Ks) are involved in the autophagic process. Here we aim to recapitulate how 3 classes of these lipid kinases differentially regulate autophagy. Generally, activation of the class I PI3K suppresses autophagy, via the well-established PI3K-AKT-MTOR (mechanistic target of rapamycin) complex 1 (MTORC1) pathway. In contrast, the class III PtdIns3K catalytic subunit PIK3C3/Vps34 forms a protein complex with BECN1 and PIK3R4 and produces phosphatidylinositol 3-phosphate (PtdIns3P), which is required for the initiation and progression of autophagy. The class II enzyme emerged only recently as an alternative source of PtdIns3P and autophagic initiator. However, the orthodox paradigm is challenged by findings that the PIK3CB catalytic subunit of class I PI3K acts as a positive regulator of autophagy, and PIK3C3 was thought to be an amino acid sensor for MTOR, which curbs autophagy. At present, a number of PtdIns3K and PI3K inhibitors, including specific PIK3C3 inhibitors, have been developed for suppression of autophagy and for clinical applications in autophagy-related human diseases.

  7. Regulatory Forum Opinion Piece*: Effective Sectioning of Spinal Cord during Regulatory-type Nonclinical Toxicity Studies.

    Science.gov (United States)

    Bolon, Brad

    2017-07-01

    Regulatory guidelines for nonclinical neurotoxicity testing require spinal cord evaluation but do not specify a trimming scheme. The Society of Toxicologic Pathology (STP) "best practices" for nervous system sampling during nonclinical general toxicity studies recommend that spinal cord be assessed in both longitudinal/oblique and transverse sections. This article defines possible longitudinal/oblique orientations, describes their benefits and challenges, and provides an expert recommendation regarding suitable trimming planes. Longitudinal parasagittal (LP) sections follow a vertical plane just lateral to the midline, revealing sensory and motor tracts but little gray matter. Longitudinal horizontal sections transect only sensory or motor tracts and variable quantities of gray matter. Oblique vertical (OV) sections angle across the spinal cord from side to side. Oblique transverse (OT) sections slant through from top (dorsal [posterior]) to bottom (ventral [anterior]). Compared to longitudinal planes, oblique orientations demonstrate considerably more gray matter and white matter. Current STP "best practices" explicitly recommend the LP and OV options; the OT orientation also will yield suitable sections while permitting assessment of anatomic symmetry. Selection among the LP, OT, and OV planes should be at the discretion of the study pathologist. The bilaterally symmetrical OT sections likely will be analyzed most easily by nonneuropathologists.

  8. Spatial fluctuations in expression of the heterocyst differentiation regulatory gene hetR in Anabaena filaments.

    Directory of Open Access Journals (Sweden)

    Laura Corrales-Guerrero

    2015-04-01

    Full Text Available Under nitrogen deprivation, filaments of the cyanobacterium Anabaena undergo a process of development, resulting in a one-dimensional pattern of nitrogen-fixing heterocysts separated by about ten photosynthetic vegetative cells. Many aspects of gene expression before nitrogen deprivation and during the developmental process remain to be elucidated. Furthermore, the coupling of gene expression fluctuations between cells along a multicellular filament is unknown. We studied the statistics of fluctuations of gene expression of HetR, a transcription factor essential for heterocyst differentiation, both under steady-state growth in nitrogen-rich conditions and at different times following nitrogen deprivation, using a chromosomally-encoded translational hetR-gfp fusion. Statistical analysis of fluorescence at the individual cell level in wild-type and mutant filaments demonstrates that expression fluctuations of hetR in nearby cells are coupled, with a characteristic spatial range of circa two to three cells, setting the scale for cellular interactions along a filament. Correlations between cells predominantly arise from intercellular molecular transfer and less from cell division. Fluctuations after nitrogen step-down can build up on those under nitrogen-replete conditions. We found that under nitrogen-rich conditions, basal, steady-state expression of the HetR inhibitor PatS, cell-cell communication influenced by the septal protein SepJ and positive HetR auto-regulation are essential determinants of fluctuations in hetR expression and its distribution along filaments. A comparison between the expression of hetR-gfp under nitrogen-rich and nitrogen-poor conditions highlights the differences between the two HetR inhibitors PatS and HetN, as well as the differences in specificity between the septal proteins SepJ and FraC/FraD. Activation, inhibition and cell-cell communication lie at the heart of developmental processes. Our results show that proteins

  9. Spatial fluctuations in expression of the heterocyst differentiation regulatory gene hetR in Anabaena filaments.

    Science.gov (United States)

    Corrales-Guerrero, Laura; Tal, Asaf; Arbel-Goren, Rinat; Mariscal, Vicente; Flores, Enrique; Herrero, Antonia; Stavans, Joel

    2015-04-01

    Under nitrogen deprivation, filaments of the cyanobacterium Anabaena undergo a process of development, resulting in a one-dimensional pattern of nitrogen-fixing heterocysts separated by about ten photosynthetic vegetative cells. Many aspects of gene expression before nitrogen deprivation and during the developmental process remain to be elucidated. Furthermore, the coupling of gene expression fluctuations between cells along a multicellular filament is unknown. We studied the statistics of fluctuations of gene expression of HetR, a transcription factor essential for heterocyst differentiation, both under steady-state growth in nitrogen-rich conditions and at different times following nitrogen deprivation, using a chromosomally-encoded translational hetR-gfp fusion. Statistical analysis of fluorescence at the individual cell level in wild-type and mutant filaments demonstrates that expression fluctuations of hetR in nearby cells are coupled, with a characteristic spatial range of circa two to three cells, setting the scale for cellular interactions along a filament. Correlations between cells predominantly arise from intercellular molecular transfer and less from cell division. Fluctuations after nitrogen step-down can build up on those under nitrogen-replete conditions. We found that under nitrogen-rich conditions, basal, steady-state expression of the HetR inhibitor PatS, cell-cell communication influenced by the septal protein SepJ and positive HetR auto-regulation are essential determinants of fluctuations in hetR expression and its distribution along filaments. A comparison between the expression of hetR-gfp under nitrogen-rich and nitrogen-poor conditions highlights the differences between the two HetR inhibitors PatS and HetN, as well as the differences in specificity between the septal proteins SepJ and FraC/FraD. Activation, inhibition and cell-cell communication lie at the heart of developmental processes. Our results show that proteins involved in these

  10. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors

    Science.gov (United States)

    Lloyd, David J.; St Jean, David J.; Kurzeja, Robert J. M.; Wahl, Robert C.; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S.; Pennington, Lewis D.; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H.; Andrews, Kristin L.; Bartberger, Michael D.; van, Gwyneth; Galbreath, Elizabeth J.; Vonderfecht, Steven L.; Wang, Minghan; Jordan, Steven R.; Véniant, Murielle M.; Hale, Clarence

    2013-12-01

    Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

  11. Shape-dependent control of cell growth, differentiation, and apoptosis: switching between attractors in cell regulatory networks

    Science.gov (United States)

    Huang, S.; Ingber, D. E.

    2000-01-01

    Development of characteristic tissue patterns requires that individual cells be switched locally between different phenotypes or "fates;" while one cell may proliferate, its neighbors may differentiate or die. Recent studies have revealed that local switching between these different gene programs is controlled through interplay between soluble growth factors, insoluble extracellular matrix molecules, and mechanical forces which produce cell shape distortion. Although the precise molecular basis remains unknown, shape-dependent control of cell growth and function appears to be mediated by tension-dependent changes in the actin cytoskeleton. However, the question remains: how can a generalized physical stimulus, such as cell distortion, activate the same set of genes and signaling proteins that are triggered by molecules which bind to specific cell surface receptors. In this article, we use computer simulations based on dynamic Boolean networks to show that the different cell fates that a particular cell can exhibit may represent a preprogrammed set of common end programs or "attractors" which self-organize within the cell's regulatory networks. In this type of dynamic network model of information processing, generalized stimuli (e.g., mechanical forces) and specific molecular cues elicit signals which follow different trajectories, but eventually converge onto one of a small set of common end programs (growth, quiescence, differentiation, apoptosis, etc.). In other words, if cells use this type of information processing system, then control of cell function would involve selection of preexisting (latent) behavioral modes of the cell, rather than instruction by specific binding molecules. Importantly, the results of the computer simulation closely mimic experimental data obtained with living endothelial cells. The major implication of this finding is that current methods used for analysis of cell function that rely on characterization of linear signaling pathways or

  12. Effects of Regulatory Self-Questioning on Secondary-Level Students' Problem-Solving Performance

    Science.gov (United States)

    Pate, Michael L.; Miller, Greg

    2011-01-01

    A randomized posttest-only control group experimental design was used to determine the effects of regulatory self-questioning on secondary-level career and technical education students' electrical circuit theory test scores. Students who participated in the self-questioning group were asked to answer a list of regulatory questions as they solved…

  13. A combined park management framework based on regulatory and behavioral strategies: use of visitors' knowledge to assess effectiveness.

    Science.gov (United States)

    Papageorgiou, K

    2001-07-01

    In light of the increasing mandate for greater efficiency in conservation of natural reserves such as national parks, the present study suggests educational approaches as a tool to achieve conservation purposes. Currently, the management of human-wildlife interactions is dominated by regulatory strategies, but considerable potential exists for environmental education to enhance knowledge in the short run and to prompt attitude change in the long run. A framework for conservation based on both traditional regulatory- and behavior-oriented strategies was proposed whereby the level of knowledge that park visitors have acquired comprises an obvious outcome and establishes a basis upon which the effectiveness of regulatory- and behavior-based regimes could be assessed. The perceptions regarding park-related issues of two distinct visitor groups (locals and nonlocals) are summarized from a survey undertaken in Vikos-Aoos national park. The findings suggest a superficial knowledge for certain concepts but little profound understanding of the content of such concepts, indicating that knowledge-raising efforts should go a long way towards establishing a positive attitude for the resource. Visitors' poor knowledge of the park's operation regulation contest the efficiency of the presently dominant regulatory management regime. While geographical distances did not appear to significantly differentiate knowledge between the two groups, wilderness experience (as certified by visits to other parks) was proved to be an impetus for generating substantial learner interest in critical park issues among nonlocal visitors. School education and media were found to be significant knowledge providers.

  14. Comparison of stationary and oscillatory dynamics described by differential equations and Boolean maps in transcriptional regulatory circuits

    Energy Technology Data Exchange (ETDEWEB)

    Ye Weiming [Department of Physics, Beijing Normal University, Beijing 100875 (China); Beijing-Hong Kong-Singapore Joint Center of Nonlinear and Complex Systems, Beijing Normal University Branch, Beijing (China); Li Pengfei; Huang Xuhui; Xia Qinzhi; Mi Yuanyuan [Department of Physics, Beijing Normal University, Beijing 100875 (China); Chen Runsheng, E-mail: crs@sun5.ibp.ac.c [Bioinformatics Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Hu Gang, E-mail: ganghu@bnu.edu.c [Department of Physics, Beijing Normal University, Beijing 100875 (China); Beijing-Hong Kong-Singapore Joint Center of Nonlinear and Complex Systems, Beijing Normal University Branch, Beijing (China)

    2010-10-25

    Exploring the principle and relationship of gene transcriptional regulations (TR) has been becoming a generally researched issue. So far, two major mathematical methods, ordinary differential equation (ODE) method and Boolean map (BM) method have been widely used for these purposes. It is commonly believed that simplified BMs are reasonable approximations of more realistic ODEs, and both methods may reveal qualitatively the same essential features though the dynamical details of both systems may show some differences. In this Letter we exhaustively enumerated all the 3-gene networks and many autonomous randomly constructed TR networks with more genes by using both the ODE and BM methods. In comparison we found that both methods provide practically identical results in most of cases of steady solutions. However, to our great surprise, most of network structures showing periodic cycles with the BM method possess only stationary states in ODE descriptions. These observations strongly suggest that many periodic oscillations and other complicated oscillatory states revealed by the BM rule may be related to the computational errors of variable and time discretizations and rarely have correspondence in realistic biology transcriptional regulatory circuits.

  15. Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.

    Science.gov (United States)

    Thome, Joseph J C; Bickham, Kara L; Ohmura, Yoshiaki; Kubota, Masaru; Matsuoka, Nobuhide; Gordon, Claire; Granot, Tomer; Griesemer, Adam; Lerner, Harvey; Kato, Tomoaki; Farber, Donna L

    2016-01-01

    It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life.

  16. Brachyury and SMAD signalling collaboratively orchestrate distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells.

    Science.gov (United States)

    Faial, Tiago; Bernardo, Andreia S; Mendjan, Sasha; Diamanti, Evangelia; Ortmann, Daniel; Gentsch, George E; Mascetti, Victoria L; Trotter, Matthew W B; Smith, James C; Pedersen, Roger A

    2015-06-15

    The transcription factor brachyury (T, BRA) is one of the first markers of gastrulation and lineage specification in vertebrates. Despite its wide use and importance in stem cell and developmental biology, its functional genomic targets in human cells are largely unknown. Here, we use differentiating human embryonic stem cells to study the role of BRA in activin A-induced endoderm and BMP4-induced mesoderm progenitors. We show that BRA has distinct genome-wide binding landscapes in these two cell populations, and that BRA interacts and collaborates with SMAD1 or SMAD2/3 signalling to regulate the expression of its target genes in a cell-specific manner. Importantly, by manipulating the levels of BRA in cells exposed to different signalling environments, we demonstrate that BRA is essential for mesoderm but not for endoderm formation. Together, our data illuminate the function of BRA in the context of human embryonic development and show that the regulatory role of BRA is context dependent. Our study reinforces the importance of analysing the functions of a transcription factor in different cellular and signalling environments.

  17. Adoptive transfer of bone marrow-derived dendritic cells decreases inhibitory and regulatory T-cell differentiation and improves survival in murine polymicrobial sepsis.

    Science.gov (United States)

    Wang, Hong-Wei; Yang, Wen; Gao, Lei; Kang, Jia-Rui; Qin, Jia-Jian; Liu, Yue-Ping; Lu, Jiang-Yang

    2015-05-01

    A decrease in the number of dendritic cells (DCs) is a major cause of post-sepsis immunosuppression and opportunistic infection and is closely associated with poor prognosis. Increasing the number of DCs to replenish their numbers post sepsis can improve the condition. This therapeutic approach could improve recovery after sepsis. Eighty C57BL/6 mice were subjected to sham or caecal ligation and puncture (CLP) surgery. Mice were divided into four groups: (i) Sham + vehicle, (ii) Sham + DC, (iii) CLP + vehicle, and (iv) CLP + DC. Bone-marrow-derived DCs (BMDCs) were administered at 6, 12 and 24 hr after surgery. After 3 days, we assessed serum indices of organ function (alanine aminotransferase, aspartate aminotransferase, creatinine, amylase and lipase), organ tissue histopathology (haematoxylin and eosin staining), cytokine [interferon-γ (IFN-γ), tumour necrosis factor-α, interleukin-12p70 (IL-12p70), IL-6 and IL-10] levels in the serum, programmed death-1 (PD-1) expression on T cells, regulatory T-cell differentiation in the spleen, and the survival rate (monitored for 7 days). BMDC transfer resulted in the following changes: a significant reduction in damage to the liver, kidney and pancreas in the CLP-septic mice as well as in the pathological changes seen in the liver, lung, small intestine and pancreas; significantly elevated levels of the T helper type 1 (Th1) cytokines IFN-γ and IL-12p70 in the serum; decreased levels of the Th2 cytokines IL-6 and IL-10 in the serum; reduced expression of PD-1 molecules on CD4(+) T cells; reduced the proliferation and differentiation of splenic suppressor T cells and CD4(+)  CD25(+)  Foxp3(+) regulatory T cells, and a significant increase in the survival rate of the septic animals. These results show that administration of BMDCs may have modulated the differentiation and immune function of T cells and contributed to alleviate immunosuppression, hence reducing organ damage and mortality post sepsis. Hence

  18. Determinants of Effective Information Transfer in International Regulatory Standards Adoption

    Science.gov (United States)

    Popescu, Denisa

    2010-01-01

    The role of international regulatory standards within the current global environment has become of the most importance. The age of the global system and free market capitalism carried us into the unprecedented age of regulations, and standard setting. Regulations are now becoming the emerging mode of global governance. This study focuses on…

  19. Pref-1 in brown adipose tissue: specific involvement in brown adipocyte differentiation and regulatory role of C/EBPδ.

    Science.gov (United States)

    Armengol, Jordi; Villena, Josep A; Hondares, Elayne; Carmona, María C; Sul, Hei Sook; Iglesias, Roser; Giralt, Marta; Villarroya, Francesc

    2012-05-01

    Pref-1 (pre-adipocyte factor-1) is known to play a central role in regulating white adipocyte differentiation, but the role of Pref-1 in BAT (brown adipose tissue) has not been analysed. In the present study we found that Pref-1 expression is high in fetal BAT and declines progressively after birth. However, Pref-1-null mice showed unaltered fetal development of BAT, but exhibited signs of over-activation of BAT thermogenesis in the post-natal period. In C/EBP (CCAAT/enhancer-binding protein) α-null mice, a rodent model of impaired fetal BAT differentiation, Pref-1 was dramatically overexpressed, in association with reduced expression of the Ucp1 (uncoupling protein 1) gene, a BAT-specific marker of thermogenic differentiation. In brown adipocyte cell culture models, Pref-1 was mostly expressed in pre-adipocytes and declined with brown adipocyte differentiation. The transcription factor C/EBPδ activated the Pref-1 gene transcription in brown adipocytes, through binding to the proximal promoter region. Accordingly, siRNA (small interfering RNA)-induced C/EBPδ knockdown led to reduced Pref-1 gene expression. This effect is consistent with the observed overexpression of C/EBPδ in C/EBPα-null BAT and high expression of C/EBPδ in brown pre-adipocytes. Dexamethasone treatment of brown pre-adipocytes suppressed Pref-1 down-regulation occurring throughout the brown adipocyte differentiation process, increased the expression of C/EBPδ and strongly impaired expression of the thermogenic markers UCP1 and PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator-α]. However, it did not alter normal fat accumulation or expression of non-BAT-specific genes. Collectively, these results specifically implicate Pref-1 in controlling the thermogenic gene expression program in BAT, and identify C/EBPδ as a novel transcriptional regulator of Pref-1 gene expression that may be related to the specific role of glucocorticoids in BAT differentiation.

  20. Effects of parabens on adipocyte differentiation.

    Science.gov (United States)

    Hu, Pan; Chen, Xin; Whitener, Rick J; Boder, Eric T; Jones, Jeremy O; Porollo, Aleksey; Chen, Jiangang; Zhao, Ling

    2013-01-01

    Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben. Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation. However, research on the effects of parabens on health is limited, and the effects of parabens on adipogenesis have not been systematically studied. Here, we report that (1) parabens promote adipogenesis (or adipocyte differentiation) in murine 3T3-L1 cells, as revealed by adipocyte morphology, lipid accumulation, and mRNA expression of adipocyte-specific markers; (2) the adipogenic potency of parabens is increased with increasing length of the linear alkyl chain in the following potency ranking order: methyl- parabens, and the structurally related benzoic acid (without the OH group) are inactive in promoting 3T3-L1 adipocyte differentiation; (3) parabens activate glucocorticoid receptor and/or peroxisome proliferator-activated receptor γ in 3T3-L1 preadipocytes; however, no direct binding to, or modulation of, the ligand binding domain of the glucocorticoid receptor by parabens was detected by glucocorticoid receptor competitor assays; and lastly, (4) parabens, butyl- and benzylparaben in particular, also promote adipose conversion of human adipose-derived multipotent stromal cells. Our results suggest that parabens may contribute to obesity epidemic, and the role of parabens in adipogenesis in vivo needs to be examined further.

  1. Topological effects of data incompleteness of gene regulatory networks

    CERN Document Server

    Sanz, J; Borge-Holthoefer, J; Moreno, Y

    2012-01-01

    The topological analysis of biological networks has been a prolific topic in network science during the last decade. A persistent problem with this approach is the inherent uncertainty and noisy nature of the data. One of the cases in which this situation is more marked is that of transcriptional regulatory networks (TRNs) in bacteria. The datasets are incomplete because regulatory pathways associated to a relevant fraction of bacterial genes remain unknown. Furthermore, direction, strengths and signs of the links are sometimes unknown or simply overlooked. Finally, the experimental approaches to infer the regulations are highly heterogeneous, in a way that induces the appearance of systematic experimental-topological correlations. And yet, the quality of the available data increases constantly. In this work we capitalize on these advances to point out the influence of data (in)completeness and quality on some classical results on topological analysis of TRNs, specially regarding modularity at different level...

  2. The Effect of Bone Marrow Mesenchymal Stem Cells on Vitamin D3 Induced Monocytic Differentiation of U937 Cells

    OpenAIRE

    Molaeipour, Zahra; Shamsasanjan, karim; Movassaghpour, Ali Akbari; Akbarzadehlaleh, Parvin; Sabaghi, Fatemeh; Saleh, Mahshid

    2016-01-01

    Purpose: Mesenchymal stem cells (MSCs) are key components of the hematopoietic stem cells (HSCs) niche. They control the process of hematopoiesis by secreting regulatory cytokines, growth factors and expression of important cell adhesion molecules for cell-tocell interactions. In this research, we have investigated the effect of bone marrow derived MSCs on monocytic differentiation of U937 cells line.

  3. Regulatory volume decrease in Leishmania mexicana: effect of anti-microtubule drugs

    Directory of Open Access Journals (Sweden)

    Francehuli Dagger

    2013-02-01

    Full Text Available The trypanosomatid cytoskeleton is responsible for the parasite's shape and it is modulated throughout the different stages of the parasite's life cycle. When parasites are exposed to media with reduced osmolarity, they initially swell, but subsequently undergo compensatory shrinking referred to as regulatory volume decrease (RVD. We studied the effects of anti-microtubule (Mt drugs on the proliferation of Leishmania mexicana promastigotes and their capacity to undergo RVD. All of the drugs tested exerted antiproliferative effects of varying magnitudes [ansamitocin P3 (AP3> trifluoperazine > taxol > rhizoxin > chlorpromazine]. No direct relationship was found between antiproliferative drug treatment and RVD. Similarly, Mt stability was not affected by drug treatment. Ansamitocin P3, which is effective at nanomolar concentrations, blocked amastigote-promastigote differentiation and was the only drug that impeded RVD, as measured by light dispersion. AP3 induced 2 kinetoplasts (Kt 1 nucleus cells that had numerous flagella-associated Kts throughout the cell. These results suggest that the dramatic morphological changes induced by AP3 alter the spatial organisation and directionality of the Mts that are necessary for the parasite's hypotonic stress-induced shape change, as well as its recovery.

  4. Differentiation state-specific mitochondrial dynamic regulatory networks are revealed by global transcriptional analysis of the developing chicken lens.

    Science.gov (United States)

    Chauss, Daniel; Basu, Subhasree; Rajakaruna, Suren; Ma, Zhiwei; Gau, Victoria; Anastas, Sara; Brennan, Lisa A; Hejtmancik, J Fielding; Menko, A Sue; Kantorow, Marc

    2014-06-13

    The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that requires a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium and maturing fiber cells of the embryonic Gallus gallus (chicken) lens. Our analysis detected more than 15,000 unique transcripts expressed by the embryonic chicken lens. Of these, more than 3000 transcripts exhibited significant differences in expression between lens epithelial cells and fiber cells. Multiple transcripts coding for separate mitochondrial homeostatic and degradation mechanisms were identified to exhibit preferred patterns of expression in lens epithelial cells that require mitochondria relative to lens fiber cells that require mitochondrial elimination. These included differences in the expression levels of metabolic (DUT, PDK1, SNPH), autophagy (ATG3, ATG4B, BECN1, FYCO1, WIPI1), and mitophagy (BNIP3L/NIX, BNIP3, PARK2, p62/SQSTM1) transcripts between lens epithelial cells and lens fiber cells. These data provide a comprehensive window into all genes transcribed by the lens and those mitochondrial regulatory and degradation pathways that function to maintain mitochondrial populations in the lens epithelium and to eliminate mitochondria in maturing lens fiber cells.

  5. [The effect of extremely low doses of the novel regulatory plant proteins ].

    Science.gov (United States)

    Krasnov, M S; Margasiuk, D V; Iamskov, I A; Iamskova, V P

    2003-01-01

    Searching and study on regulatory proteins, which can keep under control the scope of important processes as like as cell adhesion, proliferation, differentiation and morphogenesis, is an actual aim of the current biochemistry. Recently we have identified S-100 proteins in plants of following species: plantain (Plantago major L.), aloe (Aloe arborescens L.), and bilberry (Vaccinum myrtillus L.). Extraction and purification of S-100 proteins gotten from these plants were performed by the method we developed earlier for adhesion proteins of animal tissues. Homogeneity of the studied plant proteins was evaluated and confirmed by HPLC and SDS-electrophoresis in PAAG. Both, plant and animal proteins have appeared to be biologically active at extremely low doses. The tests were performed by adhesiometrical method in short-term tissue culture of mouse's liver in vitro. As a result it was established that the plant proteins insert a membranotropic effect being added in extremely low doses, corresponding to 10(-10)-10(-13) mg/ml. Keeping in mind that the plantain is well known remedy for wound protection and healing, in several experiments we studied the biological effect of plant S-100 proteins on animal cells. It was found that S-100 proteins obtained from plantain influences proliferation of human fibroblasts in vitro. It was found that after the treatment with this protein in low doses the cell growth rate increases essentially.

  6. A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells.

    Directory of Open Access Journals (Sweden)

    Yosuke Masubuchi

    Full Text Available BACKGROUND: Sweet taste receptor is expressed not only in taste buds but also in nongustatory organs such as enteroendocrine cells and pancreatic beta-cells, and may play more extensive physiological roles in energy metabolism. Here we examined the expression and function of the sweet taste receptor in 3T3-L1 cells. METHODOLOGY/PRINCIPAL FINDINGS: In undifferentiated preadipocytes, both T1R2 and T1R3 were expressed very weakly, whereas the expression of T1R3 but not T1R2 was markedly up-regulated upon induction of differentiation (by 83.0 and 3.8-fold, respectively at Day 6. The α subunits of Gs (Gαs and G14 (Gα14 but not gustducin were expressed throughout the differentiation process. The addition of sucralose or saccharin during the first 48 hours of differentiation considerably reduced the expression of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (C/EBPα at Day 2, the expression of aP2 at Day 4 and triglyceride accumulation at Day 6. These anti-adipogenic effects were attenuated by short hairpin RNA-mediated gene-silencing of T1R3. In addition, overexpression of the dominant-negative mutant of Gαs but not YM-254890, an inhibitor of Gα14, impeded the effects of sweeteners, suggesting a possible coupling of Gs with the putative sweet taste-sensing receptor. In agreement, sucralose and saccharin increased the cyclic AMP concentration in differentiating 3T3-L1 cells and also in HEK293 cells heterologously expressing T1R3. Furthermore, the anti-adipogenic effects of sweeteners were mimicked by Gs activation with cholera toxin but not by adenylate cyclase activation with forskolin, whereas small interfering RNA-mediated knockdown of Gαs had the opposite effects. CONCLUSIONS: 3T3-L1 cells express a functional sweet taste-sensing receptor presumably as a T1R3 homomer, which mediates the anti-adipogenic signal by a Gs-dependent but cAMP-independent mechanism.

  7. Na/H Exchanger Regulatory Factors Control Parathyroid Hormone Receptor Signaling by Facilitating Differential Activation of Gα Protein Subunits*

    Science.gov (United States)

    Wang, Bin; Ardura, Juan A.; Romero, Guillermo; Yang, Yanmei; Hall, Randy A.; Friedman, Peter A.

    2010-01-01

    The Na/H exchanger regulatory factors, NHERF1 and NHERF2, are adapter proteins involved in targeting and assembly of protein complexes. The parathyroid hormone receptor (PTHR) interacts with both NHERF1 and NHERF2. The NHERF proteins toggle PTHR signaling from predominantly activation of adenylyl cyclase in the absence of NHERF to principally stimulation of phospholipase C when the NHERF proteins are expressed. We hypothesized that this signaling switch occurs at the level of the G protein. We measured G protein activation by [35S]GTPγS binding and Gα subtype-specific immunoprecipitation using three different cellular models of PTHR signaling. These studies revealed that PTHR interactions with NHERF1 enhance receptor-mediated stimulation of Gαq but have no effect on stimulation of Gαi or Gαs. In contrast, PTHR associations with NHERF2 enhance receptor-mediated stimulation of both Gαq and Gαi but decrease stimulation of Gαs. Consistent with these functional data, NHERF2 formed cellular complexes with both Gαq and Gαi, whereas NHERF1 was found to interact only with Gαq. These findings demonstrate that NHERF interactions regulate PTHR signaling at the level of G proteins and that NHERF1 and NHERF2 exhibit isotype-specific effects on G protein activation. PMID:20562104

  8. Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation

    Directory of Open Access Journals (Sweden)

    Hansen Jacob B

    2011-05-01

    Full Text Available Abstract Background Although many molecular regulators of adipogenesis have been identified a comprehensive catalogue of components is still missing. Recent studies showed that the retinoblastoma protein (pRb was expressed in the cell cycle and late cellular differentiation phase during adipogenesis. To investigate this dual role of pRb in the early and late stages of adipogenesis we used microarrays to perform a comprehensive systems-level analysis of the common transcriptional program of the classic 3T3-L1 preadipocyte cell line, wild-type mouse embryonic fibroblasts (MEFs, and retinoblastoma gene-deficient MEFs (Rb-/- MEFs. Findings Comparative analysis of the expression profiles of 3T3-L1 cells and wild-type MEFs revealed genes involved specifically in early regulation of the adipocyte differentiation as well as secreted factors and signaling molecules regulating the later phase of differentiation. In an attempt to identify transcription factors regulating adipogenesis, bioinformatics analysis of the promoters of coordinately and highly expressed genes was performed. We were able to identify a number of high-confidence target genes for follow-up experimental studies. Additionally, combination of experimental data and computational analyses pinpointed a feedback-loop between Pparg and Foxo1. To analyze the effects of the retinoblastoma protein at the transcriptional level we chose a perturbated system (Rb-/- MEFs for comparison to the transcriptional program of wild-type MEFs. Gene ontology analysis of 64 deregulated genes showed that the Rb-/- MEF model exhibits a brown(-like adipocyte phenotype. Additionally, the analysis results indicate a different or additional role for pRb family member involvement in the lineage commitment. Conclusion In this study a number of commonly modulated genes during adipogenesis in 3T3-L1 cells and MEFs, potential transcriptional regulation mechanisms, and differentially regulated targets during adipocyte

  9. Subsets of human natural killer cells and their regulatory effects

    Science.gov (United States)

    Fu, Binqing; Tian, Zhigang; Wei, Haiming

    2014-01-01

    Human natural killer (NK) cells have distinct functions as NKtolerant, NKcytotoxic and NKregulatory cells and can be divided into different subsets based on the relative expression of the surface markers CD27 and CD11b. CD27+ NK cells, which are abundant cytokine producers, are numerically in the minority in human peripheral blood but constitute the large population of NK cells in cord blood, spleen, tonsil and decidua tissues. Recent data suggest that these NK cells may have immunoregulatory properties under certain conditions. In this review, we will focus on these new NK cell subsets and discuss how regulatory NK cells may serve as rheostats or sentinels in controlling inflammation and maintaining immune homeostasis in various organs. PMID:24303897

  10. High Dimensional ODEs Coupled with Mixed-Effects Modeling Techniques for Dynamic Gene Regulatory Network Identification.

    Science.gov (United States)

    Lu, Tao; Liang, Hua; Li, Hongzhe; Wu, Hulin

    2011-01-01

    Gene regulation is a complicated process. The interaction of many genes and their products forms an intricate biological network. Identification of this dynamic network will help us understand the biological process in a systematic way. However, the construction of such a dynamic network is very challenging for a high-dimensional system. In this article we propose to use a set of ordinary differential equations (ODE), coupled with dimensional reduction by clustering and mixed-effects modeling techniques, to model the dynamic gene regulatory network (GRN). The ODE models allow us to quantify both positive and negative gene regulations as well as feedback effects of one set of genes in a functional module on the dynamic expression changes of the genes in another functional module, which results in a directed graph network. A five-step procedure, Clustering, Smoothing, regulation Identification, parameter Estimates refining and Function enrichment analysis (CSIEF) is developed to identify the ODE-based dynamic GRN. In the proposed CSIEF procedure, a series of cutting-edge statistical methods and techniques are employed, that include non-parametric mixed-effects models with a mixture distribution for clustering, nonparametric mixed-effects smoothing-based methods for ODE models, the smoothly clipped absolute deviation (SCAD)-based variable selection, and stochastic approximation EM (SAEM) approach for mixed-effects ODE model parameter estimation. The key step, the SCAD-based variable selection of the proposed procedure is justified by investigating its asymptotic properties and validated by Monte Carlo simulations. We apply the proposed method to identify the dynamic GRN for yeast cell cycle progression data. We are able to annotate the identified modules through function enrichment analyses. Some interesting biological findings are discussed. The proposed procedure is a promising tool for constructing a general dynamic GRN and more complicated dynamic networks.

  11. PD-L1 Blockade Differentially Impacts Regulatory T Cells from HIV-Infected Individuals Depending on Plasma Viremia.

    Directory of Open Access Journals (Sweden)

    Cristina Peligero

    2015-12-01

    Full Text Available Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells, which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment. However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject's plasma viremia.

  12. Global mapping of cell type-specific open chromatin by FAIRE-seq reveals the regulatory role of the NFI family in adipocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Hironori Waki

    2011-10-01

    Full Text Available Identification of regulatory elements within the genome is crucial for understanding the mechanisms that govern cell type-specific gene expression. We generated genome-wide maps of open chromatin sites in 3T3-L1 adipocytes (on day 0 and day 8 of differentiation and NIH-3T3 fibroblasts using formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq. FAIRE peaks at the promoter were associated with active transcription and histone modifications of H3K4me3 and H3K27ac. Non-promoter FAIRE peaks were characterized by H3K4me1+/me3-, the signature of enhancers, and were largely located in distal regions. The non-promoter FAIRE peaks showed dynamic change during differentiation, while the promoter FAIRE peaks were relatively constant. Functionally, the adipocyte- and preadipocyte-specific non-promoter FAIRE peaks were, respectively, associated with genes up-regulated and down-regulated by differentiation. Genes highly up-regulated during differentiation were associated with multiple clustered adipocyte-specific FAIRE peaks. Among the adipocyte-specific FAIRE peaks, 45.3% and 11.7% overlapped binding sites for, respectively, PPARγ and C/EBPα, the master regulators of adipocyte differentiation. Computational motif analyses of the adipocyte-specific FAIRE peaks revealed enrichment of a binding motif for nuclear family I (NFI transcription factors. Indeed, ChIP assay showed that NFI occupy the adipocyte-specific FAIRE peaks and/or the PPARγ binding sites near PPARγ, C/EBPα, and aP2 genes. Overexpression of NFIA in 3T3-L1 cells resulted in robust induction of these genes and lipid droplet formation without differentiation stimulus. Overexpression of dominant-negative NFIA or siRNA-mediated knockdown of NFIA or NFIB significantly suppressed both induction of genes and lipid accumulation during differentiation, suggesting a physiological function of these factors in the adipogenic program. Together, our

  13. 77 FR 66888 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-11-07

    ... conduct manual cabinet trading. B. Self-Regulatory Organization's Statement on Burden on Competition The... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... have been prepared by the self-regulatory organization. The Commission is publishing this notice to...

  14. 77 FR 1545 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-01-10

    ....15c3-5. Because these are NYSE Arca proprietary firms, the regulatory risk of extending the time to... COMMISSION Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of... Regulatory Authority Members to March 31, 2012 January 4, 2012. Pursuant to Section 19(b)(1) \\1\\ of...

  15. 77 FR 52090 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-08-28

    ... Regulatory Bulletin any applicable minimum, maximum and/or default settings for the Risk Limitation... Regulatory Bulletin the applicable time period(s) for the Risk Limitation Mechanisms proposed under Rule... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness...

  16. Differential control of immune cell homeostasis by Foxp3(+) regulatory T cells in murine peripheral lymph nodes and spleen.

    Science.gov (United States)

    Milanez-Almeida, Pedro; Klawonn, Frank; Meyer-Hermann, Michael; Huehn, Jochen

    2014-09-01

    Foxp3(+) regulatory T cells (Tregs) hamper efficient immune responses to tumors and chronic infections. Therefore, depletion of Foxp3(+) Tregs has been proposed as therapeutic option to boost immune responses and to improve vaccinations. Although Treg-mediated control of T cell homeostasis is well established, Foxp3(+) Treg interaction with other immune cell subsets is only incompletely understood. Thus, the present study aimed at examining dynamic effects of experimental Foxp3(+) Treg depletion on a broad range of immune cell subsets, including B cells, natural killer cells, and myeloid cells. Striking differences were observed when peripheral lymph nodes (LN) and spleen were compared. B cells, for example, showed a massive and long-lasting accumulation only in LN but not in spleen of transiently Treg-depleted mice. In contrast, monocyte-derived dendritic cells, which are potent inducers of T cell responses, also accumulated selectively, but only transiently in LN, suggesting that this cell population is under very strict control of Foxp3(+) Tregs. In summary, the observations described here provide insights into the dynamics of immune cells after selective depletion of Foxp3(+) Tregs. This will allow a better prediction of the impact of Treg ablation in translational studies that aim at boosting immune responses and vaccinations.

  17. SMCis: An Effective Algorithm for Discovery of Cis-Regulatory Modules

    Science.gov (United States)

    Guo, Haitao; Huo, Hongwei; Yu, Qiang

    2016-01-01

    The discovery of cis-regulatory modules (CRMs) is a challenging problem in computational biology. Limited by the difficulty of using an HMM to model dependent features in transcriptional regulatory sequences (TRSs), the probabilistic modeling methods based on HMMs cannot accurately represent the distance between regulatory elements in TRSs and are cumbersome to model the prevailing dependencies between motifs within CRMs. We propose a probabilistic modeling algorithm called SMCis, which builds a more powerful CRM discovery model based on a hidden semi-Markov model. Our model characterizes the regulatory structure of CRMs and effectively models dependencies between motifs at a higher level of abstraction based on segments rather than nucleotides. Experimental results on three benchmark datasets indicate that our method performs better than the compared algorithms. PMID:27637070

  18. Effects of Uniform and Differential Rotation on Stellar Pulsations

    OpenAIRE

    Lovekin, C. C.; Deupree, R. G.; Clement, M.J.

    2008-01-01

    We have investigated the effects of uniform rotation and a specific model for differential rotation on the pulsation frequencies of 10 \\Msun\\ stellar models. Uniform rotation decreases the frequencies for all modes. Differential rotation does not appear to have a significant effect on the frequencies, except for the most extreme differentially rotating models. In all cases, the large and small separations show the effects of rotation at lower velocities than do the individual frequencies. Unf...

  19. Effective action for stochastic partial differential equations

    Energy Technology Data Exchange (ETDEWEB)

    Hochberg, David [Laboratorio de Astrofisica Espacial y Fisica Fundamental, Apartado 50727, 28080 Madrid, (Spain); Centro de Astrobiologia, INTA, Carratera Ajalvir, Km. 4, 28850 Torrejon, Madrid, (Spain); Molina-Paris, Carmen [Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Perez-Mercader, Juan [Laboratorio de Astrofisica Espacial y Fisica Fundamental, Apartado 50727, 28080 Madrid, (Spain); Visser, Matt [Physics Department, Washington University, Saint Louis, Missouri 63130-4899 (United States)

    1999-12-01

    Stochastic partial differential equations (SPDEs) are the basic tool for modeling systems where noise is important. SPDEs are used for models of turbulence, pattern formation, and the structural development of the universe itself. It is reasonably well known that certain SPDEs can be manipulated to be equivalent to (nonquantum) field theories that nevertheless exhibit deep and important relationships with quantum field theory. In this paper we systematically extend these ideas: We set up a functional integral formalism and demonstrate how to extract all the one-loop physics for an arbitrary SPDE subject to arbitrary Gaussian noise. It is extremely important to realize that Gaussian noise does not imply that the field variables undergo Gaussian fluctuations, and that these nonquantum field theories are fully interacting. The limitation to one loop is not as serious as might be supposed: Experience with quantum field theories (QFTs) has taught us that one-loop physics is often quite adequate to give a good description of the salient issues. The limitation to one loop does, however, offer marked technical advantages: Because at one loop almost any field theory can be rendered finite using zeta function technology, we can sidestep the complications inherent in the Martin-Siggia-Rose formalism (the SPDE analog of the Becchi-Rouet-Stora-Tyutin formalism used in QFT) and instead focus attention on a minimalist approach that uses only the physical fields (this ''direct approach'' is the SPDE analog of canonical quantization using physical fields). After setting up the general formalism for the characteristic functional (partition function), we show how to define the effective action to all loops, and then focus on the one-loop effective action and its specialization to constant fields: the effective potential. The physical interpretation of the effective action and effective potential for SPDEs is addressed and we show that key features carry over from

  20. Effective action for stochastic partial differential equations.

    Science.gov (United States)

    Hochberg, D; Molina-París, C; Pérez-Mercader, J; Visser, M

    1999-12-01

    Stochastic partial differential equations (SPDEs) are the basic tool for modeling systems where noise is important. SPDEs are used for models of turbulence, pattern formation, and the structural development of the universe itself. It is reasonably well known that certain SPDEs can be manipulated to be equivalent to (nonquantum) field theories that nevertheless exhibit deep and important relationships with quantum field theory. In this paper we systematically extend these ideas: We set up a functional integral formalism and demonstrate how to extract all the one-loop physics for an arbitrary SPDE subject to arbitrary Gaussian noise. It is extremely important to realize that Gaussian noise does not imply that the field variables undergo Gaussian fluctuations, and that these nonquantum field theories are fully interacting. The limitation to one loop is not as serious as might be supposed: Experience with quantum field theories (QFTs) has taught us that one-loop physics is often quite adequate to give a good description of the salient issues. The limitation to one loop does, however, offer marked technical advantages: Because at one loop almost any field theory can be rendered finite using zeta function technology, we can sidestep the complications inherent in the Martin-Siggia-Rose formalism (the SPDE analog of the Becchi-Rouet-Stora-Tyutin formalism used in QFT) and instead focus attention on a minimalist approach that uses only the physical fields (this "direct approach" is the SPDE analog of canonical quantization using physical fields). After setting up the general formalism for the characteristic functional (partition function), we show how to define the effective action to all loops, and then focus on the one-loop effective action and its specialization to constant fields: the effective potential. The physical interpretation of the effective action and effective potential for SPDEs is addressed and we show that key features carry over from QFT to the case of

  1. Effect of leukemia inhibitory factor on embryonic stem cell differentiation: implications for supporting neuronal differentiation

    Institute of Scientific and Technical Information of China (English)

    Zhao HE; Jing-jing LI; Chang-hong ZHEN; Lin-ying FENG; Xiao-yan DING

    2006-01-01

    Aim: Leukemia inhibitory factor (LIF), a pleiotropic cytokine, has been used extensively in the maintenance of mouse embryonic stem cell pluripotency. In this current work, we examined the effect of the LIF signaling pathway in embryonic stem (ES) cell differentiation to a neural fate. Methods: In the presence of LIF (1000 U/mL), the production of neuronal cells derived from embryoid bodies (EB)was tested under various culture conditions. Inhibition of the LIF pathway was examined with specific inhibitors. The effects of cell apoptosis and proliferation on neural differentiation were examined. ES cell differentiation into three-gem layers was compared. Results: Under various culture conditions, neuronal differentiation was increased in the presence of LIF. Blocking the LIF-activated STAT3signaling pathway with specific inhibitors abolished the neuronal differentiation of ES cells, whereas inhibition of the LIF-activated MEK signaling pathway impaired the differentiation of ES cells toward a glial fate. LIF suppressed cell apoptosis and promoted cell proliferation during ES cell differentiation. LIF inhibited the differentiation of ES cells to both mesoderm and extraembryonic endoderm fates, but enhanced the determination of neural progenitors. Conclusion:These results suggest that LIF plays a positive role during the differentiation of ES cells into neuronal cells.

  2. Time perspective and social preference in older and younger adults: Effects of self-regulatory fatigue.

    Science.gov (United States)

    Segerstrom, Suzanne C; Geiger, Paul J; Combs, Hannah L; Boggero, Ian A

    2016-09-01

    Socioemotional selectivity theory predicts that when perceived time in life is limited, people will prefer emotionally close social partners over less emotionally rewarding partners. Regulating social choices with regard to time perspective can make the best use of time with regard to well-being. However, doing so may depend on the self-regulatory capacity of the individual. Two studies, 1 with younger adults (N = 101) and 1 with younger (N = 42) and older (N = 39) adults, experimentally tested the effects of time perspective and self-regulatory fatigue on preferences for emotionally close partners and knowledgeable partners. In both studies and across younger and older adults, when self-regulatory fatigue was low, the perception of limited time resulted in a greater preference for close social partners relative to knowledgeable social partners. However, this shift was eliminated by self-regulatory fatigue. In Study 2, when fatigued, younger adults preferred close social partners to knowledgeable partners across time perspectives; older adults preferred close and knowledgeable partners more equally across time perspectives. These findings have implications for social decision-making and satisfaction among people who experience chronic self-regulatory fatigue. They also contradict previous suggestions that only younger adults are susceptible to self-regulatory fatigue. (PsycINFO Database Record

  3. The Regulatory Effect of Natural Killer Cells: Do "NK-reg Cells" Exist?

    Institute of Scientific and Technical Information of China (English)

    Cai Zhang; Jian Zhang; Zhigang Tian

    2006-01-01

    The most important progress in immunology in the last decade is the description of regulatory lymphocytes, among which Treg cells and regulatory NKT cells are much attractive to not only immunologists but also almost all biomedical researchers. Meanwhile, it is noted that NK cells are not only "Killers" but also regulate innate and adaptive immunity, especially in early stage, by secreting cytokines and cell-cell contact. In this review, we are going to briefly summarize the progresses in regulatory lymphocytes including T cells (Treg, Tr1, Th3), NKT cells and NK cells, and then extensively introduce the positive regulatory function of NK cells in both normal immune response and in disease condition (tumor, infection and autoimmunity), and finally, to focus on the most latest progression in the negative regulatory effects of NK cells on normal and pathogenic immune response. In conclusion, we speculate that a "regulatory NK (NK-reg)" cell subset exist and need to explore. Cellular & Molecular Immunology. 2006;3(4):241-254.

  4. Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation

    DEFF Research Database (Denmark)

    Hakim-Weber, Robab; Krogsdam, Anne-M; Jørgensen, Claus;

    2011-01-01

    this dual role of pRb in the early and late stages of adipogenesis we used microarrays to perform a comprehensive systems-level analysis of the common transcriptional program of the classic 3T3-L1 preadipocyte cell line, wild-type mouse embryonic fibroblasts (MEFs), and retinoblastoma gene-deficient MEFs...... of experimental data and computational analyses pinpointed a feedback-loop between Pparg and Foxo1.To analyze the effects of the retinoblastoma protein at the transcriptional level we chose a perturbated system (Rb-/- MEFs) for comparison to the transcriptional program of wild-type MEFs. Gene ontology analysis......Although many molecular regulators of adipogenesis have been identified a comprehensive catalogue of components is still missing. Recent studies showed that the retinoblastoma protein (pRb) was expressed in the cell cycle and late cellular differentiation phase during adipogenesis. To investigate...

  5. 特质性与情境性调节定向匹配效应的一致性%The Coincidence between the Regulatory Fit Effects Based on Chronic Regulatory Focus and Situational Regulatory Focus

    Institute of Scientific and Technical Information of China (English)

    汪玲; 林晖芸; 逄晓鸣

    2011-01-01

    Regulatory fit theory proposes that the fit between regulatory focus and information frame will strengthen the individual's evaluation on the information, as well as the affect and motivation. However, the regulatory focus involves two different types: situational focus and chronic focus, the former is induced by environmental factors, while the latter reflects stable personality. Thus, an interesting question is, whether the regulatory fits based on different types of regulatory focus have the same effect? And this is the purpose of the present study.Experiment 1 adopted 2 (chronic regulatory focus: promotion vs. prevention) ×2 (information frame:positive vs. negative) between-subjects design to explore the influence of regulatory fit between chronic focus and information frame upon the effect of persuasion. Experiment 2 also adopted 2 (situational regulatory focus:promotion vs. prevention) ×2 (information frame: positive vs. negative) between-subjects design to explore the effect of regulatory fit between situational focus and information frame upon the effect of persuasion. Data were collected from 166 college students (113 in Experiment 1 and 53 in Experiment 2).In experiment 1, MANOVA revealed significant interactions between regulatory focus and information frame on the information value and mood intensity, while in experiment 2, in addition to information value and mood intensity, MANOVA revealed significant interaction on behavior intention. Taken together, results showed the regulatory fit based on chronic regulatory focus and the regulatory fit based on situational regulatory focus have the same influence on information value and mood intensity (they both improve the value of information and increase the intensity of mood); however, they have different influence on behavior intention (the former has no impact on behavior intention while the latter can improve behavior intention).This conclusion is beneficial to understand the difference between chronic

  6. Does Self-Regulatory Efficacy Matter? Effects of Punishment Certainty and Punishment Severity on Organizational Deviance

    Directory of Open Access Journals (Sweden)

    Kabiru Maitama Kura

    2015-06-01

    Full Text Available Extant empirical research has reported conflicting findings with respect to the effects of punishment certainty and punishment severity on organizational deviance, suggesting the need to introduce a moderator. The present study tested whether self-regulatory efficacy matters on the relationships among punishment certainty, punishment severity, and organizational deviance. Drawing on deterrence and self-efficacy theories, this study examined the effects of punishment certainty, punishment severity, and self-regulatory efficacy on organizational deviance among 197 employed postgraduate students who enrolled in the Master of Business Administration program at two large universities located in the north-west geopolitical zone of Nigeria. We used self-administered questionnaires to collect data. Using Partial Least Squares Structural Equation Modeling (PLS-SEM, we found a significant negative relationship between punishment certainty and organizational deviance. Similarly, the results indicated that punishment severity had a significant negative relationship with organizational deviance. The study also found a significant negative relationship between self-regulatory efficacy and organizational deviance. As expected, self-regulatory efficacy was found to moderate the relationship between punishment certainty and organizational deviance. On the contrary, no significant interaction effect was found between self-regulatory efficacy and punishment severity. Implications of the study in the Nigerian context have been discussed.

  7. 78 FR 62921 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-10-22

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness... marketed by the Exchange by featuring and advertising them on the Exchange's Web site. Market-Q will be... comments on the proposed rule change. III. Date of Effectiveness of the Proposed Rule Change and Timing...

  8. Linking Hematopoietic Differentiation to Co-Expressed Sets of Pluripotency-Associated and Imprinted Genes and to Regulatory microRNA-Transcription Factor Motifs

    Science.gov (United States)

    Hamed, Mohamed; Trumm, Johannes; Spaniol, Christian; Sethi, Riccha; Irhimeh, Mohammad R.; Fuellen, Georg; Paulsen, Martina

    2017-01-01

    Maintenance of cell pluripotency, differentiation, and reprogramming are regulated by complex gene regulatory networks (GRNs) including monoallelically-expressed imprinted genes. Besides transcriptional control, epigenetic modifications and microRNAs contribute to cellular differentiation. As a model system for studying the capacity of cells to preserve their pluripotency state and the onset of differentiation and subsequent specialization, murine hematopoiesis was used and compared to embryonic stem cells (ESCs) as a control. Using published microarray data, the expression profiles of two sets of genes, pluripotent and imprinted, were compared to a third set of known hematopoietic genes. We found that more than half of the pluripotent and imprinted genes are clearly upregulated in ESCs but subsequently repressed during hematopoiesis. The remaining genes were either upregulated in hematopoietic progenitors or in differentiated blood cells. The three gene sets each consist of three similarly behaving gene groups with similar expression profiles in various lineages of the hematopoietic system as well as in ESCs. To explain this co-regulation behavior, we explored the transcriptional and post-transcriptional mechanisms of pluripotent and imprinted genes and their regulator/target miRNAs in six different hematopoietic lineages. Therewith, lineage-specific transcription factor (TF)-miRNA regulatory networks were generated and their topologies and functional impacts during hematopoiesis were analyzed. This led to the identification of TF-miRNA co-regulatory motifs, for which we validated the contribution to the cellular development of the corresponding lineage in terms of statistical significance and relevance to biological evidence. This analysis also identified key miRNAs and TFs/genes that might play important roles in the derived lineage networks. These molecular associations suggest new aspects of the cellular regulation of the onset of cellular differentiation and

  9. Evaluating Differential Effects Using Regression Interactions and Regression Mixture Models

    Science.gov (United States)

    Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung

    2015-01-01

    Research increasingly emphasizes understanding differential effects. This article focuses on understanding regression mixture models, which are relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their…

  10. Potential toxic effects of glyphosate and its commercial formulations below regulatory limits.

    Science.gov (United States)

    Mesnage, R; Defarge, N; Spiroux de Vendômois, J; Séralini, G E

    2015-10-01

    Glyphosate-based herbicides (GlyBH), including Roundup, are the most widely used pesticides worldwide. Their uses have increased exponentially since their introduction on the market. Residue levels in food or water, as well as human exposures, are escalating. We have reviewed the toxic effects of GlyBH measured below regulatory limits by evaluating the published literature and regulatory reports. We reveal a coherent body of evidence indicating that GlyBH could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects. It includes teratogenic, tumorigenic and hepatorenal effects. They could be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time. Some effects were detected in the range of the recommended acceptable daily intake. Toxic effects of commercial formulations can also be explained by GlyBH adjuvants, which have their own toxicity, but also enhance glyphosate toxicity. These challenge the assumption of safety of GlyBH at the levels at which they contaminate food and the environment, albeit these levels may fall below regulatory thresholds. Neurodevelopmental, reproductive, and transgenerational effects of GlyBH must be revisited, since a growing body of knowledge suggests the predominance of endocrine disrupting mechanisms caused by environmentally relevant levels of exposure.

  11. Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation

    NARCIS (Netherlands)

    Morikawa, Hiromasa; Ohkura, Naganari; Vandenbon, Alexis; Itoh, Masayoshi; Nagao-Sato, Sayaka; Kawaji, Hideya; Lassmann, Timo; Carninci, Piero; Hayashizaki, Yoshihide; Forrest, Alistair R R; Standley, Daron M; Date, Hiroshi; Sakaguchi, Shimon; Clevers, Hans

    2014-01-01

    Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA

  12. Regulatory focus and burnout in nurses: The mediating effect of perception of transformational leadership.

    Science.gov (United States)

    Shi, Rui; Zhang, Shilei; Xu, Hang; Liu, Xufeng; Miao, Danmin

    2015-12-01

    This correlation study investigated the relationship between nurses' regulatory focus and burnout, as mediated by their perceptions of transformational leadership, using a cross-sectional research design with anonymous questionnaires. In July-August 2012, data were collected from 378 nurses from three hospitals in Shaanxi Province, China, using self-report questionnaires for measuring the nurses' regulatory focus, their level of burnout and their perception of whether the leadership of their supervisor was transformational. Structural equation modelling and bootstrapping procedures were used to identify the mediating effect of their perceptions of transformational leadership. The results supported our hypothesized model. The type of regulatory focus emerged as a significant predictor of burnout. Having a perception of transformational leadership partially mediated the relationship between regulatory focus and burnout. Having a promotion focus reduced burnout when the participants perceived transformational leadership, whereas having a prevention focus exhibited the opposite pattern. The mediating effect of the perception of transformational leadership suggests that a promotion focus may help diminish burnout, directly and indirectly. Nurse managers must be aware of the role of a regulatory focus and cultivate promotion focus in their followers.

  13. Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1.

    Directory of Open Access Journals (Sweden)

    Zabrina L Brumme

    2007-07-01

    Full Text Available Despite the formidable mutational capacity and sequence diversity of HIV-1, evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways. Population-based analyses of clinically derived HIV sequences may be used to identify immune escape mutations in viral genes; however, prior attempts to identify such mutations have been complicated by the inability to discriminate active immune selection from virus founder effects. Furthermore, the association between mutations arising under in vivo immune selection and disease progression for highly variable pathogens such as HIV-1 remains incompletely understood. We applied a viral lineage-corrected analytical method to investigate HLA class I-associated sequence imprinting in HIV protease, reverse transcriptase (RT, Vpr, and Nef in a large cohort of chronically infected, antiretrovirally naïve individuals. A total of 478 unique HLA-associated polymorphisms were observed and organized into a series of "escape maps," which identify known and putative cytotoxic T lymphocyte (CTL epitopes under selection pressure in vivo. Our data indicate that pathways to immune escape are predictable based on host HLA class I profile, and that epitope anchor residues are not the preferred sites of CTL escape. Results reveal differential contributions of immune imprinting to viral gene diversity, with Nef exhibiting far greater evidence for HLA class I-mediated selection compared to other genes. Moreover, these data reveal a significant, dose-dependent inverse correlation between HLA-associated polymorphisms and HIV disease stage as estimated by CD4(+ T cell count. Identification of specific sites and patterns of HLA-associated polymorphisms across HIV protease, RT, Vpr, and Nef illuminates regions of the genes encoding these products under active immune selection pressure in vivo. The high density of HLA-associated polymorphisms in Nef compared to other

  14. TRADE EFFECTS: REGULATORY, ACCOUNTING PRACTICES AND REPORTING OF INFORMATION RELATED

    OpenAIRE

    ARISTIŢA ROTILĂ

    2014-01-01

    It is known that within trade relations providers often credit customers for the value of goods or services which are the subject of conducted commercial transactions, this aspect being materialized in the issuance and acceptance of a trade effect. From the time of acceptance until maturity / settlement, trade effects should be reflected separately in the accounts and, to the extent that were not settled until the end of exercise, their value must be presented in the financial ...

  15. TRADE EFFECTS: REGULATORY, ACCOUNTING PRACTICES AND REPORTING OF INFORMATION RELATED

    Directory of Open Access Journals (Sweden)

    ARISTIŢA ROTILĂ

    2014-05-01

    Full Text Available It is known that within trade relations providers often credit customers for the value of goods or services which are the subject of conducted commercial transactions, this aspect being materialized in the issuance and acceptance of a trade effect. From the time of acceptance until maturity / settlement, trade effects should be reflected separately in the accounts and, to the extent that were not settled until the end of exercise, their value must be presented in the financial statements. Based on analysis of the Romanian accounting regulations, also taking into consideration the opinions expressed in specific literature concerning accounting reflection of trade effects, in this article we try to point out some aspects which, in our opinion, require clarification. We also want to point out some contradictions / inconsistencies regarding the reporting of information on the trade effects, specifically between the text of accounting regulations concerning the definition of accounting structures „cash and bank accounts” and “short term investments” and their contents when presented as positions in the balance sheet structure. In relation to the issues raised we try to prove the effects on the indicators concerning financial position and to make some suggestions that would have effects on Romanian accounting regulations, namely the improvement of financial reporting performed by the economic operators.

  16. Phosphorylation-dependent differential regulation of plant growth, cell death, and innate immunity by the regulatory receptor-like kinase BAK1

    DEFF Research Database (Denmark)

    Schwessinger, Benjamin; Roux, Milena; Kadota, Yasuhiro;

    2011-01-01

    Plants rely heavily on receptor-like kinases (RLKs) for perception and integration of external and internal stimuli. The Arabidopsis regulatory leucine-rich repeat RLK (LRR-RLK) BAK1 is involved in steroid hormone responses, innate immunity, and cell death control. Here, we describe the different......Plants rely heavily on receptor-like kinases (RLKs) for perception and integration of external and internal stimuli. The Arabidopsis regulatory leucine-rich repeat RLK (LRR-RLK) BAK1 is involved in steroid hormone responses, innate immunity, and cell death control. Here, we describe...... the differential regulation of three different BAK1-dependent signaling pathways by a novel allele of BAK1, bak1-5. Innate immune signaling mediated by the BAK1-dependent RKs FLS2 and EFR is severely compromised in bak1-5 mutant plants. However, bak1-5 mutants are not impaired in BR signaling or cell death control...... of FLS2 or EFR with BAK1 in planta, revealing another pathway specific mechanistic difference. The specific suppression of FLS2- and EFR-dependent signaling in bak1-5 is not due to a differential interaction of BAK1-5 with the respective ligand-binding RK but requires BAK1-5 kinase activity. Overall our...

  17. The effects of intrinsic noise on the behaviour of bistable cell regulatory systems under quasi-steady state conditions

    CERN Document Server

    de la Cruz, Roberto; Spill, Fabian; Alarcón, Tomás

    2015-01-01

    We analyse the effect of intrinsic fluctuations on the properties of bistable stochastic systems with time scale separation operating under1 quasi-steady state conditions. We first formulate a stochastic generalisation of the quasi-steady state approximation based on the semi-classical approximation of the partial differential equation for the generating function associated with the Chemical Master Equation. Such approximation proceeds by optimising an action functional whose associated set of Euler-Lagrange (Hamilton) equations provide the most likely fluctuation path. We show that, under appropriate conditions granting time scale separation, the Hamiltonian can be re-scaled so that the set of Hamilton equations splits up into slow and fast variables, whereby the quasi-steady state approximation can be applied. We analyse two particular examples of systems whose mean-field limit has been shown to exhibit bi-stability: an enzyme-catalysed system of two mutually-inhibitory proteins and a gene regulatory circui...

  18. The role of Smad Ubiquitin Regulatory Factor-1: SMURF1 in the differentiation 3T3-L1

    OpenAIRE

    Muñiz Diego, María del Carmen

    2013-01-01

    The Smad Ubiquitin Regulatory Factor-1: SMURF1 is an E3 ligase. This E3 ligase has been linked to several important biological pathways, including the bone morphogenetic protein pathway, the non-canonical Wnt pathway and the mitogen-activated protein kinase pathway. Multiple functions of Smurf1 have been discovered in cell growth and morphogenesis, cell migration, cell polarity and autophagy. Previous studies, in 2003, have demonstrated that overexpression of Smurf1 induces proteasomal degrad...

  19. 78 FR 9763 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-02-11

    ... non- Member to connect into the Exchange at the data centers where Exchange servers are located... From the Federal Register Online via the Government Publishing Office ] SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

  20. 75 FR 78791 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-12-16

    ...-member to literally plug into the Exchange at the data centers where the Exchange's servers are located... From the Federal Register Online via the Government Publishing Office ] SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

  1. 78 FR 9749 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-02-11

    ... non- Member to connect into the Exchange at the data centers where Exchange servers are located... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

  2. 75 FR 78794 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-12-16

    ...-member to literally plug into the Exchange at the data centers where the Exchange's servers are located... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

  3. 78 FR 19350 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-03-29

    ... physical ports to access the Exchange at the primary data center where the Exchange's servers are located... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

  4. Reducing the Effect of Stereotype Threat: The Role of Coaction Contexts and Regulatory Fit

    Science.gov (United States)

    Wen, Fangfang; Zuo, Bin; Wu, Yang; Dong, Xuanhao; Wang, Wei

    2016-01-01

    Two experiments examined the effects of competition and cooperation contexts, as well as regulatory fit, on reducing the negative influence of stereotype threat. Experiment 1 demonstrated that in high stereotype threat conditions, participants in the cooperation context scored significantly higher on a math test than those in the competition…

  5. 75 FR 80097 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

    Science.gov (United States)

    2010-12-21

    ... COMMISSION Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule Change by NYSE Amex LLC Establishing Strike Price Intervals of $1 and Increasing Position and Exercise Limits With Respect to Options on the KBW Bank Index December 15, 2010. Pursuant to Section 19(b)(1)...

  6. The persuasive effects of framing messages on fruit and vegetable consumption according to regulatory focus theory

    NARCIS (Netherlands)

    Dijkstra, Arie; Rothman, Alexander; Pietersma, Suzanne

    2011-01-01

    According to Regulatory Focus theory (RFT), outcomes in persuasive messages can be framed in four different ways, as gains, non-gains, losses or non-losses. In study 1, the persuasiveness of all four frames was compared and the presence/absence effect that was expected on the basis of the feature-po

  7. Regulatory fit effects for injunctive versus descriptive social norms: Evidence from the promotion of sustainable products

    NARCIS (Netherlands)

    Melnyk, V.; Herpen, van E.; Fischer, A.R.H.; Trijp, van J.C.M.

    2013-01-01

    Consumers face marketing messages using social norms in many situations where different goals are dominant. This research examines moderating effects of regulatory focus for descriptive and injunctive norms in the promotion of sustainable products. More specifically, it shows that descriptive norms

  8. 75 FR 78783 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-12-16

    ... and open market and a national market system and, in general, to protect investors and the public... COMMISSION Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend EDGA Rule 11.14 To Extend the Operation of a Pilot Pursuant to...

  9. 75 FR 78787 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-12-16

    ... and open market and a national market system and, in general, to protect investors and the public... COMMISSION Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend EDGX Rule 11.14 To Extend the Operation of a Pilot Pursuant to...

  10. 77 FR 4608 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-01-30

    ... of a free and open market and a national market system and, in general, to protect investors and the... COMMISSION Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend EDGA Rule 11.14 To Extend the Operation of the Single Stock...

  11. 77 FR 4606 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-01-30

    ... of a free and open market and a national market system and, in general, to protect investors and the... COMMISSION Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend EDGX Rule 11.14 To Extend the Operation of the Single Stock...

  12. The Effect of Blog Use on Self-Regulatory Learning of Prospective German Language Teachers

    Science.gov (United States)

    Seyhan Yucel, Mukadder

    2013-01-01

    The purpose of the study was to examine the effect of blog use on self-regulatory learning of prospective German language teachers. The study is semi-experimental. Pretest-posttest, experiment control model was used. Blog activities were conducted as extensive beyond classroom activities only for the experiment group. As the data collection tool…

  13. 78 FR 37644 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-06-21

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. June 17, 2013. Pursuant to...\\ notice is hereby given that on June 4, 2013, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'')...

  14. 77 FR 58195 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-09-19

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. September 13, 2012. Pursuant... thereunder,\\2\\ notice is hereby given that on August 31, 2012, BATS Exchange, Inc. (the ``Exchange''...

  15. 78 FR 77736 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-12-24

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change To Modify BATS Options Market Maker Continuous Quoting Obligation Rules... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 5, 2013, BATS Exchange, Inc....

  16. 78 FR 8617 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-02-06

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend BATS Rules Related to Price Sliding Functionality January 31, 2013... thereunder,\\2\\ notice is hereby given that on January 25, 2013, BATS Exchange, Inc. (the ``Exchange''...

  17. 76 FR 26331 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-05-06

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change To Extend the Trading Hours of BATS Options for Certain Products May 2... 19b-4 thereunder,\\2\\ notice is hereby given that, on April 26, 2011, BATS Exchange, Inc....

  18. 78 FR 51235 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-08-20

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. August 14, 2013. Pursuant to...\\ notice is hereby given that on August 7, 2013, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'')...

  19. 78 FR 62804 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-10-22

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. October 11, 2013. Pursuant to...\\ notice is hereby given that on October 1, 2013, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'')...

  20. 78 FR 7826 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-02-04

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend BATS Rules in Connection With the Elimination of Discretionary Orders for BATS Options January 29, 2013. Pursuant to Section 19(b)(1) of the Securities Exchange Act...

  1. 75 FR 66170 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-10-27

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. October 21, 2010. Pursuant to...\\ notice is hereby given that on October 14, 2010, BATS Exchange, Inc. (``BATS'' or the ``Exchange'')...

  2. 77 FR 35735 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-06-14

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. June 8, 2012. Pursuant to... is hereby given that on May 31, 2012, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'') filed...

  3. 76 FR 9841 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-02-22

    ... FR 51295 (August 19, 2010) (order approving application of BATS Y-Exchange, Inc. for registration as... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend BATS Rule 11.13, Entitled ``Order Execution'' February 15,...

  4. 76 FR 57092 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-09-15

    ... Act Release No. 65133 (August 15, 2011), 76 FR 52032 (August 19, 2011) (SR-BATS-2011-029). The... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Offer a Bulk-Quoting Interface To All Users of BATS Options September...

  5. 78 FR 51261 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-08-20

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. August 14, 2013. Pursuant to...\\ notice is hereby given that on August 1, 2013, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'')...

  6. 78 FR 61422 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-10-03

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change To Modify the Trading Halt Rule of BATS Options September 27, 2013... thereunder,\\2\\ notice is hereby given that, on September 20, 2013, BATS Exchange, Inc. (the ``Exchange''...

  7. 77 FR 23307 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-04-18

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. April 12, 2012. Pursuant to... is hereby given that on April 2, 2012, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'') filed...

  8. 77 FR 35719 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-06-14

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Adopt Rules Related to Risk Management Functionality for BATS Options June... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 1, 2012, BATS Exchange, Inc....

  9. 75 FR 66183 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-10-27

    ...), 75 FR 51295 (August 19, 2010) (order approving application of BATS Y-Exchange, Inc. for registration... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change by BATS Exchange, Inc. To Amend BATS Rule 11.13, Entitled ``Order...

  10. 76 FR 50803 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-08-16

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. August 10, 2011. Pursuant to...\\ notice is hereby given that on July 29, 2011, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'')...

  11. 77 FR 5588 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-02-03

    ... forth below. \\6\\ See Securities Exchange Act Release No. 65619 (October 25, 2011), 76 FR 67238 (October... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. January 30, 2012. Pursuant...

  12. 75 FR 20418 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-04-19

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. April 9, 2010. Pursuant to...\\ notice is hereby given that on March 31, 2010, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'')...

  13. 75 FR 27847 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-05-18

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. May 11, 2010. Pursuant to...\\ notice is hereby given that on May 4, 2010, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'') filed...

  14. 78 FR 56955 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-09-16

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. September 10, 2013. Pursuant... thereunder,\\2\\ notice is hereby given that on August 30, 2013, BATS Exchange, Inc. (the ``Exchange''...

  15. 75 FR 11951 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-03-12

    ... equity options on the Exchange. See Securities Exchange Act Release No. 61419 (January 26, 2010), 75 FR... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. March 4, 2010. Pursuant...

  16. 77 FR 8310 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-02-14

    ... 4, 2012), 77 FR 1532 (January 10, 2012) (SR-Phlx-2011-185) (notice of filing and immediate..., 2011), 76 FR 78322 (December 16, 2011) (SR-Phlx-2011-162) (notice of filing and immediate effectiveness... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate...

  17. 78 FR 16750 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-03-18

    ...'').\\5\\ \\5\\ See Securities Exchange Act Release No. 67091 (May 31, 2012), 77 FR 33498 (June 6, 2012) (the... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Modify the Operation of Market Orders for BATS Options March 12,...

  18. 76 FR 20414 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-04-12

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Related to Fees for Use of BATS Exchange, Inc. April 6, 2011. Pursuant to...\\ notice is hereby given that, on April 1, 2011, BATS Exchange, Inc. (the ``Exchange'' or ``BATS'')...

  19. 78 FR 53814 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-08-30

    ... (July 30, 2013), 78 FR 47469 (Aug. 5, 2013) (SR-CBOE-2013-078); Securities Exchange Act Release No... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change Related to Registration and Continuing Education Fees for BATS...

  20. 76 FR 12155 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-03-04

    ..., 2009), 74 FR 11386 (March 17, 2009). In order to allow Members sufficient time to review and complete... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change by BATS Exchange, Inc. to Adopt BATS Rule 11.21, entitled ``Input of...

  1. Host-dependent control of early regulatory and effector T-cell differentiation underlies the genetic susceptibility of RAG2-deficient mouse strains to transfer colitis.

    Science.gov (United States)

    Valatas, V; He, J; Rivollier, A; Kolios, G; Kitamura, K; Kelsall, B L

    2013-05-01

    De novo differentiation of CD4(+)Foxp3(+) regulatory T cells (induced (i) Tregs) occurs preferentially in the gut-associated lymphoid tissues (GALT). We addressed the contribution of background genetic factors in affecting the balance of iTreg, T helper type 1 (Th1), and Th17 cell differentiation in GALT in vivo following the transfer of naive CD4(+)CD45RB(high) T cells to strains of RAG2-deficient mice with differential susceptibility to inflammatory colitis. iTregs represented up to 5% of CD4(+) T cells in mesenteric lymph nodes of less-susceptible C57BL/6 RAG2(-/-) mice compared with <1% in highly susceptible C57BL/10 RAG2(-/-) mice 2 weeks following T-cell transfer before the onset of colitis. Early Treg induction was correlated inversely with effector cell expansion and the severity of colitis development, was controlled primarily by host and not T-cell-dependent factors, and was strongly associated with interleukin-12 (IL-12)/23 production by host CD11c(+)CD103(+) dendritic cells. These data highlight the importance of genetic factors regulating IL-12/23 production in controlling the balance between iTreg differentiation and effector-pathogenic CD4(+) T-cell expansion in lymphopenic mice and indicate a direct role for iTregs in the regulation of colonic inflammation in vivo.

  2. The Effect of Bone Marrow Mesenchymal Stem Cells on Vitamin D3 Induced Monocytic Differentiation of U937 Cells

    OpenAIRE

    Zahra Molaeipour; Karim Shamsasanjan; Ali Akbari Movassaghpour; Parvin Akbarzadehlaleh; Fatemeh Sabaghi; Mahshid Saleh

    2016-01-01

    Purpose: Mesenchymal stem cells (MSCs) are key components of the hematopoietic stem cells (HSCs) niche. They control the process of hematopoiesis by secreting regulatory cytokines, growth factors and expression of important cell adhesion molecules for cell-to-cell interactions. In this research, we have investigated the effect of bone marrow derived MSCs on monocytic differentiation of U937 cells line. Methods: U937 cells were cultured in both direct co-culture with...

  3. Cation induced differential effect on structural and functional properties of Mycobacterium tuberculosis α-Isopropylmalate synthase

    Directory of Open Access Journals (Sweden)

    Bhakuni Vinod

    2007-06-01

    Full Text Available Abstract Background α-isopropylmalate synthase (MtαIPMS, an enzyme that catalyzes the first committed step of the leucine biosynthetic pathway of Mycobacterium tuberculosis is a potential drug target for the anti-tuberculosis drugs. Cations induce differential effect of activation and inhibition of MtαIPMS. To date no concrete mechanism for such an opposite effect of similarly charged cations on the functional activity of enzyme has been presented. Results Effect of cations on the structure and function of the MtαIPMS has been studied in detail. The studies for the first time demonstrate that different cations interact specifically at different sites in the enzyme and modulate the enzyme structure differentially. The inhibitors Zn2+ and Cd2+ ions interact directly with the catalytic domain of the enzyme and induce unfolding/denaturation of the domain. The activator K+ also interacts with the catalytic TIM barrel domain however, it does not induce any significant effect on the enzyme structure. Studies with isolated catalytic TIM barrel domain showed that it can carry out the catalytic function on its own but probably requires the non-catalytic C-terminal domain for optimum functioning. An important observation was that divalent cations induce significant interaction between the regulatory and the catalytic domain of MtαIPMS thus inducing structural cooperativity in the enzyme. This divalent cation induced structural cooperativity might result in modulation of activity of the catalytic domain by regulatory domain. Conclusion The studies for the first time demonstrate that different cations bind at different sites in the enzyme leading to their differential effects on the structure and functional activity of the enzyme.

  4. Mixed effects in stochastic differential equation models

    DEFF Research Database (Denmark)

    Ditlevsen, Susanne; De Gaetano, Andrea

    2005-01-01

    maximum likelihood; pharmacokinetics; population estimates; random effects; repeated measurements; stochastic processes......maximum likelihood; pharmacokinetics; population estimates; random effects; repeated measurements; stochastic processes...

  5. Effects of inorganic lead on the differentiation and growth of cultured hippocampal and neuroblastoma cells.

    Science.gov (United States)

    Audesirk, T; Audesirk, G; Ferguson, C; Shugarts, D

    1991-01-01

    Lead exposure has devastating effects on the developing nervous system, and has been implicated in variety of behavioral and cognitive deficits as well as neural morphological abnormalities. Since lead impacts many calcium-dependent processes, one likely mechanism of lead toxicity is its disruption of calcium dependent processes, among which is neuronal differentiation. We investigated the effects of inorganic lead on survival and several parameters of differentiation of cultured neurons. Three different cell types were used: Rat hippocampal neurons (a primary CNS cell type), B50 rat neuroblastoma cells (a transformed CNS-derived cell line), and N1E-115 mouse neuroblastoma cells (a transformed peripherally-derived cell line). Lead concentrations ranged from low nM to 1 mM. Lead effects differed considerably among the three cell types, with B50 cells least affected. Lead effects were generally multimodal, with fewest effects observed at intermediate concentrations. Lead inhibited neurite initiation in hippocampal neurons, but stimulated initiation in N1E-115 cells. In those cells that differentiated, lead increased dendrite numbers in hippocampal neurons and neurite numbers in N1E-115 cells. Lead exposure increased both the length and the degree of branching of axons in hippocampal neurons and the length of neurites in N1E-115 cells. We hypothesize that lead impacts multiple regulatory processes that influence neuron survival and differentiation, and that its effects show differing dose-dependencies. The differing responses of the different cell types to lead suggests that differentiation may be regulated in different ways by the three types of cells. Alternatively, or additionally, the cell types may differ in their ability to compensate for, sequester, or expel lead.

  6. Differentiation of ICOS+ and ICOS- recent thymic emigrant regulatory T cells (RTE T regs) during normal pregnancy, pre-eclampsia and HELLP syndrome.

    Science.gov (United States)

    Wagner, M I; Jöst, M; Spratte, J; Schaier, M; Mahnke, K; Meuer, S; Zeier, M; Steinborn, A

    2016-01-01

    Two different subsets of naturally occurring regulatory T cells (nTregs), defined by their expression of the inducible co-stimulatory (ICOS) molecule, are produced by the human thymus. To examine the differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) recent thymic emigrant (RTE) T regs during normal pregnancy and in the presence of pre-eclampsia or haemolysis elevated liver enzymes low platelet (HELLP)-syndrome, we used six-colour flow cytometric analysis to determine the changes in the composition of the ICOS(+) and ICOS(-) T reg pools with CD45RA(+) CD31(+) RTE T regs, CD45RA(+) CD31(-) mature naive (MN) T regs, CD45RA(-) CD31(+) and CD45RA(-) CD31(-) memory Tregs. With the beginning of pregnancy until term, we observed a strong differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE, but not CD45RA(+) CD31(-) MN T regs, into CD45RA(-) CD31(-) memory T regs. At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS(+) CD45RA(-) CD31(-) memory T regs. However, in the presence of pre-eclampsia, there was a significantly increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs into CD45RA(-) CD31(+) memory T regs, wherein the lacking differentiation into CD45RA(-) CD31(-) memory T regs was partially replaced by the increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(-) MN Tregs into CD45RA(-) CD31(-) memory T regs. In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA(-) CD31(-) MN T regs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS(+) and ICOS(-) T regs, which were shown to be significantly less suppressive in pre-eclampsia patients, but not in HELLP syndrome patients. Hence, our findings propose that the regular differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs ensures a healthy pregnancy course, while their disturbed differentiation is

  7. Case Study for Effectiveness Analysis on Nuclear Regulatory Infrastructure Support for Emerging Nuclear Energy Countries

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y. E.; Byeon, M. J.; Yoo, J. W.; Lee, J. M.; Lim, J. H. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2016-10-15

    The donor countries need to make decisions on various steps such as whether to fully accept newcomers’ requests, the depth of support, and how the supportive action will be carried out. Such is not an easy task due to limited time, resources, manpower, etc. Thus, creating an infrastructure to support emerging nuclear energy countries is needed. This paper suggests the resource portfolio concept used in business management and aims to analyze the validity of supporting the new entrants’ development of regulatory infrastructure as a case study. This study tries to develop a very simple Excel-based tool for assessing the supporting strategy quantitatively and screening the activities that is projected to be less effective and attractive. There are many countries, so called newcomers, which have expressed interests in developing their own nuclear power program. It has been recognized by the international community that every country considering embarking upon their own nuclear power program should establish their nuclear safety infrastructure to sustain a high level of nuclear safety. The newcomers have requested for considerable assistance from the IAEA and they already have bilateral cooperation programs with the advanced countries with matured nuclear regulatory programs. Currently, the regulatory bodies that provide support are confronted with two responsibilities as follows; the primary objective of the regulatory bodies is to ensure that the operator fulfills the responsibility to protect human health.

  8. BDC12-4.1 T-cell receptor transgenic insulin-specific CD4 T cells are resistant to in vitro differentiation into functional Foxp3+ T regulatory cells.

    Science.gov (United States)

    Sarikonda, Ghanashyam; Fousteri, Georgia; Sachithanantham, Sowbarnika; Miller, Jacqueline F; Dave, Amy; Juntti, Therese; Coppieters, Ken T; von Herrath, Matthias

    2014-01-01

    The infusion of ex vivo-expanded autologous T regulatory (Treg) cells is potentially an effective immunotherapeutic strategy against graft-versus-host disease (GvHD) and several autoimmune diseases, such as type 1 diabetes (T1D). However, in vitro differentiation of antigen-specific T cells into functional and stable Treg (iTreg) cells has proved challenging. As insulin is the major autoantigen leading to T1D, we tested the capacity of insulin-specific T-cell receptor (TCR) transgenic CD4(+) T cells of the BDC12-4.1 clone to convert into Foxp3(+) iTreg cells. We found that in vitro polarization toward Foxp3(+) iTreg was effective with a majority (>70%) of expanded cells expressing Foxp3. However, adoptive transfer of Foxp3(+) BDC12-4.1 cells did not prevent diabetes onset in immunocompetent NOD mice. Thus, in vitro polarization of insulin-specific BDC12-4.1 TCR transgenic CD4(+) T cells toward Foxp3+ cells did not provide dominant tolerance in recipient mice. These results highlight the disconnect between an in vitro acquired Foxp3(+) cell phenotype and its associated in vivo regulatory potential.

  9. 77 FR 35462 - Self-Regulatory Organizations; ICE Clear Credit LLC; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-06-13

    ... control of ICC or for which it is responsible. \\6\\ 15 U.S.C. 78q-1(b)(3)(F). (B) Self-Regulatory... COMMISSION Self-Regulatory Organizations; ICE Clear Credit LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend Schedule 502 of the ICE Clear Credit LLC Rules To Amend the...

  10. 75 FR 69492 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-11-12

    ... facility or system which BX operates or controls. The amended fee schedule applies to all subscribers... COMMISSION Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness... comments on the proposed rule change from interested persons. I. Self-Regulatory Organization's Statement...

  11. Physiological and regulatory effects of controlled overproduction of five cold shock proteins of Lactococcus lactis

    NARCIS (Netherlands)

    Wouters, J.A.; Mailhes, M.; Rombouts, F.M.; Vos, de W.M.; Kuipers, O.P.; Abee, T.

    2000-01-01

    The physiological and regulatory effects of overproduction of five cold shock proteins (CSPs) of Lactococcus lactis were studied. CspB, CspD, and CspE could be overproduced at high levels (up to 19␘f the total protein), whereas for CspA and CspC limited overproduction (0.3 to 0.5␘f the total protein

  12. Effects of Parabens on Adipocyte Differentiation

    OpenAIRE

    Hu, Pan; Chen, Xin; Whitener, Rick J.; Boder, Eric T.; Jones, Jeremy O.; Porollo, Aleksey; Chen, Jiangang; Zhao, Ling

    2012-01-01

    Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben. Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation. However, research on the effects of parabens on health is limited, and the effects of parabens on adipogenesis have ...

  13. Effects of Different Regulatory Methods on Improvement of Greenhouse Saline Soils, Tomato Quality, and Yield

    Directory of Open Access Journals (Sweden)

    Hou Maomao

    2014-01-01

    Full Text Available To identify effective regulatory methods scheduling with the compromise between the soil desalination and the improvement of tomato quality and yield, a 3-year field experiment was conducted to evaluate and compare the effect of straw mulching and soil structure conditioner and water-retaining agent on greenhouse saline soils, tomato quality, and yield. A higher salt removing rate of 80.72% in plough layer with straw mulching was obtained based on the observation of salt mass fraction in 0~20 cm soil layer before and after the experiment. Salts were also found to move gradually to the deeper soil layer with time. Straw mulching enhanced the content of soil organic matter significantly and was conductive to reserve soil available N, P, and K, while available P and K in soils of plough layer with soil structure conditioner decreased obviously; thus a greater usage of P fertilizer and K fertilizer was needed when applying soil structure conditioner. Considering the evaluation indexes including tomato quality, yield, and desalination effects of different regulatory methods, straw mulching was recommended as the main regulatory method to improve greenhouse saline soils in south China. Soil structure conditioner was the suboptimal method, which could be applied in concert with straw mulching.

  14. A strategy for regulatory action when new adverse effects of a licensed product emerge.

    Science.gov (United States)

    Aronson, Jeffrey K; Price, Deirdre; Ferner, Robin E

    2009-01-01

    Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development.

  15. Differential Effects of Two T Group Styles

    Science.gov (United States)

    Boller, Jon D.

    1974-01-01

    This article presents a rationale for examining the effects of the T group on introverts and extroverts. Results indicate that the sensory awareness group is more profitable to both personality types and that there is a direct relationship between personality type and profit in a T group. (Author)

  16. The Differential Effects of Repeating Kindergarten

    Science.gov (United States)

    Burkam, David T.; LoGerfo, Laura; Ready, Doug; Lee, Valerie E.

    2007-01-01

    We use the Early Childhood Longitudinal Study to investigate national patterns addressing (a) who repeats kindergarten, and (b) the subsequent cognitive effects of this event. Using OLS regression techniques, we investigate 1st-time kindergartners who are promoted, 1st-time kindergartners who are retained, and children who are already repeating…

  17. Differential Interpolation Effects in Free Recall

    Science.gov (United States)

    Petrusic, William M.; Jamieson, Donald G.

    1978-01-01

    Attempts to determine whether a sufficiently demanding and difficult interpolated task (shadowing, i.e., repeating aloud) would decrease recall for earlier-presented items as well as for more recent items. Listening to music was included as a second interpolated task. Results support views that serial position effects reflect a single process.…

  18. Ferroelectric Field-Effect Transistor Differential Amplifier Circuit Analysis

    Science.gov (United States)

    Phillips, Thomas A.; MacLeod, Todd C.; Ho, Fat D.

    2008-01-01

    There has been considerable research investigating the Ferroelectric Field-Effect Transistor (FeFET) in memory circuits. However, very little research has been performed in applying the FeFET to analog circuits. This paper investigates the use of FeFETs in a common analog circuit, the differential amplifier. The two input Metal-Oxide-Semiconductor (MOS) transistors in a general MOS differential amplifier circuit are replaced with FeFETs. Resistors are used in place of the other three MOS transistors. The FeFET model used in the analysis has been previously reported and was based on experimental device data. Because of the FeFET hysteresis, the FeFET differential amplifier has four different operating modes depending on whether the FeFETs are positively or negatively polarized. The FeFET differential amplifier operation in the different modes was analyzed by calculating the amplifier voltage transfer and gain characteristics shown in figures 2 through 5. Comparisons were made between the FeFET differential amplifier and the standard MOS differential amplifier. Possible applications and benefits of the FeFET differential amplifier are discussed.

  19. The Effect of Spaceflight on Cartilage Cell Cycle and Differentiation

    Science.gov (United States)

    Doty, Stephen B.; Stiner, Dalina; Telford, William G.

    2000-01-01

    In vivo studies have shown that spaceflight results in loss of bone and muscle. In an effort to understand the mechanisms of these changes, cell cultures of cartilage, bone and muscle have been subjected to spaceflight to study the microgravity effects on differentiated cells. However it now seems possible that the cell differentiation process itself may be the event(s) most affected by spaceflight. For example, osteoblast-like cells have been shown to have reduced cellular activity in microgravity due to an underdifferentiated state (Carmeliet, et al, 1997). And reduced human lymphocyte growth in spaceflight was related to increased apoptosis (Lewis, et al, 1998). Which brings us to the question of whether reduced cellular activity in space is due to an effect on the differentiated cell, an effect on the cell cycle and cell proliferation, or an effect on cell death. This question has not been specifically addressed on previous flights and was the question behind die present study.

  20. Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation

    DEFF Research Database (Denmark)

    Hakim-Weber, Robab; Krogsdam, Anne-M; Jørgensen, Claus

    2011-01-01

    Although many molecular regulators of adipogenesis have been identified a comprehensive catalogue of components is still missing. Recent studies showed that the retinoblastoma protein (pRb) was expressed in the cell cycle and late cellular differentiation phase during adipogenesis. To investigate...... of 64 deregulated genes showed that the Rb-/- MEF model exhibits a brown(-like) adipocyte phenotype. Additionally, the analysis results indicate a different or additional role for pRb family member involvement in the lineage commitment. CONCLUSION: In this study a number of commonly modulated genes...

  1. How effective is the revised regulatory code for alcohol advertising in Australia?

    Science.gov (United States)

    Jones, Sandra C; Hall, Danika; Munro, Geoffrey

    2008-01-01

    Australia, like several other countries, has a self-regulatory approach to advertising. However, in recent years the effectiveness of the regulatory system has been questioned, and there have been increasing public calls for an overhaul of the system. Following a formal review in 2003, the Ministerial Council on Drug Strategy proposed a revised Alcoholic Beverages Advertising Code (ABAC), which came into operation in 2004. The purpose of the present study was to examine the effectiveness of this revised system. From May 2004 until March 2005 television and magazine advertising campaigns were monitored for alcohol products. Over this period 14 complaints against alcohol advertisements were lodged with the self-regulatory board, and the authors recruited an independent expert panel to assess the advertisements and complaints. In eight of the 14 cases a majority of the judges perceived the advertisement to be in breach of the code, and in no cases did a majority perceive no breach. Conversely, however, none of the complaints were upheld by the Advertising Standards Board (ASB) and only one by the ABAC Panel. The results of this study suggest that the decisions made by the ASB in relation to complaints against alcohol advertisements are not in harmony with the judgement of independent experts, and that the ASB may not be performing an adequate job of representing community standards or protecting the community from offensive or inappropriate advertisements. Further, it appears that the revisions to the ABAC code, and associated processes, have not reduced the problems associated with alcohol advertising in Australia.

  2. Discrimination of direct and indirect interactions in a network of regulatory effects.

    Science.gov (United States)

    Tresch, Achim; Beissbarth, T; Sültmann, H; Kuner, R; Poustka, A; Buness, A

    2007-11-01

    The matter of concern are algorithms for the discrimination of direct from indirect regulatory effects from an interaction graph built up by error-prone measurements. Many of these algorithms can be cast as a rule for the removal of a single edge of the graph, such that the remaining graph is still consistent with the data. A set of mild conditions is given under which iterated application of such a rule leads to a unique minimal consistent graph. We show that three of the common methods for direct interactions search fulfill these conditions, thus providing a justification of their use. The main issues a reconstruction algorithm has to deal with, are the noise in the data, the presence of regulatory cycles, and the direction of the regulatory effects. We introduce a novel rule that, in contrast to the previously mentioned methods, simultaneously takes into account all these aspects. An efficient algorithm for the computation of the minimal graph is given, whose time complexity is cubic in the number of vertices of the graph. Finally, we demonstrate the utility of our method in a simulation study.

  3. Yersinia pseudotuberculosis supports Th17 differentiation and limits de novo regulatory T cell induction by directly interfering with T cell receptor signaling.

    Science.gov (United States)

    Pasztoi, Maria; Bonifacius, Agnes; Pezoldt, Joern; Kulkarni, Devesha; Niemz, Jana; Yang, Juhao; Teich, René; Hajek, Janina; Pisano, Fabio; Rohde, Manfred; Dersch, Petra; Huehn, Jochen

    2017-04-04

    Adaptive immunity critically contributes to control acute infection with enteropathogenic Yersinia pseudotuberculosis; however, the role of CD4(+) T cell subsets in establishing infection and allowing pathogen persistence remains elusive. Here, we assessed the modulatory capacity of Y. pseudotuberculosis on CD4(+) T cell differentiation. Using in vivo assays, we report that infection with Y. pseudotuberculosis resulted in enhanced priming of IL-17-producing T cells (Th17 cells), whereas induction of Foxp3(+) regulatory T cells (Tregs) was severely disrupted in gut-draining mesenteric lymph nodes (mLNs), in line with altered frequencies of tolerogenic and proinflammatory dendritic cell (DC) subsets within mLNs. Additionally, by using a DC-free in vitro system, we could demonstrate that Y. pseudotuberculosis can directly modulate T cell receptor (TCR) downstream signaling within naïve CD4(+) T cells and Tregs via injection of effector molecules through the type III secretion system, thereby affecting their functional properties. Importantly, modulation of naïve CD4(+) T cells by Y. pseudotuberculosis resulted in an enhanced Th17 differentiation and decreased induction of Foxp3(+) Tregs in vitro. These findings shed light to the adjustment of the Th17-Treg axis in response to acute Y. pseudotuberculosis infection and highlight the direct modulation of CD4(+) T cell subsets by altering their TCR downstream signaling.

  4. Eosinophils from Murine Lamina Propria Induce Differentiation of Naive T Cells into Regulatory T Cells via TGF-β1 and Retinoic Acid.

    Directory of Open Access Journals (Sweden)

    Hong-Hu Chen

    Full Text Available Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP that displayed high aldehyde dehydrogenase (ALDH activity, a rate-limiting step during all-trans retinoic acid (ATRA synthesis, and expressed TGF-β1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-β1 or ATRA. Peripheral blood (PB eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils as effective inducers of Treg cell differentiation through a mechanism dependent on TGF-β1 and ATRA.

  5. Differential Capillary Effect Model of Fabric and Its Application

    Institute of Scientific and Technical Information of China (English)

    王其; 冯勋伟

    2003-01-01

    The concept of the differential capillary effect was presented by foreign scholars several years ago, and the principle was used to design sportswear fabrics with good wet permeability and good drying functions for famous sports teams. Because the differential capillary effect model was not established in theory,it was impossible to fulfill the best functions. In this paper, by setting up the differential capillary effect of fabric, the factors to influence wet permeability and drying functions of the model is discussed in theory, and the means to optimize the design of the fabric is presented and proven practically by the experiment. The optimum fabric with good permeability and good drying functions can be designed using the model at last.

  6. Differentially expressed plasma microRNAs and the potential regulatory function of Let-7b in chronic thromboembolic pulmonary hypertension.

    Science.gov (United States)

    Guo, Lijuan; Yang, Yuanhua; Liu, Jie; Wang, Lei; Li, Jifeng; Wang, Ying; Liu, Yan; Gu, Song; Gan, Huili; Cai, Jun; Yuan, Jason X-J; Wang, Jun; Wang, Chen

    2014-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1) thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2) Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3) ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by

  7. NADPH Oxidases NOX-1 and NOX-2 Require the Regulatory Subunit NOR-1 To Control Cell Differentiation and Growth in Neurospora crassa▿ †

    Science.gov (United States)

    Cano-Domínguez, Nallely; Álvarez-Delfín, Karen; Hansberg, Wilhelm; Aguirre, Jesús

    2008-01-01

    We have proposed that reactive oxygen species (ROS) play essential roles in cell differentiation. Enzymes belonging to the NADPH oxidase (NOX) family produce superoxide in a regulated manner. We have identified three distinct NOX subfamilies in the fungal kingdom and have shown that NoxA is required for sexual cell differentiation in Aspergillus nidulans. Here we show that Neurospora crassa NOX-1 elimination results in complete female sterility, decreased asexual development, and reduction of hyphal growth. The lack of NOX-2 did not affect any of these processes but led instead to the production of sexual spores that failed to germinate, even in the presence of exogenous oxidants. The elimination of NOR-1, an ortholog of the mammalian Nox2 regulatory subunit gp67phox, also caused female sterility, the production of unviable sexual spores, and a decrease in asexual development and hyphal growth. These results indicate that NOR-1 is required for NOX-1 and NOX-2 functions at different developmental stages and establish a link between NOX-generated ROS and the regulation of growth. Indeed, NOX-1 was required for the increased asexual sporulation previously observed in mutants without catalase CAT-3. We also analyzed the function of the penta-EF calcium-binding domain protein PEF-1 in N. crassa. Deletion of pef-1 resulted in increased conidiation but, in contrast to what occurs in Dictyostelium discoideum, the mutation of this peflin did not suppress the phenotypes caused by the lack of NOX-1. Our results support the role of ROS as critical cell differentiation signals and highlight a novel role for ROS in regulation of fungal growth. PMID:18567788

  8. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy.

    Science.gov (United States)

    Bae, Min-Jung; See, Hye-Jeong; Choi, Gyeyoung; Kang, Chang-Yuil; Shon, Dong-Hwa; Shin, Hee Soon

    2016-01-01

    The prevalence of allergic disorders including atopic dermatitis (AD) and food allergy (FA) has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB) extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3(+)CD4(+) regulatory T cells (Tregs). The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3(+)CD4(+) Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3(+)CD4(+) Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  9. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy

    Directory of Open Access Journals (Sweden)

    Min-Jung Bae

    2016-01-01

    Full Text Available The prevalence of allergic disorders including atopic dermatitis (AD and food allergy (FA has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3+CD4+ regulatory T cells (Tregs. The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3+CD4+ Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3+CD4+ Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  10. When planning is not enough: the self-regulatory effect of implementation intentions on changing snacking habits.

    Science.gov (United States)

    Tam, Leona; Bagozzi, Richard P; Spanjol, Jelena

    2010-05-01

    This study examined whether matching implementation intentions to people's regulatory orientation affects the effectiveness of changing unhealthy snacking habits. Participants' regulatory orientation was either measured (as a chronic trait) or manipulated (as a situational state), and participants were randomly assigned to implementation intention conditions to eat more healthy snacks or avoid eating unhealthy ones. A self-reported online food diary of healthy and unhealthy snacks over a 2-day period. Participants with weak unhealthy snacking habits consumed more healthy snacks when forming any type of implementation intentions (regardless of match or mismatch with their regulatory orientation), while participants with strong unhealthy snacking habits consumed more healthy snacks only when forming implementation intentions that matched their regulatory orientations. RESULTS suggest that implementation intentions that match regulatory orientation heighten motivation intensity and put snacking under intentional control for people with strong unhealthy snacking habits. (c) 2010 APA, all rights reserved.

  11. [Rethinking on application of "syndrome differentiation through formula effect assessment"].

    Science.gov (United States)

    Tang, Shi-huan; Yang, Hong-jun; Huang, Lu-qi

    2007-03-01

    By summarizing the state of application of "syndrome differentiation through formula effect assessment", it was pointed out that several problems exist in this kind of study, mainly the irrational setting of experimental control group, over simplified pharmacodynamic indexes, and negligence of study on "correspondence between drug and disease", etc. The authors proposed accordingly the thinking methods and strategy in the study on "syndrome differentiation through formula effect assessment" should be setting control properly, taken "correspondence between disease and syndrome" as the key point, and to define clearly the criteria for evaluating the efficacy of formula as the premise.

  12. The regulatory effects of low-dose ionizing radiation on Ikaros-autotaxin interaction

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hana; Cho, Seong Jun; Kim, Sung Jin; Nam, Seon Young; Yang, Kwang Hee [KHNP Radiation Health Institute, Korea Hydro and Nuclear Power Co, Seoul (Korea, Republic of)

    2016-11-15

    Ikaros, a transcription factor containing zinc-finger motif, has known as a critical regulator of hematopoiesis in immune system. Ikaros protein modulates the transcription of target genes via binding to the regulatory elements of the genes promoters. However the regulatory function of Ikaros in other organelle except nuclear remains to be determined. This study explored radiation-induced modulatory function of Ikaros in cytoplasm. The results showed that Ikaros protein lost its DNA binding ability after LDIR (low-dose ionizing radiation) exposure. Cell fractionation and Western blot analysis showed that Ikaros protein was translocated into cytoplasm from nuclear by LDIR. This was confirmed by immunofluorescence assay. We identified Autotaxin as a novel protein which potentially interacts with Ikaros through in vitro protein-binding screening. Co-immunoprecipitation assay revealed that Ikaros and Autotaxin are able to bind each other. Autotaxin is a crucial enzyme generating lysophosphatidic acid (LPA), a phospholipid mediator, which has potential regulatory effects on immune cell growth and motility. Our results indicate that LDIR potentially regulates immune system via protein-protein interaction of Ikaros and Autotaxin.

  13. Regulatory benefit-risk assessment and comparative effectiveness research: strangers, bedfellows or strange bedfellows?

    Science.gov (United States)

    Garrison, Louis P

    2010-01-01

    Over the past 5 years, we have witnessed growing interest in both comparative effectiveness research (CER) and regulatory benefit-risk assessment (BRA). Both deal with benefits and harms, although at different stages of the product lifecycle. There are growing pressures for a more systematic and quantitative approach to regulatory BRA. However, there is also a need for CER - beyond the evidence that can reasonably be generated during pre-launch product development. Important regulatory and policy questions include the following: What would be a level playing field across disease areas and companies? Who should bear the costs of these studies? What role can benefit-risk modelling play? What is the value of research and how is it related to the prevalence of disease? What is the relationship between uncertainty and the value of evidence? We need to recognize the lifecycle nature of evidence generation, moving from the regulatory setting to the real world and affecting potentially hundreds of thousands, or even millions, of patients worldwide. We need to emphasize not only the public goods nature of information embedded in innovations, but also that it is global. Finally, we need to more systematically explore the benefits and costs of gathering further information - the value of research - recognizing that doing this requires a model or methodology, which we have, for systematically appraising our current state of knowledge and what could be gained from further research. All said, it would seem that BRA and CER should be neither strangers nor strange bedfellows, but may need to be coaxed into being bedfellows.

  14. Optimal Control of Gene Regulatory Networks with Effectiveness of Multiple Drugs: A Boolean Network Approach

    Science.gov (United States)

    Kobayashi, Koichi; Hiraishi, Kunihiko

    2013-01-01

    Developing control theory of gene regulatory networks is one of the significant topics in the field of systems biology, and it is expected to apply the obtained results to gene therapy technologies in the future. In this paper, a control method using a Boolean network (BN) is studied. A BN is widely used as a model of gene regulatory networks, and gene expression is expressed by a binary value (0 or 1). In the control problem, we assume that the concentration level of a part of genes is arbitrarily determined as the control input. However, there are cases that no gene satisfying this assumption exists, and it is important to consider structural control via external stimuli. Furthermore, these controls are realized by multiple drugs, and it is also important to consider multiple effects such as duration of effect and side effects. In this paper, we propose a BN model with two types of the control inputs and an optimal control method with duration of drug effectiveness. First, a BN model and duration of drug effectiveness are discussed. Next, the optimal control problem is formulated and is reduced to an integer linear programming problem. Finally, numerical simulations are shown. PMID:24058904

  15. A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

    Directory of Open Access Journals (Sweden)

    Giannakou C

    2016-06-01

    Full Text Available Christina Giannakou,1,2 Margriet VDZ Park,1 Wim H de Jong,1 Henk van Loveren,1,2 Rob J Vandebriel,1 Robert E Geertsma1 1Centre for Health Protection, National Institute for Public Health and the Environment (RIVM, Bilthoven, 2Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands Abstract: Nanomaterials (NMs are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome

  16. Regulatory Effect of Estrogen, Progestin and HB-EGF on the Expression of HOXA10 Gene in Ishikawa Cells

    Institute of Scientific and Technical Information of China (English)

    LIU Xuemei; ZHU Guijin; ZHONG Gang

    2007-01-01

    HOXA10 gene plays an essential role in differentiation of the endometrium and in human reproduction. The aim of this study was to investigate the regulatory effect of sex steroids and HB-EGF on HOXA10 gene in Ishikawa cells. Ishikawa cells were incubated with 17-beta estradiol (10-8 mol/L), medroxyprogesterone acetate (MPA) (10-6 mol/L), RU486 (10-5 mol/L) or HB-EGF (10 ng/mL) for 48 h respectively. The expression of HOXA10 gene was detected by immunofluorescence,reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Our results showed that either estrogen alone, progestin alone or progestin combined with estrogen could significantly increase the expression of HOXA10 gene 48 h after the treatment (P<0.05). But estrogen combined with progestin and RU486 could inhibit the up-regulation by estrogen and progestin. HB-EGF could elevate the expression of HOXA10 gene 48 h after the treatment (P<0.05). It is concluded that both estrogen and progestin can up-regulate the expression of HOXA10 gene in Ishikawa cells, but RU486 can inhibit the effect and HB-EGF can elevate the expression level of HOXA10 gene.

  17. Differential Diffusion Effects in Numerical Simulations on Smoke Toxicity Evaluation

    Directory of Open Access Journals (Sweden)

    Pan Longwei

    2016-01-01

    Full Text Available With the increasing frequency of fire caused by construction materials, smoke toxicity evaluation plays a key role in related fields. Numerical simulation has become a popular method to predict the toxicity of smoke. A computational study of differential diffusion effects on smoke toxicity evaluation is proposed in this study. Further, an effective Lewis number model derived from the Reynolds-averaged form of the Navier-stokes (RANS transport equations is proposed in turbulent flames. The accuracy of the study is illustrated for a polyurethane foam fire in a 1/5 scale vertical shaft. The temperature and the concentrations of smoke composition are mainly discussed. From the comparison of the calculations with the direct numerical simulations (DNS data it is observed that the temperature and mass fractions of species agree well with the DNS data when differential diffusion effects are taken into account. On the other hand, these numerical results are overestimated if differential diffusion effects are neglected. The FED values indicate that differential diffusion has a strong influence on smoke toxicity evaluation when using N-Gas model.

  18. Interleukin 35 Rescues Regulatory B Cell Function, but the Effect Is Dysregulated in Ulcerative Colitis.

    Science.gov (United States)

    Wang, Shaoxuan; Qin, Chengyong

    2017-05-01

    Ulcerative colitis (UC) is a long-time inflammatory condition arising from aberrant immune activation in the colon and the rectum. Interleukin (IL)-35 plays critical roles in autoimmune disorders. In this study, we explored the pathways of IL-35 in affecting UC. First, peripheral blood mononuclear cells (PBMCs) from UC patients were obtained. Pretreating PBMCs with IL-35 resulted in significantly elevated IL-10 production from whole PBMCs as well as B cells, whereas pretreating PBMCs with IL-12 or IL-27 did not demonstrate a similar effect. IL-35 suppressed the proliferation of CD4(+)CD25(-) conventional T cells, CD4(+)CD25(+) regulatory T (Treg) cells, and CD8(+) T cells, but did not inhibit the proliferation of B cells. IL-35-mediated IL-10 secretion in B cells did not require the presence of Treg cells. After treatment with IL-35, B cells from UC patients presented significantly enhanced regulatory function, characterized by inhibiting cell proliferation and interferon (IFN)-γ, IL-17, and tumor necrosis factor (TNF)-α secretion from autologous CD4(+)CD25(-) T cells and CD8(+) T cells, which was dependent on IL-10 signaling. However, IL-35-treatment did not demonstrate an effect on regulating IL-5 and IL-13 responses. These discoveries identified a Th1, Th17, and CD8(+) T cell-targeting role of IL-35 in UC patients. Next, we examined the IL-35 expression in the intestinal mucosal in UC patients. Data showed that both noninflamed and inflamed tissues from UC patients presented significantly lower IL-35 secretion compared to healthy control tissues, which was associated with suppressed p35 transcription. UC patients with higher IL-35 also presented higher IL-10 secretion in gut mucosa. Together, our study identified that IL-35 could mediate anti-inflammatory function through promoting regulatory B cell functions, but this effect was suppressed in UC patients.

  19. Differential Effects of Tacrolimus versus Sirolimus on the Proliferation, Activation and Differentiation of Human B Cells.

    Directory of Open Access Journals (Sweden)

    Opas Traitanon

    Full Text Available The direct effect of immunosuppressive drugs calcineurin inhibitor (Tacrolimus, TAC and mTOR inhibitor (Sirolimus, SRL on B cell activation, differentiation and proliferation is not well documented. Purified human B cells from healthy volunteers were stimulated through the B Cell Receptor with Anti-IgM + anti-CD40 + IL21 in the absence / presence of TAC or SRL. A variety of parameters of B cell activity including activation, differentiation, cytokine productions and proliferation were monitored by flow cytometry. SRL at clinically relevant concentrations (6 ng/ml profoundly inhibited CD19(+ B cell proliferation compared to controls whereas TAC at similar concentrations had a minimal effect. CD27(+ memory B cells were affected more by SRL than naïve CD27- B cells. SRL effectively blocked B cell differentiation into plasma cells (CD19(+CD138(+ and Blimp1(+/Pax5(low cells even at low dose (2 ng/ml, and totally eliminated them at 6 ng/ml. SRL decreased absolute B cell counts, but the residual responding cells acquired an activated phenotype (CD25(+/CD69(+ and increased the expression of HLA-DR. SRL-treated stimulated B cells on a per cell basis were able to enhance the proliferation of allogeneic CD4(+CD25(- T cells and induce a shift toward the Th1 phenotype. Thus, SRL and TAC have different effects on B lymphocytes. These data may provide insights into the clinical use of these two agents in recipients of solid organ transplants.

  20. Effect of heat flux on differential rotation in turbulent convection

    CERN Document Server

    Kleeorin, N

    2006-01-01

    We studied the effect of the turbulent heat flux on the Reynolds stresses in a rotating turbulent convection. To this end we solved a coupled system of dynamical equations which includes the equations for the Reynolds stresses, the entropy fluctuations and the turbulent heat flux. We used a spectral $\\tau$ approximation in order to close the system of dynamical equations. We found that the ratio of the contributions to the Reynolds stresses caused by the turbulent heat flux and the anisotropic eddy viscosity is of the order of $\\sim 10 (L_\\rho / l_0)^2$, where $l_{0}$ is the maximum scale of turbulent motions and $L_\\rho$ is the fluid density variation scale. This effect is crucial for the formation of the differential rotation and should be taken into account in the theories of the differential rotation of the Sun, stars and planets. In particular, we demonstrated that this effect may cause the differential rotation which is comparable with the typical solar differential rotation.

  1. Adapting to an initial self-regulatory task cancels the ego depletion effect.

    Science.gov (United States)

    Dang, Junhua; Dewitte, Siegfried; Mao, Lihua; Xiao, Shanshan; Shi, Yucai

    2013-09-01

    The resource-based model of self-regulation provides a pessimistic view of self-regulation that people are destined to lose their self-control after having engaged in any act of self-regulation because these acts deplete the limited resource that people need for successful self-regulation. The cognitive control theory, however, offers an alternative explanation and suggests that the depletion effect reflects switch costs between different cognitive control processes recruited to deal with demanding tasks. This account implies that the depletion effect will not occur once people have had the opportunity to adapt to the self-regulatory task initially engaged in. Consistent with this idea, the present study showed that engaging in a demanding task led to performance deficits on a subsequent self-regulatory task (i.e. the depletion effect) only when the initial demanding task was relatively short but not when it was long enough for participants to adapt. Our results were unrelated to self-efficacy, mood, and motivation.

  2. Effects of FGFR Signaling on Cell Proliferation and Differentiation of Apert Dental Cells.

    Science.gov (United States)

    Lu, Changming; Huguley, Samuel; Cui, Chun; Cabaniss, Lauren B; Waite, Peter D; Sarver, David M; Mamaeva, Olga A; MacDougall, Mary

    2016-01-01

    The Apert syndrome is a rare congenital disorder most often arising from S252W or P253R mutations in fibroblast growth factor receptor (FGFR2). Numerous studies have focused on the regulatory role of Apert FGFR2 signaling in bone formation, whereas its functional role in tooth development is largely unknown. To investigate the role of FGFR signaling in cell proliferation and odontogenic differentiation of human dental cells in vitro, we isolated dental pulp and enamel organ epithelia (EOE) tissues from an Apert patient carrying the S252W FGFR2 mutation. Apert primary pulp and EOE cells were established and shown to exhibit normal morphology and express alkaline phosphatase under differentiation conditions. Similar to control cells, Apert dental pulp and EOE cells expressed all FGFRs, with highest levels of FGFR1 followed by FGFR2 and low levels of FGFR3 and FGFR4. However, Apert cells had increased cell growth compared with control cells. Distinct from previous findings in osteoblast cells, gain-of-function S252W FGFR2 mutation did not upregulate the expression of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFRα), but elevated extracellular signal-regulated kinase (ERK) signaling in cells after EGF stimulation. Unexpectedly, there was little effect of the S252W mutation on odontogenic gene expression in dental pulp and EOE cells. However, after inhibition of total FGFR signaling or ERK signaling, the expression of odontogenic genes was upregulated in both dental cell types, indicating the negative effect of whole FGFR signaling on odontogenic differentiation. This study provides novel insights on FGFR signaling and a common Apert FGFR2 mutation in the regulation of odontogenic differentiation of dental mesenchymal and epithelial cells.

  3. 77 FR 39302 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-07-02

    ... designed to manage the financial, regulatory and other risks of this business activity. These controls... certain regulatory risk management controls that, among other things, prevent the entry of orders unless... have been pre- approved and authorized by the broker-dealer. These regulatory risk management...

  4. 77 FR 61449 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-10-09

    ..., regulatory and other risks of this business activity. These controls include financial risk management... entry of erroneous orders. In addition, the Market Access Rule requires certain regulatory risk... authorized by the broker-dealer. These regulatory risk management controls also include measures designed...

  5. 77 FR 39300 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-07-02

    ... designed to manage the financial, regulatory and other risks of this business activity. These controls... certain regulatory risk management controls that, among other things, prevent the entry of orders unless... have been pre- approved and authorized by the broker-dealer. These regulatory risk management...

  6. 77 FR 61463 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-10-09

    ..., regulatory and other risks of this ] business activity. These controls include financial risk management... entry of erroneous orders. In addition, the Market Access Rule requires certain regulatory risk... authorized by the broker-dealer. These regulatory risk management controls also include measures designed...

  7. The effects of intrinsic noise on the behaviour of bistable cell regulatory systems under quasi-steady state conditions

    Energy Technology Data Exchange (ETDEWEB)

    Cruz, Roberto; Alarcón, Tomás de la [Centre de Recerca Matemàtica. Edifici C, Campus de Bellaterra, 08193 Bellaterra (Barcelona) (Spain); Departament de Matemàtiques, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Guerrero, Pilar [Department of Mathematics, University College London, Gower Street, London WC1E 6BT (United Kingdom); Spill, Fabian [Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, Massachusetts 02215 (United States); Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 (United States)

    2015-08-21

    We analyse the effect of intrinsic fluctuations on the properties of bistable stochastic systems with time scale separation operating under quasi-steady state conditions. We first formulate a stochastic generalisation of the quasi-steady state approximation based on the semi-classical approximation of the partial differential equation for the generating function associated with the chemical master equation. Such approximation proceeds by optimising an action functional whose associated set of Euler-Lagrange (Hamilton) equations provides the most likely fluctuation path. We show that, under appropriate conditions granting time scale separation, the Hamiltonian can be re-scaled so that the set of Hamilton equations splits up into slow and fast variables, whereby the quasi-steady state approximation can be applied. We analyse two particular examples of systems whose mean-field limit has been shown to exhibit bi-stability: an enzyme-catalysed system of two mutually inhibitory proteins and a gene regulatory circuit with self-activation. Our theory establishes that the number of molecules of the conserved species is order parameters whose variation regulates bistable behaviour in the associated systems beyond the predictions of the mean-field theory. This prediction is fully confirmed by direct numerical simulations using the stochastic simulation algorithm. This result allows us to propose strategies whereby, by varying the number of molecules of the three conserved chemical species, cell properties associated to bistable behaviour (phenotype, cell-cycle status, etc.) can be controlled.

  8. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  9. The composite regulatory basis of the large X-effect in mouse speciation.

    Science.gov (United States)

    Larson, Erica L; Keeble, Sara; Vanderpool, Dan; Dean, Matthew D; Good, Jeffrey M

    2016-12-20

    The disruption of meiotic sex chromosome inactivation (MSCI) has been proposed to be a major developmental mechanism underlying the rapid evolution of hybrid male sterility. We tested this idea by analyzing cell-specific gene expression across spermatogenesis in two lineages of house mice and their sterile and fertile reciprocal hybrids. We found pervasive disruption of sex chromosome gene expression in sterile hybrids at every stage of spermatogenesis. Failure of MSCI was developmentally preceded by increased silencing of autosomal genes, supporting the hypothesis that divergence at the hybrid incompatibility gene, Prdm9, results in increased rates of autosomal asynapsis which in turn triggers widespread silencing of unsynapsed chromatin. We also detected opposite patterns of postmeiotic overexpression or hyper-repression of the sex chromosomes in reciprocal hybrids, supporting the hypothesis that genomic conflict has driven functional divergence that leads to deleterious X-Y dosage imbalances in hybrids. Our developmental timeline also exposed more subtle patterns of mitotic misregulation on the X chromosome, a previously undocumented stage of spermatogenic disruption in this cross. These results indicate that multiple hybrid incompatibilities have converged on a common regulatory phenotype, the disrupted expression of the sex chromosomes during spermatogenesis. Collectively, these data reveal a composite regulatory basis to hybrid male sterility in mice that helps resolve the mechanistic underpinnings of the well-documented large X-effect in mice speciation. We propose that the inherent sensitivity of spermatogenesis to X-linked regulatory disruption has the potential to be a major driver of reproductive isolation in species with chromosomal sex determination.

  10. Differential effects of eicosapentaenoic acid and docosahexaenoic acid in promoting the differentiation of 3T3-L1 preadipocytes.

    Science.gov (United States)

    Murali, Ganesan; Desouza, Cyrus V; Clevenger, Michelle E; Ramalingam, Ramesh; Saraswathi, Viswanathan

    2014-01-01

    The objective of this study was to determine the effects of enrichment with n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the differentiation of 3T3-L1 preadipocytes. Enrichment with DHA but not EPA significantly increased the differentiation markers compared to control differentiated cells. DHA compared to EPA treatment led to a greater increase in adiponectin secretion and, conditioned media collected from DHA treated cells inhibited monocyte migration. Moreover, DHA treatment resulted in inhibition of pro-inflammatory signaling pathways. DHA treated cells predominantly accumulated DHA in phospholipids whereas EPA treatment led to accumulation of both EPA and its elongation product docosapentaenoic acid (DPA), an n-3 fatty acid. Of note, adding DPA to DHA inhibited DHA-induced differentiation. The differential effects of EPA and DHA on preadipocyte differentiation may be due, in part, to differences in their intracellular modification which could impact the type of n-3 fatty acids incorporated into the cells.

  11. Differential effects of arousal in positive and negative autobiographical memories.

    Science.gov (United States)

    Ford, Jaclyn Hennessey; Addis, Donna Rose; Giovanello, Kelly S

    2012-01-01

    Autobiographical memories are characterised by a range of emotions and emotional reactions. Recent research has demonstrated that differences in emotional valence (positive vs. negative emotion) and arousal (the degree of emotional intensity) differentially influence the retrieved memory narrative. Although the mnemonic effects of valence and arousal have both been heavily studied, it is currently unclear whether the effects of emotional arousal are equivalent for positive and negative autobiographical events. In the current study, multilevel models were used to examine differential effects of emotional valence and arousal on the richness of autobiographical memory retrieval both between and within subjects. Thirty-four young adults were asked to retrieve personal autobiographical memories associated with popular musical cues and to rate the valence, arousal and richness of these events. The multilevel analyses identified independent influences of valence and intensity upon retrieval characteristics at the within- and between-subject levels. In addition, the within-subject interactions between valence and arousal highlighted differential effects of arousal for positive and negative memories. These findings have important implications for future studies of emotion and memory, highlighting the importance of considering both valence and arousal when examining the role emotion plays in the richness of memory representation.

  12. When do chronic differences in self-regulation count? Regulatory focus effects in easy and difficult soccer tasks.

    Science.gov (United States)

    Vogel, Tobias; Genschow, Oliver

    2013-04-01

    Research on regulatory focus theory (Higgins, 1997) suggests that performance increases if instructions fit with sportspersons' dispositions. Sportspersons who chronically focus on wins (i.e., promotion-oriented individuals) perform best if instructions frame the objective as a promotion goal (e.g., "Try to hit!"). By contrast, sportspersons who chronically focus on losses (i.e., prevention-oriented individuals) perform best if instructions frame the objective as a prevention goal (e.g., "Try not to miss!"). Recent theorizing also suggests that regulatory focus interacts with task difficulty. In an experiment, we assessed soccer performance as a function of chronic focus, instructional focus, and task difficulty. Results support that task difficulty moderates the effects of fit on performance; fitting instructions to match the sportsperson's chronic regulatory focus improved performance in the easy rather than the difficult task. Findings are discussed regarding the role of regulatory fit in altering subjective pressure during sports performance.

  13. Temperature effect on proliferation and differentiation of satellite cells from turkeys with different growth rates.

    Science.gov (United States)

    Clark, D L; Coy, C S; Strasburg, G M; Reed, K M; Velleman, S G

    2016-04-01

    Poultry selected for growth have an inefficient thermoregulatory system and are more sensitive to temperature extremes. Satellite cells are precursors to skeletal muscle and mediate all posthatch muscle growth. Their physiological functions are affected by temperature. The objective of the current study was to determine how temperature affects satellite cells isolated from the pectoralis major (p. major) muscle (breast muscle) of turkeys selected for increased 16 wk body weight (F line) in comparison to a randombred control line (RBC2) from which the F line originated. Pectoralis major muscle satellite cells were thermally challenged by culturing between 33°C and 43°C to analyze the effects of cold and heat on proliferation and differentiation as compared to control temperature of 38°C. Expression levels of myogenic regulatory factors: myogenic differentiation factor 1 (MYOD1) and myogenin (MYOG) were quantified by quantitative polymerase chain reaction (qPCR). At all sampling times, proliferation increased at a linear rate across temperature in both the RBC2 and F lines. Differentiation also increased at a linear rate across temperature from 33 to 41°C at all sampling times in both the F and RBC2 lines. Satellite cells isolated from F line turkeys were more sensitive to both hot and cold temperatures as proliferation and differentiation increased to a greater extent across temperature (33 to 43°C) when compared with the RBC2 line. Expression of MYOD1 and MYOG increased as temperatures increased from 33 to 41°C at all sampling times in both the F and RBC2 lines. These results demonstrate that satellite cell function is sensitive to both cold and hot temperatures and p. major muscle satellite cells from F line turkeys are more sensitive to temperature extremes than RBC2 satellite cells.

  14. The effect of rules on differential reinforcement of other behavior.

    Science.gov (United States)

    Watts, Amanda C; Wilder, David A; Gregory, Meagan K; Leon, Yanerys; Ditzian, Kyle

    2013-01-01

    Previous research on the treatment of problem behavior has shown differential reinforcement of other behavior (DRO) to be an effective behavior-reduction procedure. However, the extent to which presession descriptions of the DRO contingency enhance intervention effects has not been examined. In the current study, we compared a condition in which a presession rule that described the DRO contingency was given to a condition in which no rule was given for 4 participants. The target behavior was toy play, which served as an analogue to problem behavior maintained by automatic reinforcement. Results showed that DRO was more efficient for 1 participant and more effective for 2 participants when a rule was given.

  15. The Effectiveness of Self-regulatory Speech Training for Planning and Problem Solving in Children with Specific Language Impairment.

    Science.gov (United States)

    Abdul Aziz, Safiyyah; Fletcher, Janet; Bayliss, Donna M

    2016-08-01

    Self-regulatory speech has been shown to be important for the planning and problem solving of children. Our intervention study, including comparisons to both wait-list and typically developing controls, examined the effectiveness of a training programme designed to improve self-regulatory speech, and consequently, the planning and problem solving performance of 87 (60 males, 27 females) children aged 4-7 years with Specific Language Impairment (SLI) who were delayed in their self-regulatory speech development. The self-regulatory speech and Tower of London (TOL) performance of children with SLI who received the intervention initially or after a waiting period was compared with that of 80 (48 male, 32 female) typically developing children who did not receive any intervention. Children were tested at three time points: Time 1- prior to intervention; Time 2 - after the first SLI group had received training and the second SLI group provided a wait-list control; and Time 3 - when the second SLI group had received training. At Time 1 children with SLI produced less self-regulatory speech and were impaired on the TOL relative to the typically developing children. At Time 2, the TOL performance of children with SLI in the first training group improved significantly, whereas there was no improvement for the second training group (the wait-list group). At Time 3, the second training group improved their TOL performance and the first group maintained their performance. No significant differences in TOL performance were evident between typically developing children and those with SLI at Time 3. Moreover, decreases in social speech and increases in inaudible muttering following self-regulatory speech training were associated with improvements in TOL performance. Together, the results show that self-regulatory speech training was effective in increasing self-regulatory speech and in improving planning and problem solving performance in children with SLI.

  16. Ethics and Regulatory Challenges and Opportunities in Patient-Centered Comparative Effectiveness Research.

    Science.gov (United States)

    Sugarman, Jeremy

    2016-04-01

    The Affordable Care Act includes provisions for the conduct of large-scale, patient-centered comparative effectiveness research. Such efforts aim toward the laudable moral goal of having evidence to improve health care decision making. Nevertheless, these pragmatic clinical research efforts that typically pose minimal incremental risk and are enmeshed in routine care settings perhaps surprisingly encounter an array of ethics and regulatory challenges and opportunities for academic health centers. An emphasis on patient-centeredness forces an examination of the appropriateness of traditional methods used to protect the rights, interests, and welfare of participants. At the same time, meaningful collaboration with patients throughout the research process also necessitates ensuring that novel approaches to research (including recruitment and consent) entail necessary protections regarding such issues as privacy. As the scientific and logistical aspects of this research are being developed, substantial attention is being focused on the accompanying ethics and regulatory issues that have emerged, which should help to facilitate ethically appropriate research in a variety of contexts.

  17. The regulatory effect of miRNAs is a heritable genetic trait in humans

    Directory of Open Access Journals (Sweden)

    Geeleher Paul

    2012-08-01

    Full Text Available Abstract Background microRNAs (miRNAs have been shown to regulate the expression of a large number of genes and play key roles in many biological processes. Several previous studies have quantified the inhibitory effect of a miRNA indirectly by considering the expression levels of genes that are predicted to be targeted by the miRNA and this approach has been shown to be robust to the choice of prediction algorithm. Given a gene expression dataset, Cheng et al. defined the regulatory effect score (RE-score of a miRNA as the difference in the gene expression rank of targets of the miRNA compared to non-targeted genes. Results Using microarray data from parent-offspring trios from the International HapMap project, we show that the RE-score of most miRNAs is correlated between parents and offspring and, thus, inter-individual variation in RE-score has a genetic component in humans. Indeed, the mean RE-score across miRNAs is correlated between parents and offspring, suggesting genetic differences in the overall efficiency of the miRNA biogenesis pathway between individuals. To explore the genetics of this quantitative trait further, we carried out a genome-wide association study of the mean RE-score separately in two HapMap populations (CEU and YRI. No genome-wide significant associations were discovered; however, a SNP rs17409624, in an intron of DROSHA, was significantly associated with mean RE-score in the CEU population following permutation-based control for multiple testing based on all SNPs mapped to the canonical miRNA biogenesis pathway; of 244 individual miRNA RE-scores assessed in the CEU, 214 were associated (p p = 0.04 with mean RE-score in the YRI population. Interestingly, the same SNP was associated with 17 (8.5% of all expressed miRNA expression levels in the CEU. We also show here that the expression of the targets of most miRNAs is more highly correlated with global changes in miRNA regulatory effect than with the expression of

  18. Real parameter optimization by an effective differential evolution algorithm

    Directory of Open Access Journals (Sweden)

    Ali Wagdy Mohamed

    2013-03-01

    Full Text Available This paper introduces an Effective Differential Evolution (EDE algorithm for solving real parameter optimization problems over continuous domain. The proposed algorithm proposes a new mutation rule based on the best and the worst individuals among the entire population of a particular generation. The mutation rule is combined with the basic mutation strategy through a linear decreasing probability rule. The proposed mutation rule is shown to promote local search capability of the basic DE and to make it faster. Furthermore, a random mutation scheme and a modified Breeder Genetic Algorithm (BGA mutation scheme are merged to avoid stagnation and/or premature convergence. Additionally, the scaling factor and crossover of DE are introduced as uniform random numbers to enrich the search behavior and to enhance the diversity of the population. The effectiveness and benefits of the proposed modifications used in EDE has been experimentally investigated. Numerical experiments on a set of bound-constrained problems have shown that the new approach is efficient, effective and robust. The comparison results between the EDE and several classical differential evolution methods and state-of-the-art parameter adaptive differential evolution variants indicate that the proposed EDE algorithm is competitive with , and in some cases superior to, other algorithms in terms of final solution quality, efficiency, convergence rate, and robustness.

  19. The effect of regulatory mode on procrastination: Bi-stable parahippocampus connectivity with dorsal anterior cingulate and anterior prefrontal cortex.

    Science.gov (United States)

    Zhang, Chenyan; Ni, Yan; Feng, Tingyong

    2017-06-30

    Previous research has elucidated that procrastination can be influenced by regulatory mode orientations. However, the neural mechanism of regulatory modes affecting procrastination is not well understood. To address this question, we employed resting-state functional magnetic resonance imaging (RS-fMRI) to test the influence of two regulatory modes (assessment and locomotion) on procrastination. The behavioral results showed that procrastination was positively correlated with assessment orientation but negatively correlated with locomotion orientation. Neuroimaging results indicated that the functional connectivity between parahippocampal cortex (PHC) and dorsal anterior cingulate (dACC) was negatively correlated with assessment scores, while the functional connectivity between anterior prefrontal cortex (aPFC) and parahippocampal cortex (PHC) was negatively correlated with locomotion scores. Critically, mediation analysis showed that the different effects of two distinct regulatory modes on procrastination were mediated by PHC-dACC and aPFC-PHC functional connectivity respectively. These results suggested that people's procrastination could be predicted by regulatory mode orientations, which is mediated by PHC connectivity with dACC and aPFC respectively. The present study extends our knowledge on procrastination and provides neural mechanism for understanding the link between regulatory mode orientations and procrastination. Copyright © 2017. Published by Elsevier B.V.

  20. Schwinger effect and negative differential conductivity in holographic models

    Directory of Open Access Journals (Sweden)

    Shankhadeep Chakrabortty

    2015-01-01

    Full Text Available The consequences of the Schwinger effect for conductivity are computed for strong coupling systems using holography. The one-loop diagram on the flavor brane introduces an O(λNc imaginary part in the effective action for a Maxwell flavor gauge field. This in turn introduces a real conductivity in an otherwise insulating phase of the boundary theory. Moreover, in certain regions of parameter space the differential conductivity is negative. This is computed in the context of the Sakai–Sugimoto model.

  1. The dual effects of leading for safety: The mediating role of employee regulatory focus.

    Science.gov (United States)

    Kark, Ronit; Katz-Navon, Tal; Delegach, Marianna

    2015-09-01

    This study examined the underlying mechanisms through which transformational and transactional leadership influence employee safety behaviors. Linking leadership theory with self-regulatory focus (SRF) theory, we examined a model of dual effects of leadership on safety initiative and safety compliance behaviors as mediated by promotion and prevention self-regulations. We conducted an experimental study (N = 107), an online study (N = 99) and a field study (N = 798 employees and 49 managers). Results demonstrated that followers' situational promotion focus mediated the positive relationship between transformational leadership and safety initiative behaviors. Through all 3 studies, transactional active leadership was positively associated with followers' situational prevention focus, however, the association between followers' prevention focus and safety compliance behaviors was inconsistent, showing the expected mediation relationships in the experimental setting, but not in the online and field studies. We discuss theoretical and practical implications of the findings. (c) 2015 APA, all rights reserved).

  2. Differential depletion of total T cells and regulatory T cells and prolonged allotransplant survival in CD3Ɛ humanized mice treated with polyclonal anti human thymocyte globulin

    Science.gov (United States)

    Buszko, Maja; Cardini, Benno; Oberhuber, Rupert; Oberhuber, Lukas; Jakic, Bojana; Beierfuss, Anja; Wick, Georg; Cappellano, Giuseppe

    2017-01-01

    Thymoglobulin (ATG) is a polyclonal rabbit antibody against human thymocytes used as a T cell-depleting agent to prevent or treat allotransplant rejection. The aim of the present study was to investigate the effect of low dose ATG treatment exclusively on T cells using a humanized BALB/c human CD3Ɛ transgenic mouse model expressing both human and murine T cell receptors (TCR). Mice received a single intravenous (i.v.) injection of ATG. Blood and peripheral lymphoid organs were obtained after different time points. We found a significant T cell depletion in this mouse model. In addition, regulatory T cells (Tregs) proved to be less sensitive to depletion than the rest of T cells and the Treg:non-Treg ratio was therefore increased. Finally, we also investigated the effect of ATG in a heterotopic allogenic murine model of heart transplantation. Survival and transplant function were significantly prolonged in ATG-treated mice. In conclusion, we showed (a) an immunosuppressive effect of ATG in this humanized mouse model which is exclusively mediated by reactivity against human CD3Ɛ; (b) provided evidence for a relative resistance of Tregs against this regimen; and (c) demonstrated the immunomodulatory effect of ATG under these experimental circumstances by prolongation of heart allograft survival. PMID:28257450

  3. Mucosally induced immunological tolerance, regulatory T cells and the adjuvant effect by cholera toxin B subunit.

    Science.gov (United States)

    Sun, J-B; Czerkinsky, C; Holmgren, J

    2010-01-01

    Induction of peripheral immunological tolerance by mucosal administration of selected antigens (Ags) ('oral tolerance') is an attractive, yet medically little developed, approach to prevent or treat selected autoimmune or allergic disorders. A highly effective way to maximize oral tolerance induction for immunotherapeutic purposes is to administer the relevant Ag together with, and preferably linked to the non-toxic B subunit protein of cholera toxin (CTB). Oral, nasal or sublingual administration of such Ag/CTB conjugates or gene fusion proteins have been found to induce tolerance with superior efficiency compared with administration of Ag alone, including the suppression of various autoimmune disorders and allergies in animal models. In a proof-of-concept clinical trial in patients with Behcet's disease, this was extended with highly promising results to prevent relapse of autoimmune uveitis. Tolerization by mucosal Ag/CTB administration results in a strong increase in Ag-specific regulatory CD4(+) T cells, apparently via two separate pathways: one using B cells as APCs and leading to a strong expansion of Foxp3(+) Treg cells which can both suppress and mediate apoptotic depletion of effector T cells, and one being B cell-independent and associated with development of Foxp3(-) regulatory T cells that express membrane latency-associated peptide and transforming growth factor (TGF-beta) and/or IL-10. The ability of CTB to dramatically increase mucosal Ag uptake and presentation by different APCs through binding to GM1 ganglioside (which makes most B cells effective APCs irrespective of their Ag specificity), together with CTB-mediated stimulation of TGF-beta and IL-10 production and inhibition of IL-6 formation may explain the dramatic potentiation of oral tolerance by mucosal Ags presented with CTB.

  4. The Effect of Bone Marrow Mesenchymal Stem Cells on Vitamin D3 Induced Monocytic Differentiation of U937 Cells

    Science.gov (United States)

    Molaeipour, Zahra; Shamsasanjan, Karim; Movassaghpour, Ali Akbari; Akbarzadehlaleh, Parvin; Sabaghi, Fatemeh; Saleh, Mahshid

    2016-01-01

    Purpose: Mesenchymal stem cells (MSCs) are key components of the hematopoietic stem cells (HSCs) niche. They control the process of hematopoiesis by secreting regulatory cytokines, growth factors and expression of important cell adhesion molecules for cell-tocell interactions. In this research, we have investigated the effect of bone marrow derived MSCs on monocytic differentiation of U937 cells line. Methods: U937 cells were cultured in both direct co-culture with MSCs and MSCs conditioned medium (C.M) driven. This study used 1,25-dihydroxyvitamin D3(VitD3) as inductor of monocytic differentiation and U937 cells treated with VitD3 morphology was examined by Wright Giemsa staining. CD14 monocytic differentiation marker was measured by flow cytometry and monocytic gene expression was assessed by real time polymerase chain reaction (RT PCR). Results: The results of flow cytometric analysis showed that CD14 expression of U937 increased. The higher effect of MSCs co-culture on CD14 expression in U937 cells was observed, compared to the conditioned medium. Among ten monocytic related genes which were screened that was observed increase in 5 genes in which CXCR4 and CSF2RA showed significant increase. Conclusion: The results obtained show that MSCs have supportive effect on the monocytic differentiation of U937 cells. However, a distinct mechanism of that remains unclear. PMID:27123414

  5. Selection for niche differentiation in plant communities increases biodiversity effects.

    Science.gov (United States)

    Zuppinger-Dingley, Debra; Schmid, Bernhard; Petermann, Jana S; Yadav, Varuna; De Deyn, Gerlinde B; Flynn, Dan F B

    2014-11-06

    In experimental plant communities, relationships between biodiversity and ecosystem functioning have been found to strengthen over time, a fact often attributed to increased resource complementarity between species in mixtures and negative plant-soil feedbacks in monocultures. Here we show that selection for niche differentiation between species can drive this increasing biodiversity effect. Growing 12 grassland species in test monocultures and mixtures, we found character displacement between species and increased biodiversity effects when plants had been selected over 8 years in species mixtures rather than in monocultures. When grown in mixtures, relative differences in height and specific leaf area between plant species selected in mixtures (mixture types) were greater than between species selected in monocultures (monoculture types). Furthermore, net biodiversity and complementarity effects were greater in mixtures of mixture types than in mixtures of monoculture types. Our study demonstrates a novel mechanism for the increase in biodiversity effects: selection for increased niche differentiation through character displacement. Selection in diverse mixtures may therefore increase species coexistence and ecosystem functioning in natural communities and may also allow increased mixture yields in agriculture or forestry. However, loss of biodiversity and prolonged selection of crops in monoculture may compromise this potential for selection in the longer term.

  6. Circadian phase has profound effects on differential expression analysis.

    Directory of Open Access Journals (Sweden)

    Polly Yingshan Hsu

    Full Text Available Circadian rhythms are physiological and behavioral cycles with a period of approximately 24 hours that are generated by an endogenous clock, or oscillator. Found in diverse organisms, they are precisely controlled and provide growth and fitness benefits. Numerous microarray studies examining circadian control of gene expression have reported that a substantial fraction of the genomes of many organisms is clock-controlled. Here we show that a long-period mutant in Arabidopsis, rve8-1, has a global alteration in phase of all clock-controlled genes. After several days in constant environmental conditions, at which point the mutant and control plants have very different circadian phases, we found 1557 genes to be differentially expressed in rve8-1, almost all of which are clock-regulated. However, after adjusting for this phase difference, only a handful show overall expression level differences between rve8-1 and wild type. Thus the apparent differential expression is mainly due to the phase difference between these two genotypes. These findings prompted us to examine the effect of phase on gene expression within a single genotype. Using samples of wild-type plants harvested at thirty-minute intervals, we demonstrated that even this small difference in circadian phase significantly influences the results of differential expression analysis. Our study demonstrates the robust influence of the circadian clock on the transcriptome and provides a cautionary note for all biologists performing genome-level expression analysis.

  7. THE AUTOCRINE REGULATORY EFFECT OF VASOACTIVE INTESTINAL PEPTIDE ON THE GROWTH OF HUMAN PANCREATIC CARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    陈元方; 陈潜; 陆国钧; 范振符; 钟守先

    1994-01-01

    In the present study, the effets of VIP on the growth of two human pancreatic carcinoma cell lines PU-PAH-1 and PANC-1 were determined using tritiated thymidine incorporation, VIP receptors, intracellular cAMP and polyamings were investlsa.ted, The results indicated that VIP at a concentcation of 10-8mol/L to 10-7 mol/L can significantly Stimulate the growth of PU-PAN-1 cells but not PANC-1 cells, This effect is dose-dependent and abolished by VIP receptor antagonist, [4-CI-Phe6 , Leu7] VIP, suggesting VIP receptors in PU-PAN-1 cells maymediate this effect. VIP can markedly elevate the levels of intracellular cAMP and polyammes in PU-PAN-1 cells,indicating that the growth-promoting effect stimulated by VIP may be via a rapid increase in the biosynth~es of cAMP and polyamines. In addition, the VIP-antibody ir2Libited the growth of PU-PAN-1 cells in serum-free culture medium. The results above suggested that VIP has an autoctine regulatory effect on this pancreatic carcinoma cell line(PU-PAN-1).

  8. Differential effects of detergents on keratinocyte gene expression.

    Science.gov (United States)

    van Ruissen, F; Le, M; Carroll, J M; van der Valk, P G; Schalkwijk, J

    1998-04-01

    We have studied the effect of various detergents on keratinocyte gene expression in vitro, using an anionic detergent (sodium dodecyl sulfate), a cationic detergent cetyltrimethylammoniumbromide (CTAB), and two nonionic detergents, Nonidet P-40 and Tween-20. We measured the effect of these detergents on direct cellular toxicity (lactate dehydrogenase release), on the expression of markers for normal differentiation (cytokeratin 1 and involucrin expression), and on disturbed keratinocyte differentiation (SKALP) by northern blot analysis. As reported in other studies, large differences were noted in direct cellular toxicity. In a culture model that mimics normal epidermal differentiation we found that low concentrations of sodium dodecyl sulfate could induce the expression of SKALP, a proteinase inhibitor that is not normally expressed in human epidermis but is found in hyperproliferative skin. Sodium dodecyl sulfate caused upregulation of involucrin and downregulation of cytokeratin 1 expression, which is associated with the hyperproliferative/inflammatory epidermal phenotype found in psoriasis, wound healing, and skin irritation. These changes were not induced after treatment of cultures with CTAB, Triton X-100, and Nonidet-P40. This effect appeared to be specific for the class of anionic detergents because sodium dodecyl benzene sulfonate and sodium laurate also induced SKALP expression. These in vitro findings showed only a partial correlation with the potential of different detergents to induce clinical, biophysical, and cell biologic changes in vivo in human skin. Both sodium dodecyl sulfate and CTAB were found to cause induction and upregulation of SKALP and involucrin at low doses following a 24 h patch test, whereas high concentrations of Triton X-100 did not. Sodium dodecyl sulfate induced higher rates of transepidermal water loss, whereas CTAB treated skin showed more signs of cellular toxicity. We conclude that the action of anionic detergents on

  9. Interacting Effects of TSH and Insulin on Human Differentiated Adipocytes.

    Science.gov (United States)

    Felske, D; Gagnon, A; Sorisky, A

    2015-08-01

    Subclinical hypothyroidism, characterized by an isolated rise in TSH serum levels with normal thyroid function, is a pro-inflammatory state associated with insulin resistance. Adipocytes express TSH receptors, but it is not known if TSH can directly inhibit insulin signaling. Using primary human differentiated adipocytes, we examined the effects of TSH on insulin-stimulated Akt phosphorylation, and whether conventional PKC (cPKC) were involved. The effect of insulin on TSH-stimulated lipolysis was also investigated. TSH inhibited insulin-stimulated Akt phosphorylation in adipocytes by 54%. TSH activated cPKC, and Gö6976, a PKCα and -β1 inhibitor, prevented the inhibitory effect of TSH on the insulin response. Insulin reduced the ability of TSH to activate cPKC and to stimulate lipolysis.Our data reveal novel interactions between TSH and insulin. TSH inhibits insulin-stimulated Akt signaling in a cPKC-dependent fashion, whereas insulin blocks TSH-stimulated cPKC activity and lipolysis. TSH and insulin act on differentiated human adipocytes to modulate their respective intracellular signals. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Misregulation of spermatogenesis genes in Drosophila hybrids is lineage-specific and driven by the combined effects of sterility and fast male regulatory divergence.

    Science.gov (United States)

    Gomes, S; Civetta, A

    2014-09-01

    Hybrid male sterility is a common outcome of crosses between different species. Gene expression studies have found that a number of spermatogenesis genes are differentially expressed in sterile hybrid males, compared with parental species. Late-stage sperm development genes are particularly likely to be misexpressed, with fewer early-stage genes affected. Thus, a link has been posited between misexpression and sterility. A more recent alternative explanation for hybrid gene misexpression has been that it is independent of sterility and driven by divergent evolution of male-specific regulatory elements between species (faster male hypothesis). The faster male hypothesis predicts that misregulation of spermatogenesis genes should be independent of sterility and approximately the same in both hybrids, whereas sterility should only affect gene expression in sterile hybrids. To test the faster male hypothesis vs. the effect of sterility on gene misexpression, we analyse spermatogenesis gene expression in different species pairs of the Drosophila phylogeny, where hybrid male sterility occurs in only one direction of the interspecies cross (i.e. unidirectional sterility). We find significant differences among genes in misexpression with effects that are lineage-specific and caused by sterility or fast male regulatory divergence. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  11. A regulatory effect of IL-21 on T follicular helper-like cell and B cell in rheumatoid arthritis.

    Science.gov (United States)

    Liu, Rui; Wu, Qian; Su, Dinglei; Che, Nan; Chen, Haifeng; Geng, Linyu; Chen, Jinyun; Chen, Wanjun; Li, Xia; Sun, Lingyun

    2012-11-23

    Interleukin (IL)-21 is a member of type I cytokine family. Recent studies indicate that IL-21 can promote T follicular helper (Tfh) cell differentiation and survival, a specialized T cell subset which provides help for B cell. It can also regulate the activation, proliferation and differentiation of human B cell and immunoglobulin (Ig) production as well as isotype switching of plasma cell. Rheumatoid arthritis (RA) is characterized by auto-antibodies overproduction such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody, suggesting a pivotal role of Tfh cell and B cell in the pathogenesis of RA. This study aimed to investigate whether IL-21 had a regulatory effect on Tfh cell and B cell in RA. Serum IL-21 concentrations were measured by ELISA. The correlations between serum IL-21 levels and clinical features of RA patients were analyzed by Spearman's rank test. The percentages of Tfh-like cells, IL-21 receptor (R) expression on Tfh-like cells and B cells in peripheral blood (PB) were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) were stimulated by rIL-21 (100 ng/ml) in the presence or absence of anti-CD40 and/or anti-IgM, and changes of IL-21R, activation-associated surface markers (CD25, CD69 and CD40), the proliferation, apoptosis and differentiation of B cells were analyzed by flow cytometry. Production of IgG and IgM in the culture supernatants was determined by ELISA. The results showed that the serum IL-21 levels in RA patients were significantly higher than that of healthy controls (HC). IL-21 concentrations were positively correlated with 28-joint count disease activity score (DAS28) and anti-CCP antibody in RA patients with high IL-21 levels. Furthermore, the frequencies of peripheral CXCR5+PD-1+CD4+ Tfh-like cells markedly increased in RA patients and the percentages of Tfh-like cells were positively correlated with DAS28 and anti-CCP antibody levels. Moreover, elevated IL-21 levels were also

  12. Na/H exchanger regulatory factors control parathyroid hormone receptor signaling by facilitating differential activation of G(alpha) protein subunits.

    Science.gov (United States)

    Wang, Bin; Ardura, Juan A; Romero, Guillermo; Yang, Yanmei; Hall, Randy A; Friedman, Peter A

    2010-08-27

    The Na/H exchanger regulatory factors, NHERF1 and NHERF2, are adapter proteins involved in targeting and assembly of protein complexes. The parathyroid hormone receptor (PTHR) interacts with both NHERF1 and NHERF2. The NHERF proteins toggle PTHR signaling from predominantly activation of adenylyl cyclase in the absence of NHERF to principally stimulation of phospholipase C when the NHERF proteins are expressed. We hypothesized that this signaling switch occurs at the level of the G protein. We measured G protein activation by [(35)S]GTPgammaS binding and G(alpha) subtype-specific immunoprecipitation using three different cellular models of PTHR signaling. These studies revealed that PTHR interactions with NHERF1 enhance receptor-mediated stimulation of G(alpha)(q) but have no effect on stimulation of G(alpha)(i) or G(alpha)(s). In contrast, PTHR associations with NHERF2 enhance receptor-mediated stimulation of both G(alpha)(q) and G(alpha)(i) but decrease stimulation of G(alpha)(s). Consistent with these functional data, NHERF2 formed cellular complexes with both G(alpha)(q) and G(alpha)(i), whereas NHERF1 was found to interact only with G(alpha)(q). These findings demonstrate that NHERF interactions regulate PTHR signaling at the level of G proteins and that NHERF1 and NHERF2 exhibit isotype-specific effects on G protein activation.

  13. The persuasive effects of framing messages on fruit and vegetable consumption according to regulatory focus theory.

    Science.gov (United States)

    Dijkstra, Arie; Rothman, Alexander; Pietersma, Suzanne

    2011-08-01

    According to Regulatory Focus theory (RFT), outcomes in persuasive messages can be framed in four different ways, as gains, non-gains, losses or non-losses. In study 1, the persuasiveness of all four frames was compared and the presence/absence effect that was expected on the basis of the feature-positive effect was verified: Statements about present outcomes (gain, loss) were more persuasive than those about absent outcomes (non-gain, non-loss). However, this study failed to support the prediction that a gain-framed message would be more persuasive than a loss-framed message when promoting a prevention behaviour. Study 2 was designed to examine the latter finding. It was hypothesised that the threat posed by the loss-framed message in study 1 was too low to elicit a defensive reaction. Therefore, in study 2, the personal relevance of the gain and the loss framed message was manipulated. Consistent with predictions, the gain-framed message was more persuasive than the loss-framed message, but only when the message was personalised to increase self-relevance. Moreover, the effect was due to a significant drop in persuasion in the loss condition, probably caused by a defensive reaction. These data shed a new light on the findings of past framing studies.

  14. An Effect Size Measure for Raju's Differential Functioning for Items and Tests

    Science.gov (United States)

    Wright, Keith D.; Oshima, T. C.

    2015-01-01

    This study established an effect size measure for differential functioning for items and tests' noncompensatory differential item functioning (NCDIF). The Mantel-Haenszel parameter served as the benchmark for developing NCDIF's effect size measure for reporting moderate and large differential item functioning in test items. The effect size of…

  15. Differential effect of visual motion adaption upon visual cortical excitability.

    Science.gov (United States)

    Lubeck, Astrid J A; Van Ombergen, Angelique; Ahmad, Hena; Bos, Jelte E; Wuyts, Floris L; Bronstein, Adolfo M; Arshad, Qadeer

    2017-03-01

    The objectives of this study were 1) to probe the effects of visual motion adaptation on early visual and V5/MT cortical excitability and 2) to investigate whether changes in cortical excitability following visual motion adaptation are related to the degree of visual dependency, i.e., an overreliance on visual cues compared with vestibular or proprioceptive cues. Participants were exposed to a roll motion visual stimulus before, during, and after visual motion adaptation. At these stages, 20 transcranial magnetic stimulation (TMS) pulses at phosphene threshold values were applied over early visual and V5/MT cortical areas from which the probability of eliciting a phosphene was calculated. Before and after adaptation, participants aligned the subjective visual vertical in front of the roll motion stimulus as a marker of visual dependency. During adaptation, early visual cortex excitability decreased whereas V5/MT excitability increased. After adaptation, both early visual and V5/MT excitability were increased. The roll motion-induced tilt of the subjective visual vertical (visual dependence) was not influenced by visual motion adaptation and did not correlate with phosphene threshold or visual cortex excitability. We conclude that early visual and V5/MT cortical excitability is differentially affected by visual motion adaptation. Furthermore, excitability in the early or late visual cortex is not associated with an increase in visual reliance during spatial orientation. Our findings complement earlier studies that have probed visual cortical excitability following motion adaptation and highlight the differential role of the early visual cortex and V5/MT in visual motion processing.NEW & NOTEWORTHY We examined the influence of visual motion adaptation on visual cortex excitability and found a differential effect in V1/V2 compared with V5/MT. Changes in visual excitability following motion adaptation were not related to the degree of an individual's visual dependency.

  16. Regulatory effect of miR-149 on interleukin-6 expression in silica-induced pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    范晶晶

    2014-01-01

    Objective To investigate the regulatory effect of miR-149 on interleukin-6(IL-6)expression in silica-induced pulmonary fibrosis.Methods A mouse model of pulmonary fibrosis was established using silica dust;the level of miR-149 in the lung tissues of mice with silicainduced pulmonary fibrosis was measured by quantitative

  17. 78 FR 39036 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-06-28

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...\\ notice is hereby given that, on June 11, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with... Proposed Rule Change 1. Purpose NYSE MKT proposes to amend its listing standard for Reverse...

  18. 78 FR 37860 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-06-24

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... hereby given that on June 10, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with...

  19. 78 FR 79053 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-12-27

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of..., 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange...

  20. 78 FR 75642 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-12-12

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... 26, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and...

  1. 77 FR 35437 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-06-13

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... hereby given that on May 31, 2012, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the... Exchange proposes to amend the Fee Schedule to reflect the Exchange's name change to NYSE MKT LLC....

  2. 78 FR 60362 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-10-01

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... on September 13, 2013, NYSE MKT LLC (``NYSE MKT'' or ``Exchange'') filed with the Securities...

  3. 77 FR 53952 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-09-04

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending NYSE MKT Rules 103B(IX)--Equities and 504--Equities To Provide That a..., 2012, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange...

  4. 77 FR 41859 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-07-16

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Deleting NYSE MKT LLC Rule 440A--Equities, Which Addresses Telemarketing, and Adopting New NYSE MKT LLC Rule 3230--Equities, To Conform to FINRA's Telemarketing Rule July 10, 2012....

  5. 78 FR 26677 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-05-07

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of..., on April 19, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities...

  6. 78 FR 1290 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-01-08

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending NYSE MKT Rule 500--Equities To Extend the Operation of the Pilot Program That..., NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange Commission...

  7. 77 FR 40107 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-07-06

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... on June 15, 2012, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities...

  8. 78 FR 63551 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-10-24

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... on October 7, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities...

  9. 77 FR 45404 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-07-31

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending NYSE MKT Rule 500--Equities To Extend the Operation of the Pilot Program That..., NYSE MKT LLC (``NYSE MKT'' or ``Exchange'') filed with the Securities and Exchange...

  10. 78 FR 34689 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-06-10

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... on May 24, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities...

  11. 77 FR 51592 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-08-24

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... Name From NYSE Amex LLC (``NYSE Amex'') to NYSE MKT LLC August 20, 2012. Pursuant to Section 19(b)(1... given that, on August 9, 2012, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the...

  12. 78 FR 27459 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-05-10

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... Rule 19b-4 thereunder,\\3\\ notice is hereby given that on April 25, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange Commission (the ``Commission'') the...

  13. 77 FR 46144 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-08-02

    ...-2012-29] Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending the NYSE MKT Equities Price List To Change Certain Fees Relating to Trading...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that, on July 20, 2012, NYSE MKT LLC...

  14. 77 FR 56685 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-09-13

    ... [Federal Register Volume 77, Number 178 (Thursday, September 13, 2012)] [Notices] [Page 56685] [FR Doc No: C1-2012-21385] SECURITIES AND EXCHANGE COMMISSION [Release No. 34-67719; File No. SR-NYSEMKT-2012-40] Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness...

  15. 78 FR 38769 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-06-27

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of..., NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange Commission...

  16. 78 FR 48535 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-08-08

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... on July 30, 2013, NYSE MKT LLC (``NYSE MKT'' or ``Exchange'') filed with the Securities and Exchange... Commission on a pilot basis. Pursuant to NYSE MKT Rule 107C(m)--Equities, the pilot period for the Program...

  17. 78 FR 46399 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-07-31

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... thereunder,\\3\\ notice is hereby given that on July 17, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE...

  18. 78 FR 74197 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-12-10

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending the NYSE MKT Equities Price List and the NYSE Amex Options Fee Schedule in..., NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange Commission...

  19. 78 FR 50471 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-08-19

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...\\ notice is hereby given that on August 1, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with... organizations, as that term is defined in the definitions section of the General and Floor Rules of the NYSE...

  20. 77 FR 66902 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-11-07

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...\\ notice is hereby given that, on October 19, 2012, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed... charge imposed by the NYSE MKT. \\13\\ 15 U.S.C. 78s(b)(3)(A). \\14\\ 17 CFR 240.19b-4(f)(2). ] At any...

  1. 77 FR 40671 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-07-10

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of..., 2012, NYSE MKT LLC (``NYSE MKT'' or ``Exchange'') filed with the Securities and Exchange Commission..., Senior Floor Officials and Executive Floor Governors), or both.\\4\\ \\3\\ 15 U.S.C. 78f. \\4\\ See NYSE...

  2. 77 FR 41824 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-07-16

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Deleting NYSE MKT LLC Rule 428(a), Which Addresses Telephone Solicitation, and Amending NYSE MKT LLC Rule 429, Which Addresses Telemarketing, To Adopt New Rule Text To Conform to...

  3. 78 FR 54943 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-09-06

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange Commission... acquired the American Stock Exchange LLC, now known as NYSE MKT.\\3\\ As part of the integration of...

  4. 77 FR 75225 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-12-19

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...\\ and Rule 19b-4 thereunder,\\3\\ notice is hereby given that on December 7, 2012, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange Commission (the ``Commission'')...

  5. 77 FR 70197 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-11-23

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending NYSE MKT Rule 123C--Equities To Add New Supplementary Material .40 To Clarify... MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange Commission...

  6. 78 FR 33866 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-06-05

    ...-2013-42] Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending NYSE MKT Rule 980NY, To Remove Provisions Governing How the Complex Matching... is hereby given that on May 17, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with...

  7. 77 FR 76158 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-12-26

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend Section 140 of the NYSE MKT LLC Company Guide To Introduce an Initial... ``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 6, 2012, NYSE MKT...

  8. 77 FR 75462 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-12-20

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending Section 102(a) of the NYSE MKT Company Guide To Eliminate an Erroneous...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 4, 2012, NYSE MKT...

  9. 78 FR 38779 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-06-27

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... on June 17, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities...

  10. 78 FR 16544 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-03-15

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... 26, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities and Exchange... until executed in full or cancelled. See NYSE MKT Rule 13--Equities. STPN Result 2: S would...

  11. 78 FR 16905 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-03-19

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... thereunder,\\2\\ notice is hereby given that on March 5, 2013, NYSE MKT LLC (``NYSE MKT'' or...

  12. 78 FR 38762 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-06-27

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending NYSE MKT Rule 500--Equities To Extend the Operation of the Pilot Program That..., NYSE MKT LLC (``NYSE MKT'' or ``Exchange'') filed with the Securities and Exchange...

  13. 77 FR 59442 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-09-27

    ...-NYSEMKT-2012-45] Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending Sections 1203(a) and 1205(b) of the NYSE MKT Company Guide...\\ notice is hereby given that on September 7, 2012, NYSE MKT LLC (``NYSE MKT'' or ``Exchange'') filed...

  14. 78 FR 64255 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-10-28

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... on October 11, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with the Securities...

  15. 77 FR 77172 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-12-31

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending the NYSE MKT LLC Price List To Specify Pricing that is Currently Applicable... 19b-4 thereunder,\\2\\ notice is hereby given that, on December 14, 2012, NYSE MKT LLC (the...

  16. 78 FR 16332 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-03-14

    ... From the Federal Register Online via the Government Publishing Office ] SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... thereunder,\\3\\ notice is hereby given that on March 5, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE...

  17. 77 FR 71846 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-12-04

    ... COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... thereunder,\\2\\ notice is hereby given that on November 14, 2012, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT... platform to trade those securities. The Exchange also adopted equity trading rules for NYSE MKT based...

  18. 77 FR 77154 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-12-31

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... thereunder,\\2\\ notice is hereby given that on December 10, 2012, NYSE MKT LLC (the ``Exchange'' or ``NYSE...

  19. 78 FR 16554 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-03-15

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of... hereby given that on February 26, 2013, NYSE MKT LLC (the ``Exchange'' or ``NYSE MKT'') filed with...

  20. The additive effect of regulatory activities on top of intelligence in relation to academic performance in higher education

    NARCIS (Netherlands)

    Minnaert, A; Janssen, PJ

    1999-01-01

    This study investigated the additive, beneficial effect of regulatory activities on top of verbal, numerical, and diagrammatic intelligence in the prediction of academic performance. About 500 freshmen of different study domains participated in this research. The findings supported both the mixed an

  1. Physiological and Regulatory Effects of Controlled Overproduction of Five Cold Shock Proteins of Lactococcus lactis MG1363

    NARCIS (Netherlands)

    Wouters, Jeroen A.; Mailhes, Marielle; Rombouts, Frank M.; Vos, Willem M. de; Kuipers, Oscar P.; Abee, Tjakko

    2000-01-01

    The physiological and regulatory effects of overproduction of five cold shock proteins (CSPs) of Lactococcus lactis were studied. CspB, CspD, and CspE could be overproduced at high levels (up to 19% of the total protein), whereas for CspA and CspC limited overproduction (0.3 to 0.5% of the total pro

  2. 77 FR 14452 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-03-09

    ..., and that such determinations will be made pursuant to procedures of BOX Market Operations Center... free and open market and a national market system, and, in general to protect investors and the public... COMMISSION Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

  3. The regulatory effects of Bifidobacterium infantis on the secretomotor activity of the enteric nervous system

    Directory of Open Access Journals (Sweden)

    Najma Javed

    2013-01-01

    Full Text Available Background: Bifidobacterium infantis (BI and other probiotics are non-pathogenic living organisms that have gained increased attention for their possible therapeutic implications on the health of the digestive tract. The mechanisms by which probiotics exert their effects are largely unknown.Aims: This study explored the protective and regulatory effect of oral BI on the enteric nervous system in the 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis rats. Materials and Methods: Electrical field stimulation and chemical stimulation by 5 hydroxytryptamine or serotonin were used to elicit changes in short-circuit current response of the colonic rat tissue. Results: BI-fed colitis rats expressed trends of higher secretomotor activity and revealed signs of decreased macroscopic inflammatory damage when compared to sham-fed colitis rats, suggesting a protective and preventative role of oral BI. Conclusion: These findings may provide additional insights for understanding the prophylactic and therapeutic value of specific probiotics in intestinal inflammatory disorders, offering the possibility of a non-invasive alternative to toxic and immune-compromising drugs.

  4. Immune enhancing effects of Echinacea purpurea root extract by reducing regulatory T cell number and function.

    Science.gov (United States)

    Kim, Hyung-Ran; Oh, Sei-Kwan; Lim, Woosung; Lee, Hyeon Kook; Moon, Byung-In; Seoh, Ju-Young

    2014-04-01

    Echinacea purpurea preparations (EPs) have been traditionally used for the treatment of various infections and also for wound healing. Accumulating evidence suggests their immunostimulatory effects. Regulatory T cells (Tregs) are known to play a key role in immune regulation in vivo. However, there have been no reports so far on the effects of EP on the frequency or function of Tregs in vivo. Therefore, in the present study, we investigated the quantitative and functional changes in Tregs by in vivo administration with EP. The frequencies of CD4+FoxP3+ and CD4+CD25+ Tregs in the spleens of BALB/c mice administered with EP for 3 weeks were investigated by flow cytometry. The suppressive function of CD4CD25+ Tregs in association with the proliferative activity of CD4+CD25 effector T cells (Teffs) and the feeder function of CD4 antigen-presenting cells (APCs) were analyzed by carboxyfluorescein succinimidyl ester-dilution assay. The results showed a lowered frequency of CD4+FoxP3+ and CD4+CD25+ Tregs and attenuated suppressive function of CD4+CD25+ Tregs, while the feeder function of APCs was enhanced in the EP-administered mice. On the other hand, the proliferative activity of Teffs was not significantly different in the EP-administered mice. The results suggest that decreased number and function of Tregs, in association with the enhanced feeder function of APCs, may contribute to the enhancement of immune function by EP.

  5. The Effectiveness of the Regulatory Regime for Black Carbon Mitigation in the Arctic

    Directory of Open Access Journals (Sweden)

    Daria Shapovalova

    2016-11-01

    Full Text Available In addition to being a hazardous air pollutant, Black Carbon is the second-largest contributor to Arctic warming. Its mitigation is being addressed at the international regulatory level by the Arctic Council and the Convention on Long-Range Transboundary Air Pollution (CLRTAP. Whilst the Convention and its protocols are binding documents, the Black Carbon regulation under their framework appears to have ‘soft law’ characteristics. At the same time, the voluntary Black Carbon and Methane Framework, adopted by the Arctic Council, demonstrates positive compliance and follow-up dynamics compared to earlier norm-creating attempts. This paper argues that the nature of the norm (binding or non-binding is not the decisive factor regarding effective implementation in the Arctic region. Current efforts to mitigate Black Carbon by means of a non-binding Arctic Council Black Carbon and Methane Framework represent an improvement in the Council's normative function and may have more effect on the behaviour of Arctic States than relevant provisions under the Gothenburg Protocol to the CLRTAP. To support this argument, the first section presents an overview of the Arctic Council as an actor in Arctic policy-making. It then provides an assessment of current efforts to combat Black Carbon carried out by the Arctic Council and the CLRTAP.

  6. Mapping cis- and trans-regulatory effects across multiple tissues in twins

    Science.gov (United States)

    Grundberg, Elin; Small, Kerrin S.; Hedman, Åsa K.; Nica, Alexandra C.; Buil, Alfonso; Keildson, Sarah; Bell, Jordana T.; Yang, Tsun-Po; Meduri, Eshwar; Barrett, Amy; Nisbett, James; Sekowska, Magdalena; Wilk, Alicja; Shin, So-Youn; Glass, Daniel; Travers, Mary; Min, Josine L.; Ring, Sue; Ho, Karen; Thorleifsson, Gudmar; Kong, Augustine; Thorsteindottir, Unnur; Ainali, Chrysanthi; Dimas, Antigone S.; Hassanali, Neelam; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lowe, Christopher E.; Di Meglio, Paola; Montgomery, Stephen B.; Parts, Leopold; Potter, Simon; Surdulescu, Gabriela; Tsaprouni, Loukia; Tsoka, Sophia; Bataille, Veronique; Durbin, Richard; Nestle, Frank O.; O’Rahilly, Stephen; Soranzo, Nicole; Lindgren, Cecilia M.; Zondervan, Krina T.; Ahmadi, Kourosh R.; Schadt, Eric E.; Stefansson, Kari; Smith, George Davey; McCarthy, Mark I.; Deloukas, Panos; Dermitzakis, Emmanouil T.; Spector, Tim D.

    2013-01-01

    Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many eQTL studies typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. Using identity-by-descent estimates, we show that at least 40% of the total heritable cis-effect on expression cannot be accounted for by common cis-variants, a finding which exposes the contribution of low frequency and rare regulatory variants with respect to both transcriptional regulation and complex trait susceptibility. We show that a substantial proportion of gene expression heritability is trans to the structural gene and identify several replicating trans-variants which act predominantly in a tissue-restricted manner and may regulate the transcription of many genes. PMID:22941192

  7. Differential expression analysis and regulatory network reconstruction for genes associated with muscle growth and adipose deposition in obese and lean pigs

    Institute of Scientific and Technical Information of China (English)

    Mingzhou Li; Xuewei Li; Li Zhu; Xiaokun Teng; Huasheng Xiao; Surong Shuai; Lei Chen; Qiang Li; Yujiao Guo

    2008-01-01

    During the growth and development of skeletal muscle cells and adipose cells, the regulatory mechanism of micro-effect polygenes determines porcine meat quality, carcass characteristics and other relative quantitative traits. Obese and lean type pig breeds show obvious differences in muscle growth and adipose deposition; however, the molecular mechanism underlying this phenotypic variation remains unknown. We used pathway-focused oligo microarray studies to examine the expression changes of 140 genes associated with muscle growth and adipose deposition in longissimus dorsi muscle at six growth stages (birth, 1, 2, 3, 4 and 5 months) of Landrace (a leaner, Western breed) and Taihu pigs (a fatty, indigenous, Chinese breed). Variance analysis (ANOVA) revealed that differences in the expression of 18 genes in Landrace pigs and three genes in Taihu pigs were very significant (FDR-adjusted permutation, P<0.01) and differences for 22 genes in Landrace pigs and seven genes in Taihu pigs were significant (FDR-adjusted permutation, P<0.05) among six growth stages. Clustering analysis revealed a high level of significance (FDR-adjusted, P<0.01) for four gene expression patterns, in which genes that strongly up-regulated were mainly associated with the positive regulation of myofiber formation and fatty acid biogenesis and genes that strongly down-regulated were mainly associated with the inhibition of cell proliferation and positive regulation of fatty acid P-oxidation. Based on a dynamic Bayesian network (DBN) model, gene regulatory networks (GRNs) were reconstructed from time-series data for each pig breed. These two GRNs initially revealed the distinct differences in physiological and biochemical aspects of muscle growth and adipose deposition between the two pig breeds; from these results, some potential key genes could be identified. Quantitative real-time RT-PCR (QRT-PCR) was used to verify the microarray data for five modulated genes, and a good correlation between the

  8. Regulatory Foci and Organizational Commitment

    Science.gov (United States)

    Markovits, Yannis; Ullrich, Johannes; van Dick, Rolf; Davis, Ann J.

    2008-01-01

    We use regulatory focus theory to derive specific predictions regarding the differential relationships between regulatory focus and commitment. We estimated a structural equation model using a sample of 520 private and public sector employees and found in line with our hypotheses that (a) promotion focus related more strongly to affective…

  9. Distinct Regulatory Changes Underlying Differential Expression of TEOSINTE BRANCHED1-CYCLOIDEA-PROLIFERATING CELL FACTOR Genes Associated with Petal Variations in Zygomorphic Flowers of Petrocosmea spp. of the Family Gesneriaceae.

    Science.gov (United States)

    Yang, Xia; Zhao, Xiao-Ge; Li, Chao-Qun; Liu, Jing; Qiu, Zhi-Jing; Dong, Yang; Wang, Yin-Zheng

    2015-11-01

    CYCLOIDEA (CYC)-like genes, belonging to the plant-specific TCP transcription factor family that is named after TEOSINTE BRANCHED1 (TB1) from maize (Zea mays), CYC from Antirrhinum majus, and the PROLIFERATING CELL FACTORS (PCF) from rice (Oryza sativa), have conserved dorsal identity function in patterning floral zygomorphy mainly through specific expression in dorsal petals of a flower. Their expression changes are usually related to morphological diversity of zygomorphic flowers. However, it is still a challenge to elucidate the molecular mechanism underlying their expression differentiation. It is also unknown whether CINCINNATA (CIN)-like TCP genes, locally controlling cell growth and proliferation, are involved in the evolution of floral zygomorphy. To address these questions, we selected two closely related species, i.e. Petrocosmea glabristoma and Petrocosmea sinensis, with distinct petal morphology to conduct expression, hybridization, mutant, and allele-specific expression analyses. The results show that the size change of the dorsal petals between the two species is mainly mediated by the expression differentiation of CYC1C and CYC1D, while the shape variation of all petals is related to the expression change of CIN1. In reciprocal F1 hybrids, the expression of CYC1C, CYC1D, and CIN1 conforms to an additive inheritance mode, consistent with the petal phenotypes of hybrids. Through allele-specific expression analyses, we find that the expression differentiation of these TCP genes is underlain by distinctly different types of regulatory changes. We suggest that highly redundant paralogs with identical expression patterns and interspecific expression differentiation may be controlled by remarkably different regulatory pathways because natural selection may favor different regulatory modifications rather than coding sequence changes of key developmental genes in generating morphological diversity. © 2015 American Society of Plant Biologists. All Rights

  10. Distinct Regulatory Changes Underlying Differential Expression of TEOSINTE BRANCHED1-CYCLOIDEA-PROLIFERATING CELL FACTOR Genes Associated with Petal Variations in Zygomorphic Flowers of Petrocosmea spp. of the Family Gesneriaceae1[OPEN

    Science.gov (United States)

    Yang, Xia; Zhao, Xiao-Ge; Li, Chao-Qun; Liu, Jing; Qiu, Zhi-Jing; Dong, Yang; Wang, Yin-Zheng

    2015-01-01

    CYCLOIDEA (CYC)-like genes, belonging to the plant-specific TCP transcription factor family that is named after TEOSINTE BRANCHED1 (TB1) from maize (Zea mays), CYC from Antirrhinum majus, and the PROLIFERATING CELL FACTORS (PCF) from rice (Oryza sativa), have conserved dorsal identity function in patterning floral zygomorphy mainly through specific expression in dorsal petals of a flower. Their expression changes are usually related to morphological diversity of zygomorphic flowers. However, it is still a challenge to elucidate the molecular mechanism underlying their expression differentiation. It is also unknown whether CINCINNATA (CIN)-like TCP genes, locally controlling cell growth and proliferation, are involved in the evolution of floral zygomorphy. To address these questions, we selected two closely related species, i.e. Petrocosmea glabristoma and Petrocosmea sinensis, with distinct petal morphology to conduct expression, hybridization, mutant, and allele-specific expression analyses. The results show that the size change of the dorsal petals between the two species is mainly mediated by the expression differentiation of CYC1C and CYC1D, while the shape variation of all petals is related to the expression change of CIN1. In reciprocal F1 hybrids, the expression of CYC1C, CYC1D, and CIN1 conforms to an additive inheritance mode, consistent with the petal phenotypes of hybrids. Through allele-specific expression analyses, we find that the expression differentiation of these TCP genes is underlain by distinctly different types of regulatory changes. We suggest that highly redundant paralogs with identical expression patterns and interspecific expression differentiation may be controlled by remarkably different regulatory pathways because natural selection may favor different regulatory modifications rather than coding sequence changes of key developmental genes in generating morphological diversity. PMID:26351309

  11. Effects of low-doses of Bacillus spp. from permafrost on differentiation of bone marrow cells.

    Science.gov (United States)

    Kalyonova, L F; Novikova, M A; Kostolomova, E G

    2015-01-01

    The effects of a new microorganism species (Bacillus spp., strain M3) isolated from permafrost specimens from Central Yakutia (Mamontova Mountain) on the bone marrow hemopoiesis were studied on laboratory mice. Analysis of the count and immunophenotype of bone marrow cells indicated that even in low doses (1000-5000 microbial cells) these microorganisms modulated hemopoiesis and lymphopoiesis activity. The percentage of early hemopoietic precursors (CD117(+)CD34(-)) increased, intensity of lymphocyte precursor proliferation and differentiation (CD25(+)CD44(-)) decreased, and the percentage of lymphocytes released from the bone marrow (CD25(+)CD44(+)) increased on day 21 after injection of the bacteria. These changes in activity of hemopoiesis were associated with changes in the level of regulatory T lymphocytes (reduced expression of TCRαβ) and were most likely compensatory. The possibility of modulating hemopoiesis activity in the bone marrow by low doses of one microorganism strain isolated from the permafrost could be useful for evaluating the effects of other low dose bacteria on the bone marrow hemopoiesis.

  12. Wage differentials in Jordan: effects on integrated labour market.

    Science.gov (United States)

    Share, M A

    1987-06-01

    The emigration of Jordanian workers has benefited the country by reducing the scale of unemployment that existed in the 1960s and early 1970s. In addition, workers' remittances have had a favorable effect on the Jordanian balance of payments and contributed to increases in wage rates and demands for labor. Any shortages of labor resulting from the emigration flow appear to have been offset by the importation of workers from neighboring countries. A sample survey encompassing 495 foreign workers in Jordan and 518 Jordanian workers indicates that immigrant workers' wages are below those of Jordanian workers and considerably below the wages that Jordanian workers earn abroad. The average monthly wage for the Jordanians in the sample was JD 193.03 compared to JD 132.93 for the immigrants--a 45% difference. Over half of the immigrants surveyed earned under JD 99/month, while only 26% of the Jordanian workers were in this low income category. In part this wage differential is caused by the high proportions of immigrant workers employed in the clerical and unskilled occupational groups, where they are paid only half the wages earned by Jordanians engaged in the same occupations. A similar differential was observed in the average amount of monthly remittances to home countries: in 1982, Jordanians working abroad remitted an average of JD 77.5/worker compared with JD 59/worker remitted by foreign workers employed in Jordan. On balance, it appears that Jordan is a net gainer from the process of labor import and export.

  13. The Effect of Regulatory Harmonization on Cross-border Labor Migration: Evidence from the Accounting Profession

    OpenAIRE

    2015-01-01

    The paper examines whether international regulatory harmonization increases cross-border labor migration. To study this question, we analyze European Union (EU) initiatives that harmonized accounting and auditing standards. Regulatory harmonization should reduce economic mobility barriers, essentially making it easier for accounting professionals to move across countries. Our research design compares the cross-border migration of accounting professionals relative to tightly-matched other prof...

  14. Effects of differentiation on the geodynamics of the early Earth

    Science.gov (United States)

    Piccolo, Andrea; Kaus, Boris; White, Richard; Johnson, Tim

    2016-04-01

    Archean geodynamic processes are not well understood, but there is general agreement that the mantle potential temperature was higher than present, and that as a consequence significant amounts of melt were produced both in the mantle and any overlying crust. This has likely resulted in crustal differentiation. An early attempt to model the geodynamic effects of differentiation was made by Johnson et al. (2014), who used numerical modeling to investigate the crust production and recycling in conjunction with representative phase diagrams (based on the inferred chemical composition of the primary melt in accordance with the Archean temperature field). The results of the simulations show that the base of the over-thickened primary basaltic crust becomes gravitational unstable due to the mineral assemblage changes. This instability leads to the dripping of dense material into the mantle, which causes an asthenospheric return flow, local partial melting and new primary crust generation that is rapidly recycled in to mantle. Whereas they gave important insights, the previous simulations were simplified in a number of aspects: 1) the rheology employed was viscous, and both elasticity and pressure-dependent plasticity were not considered; 2) extracted mantle melts were 100% transformed into volcanic rocks, whereas on the present day Earth only about 20-30% are volcanic and the remainder is plutonic; 3) the effect of a free surface was not studied in a systematic manner. In order to better understand how these simplifications affect the geodynamic models, we here present additional simulations to study the effects of each of these parameters. Johnson, T.E., Brown, M., Kaus, B., and VanTongeren, J.A., 2014, Delamination and recycling of Archaean crust caused by gravitational instabilities: Nature Geoscience, v. 7, no. 1, p. 47-52, doi: 10.1038/NGEO2019.

  15. Testosterone replacement effectively inhibits the development of experimental autoimmune orchitis in rats: evidence for a direct role of testosterone on regulatory T cell expansion.

    Science.gov (United States)

    Fijak, Monika; Schneider, Eva; Klug, Jörg; Bhushan, Sudhanshu; Hackstein, Holger; Schuler, Gerhard; Wygrecka, Malgorzata; Gromoll, Jörg; Meinhardt, Andreas

    2011-05-01

    Despite the immune-privileged status of the male genital tract, infection and inflammation of the male genital tract are important etiological factors in male infertility. A common observation in clinical and experimental orchitis as well as in systemic infection and inflammation are decreased levels of testosterone. Emerging data point to an immunosuppressive role of testosterone. In our study, we substituted testosterone levels in experimental autoimmune orchitis (EAO) in rat by s.c. testosterone implants. EAO development was reduced to 17% when animals were treated with low-dose testosterone implants (3 cm long, EAO+T3) and to 33% when rats were supplied with high-dose testosterone implants (24 cm, EAO+T24) compared with 80% of animals developing disease in the EAO control group. In the testis, testosterone replacement in EAO animals prevented the accumulation of macrophages and significantly reduced the number of CD4(+) T cells with a strong concomitant increase in the number of regulatory T cells (CD4(+)CD25(+)Foxp3(+)) compared with EAO control. In vitro testosterone treatment of naive T cells led to an expansion of the regulatory T cell subset with suppressive activity and ameliorated MCP-1-stimulated chemotaxis of T lymphocytes in a Transwell assay. Moreover, expression of proinflammatory mediators such as MCP-1, TNF-α, and IL-6 in the testis and secretion of Th1 cytokines such as IFN-γ and IL-2 by mononuclear cells isolated from testicular draining lymph nodes were decreased in the EAO+T3 and EAO+T24 groups. Thus, our study shows an immunomodulatory and protective effect of testosterone substitution in the pathogenesis of EAO and suggests androgens as a new factor in the differentiation of regulatory T cells.

  16. Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation

    DEFF Research Database (Denmark)

    Hansen, L. H.; Madsen, B; Teisner, Børge

    1998-01-01

    . A possible role for Pref-1/FA1 in mediating the antiadipogenic effect of GH was indicated by the observation that FA1 inhibited differentiation as effectively as GH. These data suggest that GH exerts its inhibitory activity in adipocyte differentiation at a step after the induction of ADD1 but before...... the induction of genes required for terminal differentiation....

  17. Erythropoietin and the effect of oxygen during proliferation and differentiation of human neural progenitor cells

    Directory of Open Access Journals (Sweden)

    Frech Moritz J

    2010-12-01

    Full Text Available Abstract Background Hypoxia plays a critical role in various cellular mechanisms, including proliferation and differentiation of neural stem and progenitor cells. In the present study, we explored the impact of lowered oxygen on the differentiation potential of human neural progenitor cells, and the role of erythropoietin in the differentiation process. Results In this study we demonstrate that differentiation of human fetal neural progenitor cells under hypoxic conditions results in an increased neurogenesis. In addition, expansion and proliferation under lowered oxygen conditions also increased neuronal differentiation, although proliferation rates were not altered compared to normoxic conditions. Erythropoietin partially mimicked these hypoxic effects, as shown by an increase of the metabolic activity during differentiation and protection of differentiated cells from apoptosis. Conclusion These results provide evidence that hypoxia promotes the differentiation of human fetal neural progenitor cells, and identifies the involvement of erythropoietin during differentiation as well as different cellular mechanisms underlying the induction of differentiation mediated by lowered oxygen levels.

  18. Segregation of regulatory polymorphisms with effects on the gluteus medius transcriptome in a purebred pig population.

    Directory of Open Access Journals (Sweden)

    Angela Cánovas

    Full Text Available BACKGROUND: The main goal of the present study was to analyse the genetic architecture of mRNA expression in muscle, a tissue with an outmost economic importance for pig breeders. Previous studies have used F(2 crosses to detect porcine expression QTL (eQTL, so they contributed with data that mostly represents the between-breed component of eQTL variation. Herewith, we have analysed eQTL segregation in an outbred Duroc population using two groups of animals with divergent fatness profiles. This approach is particularly suitable to analyse the within-breed component of eQTL variation, with a special emphasis on loci involved in lipid metabolism. METHODOLOGY/PRINCIPAL FINDINGS: GeneChip Porcine Genome arrays (Affymetrix were used to determine the mRNA expression levels of gluteus medius samples from 105 Duroc barrows. A whole-genome eQTL scan was carried out with a panel of 116 microsatellites. Results allowed us to detect 613 genome-wide significant eQTL unevenly distributed across the pig genome. A clear predominance of trans- over cis-eQTL, was observed. Moreover, 11 trans-regulatory hotspots affecting the expression levels of four to 16 genes were identified. A Gene Ontology study showed that regulatory polymorphisms affected the expression of muscle development and lipid metabolism genes. A number of positional concordances between eQTL and lipid trait QTL were also found, whereas limited evidence of a linear relationship between muscle fat deposition and mRNA levels of eQTL regulated genes was obtained. CONCLUSIONS/SIGNIFICANCE: Our data provide substantial evidence that there is a remarkable amount of within-breed genetic variation affecting muscle mRNA expression. Most of this variation acts in trans and influences biological processes related with muscle development, lipid deposition and energy balance. The identification of the underlying causal mutations and the ascertainment of their effects on phenotypes would allow gaining a

  19. Synergistic and regulatory effects of orbitofrontal cortex on amygdala-dependent appetitive behavior.

    Science.gov (United States)

    Roberts, A C; Reekie, Y; Braesicke, K

    2007-12-01

    This paper will review two avenues of our research in marmosets that have focused on the role of the orbitofrontal cortex (OFC) in amygdala-dependent appetitive behavior. The first demonstrates the important contribution of both the OFC and the amygdala to conditioned reinforcement (CRF). The second reveals the regulatory effects of the OFC on amygdala-dependent autonomic and behavioral arousal in appetitive conditioning. The process of CRF is one way in which an environmental cue can guide emotional behavior. As a consequence of its previous relationship with reward, a cue can take on affective value and reinforce behavior. Lesion studies in marmosets are described that show that CRF is dependent upon both the amygdala and OFC. The synergistic interactions between these structures that have been shown to underlie other aspects of reward processing are then considered with respect to CRF. The results are contrasted with those that show the importance of the OFC in suppressing positive affective responses elicited by the amygdala in response to a conditioned stimulus (CS). Specifically, it will be shown that the OFC is involved in the rapid suppression of conditioned autonomic arousal upon CS withdrawal and in the co-ordination of conditioned autonomic and behavioral responses when adapting to changing reward contingencies. It will be argued that, overall, the OFC plays a critical role in the context-dependent regulation of positive affective responding governed by external cues, in keeping with a role in executive control.

  20. Effect of chorioamnionitis on regulatory T cells in moderate/late preterm neonates☆

    Science.gov (United States)

    Rueda, Cesar M.; Wells, Casey B.; Gisslen, Tate; Jobe, Alan H.; Kallapur, Suhas G.; Chougnet, Claire A.

    2014-01-01

    Regulatory T-cells (Treg) have a protective role for the control of immune activation and tissue damage. The effects of chorioamnionitis (chorio) on Treg in moderate/late preterm newborns are not known. We hypothesized that infants exposed to chorio would have decreased Treg frequency and/or function. We isolated mononuclear cells from adult peripheral blood and cord blood from term and moderate/late preterm infants who were classified for severity of chorio exposure. Mononuclear cells were analyzed by flow cytometry for Treg frequency and phenotype. Treg suppression of activation of conventional T-cells (Tcon) was also quantified. Treg frequencies were similar in all groups of neonates, but lower than that found in adults. Newborn Treg had a naïve phenotype, with decreased levels of CD45RO, HLA-DR, CD39 and TIGIT compared to adult Treg and chorio did not affect the phenotype. Treg from preterm newborns exposed to severe chorio had higher expression of Ki67 compared to the other groups. Treg from preterm newborns were less suppressive than Treg from adults or term, and the level of suppression was reduced with severe chorio. Relative to term, Treg frequency and phenotype were not affected by prematurity and chorio but their functionality was decreased. Lower Treg activity may contribute to inflammation in newborns that is often associated with chorioamnionitis. PMID:25451985

  1. The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.

    Science.gov (United States)

    Soffritti, Morando; Padovani, Michela; Tibaldi, Eva; Falcioni, Laura; Manservisi, Fabiana; Belpoggi, Fiorella

    2014-04-01

    Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health.

  2. The effectiveness of a regulatory strategy in containing hospital costs. The Ontario experience, 1967-1981.

    Science.gov (United States)

    Detsky, A S; Stacey, S R; Bombardier, C

    1983-07-21

    This study documents the increases in real inputs (e.g., labor and equipment) employed in Ontario's hospital sector between 1968 and 1981--a period of universal government-financed hospital insurance and a government regulatory strategy involving global budgeting. Total expenditures in Ontario increased by only 16 per cent in terms of real inputs, as compared with an increase of 101 per cent in the United States. Real inputs per patient-day increased at a mean annual rate of 0.68 per cent in Ontario versus 5.19 per cent in the United States (P less than 0.001). Real inputs per admission decreased at a mean annual rate of 1.12 per cent in Ontario, as compared with an increase of 4.15 per cent in the United States (P less than 0.0001). We conclude that regulation can contain the growth of real inputs employed in the hospital sector even in the face of an incentive structure that does not promote cost consciousness on the part of patients or physicians. Although the effect of this strategy on the quality of care is unknown, so far it appears to have been politically acceptable in Ontario.

  3. Effect of Zinc on Appetite Regulatory Peptides in the Hypothalamus of Salmonella-Challenged Broiler Chickens.

    Science.gov (United States)

    Hu, Xiyi; Sheikhahmadi, Ardashir; Li, Xianlei; Wang, Yufeng; Jiao, Hongchao; Lin, Hai; Zhang, Bingkun; Song, Zhigang

    2016-07-01

    The effects of dietary Zinc (Zn) supplementation on the gene expression of appetite regulatory peptides were investigated in Salmonella-infected broiler chickens. Broiler chickens (Arbor Acres, 1 day old) were allocated randomly into 24 pens of 10 birds. The chickens from 12 pens were fed with basal diet and the other with basal diet supplemented with Zn (ZnSO4·H2O, 120 mg/kg). At 5 days of age, the chickens were divided into 4 treatments with 6 pens: basal diet; basal diet and Salmonella challenge; Zn-supplemented diet; Zn-supplemented diet and Salmonella challenge. At 42 days of age, the hypothalamus from 6 chickens per treatment (1 chicken per pen) was individually collected for gene expression determination. Results showed that dietary supplementation of Zn reduced the gene expression of hypothalamic ghrelin and tumor necrosis factor alpha (TNF-α) (P hypothalamus of Salmonella-challenged broilers.

  4. Consumption of probiotics increases the effect of regulatory T cells in transfer colitis.

    Science.gov (United States)

    Petersen, Emil Rathsach; Claesson, Mogens Helweg; Schmidt, Esben Gjerløff Wedebye; Jensen, Simon Skjøde; Ravn, Peter; Olsen, Jørgen; Ouwehand, Arthur C; Kristensen, Nanna Ny

    2012-01-01

    Probiotics may alter immune regulation. Recently, we showed that the probiotic bacteria Lactobacillus acidophilus NCFM™ influenced the activity of regulatory T cells (Tregs) in vitro. The aim of the present work was to demonstrate if L. acidophilus NCFM™ also affects the function of Tregs in vivo. Development of colitis after transfer of CD4+CD25- T cells and protection from colitis by Tregs was studied in immunodeficient SCID mice which were simultaneously tube-fed with L. acidophilus NCFM™ or L. salivarius Ls-33 for 5 weeks. Probiotic-fed SCID mice transplanted with low numbers of Tregs in addition to the disease-inducing T cells were completely protected from colitis. This was in contrast to the control group, which showed intermediate levels of inflammation. In addition, feeding with probiotics lowered serum levels of inflammatory cytokines in both colitic mice and in mice protected from colitis by Tregs. Gene expression patterns of rectum samples of protected mice that receive either one of the probiotics showed a closer resemblance to naïve SCID mice than did patterns of the control group. The mechanism of action of the probiotics appears to be an indirect effect by inducing a Treg-favorable environment rather than a direct effect on the Tregs. L. acidophilus NCFM™ and L. salivarius Ls-33 feeding of SCID mice increases the in vivo effect of Tregs, resulting in a gene expression pattern in the rectum resembling that of the naïve SCID mouse. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  5. In vitro induced regulatory T cells are unique from endogenous regulatory T cells and effective at suppressing late stages of ongoing autoimmunity.

    Directory of Open Access Journals (Sweden)

    Thanh-Long M Nguyen

    Full Text Available Strategies to boost the numbers and functions of regulatory T cells (Tregs are currently being tested as means to treat autoimmunity. While Tregs have been shown to be effective in this role, strategies to manipulate Tregs to effectively suppress later stages of ongoing diseases need to be established. In this study, we evaluated the ability of TGF-β-induced Tregs (iTregs specific for the major self-antigen in autoimmune gastritis to suppress established autoimmune gastritis in mice. When transferred into mice during later stages of disease, iTregs demethylated the Foxp3 promoter, maintained Foxp3 expression, and suppressed effector T cell proliferation. More importantly, these iTregs were effective at stopping disease progression. Untreated mice had high numbers of endogenous Tregs (enTregs but these were unable to stop disease progression. In contrast, iTregs, were found in relatively low numbers in treated mice, yet were effective at stopping disease progression, suggesting qualitative differences in suppressor functions. We identified several inhibitory receptors (LAG-3, PD-1, GARP, and TNFR2, cytokines (TGF-β1 and IL12p35, and transcription factors (IRF4 and Tbet expressed at higher levels by iTregs compared to enTregs isolated form mice with ongoing disease, which likely accounts for superior suppressor ability in this disease model. These data support efforts to use iTregs in therapies to treat establish autoimmunity, and show that iTregs are more effective than enTregs at suppressing inflammation in this disease model.

  6. Genetic differential susceptibility to the effects of parenting.

    Science.gov (United States)

    Belsky, Jay; van IJzendoorn, Marinus H

    2017-06-01

    Intervention efforts aimed at remediating or preventing problems in children typically prove only moderately effective due to substantial heterogeneity in their efficacy. It thus becomes important to account for such variation in intervention efficacy. Here we summarize illustrative evidence that, due to their genetic make-up, some children benefit more from interventions targeting parenting than do others. Whereas some work documents the role of single, 'candidate' genes, other work reveals the utility of compositing multiple genes and genetic pathways. Collectively, this research extends prior observational work indicating that children most negatively affected by adverse experiences also benefit the most from supportive ones, while underscoring the need for research illuminating underlying neurobiological mechanisms that instantiate differential susceptibility to environmental influences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Perceptual differentiation and category effects in normal object recognition

    DEFF Research Database (Denmark)

    Gerlach, Christian; Law, I; Gade, A

    1999-01-01

    on artefacts in the difficult object decision tasks. Natural objects also recruited larger parts of the right inferior temporal and anterior fusiform gyri compared with artefacts as task difficulty increased. Differences in the amount of activation in these regions may reflect the greater perceptual......The purpose of the present PET study was (i) to investigate the neural correlates of object recognition, i.e. the matching of visual forms to memory, and (ii) to test the hypothesis that this process is more difficult for natural objects than for artefacts. This was done by using object decision...... tasks where subjects decided whether pictures represented real objects or non-objects. The object decision tasks differed in their difficulty (the degree of perceptual differentiation needed to perform them) and in the category of the real objects used (natural objects versus artefacts). A clear effect...

  8. Differential Effects of Brain Disorders on Structural and Functional Connectivity

    Science.gov (United States)

    Vega-Pons, Sandro; Olivetti, Emanuele; Avesani, Paolo; Dodero, Luca; Gozzi, Alessandro; Bifone, Angelo

    2017-01-01

    Different measures of brain connectivity can be defined based on neuroimaging read-outs, including structural and functional connectivity. Neurological and psychiatric conditions are often associated with abnormal connectivity, but comparing the effects of the disease on different types of connectivity remains a challenge. In this paper, we address the problem of quantifying the relative effects of brain disease on structural and functional connectivity at a group level. Within the framework of a graph representation of connectivity, we introduce a kernel two-sample test as an effective method to assess the difference between the patients and control group. Moreover, we propose a common representation space for structural and functional connectivity networks, and a novel test statistics to quantitatively assess differential effects of the disease on different types of connectivity. We apply this approach to a dataset from BTBR mice, a murine model of Agenesis of the Corpus Callosum (ACC), a congenital disorder characterized by the absence of the main bundle of fibers connecting the two hemispheres. We used normo-callosal mice (B6) as a comparator. The application of the proposed methods to this data-set shows that the two types of connectivity can be successfully used to discriminate between BTBR and B6, meaning that both types of connectivity are affected by ACC. However, our novel test statistics shows that structural connectivity is significantly more affected than functional connectivity, consistent with the idea that functional connectivity has a robust topology that can tolerate substantial alterations in its structural connectivity substrate. PMID:28119556

  9. Differential effects of glucocorticoids on energy homeostasis in Syrian hamsters.

    Science.gov (United States)

    Solomon, Matia B; Sakai, Randall R; Woods, Stephen C; Foster, Michelle T

    2011-08-01

    Syrian hamsters, like many humans, increase food intake and body adiposity in response to stress. We hypothesized that glucocorticoids (cortisol and corticosterone) mediate these stress-induced effects on energy homeostasis. Because Syrian hamsters are dual secretors of cortisol and corticosterone, differential effects of each glucocorticoid on energy homeostasis were investigated. First, adrenal intact hamsters were injected with varying physiological concentrations of cortisol, corticosterone, or vehicle to emulate our previously published defeat regimens (i.e., 1 injection/day for 5 days). Neither food intake nor body weight was altered following glucocorticoid injections. Therefore, we investigated the effect of sustained glucocorticoid exposure on energy homeostasis. This was accomplished by implanting hamsters with supraphysiological steady-state pellets of cortisol, corticosterone, or cholesterol as a control. Cortisol, but not corticosterone, significantly decreased food intake, body mass, and lean and fat tissue compared with controls. Despite decreases in body mass and adiposity, cortisol significantly increased circulating free fatty acids, triglyceride, cholesterol, and hepatic triglyceride concentrations. Although corticosterone did not induce alterations in any of the aforementioned metabolic end points, Syrian hamsters were responsive to the effects of corticosterone since glucocorticoids both induced thymic involution and decreased adrenal mass. These findings indicate that cortisol is the more potent glucocorticoid in energy homeostasis in Syrian hamsters. However, the data suggest that cortisol alone does not mediate stress-induced increases in food intake or body mass in this species.

  10. Interferon Regulatory Factor-1 Exerts Inhibitory Effect on Neointimal Formation after Vascular Injury

    Institute of Scientific and Technical Information of China (English)

    Zhen Li; Zhong-gao Wang; Ce Bian; Xiao-dong Chen; Jian-wen Li; Xiu Chen; Bing Han; Gao-feng Hou; Jian Chu; Qi Cui

    2009-01-01

    To investigate the effect of interferon regulatory factors (IRFs) on neointimal formation after vascular injury in the mouse, and its possible mechanism.Methods Vascular injury was induced by polyethylene cuff placement around the left femoral artery of IRF-1-deficient mice and C57BL/6J mice. The mRNA expressions of IRF-1, IRF-2, angiotensin Ⅱ type 2 (AT) receptor, interleukin-1β converting enzyme (ICE), inducible nitric oxide synthase (iNOS) were detected by RT-PCR and immunohistochemical staining.Results Neointimal formation after vascular injury was significantly greater in IRF-1-deficient mice than that in C57BL/6J mice (P<0.05). In contrast, TUNEL-positive nuclei to total nuclei in the neointima and media in vascular smooth muscle cell (VSMC) in the injured artery significantly attenuated in IRF-1-deficient mice compared to C57BL/6J mice (P<0.05). The expressions of AT2 receptor as well as pro-apoptotic genes such as ICE and iNOS in C57BL/6J mice were up-regulated in response to vascular injury, but this upregulation was attenuated in IRF-1-deficient mice.Conclusions Our results suggest that IRF-1 induces VSMC apoptosis and inhibits neointimal formation after vascular injury at least partly due to the upregulation of AT2 receptor, ICE and iNOS expressions. These results indicate that IRF-1 exerts an inhibitory effect on neointimal formation through the induction of apoptosis inVSMCs.

  11. Effects of pseudophosphorylation mutants on the structural dynamics of smooth muscle myosin regulatory light chain

    Science.gov (United States)

    Espinoza-Fonseca, L. Michel; Colson, Brett A.; Thomas, David D.

    2014-01-01

    We have performed 50 independent molecular dynamics (MD) simulations to determine the effect of pseudophosphorylation mutants on the structural dynamics of smooth muscle myosin (SMM) regulatory light chain (RLC). We previously showed that the N-terminal phosphorylation domain of RLC simultaneously populates two structural states in equilibrium, closed and open, and that phosphorylation at S19 induces a modest shift toward the open state, which is sufficient to activate smooth muscle. However, it remains unknown why pseudophosphorylation mutants poorly mimic phosphorylation-induced activation of SMM. We performed MD simulations of unphosphorylated, phosphorylated, and three pseudophosphorylatedRLC mutants: S19E, T18D/S19D and T18E/S19E. We found that the S19E mutation does not shift the equilibrium toward the open state, indicating that simple charge replacement at position S19 does not mimic the activating effect of phosphorylation, providing a structural explanation for previously published functional data. In contrast, mutants T18D/S19D and T18E/S19E shift the equilibrium toward the open structure and partially activate in vitro motility, further supporting the model that an increase in the mol fraction of the open state is coupled to SMM motility. Structural analyses of the doubly-charged pseudophosphorylation mutants suggest that alterations in an interdomain salt bridge between residues R4 and D100 results in impaired signal transmission from RLC to the catalytic domain of SMM, which explains the low ATPase activity of these mutants. Our results demonstrate that phosphorylation produces a unique structural balance in the RLC. These observations have important implications for our understanding of the structural aspects of activation and force potentiation in smooth and striated muscle. PMID:25091814

  12. Combined effect of regulatory polymorphisms on transcription of UGT1A1 as a cause of Gilbert syndrome

    Directory of Open Access Journals (Sweden)

    Sato Hiroshi

    2010-06-01

    Full Text Available Abstract Background Gilbert syndrome is caused by defects in bilirubin UDP-glucuronosyltransferase (UGT1A1. The most common variation believed to be involved is A(TA7TAA. Although several polymorphisms have been found to link with A(TA7TAA, the combined effect of regulatory polymorphisms in the development of Gilbert syndrome remains unclear. Methods In an analysis of 15 patients and 60 normal subjects, we detected 14 polymorphisms and nine haplotypes in the regulatory region. We classified the 4-kbp regulatory region of the patients into: the TATA box including A(TA7TAA; a phenobarbital responsive enhancer module including c.-3275T>G; and a region including other ten linked polymorphisms. The effect on transcription of these polymorphisms was studied. Results All haplotypes with A(TA7TAA had c.-3275T>G and additional polymorphisms. In an in-vitro expression study of the 4-kbp regulatory region, A(TA7TAA alone did not significantly reduce transcription. In contrast, c.-3275T>G reduced transcription to 69% of that of wild type, and the linked polymorphisms reduced transcription to 88% of wild type. Transcription of the typical regulatory region of the patients was 56% of wild type. Co-expression of constitutive androstane receptor (CAR increased the transcription of wild type by a factor of 4.3. Each polymorphism by itself did not reduce transcription to the level of the patients, however, even in the presence of CAR. Conclusions These results imply that co-operation of A(TA7TAA, c.-3275T>G and the linked polymorphisms is necessary in causing Gilbert syndrome.

  13. Differentiation mechanism and function of the cereal aleurone cells and hormone effects on them.

    Science.gov (United States)

    Zheng, Yankun; Wang, Zhong

    2014-11-01

    The cereal aleurone cells differentiate from the endosperm epidermis with the exception of endosperm transfer cells. Aleurone cells contain proteins, lipids, and minerals, and are important for digesting the endosperm storage products to nurse the embryo under effects of several hormones during the seed germination. The differentiation of aleurone cells is related to location effect and special gene expression. Moreover, the differentiation of aleurone cells is probably affected by the cues from maternal tissues. In the paper, differentiation mechanism and function of aleurone cells and hormone effects on them are reviewed. Some speculations about the differentiation mechanism of aleurone cells are given here.

  14. Parametric Studies for Scenario Earthquakes: Site Effects and Differential Motion

    Science.gov (United States)

    Panza, G. F.; Panza, G. F.; Romanelli, F.

    2001-12-01

    In presence of strong lateral heterogeneities, the generation of local surface waves and local resonance can give rise to a complicated pattern in the spatial groundshaking scenario. For any object of the built environment with dimensions greater than the characteristic length of the ground motion, different parts of its foundations can experience severe non-synchronous seismic input. In order to perform an accurate estimate of the site effects, and of differential motion, in realistic geometries, it is necessary to make a parametric study that takes into account the complex combination of the source and propagation parameters. The computation of a wide set of time histories and spectral information, corresponding to possible seismotectonic scenarios for different source and structural models, allows us the construction of damage scenarios that are out of reach of stochastic models. Synthetic signals, to be used as seismic input in a subsequent engineering analysis, e.g. for the design of earthquake-resistant structures or for the estimation of differential motion, can be produced at a very low cost/benefit ratio. We illustrate the work done in the framework of a large international cooperation following the guidelines of the UNESCO IUGS IGCP Project 414 "Realistic Modeling of Seismic Input for Megacities and Large Urban Areas" and show the very recent numerical experiments carried out within the EC project "Advanced methods for assessing the seismic vulnerability of existing motorway bridges" (VAB) to assess the importance of non-synchronous seismic excitation of long structures. >http://www.ictp.trieste.it/www_users/sand/projects.html

  15. Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin

    NARCIS (Netherlands)

    Bovenschen, H.J.; Kerkhof, P.C. van de; Erp, P.E. van; Woestenenk, R.M.; Joosten, I.; Koenen, H.J.P.M.

    2011-01-01

    Psoriasis is an autoimmune-related chronic inflammatory skin disease that is strongly associated with IL-23 and T helper-17 (Th17) effector cytokines. In addition, CD4+CD25(high) regulatory T-cell (Treg) function appeared to be impaired in psoriasis. CD4+CD25(high)Foxp3+ Tregs are typically consider

  16. Identification and monitoring of effector and regulatory T cells during experimental arthritis based on differential expression of CD25 and CD134

    NARCIS (Netherlands)

    E.N.M. Nolte-'t Hoen (Esther); E.P.J. Boot (Elmieke); J.P.A. Wagenaar-Hilbers (Josée); J.H.M. van Bilsen (Jolanda); G.J.A. Arkesteijn (Ger); G. Storm (Gert); L.A. Everse (Linda); W. van Eden (Willem); M.H.M. Wauben (Marca)

    2008-01-01

    textabstractMajor problems in the analysis of CD4+effector cell and regulatory T cell (Treg) populations in an activated immune system are caused by the facts that both cell types can express CD25 and that the discriminatory marker forkhead box p3 can only be analyzed in nonviable (permeabilized) ce

  17. Identification and monitoring of effector and regulatory T cells during experimental arthritis based on differential expression of CD25 and CD134

    NARCIS (Netherlands)

    Nolte-'t Hoen, E.N.M.; Boot, E.P.J.; Wagenaar-Hilbers, J.P.A.; Bilsen, J.H.M. van; Arkesteijn, G.J.A.; Storm, G.; Everse, L.A.; Eden, W. van; Wauben, M.H.M.

    2008-01-01

    Major problems in the analysis of CD4+ effector cell and regulatory T cell (Treg) populations in an activated immune system are caused by the facts that both cell types can express CD25 and that the discriminatory marker forkhead box p3 can only be analyzed in nonviable (permeabilized) cells. Here,

  18. Differential impact of interferon regulatory factor 7 in the initiation of the type I interferon response in the LCMV infected CNS versus the periphery

    DEFF Research Database (Denmark)

    Christensen, Jeanette Erbo; Fenger, Christina; Issazadeh-Navikas, Shohreh

    2012-01-01

    Interferon (IFN) regulatory factors (IRFs) are a family of transcription factors involved in regulating type I IFN genes and other genes participating in the early antiviral host response. To better understand the mechanisms involved in virus-induced central nervous system (CNS) inflammation, we...

  19. Ruthenium endemic isotope effects in chondrites and differentiated meteorites

    Science.gov (United States)

    Chen, J. H.; Papanastassiou, D. A.; Wasserburg, G. J.

    2010-07-01

    We report on the abundances of Ru isotopes in (1) iron meteorites, (2) stony-iron meteorites (pallasites), (3) ordinary and carbonaceous chondrites, and (4) in refractory inclusions from the carbonaceous meteorite Allende. We have developed improved Multiple-Collector, Negative-ion Thermal Ionization Mass Spectrometric (MC-NTIMS) techniques for Ru, with high ionization efficiency of 4% and with chemical separation techniques for Ru, which reduce mass interferences to the ppm level, so that no mass interference corrections needed to be applied. Our data were normalized to 99Ru/ 101Ru to correct for mass-dependent fractionation. We find no Ru isotopic effects in the ordinary chondrites and group IAB iron meteorites we have measured. There are significant effects (deficits) in the pure s-process nuclide 100Ru, in the Allende whole-rock and in refractory inclusions of up to 1.7 parts in 10,000 (ɛu). There are also endemic deficits in 100Ru in iron meteorites and in pallasites of up to 1.1 ɛu. The Ru data suggest a wide spread and large scale heterogeneity in p-, s-, and r-process components resulting in a deficit in s-process nuclides or enhancements in both p- and r-process nuclides, in refractory siderophiles condensing in the early solar nebula. In contrast, the data on bulk Murchison suggest an excess in 100Ru and in 104Ru, which are distinct from the rest of the measured patterns. Our results establish the presence of significant isotopic heterogeneity for Ru in the early solar nebula. The observation of endemic Ru effects in planetary differentiates, such as iron meteorites and pallasites, must reflect the siderophile nature of Ru and the preservation in condensing FeNi metal of refractory metal condensate grains formed in the early solar nebula. Once incorporated in the metal phase, the refractory siderophiles remained in the metal phase through the melting and differentiation of planetesimals to form FeNi cores and silicate mantles and crusts.

  20. Effects of estrogen on CD4+CD25+ regulatory T cell in peripheral blood during pregnancy

    Institute of Scientific and Technical Information of China (English)

    Yuan-Huan Xiong; Zhen Yuan; Li He

    2013-01-01

    Objective:To investigate the effects of estrogen (E2) level on regulatory T cells (Treg) in peripheral blood during pregnancy. Methods:A total of 30 healthy non-pregnant women were selected as control group, 90 pregnant women of early, middle and late pregnancy and 30 postpartum women at 1 month after parturition were selected as experimental groups including early pregnancy group, middle pregnancy group and late pregnancy group;the proportions of CD4+CD25+Treg and CD4+CD25+CD127-Treg among CD4+T cells were detected by flow cytometry;the serum estrogen content in peripheral blood was detected by electrochemical immune luminescence method. Results: E2 level was coincident with the change of Tregs number during pregnancy. The estrogen content in peripheral blood increased gradually from early pregnancy to late pregnancy, then decreased significantly after parturition, and the level at 1 month after parturition down to the level in non-pregnancy group (P>0.05);the level of E2 in pregnancy groups were significantly higher than those in non-pregnancy group (P0.05);the proportions in middle and late pregnancy groups were significantly higher than those in early pregnancy group (P0.05). There was correlation between Tregs number with estrogen level during pregnancy. The proportion of CD4+CD25+ Treg and CD4+CD25+CD127- Treg were positively correlated with estrogen level. Conclusions:High proportion of CD4+CD25+Treg and CD4+CD25+CD127-Treg is closely related to the high level of E2 during pregnancy. It suggested that high level of estrogen may induce an increase of CD4+CD25+Treg in peripheral blood, and then influence the immune function of pregnant women. The results of this experiment might play an important role of estrogen in immune-modulation during pregnancy.

  1. Effect of radiologic contrast media on cell volume regulatory mechanisms in human red blood cells.

    Science.gov (United States)

    Galtung, Hilde Kanli; Sørlundsengen, Vibeke; Sakariassen, Kjell S; Benestad, Haakon B

    2002-08-01

    The authors performed this study to evaluate cell volume regulation in human red blood cells (RBCs) after incubation in solutions of three contrast media: iohexol (830 mOsm), ioxaglate (520 mOsm), and iodixanol (300 mOsm). Whole blood sampled from six healthy subjects was exposed to Ringer solutions containing 25% or 5% vol/vol iohexol (final osmolality, 440 or 340 mOsm, respectively), ioxaglate (final osmolality, 395 or 335 mOsm, respectively), iodixanol (final osmolality, 330 or 315 mOsm, respectively), or NaCl (control solutions with the same osmolality as that of the contrast media). In some experiments, control RBCs were subjected to a hyposmotic solution (100 mOsm). RBC volumes were obtained with a Coulter counter. The RBCs showed normal regulatory cell shrinkage after hyposmotically induced swelling. All 25% vol/vol contrast material solutions and their control solutions induced RBC shrinkage (range, 6% +/- 1 [standard error] to 22% +/- 3). The same was true for cells exposed to 5% vol/vol contrast material (range, 4% +/- 1 to 7% +/- 1). The shrinkage phase was followed by cell swelling (10% +/- 2 to 20% +/- 2 for 25% contrast material and their control solutions and 8% +/- 1 to 15% +/- 2 for 5% contrast material and their control solutions). No contrast material-exposed RBCs increased their volumes to the level reached with their control solutions. RBCs exposed to hyperosmotic iohexol, ioxaglate, or iodixanol solutions shrank and then swelled. The degree of shrinkage and subsequent swelling could not be explained simply with the osmolality of the test solutions. Physicochemical properties of the contrast media must be involved, putatively affecting electrolyte fluxes over the RBC membrane. Possible targets of these effects are the K+/Cl- symporter, K+ channels, and the Na+/K+/Cl- symporter.

  2. Effect of 1,25-Dihydroxyvitamin D3 on Regulatory T Cells in Ovariectomized Mice

    Institute of Scientific and Technical Information of China (English)

    LIU Jun Chen; ZHOU Chen Hui; ZHANG Xue; CHEN Yan; XU Bi Lian; CUI Liao; XU Dao Hua

    2014-01-01

    ObjectiveTo investigate thecorrelation betweenregulatory T(Treg) cellsand postmenopausal osteoporosis andthe antiosteoporotic effect of 1,25-dihydroxyvitamin D3[1,25(OH)2D3] in relation to Treg cells. MethodsFifty femaleBALB/c mice were randomly divided into five groups: the basal control (BAS), Sham,ovariectomy (OVX),OVX+diethylstilbestrol (OVX+DES), andOVX+1,25(OH)2D3.Tibias were harvested andprocessed with decalcification for quantitative bone histomorphometry.Femurs were stained by immunohistochemistry to detectFoxp3 protein expression.Spleens wereused to detect Treg andFoxp3 gene expressionby flow cytometry andquantitative RT-PCR, respectively. ResultsIn comparison withthe Sham group,a significant decrease was found inthe OVX group in such indices as trabecular bone volume/total tissue area (BV/TV), trabecularnumber (Tb.N) and trabecular thickness (Tb.Th).1,25(OH)2D3andDESpartlyprevented the decrease in BV/TV, Tb.N, Tb.Th inOVX mice.Treg cell number, Foxp3 mRNA expression in spleen andFoxp3 protein expression in femur significantly decreasedinthe OVX-treated group compared withthose in thesham group.1,25(OH)2D3 andDES significantlyincreased Treg cell number andFoxp3 expression.Treg cellsand Foxp3 gene expression were related to bonehistomorphometricparameters. ConclusionThedecrease inTreg cell numbersis relevant to the postmenopausal osteoporosis. The antiosteoporosis of1,25(OH)2D3 is related to regulatory T cells.

  3. Differential effects of planktonic and biofilm MRSA on human fibroblasts.

    Science.gov (United States)

    Kirker, Kelly R; James, Garth A; Fleckman, Philip; Olerud, John E; Stewart, Philip S

    2012-01-01

    Bacteria colonizing chronic wounds often exist as biofilms, yet their role in chronic wound pathogenesis remains unclear. Staphylococcus aureus biofilms induce apoptosis in dermal keratinocytes, and given that chronic wound biofilms also colonize dermal tissue, it is important to investigate the effects of bacterial biofilms on dermal fibroblasts. The effects of a predominant wound pathogen, methicillin-resistant S. aureus, on normal, human, dermal fibroblasts were examined in vitro. Cell-culture medium was conditioned with equivalent numbers of either planktonic or biofilm methicillin-resistant S. aureus and then fed to fibroblast cultures. Fibroblast response was evaluated using scratch, viability, and apoptosis assays. The results suggested that fibroblasts experience the same fate when exposed to the soluble products of either planktonic or biofilm methicillin-resistant S. aureus, namely limited migration followed by death. Enzyme-linked immunosorbent assays demonstrated that fibroblast production of cytokines, growth factors, and proteases were differentially affected by planktonic and biofilm-conditioned medium. Planktonic-conditioned medium induced more interleukin-6, interleukin-8, vascular endothelial growth factor, transforming growth factor-β1, heparin-bound epidermal growth factor, matrix metalloproteinase-1, and metalloproteinase-3 production in fibroblasts than the biofilm-conditioned medium. Biofilm-conditioned medium induced more tumor necrosis factor-α production in fibroblasts compared with planktonic-conditioned medium, and suppressed metalloproteinase-3 production compared with controls.

  4. The good and bad of being fair: effects of procedural and interpersonal justice behaviors on regulatory resources.

    Science.gov (United States)

    Johnson, Russell E; Lanaj, Klodiana; Barnes, Christopher M

    2014-07-01

    The justice literature has paid considerable attention to the beneficial effects of fair behaviors for recipients of such behaviors. It is possible, however, that exhibiting fair behaviors may come at a cost for actors. In this article, we integrate ego depletion theory with organizational justice research in order to examine the consequences of justice behaviors for actors. We used an experience-sampling method in a sample of managerial employees to examine the relations of performing procedural justice and interpersonal justice behaviors with subsequent changes in actors' regulatory resources. Our results indicate that procedural justice behaviors are draining, whereas interpersonal justice behaviors are replenishing for actors. Depletion, in turn, adversely affected the performance of citizenship behavior, and depletion mediated relations of justice behavior with citizenship. Furthermore, 2 traits that impact self-regulatory skills--extraversion and neuroticism--moderated the replenishing effects of engaging in interpersonal justice behaviors. We conclude by discussing implications and avenues for future research.

  5. Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function.

    Science.gov (United States)

    Detaille, Dominique; Guigas, Bruno; Leverve, Xavier; Wiernsperger, Nicolas; Devos, Pierre

    2002-04-01

    From recent findings about the indirect effect of metformin (MET) targeted on the respiratory chain complex I, we reconsidered this question and tried to determine the causality of any alteration at this enzymatic level using Xenopus laevis oocytes. Addition of MET (50 microM) reduced by 40% the rotenone-sensitive activity of complex I only in incubating intact oocytes but not in mitochondria isolated by differential centrifugation. The drug prior injected inside these cells had also no measurable effect. In spite of this and the weak binding of MET to the mitochondrial fraction, there was a fairly good correlation between the marked inhibitory action of MET on complex I and its progressive appearance within the oocyte cytoplasm. The intriguing observation that MET as a liposomal form was again able to exert its role when added directly to isolated mitochondria is in accordance with a membrane-mediated uptake and vesicular routing of MET. Furthermore, a temperature-dependent effect was clearly shown. At 4 degrees, oocytes failed to take up efficiently MET and accordingly its subsequent action on respiration was therefore lost. Likewise, MET transport was hindered and inhibition of complex I totally disappeared when a structural analog, asymmetrical dimethylarginine (ADMA), was placed together with MET either at an identical concentration or in excess. These data strongly support the view that MET may recognise some specific membranous sites, likely belonging to effector systems, before penetrating the cell in a bound state via an obscure endocytotic event which still has to be identified.

  6. 76 FR 63686 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-10-13

    .../time execution algorithm for System orders and states, in relevant part, that the System will execute... auction and electronic market structures that differentiate certain order priority and execution...

  7. Conservation of apoptosis as an immune regulatory mechanism: effects of cortisol and cortisone on carp lymphocytes.

    NARCIS (Netherlands)

    Weyts, F.A.A.; Verburg-van Kemenade, B.M.L.; Flik, G.; Lambert, J.G.D.; Wendelaar Bonga, S.E.

    1997-01-01

    This is the first study to show that apoptosis as an immune regulatory mechanism is conserved in fish, demonstrating its importance in maintaining immunological homeostasis. The data further show that this mechanism is subject to control by glucocorticosteroids. Carp plasma cortisol concentrations

  8. Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P;

    1995-01-01

    injury. In the current study, we sought to determine whether endogenous IL-10 is playing a regulatory role in the lung inflammatory response. On the basis of lung mRNA and ELISA measurements, IL-10 induction was found during development of inflammation in the IgG immune complex model of lung injury...

  9. 75 FR 57092 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

    Science.gov (United States)

    2010-09-17

    ... Congress's conclusion that the evolution of self-regulatory organization governance and competitive market..., NYSEArca, and BATS. Any ATS or BD can combine with any other ATS, BD, or multiple ATSs or BDs to produce... production and sale of proprietary data products, as BATS and Arca did before registering as exchanges...

  10. Conservation of apoptosis as an immune regulatory mechanism: effects of cortisol and cortisone on carp lymphocytes.

    NARCIS (Netherlands)

    Weyts, F.A.A.; Verburg-van Kemenade, B.M.L.; Flik, G.; Lambert, J.G.D.; Wendelaar Bonga, S.E.

    1997-01-01

    This is the first study to show that apoptosis as an immune regulatory mechanism is conserved in fish, demonstrating its importance in maintaining immunological homeostasis. The data further show that this mechanism is subject to control by glucocorticosteroids. Carp plasma cortisol concentrations i

  11. 76 FR 1208 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-01-07

    ... Release Nos. 62663 (August 9, 2010), 75 FR 49543 (August 13, 2010) (SR-NASDAQ-2010-077) (order approving... (August 10, 2010), 75 FR 50020 (August 16, 2010) (SR-EDGA-2010-06) (order approving fees for both 1G and... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate...

  12. 78 FR 23965 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-04-23

    ... Securities Exchange Act Release No. 68752 (January 29, 2013), 78 FR 7826 (February 4, 2013) (SR-BATS-2013-003... Release No. 69121 (March 12, 2013), 78 FR 16750 (March 18, 2013) (SR-BATS-2013-014) (notice of filing and... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate...

  13. 77 FR 50199 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2012-08-20

    ... Securities Exchange Act Release No. 67093 (June 1, 2012), 77 FR 33798 (June 7, 2012) (SR-BATS-2012-018). \\10... Exchange at $10.11. See Securities Exchange Act Release No. 64475 (May 12, 2011), 76 FR 28830, 28832 (May... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate...

  14. Effect of Salmonella infection on cecal tonsil regulatory T cell properties in chickens

    Science.gov (United States)

    Two experiments were conducted to study Regulatory T cell (Treg) properties post-Salmonella infection in broiler birds. Four-day-old broiler chicks were orally infected with 5x106 CFU/ml Salmonella enteritidis or sterile PBS (control). Samples were collected at 4, 7, 10, and 14 d post-infection. ...

  15. Addressing transatlantic regulatory barriers: can the US and the EU create an effective equivalency instrument?

    NARCIS (Netherlands)

    Mathis, J.; Fahey, E.; Curtin, D.

    2014-01-01

    This chapter proposes and assesses a legal regulatory recognition instrument to address non-tariff barriers to trade for goods and services in a US and EU transatlantic regional trade agreement. The procedure would make a factual determination that the underlying levels of protection sought to be gu

  16. 78 FR 26669 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-05-07

    ... physical port and choose the method of connectivity based on their specific needs. B. Self-Regulatory... connectivity, including port fee access, would serve to impair an exchange's ability to compete for order flow...-06,\\4\\ the Exchange adopted an annual fee per physical port utilized by Members and non-Members...

  17. 78 FR 78447 - Self-Regulatory Organizations; Topaz Exchange, LLC; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2013-12-26

    ..., the Exchange proposes to revise the relevant language in its Schedule of Fees to state that Priority... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Topaz Exchange, LLC; Notice of Filing and Immediate...

  18. 76 FR 74092 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-11-30

    ... filing, the Exchange proposes to amend the language of two routing options contained in Rule 11.9(b)(3... From the Federal Register Online via the Government Publishing Office ] SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate...

  19. 76 FR 74090 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2011-11-30

    ... filing, the Exchange proposes to amend the language of two routing options contained in Rule 11.9(b)(3... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate...

  20. Professional development to differentiate kindergarten Tier 1 instruction: Can already effective teachers improve student outcomes by differentiating Tier 1 instruction?

    Science.gov (United States)

    Otaiba, Stephanie Al; Folsom, Jessica S.; Wanzek, Jeannie; Greulich, Luana; Wasche, Jessica; Schatschneider, Christopher; Connor, Carol

    2015-01-01

    Two primary purposes guided this quasi-experimental within-teacher study: (1) to examine changes from baseline through two years of professional development (Individualizing Student Instruction) in kindergarten teachers’ differentiation of Tier 1 literacy instruction; (2) to examine changes in reading and vocabulary of three cohorts of the teachers’ students (n = 416). Teachers’ instruction was observed and students were assessed on standardized measures of vocabulary and word reading. Results suggested that teachers significantly increased their differentiation and students showed significantly greater word reading outcomes relative to baseline. No change was observed for vocabulary. Results have implications for supporting teacher effectiveness through technology-supported professional development. PMID:27346927

  1. Differentiation state determines neural effects on microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Muffley, Lara A., E-mail: muffley@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Pan, Shin-Chen, E-mail: pansc@mail.ncku.edu.tw [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Smith, Andria N., E-mail: gnaunderwater@gmail.com [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Ga, Maricar, E-mail: marga16@uw.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Hocking, Anne M., E-mail: ahocking@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Gibran, Nicole S., E-mail: nicoleg@u.washington.edu [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)

    2012-10-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. Black-Right-Pointing-Pointer Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate

  2. Anti-Differentiation Effect of Oncogenic Met Receptor in Terminally-Differentiated Myotubes

    Directory of Open Access Journals (Sweden)

    Valentina Sala

    2015-02-01

    Full Text Available Activation of the hepatocyte growth factor/Met receptor is involved in muscle regeneration, through promotion of proliferation and inhibition of differentiation in myogenic stem cells (MSCs. We previously described that the specific expression of an oncogenic version of the Met receptor (Tpr–Met in terminally-differentiated skeletal muscle causes muscle wasting in vivo. Here, we induced Tpr–Met in differentiated myotube cultures derived from the transgenic mouse. These cultures showed a reduced protein level of myosin heavy chain (MyHC, increased phosphorylation of Erk1,2 MAPK, the formation of giant sacs of myonuclei and the collapse of elongated myotubes. Treatment of the cultures with an inhibitor of the MAPK kinase pathway or with an inhibitor of the proteasome increased the expression levels of MyHC. In addition, the inhibition of the MAPK kinase pathway prevented the formation of myosacs and myotube collapse. Finally, we showed that induction of Tpr–Met in primary myotubes was unable to produce endoreplication in their nuclei. In conclusion, our data indicate that multinucleated, fused myotubes may be forced to disassemble their contractile apparatus by the Tpr–Met oncogenic factor, but they resist the stimulus toward the reactivation of the cell cycle.

  3. Differential effects of a gelatinase inhibitor on adipocyte differentiation and adipose tissue development.

    Science.gov (United States)

    Van Hul, Matthias; Bauters, Dries; Lijnen, Roger H

    2013-10-01

    (1) A potential role for the gelatinases in adipocyte differentiation in vitro and adipose tissue development in vivo was investigated using the gelatinase inhibitor tolylsam ((R)-3-methyl-2-[4-(3-p-tolyl-[1,2,4]oxadiazol-5-yl)-benzenesulphonylamino]-butyric acid). (2) Differentiation of murine 3T3-F442A preadipocytes (12 days after reaching confluence) into mature adipocytes in vitro was promoted in the presence of tolylsam (10-100 μmol/L). (3) De novo development of fat tissue in nude mice injected with preadipocytes and kept on a high-fat diet was significantly impaired following treatment with tolylsam (100 mg/kg per day for 4 weeks). (4) Adipose tissue development in matrix metalloproteinase (MMP)-2 deficient mice, kept on a high-fat diet, was significantly impaired following administration of tolylsam (100 mg/kg per day for 15 weeks). This was associated with markedly enhanced metabolic rate. (5) Treatment of MMP-2-deficient mice with tolylsam (100 mg/kg per day, 15 weeks) was associated with the preservation of collagen and a reduction in blood vessel size in adipose tissues in vivo. (6) Furthermore, plasma levels of triglycerides and free fatty acids were reduced by tolylsam treatment of MMP-2-deficient mice (100 mg/kg per day, 15 weeks), whereas nutrient adsorption in the intestine was not affected. (7) The results of the present study indicate that tolylsam promotes preadipocyte differentiation in vitro, but impairs adipose tissue development in vivo.

  4. Effect of Low Power Laser Irradiation on the Ability of Cell Growth and Myogenic Differentiation of Myoblasts Cultured In Vitro

    Directory of Open Access Journals (Sweden)

    Cui-Ping Zhang

    2014-01-01

    Full Text Available As a therapeutic modality, low power laser irradiation (LPLI has been used clinically in the treatment of skeletal muscle injuries and other myopathic conditions, but the cellular and molecular mechanisms attributed to this therapy were still unclear. Myoblasts are a type of myogenic stem cells quiescence in mature skeletal muscle fibers and are considered as the source cells during the regenerating process. The purpose of this paper was to investigate the effects of LPLI on the proliferation and myogenic differentiation of the cultured myoblasts and to find out the major candidates responsible for LPLI-induced muscle regeneration in vivo. In this study, primary rat myoblasts were exposed to helium-neon (He-Ne laser. Cell proliferation, differentiation, and the cellular responses to LPLI were monitored by using morphological observation and molecular biological methods. It was found that LPLI at a certain fluence could increase the cell growth potential for myoblasts and further induce more cells entering into S phase of the mitotic cycle as indicated by high levels of bromodeoxyuridine (BrdU incorporation, while at the same time inhibiting their in vitro differentiation and decreasing the expression of myogenic regulatory genes to a certain extent. Taken together, these results provide experimental evidence for the clinical applications of LPLI in regenerating skeletal muscle.

  5. Regulatory effect of paraprobiotic Lactobacillus gasseri CP2305 on gut environment and function

    Directory of Open Access Journals (Sweden)

    Tomonori Sugawara

    2016-03-01

    Full Text Available Background: Lactobacillus gasseri CP2305 (CP2305 is a strain of Lactobacillus isolated from a stool sample from a healthy adult that showed beneficial effects on health as a paraprobiotic. In a previous study, we demonstrated that CP2305-fermented heat-treated milk modified gut functions more than artificially acidified sour milk. Thus, the regulatory activity of the former beverage was attributed to the inactivated CP2305 cells. Objective: The aim of this study was to elucidate the contribution of non-viable paraprobiotic CP2305 cells to regulating human gut functions. We thus conducted a randomized, placebo-controlled, double-blinded parallel group trial. Design: The trial included 118 healthy participants with relatively low or high stool frequencies. The test beverage was prepared by adding 1×1010 washed, heat-treated, and dried CP2305 cells directly to the placebo beverage. The participants ingested a bottle of the assigned beverage daily for 3 weeks and answered daily questionnaires about defecation and quality of life. Fecal samples were collected and the fecal characteristics, microbial metabolite contents of the feces and composition of fecal microbiota were evaluated. Results: The number of evacuations and the scores for fecal odors were significantly improved in the group that consumed the CP2305-containing beverage compared with those of the group that consumed the placebo (p=0.035 and p=0.040, respectively. Regarding the fecal contents of microbial metabolites, the level of fecal p-cresol was significantly decreased in the CP2305 group relative to that of the placebo group (p=0.013. The Bifidobacterium content of the intestinal microbiota was significantly increased in the CP2305 group relative to that of the placebo group (p<0.008, whereas the content of Clostridium cluster IV was significantly decreased (p<0.003. The parasympathetic nerve activity of the autonomic nervous system became dominant and the total power of autonomic

  6. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Seong-Il [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Ko, Hee-Chul [Jeju Sasa Industry Development Agency, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Shin, Hye-Sun; Kim, Hyo-Min; Hong, Youn-Suk [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Lee, Nam-Ho [Department of Chemistry, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Kim, Se-Jae, E-mail: sjkim@jejunu.ac.kr [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Jeju Sasa Industry Development Agency, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of)

    2011-06-17

    Highlights: {yields} Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. {yields} Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. {yields} Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. {yields} Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from the edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), CCAAT/enhancer-binding protein {alpha} (C/EBP{alpha}), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPAR{gamma}, C/EBP{alpha}, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.

  7. Differential Effect of Plant Lipids on Membrane Organization

    Science.gov (United States)

    Grosjean, Kevin; Mongrand, Sébastien; Beney, Laurent; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia

    2015-01-01

    The high diversity of the plant lipid mixture raises the question of their respective involvement in the definition of membrane organization. This is particularly the case for plant plasma membrane, which is enriched in specific lipids, such as free and conjugated forms of phytosterols and typical phytosphingolipids, such as glycosylinositolphosphoceramides. This question was here addressed extensively by characterizing the order level of membrane from vesicles prepared using various plant lipid mixtures and labeled with an environment-sensitive probe. Fluorescence spectroscopy experiments showed that among major phytosterols, campesterol exhibits a stronger ability than β-sitosterol and stigmasterol to order model membranes. Multispectral confocal microscopy, allowing spatial analysis of membrane organization, demonstrated accordingly the strong ability of campesterol to promote ordered domain formation and to organize their spatial distribution at the membrane surface. Conjugated sterol forms, alone and in synergy with free sterols, exhibit a striking ability to order membrane. Plant sphingolipids, particularly glycosylinositolphosphoceramides, enhanced the sterol-induced ordering effect, emphasizing the formation and increasing the size of sterol-dependent ordered domains. Altogether, our results support a differential involvement of free and conjugated phytosterols in the formation of ordered domains and suggest that the diversity of plant lipids, allowing various local combinations of lipid species, could be a major contributor to membrane organization in particular through the formation of sphingolipid-sterol interacting domains. PMID:25575593

  8. Sexual selection and the differential effect of polyandry.

    Science.gov (United States)

    Collet, Julie; Richardson, David S; Worley, Kirsty; Pizzari, Tommaso

    2012-05-29

    In principle, widespread polyandry (female promiscuity) creates potential for sexual selection in males both before and after copulation. However, the way polyandry affects pre- and postcopulatory episodes of sexual selection remains little understood. Resolving this fundamental question has been difficult because it requires extensive information on mating behavior as well as paternity for the whole male population. Here we show that in replicate seminatural groups of red junglefowl, Gallus gallus, polyandry eroded variance in male mating success, which simultaneously weakened the overall intensity of sexual selection but increased the relative strength of postcopulatory episodes. We further illustrate the differential effect of polyandry on pre- and postcopulatory sexual selection by considering the case of male social status, a key determinant of male reproductive success in this species. In low-polyandry groups, however, status was strongly sexually selected before copulation because dominants mated with more females. In high-polyandry groups, sexual selection for status was weakened and largely restricted after copulation because dominants defended paternity by mating repeatedly with the same female. These results reveal polyandry as a potent and dynamic modulator of sexual selection episodes.

  9. Differential stimulation of VEGF-C production by adhesion/growth-regulatory galectins and plant lectins in human breast cancer cells.

    Science.gov (United States)

    Timoshenko, Alexander V; Kaltner, Herbert; André, Sabine; Gabius, Hans-Joachim; Lala, Peeyush K

    2010-12-01

    The present study tested the hypothesis that the production of vascular endothelial growth factor C (VEGF-C), a key lymphangiogenic factor, by human breast cancer cells can be stimulated by human lectins, using plant lectins as controls. The effects of human galectins and five plant lectins reacting with distinct determinants of N- and O-glycans on the accumulation of VEGF-C in serum-free cell culture media of human breast cancer cells endowed with high (MDA-MB-231) and low (MCF7, T-47D, and SK-BR-3) VEGF-C-producing abilities were examined. All tested lectins stimulated VEGF-C production by MDA-MB-231 cells, albeit with different potency. Concanavalin A, but not galectins, was also able to stimulate VEGF-C production by low VEGF-C-producing cell lines MCF7 and T-47D. Both VEGF-C mRNA and protein were strongly up-regulated in SK-BR-3 cells by concanavalin A and wheat germ agglutinin, but not jacalin. The differential response of breast cancer cell lines separated by the endogenous level of VEGF-C production suggests that galectins may contribute to tumor-associated lymphangiogenesis in a cell-specific manner.

  10. Second-generation histone deacetylase 6 inhibitors enhance the immunosuppressive effects of Foxp3+ T-regulatory cells.

    Science.gov (United States)

    Kalin, Jay H; Butler, Kyle V; Akimova, Tatiana; Hancock, Wayne W; Kozikowski, Alan P

    2012-01-26

    Second-generation Tubastatin A analogues were synthesized and evaluated for their ability to inhibit selectively histone deacetylase 6 (HDAC6). Substitutions to the carboline cap group were well-tolerated with substitution at the 2-position of both β- and γ-carbolines being optimal for HDAC6 activity and selectivity. Some compounds in this series were determined to have subnanomolar activity at HDAC6 with more than 7000 fold selectivity for HDAC6 versus HDAC1. Selected compounds were then evaluated for their ability to augment the immunosuppressive effect of Foxp3+ regulatory T cells. All compounds tested were found to enhance the ability of regulatory T cells to inhibit the mitotic division of effector T cells both in vitro and in vivo, suggesting that further investigation into the use of these compounds for the treatment of autoimmune disorders is warranted.

  11. EGF Uptake and Degradation Assay to Determine the Effect of HTLV Regulatory Proteins on the ESCRT-Dependent MVB Pathway.

    Science.gov (United States)

    Murphy, Colin; Sheehy, Noreen

    2017-01-01

    The endosomal sorting complex required for transport (ESCRT) pathway plays key roles in multivesicular bodies (MVBs) formation and lysosomal degradation of membrane receptors, viral budding, and midbody abscission during cytokinesis. The epidermal growth factor receptor (EGFR) is regarded as a prototypical cargo of the MVB/ESCRT pathway and following stimulation by epidermal growth factor (EGF) EGFR/EGF complexes are internalized, sorted into MVBs, and degraded by lysosomes or recycled back to the cell membrane. Here, we describe an assay to analyze the effect of human T-cell leukemia (HTLV) regulatory proteins on the functionality of ESCRT-dependent MVB/lysosomal trafficking of EGFR/EGF complexes. This is performed by direct visualization and quantification of the rate of EGF-Alexa595/EGFR internalization and degradation in HeLa cells expressing HTLV regulatory proteins by immunofluorescence and western blot.

  12. The Discovery,Origin,Differentiation and Activation of Regulatory B Cells%调节性 B 细胞的发现、起源和分化及激活

    Institute of Scientific and Technical Information of China (English)

    张怡舜(综述); 陈思娇; 宋今丹(审校)

    2015-01-01

    B细胞的主要功能是分泌抗体和呈递抗原,并以此起始和活化免疫系统发挥正性调节作用。新近研究表明,一类具有负性免疫调节功能的 B 细胞亚群———调节性 B 细胞(Gregs)可通过细胞间直接接触和分泌白细胞介素10等方式下调免疫应答。 Bregs 在许多疾病中发挥着重要的调节作用。 Bregs 的发现、起源、分化将为全面、深入了解自身免疫病免疫耐受的机制,及寻找更合理的自身免疫病治疗方法提供理论依据和新的研究方向。%The main function of Bcells is secreting antibodies,antigen presentation and activating the immune system,so Bcells play a positive regulatory role in immune responses.Recent studies have shown that there is a B cell subset with the function of negative regulation-regulatory Bcells(Bregs). They can down regulate the immune reaction through direct contact with other immune cells or secretion of IL-10 etc.At the same time,Bregs play an important regulatory role in many diseases.The discovery, origin,differentiation and activation of regulatory Bcells will provide the theory basis and the new research direction for the comprehensive,in-depth understanding of immune tolerance mechanisms of autoimmune disease,and for the more reasonable treatment of autoimmune diseases.

  13. Intergroup differentiation in computer-mediated communication : Effects of depersonalization

    NARCIS (Netherlands)

    Postmes, T; Spears, R; Lea, M

    2002-01-01

    Two studies examined intergroup discussions via computer-mediated communication systems. It was hypothesized that depersonalization, in comparison with individuated interaction, would increase the tendency for intergroup differentiation in attitudes and stereotypes, In Study 1, 24 groups communicate

  14. The Effects of TLR Activation on T-Cell Development and Differentiation

    Directory of Open Access Journals (Sweden)

    Bo Jin

    2012-01-01

    Full Text Available Invading pathogens have unique molecular signatures that are recognized by Toll-like receptors (TLRs resulting in either activation of antigen-presenting cells (APCs and/or costimulation of T cells inducing both innate and adaptive immunity. TLRs are also involved in T-cell development and can reprogram Treg cells to become helper cells. T cells consist of various subsets, that is, Th1, Th2, Th17, T follicular helper (Tfh, cytotoxic T lymphocytes (CTLs, regulatory T cells (Treg and these originate from thymic progenitor thymocytes. T-cell receptor (TCR activation in distinct T-cell subsets with different TLRs results in differing outcomes, for example, activation of TLR4 expressed in T cells promotes suppressive function of regulatory T cells (Treg, while activation of TLR6 expressed in T cells abrogates Treg function. The current state of knowledge of regarding TLR-mediated T-cell development and differentiation is reviewed.

  15. The effect of scale-free topology on the robustness and evolvability of genetic regulatory networks

    OpenAIRE

    Greenbury, Sam F.; Johnston, Iain G.; Matthew A Smith; Doye, Jonathan P. K.; Louis, Ard A.

    2010-01-01

    Abstract We investigate how scale-free (SF) and Erdos-Renyi (ER) topologies affect the interplay between evolvability and robustness of model gene regulatory networks with Boolean threshold dynamics. In agreement with Oikonomou and Cluzel (2006) we find that networks with SFin topologies, that is SF topology for incoming nodes and ER topology for outgoing nodes, are significantly more evolvable towards specific oscillatory targets than networks with ER topology for both incoming an...

  16. The evolutionary capacitor HSP90 buffers the regulatory effects of mammalian endogenous retroviruses.

    Science.gov (United States)

    Hummel, Barbara; Hansen, Erik C; Yoveva, Aneliya; Aprile-Garcia, Fernando; Hussong, Rebecca; Sawarkar, Ritwick

    2017-03-01

    Understanding how genotypes are linked to phenotypes is important in biomedical and evolutionary studies. The chaperone heat-shock protein 90 (HSP90) buffers genetic variation by stabilizing proteins with variant sequences, thereby uncoupling phenotypes from genotypes. Here we report an unexpected role of HSP90 in buffering cis-regulatory variation affecting gene expression. By using the tripartite-motif-containing 28 (TRIM28; also known as KAP1)-mediated epigenetic pathway, HSP90 represses the regulatory influence of endogenous retroviruses (ERVs) on neighboring genes that are critical for mouse development. Our data based on natural variations in the mouse genome show that genes respond to HSP90 inhibition in a manner dependent on their genomic location with regard to strain-specific ERV-insertion sites. The evolutionary-capacitor function of HSP90 may thus have facilitated the exaptation of ERVs as key modifiers of gene expression and morphological diversification. Our findings add a new regulatory layer through which HSP90 uncouples phenotypic outcomes from individual genotypes.

  17. Effect of roscovitine on intracellular calcium dynamics: differential enantioselective responses.

    Science.gov (United States)

    Tamma, Grazia; Ranieri, Marianna; Di Mise, Annarita; Spirlì, Alessia; Russo, Annamaria; Svelto, Maria; Valenti, Giovanna

    2013-12-02

    Cyclin-dependent kinases (CDKs) inhibitors have emerged as interesting therapeutic candidates. Of these, (S)-roscovitine has been proposed as potential neuroprotective molecule for stroke while (R)-roscovitine is currently entering phase II clinical trials against cancers and phase I clinical tests against glomerulonephritis. In addition, (R)-roscovitine has been suggested as potential antihypertensive and anti-inflammatory drug. Dysfunction of intracellular calcium balance is a common denominator of these diseases, and the two roscovitine enantiomers (S and R) are known to modulate calcium voltage channel activity differentially. Here, we provide a detailed description of short- and long-term responses of roscovitine on intracellular calcium handling in renal epithelial cells. Short-term exposure to (S)-roscovitine induced a cytosolic calcium peak, which was abolished after stores depletion with cyclopiazonic acid (CPA). Instead, (R)-roscovitine caused a calcium peak followed by a small calcium plateau. Cytosolic calcium response was prevented after stores depletion. Bafilomycin, a selective vacuolar H(+)-ATPase inhibitor, abolished the small calcium plateau. Long-term exposure to (R)-roscovitine significantly reduced the basal calcium level compared to control and (S)-roscovitine treated cells. However, both enantiomers increased calcium accumulation in the endoplasmic reticulum (ER). Consistently, cells treated with (R)-roscovitine showed a significant increase in SERCA activity, whereas (S)-roscovitine incubation resulted in a reduced PMCA expression. We also found a tonic decreased ability to release calcium from the ER, likely via IP3 signaling, under treatment with (S)- or (R)-roscovitine. Together our data revealed that (S)-roscovitine and (R)-roscovitine exert distinct enantiospecific effects on intracellular calcium signaling in renal epithelial cells. This distinct pharmacological profile can be relevant for roscovitine clinical use.

  18. Trust, regulatory processes and NICE decision-making: Appraising cost-effectiveness models through appraising people and systems.

    Science.gov (United States)

    Brown, Patrick; Hashem, Ferhana; Calnan, Michael

    2016-02-01

    This article presents an ethnographic study of regulatory decision-making regarding the cost-effectiveness of expensive medicines at the National Institute for Health and Care Excellence (NICE) in England. We explored trust as one important mechanism by which problems of complexity and uncertainty were resolved. Existing studies note the salience of trust for regulatory decisions, by which the appraisal of people becomes a proxy for appraising technologies themselves. Although such (dis)trust in manufacturers was one important influence, we describe a more intricate web of (dis)trust relations also involving various expert advisors, fellow committee members and committee Chairs. Within these complex chains of relations, we found examples of both more blind-acquiescent and more critical-Investigative forms of trust as well as, at times, pronounced distrust. Difficulties in overcoming uncertainty through other means obliged trust in some contexts, although not in others. (Dis)trust was constructed through inferences involving abstract systems alongside actors' oral and written presentations-of-self. Systemic features and 'forced options' to trust indicate potential insidious processes of regulatory capture.

  19. Who Are You More Likely to Help? The Effects of Expected Outcomes and Regulatory Focus on Prosocial Performance.

    Science.gov (United States)

    Xiao, Fengqiu; Zheng, Zhiwei; Zhang, Heyi; Xin, Ziqiang; Chen, Yinghe; Li, Yiwei

    2016-01-01

    Prosocial behavior refers to a broad category of actions that benefit other people or the society. Compared with other factors that affect prosocial performance, prosocial outcomes, consisting of prosocial gains and prosocial non-losses have received less attention up to now. In the current research, we explored the influences of different types of expected outcomes and regulatory focus on prosocial performance. Studies 1a and 1b examined the differences in prosocial performance elicited by prosocial gain (e.g., enhancing others' access to clean water) and prosocial non-loss outcomes (e.g., protecting others from suffering dirty water). We found that the expected prosocial non-loss outcomes induced greater prosocial performance compared with the expected prosocial gain outcomes. Studies 2a and 2b examined the effects of dispositional and situational regulatory focus on prosocial loss aversion. We found that differences in prosocial performance between two expected prosocial outcomes were reduced when promotion focus was primed; whereas a primed prevention focus did not significantly increase this difference. Additionally, participants displayed a greater prosocial loss aversion in the prevention focus condition than in the promotion focus condition. The reason for the non-significant interaction between regulatory focus and expected prosocial outcome was discussed.

  20. The effect of self-regulatory and metacognitive strategy instruction on impoverished students' assessment achievement in physics

    Science.gov (United States)

    Fouche, Jaunine

    The purpose of this nonequivalent control group design study was to evaluate the effectiveness of metacognitive and self-regulatory strategy use on the assessment achievement of 215 9th-grade, residential physics students from low socioeconomic status (low-SES) backgrounds. Students from low-SES backgrounds often lack the self-regulatory habits and metacognitive strategies to improve academic performance. In an effort to increase these scores and to increase student self-regulation and metacognition with regard to achievement in physics, this study investigated the use of metacognitive and self-regulatory strategies specifically as they apply to students' use of their own assessment data. Traditionally, student performance data is used by adults to inform instructional and curricular decisions. However, students are rarely given or asked to evaluate their own performance data. Moreover, students are not shown how to use this data to plan for or inform their own learning. It was found that students in the overall and algebra-ready treatment groups performed significantly better than their control group peers. These results are favorable for inclusion of strategies involving self-regulation and metacognition in secondary physics classrooms. Although these results may be applicable across residential, impoverished populations, further research is needed with non-residential populations.

  1. Regulatory reform for natural gas pipelines: The effect on pipeline and distribution company share prices

    Science.gov (United States)

    Jurman, Elisabeth Antonie

    1997-08-01

    The natural gas shortages in the 1970s focused considerable attention on the federal government's role in altering energy consumption. For the natural gas industry these shortages eventually led to the passage of the Natural Gas Policy Act (NGPA) in 1978 as part of the National Energy Plan. A series of events in the decade of the 1980s has brought about the restructuring of interstate natural gas pipelines which have been transformed by regulators and the courts from monopolies into competitive entities. This transformation also changed their relationship with their downstream customers, the LDCs, who no longer had to deal with pipelines as the only merchants of gas. Regulatory reform made it possible for LDCs to buy directly from producers using the pipelines only for delivery of their purchases. This study tests for the existence of monopoly rents by analyzing the daily returns of natural gas pipeline and utility industry stock price data from 1982 to 1990, a period of regulatory reform for the natural gas industry. The study's main objective is to investigate the degree of empirical support for claims that regulatory reforms increase profits in the affected industry, as the normative theory of regulation expects, or decrease profits, as advocates of the positive theory of regulation believe. I also test Norton's theory of risk which predicts that systematic risk will increase for firms undergoing deregulation. Based on a sample of twelve natural gas pipelines, and 25 utilities an event study concept was employed to measure the impact of regulatory event announcements on daily natural gas pipeline or utility industry stock price data using a market model regression equation. The results of this study provide some evidence that regulatory reforms did not increase the profits of pipeline firms, confirming the expectations of those who claim that excess profits result from regulation and will disappear, once that protection is removed and the firms are operating in

  2. Modulatory effects of quercetin on proliferation and differentiation of the human colorectal cell line Caco-2

    NARCIS (Netherlands)

    Dihal, A.A.; Woutersen, R.A.; Ommen, B.v.; Rietjens, I.M.C.M.; Stierum, R.H.

    2006-01-01

    The effect of the dietary flavonoid quercetin was investigated on proliferation and differentiation of the human colon cancer cell line Caco-2. Confluent Caco-2 monolayers exposed to quercetin showed a biphasic effect on cell proliferation and a decrease in cell differentiation (0.001

  3. Modulatory effects of quercetin on proliferation and differentiation of the human colorectal cell line Caco-2

    NARCIS (Netherlands)

    Dihal, A.A.; Woutersen, R.A.; Ommen, B.v.; Rietjens, I.M.C.M.; Stierum, R.H.

    2006-01-01

    The effect of the dietary flavonoid quercetin was investigated on proliferation and differentiation of the human colon cancer cell line Caco-2. Confluent Caco-2 monolayers exposed to quercetin showed a biphasic effect on cell proliferation and a decrease in cell differentiation (0.001

  4. Effect of Multiple Testing Adjustment in Differential Item Functioning Detection

    Science.gov (United States)

    Kim, Jihye; Oshima, T. C.

    2013-01-01

    In a typical differential item functioning (DIF) analysis, a significance test is conducted for each item. As a test consists of multiple items, such multiple testing may increase the possibility of making a Type I error at least once. The goal of this study was to investigate how to control a Type I error rate and power using adjustment…

  5. Assimilation and contrast effects: the role of self-construal and regulatory focus as moderators in collectivistic cultures of honour.

    Science.gov (United States)

    Puente-Díaz, Rogelio

    2014-06-01

    Human judgments are context dependent. When answering a question about one's overall satisfaction with life, a previous question about one's romantic life might pose redundancy problems influencing one's judgment of life satisfaction, something known as item order effects. However, in order to detect such redundancy, one needs to pay attention to the context of the conversation. Any variable that influences the amount of attention given the context of the conversation can determine whether the presumed redundancy is detected or not. In three studies, two experiments and one correlational study, we tested the influence of induced self-construal (study 1) and self-regulatory focus (study 2) and self-regulatory focus measured as an individual difference variable (study 3) as moderators of context effects among college students from Mexico. In study 1, participants induced to have an independent mindset were less likely to detect the redundancy posed by two questions, resulting, as predicted, in a contrast effect. In study 3, participants with lower levels of prevention focus were less likely to detect the redundancy posed by the same two questions as study 1, resulting, as predicted, in an assimilation effect. The implications of the results were discussed within the framework of the inclusion/exclusion model.

  6. Cerebral pathology and neuropsychological effects. Differential effects of cranial radiation as a function of age

    Energy Technology Data Exchange (ETDEWEB)

    Dowell, R.E. Jr.; Copeland, D.R.

    Cranial radiation therapy (CRT) has been associated with an increased incidence of neuropsychological impairments and pathologic changes in the CNS among children. However, findings regarding a causal relationship between CRT and neurobehavioral impairments and the differential impact of CRT as a function of treatment age have been equivocal. Inconsistent findings may be attributed to the current research focus on description of impairments to the neglect of a larger theoretical framework and the failure of investigators to integrate findings from the various disciplines involved in assessing CRT effects. Two theories regarding the etiology of CRT effects on neuropsychological functions have been proposed. The myelination hypothesis suggests that CRT effects are attributable to direct effects on myelin synthesis. Findings indicating that the child is in a state of particular vulnerability to teratogens due to the rapid growth phase of myelin during the first 48 months of life provide the basis for this hypothesis. The myelination hypothesis predicts a differential effect for CRT as a function of age/maturation. The vascular hypothesis proposes that CRT effects are due to pathological changes in vascular tissues. Results indicating prominent white matter changes among some CRT recipients provide the basis for this hypothesis. The vascular hypothesis predicts no age effect or an inverse age effect; it places more emphasis on the relationship between indices of cerebral blood flow and neuropsychological test performance. Two basic mechanisms underlying the effects of CRT are outlined to provide a theoretical framework on which future research may be based. 29 references.

  7. Politically Induced Regulatory Risk and Independent Regulatory Agencies

    OpenAIRE

    Strausz, Roland

    2015-01-01

    Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

  8. Hsa-miR-590-5p Interaction with SMAD3 Transcript Supports Its Regulatory Effect on The TGFβ Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Meisam Jafarzadeh

    2016-04-01

    Full Text Available Objective: SMAD proteins are the core players of the transforming growth factor-beta (TGFβ signaling pathway, a pathway which is involved in cell proliferation, differentiation and migration. On the other hand, hsa-miRNA-590-5p (miR-590-5p is known to have a negative regulatory effect on TGFβ signaling pathway receptors. Since, RNAhybrid analysis suggested SMAD3 as a bona fide target gene for miR-590, we intended to investigate the effect of miR-590-5p on SMAD3 transcription. Materials and Methods: In this experimental study, miR-590-5p was overexpressed in different cell lines and its increased expression was detected through quantitative reverse transcription-polymerase chain reaction (RT-qPCR. Western blot analysis was then used to investigate the effect of miR-590-5p overexpression on SMAD3 protein level. Next, the direct interaction of miR-590-5p with the 3´-UTR sequence of SMAD3 transcript was investigated using the dual luciferase assay. Finally, flow cytometery was used to investigate the effect of miR-590-5p overexpression on cell cycle progression in HeLa and SW480 cell lines. Results: miR-590-5p was overexpressed in the SW480 cell line and its overexpression resulted in significant reduction of the SMAD3 protein level. Consistently, direct interaction of miR-590-5p with 3´-UTR sequence of SMAD3 was detected. Finally, miR-590-5p overexpression did not show a significant effect on cell cycle progression of Hela and SW480 cell lines. Conclusion: Consistent with previous reports about the negative regulatory effect of miR-590 on TGFβ receptors, our data suggest that miR-590-5p also attenuates the TGFβ signaling pathway through down-regulation of SMAD3.

  9. Differential effects of Smad3 targeting in a murine model of chronic kidney disease

    DEFF Research Database (Denmark)

    Kellenberger, Terese; Krag, Søren; Danielsen, Carl Christian;

    2013-01-01

    -β1-induced glomerular basement membrane thickening is not shown. The amount and distribution profile of MMP-2 may suggest a role of the enzyme herein. We conclude that Smad3 targeting is not exclusively beneficial as Smad3 has diverse transcriptional regulatory effects in different cell types...

  10. Growth factor TGF-β induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop.

    Science.gov (United States)

    Liao, Yalin; Zhang, Man; Lönnerdal, Bo

    2013-01-01

    TGF-β is a potent pleiotropic factor that promotes small intestinal cell differentiation. The role of microRNAs in the TGF-β induction of intestinal epithelial phenotype is largely unknown. We hypothesized that microRNAs are functionally involved in TGF-β-induced intestinal cell growth. In this study, TGF-β caused a morphological change of IEC-6 cells and stimulated expression of the epithelial cell markers alkaline phosphatase, villin, and aminopeptidase N. By global microRNA profiling during TGF-β-induced intestinal crypt cell (IEC-6) differentiation, we identified 19 differentially expressed microRNAs. We showed by real-time Q-PCR that miR-146b expression increased rapidly after TGF-β treatment; sequence analysis and in vitro assays revealed that miR-146b targets SIAH2, an E3 ubiquitin ligase, with decreased protein expression upon IEC-6 cell differentiation. Transfection of miR-146b inhibitor before TGF-β treatment blocked the down-regulation of SIAH2 in response to TGF-β. Moreover, SIAH2 over-expression during TGF-β treatment caused a significant decrease in Smad7 protein expression in IEC-6 cells. Furthermore, activation of the ERK1/2 pathway is active in the up-regulation of miR-146b by TGF-β. These findings suggest a novel mechanism whereby TGF-β signaling during IEC-6 cell differentiation may be modulated in part by microRNAs, and we propose a key role for miR-146b in the homeostasis of growth factor TGF-β signaling through a negative feedback regulation involving down-regulation of SIAH2 repressed Smad7 activities.

  11. The air quality and regional climate effects of widespread solar power generation under a changing regulatory environment

    Science.gov (United States)

    Millstein, D.; Zhai, P.; Menon, S.

    2011-12-01

    Over the past decade significant reductions of NOx and SOx emissions from coal burning power plants in the U.S. have been achieved due to regulatory action and substitution of new generation towards natural gas and wind power. Low natural gas prices, ever decreasing solar generation costs, and proposed regulatory changes, such as to the Cross State Air Pollution Rule, promise further long-run coal power plant emission reductions. Reduced power plant emissions have the potential to affect ozone and particulate air quality and influence regional climate through aerosol cloud interactions and visibility effects. Here we investigate, on a national scale, the effects on future (~2030) air quality and regional climate of power plant emission regulations in contrast to and combination with policies designed to aggressively promote solar electricity generation. A sophisticated, economic and engineering based, hourly power generation dispatch model is developed to explore the integration of significant solar generation resources (>10% on an energy basis) at various regions across the county, providing detailed estimates of substitution of solar generation for fossil fuel generation resources. Future air pollutant emissions from all sectors of the economy are scaled based on the U.S. Environmental Protection Agency's National Emission Inventory to account for activity changes based on population and economic projections derived from county level U.S. Census data and the Energy Information Administration's Annual Energy Outlook. Further adjustments are made for technological and regulatory changes applicable within various sectors, for example, emission intensity adjustments to on-road diesel trucking due to exhaust treatment and improved engine design. The future year 2030 is selected for the emissions scenarios to allow for the development of significant solar generation resources. A regional climate and air quality model (Weather Research and Forecasting, WRF model) is

  12. Delay-independent stability of genetic regulatory networks.

    Science.gov (United States)

    Wu, Fang-Xiang

    2011-11-01

    Genetic regulatory networks can be described by nonlinear differential equations with time delays. In this paper, we study both locally and globally delay-independent stability of genetic regulatory networks, taking messenger ribonucleic acid alternative splicing into consideration. Based on nonnegative matrix theory, we first develop necessary and sufficient conditions for locally delay-independent stability of genetic regulatory networks with multiple time delays. Compared to the previous results, these conditions are easy to verify. Then we develop sufficient conditions for global delay-independent stability for genetic regulatory networks. Compared to the previous results, this sufficient condition is less conservative. To illustrate theorems developed in this paper, we analyze delay-independent stability of two genetic regulatory networks: a real-life repressilatory network with three genes and three proteins, and a synthetic gene regulatory network with five genes and seven proteins. The simulation results show that the theorems developed in this paper can effectively determine the delay-independent stability of genetic regulatory networks.

  13. Differential Effects of Methyl-4-Phenylpyridinium Ion, Rotenone, and Paraquat on Differentiated SH-SY5Y Cells

    Directory of Open Access Journals (Sweden)

    João Barbosa Martins

    2013-01-01

    Full Text Available Paraquat (PQ, a cationic nonselective bipyridyl herbicide, has been used as neurotoxicant to modulate Parkinson’s disease in laboratory settings. Other compounds like rotenone (ROT, a pesticide, and 1-methyl-4-phenylpyridinium ion (MPP+ have been widely used as neurotoxicants. We compared the toxicity of these three neurotoxicants using differentiated dopaminergic SH-SY5Y human cells, aiming to elucidate their differential effects. PQ-induced neurotoxicity was shown to be concentration and time dependent, being mitochondrial dysfunction followed by neuronal death. On the other hand, cells exposure to MPP+ induced mitochondrial dysfunction, but not cellular lyses. Meanwhile, ROT promoted both mitochondrial dysfunction and neuronal death, revealing a biphasic pattern. To further elucidate PQ neurotoxic mechanism, several protective agents were used. SH-SY5Y cells pretreatment with tiron (TIR and 2-hydroxybenzoic acid sodium salt (NaSAL, both antioxidants, and Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, a nitric oxide synthase inhibitor, partially protected against PQ-induced cell injury. Additionally, 1-(2-[bis(4-fluorophenylmethoxy]ethyl-4-(3-phenyl-propylpiperazine (GBR 12909, a dopamine transporter inhibitor, and cycloheximide (CHX, a protein synthesis inhibitor, also partially protected against PQ-induced cell injury. In conclusion, we demonstrated that PQ, MPP+, and ROT exerted differential toxic effects on dopaminergic cells. PQ neurotoxicity occurred through exacerbated oxidative stress, with involvement of uptake through the dopamine transporter and protein synthesis.

  14. Expression of human transferrin can be regulated effectively by rabbit transferrin regulatory elements in transgenic mice.

    Science.gov (United States)

    Yan, Jingbin; Gong, Xiuli; Pan, Shubiao; Guo, Xinbing; Ren, Zhaorui; Zeng, Yitao

    2014-06-01

    Human transferrin (hTF) belongs to the iron-binding glycoprotein family. It plays an important role in iron transport throughout the body. Transgenic mice are a good model to study how to produce functional hTF on a large-scale. We have improved the expression of hTF and investigated its regulatory mechanism in transgenic mice. Three expression constructs were prepared in which hTF expression was controlled by different regulatory cassettes of rabbit transferrin (rTF). hTF was secreted into serum of transgenic mice when its expression was controlled by the rTF promoter and enhancer, whereas the rTF enhancer in tandem with the rTF promoter repressed hTF secretion into milk. A significant inverse relationship between methylation of the rTF promoter and hTF expression was observed in liver, heart, mammary gland, and muscle of transgenic mice. The highest concentration of hTF was 700 μg/ml in milk.

  15. Effects of delay and noise in a negative feedback regulatory motif

    Science.gov (United States)

    Palassini, Matteo; Dies, Marta

    2009-03-01

    The small copy number of the molecules involved in gene regulation can induce nontrivial stochastic phenomena such as noise-induced oscillations. An often neglected aspect of regulation dynamics are the delays involved in transcription and translation. Delays introduce analytical and computational complications because the dynamics is non-Markovian. We study the interplay of noise and delays in a negative feedback model of the p53 core regulatory network. Recent experiments have found pronounced oscillations in the concentrations of proteins p53 and Mdm2 in individual cells subjected to DNA damage. Similar oscillations occur in the Hes-1 and NK-kB systems, and in circadian rhythms. Several mechanisms have been proposed to explain this oscillatory behaviour, such as deterministic limit cycles, with and without delay, or noise-induced excursions in excitable models. We consider a generic delayed Master Equation incorporating the activation of Mdm2 by p53 and the Mdm2-promoted degradation of p53. In the deterministic limit and for large delays, the model shows a Hopf bifurcation. Via exact stochastic simulations, we find strong noise-induced oscillations well outside the limit-cycle region. We propose that this may be a generic mechanism for oscillations in gene regulatory systems.

  16. Transcriptional network structure has little effect on the rate of regulatory evolution in yeast.

    Science.gov (United States)

    Kopp, Artyom; McIntyre, Lauren M

    2012-08-01

    Studies in evolutionary developmental biology suggest that the structure of genetic pathways may bias the fixation of natural variation toward particular nodes in these pathways. In an attempt to test this trend genome wide, we integrated several previously published data sets to examine whether the position of genes in the whole-genome transcriptional network of Saccharomyces cerevisiae is associated with the amount of cis-regulatory expression divergence between S. cerevisiae and its sibling species Saccharomyces paradoxus. We find little evidence for an association between connectivity and divergence in the global network that combines data from multiple conditions. However, relationships between connectivity and divergence are apparent in some of the smaller subnetworks. Despite a slight tendency for genes with more transcriptional interactions to show greater divergence, these differences explain no more than a small fraction of variation in evolutionary rates. These results suggest that the systems biology focus on large interactomes may miss some critical details of local interactions. More detailed experimental analysis will be needed to define the genetic pathways that control specific phenotypic traits and quantify the rate of regulatory changes at different points in these pathways.

  17. The Effects of Rising Interest Rates on Electric Utility Stock Prices: Regulatory Considerations and Approaches

    Energy Technology Data Exchange (ETDEWEB)

    Kihm, Steve [Seventhwave, Madison, WI (United States); Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cappers, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2017-07-26

    This technical brief identifies conditions under which utility regulators should consider implementing policy approaches that seek to mitigate negative outcomes due to an increase in interest rates. Interest rates are a key factor in determining a utility’s cost of equity and investors find value when returns exceed the cost of equity. Through historical observations of periods of rising and falling interest rates and application of a pro forma financial tool, we identify the key drivers of utility stock valuations and estimate the degree to which those valuations might be affected by increasing interest rates.3 We also analyze the efficacy of responses by utility regulators to mitigate potential negative financial impacts. We find that regulators have several possible approaches to mitigate a decline in value in an environment of increasing interest rates, though regulators must weigh the tradeoffs of improving investor value with potential increases in customer costs. Furthermore, the range of approaches reflects today’s many different electric utility regulatory models and regulatory responses to a decline in investor value will fit within state-specific models.

  18. Infant, maternal, and familial predictors and correlates of regulatory problems in early infancy: The differential role of infant temperament and maternal anxiety and depression.

    Science.gov (United States)

    Martini, Julia; Petzoldt, Johanna; Knappe, Susanne; Garthus-Niegel, Susan; Asselmann, Eva; Wittchen, Hans-Ulrich

    2017-09-01

    Excessive infant crying, feeding and sleeping problems are likely to emerge from the complex interplay of various factors. To investigate the role of infant (e.g., temperament), maternal (e.g., anxiety and depressive disorders), and familial (e.g., social support) factors as potential precursors of infant regulatory problems. Prospective-longitudinal study. 286 mother-infant dyads were investigated from early pregnancy until 16 months postpartum via questionnaires and interviews. Regulatory problems at 2, 4 and 16 months postpartum assessed by standardized diagnostic interviews. Fussy infant temperament and maternal anxiety disorders were associated with excessive infant crying (OR=1.16, 95%CI:1.05-1.29, OR=3.28, 95%CI:1.16-9.26) and feeding problems (OR=1.05, 95%CI:1.01-1.11, OR=2.27, 95%CI:1.36-3.80) whereas maternal depressive disorders were associated with infant sleeping problems (OR=2.55, 95%CI:1.06-6.11). Moreover, high maternal age (OR=0.86, 95%CI:0.75-0.98) was associated with a lower risk for excessive crying and being a single mother (OR=0.16, 95%CI:0.03-0.73) and cognitive reappraisal to regulate emotions (OR: 0.59, 95%CI:0.36-0.96) was associated with a lower risk for sleeping problems. Excessive infant crying and feeding problems may be related to interactional deficits of anxious mothers who perceive their infants as "difficult" during soothing or feeding situations. Sleeping problems may be transmitted already during pregnancy by an altered sleep-wake-rhythm of mothers with a history of depression or by a genetic predisposition. Therapeutic interventions should focus on maternal anxiety and depression, behavior management techniques to cope with difficult situations with "fussy" infants and potential protective factors (e.g. favorable maternal emotion regulation) to address crying, feeding and sleeping problems. Copyright © 2017. Published by Elsevier B.V.

  19. COST EFFECTIVE REGULATORY APPROACHES TO ENHANCE DOMESTIC OIL & GAS PRODUCTION AND ENSURE THE PROTECTION OF THE ENVIRONMENT

    Energy Technology Data Exchange (ETDEWEB)

    Ben Grunewald; Paul Jehn; Tom Gillespie; Ben Binder

    2004-12-21

    The Environmental Information Management Suite/Risk Based Data Management System (EIMS/RBDMS) and Cost Effective Regulatory Approach (CERA) programs continue to be successful. All oil and gas state regulatory programs participate in these efforts. Significant accomplishments include: streamline regulatory approaches, enhancing environmental protection, and making oil and gas data available via the Internet. Oil and gas companies worldwide now have access to data on state web sites. This reduces the cost of exploration and enables companies to develop properties in areas that would have been cost prohibited for exploration. Early in project, GWPC and State Oil and Gas agencies developed the EIMS and CERA strategic plan to prioritize long term development and implementation. The planning process identifies electronic commerce and coal bed methane as high priorities. The group has involved strategic partners in industry and government to develop a common data exchange process. Technical assistance to Alaska continues to improve their program management capabilities. New initiatives in Alaska include the development of an electronic permit tracking system. This system allows managers to expedite the permitting process. Nationwide, the RBDMS system is largely completed with 22 states and one Indian Nation now using this nationally accepted data management system. Additional remaining tasks include routine maintenance and the installation of the program upon request for the remaining oil and gas states. The GWPC in working with the BLM and MMS to develop an XML schema to facilitate electronic permitting and reporting (Appendix A, B, and C). This is a significant effort and, in years to come, will increase access to federal lands by reducing regulatory barriers. The new initiatives are coal bed methane and e-commerce. The e-commerce program will provide industry and BLM/MMS access to the millions of data points housed in the RBDMS system. E-commerce will streamline

  20. The PaPsr1 and PaWhi2 genes are members of the regulatory network that connect stationary phase to mycelium differentiation and reproduction in Podospora anserina.

    Science.gov (United States)

    Timpano, Hélène; Chan Ho Tong, Laetitia; Gautier, Valérie; Lalucque, Hervé; Silar, Philippe

    2016-09-01

    In filamentous fungi, entrance into stationary phase is complex as it is accompanied by several differentiation and developmental processes, including the synthesis of pigments, aerial hyphae, anastomoses and sporophores. The regulatory networks that control these processes are still incompletely known. The analysis of the "Impaired in the development of Crippled Growth (IDC)" mutants of the model filamentous ascomycete Podospora anserina has already yielded important information regarding the pathway regulating entrance into stationary phase. Here, the genes affected in two additional IDC mutants are identified as orthologues of the Saccharomyces cerevisiae WHI2 and PSR1 genes, known to regulate stationary phase in this yeast, arguing for a conserved role of these proteins throughout the evolution of ascomycetes.

  1. 75 FR 41912 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

    Science.gov (United States)

    2010-07-19

    ... Securities will trade in accordance with these rule changes and the pricing for odd-lots will be the same as... pricing for Exchange- listed securities and Nasdaq Securities is that, because there will not be an... differentiated pricing for such transactions. The Exchange notes that the initial pricing proposed herein is...

  2. 75 FR 47039 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of a Proposed Rule...

    Science.gov (United States)

    2010-08-04

    ... Change by OneChicago, Amending Rule 419(a), Regulatory Halts July 28, 2010. Pursuant to Section 19(b)(7... thereto, to make it clear that a ``regulatory halt''applies not only to the suspending of all trading...

  3. The effects of labor on differential gene expression in parturient women, placentas, and fetuses at term pregnancy

    Directory of Open Access Journals (Sweden)

    Hsiu-Huei Peng

    2011-11-01

    Full Text Available Labor and its associated pain are thought to have unique impacts on parturient women. The goal of this study was to investigate the effects of labor and associated pain on differential gene expression profiles in the maternal, fetal, and placental compartments. We used microarrays to analyze maternal blood (MB, fetal cord blood (CB, and placental tissue samples in pregnant women after term vaginal deliveries (laboring group and in term pregnant women after scheduled Ceasarean sections (nonlaboring group. The upregulated genes in the MB of the laboring group are involved in cytokine and nuclear factor-kappa B signaling pathways, regulation of the networks of toll-like receptor 4, and suppressor of cytokine signaling 3. Upregulated genes in the CB of the laboring group are involved in responding to stress and stimuli by regulating the network genes of the T-cell receptor beta locus and the FK506 binding protein 8. Differentially expressed genes in the placenta of the laboring group are involved in nitric oxide transport, gas transport, response to hydrostatic pressure, oxygen transport, acute phase responses, and the tumor necrosis factor-mediated signaling pathway, which are important during the transient hypoxemia and hypoperfusion that occur in the placenta during uterine contractions. Interestingly, few of the genes exhibited simultaneous changes in all three compartments, indicating that different pathways and complex interactions may be involved in human labor. In conclusion, human labor and its associated pain elicit unique gene regulatory changes in MB, placenta, and CB.

  4. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  5. Effect of house dust mite immunotherapy on interleukin-10-secreting regulatory T cells in asthmatic children

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; XIANG Li; LIU Yong-ge; WANG Yong-hong; SHEN Kun-ling

    2010-01-01

    Background Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response.Interleukin-10 (IL-10) plays a crucial role in inducing allergen-specific tolerance.However the reports of the changes of IL-10 in house dust mite (HDM)-specific immunotherapy were varied.The aim of this study was to evaluate the function of IL-10-secreting regulatory T cells in asthma children successfully treated with HDM immunotherapy.Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 27 patients following 1.5--2 years of HDM-specific immunotherapy (SIT, SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthmagroup).After 48 hours of in vitro stimulation with HDM extracts, IL-10-secreting regulatory T cells were measured by four colour flow cytometry.Sera were tested for allergen-specific IgG4 and IgE using the Immuno CAP 100 assay.Results PBMCs from children undergoing immunotherapy following HDM extracts stimuli produced significantly more IL-10 compared with the asthma group.The frequency of iTreg cells and aTreg cells increased in SIT group after HDM stimulation, while it was not affected in the asthma group.Among the iTreg cells and aTreg cells, the frequency of CD4+CD25-Foxp3-IL-10+ Treg cells increased the most which was 2 times higher than that in unstimulated cultures in SIT group.The levels of HDM-specific IgG4 of SIT group was significiently higher compared with asthma group, but there was no correlation of the levels of HDM-specific IgG4 and IL-10 secreting Treg cells.Conclusions HDM-specific immunotherapy can successfully upregulate the frequency of IL-10-secreting Treg cells.CD4+CD25-Foxp3-IL-10+ Treg cells may play a key role in inducing the immune tolerance in HDM-specific immunotherapy.

  6. Logical knowledge representation of regulatory relations in biomedical pathways

    DEFF Research Database (Denmark)

    Zambach, Sine; Hansen, Jens Ulrik

    2010-01-01

    Knowledge on regulatory relations, in for example regulatory pathways in biology, is used widely in experiment design by biomedical researchers and in systems biology. The knowledge has typically either been represented through simple graphs or through very expressive differential equation...

  7. Logical knowledge representation of regulatory relations in biomedical pathways

    DEFF Research Database (Denmark)

    Zambach, Sine; Hansen, Jens Ulrik

    2010-01-01

    Knowledge on regulatory relations, in for example regulatory pathways in biology, is used widely in experiment design by biomedical researchers and in systems biology. The knowledge has typically either been represented through simple graphs or through very expressive differential equation...

  8. Differential Effectiveness of Three Color Treatments in Learning Geometric Concepts via Computer-Guided Teaching.

    Science.gov (United States)

    Hativa, Nira; Teper, Avigdor

    1988-01-01

    Discussion of the use of color in microcomputer-based educational software focuses on a study of Israeli ninth graders that examined the differential effects of three color treatments on the learning of geometric concepts by students with differential aptitudes. Hypotheses tested are described and results are analyzed. (28 references) (Author/LRW)

  9. Differential Susceptibility to the Effects of Child Temperament on Maternal Warmth and Responsiveness

    Science.gov (United States)

    Lee, Eunju J.

    2013-01-01

    A child's difficult temperament can elicit negative parenting and inhibit positive parenting behavior. However, mothers appear to be differentially susceptible to child temperament. The author examined the differential susceptibility to the effects of a child's temperament on the mother-child interaction style (i.e., maternal warmth and…

  10. The Effect of Differentiation Approach Developed on Creativity of Gifted Students: Cognitive and Affective Factors

    Science.gov (United States)

    Altintas, Esra; Özdemir, Ahmet S.

    2015-01-01

    The aim of the study is to develop a differentiation approach for the mathematics education of gifted middle school students and to determine the effect of the differentiation approach on creative thinking skills of gifted students based on both cognitive and affective factors. In this context, the answer to the following question was searched:…

  11. Differential Parenting and Children's Behavioral Problems: Curvilinear Associations and Mother-Father Combined Effects

    Science.gov (United States)

    Meunier, Jean Christophe; Bisceglia, Rossana; Jenkins, Jennifer M.

    2012-01-01

    In this study the associations between mothers' and fathers' differential parenting and children's oppositional and emotional problems were examined. A curvilinear relationship between differential parenting and children's outcomes was hypothesized, as well as the combined effect of mothers' and fathers' parenting. Data came from a community…

  12. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells.

    Science.gov (United States)

    Niedbala, Wanda; Wei, Xiao-Qing; Cai, Beilei; Hueber, Axel J; Leung, Bernard P; McInnes, Iain B; Liew, Foo Y

    2007-11-01

    Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12 have been reported to form a heterodimeric hematopoietin in human and mouse. We have constructed a heterodimeric protein covalently linking EBI3 and p35, to form a novel cytokine which we now call IL-35. The Fc fusion protein of IL-35 induced proliferation of murine CD4(+)CD25(+) and CD4(+)CD25(-) T cells when stimulated with immobilized anti-CD3 and anti-CD28 antibodies in vitro. The IL-35-expanded CD4(+)CD25(+) T cell population expressed Foxp3 and produced elevated levels of IL-10, whereas the IL-35-induced CD4(+)CD25(-) T cells produced IFN-gamma but not IL-4. The in vitro expanded CD4(+)CD25(+) T cells retained their suppressive functions against CD4(+)CD25(-) effector cells. Furthermore, when cultured with soluble anti-CD3 antibody and antigen-presenting cells, IL-35 suppressed the proliferation of CD4(+)CD25(-) effector cells. Moreover, IL-35 inhibited the differentiation of Th17 cells in vitro. In vivo, IL-35 effectively attenuated established collagen-induced arthritis in mice, with concomitant suppression of IL-17 production but enhanced IFN-gamma synthesis. Thus, IL-35 is a novel anti-inflammatory cytokine suppressing the immune response through the expansion of regulatory T cells and suppression of Th17 cell development.

  13. Consumption of probiotics increases the effect of regulatory T cells in transfer colitis

    DEFF Research Database (Denmark)

    Petersen, Emil Rathsach; Claesson, Mogens Helweg; Schmidt, Esben Gjerløff Wedebye

    2012-01-01

    BACKGROUND: Probiotics may alter immune regulation. Recently, we showed that the probiotic bacteria Lactobacillus acidophilus NCFM™ influenced the activity of regulatory T cells (Tregs) in vitro. The aim of the present work was to demonstrate if L. acidophilus NCFM™ also affects the function...... of Tregs in vivo. METHODS: Development of colitis after transfer of CD4+CD25- T cells and protection from colitis by Tregs was studied in immunodeficient SCID mice which were simultaneously tube-fed with L. acidophilus NCFM™ or L. salivarius Ls-33 for 5 weeks. RESULTS: Probiotic-fed SCID mice transplanted...... with low numbers of Tregs in addition to the disease-inducing T cells were completely protected from colitis. This was in contrast to the control group, which showed intermediate levels of inflammation. In addition, feeding with probiotics lowered serum levels of inflammatory cytokines in both colitic mice...

  14. Comparative analysis of acute and chronic corticosteroid pharmacogenomic effects in rat liver: Transcriptional dynamics and regulatory structures

    Directory of Open Access Journals (Sweden)

    DuBois Debra C

    2010-10-01

    Full Text Available Abstract Background Comprehensively understanding corticosteroid pharmacogenomic effects is an essential step towards an insight into the underlying molecular mechanisms for both beneficial and detrimental clinical effects. Nevertheless, even in a single tissue different methods of corticosteroid administration can induce different patterns of expression and regulatory control structures. Therefore, rich in vivo datasets of pharmacological time-series with two dosing regimens sampled from rat liver are examined for temporal patterns of changes in gene expression and their regulatory commonalities. Results The study addresses two issues, including (1 identifying significant transcriptional modules coupled with dynamic expression patterns and (2 predicting relevant common transcriptional controls to better understand the underlying mechanisms of corticosteroid adverse effects. Following the orientation of meta-analysis, an extended computational approach that explores the concept of agreement matrix from consensus clustering has been proposed with the aims of identifying gene clusters that share common expression patterns across multiple dosing regimens as well as handling challenges in the analysis of microarray data from heterogeneous sources, e.g. different platforms and time-grids in this study. Six significant transcriptional modules coupled with typical patterns of expression have been identified. Functional analysis reveals that virtually all enriched functions (gene ontologies, pathways in these modules are shown to be related to metabolic processes, implying the importance of these modules in adverse effects under the administration of corticosteroids. Relevant putative transcriptional regulators (e.g. RXRF, FKHD, SP1F are also predicted to provide another source of information towards better understanding the complexities of expression patterns and the underlying regulatory mechanisms of those modules. Conclusions We have proposed a

  15. Effect of Black Tea Consumption on Intracellular Cytokines, Regulatory T Cells and Metabolic Biomarkers in Type 2 Diabetes Patients.

    Science.gov (United States)

    Mahmoud, Fadia; Haines, David; Al-Ozairi, Ebaa; Dashti, Ali

    2016-03-01

    The present study was undertaken to evaluate the effects of black tea intake on inflammatory cytokines and metabolic biomarkers in Type 2 diabetes mellitus (T2DM). Thirty patients with T2DM were randomly assigned either to a High Intake (HI) group, consuming three cups (600 mL) of black tea per day; and a Low Intake (LI) group, administered 1 cup (200 mL) per day, each during a 12-week period. Intracellular cytokine expression, regulatory T cells (Treg), glycemic and lipid profiles were measured at baseline and following the tea intake period. Tea consumption correlated with major effects measured in peripheral blood of subjects that included significantly reduced glycated hemoglobin (HbA1c) levels, along with increased regulatory T cells CD3+ CD4+ CD25+ FOXP3, CD3+ CD4+ IL-10+ cells (an immunosuppressive phenotype), reduced (pro-inflammatory) CD3+ CD4+ IL-17+ cells and reduced Th1-associated CD3+ CD4+ IFN-Υ+ cells. Tea consumption was also observed to abolish the significance of an inverse correlation between total serum cholesterol and representation of CD4+ IL-4+ T cells, which may reflect protection against atopy-related oxidative stress. Outcomes of this study describe both advantages and limitations to consumption of black tea as an aid to sustained health maintenance by persons at-risk for TD2M and related obesity-associated metabolic syndromes.

  16. Differential expression of B-crystallin and Hsp27 in skeletal muscle during continuous contractile activity. Relationship to myogenic regulatory factors.

    Science.gov (United States)

    Neufer, P D; Benjamin, I J

    1996-09-27

    AlphaB-crystallin (alphaBC) is a major structural protein (22 kDa) of the ocular lens as well as a bona fide heat shock protein in non-lens tissue. The alphaBC gene is abundantly expressed in tissues with high oxidative capacity, including the heart and type I skeletal muscle fibers, and is regulated by the MyoD family of basic helix-loop-helix transcription factors during myogenesis. To test the hypothesis that alphaBC expression may be directly regulated by the demand for oxidative metabolism, we examined the expression of alphaBC and the ancestral-related Hsp27 in rabbit tibialis anterior muscle subjected to continuous low frequency motor nerve stimulation (3 V, 10 Hz). alphaBC mRNA and protein increased within the 1st day of continuous contractile activity (5- and 2.5-fold, respectively) and achieved maximum levels (>20-and 4-fold, respectively) after 21 d of stimulation. Hsp27 mRNA and protein levels also increased with stimulation, but with a less specific and dramatic induction pattern. In agreement with the Northern analysis, in situ hybridization performed on cross sections from tibialis anterior muscle revealed progressively increasing alphaBC transcript signal, localized in a ringlet pattern, from 1 through 21 days of stimulation. Serial sections subjected to myosin immunohistochemistry revealed that alphaBC expression was confined to slow-twitch type I and a subpopulation of fast twitch type II fibers after 1 day but present in nearly all fibers after 21 days of stimulation. Transcript levels of all four myogenic regulatory factors (MyoD, myogenin, myf-5, and MRF4) also increased with stimulation in a pattern temporally similar with alphaBC, suggesting that expression of alphaBC in response to stimulation may, in part, be regulated through myogenic regulatory factor(s) interaction with the canonical E-box element located within the alphaBC promotor. These data demonstrate that expression of the small heat shock protein, alphaBC, is rapidly induced

  17. Fourth-order partial differential equations for effective image denoising

    Directory of Open Access Journals (Sweden)

    Seongjai Kim

    2009-04-01

    Full Text Available This article concerns mathematical image denoising methods incorporating fourth-order partial differential equations (PDEs. We introduce and analyze piecewise planarity conditions (PPCs with which unconstrained fourth-order variational models in continuum converge to a piecewise planar image. It has been observed that fourth-order variational models holding PPCs can restore better images than models without PPCs and second-order models. Numerical schemes are presented in detail and various examples in image denoising are provided to verify the claim.

  18. Differential coupling of Arg- and Gly389 polymorphic forms of the β1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs

    OpenAIRE

    2008-01-01

    The β1-adrenergic receptor (β1AR; ADRB1) polymorphism Arg389Gly is located in an intracellular loop and is associated with distinct human and mouse cardiovascular phenotypes. To test the hypothesis that β1-Arg389 and β1-Gly389 alleles could differentially couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP signaling, we performed comparative gene expression profile analyses on hearts from wild-type and transgenic mice that expressed either human β1-Arg389 or β1-Gly389 rece...

  19. Identification and monitoring of effector and regulatory T cells during experimental arthritis based on differential expression of CD25 and CD134.

    Science.gov (United States)

    Nolte-'t Hoen, Esther N M; Boot, Elmieke P J; Wagenaar-Hilbers, Josée P A; van Bilsen, Jolanda H M; Arkesteijn, Ger J A; Storm, Gert; Everse, Linda A; van Eden, Willem; Wauben, Marca H M

    2008-01-01

    Major problems in the analysis of CD4+ effector cell and regulatory T cell (Treg) populations in an activated immune system are caused by the facts that both cell types can express CD25 and that the discriminatory marker forkhead box p3 can only be analyzed in nonviable (permeabilized) cells. Here, we show that CD134 (OX40) can be used as a discriminatory marker combined with CD25 to isolate and characterize viable CD4+ effector cells and Tregs. Before and during adjuvant arthritis in rats, coexpression of CD134 and CD25 identified activated Tregs consistently, as these T cells proliferated poorly to disease-associated antigens and were suppressive in vitro and in vivo. Depending on the time of isolation and location, CD4+ T cell populations expressing CD134 or CD25 contained effector/memory T cells. Analysis of the function, phenotype, and amount of the CD4+ T cell subsets in different lymph node stations revealed spatiotemporal differences in effector cell and Treg compartments during experimental arthritis.

  20. Differential control by IHF and cAMP of two oppositely oriented genes, hpt and gcd, in Escherichia coli: significance of their partially overlapping regulatory elements.

    Science.gov (United States)

    Izu, H; Ito, S; Elias, M D; Yamada, M

    2002-01-01

    The hpt gene, which encodes hypoxanthine phosphoribosyltransferase, is located next to, but transcribed in the opposite direction to, the gcd gene, which codes for a membrane-bound glucose dehydrogenase, at 3.1 min on the Escherichia coli genome. In their promoter-operator region, putative regulatory elements for integration host factor (IHF) and for the complex comprising 3', 5'-cyclic AMP (cAMP) and its receptor protein (CRP) are present, and they overlap the promoters for hpt and gcd, respectively. The involvement of IHF and cAMP-CRP, as well as the corresponding putative cis-acting elements, in the expression of the two genes was investigated by using lacZ operon fusions. In an adenylate cyclase-deficient strain, addition of cAMP increased the expression of hpt and reduced the expression of gcd. In agreement with this observation, the introduction of mutations into the putative binding element for the cAMP-CRP complex enhanced the expression of gcd. In contrast, mutations introduced into the putative IHF-binding elements increased the level of hpt expression. Similar results were obtained with IHF-defective strains. Thus, the expression of the two genes is regulated in a mutually exclusive manner. Additional experiments with mutations at the -10 sequence of the gcd promoter suggest that the binding of RNA polymerase to the hpt promoter interferes with the interaction of RNA polymerase with the gcd promoter, and vice versa.

  1. Differential Expression of Myogenic Regulatory Factor Genes in the Skeletal Muscles of Tambaqui Colossoma macropomum (Cuvier 1818 from Amazonian Black and Clear Water

    Directory of Open Access Journals (Sweden)

    F. A. Alves-Costa

    2013-01-01

    Full Text Available Hypothesizing that the Amazonian water system differences would affect the expression of muscle growth-related genes in juvenile tambaqui Colossoma macropomum (Cuvier 1818, this study aimed to analyze the morphometric data and expression of myogenic regulatory factors (MRFs in the white and red muscle from tambaqui obtained from clear and black Amazonian water systems. All of the MRF transcript levels (myod, myf5, myogenin, and mrf4 were significantly lower in the red muscle from black water fish in comparison to clear water fish. However, in white muscle, only the myod transcript level was significantly decreased in the black water tambaqui. The changes in MRFs gene expression in muscle fibers of tambaqui from black water system provide relevant information about the environmental influence as that of water systems on gene expression of muscle growth related genes in the C. macropomum. Our results showed that the physical and chemical water characteristics change the expression of genes that promote muscle growth, and these results may be also widely applicable to future projects that aim to enhance muscle growth in fish that are of substantial interest to the aquaculture.

  2. Effect of growth and differentiation factor 6 on the tenogenic differentiation of bone marrow-derived mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    CHAI Wei; NI Ming; RUI Yun-feng; ZHANG Kai-yi; ZHANG Qiang; XU Liang-liang; CHAN Kai-ming

    2013-01-01

    Background Recent studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) had risk of ectopic bone formation.In this study,we aimed to investigate the effect of growth and differentiation factor 6 (GDF-6) on the tenogenic differentiation of BMSCs in vitro,and then combined with small intestine submucous (SIS) to promote tendon regeneration in vivo.Methods The BMSCs were isolated from the green fluorescent protein (GFP) rats,and were characterized by multi-differentiation assays following our previous study protocol.BMSCs cultured with different concentrations of GDF-6,without growth factors served as control.After 2 weeks,mRNA expression and protein expression of tendon specific markers were examined by qRT-PCR and Western blotting to define an optimal concentration of GDF-6.Mann-Whitney U-test was used to compare the difference in relative mRNA expression among all groups; P ≤0.05 was regarded as statistically significant.The GDF-6 treated BMSCs combined with SIS were implanted in nude mice and SD rat acute patellar tendon injury model,the BMSCs combined with SIS served as control.After 12 and 4 weeks in nude mice and tendon injury model,the samples were collected for histology.Results After the BMSCs were treated with different concentration of GDF-6 for 2 weeks,the fold changes of the specific markers (Tenomodulin and Scleraxis) mRNA expression were significantly higher in GDF-6 (20 ng/ml) group (P ≤0.05),which was also confirmed by Western blotting result.The BMSCs became parallel in orientation after GDF-6 (20 ng/ml) treatment,but the BMSCs in control group were randomly oriented.The GDF-6 (20 ng/ml) treated BMSCs were combined with SIS,and were implanted in nude mice for 12 weeks,the histology showed neo-tendon formation.In the SD rat patellar tendon window injury model,the histology also indicated the GDF-6 (20 ng/ml) treated BMSCs combined with SIS could promote tendon regeneration.Conclusions GDF-6 has tenogenic effect on the tenogenic

  3. EFFECT OF LOW SELENIUM ON CHONDROCYTE DIFFERENTIATION AND DIFFERENTIAL EXPRESSION OF COLLAGEN TYPES Ⅰ , Ⅱ AND X IN ARTICULAR CARTILAGE FROM MINI-PIGS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective According to the distribution of low selenium areas, low nutrition state of the residents and the affecting cartilage growth and articular cartilage of Kashin-Beck Disease(KBD),the chondrocyte differentia- tion and differential expression of collagen types Ⅰ , Ⅱ and Ⅹ in articular cartilage from Chinese mini-pigs treated with low selenium were investigated in order to gain insight into the effects of these conditions on chondrocyte differ- entiation in KBD cartilage. Mothods Eleven male juvenile mini-pigs, aged from 4 weeks to 6 weeks after birth, were divided into 3 groups. The Se content in the diet of the “low Se” group was 0. 035mg/kg diet, and 0. 175 mg/kg diet in the control. For Se-supplemented group 0. 390mg /kg diet was added. The content of Se in blood was assayed at the beginning and at the end of each experiment. Samples of articular cartilage were taken from the right femur condylus, and collagen types Ⅰ , Ⅱ and Ⅹ in articular cartilage were analyzed by immunohistochemistry and in situ hybridization. Results ①All cartilage samples from juvenile mini-pigs fed with low selenium diet revealed a re- duction in type Ⅹ collagen mRNA expression in the hypertrophic chondrocytes as shown by in situ hybridization, and reduced type Ⅹ collagen deposition in the lower hypertrophic zone as shown by immunohistochemistry. ②Addition of selenium to the diet restored the type Ⅹ collagen to normal level. ③Type Ⅱ collagen was evenly distributed over the entire articular cartilage in all experimental and control groups. Type Ⅱ collagen mRNA signals were most prominent in the upper articular layer as well as in the hypertrophic zone in all groups. Type Ⅱ collagen expression was restrict- ed to the zone of endochondral ossification in all experimental groups and the control. Conclusion Low selenium has an down-regulatory role on the synthesis and deposition of collagen type Ⅹ in hypertrophic chondrocytes in articular cartilage of

  4. Social support influences on eating awareness in children and adolescents: the mediating effect of self-regulatory strategies.

    Science.gov (United States)

    Gaspar de Matos, Margarida; Palmeira, Antonio L; Gaspar, Tania; De Wit, John B F; Luszczynska, Aleksandra

    2016-01-01

    The impact of the social environment on healthy eating awareness results from complex interactions among physical, economic, cultural, interpersonal and individual characteristics. This study investigated the impact of social support and social influence on healthy eating awareness, controlling for socio-economic status, gender and age. Additionally, the mediating effect of self-regulation strategies was examined. A total of 2764 children and adolescents aged 10-17 from four European countries completed self-report measures on healthy eating awareness, social influence and the use of self-regulation strategies. Healthy eating awareness and the use of self-regulation strategies were more likely to occur among younger participants. An interaction between gender and age was related to the use of some self-regulation strategies; compared to girls, boys decreased the use of self-regulation strategies more from pre-adolescence to adolescence. Peer social influence was associated with more unhealthy eating in older participants. Results suggest a need to promote self-regulatory competences among young people in order to assist them with regulating their eating behaviours, especially in the presence of peers. Both school-based interventions and family-based interventions, focusing on self-regulation cognitions and social (peer) influence, could help children and adolescents to use self-regulatory strategies which are essential to eat healthier.

  5. Differential Effect of Amphetamine Optical Isomers on Bender Gestalt Performance of the Minimally Brain Dysfunctioned

    Science.gov (United States)

    Arnold, L. Eugene; And Others

    1978-01-01

    The differential effect of amphetamine optical isomers on Bender Gestalt performance was examined in 31 hyperkinetic minimally brain dysfunctioned children between the ages of 4 and 12 years, using a double-blind Latin-square crossover comparison. (Author)

  6. Properties of Differential Scattering Section Based on Multi-photon Nonlinear Compton Effect

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Properties of damping electrons in collision with photons based on multi-photon nonlinear Compton effect are investigated. The expressions of the differential scattering section are derived. Several useful conclusions are drawn.

  7. Differential effects of problem-solving demands on individual and collaborative learning outcomes

    NARCIS (Netherlands)

    Kirschner, Femke; Paas, Fred; Kirschner, Paul A.; Janssen, Jeroen

    2011-01-01

    Kirschner, F., Paas, F., Kirschner, P. A., & Janssen, J. (2011). Differential effects of problem-solving demands on individual and collaborative learning outcomes. Learning and Instruction, 21, 587-599.

  8. Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation

    DEFF Research Database (Denmark)

    Kratchmarova, Irina; Blagoev, Blagoy; Haack-Sorensen, M.

    2005-01-01

    Closely related signals often lead to very different cellular outcomes. We found that the differentiation of human mesenchymal stem cells into bone-forming cells is stimulated by epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF). We used mass spectrometry-based proteomics...... it as a possible control point. Indeed, chemical inhibition of PI3K in PDGF-stimulated cells removed the differential effect of the two growth factors, bestowing full differentiation effect onto PDGF. Thus, quantitative proteomics can directly compare entire signaling networks and discover critical differences...... capable of changing cell fate....

  9. Effects of childhood poverty and chronic stress on emotion regulatory brain function in adulthood.

    Science.gov (United States)

    Kim, Pilyoung; Evans, Gary W; Angstadt, Michael; Ho, S Shaun; Sripada, Chandra S; Swain, James E; Liberzon, Israel; Phan, K Luan

    2013-11-12

    Childhood poverty has pervasive negative physical and psychological health sequelae in adulthood. Exposure to chronic stressors may be one underlying mechanism for childhood poverty-health relations by influencing emotion regulatory systems. Animal work and human cross-sectional studies both suggest that chronic stressor exposure is associated with amygdala and prefrontal cortex regions important for emotion regulation. In this longitudinal functional magnetic resonance imaging study of 49 participants, we examined associations between childhood poverty at age 9 and adult neural circuitry activation during emotion regulation at age 24. To test developmental timing, concurrent, adult income was included as a covariate. Adults with lower family income at age 9 exhibited reduced ventrolateral and dorsolateral prefrontal cortex activity and failure to suppress amygdala activation during effortful regulation of negative emotion at age 24. In contrast to childhood income, concurrent adult income was not associated with neural activity during emotion regulation. Furthermore, chronic stressor exposure across childhood (at age 9, 13, and 17) mediated the relations between family income at age 9 and ventrolateral and dorsolateral prefrontal cortex activity at age 24. The findings demonstrate the significance of childhood chronic stress exposures in predicting neural outcomes during emotion regulation in adults who grew up in poverty.

  10. Effects of regulatory reforms in the electricity supply industry on electricity prices in developing countries

    Energy Technology Data Exchange (ETDEWEB)

    Nagayama, Hiroaki [Kyoto University, Yoshida-honmachi, Kyoto (Japan). Graduate School of Energy Science, Department of Socio-Environmental Energy Science

    2007-06-15

    Electric power sector reforms in the electricity supply industry have had an impact on industrial and household prices in developing countries in Latin America, the former Soviet Union, and Eastern Europe. Using original panel data for 83 countries during the period from 1985 to 2002, we examine how each policy instrument of the reform measures influenced electricity prices for countries in the above regions. We found that variables such as entry of independent power producers (IPP), unbundling of generation and transmission, establishment of a regulatory agency, and the introduction of a wholesale spot market have had a variety of impacts on electricity prices, some of which were not always consistent with expected results. The research findings suggest that neither unbundling nor introduction of a wholesale pool market on their own necessarily reduces the electric power price. In fact, contrary to expectations, there was a tendency for the price to rise. However, coexistent with an independent regulator, unbundling may work to reduce electricity prices. Privatization and the introduction of foreign IPP and retail competition lower electricity prices in some regions, but not all. (author)

  11. Effects of oral creatine and resistance training on myogenic regulatory factor expression.

    Science.gov (United States)

    Willoughby, Darryn S; Rosene, John M

    2003-06-01

    This study examined 12 wk of creatine (Cr) supplementation and heavy resistance training on skeletal muscle creatine kinase (M-CK) mRNA expression and the mRNA and protein expression of the myogenic regulatory factors Myo-D, myogenin, MFR-4, and Myf5. Twenty-two untrained males were randomly assigned to either a control (CON), placebo (PLC), or Cr (CRT) group in a double-blind fashion. Muscle biopsies were obtained before and after training. PLC and CRT trained thrice weekly using 3 sets of 6-8 repetitions at 85-90% 1-RM on the leg press, knee extension, and knee curl exercises. CRT ingested 6 g.d-1 of Cr for 12 wk while PLC consumed the equal amount of placebo. After training, M-CK mRNA expression, as well as myogenin and MRF-4 mRNA and protein expression, were found to be significantly greater for CRT compared with PLC and CON, whereas PLC was also significantly different from CON (P 0.05). M-CK mRNA was correlated with myogenin (r = 0.916) and MRF-4 (r = 0.883) protein (P resistance training, Cr supplementation increases M-CK mRNA expression, likely due to concomitant increases in the expression of myogenin and MRF-4. Therefore, increases in myogenin and MRF-4 mRNA and protein may play a role in increasing myosin heavy chain expression, already shown to occur with Cr supplementation.

  12. Effect of Salmonella infection on cecal tonsil regulatory T cell properties in chickens.

    Science.gov (United States)

    Shanmugasundaram, Revathi; Kogut, Michael H; Arsenault, Ryan J; Swaggerty, Christina L; Cole, Kimberly; Reddish, John M; Selvaraj, Ramesh K

    2015-08-01

    Two studies were conducted to study regulatory T cell [Treg (CD4⁺CD25⁺)] properties during the establishment of a persistent intestinal infection in broiler chickens. Four-day-old broiler chicks were orally gavaged with 5 × 10⁶ CFU/mL Salmonella enteritidis (S. enteritidis) or sterile PBS (control). Samples were collected at 4, 7, 10, and 14 d postinfection. There was a significant (P 0.05) when compared to that of noninfected control birds. At a lower effector/responder cell ratio of 0.25:1, CD4⁺CD25⁺ cells from cecal tonsils of Salmonella-infected birds suppressed T cell proliferation at d 7 and 14 post-S. enteritidis infection, while CD4⁺CD25⁺ cells from noninfected control groups did not suppress T cell proliferation. In the second studu, 1-day-old chickens were orally gavaged with PBS (control) or 1.25 × 10⁸ CFU/bird S. enteritidis. At 7 and 21 d post-Salmonella infection, CD25⁺ cells collected from cecal tonsils of S. enteritidis-infected birds and restimulated in vitro with Salmonella antigen had higher (P 0.05) between the Salmonella-infected and control birds. In conclusion, a persistent intestinal S. enteritidis infection increased the Treg percentage, suppressive properties, and IL-10 mRNA amounts in the cecal tonsils of broiler birds.

  13. Differential Association of the Na+/H+ Exchanger Regulatory Factor (NHERF Family of Adaptor Proteins with the Raft- and the Non-Raft Brush Border Membrane Fractions of NHE3

    Directory of Open Access Journals (Sweden)

    Ayesha Sultan

    2013-11-01

    Full Text Available Background/Aims: Trafficking, brush border membrane (BBM retention, and signal-specific regulation of the Na+/H+ exchanger NHE3 is regulated by the Na+/H+ Exchanger Regulatory Factor (NHERF family of PDZ-adaptor proteins, which enable the formation of multiprotein complexes. It is unclear, however, what determines signal specificity of these NHERFs. Thus, we studied the association of NHE3, NHERF1 (EBP50, NHERF2 (E3KARP, and NHERF3 (PDZK1 with lipid rafts in murine small intestinal BBM. Methods: Detergent resistant membranes (“lipid rafts” were isolated by floatation of Triton X-incubated small intestinal BBM from a variety of knockout mouse strains in an Optiprep step gradient. Acid-activated NHE3 activity was measured fluorometrically in BCECF-loaded microdissected villi, or by assessment of CO2/HCO3- mediated increase in fluid absorption in perfused jejunal loops of anethetized mice. Results: NHE3 was found to partially associate with lipid rafts in the native BBM, and NHE3 raft association had an impact on NHE3 transport activity and regulation in vivo. NHERF1, 2 and 3 were differentially distributed to rafts and non-rafts, with NHERF2 being most raft-associated and NHERF3 entirely non-raft associated. NHERF2 expression enhanced the localization of NHE3 to membrane rafts. The use of acid sphingomyelinase-deficient mice, which have altered membrane lipid as well as lipid raft composition, allowed us to test the validity of the lipid raft concept in vivo. Conclusions: The differential association of the NHERFs with the raft-associated and the non-raft fraction of NHE3 in the brush border membrane is one component of the differential and signal-specific NHE3 regulation by the different NHERFs.

  14. The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Sharma, Dileep; Hamlet, Stephen Mark; Petcu, Eugen Bogdan; Ivanovski, Saso

    2016-02-09

    The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ).

  15. Differential microstrip lines with reduced crosstalk and common mode effect based on spoof surface plasmon polaritons.

    Science.gov (United States)

    Wu, Jin Jei; Hou, Da Jun; Liu, Kexin; Shen, Linfang; Tsai, Chi An; Wu, Chien Jang; Tsai, Dichi; Yang, Tzong-Jer

    2014-11-03

    We apply the concept of spoof surface plasmon polaritons (SPPs) to the design of differential microstrip lines by introducing periodic subwavelength corrugations on their edges. The dispersion relation and field distribution of those lines are analyzed numerically. And then through designing practical coupling circuits, we found that compared with conventional differential microstrip lines, the electromagnetic field can be strongly confined inside the grooves of the corrugated microstrip lines, so the crosstalk between the differential pair and the adjacent microstrip lines is greatly reduced, and the conversion from the differential signal to the common mode signal can also be effectively suppressed. The propagation length of those lines is also very long in a wide band. Moreover, the experimental results in time domain demonstrate those lines perform very well in high-speed circuit. Therefore, those novel kinds of spoof SPPs based differential microstrip lines can be widely utilized in high-density microwave circuits and guarantee signal integrity in high-speed systems.

  16. The effect of scale-free topology on the robustness and evolvability of genetic regulatory networks.

    Science.gov (United States)

    Greenbury, Sam F; Johnston, Iain G; Smith, Matthew A; Doye, Jonathan P K; Louis, Ard A

    2010-11-01

    We investigate how scale-free (SF) and Erdos-Rényi (ER) topologies affect the interplay between evolvability and robustness of model gene regulatory networks with Boolean threshold dynamics. In agreement with Oikonomou and Cluzel (2006) we find that networks with SF(in) topologies, that is SF topology for incoming nodes and ER topology for outgoing nodes, are significantly more evolvable towards specific oscillatory targets than networks with ER topology for both incoming and outgoing nodes. Similar results are found for networks with SF(both) and SF(out) topologies. The functionality of the SF(out) topology, which most closely resembles the structure of biological gene networks (Babu et al., 2004), is compared to the ER topology in further detail through an extension to multiple target outputs, with either an oscillatory or a non-oscillatory nature. For multiple oscillatory targets of the same length, the differences between SF(out) and ER networks are enhanced, but for non-oscillatory targets both types of networks show fairly similar evolvability. We find that SF networks generate oscillations much more easily than ER networks do, and this may explain why SF networks are more evolvable than ER networks are for oscillatory phenotypes. In spite of their greater evolvability, we find that networks with SF(out) topologies are also more robust to mutations (mutational robustness) than ER networks. Furthermore, the SF(out) topologies are more robust to changes in initial conditions (environmental robustness). For both topologies, we find that once a population of networks has reached the target state, further neutral evolution can lead to an increase in both the mutational robustness and the environmental robustness to changes in initial conditions.

  17. Effect of adoptive transfer or depletion of regulatory T cells on triptolide-induced liver injury

    Directory of Open Access Journals (Sweden)

    Xinzhi eWang

    2016-04-01

    Full Text Available ObjectiveThe aim of this study is to clarify the role of regulatory T cell (Treg in triptolide (TP-induced hepatotoxicity. MethodsFemale C57BL/6 mice received either adoptive transfer of Tregs or depletion of Tregs, then underwent TP administration and were sacrificed 24 hours after TP administration. Liver injury was determined according to ALT and AST levels in serum and histopathological change in liver tissue. Hepatic frequencies of Treg cells and the mRNA expression levles of transcription factor FoxP3 and RORγt, IL-10, SOCS and Notch/Notch ligand were investigated.ResultsDuring TP-induced liver injury, hepatic Treg and IL-10 decreased, while Th17 cell transcription factor RORγt, SOCS signaling and Notch signaling increased, accompanied with liver inflammation. Adoptive transfer of Tregs ameliorated the severity of TP-induced liver injury, accompanied with increased levels of hepatic Treg and IL-10. Adoptive transfer of Tregs remarkably inhibited the expression of RORγt, SOCS3, Notch1 and Notch3. On the contrary, depletion of Treg cells in TP-administered mice resulted in a notable increase of RORγt, SOCS1, SOCS3 and Notch3, while the Treg and IL-10 of liver decreased. Consistent with the exacerbation of liver injury, higher serum levels of ALT and AST were detected in Treg-depleted mice. ConclusionsThese results showed that adoptive transfer or depletion of Tregs attenuated or aggravated TP-induced liver injury, suggesting that Tregs could play important roles in the progression of liver injury. SOCS proteins and Notch signaling affected Tregs, which may contribute to the pathogenesis of TP-induced hepatotoxicity.

  18. THE REGULATORY EFFECT OF NUCLEOSIDE DIPHOSPHATE KINASE ON G-PROTEIN AND G-PROTEIN MEDIATED PHOSPHOLIPASE C

    Institute of Scientific and Technical Information of China (English)

    张德昌; 张宽仁

    1995-01-01

    The effect of nueleoside diphosphate kinase (NDPK) on the activity of guanine nueleotide regulatory protein (G-protein) mediated phospholipase C (PLC) and on the [35S ] GTPTτS binding of G-protein was investigated in this work in order to demonstrate the mechanism behind the regulation of G-protein and its effector PLC by NDPK. The stimulation of PLC in turkey erythrocyte membrane by both GTP and GTPτS indicated that the PLC stimulation was msdiated by G-protein, NDPK alone stimulated PLC activity, as well as the stimulation in the presence of GTP and GDP, in a dose-dependent manner. However, NDPK inhibited GTPτS-stimulated PLC, Furthermore, NDPK inhibited [35S] GTPτS binding of purified Gi-protein in a non-competitive manner. A hypothesis implying an important role of direct interaction of G-protein and NDPK in the regulation of their functions is suggested and discussed.

  19. An effective inducer of dopaminergic neuron-like differentiation

    Institute of Scientific and Technical Information of China (English)

    Wenyu Fu; Cui Lv; Wenxin Zhuang; Dandan Chen; E Lv; Fengjie Li; Xiaocui Wang

    2013-01-01

    Rat bone marrow-derived mesenchymal stem cells were cultured and passaged in vitro. After induction with basic fibroblast growth factor for 24 hours, passage 3 bone marrow-derived mesenchymal stem cells were additionally induced into dopaminergic neurons using three different combinations with basic fibroblast growth factor as follows: 20% Xiangdan injection; all-trans retinoic acid + glial-derived neurotrophic factor; or sonic hedgehog + fibroblast growth factor 8. Results suggest that the bone marrow-derived mesenchymal stem cells showed typical neuronal morphological characteristics after induction. In particular, after treatment with sonic hedgehog + fibroblast growth factor 8, the expressions of nestin, neuron-specific enolase, microtubuleassociated protein 2, tyrosine hydroxylase and vesicular monoamine transporter-2 in cells were significantly increased. Moreover, the levels of catecholamines in the culture supernatant were significantly increased. These findings indicate that Xiangdan injection, all-trans retinoic acid + glial-derived neurotrophic factor, and sonic hedgehog + fibroblast growth factor 8 can all induce dopaminergic neuronal differentiation from bone marrow-derived mesenchymal stem cells. In particular, the efficiency of sonic hedgehog + fibroblast growth factor 8 was highest.

  20. 77 FR 1524 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2012-01-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving..., 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and... effective date of the proposed rule change in a Regulatory Notice to be published no later than 60...

  1. Biological Sensitivity to Family Income: Differential Effects on Early Executive Functioning.

    Science.gov (United States)

    Obradović, Jelena; Portilla, Ximena A; Ballard, Parissa J

    2016-01-01

    The study examined how the interplay between children's cortisol response and family income is related to executive function (EF) skills. The sample included one hundred and two 5- to 6-year-olds (64% minority). EF skills were measured using laboratory tasks and observer ratings. Physiological reactivity was assessed via cortisol response during a laboratory visit. A consistent, positive association between family income and EF skills emerged only for children who showed high cortisol response, a marker of biological sensitivity to context. In contrast, family income was not related to EF skills in children who displayed low cortisol response. Follow-up analyses revealed a disordinal interaction, suggesting that differential susceptibility can be detected at the level of basic cognitive and self-regulatory skills that support adaptive functioning.

  2. Some Differential Effects of Two Training Group Styles.

    Science.gov (United States)

    Boller, Jon D.

    Concurrent with the increasing interest in the training group (T-Group) as a source of growth and personal awareness for its participants, is a need to examine the effects of the T-group on certain personality types. This paper presents a rationale for examining the effects of the T-group on introverts and extroverts. Two T-group styles were…

  3. Effect Of Differential Pretraining On Client Self-Disclosure

    Science.gov (United States)

    Stone, Gerald L.; Stebbins, Larry W.

    1975-01-01

    This research studied the effectiveness of pretraining procedures in teaching college students to self-disclose. Three modeling procedures were used to teach this verbal skill: video model, audio model, and no model. Results indicated the video model group was the most effective followed by the audio model group. No sex differences were found.…

  4. Differential Effects of Phonological Priming on Chinese Character Recognition.

    Science.gov (United States)

    Weekes, B. S.; Chen, M. J.; Lin, Y-B.

    1998-01-01

    Finds phonological priming effects on compound targets (characters containing separate radical components); no evidence of phonological priming on integrated targets (those not containing separate radicals); semantic priming effects on both compound and integrated target recognition, suggesting that phonological and semantic activation are…

  5. Exploring Differential Effects of Mathematics Courses on Mathematics Achievement

    Science.gov (United States)

    Ma, Xin; McIntyre, Laureen J.

    2005-01-01

    Using data from the Longitudinal Study of Mathematics Participation (N = 1,518 students from 34 schools), we investigated the effects of pure and applied mathematics courses on mathematics achievement, controlling for prior mathematics achievement. Results of multilevel modelling showed that the effects of pure mathematics were significant after…

  6. Detection of tissue-specific effects by methotrexate on differentiating mouse embryonic stem cells.

    Science.gov (United States)

    Pellizzer, Cristian; Bello, Ezia; Adler, Sarah; Hartung, Thomas; Bremer, Susanne

    2004-10-01

    Pluripotent embryonic stem (ES) cells offer a unique possibility to monitor the differentiation of several cell types in vitro. This study attempts to identify marker genes during in vitro cell differentiation of murine ES cells and allow a prediction of chemical effects on cell differentiation of specific target tissues. The study focused on the expression pattern of key genes involved in cardiomyocyte and osteoblast differentiation: Oct-4, Brachyury, Nkx2.5, alpha myosin heavy chain, Cbfa1, and Osteocalcin. Methotrexate was selected due to its well-characterized teratogenic effects. Several in vivo studies have demonstrated the specific interactions of methotrexate with bone formation whereas the cardiovascular system is not specifically affected after exposure to low concentration. The capability of murine ES cells to differentiate in vitro into cardiomyocytes as well as into osteoblasts have been used to demonstrate the target cell specificity in vitro, at non-cytotoxic concentration. Exposure of differentiating ES cells did not result in any gene profile modification of the selected cardiomyocyte specific genes, whereas the expression of osteoblast specific key genes, Cbfa1 and Osteocalcin, decreased. At the latter stages of skeletal differentiation we observed a 30% decrease in gene expression for Cbfa1 and a 60% decrease for Osteocalcin, with reference to the control. Early marker genes for undifferentiated cells and mesodermal cells were not modified after methotrexate treatment. These results show the possibility to integrate specific in vitro tests for teratogenicity in a test strategy for developmental toxicity. 2004 Wiley-Liss, Inc.

  7. Differential effects of Sp cellular transcription factors on viral promoter activation by varicella-zoster virus (VZV) IE62 protein.

    Science.gov (United States)

    Khalil, Mohamed I; Ruyechan, William T; Hay, John; Arvin, Ann

    2015-11-01

    The immediate early (IE) 62 protein is the major varicella-zoster virus (VZV) regulatory factor. Analysis of the VZV genome revealed 40 predicted GC-rich boxes within 36 promoters. We examined effects of ectopic expression of Sp1-Sp4 on IE62- mediated transactivation of three viral promoters. Ectopic expression of Sp3 and Sp4 enhanced IE62 activation of ORF3 and gI promoters while Sp3 reduced IE62 activation of ORF28/29 promoter and VZV DNA replication. Sp2 reduced IE62 transactivation of gI while Sp1 had no significant influence on IE62 activation with any of these viral promoters. Electrophoretic mobility shift assays (EMSA) confirmed binding of Sp1 and Sp3 but not Sp2 and Sp4 to the gI promoter. Sp1-4 bound to IE62 and amino acids 238-258 of IE62 were important for the interaction with Sp3 and Sp4 as well as Sp1. This work shows that Sp family members have differential effects on IE62-mediated transactivation in a promoter-dependent manner.

  8. Serial founder effects and genetic differentiation during worldwide range expansion of monarch butterflies

    Science.gov (United States)

    Pierce, Amanda A.; Zalucki, Myron P.; Bangura, Marie; Udawatta, Milan; Kronforst, Marcus R.; Altizer, Sonia; Haeger, Juan Fernández; de Roode, Jacobus C.

    2014-01-01

    Range expansions can result in founder effects, increasing genetic differentiation between expanding populations and reducing genetic diversity along the expansion front. However, few studies have addressed these effects in long-distance migratory species, for which high dispersal ability might counter the effects of genetic drift. Monarchs (Danaus plexippus) are best known for undertaking a long-distance annual migration in North America, but have also dispersed around the world to form populations that do not migrate or travel only short distances. Here, we used microsatellite markers to assess genetic differentiation among 18 monarch populations and to determine worldwide colonization routes. Our results indicate that North American monarch populations connected by land show limited differentiation, probably because of the monarch's ability to migrate long distances. Conversely, we found high genetic differentiation between populations separated by large bodies of water. Moreover, we show evidence for serial founder effects across the Pacific, suggesting stepwise dispersal from a North American origin. These findings demonstrate that genetic drift played a major role in shaping allele frequencies and created genetic differentiation among newly formed populations. Thus, range expansion can give rise to genetic differentiation and declines in genetic diversity, even in highly mobile species. PMID:25377462

  9. The Effects of High Glucose on Adipogenic and Osteogenic Differentiation of Gestational Tissue-Derived MSCs

    Directory of Open Access Journals (Sweden)

    Weerawan Hankamolsiri

    2016-01-01

    Full Text Available Most type 2 diabetic patients are obese who have increased number of visceral adipocytes. Those visceral adipocytes release several factors that enhance insulin resistance making diabetic treatment ineffective. It is known that significant percentages of visceral adipocytes are derived from mesenchymal stem cells and high glucose enhances adipogenic differentiation of mouse bone marrow-derived MSCs (BM-MSCs. However, the effect of high glucose on adipogenic differentiation of human bone marrow and gestational tissue-derived MSCs is still poorly characterized. This study aims to investigate the effects of high glucose on proliferation as well as adipogenic and osteogenic differentiation of human MSCs derived from bone marrow and several gestational tissues including chorion, placenta, and umbilical cord. We found that high glucose reduced proliferation but enhanced adipogenic differentiation of all MSCs examined. The expression levels of some adipogenic genes were also upregulated when MSCs were cultured in high glucose. Although high glucose transiently downregulated the expression levels of some osteogenic genes examined, its effect on the osteogenic differentiation levels of the MSCs is not clearly demonstrated. The knowledge gained from this study will increase our understanding about the effect of high glucose on adipogenic differentiation of MSCs and might lead to an improvement in the diabetic treatment in the future.

  10. The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells.

    Science.gov (United States)

    Pourgholaminejad, Arash; Aghdami, Nasser; Baharvand, Hossein; Moazzeni, Seyed Mohammad

    2016-09-01

    Mesenchymal stem cells (MSCs), as cells with potential clinical utilities, have demonstrated preferential incorporation into inflammation sites. Immunophenotype and immunomodulatory functions of MSCs could alter by inflamed-microenvironments due to the local pro-inflammatory cytokine milieu. A major cellular mediator with specific function in promoting inflammation and pathogenicity of autoimmunity are IL-17-producing T helper 17 (Th17) cells that polarize in inflamed sites in the presence of pro-inflammatory cytokines such as Interleukin-1β (IL-1β), IL-6 and IL-23. Since MSCs are promising candidate for cell-based therapeutic strategies in inflammatory and autoimmune diseases, Th17 cell polarizing factors may alter MSCs phenotype and function. In this study, human bone-marrow-derived MSCs (BM-MSC) and adipose tissue-derived MSCs (AD-MSC) were cultured with or without IL-1β, IL-6 and IL-23 as pro-inflammatory cytokines. The surface markers and their differentiation capacity were measured in cytokine-untreated and cytokine-treated MSCs. MSCs-mediated immunomodulation was analyzed by their regulatory effects on mixed lymphocyte reaction (MLR) and the level of IL-10, TGF-β, IL-4, IFN-γ and TNF-α production as immunomodulatory cytokines. Pro-inflammatory cytokines showed no effect on MSCs morphology, immunophenotype and co-stimulatory molecules except up-regulation of CD45. Adipogenic and osteogenic differentiation capacity increased in CD45+ MSCs. Moreover, cytokine-treated MSCs preserved the suppressive ability of allogeneic T cell proliferation and produced higher level of TGF-β and lower level of IL-4. We concluded pro-inflammatory cytokines up-regulate the efficacy of MSCs in cell-based therapy of degenerative, inflammatory and autoimmune disorders.

  11. Molecular cloning, expression pattern analysis of porcine Rb1 gene and its regulatory roles during primary dedifferentiated fat cells adipogenic differentiation.

    Science.gov (United States)

    Hu, Xiaoming; Luo, Pei; Peng, Xuewu; Song, Tongxing; Zhou, Yuanfei; Wei, Hongkui; Peng, Jian; Jiang, Siwen

    2015-04-01

    Adipocytes are the main constituent of adipose tissue and are considered to be a corner stone in the homeostatic control of whole body metabolism. Recent reports evidenced that retinoblastoma 1 (Rb1) gene plays an important role in fat development and adipogenesis in mice. Here, we cloned the partial cDNA sequences of the porcine Rb1 gene which contains the complete coding sequences (CDS) of 2820bp encoding a protein of 939 amino acids. Bioinformatic analysis revealed that the CDS of porcine Rb1 was highly identical with those of cattle, human and mice. The porcine Rb1 has three typical conserved structural domains, including Rb-A pocket domain, CYCLIN domain and C-terminus domain, and the phylogenetic tree indicates a closer genetic relationship with cattle and human. Tissue distribution analysis showed that Rb1 expression appeared to be ubiquitously in various tissues, being higher in heart, liver, muscle, and stomach. Furthermore, significant downregulation of Rb1 was found at the initial stage of dedifferentiated fat (DFAT) cells adipogenic differentiation. With the knockdown of the Rb1 expression by siRNA, the number of DFAT cells recruited to white rather than brown adipogenesis was promoted, and mRNA levels of adipogenic markers, such as PPARγ, aP2, LPL and adiponectin and protein expression of PPARγ and adiponectin were increased after hormone stimulation. The underlying mechanisms may be that knockdown of Rb1 promotes the mitotic clonal expansion and PPARγ expression by derepressing the transcriptional activity of E2F so as to facilitate the first steps of adipogenesis. In summary, we cloned and characterized an important negative regulator in adipogenic commitment of porcine DFAT cells.

  12. An effective analytic approach for solving nonlinear fractional partial differential equations

    Science.gov (United States)

    Ma, Junchi; Zhang, Xiaolong; Liang, Songxin

    2016-08-01

    Nonlinear fractional differential equations are widely used for modelling problems in applied mathematics. A new analytic approach with two parameters c1 and c2 is first proposed for solving nonlinear fractional partial differential equations. These parameters are used to improve the accuracy of the resulting series approximations. It turns out that much more accurate series approximations are obtained by choosing proper values of c1 and c2. To demonstrate the applicability and effectiveness of the new method, two typical fractional partial differential equations, the nonlinear gas dynamics equation and the nonlinear KdV-Burgers equation, are solved.

  13. Differential effects of MDMA and methylphenidate on social cognition.

    Science.gov (United States)

    Schmid, Yasmin; Hysek, Cédric M; Simmler, Linda D; Crockett, Molly J; Quednow, Boris B; Liechti, Matthias E

    2014-09-01

    Social cognition is important in everyday-life social interactions. The social cognitive effects of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate (both used for neuroenhancement and as party drugs) are largely unknown. We investigated the acute effects of MDMA (75 mg), methylphenidate (40 mg) and placebo using the Facial Emotion Recognition Task, Multifaceted Empathy Test, Movie for the Assessment of Social Cognition, Social Value Orientation Test and the Moral Judgment Task in a cross-over study in 30 healthy subjects. Additionally, subjective, autonomic, pharmacokinetic, endocrine and adverse drug effects were measured. MDMA enhanced emotional empathy for positive emotionally charged situations in the MET and tended to reduce the recognition of sad faces in the Facial Emotion Recognition Task. MDMA had no effects on cognitive empathy in the Multifaceted Empathy Test or social cognitive inferences in the Movie for the Assessment of Social Cognition. MDMA produced subjective 'empathogenic' effects, such as drug liking, closeness to others, openness and trust. In contrast, methylphenidate lacked such subjective effects and did not alter emotional processing, empathy or mental perspective-taking. MDMA but not methylphenidate increased the plasma levels of oxytocin and prolactin. None of the drugs influenced moral judgment. Effects on emotion recognition and emotional empathy were evident at a low dose of MDMA and likely contribute to the popularity of the drug.

  14. Differential effects on pain intensity and unpleasantness of two meditation practices.

    Science.gov (United States)

    Perlman, David M; Salomons, Tim V; Davidson, Richard J; Lutz, Antoine

    2010-02-01

    Pain is an unpleasant sensory and emotional experience that can be regulated by many different cognitive mechanisms. We compared the regulatory qualities of two different meditation practices during noxious thermal stimuli: Focused Attention, directed at a fixation cross away from the stimulation, which could regulate negative affect through a sensory gating mechanism; and Open Monitoring, which could regulate negative affect through a mechanism of nonjudgmental, nonreactive awareness of sensory experience. Here, we report behavioral data from a comparison between novice and long-term meditation practitioners (long-term meditators, LTMs) using these techniques. LTMs, compared to novices, had a significant reduction of self-reported unpleasantness, but not intensity, of painful stimuli while practicing Open Monitoring. No significant effects were found for FA. This finding illuminates the possible regulatory mechanism of meditation-based clinical interventions like Mindfulness-Based Stress Reduction (MBSR). Implications are discussed in the broader context of training-induced changes in trait emotion regulation.

  15. Effects of Extremely Low Frequency Electromagnetic Fields on Growth and Differentiation of ’Physarum polycephalum’

    Science.gov (United States)

    1975-04-01

    AD-AO10 187 EFFECTS OF EXTREMELY LOW FREQUENCY ELECTRO- MAGNETIC FIELDS ON GROWTH AND DIFFERENTIATION OF ’ PHYSARUM POLYCEPHALUM ’ E. M. Guodman, et al...LExtremely Low Prequency Electromagnetic Fields on Growth and Differentiation of Physarum polycephalum Technical Report Phase I (Continuous Wave) by...that weak, alternating electromagnetic fields (60 or 75 Hz, 2.0 G, 0.7 V/n) affect the cell cycle of Physarum polycephalum by increasing the interval

  16. Effects of Multiwalled Carbon Nanotube Reinforced Collagen Scaffolds on the Osteogenic Differentiation of Mesenchymal Stem Cells

    OpenAIRE

    Rena Baktur; Sang-Hee Yoon; Soonjo Kwon

    2013-01-01

    With recent advances in nanotechnology, carbon nanotubes (CNTs) have been extensively studied as substrates for cell culture, drug delivery systems, and medical implant materials. However, surprisingly little is known about the effect of CNTs on collective cellular processes (e.g., adhesion, proliferation, and differentiation). This leads to the need for quantitative characterization of the proliferation, differentiation, and mineralization of mesenchymal stem cells (MSCs) on multiwalled CNT-...

  17. Differential effects of collagen prolyl 3-hydroxylation on skeletal tissues.

    Directory of Open Access Journals (Sweden)

    Erica P Homan

    2014-01-01

    Full Text Available Mutations in the genes encoding cartilage associated protein (CRTAP and prolyl 3-hydroxylase 1 (P3H1 encoded by LEPRE1 were the first identified causes of recessive Osteogenesis Imperfecta (OI. These proteins, together with cyclophilin B (encoded by PPIB, form a complex that 3-hydroxylates a single proline residue on the α1(I chain (Pro986 and has cis/trans isomerase (PPIase activity essential for proper collagen folding. Recent data suggest that prolyl 3-hydroxylation of Pro986 is not required for the structural stability of collagen; however, the absence of this post-translational modification may disrupt protein-protein interactions integral for proper collagen folding and lead to collagen over-modification. P3H1 and CRTAP stabilize each other and absence of one results in degradation of the other. Hence, hypomorphic or loss of function mutations of either gene cause loss of the whole complex and its associated functions. The relative contribution of losing this complex's 3-hydroxylation versus PPIase and collagen chaperone activities to the phenotype of recessive OI is unknown. To distinguish between these functions, we generated knock-in mice carrying a single amino acid substitution in the catalytic site of P3h1 (Lepre1(H662A . This substitution abolished P3h1 activity but retained ability to form a complex with Crtap and thus the collagen chaperone function. Knock-in mice showed absence of prolyl 3-hydroxylation at Pro986 of the α1(I and α1(II collagen chains but no significant over-modification at other collagen residues. They were normal in appearance, had no growth defects and normal cartilage growth plate histology but showed decreased trabecular bone mass. This new mouse model recapitulates elements of the bone phenotype of OI but not the cartilage and growth phenotypes caused by loss of the prolyl 3-hydroxylation complex. Our observations suggest differential tissue consequences due to selective inactivation of P3H1 hydroxylase

  18. Differential effects of dietary oils on emotional and cognitive behaviors.

    Directory of Open Access Journals (Sweden)

    Keiko Kato

    Full Text Available Several dietary oils have been used preventatively and therapeutically in the setting of neurological disease. However, the mechanisms underlying their influence on brain function and metabolism remain unknown. It was investigated whether 3 types of dietary oils affected emotional behaviors in mice. Wild-type (WT mice and sialyltransferase ST3Gal IV-knockout (KO mice, which exhibit increased emotional and cognitive behaviors, were fed diets containing 20% dietary oils from post-weaning to adulthood. Mice were fed pellets made from control feed AIN93G powder containing 18% fish oil, soybean oil, or a mixture of 1-palmitoyl-2-oleoyl-3-palmitoyl glycerol (POP and 1-stearoyl-2-oleoyl-3-stearoyl glycerol (SOS, plus 2% soybean oil. Once mice reached adulthood, they were subjected to fear conditioning test to measure cognitive anxiety and forced swim test to measure depression. WT mice fed the POP-SOS diet showed a 0.6-fold decrease in percent freezing with contextual fear compared with WT mice fed the control diet. KO mice fed the fish oil diet showed a 1.4-fold increase in percent freezing with contextual fear compared with KO mice fed the control diet. These findings indicate that response to contextual fear was improved in WT mice that consumed POP-SOS but aggravated in KO mice that consumed fish oils. Furthermore, KO mice showed a 0.4-fold decrease in percent freezing in response to tone fear when they were fed POP-SOS diet compared to a control diet. Thus, POP-SOS diet reduced tone fear level of KO mice until the same level of WT mice. Finally, KO mice fed the soybean oil diet showed a 1.7-fold increase in immobility in the forced swim test compared to KO mice fed the control diet. Taken together, oil-rich diets differentially modulate anxiety and depression in normal and anxious mice. Oils rich in saturated fatty acids may alleviate anxiety more strongly than other oils.

  19. Analysis of the effects of hydroquinone and arbutin on the differentiation of melanocytes.

    Science.gov (United States)

    Inoue, Yu; Hasegawa, Seiji; Yamada, Takaaki; Date, Yasushi; Mizutani, Hiroshi; Nakata, Satoru; Matsunaga, Kayoko; Akamatsu, Hirohiko

    2013-01-01

    Hydroquinone (HQ) is a chemical compound that inhibits the functions of melanocytes and has long been known for its skin-whitening effect. According to previous studies, the Tyrosinase (Tyr) activity inhibitory effect and melanocyte-specific cell toxicity are known depigmenting mechanisms; however, details of the underlying mechanisms are unknown. Arbutin (Arb) is also known for its Tyr activity inhibitory effect and is commonly used as a skin-whitening agent. However, the detailed depigmenting mechanism of Arb is also not yet fully understood. Few studies have attempted to elucidate the effects of HQ and Arb on undifferentiated melanocytes. In this study, we examined the effects of HQ and Arb throughout each stage of differentiation of melanocytes using a mouse embryonic stem cell (ESC) culture system to induce melanocytes. The results showed that HQ in particular downregulated the early stage of differentiation, in which neural crest cells were generated, and the late stage of differentiation, in which melanogenesis became active. On the other hand, Arb had no effect on the differentiation of melanocytes, and only suppressed melanogenesis by specifically suppressing elevations in Tyr expression in the late stage of differentiation.

  20. Regulatory odour model development: Survey of modelling tools and datasets with focus on building effects

    DEFF Research Database (Denmark)

    Olesen, H. R.; Løfstrøm, P.; Berkowicz, R.;

    dispersion models for estimating local concentration levels in general. However, the report focuses on some particular issues, which are relevant for subsequent work on odour due to animal production. An issue of primary concern is the effect that buildings (stables) have on flow and dispersion. The handling...... of building effects is a complicated problem, and a major part of the report is devoted to the treatment of building effects in dispersion models...

  1. Effect of BMP-2 Delivery Mode on Osteogenic Differentiation of Stem Cells

    Science.gov (United States)

    Kim, Yong-Jin; Kim, Ki-Suk; Jang, Hyon-Seok; Chung, Hyung-Min

    2017-01-01

    Differentiation of stem cells is an important strategy for regeneration of defective tissue in stem cell therapy. Bone morphogenetic protein-2 (BMP-2) is a well-known osteogenic differentiation factor that stimulates stem cell signaling pathways by activating transmembrane type I and type II receptors. However, BMPs have a very short half-life and may rapidly lose their bioactivity. Thus, a BMP delivery system is required to take advantage of an osteoinductive effect for osteogenic differentiation. Previously, BMP delivery has been designed and evaluated for osteogenic differentiation, focusing on carriers and sustained release system for delivery of BMPs. The effect of the delivery mode in cell culture plate on osteogenic differentiation potential was not evaluated. Herein, to investigate the effect of delivery mode on osteogenic differentiation of BM-MSCs in this study, we fabricated bottom-up release and top-down release systems for culture plate delivery of BMP-2. And also, we selected Arg-Gly-Asp- (RGD-) conjugated alginate hydrogel for BMP-2 delivery because alginate is able to release BMP-2 in a sustained manner and it is a biocompatible material. After 7 days of culture, the bottom-up release system in culture plate significantly stimulated alkaline phosphate activity of human bone marrow-mesenchymal stem cells. The present study highlights the potential value of the tool in stem cell therapy. PMID:28197209

  2. Analysis of the erythroid differentiation effect of flavonoid apigenin on K562 human chronic leukemia cells.

    Science.gov (United States)

    Isoda, Hiroko; Motojima, Hideko; Onaga, Shoko; Samet, Imen; Villareal, Myra O; Han, Junkyu

    2014-09-05

    The erythroid differentiation-inducing effect of apigenin and its derivatives on human chronic myeloid leukemia K562 has been reported but the functional group in its structure responsible for the effect has not yet been elucidated. Here, we determined the moiety responsible for the erythroid differentiation induction effect of apigenin by using different flavonoids to represent the functional groups in its structure. In addition, we compared apigenin and apigetrin, a flavonoid similar in structure to apigenin except for the glycoside in its structure. Morphological changes as well as expressions of specific markers in K562 cells treated with apigenin were compared with those treated with apigetrin, flavone, 7-hydroxyflavone, chrysin, luteolin, or naringenin. The anti-proliferative and erythroid differentiation-inducing effect of apigenin and the five flavonoids were then investigated and their effects on the α, β, and γ globin genes expressions were compared using real-time PCR. Results of the comparison between apigenin and apigetrin revealed that the glycoside part of apigetrin does not have a role in the induction of cell differentiation. Based on glycophorin A expression, the potency of the other flavonoids for induction of differentiation, was: apigenin>chrysin>flavone/7-hydroxyflavone>luteolin/naringenin. Results of the analysis of the relationship between the structure and function of the flavonoids suggest that the apigenin-induced K562 cell differentiation was due to the 2-3 double bond and hydroxyl groups in its structure. This is the first study that identified the specific functional group in apigenin that impact the erythroid differentiation effect in K562 cells.

  3. The Political Economy of Regulatory Risk

    OpenAIRE

    Roland Strausz

    2009-01-01

    I investigate the argument that, in a two–party system with different regulatory objectives, political uncertainty generates regulatory risk. I show that this risk has a fluctuation effect that hurts both parties and an output–expansion effect that benefits one party. Consequently, at least one party dislikes regulatory risk. Moreover, both political parties gain from eliminating regulatory risk when political divergence is small or the winning probability of the regulatory–risk–averse party ...

  4. The political economy of regulatory risk

    OpenAIRE

    Strausz, Roland

    2009-01-01

    I investigate the argument that, in a twoparty system with different regulatory objectives, political uncertainty generates regulatory risk. I show that this risk has a fluctuation effect that hurts both parties and an outputexpansion effect that benefits one party. Consequently, at least one party dislikes regulatory risk. Moreover, both political parties gain from eliminating regulatory risk when political divergence is small or the winning probability of the regulatoryriskaverse party is n...

  5. Differential effects of bisphosphonates on breast cancer cell lines

    NARCIS (Netherlands)

    Verdijk, R.; Franke, H.R.; Wolbers, F.; Vermes, I.

    2007-01-01

    Bisphosphonates may induce direct anti-tumor effects in breast cancers cells in virtro. In this study, six bisphosphonates were administered to three breast caner cell lines. Cell proliferation was measured by quantification of th expressio of Cyclin D1 mRNA. Apoptosis was determined by flow cytome

  6. Differential effect of opioids in patients with chronic pancreatitis

    DEFF Research Database (Denmark)

    Staahl, Camilla; Dimcevski, Georg; Andersen, Søren Due

    2007-01-01

    and morphine on experimental pain in patients with pain caused by chronic pancreatitis. MATERIAL AND METHODS: Ten patients took part in this blinded, cross-over study. The analgesic effects of morphine (30 mg, oral), oxycodone (15 mg, oral) and placebo were tested against multimodal (mechanical, thermal...

  7. Effects of Differential Feedback on Students' Examination Performance

    Science.gov (United States)

    Lipnevich, Anastasiya A.; Smith, Jeffrey K.

    2009-01-01

    The effects of feedback on performance and factors associated with it were examined in a large introductory psychology course. The experiment involved college students (N = 464) working on an essay examination under 3 conditions: no feedback, detailed feedback that was perceived by participants to be provided by the course instructor, and detailed…

  8. Differential effects of head-mounted displays on visual performance.

    Science.gov (United States)

    Schega, Lutz; Hamacher, Daniel; Erfuth, Sandra; Behrens-Baumann, Wolfgang; Reupsch, Juliane; Hoffmann, Michael B

    2014-01-01

    Head-mounted displays (HMDs) virtually augment the visual world to aid visual task completion. Three types of HMDs were compared [look around (LA); optical see-through with organic light emitting diodes and virtual retinal display] to determine whether LA, leaving the observer functionally monocular, is inferior. Response times and error rates were determined for a combined visual search and Go-NoGo task. The costs of switching between displays were assessed separately. Finally, HMD effects on basic visual functions were quantified. Effects of HMDs on visual search and Go-NoGo task were small, but for LA display-switching costs for the Go-NoGo-task the effects were pronounced. Basic visual functions were most affected for LA (reduced visual acuity and visual field sensitivity, inaccurate vergence movements and absent stereo-vision). LA involved comparatively high switching costs for the Go-NoGo task, which might indicate reduced processing of external control cues. Reduced basic visual functions are a likely cause of this effect.

  9. Do Some Schools Narrow the Gap? Differential School Effectiveness Revisited

    Science.gov (United States)

    Strand, Steve

    2016-01-01

    Relatively little research has explored whether schools differ in their effectiveness for different group of pupils (e.g. by ethnicity, poverty or gender), for different curriculum subjects (e.g. English, mathematics or science) or over time (different cohorts). This paper uses multilevel modelling to analyse the national test results at age 7 and…

  10. Sex Differentials in the Effect of Remarriage of Global Happiness.

    Science.gov (United States)

    White, Lynn K.

    1979-01-01

    Examined the effect of divorce and remarriage on global happiness. Remarried men report themselves significantly more happy than men in first marriages. Remarried women are less happy. Observed differences in global happiness seem to be systematically related to differences in social integration, socioeconomic status, and general and marital…

  11. Exploring differential effects of supervisor support on transfer of training

    NARCIS (Netherlands)

    Nijman, D.J.J.M.; Nijhof, W.J.; Wognum, A.A.M.; Veldkamp, B.P.

    2006-01-01

    Purpose – The purpose of this article is to provide further insight into the relationship between supervisor support and transfer of training, by taking into account the effects of other transfer‐influencing factors in a systemic approach of the transfer process. Design/methodology/approach – A rev

  12. Differential effects of environment on potato phenylpropanoid and carotenoid expression

    OpenAIRE

    2012-01-01

    Abstract Background Plant secondary metabolites, including phenylpropanoids and carotenoids, are stress inducible, have important roles in potato physiology and influence the nutritional value of potatoes. The type and magnitude of environmental effects on tuber phytonutrients is unclear, especially under modern agricultural management that minimizes stress. Understanding factors that influence tuber secondary metabolism could facilitate production of more nutritious crops. Metabolite pools o...

  13. Differential Effects of Learning Games on Mathematics Proficiency

    Science.gov (United States)

    Chang, Mido; Evans, Michael A.; Kim, Sunha; Norton, Anderson; Samur, Yavuz

    2015-01-01

    This study examined the effects of a learning game, [The Math App] on the mathematics proficiency of middle school students. For the study, researchers recruited 306 students, Grades 6-8, from two schools in rural southwest Virginia. Over a nine-week period, [The Math App] was deployed as an intervention for investigation. Students were assigned…

  14. The effects of Ganoderma lucidum herba pharmacopuncture on 3T3-L1 preadipocyte differentiation

    Directory of Open Access Journals (Sweden)

    Chea-woo Lee

    2008-09-01

    Full Text Available Objective : The purpose of this study is to investigate the effects of Ganoderma lucidum herba pharmacopuncture (GHP on the adipogenesis in 3T3-L1 preadipocytes. Methods : 3T3- L1 preadipocytes were differentiated with adipogenic reagents by incubating for 2 days in the absence or presence of GHP ranging from 1 and 2%. The effect of GHP on cell proliferation of 3T3-L1 preadipocytes was investigated using MTT assay. The effect of GHP on adipogenesis was examined by Oil red O staining and measuring glycerol-3-phosphate dehydrogenase (GPDH and intracellular triglyceride (TG content. Results : Following results were obtained from the preadipocyte proliferation and adipocyte differentiation of 3T3-L1. We observed no effect of GHP on preadipocyte proliferation. GHP inhibited adipogenesis, the activity of GPDH and accumulation of intracellular TG content. Conclusions : These results suggest that GHP inhibit differentiation of preadipocyte.

  15. Effects of gadolinium on proliferation, differentiation and calcification of primary mouse osteoblasts in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jinchao; LI Yaping; ZHANG Qun; HAO Xiaohong; WANG Shuxiang

    2012-01-01

    To evaluate the effects of Gd on proliferation,differentiation and mineralization function of primary osteoblasts (OBs) in vitro,we tested cell viability by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay,cell differentiation by alkaline phosphatase (ALP) activity assay,synthesis of type I collagen,and oil red O and alizarin red S (ARS) stain assays.The results indicated that effects of Gd on the proliferation,osteogenic differentiation,mineralization function and adipocytic transdifferentiation of primary OBs depended on concentration and incubation time,but were not dose-dependent.It was suggested that the effect of Gd on bone metabolism was complicated,and concentration and culture time were key factors for switching the biological effects of Gd from damage to protection.

  16. Co-effects of matrix low elasticity and aligned topography on stem cell neurogenic differentiation and rapid neurite outgrowth

    Science.gov (United States)

    Yao, Shenglian; Liu, Xi; Yu, Shukui; Wang, Xiumei; Zhang, Shuming; Wu, Qiong; Sun, Xiaodan; Mao, Haiquan

    2016-05-01

    The development of novel biomaterials that deliver precise regulatory signals to direct stem cell fate for nerve regeneration is the focus of current intensive research efforts. In this study, a hierarchically aligned fibrillar fibrin hydrogel (AFG) that was fabricated through electrospinning and the concurrent molecular self-assembly process mimics both the soft and oriented features of nerve tissue, thus providing hybrid biophysical cues to instruct cell behavior in vitro and in vivo. The electrospun hydrogels were examined by scanning electron microscopy (SEM), polarized light microscopy, small angle X-ray scattering assay and atomic force microscopy (AFM), showing a hierarchically linear-ordered structure from the nanoscale to the macroscale with a soft elastic character (elasticity ~1 kPa). We found that this low elasticity and aligned topography of AFG exhibit co-effects on promoting the neurogenic differentiation of human umbilical cord mesenchymal stem cells (hUMSCs) in comparison to random fibrin hydrogel (RFG) and tissue culture plate (TCP) control after two week cell culture in growth medium lacking supplementation with soluble neurogenic induction factors. In addition, AFG also induces dorsal root ganglion (DRG) neurons to rapidly project numerous long neurite outgrowths longitudinally along the AFG fibers for a total neurite extension distance of 1.96 mm in three days in the absence of neurotrophic factor supplementation. Moreover, the AFG implanted in a rat T9 dorsal hemisection spinal cord injury model was found to promote endogenous neural cell fast migration and axonal invasion along AFG fibers, resulting in aligned tissue cables in vivo. Our results suggest that matrix stiffness and aligned topography may instruct stem cell neurogenic differentiation and rapid neurite outgrowth, providing great promise for biomaterial design for applications in nerve regeneration.The development of novel biomaterials that deliver precise regulatory signals to

  17. Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation.

    LENUS (Irish Health Repository)

    Whelan, M C

    2012-01-31

    Obstacles to effective immunotherapeutic anti-cancer approaches include poor immunogenicity of the tumour cells and the presence of tolerogenic mechanisms in the tumour microenvironment. We report an effective immune-based treatment of weakly immunogenic, growing solid tumours using a locally delivered immunogene therapy to promote development of immune effector responses in the tumour microenvironment and a systemic based T regulatory cell (Treg) inactivation strategy to potentiate these responses by elimination of tolerogenic or immune suppressor influences. As the JBS fibrosarcoma is weakly immunogenic and accumulates Treg in its microenvironment with progressive growth, we used this tumour model to test our combined immunotherapies. Plasmids encoding GM-CSF and B7-1 were electrically delivered into 100 mm(3) tumours; Treg inactivation was accomplished by systemic administration of anti-CD25 antibody (Ab). Using this approach, we found that complete elimination of tumours was achieved at a level of 60% by immunogene therapy, 25% for Treg inactivation and 90% for combined therapies. Moreover, we found that these responses were immune transferable, systemic, tumour specific and durable. Combined gene-based immune effector therapy and Treg inactivation represents an effective treatment for weakly antigenic solid growing tumours and that could be considered for clinical development.

  18. Tiered Instruction: An Effective Strategy to Differentiation of Instruction

    Directory of Open Access Journals (Sweden)

    Yahya BELER

    2011-08-01

    Full Text Available This study aimed to examine the effects of a tiered instructional design on classroom management, attitude and the learning level of students. The instructional program was prepared for an introductory science course for 3rd grade students. The case study research method was used. Observation form, teacher and student interview forms were used to collect data. The teaching program was planned using a tiered instruction method for nine subjects of the “Yesterday, Today, Tomorrow” curriculum theme. The teacher made a short presentation and then students were classified into ability groups. Finally, each group completed learning activity via individual and group tasks based on activities appropriate to their abilities. The results indicate that tiered instruction had positive effects on the learning outcomes of students. All groups completed the classroom activities easily, which increased their motivation. Students participated in activities voluntarily and enthusiastically.

  19. Differential effects of stress and glucocorticoids on adult neurogenesis.

    Science.gov (United States)

    Schoenfeld, Timothy J; Gould, Elizabeth

    2013-01-01

    Stress is known to inhibit neuronal growth in the hippocampus. In addition to reducing the size and complexity of the dendritic tree, stress and elevated glucocorticoid levels are known to inhibit adult neurogenesis. Despite the negative effects of stress hormones on progenitor cell proliferation in the hippocampus, some experiences which produce robust increases in glucocorticoid levels actually promote neuronal growth. These experiences, including running, mating, enriched environment living, and intracranial self-stimulation, all share in common a strong hedonic component. Taken together, the findings suggest that rewarding experiences buffer progenitor cells in the dentate gyrus from the negative effects of elevated stress hormones. This chapter considers the evidence that stress and glucocorticoids inhibit neuronal growth along with the paradoxical findings of enhanced neuronal growth under rewarding conditions with a view toward understanding the underlying biological mechanisms.

  20. Gender-Differentiated Language and Effective Inter-gender Communication

    Institute of Scientific and Technical Information of China (English)

    HUANG Bing

    2014-01-01

    This paper discusses firstly the main differences between men’s and women’s speech in everyday communication among English native speakers, and then analyses the effects on inter-gender communication. It reduces English learners in China barriers when they communicate with English native speakers in different situations and gives domestic English teachers some en-lightenment when they foster students’communication competence.