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  1. Mycophenolic acid induces ATP-binding cassette transporter A1 (ABCA1) expression through the PPAR{gamma}-LXR{alpha}-ABCA1 pathway

    SciTech Connect

    Xu, Yanni; Lai, Fangfang; Xu, Yang

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Using an ABCA1p-LUC HepG2 cell line, we found that MPA upregulated ABCA1 expression. Black-Right-Pointing-Pointer MPA induced ABCA1 and LXR{alpha} protein expression in HepG2 cells. Black-Right-Pointing-Pointer PPAR{gamma} antagonist GW9662 markedly inhibited MPA-induced ABCA1 and LXR{alpha} protein expression. Black-Right-Pointing-Pointer The effect of MPA upregulating ABCA1 was due mainly to activation of the PPAR{gamma}-LXR{alpha}-ABCA1 pathway. -- Abstract: ATP-binding cassette transporter A1 (ABCA1) promotes cholesterol and phospholipid efflux from cells to lipid-poor apolipoprotein A-I and plays an important role in atherosclerosis. In a previous study, we developed a high-throughput screening method using an ABCA1p-LUC HepG2 cell line to find upregulators of ABCA1.more » Using this method in the present study, we found that mycophenolic acid (MPA) upregulated ABCA1 expression (EC50 = 0.09 {mu}M). MPA upregulation of ABCA1 expression was confirmed by real-time quantitative reverse transcription-PCR and Western blot analysis in HepG2 cells. Previous work has indicated that MPA is a potent agonist of peroxisome proliferator-activated receptor gamma (PPAR{gamma}; EC50 = 5.2-9.3 {mu}M). Liver X receptor {alpha} (LXR{alpha}) is a target gene of PPAR{gamma} and may directly regulate ABCA1 expression. Western blot analysis showed that MPA induced LXR{alpha} protein expression in HepG2 cells. Addition of PPAR{gamma} antagonist GW9662 markedly inhibited MPA-induced ABCA1 and LXR{alpha} protein expression. These data suggest that MPA increased ABCA1 expression mainly through activation of PPAR{gamma}. Thus, the effects of MPA on upregulation of ABCA1 expression were due mainly to activation of the PPAR{gamma}-LXR{alpha}-ABCA1 signaling pathway. This is the first report that the antiatherosclerosis activity of MPA is due to this mechanism.« less

  2. Purification and ATPase activity of human ABCA1.

    PubMed

    Takahashi, Kei; Kimura, Yasuhisa; Kioka, Noriyuki; Matsuo, Michinori; Ueda, Kazumitsu

    2006-04-21

    ATP-binding cassette protein A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein metabolism. Apolipoprotein A-I binds to ABCA1 and cellular cholesterol and phospholipids, mainly phosphatidylcholine, are loaded onto apoA-I to form pre-beta high density lipoprotein (HDL). It is proposed that ABCA1 translocates phospholipids and cholesterol directly or indirectly to form pre-beta HDL. To explore the mechanism of ABCA1-mediated pre-beta HDL formation, we expressed human ABCA1 in insect Sf9 cells and purified it. Trypsin limited-digestion of purified ABCA1 in the detergent-soluble form suggested that it retained conformation similar to ABCA1 expressed in the membranes of human fibroblast WI-38 cells. Purified ABCA1 showed robust ATPase activity when reconstituted in liposomes made of synthetic phosphatidylcholine. ABCA1 showed lower ATPase activity when reconstituted in liposomes containing phosphatidylserine, phosphatidylethanolamine, or phosphatidylglycerol and also showed weak specificity in acyl chain species. ATPase activity was reduced by the addition of cholesterol and decreased by 25% in the presence of 20% cholesterol. Beta-sitosterol and campesterol showed similar inhibitory effects but stigmasterol did not, suggesting structure-specific interaction between ABCA1 and sterols. Glibenclamide suppressed ABCA1 ATPase, suggesting that it inhibits apoA-I-dependent cellular cholesterol efflux by suppressing ABCA1 ATPase activity. These results suggest that the ATPase activity of ABCA1 is stimulated preferentially by phospholipids with choline head groups, phosphatidylcholine and sphingomyelin. This study with purified human ABCA1 provides the first biochemical basis of the mechanism for HDL formation mediated by ABCA1.

  3. Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells.

    PubMed

    Bared, Salim Maa; Buechler, Christa; Boettcher, Alfred; Dayoub, Rania; Sigruener, Alexander; Grandl, Margot; Rudolph, Christian; Dada, Ashraf; Schmitz, Gerd

    2004-12-01

    The ATP-binding cassette transporter A1 (ABCA1) facilitates the cellular release of cholesterol and choline-phospholipids to apolipoprotein A-I (apoA-I) and several studies indicate that vesicular transport is associated with ABCA1 function. Syntaxins play a major role in vesicular fusion and have also been demonstrated to interact with members of the ABC-transporter family. Therefore, we focused on the identification of syntaxins that directly interact with ABCA1. The expression of syntaxins and ABCA1 in cultured human monocytes during M-CSF differentiation and cholesterol loading was investigated and syntaxins 3, 6, and 13 were found induced in foam cells together with ABCA1. Immunoprecipitation experiments revealed a direct association of syntaxin 13 and full-length ABCA1, whereas syntaxin 3 and 6 failed to interact with ABCA1. The colocalization of ABCA1 and syntaxin 13 was also shown by immunofluorescence microscopy. Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels and hence to a significant decrease in apoA-I-dependent choline-phospholipid efflux. ABCA1 is localized in Lubrol WX-insoluble raft microdomains in macrophages and syntaxin 13 and flotillin-1 were also detected in these detergent resistant microdomains along with ABCA1. Syntaxin 13, flotillin-1, and ABCA1 were identified as phagosomal proteins, indicating the involvement of the phagosomal compartment in ABCA1-mediated lipid efflux. In addition, the uptake of latex phagobeads by fibroblasts with mutated ABCA1 was enhanced when compared with control cells and the recombinant expression of functional ABCA1 normalized the phagocytosis rate in Tangier fibroblasts. It is concluded that ABCA1 forms a complex with syntaxin 13 and flotillin-1, residing at the plasma membrane and in phagosomes that are partially located in raft microdomains.

  4. Association of ABCA1 with Syntaxin 13 and Flotillin-1 and Enhanced Phagocytosis in Tangier Cells

    PubMed Central

    Bared, Salim Maa; Buechler, Christa; Boettcher, Alfred; Dayoub, Rania; Sigruener, Alexander; Grandl, Margot; Rudolph, Christian; Dada, Ashraf; Schmitz, Gerd

    2004-01-01

    The ATP-binding cassette transporter A1 (ABCA1) facilitates the cellular release of cholesterol and choline-phospholipids to apolipoprotein A-I (apoA-I) and several studies indicate that vesicular transport is associated with ABCA1 function. Syntaxins play a major role in vesicular fusion and have also been demonstrated to interact with members of the ABC-transporter family. Therefore, we focused on the identification of syntaxins that directly interact with ABCA1. The expression of syntaxins and ABCA1 in cultured human monocytes during M-CSF differentiation and cholesterol loading was investigated and syntaxins 3, 6, and 13 were found induced in foam cells together with ABCA1. Immunoprecipitation experiments revealed a direct association of syntaxin 13 and full-length ABCA1, whereas syntaxin 3 and 6 failed to interact with ABCA1. The colocalization of ABCA1 and syntaxin 13 was also shown by immunofluorescence microscopy. Silencing of syntaxin 13 by small interfering RNA (siRNA) led to reduced ABCA1 protein levels and hence to a significant decrease in apoA-I–dependent choline-phospholipid efflux. ABCA1 is localized in Lubrol WX–insoluble raft microdomains in macrophages and syntaxin 13 and flotillin-1 were also detected in these detergent resistant microdomains along with ABCA1. Syntaxin 13, flotillin-1, and ABCA1 were identified as phagosomal proteins, indicating the involvement of the phagosomal compartment in ABCA1-mediated lipid efflux. In addition, the uptake of latex phagobeads by fibroblasts with mutated ABCA1 was enhanced when compared with control cells and the recombinant expression of functional ABCA1 normalized the phagocytosis rate in Tangier fibroblasts. It is concluded that ABCA1 forms a complex with syntaxin 13 and flotillin-1, residing at the plasma membrane and in phagosomes that are partially located in raft microdomains. PMID:15469992

  5. ABCA1 and biogenesis of HDL.

    PubMed

    Yokoyama, Shinji

    2006-02-01

    Mammalian somatic cells do not catabolize cholesterol and therefore export it for sterol homeostasis at cell and whole body levels. This mechanism may reduce intracellularly accumulated excess cholesterol, and thereby would contribute to the prevention or cure of the initial stage of atherosclerotic vascular lesion. High-density lipoprotein (HDL) plays a central role in this reaction by removing cholesterol from cells and transporting it to the liver, the major cholesterol catabolic site. Two independent mechanisms have been identified for cellular cholesterol release. The first is non-specific diffusion-mediated cholesterol "efflux" from the cell surface, in which cholesterol is trapped by various extracellular acceptors including lipoproteins. Extracellular cholesterol esterification of HDL provides a driving force for the net removal of cell cholesterol by this pathway, and some cellular factors may enhance this reaction. The other mechanism is an apolipoprotein-mediated process to generate new HDL particles by removing cellular phospholipid and cholesterol. This reaction is mediated by a membrane protein ATP-binding cassette transporter A1 (ABCA1), and lipid-free or lipid-poor helical apolipoproteins recruit cellular phospholipid and cholesterol to assemble HDL particles. The reaction is composed of two elements: the assembly of HDL particles with phospholipid by apolipoprotein, and cholesterol enrichment in HDL. ABCA1 is essential for the former step and the latter requires further intracellular events. ABCA1 is a rate-limiting factor of HDL assembly and is regulated by transcriptional and post-transcriptional factors. Post-transcriptional regulation of ABCA1 involves modulation of its calpain-mediated degradation.

  6. Seminal Plasma Characteristics and Expression of ATP-binding Cassette Transporter A1 (ABCA1) in Canine Spermatozoa from Ejaculates with Good and Bad Freezability.

    PubMed

    Schäfer-Somi, S; Palme, N

    2016-04-01

    The composition of seminal plasma and the localization of the ATP-binding cassette transporter A1 (ABCA1) in spermatozoa from good and bad freezers were compared to frozen-thawed spermatozoa from the same dog. Ejaculates were obtained from 31 stud dogs, and the sperm-rich fraction (SRF) was kept for analysis. One aliquot was used for the analysis of concentration, progressive motility (P; CASA), viability (V; CASA) and leucocyte count, and the analysis was performed by flow cytometry (FITC-PNA/PI), SCSA and HOST. In seminal plasma, concentration of albumin, cholesterol, calcium, inorganic phosphate, sodium, potassium, zinc and copper was measured. Semen smears were prepared and evaluated for the expression of ABCA1. The remainder of each ejaculate was frozen. After thawing, the quality assessment was repeated and further smears were prepared. According to post-thaw semen quality, dogs were assigned to good freezers (n = 20) or bad freezers (n = 11), the latter were defined as < 50% progressive motility and/or > 40% morphologically abnormal sperm and/or < 50% viability. Bad freezers were older than good freezers (5.3 vs 3.4 years, p < 0.05). In bad freezers, the percentage of sperm with ABCA1 signal in the acrosome was lower (26.3% vs 35.7%, p < 0.01) and the percentage of sperm with complete loss of ABCA1 signal higher (46.7% vs 30%, p < 0.01); the percentage of dead spermatozoa was higher (36.1% vs 25.5%, p < 0.05), and the concentration of cholesterol and sodium in seminal plasma was lower than in good freezers (p < 0.05). We conclude that in thawed bad freezer sperm, an increase in acrosome damages coincided with an increased loss of cholesterol transporters and cell death, and a lower cholesterol concentration in seminal plasma. Follow-up studies revealed whether a relation exists between these findings. © 2016 Blackwell Verlag GmbH.

  7. Deficiency in the Lipid Exporter ABCA1 Impairs Retrograde Sterol Movement and Disrupts Sterol Sensing at the Endoplasmic Reticulum*♦

    PubMed Central

    Yamauchi, Yoshio; Iwamoto, Noriyuki; Rogers, Maximillian A.; Abe-Dohmae, Sumiko; Fujimoto, Toyoshi; Chang, Catherine C. Y.; Ishigami, Masato; Kishimoto, Takuma; Kobayashi, Toshihide; Ueda, Kazumitsu; Furukawa, Koichi; Chang, Ta-Yuan; Yokoyama, Shinji

    2015-01-01

    Cellular cholesterol homeostasis involves sterol sensing at the endoplasmic reticulum (ER) and sterol export from the plasma membrane (PM). Sterol sensing at the ER requires efficient sterol delivery from the PM; however, the macromolecules that facilitate retrograde sterol transport at the PM have not been identified. ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol and phospholipid export to apolipoprotein A-I for the assembly of high density lipoprotein (HDL). Mutations in ABCA1 cause Tangier disease, a familial HDL deficiency. Several lines of clinical and experimental evidence suggest a second function of ABCA1 in cellular cholesterol homeostasis in addition to mediating cholesterol efflux. Here, we report the unexpected finding that ABCA1 also plays a key role in facilitating retrograde sterol transport from the PM to the ER for sterol sensing. Deficiency in ABCA1 delays sterol esterification at the ER and activates the SREBP-2 cleavage pathway. The intrinsic ATPase activity in ABCA1 is required to facilitate retrograde sterol transport. ABCA1 deficiency causes alternation of PM composition and hampers a clathrin-independent endocytic activity that is required for ER sterol sensing. Our finding identifies ABCA1 as a key macromolecule facilitating bidirectional sterol movement at the PM and shows that ABCA1 controls retrograde sterol transport by modulating a certain clathrin-independent endocytic process. PMID:26198636

  8. ABCA1 agonist peptides for the treatment of disease

    DOE PAGES

    Bielicki, John K.

    2016-02-01

    Purpose of review The review summarizes information pertaining to the preclinical development of new apolipoprotein (apo) E mimetic peptides that stimulate cellular cholesterol efflux. Recent findings Small α-helical peptides based on the C-terminal domain of apoE have been developed for therapeutic applications. These peptides stimulate cellular cholesterol efflux via the ATP-binding cassette transporter A1 (ABCA1) with high potency, like native apolipoproteins on a molar basis. This potent activity has been related to the unique ability of these peptides to maintain α-helix structure upon dilution. Recent structure-activity studies improving the safety features of these mimetic peptides have greatly improved their potentialmore » for clinical use. Structural features of the class A α-helix motif that induce muscle toxicity and hypertriglyceridemia have been identified. These may have implications for the design of other HDL mimetic peptides. Summary ABCA1 is an integral membrane protein that plays a central role in biology. Its principal function is to mediate the efflux of cholesterol and phospholipid from cells to extracellular apo, preventing a build-up of excess cholesterol in membranes. This process generates HDL particles that perform a variety of functions to protect against disease. A number of these functions can be viewed as directly or indirectly supporting ABCA1 activity, thus constituting a positive feedback system to optimize cellular lipid efflux responses and disease prevention. Consequently, therapeutic approaches that mimic the activities of apos may prove highly effective to combat disease. One such approach involves the use of peptides. The broad biological relevance of ABCA1 suggests these apo mimetic peptides may be useful for the treatment of a number of diseases, such as atherosclerosis, diabetes, and Alzheimer's disease.« less

  9. ABCA1 agonist peptides for the treatment of disease

    SciTech Connect

    Bielicki, John K.

    Purpose of review The review summarizes information pertaining to the preclinical development of new apolipoprotein (apo) E mimetic peptides that stimulate cellular cholesterol efflux. Recent findings Small α-helical peptides based on the C-terminal domain of apoE have been developed for therapeutic applications. These peptides stimulate cellular cholesterol efflux via the ATP-binding cassette transporter A1 (ABCA1) with high potency, like native apolipoproteins on a molar basis. This potent activity has been related to the unique ability of these peptides to maintain α-helix structure upon dilution. Recent structure-activity studies improving the safety features of these mimetic peptides have greatly improved their potentialmore » for clinical use. Structural features of the class A α-helix motif that induce muscle toxicity and hypertriglyceridemia have been identified. These may have implications for the design of other HDL mimetic peptides. Summary ABCA1 is an integral membrane protein that plays a central role in biology. Its principal function is to mediate the efflux of cholesterol and phospholipid from cells to extracellular apo, preventing a build-up of excess cholesterol in membranes. This process generates HDL particles that perform a variety of functions to protect against disease. A number of these functions can be viewed as directly or indirectly supporting ABCA1 activity, thus constituting a positive feedback system to optimize cellular lipid efflux responses and disease prevention. Consequently, therapeutic approaches that mimic the activities of apos may prove highly effective to combat disease. One such approach involves the use of peptides. The broad biological relevance of ABCA1 suggests these apo mimetic peptides may be useful for the treatment of a number of diseases, such as atherosclerosis, diabetes, and Alzheimer's disease.« less

  10. Cellular Cholesterol Accumulation Facilitates Ubiquitination and Lysosomal Degradation of Cell Surface-Resident ABCA1.

    PubMed

    Mizuno, Tadahaya; Hayashi, Hisamitsu; Kusuhara, Hiroyuki

    2015-06-01

    By excreting cellular cholesterol to apolipoprotein A-I, ATP-binding cassette transporter A1 (ABCA1) mediates the biogenesis of high-density lipoprotein in hepatocytes and prevents foam cell formation from macrophages. We recently showed that cell surface-resident ABCA1 (csABCA1) undergoes ubiquitination and later lysosomal degradation through the endosomal sorting complex required for transport system. Herein, we investigated the relevance of this degradation pathway to the turnover of csABCA1 in hypercholesterolemia. Immunoprecipitation and cell surface-biotinylation studies with HepG2 cells and mouse peritoneal macrophages showed that the ubiquitination level and degradation of csABCA1 were facilitated by treatment with a liver X receptor (LXR) agonist and acetylated low-density lipoprotein. The effects of an LXR agonist and acetylated low-density lipoprotein on the degradation of csABCA1 were repressed completely by treatment with bafilomycin, an inhibitor of lysosomal degradation, and by depletion of tumor susceptibility gene 101, a major component of endosomal sorting complex required for transport-I. RNAi analysis indicated that LXRβ inhibited the accelerated lysosomal degradation of csABCA1 by the LXR agonist, regardless of its transcriptional activity. Cell surface coimmunoprecipitation with COS1 cells expressing extracellularly hemagglutinin-tagged ABCA1 showed that LXRβ interacted with csABCA1 and inhibited the ubiquitination of csABCA1. Immunoprecipitates with anti-ABCA1 antibodies from the liver plasma membranes showed less LXRβ and a higher ubiquitination level of ABCA1 in high-fat diet-fed mice than in normal chow-fed mice. Under conditions of high cellular cholesterol content, csABCA1 became susceptible to ubiquitination by dissociation of LXRβ from csABCA1, which facilitated the lysosomal degradation of csABCA1 through the endosomal sorting complex required for transport system. © 2015 American Heart Association, Inc.

  11. ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity.

    PubMed

    de Haan, Willeke; Bhattacharjee, Alpana; Ruddle, Piers; Kang, Martin H; Hayden, Michael R

    2014-03-01

    Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. ABCA1 plays a major role in cholesterol efflux, suggesting a role for ABCA1 in maintaining cholesterol homeostasis in the adipocyte. However, the impact of adipocyte ABCA1 on adipose tissue function and glucose metabolism is unknown. Our aim was to determine the impact of adipocyte ABCA1 on adipocyte lipid metabolism, body weight, and glucose metabolism in vivo. To address this, we used mice lacking ABCA1 specifically in adipocytes (ABCA1(-ad/-ad)). When fed a high-fat, high-cholesterol diet, ABCA1(-ad/-ad) mice showed increased cholesterol and triglyceride stores in adipose tissue, developed enlarged fat pads, and had increased body weight. Associated with these phenotypic changes, we observed significant changes in the expression of genes involved in cholesterol and glucose homeostasis, including ldlr, abcg1, glut-4, adiponectin, and leptin. ABCA1(-ad/-ad) mice also demonstrated impaired glucose tolerance, lower insulin sensitivity, and decreased insulin secretion. We conclude that ABCA1 in adipocytes influences adipocyte lipid metabolism, body weight, and whole-body glucose homeostasis.

  12. ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity[S

    PubMed Central

    de Haan, Willeke; Bhattacharjee, Alpana; Ruddle, Piers; Kang, Martin H.; Hayden, Michael R.

    2014-01-01

    Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. ABCA1 plays a major role in cholesterol efflux, suggesting a role for ABCA1 in maintaining cholesterol homeostasis in the adipocyte. However, the impact of adipocyte ABCA1 on adipose tissue function and glucose metabolism is unknown. Our aim was to determine the impact of adipocyte ABCA1 on adipocyte lipid metabolism, body weight, and glucose metabolism in vivo. To address this, we used mice lacking ABCA1 specifically in adipocytes (ABCA1−ad/−ad). When fed a high-fat, high-cholesterol diet, ABCA1−ad/−ad mice showed increased cholesterol and triglyceride stores in adipose tissue, developed enlarged fat pads, and had increased body weight. Associated with these phenotypic changes, we observed significant changes in the expression of genes involved in cholesterol and glucose homeostasis, including ldlr, abcg1, glut-4, adiponectin, and leptin. ABCA1−ad/−ad mice also demonstrated impaired glucose tolerance, lower insulin sensitivity, and decreased insulin secretion. We conclude that ABCA1 in adipocytes influences adipocyte lipid metabolism, body weight, and whole-body glucose homeostasis. PMID:24443560

  13. Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults

    PubMed Central

    2013-01-01

    Background In a marker-trait association study we estimated the statistical significance of 65 single nucleotide polymorphisms (SNP) in 23 candidate genes on HDL levels of two independent Caucasian populations. Each population consisted of men and women and their HDL levels were adjusted for gender and body weight. We used a linear regression model. Selected genes corresponded to folate metabolism, vitamins B-12, A, and E, and cholesterol pathways or lipid metabolism. Methods Extracted DNA from both the Sacramento and Beltsville populations was analyzed using an allele discrimination assay with a MALDI-TOF mass spectrometry platform. The adjusted phenotype, y, was HDL levels adjusted for gender and body weight only statistical analyses were performed using the genotype association and regression modules from the SNP Variation Suite v7. Results Statistically significant SNP (where P values were adjusted for false discovery rate) included: CETP (rs7499892 and rs5882); SLC46A1 (rs37514694; rs739439); SLC19A1 (rs3788199); CD36 (rs3211956); BCMO1 (rs6564851), APOA5 (rs662799), and ABCA1 (rs4149267). Many prior association trends of the SNP with HDL were replicated in our cross-validation study. Significantly, the association of SNP in folate transporters (SLC46A1 rs37514694 and rs739439; SLC19A1 rs3788199) with HDL was identified in our study. Conclusions Given recent literature on the role of niacin in the biogenesis of HDL, focus on status and metabolism of B-vitamins and metabolites of eccentric cleavage of β-carotene with lipid metabolism is exciting for future study. PMID:23656756

  14. The R230C variant of the ATP binding cassette protein A1 (ABCA1) gene is associated with a decreased response to glyburide therapy in patients with type 2 diabetes mellitus.

    PubMed

    Aguilar-Salinas, Carlos A; Muñoz-Hernandez, Linda Liliana; Cobos-Bonilla, Monica; Ramírez-Márquez, Marcos Rafael; Ordoñez-Sanchez, Maria Luisa; Mehta, Roopa; Medina-Santillan, Roberto; Tusie-Luna, Maria Teresa

    2013-05-01

    To test the hypothesis that persons with the R230C allele of ABCA1 show a decreased glycemic response to glyburide. This polymorphism is exclusively found in Ameri-indian populations and is associated with type 2 diabetes. This is a single blind controlled study including participants with type 2 diabetes (fasting glucose levels 126-250 mg/dl and HbA1c 7%-10%) managed with metformin and a lifestyle program. Each person with the risk allele (R230C) was matched by age, gender and BMI to three others with the wild type variant (R230R). Following a four week stabilization period, only participants with a greater than 70% adherence to metformin and a stable body weight were prescribed glyburide therapy for a further 16 weeks. The main outcome variable was the glyburide dose required to achieve treatment goals. No significant difference was observed in the glucose lowering effect of glyburide between subjects with the R230C and R230R alleles. However, the dose of sulfonylurea was significantly higher in the R230C participants compared with the R230R subjects (3.3±2.1 vs 6.3±5 mg/day, p<0.001). A higher percentage of R230C participants required at least 5mg of glyburide per day to achieve treatment goals. The glyburide dose was determined by the presence of the risk allele, among other factors. Patients with type 2 diabetes who have the R230C allele of ABCA1 needed a higher dose of glyburide in order to achieve the same glucose lowering effect as that in persons with the wild type variant. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein modulates ABCA1 trafficking and function

    PubMed Central

    Lin, Sisi; Zhou, Chun; Neufeld, Edward; Wang, Yu-Hua; Xu, Suo-Wen; Lu, Liang; Wang, Ying; Liu, Zhi-Ping; Li, Dong; Li, Cuixian; Chen, Shaorui; Le, Kang; Huang, Heqing; Liu, Peiqing; Moss, Joel; Vaughan, Martha; Shen, Xiaoyan

    2013-01-01

    Objective Cell surface localization and intracellular trafficking of ATP-binding cassette transporter A-1 (ABCA1) are essential for its function. However, regulation of these activities is still largely unknown. Brefeldin A (BFA), a uncompetitive inhibitor of brefeldin A-inhibited guanine nucleotide-exchange proteins (BIGs), disturbs the intracellular distribution of ABCA1, and thus inhibits cholesterol efflux. This study aimed to define the possible roles of BIGs in regulating ABCA1 trafficking and cholesterol efflux, and further to explore the potential mechanism. Methods and Results By vesicle immunoprecipitation, we found that BIG1 was associated with ABCA1 in vesicles preparation from rat liver. BIG1 depletion reduced surface ABCA1 on HepG2 cells and inhibited by 60% cholesterol release. In contrast, BIG1 over-expression increased surface ABCA1 and cholesterol secretion. With partial restoration of BIG1 through over-expression in BIG1-depleted cells, surface ABCA1 was also restored. Biotinylation and glutathione cleavage revealed that BIG1 siRNA dramatically decreased the internalization and recycling of ABCA1. This novel function of BIG1 was dependent on the guanine nucleotide-exchange activity and achieved through activation of ADP-ribosylation factor 1 (ARF1). Conclusions BIG1, through its ability to activate ARF1, regulates cell surface levels and function of ABCA1, indicating a transcription-independent mechanism for controlling ABCA1 action. PMID:23220274

  16. Functional rescue of mutant ABCA1 proteins by sodium 4-phenylbutyrate.

    PubMed

    Sorrenson, Brie; Suetani, Rachel J; Williams, Michael J A; Bickley, Vivienne M; George, Peter M; Jones, Gregory T; McCormick, Sally P A

    2013-01-01

    Mutations in the ATP-binding cassette transporter A1 (ABCA1) are a major cause of decreased HDL cholesterol (HDL-C), which infers an increased risk of cardiovascular disease (CVD). Many ABCA1 mutants show impaired localization to the plasma membrane. The aim of this study was to investigate whether the chemical chaperone, sodium 4-phenylbutyrate (4-PBA) could improve cellular localization and function of ABCA1 mutants. Nine different ABCA1 mutants (p.A594T, p.I659V, p.R1068H, p.T1512M, p.Y1767D, p.N1800H, p.R2004K, p.A2028V, p.Q2239N) expressed in HEK293 cells, displaying different degrees of mislocalization to the plasma membrane and discrete impacts on cholesterol efflux, were subject to treatment with 4-PBA. Treatment restored localization to the plasma membrane and increased cholesterol efflux function for the majority of mutants. Treatment with 4-PBA also increased ABCA1 protein expression in all transfected cell lines. In fibroblast cells obtained from low HDL-C subjects expressing two of the ABCA1 mutants (p.R1068H and p.N1800H), 4-PBA increased cholesterol efflux without any increase in ABCA1 expression. Our study is the first to investigate the effect of the chemical chaperone, 4-PBA on ABCA1 and shows that it is capable of restoring plasma membrane localization and enhancing the cholesterol efflux function of mutant ABCA1s both in vitro and ex vivo. These results suggest 4-PBA may warrant further investigation as a potential therapy for increasing cholesterol efflux and HDL-C levels.

  17. Gender-specific association of ATP-binding cassette transporter 1 (ABCA1) polymorphisms with the risk of late-onset Alzheimer's disease.

    PubMed

    Sundar, Purnima Desai; Feingold, Eleanor; Minster, Ryan L; DeKosky, Steven T; Kamboh, M Ilyas

    2007-06-01

    Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder caused by a complex interaction of genetic and environmental factors. Increasing evidence highlights a potential role for cholesterol in the pathophysiology of AD. The ABCA1 gene, located in close vicinity to the 9q linkage peaks identified by genome-wide AD linkage studies, plays an important role in cellular cholesterol efflux, and is likely a good candidate gene. However, results from published genetic association studies between ABCA1 and AD are ambiguous. In the present study, we examined the role of two ABCA1 polymorphisms, R219K (rs2230806) and G-17C (rs2740483) in modifying the risk of late-onset AD (LOAD) in a large American white cohort of 992 AD cases and 699 controls. We observed significant gender x R219K interaction (p=0.00008). Female carriers of the 219K allele showed a 1.75-fold increased risk of developing AD compared to non-219K carrier females (95% CI 1.34-2.29; p=0.00004). The overall two-site haplotype distribution was also significant between female AD cases and controls (p=0.017). The risk associated with the R219K polymorphism was independent of the recently reported significant association in the ubiquilin (UBQLN1) gene in this region on chromosome 9q. Our data suggest a gender-specific and APOE and UBQLN1 independent association between the ABCA1/R219K polymorphism and LOAD.

  18. Evaluation of the Association Between Common Genetic Variants Near the ABCA1 Gene and Primary Angle Closure Glaucoma in a Han Chinese Population.

    PubMed

    Luo, Huaichao; Chen, Yuhong; Ye, Zimeng; Sun, Xinghuai; Shi, Yi; Luo, Qian; Gong, Bo; Shuai, Ping; Yang, Jiyun; Zhou, Yu; Liu, Xiaoqi; Zhang, Kaijiong; Tan, Chang; Li, Yuanfeng; Lin, Ying; Yang, Zhenglin

    2015-10-01

    Recently, three large genome-wide association studies have identified multiple variants associated with primary open angle glaucoma (POAG) near the ABCA1 gene. Considering that POAG and primary angle closure glaucoma (PACG) share many similar clinical manifestations, the present study was conducted to investigate whether these genetic variants were also associated with PACG in a Han Chinese population. A case-control association study of 1122 cases (PACG/PAC) and 1311 normal, matched controls was undertaken. Seven single-nucleotide polymorphisms (SNPs) near the ABCA1 gene, including rs2422493, rs2487042, rs2472496, rs2472493, rs2487032, rs2472459, and rs2472519, were genotyped. Genotype and allele frequencies were assessed using χ² tests. Linkage disequilibrium (LD) structure was analyzed by computer software. Among the SNPs genotyped, no association was observed between these SNPs and PACG. However, we discovered that two haplotypes, CATTTAC (corrected P = 0.048) and CGCCCGC (corrected P = 0.048), remained significantly associated with PACG/PAC after Bonferroni correction. Subjects with the CATTTAC haplotype have a 1.71-fold increased possibility of having PACG/PAC, whereas subjects with the CGCCCGC haplotype have 0.47-fold decreased possibility of developing PACG. Our findings suggest that the genetic backgrounds of PACG and POAG might be different. However, whether or not ABCA1 plays a role in the development of PACG is still not made certain by this study. Thus, further research is needed to find the role of ABCA1 in the progress of PACG.

  19. Differences in ABCA1 R219K Polymorphisms and Serum Indexes in Alzheimer and Parkinson Diseases in Northern China

    PubMed Central

    Ya, Lagai; Lu, Zuneng

    2017-01-01

    Background ABCA1 R219K single-nucleotide polymorphisms (SNPs) was related to Alzheimer disease (AD) but not Parkinson disease (PD). Here, we analyzed the associations among ABCA1 R219K distribution, serum biomarkers, AD, and PD in a population in northern China. Material/Methods We used the Mini-Mental State Examination (MMSE) and the Hoehn and Yahr scale (H-Y) to evaluate AD and PD progression, separately. ABCA1 R219K was analyzed by matrix-assisted laser desorption ionization time of flight time mass spectrometry (MALDI-TOF-MS). Serum indexes were determined by enzyme-linked immunosorbent assay (ELISA). Results ABCA1 R219K RR+RK genotype frequency in AD and PD patients was lower than that in normal controls (NC), while ABCA1 R219K KK genotype frequency was significantly higher. ABCA1 R219K RR genotype frequency in AD patients and NC was lower than that in PD patients, while ABCA1 R219K RK+KK genotype frequency was significantly higher. ABCA1 R219K RR genotype was positively correlated to MMSE value in AD patients, while ABCA1 R219K KK genotype was negatively correlated to H-Y value in PD patients. Serum factors were significantly different among AD and PD patients and NC. Serum ABCA1, ApoA1, ApoA2, ApoB, HDL, TC, IL-1β, IL-6, and TNF-α were significantly different between AD and PD patients. Conclusions ABCA1 R219K R allele was the risk factor inducing abnormal serum levels of ApoA2, LDL, and TG in AD patients, and abnormal levels of serum ABCA1, HDL, IL-1β, IL-6, and TNF-α in PD patients, while ABCA1 R219K K allele was the risk factor inducing lower ABCA1 in AD patients. IL-1β, IL-6, and TNF-α were negatively correlated to MMSE in AD patients but positively correlated to H-Y in PD patients, while HDL was positively related to H-Y in PD patients. PMID:28943632

  20. Differences in ABCA1 R219K Polymorphisms and Serum Indexes in Alzheimer and Parkinson Diseases in Northern China.

    PubMed

    Ya, Lagai; Lu, Zuneng

    2017-09-25

    BACKGROUND ABCA1 R219K single-nucleotide polymorphisms (SNPs) was related to Alzheimer disease (AD) but not Parkinson disease (PD). Here, we analyzed the associations among ABCA1 R219K distribution, serum biomarkers, AD, and PD in a population in northern China. MATERIAL AND METHODS We used the Mini-Mental State Examination (MMSE) and the Hoehn and Yahr scale (H-Y) to evaluate AD and PD progression, separately. ABCA1 R219K was analyzed by matrix-assisted laser desorption ionization time of flight time mass spectrometry (MALDI-TOF-MS). Serum indexes were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS ABCA1 R219K RR+RK genotype frequency in AD and PD patients was lower than that in normal controls (NC), while ABCA1 R219K KK genotype frequency was significantly higher. ABCA1 R219K RR genotype frequency in AD patients and NC was lower than that in PD patients, while ABCA1 R219K RK+KK genotype frequency was significantly higher. ABCA1 R219K RR genotype was positively correlated to MMSE value in AD patients, while ABCA1 R219K KK genotype was negatively correlated to H-Y value in PD patients. Serum factors were significantly different among AD and PD patients and NC. Serum ABCA1, ApoA1, ApoA2, ApoB, HDL, TC, IL-1β, IL-6, and TNF-α were significantly different between AD and PD patients. CONCLUSIONS ABCA1 R219K R allele was the risk factor inducing abnormal serum levels of ApoA2, LDL, and TG in AD patients, and abnormal levels of serum ABCA1, HDL, IL-1b, IL-6, and TNF-α in PD patients, while ABCA1 R219K K allele was the risk factor inducing lower ABCA1 in AD patients. IL-1β, IL-6, and TNF-α were negatively correlated to MMSE in AD patients but positively correlated to H-Y in PD patients, while HDL was positively related to H-Y in PD patients.

  1. Pim-1L Protects Cell Surface-Resident ABCA1 From Lysosomal Degradation in Hepatocytes and Thereby Regulates Plasma High-Density Lipoprotein Level.

    PubMed

    Katsube, Akira; Hayashi, Hisamitsu; Kusuhara, Hiroyuki

    2016-12-01

    ATP-binding cassette transporter A1 (ABCA1) exerts an atheroprotective action through the biogenesis of high-density lipoprotein in hepatocytes and prevents the formation of foam cells from macrophages. Controlling ABCA1 is a rational approach to improving atherosclerotic cardiovascular disease. Although much is known about the regulatory mechanism of ABCA1 synthesis, the molecular mechanism underpinning its degradation remains to be clearly described. ABCA1 possesses potential sites of phosphorylation by serine/threonine-protein kinase Pim-1 (Pim-1). Pim-1 depletion decreased the expression of cell surface-resident ABCA1 (csABCA1) and apolipoprotein A-I-mediated [ 3 H]cholesterol efflux in the human hepatoma cell line HepG2, but not in peritoneal macrophages from mice. In vitro kinase assay, immunoprecipitation, and immunocytochemistry suggested phosphorylation of csABCA1 by the long form of Pim-1 (Pim-1L). Cell surface biotinylation indicated that Pim-1L inhibited lysosomal degradation of csABCA1 involving the liver X receptor β, which interacts with csABCA1 and thereby protects it from ubiquitination and subsequent lysosomal degradation. Cell surface coimmunoprecipitation with COS-1 cells expressing extracellularly hemagglutinin-tagged ABCA1 showed that Pim-1L-mediated phosphorylation of csABCA1 facilitated the interaction between csABCA1 and liver X receptor β and thereby stabilized the csABCA1-Pim-1L complex. Mice deficient in Pim-1 kinase activity showed lower expression of ABCA1 in liver plasma membranes and lower plasma high-density lipoprotein levels than control mice. Pim-1L protects hepatic csABCA1 from lysosomal degradation by facilitating the physical interaction between csABCA1 and liver X receptor β and subsequent stabilization of the csABCA1-Pim-1L complex and thereby regulates the circulating level of high-density lipoprotein. Our findings may aid the development of high-density lipoprotein-targeted therapy. © 2016 American Heart Association

  2. Modulation of ABCA1 by an LXR Agonist Reduces Beta-Amyloid Levels and Improves Outcome after Traumatic Brain Injury

    PubMed Central

    Loane, David J.; Washington, Patricia M.; Vardanian, Lilit; Pocivavsek, Ana; Hoe, Hyang-Sook; Duff, Karen E.; Cernak, Ibolja; Rebeck, G. William; Faden, Alan I.

    2011-01-01

    Abstract Traumatic brain injury (TBI) increases brain beta-amyloid (Aβ) in humans and animals. Although the role of Aβ in the injury cascade is unknown, multiple preclinical studies have demonstrated a correlation between reduced Aβ and improved outcome. Therefore, therapeutic strategies that enhance Aβ clearance may be beneficial after TBI. Increased levels of ATP-binding cassette A1 (ABCA1) transporters can enhance Aβ clearance through an apolipoprotein E (apoE)-mediated pathway. By measuring Aβ and ABCA1 after experimental TBI in C57BL/6J mice, we found that Aβ peaked early after injury (1–3 days), whereas ABCA1 had a delayed response (beginning at 3 days). As ABCA1 levels increased, Aβ levels returned to baseline levels—consistent with the known role of ABCA1 in Aβ clearance. To test if enhancing ABCA1 levels could block TBI-induced Aβ, we treated TBI mice with the liver X-receptor (LXR) agonist T0901317. Pre- and post-injury treatment increased ABCA1 levels at 24 h post-injury, and reduced the TBI-induced increase in Aβ. This reduction in Aβ was not due to decreased amyloid precursor protein processing, or a shift in the solubility of Aβ, indicating enhanced clearance. T0901317 also limited motor coordination deficits in injured mice and reduced brain lesion volume. These data indicate that activation of LXR can reduce Aβ accumulation after TBI, and is accompanied by improved functional recovery. PMID:21175399

  3. Puerarin promotes ABCA1-mediated cholesterol efflux and decreases cellular lipid accumulation in THP-1 macrophages.

    PubMed

    Li, Cong-Hui; Gong, Duo; Chen, Ling-Yan; Zhang, Min; Xia, Xiao-Dan; Cheng, Hai-Peng; Huang, Chong; Zhao, Zhen-Wang; Zheng, Xi-Long; Tang, Xiao-Er; Tang, Chao-Ke

    2017-09-15

    It was reported that puerarin decreases the total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and increases high-density lipoprotein cholesterol (HDL-C) level, but the underlying mechanism is unclear. This study was designed to determine whether puerarin decreased lipid accumulation via up-regulation of ABCA1-mediated cholesterol efflux in THP-1 macrophage-derived foam cells. Our results showed that puerarin significantly promoted the expression of ATP-binding cassette transporter A1 (ABCA1) mRNA and protein via the AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma (PPARγ)-liver X receptor-alpha (LXR-α) pathway and decreased cellular lipid accumulation in human THP-1 macrophage-derived foam cells. The miR-7 directly targeted 3' untranslated region of STK11 (Serine/Threonine Kinase 11), which activated the AMPK pathway. Transfection with miR-7 mimic significantly reduced STK11 expression in puerarin-treated macrophages, decreased the phosphorylation of AMPK, down-regulated the expression of the PPARγ-LXR-α-ABCA1 expression. Additionally, treatment with miR-7 decreased cholesterol efflux and increased cholesterol levels in THP-1 macrophage-derived foam cells. Our study demonstrates that puerarin promotes ABCA1-mediated cholesterol efflux and decreases intracellular cholesterol levels through the pathway involving miR-7, STK11, and the AMPK-PPARγ-LXR-α-ABCA1 cascade. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Investigation of ABCA1 C69T polymorphism in patients with type 2 diabetes mellitus.

    PubMed

    Ergen, H Arzu; Zeybek, Umit; Gök, Ozlem; Karaali, Z Ermis

    2012-01-01

    Non insulin dependent diabetes mellitus is the most common type of diabetes. Genetic factors, lipid profiles, hypertension are potential risk factors for diabetes mellitus. Adenosine binding cassette transporter proteins 1 (ABCA1) plays a role in cholesterol metabolism, especially high density lipoprotein (HDL-cholesterol). There are multiple mechanisms by which HDL-cholesterol can be atheroprotective, it is clear that the relative activity of ABCA1 plays a major role. We aimed to investigate association of ABCA1 C69T gene polymorphism with lipid levels in Turkish type 2 diabetic patients. After isolation of DNA by ethanol precipitation we determined ABCA1 gene polymorphism by using polimerase chain reaction--restriction fragment lenght polymorphism (PCR-RFLP) method in 107 type 2 diabetic patients and 50 healthy controls. We have observed that the frequency of TT genotype is significantly higher in healthy controls compared to patients (14% vs. 3%; P = 0.008). Also frequency of T allele was higher in controls than in patients (34% vs. 21%; P = 0.020; OR (95% CI) = 0.52 (0.30-0.88)). There was no association of lipid levels and ABCA1 C69T polymorphism subgroups. We have found significantly higher frequency of both T allele and genotype in control group when compared to patients that made us think that T allele may be a protective factor against diabetes mellitus. But, we could not find a relationship between genotypes and lipid concentrations in our two groups. Larger studies will help us to understand the relationship between ABCA1 C69T genotype and lipid parameters in diabetes mellitus.

  5. Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol[S

    PubMed Central

    Zhu, Xuewei; Owen, John S.; Wilson, Martha D.; Li, Haitao; Griffiths, Gary L.; Thomas, Michael J.; Hiltbold, Elizabeth M.; Fessler, Michael B.; Parks, John S.

    2010-01-01

    We previously showed that macrophages from macrophage-specific ATP-binding cassette transporter A1 (ABCA1) knockout (Abca1-M/-M) mice had an enhanced proinflammatory response to the Toll-like receptor (TLR) 4 agonist, lipopolysaccharide (LPS), compared with wild-type (WT) mice. In the present study, we demonstrate a direct association between free cholesterol (FC), lipid raft content, and hyper-responsiveness of macrophages to LPS in WT mice. Abca1-M/-M macrophages were also hyper-responsive to specific agonists to TLR2, TLR7, and TLR9, but not TLR3, compared with WT macrophages. We hypothesized that ABCA1 regulates macrophage responsiveness to TLR agonists by modulation of lipid raft cholesterol and TLR mobilization to lipid rafts. We demonstrated that Abca1-M/-M vs. WT macrophages contained 23% more FC in isolated lipid rafts. Further, mass spectrometric analysis suggested raft phospholipid composition was unchanged. Although cell surface expression of TLR4 was similar between Abca1-M/-M and WT macrophages, significantly more TLR4 was distributed in membrane lipid rafts in Abca1-M/-M macrophages. Abca1-M/-M macrophages also exhibited increased trafficking of the predominantly intracellular TLR9 into lipid rafts in response to TLR9-specific agonist (CpG). Collectively, our data suggest that macrophage ABCA1 dampens inflammation by reducing MyD88-dependent TLRs trafficking to lipid rafts by selective reduction of FC content in lipid rafts. PMID:20650929

  6. Intestinal ABCA1 directly contributes to HDL biogenesis in vivo

    PubMed Central

    Brunham, Liam R.; Kruit, Janine K.; Iqbal, Jahangir; Fievet, Catherine; Timmins, Jenelle M.; Pape, Terry D.; Coburn, Bryan A.; Bissada, Nagat; Staels, Bart; Groen, Albert K.; Hussain, M. Mahmood; Parks, John S.; Kuipers, Folkert; Hayden, Michael R.

    2006-01-01

    Plasma HDL cholesterol levels are inversely related to risk for atherosclerosis. The ATP-binding cassette, subfamily A, member 1 (ABCA1) mediates the rate-controlling step in HDL particle formation, the assembly of free cholesterol and phospholipids with apoA-I. ABCA1 is expressed in many tissues; however, the physiological functions of ABCA1 in specific tissues and organs are still elusive. The liver is known to be the major source of plasma HDL, but it is likely that there are other important sites of HDL biogenesis. To assess the contribution of intestinal ABCA1 to plasma HDL levels in vivo, we generated mice that specifically lack ABCA1 in the intestine. Our results indicate that approximately 30% of the steady-state plasma HDL pool is contributed by intestinal ABCA1 in mice. In addition, our data suggest that HDL derived from intestinal ABCA1 is secreted directly into the circulation and that HDL in lymph is predominantly derived from the plasma compartment. These data establish a critical role for intestinal ABCA1 in plasma HDL biogenesis in vivo. PMID:16543947

  7. Hepatic Overexpression of Endothelial Lipase Lowers HDL (High-Density Lipoprotein) but Maintains Reverse Cholesterol Transport in Mice: Role of SR-BI (Scavenger Receptor Class B Type I)/ABCA1 (ATP-Binding Cassette Transporter A1)-Dependent Pathways.

    PubMed

    Takiguchi, Shunichi; Ayaori, Makoto; Yakushiji, Emi; Nishida, Takafumi; Nakaya, Kazuhiro; Sasaki, Makoto; Iizuka, Maki; Uto-Kondo, Harumi; Terao, Yoshio; Yogo, Makiko; Komatsu, Tomohiro; Ogura, Masatsune; Ikewaki, Katsunori

    2018-05-10

    Reverse cholesterol transport (RCT) is a major mechanism by which HDL (high-density lipoprotein) protects against atherosclerosis. Endothelial lipase (EL) reportedly reduces HDL levels, which, in theory, would increase atherosclerosis. However, it remains unclear whether EL affects RCT in vivo. Adenoviral vectors expressing EL or luciferase were intravenously injected into mice, and a macrophage RCT assay was performed. As expected, hepatic EL overexpression markedly reduced HDL levels. In parallel, plasma 3 H-cholesterol counts from the EL-expressing mice decreased by 85% compared with control. Surprisingly, there was no difference in fecal 3 H-cholesterol excretion between the groups. Kinetic studies revealed increased catabolism/hepatic uptake of 3 HDL-cholesteryl ether, resulting in no change in fecal HDL-cholesteryl ester excretion in the mice. To explore underlying mechanisms for the preservation of RCT despite low HDL levels in the EL-expressing mice, we investigated the effects of hepatic SR-BI (scavenger receptor class B type I) knockdown. RCT assay revealed that knockdown of SR-BI alone reduced fecal excretion of macrophage-derived 3 H-cholesterol. Interestingly, hepatic EL overexpression under SR-BI inhibition further attenuated fecal tracer counts as compared with control. Finally, we observed that EL overexpression enhanced in vivo RCT under pharmacological inhibition of hepatic ABCA1 (ATP-binding cassette transporter A1) by probucol. Hepatic EL expression compensates for reduced macrophage-derived cholesterol efflux to plasma because of low HDL levels by promoting cholesterol excretion to bile/feces via an SR-BI pathway, maintaining overall RCT in vivo. In contrast, EL-modified HDL might negatively regulate RCT via hepatic ABCA1. Despite extreme hypoalphalipoproteinemia, RCT is maintained in EL-expressing mice via SR-BI/ABCA1-dependent pathways. © 2018 American Heart Association, Inc.

  8. ABCA1, ABCG1 and SR-BI: hormonal regulation in primary rat hepatocytes and human cell lines

    PubMed Central

    Sporstøl, Marita; Mousavi, Seyed Ali; Eskild, Winnie; Roos, Norbert; Berg, Trond

    2007-01-01

    Background Scavenger receptor type B class I (SR-BI), ABC transporter A1 (ABCA1) -and G1 (ABCG1) all play important roles in the reverse cholesterol transport. Reverse cholesterol transport is a mechanism whereby the body can eliminate excess cholesterol. Here, the regulation of SR-BI, ABCA1, and ABCG1 by dexamethasone (a synthetic glucocorticoid) and insulin were studied in order to gain more insight into the role of these two hormones in the cholesterol metabolism. Results By use of real time RT-PCR and Western blotting we examined the expression of our target genes. The results show that SR-BI, ABCA1 and ABCG1 mRNA expression increased in response to dexamethasone while insulin treatment reduced the expression in primary rat hepatocytes. The stimulatory effect of dexamethasone was reduced by the addition of the anti-glucocorticoid mifepristone. In HepG2 cells and THP-1 macrophages, however, the effect of dexamethasone was absent or inhibitory with no significant change in the presence of mifepristone. The latter observation may be a result of the low protein expression of glucocorticoid receptor (GR) in these cell lines. Conclusion Our results illustrates that insulin and glucocorticoids, two hormones crucial in the carbohydrate metabolism, also play an important role in the regulation of genes central in reverse cholesterol transport. We found a marked difference in mRNA expression between the primary cells and the two established cell lines when studying the effect of dexamethasone which may result from the varying expression levels of GR. PMID:17241464

  9. ABCA1, ABCG1 and SR-BI: hormonal regulation in primary rat hepatocytes and human cell lines.

    PubMed

    Sporstøl, Marita; Mousavi, Seyed Ali; Eskild, Winnie; Roos, Norbert; Berg, Trond

    2007-01-22

    Scavenger receptor type B class I (SR-BI), ABC transporter A1 (ABCA1) -and G1 (ABCG1) all play important roles in the reverse cholesterol transport. Reverse cholesterol transport is a mechanism whereby the body can eliminate excess cholesterol. Here, the regulation of SR-BI, ABCA1, and ABCG1 by dexamethasone (a synthetic glucocorticoid) and insulin were studied in order to gain more insight into the role of these two hormones in the cholesterol metabolism. By use of real time RT-PCR and Western blotting we examined the expression of our target genes. The results show that SR-BI, ABCA1 and ABCG1 mRNA expression increased in response to dexamethasone while insulin treatment reduced the expression in primary rat hepatocytes. The stimulatory effect of dexamethasone was reduced by the addition of the anti-glucocorticoid mifepristone. In HepG2 cells and THP-1 macrophages, however, the effect of dexamethasone was absent or inhibitory with no significant change in the presence of mifepristone. The latter observation may be a result of the low protein expression of glucocorticoid receptor (GR) in these cell lines. Our results illustrates that insulin and glucocorticoids, two hormones crucial in the carbohydrate metabolism, also play an important role in the regulation of genes central in reverse cholesterol transport. We found a marked difference in mRNA expression between the primary cells and the two established cell lines when studying the effect of dexamethasone which may result from the varying expression levels of GR.

  10. IL-8 negatively regulates ABCA1 expression and cholesterol efflux via upregulating miR-183 in THP-1 macrophage-derived foam cells.

    PubMed

    Tang, Xiao-Er; Li, Heng; Chen, Ling-Yan; Xia, Xiao-Dan; Zhao, Zhen-Wang; Zheng, Xi-Long; Zhao, Guo-Jun; Tang, Chao-Ke

    2018-04-24

    Previous studies suggest that IL-8 has an important role in the regulation of cholesterol efflux, but whether miRNAs are involved in this process is still unknown. The purpose of this study is to explore whether IL-8 promotes cholesterol accumulation by enhancing miR-183 expression in macrophages and its underlying mechanism. Treatment of THP-1 macrophage-derived foam cells with IL-8 decreased ABCA1 expression and cholesterol efflux. Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-183 was highly conserved during evolution and directly inhibited ABCA1 protein and mRNA expression by targeting ABCA1 3'UTR. MiR-183 directly regulated endogenous ABCA1 expression levels. Furthermore, IL-8 enhanced the expression of miR-183 and decrease ABCA1 expression. Cholesterol transport assays confirmed that IL-8 dramatically inhibited apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux by increasing miR-183 expression. In contrast, treatment with anti-IL-8 antibody reversed these effects. IL-8 enhances the expression of miR-183, which then inhibits ABCA1 expression and cholesterol efflux. Our studies suggest that the IL-8-miR-183-ABCA1 axis may play an intermediary role in the development of atherosclerosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Assembly of high density lipoprotein by the ABCA1/apolipoprotein pathway.

    PubMed

    Yokoyama, Shinji

    2005-06-01

    Mammalian somatic cells do not catabolize cholesterol and therefore need to export it for sterol homeostasis at the levels of cells and whole bodies. This mechanism may reduce intracellularly accumulated cholesterol in excess, and thereby would contribute to the prevention or cure of the initial stage of atherosclerotic vascular lesions. HDL is thought to play a main role in this reaction on the basis of epidemiological evidence and in-vitro experimental data. Two independent mechanisms have been identified for this reaction. One is non-specific diffusion-mediated cholesterol 'efflux' from the cell surface, and cholesterol is trapped by various extracellular acceptors including lipoproteins. Extracellular cholesterol esterification on HDL provides a driving force for the net removal of cell cholesterol, and some cellular factors may enhance this reaction. The other mechanism is an apolipoprotein-mediated process to generate HDL by removing cellular phospholipid and cholesterol. This reaction is mediated by a membrane protein ABCA1, and lipid-free or lipid-poor helical apolipoproteins recruit cellular phospholipid and cholesterol to assemble HDL particles. The reaction is composed of two elements: the assembly of HDL particles with phospholipid by apolipoprotein, and cholesterol enrichment in HDL. ABCA1 is essential for the former step, and the latter step requires further intracellular events. ABCA1 is a rate-limiting factor of HDL assembly and is regulated by transcriptional factors and posttranscriptional factors. Posttranscriptional regulation of ABCA1 involves the modulation of its calpain-mediated degradation.

  12. ABCA1 gene variants regulate postprandial lipid metabolism in healthy men

    PubMed Central

    Delgado-Lista, Javier; Perez-Martinez, Pablo; Perez-Jimenez, Francisco; Garcia-Rios, Antonio; Fuentes, Francisco; Marin, Carmen; Gómez-Luna, Purificación; Camargo, Antonio; Parnell, Laurence D; Ordovas, Jose Maria; Lopez-Miranda, Jose

    2010-01-01

    Objective Genetic variants of ABCA1, an ATP-binding cassette (ABC) transporter, have been linked to altered atherosclerosis progression and fasting lipid concentration, mainly high density lipoproteins (HDL) and Apolipoprotein A1 (APOA1), but results from different studies have been inconsistent. Methods and results In order to further characterize the effects of ABCA1 variants in human postprandial lipid metabolism, we studied the influence of three single nucleotide polymorphisms (SNPs) [i27943 (rs2575875); i48168 (rs4149272); R219K (rs2230806)] in the postprandial lipemia of 88 normolipidemic young men, who were given a fatty meal. For i27943 and i48168 SNPs, fasting and postprandial values of APOA1 were higher, and postprandial lipemia was much lower in homozygotes for the major alleles, for total triglycerides in plasma, and large-triglyceride rich lipoproteins (TRL) triglycerides. These persons also showed higher APOA1/APOB ratio. Major allele homozygotes for i48168 and i27943 showed additionally higher HDL and lower postprandial Apolipoprotein B (ApoB). Conclusions Our work shows that major allele homozygotes for ABCA1 SNPs i27943 and i48168 have a lower postprandial response as compared to minor allele carriers. This finding may further characterize the role of ABCA1 in lipid metabolism. PMID:20185793

  13. A novel compound inhibits rHDL assembly and blocks nascent HDL biogenesis downstream of apoAI binding to ABCA1 expressing cells

    PubMed Central

    Lyssenko, Nicholas N.; Brubaker, Gregory; Smith, Bradley D.; Smith, Jonathan D.

    2011-01-01

    Objective Nascent high-density lipoprotein (HDL) particles form from cellular lipids and extracellular lipid-free apolipoprotein AI (apoAI) in a process mediated by ATP-binding cassette transporter A1 (ABCA1). We have sought out compounds that inhibit nascent HDL biogenesis without affecting ABCA1 activity. Methods and Results Reconstituted HDL (rHDL) formation and cellular cholesterol efflux assays were used to show that two compounds that bond via hydrogen with phospholipids inhibit rHDL and nascent HDL production. In rHDL formation assays, the inhibitory effect of compound 1 (methyl 3α-acetoxy-7α,12α-di[(phenylaminocarbonyl)amino]-5β-cholan-24-oate), the more active of the two, depended on its ability to associate with phospholipids. In cell assays, compound 1 suppressed ABCA1-mediated cholesterol efflux to apoAI, the 18A peptide, and taurocholate with high specificity, without affecting ABCA1-independent cellular cholesterol efflux to HDL and endocytosis of acetylated low-density lipoprotein (AcLDL) and transferrin. Furthermore, compound 1 did not affect ABCA1 activity adversely, as ABCA1-mediated shedding of microparticles proceeded unabated and apoAI binding to ABCA1-expressing cells increased in its presence. Conclusions The inhibitory effects of compound 1 support a three-step model of nascent HDL biogenesis: plasma membrane remodeling by ABCA1, apoAI binding to ABCA1, and lipoprotein particle assembly. The compound inhibits the final step, causing accumulation of apoAI in ABCA1-expressing cells. PMID:21836073

  14. Proteomic Analysis of ABCA1-Null Macrophages Reveals a Role for Stomatin-Like Protein-2 in Raft Composition and Toll-Like Receptor Signaling.

    PubMed

    Chowdhury, Saiful M; Zhu, Xuewei; Aloor, Jim J; Azzam, Kathleen M; Gabor, Kristin A; Ge, William; Addo, Kezia A; Tomer, Kenneth B; Parks, John S; Fessler, Michael B

    2015-07-01

    Lipid raft membrane microdomains organize signaling by many prototypical receptors, including the Toll-like receptors (TLRs) of the innate immune system. Raft-localization of proteins is widely thought to be regulated by raft cholesterol levels, but this is largely on the basis of studies that have manipulated cell cholesterol using crude and poorly specific chemical tools, such as β-cyclodextrins. To date, there has been no proteome-scale investigation of whether endogenous regulators of intracellular cholesterol trafficking, such as the ATP binding cassette (ABC)A1 lipid efflux transporter, regulate targeting of proteins to rafts. Abca1(-/-) macrophages have cholesterol-laden rafts that have been reported to contain increased levels of select proteins, including TLR4, the lipopolysaccharide receptor. Here, using quantitative proteomic profiling, we identified 383 proteins in raft isolates from Abca1(+/+) and Abca1(-/-) macrophages. ABCA1 deletion induced wide-ranging changes to the raft proteome. Remarkably, many of these changes were similar to those seen in Abca1(+/+) macrophages after lipopolysaccharide exposure. Stomatin-like protein (SLP)-2, a member of the stomatin-prohibitin-flotillin-HflK/C family of membrane scaffolding proteins, was robustly and specifically increased in Abca1(-/-) rafts. Pursuing SLP-2 function, we found that rafts of SLP-2-silenced macrophages had markedly abnormal composition. SLP-2 silencing did not compromise ABCA1-dependent cholesterol efflux but reduced macrophage responsiveness to multiple TLR ligands. This was associated with reduced raft levels of the TLR co-receptor, CD14, and defective lipopolysaccharide-induced recruitment of the common TLR adaptor, MyD88, to rafts. Taken together, we show that the lipid transporter ABCA1 regulates the protein repertoire of rafts and identify SLP-2 as an ABCA1-dependent regulator of raft composition and of the innate immune response. © 2015 by The American Society for Biochemistry and

  15. Proteomic Analysis of ABCA1-Null Macrophages Reveals a Role for Stomatin-Like Protein-2 in Raft Composition and Toll-Like Receptor Signaling*

    PubMed Central

    Chowdhury, Saiful M.; Zhu, Xuewei; Aloor, Jim J.; Azzam, Kathleen M.; Gabor, Kristin A.; Ge, William; Addo, Kezia A.; Tomer, Kenneth B.; Parks, John S.; Fessler, Michael B.

    2015-01-01

    Lipid raft membrane microdomains organize signaling by many prototypical receptors, including the Toll-like receptors (TLRs) of the innate immune system. Raft-localization of proteins is widely thought to be regulated by raft cholesterol levels, but this is largely on the basis of studies that have manipulated cell cholesterol using crude and poorly specific chemical tools, such as β-cyclodextrins. To date, there has been no proteome-scale investigation of whether endogenous regulators of intracellular cholesterol trafficking, such as the ATP binding cassette (ABC)A1 lipid efflux transporter, regulate targeting of proteins to rafts. Abca1−/− macrophages have cholesterol-laden rafts that have been reported to contain increased levels of select proteins, including TLR4, the lipopolysaccharide receptor. Here, using quantitative proteomic profiling, we identified 383 proteins in raft isolates from Abca1+/+ and Abca1−/− macrophages. ABCA1 deletion induced wide-ranging changes to the raft proteome. Remarkably, many of these changes were similar to those seen in Abca1+/+ macrophages after lipopolysaccharide exposure. Stomatin-like protein (SLP)-2, a member of the stomatin-prohibitin-flotillin-HflK/C family of membrane scaffolding proteins, was robustly and specifically increased in Abca1−/− rafts. Pursuing SLP-2 function, we found that rafts of SLP-2-silenced macrophages had markedly abnormal composition. SLP-2 silencing did not compromise ABCA1-dependent cholesterol efflux but reduced macrophage responsiveness to multiple TLR ligands. This was associated with reduced raft levels of the TLR co-receptor, CD14, and defective lipopolysaccharide-induced recruitment of the common TLR adaptor, MyD88, to rafts. Taken together, we show that the lipid transporter ABCA1 regulates the protein repertoire of rafts and identify SLP-2 as an ABCA1-dependent regulator of raft composition and of the innate immune response. PMID:25910759

  16. Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from THP‐1‐derived macrophages

    PubMed Central

    Wang, Limei; Palme, Veronika; Rotter, Susanne; Schilcher, Nicole; Cukaj, Malsor; Wang, Dongdong; Ladurner, Angela; Heiss, Elke H.; Stangl, Herbert; Dirsch, Verena M.

    2016-01-01

    1 Scope Increased macrophage cholesterol efflux (ChE) is considered to have anti‐atherosclerotic effect counteracting cardiovascular disease. The principle pungent ingredient of the fruits of Piper nigrum, piperine, is identified in this study as a ChE inducer in THP‐1‐derived macrophages, and mechanisms underlying this effect are explored. 2 Methods and results Without affecting cell viability, piperine concentration‐dependently enhances ChE in THP‐1‐derived macrophages from 25 to 100 μM. The expression level of the key cholesterol transporter protein ATP‐binding cassette transporter A1 (ABCA1) is significantly upregulated by piperine, as revealed by western blot analyses. However, two other ChE‐mediating transporter proteins, ATP‐binding cassette transporter G1 (ABCG1) and scavenger receptor class B member 1 (SR‐B1), remain unaffected. Piperine exerts no influence on ABCA1 mRNA levels, but significantly inhibits the degradation of ABCA1, as evident by an increased half‐life of the protein in the presence of cycloheximide. Furthermore, it is found that piperine likely interferes with the calpain‐mediated ABCA1 degradation pathway and exhibits significant inhibition of calpain activity. 3 Conclusion Our findings suggest that piperine promotes ChE in THP‐1‐derived macrophages by upregulation of ABCA1, which might be mediated by inhibition of calpain activity. This novel bioactivity makes the dietary constituent piperine a good candidate to be further explored for therapeutic or preventive applications in the context of atherosclerosis. PMID:27862930

  17. MicroRNA-20a/b regulates cholesterol efflux through post-transcriptional repression of ATP-binding cassette transporter A1.

    PubMed

    Liang, Bin; Wang, Xin; Song, Xiaosu; Bai, Rui; Yang, Huiyu; Yang, Zhiming; Xiao, Chuanshi; Bian, Yunfei

    2017-09-01

    ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in reverse cholesterol transport and exhibits anti-atherosclerosis effects. Some microRNAs (miRs) regulate ABCA1 expression, and recent studies have shown that miR-20a/b might play a critical role in atherosclerotic diseases. Here, we attempted to clarify the potential contribution of miR-20a/b in post-transcriptional regulation of ABCA1, cholesterol efflux, and atherosclerosis. We performed bioinformatics analysis and found that miR-20a/b was highly conserved and directly bound to ABCA1 mRNA with low binding free energy. Luciferase-reporter assay also confirmed that miR-20a/b significantly reduced luciferase activity associated with the ABCA1 3' untranslated region reporter construct. Additionally, miR-20a/b decreased ABCA1 expression, which, in turn, decreased cholesterol efflux and increased cholesterol content in THP-1 and RAW 264.7 macrophage-derived foam cells. In contrast, miR-20a/b inhibitors increased ABCA1 expression and cholesterol efflux, decreased cholesterol content, and inhibited foam-cell formation. Consistent with our in vitro results, miR-20a/b-treated ApoE -/- mice showed decreased ABCA1expression in the liver and reductions of reverse cholesterol transport in vivo. Furthermore, miR-20a/b regulated the formation of nascent high-density lipoprotein and promoted atherosclerotic development, whereas miR-20a/b knockdown attenuated atherosclerotic formation. miR-20 is a new miRNA capable of targeting ABCA1 and regulating ABCA1 expression. Therefore, miR-20 inhibition constitutes a new strategy for ABCA1-based treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Silymarin Constituents Enhance ABCA1 Expression in THP-1 Macrophages

    PubMed Central

    Wang, Limei; Rotter, Susanne; Ladurner, Angela; Heiss, Elke H.; Oberlies, Nicholas H.; Dirsch, Verena M.; Atanasov, Atanas G.

    2016-01-01

    Silymarin is a hepatoprotective mixture of flavonolignans and flavonoids extracted from the seeds of milk thistle (Silybum marianum L. Gaertn). This study investigates the effect of major bioactive constituents from silymarin, silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, isosilychristin, and taxifolin, on the expression of ABCA1, an important cholesterol efflux transporter, in THP-1-derived macrophages. Four of the studied compounds, isosilybin A, silybin B, silychristin and isosilychristin, were found to significantly induce ABCA1 protein expression without affecting cell viability. Moreover, isosilybin A, a partial PPARγ agonist, was found to promote cholesterol efflux from THP-1 macrophages in a concentration-dependent manner. These findings first show ABCA1 protein up-regulating activity of active constituents of silymarin and provide new avenues for their further study in the context of cardiovascular disease. PMID:26729088

  19. Silymarin Constituents Enhance ABCA1 Expression in THP-1 Macrophages.

    PubMed

    Wang, Limei; Rotter, Susanne; Ladurner, Angela; Heiss, Elke H; Oberlies, Nicholas H; Dirsch, Verena M; Atanasov, Atanas G

    2015-12-31

    Silymarin is a hepatoprotective mixture of flavonolignans and flavonoids extracted from the seeds of milk thistle (Silybum marianum L. Gaertn). This study investigates the effect of major bioactive constituents from silymarin, silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, isosilychristin, and taxifolin, on the expression of ABCA1, an important cholesterol efflux transporter, in THP-1-derived macrophages. Four of the studied compounds, isosilybin A, silybin B, silychristin and isosilychristin, were found to significantly induce ABCA1 protein expression without affecting cell viability. Moreover, isosilybin A, a partial PPARγ agonist, was found to promote cholesterol efflux from THP-1 macrophages in a concentration-dependent manner. These findings first show ABCA1 protein up-regulating activity of active constituents of silymarin and provide new avenues for their further study in the context of cardiovascular disease.

  20. On the mechanism for PPAR agonists to enhance ABCA1 gene expression

    PubMed Central

    Ogata, Masaki; Tsujita, Maki; Hossain, Mohammad Anwar; Akita, Nobukatsu; Gonzalez, Frank J.; Staels, Bart; Suzuki, Shogo; Fukutomi, Tatsuya; Kimura, Genjiro; Yokoyama, Shinji

    2009-01-01

    Expression of ATP binding cassette transporter A1 (ABCA1), a major regulator of high density lipoprotein (HDL) biogenesis, is known to be up-regulated by the transcription factor liver X receptor (LXR) α, and expression is further enhanced by activation of the peroxisome proliferator activated receptors (PPARs). We investigated this complex regulatory network using specific PPAR agonists: four fibrates (fenofibrate, bezafibrate, gemfibrozil and LY518674), a PPAR δ agonist (GW501516) and a PPAR γ agonist (pioglitazone). All of these compounds increased the expression of LXRs, PPARs and ABCA1 mRNAs, and associated apoA-I-mediated lipid release in THP-1 macrophage, WI38 fibroblast and mouse fibroblast. When mouse fibroblasts lacking expression of PPAR α were examined, the effects of fenofibrate and LY518674 were markedly diminished while induction by other ligands were retained. The PPAR α promoter was activated by all of these compounds in an LXR α-dependent manner, and partially in a PPAR α-dependent manner, in mouse fibroblast. The LXR responsive element (LXRE)-luciferase activity was enhanced by all the compounds in an LXR α-dependent manner in mouse fibroblast. This activation was exclusively PPAR α-dependent by fenofibrate and LY518674, but nonexclusively by the others. We conclude that PPARs and LXRs are involved in the regulation of ABCA1 expression and HDL biogenesis in a cooperative signal transduction pathway. PMID:19201410

  1. PPAR{gamma} activates ABCA1 gene transcription but reduces the level of ABCA1 protein in HepG2 cells

    SciTech Connect

    Mogilenko, Denis A., E-mail: denis@iem.sp.ru; Department of Embryology, St. Petersburg State University, 199034 St. Petersburg; Shavva, Vladimir S.

    Research highlights: {yields} PPAR{gamma} activates ABCA1 gene expression but decreases ABCA1 protein content in human hepatoma cell line HepG2. {yields} Treatment of HepG2 cells with PPAR{gamma} agonist GW1929 leads to dissociation of LXR{beta} from ABCA1-LXR{beta} complex. {yields} Inhibition of protein kinases MEK1/2 abolishes PPAR{gamma}-mediated dissociation of LXR{beta} from ABCA1/LXR{beta} complex. {yields} Activation of PPAR{gamma} leads to increasing of the level of LXR{beta} associated with LXRE within ABCA1 gene promoter. -- Abstract: Synthesis of ABCA1 protein in liver is necessary for high-density lipoproteins (HDL) formation in mammals. Nuclear receptor PPAR{gamma} is known as activator of ABCA1 expression, but details of PPAR{gamma}-mediatedmore » regulation of ABCA1 at both transcriptional and post-transcriptional levels in hepatocytes have not still been well elucidated. In this study we have shown, that PPAR{gamma} activates ABCA1 gene transcription in human hepatoma cells HepG2 through increasing of LXR{beta} binding with promoter region of ABCA1 gene. Treatment of HepG2 cells with PPAR{gamma} agonist GW1929 leads to dissociation of LXR{beta} from ABCA1/LXR{beta} complex and to nuclear translocation of this nuclear receptor resulting in reduction of ABCA1 protein level 24 h after treatment. Inhibition of protein kinases MEK1/2 abolishes PPAR{gamma}-mediated dissociation of LXR{beta} from ABCA1/LXR{beta} complex, but does not block PPAR{gamma}-dependent down-regulation of ABCA1 protein in HepG2 cells. These data suggest that PPAR{gamma} may be important for regulation of the level of hepatic ABCA1 protein and indicate the new interplays between PPAR{gamma}, LXR{beta} and MEK1/2 in regulation of ABCA1 mRNA and protein expression.« less

  2. Activation of Liver X Receptor Decreases Atherosclerosis in Ldlr−/− mice in the Absence of ABCA1 and ABCG1 in Myeloid Cells

    PubMed Central

    Kappus, Mojdeh S.; Murphy, Andrew J.; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L.; Tall, Alan R.; Westerterp, Marit

    2014-01-01

    Objective Liver X Receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly up-regulate genes involved in reverse cholesterol transport (RCT) and (2) exert anti-inflammatory effects mediated by transrepression of NFκB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate RCT, would abolish the beneficial effects of LXR activation on atherosclerosis. Approach and Results LXR activator T0901317 (T0) substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr−/− mice were transplanted with Abca1−/−Abcg1−/− or wild-type bone marrow (BM) and fed a Western-type diet (WTD) for 6 weeks with or without T0 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0 markedly decreased lesion area, complexity and inflammatory cell infiltration in the Abca1−/−Abcg1−/− BM transplanted mice. To investigate whether this was due to macrophage Abca1/g1 deficiency, Ldlr−/− mice were transplanted with LysmCreAbca1fl/flAbcg1fl/fl or Abca1fl/flAbcg1fl/fl BM and fed WTD with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups and the decrease was more prominent in the LysmCreAbca1fl/flAbcg1fl/fl group. Conclusions The results suggest that anti-inflammatory effects of LXR activators are of key importance to their anti-atherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to trans-repress inflammatory genes. PMID:24311381

  3. 7-ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages.

    PubMed

    Chi, Yan; Wang, Le; Liu, Yuanyuan; Ma, Yanhua; Wang, Renjun; Han, Xiaofei; Qiao, Hui; Lin, Jiabin; Matsuura, Eiji; Liu, Shuqian; Liu, Qingping

    2014-06-01

    ATP binding cassette transporter A1 (ABCA1) is a member of the ATP-binding cassette transporter family. It plays an essential role in mediating the efflux of excess cholesterol. It is known that peroxisome proliferator-activated receptor gamma (PPARγ) promoted ABCA1 expression. We previously found 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) upregulated ABCA1 partially through CD36 mediated signals. In the present study, we intended to test if PPARγ signally is involved in the upregulation mediated by oxLig-1. First, we docked oxLig-1 and the ligand-binding domain (LBD) of PPARγ by using AutoDock 3.05 and subsequently confirmed the binding by ELISA assay. Western blotting analyses showed that oxLig-1 induces liver X receptor alpha (LXRα), PPARγ and consequently ABCA1 expression. Furthermore, oxLig-1 significantly enhanced ApoA-I-mediated cholesterol efflux. Pretreatment with an inhibitor for PPARγ (GW9662) or/and LXRα (GGPP) attenuated oxLig-1-induced ABCA1 expression. Under PPARγ knockdown by using PPARγ-shRNA, oxLig-1-induced ABCA1 expression and cholesterol efflux in THP-1 macrophages was blocked by 62% and 25% respectively. These observations suggest that oxLig-1 is a novel PPARγ agonist, promoting ApoA-I-mediated cholesterol efflux from THP-1 macrophages by increasing ABCA1 expression via induction of PPARγ. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Deficiency of ABCA1 and ABCG1 in Macrophages Increases Inflammation and Accelerates Atherosclerosis in Mice

    PubMed Central

    Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Pagler, Tamara A.; Vengrenyuk, Yuliya; Kappus, Mojdeh S.; Gorman, Darren J.; Nagareddy, Prabhakara R.; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S.; Welch, Carrie; Fisher, Edward A.; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R.

    2013-01-01

    Rationale Plasma HDL levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is due to the ability of HDL to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. Objective To assess the role of macrophage cholesterol efflux pathways in atherogenesis. Methods and Results We developed MAC-ABCDKO mice with efficient deletion of the ATP Binding Cassette Transporters A1 and G1 (ABCA1 and ABCG1) in macrophages but not in hematopoietic stem or progenitor populations. MAC-ABCDKO bone marrow (BM) was transplanted into Ldlr-/- recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared to controls. On the Western type diet (WTD), MAC-ABCDKO BM transplanted Ldlr-/- mice had disproportionate atherosclerosis, considering they also had lower VLDL/LDL cholesterol levels than controls. ABCA1/G1 deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, WTD-fed MAC-ABCDKO BM transplanted Ldlr-/- mice displayed monocytosis and neutrophilia in the absence of HSPC proliferation. Mechanistic studies revealed increased expression of M-CSF and G-CSF in splenic macrophage foam cells, driving BM monocyte and neutrophil production. Conclusion These studies 1) show that macrophage deficiency of ABCA1/G1 is pro-atherogenic likely by promoting plaque inflammation and 2) uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways. PMID:23572498

  5. Advanced glycation end products affect cholesterol homeostasis by impairing ABCA1 expression on macrophages.

    PubMed

    Kamtchueng Simo, Olivier; Ikhlef, Souade; Berrougui, Hicham; Khalil, Abdelouahed

    2017-08-01

    Reverse cholesterol transport (RCT), which is intimately linked to high-density lipoproteins (HDLs), plays a key role in cholesterol homeostasis and the prevention of atherosclerosis. The goal of the present study was to investigate the effect of aging and advanced glycation end products (AGEs) on RCT as well as on other factors that may affect the antiatherogenic property of HDLs. The transfer of macrophage-derived cholesterol to the plasma and liver and then to the feces for elimination was significantly lower in aged mice than in young mice. Chronic injection of d -galactose (D-gal) or AGEs also significantly reduced RCT (65.3% reduction in [ 3 H]cholesterol levels in the plasma of D-gal-treated mice after 48 h compared with control mice, P < 0.01). The injection of both D-gal and aminoguanidine hydrochloride increased [ 3 H]cholesterol levels in the plasma, although the levels were lower than those of control mice. The in vitro incubation of HDLs with dicarbonyl compounds increased the carbonyl and conjugated diene content of HDLs and significantly reduced PON1 paraoxonase activity (87.4% lower than control HDLs, P < 0.0001). Treating J774A.1 macrophages with glycated fetal bovine serum increased carbonyl formation (39.5% increase, P < 0.003) and reduced ABCA1 protein expression and the capacity of macrophages to liberate cholesterol (69.1% decrease, P < 0.0001). Our results showed, for the first time, that RCT is altered with aging and that AGEs contribute significantly to this alteration.

  6. ABCA1, ABCG1, and ABCG4 are distributed to distinct membrane meso-domains and disturb detergent-resistant domains on the plasma membrane.

    PubMed

    Sano, Osamu; Ito, Shiho; Kato, Reiko; Shimizu, Yuji; Kobayashi, Aya; Kimura, Yasuhisa; Kioka, Noriyuki; Hanada, Kentaro; Ueda, Kazumitsu; Matsuo, Michinori

    2014-01-01

    ATP-binding cassette A1 (ABCA1), ABCG1, and ABCG4 are lipid transporters that mediate the efflux of cholesterol from cells. To analyze the characteristics of these lipid transporters, we examined and compared their distributions and lipid efflux activity on the plasma membrane. The efflux of cholesterol mediated by ABCA1 and ABCG1, but not ABCG4, was affected by a reduction of cellular sphingomyelin levels. Detergent solubility and gradient density ultracentrifugation assays indicated that ABCA1, ABCG1, and ABCG4 were distributed to domains that were solubilized by Triton X-100 and Brij 96, resistant to Triton X-100 and Brij 96, and solubilized by Triton X-100 but resistant to Brij 96, respectively. Furthermore, ABCG1, but not ABCG4, was colocalized with flotillin-1 on the plasma membrane. The amounts of cholesterol extracted by methyl-β-cyclodextrin were increased by ABCA1, ABCG1, or ABCG4, suggesting that cholesterol in non-raft domains was increased. Furthermore, ABCG1 and ABCG4 disturbed the localization of caveolin-1 to the detergent-resistant domains and the binding of cholera toxin subunit B to the plasma membrane. These results suggest that ABCA1, ABCG1, and ABCG4 are localized to distinct membrane meso-domains and disturb the meso-domain structures by reorganizing lipids on the plasma membrane; collectively, these observations may explain the different substrate profiles and lipid efflux roles of these transporters.

  7. ABCA1, ABCG1, and ABCG4 Are Distributed to Distinct Membrane Meso-Domains and Disturb Detergent-Resistant Domains on the Plasma Membrane

    PubMed Central

    Sano, Osamu; Ito, Shiho; Kato, Reiko; Shimizu, Yuji; Kobayashi, Aya; Kimura, Yasuhisa; Kioka, Noriyuki; Hanada, Kentaro; Ueda, Kazumitsu; Matsuo, Michinori

    2014-01-01

    ATP-binding cassette A1 (ABCA1), ABCG1, and ABCG4 are lipid transporters that mediate the efflux of cholesterol from cells. To analyze the characteristics of these lipid transporters, we examined and compared their distributions and lipid efflux activity on the plasma membrane. The efflux of cholesterol mediated by ABCA1 and ABCG1, but not ABCG4, was affected by a reduction of cellular sphingomyelin levels. Detergent solubility and gradient density ultracentrifugation assays indicated that ABCA1, ABCG1, and ABCG4 were distributed to domains that were solubilized by Triton X-100 and Brij 96, resistant to Triton X-100 and Brij 96, and solubilized by Triton X-100 but resistant to Brij 96, respectively. Furthermore, ABCG1, but not ABCG4, was colocalized with flotillin-1 on the plasma membrane. The amounts of cholesterol extracted by methyl-β-cyclodextrin were increased by ABCA1, ABCG1, or ABCG4, suggesting that cholesterol in non-raft domains was increased. Furthermore, ABCG1 and ABCG4 disturbed the localization of caveolin-1 to the detergent-resistant domains and the binding of cholera toxin subunit B to the plasma membrane. These results suggest that ABCA1, ABCG1, and ABCG4 are localized to distinct membrane meso-domains and disturb the meso-domain structures by reorganizing lipids on the plasma membrane; collectively, these observations may explain the different substrate profiles and lipid efflux roles of these transporters. PMID:25302608

  8. Reduced Plasma HDL Cholesterol in Hyperthyroid Mice Coincides with Decreased Hepatic ABCA1 Expression

    PubMed Central

    TANCEVSKI, IVAN; WEHINGER, ANDREAS; DEMETZ, EGON; ELLER, PHILIPP; DUWENSEE, KRISTINA; HUBER, JULIA; HOCHEGGER, KATHRIN; SCHGOER, WILFRIED; FIEVET, CATHERINE; STELLAARD, FRANS; RUDLING, MATS; PATSCH, JOSEF R.; RITSCH, ANDREAS

    2010-01-01

    The aim of the study was to investigate the influence of severe hyperthyroidism on plasma high-density lipoprotein cholesterol (HDL-C). Recently, it was shown in mice that increasing doses of triiodothyronine (T3) upregulate hepatic expression of scavenger receptor-BI (SR-BI), resulting in increased clearance of plasma HDL-C. Here we show that severe hyperthyroidism in mice did not affect hepatic expression of SR-BI, but reduced hepatic expression of ATP-binding cassette transporter 1 (ABCA1), accompanied by a 40%-reduction of HDL-C. Sterol content of bile, liver and feces was markedly increased, accompanied by upregulation of hepatic CYP7A1, and ATP-binding cassette half-transporter ABCG5, which is known to promote biliary sterol secretion upon dimerization with ABCG8. Both control and hyperthyroid mice exerted identical plasma clearance of intravenously injected [3H] HDL-C, supporting the view that severe hyperthyroidism does not affect HDL-C clearance, but rather its formation via hepatic ABCA1. PMID:18388200

  9. Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is protective against cancer

    PubMed Central

    Zamanian-Daryoush, Maryam; Lindner, Daniel J.; DiDonato, Joseph A.; Wagner, Matthew; Buffa, Jennifer; Rayman, Patricia; Parks, John S.; Westerterp, Marit; Tall, Alan R.; Hazen, Stanley L.

    2017-01-01

    Increased circulating levels of apolipoprotein A-I (apoA-I), the major protein of high-density lipoprotein (HDL), by genetic manipulation or infusion, protects against melanoma growth and metastasis. Herein, we explored potential roles in melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of apoA-I and HDL sterol and lipid transport function. In a syngeneic murine melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor volume, indicating host SR-B1 does not directly contribute to HDL-associated anti-tumor activity. In mice with myeloid-specific loss of ABCA1 (Abca1−M/−M; A1−M/−M), tumor growth was inhibited by ∼4.8-fold relative to wild type (WT) animals. Abcg1−M/−M (G1−M/−M) animals were also protected by 2.5-fold relative to WT, with no further inhibition of tumor growth in Abca1/Abcg1 myeloid-specific double knockout animals (DKO). Analyses of tumor-infiltrating immune cells revealed a correlation between tumor protection and decreased presence of the immune suppressive myeloid-derived suppressor cell (MDSC) subsets, Ly-6G+Ly-6CLo and Ly-6GnegLy-6CHi cells. The growth of the syngeneic MB49 murine bladder cancer cells was also inhibited in A1−M/−M mice. Collectively, our studies provide further evidence for an immune modulatory role for cholesterol homeostasis pathways in cancer. PMID:29069761

  10. Genetic variants of ABCA1 modify Alzheimer disease risk and quantitative traits related to beta-amyloid metabolism.

    PubMed

    Katzov, Hagit; Chalmers, Katy; Palmgren, Juni; Andreasen, Niels; Johansson, Boo; Cairns, Nigel J; Gatz, Margaret; Wilcock, Gordon K; Love, Seth; Pedersen, Nancy L; Brookes, Anthony J; Blennow, Kaj; Kehoe, Patrick G; Prince, Jonathan A

    2004-04-01

    Linkage studies have provided evidence that one or more loci on chromosome 9q influence Alzheimer disease (AD). The gene encoding the ATP-binding cassette A1 transporter (ABCA1) resides within proximity of previously identified linkage peaks and represents a plausible biological candidate for AD due to its central role in cellular lipid homeostasis. Several single nucleotide polymorphisms (SNPs) spanning ABCA1 have been genotyped and haplotype-based association analyses performed in four independent case-control samples, consisting of over 1,750 individuals from three European populations representing both early and late-onset AD. Prominent effects were observed for a common (H2) and rarer haplotype (H5) that were enriched in AD cases across studied populations (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.36-1.82; P<0.00001 and OR 2.90; 95% CI 2.54-3.27; P<0.00001, respectively). Two other common haplotypes in the studied region (H1 and H3) were significantly under-represented in AD cases, suggesting that they may harbor alleles that decrease disease risk (OR 0.79, 95% CI 0.64-0.94; P=0.0065 and OR 0.70, 95% CI 0.46-0.93; P=0.011, respectively). While findings were significant in both early and late-onset samples, haplotype effects were more distinct in early-onset materials. For late-onset samples, ancillary evidence was obtained that both single marker alleles and haplotypes of ABCA1 contribute to variable cerebrospinal fluid tau and beta amyloid (Abeta42) protein levels, and brain Abeta load. Results indicate that variants of ABCA1 may affect the risk of AD, providing further support for a genetic link between AD and cholesterol metabolism. Copyright 2004 Wiley-Liss, Inc.

  11. The ABCA1 domain responsible for interaction with HIV-1 Nef is conformational and not linear

    PubMed Central

    Jacob, Daria; Hunegnaw, Ruth; Sabyrzyanova, Tatyana A.; Pushkarsky, Tatiana; Chekhov, Vladimir O.; Adzhubei, Alexei A.; Kalebina, Tatyana S.; Bukrinsky, Michael

    2014-01-01

    HIV-1 Nef is an accessory protein responsible for inactivation of a number of host cell proteins essential for anti-viral immune responses. In most cases, Nef binds to the target protein and directs it to a degradation pathway. Our previous studies demonstrated that Nef impairs activity of the cellular cholesterol transporter, ABCA1, and that Nef interacts with ABCA1. Mutation of the 2226DDDHLK motif in the C-terminal cytoplasmic tail of ABCA1 disrupted interaction with Nef. Here, we tested Nef interaction with the ABCA1 C-terminal cytoplasmic fragment using yeast 2-hybrid system assay and co-immunoprecipitation analysis in human cells. Surprisingly, analysis in a yeast 2-hybrid system did not reveal any interaction between Nef and the C-terminal cytoplasmic fragment of ABCA1. Using coimmunoprecipitation from HEK 293T cells expressing these polypeptides, only a very weak interaction could be detected. The 2226DDDHLK motif in the C-terminal cytoplasmic tail of ABCA1 found previously to be essential for interaction between ABCA1 and Nef is insufficient to bestow strong binding to Nef. Molecular modeling suggested that interaction with Nef may be mediated by a conformational epitope composed of the sequences within the cytoplasmic loop of ABCA1 and the C-terminal cytoplasmic domain. Studies are now underway to characterize this epitope. PMID:24406162

  12. Ligand, receptor, and cell type-dependent regulation of ABCA1 and ABCG1 mRNA in prostate cancer epithelial cells

    USDA-ARS?s Scientific Manuscript database

    Recent evidence suggests that the liver X receptor (LXR) is a potential anti-cancer target in prostate carcinoma. There is little characterization, however, of how the two major isoforms LXRa or LXRß regulate the LXR-responsive genes ATP-binding cassette sub-family A 1 (ABCA1) and sub-family member ...

  13. Hydrogen Sulfide Up-Regulates the Expression of ATP-Binding Cassette Transporter A1 via Promoting Nuclear Translocation of PPARα

    PubMed Central

    Li, Dong; Xiong, Qinghui; Peng, Jin; Hu, Bin; Li, Wanzhen; Zhu, Yizhun; Shen, Xiaoyan

    2016-01-01

    ATP binding cassette transporter A1 (ABCA1) plays a key role in atherogenesis. Hydrogen sulfide (H2S), a gasotransmitter, has been reported to play an anti-atherosclerotic role. However, the underlying mechanisms are largely unknown. In this study we examined whether and how H2S regulates ABCA1 expression. The effect of H2S on ABCA1 expression and lipid metabolism were assessed in vitro by cultured human hepatoma cell line HepG2, and in vivo by ApoE−/− mice with a high-cholesterol diet. NaHS (an exogenous H2S donor) treatment significantly increased the expression of ABCA1, ApoA1, and ApoA2 and ameliorated intracellular lipid accumulation in HepG2 cells. Depletion of the endogenous H2S generator cystathionine γ-lyase (CSE) by small RNA interference (siRNA) significantly decreased the expression of ABCA1 and resulted in the accumulation of lipids in HepG2 cells. In vivo NaHS treatment significantly reduced the serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL), diminished atherosclerotic plaque size, and increased hepatic ABCA1 expression in fat-fed ApoE−/− mice. Further study revealed that NaHS upregulated ABCA1 expression by promoting peroxisome proliferator-activated receptor α (PPARα) nuclear translocation. H2S up-regulates the expression of ABCA1 by promoting the nuclear translocation of PPARα, providing a fundamental mechanism for the anti-atherogenic activity of H2S. H2S may be a promising potential drug candidate for the treatment of atherosclerosis. PMID:27136542

  14. Hydrogen Sulfide Up-Regulates the Expression of ATP-Binding Cassette Transporter A1 via Promoting Nuclear Translocation of PPARα.

    PubMed

    Li, Dong; Xiong, Qinghui; Peng, Jin; Hu, Bin; Li, Wanzhen; Zhu, Yizhun; Shen, Xiaoyan

    2016-04-29

    ATP binding cassette transporter A1 (ABCA1) plays a key role in atherogenesis. Hydrogen sulfide (H₂S), a gasotransmitter, has been reported to play an anti-atherosclerotic role. However, the underlying mechanisms are largely unknown. In this study we examined whether and how H₂S regulates ABCA1 expression. The effect of H₂S on ABCA1 expression and lipid metabolism were assessed in vitro by cultured human hepatoma cell line HepG2, and in vivo by ApoE(-/-) mice with a high-cholesterol diet. NaHS (an exogenous H₂S donor) treatment significantly increased the expression of ABCA1, ApoA1, and ApoA2 and ameliorated intracellular lipid accumulation in HepG2 cells. Depletion of the endogenous H₂S generator cystathionine γ-lyase (CSE) by small RNA interference (siRNA) significantly decreased the expression of ABCA1 and resulted in the accumulation of lipids in HepG2 cells. In vivo NaHS treatment significantly reduced the serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL), diminished atherosclerotic plaque size, and increased hepatic ABCA1 expression in fat-fed ApoE(-/-) mice. Further study revealed that NaHS upregulated ABCA1 expression by promoting peroxisome proliferator-activated receptor α (PPARα) nuclear translocation. H₂S up-regulates the expression of ABCA1 by promoting the nuclear translocation of PPARα, providing a fundamental mechanism for the anti-atherogenic activity of H₂S. H₂S may be a promising potential drug candidate for the treatment of atherosclerosis.

  15. HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation.

    PubMed

    Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Cholez, Guy; Ackermann, Rose; Sy, Gavin; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

    2015-01-01

    CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse "flow cessation model," in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively. These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that high doses of HDL and CER-001 induce a rapid and

  16. Cellular cholesterol regulates ubiquitination and degradation of the cholesterol export proteins ABCA1 and ABCG1.

    PubMed

    Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C; Brown, Andrew J; Sandoval, Cecilia; Hallab, Jeannette C; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

    2014-03-14

    The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes.

  17. Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

    PubMed Central

    Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

    2014-01-01

    The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

  18. Hsp27 promotes ABCA1 expression and cholesterol efflux through the PI3K/PKCζ/Sp1 pathway in THP-1 macrophages.

    PubMed

    Kuang, Hai-Jun; Zhao, Guo-Jun; Chen, Wu-Jun; Zhang, Min; Zeng, Gao-Feng; Zheng, Xi-Long; Tang, Chao-Ke

    2017-09-05

    Heat shock protein 27 (Hsp27) is a putative biomarker and therapeutic target in atherosclerosis. This study was to explore the potential mechanisms underlying Hsp27 effects on ATP-binding cassette transporter A1 (ABCA1) expression and cellular cholesterol efflux. THP-1 macrophage-derived foam cells were infected with adenovirus to express wild-type Hsp27, hyper-phosphorylated Hsp27 mimic (3D Hsp27), antisense Hsp27 or hypo-phosphorylated Hsp27 mimic (3A Hsp27). Wild-type and 3D Hsp27 were found to up-regulate ABCA1 mRNA and protein expression and increase cholesterol efflux from cells. Expression of antisense or 3A Hsp27 suppressed the expression of ABCA1 and cholesterol efflux. Furthermore, over-expression of wild-type and 3D Hsp27 significantly increased the levels of phosphorylated specificity protein 1 (Sp1), protein kinase C ζ (PKCζ) and phosphatidylinositol 3-kinase (PI3K). In addition, the up-regulation of ABCA1 expression and cholesterol efflux induced by 3D Hsp27 was suppressed by inhibition of Sp1, PKCζ and PI3K with specific kinase inhibitors. Taken together, our results revealed that Hsp27 may up-regulate the expression of ABCA1 and promotes cholesterol efflux through activation of the PI3K/PKCζ/Sp1 signal pathway in THP-1 macrophage-derived foam cells. Our findings may partly explain the mechanisms underlying the anti-atherogenic effect of Hsp27. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Evidence That Chromium Modulates Cellular Cholesterol Homeostasis and ABCA1 Functionality Impaired By Hyperinsulinemia

    PubMed Central

    Sealls, Whitney; Penque, Brent A.; Elmendorf, Jeffrey S.

    2011-01-01

    Objective Trivalent chromium (Cr3+) is an essential micronutrient. Findings since the 1950s suggest that Cr3+ might benefit cholesterol homeostasis. Here we present mechanistic evidence in support of this role of Cr3+. Method and Results High-density lipoprotein cholesterol generation in 3T3-L1 adipocytes, rendered ineffective by hyperinsulinemia, known to accompany disorders of lipid metabolism was corrected by Cr3+. Mechanistically, Cr3+ reversed hyperinsulinemia-induced cellular cholesterol accrual and associated defects in cholesterol transporter ABCA1 trafficking and apolipoprotein A1-mediated cholesterol efflux. Moreover, direct activation of AMP-activated protein kinase (AMPK), known to be activated by Cr3+, and/or inhibition of hexosamine biosynthesis pathway (HBP) activity, known to be elevated by hyperinsulinemia, mimics Cr3+ action. Conclusion These findings suggest a mechanism of Cr3+ action that fits with long-standing claims of its role in cholesterol homeostasis. Furthermore, these data implicate a mechanistic basis for the coexistence of dyslipidemia with hyperinsulinemia. PMID:21311039

  20. The cholesterol transporter ABCA1 is expressed in stallion spermatozoa and reproductive tract tissues.

    PubMed

    Merkl, M; Ertl, R; Handschuh, S; Aurich, C; Schäfer-Somi, S

    2016-04-01

    In the present study, we assessed the presence of the ATP-binding-cassette (ABC) transporter molecules ABCA1 in spermatozoa of adult stallions and in testicular and epididymal tissue of prepubertal and adult stallions. For this purpose, semen samples from six fertile Shetland pony stallions aged 4 to 19 years were collected. Semen was collected from each stallion on three consecutive days. Ejaculates were analyzed immediately after collection, and only ejaculates meeting minimal requirements for fertile stallions were further evaluated. ABCA1 immunosignal was localized after staining of semen smears with different antibodies and counterstaining with Fluorescein isothiocyanate (FITC)-peanut agglutinin (PNA) and 4',6-Diamidin-2-phenylindol (DAPI). In a total of three samples, capacitation and acrosome reaction were induced by means of capacitation medium and progesterone substitution, respectively. Testicular and epididymal tissues were obtained from five prepubertal stallions aged 8 to 12 months and five adult stallions aged 4 to 9 years. For quantitative RT-PCR (qPCR), testicular and epididymal tissue of another seven adult (aged 1.5-14.5 years) and five prepupertal stallions (6-8 months) was used. For immunohistochemistry, sections from the caput, corpus, and cauda of the testes and epididymes were stained with the same specific antibodies as for immunocytochemistry. In stallion spermatozoa, strong immunosignal for ABCA1 was detected in the acrosomal area, the equatorial zone, and the principle piece of the flagellum but not in the caudal part of the head and the midpiece. In damaged or acrosome-reacted spermatozoa the FITC-PNA signal vanished together with the ABCA1 signal in most spermatozoa. In testicular tissue, strong immunostaining for ABCA1 was mainly visible in the heads and flagella of round spermatids and weaker signals in late spermatids and released spermatozoa. No staining was assessed in the Sertoli cells and spermatogonia of adult stallions, whereas

  1. Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells

    PubMed Central

    Lin, Xiao-Long; Hu, Hui-Jun; Liu, Yuan-Bo; Hu, Xue-Mei; Fan, Xiao-Juan; Zou, Wei-Wen; Pan, Yong-Quan; Zhou, Wen-Quan; Peng, Min-Wen; Gu, Cai-Hong

    2017-01-01

    Allicin is considered anti-atherosclerotic due to its antioxidant and anti-inflammatory effects, which makes it an important drug for the prevention and treatment of atherosclerosis. However, the effects of allicin on foam cells are unclear. Thus, in this study, we examined the effects of allicin on lipid accumulation via peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) in THP-1 macrophage-derived foam cells. THP-1 cells were exposed to 100 nM phorbol myristate acetate (PMA) for 24 h, and then to oxydized low-density lipoprotein (ox-LDL; 50 mg/ml) to induce foam cell formation. The results of Oil Red O staining and high-performance liquid chromatography (HPLC) revealed showed that pre-treatment of the foam cells with allicin decreased total cholesterol, free cholesterol (FC) and cholesterol ester levels in cells, and also decreased lipid accumulation. Moreover, allicin upregulated ATP binding cassette transporter A1 (ABCA1) expression and promoted cholesterol efflux. However, these effects were significantly abolished by transfection with siRNA targeting ABCA1. Furthermore, PPARγ/LXRα signaling was activated by allicin treatment. The allicin-induced upregulation of ABCA1 expression was also abolished by PPARγ inhibitor (GW9662) and siRNA or LXRα siRNA co-treatment. Overall, our data demonstrate that the allicin-induced upregulation of ABCA1 promotes cholesterol efflux and reduces lipid accumulation via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells. PMID:28440421

  2. Glucagon-like peptide-1 contributes to increases ABCA1 expression by downregulating miR-758 to regulate cholesterol homeostasis.

    PubMed

    Yao, Yue; Li, Qiang; Gao, Ping; Wang, Wei; Chen, Lili; Zhang, Jinchao; Xu, Yi

    2018-03-04

    Abnormal regulation of lipid metabolism is associated with type 2 diabetes mellitus (T2DM). GLP-1 as a new treatment for T2DM, has unique effects in modulating cholesterol homeostasis. However, the mechanism of this effect is largely missing. The aim of this study was to determine the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. The cell viability was determined, and caspase-3 was used to detect the effects of GLP-1 on cholesterol-induced apoptosis. The alterations of miR-758 and ATP-binding cassette transporter A1 (ABCA1) resulting from cholesterol incubation or GLP-1 were detected by qRT-PCR and Western blot assays. Overexpression of miR-758 abrogated the GLP-1-mediated ABCA1 expression, and conversely, down-regulation of miR-758 aggravated GLP-1's action and revealed significant promotion effects. BODIPY-Cholesterol efflux assay revealed that treatment with miR-758 inhibitor significantly enhanced ABCA1-dependent cholesterol efflux, resulting in reduced total cholesterol. Furthermore, Oil red O staining and cholesterol measurement were used to detect lipid accumulation. As a result, cholesterol significantly attenuated cell viability, promoted cell apoptosis, and facilitated lipid accumulation, and these effects were reversed by GLP-1. This study provides evidence that, in HepG2 cells, GLP-1 may affect cholesterol homeostasis by regulating the expression of miR-758 and ABCA1. These data can inform the development of biomarkers for miR-758, and potentially other drugs, on the key pathways of lipid metabolism. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Lactobacillus acidophilus K301 Inhibits Atherogenesis via Induction of 24 (S), 25-Epoxycholesterol-Mediated ABCA1 and ABCG1 Production and Cholesterol Efflux in Macrophages

    PubMed Central

    Kim, Hye Sun; Park, Woo Jung; Kim, Joo-Yun; Chung, Dae Kyun

    2016-01-01

    Lactobacillus acidophilus species are well-known probiotics with the beneficial activity of regulating cholesterol levels. In this study, we showed that L. acidophilus K301 reduced the level of cholesterol through reverse transport in macrophages. L. acidophilus K301 upregulated the mRNA and protein levels of genes such as ATP-binding cassette A1 (ABCA1) and ATP-binding cassette G1 (ABCG1) under the control of liver X receptor (LXR), resulting in increased apoA-I-dependent cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. L. acidophilus K301 induced both ABCA1 and ABCG1 through the endogenous LXR agonist 24(S), 25-epoxcycholesterol, which is synthesized by intracellular cholesterol synthetic pathways. In vivo studies using L. acidophilus K301-treated ApoE-/- mice showed reduced accumulation of lipoproteins in the arterial lumen. The inhibitory effects of L. acidophilus K301 on accumulation of lipoprotein in atherosclerotic plaques were mediated by the induction of squalene reductase (SQLE) and oxidosqualene cyclase (OSC) and resulted in ABCA1-mediated cholesterol efflux. Taken together, our findings revealed that Lactobacillus acidophilus K301 regulates the expression of genes related to cholesterol reverse transport via the induction of endogenous LXR agonist, suggesting the therapeutic potential of Lactobacillus acidophilus K301 as an anti-atherosclerotic agent. PMID:27120199

  4. Lactobacillus acidophilus K301 Inhibits Atherogenesis via Induction of 24 (S), 25-Epoxycholesterol-Mediated ABCA1 and ABCG1 Production and Cholesterol Efflux in Macrophages.

    PubMed

    Hong, Yi-Fan; Kim, Hangeun; Kim, Hye Sun; Park, Woo Jung; Kim, Joo-Yun; Chung, Dae Kyun

    2016-01-01

    Lactobacillus acidophilus species are well-known probiotics with the beneficial activity of regulating cholesterol levels. In this study, we showed that L. acidophilus K301 reduced the level of cholesterol through reverse transport in macrophages. L. acidophilus K301 upregulated the mRNA and protein levels of genes such as ATP-binding cassette A1 (ABCA1) and ATP-binding cassette G1 (ABCG1) under the control of liver X receptor (LXR), resulting in increased apoA-I-dependent cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. L. acidophilus K301 induced both ABCA1 and ABCG1 through the endogenous LXR agonist 24(S), 25-epoxcycholesterol, which is synthesized by intracellular cholesterol synthetic pathways. In vivo studies using L. acidophilus K301-treated ApoE-/- mice showed reduced accumulation of lipoproteins in the arterial lumen. The inhibitory effects of L. acidophilus K301 on accumulation of lipoprotein in atherosclerotic plaques were mediated by the induction of squalene reductase (SQLE) and oxidosqualene cyclase (OSC) and resulted in ABCA1-mediated cholesterol efflux. Taken together, our findings revealed that Lactobacillus acidophilus K301 regulates the expression of genes related to cholesterol reverse transport via the induction of endogenous LXR agonist, suggesting the therapeutic potential of Lactobacillus acidophilus K301 as an anti-atherosclerotic agent.

  5. A survey of ABCA1 sequence variation confirms association with dementia

    PubMed Central

    Reynolds, Chandra A.; Hong, Mun-Gwan; Eriksson, Ulrika K.; Blennow, Kaj; Bennet, Anna M.; Johansson, Boo; Malmberg, Bo; Berg, Stig; Wiklund, Fredrik; Gatz, Margaret; Pedersen, Nancy L.; Prince, Jonathan A.

    2009-01-01

    We and others have conducted targeted genetic association analyses of ABCA1 in relation to Alzheimer disease risk with a resultant mixture of both support and refutation, but all previous studies have been based upon only a few markers. Here, a detailed survey of genetic variation in the ABCA1 region has been performed in a total of 1567 Swedish dementia cases (including 1275 with Alzheimer disease) and 2203 controls, providing evidence of association with maximum significance at marker rs2230805 (OR = 1.39; 95% CI 1.23–1.57, P = 7.7 × 10−8). Haplotype-based tests confirmed association of this genomic region after excluding rs2230805, and imputation did not reveal additional markers with greater support. Significantly associating markers reside in two distinct linkage disequilibrium blocks with maxima near the promoter and in the terminal exon of a truncated ABCA1 splice-form. The putative risk allele of rs2230805 was also found to be associated with reduced cerebrospinal fluid levels of β-amyloid. The strongest evidence of association was obtained when all forms of dementia were considered together, but effect sizes were similar when only confirmed Alzheimer disease cases were assessed. Results further implicate ABCA1 in dementia, reinforcing the putative involvement of lipid transport in neurodegenerative disease. PMID:19606474

  6. Large-scale deletions of the ABCA1 gene in patients with hypoalphalipoproteinemia.

    PubMed

    Dron, Jacqueline S; Wang, Jian; Berberich, Amanda J; Iacocca, Michael A; Cao, Henian; Yang, Ping; Knoll, Joan; Tremblay, Karine; Brisson, Diane; Netzer, Christian; Gouni-Berthold, Ioanna; Gaudet, Daniel; Hegele, Robert A

    2018-06-04

    Copy-number variations (CNVs) have been studied in the context of familial hypercholesterolemia but have not yet been evaluated in patients with extremes of high-density lipoprotein (HDL) cholesterol levels. We evaluated targeted next-generation sequencing data from patients with very low HDL cholesterol (i.e. hypoalphalipoproteinemia) using the VarSeq-CNV caller algorithm to screen for CNVs disrupting the ABCA1, LCAT or APOA1 genes. In four individuals, we found three unique deletions in ABCA1: a heterozygous deletion of exon 4, a heterozygous deletion spanning exons 8 to 31, and a heterozygous deletion of the entire ABCA1 gene. Breakpoints were identified using Sanger sequencing, and the full-gene deletion was also confirmed using exome sequencing and the Affymetrix CytoScanTM HD Array. Before now, large-scale deletions in candidate HDL genes have not been associated with hypoalphalipoproteinemia; our findings indicate that CNVs in ABCA1 may be a previously unappreciated genetic determinant of low HDL cholesterol levels. By coupling bioinformatic analyses with next-generation sequencing data, we can successfully assess the spectrum of genetic determinants of many dyslipidemias, now including hypoalphalipoproteinemia. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

    SciTech Connect

    Ohara, Kazuaki, E-mail: Kazuaki_Ohara@kirin.co.jp; Wakabayashi, Hideyuki; Taniguchi, Yoshimasa

    Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXRα. •Q3GA induced ABCA1 via LXRα activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found thatmore » quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.« less

  8. ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis.

    PubMed

    Yamauchi, Yoshio; Yokoyama, Shinji; Chang, Ta-Yuan

    2016-01-01

    Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  9. ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

    PubMed Central

    Yamauchi, Yoshio; Yokoyama, Shinji; Chang, Ta-Yuan

    2016-01-01

    Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway. PMID:26497474

  10. HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation

    PubMed Central

    Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Cholez, Guy; Ackermann, Rose; Sy, Gavin; Keyserling, Constance; Lalwani, Narendra; Paolini, John F.; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

    2015-01-01

    Objective CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). Methods and Results CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse “flow cessation model,” in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively. Conclusions These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that

  11. Amphipathic Polyproline Peptides Stimulate Cholesterol Efflux by the ABCA1 Transporter

    PubMed Central

    Sviridov, D.O.; Drake, S.K.; Freeman, L.A.; Remaley, A.T.

    2016-01-01

    ApoA-I mimetics are short synthetic peptides that contain an amphipathic αα-helix and stimulate cholesterol efflux by the ABCA1 transporter in a detergent-like extraction mechanism. We investigated the use of amphipathic peptides with a polypro helix for stimulating cholesterol efflux by ABCA1. Polypro peptides were synthesized with modified prolines, containing either a hydrophobic phenol group (Prop) or a polar N-acetylgalactosamine (Prog) attached to the pyrrolidine ring and were designated as either PP-2, 3, 4, or 5, depending on the number of 3 amino acid repeat units (Prop - Prog - Prop). Based on molecular modeling, these peptides were predicted to be relatively rigid and to bind to a phospholipid bilayer. By CD spectroscopy, PP peptides formed a Type-II polypro helix in an aqueous solution. PP-2 was inactive in promoting cholesterol efflux, but peptides with more than 2 repeat units were active. PP-4 showed a similar Vmax as a much longer amphipathic α-αhelical peptide, containing 37 amino acids, but had a Km that was approximately 20-fold lower. PP peptides were specific in that they did not stimulate cholesterol efflux from cells not expressing ABCA1 and were also non-cytotoxic. Addition of PP-3, 4 and 5 to serum promoted the formation of smaller size HDL species (7 nM) and increased its capacity for ABCA1-dependent cholesterol efflux by approximately 20-35% (p<0.05). Because of their relatively small size and increased potency, amphipathic peptides with a polypro helix may represent an alternative structural motif for the development of apoA-I mimetic peptides. PMID:26879139

  12. miR-27b inhibits LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels in mice

    PubMed Central

    Goedeke, Leigh; Rotllan, Noemi; Ramírez, Cristina M.; Aranda, Juan F.; Canfrán-Duque, Alberto; Araldi, Elisa; Fernández-Hernando, Ana; Langhi, Cedric; de Cabo, Rafael; Baldán, Ángel; Suárez, Yajaira; Fernández-Hernando, Carlos

    2015-01-01

    Rationale Recently, there has been significant interest in the therapeutic administration of miRNA mimics and inhibitors to treat cardiovascular disease. In particular, miR-27b has emerged as a regulatory hub in cholesterol and lipid metabolism and potential therapeutic target for treating atherosclerosis. Despite this, the impact of miR-27b on lipid levels in vivo remains to be determined. As such, here we set out to further characterize the role of miR-27b in regulating cholesterol metabolism in vitro and to determine the effect of miR-27b overexpression and inhibition on circulating and hepatic lipids in mice. Methods and Results Our results identify miR-27b as an important regulator of LDLR activity in human and mouse hepatic cells through direct targeting of LDLR and LDLRAP1. In addition, we report that modulation of miR-27b expression affects ABCA1 protein levels and cellular cholesterol efflux to ApoA1 in human hepatic Huh7 cells. Overexpression of pre-miR-27b in the livers of wild-type mice using AAV8 vectors increased pre-miR-27b levels 50–fold and reduced hepatic ABCA1 and LDLR expression by 50% and 20%, respectively, without changing circulating and hepatic cholesterol and triglycerides. To determine the effect of endogenous miR-27b on circulating lipids, wild-type mice were fed a Western diet for one month and injected with 5 mg/kg of LNA control or LNA anti-miR-27b oligonucleotides. Following two weeks of treatment, the expression of ABCA1 and LDLR were increased by 10–20% in the liver, demonstrating effective inhibition of miR-27b function. Intriguingly, no differences in circulating and hepatic lipids were observed between treatment groups. Conclusions The results presented here provide evidence that short-term modulation of miR-27b expression in wild-type mice regulates hepatic LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels. PMID:26520906

  13. Association studies of several cholesterol-related genes (ABCA1, CETP and LIPC) with serum lipids and risk of Alzheimer’s disease

    PubMed Central

    2012-01-01

    Objectives Accumulating evidence suggested that dysregulation of cholesterol homeostasis might be a major etiologic factor in initiating and promoting neurodegeneration in Alzheimer’s disease (AD). ATP-binding cassette transporter A1 (ABCA1), hepatic lipase (HL, coding genes named LIPC) and cholesteryl ester transfer protein (CETP) are important components of high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) implicated in atherosclerosis and neurodegenerative diseases. In the present study, we will investigate the possible association of several common polymorphisms (ABCA1R219K, CETPTaqIB and LIPC-250 G/A) with susceptibility to AD and plasma lipid levels. Methods Case–control study of 208 Han Chinese (104 AD patients and 104 non-demented controls) from Changsha area in Hunan Province was performed using the PCR-RFLP analysis. Cognitive decline was assessed using Mini Mental State Examination (MMSE) as a standardized method. Additionally, fasting lipid profile and the cognitive testing scores including Wechsler Memory Scale (WMS) and Wisconsin Card Sorting Test (WCST) were recorded. Results and conclusions We found significant differences among the genotype distributions of these three genes in AD patients when compared with controls. But after adjusting other factors, multivariate logistic regression analysis showed only ABCA1R219K (B = −0.903, P = 0.005, OR = 0.405, 95%CI:0.217-0.758) and LIPC-250 G/A variants(B = −0.905, P = 0.018, OR = 0.405, 95%CI:0.191-0.858) were associated with decreased AD risk. There were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) and apolipoproteinA-I in the carriers of KK genotype and K allele (P < 0.05), and B2B2 genotype of CETP Taq1B showed significant association with higher HDL-C levels than other genotypes (F = 5.598, P = 0.004), while -250 G/A polymorphisms had no significant effect on HDL-C. In total population, subjects

  14. Tangshen Formula Attenuates Diabetic Nephropathy by Promoting ABCA1-Mediated Renal Cholesterol Efflux in db/db Mice.

    PubMed

    Liu, Peng; Peng, Liang; Zhang, Haojun; Tang, Patrick Ming-Kuen; Zhao, Tingting; Yan, Meihua; Zhao, Hailing; Huang, Xiaoru; Lan, Huiyao; Li, Ping

    2018-01-01

    The commonly prescribed Tangshen Formula (TSF) is a traditional Chinese formulation that has been shown to reduce plasma lipid metabolism and proteinuria and improve the estimated glomerular filtration rate (eGFR) in patients with diabetic kidney disease. This study investigated the underlying mechanism whereby TSF regulates renal lipid accumulation and ameliorates diabetic renal injuries in spontaneous diabetic db/db mice and in vitro in sodium palmitate (PA)-stimulated and Abca1-SiRNA-transfected mouse tubular epithelial cells (mTECs). The results revealed that TSF treatment significantly ameliorated the renal injuries by lowering urinary albumin excretion and improving renal tissue injuries in diabetic (db/db) mice. Interestingly, the treatment with TSF also resulted in decreased cholesterol levels in the renal tissues of db/db mice, which was associated with increased expression of the peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), the Liver X receptors (LXR), and ATP-binding cassette subfamily A member 1 (ABCA1), suggesting that TSF might attenuate diabetic kidney injury via a mechanism associated with improving cholesterol efflux in the diabetic kidney. This was investigated in vitro in mTECs, and the results showed that TSF reduced the PA-stimulated cholesterol accumulation in mTECs. Mechanistically, the addition of TSF was capable of reversing PA-induced downregulation of PGC-1α, LXR, and ABCA1 expression and cholesterol accumulation in mTECs, suggesting that TSF might act the protection via the PGC-1α-LXR-ABCA1 pathway to improve the cholesterol efflux in the renal tissues of db/db mice. This was further confirmed by silencing ABCA1 to block the promotive effect of TSF on cholesterol efflux in vitro . In conclusion, TSF might ameliorate diabetic kidney injuries by promoting ABCA1-mediated renal cholesterol efflux.

  15. 13-hydroxy linoleic acid increases expression of the cholesterol transporters ABCA1, ABCG1 and SR-BI and stimulates apoA-I-dependent cholesterol efflux in RAW264.7 macrophages

    PubMed Central

    2011-01-01

    Background Synthetic activators of peroxisome proliferator-activated receptors (PPARs) stimulate cholesterol removal from macrophages through PPAR-dependent up-regulation of liver × receptor α (LXRα) and subsequent induction of cholesterol exporters such as ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type 1 (SR-BI). The present study aimed to test the hypothesis that the hydroxylated derivative of linoleic acid (LA), 13-HODE, which is a natural PPAR agonist, has similar effects in RAW264.7 macrophages. Methods RAW264.7 macrophages were treated without (control) or with LA or 13-HODE in the presence and absence of PPARα or PPARγ antagonists and determined protein levels of LXRα, ABCA1, ABCG1, SR-BI, PPARα and PPARγ and apolipoprotein A-I mediated lipid efflux. Results Treatment of RAW264.7 cells with 13-HODE increased PPAR-transactivation activity and protein concentrations of LXRα, ABCA1, ABCG1 and SR-BI when compared to control treatment (P < 0.05). In addition, 13-HODE enhanced cholesterol concentration in the medium but decreased cellular cholesterol concentration during incubation of cells with the extracellular lipid acceptor apolipoprotein A-I (P < 0.05). Pre-treatment of cells with a selective PPARα or PPARγ antagonist completely abolished the effects of 13-HODE on cholesterol efflux and protein levels of genes investigated. In contrast to 13-HODE, LA had no effect on either of these parameters compared to control cells. Conclusion 13-HODE induces cholesterol efflux from macrophages via the PPAR-LXRα-ABCA1/SR-BI-pathway. PMID:22129452

  16. The E3 ubiquitin ligase, HECTD1, is involved in ABCA1-mediated cholesterol export from macrophages.

    PubMed

    Aleidi, Shereen M; Yang, Alryel; Sharpe, Laura J; Rao, Geetha; Cochran, Blake J; Rye, Kerry-Anne; Kockx, Maaike; Brown, Andrew J; Gelissen, Ingrid C

    2018-04-01

    The ABC lipid transporters, ABCA1 and ABCG1, are essential for maintaining lipid homeostasis in cells such as macrophages by exporting excess cholesterol to extracellular acceptors. These transporters are highly regulated at the post-translational level, including protein ubiquitination. Our aim was to investigate the role of the E3 ubiquitin ligase HECTD1, recently identified as associated with ABCG1, on ABCG1 and ABCA1 protein levels and cholesterol export function. Here, we show that HECTD1 protein is widely expressed in a range of human and murine primary cells and cell lines, including macrophages, neuronal cells and insulin secreting β-cells. siRNA knockdown of HECTD1 unexpectedly decreased overexpressed ABCG1 protein levels and cell growth, but increased native ABCA1 protein in CHO-K1 cells. Knockdown of HECTD1 in unloaded THP-1 macrophages did not affect ABCG1 but significantly increased ABCA1 protein levels, in wild-type as well as THP-1 cells that do not express ABCG1. Cholesterol export from macrophages to apoA-I over time was increased after knockdown of HECTD1, however these effects were not sustained in cholesterol-loaded cells. In conclusion, we have identified a new candidate, the E3 ubiquitin ligase HECTD1, that may be involved in the regulation of ABCA1-mediated cholesterol export from unloaded macrophages to apoA-I. The exact mechanism by which this ligase affects this pathway remains to be elucidated. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking.

    PubMed

    Chen, Meimei; Yang, Fafu; Kang, Jie; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

    2016-11-29

    In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators.

  18. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans

    PubMed Central

    Acuña-Alonzo, Víctor; Flores-Dorantes, Teresa; Kruit, Janine K.; Villarreal-Molina, Teresa; Arellano-Campos, Olimpia; Hünemeier, Tábita; Moreno-Estrada, Andrés; Ortiz-López, Ma Guadalupe; Villamil-Ramírez, Hugo; León-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramírez-Jiménez, Salvador; Sikora, Martin; Zhang, Lin-Hua; Pape, Terry D.; de Ángeles Granados-Silvestre, Ma; Montufar-Robles, Isela; Tito-Alvarez, Ana M.; Zurita-Salinas, Camilo; Bustos-Arriaga, José; Cedillo-Barrón, Leticia; Gómez-Trejo, Celta; Barquera-Lozano, Rodrigo; Vieira-Filho, Joao P.; Granados, Julio; Romero-Hidalgo, Sandra; Huertas-Vázquez, Adriana; González-Martín, Antonio; Gorostiza, Amaya; Bonatto, Sandro L.; Rodríguez-Cruz, Maricela; Wang, Li; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A.; Lisker, Ruben; Moises, Regina S.; Menjivar, Marta; Salzano, Francisco M.; Knowler, William C.; Bortolini, M. Cátira; Hayden, Michael R.; Baier, Leslie J.; Canizales-Quinteros, Samuel

    2010-01-01

    It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 × 10−11) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations. PMID:20418488

  19. Insulin-like Growth Factor 1 Regulates the Expression of ATP-Binding Cassette Transporter A1 in Pancreatic Beta Cells.

    PubMed

    Lyu, J; Imachi, H; Iwama, H; Zhang, H; Murao, K

    2016-05-01

    ATP-binding cassette transporter A1 (ABCA1) in pancreatic beta cells influences insulin secretion and cholesterol homeostasis. The present study investigates whether insulin-like growth factor 1 (IGF-1), which mediates stimulation of ABCA1 gene expression, could also interfere with the phosphatidylinositol 3-kinase (PI3-K) cascade.ABCA1 expression was examined by real-time polymerase chain reaction (PCR), Western blot analysis, and a reporter gene assay in rat insulin-secreting INS-1 cells incubated with IGF-1. The binding of forkhead box O1 (FoxO1) protein to the ABCA1 promoter was assessed by a chromatin immunoprecipitation (ChIP) assay. ABCA1 protein levels increased in response to rising concentrations of IGF-1. Real-time PCR analysis showed a significant increase in ABCA1 mRNA expression. However, both effects were suppressed after silencing the IGF-1 receptor. In parallel with its effect on endogenous ABCA1 mRNA levels, IGF-1 induced the activity of a reporter construct containing the ABCA1 promoter, while it was abrogated by LY294002, a specific inhibitor of PI3-K. Constitutively active Akt stimulated activity of the ABCA1 promoter, and a dominant-negative mutant of Akt or mutagenesis of the FoxO1 response element in the ABCA1 promoter abolished the ability of IGF-1 to stimulate promoter activity. A ChIP assay showed that FoxO1 mediated its transcriptional activity by directly binding to the ABCA1 promoter region. The knockdown of FoxO1 disrupted the effect of IGF-1 on ABCA1 expression. Furthermore, IGF-1 promoted cholesterol efflux and reduced the pancreatic lipotoxicity. These results demonstrate that the PI3-K/Akt/FoxO1 pathway contributes to the regulation of ABCA1 expression in response to IGF-1 stimulation. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Apo AI/ABCA1-dependent and HDL3-mediated lipid efflux from compositionally distinct cholesterol-based microdomains.

    PubMed

    Drobnik, Wolfgang; Borsukova, Hana; Böttcher, Alfred; Pfeiffer, Alexandra; Liebisch, Gerhard; Schütz, Gerhard J; Schindler, Hansgeorg; Schmitz, Gerd

    2002-04-01

    We have investigated whether a raft heterogeneity exists in human monocyte-derived macrophages and fibroblasts and whether these microdomains are modulated by lipid efflux. Triton X-100 (Triton) or Lubrol WX (Lubrol) detergent-resistant membranes from cholesterol-loaded monocytes were associated with the following findings: (i) Lubrol-DRM contained most of the cellular cholesterol and at least 75% of Triton-detergent-resistant membranes. (ii) 'Lubrol rafts', defined by their solubility in Triton but insolubility in Lubrol, were enriched in unsaturated phosphatidylcholine and showed a lower cholesterol to choline-phospholipid ratio compared to Triton rafts. (iii) CD14 and CD55 were recovered in Triton- and Lubrol-detergent-resistant membranes, whereas CD11b was found exclusively in Triton DRM. ABCA1 implicated in apo AI-mediated lipid efflux and CDC42 were partially localized in Lubrol- but not in Triton-detergent-resistant membranes. (iv) Apo AI preferentially depleted cholesterol and choline-phospholipids from Lubrol rafts, whereas HDL3 additionally decreased the cholesterol content of Triton rafts. In fibroblasts, neither ABCA1 nor CDC42 was found in Lubrol rafts, and both apo AI and HDL3 reduced the lipid content in Lubrol- as well as in Triton-detergent-resistant membranes. In summary, we provide evidence for the existence of compositionally distinct membrane microdomains in human cells and their modulation by apo AI/ABCA1-dependent and HDL3-mediated lipid efflux.

  1. MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1.

    PubMed

    Lv, Yun-Cheng; Tang, Yan-Yan; Peng, Juan; Zhao, Guo-Jun; Yang, Jing; Yao, Feng; Ouyang, Xin-Ping; He, Ping-Ping; Xie, Wei; Tan, Yu-Lin; Zhang, Min; Liu, Dan; Tang, Deng-Pei; Cayabyab, Francisco S; Zheng, Xi-Long; Zhang, Da-Wei; Tian, Guo-Ping; Tang, Chao-Ke

    2014-09-01

    Macrophage accumulation of cholesterol leads to foam cell formation which is a major pathological event of atherosclerosis. Recent studies have shown that microRNA (miR)-19b might play an important role in cholesterol metabolism and atherosclerotic diseases. Here, we have identified miR-19b binding to the 3'UTR of ATP-binding cassette transporter A1 (ABCA1) transporters, and further determined the potential roles of this novel interaction in atherogenesis. To investigate the molecular mechanisms involved in a miR-19b promotion of macrophage cholesterol accumulation and the development of aortic atherosclerosis. We performed bioinformatics analysis using online websites, and found that miR-19b was highly conserved during evolution and directly bound to ABCA1 mRNA with very low binding free energy. Luciferase reporter assay confirmed that miR-19b bound to 3110-3116 sites within ABCA1 3'UTR. MiR-19b directly regulated the expression levels of endogenous ABCA1 in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by qRT-PCR and western blot. Cholesterol transport assays revealed that miR-19b dramatically suppressed apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux, resulting in the increased levels of total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) as revealed by HPLC. The excretion of (3)H-cholesterol originating from cholesterol-laden MPMs into feces was decreased in mice overexpressing miR-19b. Finally, we evaluated the proatherosclerotic role of miR-19b in apolipoprotein E deficient (apoE(-/-)) mice. Treatment with miR-19b precursor reduced plasma high-density lipoprotein (HDL) levels, but increased plasma low-density lipoprotein (LDL) levels. Consistently, miR-19b precursor treatment increased aortic plaque size and lipid content, but reduced collagen content and ABCA1 expression. In contrast, treatment with the inhibitory miR-19b antisense oligonucleotides (ASO) prevented or

  2. Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population.

    PubMed

    Villalobos-Comparán, Marisela; Antuna-Puente, Bárbara; Villarreal-Molina, María Teresa; Canizales-Quinteros, Samuel; Velázquez-Cruz, Rafael; León-Mimila, Paola; Villamil-Ramírez, Hugo; González-Barrios, Juan Antonio; Merino-García, José Luis; Thompson-Bonilla, María Rocío; Jarquin, Diego; Sánchez-Hernández, Osvaldo Erik; Rodríguez-Arellano, Martha Eunice; Posadas-Romero, Carlos; Vargas-Alarcón, Gilberto; Campos-Pérez, Francisco; Quiterio, Manuel; Salmerón-Castro, Jorge; Carnevale, Alessandra; Romero-Hidalgo, Sandra

    2017-05-02

    The aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations. A total of 3938 adults and 636 school-aged children from Central Mexico were genotyped for both polymorphisms. Subcutaneous and visceral adipose tissue biopsies from 22 class III obesity patients were analyzed for FTO and ABCA1 mRNA expression. Generalized linear models were used to test for associations and gene-gene interactions affecting BMI, WC and FTO expression. FTO and ABCA1 risk alleles were not individually associated with higher BMI or WC. However, in the absence of the ABCA1 risk allele, the FTO risk variant was significantly associated with higher BMI (P = 0.043) and marginally associated with higher WC (P = 0.067), as reported in Europeans. The gene-gene interaction affecting BMI and WC was statistically significant only in adults. FTO mRNA expression in subcutaneous abdominal adipose tissue according to ABCA1 genotype was consistent with these findings. This is the first report showing evidence of FTO and ABCA1 gene variant interactions affecting BMI, which may explain previously reported population differences. Further studies are needed to confirm this interaction.

  3. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function

    PubMed Central

    Kara, Firas M.; Chitu, Violeta; Sloane, Jennifer; Axelrod, Matthew; Fredholm, Bertil B.; Stanley, E. Richard; Cronstein, Bruce N.

    2010-01-01

    Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A1R, A2AR, A2BR, and A3R). Because A1R occupancy promotes fusion of human monocytes to form giant cells in vitro, we determined whether A1R occupancy similarly promotes osteoclast function and formation. Bone marrow cells (BMCs) were harvested from C57Bl/6 female mice or A1R-knockout mice and their wild-type (WT) littermates and differentiated into osteoclasts in the presence of colony stimulating factor-1 and receptor activator of NF-κB ligand in the presence or absence of the A1R antagonist 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX). Osteoclast morphology was analyzed in tartrate-resistant acid phosphatase or F-actin-stained samples, and bone resorption was evaluated by toluidine blue staining of dentin. BMCs from A1R-knockout mice form fewer osteoclasts than BMCs from WT mice, and the A1R antagonist DPCPX inhibits osteoclast formation (IC50=1 nM), with altered morphology and reduced ability to resorb bone. A1R blockade increased ubiquitination and degradation of TRAF6 in RAW264.7 cells induced to differentiate into osteoclasts. These studies suggest a critical role for adenosine in bone homeostasis via interaction with adenosine A1R and further suggest that A1R may be a novel pharmacologic target to prevent the bone loss associated with inflammatory diseases and menopause.—Kara, F. M., Chitu, V., Sloane, J., Axelrod, M., Fredholm, B. B., Stanley, R., Cronstein, B. N. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function. PMID:20181934

  4. Lipid Absorption Defects in Intestine-specific Microsomal Triglyceride Transfer Protein and ATP-binding Cassette Transporter A1-deficient Mice*

    PubMed Central

    Iqbal, Jahangir; Parks, John S.; Hussain, M. Mahmood

    2013-01-01

    We have previously described apolipoprotein B (apoB)-dependent and -independent cholesterol absorption pathways and the role of microsomal triglyceride transfer protein (MTP) and ATP-binding cassette transporter A1 (ABCA1) in these pathways. To assess the contribution of these pathways to cholesterol absorption and to determine whether there are other pathways, we generated mice that lack MTP and ABCA1, individually and in combination, in the intestine. Intestinal deletions of Mttp and Abca1 decreased plasma cholesterol concentrations by 45 and 24%, respectively, whereas their combined deletion reduced it by 59%. Acute cholesterol absorption was reduced by 28% in the absence of ABCA1, and it was reduced by 92–95% when MTP was deleted in the intestine alone or together with ABCA1. MTP deficiency significantly reduced triglyceride absorption, although ABCA1 deficiency had no effect. ABCA1 deficiency did not affect cellular lipids, but Mttp deficiency significantly increased intestinal levels of triglycerides and free fatty acids. Accumulation of intestinal free fatty acids, but not triglycerides, in Mttp-deficient intestines was prevented when mice were also deficient in intestinal ABCA1. Combined deficiency of these genes increased intestinal fatty acid oxidation as a consequence of increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and carnitine palmitoyltransferase 1α (CPT1α). These studies show that intestinal MTP and ABCA1 are critical for lipid absorption and are the main determinants of plasma and intestinal lipid levels. Reducing their activities might lower plasma lipid concentrations. PMID:24019513

  5. Proteomic analysis of HDL from inbred mouse strains implicates APOE associated with HDL in reduced cholesterol efflux capacity via the ABCA1 pathway[S

    PubMed Central

    Pamir, Nathalie; Hutchins, Patrick; Ronsein, Graziella; Vaisar, Tomas; Reardon, Catherine A.; Getz, Godfrey S.; Lusis, Aldons J.; Heinecke, Jay W.

    2016-01-01

    Cholesterol efflux capacity associates strongly and negatively with the incidence and prevalence of human CVD. We investigated the relationships of HDL’s size and protein cargo with its cholesterol efflux capacity using APOB-depleted serum and HDLs isolated from five inbred mouse strains with different susceptibilities to atherosclerosis. Like humans, mouse HDL carried >70 proteins linked to lipid metabolism, the acute-phase response, proteinase inhibition, and the immune system. HDL’s content of specific proteins strongly correlated with its size and cholesterol efflux capacity, suggesting that its protein cargo regulates its function. Cholesterol efflux capacity with macrophages strongly and positively correlated with retinol binding protein 4 (RBP4) and PLTP, but not APOA1. In contrast, ABCA1-specific cholesterol efflux correlated strongly with HDL’s content of APOA1, APOC3, and APOD, but not RBP4 and PLTP. Unexpectedly, APOE had a strong negative correlation with ABCA1-specific cholesterol efflux capacity. Moreover, the ABCA1-specific cholesterol efflux capacity of HDL isolated from APOE-deficient mice was significantly greater than that of HDL from wild-type mice. Our observations demonstrate that the HDL-associated APOE regulates HDL’s ABCA1-specific cholesterol efflux capacity. These findings may be clinically relevant because HDL’s APOE content associates with CVD risk and ABCA1 deficiency promotes unregulated cholesterol accumulation in human macrophages. PMID:26673204

  6. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma

    PubMed Central

    Fogarty, Rhys; Sharma, Shiwani; Hewitt, Alex W.; Martin, Sarah; Law, Matthew H.; Cremin, Katie; Bailey, Jessica N. Cooke; Loomis, Stephanie J.; Pasquale, Louis R.; Haines, Jonathan L.; Hauser, Michael A.; Viswanathan, Ananth C.; McGuffin, Peter; Topouzis, Fotis; Foster, Paul J.; Graham, Stuart L; Casson, Robert J; Chehade, Mark; White, Andrew J; Zhou, Tiger; Souzeau, Emmanuelle; Landers, John; Fitzgerald, Jude T; Klebe, Sonja; Ruddle, Jonathan B; Goldberg, Ivan; Healey, Paul R; Mills, Richard A.; Wang, Jie Jin; Montgomery, Grant W.; Martin, Nicholas G.; Radford-Smith, Graham; Whiteman, David C.; Brown, Matthew A.; Wiggs, Janey L.; Mackey, David A; Mitchell, Paul; MacGregor, Stuart; Craig, Jamie E.

    2014-01-01

    Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 advanced POAG cases and 1,992 controls. Association of the top SNPs from the discovery stage was investigated in two Australian replication cohorts (total 932 cases, 6,862 controls) and two US replication cohorts (total 2,616 cases, 2,634 controls). Meta-analysis of all cohorts revealed three novel loci associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493 [G] OR=1.31, P= 2.1 × 10−19), within AFAP1 (rs4619890 [G] OR=1.20, P= 7.0 × 10−10) and within GMDS (rs11969985 [G] OR=1.31, and P= 7.7 × 10−10). Using RT-PCR and immunolabelling, we also showed that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells. PMID:25173105

  7. High glucose upregulates BACE1-mediated Aβ production through ROS-dependent HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization in SK-N-MC cells

    PubMed Central

    Lee, Hyun Jik; Ryu, Jung Min; Jung, Young Hyun; Lee, Sei-Jung; Kim, Jeong Yeon; Lee, Sang Hun; Hwang, In Koo; Seong, Je Kyung; Han, Ho Jae

    2016-01-01

    There is an accumulation of evidence indicating that the risk of Alzheimer’s disease is associated with diabetes mellitus, an indicator of high glucose concentrations in blood plasma. This study investigated the effect of high glucose on BACE1 expression and amyloidogenesis in vivo, and we present details of the mechanism associated with those effects. Our results, using ZLC and ZDF rat models, showed that ZDF rats have high levels of amyloid-beta (Aβ), phosphorylated tau, BACE1, and APP-C99. In vitro result with mouse hippocampal neuron and SK-N-MC, high glucose stimulated Aβ secretion and apoptosis in a dose-dependent manner. In addition, high glucose increased BACE1 and APP-C99 expressions, which were reversed by a reactive oxygen species (ROS) scavenger. Indeed, high glucose increased intracellular ROS levels and HIF-1α expression, associated with regulation of BACE1 and Liver X Receptor α (LXRα). In addition, high glucose induced ATP-binding cassette transporter A1 (ABCA1) down-regulation, was associated with LXR-induced lipid raft reorganization and BACE1 localization on the lipid raft. Furthermore, silencing of BACE1 expression was shown to regulate Aβ secretion and apoptosis of SK-N-MC. In conclusion, high glucose upregulates BACE1 expression and activity through HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization, leading to Aβ production and apoptosis of SK-N-MC. PMID:27829662

  8. Neopterin negatively regulates expression of ABCA1 and ABCG1 by the LXRα signaling pathway in THP-1 macrophage-derived foam cells.

    PubMed

    Yan, Jin-quan; Tan, Chun-zhi; Wu, Jin-hua; Zhang, Dong-cui; Chen, Ji-ling; Zeng, Bin-yuan; Jiang, Yu-ping; Nie, Jin; Liu, Wei; Liu, Qin; Dai, Hao

    2013-07-01

    To investigate the effects of neopterin on ABCA1 expression and cholesterol efflux in human THP-1 macrophage-derived foam cells, and to explore the role of the liver X receptor alpha (LXRα) involved. In the present study, THP-1 cells were pre-incubated with ox-LDL to become foam cells. The protein and mRNA expression were examined by Western blot assays and real-time quantitative PCR, respectively. Liquid scintillation counting and high performance liquid chromatography assays were used to test cellular cholesterol efflux and cholesterol content. Neopterin decreased ABCA1 expression and cholesterol efflux in a time- and concentration-dependent manner in THP-1 macrophage-derived foam cells, and the LXRα siRNA can reverse the inhibitory effects induced by neopterin. Neoterin has a negative regulation on ABCA1 expression via the LXRα signaling pathway, which suggests the aggravated effects of neopterin on atherosclerosis.

  9. Novel Apo E-Derived ABCA1 Agonist Peptide (CS-6253) Promotes Reverse Cholesterol Transport and Induces Formation of preβ-1 HDL In Vitro

    PubMed Central

    Hafiane, Anouar; Bielicki, John K.; Johansson, Jan O.; Genest, Jacques

    2015-01-01

    Apolipoprotein (apo) mimetic peptides replicate some aspects of HDL function. We have previously reported the effects of compound ATI-5261 on its ability to replicate many functions of native apo A-I in the process of HDL biogenesis. ATI-5261 induced muscle toxicity in wild type C57Bl/6 mice, increased CPK, ALT and AST and increase in triglyceride (Tg) levels. Aromatic phenylalanine residues on the non-polar face of ATI-5261, together with positively charged arginine residues at the lipid-water interface were responsible for these effects. This information was used to create a novel analog (CS-6253) that was non-toxic. We evaluated this peptide designed from the carboxyl terminus of apo E, in its ability to mimic apo A-I functionality. Our data shows that the lipidated particles generated by incubating cells overexpressing ABCA1 with lipid free CS-6253 enhances the rate of ABCA1 lipid efflux with high affinity interactions with native ABCA1 oligomeric forms and plasma membrane micro-domains. Interaction between ABCA1 and lipid free CS-6253 resulted in formation of nascent HDL-CS-6253 particles that are actively remodeled in plasma. Mature HDL-CS-6253 particles deliver cholesterol to liver cells via SR-BI in-vitro. CS-6253 significantly increases cholesterol efflux in murine macrophages and in human THP-1 macrophage-derived foam cells expressing ABCA1. Addition of CS-6253 to plasma dose-dependently displaced apo A-I from α-HDL particles and led to de novo formation of preβ-1 HDL that stimulates ABCA1 dependent cholesterol efflux efficiently. When incubated with human plasma CS-6253 was also found to bind with HDL and LDL and promoted the transfer of cholesterol from HDL to LDL predominantly. Our data shows that CS-6253 mimics apo A-I in its ability to promote ABCA1-mediated formation of nascent HDL particles, and enhances formation of preβ-1 HDL with increase in the cycling of apo A-I between the preβ and α-HDL particles in-vitro. These mechanisms are

  10. Novel apo E-derived ABCA1 agonist peptide (CS-6253) promotes reverse cholesterol transport and induces formation of preβ-1 HDL in vitro

    DOE PAGES

    Hafiane, Anouar; Bielicki, John K.; Johansson, Jan O.; ...

    2015-07-24

    Apolipoprotein (apo) mimetic peptides replicate some aspects of HDL function. We have previously reported the effects of compound ATI-5261 on its ability to replicate many functions of native apo A-I in the process of HDL biogenesis. ATI-5261 induced muscle toxicity in wild type C57Bl/6 mice, increased CPK, ALT and AST and increase in triglyceride (Tg) levels. Aromatic phenylalanine residues on the non-polar face of ATI-5261, together with positively charged arginine residues at the lipid-water interface were responsible for these effects. This information was used to create a novel analog (CS-6253) that was non-toxic. We evaluated this peptide designed from themore » carboxyl terminus of apo E, in its ability to mimic apo A-I functionality. Our data shows that the lipidated particles generated by incubating cells overexpressing ABCA1 with lipid free CS-6253 enhances the rate of ABCA1 lipid efflux with high affinity interactions with native ABCA1 oligomeric forms and plasma membrane micro-domains. Interaction between ABCA1 and lipid free CS-6253 resulted in formation of nascent HDL-CS-6253 particles that are actively remodeled in plasma. Mature HDL-CS-6253 particles deliver cholesterol to liver cells via SR-BI in-vitro. CS-6253 significantly increases cholesterol efflux in murine macrophages and in human THP-1 macrophage-derived foam cells expressing ABCA1. Addition of CS-6253 to plasma dose-dependently displaced apo A-I from α-HDL particles and led to de novo formation of preβ-1 HDL that stimulates ABCA1 dependent cholesterol efflux efficiently. When incubated with human plasma CS-6253 was also found to bind with HDL and LDL and promoted the transfer of cholesterol from HDL to LDL predominantly. Our data shows that CS-6253 mimics apo A-I in its ability to promote ABCA1-mediated formation of nascent HDL particles, and enhances formation of preβ-1 HDL with increase in the cycling of apo A-I between the preβ and α-HDL particles in-vitro. These mechanisms are

  11. Eicosapentaenoic acid membrane incorporation impairs ABCA1-dependent cholesterol efflux via a protein kinase A signaling pathway in primary human macrophages.

    PubMed

    Fournier, Natalie; Tardivel, Sylviane; Benoist, Jean-François; Vedie, Benoît; Rousseau-Ralliard, Delphine; Nowak, Maxime; Allaoui, Fatima; Paul, Jean-Louis

    2016-04-01

    A diet rich in n-3/n-6 polyunsaturated fatty acids (PUFAs) is cardioprotective. Dietary PUFAs affect the cellular phospholipids composition, which may influence the function of membrane proteins. We investigated the impact of the membrane incorporation of several PUFAs on ABCA1-mediated cholesterol efflux, a key antiatherogenic pathway. Arachidonic acid (AA) (C20:4 n-6) and docosahexaenoic acid (DHA) (C22:6 n-3) decreased or increased cholesterol efflux from J774 mouse macrophages, respectively, whereas they had no effect on efflux from human monocyte-derived macrophages (HMDM). Importantly, eicosapentaenoic acid (EPA) (C20:5 n-3) induced a dose-dependent reduction of ABCA1 functionality in both cellular models (-28% for 70μM of EPA in HMDM), without any alterations in ABCA1 expression. These results show that PUFA membrane incorporation does not have the same consequences on cholesterol efflux from mouse and human macrophages. The EPA-treated HMDM exhibited strong phospholipid composition changes, with high levels of both EPA and its elongation product docosapentaenoic acid (DPA) (C22:5 n-3), which is associated with a decreased level of AA. In HMDM, EPA reduced the ATPase activity of the membrane transporter. Moreover, the activation of adenylate cyclase by forskolin and the inhibition of cAMP phosphodiesterase by isobutylmethylxanthine restored ABCA1 cholesterol efflux in EPA-treated human macrophages. In conclusion, EPA membrane incorporation reduces ABCA1 functionality in mouse macrophages as well as in primary human macrophages and this effect seems to be PKA-dependent in human macrophages. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Prenatal Ethanol Exposure Up-Regulates the Cholesterol Transporters ATP-Binding Cassette A1 and G1 and Reduces Cholesterol Levels in the Developing Rat Brain.

    PubMed

    Zhou, Chunyan; Chen, Jing; Zhang, Xiaolu; Costa, Lucio G; Guizzetti, Marina

    2014-11-01

    Cholesterol plays a pivotal role in many aspects of brain development; reduced cholesterol levels during brain development, as a consequence of genetic defects in cholesterol biosynthesis, leads to severe brain damage, including microcephaly and mental retardation, both of which are also hallmarks of the fetal alcohol syndrome. We had previously shown that ethanol up-regulates the levels of two cholesterol transporters, ABCA1 (ATP binding cassette-A1) and ABCG1, leading to increased cholesterol efflux and decreased cholesterol content in astrocytes in vitro. In the present study we investigated whether similar effects could be seen in vivo. Pregnant Sprague-Dawley rats were fed liquid diets containing 36% of the calories from ethanol from gestational day (GD) 6 to GD 21. A pair-fed control groups and an ad libitum control group were included in the study. ABCA1 and ABCG1 protein expression and cholesterol and phospholipid levels were measured in the neocortex of female and male fetuses at GD 21. Body weights were decreased in female fetuses as a consequence of ethanol treatments. ABCA1 and ABCG1 protein levels were increased, and cholesterol levels were decreased, in the neocortex of ethanol-exposed female, but not male, fetuses. Levels of phospholipids were unchanged. Control female fetuses fed ad libitum displayed an up-regulation of ABCA1 and a decrease in cholesterol content compared with pair-fed controls, suggesting that a compensatory up-regulation of cholesterol levels may occur during food restriction. Maternal ethanol consumption may affect fetal brain development by increasing cholesterol transporters' expression and reducing brain cholesterol levels. © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  13. Effects of miR-33a-5P on ABCA1/G1-Mediated Cholesterol Efflux under Inflammatory Stress in THP-1 Macrophages

    PubMed Central

    Mao, Min; Lei, Han; Liu, Qing; Chen, Yaxi; Zhao, Lei; Li, Qing; Luo, Suxin; Zuo, Zhong; He, Quan; Huang, Wei; Zhang, Nan; Zhou, Chao; Ruan, Xiong Z.

    2014-01-01

    The present study is to investigate whether inflammatory cytokines inhibit ABCA1/ABCG1-mediated cholesterol efflux by regulating miR-33a-5P in THP-1 macrophages. We used interleukin-6 and tumor necrosis factor-alpha in the presence or absence of native low density lipoprotein (LDL) to stimulate THP-1 macrophages. THP-1 macrophages were infected by either control lentivirus vectors or lentivirus encoding miR-33a-5P or antisense miR-33a-5P. The effects of inflammatory cytokines, miR-33a-5P and antisense miR-33a-5P on intracellular lipids accumulation and intracellular cholesterol contents were assessed by oil red O staining and quantitative intracellular cholesterol assay. ApoA-I-mediated cholesterol efflux was examined using the fluorescent sterol (BODIPY-cholesterol). The gene and protein expressions of the molecules involved in cholesterol trafficking were examined using quantitative real-time polymerase chain reaction and Western blotting. Inflammatory cytokines or miR-33a-5P increased intracellular lipid accumulation and decreased apoA-I-mediated cholesterol efflux via decreasing the expression of ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. However, antisense miR-33a-5P reversed the effects of inflammatory cytokines on intracellular lipid accumulation, cholesterol efflux, and the expression of miR-33a-5P, ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. This study indicated that inflammatory cytokines inhibited ABCA1/ABCG1-mediated cholesterol efflux by up-regulating miR-33a-5P in THP-1 macrophages. PMID:25329888

  14. Effects of miR-33a-5P on ABCA1/G1-mediated cholesterol efflux under inflammatory stress in THP-1 macrophages.

    PubMed

    Mao, Min; Lei, Han; Liu, Qing; Chen, Yaxi; Zhao, Lei; Li, Qing; Luo, Suxin; Zuo, Zhong; He, Quan; Huang, Wei; Zhang, Nan; Zhou, Chao; Ruan, Xiong Z

    2014-01-01

    The present study is to investigate whether inflammatory cytokines inhibit ABCA1/ABCG1-mediated cholesterol efflux by regulating miR-33a-5P in THP-1 macrophages. We used interleukin-6 and tumor necrosis factor-alpha in the presence or absence of native low density lipoprotein (LDL) to stimulate THP-1 macrophages. THP-1 macrophages were infected by either control lentivirus vectors or lentivirus encoding miR-33a-5P or antisense miR-33a-5P. The effects of inflammatory cytokines, miR-33a-5P and antisense miR-33a-5P on intracellular lipids accumulation and intracellular cholesterol contents were assessed by oil red O staining and quantitative intracellular cholesterol assay. ApoA-I-mediated cholesterol efflux was examined using the fluorescent sterol (BODIPY-cholesterol). The gene and protein expressions of the molecules involved in cholesterol trafficking were examined using quantitative real-time polymerase chain reaction and Western blotting. Inflammatory cytokines or miR-33a-5P increased intracellular lipid accumulation and decreased apoA-I-mediated cholesterol efflux via decreasing the expression of ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. However, antisense miR-33a-5P reversed the effects of inflammatory cytokines on intracellular lipid accumulation, cholesterol efflux, and the expression of miR-33a-5P, ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. This study indicated that inflammatory cytokines inhibited ABCA1/ABCG1-mediated cholesterol efflux by up-regulating miR-33a-5P in THP-1 macrophages.

  15. IL-17A, MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease.

    PubMed

    Akbulut, Ulas Emre; Emeksiz, Hamdi Cihan; Citli, Senol; Cebi, Alper Han; Korkmaz, Hatice Ayca Ata; Baki, Gaye

    2018-05-05

    The prevalence of non-alcoholic fatty liver disease in children has risen significantly, owing to the worldwide childhood obesity epidemic in the last two decades. Non-alcoholic fatty liver disease is closely linked to sedentary lifestyle, increased body mass index, and visceral adiposity. In addition, individual genetic variations also have a role in the development and progression of non-alcoholic fatty liver disease. The aim of this study was to investigate the gene polymorphisms of MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313), and IL-17A (-197 G/A) (rs2275913) in obese Turkish children with non-alcoholic fatty liver disease. The study recruited 186 obese children aged 10-17 years, including 101 children with non-alcoholic fatty liver disease and 85 children without non-alcoholic fatty liver disease. Anthropometric measurements, insulin resistance, a liver panel, a lipid profile, liver ultrasound examination, and genotyping of the four variants were performed. No difference was found between the groups in respect to age and gender, body mass index, waist/hip ratio, or body fat ratio. In addition to the elevated ALT levels, AST and GGT levels were found significantly higher in the non-alcoholic fatty liver disease group compared to the non non-alcoholic fatty liver disease group (p<0.05). The A-allele of IL-17A (-197 G/A) (rs2275913) was associated with non-alcoholic fatty liver disease (odds ratio 2.05, 95% confidence interval: 1.12-3.77, p=0.02). The findings of this study suggest that there may be an association between IL-17A (-197 G/A) (rs2275913) polymorphism and non-alcoholic fatty liver disease development in obese Turkish children. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  16. Activation of liver X receptor decreases atherosclerosis in Ldlr⁻/⁻ mice in the absence of ATP-binding cassette transporters A1 and G1 in myeloid cells.

    PubMed

    Kappus, Mojdeh S; Murphy, Andrew J; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L; Tall, Alan R; Westerterp, Marit

    2014-02-01

    Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate reverse cholesterol transport, would abolish the beneficial effects of LXR activation on atherosclerosis. LXR activator T0901317 substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr(-/-) mice were transplanted with Abca1(-/-)Abcg1(-/-) or wild-type bone marrow (BM) and fed a Western-type diet for 6 weeks with or without T0901317 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0901317 markedly decreased lesion area, complexity, and inflammatory cell infiltration in the Abca1(-/-)Abcg1(-/-) BM-transplanted mice. To investigate whether this was because of macrophage Abca1/g1 deficiency, Ldlr(-/-) mice were transplanted with LysmCreAbca1(fl/fl)Abcg1(fl/fl) or Abca1(fl/fl)Abcg1(fl/fl) BM and fed Western-type diet with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups, and the decrease was more prominent in the LysmCreAbca1(fl/fl)Abcg1(fl/fl) group. The results suggest that anti-inflammatory effects of LXR activators are of key importance to their antiatherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to transrepress inflammatory genes.

  17. The detection of autoantibodies to ATP-binding cassette transporter A1 and its role in the pathogenesis of atherosclerosis in patients with systemic lupus erythematosus.

    PubMed

    Zeng, Ting; Li, Shu-Jie; Ao, Wen; Zheng, Hui; Wu, Feng-Xia; Chen, Yi; Yang, Cheng-De

    2012-11-01

    To investigate the prevalence of autoantibodies against ATP-binding cassette transporter A1 (ABCA1) in SLE patients, and evaluate the association between anti-ABCA1 autoantibodies and atherosclerosis in SLE. The sera of 75 SLE patients and 75 healthy controls were tested by immunoblotting. Then, we examined the effect of anti-ABCA1 autoantibodies on cholesterol efflux in vitro. The prevalence of anti-ABCA1 antibodies in SLE patients was significantly higher than the controls (p<0.05). The prevalence in the SLE-plaque group was higher than that in the SLE-non-plaque group (p<0.05). The IgG purified from anti-ABCA1-antibody positive sera can inhibit cellular cholesterol efflux from THP-1 cells in vitro with a significantly higher inhibition ratio than that of the healthy controls. Our observations suggest that anti-ABCA1 autoantibodies are involved in the pathogenesis of lupus atherosclerosis and that autoantibodies against ABCA1 may act as biomarkers for atherosclerosis in SLE. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  18. The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis.

    PubMed

    Au, Anthony; Griffiths, Lyn R; Irene, Looi; Kooi, Cheah Wee; Wei, Loo Keat

    2017-10-01

    Genetic studies have been reported on the association between APOA5, APOB, APOC3 and ABCA1 gene polymorphisms and ischemic stroke, but results remain controversial. Hence, this meta-analysis aimed to infer the causal relationships of APOA5 (rs662799, rs3135506), APOB (rs693, rs1042031, rs1801701), APOC3 (rs4520, rs5128, rs2854116, rs2854117) and ABCA1 rs2230806 with ischemic stroke risk. A systematic review was performed for all the articles retrieved from multiple databases, up until March 2017. Data were extracted from all eligible studies, and meta-analysis was carried out using RevMan 5.3 and R package 3.2.1. The strength of association between each studied polymorphism and ischemic stroke risk was measured as odds ratios (ORs) and 95% confidence intervals (CIs), under fixed- and random-effect models. A total of 79 studies reporting on the association between the studied polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799 (ORs = 1.23-1.43), allelic and over-dominant models of APOA5 rs3135506 (ORs = 1.77-1.97), APOB rs1801701 (ORs = 1.72-2.13) and APOB rs1042031 (ORs = 1.66-1.88) as well as dominant model of ABCA1 rs2230806 (OR = 1.31) were significantly associated with higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and the other five polymorphisms, namely ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model. The present meta-analysis confirmed a significant association of APOA5 rs662799 CC, APOA5 rs3135506 CG, APOB rs1801701 GA, APOB rs1042031 GA and ABCA1 rs2230806 GG with increased risk of ischemic stroke. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Play

    NASA Astrophysics Data System (ADS)

    Harteveld, Casper

    Designing a game with a serious purpose involves considering the worlds of Reality and Meaning yet it is undeniably impossible to create a game without a third world, one that is specifically concerned with what makes a game a game: the play elements. This third world, the world of people like designers and artists, and disciplines as computer science and game design, I call the world of Play and this level is devoted to it. The level starts off with some of the misperceptions people have of play. Unlike some may think, we play all the time, even when we grow old—this was also very noticeable in designing the game Levee Patroller as the team exhibited very playful behavior at many occasions. From there, I go into the aspects that characterize this world. The first concerns the goal of the game. This relates to the objectives people have to achieve within the game. This is constituted by the second aspect: the gameplay. Taking actions and facing challenges is subsequently constituted by a gameworld, which concerns the third aspect. And all of it is not possible without the fourth and final aspect, the type of technology that creates and facilitates the game. The four aspects together make up a “game concept” and from this world such a concept can be judged on the basis of three closely interrelated criteria: engagement, immersion, and fun.

  20. Heart ABCA1 and PPAR- α Genes Expression Responses in Male rats: Effects of High Intensity Treadmill Running Training and Aqueous Extraction of Black Crataegus-Pentaegyna.

    PubMed

    Ghanbari-Niaki, Abbass; Ghanbari-Abarghooi, Safieyh; Rahbarizadeh, Fatemeh; Zare-Kookandeh, Navabeh; Gholizadeh, Monireh; Roudbari, Fatemeh; Zare-Kookandeh, Asghar

    2013-11-01

    Heart as a high metabolic and aerobic tissue is consuming lipid as a fuel for its energy provision at rest during light and moderate exercise, except when lactate level is higher in blood circulation. It has been shown that any type of regular exercise and crataegus species would improve cardiovascular function and minimizes several risk factors via stimulating lipid metabolism by acting on enzymes and genes expression such as ABCA1 and PPAR α which are involving in this process. Twenty Wistar male rats (4-6 weeks old, 140-173 g weight) were used. Animals were randomly classified into training (n = 10) and control (n = 10) groups and then divided into saline-control (SC), saline-training (ST), Crataegus-Pentaegyna -control (CPC), and Crataegus-Pentaegyna -training (CPT) groups. Training groups have performed a high-intensity running program (at 34 m/min (0% grade), 60 min/day, 5 days/week) on a motor-driven treadmill for eight weeks. Animals were orally fed with Crataegus-Pentaegyna extraction (500mg/kg) and saline solution for six weeks. Seventy- two hours after the last training session, rats were sacrificed, hearts were excised, cleaned and immediately frozen in liquid nitrogen and stored at -80 °C until RNA extraction. Plasma also was collected for plasma variable measurements. Statistical analysis was performed using a two way analysis of variance, and significance was accepted at P < 0.05. A non-significant (P < 0.4, P < 0.79, respectively) increase in ABCA1 and PPAR α genes expression was accompanied by a significant (P < 0.01, P < 0.04, P < 0.04, respectively) reduction in TC, TG, and VLDL-C levels in Crataegus-Pentaegyna groups. Our findings show that a high intensity treadmill running was able to express ABCA1 and PPAR α in rat heart. Data also possibly indicate that the Crataeguse-Pentaegyna supplementation solely could mimic training effect on the mentioned genes and lipid profiles via different mechanism(s).

  1. Heart ABCA1 and PPAR- α Genes Expression Responses in Male rats: Effects of High Intensity Treadmill Running Training and Aqueous Extraction of Black Crataegus-Pentaegyna

    PubMed Central

    Ghanbari-Niaki, Abbass; Ghanbari-Abarghooi, Safieyh; Rahbarizadeh, Fatemeh; Zare-Kookandeh, Navabeh; Gholizadeh, Monireh; Roudbari, Fatemeh; Zare-Kookandeh, Asghar

    2013-01-01

    Introduction: Heart as a high metabolic and aerobic tissue is consuming lipid as a fuel for its energy provision at rest during light and moderate exercise, except when lactate level is higher in blood circulation. It has been shown that any type of regular exercise and crataegus species would improve cardiovascular function and minimizes several risk factors via stimulating lipid metabolism by acting on enzymes and genes expression such as ABCA1 and PPAR α which are involving in this process. Materials and Methods: Twenty Wistar male rats (4-6 weeks old, 140-173 g weight) were used. Animals were randomly classified into training (n = 10) and control (n = 10) groups and then divided into saline-control (SC), saline-training (ST), Crataegus-Pentaegyna -control (CPC), and Crataegus-Pentaegyna -training (CPT) groups. Training groups have performed a high-intensity running program (at 34 m/min (0% grade), 60 min/day, 5 days/week) on a motor-driven treadmill for eight weeks. Animals were orally fed with Crataegus-Pentaegyna extraction (500mg/kg) and saline solution for six weeks. Seventy- two hours after the last training session, rats were sacrificed, hearts were excised, cleaned and immediately frozen in liquid nitrogen and stored at -80 °C until RNA extraction. Plasma also was collected for plasma variable measurements. Statistical analysis was performed using a two way analysis of variance, and significance was accepted at P < 0.05. Results: A non-significant (P < 0.4, P < 0.79, respectively) increase in ABCA1 and PPAR α genes expression was accompanied by a significant (P < 0.01, P < 0.04, P < 0.04, respectively) reduction in TC, TG, and VLDL-C levels in Crataegus-Pentaegyna groups. Conclusions: Our findings show that a high intensity treadmill running was able to express ABCA1 and PPAR α in rat heart. Data also possibly indicate that the Crataeguse-Pentaegyna supplementation solely could mimic training effect on the mentioned genes and lipid profiles via

  2. Differential regulation of ATP binding cassette protein A1 expression and ApoA-I lipidation by Niemann-Pick type C1 in murine hepatocytes and macrophages.

    PubMed

    Wang, Ming-Dong; Franklin, Vivian; Sundaram, Meenakshi; Kiss, Robert S; Ho, Kenneth; Gallant, Michel; Marcel, Yves L

    2007-08-03

    Niemann-Pick type C1 (Npc1) protein inactivation results in lipid accumulation in late endosomes and lysosomes, leading to a defect of ATP binding cassette protein A1 (Abca1)-mediated lipid efflux to apolipoprotein A-I (apoA-I) in macrophages and fibroblasts. However, the role of Npc1 in Abca1-mediated lipid efflux to apoA-I in hepatocytes, the major cells contributing to HDL formation, is still unknown. Here we show that, whereas lipid efflux to apoA-I in Npc1-null macrophages is impaired, the lipidation of endogenously synthesized apoA-I by low density lipoprotein-derived cholesterol or de novo synthesized cholesterol or phospholipids in Npc1-null hepatocytes is significantly increased by about 1-, 3-, and 8-fold, respectively. The increased cholesterol efflux reflects a major increase of Abca1 protein in Npc1-null hepatocytes, which contrasts with the decrease observed in Npc1-null macrophages. The increased Abca1 expression is largely post-transcriptional, because Abca1 mRNA is only slightly increased and Lxr alpha mRNA is not changed, and Lxr alpha target genes are reduced. This differs from the regulation of Abcg1 expression, which is up-regulated at both mRNA and protein levels in Npc1-null cells. Abca1 protein translation rate is higher in Npc1-null hepatocytes, compared with wild type hepatocytes as measured by [(35)S]methionine incorporation, whereas there is no difference for the degradation of newly synthesized Abca1 in these two types of hepatocytes. Cathepsin D, which we recently identified as a positive modulator of Abca1, is markedly increased at both mRNA and protein levels by Npc1 inactivation in hepatocytes but not in macrophages. Consistent with this, inhibition of cathepsin D with pepstatin A reduced the Abca1 protein level in both Npc1-inactivated and WT hepatocytes. Therefore, Abca1 expression is specifically regulated in hepatocytes, where Npc1 activity modulates cathepsin D expression and Abca1 protein translation rate.

  3. Increase in HDL-C concentration by a dietary portfolio with soy protein and soluble fiber is associated with the presence of the ABCA1R230C variant in hyperlipidemic Mexican subjects.

    PubMed

    Guevara-Cruz, Martha; Tovar, Armando R; Larrieta, Elena; Canizales-Quinteros, Samuel; Torres, Nimbe

    2010-01-01

    A dietary portfolio has been used to reduce blood lipids in hyperlipidemic subjects. To increase the effectiveness of these dietary treatments in specific populations, it is important to study the genetic variability associated with the development of certain types of hyperlipidemias. Low plasma high-density lipoprotein cholesterol (HDL-C) levels are the most common dyslipidemia in Mexican adults and are coupled with the presence of the ABCA1 R230C genotype. Therefore, the aim of this study was to assess the response of HDL-C concentration to a dietary portfolio in a group of Mexican hyperlipidemic subjects with ABCA1R230C (rs9282541) and R219K (rs2230806) polymorphisms. Forty-three hyperlipidemic subjects (20 men and 23 women) were given a low saturated fat (LSF) diet for one month, followed by a LSF diet that included 25g of soy protein and 15g of soluble fiber daily for 2months. We analyzed two ABCA1 polymorphisms and studied their association with serum lipids before and after treatment. Hyperlipidemic subjects with the ABCA1 R230C genotype showed lower HDL-C concentrations at the beginning of the study and were better responders to the dietary treatment than subjects with the ABCA1 R230R genotype (+4.6% vs. +14.6%) (p=.05). According to gender and the presence of the R230C genotype, women responded more significantly to the dietary treatment, reflected by an increase of 21.9% in HDL concentration (p=.022), than women with R230R genotype who only experienced an increase of 2.7% in HDL-C concentration. There was no association between the presence of the ABCA1 R219K variant (p=.544) and HDL concentration. Hyperlipidemic Mexican subjects with the ABCA1 R230C genotype showed lower HDL-concentrations and were better responders to dietary portfolio treatments for increasing HDL-C concentrations than subjects with the R230R genotype. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

    PubMed Central

    2011-01-01

    Background Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients. In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study. Results In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes. Conclusions We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes. PMID:22035022

  5. Gene-Gene Combination Effect and Interactions among ABCA1, APOA1, SR-B1, and CETP Polymorphisms for Serum High-Density Lipoprotein-Cholesterol in the Japanese Population

    PubMed Central

    Nakamura, Akihiko; Niimura, Hideshi; Kuwabara, Kazuyo; Takezaki, Toshiro; Morita, Emi; Wakai, Kenji; Hamajima, Nobuyuki; Nishida, Yuichiro; Turin, Tanvir Chowdhury; Suzuki, Sadao; Ohnaka, Keizo; Uemura, Hirokazu; Ozaki, Etsuko; Hosono, Satoyo; Mikami, Haruo; Kubo, Michiaki; Tanaka, Hideo

    2013-01-01

    Background/Objective Gene-gene interactions in the reverse cholesterol transport system for high-density lipoprotein-cholesterol (HDL-C) are poorly understood. The present study observed gene-gene combination effect and interactions between single nucleotide polymorphisms (SNPs) in ABCA1, APOA1, SR-B1, and CETP in serum HDL-C from a cross-sectional study in the Japanese population. Methods The study population comprised 1,535 men and 1,515 women aged 35–69 years who were enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. We selected 13 SNPs in the ABCA1, APOA1, CETP, and SR-B1 genes in the reverse cholesterol transport system. The effects of genetic and environmental factors were assessed using general linear and logistic regression models after adjusting for age, sex, and region. Principal Findings Alcohol consumption and daily activity were positively associated with HDL-C levels, whereas smoking had a negative relationship. The T allele of CETP, rs3764261, was correlated with higher HDL-C levels and had the highest coefficient (2.93 mg/dL/allele) among the 13 SNPs, which was statistically significant after applying the Bonferroni correction (p<0.001). Gene-gene combination analysis revealed that CETP rs3764261 was associated with high HDL-C levels with any combination of SNPs from ABCA1, APOA1, and SR-B1, although no gene-gene interaction was apparent. An increasing trend for serum HDL-C was also observed with an increasing number of alleles (p<0.001). Conclusions The present study identified a multiplier effect from a polymorphism in CETP with ABCA1, APOA1, and SR-B1, as well as a dose-dependence according to the number of alleles present. PMID:24376512

  6. HDL-cholesterol concentration in pregnant Chinese Han women of late second trimester associated with genetic variants in CETP, ABCA1, APOC3, and GALNT2.

    PubMed

    Cui, Mingxuan; Li, Wei; Ma, Liangkun; Ping, Fan; Liu, Juntao; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

    2017-08-22

    To investigate whether HDL-C level in pregnant Chinese Han women of late second trimester correlated with loci in high-density lipoprotein-cholesterol (HDL-C)-related genes found in genome-wide association studies (GWAS). Seven single-nucleotide polymorphisms (rs3764261 in CETP , rs1532085 in LIPC , rs7241918 in LIPG , rs1883025 in ABCA1 , rs4225 in APOC3 , rs1059611 in LPL , and rs16851339 in GALNT2 ) were genotyped using the Sequenom MassArray system for 1,884 pregnant women. The following polymorphisms were statistically associated with HDL-C level after adjusting for age, gestational week, pre-pregnancy BMI and state of GDM or HOMAIR: (i) rs3764261 (b = -0.055 mmol/L, 95% CI -0.101 to -0.008, p = 0.021), (ii) rs1883025 (b = -0.054 mmol/L, 95% CI -0.097 to -0.012, p = 0.013), (iii) rs4225 (b = -0.071 mmol/L, 95% CI -0.116 to -0.027, p = 1.79E-3) and (iv) rs16851339 (b = -0.064 mmol/L, 95% CI -0.120 to -0.008, p = 0.025). The more risk alleles the pregnant women have, the lower the plasma HDL-C levels of the subjects are. Several risk alleles found to be related to HDL-C in GWAS are also associated with HDL-C levels in pregnant Chinese Han women and these risk loci contribute additively to low HDL-C levels.

  7. HDL-cholesterol concentration in pregnant Chinese Han women of late second trimester associated with genetic variants in CETP, ABCA1, APOC3, and GALNT2

    PubMed Central

    Cui, Mingxuan; Li, Wei; Ma, Liangkun; Ping, Fan; Liu, Juntao; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

    2017-01-01

    Objective To investigate whether HDL-C level in pregnant Chinese Han women of late second trimester correlated with loci in high-density lipoprotein-cholesterol (HDL-C)-related genes found in genome-wide association studies (GWAS). Methods Seven single-nucleotide polymorphisms (rs3764261 in CETP, rs1532085 in LIPC, rs7241918 in LIPG, rs1883025 in ABCA1, rs4225 in APOC3, rs1059611 in LPL, and rs16851339 in GALNT2) were genotyped using the Sequenom MassArray system for 1,884 pregnant women. Results The following polymorphisms were statistically associated with HDL-C level after adjusting for age, gestational week, pre-pregnancy BMI and state of GDM or HOMAIR: (i) rs3764261 (b = -0.055 mmol/L, 95% CI -0.101 to -0.008, p = 0.021), (ii) rs1883025 (b = -0.054 mmol/L, 95% CI -0.097 to -0.012, p = 0.013), (iii) rs4225 (b = -0.071 mmol/L, 95% CI -0.116 to -0.027, p = 1.79E-3) and (iv) rs16851339 (b = -0.064 mmol/L, 95% CI -0.120 to -0.008, p = 0.025). The more risk alleles the pregnant women have, the lower the plasma HDL-C levels of the subjects are. Conclusions Several risk alleles found to be related to HDL-C in GWAS are also associated with HDL-C levels in pregnant Chinese Han women and these risk loci contribute additively to low HDL-C levels. PMID:28915626

  8. Novel association of the R230C variant of the ABCA1 gene with high triglyceride levels and low high-density lipoprotein cholesterol levels in Mexican school-age children with high prevalence of obesity.

    PubMed

    Gamboa-Meléndez, Marco Alberto; Galindo-Gómez, Carlos; Juárez-Martínez, Liliana; Gómez, F Enrique; Diaz-Diaz, Eulises; Ávila-Arcos, Marco Antonio; Ávila-Curiel, Abelardo

    2015-08-01

    Metabolic syndrome (MetS) is a disorder that includes a cluster of several risk factors for the development of type 2 diabetes and cardiovascular disease. The R230C variant of the ABCA1 gene has been associated with low HDL-cholesterol in several studies, but its association with MetS in children remains to be determined. The aim of this study was to analyze the association of the R230C variant with MetS and other metabolic traits in school-aged Mexican children. The study was performed in seven urban primary schools in the State of Mexico. Four hundred thirty-two Mexican school-age children 6-13 years old were recruited. MetS was identified using the International Diabetes Federation definition. The R230C variant of the ABCA1 gene was genotyped to seek associations with MetS and other metabolic traits. The prevalence of MetS was 29% in children aged 10-13 years. The R230C variant was not associated with MetS (OR = 1.65; p = 0.139). Furthermore, in the whole population, the R230C variant was associated with low HDL-cholesterol levels (β coefficient = -3.28, p <0.001). Interestingly, in the total population we found a novel association of this variant with high triglyceride levels (β coefficient = 14.34; p = 0.027). We found a new association of the R230C variant of the ABCA1 gene with high triglyceride levels. Our findings also replicate the association of this variant with low HDL-cholesterol levels in Mexican school-age children. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  9. Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCOM1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults

    USDA-ARS?s Scientific Manuscript database

    In a marker-trait association study we estimated the statistical significance of 65 single nucleotide polymorphisms (SNP) in 23 candidate genes on HDL levels of two independent Caucasian populations. Each population consisted of men and women and their HDL levels were adjusted for gender and body we...

  10. Inhibition of cholesterol absorption associated with a PPAR alpha-dependent increase in ABC binding cassette transporter A1 in mice.

    PubMed

    Knight, Brian L; Patel, Dilip D; Humphreys, Sandy M; Wiggins, David; Gibbons, Geoffrey F

    2003-11-01

    Dietary supplementation with the peroxisome proliferator-activated receptor alpha (PPAR alpha) ligand WY 14,643 gave rise to a 4- to 5-fold increase in the expression of mRNA for the ATP binding cassette transporter A1 (ABCA1) in the intestine of normal mice. There was no effect in the intestine of PPAR alpha-null mice. Consumption of a high-cholesterol diet also increased intestinal ABCA1 expression. The effects of WY 14,643 and the high-cholesterol diet were not additive. WY 14,643 feeding reduced intestinal absorption of cholesterol in the normal mice, irrespective of the dietary cholesterol concentration, and this resulted in lower diet-derived cholesterol and cholesteryl ester concentrations in plasma and liver. At each concentration of dietary cholesterol, there was a similar significant inverse correlation between intestinal ABCA1 mRNA content and the amount of cholesterol absorbed. The fibrate-induced changes in the intestines of the normal mice were accompanied by an increased concentration of the mRNA encoding the sterol-regulatory element binding protein-1c gene (SREBP-1c), a known target gene for the oxysterol receptor liver X receptor alpha (LXR alpha). There was a correlation between intestinal ABCA1 mRNA and SREBP-1c mRNA contents, but not between SREBP-1c mRNA content and cholesterol absorption. These results suggest that PPAR alpha influences cholesterol absorption through modulating ABCA1 activity in the intestine by a mechanism involving LXR alpha.

  11. Tomato HsfA1a plays a critical role in plant drought tolerance by activating ATG genes and inducing autophagy

    PubMed Central

    Wang, Yu; Cai, Shuyu; Yin, Lingling; Shi, Kai; Xia, Xiaojian; Zhou, Yanhong; Yu, Jingquan; Zhou, Jie

    2015-01-01

    Autophagy plays critical roles in plant responses to stress. In contrast to the wealth of information concerning the core process of plant autophagosome assembly, our understanding of the regulation of autophagy is limited. In this study, we demonstrated that transcription factor HsfA1a played a critical role in tomato tolerance to drought stress, in part through its positive role in induction of autophagy under drought stress. HsfA1a expression was induced by drought stress. Virus-induced HsfA1a gene silencing reduced while its overexpression increased plant drought tolerance based on both symptoms and membrane integrity. HsfA1a-silenced plants were more sensitive to endogenous ABA-mediated stomatal closure, while its overexpression lines were resistant under drought stress, indicating that phytohormone ABA did not play a major role in HsfA1a-induced drought tolerance. On the other hand, HsfA1a-silenced plants increased while its overexpression decreased the levels of insoluble proteins which were highly ubiquitinated under drought stress. Furthermore, drought stress induced numerous ATGs expression and autophagosome formation in wild-type plants. The expression of ATG10 and ATG18f, and the formation of autophagosomes were compromised in HsfA1a-silenced plants but were enhanced in HsfA1a-overexpressing plants. Both electrophoretic mobility shift assay and chromatin immunoprecipitation coupled with qPCR analysis revealed that HsfA1a bound to ATG10 and ATG18f gene promoters. Silencing of ATG10 and ATG18f reduced HsfA1a-induced drought tolerance and autophagosome formation in plants overexpressing HsfA1a. These results demonstrate that HsfA1a induces drought tolerance by activating ATG genes and inducing autophagy, which may promote plant survival by degrading ubiquitinated protein aggregates under drought stress. PMID:26649940

  12. Does attention play a role in dynamic receptive field adaptation to changing acoustic salience in A1?

    PubMed

    Fritz, Jonathan B; Elhilali, Mounya; David, Stephen V; Shamma, Shihab A

    2007-07-01

    Acoustic filter properties of A1 neurons can dynamically adapt to stimulus statistics, classical conditioning, instrumental learning and the changing auditory attentional focus. We have recently developed an experimental paradigm that allows us to view cortical receptive field plasticity on-line as the animal meets different behavioral challenges by attending to salient acoustic cues and changing its cortical filters to enhance performance. We propose that attention is the key trigger that initiates a cascade of events leading to the dynamic receptive field changes that we observe. In our paradigm, ferrets were initially trained, using conditioned avoidance training techniques, to discriminate between background noise stimuli (temporally orthogonal ripple combinations) and foreground tonal target stimuli. They learned to generalize the task for a wide variety of distinct background and foreground target stimuli. We recorded cortical activity in the awake behaving animal and computed on-line spectrotemporal receptive fields (STRFs) of single neurons in A1. We observed clear, predictable task-related changes in STRF shape while the animal performed spectral tasks (including single tone and multi-tone detection, and two-tone discrimination) with different tonal targets. A different set of task-related changes occurred when the animal performed temporal tasks (including gap detection and click-rate discrimination). Distinctive cortical STRF changes may constitute a "task-specific signature". These spectral and temporal changes in cortical filters occur quite rapidly, within 2min of task onset, and fade just as quickly after task completion, or in some cases, persisted for hours. The same cell could multiplex by differentially changing its receptive field in different task conditions. On-line dynamic task-related changes, as well as persistent plastic changes, were observed at a single-unit, multi-unit and population level. Auditory attention is likely to be pivotal in

  13. Tyrosine 192 in apolipoprotein A-I is the major site of nitration and chlorination by myeloperoxidase, but only chlorination markedly impairs ABCA1-dependent cholesterol transport.

    PubMed

    Shao, Baohai; Bergt, Constanze; Fu, Xiaoyun; Green, Pattie; Voss, John C; Oda, Michael N; Oram, John F; Heinecke, Jay W

    2005-02-18

    High density lipoprotein (HDL) isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of 3-nitrotyrosine and 3-chlorotyrosine. Myeloperoxidase (MPO) is the only known source of 3-chlorotyrosine in humans, indicating that MPO oxidizes HDL in vivo. In the current studies, we used tandem mass spectrometry to identify the major sites of tyrosine oxidation when lipid-free apolipoprotein A-I (apoA-I), the major protein of HDL, was exposed to MPO or peroxynitrite (ONOO(-)). Tyrosine 192 was the predominant site of both nitration and chlorination by MPO and was also the major site of nitration by ONOO(-). Electron paramagnetic spin resonance studies of spin-labeled apoA-I revealed that residue 192 was located in an unusually hydrophilic environment. Moreover, the environment of residue 192 became much more hydrophobic when apoA-I was incorporated into discoidal HDL, and Tyr(192) of HDL-associated apoA-I was a poor substrate for nitration by both myeloperoxidase and ONOO(-), suggesting that solvent accessibility accounted in part for the reactivity of Tyr(192). The ability of lipid-free apoA-I to facilitate ATP-binding cassette transporter A1 cholesterol transport was greatly reduced after chlorination by MPO. Loss of activity occurred in concert with chlorination of Tyr(192). Both ONOO(-) and MPO nitrated Tyr(192) in high yield, but unlike chlorination, nitration minimally affected the ability of apoA-I to promote cholesterol efflux from cells. Our results indicate that Tyr(192) is the predominant site of nitration and chlorination when MPO or ONOO(-) oxidizes lipid-free apoA-I but that only chlorination markedly reduces the cholesterol efflux activity of apoA-I. This impaired biological activity of chlorinated apoA-I suggests that MPO-mediated oxidation of HDL might contribute to the link between inflammation and cardiovascular disease.

  14. Presynaptic M1, M2, and A1 receptors play roles in tetanic fade induced by pancuronium or cisatracurium.

    PubMed

    Bornia, Elaine Campana Sanches; Bando, Erika; Machinski, Miguel; Pereira, Monalisa Wolski; Alves-Do-Prado, Wilson

    2009-01-01

    We investigated whether presynaptic facilitatory M1 and/or inhibitory M2 muscarinic receptors contributed to pancuronium- and cisatracurium-induced tetanic fade. Phrenic nerve-diaphragm muscle preparations of rats were indirectly stimulated with tetanic frequency (75 +/- 3.3 Hz; mean +/- SD). Doses of pancuronium, cisatracurium, hexamethonium, and d-tubocurarine for producing approximately 25% fade were determined. The effects of pirenzepine and methoctramine, blockers of presynaptic M1 and M2 receptors, respectively, on the tetanic fade were investigated. The concentrations required for approximately 25% fade were 413 microM for hexamethonium (26.8 +/- 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 +/- 2.55% fade), 0.32 microM for pancuronium (25.4 +/- 2.2% fade), and 0.32 microM for cisatracurium (24.7 +/- 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 microM, attenuated the fade induced by hexamethonium (to 16.0 +/- 2.5% fade), d-tubocurarine (to 6.0 +/- 1.6 fade), pancuronium (to 8.0 +/- 4.0% fade), and cisatracurium (to 11.0 +/- 3.3% fade). 10 nM pirenzepine attenuated only the fades produced by pancuronium (to 5.0 +/- 0.11% fade) and cisatracurium (to 13.3 +/- 5.3% fade). Cisatracurium (0.32 microM) showed antiacetylcholinesterase activity (in plasma, 14.2 +/- 1.6%; 6%; in erythrocyt 17.2 +/- 2.66%) similar to that of pancuronium (0.32 microM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium. The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine.

  15. On play and playing.

    PubMed

    Rudan, Dusko

    2013-12-01

    The paper offers a review of the development of the concept of play and playing. The true beginnings of the development of the theories of play are set as late as in the 19th century. It is difficult to define play as such; it may much more easily be defined through its antipode--work. In the beginning, play used to be connected with education; it was not before Freud's theory of psychoanalysis and Piaget's developmental psychology that the importance of play in a child's development began to be explained in more detail. The paper further tackles the role of play in the adult age. Detailed attention is paid to psychodynamic and psychoanalytic authors, in particular D. W. Winnicott and his understanding of playing in the intermediary (transitional) empirical or experiential space. In other words, playing occupies a space and time of its own. The neuroscientific concept of playing is also tackled, in the connection with development as well.

  16. SciTech Connect

    Wang, Yan; Wu, Jian-Feng; Tang, Yan-Yan

    Highlights: • U II reduces cholesterol efflux in THP-1 macrophages. • U II decreases the expression of ABCA1. • Inhibition of the ERK/NF-κB pathway reduces U II effects on ABCA1 expression and cholesterol efflux. - Abstract: Objective: Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages. Methods and results: Cultured THP-1 macrophages were treated withmore » U II, followed by measuring the intracellular lipid contents, cholesterol efflux and ABCA1 levels. The results showed that U II dramatically decreased ABCA1 levels and impaired cholesterol efflux. However, the effects of U II on ABCA1 protein expression and cellular cholesterol efflux were partially reversed by inhibition of extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF-κB) activity, suggesting the potential roles of ERK1/2 and NF-κB in ABCA1 expression, respectively. Conclusion: Our current data indicate that U II may have promoting effects on the progression of atherosclerosis, likely through suppressing ABCA1 expression via activation of the ERK/NF-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation.« less

  17. Bilirubin Decreases Macrophage Cholesterol Efflux and ATP-Binding Cassette Transporter A1 Protein Expression.

    PubMed

    Wang, Dongdong; Tosevska, Anela; Heiß, Elke H; Ladurner, Angela; Mölzer, Christine; Wallner, Marlies; Bulmer, Andrew; Wagner, Karl-Heinz; Dirsch, Verena M; Atanasov, Atanas G

    2017-04-28

    Mild but chronically elevated circulating unconjugated bilirubin is associated with reduced total and low-density lipoprotein cholesterol concentration, which is associated with reduced cardiovascular disease risk. We aimed to investigate whether unconjugated bilirubin influences macrophage cholesterol efflux, as a potential mechanism for the altered circulating lipoprotein concentrations observed in hyperbilirubinemic individuals. Cholesterol efflux from THP-1 macrophages was assessed using plasma obtained from normo- and hyperbilirubinemic (Gilbert syndrome) humans (n=60 per group) or (heterozygote/homozygote Gunn) rats (n=20 per group) as an acceptor. Hyperbilirubinemic plasma from patients with Gilbert syndrome and Gunn rats induced significantly reduced cholesterol efflux compared with normobilirubinemic plasma. Unconjugated bilirubin (3-17.1 μmol/L) exogenously added to plasma- or apolipoprotein A1-supplemented media also decreased macrophage cholesterol efflux in a concentration- and time-dependent manner. We also showed reduced protein expression of the ATP-binding cassette transporter A1 (ABCA1), a transmembrane cholesterol transporter involved in apolipoprotein A1-mediated cholesterol efflux, in THP-1 macrophages treated with unconjugated bilirubin and in peripheral blood mononuclear cells obtained from hyperbilirubinemic individuals. Furthermore, we demonstrated that bilirubin accelerates the degradation rate of the ABCA1 protein in THP-1 macrophages. Cholesterol efflux from THP-1 macrophages is decreased in the presence of plasma obtained from humans and rats with mild hyperbilirubinemia. A direct effect of unconjugated bilirubin on cholesterol efflux was demonstrated and is associated with decreased ABCA1 protein expression. These data improve our knowledge concerning bilirubin's impact on cholesterol transport and represent an important advancement in our understanding of bilirubin's role in cardiovascular disease. © 2017 The Authors. Published on

  18. Orphan nuclear receptor oestrogen-related receptor γ (ERRγ) plays a key role in hepatic cannabinoid receptor type 1-mediated induction of CYP7A1 gene expression

    PubMed Central

    Zhang, Yaochen; Kim, Don-Kyu; Lee, Ji-Min; Park, Seung Bum; Jeong, Won-IL; Kim, Seong Heon; Lee, In-Kyu; Lee, Chul-Ho; Chiang, John Y.L.; Choi, Hueng-Sik

    2017-01-01

    Bile acids are primarily synthesized from cholesterol in the liver and have important roles in dietary lipid absorption and cholesterol homoeostasis. Detailed roles of the orphan nuclear receptors regulating cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis, have not yet been fully elucidated. In the present study, we report that oestrogen-related receptor γ (ERRγ) is a novel transcriptional regulator of CYP7A1 expression. Activation of cannabinoid receptor type 1 (CB1 receptor) signalling induced ERRγ-mediated transcription of the CYP7A1 gene. Overexpression of ERRγ increased CYP7A1 expression in vitro and in vivo, whereas knockdown of ERRγ attenuated CYP7A1 expression. Deletion analysis of the CYP7A1 gene promoter and a ChIP assay revealed an ERRγ -binding site on the CYP7A1 gene promoter. Small heterodimer partner (SHP) inhibited the transcriptional activity of ERRγ and thus regulated CYP7A1 expression. Overexpression of ERRγ led to increased bile acid levels, whereas an inverse agonist of ERRγ, GSK5182, reduced CYP7A1 expression and bile acid synthesis. Finally, GSK5182 significantly reduced hepatic CB1 receptor-mediated induction of CYP7A1 expression and bile acid synthesis in alcohol-treated mice. These results provide the molecular mechanism linking ERRγ and bile acid metabolism. PMID:26348907

  19. New Play.

    ERIC Educational Resources Information Center

    Lersten, Kenneth C.

    There have been many theories and hypotheses about play, one of which is the equation of play with "transcendence." Play may have the ingredients to allow us to transcend and, for a moment, remythologize life. There have been recent authors who have given play the status of theology, indicating that play contains elements also found in religion.…

  20. Play Therapy

    PubMed Central

    Kool, Ritesh

    2010-01-01

    Play therapy represents a unique form of treatment that is not only geared toward young children, but is translated into a language children can comprehend and utilize—the language of play. For the referring provider or practitioner, questions may remain regarding the nature, course, and efficacy of play therapy. This article reviews the theoretical underpinnings of play therapy, some practical considerations, and finally a summary of the current state of research in regard to play therapy. The authors present the practicing psychiatrist with a road map for referring a patient to play therapy or initiating it in appropriate cases. PMID:21103141

  1. Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice.

    PubMed

    Westerterp, Marit; Murphy, Andrew J; Wang, Mi; Pagler, Tamara A; Vengrenyuk, Yuliya; Kappus, Mojdeh S; Gorman, Darren J; Nagareddy, Prabhakara R; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S; Welch, Carrie; Fisher, Edward A; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R

    2013-05-24

    Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. To assess the role of macrophage cholesterol efflux pathways in atherogenesis. We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABC(DKO) mice) but not in hematopoietic stem or progenitor populations. MAC-ABC(DKO) bone marrow (BM) was transplanted into Ldlr(-/-) recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet-fed MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production. These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

  2. Play Therapy

    PubMed Central

    Lawver, Timothy; Blankenship, Kelly

    2008-01-01

    Play therapy is a treatment modality in which the therapist engages in play with the child. Its use has been documented in a variety of settings and with a variety of diagnoses. Treating within the context of play brings the therapist and the therapy to the level of the child. By way of an introduction to this approach, a case is presented of a six-year-old boy with oppositional defiant disorder. The presentation focuses on the events and interactions of a typical session with an established patient. The primary issues of the session are aggression, self worth, and self efficacy. These themes manifest themselves through the content of the child’s play and narration of his actions. The therapist then reflects these back to the child while gently encouraging the child toward more positive play. Though the example is one of nondirective play therapy, a wide range of variation exists under the heading of play therapy. PMID:19724720

  3. Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.

    PubMed

    Mistry, Hiten D; Kurlak, Lesia O; Mansour, Yosef T; Zurkinden, Line; Mohaupt, Markus G; Escher, Geneviève

    2017-06-01

    Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples ( P < 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia ( P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia ( P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  4. Pretend play.

    PubMed

    Weisberg, Deena Skolnick

    2015-01-01

    Pretend play is a form of playful behavior that involves nonliteral action. Although on the surface this activity appears to be merely for fun, recent research has discovered that children's pretend play has connections to important cognitive and social skills, such as symbolic thinking, theory of mind, and counterfactual reasoning. The current article first defines pretend play and then reviews the arguments and evidence for these three connections. Pretend play has a nonliteral correspondence to reality, hence pretending may provide children with practice with navigating symbolic relationships, which may strengthen their language skills. Pretend play and theory of mind reasoning share a focus on others' mental states in order to correctly interpret their behavior, hence pretending and theory of mind may be mutually supportive in development. Pretend play and counterfactual reasoning both involve representing nonreal states of affairs, hence pretending may facilitate children's counterfactual abilities. These connections make pretend play an important phenomenon in cognitive science: Studying children's pretend play can provide insight into these other abilities and their developmental trajectories, and thereby into human cognitive architecture and its development. © 2015 John Wiley & Sons, Ltd.

  5. Retinoic Acid Isomers Up-Regulate ATP Binding Cassette A1 and G1 and Cholesterol Efflux in Rat Astrocytes: Implications for Their Therapeutic and Teratogenic Effects

    PubMed Central

    Chen, Jing; Costa, Lucio G.

    2011-01-01

    Recent studies suggest that retinoids may be effective in the treatment of Alzheimer's disease, although exposure to an excess of retinoids during gestation causes teratogenesis. Cholesterol is essential for brain development, but high levels of cholesterol have been associated with Alzheimer's disease. We hypothesized that retinoic acid may affect cholesterol homeostasis in rat astrocytes, which regulate cholesterol distribution in the brain, through the up-regulation of cholesterol transporters ATP binding cassette (Abc)a1 and Abcg1. Tretinoin, 13-cis retinoic acid (13-cis-RA), 9-cis-RA, and the selective retinoid X receptor (RXR) agonist methoprene significantly increased cholesterol efflux induced by cholesterol acceptors and protein levels of Abca1 by 2.3- (±0.25), 3.6- (±0.42), 4.1- (±0.5), and 1.75- (±0.43) fold, respectively, and Abcg1 by 2.1- (±0.26), 2.2- (±0.33), 2.5- (±0.23), and 2.2- (±0.21) fold, respectively. 13-cis-RA and 9-cis-RA also significantly increased mRNA levels of Abca1 (maximal induction 7.3 ± 0.42 and 2.7 ± 0.17, respectively) and Abcg1 (maximal induction 2.0 ± 0.18 and 1.8 ± 0.09, respectively), and the levels of membrane-bound Abca1 (2.5 ± 0.3 and 2.5 ± 0.40-fold increase, respectively), whereas they significantly decreased intracellular cholesterol content without affecting cholesterol synthesis. The effect of 9-cis-RA on cholesterol homeostasis in astrocytes can be ascribed to the activation of RXR, whereas the effects of 13-cis-RA and tretinoin were independent of either RXRs or retinoic acid receptors. These findings suggest that retinoids affect cholesterol homeostasis in astrocytes and that this effect may be involved in both their therapeutic and teratogenic actions. PMID:21628419

  6. Diosgenin inhibits atherosclerosis via suppressing the MiR-19b-induced downregulation of ATP-binding cassette transporter A1.

    PubMed

    Lv, Yun-cheng; Yang, Jing; Yao, Feng; Xie, Wei; Tang, Yan-yan; Ouyang, Xin-ping; He, Ping-ping; Tan, Yu-lin; Li, Liang; Zhang, Min; Liu, Dan; Cayabyab, Francisco S; Zheng, Xi-Long; Tang, Chao-ke

    2015-05-01

    Diosgenin (Dgn), a structural analogue of cholesterol, has been reported to have the hypolipidemic and antiatherogenic properties, but the underlying mechanisms are not fully understood. Given the key roles of macrophages in cholesterol metabolism and atherogenesis, it is critical to investigate macrophage cholesterol efflux and development of atherosclerotic lesion after Dgn treatment. This study was designed to evaluate the potential effects of Dgn on macrophage cholesterol metabolism and the development of aortic atherosclerosis, and to explore its underlying mechanisms. Dgn significantly up-regulated the expression of ATP-binding cassette transporter A1 (ABCA1) protein, but didn't affect liver X receptor α levels in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by western blotting. The miR-19b levels were markedly down-regulated in Dgn-treated THP-1 macrophages/MPM-derived foam cells. Cholesterol transport assays revealed that treatment with Dgn alone or together with miR-19b inhibitor notably enhanced ABCA1-dependent cholesterol efflux, resulting in the reduced levels of total cholesterol, free cholesterol and cholesterol ester as determined by high-performance liquid chromatography. The fecal 3H-sterol originating from cholesterol-laden MPMs was increased in apolipoprotein E knockout mice treated with Dgn or both Dgn and antagomiR-19b. Treatment with Dgn alone or together with antagomiR-19b elevated plasma high-density lipoprotein levels, but reduced plasma low-density lipoprotein levels. Accordingly, aortic lipid deposition and plaque area were reduced, and collagen content and ABCA1 expression were increased in mice treated with Dgn alone or together with antagomiR-19b. However, miR-19b overexpression abrogated the lipid-lowering and atheroprotective effects induced by Dgn. The present study demonstrates that Dgn enhances ABCA1-dependent cholesterol efflux and inhibits aortic atherosclerosis

  7. Playing Shakespeare.

    ERIC Educational Resources Information Center

    Bashian, Kathleen Ryniker

    1993-01-01

    Describes a yearlong project at 12 Catholic middle schools in the Diocese of Arlington, Virginia, to incorporate the plays of William Shakespeare into the curriculum. Teachers attended university lectures and directed students in performances of the plays. Concludes that Shakespeare can be understood and enjoyed by middle school students. (BCY)

  8. Shadow Play

    ERIC Educational Resources Information Center

    Trundle, Kathy Cabe; Hilson, Margilee P.

    2012-01-01

    A bunny rabbit playfully hops across the wall. Then hands realign and fingers shift to make a hawk soar toward the ceiling. Most children have enjoyed the delightful experience of playing with shadow puppets. The authors build on this natural curiosity to help students link shadows to complex astronomical concepts such as seasons. The…

  9. Play & Play Grounds. A Report.

    ERIC Educational Resources Information Center

    Stone, Jeannette Galambos

    Using camera and tape recorder, a photographer and an early childhood specialist explored as a team the universe of children's outdoor play, seeking worthy and innovative ideas and stressing urban playground problems and solutions. The resulting photographs and text focus on (1) the characteristics of play, (2) the nature of playgrounds, and (3)…

  10. The ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ9Vδ2 T cell activation by dendritic cells

    PubMed Central

    Castella, Barbara; Kopecka, Joanna; Sciancalepore, Patrizia; Mandili, Giorgia; Foglietta, Myriam; Mitro, Nico; Caruso, Donatella; Novelli, Francesco; Riganti, Chiara; Massaia, Massimo

    2017-01-01

    Vγ9Vδ2 T cells are activated by phosphoantigens, such as isopentenyl pyrophosphate (IPP), which is generated in the mevalonate pathway of antigen-presenting cells. IPP is released in the extracellular microenvironment via unknown mechanisms. Here we show that the ATP-binding cassette transporter A1 (ABCA1) mediates extracellular IPP release from dendritic cells (DC) in cooperation with apolipoprotein A-I (apoA-I) and butyrophilin-3A1. IPP concentrations in the supernatants are sufficient to induce Vγ9Vδ2 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA). ZA treatment increases ABCA1 and apoA-I expression via IPP-dependent LXRα nuclear translocation and PI3K/Akt/mTOR pathway inhibition. These results close the mechanistic gap in our understanding of extracellular IPP release from DC and provide a framework to fine-tune Vγ9Vδ2 T cell activation via mevalonate and PI3K/Akt/mTOR pathway modulation. PMID:28580927

  11. Sweet Play

    ERIC Educational Resources Information Center

    Leung, Shuk-kwan S.; Lo, Jane-Jane

    2010-01-01

    This article features Sweet play math, a "math by the month" activity that involves decorating and making sugar cubes. Teachers may want to substitute straws, paper squares, alphabet blocks, or such commercially made manipulatives as Unifix[R] cubes for the real sweets. Given no allergy concerns, teachers and students alike would enjoy some sweet…

  12. Playing Teacher.

    ERIC Educational Resources Information Center

    Gilbert, Juan E.

    The acceptance of animation technologies is increasing. Video games, such as Sony PlayStation (SONY, 2002), have become part of the culture for young people from kindergarten through undergraduate school. Animation technologies have been implemented into educational systems in the form of animated pedagogical agents (Johnson, 2000). The research…

  13. Water Play

    ERIC Educational Resources Information Center

    Cline, Jane E.; Smith, Brandy A.

    2016-01-01

    The inclusion of activities to develop sensory awareness, spatial thinking, and physical dexterity, operationalized through hands-on science lessons such as water play, have long been part of early childhood education. This practical article addresses Next Generation Science Standards K-2 ETS1-3 and K-2 ETS1-2 by having four-year-old…

  14. Clay Play

    ERIC Educational Resources Information Center

    Rogers, Liz; Steffan, Dana

    2009-01-01

    This article describes how to use clay as a potential material for young children to explore. As teachers, the authors find that their dialogue about the potential of clay as a learning medium raises many questions: (1) What makes clay so enticing? (2) Why are teachers noticing different play and conversation around the clay table as compared to…

  15. Game playing.

    PubMed

    Rosin, Christopher D

    2014-03-01

    Game playing has been a core domain of artificial intelligence research since the beginnings of the field. Game playing provides clearly defined arenas within which computational approaches can be readily compared to human expertise through head-to-head competition and other benchmarks. Game playing research has identified several simple core algorithms that provide successful foundations, with development focused on the challenges of defeating human experts in specific games. Key developments include minimax search in chess, machine learning from self-play in backgammon, and Monte Carlo tree search in Go. These approaches have generalized successfully to additional games. While computers have surpassed human expertise in a wide variety of games, open challenges remain and research focuses on identifying and developing new successful algorithmic foundations. WIREs Cogn Sci 2014, 5:193-205. doi: 10.1002/wcs.1278 CONFLICT OF INTEREST: The author has declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2014 John Wiley & Sons, Ltd.

  16. Designing Out the Play: Accessibility and Playfulness in Inclusive Play.

    PubMed

    Holt, Raymond; Beckett, Angharad

    2017-01-01

    Play is an important part of child development, yet disabled children are often excluded from the opportunity to play, either due to lack of accessible toys and games, or social pressures. This paper presents a case study reflecting on the development of Button Bash: a switch accessible game intended to encourage inclusive play between disabled and non-disabled children. In particular, the paper focuses on how changes intended to make the game more accessible tended to make it less playful, and reflects on the relationship between playfulness and accessibility.

  17. Three cysteine residues of SLC52A1, a receptor for the porcine endogenous retrovirus-A (PERV-A), play a critical role in cell surface expression and infectivity.

    PubMed

    Colon-Moran, Winston; Argaw, Takele; Wilson, Carolyn A

    2017-07-01

    Porcine endogenous retrovirus-A (PERV-A), a gammaretrovirus, infects human cells in vitro, thus raising the potential risk of cross-species transmission in xenotransplantation. Two members of the solute carrier family 52 (SLC52A1 and SLC52A2) are PERV-A receptors. Site-directed mutagenesis of the cDNA encoding SLC52A1 identified that only one of two putative glycosylation signals is occupied by glycans. In addition, we showed that glycosylation of SLC52A1 is not necessary for PERV-A receptor function. We also identified that at a minimum, three cysteine residues are sufficient for SLC52A1 cell surface expression. Mutation of cysteine at position 365 and either of the two cysteine residues in the C-terminal tail at positions 442 or 446 reduced SLC52A1 surface expression and PERV-A infection suggesting that these residues may contribute to overall structural stability and receptor function. Understanding interactions between PERV-A and its cellular receptor may provide novel strategies to prevent zoonotic infection in the setting of xenotransplantation. Published by Elsevier Inc.

  18. Play to learn, teach by play.

    PubMed

    Palagi, Elisabetta; Stanyon, Roscoe; Demuru, Elisa

    2015-01-01

    The synthesis provided by Kline in the target article is noteworthy, but ignores the inseparable role of play in the evolution of learning and teaching in both humans and other animals. Play is distinguished and advantaged by its positive feedback reinforcement through pleasure. Play, especially between adults and infants, is probably the platform from which human learning and teaching evolved.

  19. Play Therapy: A Review

    ERIC Educational Resources Information Center

    Porter, Maggie L.; Hernandez-Reif, Maria; Jessee, Peggy

    2009-01-01

    This article discusses the current issues in play therapy and its implications for play therapists. A brief history of play therapy is provided along with the current play therapy approaches and techniques. This article also touches on current issues or problems that play therapists may face, such as interpreting children's play, implementing…

  20. Training in Fantasy Play.

    ERIC Educational Resources Information Center

    Smith, Peter K.

    1983-01-01

    Outcomes of fantasy play training were compared with those of nonfantasy/skills training in English nursery classes and play groups. Children receiving fantasy play training engaged in cooperative play more than did those receiving skills training, played more often in larger subgroups, and were more physically active. Most effects were present at…

  1. Play Therapy. ERIC Digest.

    ERIC Educational Resources Information Center

    Landreth, Garry; Bratton, Sue

    Play therapy is based on developmental principles and, thus, provides, through play, developmentally appropriate means of expression and communication for children. Therefore, skill in using play therapy is an essential tool for mental health professionals who work with children. Therapeutic play allows children the opportunity to express…

  2. The Play of Psychotherapy

    ERIC Educational Resources Information Center

    Marks-Tarlow, Terry

    2012-01-01

    The author reviews the role of play within psychotherapy. She does not discuss the formal play therapy especially popular for young children, nor play from the Jungian perspective that encourages the use of the sand tray with adults. Instead, she focuses on the informal use of play during psychotherapy as it is orchestrated intuitively. Because…

  3. Children's Empowerment in Play

    ERIC Educational Resources Information Center

    Canning, Natalie

    2007-01-01

    This article examines the level of empowerment and autonomy children can create in their play experiences. It examines the play discourses that children build and maintain and considers the importance of play contexts in supporting children's emotional and social development. These aspects of play are often unseen or misunderstood by the adult…

  4. Dimensions of Play Experience.

    ERIC Educational Resources Information Center

    Mansell, Maureen

    1980-01-01

    Draws the connection between childhood play and the unifying, actualizing effects of play in human experience. Examines the concept of play and its integrative function from multidisciplinary perspectives, giving a paradigm for looking at the play process in other expressive forms such as ritual, art, and aesthetic experience. (JMF)

  5. Child's Play: Therapist's Narrative

    PubMed Central

    Reddy, Rajakumari P.; Hirisave, Uma

    2014-01-01

    Play has been recognized as an essential component to children's healthy development. Schools of play therapy differ philosophically and technically, but they all embrace the therapeutic and developmental properties of play. This case report is an illustration of how a 6-year-old child with emotional disorder was facilitated to express concerns in child-centered play therapy. The paper discusses the therapist's narration of the child's play. PMID:24860228

  6. Play: early and eternal.

    PubMed Central

    Mears, C E; Harlow, H F

    1975-01-01

    A systematic 12-week investigation of development of play behavior was conducted with eight socially reared rhesus monkey infants. A new, basic and primary play form termed self-motion play or peragration was identified and examined. This behavior follows a human model which includes a wide range of pleasurable activities involving motion of the body through space, e.g., rocking, swinging, running, leaping, and water or snow skiing. It can be argued that self-motion play is the initial primate play form and because of its persistence constitutes a reinforcing agent for maintaining many complex patterns and even pastimes. Monkey self-motion play in the present study was divided into five separate patterns in order to compare the relative importance of social and individual peragration play, the role of apparatus and the overall developmental relationships between the different individual and social self-motion play patterns. The data showed that from 90 to 180 days of age self-motion play was independent of other forms of play, that individual self-motion play appeared earlier and with significantly greater increases in frequency than did social self-motion play, and that apparatus was a necessary component for significant increases in social self-motion play. Other findings were that self-motion play existed independent of locomotion and, though initiated by exploration, was separate from it. Therapeutic implications of self-motion play were discussed. Images PMID:1057178

  7. Alibis for Adult Play

    PubMed Central

    2017-01-01

    The social meanings of play sit at odds with norms of responsible and productive adult conduct. To be “caught” playing as an adult therefore risks embarrassment. Still, many designers want to create enjoyable, nonembarrassing play experiences for adults. To address this need, this article reads instances of spontaneous adult play through the lens of Erving Goffman’s theory of the interaction order to unpack conditions and strategies for nonembarrassing adult play. It identifies established frames, segregated audiences, scripts supporting smooth performance, managing audience awareness, role distancing, and, particularly, alibis for play: Adults routinely provide alternative, adult-appropriate motives to account for their play, such as child care, professional duties, creative expression, or health. Once legitimized, the norms and rules of play themselves then provide an alibi for behavior that would risk being embarrassing outside play. PMID:29706842

  8. Role-Playing Mitosis.

    ERIC Educational Resources Information Center

    Wyn, Mark A.; Stegink, Steven J.

    2000-01-01

    Introduces a role playing activity that actively engages students in the learning process of mitosis. Students play either chromosomes carrying information, or cells in the cell membrane. (Contains 11 references.) (Author/YDS)

  9. [Play therapy in hospital].

    PubMed

    Gold, Katharina; Grothues, Dirk; Leitzmann, Michael; Gruber, Hans; Melter, Michael

    2012-01-01

    The following article presents an overview of current research studies on play therapy in the hospital. It highlights individual diagnoses for which play therapy has shown reasonable success. The aim of this review is to describe the current status of the scientific debate on play therapy for sick children in order to allow conclusions regarding the indications for which play therapy is or might be useful.

  10. Play Is the Way

    ERIC Educational Resources Information Center

    Gross, Steve; Sanderson, Rebecca Cornelli

    2012-01-01

    Historically, play has been viewed as a frivolous break from important endeavors like working and learning when, in fact, a child's ability to fully and freely engage in play is essential to their learning, productivity, and overall development. A natural drive to play is universal across all young mammals. Children from every society on earth…

  11. Playing against the Game

    ERIC Educational Resources Information Center

    Remmele, Bernd

    2017-01-01

    The paper first outlines a differentiation of play/game-motivations that include "negative" attitudes against the play/game itself like cheating or spoilsporting. This problem is of particular importance in concern of learning games because they are not "played" for themselves--at least in the first place--but due to an…

  12. The Excellence of Play.

    ERIC Educational Resources Information Center

    Moyles, Janet R., Ed.

    Recognizing that for young children, play is a tool for learning, this book compiles contributions by different authors, reflecting both up-to-date research and current classroom practice as they relate to children's play. Part 1 of the book explores the value of play as a cross-cultural concept as well as one rooted in the Western world. Gender…

  13. Science as Play

    ERIC Educational Resources Information Center

    Raymo, Chester

    1973-01-01

    Analyzes the nature and characteristics of the scientific endeavor to compare with that of children's play. Describes science as a form of religious sacred play which creates a world of make-believe that one may enter if one chooses to play. (CC)

  14. The Pedagogy of Play

    ERIC Educational Resources Information Center

    Giesbrecht, Sheila

    2012-01-01

    Play is important. Environmental educators Sobel and Louv write about the relationship between children and outside play and suggest that early transcendental experiences within nature allow children to develop empathetic orientations towards the natural world. Children who play out-of-doors develop an appreciation for the environment and…

  15. Genetic variant of V825I in the ATP-binding cassette transporter A1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

    PubMed Central

    2011-01-01

    Background Several genetic variants in the ATP-binding cassette transporter A1 (ABCA1) gene have associated with modifications of serum high-density lipoprotein cholesterol (HDL-C) levels and the susceptibility for coronary heart disease, but the findings are still controversial in diverse racial/ethnic groups. Bai Ku Yao is an isolated subgroup of the Yao minority in southern China. The present study was undertaken to detect the possible association of V825I (rs2066715) polymorphism in the ABCA1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 677 subjects of Bai Ku Yao and 646 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Polymerase chain reaction and restriction fragment length polymorphism assay combined with gel electrophoresis were performed for the genotyping of V825I variant, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC), HDL-C, apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of G and A alleles was 57.4% and 42.6% in Bai Ku Yao, and 57.7% and 42.3% in Han (P > 0.05); respectively. The frequency of GG, GA and AA genotypes was 33.7%, 47.4% and 18.9% in Bai Ku Yao, and 33.4%, 48.6% and 18.0% in Han (P > 0.05); respectively. There was no difference in the genotypic and allelic frequencies between males and females in the both ethnic groups. The subjects with AA genotype in Bai Ku Yao had higher serum TC levels than the subjects with GG and GA genotypes (P < 0.05). The participants with AA genotype in Han had lower serum HDL-C and ApoAI levels than the participants with GG and GA genotypes (P < 0.05 for each), but these results were found in males but not in females. Multivariate linear regression analysis showed that the levels of TC in Bai Ku Yao and HDL-C and ApoAI in male Han were correlated with genotypes (P < 0

  16. An Invitation to Play.

    ERIC Educational Resources Information Center

    Lange, Jenny; Zieher, Connie

    The manual is intended to provide suggestions for play to parents of young children with exceptional educational needs. Nineteen types of activities are described and pictured, including make believe with boxes, dress-up activities, kitchen play, bubbles, small motor activities using beans and buttons, use of throw-away materials, painting,…

  17. Playing for Peace.

    ERIC Educational Resources Information Center

    Zarrella, Maureen

    1998-01-01

    Play for Peace brings children of conflicting cultures together through cooperative play. Partner organizations and volunteers in areas such as the Balkans and urban Chicago support the training of teenage facilitators, who learn through experience how to facilitate cooperative, noncompetitive games for children aged 6-10. (SV)

  18. Communication in Symbolic Play.

    ERIC Educational Resources Information Center

    Umek, Ljubica Marjanovic; Musek, Petra Lesnik; Kranjc, Simona

    2001-01-01

    Analyzed records of Slovene children's speech from a linguistic point of view and established differences in communication patterns with regard to the children's ages and the type of symbolic play. Found a shift in play from make-believe with regard to objects to roleplay related to social context. The older the child, the more language functions…

  19. Play and Digital Media

    ERIC Educational Resources Information Center

    Johnson, James E.; Christie, James F.

    2009-01-01

    This article examines how play is affected by computers and digital toys. Research indicates that when computer software targeted at children is problem-solving oriented and open-ended, children tend to engage in creative play and interact with peers in a positive manner. On the other hand, drill-and-practice programs can be quite boring and limit…

  20. Let's Just Play

    ERIC Educational Resources Information Center

    Schmidt, Janet

    2003-01-01

    Children have a right to play. The idea is so simple it seems self-evident. But a stroll through any toy superstore, or any half-hour of so-called "children's" programming on commercial TV, makes it clear that violence, not play, dominates what's being sold. In this article, the author discusses how teachers and parents share the responsibility in…

  1. Guidelines for Medical Play.

    ERIC Educational Resources Information Center

    Ostrenga, Mary Anne

    Medical play can be used as a tool to aid children in coping with stress related to hospitalization, surgery, medical care, and illness. Providing children with adequate guidance and appropriate supplies necessary for medical play, prepares children for medical experiences by enabling them to express their thoughts and feelings. Before attempting…

  2. Growing Up with Play

    ERIC Educational Resources Information Center

    Katch, Jane

    2008-01-01

    Many adults are afraid of boys' play today, believing that the aggression that is so common in boys' fantasies is dangerous and might make them become violent men. This personal reflection describes the importance of multiage play in showing little boys how to become big boys while encouraging empathy and emotional growth in older boys. The author…

  3. The Play's the Thing

    ERIC Educational Resources Information Center

    Bateman, Barbara

    2005-01-01

    The modern special education theater in the United States has hosted many plays, none with a larger or more diverse cast than the learning disabilities (LD) play. During the prologue, the children with LD were waiting in the wings, not yet identified as LD but there, nonetheless. With the advent of compulsory education in this country, awareness…

  4. Return to Play

    ERIC Educational Resources Information Center

    Mangan, Marianne

    2013-01-01

    Call it physical activity, call it games, or call it play. Whatever its name, it's a place we all need to return to. In the physical education, recreation, and dance professions, we need to redesign programs to address the need for and want of play that is inherent in all of us.

  5. The Fear of Play

    ERIC Educational Resources Information Center

    Almon, Joan

    2009-01-01

    Real play--play that is initiated and directed by children and that bubbles up from within the child rather than being imposed by adults--has largely disappeared from the landscape of childhood in the United States. There are many reasons for this, such as the long hours spent in front of screens each day or in activities organized by adults. In…

  6. Family Play Therapy.

    ERIC Educational Resources Information Center

    Ariel, Shlomo

    This paper examines a case study of family play therapy in Israel. The unique contributions of play therapy are evaluated including the therapy's accessibility to young children, its richness and flexibility, its exposure of covert patterns, its wealth of therapeutic means, and its therapeutic economy. The systematization of the therapy attempts…

  7. Computers and Play.

    ERIC Educational Resources Information Center

    Colker, Larry

    Viewing computers in various forms as developmentally appropriate objects for children, this discussion provides a framework for integrating conceptions of computers and conceptions of play. Several instances are cited from the literature in which explicit analogies have been made between computers and playthings or play environments.…

  8. The Therapeutic Play Group.

    ERIC Educational Resources Information Center

    Schiffer, Mortimer

    A discussion of group play therapy includes chapters on the school as a setting for treating emotionally disturbed children and focuses on suggestions for group workers. A synopsis of the play group treatment process precedes a description of considerations in organizing groups and methods for working with the children. Recommendations are made…

  9. Play, Policy & Practice.

    ERIC Educational Resources Information Center

    Klugman, Edgar, Ed.

    In 1992, the U.S.-Israel Binational Science Foundation (BSF), in conjunction with Wheelock College (Boston), sponsored its second workshop on children's play, entitled "Play and Cognitive Ability: The Cultural Context." This volume reflects the presentations and discussions held at the workshop, offering perspectives on children's play…

  10. Play Spaces in Denmark.

    ERIC Educational Resources Information Center

    Mitchell, Edna; Anderson, Robert T.

    1980-01-01

    Describes the variety of play spaces found in urban areas in Denmark: in banks, stores and individual businesses, neighborhood parks and small pocket playgrounds, specialized adventure and traffic playgrounds with supervised activities, and commercial amusement parks. (CM)

  11. Looking into Children's Play Communities

    ERIC Educational Resources Information Center

    Mabry, Mark; Fucigna, Carolee

    2009-01-01

    Play, particularly children's sociodramatic play, is the cornerstone of early childhood classrooms in the United States. Early childhood educators learn and expound mantras of "the value of play," "play-based programs," "children learning through play," and "play as child's work." They strive to promote the importance of making a place for play in…

  12. Girls' Physically Active Play and Parental Behavior.

    ERIC Educational Resources Information Center

    Tauber, Margaret A.

    Sex differences in children's physical activity levels, and associations between girls' activity level, childrearing characteristics and parent-child play behavior were investigated in a quasi-naturalistic situation. As part of a longitudinal project, 144 third grade children were videotaped in a 1-hour play session with one of their parents. A…

  13. A sensitive assay for ABCA1-mediated cholesterol efflux using BODIPY -cholesterol

    USDA-ARS?s Scientific Manuscript database

    Studies have shown a negative association between cellular cholesterol efflux and coronary artery disease (CAD). Standard protocol for quantifying cholesterol efflux involves labeling cells with [(3)H]cholesterol and measuring release of the labeled sterol. Using [(3)H]cholesterol is not ideal for...

  14. Playing To Learn.

    ERIC Educational Resources Information Center

    Mann, Dale; Shakeshaft, Charol; Kottkamp, Robert; Becker, Jonathan

    2000-01-01

    A study to determine effects of Lightspan Partnership Inc.'s interactive materials on student achievement in a Denver- area elementary school revealed higher reading and math test scores for Lightspan schools, compared to control schools. This serious play curriculum, assisted by parents, benefited neediest kids most. (MLH)

  15. Want to Play Geometry?

    ERIC Educational Resources Information Center

    Kaufmann, Matthew L.; Bomer, Megan A.; Powell, Nancy Norem

    2009-01-01

    Students enter the geometry classroom with a strong concept of fairness and a sense of what it means to "play by the rules," yet many students have difficulty understanding the postulates, or rules, of geometry and their implications. Although they may never have articulated the properties of an axiomatic system, they have gained a practical…

  16. The Games Children Play

    ERIC Educational Resources Information Center

    Padak, Nancy; Rasinski, Timothy

    2008-01-01

    The games that children play are not just for fun-they often lead to important skill development. Likewise, word games are fun opportunities for parents and children to spend time together and for children to learn a lot about sounds and words. In this Family Involvement column, the authors describe 12 easy-to-implement word games that parents and…

  17. Abstraction through Game Play

    ERIC Educational Resources Information Center

    Avraamidou, Antri; Monaghan, John; Walker, Aisha

    2012-01-01

    This paper examines the computer game play of an 11-year-old boy. In the course of building a virtual house he developed and used, without assistance, an artefact and an accompanying strategy to ensure that his house was symmetric. We argue that the creation and use of this artefact-strategy is a mathematical abstraction. The discussion…

  18. "Playing" with Science

    ERIC Educational Resources Information Center

    Allen, Dave

    2012-01-01

    When faced with a multitude of tasks, any opportunity to "kill two birds with one stone" is welcome. Drama has always excited the author: as a child performing in plays, later as a student and now as a teacher directing performances and improvising within lessons. The author was lucky enough to have inspirational teachers during his…

  19. Playing with Science

    ERIC Educational Resources Information Center

    Vieyra, Rebecca; Edwards, Teon; Rowe, Elizabeth; Asbell-Clarke, Jodi

    2015-01-01

    Gaming is becoming an effective form of learning and assessment and shouldn't be overlooked in an increasingly technological world. The games described in this article ("Impulse," "Quantum Spectre," and "Ravenous"), entertaining enough to be played by the general public, are also appropriate and useful in a classroom…

  20. Play's Importance in School

    ERIC Educational Resources Information Center

    Sandberg, Anette; Heden, Rebecca

    2011-01-01

    The purpose of this study is to contribute knowledge on and gain an understanding of elementary school teachers' perspectives on the function of play in children's learning processes. The study is qualitative with a hermeneutical approach and has George Herbert Mead as a theoretical frame of reference. Interviews have been carried out with seven…

  1. One Play a Day

    ERIC Educational Resources Information Center

    Blankenship, Mark

    2007-01-01

    Undergraduate theater students rarely get the chance to work on a major world premiere, but this year hundreds of them will. Currently, more than 70 colleges and universities are participating in "365 Days/365 Plays," an ambitious project from Pulitzer Prize-winning playwright Suzan-Lori Parks. Every week, as they mount their portion of this epic…

  2. Integrated Play Groups

    ERIC Educational Resources Information Center

    Glovak, Sandra

    2007-01-01

    As an occupational therapist running social play groups with sensory integration for children on the autism spectrum, the author frequently doubted the wisdom of combining several children on the spectrum into a group. In fact, as the owner of a clinic she said, "No more!" The groups seemed like a waste of parents' time and money, and she refused…

  3. The Paradoxes of Play.

    ERIC Educational Resources Information Center

    Rokosz, Francis M.

    1988-01-01

    The article makes a case against the structuring of intramural sports programs on the basis of the varsity athletics model, arguing that the latter model's components of competition and aggression mar the former's intrinsic rewards of play, creativity, and enhanced human relationships. (CB)

  4. Children as Playing Citizens

    ERIC Educational Resources Information Center

    Grindheim, Liv Torunn

    2017-01-01

    In this article, play is understood as activities of major importance for child-citizens and as activities that constitute various ways of participating. The researcher joined children in three early childhood education institutions in Norway in their activities and categorised their participation in their everyday life. The study depicts that, in…

  5. Statistics at Play

    ERIC Educational Resources Information Center

    English, Lyn D.

    2014-01-01

    An exciting event had occurred for the grade 3 classes at Woodlands State School. A new play space designated for the older grades had now been opened to the third graders. In sharing their excitement over this "real treat, real privilege," the teachers invited the children to find out more about playgrounds and, in particular, their new…

  6. Playing tricks to ions

    NASA Astrophysics Data System (ADS)

    Leibfried, Dietrich

    2017-01-01

    Ted Hänsch's career is defined by breaking new ground in experimental physics. Curiosity, vivid imagination, deep understanding, patience and tenacity are part of the winning formula, but perhaps an equally important ingredient may be Ted's favorite past-time of exploring new tricks in his "Spiellabor" (play-lab), that often resurfaced as key ingredients in rather serious experiments later. On the occasion of Ted's 75th birthday, a few past and potential future experiments with trapped ions are playfully surveyed here. Some of these tricks are already part of the trade, some are currently emerging and a few are mostly speculation today. Maybe some of the latter will be realized and even prove useful in the future.

  7. PlayStation purpura.

    PubMed

    Robertson, Susan J; Leonard, Jane; Chamberlain, Alex J

    2010-08-01

    A 16-year-old boy presented with a number of asymptomatic pigmented macules on the volar aspect of his index fingers. Dermoscopy of each macule revealed a parallel ridge pattern of homogenous reddish-brown pigment. We propose that these lesions were induced by repetitive trauma from a Sony PlayStation 3 (Sony Corporation, Tokyo, Japan) vibration feedback controller. The lesions completely resolved following abstinence from gaming over a number of weeks. Although the parallel ridge pattern is typically the hallmark for early acral lentiginous melanoma, it may be observed in a limited number of benign entities, including subcorneal haematoma.

  8. Farm Hall: The Play

    NASA Astrophysics Data System (ADS)

    Cassidy, David C.

    2013-03-01

    It's July 1945. Germany is in defeat and the atomic bombs are on their way to Japan. Under the direction of Samuel Goudsmit, the Allies are holding some of the top German nuclear scientists-among them Heisenberg, Hahn, and Gerlach-captive in Farm Hall, an English country manor near Cambridge, England. As secret microphones record their conversations, the scientists are unaware of why they are being held or for how long. Thinking themselves far ahead of the Allies, how will they react to the news of the atomic bombs? How will these famous scientists explain to themselves and to the world their failure to achieve even a chain reaction? How will they come to terms with the horror of the Third Reich, their work for such a regime, and their behavior during that period? This one-act play is based upon the transcripts of their conversations as well as the author's historical work on the subject.

  9. Playing My Heart Out: Original Play as Adventure.

    ERIC Educational Resources Information Center

    Donaldson, O. Fred

    1999-01-01

    "Original" play denotes play that is pre-cultural--before conceptualizations and learned responses. Four anecdotes about play with an infant with Down's syndrome, a child with leukemia, a lioness, and a dying woman illustrate the connections between beings and between the ordinary and the sacred during trusting, fearless, playful encounters. (SV)

  10. Imagination, Playfulness, and Creativity in Children's Play with Different Toys

    ERIC Educational Resources Information Center

    Mo????ller, Signe?? Juhl?

    2015-01-01

    Based on a four-month experimental study of preschool children's play with creative-construction and social-fantasy toys, the author examines the in?uence of both types of toys on the play of preschool children. Her comparative analysis considers the impact of transformative play on the development of imagination during play activities and…

  11. Word Play: Scaffolding Language Development through Child-Directed Play

    ERIC Educational Resources Information Center

    Wasik, Barbara A.; Jacobi-Vessels, Jill L.

    2017-01-01

    Play is an important activity in young children's lives. It is how children explore their world and build knowledge. Although free play, which is play that is totally child directed, contributes to children's learning, self-regulation and motivation, adults' participation in children's play is critical in their development, especially their…

  12. Play as Regulation: Promoting Self-Regulation through Play

    ERIC Educational Resources Information Center

    Foley, Gilbert M.

    2017-01-01

    The nature of play and an overview of the stages of play in the first 5 years of childhood are discussed. The core features of sensorimotor, functional, and symbolic play are identified. Vignettes describing how play serves a regulatory function punctuate each section. A conceptual framework for the construct of regulation is presented and…

  13. Child's Play: Revisiting Play in Early Childhood Settings.

    ERIC Educational Resources Information Center

    Dau, Elizabeth, Ed.; Jones, Elizabeth, Ed.

    Noting that play is an essential aspect of learning for young children, this book presents a collection of articles on children's play in Australia. Part 1, "Play, Development, and Learning," contains the following chapters: (1) "The Role of Play in Development and Learning" (Ann Glover); (2) "Stop, Look, and Listen:…

  14. Pause, play, repeat

    PubMed Central

    Sansó, Miriam; Fisher, Robert P

    2013-01-01

    Cyclin-dependent kinases (CDKs) play a central role in governing eukaryotic cell division. It is becoming clear that the transcription cycle of RNA polymerase II (RNAP II) is also regulated by CDKs; in metazoans, the cell cycle and transcriptional CDK networks even share an upstream activating kinase, which is itself a CDK. From recent chemical-genetic analyses we know that CDKs and their substrates control events both early in transcription (the transition from initiation to elongation) and late (3′ end formation and transcription termination). Moreover, mutual dependence on CDK activity might couple the “beginning” and “end” of the cycle, to ensure the fidelity of mRNA maturation and the efficient recycling of RNAP II from sites of termination to the transcription start site (TSS). As is the case for CDKs involved in cell cycle regulation, different transcriptional CDKs act in defined sequence on multiple substrates. These phosphorylations are likely to influence gene expression by several mechanisms, including direct, allosteric effects on the transcription machinery, co-transcriptional recruitment of proteins needed for mRNA-capping, splicing and 3′ end maturation, dependent on multisite phosphorylation of the RNAP II C-terminal domain (CTD) and, perhaps, direct regulation of RNA-processing or histone-modifying machinery. Here we review these recent advances, and preview the emerging challenges for transcription-cycle research. PMID:23756342

  15. Playful Learning and Montessori Education

    ERIC Educational Resources Information Center

    Lillard, Angeline S.

    2013-01-01

    Although Montessori education is often considered a form of playful learning, Maria Montessori herself spoke negatively about a major component of playful learning--pretend play, or fantasy--for young children. In this essay, the author discusses this apparent contradiction: how and why Montessori education includes elements of playful learning…

  16. The Upside of Videogame Playing.

    PubMed

    Jackson, Linda A

    2012-12-01

    In our research on the relationship between videogame playing and cognitive outcomes we found that children (n=481, 12 year olds) who played videogames more were more creative than those who played them less. Here we summarize these findings and propose new research to identify mediating cognitive factors influenced by videogame playing.

  17. Play Therapy in Elementary Schools

    ERIC Educational Resources Information Center

    Landreth, Garry L.; Ray, Dee C.; Bratton, Sue C.

    2009-01-01

    Because the child's world is a world of action and activity, play therapy provides the psychologist in elementary-school settings with an opportunity to enter the child's world. In the play therapy relationship, toys are like the child's words and play is the child's language. Therefore, children play out their problems, experiences, concerns, and…

  18. Play and Positive Group Dynamics

    ERIC Educational Resources Information Center

    Thompson, Pam; White, Samantha

    2010-01-01

    Play is an important part of a child's life and essential to learning and development (Vygotsky, 1978). It is vital that students participate in play and that play be conducted in a restorative manner. Play allows a variety of group dynamics to emerge. Irvin Yalom (1995) identifies 11 curative factors of the group experience. These factors include…

  19. The Child's Right To Play.

    ERIC Educational Resources Information Center

    Morris, Beverley

    This paper argues that play is an important and fundamental educational process and that the child's right to play should be respected. The paper also comments on the 1990 Tokyo International Conference on the Child's Right to Play. Several issues related to children's play, both in and out of school, are discussed. The focus is on the state of…

  20. Asbestos in play sand

    SciTech Connect

    Langer, A.M.; Nolan, R.P.

    1987-04-02

    A letter in the New England Journal of Medicine (Oct. 2 issue) stated that a carbonate sand marketed in New Jersey was contaminated with 2 to 4 percent tremolite asbestos. The authors were called on by one of the federal agencies to repeat the analysis of this sand, specifically for its asbestos content. The sand was pulverized and immersed in oils with known refractive indexes, and the predominant amphibole was characterized by polarized light microscopy. The optical characteristics were noted, and the indexes of refraction were measured and found to be consistent with tremolite. On the basis of optical characterization,more » the authors concluded that all the tremolite visualized with light microscopy consisted of large, single cleavage fragments and was not asbestiform. They used the technique of x-ray diffraction, as did the author of the original report, which showed the presence of an amphibole mineral (probably tremolite) in the carbonate sand. The technique was not used, and cannot be used, to distinguish between the tremolite habits (asbestiform or nonasbestiform). An acid-insoluble residue, recovered from the carbonate sand, was examined by analytic electron microscopy. The tremolite grains were observed to consist of single untwinned, crystalline fragments. Few defects were noted. Selected area electron diffraction nets were indicative of fragments lying near or at the common amphibole cleavage plane. These characteristics are consistent with cleavage fragments and not asbestos. Aspect ratios reflected short particles (less than 5.1). On the basis of their examination of the carbonate play sand, they conclude that it did not contain tremolite asbestos.« less

  1. Rough and Tumble Play 101

    ERIC Educational Resources Information Center

    Carlson, Frances

    2009-01-01

    Many people fear that play-fighting or rough and tumble play is the same as real fighting. There is also a fear that this rough play will become real fighting if allowed to continue. Most of all, parents and teachers fear that during the course of rough and tumble play a child may be hurt. To provide for and allow children to play rough without…

  2. Solar Power at Play

    NASA Astrophysics Data System (ADS)

    2007-03-01

    For the very first time, astronomers have witnessed the speeding up of an asteroid's rotation, and have shown that it is due to a theoretical effect predicted but never seen before. The international team of scientists used an armada of telescopes to discover that the asteroid's rotation period currently decreases by 1 millisecond every year, as a consequence of the heating of the asteroid's surface by the Sun. Eventually it may spin faster than any known asteroid in the solar system and even break apart. ESO PR Photo 11a/07 ESO PR Photo 11a/07 Asteroid 2000 PH5 "The Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) effect is believed to alter the way small bodies in the Solar System rotate," said Stephen Lowry (Queens University Belfast, UK), lead-author of one of the two companion papers in which this work is reported [1, 2]. "The warming caused by sunlight hitting the surfaces of asteroids and meteoroids leads to a gentle recoil effect as the heat is released," he added. "By analogy, if one were to shine light on a propeller over a long enough period, it would start spinning." Although this is an almost immeasurably weak force, its effect over millions of years is far from negligible. Astronomers believe the YORP effect may be responsible for spinning some asteroids up so fast that they break apart, perhaps leading to the formation of double asteroids. Others may be slowed down so that they take many days to complete a full turn. The YORP effect also plays an important role in changing the orbits of asteroids between Mars and Jupiter, including their delivery to planet-crossing orbits, such as those of near-Earth asteroids. Despite its importance, the effect has never been seen acting on a solar system body, until now. Using extensive optical and radar imaging from powerful Earth-based observatories, astronomers have directly observed the YORP effect in action on a small near-Earth asteroid, known as (54509) 2000 PH5. Shortly after its discovery in 2000, it was

  3. Learning, Play, and Your Newborn

    MedlinePlus

    ... Staying Safe Videos for Educators Search English Español Learning, Play, and Your Newborn KidsHealth / For Parents / Learning, ... Some Other Ideas Print What Is My Newborn Learning? Play is the chief way that infants learn ...

  4. Parental Involvement In Play Therapy

    ERIC Educational Resources Information Center

    Ohlson, E. Lamonte

    1976-01-01

    Play therapy acts as a medium of expression for children. The purpose of this article is to outline a methodological approach as well as to emphasize the necessity of including the parent in the play therapy situation. (Author)

  5. Problematic game play: the diagnostic value of playing motives, passion, and playing time in men.

    PubMed

    Kneer, Julia; Rieger, Diana

    2015-04-30

    Internet gaming disorder is currently listed in the DSM-not in order to diagnose such a disorder but to encourage research to investigate this phenomenon. Even whether it is still questionable if Internet Gaming Disorder exists and can be judged as a form of addiction, problematic game play is already very well researched to cause problems in daily life. Approaches trying to predict problematic tendencies in digital game play have mainly focused on playing time as a diagnostic criterion. However, motives to engage in digital game play and obsessive passion for game play have also been found to predict problematic game play but have not yet been investigated together. The present study aims at (1) analyzing if obsessive passion can be distinguished from problematic game play as separate concepts, and (2) testing motives of game play, passion, and playing time for their predictive values for problematic tendencies. We found (N = 99 males, Age: M = 22.80, SD = 3.81) that obsessive passion can be conceptually separated from problematic game play. In addition, the results suggest that compared to solely playing time immersion as playing motive and obsessive passion have added predictive value for problematic game play. The implications focus on broadening the criteria in order to diagnose problematic playing.

  6. Problematic Game Play: The Diagnostic Value of Playing Motives, Passion, and Playing Time in Men

    PubMed Central

    Kneer, Julia; Rieger, Diana

    2015-01-01

    Internet gaming disorder is currently listed in the DSM—not in order to diagnose such a disorder but to encourage research to investigate this phenomenon. Even whether it is still questionable if Internet Gaming Disorder exists and can be judged as a form of addiction, problematic game play is already very well researched to cause problems in daily life. Approaches trying to predict problematic tendencies in digital game play have mainly focused on playing time as a diagnostic criterion. However, motives to engage in digital game play and obsessive passion for game play have also been found to predict problematic game play but have not yet been investigated together. The present study aims at (1) analyzing if obsessive passion can be distinguished from problematic game play as separate concepts, and (2) testing motives of game play, passion, and playing time for their predictive values for problematic tendencies. We found (N = 99 males, Age: M = 22.80, SD = 3.81) that obsessive passion can be conceptually separated from problematic game play. In addition, the results suggest that compared to solely playing time immersion as playing motive and obsessive passion have added predictive value for problematic game play. The implications focus on broadening the criteria in order to diagnose problematic playing. PMID:25942516

  7. Preschoolers' Thinking during Block Play

    ERIC Educational Resources Information Center

    Piccolo, Diana L.; Test, Joan

    2010-01-01

    Children build foundations for mathematical thinking in early play and exploration. During the preschool years, children enjoy exploring mathematical concepts--such as patterns, shape, spatial relationships, and measurement--leading them to spontaneously engage in mathematical thinking during play. Block play is one common example that engages…

  8. Mathematical Adventures in Role Play

    ERIC Educational Resources Information Center

    Tyce, Constance

    2002-01-01

    The provision of role play is vital in every early years setting. It provides opportunities for the development of all areas of learning. With careful thought and planning, all role play situations can provide children with mathematical adventures. Many examples of good quality role play had been observed in a variety of settings throughout…

  9. Piaget, Play and Cognition, Revisited.

    ERIC Educational Resources Information Center

    Sutton-Smith, Brian

    Piaget's early contribution to theorizing about play is discussed critically with reference to three major interrelated problems. These are: (1) that despite their equipotentiality in Piaget's theory of intelligence, imitation and play are not conceptualized as making an equal contribution to cognition, play taking a subordinate role; (2) that…

  10. Play Memories and Place Identity.

    ERIC Educational Resources Information Center

    Sandberg, Anette

    2003-01-01

    This retrospective study examined play memories from childhood to adulthood of 478 university students between ages 20 and 62 as exhibited in drawings of play memories and questionnaire responses. The study focused on the role of the physical environment and place identity in play memories and individual identity development. Findings showed that…

  11. Play Therapy in School Counseling

    ERIC Educational Resources Information Center

    Trice-Black, Shannon; Bailey, Carrie Lynn; Kiper Riechel, Morgan E.

    2013-01-01

    Play therapy is an empirically supported intervention used to address a number of developmental issues faced in childhood. Through the natural language of play, children and adolescents communicate feelings, thoughts, and experiences. Schools provide an ideal setting for play therapy in many ways; however, several challenges exist in implementing…

  12. Play Therapy: Basics and Beyond.

    ERIC Educational Resources Information Center

    Kottman, Terry

    This book provides an atheoretical orientation to basic concepts involved in play therapy and an introduction to different skills used in play therapy. The demand for mental professionals and school counselors who have training and expertise in using play as a therapeutic tool when working with children has increased tremendously. In response to…

  13. Play in Evolution and Development

    ERIC Educational Resources Information Center

    Pellegrini, Anthony D.; Dupuis, Danielle; Smith, Peter K.

    2007-01-01

    In this paper we examine the role of play in human ontogeny and phylogeny, following Surplus Resource Theory. We consider how juveniles use play to sample their environment in order to develop adaptive behaviors. We speculate about how innovative behaviors developed in play in response to environmental novelty may influence subsequent evolutionary…

  14. The Importance of Being Playful.

    ERIC Educational Resources Information Center

    Bodrova, Elena; Leong, Deborah J.

    2003-01-01

    Recent research provides evidence of the strong connections between quality of play in preschool years and children's readiness for school instruction. Mature play, characterized by imaginary situations, multiple roles, clearly defined rules, flexible themes, language development, length of play, helps students' cognitive development. (Contains 12…

  15. The Biology of Human Play.

    ERIC Educational Resources Information Center

    Byers, John A.

    1998-01-01

    Maintains that the "getting into shape" hypothesis of explaining the inverted-U distribution of exercise play across age is likely incorrect. Argues that the biological study of human physical activity play, as recommended by Pellegrini and Smith (1998), will reveal whether physical activity play represents an example of…

  16. FATHER PLAY: IS IT SPECIAL?

    PubMed

    Cabrera, Natasha J; Roggman, Lori

    2017-11-01

    Both mothers and fathers play with their children, but research on parent-child play interactions is conducted with mothers three times more often than it is with fathers. The articles in this special issue address this gap by focusing on the nature and quality of father-child play, across cultural contexts, and considering whether father play offers something unique and special for early human development, in infancy or early childhood. The studies show that fathers can be just as developmentally supportive as are mothers in terms of being playful and engaged with their children in ways that are related to greater child socioemotional competence, emotion regulation, and vocabulary, and to less aggression, anxiety, and negativity. We encourage future research to examine the cultural influences, family system dynamics, and specificity of timing and types of father-child play in relation to children's developmental competence. © 2017 Michigan Association for Infant Mental Health.

  17. The Influence of Play Material on Discourse during Play.

    ERIC Educational Resources Information Center

    Burroughs, Elizabeth I.; Murray, Sharon E.

    1992-01-01

    Evaluation of the conversational behavior of 36 children (ages 48-59 months) playing in dyads with 3 different materials (modeling dough, a farm set, and animal puppets) found that each toy elicited the same amount of talking, though there were differences in discourse structure attributable to play materials. (DB)

  18. Children's Play in Diverse Cultures. Children's Play in Society Series.

    ERIC Educational Resources Information Center

    Roopnarine, Jaipaul L., Ed.; And Others

    This book illuminates play as a universal and culture-specific activity. It provides needed information about the behavior of children in diverse cultural contexts as well as about the play of children in unassimilated cultural or subcultural contexts. It offers readers the opportunity to develop greater sensitivity to and better understanding of…

  19. The Power of Outdoor Play and Play in Natural Environments

    ERIC Educational Resources Information Center

    Kemple, Kristen M.; Oh, JiHyun; Kenney, Elizabeth; Smith-Bonahue, Tina

    2016-01-01

    Young children's outdoor play serves important and diverse purposes, including physical exercise and opportunities for growth in all developmental areas. Unfortunately, the amount of time that children spend engaged in unstructured, child-directed outdoor play has diminished significantly in the past generation. In this article, the authors…

  20. Challenging Notions of Gendered Game Play: Teenagers Playing the Sims

    ERIC Educational Resources Information Center

    Beavis, Catherine; Charles, Claire

    2005-01-01

    This paper challenges notions of gendered game playing practice implicit in much research into young women's involvement with the computer gaming culture. It draws on a study of Australian teenagers playing "The Sims Deluxe" as part of an English curriculum unit and insights from feminist media studies to explore relationships between…

  1. Playing with the Multiple Intelligences: How Play Helps Them Grow

    ERIC Educational Resources Information Center

    Eberle, Scott G.

    2011-01-01

    Howard Gardner first posited a list of "multiple intelligences" as a liberating alternative to the assumptions underlying traditional IQ testing in his widely read study "Frames of Mind" (1983). Play has appeared only in passing in Gardner's thinking about intelligence, however, even though play instructs and trains the verbal, interpersonal,…

  2. Well Played: The Origins and Future of Playfulness

    ERIC Educational Resources Information Center

    Gordon, Gwen

    2014-01-01

    In this article, the author synthesizes research from several disciplines to shed light on play's central role in healthy development. Gordon builds on research in attachment theory that correlates secure attachment in infancy with adult well-being to demonstrate how playfulness might be a lifelong outcome of secure attachment and a primary…

  3. Playing It Safe: Risk Management for Games Play.

    ERIC Educational Resources Information Center

    Halliday, Nancy

    1996-01-01

    Considering the players, the game, and the environment in which games are played can make games play at camp safer, more successful, and more enjoyable. Presents factors concerning the players, the game, roughhousing, excessive competitiveness, the environment, space, boundaries, weather, time, and overall game objectives that need to be…

  4. Symbolic play and language development.

    PubMed

    Orr, Edna; Geva, Ronny

    2015-02-01

    Symbolic play and language are known to be highly interrelated, but the developmental process involved in this relationship is not clear. Three hypothetical paths were postulated to explore how play and language drive each other: (1) direct paths, whereby initiation of basic forms in symbolic action or babbling, will be directly related to all later emerging language and motor outputs; (2) an indirect interactive path, whereby basic forms in symbolic action will be associated with more complex forms in symbolic play, as well as with babbling, and babbling mediates the relationship between symbolic play and speech; and (3) a dual path, whereby basic forms in symbolic play will be associated with basic forms of language, and complex forms of symbolic play will be associated with complex forms of language. We micro-coded 288 symbolic vignettes gathered during a yearlong prospective bi-weekly examination (N=14; from 6 to 18 months of age). Results showed that the age of initiation of single-object symbolic play correlates strongly with the age of initiation of later-emerging symbolic and vocal outputs; its frequency at initiation is correlated with frequency at initiation of babbling, later-emerging speech, and multi-object play in initiation. Results support the notion that a single-object play relates to the development of other symbolic forms via a direct relationship and an indirect relationship, rather than a dual-path hypothesis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Outdoor Play: Combating Sedentary Lifestyles

    ERIC Educational Resources Information Center

    Thigpen, Betsy

    2007-01-01

    Increasingly sedentary lifestyles are contributing to overweight and other health concerns as children spend less and less time outside engaged in active play. Outdoor play provides important opportunities to explore the natural world, interact with peers, engage in vigorous physical activity, and learn about our environment. However, outdoor…

  6. Solitary Play: Some Functional Reconsiderations

    ERIC Educational Resources Information Center

    Moore, Nancy V.; And Others

    1974-01-01

    Solitary play in six kindergarten children was observed and coded for frequency and type in order to resolve iscrepancies in a Sex Birth Order interaction. Several facts concerning solitary play as indicative of independence and maturity are noted. (Author/ED)

  7. The Child's Right To Play.

    ERIC Educational Resources Information Center

    Guddemi, Marcy

    Several factors are eroding children's right to play. The first is continuing poverty throughout the world. This factor is evident in underdeveloped countries and the inner cities of industrialized countries. Changing cultural values are a second factor in developed societies where indifference toward the importance of play is prevalent. The many…

  8. The Play of Socratic Dialogue

    ERIC Educational Resources Information Center

    Smith, Richard

    2011-01-01

    Proponents of philosophy for children generally see themselves as heirs to the "Socratic" tradition. They often claim too that children's aptitude for play leads them naturally to play with abstract, philosophical ideas. However in Plato's dialogues we find in the mouth of "Socrates" many warnings against philosophising with the young. Those…

  9. Invention at Play. Educators' Manual.

    ERIC Educational Resources Information Center

    Judd, Michael; Lacasse, Jane; Smith, Monica; Reilly, Katie

    A Smithsonian exhibition was developed that looked at invention in an innovative way. It aimed to encourage visitors to make connections between their own lives and abilities and those of inventors. The role of play in the invention process was examined. Play is a universal and familiar activity and can help people find the link between their own…

  10. Making Play Work for Education

    ERIC Educational Resources Information Center

    Weisberg, Deena Skolnick; Kittredge, Audrey K.; Hirsh-Pasek, Kathy; Golinkoff, Roberta Michnick; Klahr, David

    2015-01-01

    Children, especially in the preschool years, learn a tremendous amount through play. Research on guided play demonstrates how schools can couple a curriculum-centered preschool program with a developmentally appropriate pedagogical approach to classroom teaching. However, to fully test this claim, we need a clear definition of the term…

  11. Including "Everyone" in Outdoor Play.

    ERIC Educational Resources Information Center

    Flynn, Lynda L.; Kieff, Judith

    2002-01-01

    Presents guidelines for outdoor play that are important when young children have special needs. Details a decision-making process for planning adaptations and practical strategies for making adaptations and interventions to enhance outdoor play for children with special needs. Lists adaptations for a child who is blind, is deaf, has physical…

  12. Engaging Families through Artful Play

    ERIC Educational Resources Information Center

    Brown, Robert

    2015-01-01

    This paper explores how aligned arts and play experiences can extend child and family engagement in a public outdoor space. The importance of outdoor play for children is strongly advocated and in response local governments provide playgrounds and recreational open spaces. To extend further the experiences afforded in such spaces some local…

  13. The Fractal Self at Play

    ERIC Educational Resources Information Center

    Marks-Tarlow, Terry

    2010-01-01

    In this article, the author draws on contemporary science to illuminate the relationship between early play experiences, processes of self-development, and the later emergence of the fractal self. She argues that orientation within social space is a primary function of early play and developmentally a two-step process. With other people and with…

  14. Empowering Groups that Enable Play

    ERIC Educational Resources Information Center

    Wilson, David Sloan; Marshall, Danielle; Iserhott, Hindi

    2011-01-01

    Creating play environments for children usually requires groups of adults working together. An extensive scientific literature describes how groups function to achieve shared goals in general terms, and groups attempting to empower play may find this literature useful. Design principles for managing natural resources, identified by Elinor Ostrom…

  15. The Social Competence of Play.

    ERIC Educational Resources Information Center

    Fein, Greta G.

    This is a study of how young children gain social competence through pretend play or role playing. Subjects were 38 Caucasian children (19 females, 19 males) who were observed at four ages: 12, 18, 24 and 30 months. The same set of toys, which included a doll, a saucepan, doll bottles, coffee mug, teacup, teaspoon, doll crib, blanket, toy phone…

  16. Young Children and War Play.

    ERIC Educational Resources Information Center

    Carlsson-Paige, Nancy; Levin, Diane E.

    1988-01-01

    In a recent survey of parents and early childhood professionals the prevalence of war play among children and an increase in the amount of violence in children's play was noted. Outlines how the deregulation of children's television during the Reagan administration has affected children's exposure to violence in children's television programming.…

  17. Niger Delta play types, Nigeria

    SciTech Connect

    Akinpelu, A.O.

    Exploration databases can be more valuable when sorted by play type. Play specific databases provide a system to organize E & P data used in evaluating the range of values of parameters for reserve estimation and risk assessment. It is important both in focusing the knowledge base and in orienting research effort. A play in this context is any unique combination of trap, reservoir and source properties with the right dynamics of migration and preservation that results in hydrocarbon accumulation. This definitions helps us to discriminate the subtle differences found with these accumulation settings. About 20 play types were identifiedmore » around the Niger Delta oil province in Nigeria. These are grouped into three parts: (1) The proven plays-constituting the bulk of exploration prospects in Nigeria today. (2) The unproven or semi-proven plays usually with some successes recorded in a few tries but where knowledge is still inadequate. (3) The unproven or analogous play concept. These are untested but geologically sound ideas which may or may not have been tried elsewhere. With classification and sub grouping of these play types into specific databases, intrinsic attributes and uniqueness of each of them with respect to the four major risk elements and the eight parameters for reserve estimation can be better understood.« less

  18. Transmedia Play: Literacy across Media

    ERIC Educational Resources Information Center

    Alper, Meryl; Herr-Stephenson, Rebecca

    2013-01-01

    Transmedia play is a new way to understand how children develop critical media literacy and new media literacies through their interactions with contemporary media that links stories and structures across platforms. This essay highlights five characteristics of transmedia play that make it particularly useful for learning:…

  19. Analysing playing using the note-time playing path.

    PubMed

    de Graaff, Deborah L E; Schubert, Emery

    2011-03-01

    This article introduces a new method of data analysis that represents the playing of written music as a graph. The method, inspired by Miklaszewski, charts low-level note timings from a sound recording of a single-line instrument using high-precision audio-to-MIDI conversion software. Note onset times of pitch sequences are then plotted against the score-predicted timings to produce a Note-Time Playing Path (NTPP). The score-predicted onset time of each sequentially performed note (horizontal axis) unfolds in performed time down the page (vertical axis). NTPPs provide a visualisation that shows (1) tempo variations, (2) repetitive practice behaviours, (3) segmenting of material, (4) precise note time positions, and (5) time spent on playing or not playing. The NTPP can provide significant new insights into behaviour and cognition of music performance and may also be used to complement established traditional approaches such as think-alouds, interviews, and video coding.

  20. MicroRNA 302a is a novel modulator of cholesterol homeostasis and atherosclerosis

    PubMed Central

    Meiler, Svenja; Baumer, Yvonne; Toulmin, Emma; Seng, Kosal; Boisvert, William A.

    2014-01-01

    Objective Macrophage foam cell formation is a key feature of atherosclerosis. Recent studies have shown that specific microRNAs (miRs) are regulated in modified low-density lipoprotein (LDL)- treated macrophages, which can affect the cellular cholesterol homeostasis. Undertaking a genome-wide screen of microRNAs regulated in primary macrophages by modified LDL, miR-302a emerged as a potential candidate that may play a key role in macrophage cholesterol homeostasis. Approach and Results The objective of this study was to assess the involvement of miR-302a in macrophage lipid homeostasis and if it can influence circulating lipid levels and atherosclerotic development when it is inhibited in a murine atherosclerosis model. We found that transfection of primary macrophages with either miR-302a or anti-miR-302a regulated the expression of ATP-binding cassette (ABC) transporter ABCA1 mRNA and protein. Luciferase reporter assays showed that miR-302a repressed the 3′UTR activity of mouse Abca1 by 48% and human ABCA1 by 45%. Additionally, transfection of murine macrophages with miR-302a attenuated cholesterol efflux to apolipoprotein A-1 (apoA-1) by 38%. Long-term in vivo administration of anti-miR-302a to mice with LDL receptor deficiency (Ldlr−/−) fed an atherogenic diet led to an increase in ABCA1 in the liver and aorta as well as an increase in circulating plasma HDL levels by 35% compared with that of control mice. The anti-miR-302a-treated mice also displayed reduced atherosclerotic plaque size by approximately 25% as well as a more stable plaque morphology with reduced signs of inflammation. Conclusions These studies identify miR-302a as a novel modulator of cholesterol efflux and a potential therapeutic target for suppressing atherosclerosis. PMID:25524771

  1. MicroRNA 302a is a novel modulator of cholesterol homeostasis and atherosclerosis.

    PubMed

    Meiler, Svenja; Baumer, Yvonne; Toulmin, Emma; Seng, Kosal; Boisvert, William A

    2015-02-01

    Macrophage foam cell formation is a key feature of atherosclerosis. Recent studies have shown that specific microRNAs (miRs) are regulated in modified low-density lipoprotein-treated macrophages, which can affect the cellular cholesterol homeostasis. Undertaking a genome-wide screen of miRs regulated in primary macrophages by modified low-density lipoprotein, miR-302a emerged as a potential candidate that may play a key role in macrophage cholesterol homeostasis. The objective of this study was to assess the involvement of miR-302a in macrophage lipid homeostasis and if it can influence circulating lipid levels and atherosclerotic development when it is inhibited in a murine atherosclerosis model. We found that transfection of primary macrophages with either miR-302a or anti-miR-302a regulated the expression of ATP-binding cassette (ABC) transporter ABCA1 mRNA and protein. Luciferase reporter assays showed that miR-302a repressed the 3' untranslated regions (UTR) activity of mouse Abca1 by 48% and human ABCA1 by 45%. In addition, transfection of murine macrophages with miR-302a attenuated cholesterol efflux to apolipoprotein A-1 (apoA-1) by 38%. Long-term in vivo administration of anti-miR-302a to mice with low-density lipoprotein receptor deficiency (Ldlr(-/-)) fed an atherogenic diet led to an increase in ABCA1 in the liver and aorta as well as an increase in circulating plasma high-density lipoprotein levels by 35% compared with that of control mice. The anti-miR-302a-treated mice also displayed reduced atherosclerotic plaque size by ≈25% and a more stable plaque morphology with reduced signs of inflammation. These studies identify miR-302a as a novel modulator of cholesterol efflux and a potential therapeutic target for suppressing atherosclerosis. © 2014 American Heart Association, Inc.

  2. Playful biometrics: controversial technology through the lens of play.

    PubMed

    Ellerbrok, Ariane

    2011-01-01

    This article considers the role of play in the context of technological emergence and expansion, particularly as it relates to recently emerging surveillance technologies. As a case study, I consider the trajectory of automated face recognition—a biometric technology of numerous applications, from its more controversial manifestations under the rubric of national security to a clearly emerging orientation toward play. This shift toward “playful” biometrics—or from a technology traditionally coded as “hard” to one now increasingly coded as “soft”—is critical insofar as it renders problematic the traditional modes of critique that have, up until this point, challenged the expansion of biometric systems into increasingly ubiquitous realms of everyday life. In response to this dynamic, I propose theorizing the expansion of face recognition specifically in relation to “play,” a step that allows us to broaden the critical space around newly emerging playful biometrics, as well as playful surveillance more generally. In addition, play may also have relevance for theorizing other forms of controversial technology, particularly given its potential role in processes of obfuscation, normalization, and marginalization.

  3. Inhibition of mitogen-activated protein kinase Erk1/2 promotes protein degradation of ATP binding cassette transporters A1 and G1 in CHO and HuH7 cells.

    PubMed

    Mulay, Vishwaroop; Wood, Peta; Manetsch, Melanie; Darabi, Masoud; Cairns, Rose; Hoque, Monira; Chan, Karen Cecilia; Reverter, Meritxell; Alvarez-Guaita, Anna; Rye, Kerry-Anne; Rentero, Carles; Heeren, Joerg; Enrich, Carlos; Grewal, Thomas

    2013-01-01

    Signal transduction modulates expression and activity of cholesterol transporters. We recently demonstrated that the Ras/mitogen-activated protein kinase (MAPK) signaling cascade regulates protein stability of Scavenger Receptor BI (SR-BI) through Proliferator Activator Receptor (PPARα) -dependent degradation pathways. In addition, MAPK (Mek/Erk 1/2) inhibition has been shown to influence liver X receptor (LXR) -inducible ATP Binding Cassette (ABC) transporter ABCA1 expression in macrophages. Here we investigated if Ras/MAPK signaling could alter expression and activity of ABCA1 and ABCG1 in steroidogenic and hepatic cell lines. We demonstrate that in Chinese Hamster Ovary (CHO) cells and human hepatic HuH7 cells, extracellular signal-regulated kinase 1/2 (Erk1/2) inhibition reduces PPARα-inducible ABCA1 protein levels, while ectopic expression of constitutively active H-Ras, K-Ras and MAPK/Erk kinase 1 (Mek1) increases ABCA1 protein expression, respectively. Furthermore, Mek1/2 inhibitors reduce ABCG1 protein levels in ABCG1 overexpressing CHO cells (CHO-ABCG1) and human embryonic kidney 293 (HEK293) cells treated with LXR agonist. This correlates with Mek1/2 inhibition reducing ABCG1 cell surface expression and decreasing cholesterol efflux onto High Density Lipoproteins (HDL). Real Time reverse transcriptase polymerase chain reaction (RT-PCR) and protein turnover studies reveal that Mek1/2 inhibitors do not target transcriptional regulation of ABCA1 and ABCG1, but promote ABCA1 and ABCG1 protein degradation in HuH7 and CHO cells, respectively. In line with published data from mouse macrophages, blocking Mek1/2 activity upregulates ABCA1 and ABCG1 protein levels in human THP1 macrophages, indicating opposite roles for the Ras/MAPK pathway in the regulation of ABC transporter activity in macrophages compared to steroidogenic and hepatic cell types. In summary, this study suggests that Ras/MAPK signaling modulates PPARα- and LXR-dependent protein degradation

  4. A multiverse play divides opinion

    NASA Astrophysics Data System (ADS)

    Crease, Robert P.

    2015-03-01

    The stage lights rise. A man and woman meet in a cute way - "Do you know why it's impossible to lick the tips of your elbows?" she asks - they chat momentarily, and separate. The play is Constellations by Nick Payne.

  5. Play for Children in Hospital

    ERIC Educational Resources Information Center

    Hardgrove, Carol; And Others

    1976-01-01

    Contains six short articles on therapeutic play. Each article is an edited version of a paper delivered at the XIV World Congress of Pediatrics in Buenos Aires on the subject of children in the hospital. (JMB)

  6. Children's Play in Multifamily Housing

    ERIC Educational Resources Information Center

    Becker, Franklin D.

    1976-01-01

    Using formal and informal interviews and systematic and casual observations, children's play facilities in seven multifamily housing developments for moderate and low income families were evaluated. Results of the evaluation for both children and adults are reported. (RH)

  7. Digital Play: A New Classification

    ERIC Educational Resources Information Center

    Marsh, Jackie; Plowman, Lydia; Yamada-Rice, Dylan; Bishop, Julia; Scott, Fiona

    2016-01-01

    This paper draws on an ESRC-funded study of play and creativity in preschool-aged children's use of apps in the UK. The main objectives of the study were to collect information about access to and use of apps in the home, establish the most popular apps and identify the features of those apps that are successful in promoting play and creativity. A…

  8. Let's 'play' with molecular pharmacology.

    PubMed

    Choudhury, Supriyo; Pradhan, Richeek; Sengupta, Gairik; Das, Manisha; Chatterjee, Manojit; Roy, Ranendra Kumar; Chatterjee, Suparna

    2015-01-01

    Understanding concepts of molecular mechanisms of drug action involves sequential visualization of physiological processes and drug effects, a task that can be difficult at an undergraduate level. Role-play is a teaching-learning methodology whereby active participation of students as well as clear visualization of the phenomenon is used to convey complex physiological concepts. However, its use in teaching drug action, a process that demands understanding of a second level of complexity over the physiological process, has not been investigated. We hypothesized that role-play can be an effective and well accepted method for teaching molecular pharmacology. In an observational study, students were guided to perform a role-play on a selected topic involving drug activity. Students' gain in knowledge was assessed comparing validated pre- and post-test questionnaires as well as class average normalized gain. The acceptance of role-play among undergraduate medical students was evaluated by Likert scale analysis and thematic analysis of their open-ended written responses. Significant improvement in knowledge (P < 0.001) was noted in the pre- to post-test knowledge scores, while a high gain in class average normalized score was evident. In Likert scale analysis, most students (93%) expressed that role-play was an acceptable way of teaching. In a thematic analysis, themes of both strengths and weaknesses of the session emerged. Role-play can be effectively utilized while teaching selected topics of molecular pharmacology in undergraduate medical curricula.

  9. The “Beta-Clasp” model of apolipoprotein A-I - a lipid-free solution structure determined by electron paramagnetic resonance spectroscopy

    PubMed Central

    Lagerstedt, Jens O.; Budamagunta, Madhu S.; Liu, Grace S.; DeValle, Nicole C.; Voss, John C.; Oda, Michael N.

    2012-01-01

    Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and plays a central role in cholesterol metabolism. The lipid-free / lipid-poor form of apoA-I is the preferred substrate for the ATP-binding cassette transporter A1 (ABCA1). The interaction of apoA-I with ABCA1 leads to the formation of cholesterol laden high density lipoprotein (HDL) particles, a key step in reverse cholesterol transport and the maintenance of cholesterol homeostasis. Knowledge of the structure of lipid-free apoA-I is essential to understanding its critical interaction with ABCA1 and the molecular mechanisms underlying HDL biogenesis. We therefore examined the structure of lipid-free apoA-I by electron paramagnetic resonance spectroscopy (EPR). Through site directed spin label EPR, we mapped the secondary structure of apoA-I and identified sites of spin coupling as residues 26, 44, 64, 167, 217 and 226. We capitalize on the fact that lipid-free apoA-I self-associates in an anti-parallel manner in solution. We employed these sites of spin coupling to define the central plane in the dimeric apoA-I complex. Applying both the constraints of dipolar coupling with the EPR-derived pattern of solvent accessibility, we assembled the secondary structure into a tertiary context, providing a solution structure for lipid-free apoA-I. PMID:22245143

  10. Why Play Outside? Problematising Outdoor Play as a Biopedagogical Task

    ERIC Educational Resources Information Center

    Robinson, Daniel B.; Barrett, Joe

    2017-01-01

    Although outdoor play has been widely recognised for the many benefits it affords children, some have rationalised the need for it based on goals related to physical health. More specifically, these instrumental goals have been closely related to obesity, overweight, and/or physical (in)activity. Adhering to obesity discourses and the notion of a…

  11. Parent-Child Play across Cultures: Advancing Play Research

    ERIC Educational Resources Information Center

    Roopnarine, Jaipaul L.; Davidson, Kimberly L.

    2015-01-01

    In this article, the authors argue for a greater understanding of children's play across cultures through better integration of scientific thinking about the developed and developing societies, through consideration of socialization beliefs and goals, and, finally, through the use of more complex models in research investigations. They draw on…

  12. Rollovers during play: Complementary perspectives.

    PubMed

    Smuts, Barbara; Bauer, Erika; Ward, Camille

    2015-07-01

    In this commentary, we compare and contrast Norman et al.s' findings on rollovers during dog play (Norman et al., 2015; the "target article") with our work on dog play fighting (Bauer and Smuts, 2007; Ward et al., 2008). We first review our major findings and then correct some errors in the target article's descriptions of our work. We then further explore the concept of "defensive" rollovers proposed in the target article. We conclude that a combination of the target article's approach and ours should inform future investigations of dog rollovers. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Teaching Shakespeare Through Play Production.

    ERIC Educational Resources Information Center

    Stodder, Joseph H.

    1995-01-01

    A performance-oriented approach to teaching William Shakespeare's literature has been found to be effective and enthusiastically received by college students. Ten years of teaching Shakespeare through full play production has shown that the rewards, eloquently expressed in the testimony of students, more than compensate for extra work required of…

  14. Fort Play Children Recreate Recess

    ERIC Educational Resources Information Center

    Powell, Mark

    2007-01-01

    Recess beckons well before it actually arrives. Its allure can be heard in children's lunchtime conversations as they discuss imaginary roles, plans, alliances and teams, with an obvious appetite for play and its unbounded possibility. For some children, recess provides the most important reasons to come to school. In team sports, games of chase…

  15. Science Adventures in Children's Play.

    ERIC Educational Resources Information Center

    Rieger, Edythe

    The stated purpose of this pamphlet is to suggest simple, natural, interesting experiences in children's play that have science implications. It tells how the teacher may capitalize on the innate curiosity of children by incorporating science discovery in daily classroom experiences. This how-to-do-it manual directs map-making and activities for…

  16. Teaching Technical Skills through Play.

    ERIC Educational Resources Information Center

    Gullion, Laurie

    The value of light-hearted play in teaching technical recreational sport skills is immense. Children as well as adults can learn more quickly and completely with a games-oriented approach. Often without realizing the hidden goal of excellent skiing or paddling, participants respond to intriguing tasks in a game, immerse themselves in good…

  17. Moral Education through Play Therapy

    ERIC Educational Resources Information Center

    Mahalle, Salwa; Zakaria, Gamal Abdul Nasir; Nawi, Aliff

    2014-01-01

    This paper will discuss on how sand therapy (as one type of play therapies) can be applied as an additional technique or approach in counseling. The research questions for this study are to see what are the development, challenges faced by the therapist during the sessions given and how sand therapy can aid to the progress of the client. It is a…

  18. Child-Centered Play Therapy

    ERIC Educational Resources Information Center

    VanFleet, Rise; Sywulak, Andrea E.; Sniscak, Cynthia Caparosa

    2010-01-01

    Highly practical, instructive, and authoritative, this book vividly describes how to conduct child-centered play therapy. The authors are master clinicians who explain core therapeutic principles and techniques, using rich case material to illustrate treatment of a wide range of difficulties. The focus is on nondirective interventions that allow…

  19. Designing Play for Dark Times

    ERIC Educational Resources Information Center

    Yamada-Rice, Dylan

    2017-01-01

    This article reports on a knowledge-exchange network project that had the core aim of informing the development of a video game for hospitalized children. In order to do this, it brought together hospital play specialists, academics and representatives from the digital games industry to co-produce knowledge that could be used in the future…

  20. Playing Videogames: The Electronic Friend.

    ERIC Educational Resources Information Center

    Selnow, Gary W.

    1984-01-01

    Concluded that the children in this study (ages 10-14) played video games in arcades for some of the same reasons they watched television: (1) escape; (2) a sense of personal involvement in the action; and (3) a source of or substitute for companionship. (PD)

  1. Building Curriculum during Block Play

    ERIC Educational Resources Information Center

    Andrews, Nicole

    2015-01-01

    Blocks are not just for play! In this article, Nicole Andrews describes observing the interactions of three young boys enthusiastically engaged in the kindergarten block center of their classroom, using blocks in a building project that displayed their ability to use critical thinking skills, physics exploration, and the development of language…

  2. Sculpting Cells with Play Doh.

    ERIC Educational Resources Information Center

    Way, Virginia A.

    1982-01-01

    Suggests using Play Doh to mold models of the nucleus, mitochondria, and inner cellular structures. Students can conceptualize the cell's structures as three-dimensional even though they appear two-dimensional under a microscope. Includes instructions for preparing homemade dough. (Author/JN)

  3. Play: The Reversal Theory Perspective.

    ERIC Educational Resources Information Center

    Kerr, J. H.

    The intention of this theoretical paper is to present a reversal theory interpretation of play phenomena. Reversal theory, a developing theory in psychology, concerns the complex relationship between experience and motivation. One of the central charactieristics of the theory is that it attempts to understand why so much of human behavior is…

  4. Integrating Time, Place, and Play

    ERIC Educational Resources Information Center

    Gallavan, Nancy P.

    2004-01-01

    "Time, Place, and Play," is a short phrase, but is summarizes three very big concepts--history, geography, and culture--that are part of the elementary social studies curriculum. This article relates the story of how twenty-five elementary and middle school teachers, meeting over several weeks in a university class, designed a unit of study on the…

  5. Interpretive Reproduction in Children's Play

    ERIC Educational Resources Information Center

    Corsaro, William A.

    2012-01-01

    The author looks at children's play from the perspective of interpretive reproduction, emphasizing the way children create their own unique peer cultures, which he defines as a set of routines, artifacts, values, and concerns that children engage in with their playmates. The article focuses on two types of routines in the peer culture of preschool…

  6. Obama Plays Cheerleader for STEM

    ERIC Educational Resources Information Center

    Robelen, Erik W.

    2010-01-01

    Amid a struggling economy, a raft of foreign-policy headaches, and the tail end of a heated campaign season, President Barack Obama carved out time in his schedule last month to watch students in the State Dining Room demonstrate a solar-powered model car, a water-purification system, and a soccer-playing robot. The science fair was the fifth…

  7. Environmental and Cognitive Factors in Social Play.

    ERIC Educational Resources Information Center

    Vandenberg, Brian

    1981-01-01

    Results indicated that different types of play environment strongly influence preschool children's types of social play and play group size. Differences in cognitive level and social egocentrism influenced the choice of play environment. (Author/DB)

  8. Detection of an ABCA1 variant associated with type 2 diabetes mellitus susceptibility for biochemistry and genetic laboratory courses.

    PubMed

    Legorreta-Herrera, M; Mosqueda-Romo, N A; Hernández-Clemente, F; Soto-Cruz, I

    2013-01-01

    We selected diabetes mellitus for this laboratory exercise to provide students with an explicit model for scientific research concerning the association between the R230C polymorphism and susceptibility to type 2 diabetes mellitus, which is highly prevalent in the Mexican population. We used a collaborative project-based learning to engage students to direct their own learning process. Students worked in small groups with the same learning goal to research, organize data, and present seminars to experimentally genotype the C230 variant and correctly interpret their results. At the conclusion of this laboratory exercise, the students were able to demonstrate a clear understanding of the relevant biological molecular principles to genotype the C230 variant, showed technical competency to carry out the experimental protocols with proficiency, and interpret their results using statistical analyses. The students discussed their understanding of the genetic technologies and the broader social and ethical implications of the research. A randomly selected team was trained to work as a "sentinel" to monitor their classmates and ensure the proper application of techniques. Moreover, the evaluation of this exercise is shared between the students and the instructors; the students evaluate their own work and the performance of their classmates. At the end of the course, the students complete a questionnaire to anonymously provide feedback and information regarding their perception of the learning outcomes. Overall, the student feedback was positive, indicating that the exercise was useful and that it would help to prepare the students for professional practice. Copyright © 2013 Wiley-Liss, Inc.

  9. Detection of an ABCA1 Variant Associated with Type 2 Diabetes Mellitus Susceptibility for Biochemistry and Genetic Laboratory Courses

    ERIC Educational Resources Information Center

    Legorreta-Herrera, M.; Mosqueda-Romo, N. A.; Hernández-Clemente, F.; Soto-Cruz, I.

    2013-01-01

    We selected diabetes mellitus for this laboratory exercise to provide students with an explicit model for scientific research concerning the association between the R230C polymorphism and susceptibility to type 2 diabetes mellitus, which is highly prevalent in the Mexican population. We used a collaborative project-based learning to engage…

  10. Cognitive-behavioral play therapy.

    PubMed

    Knell, S M

    1998-03-01

    Discusses cognitive-behavioral play therapy (CBPT), a developmentally sensitive treatment for young children that relies on flexibility, decreased expectation for verbalizations by the child, and increased reliance on experiential approaches. The development of CBPT for preschool-age children provides a relatively unique adaptation of cognitive therapy as it was originally developed for adults. CBPT typically contains a modeling component through which adaptive coping skills are demonstrated. Through the use of play, cognitive change is communicated indirectly, and more adaptive behaviors can be introduced to the child. Modeling is tailored for use with many specific cognitive and behavioral interventions. Generalization and response prevention are important features of CBPT. With minor modifications, many of the principles of cognitive therapy, as delineated for use with adults, are applicable to young children. Case examples are presented to highlight the application of CBPT. Although CBPT has a sound therapeutic base and utilizes proven techniques, more rigorous empirical scrutiny is needed.

  11. Play and learn team building.

    PubMed

    Haas, R C; Martin, S

    1997-05-01

    In order to have a team function correctly, power must be distributed equally, with no team member having more perceived power than any other. It is this leveling of the playing field that allows the team to develop and to stimulate the creative juices of its members. This article discusses techniques that can help an organization break down the power barriers and permit its employees to become a cohesive unit--a team.

  12. Tyler sands play entices operators

    SciTech Connect

    Stremel, K.

    Encouraging seismic data and recent discoveries are causing a renewed interest in an intensive exploration effort in central Montana's Tyler play. With new subsurface information obtained from recent seismic surveys, geologists are reviewing the elusive Tyler sands from a different perspective. Several operators are competing for lease positions through farmouts and joint ventures and increased drilling activity is expected to begin within the next year.

  13. Cardiopulmonary changes during clarinet playing.

    PubMed

    Hahnengress, Maria L; Böning, Dieter

    2010-12-01

    Since playing wind instrument impedes normal respiratory functions, its effect on expiratory and blood gases as well as on cardiac function was investigated. In 15 skilled clarinettists expiratory PO(2) and PCO(2) were measured in gas drawn from a modified clarinet barrel when playing a composition (Robert Schumann's "Phantasiestücke" Op. 73 for clarinet and piano) with increasing difficulty from movement 1 to movement 3. Blood gases were measured in arterialized ear lobe blood at the end of each movement and the electrocardiogram was recorded continuously. From the expiratory gas pressures one may conclude that the most advanced players adapt their ventilation to the requirements of the composition and sustain expiration during difficult parts of the composition until hypoxic alveolar PO(2) values are reached (minimum 77 mmHg). Less trained clarinettists tend to hyperventilation or shallow breathing. Oxygen saturation in arterialized blood showed a slight step-wise decrease from movement to movement [control 96.6 ± 0.5 (SD)%, end of concert 95.6 ± 1.0%]. SO(2) was significantly higher because of possibly more effective ventilation in instrumentalists with practise time exceeding 2 h daily. Mean heart rate increased to values like during moderate to heavy physical exercise depending on artistic fitness and the difficulty of the movement (maximal individual value 173 beats/min). Additionally, a large variation might be caused through intrathoracic pressure changes, changing exertion, respiratory influences and emotion. The electrocardiogram showed no pathological events. In general, clarinet playing at a professional level imposes strain on ventilation and circulation but usually not on a pathophysiological level.

  14. Supervising the uncanny: the play within the play.

    PubMed

    Leader, Carol

    2015-11-01

    The writer offers a combined experience in analysis and the performing arts to explore uncanny aspects of the unconscious subtext of the patient's inner drama; subtext which can remain hidden from view in supervision. Freud and Jung's understanding of uncanny experience is considered together with a painting from medieval alchemy and Matte Blanco's conceptions concerning the symmetrical nature of unconscious process. Theatre and the work of the theatre director and actor in approaching the multidimensional aspects of a play are then introduced. Finally clinical case material from group supervision demonstrates how the 'theatre of therapy' and the work of the supervisory couple and group promote the emergence of a more authentic conscious asymmetrical response to the patient's 'script' that can break the 'spell' of the transference/countertransference relationship. This in turn brings meaning to the underlying and implicit 'stage directions' that the patient has been unconsciously communicating. © 2015, The Society of Analytical Psychology.

  15. Play in a Hospital. Why...? How...?

    ERIC Educational Resources Information Center

    Play Schools Association, New York, NY.

    This pamphlet provides guidelines for hospital play and recreation programs for children. A rationale for providing play activities for hospitalized children is developed and an administrative perspective on play in the hospital setting is Presented. A hospital play program initiated in 1957 by the Play Schools Association at an initial equipment…

  16. Caring About Kids: The Importance of Play.

    ERIC Educational Resources Information Center

    National Inst. of Mental Health (DHHS), Rockville, MD. Div. of Scientific and Public Information.

    In several brief sections, this pamphlet defines play, discusses how play helps a child develop, and how play changes as a child grows older, indicates the role of toys and certain play activities in promoting sex stereotypes, and identifies the role of fantasy and imagination in children's play. A discussion of the role of parents in fostering…

  17. Intensity of tennis match play

    PubMed Central

    Fernandez, J; Mendez‐Villanueva, A; Pluim, B M

    2006-01-01

    This review focuses on the characteristics of tennis players during match play and provides a greater insight into the energy demands of tennis. A tennis match often lasts longer than an hour and in some cases more than five hours. During a match there is a combination of periods of maximal or near maximal work and longer periods of moderate and low intensity activity. Match intensity varies considerably depending on the players' level, style, and sex. It is also influenced by factors such as court surface and ball type. This has important implications for the training of tennis players, which should resemble match intensity and include interval training with appropriate work to rest ratios. PMID:16632566

  18. Hand kinematics of piano playing

    PubMed Central

    Flanders, Martha; Soechting, John F.

    2011-01-01

    Dexterous use of the hand represents a sophisticated sensorimotor function. In behaviors such as playing the piano, it can involve strong temporal and spatial constraints. The purpose of this study was to determine fundamental patterns of covariation of motion across joints and digits of the human hand. Joint motion was recorded while 5 expert pianists played 30 excerpts from musical pieces, which featured ∼50 different tone sequences and fingering. Principal component analysis and cluster analysis using an expectation-maximization algorithm revealed that joint velocities could be categorized into several patterns, which help to simplify the description of the movements of the multiple degrees of freedom of the hand. For the thumb keystroke, two distinct patterns of joint movement covariation emerged and they depended on the spatiotemporal patterns of the task. For example, the thumb-under maneuver was clearly separated into two clusters based on the direction of hand translation along the keyboard. While the pattern of the thumb joint velocities differed between these clusters, the motions at the metacarpo-phalangeal and proximal-phalangeal joints of the four fingers were more consistent. For a keystroke executed with one of the fingers, there were three distinct patterns of joint rotations, across which motion at the striking finger was fairly consistent, but motion of the other fingers was more variable. Furthermore, the amount of movement spillover of the striking finger to the adjacent fingers was small irrespective of the finger used for the keystroke. These findings describe an unparalleled amount of independent motion of the fingers. PMID:21880938

  19. A1C

    MedlinePlus

    A1C is a blood test for type 2 diabetes and prediabetes. It measures your average blood glucose, or blood sugar, level over the past 3 ... A1C alone or in combination with other diabetes tests to make a diagnosis. They also use the ...

  20. Playing it cool: Characterizing social play, bout termination, and candidate play signals of juvenile and infant Tibetan macaques (Macaca thibetana).

    PubMed

    Wright, Kaitlin R; Mayhew, Jessica A; Sheeran, Lori K; Funkhouser, Jake A; Wagner, Ronald S; Sun, Li-Xing; Li, Jin-Hua

    2018-07-18

    Play behaviors and signals during playful interactions with juvenile conspecifics are important for both the social and cognitive development of young animals. The social organization of a species can also influence juvenile social play. We examined the relationships among play behaviors, candidate play signals, and play bout termination in Tibetan macaques (Macaca thibetana) during juvenile and infant social play to characterize the species play style. As Tibetan macaques are despotic and live in groups with strict linear dominance hierarchies and infrequent reconciliation, we predicted that play would be at risk of misinterpretation by both the individuals engaged in the play bout and by those watching, possibly leading to injury of the players. Animals living in such societies might need to frequently and clearly signal playful intent to play partners and other group members to avoid aggressive outcomes. We gathered video data on 21 individually-identified juvenile and infant macaques (one month to five years of age) from the Valley of the Wild Monkeys, Mt. Huangshan, China. We used all-occurrence sampling to record play behaviors and candidate play signals based on an ethogram. We predicted that play groups would use multiple candidate play signals in a variety of contexts and in association with the number of audience members in proximity to the players and play bout length. In the 283 playful interactions we scored, juvenile and infant macaques used multiple body and facial candidate play signals. Our data showed that juvenile and infant Tibetan macaques use a versatile repertoire of play behaviors and signals to sustain play.

  1. Towards Play Pedagogy: Supporting Teacher Play Practices with a Teacher Guide about Socio-Dramatic and Imaginative Play

    ERIC Educational Resources Information Center

    Loizou, Eleni

    2017-01-01

    Drawing on the work of Vygotsky on scaffolding play and research on teacher intervention and mature forms of play, we have developed a teacher guide about play which frames children's role and scenario development and provides a teacher play intervention schema. The research question explored in this study is "How does a teacher guide,…

  2. A1C test

    MedlinePlus

    ... every 3 or 6 months is recommended. Normal Results The following are the results when A1C is ... meaning of your specific test results. What Abnormal Results Mean An abnormal result means that you have ...

  3. Regulated efflux of photoreceptor outer segment-derived cholesterol by human RPE cells.

    PubMed

    Storti, Federica; Raphael, Gabriele; Griesser, Vera; Klee, Katrin; Drawnel, Faye; Willburger, Carolin; Scholz, Rebecca; Langmann, Thomas; von Eckardstein, Arnold; Fingerle, Jürgen; Grimm, Christian; Maugeais, Cyrille

    2017-12-01

    Genetic studies have linked age-related macular degeneration (AMD) to genes involved in high-density lipoprotein (HDL) metabolism, including ATP-binding cassette transporter A1 (ABCA1). The retinal pigment epithelium (RPE) handles large amounts of lipids, among others cholesterol, partially derived from internalized photoreceptor outer segments (OS) and lipids physiologically accumulate in the aging eye. To analyze the potential function of ABCA1 in the eye, we measured cholesterol efflux, the first step of HDL generation, in RPE cells. We show the expression of selected genes related to HDL metabolism in mouse and human eyecups as well as in ARPE-19 and human primary RPE cells. Immunofluorescence staining revealed localization of ABCA1 on both sides of polarized RPE cells. This was functionally confirmed by directional efflux to apolipoprotein AI (ApoA-I) of 3 H-labeled cholesterol given to the cells via serum or via OS. ABCA1 expression and activity was modulated using a liver-X-receptor (LXR) agonist and an ABCA1 neutralizing antibody, demonstrating that the efflux was ABCA1-dependent. We concluded that the ABCA1-mediated lipid efflux pathway, and hence HDL biosynthesis, is functional in RPE cells towards both the basal (choroidal) and apical (subretinal) space. Impaired activity of the pathway might cause age-related perturbations of lipid homeostasis in the outer retina and thus may contribute to disease development and/or progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Children's Spontaneous Play in Writer's Workshop

    ERIC Educational Resources Information Center

    Lysaker, Judith T.; Wheat, Jennifer; Benson, Emily

    2010-01-01

    Research on the relationship between literacy and play has a rich history. Yet few studies have examined children's use of spontaneous play during literacy events as children are learning to read and write. This case study examines the use of play and the quality of playfulness in a kindergarten/first grade multiage classroom during Writer's…

  5. Play Therapy: Voice of a Silent Scream

    ERIC Educational Resources Information Center

    Rakesh, Annuradha; H, Uma; Srinath, Shoba

    2010-01-01

    Play Therapy is based upon the fact that play is the child's natural medium of self-expression. It is an opportunity that is given to the child to "play out" his/her feelings and problems just as, in certain types of adult therapy, an individual "talks out" his difficulties. Children use play to express feelings and thoughts.…

  6. Play Therapy: Practice, Issues, and Trends

    ERIC Educational Resources Information Center

    Homeyer, Linda E.; Morrison, Mary O.

    2008-01-01

    Play therapy is an effective means of responding to the mental health needs of young children and is widely accepted as a valuable and developmentally appropriate intervention. The authors discuss the importance of play in development, the therapeutic benefits of play, the rich history of play therapy, and recent research and current issues and…

  7. Conceptualizing the Play Policies in Preschool Curriculums

    ERIC Educational Resources Information Center

    Sener, Tulin

    2013-01-01

    This research attempted to describe the play policies in preschool institutions in Ankara, Turkey. The aim of this study is to determine the approaches of the preschools to the children's play. "Play Policy Questionnaire" administered to all directors and teachers of 20 public preschools and 20 private preschools. Play policy of each…

  8. Parent-Child Play: Descriptions and Implications.

    ERIC Educational Resources Information Center

    MacDonald, Kevin, Ed.

    This volume provides the latest research and theory in the area of children's play with their parents. It includes discussions of the basic processes involved in parent-child play, parent-child play in atypical populations of children, and parent-child play from a cross-cultural perspective. Fifteen chapters follow the introduction, "Parents and…

  9. Play and the Young Child: Musical Implications.

    ERIC Educational Resources Information Center

    Brophy, Tim

    After noting the near-universal presence of rhythmic response in play in all cultures, this paper looks first at the historical development of theories of play, and then examines current theories of play and their implications in the teaching of music to young children. The first section reviews 19th and early 20th century theories of play,…

  10. Reconceptualizing Play: Aesthetic Self-Definitions

    ERIC Educational Resources Information Center

    Guss, Faith

    2005-01-01

    This article aims to trouble the identity of children's dramatic play(ing). It contains two interweaving threads of discourse. In one thread lies a discussion of how children can trouble and extend their own identities through the aesthetic form-languages and conventions they employ and deploy in their dramatic playing/pretend playing. Whereas…

  11. How to Use (Not Abuse) Role Plays.

    ERIC Educational Resources Information Center

    Wright, Van O.

    1989-01-01

    Discusses the use of role plays in training for human communication skills, sales skills, and management skills. Rules for the application of role plays are given, steps in designing role plays are described, typical role play structures are explained, and materials for instructors and participants are discussed. (LRW)

  12. Play and Social Interaction in Middle Childhood

    ERIC Educational Resources Information Center

    Bergen, Doris; Fromberg, Doris Pronin

    2009-01-01

    This article discusses traditional and contemporary definitions of middle childhood play, the value of such play for children's development and learning, the implications of home, school, and societal practices that have resulted in changing the play scenario of middle childhood, and suggestions for assuring that play's value will be maintained…

  13. Frame Play in Early Childhood Education.

    ERIC Educational Resources Information Center

    Brostrom, Stig

    1998-01-01

    Describes frame play as a type of play in which children and teacher jointly plan the theme, roles, and actions and produce an extended imaginary play situation that can be repeated. Presents other types of play and discusses teachers' role in supporting theme development, resource organization, and environment transformation. Analyzes frame play…

  14. Active Gaming: The Future of Play?

    ERIC Educational Resources Information Center

    Witherspoon, Lisa; Manning, John P.

    2012-01-01

    The authors examine technology-driven games--especially active gaming--as an evolving form of children's play. They offer an overview of play and its developmental benefits, describe the literature on the emergence of technology-driven play, and reflect on the diminishment of physical play in contemporary culture. They suggest that active gaming,…

  15. Finger Forces in Clarinet Playing

    PubMed Central

    Hofmann, Alex; Goebl, Werner

    2016-01-01

    Clarinettists close and open multiple tone holes to alter the pitch of the tones. Their fingering technique must be fast, precise, and coordinated with the tongue articulation. In this empirical study, finger force profiles and tongue techniques of clarinet students (N = 17) and professional clarinettists (N = 6) were investigated under controlled performance conditions. First, in an expressive-performance task, eight selected excerpts from the first Weber Concerto were performed. These excerpts were chosen to fit in a 2 × 2 × 2 design (register: low–high; tempo: slow–fast, dynamics: soft–loud). There was an additional condition controlled by the experimenter, which determined the expression levels (low–high) of the performers. Second, a technical-exercise task, an isochronous 23-tone melody was designed that required different effectors to produce the sequence (finger-only, tongue-only, combined tongue-finger actions). The melody was performed in three tempo conditions (slow, medium, fast) in a synchronization-continuation paradigm. Participants played on a sensor-equipped Viennese clarinet, which tracked finger forces and reed oscillations simultaneously. From the data, average finger force (Fmean) and peak force (Fmax) were calculated. The overall finger forces were low (Fmean = 1.17 N, Fmax = 3.05 N) compared to those on other musical instruments (e.g., guitar). Participants applied the largest finger forces during the high expression level performance conditions (Fmean = 1.21 N). For the technical exercise task, timing and articulation information were extracted from the reed signal. Here, the timing precision of the fingers deteriorated the timing precision of the tongue for combined tongue-finger actions, especially for faster tempi. Although individual finger force profiles were overlapping, the group of professional players applied less finger force overall (Fmean = 0.54 N). Such sensor instruments provide useful insights into player

  16. Psychiatrists' Perceptions of Role-Playing Games.

    PubMed

    Lis, Eric; Chiniara, Carl; Biskin, Robert; Montoro, Richard

    2015-09-01

    The literature has seen a surge in research on the mental health impacts of technologies such as Facebook, video games, and massively-multiplayer online role-playing games such as World of Warcraft, but little is known regarding the mental health impact of non-video role-playing games, such as Dungeons & Dragons. The present study examines how psychiatrists' perceive role-playing games and whether they play them. Psychiatrists at a tertiary care centre in Canada completed a questionnaire assessing history of playing role-playing games and whether they associate them with psychopathology. Forty-eight psychiatrists responded. Twenty-three percent have played a role-playing game over their lifetimes. Twenty-two percent believed there was an association between psychopathology and role-playing games. A majority of psychiatrists who responded do not associate role-playing games with psychopathology. Implications for clinical practice and future research are discussed.

  17. Playing relativistic billiards beyond graphene

    NASA Astrophysics Data System (ADS)

    Sadurní, E.; Seligman, T. H.; Mortessagne, F.

    2010-05-01

    The possibility of using hexagonal structures in general, and graphene in particular, to emulate the Dirac equation is the topic under consideration here. We show that Dirac oscillators with or without rest mass can be emulated by distorting a tight-binding model on a hexagonal structure. In the quest to make a toy model for such relativistic equations, we first show that a hexagonal lattice of attractive potential wells would be a good candidate. Firstly, we consider the corresponding one-dimensional (1D) model giving rise to a 1D Dirac oscillator and then construct explicitly the deformations needed in the 2D case. Finally, we discuss how such a model can be implemented as an electromagnetic billiard using arrays of dielectric resonators between two conducting plates that ensure evanescent modes outside the resonators for transversal electric modes, and we describe a feasible experimental setup.

  18. Transforming Play: An Analysis of First-, Third-, and Fifth-Graders' Play.

    ERIC Educational Resources Information Center

    Bagley, Donna M.; Chaille, Christine

    1996-01-01

    Compared children's play with transformational objects (vehicles that change to robots) to play with representational objects (cars and figures). Found that those playing with transformers engaged in more parallel play and manipulative activity, while those with representational objects displayed more social play and more symbolic play. Found no…

  19. Play Therapy: Facilitative Use of Child's Play in Elementary School Counseling.

    ERIC Educational Resources Information Center

    Landreth, Garry L.

    1987-01-01

    Reviews five major developments in play therapy: psychoanalysis, release therapy, relationship therapy, nondirective therapy, and play therapy in school settings. Suggests ways school counselors can use play therapy. Describes play therapy facilities, location selection, and play materials. Lists objectives of play therapy and how teachers can aid…

  20. Two-Character Plays for Student Actors: A Collection of 15 One-Act Plays.

    ERIC Educational Resources Information Center

    Mauro, Robert

    Designed for workshop or classroom use, this collection of short plays for two actors is a source of material for auditions and readings and a valuable training tool for acting classes. The collection contains plays for men only, plays for women only, plays for men and women, plays with a wide variety of roles, plays of comedy and serious drama,…

  1. Exploring Play/Playfulness and Learning in the Adult and Higher Education Classroom

    ERIC Educational Resources Information Center

    Tanis, David J.

    2012-01-01

    Play and playfulness and their role in learning are researched extensively in early childhood education. However, as the child matures into an adult, play and playfulness are given less attention in the teaching and learning process. In adult education, there is very little research about play/playfulness and its significance for learning. Despite…

  2. The relative cost of children's physical play.

    PubMed

    Pellegrini; Horvat; Huberty

    1998-04-01

    There has been a long-standing debate regarding the functions of play during childhood. An important, but neglected, first step in this debate entails documenting the costs associated with play. In this study we analysed energetic costs (expressed in terms of caloric expenditure) associated with physical play in four field experiments of play in primary school children. Experiment 1 established the concurrent validity of an observational check list to estimate caloric expenditure of children's physical play. Experiment 2 compared caloric expenditure of the play (defined as all behaviour exhibited during play time) for two age groups of children during playtime outdoors and during indoor sedentary activity; caloric expenditure of outdoor activity was greater and was significantly correlated with ambient temperature. In experiment 3, children were observed during indoor play to control for the influence of ambient temperature. Outdoor physical play was more energetically costly than indoor physical play. In experiment 4, children's behaviour was observed outdoors and caloric expenditure for play, games and other activities was compared. Physical play was more costly than other forms of behaviour and games. Estimates of total energetic costs of play ranged from 6 to 15%. Results are discussed in terms of the relatively low caloric costs of play. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

  3. When Children Play. Proceedings of the International Conference on Play and Play Environments (Austin, TX, June 29-July 2, 1983).

    ERIC Educational Resources Information Center

    Frost, Joe L., Ed.; Sunderlin, Sylvia, Ed.

    This book is a compilation of 47 wide-ranging papers presented at the International Conference on Play and Play Environments. The introduction reviews both the historical recognition of the value of play by various philosophers and educators and the historical disregard for childhood that has prevailed through the centuries, particularly in…

  4. Play and Non-Play Tutoring in Pre-School Children: Is It Play or Tutoring Which Matters?

    ERIC Educational Resources Information Center

    Smith, P. K.; Syddall, Susan

    1978-01-01

    Previous studies on fantasy play tutoring are reviewed and research reported on the effect of the adult-child contact in this situation. Matched samples of preschoolers received either play or skills tutoring with equivalent tutor verbal contact. In these circumstances, differential advantages to the play-tutored children were few. (SJL)

  5. Forms of vitality play in infancy.

    PubMed

    Español, Silvia; Martínez, Mauricio; Bordoni, Mariana; Camarasa, Rosario; Carretero, Soledad

    2014-12-01

    In this paper we report a qualitative study based on the constant comparative method to initiate the systematic study of forms of vitality play. This is an unnoticed non-figurative play frame linked to early social play and temporal arts in which child and adult elaborate the dynamics of their own movements and sounds in a repetition-variation form. In the introduction we present the theoretical underpinnings and the sporadic observations we have done in previous studies. Then, by the iterative observations of the recorded material of a longitudinal case study on play during the third year of life, we generated the general category of forms of vitality play and four subcategories of display modes of forms of vitality play (improvised forms of vitality play, ritualized forms of vitality play, forms of vitality play combined with pretend play, and forms of vitality play combined with role playing) which are illustrated with descriptive narratives. We discuss the properties of the developed categories, the limits of the present study, and the need to continue systematizing the research on this playful activity.

  6. Orientation to Middle School: A Guidance Play.

    ERIC Educational Resources Information Center

    Childress, Natalie Wilson

    1982-01-01

    Presents a play that gives elementary school students a lighthearted but informative overview of middle school life. The play presents information about curriculum, lockers, physical education, materials, and classwork. Notes student reactions to the presentation. (RC)

  7. Play and Development From an Ethological Perspective

    ERIC Educational Resources Information Center

    Vandenberg, Brian

    1978-01-01

    A review of play in nonhuman animals indicates that play increases with phylogenetic status, is important for mature social development in more advanced species, reflects intentional activity, and is essential for the development of tool-using strategies. (Author)

  8. Imaginary Play Companions: Characteristics and Functions.

    ERIC Educational Resources Information Center

    Kalyan-Masih, V.

    1986-01-01

    Investigates some of the following characteristics associated with young children playing with imaginary play companions (IPCs): intelligence, parental and socioeconomic and educational background, family size, and birth order. Compares these children to those without IPCs. (HOD)

  9. The Pursuit of Play within the Curriculum

    ERIC Educational Resources Information Center

    Ortlieb, Evan T.

    2010-01-01

    Play has been traditionally recognized as an activity within early childhood education, but in actuality, it has substantial importance to learners at all levels. Since the idea of play is abstract and has no pre-determined outcomes, some teachers feel uneasy about allowing students to play with concepts and materials, especially with the advent…

  10. Pretend Play of Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Pfeifer, Luzia Iara; Pacciulio, Amanda Mota; dos Santos, Camila Abrao; dos Santos, Jair Licio; Stagnitti, Karen Ellen

    2011-01-01

    Background and Purpose: Evaluate self-initiated pretend play of children with cerebral palsy. Method: Twenty preschool children participated in the study. Pretend play ability was measured by using the child-initiated pretend play assessment culturally adapted to Brazil. Results: There were significant negative correlations between the children's…

  11. The Play Professional in the United Kingdom

    ERIC Educational Resources Information Center

    Millbank, Anna-Marie

    2005-01-01

    Playwork is a respected field of study composed of experts who have studied the theories and practices of play for the purposes of training other individuals in best practices to better facilitate children's play. The profession is founded on the belief that play is an essential childhood element and the right of every child. In this article, the…

  12. Play Culture in a Changing World

    ERIC Educational Resources Information Center

    Kalliala, Marjatta

    2005-01-01

    The cultural context in which children grow up has a powerful influence on the way they play. At a time of rapid change in post-industrial societies, childhood play is changing to reflect children's experiences. Adults need to understand that children have their own play culture, which might be different from that of the adults' own childhoods.…

  13. Play Therapy for Severe Psychological Trauma. [Videotape

    ERIC Educational Resources Information Center

    Gil, Eliana

    In this 36-minute educational video, a play and family therapist elucidates the nature of trauma, how to recognize it clinically, and how to manage its powerful effects upon children's development with the use of specific play materials and techniques. With a reenacted clinical interview, footage from an actual play therapy session, and a detailed…

  14. Game Playing: Negotiating Rules and Identities

    ERIC Educational Resources Information Center

    Winther-Lindqvist, Ditte

    2009-01-01

    Beginning with Lev Vygotsky's long-established assertion that the play of children always involves both imaginary play and rules of behavior, this article argues for a theoretical framework that connects such play with the construction of social identities in kindergarten peer groups. It begins with a discussion of Ivy Schousboe's model of the…

  15. Superheroes: An Opportunity for Prosocial Play

    ERIC Educational Resources Information Center

    De-Souza, Desalyn; Radell, Jacqueline

    2011-01-01

    Superhero play has long been thought of as violent, aggressive, and disruptive. Some argue that aggressive play should not be allowed because it exposes children to inappropriate concepts and attitudes and sends the message that the use of aggression can achieve a desired goal. However, educators know that pretend play is an avenue for healthy…

  16. Playing Fair: An Essential Element in Contracting

    ERIC Educational Resources Information Center

    Peeler, Tom

    2012-01-01

    Playing fair has a value with which people are all familiar. From the sandboxes of childhood and the competitive sports of youth to the business transactions of adulthood, people have been told how important it is to play fair. Playing fair in contracting is not only essential, it's the legal and ethical thing to do. In this article, the author…

  17. School Plays: Raising the Curtain Again.

    ERIC Educational Resources Information Center

    Zirkel, Perry A.; Gluckman, Ivan B.

    1986-01-01

    Federal courts upheld the rights of two school boards to cancel planned student plays. One play was intended as part of a secondary school's curriculum and the other was an extracurricular activity for third graders. Both plays contained controversial material. (PGD)

  18. Children in Play, Story, and School.

    ERIC Educational Resources Information Center

    Goncu, Artin, Ed.; Klein, Elisa L.

    In honor of the contributions of Greta G. Fein to the fields of developmental psychology and early childhood education, a community of scholars prepared this volume to explore how social play arises, social play's developmental and educational significance, and the ways in which social play can be promoted in early childhood settings. In addition,…

  19. Play Therapy: Role in Reading Improvement.

    ERIC Educational Resources Information Center

    Carmichael, Karla

    1991-01-01

    Reviews the literature concerning the role of play therapy (particularly sandplay and nondirected play therapy) in the improvement of reading. Suggests that the role of play therapy is to support the child, encourage the child, and build self-esteem thus creating the optimal learning environment for reading improvement. (RS)

  20. Playing Computer Games Versus Better Learning.

    ERIC Educational Resources Information Center

    Din, Feng S.; Caleo, Josephine

    This study investigated whether kindergarten students who played Sony Play Station (Lightspan) computer games learned better than peers who did not play such games. Participants were 47 African-American kindergartners from two classes of an urban school in the Northeast. A pretest and posttest with control group design was used in the study. The…

  1. Dimensions of Play: Reflections and Directions.

    ERIC Educational Resources Information Center

    Jambor, Tom

    For many children, societal changes have restricted the opportunities for and the right to play. Adults deal with these violations of children's right to play by trying to correct problems, preventing future problems, or by denying that problems can or could exist. In order to meet the challenge of preserving children's play rights, we need to be…

  2. Parental Distancing Strategies and Children's Fantasy Play.

    ERIC Educational Resources Information Center

    Perlmutter, Jane C.; Pellegrini, Anthony D.

    Effects of age and gender of preschool children and sex of parent on parental teaching strategies in a fantasy play situation were examined. Relations of parental strategies to children's fantasy play were assessed. Play sessions were held in a small playroom equipped with materials which facilitated dramatic production. The linguistic strategies…

  3. Curious Play: Children's Exploration of Nature

    ERIC Educational Resources Information Center

    Gurholt, Kirsti Pedersen; Sanderud, Jostein Rønning

    2016-01-01

    This article explores the concept of "curious play" as a theoretical framework to understand and communicate children's experiences of free play in nature. The concept emerged interactively from three sources of inspiration: an ethnographically inspired study of children playing in nature; as a critique of the concept of "risky…

  4. Play as Education in the School Curriculum.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Friedrich Froebel, an early advocate of the use of play in kindergarten teaching, argued that the ultimate goal of education was developing the creative person. According to Froebel, teachers could promote creativity through play by using gifts, occupations, and mother play songs. By contrast, Johann Herbart called for a subject centered…

  5. Contrived Role Playing and Attitude Change.

    ERIC Educational Resources Information Center

    Schwartz, Henrietta S.

    This study asked whether structured role playing and attendant experiences in extracurricular play productions were predictably associated with attitude changes in high school students. The major hypothesis was that students who participated in plays would become more open-minded and flexible and would show greater change toward more positive…

  6. Gender Differences in Students' Mathematics Game Playing

    ERIC Educational Resources Information Center

    Lowrie, Tom; Jorgensen, Robyn

    2011-01-01

    The investigation monitored the digital game-playing behaviours of 428 primary-aged students (aged 10-12 years). Chi-square analysis revealed that boys tend to spend more time playing digital games than girls while boys and girls play quite different game genres. Subsequent analysis revealed statistically significant gender differences in terms of…

  7. Short-Term Play Therapy for Children.

    ERIC Educational Resources Information Center

    Kaduson, Heidi Gerard, Ed.; Schaefer, Charles E., Ed.

    Play therapy offers a powerful means of helping children resolve a wide range of psychological difficulties, and many play approaches are ideally suited to short-term work. This book brings together leading play therapists to share their expertise on facilitating children's healing in a shorter time frame. The book provides knowledge and skills…

  8. Mimesis: Where Play and Narrative Meet

    ERIC Educational Resources Information Center

    Feldman, Carol Fleisher

    2005-01-01

    There is a great deal of narrative in play and also of play in narrative, especially in the narrative and play of young children. Part of the reason for this may be that they share an important pattern or structure in the way they work as mental instruments, "mimesis." Mimesis is a mode of representation in which the relation between the symbol…

  9. Young Children's Playfully Complex Communication: Distributed Imagination

    ERIC Educational Resources Information Center

    Alcock, Sophie

    2010-01-01

    This paper draws on research exploring young children's playful and humorous communication. It explores how playful activity mediates and connects children in complex activity systems where imagination, cognition, and consciousness become distributed across individuals. Children's playfulness is mediated and distributed via artefacts (tools, signs…

  10. Play Therapy in Political Theory: Machiavelli's Mandragola.

    ERIC Educational Resources Information Center

    Lukes, Timothy J.

    1981-01-01

    Suggests that having political science college students perform in class Machiavelli's play "Mandragola" is an excellent way to expand student's appreciation of Machiavelli. Article provides a synopsis of the play, discusses Machiavelli's intent, examines the meaning of the play, and presents classroom logistics. (RM)

  11. Empirically Based Play Interventions for Children

    ERIC Educational Resources Information Center

    Reddy, Linda A., Ed.; Files-Hall, Tara M., Ed.; Schaefer, Charles E., Ed.

    2005-01-01

    "Empirically Based Play Interventions for Children" is a compilation of innovative, well-designed play interventions, presented for the first time in one text. Play therapy is the oldest and most popular form of child therapy in clinical practice and is widely considered by practitioners to be uniquely responsive to children's developmental needs.…

  12. Effects of Rosuvastatin on the expression of the genes involved in cholesterol metabolism in rats: adaptive responses by extrahepatic tissues.

    PubMed

    Ahmadi, Yasin; Haghjoo, Amir Ghorbani; Dastmalchi, Siavoush; Nemati, Mahboob; Bargahi, Nasrin

    2018-06-30

    Statins mostly target the liver; therefore, increase in the synthesis of cholesterol by extra-hepatic tissues and then transferring this cholesterol to the liver can be regarded as adaptive responses by these tissues. In addition to cholesterol, these adaptive responses can increase isoprenoid units as the byproducts of the cholesterol biosynthesis pathway; isoprenoids play a key role in regulating cell signaling pathways and cancer development. Thus, there is a primary need for in vivo investigation of the effects of statins on the cholesterol metabolism in the extra-hepatic tissues. Eighteen male Sprague-Dawley rats were randomly divided into control (n = 9) and treatment (n = 9) groups. The treatment group was orally given 10 mg/kg/day of Rosuvastatin for 6 weeks. Then, serum lipid profile, expression levels of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), ABCA1, ABCG1 and ApoA1, and activity of HMGCR were measured in the liver, intestine and adipose tissues. Rosuvastatin significantly reduced total cholesterol and LDL-C. The expression levels of ABCA1, ABCG1, and ApoA1 in the liver and HMGCR in both liver and intestine were significantly increased in the Rosuvastatin treated-group. However, in the intestine, there were no significant differences in the expression levels of ABCA1 and ABCG1 between the study groups. Rosuvastatin had no effect on the adipose tissue. The HMGCR activity was significantly increased in the liver and intestine of the Rosuvastatin-treated group. In spite of the adipose tissue, the intestine efficiently responses to the reduced levels of cholesterol and increases its cholesterogenesis capacity. However, adipose tissue seems to play a small role in correcting cholesterol deficiency during the course of statin therapy. Copyright © 2018. Published by Elsevier B.V.

  13. Play and Mate Preference: Testing the Signal Theory of Adult Playfulness

    ERIC Educational Resources Information Center

    Chick, Garry; Yarnal, Careen; Purrington, Andrew

    2012-01-01

    The overwhelming majority of play research concerns juveniles. However, a full understanding of the phenomenon requires knowledge of play and playfulness across the life spans of those animals, including humans, who play in adulthood. The authors investigate a theory of play based on Darwin's concept of sexual selection that may account for the…

  14. Why Do the Children (Pretend) Play?

    PubMed

    Lillard, Angeline S

    2017-11-01

    Pretend play appears to be an evolved behavior because it is universal and appears on a set schedule. However, no specific functions have been determined for pretend play and empirical tests for its functions in humans are elusive. Yet animal play fighting can serve as an analog, as both activities involve as-if, metacommunicative signaling and symbolism. In the rat and some other animals, adaptive functions of play fighting include assisting social behavior and emotion regulation. Research is presented suggesting that pretend play might serve similar functions for humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters

    PubMed Central

    Rhodes, David A.; Chen, Hung-Chang; Williamson, James C.; Hill, Alfred; Yuan, Jack; Smith, Sam; Rhodes, Harriet; Trowsdale, John; Lehner, Paul J.; Herrmann, Thomas; Eberl, Matthias

    2018-01-01

    Activation of human Vγ9/Vδ2 T cells by “phosphoantigens” (pAg), the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach these problems, we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 T cell receptor (TCR) transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules, such as periplakin or RhoB, did not account for the functional variation between HeLa-L and HeLa-M cells. Instead, the data implicate a checkpoint controlling BTN3A1 stability and protein trafficking, acting at an early time point in its maturation. In addition, plasma membrane profiling was used to identify proteins upregulated in HMB-PP-treated HeLa-M. ABCG2, a member of the ATP-binding cassette (ABC) transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated with

  16. Hydrocarbon plays evaluation of eastern China

    SciTech Connect

    Wu Shou Cheng

    1991-03-01

    In eastern China there are 78 depressed basins, most of which are tilt-block basins. Each of them engenders petroleum generation except the Cretaceous sag basin of Song-Liao. These depressed basins set up in the order of older to younger depending on the change of the mantle convection. Consequently, the order of sedimentation and source-reservoir are changed and the exploration targets are also changed. Tan-Lu fault system is of great significance in NNW (early) and NEE (later) accompanying faults for exploration play. The hydrocarbon accumulation rules of these plays are: (1) As a result of the Tertiary tilt-block basins, compaction-flow basinsmore » contain similar hydrodynamic, thermodynamic, and buried pressure fields. The direction of fluid flow is from generation center of the basin to the margins. So the hydrocarbon plays are distributed nearby the generation center and circum-center belt. (2) The richness of hydrocarbon plays is controlled by the form and distribution of source rock due to structural change of the tilt-block. The richest is the center uplift play and then the low-raised play, steep slope play, gentle-slope play, and, poorest, the low-lying play. (3) A variety of the composite hydrocarbon play models are formed by the different structure models, sedimentary model, and hydrocarbon model. Most of the recovery reserves are set in one or two plays even though there are many hydrocarbon plays in a tilt-block basin. (4) There are 3 types and 25 subtypes of petroleum pools formed by the different characters of plays. Therefore, there are numerous technologies, methodologies, and strategies of petroleum exploration.« less

  17. Predictive factors of excessive online poker playing.

    PubMed

    Hopley, Anthony A B; Nicki, Richard M

    2010-08-01

    Despite the widespread rise of online poker playing, there is a paucity of research examining potential predictors for excessive poker playing. The aim of this study was to build on recent research examining motives for Texas Hold'em play in students by determining whether predictors of other kinds of excessive gambling apply to Texas Hold'em. Impulsivity, negative mood states, dissociation, and boredom proneness have been linked to general problem gambling and may play a role in online poker. Participants of this study were self-selected online poker players (N = 179) who completed an online survey. Results revealed that participants played an average of 20 hours of online poker a week and approximately 9% of the sample was classified as a problem gambler according to the Canadian Problem Gambling Index. Problem gambling, in this sample, was uniquely predicted by time played, dissociation, boredom proneness, impulsivity, and negative affective states, namely depression, anxiety, and stress.

  18. The Living Experience of Feeling Playful.

    PubMed

    Baumann, Steven L; Tanzi, Donna; Lewis, Tricia A

    2017-07-01

    The purpose of this study was to investigate the living experience of feeling playful. Parse's research method was used to answer the question: What is the structure of the living experience of feeling playful? The participants were 10 persons, ages 9 to 83, living in the United States. The central finding of the study is the living experience of feeling playful is entertaining amusements amid burdens with uplifting endeavors strengthening affiliations with blissful moments of unfettered unfolding. The living experience of feeling playful is discussed in relation to the principles of the humanbecoming paradigm and in relation to how it can inform further research.

  19. How children create their space for play?

    NASA Astrophysics Data System (ADS)

    Bobby Saragih, John Freddy; Tedja, Michael

    2017-12-01

    The phenomenon of children’s play in the urban area in Indonesia has experienced a shift; they are often seen playing in the street, sidewalk and drainage. This shift raises the question: what is interesting about the space, so that they use it as a space for play? There are metaphysical based of space that can be grasped by children senses when they utilize that particular space. This qualitative research based involving children aged between 6 and 12 years found that spatial manifestation; such as freedom, excitement and surprise are the main motivations when they use the space as their playing area.

  20. Parents' Play Beliefs and Engagement in Young Children's Play at Home

    ERIC Educational Resources Information Center

    Lin, Xunyi; Li, Hui

    2018-01-01

    Play is a fundamental concept in early childhood development and education. As partners in the child's learning, parents play a crucial role in how play is defined, valued, and practised. The present study explores the constructs of parents' beliefs about and engagement in young children's play in two coastal cities in China. A sample of 483…

  1. Play and Adversity: How the Playful Mammalian Brain Withstands Threats and Anxieties

    ERIC Educational Resources Information Center

    Siviy, Stephen M.

    2010-01-01

    Most mammals play, but they do so in a dangerous world. The dynamic relationship between the stresses created by their world and the activity of play helps to explain the evolution of play in mammals, as the author demonstrates in evidence garnered from experiments that introduce elements of fear to rats at play. The author describes the resulting…

  2. Virtual Playgrounds? Assessing the Playfulness of Massively Multiplayer Online Role-Playing Games

    ERIC Educational Resources Information Center

    Graham, Kerrie Lewis

    2010-01-01

    Millions of children and adults devote much of their leisure time to playing massively multiplayer online role-playing games (MMORPGs). Most observers commonly categorize computer games as a play activity, but this article asks whether MMORPGs contain activities that might not be play. The author examines the phenomenon of online gaming and…

  3. Do Props Matter in the Dramatic Play Center? The Effects of Prop Realism on Children's Play.

    ERIC Educational Resources Information Center

    Hogan, Claudia; Howe, Nina

    2001-01-01

    This study investigated the effects of prop realism on the play of 24 preschoolers. Observations of play sessions revealed that highly realistic props and low-realism props elicited equal amounts of group dramatic play. However, low- realism props generated greater diversity of play themes, more fantasy role enactments, and more nonintended use of…

  4. Playing with Mathematics: Play in Early Childhood as a Context for Mathematical Learning

    ERIC Educational Resources Information Center

    Mathematics Education Research Group of Australasia, 2010

    2010-01-01

    Play is an essential part of young children's lives. This symposium highlights the integral role of play in young children's mathematics learning and examines the teacher's role in facilitating and extending this. Papers examine key tenets of play, contributing to theoretical understandings and presenting data on teacher's perceptions of play and…

  5. Chinese and German Teachers' Conceptions of Play and Learning and Children's Play Behaviour

    ERIC Educational Resources Information Center

    Wu, Shu-Chen; Rao, Nirmala

    2011-01-01

    Commonalities and distinctions in Hong Kong-Chinese and German kindergarten teachers' conceptions of play and learning were examined. Six video clips of play episodes reflecting common play behavior and themes were selected from observations made during free play in two kindergartens in Hong Kong and two in Germany. Ten Chinese and seven German…

  6. Play at the Art Table: A Study of Children's Play Behaviors while Drawing.

    ERIC Educational Resources Information Center

    Escobedo, Theresa H.

    This descriptive study examined children's drawings and related language episodes to differentiate drawings exhibiting play from those exhibiting exploratory behavior. Drawings categorized as play were further analyzed to identify constructive and imaginary play. The play theory used as the basis of the study proposes that exploration and…

  7. Picture me playing: increasing pretend play dialogue of children with autism spectrum disorders.

    PubMed

    Murdock, Linda C; Hobbs, Jan Q

    2011-07-01

    This study examined the effectiveness of the Picture Me Playing intervention for increasing the play dialogue of preschool children with ASD during pretend play opportunities with typical peers. Picture Me Playing is a pictorially enhanced, script based intervention targeting character role play through a narrative vignette. A single-treatment counterbalanced design was utilized to contrast the performance of intervention and comparison groups, followed by within-subject analysis. Results indicated significant increases in play dialogue represented by both scripted and novel utterances. Results generalized to an unscripted play opportunity with novel toys.

  8. Mammalian play: training for the unexpected.

    PubMed

    Spinka, M; Newberry, R C; Bekoff, M

    2001-06-01

    In this review, we present a new conceptual framework for the study of play behavior, a hitherto puzzling array of seemingly purposeless and unrelated behavioral elements that are recognizable as play throughout the mammalian lineage. Our major new functional hypothesis is that play enables animals to develop flexible kinematic and emotional responses to unexpected events in which they experience a sudden loss of control. Specifically, we propose that play functions to increase the versatility of movements used to recover from sudden shocks such as loss of balance and falling over, and to enhance the ability of animals to cope emotionally with unexpected stressful situations. To obtain this "training for the unexpected," we suggest that animals actively seek and create unexpected situations in play through self-handicapping; that is, deliberately relaxing control over their movements or actively putting themselves into disadvantageous positions and situations. Thus, play is comprised of sequences in which the players switch rapidly between well-controlled movements similar to those used in "serious" behavior and self-handicapping movements that result in temporary loss of control. We propose that this playful switching between in-control and out-of-control elements is cognitively demanding, setting phylogenetic and ontogenetic constraints on play, and is underlain by neuroendocrinological responses that produce a complex emotional state known as "having fun." Furthermore, we propose that play is often prompted by relatively novel or unpredictable stimuli, and is thus related to, although distinct from, exploration. We present 24 predictions that arise from our new theoretical framework, examining the extent to which they are supported by the existing empirical evidence and contrasting them with the predictions of four major alternative hypotheses about play. We argue that our "training for the unexpected" hypothesis can account for some previously puzzling

  9. Role-Playing Methods in the Classroom.

    ERIC Educational Resources Information Center

    Chesler, Mark; Fox, Robert

    This book, one of three Teacher Resource Booklets on Classroom Social Relations and Learning developed at the Center for Research on Utilization of Scientific Knowledge at the University of Michigan, discusses the theoretical background of role playing and gives a step-by-step discussion of how to use role playing in the classroom. There are…

  10. Habit tic deformity secondary to guitar playing.

    PubMed

    Wu, Jashin J

    2009-03-15

    A 29-year-old man exhibited linear ridges of the right thumbnail that had been present for ten years. After he stopped playing the guitar for three months, the proximal portion of the abnormality cleared. Nail changes similar to the habit tic deformity may be produced by guitar playing.

  11. Playing with Power: An Outdoor Classroom Exploration

    ERIC Educational Resources Information Center

    Haywood-Bird, Eden

    2017-01-01

    In this ethnographic research, discovery of how preschool-aged children use play to wield their individual power in the outdoors is documented in a single classroom. Embedded as a participant-researcher and working from constructivist and critical theory orientations, the researcher seeks to understand how children use their play to construct the…

  12. Playing by Ear: Foundation or Frill?

    ERIC Educational Resources Information Center

    Woody, Robert H.

    2012-01-01

    Many people divide musicians into two types: those who can read music and those who play by ear. Formal music education tends to place great emphasis on producing musically literate performers but devotes much less attention to teaching students to make music without notation. Some would suggest that playing by ear is a specialized skill that is…

  13. Executive Functions Development and Playing Games

    ERIC Educational Resources Information Center

    Petty, Ana Lucia; de Souza, Maria Thereza C. Coelho

    2012-01-01

    The aim of this paper is to discuss executive functions and playing games, considering Piaget's work (1967) and the neuropsychological framework (Barkley, 1997, 2000; Cypel, 2007). Two questions guide the discussion: What are the intersections between playing games and the development of executive functions? Can we stimulate children with learning…

  14. Evaluative Intervention Research in Child's Play.

    ERIC Educational Resources Information Center

    Yawkey, Thomas Daniels; Fox, Frank D.

    Evaluative intervention studies which have examined the potential of imaginative play to foster young children's cognitive and social development provide the focus of this literature review. Four criteria were used to select the studies: (1) the study's focus was on the use of imaginative play to foster cognitive growth; (2) the studies were…

  15. Preschool Children's Outdoor Play Area Preferences

    ERIC Educational Resources Information Center

    Holmes, Robyn M.; Procaccino, Jill K.

    2009-01-01

    This study explores preschool children's outdoor play preferences. The sample was 40 (20 male, 20 female) primarily European-American three and four year olds. Data were collected via naturalistic observation and analyzed using repeated measures ANOVAs and MANOVAs. The independent variable was sex of child; dependent variable was play space…

  16. Restaurant Role-Play in Psychology

    ERIC Educational Resources Information Center

    Borya, Anthony

    2013-01-01

    Research methods is perceived as a technical and difficult topic by some students. Using role-play to teach it can make it more accessible, meaningful and engaging. Role-playing the familiar roles of customer and waiting staff at a restaurant and discussing the variables that may affect the size of tips can help students to learn some of the key…

  17. Outdoor Play and Learning: Policy and Practice

    ERIC Educational Resources Information Center

    Burriss, Kathleen; Burriss, Larry

    2011-01-01

    This study describes national school district policy and practice regarding elementary school children's outdoor learning and play. District representatives from 173 randomly selected school districts completed questionnaires describing policy and practice related to recess, outdoor play, outdoor curricular studies, playground materials, ADA…

  18. Play Therapy with Emotionally Damaged Adolescents.

    ERIC Educational Resources Information Center

    Wilson, Kate; Ryan, Virginia

    2002-01-01

    This article argues that non-directive play therapy offers an approach that is well suited to addressing adolescent concerns. The argument is illustrated by two accounts of therapy that show how a more traditional non-directive counseling approach was combined with play therapy by the adolescents themselves, allowing exploration of emotional…

  19. Play Therapy Practices among Elementary School Counselors

    ERIC Educational Resources Information Center

    Ray, Dee C.; Armstrong, Stephen A.; Warren, E. Scott; Balkin, Richard S.

    2005-01-01

    When elementary school counselors have a solid developmental understanding of children, play therapy might be one counseling intervention that they use with their students. Landreth (2002) has promoted the use of play therapy in schools by explaining that its objective is to help children get ready to profit from what teachers have to offer. Play…

  20. Work and Play: Are They Really Opposites?

    ERIC Educational Resources Information Center

    Rosberg, Merilee A.

    Noting that current discussion of the best way to accomplish the goal of "No Child Left Behind" has focused on the value of play versus a structured program for early education, this paper uses science education as a model for examining how children learn and the problems arising when artificial lines are drawn between work and play. The paper…

  1. The Excellence of Play. Second Edition

    ERIC Educational Resources Information Center

    Moyles, Janet, Ed.

    2005-01-01

    This second edition of "The Excellence of Play" encapsulates all of the many changes that have taken place in early childhood in the last decade. It examines the vital importance of play as a tool for learning and teaching for children and practitioners, supporting all those who work in early childhood education and care in developing and…

  2. Sack Racers at Day of Play

    NASA Image and Video Library

    2005-10-05

    From left, Mallory Doody, 5, Natalie Cambre, 3, Madison Doody, 7, and Anna Cambre, 6, get ready to compete in a sack race. The children were participants in Nickelodeon's Worldwide Day of Play celebration at Stennis Space Center (SSC) on Oct. 1. The Worldwide Day of Play is sponsored annually by Nickelodeon television network to encourage children to be physically active.

  3. Gender-Typed Play and Amniotic Testosterone

    ERIC Educational Resources Information Center

    Knickmeyer, Rebecca Christine; Wheelwright, Sally; Taylor, Kevin; Raggatt, Peter; Hackett, Gerald; Baron-Cohen, Simon

    2005-01-01

    Sex differences in play are apparent in a number of mammalian species, including humans. Prenatal testosterone may contribute to these differences. The authors report the first attempt to correlate gender-typed play in a normative sample of humans with measurements of amniotic testosterone (aT). Testosterone was measured in the amniotic fluid of…

  4. Play Therapy Behaviors of Sexually Abused Children.

    ERIC Educational Resources Information Center

    Homeyer, Linda E.; Landreth, Garry L.

    The purpose of this study was to identify play therapy behaviors of sexually abused children. Surveys were sent to members of the Association for Play Therapy, of which 249 respondents, who worked with 16 or more sexually abused children, were used. Results indicate that there are identifiable and highly interrelated PTBs of sexually abused…

  5. An Early Historical Play: The "Seinte Resurreccion"

    ERIC Educational Resources Information Center

    Perry, Anne Amari

    1978-01-01

    Analyzes the realistic characterization and plot construction of an anonymously written medieval French play. The play, which relates the story of Christ's resurrection, achieves historical realism by replacing music and chant with dialogue, using a logical plot, and limiting historical anachronism. (AV)

  6. Dimensions of Childhood Play and Toys

    ERIC Educational Resources Information Center

    Sandberg, Anette; Vuorinen, Tuula

    2008-01-01

    The purpose of this article is to describe and analyse play through a contemporary historical perspective, based upon pre-school teachers', students majoring in education, and teacher education students' descriptions of memories from their childhood regarding play and toys. The overall method is retrospective. The data consists of 111 interviews…

  7. Preschool Teacher's Conceptions of Computers and Play

    ERIC Educational Resources Information Center

    Sandberg, Anette

    2002-01-01

    There are many dimensions of play and play's significance for children's development and learning is often emphasized, but how do preschool teachers see children's use of computers in preschool? A qualitative study was done with 13 Swedish preschool teachers that had experience working with computers in preschool. The overall aim of this study was…

  8. Using Role Play to Debate Animal Testing

    ERIC Educational Resources Information Center

    Agell, Laia; Soria, Vanessa; Carrió, Mar

    2015-01-01

    The use of animals in biomedical research is a socio-scientific issue in which decision-making is complicated. In this article, we describe an experience involving a role play activity performed during school visits to the Barcelona Biomedical Research Park (PRBB) to debate animal testing. Role playing games require students to defend different…

  9. Helping Young Children See Math in Play

    ERIC Educational Resources Information Center

    Parks, Amy Noelle; Blom, Diana Chang

    2013-01-01

    The purpose of this article is to provide strategies for recognizing meaningful mathematics in common play contexts in early childhood classrooms and to offer suggestions for how teachers might intervene in these moments to help children attend to the mathematical ideas embedded in their play. In particular, the author's focus on the concepts of…

  10. Play Therapy: Basics and Beyond. Second Edition

    ERIC Educational Resources Information Center

    Kottman, Terry

    2011-01-01

    Written for use in play therapy and child counseling courses, this extraordinarily practical text provides a detailed examination of basic and advanced play therapy concepts and skills and guidance on when and how to use them. Kottman's multitheoretical approach and wealth of explicit techniques are also helpful for clinicians who want to gain…

  11. Play and the Basic Needs of Children

    ERIC Educational Resources Information Center

    Bagley, Martha

    1975-01-01

    This article discusses play as necessary for children if they are to develop satisfactorily from a social, moral, physical, or intellectual point of view. Children must be provided suitable opportunities for play, graded for age, adjusted to sex and other personal differences, and related to prevailing activities, popular interests, community…

  12. Indoor and Outdoor Play in Preschool Programs

    ERIC Educational Resources Information Center

    Kroeker, Julia

    2017-01-01

    The purpose of this study was to explain children's indoor and outdoor play in preschool programs in terms of teacher interaction, peer interaction and task orientation. Children's indoor and outdoor play behaviors were compared using the Individualized Classroom Assessment Scoring System (inCLASS). Findings included significant differences on…

  13. Playing with Technology: Is It All Bad?

    ERIC Educational Resources Information Center

    Slutsky, Ruslan; Slutsky, Mindy; DeShelter, Lori M.

    2014-01-01

    Technology now plays a very large role in the way children of all ages play. Children want access to technology, so parents and teachers must determine the best ways to present it to them. Computers are a popular form of technology for children as young as age three. With that in mind, computer games should be problem-solving oriented and…

  14. The Thing's the Play: Doing "Hamlet."

    ERIC Educational Resources Information Center

    Sowder, Wilbur H., Jr.

    1993-01-01

    Argues for the use of film in the teaching of William Shakespeare's "Hamlet" because the play was meant to be seen and heard and not just read. Outlines a method of teaching the play by which students select a scene and perform it. Gives an example of a successful student performance. (HB)

  15. Pretend Play: Antecedent of Adult Creativity

    ERIC Educational Resources Information Center

    Russ, Sandra W.

    2016-01-01

    This article reviews the theoretical and empirical literature in the area of pretend play as a predictor of adult creativity. There is strong evidence that processes expressed in pretend play are associated with measures of creativity, especially with divergent thinking. There is some evidence from longitudinal studies that this association is…

  16. Metamorphosis: Play, Spirituality and the Animal

    ERIC Educational Resources Information Center

    Bone, Jane

    2010-01-01

    Animal- and bird-becoming is an aspect of play as metamorphosis connected to spirituality in early childhood settings. The reconceptualisation of play presented here is supported by research that explored the spiritual experiences of young children in different early childhood contexts. Qualitative case study research carried out in Aotearoa New…

  17. Children's Gendered Drawings of Play Behaviours

    ERIC Educational Resources Information Center

    Akseer, Tabasum; Lao, Mary Grace; Bosacki, Sandra

    2012-01-01

    According to child psychologists, vital links exist between children's drawings and their emotional, social, and cognitive development. Previous research has explored the important relations between drawings and play in educational settings. Given the vast research that explores the ambiguous topic of children's play, according to Richer (1990),…

  18. Nonsocial Play in Preschoolers: Necessarily Evil?

    ERIC Educational Resources Information Center

    Rubin, Kenneth H.

    1982-01-01

    Examines the social, cognitive, and social-cognitive correlates of nonsocial play in 122 four-year-olds observed for 20 minutes during free play. Subjects were given a role-taking test and tests of social and impersonal problem-solving skills. Sociometric popularity and social competence, as rated by teachers, were also assessed. (Author/RH)

  19. Psychological Approaches to the Study of Play

    ERIC Educational Resources Information Center

    Bergen, Doris

    2015-01-01

    In this survey of the research on psychological approaches to play, the author outlines its various focuses on the similarities and differences in the thinking and behavior of individuals and groups in relation to play and on the environmental factors that influence these. She notes that although psychologists often use standard experimental…

  20. Teaching Peace: Alternatives to Violent Play.

    ERIC Educational Resources Information Center

    Jurek, Dianne Miller; Velazquez, Michaela

    1995-01-01

    To help combat the effects of violence on children and improve the quality and nature of play, early childhood teachers can: define violence by helping children become aware of the issue, help children resolve their own conflicts, create a peace place in the classroom, intervene when violent play occurs, evaluate media and toys, and educate…

  1. Burbank and Shkaplerov playing musical instruments

    NASA Image and Video Library

    2012-04-21

    ISS030-E-267658 (21 April 2012) --- NASA astronaut Dan Burbank, Expedition 30 commander, plays a guitar, while Russian cosmonaut Anton Shkaplerov, flight engineer, plays a musical keyboard during off-time in the Unity node of the International Space Station.

  2. Burbank and Shkaplerov playing musical instruments

    NASA Image and Video Library

    2012-04-21

    ISS030-E-267651 (21 April 2012) --- NASA astronaut Dan Burbank, Expedition 30 commander, plays a guitar, while Russian cosmonaut Anton Shkaplerov, flight engineer, plays a musical keyboard during off-time in the Unity node of the International Space Station.

  3. Drawings as Spaces for Intellectual Play

    ERIC Educational Resources Information Center

    Wood, Elizabeth; Hall, Emese

    2011-01-01

    The aims of this article are to explore the links between drawing and playing and to conceptualise drawings as spaces for intellectual play. The empirical research that supports this position is based on an interpretivist study involving 14 children aged four-six in a primary school in England. Over a one-year period, 882 drawings were collected…

  4. Observing and Planning for Play and Competence.

    ERIC Educational Resources Information Center

    Neumann, Eva A.

    This paper presents a framework useful for preschool and elementary teachers in developing a basic understanding of competency and play and their interrelationship. Specific guidelines are given for observing and planning toward increasing opportunities for competency and play. Competency is viewed as consisting of growth, risk-taking, and a…

  5. Forms of vitality play and symbolic play during the third year of life.

    PubMed

    Español, Silvia; Bordoni, Mariana; Martínez, Mauricio; Camarasa, Rosario; Carretero, Soledad

    2015-08-01

    This article focuses on the development of forms of vitality play, a recently described type of play, and links it to the development of symbolic play, one of the most studied types of play in developmental psychology. Two adult-infant dyads were videotaped longitudinally during in-house free play meetings every 15 days during the third year of life. Convergence technique was applied in order to accelerate the longitudinal study. A total of 17h 48min were registered in 28 sessions. An observational code with categories of forms of vitality play (a non-figurative play frame in which child and adult play together with the dynamics of their own movements and sounds in a repetition-variation form), symbolic play, and categories of combined patterns of both types of play was applied. The rate of each play was calculated for different age periods. Forms of vitality play is present at a constant rate during the third year of life. Symbolic play flourishes during this period. Combined play patterns are not the most frequent but are present from the beginning to the end of the third year. We suggest that FoVP favours intimate and intersubjective experiences essential to the understanding and the development of the interpersonal world; that it can be thought of as a good runway for the development of symbolic play; and that it prepares the child to participate in the temporal arts that belong to his culture. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Pretend Play: Antecedent of Adult Creativity.

    PubMed

    Russ, Sandra W

    2016-01-01

    This article reviews the theoretical and empirical literature in the area of pretend play as a predictor of adult creativity. There is strong evidence that processes expressed in pretend play are associated with measures of creativity, especially with divergent thinking. There is some evidence from longitudinal studies that this association is stable over time. Converging evidence suggests that cognitive and affective processes in pretend play are involved in adult creative production. However, there is a lack of consensus in the field as to whether engaging in pretend play actually facilitates creative thinking. In addition, many other variables (opportunity, tolerance for failure, motivation, work ethic, etc.) determine whether children with creative potential are actually creative in adulthood. In spite of the many methodological challenges in conducting research in the play area, it is important to continue investigating specific processes expressed in play and their developmental trajectories. Large samples in multisite studies would be ideal in investigating the ability of specific play processes to predict these creative processes and creative productivity in adulthood. © 2016 Wiley Periodicals, Inc.

  7. Playing up and playing down cultural identity: Introducing cultural influence and cultural variability.

    PubMed

    Ferguson, Gail M; Nguyen, Jacqueline; Iturbide, Maria I

    2017-01-01

    Cultural variability (CV) is introduced as an overlooked dimension of cultural identity development pertaining to emphasizing and de-emphasizing the influence of a single cultural identity (i.e., cultural influence [CI]) on daily interactions and behaviors. The Cultural IDentity Influence Measure (CIDIM) is introduced as a novel measure of CI and CV, and hypothesis-driven validation is conducted in two samples along with exploration of associations between CV and well-being. A multicultural sample of 242 emerging adults participated in a daily diary study (Mage = 19.95 years, SDage = 1.40) by completing up to eight daily online surveys containing the CIDIM, criterion measures (ethnic identity, other group orientation, ethnic identity salience and daily variability in salience, social desirability), and measures of personal and interpersonal well-being. A second validation sample (n = 245) completed a 1-time survey with the CIDIM and a subset of criterion measures. Results using both samples show evidence of CI and CV and demonstrate the validity, reliability, and domain-sensitivity of the CIDIM. Further, CV made unique and positive contributions to predicting interaction quality after accounting for ethnic salience and variability in ethnic salience. An analytic approach utilizing standard deviations produced near-identical results to multilevel modeling and is recommended for parsimony. Ethnic minority and majority individuals make daily adjustments to play up and play down the influence of cultural identity on their social interactions and behaviors, and these adjustments predict interpersonal well-being. Cultural influence and cultural variability contribute to our emerging understanding of cultural identity as dynamic and agentic. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. Back to Sleep, Tummy to Play

    MedlinePlus

    ... Español Text Size Email Print Share Back to Sleep, Tummy to Play Page Content ​What are the 2 most important things to remember about safe sleep practices? Healthy babies are safest when sleeping on ...

  9. Early Childhood: Discovery through Sand Play.

    ERIC Educational Resources Information Center

    McIntyre, Margaret

    1982-01-01

    Suggestions are given for using sand play to teach science related vocabulary and concepts to preschool and primary age children by using dry sand, wet sand, different sizes and shapes of spoons and containers, sieves, and funnels. (DC)

  10. Aguas!: An Introduction to Hispanic Plays.

    ERIC Educational Resources Information Center

    Saldana, Johnny

    1996-01-01

    Notes that the number of Hispanic children in schools is growing. Presents an annotated bibliography of 46 Hispanic plays, sources of information, and organizations dealing with Hispanic themes and ideas. (PA)

  11. Nystulian Play Therapy: Applications of Adlerian Psychology.

    ERIC Educational Resources Information Center

    Nystul, Michael S.

    1980-01-01

    Nystulian Play Therapy is based on Adlerian strategies. Encouragement of and respect for the child are emphasized. Teacher and parent education are important parts of a comprehensive approach to affective positive change in the child. (JAC)

  12. Mississippian Lodgepole Play, Williston Basin: A review

    SciTech Connect

    Montgomery, S.L.

    1996-06-01

    Waulsortian-type carbonate mud mounds in the lower Mississippian Lodgepole formation (Bottineau interval, Madison Group) comprise an important new oil play in the Williston basin with strong regional potential. The play is typified by wells capable of producing 1000-2500 bbl of oil per day and by reserves that have as much as 0.5-3.0 million bbl of oil per well. Currently centered in Stark County, North Dakota, along the southern flank of the basin, the play includes 38 wells, with 21 producers and 6 new fields. Initial discovery was made at a Silurian test in Dickinson field, traditionally productive from Pennsylvanian sands.more » The largest pool discovered to date is Eland field, which has 15 producers and estimated total reserves of 12-15 million bbl. This report summarizes geologic, well-log, seismic, and production data for this play, which promises to expand considerably in the years to come.« less

  13. Low Permeability Oil and Gas Plays

    EIA Publications

    The map shows boundaries, structure (elevation of the top contours), and isopachs (thickness contours) for major low permeability oil and gas plays in the lower 48 States. Additionally, related oil and gas infrastructure layers are included

  14. Playing violent video games increases intergroup bias.

    PubMed

    Greitemeyer, Tobias

    2014-01-01

    Previous research has shown how, why, and for whom violent video game play is related to aggression and aggression-related variables. In contrast, less is known about whether some individuals are more likely than others to be the target of increased aggression after violent video game play. The present research examined the idea that the effects of violent video game play are stronger when the target is a member of an outgroup rather than an ingroup. In fact, a correlational study revealed that violent video game exposure was positively related to ethnocentrism. This relation remained significant when controlling for trait aggression. Providing causal evidence, an experimental study showed that playing a violent video game increased aggressive behavior, and that this effect was more pronounced when the target was an outgroup rather than an ingroup member. Possible mediating mechanisms are discussed.

  15. 'Dora' & Kids at Day of Play

    NASA Image and Video Library

    2005-10-05

    From left, Cobie Smith, 5, and Tatume Smith, also 5, have their picture taken with 'Dora the Explorer.' The children were participants in Nickelodeon's Worldwide Day of Play celebration at Stennis Space Center (SSC) on Oct. 1. The Worldwide Day of Play is sponsored annually by Nickelodeon television network to encourage children to be physically active. Approximately 150 children participated in the event at SSC.

  16. 'Dora' & Kids at Day of Play

    NASA Technical Reports Server (NTRS)

    2005-01-01

    From left, Cobie Smith, 5, and Tatume Smith, also 5, have their picture taken with 'Dora the Explorer.' The children were participants in Nickelodeon's Worldwide Day of Play celebration at Stennis Space Center (SSC) on Oct. 1. The Worldwide Day of Play is sponsored annually by Nickelodeon television network to encourage children to be physically active. Approximately 150 children participated in the event at SSC.

  17. Adult Playfulness, Humor Styles, and Subjective Happiness.

    PubMed

    Yue, Xiao D; Leung, Chun-Lok; Hiranandani, Neelam A

    2016-12-01

    Playfulness has been referred to as a disposition that involves reframing a situation to amuse others and to make the situation more stimulating and enjoyable. It may serve to shift one's perspective when dealing with environmental threats. Despite all the benefits of playfulness towards psychological well-being, it remains a largely understudied subject in psychology, particularly in Chinese societies. Hence, this study examined the association between adult playfulness, humor styles, and subjective happiness among a sample of 166 university students in Hong Kong and 159 students in Guangzhou, who completed a self-administered questionnaire, including the Short Measure for Adult Playfulness, the Chinese Humor Styles Questionnaire, and the Subjective Happiness Scale. Results showed that adult playfulness was positively correlated with affiliative humor, self-enhancing humor, and subjective happiness in both Hong Kong and Guangzhou samples. By its implication, highly playful Chinese students preferred using affiliative and self-enhancing humor to amuse themselves and others. © The Author(s) 2016.

  18. Online role-playing for faculty development.

    PubMed

    Ladhani, Zahra; Chhatwal, Jugesh; Vyas, Rashmi; Iqbal, Mobeen; Tan, Christina; Diserens, Deborah

    2011-03-01

    There has been a rapid growth of online teaching in the past few years, yet the implementation of role-play for formal educational activities in an online setting is growing more slowly. The use of online role-playing for the development of health professions educators is virtually un-documented in the literature. In the project reported here we use role-playing as a method to motivate and increase active participation in an online web-based discussion on community-based medical education (CBME). The Foundation for Advancement of International Medical Education & Research (FAIMER(®) ) Institute hosts virtual group discussions for fellows as part of its fellowship programmes, in order to deepen their knowledge base in health professions education and research. In June 2008, a group of seven FAIMER(®) fellows and faculty members moderated an online discussion on CBME using an online role-play exercise with other fellows and faculty members. Out of a total of 102 fellows, 36 (35.3%) participated actively, which exceeded the typical percentage of list server participation. In addition, a rich discussion resulted in a comprehensive report on the goals, challenges, logistical components, role of Health Ministry policy and the possible ethical mandate of CBME in developing countries. Online role-play encouraged distributed participation among a highly diverse international group of participants, supporting the conclusion that role-playing can be used effectively with mid-career health professional faculty members in the online environment. © Blackwell Publishing Ltd 2011.

  19. Position Statement on Active Outdoor Play

    PubMed Central

    Tremblay, Mark S.; Gray, Casey; Babcock, Shawna; Barnes, Joel; Costas Bradstreet, Christa; Carr, Dawn; Chabot, Guylaine; Choquette, Louise; Chorney, David; Collyer, Cam; Herrington, Susan; Janson, Katherine; Janssen, Ian; Larouche, Richard; Pickett, William; Power, Marlene; Sandseter, Ellen Beate Hansen; Simon, Brenda; Brussoni, Mariana

    2015-01-01

    A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3–12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critical appraisal of the current literature and existing position statements, engagement of research experts (N = 9) and cross-sectorial individuals/organizations (N = 17), and an extensive stakeholder consultation process (N = 1908). More than 95% of the stakeholders consulted strongly agreed or somewhat agreed with the Position Statement; 14/17 participating individuals/organizations endorsed it; and over 1000 additional individuals and organizations requested their name be listed as a supporter. The final Position Statement on Active Outdoor Play states: “Access to active play in nature and outdoors—with its risks— is essential for healthy child development. We recommend increasing children’s opportunities for self-directed play outdoors in all settings—at home, at school, in child care, the community and nature.” The full Position Statement provides context for the statement, evidence supporting it, and a series of recommendations to increase active outdoor play opportunities to promote healthy child development. PMID:26062040

  20. Position Statement on Active Outdoor Play.

    PubMed

    Tremblay, Mark S; Gray, Casey; Babcock, Shawna; Barnes, Joel; Bradstreet, Christa Costas; Carr, Dawn; Chabot, Guylaine; Choquette, Louise; Chorney, David; Collyer, Cam; Herrington, Susan; Janson, Katherine; Janssen, Ian; Larouche, Richard; Pickett, William; Power, Marlene; Sandseter, Ellen Beate Hansen; Simon, Brenda; Brussoni, Mariana

    2015-06-08

    A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3-12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critical appraisal of the current literature and existing position statements, engagement of research experts (N=9) and cross-sectorial individuals/organizations (N=17), and an extensive stakeholder consultation process (N=1908). More than 95% of the stakeholders consulted strongly agreed or somewhat agreed with the Position Statement; 14/17 participating individuals/organizations endorsed it; and over 1000 additional individuals and organizations requested their name be listed as a supporter. The final Position Statement on Active Outdoor Play states: "Access to active play in nature and outdoors--with its risks--is essential for healthy child development. We recommend increasing children's opportunities for self-directed play outdoors in all settings--at home, at school, in child care, the community and nature." The full Position Statement provides context for the statement, evidence supporting it, and a series of recommendations to increase active outdoor play opportunities to promote healthy child development.

  1. Using role play to develop cultural competence.

    PubMed

    Shearer, Ruth; Davidhizar, Ruth

    2003-06-01

    Role play is a useful teaching strategy for nursing education. This strategy can simulate patient behaviors, as well as demonstrate nursing interventions that students must learn to be clinically competent. Role play is a dramatic technique that encourages participation to improvise behaviors that may be encountered in nurse-patient situations. Using this technique, participants may test behaviors and decisions in an experimental atmosphere without risk of negative effects in a relationship. Role play is useful in developing cultural competence because participants may experience diverse roles. Cultural competence is the ability to care for patients in a culturally sensitive and appropriate manner. In role play, students may participate as culturally diverse patients or as nurses encountering patients from different cultures. Various teaching strategies facilitate successful use of role play in the classroom, including defining a time frame, selected roles, specific objectives, references, and grading criteria. To optimize learning, the importance of exploration and analysis must be emphasized. Many benefits and potential problems accompany use of role play.

  2. Pretending to Play or Playing to Pretend: The Case of Autism.

    PubMed

    Kasari, Connie; Chang, Ya-Chih; Patterson, Stephanie

    2013-01-01

    An article by Angeline S. Lillard and others published in the January 2013 issue of Psychological Bulletin about the impact of pretend play on child development raised a number of issues about play studies and child psychology. They claimed that, contrary to current theories on the subject, the evidence of many studies does not support causal explanations of play's relationship to most childhood development. In this article, authors Kasari, Chang, and Patterson review these arguments about play and devlopment in relation to children with autism-children who show specific deficits in pretend play. They argue that the study of these children provides a unique opportunity to consider which elements in play are important and how play skills are associated with different periods of child development. They conclude that, because pretend play requires intervention for the majority of children with autism, improving pretense in these children may shed more light on the causal impact of pretense on later developing skills in children. Key words: child development and pretend play; children with autism; funtional play; intervention in play; symbol play.

  3. Playfulness, Imagination, and Creativity in Play with Toys: A Cultural-Historical Approach

    ERIC Educational Resources Information Center

    Møller, Signe Juhl

    2016-01-01

    The aim of this article is to present a wholeness perspective on the relation between creative imagination and children's activity when playing with toys. This is explored through a case retrieved from a 4-month experimental research project, specifically from a social fantasy play session. In order to analyse and examine children's play, the…

  4. Pedagogical Positioning in Play--Teachers Being inside and outside of Children's Imaginary Play

    ERIC Educational Resources Information Center

    Fleer, Marilyn

    2015-01-01

    Although there is a long tradition of play pedagogy in early childhood education, teachers have mostly taken a passive role in children's play. There are relatively few studies of the pedagogical roles adults take from inside of children's imaginary play. This paper seeks to fill this gap through presenting the findings of a study where the play…

  5. Differences in Practitioners' Understanding of Play and How This Influences Pedagogy and Children's Perceptions of Play

    ERIC Educational Resources Information Center

    McInnes, Karen; Howard, Justine; Miles, Gareth; Crowley, Kevin

    2011-01-01

    This paper presents research that examines the links between practitioners' understanding of play and its relationship to learning, their pedagogic interactions with children and children's own perceptions of their play. Previous research has shown a mismatch between practitioners' understanding of play and their practice. This research identifies…

  6. Taking Play Seriously: Children and Play in Early Childhood Education--An Exciting Challenge

    ERIC Educational Resources Information Center

    Lillemyr, Ole Fredrik

    2009-01-01

    In the book the author presents from different perspectives what is understood by the phenomenon of children's play, why it is important, and how children's play challenge and stimulate the educator or caregiver in regard of educational values and practice, with the conclusion: play has to be taken seriously. A selection of theories is introduced…

  7. Promoting Collaborative Playful Experimentation through Group Playing by Ear in Higher Education

    ERIC Educational Resources Information Center

    Varvarigou, Maria

    2017-01-01

    A group of 46, first-year, primarily classically trained, undergraduate students took part in an exploratory research study on Group Ear Playing (GEP) in higher education. The students attended the "Playing by Ear" component of the Practical Musicianship module, which adopts the materials and strategies on playing by ear in the…

  8. Responsive Play: Exploring Play as Reader Response in a First Grade Classroom

    ERIC Educational Resources Information Center

    Flint, Tori K.

    2016-01-01

    Play in the school setting is a highly contested issue in today's restrictive academic environment. Although many early childhood educators advocate the use of play in their classrooms and emphasize the importance of play for children's learning and development, children beyond the preschool and kindergarten years are not often afforded…

  9. "Prey Play": Learning about Predators and Prey through an Interactive, Role-Play Game

    ERIC Educational Resources Information Center

    Deaton, Cynthia C. M.; Dodd, Kristen; Drennon, Katherine; Nagle, Jack

    2012-01-01

    "Prey Play" is an interactive role-play activity that provides fifth-grade students with opportunities to examine predator-prey interactions. This four-part, role-play activity allows students to take on the role of a predator and prey as they reflect on the behaviors animals exhibit as they collect food and interact with one another, as well as…

  10. The Elements of Play: Toward a Philosophy and a Definition of Play

    ERIC Educational Resources Information Center

    Eberle, Scott G.

    2014-01-01

    Scholars conventionally find play difficult to define because the concept is complex and ambiguous. The author proffers a definition of play that takes into consideration its dynamic character, posits six basic elements of play (anticipation, surprise, pleasure, understanding, strength, and poise), and explores some of their emotional, physical,…

  11. Endangered Play, Endangered Development: A Constructivist View of the Role of Play in Development and Learning.

    ERIC Educational Resources Information Center

    Levin, Diane E.

    Piagetian and Vygotskian theories may be used as starting points to examine the role of play in development and learning from a constructivist perspective, including how children use play to deepen their understanding and skills, encounter new problems, and incorporate newly mastered skills into their play. Contemporary factors such as an emphasis…

  12. When play is a family business: adult play, hierarchy, and possible stress reduction in common marmosets.

    PubMed

    Norscia, Ivan; Palagi, Elisabetta

    2011-04-01

    Easy to recognize but not easy to define, animal play is a baffling behavior because it has no obvious immediate benefits for the performers. However, the absence of immediate advantages, if true, would leave adult play (costly but maintained by evolution, spanning lemurs to Homo sapiens) unexplained. Although a commonly held view maintains that play is limited by stress, an emergent hypothesis states that play can regulate stress in the short term. Here we explored this hypothesis in a captive family group of New World monkeys, Callithrix jacchus (common marmoset). We observed six subjects and gathered data on aggressive, play, and scratching behavior via focal (6 h/individual) and all occurrences sampling (115 h). We found that play levels were highest during pre-feeding, the period of maximum anxiety due to the forthcoming competition over food. Scratching (the most reliable indicator of stress in primates) and play showed opposite trends along hierarchy, with dominants scratching more and playing less than subordinates. Finally, scratching decreased after play, whereas play appeared to be unrelated to previous scratching events, symptoms of a potential stressful state. In conclusion, both play timing and hierarchical distribution indicate that play limits stress, more than vice versa, at least in the short term.

  13. What Play Therapists Do within the Therapeutic Relationship of Humanistic/Non-Directive Play Therapy

    ERIC Educational Resources Information Center

    Robinson, Sally

    2011-01-01

    Play therapists are increasingly being employed in schools, yet there is confusion among many health, education and social care practitioners about the role of play therapists. This paper explains how play therapists position themselves and what they do through an examination of the therapeutic relationship between the therapist and child. It…

  14. Playing with Technology: Mother-Toddler Interaction Scores Lower during Play with Electronic Toys

    ERIC Educational Resources Information Center

    Wooldridge, Michaela B.; Shapka, Jennifer

    2012-01-01

    To investigate play with electronic toys (battery-operated or digital), 25 mother-toddler (16-24 months old) dyads were videotaped in their homes playing with sets of age-appropriate electronic and non-electronic toys for approximately 10 min each. Parent-child interactions were coded from recorded segments of both of the play conditions using the…

  15. Can I Play with You? The Intersection of Play and Writing in a Kindergarten Classroom

    ERIC Educational Resources Information Center

    Yoon, Haeny S.

    2014-01-01

    Play is well documented as a purposeful, authentic way for children to engage in literacy practices. Although the benefits of play are widely agreed upon, there is some debate regarding its place in school. In fact, play is often marginalized in place of "back to the basics" language instruction. For kindergartners, this means word…

  16. Time perspective as a predictor of massive multiplayer online role-playing game playing.

    PubMed

    Lukavska, Katerina

    2012-01-01

    This article focuses on the relationship between the time perspective (TP) personality trait and massive multiplayer online role-playing game (MMORPG) playing. We investigate the question of frequency of playing. The TP was measured with Zimbardo's TP Inventory (ZTPI), which includes five factors-past negative, past positive, present hedonistic, present fatalistic, and future. The study used data from 154 MMORPG players. We demonstrated that TP partially explained differences within a group of players with respect to the frequency of playing. Significant positive correlations were found between present factors and the amount of time spent playing MMORPGs, and significant negative correlation was found between the future factor and the time spent playing MMORPGs. Our study also revealed the influence of future-present balance on playing time. Players who scored lower in future-present balance variables (their present score was relatively high compared with their future score) reported higher values in playing time. In contrast to referential studies on TP and drug abuse and gambling, present fatalistic TP was demonstrated to be a stronger predictor of extensive playing than present hedonistic TP, which opened the question of motivation for playing. The advantage of our study compared with other personality-based studies lies in the fact that TP is a stable but malleable personality trait with a direct link to playing behavior. Therefore, TP is a promising conceptual resource for excessive playing therapy.

  17. Observing and Assessing Young Children's Digital Play in the Early Years: Using the Digital Play Framework

    ERIC Educational Resources Information Center

    Edwards, Susan; Bird, Jo

    2017-01-01

    Early childhood education settings are characterized by the use of play-based learning and the assessment of children's play by teachers to promote further learning. A problem with technology use in early childhood settings is that little is known about how children learn to use technologies through play. This lack of knowledge makes it difficult…

  18. Play and Productivity: Enhancing the Creative Climate at Workplace Meetings with Play Cues

    ERIC Educational Resources Information Center

    West, Samuel E.; Hoff, Eva; Carlsson, Ingegerd

    2016-01-01

    The authors investigate the links between playfulness and creative organizational climates established by other research, using play cues--objects and sweets--they provide participants halfway through workplace meetings. Their findings suggest such cues significantly enhance the creative climate and playfulness in workplace meetings without…

  19. Playful Teaching Workshop Sampler. Classroom Play Ideas for Early Childhood Educators.

    ERIC Educational Resources Information Center

    Battista, Donna

    Based on Piaget's theory "children learn best by doing," play offers a natural way of learning for young children. The "Playful Teaching" Workshop Sampler offers teachers several different movement activities for incorporation into academic classroom curricula. The play ideas were presented at national and regional teaching workshops. The…

  20. Pigs, Planes, and Play-Doh: Children's Perspectives on Play as Revealed through Their Drawings

    ERIC Educational Resources Information Center

    Duncan, Pauline Agnieszka

    2015-01-01

    Play, an elusive concept despite the extensive literature on the subject, remains especially problematic for research focused on the perspective of children. The author discusses her study on children's perspectives about play, exploring drawing as a method for learning how young children conceptualize play within a social-semiotic framework. Her…

  1. Play and optimal welfare: Does play indicate the presence of positive affective states?

    PubMed

    Ahloy-Dallaire, Jamie; Espinosa, Julia; Mason, Georgia

    2017-11-16

    Play is commonly used to assess affective states in both humans and non-human animals. Play appears to be most common when animals are well-fed and not under any direct threats to fitness. Could play and playfulness therefore indicate pre-existing positive emotions, and thence optimal animal welfare? We examine this question by surveying the internal and external conditions that promote or suppress play in a variety of species, starting with humans. We find that negative affective states and poor welfare usually do suppress play (although there are notable exceptions where the opposite occurs). Furthermore, research in children suggests that beyond the frequency or total duration of play, poor welfare may additionally be reflected in qualitative aspects of this heterogeneous behaviour (e.g. display of solitary over social play; and the 'fragmentation' of play bouts) that are often overlooked in animals. There are surprisingly few studies of play in subjects with pre-existing optimal welfare or in unambiguously highly positive affective states, making it currently impossible to determine whether play can distinguish optimal or good welfare from merely neutral welfare. This therefore represents an important and exciting area for future research. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The role of play themes in non-directive play therapy.

    PubMed

    Ryan, Virginia; Edge, Andrew

    2012-07-01

    Describing the processes underlying play therapy is important for evidence based practice in child therapy. Employing play themes to describe children's play session contents is in widespread use by practitioners, but an adequate classification of these themes for non-directive play therapy practice has not yet been established. This article sets out to fill this gap by first describing how themes can be distinguished and distilled from the contents of play therapy contents. Second, a classification of main themes and sub-themes with exemplars to illustrate these concepts which is compatible with non-directive play therapy practice is set out. Finally a pilot project with experienced play therapists to test this classification in practice is suggested, along with the research questions that will need to be investigated in the shorter and longer terms.

  3. [Play therapy in social work with children].

    PubMed

    Dvarionas, Dziugas

    2002-01-01

    This article introduces the results of scientific research performed in 1995-1997 in Kaunas primary school with 1st and 2nd grade children exhibiting behavioral disorders. Play therapy, a quite novel method in the country, seeks better improvement and an achievement of a better relationship for disadvantaged children in educational process. Play group counseling, or play media counseling, is shown as an important method in working with early primary grade children, especially those who present behavioral problems in the classroom. Another important aspect of group play therapy is the concentrated relationship with the counselor. Primary school children, especially those who are disadvantaged respond more to warmth than to praise for being right and doing well. Data analysis allow us to assume that behavioral difficulties of primary school children are connected with a low rate of self-esteem and dissatisfaction with their vital activities. Main conclusions to correspond with hypothesis held for the research are: a) children exhibiting behavioral problems are less active in educational process; b) by means of systematic use of play group counseling method in school, problematic children are able to solve their difficulties and to optimize their academic improvement; c) there is a complementary relationship between child's self-esteem and his/her satisfaction with his/her vital activity.

  4. Bluetooth as a Playful Public Art Interface

    NASA Astrophysics Data System (ADS)

    Stukoff, Maria N.

    This chapter investigates how the application of emergent communication technologies assisted in the design of playful art experience in a public place. Every Passing Moment (EPM), was a mobile public artwork that tracked and recorded any discoverable Bluetooth device to automatically seed a flower in a virtual garden projected onto an urban screen. The EPM was the first public art work to run blu_box, a custom-designed Bluetooth system for mobile telephony. The aim of blu_box was to build a system that supported playful interactions between the public and an urban screen, openly accessible to anyone with a Bluetooth-enabled mobile phone. This participatory engagement was observed in EPM on three levels, namely; unconscious, conscious, and dynamic play. Furthermore, this chapter highlights how sound and face-to-face communication proved imperative in the play dynamics of EPM. In conclusion, this chapter proposes ways in which the use of emergent communication technologies in public places, especially when interfaced with urban screening platforms, can construct playful city spaces for the public at large.

  5. A Staged Reading of the Play: Reykjavik

    NASA Astrophysics Data System (ADS)

    2017-01-01

    Reykjavik is the capital of Iceland, an island country located about 500 miles northwest of Scotland in the North Atlantic. In 1986 Mikhail Gorbachev, the Chairman of the Politburo of the Soviet Union and General Secretary of the Soviet Communist Party, invited Ronald Reagan, the President of the United States, to meet with him. The play Reykjavik is a dramatic reconstruction of the two-day summit meeting during which the world leaders almost reached agreement on the total abolition of their countries' nuclear weapons. The play uses the actual transcripts of the Reykjavik meeting as well as the memoirs of both Reagan and Gorbachev. Join us for a dramatic staged reading of Reykjavik and find out how close the two superpowers, the Soviet Union and the United States, came to eliminating their nuclear weapons. He playwright is Richard Rhodes, the Pulitzer Prize-winning author of 24 books. He has written his first play, and it spins off of his research into the history of nuclear weapons. The staged reading is performed by the Washington based Tonic Theater Company: http://www.tonictheater.org/[tonictheater.org]. After the performance, the play director and actors as well as experts on nuclear disarmament will be available for a talk-back discussion of the play with the audience. Produced by Brian Schwartz, Brooklyn College and the Graduate Center of the City University of New York and Gregory Mack of the APS Washington office.

  6. Freud on play, games, and sports fanaticism.

    PubMed

    Holowchak, M Andrew

    2011-01-01

    Much has been written in the secondary literature on Freud's aggression-release perspective vis-à-vis competitive sports. Very little has been written, however, on Freud's own explicit contribution to play, games, and sport. That is likely the result of Freud's reluctance to take up them--especially from the gamesman's and sportsman's points of view. One can, however, tease out the development of Freud's thoughts on games, play, and sport through a careful examination of his corpus over time. In doing so, one finds an early view of play and games, where the drives behind those activities are self- and other-preservative, and a later view, where Freud introduces his death drive. The article ends with some notions on what Freud might have said on the fanaticism that accompanies competitive sport, had he expressly taken up the issue.

  7. Organic Functional Group Playing Card Deck

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.

    2003-04-01

    The recognition and identification of organic functional groups, while essential for chemistry and biology majors, is also very useful for non-science majors in the study of molecules in art and life. In order to make this task more palatable for the non-science major (art and communications students), the images of a traditional playing deck of cards (heart, spade, diamond, and club) have been replaced with four representations of common organic functional groups. The hierarchy rules for naming two groups in a molecule is loosely incorporated to represent the sequence (King, Queen, Jack, ?, Ace) of the deck. Students practice recognizing and identifying organic groups by playing simple card games of "Old Maid" and "Go Fish". To play games like "Poker" or "Gin", a student must not only recognize the functional groups, but also master a naming hierarchy for the organic groups.

  8. Recent Advances in General Game Playing

    PubMed Central

    Świechowski, Maciej; Park, HyunSoo; Mańdziuk, Jacek; Kim, Kyung-Joong

    2015-01-01

    The goal of General Game Playing (GGP) has been to develop computer programs that can perform well across various game types. It is natural for human game players to transfer knowledge from games they already know how to play to other similar games. GGP research attempts to design systems that work well across different game types, including unknown new games. In this review, we present a survey of recent advances (2011 to 2014) in GGP for both traditional games and video games. It is notable that research on GGP has been expanding into modern video games. Monte-Carlo Tree Search and its enhancements have been the most influential techniques in GGP for both research domains. Additionally, international competitions have become important events that promote and increase GGP research. Recently, a video GGP competition was launched. In this survey, we review recent progress in the most challenging research areas of Artificial Intelligence (AI) related to universal game playing. PMID:26380375

  9. Magical arts: the poetics of play.

    PubMed

    Jacobus, Mary

    2005-01-01

    The paper argues that links between play and magic in British Object Relations point to the persistence of aesthetic concerns within psychoanalysis. Magical thinking is present in British Object Relations psychoanalysis from its beginnings in Klein's play technique and early aesthetic writings, surfacing elsewhere in Susan Isaac's educational experiments and her theories of metaphor. Marion Milner's clinical account of the overlapping areas of illusion and symbol-formation in a boy's war-games link the primitive rituals of Frazer's "The Golden Bough" with her patient's creativity. In Winnicott's concept of the transitional object, the theory of play achieves its apotheosis as a diffusive theory of culture or "private madness," and as a paradigm for psychoanalysis itself. Tracing the non-positivistic, mystical, and poetical elements in British Object Relations underlines the extent to which aesthetics is not just entangled with psychoanalysis, but constitutive of it in its mid-twentieth century manifestations.

  10. Recent Advances in General Game Playing.

    PubMed

    Świechowski, Maciej; Park, HyunSoo; Mańdziuk, Jacek; Kim, Kyung-Joong

    2015-01-01

    The goal of General Game Playing (GGP) has been to develop computer programs that can perform well across various game types. It is natural for human game players to transfer knowledge from games they already know how to play to other similar games. GGP research attempts to design systems that work well across different game types, including unknown new games. In this review, we present a survey of recent advances (2011 to 2014) in GGP for both traditional games and video games. It is notable that research on GGP has been expanding into modern video games. Monte-Carlo Tree Search and its enhancements have been the most influential techniques in GGP for both research domains. Additionally, international competitions have become important events that promote and increase GGP research. Recently, a video GGP competition was launched. In this survey, we review recent progress in the most challenging research areas of Artificial Intelligence (AI) related to universal game playing.

  11. Cracking Bank PINs by Playing Mastermind

    NASA Astrophysics Data System (ADS)

    Focardi, Riccardo; Luccio, Flaminia L.

    The bank director was pretty upset noticing Joe, the system administrator, spending his spare time playing Mastermind, an old useless game of the 70ies. He had fought the instinct of telling him how to better spend his life, just limiting to look at him in disgust long enough to be certain to be noticed. No wonder when the next day the director fell on his chair astonished while reading, on the newspaper, about a huge digital fraud on the ATMs of his bank, with millions of Euros stolen by a team of hackers all around the world. The article mentioned how the hackers had 'played with the bank computers just like playing Mastermind', being able to disclose thousands of user PINs during the one-hour lunch break. That precise moment, a second before falling senseless, he understood the subtle smile on Joe's face the day before, while training at his preferred game, Mastermind.

  12. Toys and games in play therapy.

    PubMed

    Meschiany, A; Krontal, S

    1998-01-01

    The present article discusses the difference between play therapy with toys and play therapy with games from a psychodynamic point of view. Toys are regarded as offering the child an opportunity to develop a variety of transference reactions, while games, because of their inherent competitive characteristic, restrain the scope of possible transference reactions. The authors claim that therapists should consider these eventualities when choosing which games or toys are to be available in the therapy room. This choice might determine, in advance, the initial characteristics of the patient's transference.

  13. On the significance of adult play: what does social play tell us about adult horse welfare?

    PubMed

    Hausberger, Martine; Fureix, Carole; Bourjade, Marie; Wessel-Robert, Sabine; Richard-Yris, Marie-Annick

    2012-04-01

    Play remains a mystery and adult play even more so. More typical of young stages in healthy individuals, it occurs rarely at adult stages but then more often in captive/domestic animals, which can imply spatial, social and/or feeding deprivations or restrictions that are challenging to welfare, than in animals living in natural conditions. Here, we tested the hypothesis that adult play may reflect altered welfare states and chronic stress in horses, in which, as in several species, play rarely occurs at adult stages in natural conditions. We observed the behaviour (in particular, social play) of riding school horses during occasional outings in a paddock and measured several stress indicators when these horses were in their individual home boxes. Our results revealed that (1) the number of horses and rates of adult play appeared very high compared to field report data and (2) most stress indicators measured differed between 'players' and 'non-players', revealing that most 'playful' animals were suffering from more chronic stress than 'non-playful' horses. Frequency of play behaviour correlated with a score of chronic stress. This first discovery of a relationship between adult play and altered welfare opens new lines of research that certainly deserves comparative studies in a variety of species.

  14. On the significance of adult play: what does social play tell us about adult horse welfare?

    NASA Astrophysics Data System (ADS)

    Hausberger, Martine; Fureix, Carole; Bourjade, Marie; Wessel-Robert, Sabine; Richard-Yris, Marie-Annick

    2012-04-01

    Play remains a mystery and adult play even more so. More typical of young stages in healthy individuals, it occurs rarely at adult stages but then more often in captive/domestic animals, which can imply spatial, social and/or feeding deprivations or restrictions that are challenging to welfare, than in animals living in natural conditions. Here, we tested the hypothesis that adult play may reflect altered welfare states and chronic stress in horses, in which, as in several species, play rarely occurs at adult stages in natural conditions. We observed the behaviour (in particular, social play) of riding school horses during occasional outings in a paddock and measured several stress indicators when these horses were in their individual home boxes. Our results revealed that (1) the number of horses and rates of adult play appeared very high compared to field report data and (2) most stress indicators measured differed between `players' and `non-players', revealing that most `playful' animals were suffering from more chronic stress than `non-playful' horses. Frequency of play behaviour correlated with a score of chronic stress. This first discovery of a relationship between adult play and altered welfare opens new lines of research that certainly deserves comparative studies in a variety of species.

  15. Developmental Play Equipment for Home and School.

    ERIC Educational Resources Information Center

    Gallahue, David L.

    This book is a compilation of homemade and inexpensive developmental play equipment ideas that may be used in the home and school with preschool and elementary school children. Each equipment idea contains the objectives for its use, the materials and approximate cost, how to assemble the equipment, and a variety of activity ideas. Illustrations…

  16. Serious Play with Dynamic Plane Transformations

    ERIC Educational Resources Information Center

    King, James

    2011-01-01

    Transformations are a central organizing idea in geometry. They are included in most geometry curricula and are likely to appear with even greater emphasis in the future, given the central role they play in the "Common Core State Standards" for K-12 mathematics. One of the attractions of geometry is the ability to draw and construct the…

  17. The Play as a Dramatic Action.

    ERIC Educational Resources Information Center

    Gross, Roger

    That a play has one central action which is its formal cause is the most influential interpretative idea to emerge among theatre writers since the old model of situation/incident/complication/climax/denouement. Unfortunately, the action concept has been insufficiently developed, excessive hopes have been pinned on it, and it has become a reductive…

  18. Preadolescent Girls' and Boys' Virtual MUD Play

    ERIC Educational Resources Information Center

    Calvert, Sandra L.; Strouse, Gabrielle A.; Strong, Bonnie L.; Huffaker, David A.; Lai, Sean

    2009-01-01

    Same and opposite-sex pairs of preadolescents interacted twice in a MUD, a virtual domain where they created characters known as avatars and socially interacted with one another. Boys interacted primarily through rapid scene shifts and playful exchanges; girls interacted with one another through written dialogue. Opposite-sex pairs lagged behind…

  19. A Child's Power in Game-Play

    ERIC Educational Resources Information Center

    McLeod, Julie; Lin, Lin

    2010-01-01

    This paper is the first of its series that studies the power children have in game-play and examines its implications for teaching and learning. As a start, the paper describes a framework of power based on a synthesis of various types of power underlined in literature. The paper then looks into the power issue through observation and interviews…

  20. Will Playfulness Be Possible in University Management?

    ERIC Educational Resources Information Center

    West, Richard R.

    1979-01-01

    "Organized anarchies" is how Michael Cohen and James March have described American universities. The lack of rational-deductive organizational characteristics in higher education has encouraged it to be "playful" in a way that is "sensibly foolish." Budgetary pressures will force universities to become more…

  1. Everybody Wins! 100 Games Children Should Play.

    ERIC Educational Resources Information Center

    Schilling, Dianne; Akin, Terri

    This book presents a collection of classic and new games for early childhood educators to use with young children. Examples of classic games included are "Hide and Seek,""Hop-scotch," and "Hang Man." Also included are playful inventions which emphasize individual challenge, along with group activity, cooperation, and caring. The book's…

  2. Games To Play with Babies. Third Edition.

    ERIC Educational Resources Information Center

    Silberg, Jackie

    Intended for parents with infants, this book is a collection of 230 simple, fun-filled games that can be played with infants from birth to age 1 year. The book begins with guidelines for growth in motor, auditory, visual, language, cognitive, and self-concept skills from birth to 6 months and from 6 to 12 months. The remainder of the book presents…

  3. Playing around in Lewis Carroll's "Alice" Books

    ERIC Educational Resources Information Center

    Susina, Jan

    2010-01-01

    Mathematician Charles Dodgson's love of play and his need for rules came together in his use of popular games as part of the structure of the two famous children's books, "Alice in Wonderland" and "Through the Looking-Glass," he wrote under the pseudonym Lewis Carroll. The author of this article looks at the interplay between…

  4. The Playful and Reflective Game Designer

    ERIC Educational Resources Information Center

    Majgaard, Gunver

    2014-01-01

    A group of first-semester engineering students participated in a game design course. The aim of the course was to learn how to design computer games and programming skills by creating their own games, thereby applying their game-playing experiences to gain knowledge about game design. The aim was for students to develop a more critically…

  5. Melting Metal on a Playing Card

    ERIC Educational Resources Information Center

    Greenslade, Thomas B., Jr.

    2016-01-01

    Many of us are familiar with the demonstration of boiling water in a paper cup held over a candle or a Bunsen burner; the ignition temperature of paper is above the temperature of 100°C at which water boils under standard conditions. A more dramatic demonstration is melting tin held in a playing card. This illustration is from Tissandier's book on…

  6. Playfulness, Ideas, and Creativity: A Survey

    ERIC Educational Resources Information Center

    Bateson, Patrick; Nettle, Daniel

    2014-01-01

    This article investigates whether self-reports about playfulness are related to self-reports about creativity and the alternate uses of objects. An on-line survey was conducted of how people think about themselves. One thousand, five hundred and thirty-six people completed the survey. They were asked whether a variety of statements were very…

  7. Play in and around the Ancient Novel

    ERIC Educational Resources Information Center

    Kidd, Stephen E.

    2017-01-01

    The episodic structuring of ancient novels gives rise to the impression that they are not a serious genre in contrast to other genres like tragedy. Episodic plots tend to imply a playfulness not bound to causality but instead a spontaneity that includes the freedom to reinvent themselves. The author argues that novels like Longus's "Daphnis…

  8. A Simulation of Coevolution Using Playing Cards

    ERIC Educational Resources Information Center

    Tatina, Robert

    2007-01-01

    In this article, the author describes a simulation of a coevolutionary "arms race" and introduce a way of teaching it that lets students use the theory of natural selection to explain the outcomes of the simulation. The simulation uses the numerical cards from an UNO[R] playing card deck to represent the speeds of individuals in populations of…

  9. Writing Plays Using Creative Problem-Solving.

    ERIC Educational Resources Information Center

    Raiser, Lynne; Hinson, Shirley

    1995-01-01

    This article describes a project which involved inner city elementary grade children with disabilities in writing and performing their own plays. A four-step playwriting process focuses on theme and character development, problem finding, and writing dialogue. The project has led to improved reading skills, attention, memory skills,…

  10. Simplify Volleying through Modified Game Play

    ERIC Educational Resources Information Center

    Beaudet, Bob; Grube, Dan

    2005-01-01

    Volleyball, by its very nature, is a difficult game to play. Players at all ages have a hard time hitting the ball to their intended targets, resulting in rallies that rarely last more than one or two hits. The resulting game, then, is slow paced and boring, with a lot of standing around and little activity time. In an attempt to ease the…

  11. Washington Play Fairway Analysis Geothermal GIS Data

    DOE Data Explorer

    Corina Forson

    2015-12-15

    This file contains file geodatabases of the Mount St. Helens seismic zone (MSHSZ), Wind River valley (WRV) and Mount Baker (MB) geothermal play-fairway sites in the Washington Cascades. The geodatabases include input data (feature classes) and output rasters (generated from modeling and interpolation) from the geothermal play-fairway in Washington State, USA. These data were gathered and modeled to provide an estimate of the heat and permeability potential within the play-fairways based on: mapped volcanic vents, hot springs and fumaroles, geothermometry, intrusive rocks, temperature-gradient wells, slip tendency, dilation tendency, displacement, displacement gradient, max coulomb shear stress, sigma 3, maximum shear strain rate, and dilational strain rate at 200m and 3 km depth. In addition this file contains layer files for each of the output rasters. For details on the areas of interest please see the 'WA_State_Play_Fairway_Phase_1_Technical_Report' in the download package. This submission also includes a file with the geothermal favorability of the Washington Cascade Range based off of an earlier statewide assessment. Additionally, within this file there are the maximum shear and dilational strain rate rasters for all of Washington State.

  12. Endowment Investing: Time for a Sustainability Play?

    ERIC Educational Resources Information Center

    Pelletier, Stephen G.

    2010-01-01

    Managers of university endowment funds are paying closer attention to investing in "green" industries, commonly bundled under the umbrella "cleantech." Cleantech offers the possibility of buying in while prices are low "and" making a "green" investment play, but it also harbors the risks inherent in any emerging industry. Cleantech has varying…

  13. ADHD and Problem-Solving in Play

    ERIC Educational Resources Information Center

    Borg, Suzanne

    2009-01-01

    This paper reports a small-scale study to determine whether there is a difference in problem-solving abilities, from a play perspective, between individuals who are diagnosed as ADHD and are on medication and those not on medication. Ten children, five of whom where on medication and five not, diagnosed as ADHD predominantly inattentive type, were…

  14. Odaminodaa Ojibwemong!! = Let's Play in Ojibwe!!

    ERIC Educational Resources Information Center

    White, James L.

    The booklet contains directions for designing six word games to provide motivation, reinforcement, and review for students of all ages, from children to adults, as they learn the Ojibwe language. Step-by-step instructions are provided for making and playing Quiz Board, Tic-Tac-Toe, Concentration, Lottery, Lingo (Bingo), and Incocomp. Suggestions…

  15. Developmental Features of Children's Play with Objects.

    ERIC Educational Resources Information Center

    Vandenberg, Brian

    1981-01-01

    Examined whether the density of play continues to increase as children grow older. Four- and five-year-olds made simple constructions using few materials, six- and seven-year-olds made more constructions with more materials, and eight-to ten-year-olds made fewer but much more extensive and integrated constructions. (Author/DB)

  16. Contemporary Play Therapy: Theory, Research, and Practice

    ERIC Educational Resources Information Center

    Schaefer, Charles E., Ed.; Gerard Kaduson, Heidi, Ed.

    2006-01-01

    This highly practical book presents current developments in play therapy, including innovative applications for particular problems and populations. Contributors first discuss the latest ideas and techniques emerging from object-relations, experiential, dynamic, and narrative perspectives. Next, research evaluating the effectiveness of play…

  17. Young Children's Block Play and Mathematical Learning

    ERIC Educational Resources Information Center

    Park, Boyoung; Chae, Jeong-Lim; Boyd, Barbara Foulks

    2008-01-01

    This qualitative study investigated young children's mathematical engagement in play with wooden unit blocks. Two boys, ages 6 and 7, were independently observed completing the task of filling outlined regions with the various sets of blocks. Three major mathematical actions were observed: categorizing geometric shapes, composing a larger shape…

  18. Patriotic and Historical Plays for Young People.

    ERIC Educational Resources Information Center

    Kamerman, Sylvia E., Ed.

    The one-act, royalty-free plays in this book dramatize notable events in United States history. Historical selections include dramatizations of the Declaration of Independence, the Boston Tea Party, the Continental Army at Valley Forge, the birth of the Constitution, and George Washington crossing the Delaware and feature such historic figures as…

  19. World History Plays, Puzzles and Activities.

    ERIC Educational Resources Information Center

    Stevens, Lawrence

    This instructional resource, for grades 7-10, includes a collection of 10 plays with related learning activities. Units of study include: (1) "Alexander the Great and the Greeks"; (2) "The Black Death and the End of the Middle Ages"; (3) "Robert Clive and Imperialism"; (4) "Christopher Columbus and the Age of…

  20. Jumping Rope at Day of Play

    NASA Image and Video Library

    2005-10-05

    Sarah Dastugue, 11, leaps in the air as Libby Knox, 9, swings a jump rope. The children were participants in Nickelodeon's Worldwide Day of Play celebration at Stennis Space Center (SSC) on Oct. 1. On the day of the event, children all over the world participate in physical activities as part of the celebration.

  1. 27 CFR 9.168 - Fair Play.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Fair Play. 9.168 Section 9.168 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... located in El Dorado County, California and is located entirely within the existing Sierra Foothills and...

  2. 27 CFR 9.168 - Fair Play.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Fair Play. 9.168 Section 9.168 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... located in El Dorado County, California and is located entirely within the existing Sierra Foothills and...

  3. Block Play: Practical Suggestions for Common Dilemmas

    ERIC Educational Resources Information Center

    Tunks, Karyn Wellhousen

    2009-01-01

    Learning materials and teaching methods used in early childhood classrooms have fluctuated greatly over the past century. However, one learning tool has stood the test of time: Wood building blocks, often called unit blocks, continue to be a source of pleasure and learning for young children at play. Wood blocks have the unique capacity to engage…

  4. The Commercial Side of Virtual Play Worlds

    ERIC Educational Resources Information Center

    Kargin, Tolga

    2018-01-01

    In recent years, virtual play spaces have become enormously popular among young children around the world. As yet, though, there has been relatively little research into the ways in which children interact on such sites and what they learn in the process. This article describes a study of kids' experiences with one such virtual world, Club…

  5. Should College Athletes Be Paid to Play?

    ERIC Educational Resources Information Center

    Cooper, Kenneth J.

    2011-01-01

    Is playing big-time college sports an extracurricular activity or a job? Two law professors at Michigan State University, Robert and Amy McCormick, think it is definitely a job for football and basketball players on athletic scholarships at Division I schools. The married couple has added a new dimension to the long debate over paying athletes by…

  6. A Century of Plays by American Women.

    ERIC Educational Resources Information Center

    France, Rachel, Ed.

    Chosen for their literary quality and because they reflect the historical periods in which they were written, the 23 one-act dramas in this anthology represent the work of American female playwrights. The plays range from the realistic dramas produced in the "Little Theatres" of New York City at the turn of the century to current off-Broadway…

  7. Some Correlates of Imaginative Play in Preschoolers.

    ERIC Educational Resources Information Center

    Singer, Dorothy G.; Singer, Jerome L.

    This study examined the ways in which the spontaneous imaginative play and other social behaviors of 3- and 4-year-old children are affected by the frequency and patterns of their television viewing. The subjects were 141 children from predominantly white middle class homes. Pretesting was done to get an estimate of IQ (Peabody Picture Vocabulary…

  8. SE Great Basin Play Fairway Analysis

    DOE Data Explorer

    Adam Brandt

    2015-11-15

    Within this submission are multiple .tif images with accompanying metadata of magnetotelluric conductor occurrence, fault critical stress composite risk segment (CRS), permeability CRS, Quaternary mafic extrusions, Quaternary fault density, and Quaternary rhyolite maps. Each of these contributed to a final play fairway analysis (PFA) for the SE Great Basin study area.

  9. Raster Files for Utah Play Fairway Analysis

    DOE Data Explorer

    Wannamaker, Phil

    2017-06-16

    This submission contains raster files associated with several datasets that include earthquake density, Na/K geothermometers, fault density, heat flow, and gravity. Integrated together using spatial modeler tools in ArcGIS, these files can be used for play fairway analysis in regard to geothermal exploration.

  10. Spatial Perspective-Taking and Pretend Play.

    ERIC Educational Resources Information Center

    And Others; Matthews, Wendy Schempp

    1980-01-01

    To test the hypothesis that pretend play has a facilitatory effect on young children's spatial perspective taking, 45 children were individually engaged in fantasy or non-fantasy interactions with an adult, after which they were administered three standard perspective-taking tasks by a blind examiner. Supportive evidence was found. (Author/SJL)

  11. Playing with Liquid Foams: Learning Physical Chemistry

    ERIC Educational Resources Information Center

    Ritacco, Hernan

    2008-01-01

    Who has never played with soap bubbles? They are so beautiful and amazing, they have a perfect spherical shape and surprising tints. Foams are structures of bubbles of an incredible complexity and they are a perfect system to stimulate students' interest in the chemistry and physics of surface phenomena. In this article I propose a simple…

  12. The Communication Game: Dump and Play

    ERIC Educational Resources Information Center

    Muma, John R.

    1975-01-01

    The author identifies two operations, "dump" and "play", that take place in human communication and analyzes the communication efforts of young children (prior to age 8) in terms of the limitations in cognitive development that govern their communication. (Author/LS)

  13. Rethinking Role Play in the Reception Class

    ERIC Educational Resources Information Center

    Rogers, Sue; Evans, Julie

    2007-01-01

    Background: In 2000 the so-called "Reception" class was re-conceived (in curricular terms, at least) as the second and final year of the Foundation Stage, a distinctive educational phase for children aged 3 until entry to key stage 1 at 5 or 6 years old. The "Curriculum guidance for the Foundation Stage" endorses a play-based,…

  14. Instrument Records And Plays Back Acceleration Signals

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J.

    1994-01-01

    Small, battery-powered, hand-held instrument feeds power to accelerometer and records time-varying component of output for 15 seconds in analog form. No power needed to maintain content of memory; memory chip removed after recording and stored indefinitely. Recorded signal plays back at any time up to several years later. Principal advantages: compactness, portability, and low cost.

  15. Safety Management for Water Play Facilities.

    ERIC Educational Resources Information Center

    Thompson, Claude

    1986-01-01

    Modern aquatic facilities, which include wave pools, water slides, and shallow water activity play pools, have a greater potential for injuries and lawsuits than conventional swimming pools. This article outlines comprehensive safety management for such facilities, including potential accident identification and injury control planning. (MT)

  16. Serious Play. A Leisure Wellness Guidebook.

    ERIC Educational Resources Information Center

    Kimeldorf, Martin

    This book helps people find a way to balance their work and leisure values. Filled with inventories, worksheets, reflective riddles, journal assignments, and guides for community explorations, this workbook offers a method for rejuvenating the lost art of play and finding a better balance between work and leisure roles. Chapters 1 and 2 help…

  17. [Death by erotic asphyxiation (breath control play)].

    PubMed

    Madea, Burkhard; Hagemeier, Lars

    2013-01-01

    Most cases of sexual asphyxia are due to autoerotic activity. Asphyxia due to oronasal occlusion is mostly seen in very old or very young victims. Oronasal occlusion is also used in sadomasochistic sexual practices like "breath control play" or "erotic asphyxiation". If life saving time limitations of oronasal occlusion are not observed, conviction for homicide caused by negligence is possible.

  18. Expert Behavior in Children's Video Game Play.

    ERIC Educational Resources Information Center

    VanDeventer, Stephanie S.; White, James A.

    2002-01-01

    Investigates the display of expert behavior by seven outstanding video game-playing children ages 10 and 11. Analyzes observation and debriefing transcripts for evidence of self-monitoring, pattern recognition, principled decision making, qualitative thinking, and superior memory, and discusses implications for educators regarding the development…

  19. Microblogging Activities: Language Play and Tool Transformation

    ERIC Educational Resources Information Center

    Hattem, David

    2014-01-01

    The following is a qualitative case study presenting three vignettes exploring the use of language play while microblogging during an academically sanctioned task. Ten students and one teacher used "Twitter" in an intensive, English as a second language advanced grammar course to practice writing sentences with complex grammatical…

  20. Teaching Teachers to Play and Teach Games

    ERIC Educational Resources Information Center

    Wright, Steven; McNeill, Michael; Fry, Joan; Wang, John

    2005-01-01

    This study was designed to determine the extent to which a technical and a tactical approach to teaching a basketball unit to physical education teacher education (PETE) students would each affect their games playing abilities, perceived ability to teach, and approach preference for teaching the game. Pre- and post-unit data were collected through…

  1. Role Playing as a Leadership Development Tool

    ERIC Educational Resources Information Center

    Guenthner, Joseph F.; Moore, Lori L.

    2005-01-01

    Agribusinesses seek university graduates who have leadership ability. Role playing, one method of teaching leadership skills, is used in a university agricultural policy course. It has been a fun and effective leadership learning tool. Students improve their communication skills, conduct in-depth research about a topic of their choice, and develop…

  2. Scaffolding Productive Language Skills through Sociodramatic Play

    ERIC Educational Resources Information Center

    Galeano, Rebecca

    2011-01-01

    This article reviews how a receptive, bilingual four-year-old increased her Spanish productive-language skills over five weeks as she engaged in Spanish-language play sessions with bilingual peers. The data show her growing participation in group verbal interactions along with her growing production of her weaker language. In addition, a…

  3. [Theraplay--a direct communication play therapy].

    PubMed

    Franke, U

    1990-01-01

    This paper introduces the basic concepts and the application of the directive short-term play therapy called Theraplay. Goals and methods are illustrated by examples from the assessment (Marschak Interaction Method) and by sessions with a 6 year old regressive noncompliant mutistic twin.

  4. Skrammellegepladsen: Denmark's first adventure play area

    Treesearch

    Amanda Rae O' Connor; James F. Palmer

    2003-01-01

    This paper reviews the philosophy of the adventure playground movement and particularly the goals of the original adventure playground, Skrammellegepladsen in Copenhagen, Denmark. We then present a case study investigation of the ways that Skrammellegepladsen is used, the perceptions of the users, and the extent that the play area embodies its original philosophy. The...

  5. Hospital Clowning as Play Stimulus in Healthcare

    PubMed Central

    Anes, Laura; Obi, Marianne

    2014-01-01

    A serious illness, a chronic medical condition or a hospital bed should not deny any child her/his basic right to play, a right essential for children’s development and general wellbeing. In fact, it is in these frightening and anxious moments that play and the stimulus that it provides can help the most. This article will focus on the impacts and benefits of professional hospital clowning for the wellbeing and recovery process of ill and hospitalized children. Our experience has shown that through interactive play and humor, “clowndoctors” can create an enabling and supportive environment that facilitates children’s adaptation to the hospital setting and improves their acceptance of medical procedures and staff. While moving from bedside to bedside, RED NOSES clowndoctors encourage children’s active participation and support their natural instinct to play, fully including them in the interaction, if the children wish to do so. Therefore, clowndoctor performances offer ill children much needed stimulus, self-confidence and courage, elements fundamental to reducing their vulnerability. In this piece, a special emphasis will be put on the various approaches used by RED NOSES clowndoctors to bond and reach out to children suffering from different medical conditions. PMID:27417485

  6. The Importance of Play: Part Three

    ERIC Educational Resources Information Center

    Exceptional Parent, 2009

    2009-01-01

    Several membership companies of the International Playground Equipment Manufacturers Association (IPEMA) are helping differently-abled children to have access to play equipment and opportunities. These IPEMA membership companies, and others, are driven by the principles of Universal Design (UD), a new concept in playground design that helps ensure…

  7. Environmental Influences on Independent Collaborative Play

    ERIC Educational Resources Information Center

    Mawson, Brent

    2010-01-01

    Data from two qualitative research projects indicated a relationship between the type of early childhood setting and children's independent collaborative play. The first research project involved 22 three and four-year-old children in a daylong setting and 47 children four-year-old children in a sessional kindergarten. The second project involved…

  8. Geriatrix: A Role-Playing Game.

    ERIC Educational Resources Information Center

    Hoffman, Stephanie B.; And Others

    1985-01-01

    To sensitize medical students to the complexities of geriatric patient care, the geriatrics faculty of Upstate Medical Center's Clinical Campus developed Geriatrix, a role-playing game. Students attempt to win points in a board game containing Fact, Concept, and Crisis Squares. Crises promote exposure to ethical dilemmas and invite intense debate…

  9. The Facilitator's Role in Children's Play.

    ERIC Educational Resources Information Center

    Ford, Sylvia A.

    1993-01-01

    Examines ways child caregivers can create fun, safe, and stimulating play environment for young children. Includes discussion of several factors: (1) a carefully planned and organized physical environment; (2) routine, repetition, and consistency; (3) clearly stated expectations and limits; (4) interaction with the children; (5) behavior role…

  10. A Role-Play Rorschach Procedure

    ERIC Educational Resources Information Center

    Bricklin, Barry

    1975-01-01

    Three subjects were used in a role playing study based on the subject's own Rorschach responses. The results proved to be valuable as an aspect of therapeutic involvement. Results also help to expand and clarify the psychological meaning of Rorschach images. (Author/DEP)

  11. The Growing Culture of Nature Play

    ERIC Educational Resources Information Center

    Wood, Melody

    2013-01-01

    The importance of nature-based play has gradually become forefront in an array of research fields. From the more obvious physical benefits to the complex mental benefits, nature has proved time and time again to be the cure-all for a variety of common ailments. Richard Louv, author of the famed "Last Child in the Woods," has spawned a…

  12. Putting Play Back into the Playground

    ERIC Educational Resources Information Center

    Couper, Llyween

    2011-01-01

    During 2008 and 2009, a group of nine Resource Teachers: Learning and Behaviour (RTLB) from Canterbury met as a Community of Practice to investigate the way that play in the school playground contributes to the social competence of students. While the original concern was around the needs of students who were unable to manage their behaviour in…

  13. Problem Solvers: Solutions--Playing Basketball

    ERIC Educational Resources Information Center

    Smith, Jeffrey

    2014-01-01

    In this article, fourth grade Upper Allen Elementary School (Mechanicsburg, Pennsylvania) teacher Jeffrey Smith describes his exploration of the Playing Basketball activity. Herein he describes how he found the problem to be an effective way to review concepts associated with the measurement of elapsed time with his students. Additionally, it…

  14. Preschool Teachers' Language Use in Sociodramatic Play

    ERIC Educational Resources Information Center

    Meacham, Sohyun

    2013-01-01

    Preschool teachers' language use has been described in recent research, as preschoolers' language development is found to be an important preparation for later reading development. Based on existing research on teachers' language use in sociodramatic play, however, it is still unclear how teachers use their language specifically in sociodramatic…

  15. HARPERS FERRY, A PLAY ABOUT JOHN BROWN.

    ERIC Educational Resources Information Center

    STAVIS, BARRIE

    THIS PLAY IS A DRAMATIC RENDERING OF JOHN BROWN'S ATTACK ON THE ARMORY AT HARPERS FERRY AND HIS SUBSEQUENT TRIAL FOR TREASON. ALTHOUGH IT ADHERES TO THE FACTS OF HISTORY, THEY ARE NOT TREATED REALISTICALLY. "HARPERS FERRY" PORTRAYS BROWN AS POSSESSING A PURE IDEALISM UNTAINTED IN THE SLIGHTEST DEGREE BY MATERIALISM OR SELF-SEEKING, WHICH…

  16. Gaming: Eat Breakfast, Drink Milk, Play Xbox

    ERIC Educational Resources Information Center

    O'Hanlon, Charlene

    2007-01-01

    Plagued by one of the most overweight populaces in the country, the state of West Virginia was looking for a solution to its obesity problem that would appeal to the school-age crowd. It turned to Linda Carson, a professor at West Virginia University's School of Physical Education. Carson recalled witnessing kids lining up in an arcade to play a…

  17. Library Media Learning and Play Center.

    ERIC Educational Resources Information Center

    Faber, Therese; And Others

    Preschool educators developed a library media learning and play center to enable children to "experience" a library; establish positive attitudes about the library; and encourage respect for self, others, and property. The center had the following areas: check-in and check-out desk, quiet reading section, computer center, listening center, video…

  18. Sales Role Play: An Online Simulation

    ERIC Educational Resources Information Center

    Newberry, Robert; Collins, Marianne

    2017-01-01

    The online role play simulation as described in this article addresses critical skills as identified by practitioners and includes background materials, buyer and seller profiles, a sale/no-sale decision matrix, as well as a grading rubric, thereby facilitating a variety of selling scenarios. Both the buyer and the seller have integral roles in…

  19. Children's Spontaneous Vocalisations during Play: Aesthetic Dimensions

    ERIC Educational Resources Information Center

    Countryman, June; Gabriel, Martha; Thompson, Katherine

    2016-01-01

    This paper explores the phenomenon of spontaneous vocalisations in the self-chosen, unstructured outdoor play of children aged 3-12. Spontaneous vocalisations encompass the whole range of children's unprompted, natural, expressive vocal soundings beyond spoken language. Non-participant observations at childcare centres and on elementary school…

  20. Using Role Play To Develop Cultural Competence.

    ERIC Educational Resources Information Center

    Shearer, Ruth; Davidhizar, Ruth

    2003-01-01

    Role playing is a useful method for teaching cultural competence in nurse-patient situations. Successful implementation depends on identification of objectives and grading criteria, adequate time, guidelines for role specifications, monitoring of the process, delineation of the relationship to theory, and facilitation of constructive analysis.…