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Sample records for polimorfismo da apoe

  1. [ApoE polymorphisms and dopaminergic replacement therapy in Parkinson's disease].

    PubMed

    Cervantes-Arriaga, Amin; Rodríguez-Violante, Mayela; González-Latapí, Paulina; Dávila-Ortiz de Montellano, David José; Yescas, Petra; Alonso-Vilatela, Elisa

    2014-01-01

    INTRODUCCIÓN: se ha propuesto que la expresión de los polimorfismos de la apolipoproteína E (apoE) es un factor predisponente para el desarrollo temprano de psicosis en los pacientes con enfermedad de Parkinson. La relación entre el genotipo de la apoE y el desarrollo de complicaciones motoras es controvertida. El objetivo de esta investigación fue determinar la relación entre los polimorfismos de la apoE y su frecuencia alélica y el desarrollo de complicaciones secundarias al reemplazo dopaminérgico. MÉTODOS: se evaluaron 231 pacientes con diagnóstico de enfermedad de Parkinson. La presencia de complicaciones fue determinada por un neurólogo y se realizó la genotipificación de los polimorfismos de la apoE. Se utilizó la chi cuadrada para determinar la relación entre la presencia o ausencia de las complicaciones estudiadas y el genotipo de la apoE.

  2. Students', Guardians', and Teachers' Perceptions of Student-Led Conferences

    ERIC Educational Resources Information Center

    Orso, Charlotte Lindsey

    2013-01-01

    The purpose of the study was to examine the ELL and non-ELL students', guardians', and the English as a second language (ESL) teachers' perceptions of student-led conferences. Specifically, the study examined if ELL students' and guardians' preferences were similar to non-ELL students' and guardians' preferences…

  3. ApoE (Apolipoprotein E) Genotyping

    MedlinePlus

    ... There are no clear-cut tests to diagnose Alzheimer disease during life. Health practitioners can, however, make a reasonably accurate clinical diagnosis of AD by ruling out other potential causes of dementia and checking for a genetic predisposition to AD with APOE genotyping as supplemental ...

  4. Parents' Views of Schools' Involvement Efforts

    ERIC Educational Resources Information Center

    Rodriguez, Raymond J.; Blatz, Erin T.; Elbaum, Batya

    2014-01-01

    Individual and focus group interviews were conducted with 96 parents of students with disabilities in 18 schools to explore parents' views of schools' efforts to engage them in their child's education. A mixed-methods approach was used to identify and evaluate the relative importance of eight themes related to schools' efforts…

  5. APOE Genotyping, Cardiovascular Disease

    MedlinePlus

    ... Risk Assessment ; HDL Cholesterol ; LDL Cholesterol ; Lipid Profile ; Triglycerides Were you looking instead for APOE genotyping ordered ... the skin called xanthomas, a high level of triglycerides in the blood, and atherosclerosis that develops at ...

  6. ApoE isoform-dependent changes in hippocampal synaptic function.

    PubMed

    Korwek, Kimberly M; Trotter, Justin H; Ladu, Mary Jo; Sullivan, Patrick M; Weeber, Edwin J

    2009-05-27

    The lipoprotein receptor system in the hippocampus is intimately involved in the modulation of synaptic transmission and plasticity. The association of specific apoE isoform expression with human neurodegenerative disorders has focused attention on the role of these apoE isoforms in lipoprotein receptor-dependent synaptic modulation. In the present study, we used the apoE2, apoE3 and apoE4 targeted replacement (TR) mice along with recombinant human apoE isoforms to determine the role of apoE isoforms in hippocampus area CA1 synaptic function. While synaptic transmission is unaffected by apoE isoform, long-term potentiation (LTP) is significantly enhanced in apoE4 TR mice versus apoE2 TR mice. ApoE isoform-dependent differences in LTP induction require NMDA-receptor function, and apoE isoform expression alters activation of both ERK and JNK signal transduction. Acute application of specific apoE isoforms also alters LTP induction while decreasing NMDA-receptor mediated field potentials. Furthermore, acute apoE isoform application does not have the same effects on ERK and JNK activation. These findings demonstrate specific, isoform-dependent effects of human apoE isoforms on adult hippocampus synaptic plasticity and highlight mechanistic differences between chronic apoE isoform expression and acute apoE isoform exposure.

  7. HtrA1 Proteolysis of ApoE In Vitro Is Allele Selective.

    PubMed

    Chu, Qian; Diedrich, Jolene K; Vaughan, Joan M; Donaldson, Cynthia J; Nunn, Michael F; Lee, Kuo-Fen; Saghatelian, Alan

    2016-08-01

    Apolipoprotein E (ApoE) belongs to a large class of proteins that solubilize lipids for physiological transport. Humans have three different APOE alleles, APOE ε2, APOE ε3, and APOE ε4, and genetic studies identified ApoE4 as the strongest genetic risk factor for Alzheimer's disease (AD). People who are homozygous for ApoE4 (i.e., ApoE4/E4) are an order of magnitude more likely to develop late-onset AD (LOAD) than ApoE3/E3 carriers. Several differences between ApoE3 and ApoE4 may contribute to AD including the observation that ApoE4 is degraded to a greater extent than ApoE3 in the human brain. Experiments with high-temperature requirement serine peptidase A1 (HtrA1), which is found in the nervous system, demonstrate that HtrA1 is an allele-selective ApoE-degrading enzyme that degrades ApoE4 more quickly than ApoE3. This activity is specific to HtrA1, as similar assays with HtrA2 showed minimal ApoE4 proteolysis and trypsin had no preference between ApoE4 and ApoE3. HtrA1 has also been reported to cleave the tau protein (Tau) and the amyloid protein precursor (APP) to hinder the formation of toxic amyloid deposits associated with AD. Competition assays with ApoE4, ApoE3, and Tau revealed that ApoE4 inhibits Tau degradation. Thus, the identification of ApoE4 as an in vitro HtrA1 substrate suggests a potential biochemical mechanism that links ApoE4 regulation of AD proteins such as Tau.

  8. Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer's disease pathogenesis.

    PubMed

    Zhu, Li; Zhong, Minghao; Elder, Gregory A; Sano, Mary; Holtzman, David M; Gandy, Sam; Cardozo, Christopher; Haroutunian, Vahram; Robakis, Nikolaos K; Cai, Dongming

    2015-09-22

    The apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for developing sporadic Alzheimer's disease (AD). However, the mechanisms underlying the pathogenic nature of ApoE4 are not well understood. In this study, we have found that ApoE proteins are critical determinants of brain phospholipid homeostasis and that the ApoE4 isoform is dysfunctional in this process. We have found that the levels of phosphoinositol biphosphate (PIP2) are reduced in postmortem human brain tissues of ApoE4 carriers, in the brains of ApoE4 knock-in (KI) mice, and in primary neurons expressing ApoE4 alleles compared with those levels in ApoE3 counterparts. These changes are secondary to increased expression of a PIP2-degrading enzyme, the phosphoinositol phosphatase synaptojanin 1 (synj1), in ApoE4 carriers. Genetic reduction of synj1 in ApoE4 KI mouse models restores PIP2 levels and, more important, rescues AD-related cognitive deficits in these mice. Further studies indicate that ApoE4 behaves similar to ApoE null conditions, which fails to degrade synj1 mRNA efficiently, unlike ApoE3 does. These data suggest a loss of function of ApoE4 genotype. Together, our data uncover a previously unidentified mechanism that links ApoE4-induced phospholipid changes to the pathogenic nature of ApoE4 in AD.

  9. Roles of apolipoprotein E4 (ApoE4) in the pathogenesis of Alzheimer's disease: lessons from ApoE mouse models.

    PubMed

    Huang, Yadong

    2011-08-01

    ApoE4 (apolipoprotein E4) is the major known genetic risk factor for AD (Alzheimer's disease). In most clinical studies, apoE4 carriers account for 65-80% of all AD cases, highlighting the importance of apoE4 in AD pathogenesis. Emerging data suggest that apoE4, with its multiple cellular origins and multiple structural and biophysical properties, contributes to AD in multiple ways either independently or in combination with other factors, such as Aβ (amyloid β-peptide) and tau. Many apoE mouse models have been established to study the mechanisms underlying the pathogenic actions of apoE4. These include transgenic mice expressing different apoE isoforms in neurons or astrocytes, those expressing neurotoxic apoE4 fragments in neurons and human apoE isoform knock-in mice. Since apoE is expressed in different types of cells, including astrocytes and neurons, and in brains under diverse physiological and/or pathophysiological conditions, these apoE mouse models provide unique tools to study the cellular source-dependent roles of apoE isoforms in neurobiology and in the pathogenesis of AD. They also provide useful tools for discovery and development of drugs targeting apoE4's detrimental effects.

  10. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor.

    PubMed Central

    Kischkel, F C; Hellbardt, S; Behrmann, I; Germer, M; Pawlita, M; Krammer, P H; Peter, M E

    1995-01-01

    APO-1 (Fas/CD95), a member of the tumor necrosis factor receptor superfamily, induces apoptosis upon receptor oligomerization. In a search to identify intracellular signaling molecules coupling to oligomerized APO-1, several cytotoxicity-dependent APO-1-associated proteins (CAP) were immunoprecipitated from the apoptosis-sensitive human leukemic T cell line HUT78 and the lymphoblastoid B cell line SKW6.4. CAP1-3 (27-29 kDa) and CAP4 (55 kDa), instantly detectable after the crosslinking of APO-1, were associated only with aggregated (the signaling form of APO-1) and not with monomeric APO-1. CAP1 and CAP2 were identified as serine phosphorylated MORT1/FADD. The association of CAP1-4 with APO-1 was not observed with C-terminally truncated non-signaling APO-1. In addition, CAP1 and CAP2 did not associate with an APO-1 cytoplasmic tail carrying the lprcg amino acid replacement. Moreover, no APO-1-CAP association was found in the APO-1+, anti-APO-1-resistant pre-B cell line Boe. Our data suggest that in vivo CAP1-4 are the APO-1 apoptosis-transducing molecules. Images PMID:8521815

  11. VEGF Mediates ApoE4-Induced Neovascularization and Synaptic Pathology in the Choroid and Retina.

    PubMed

    Antes, Ran; Salomon-Zimri, Shiran; Beck, Susanne C; Garcia Garrido, Marina; Livnat, Tami; Maharshak, Idit; Kadar, Tamar; Seeliger, Mathias; Weinberger, Dov; Michaelson, Daniel M

    2015-01-01

    Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. Recent findings suggest that retina of apoE4 mice have synaptic and functional impairments. We presently investigated the effects of apoE4 on retinal and choroidal vasculature and the possible role of VEGF in these effects. There were no histological differences between the retinal and choroidal vasculatures of naïve apoE3 and apoE4 mice. In contrast, laserdriven choroidal injury induced higher levels of choroidal neovascularization (CNV) in apoE4 than in apoE3 mice. These effects were associated with an inflammatory response and with activation of the Muller cells and asrocytic markers gluthatione synthetase and GFAP, all of which were more pronounced in the apoE4 mice. CNV also induced a transient increase in the levels of the synaptic markers synaptophysin and PSD95 which were however similar in the apoE4 and apoE3 naive mice. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation and the associated surge in VEGF following injury. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation

  12. No association between ApoE polymorphism and febrile seizures.

    PubMed

    Lavenex, Pierre; Lavenex, Pamela Banta; Cachat, François; Gehri, Mario; Juvet, Typhaine

    2016-01-01

    Seizures associated with fever are a common pediatric problem, affecting about 2-7 % of children between 3 months and 5 years of age. Differentiation of febrile seizures from acute symptomatic seizures secondary to central nervous system infections or seizures associated with fever in children with epilepsy is essential to provide appropriate treatment and follow-up care. Here, we tested the hypothesis that children who exhibit simple febrile seizures during early childhood, but do not develop epileptic seizures later in life, might preferentially carry the ApoE2 allele of the gene coding for the apolipoprotein E. We did not find any differences in the distribution of ApoE alleles or genotypes between individuals who exhibited simple febrile seizures (n = 93) and age-matched, typically developing subjects (n = 80). We found that the observed allele and genotype frequencies did not deviate from Hardy-Weinberg equilibrium, which suggests that the frequencies of ApoE alleles and genotypes are stable in the Swiss population from which our samples were derived. Across both groups of subjects (n = 173), we found an ApoE2 allele frequency of 0.064, an ApoE3 frequency of 0.829 and an ApoE4 frequency of 0.107. Our findings are consistent with previous reports of the distribution of ApoE polymorphism for European subjects free of any neurological disorders, and show that the different alleles of the gene coding for the apolipoprotein E are not associated with the occurrence of simple febrile seizures. PMID:26233231

  13. An Anti-apoE4 Specific Monoclonal Antibody Counteracts the Pathological Effects of apoE4 In Vivo.

    PubMed

    Luz, Ishai; Liraz, Ori; Michaelson, Daniel M

    2016-06-01

    ApolipoproteinE4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD) and as such is a promising therapeutic target. This study examined the extent to which the pathological effects of apoE4 can be counteracted in vivo utilizing an immunological approach in which anti-apoE4 antibodies are applied peripherally by i.p. injections into apoE4-targeted replacement mice. Prerequisites for the successful pursuit of this objective are the availability of antibodies that specifically bind brain apoE4 and not apoE3, and demonstrating that direct application of these antibodies into the brain can counteract the effects of apoE4. Accordingly, it was shown that the antiapoE4 monoclonal antibody (mAb) 9D11 binds specifically to brain apoE4 and not apoE3. Direct i.c.v. application of mAb 9D11 prevented the apoE4-driven accumulation of Aβ in hippocampal neurons following activation of the amyloid cascade by inhibiting the Aβ-degrading enzyme neprilysin. These findings provide a proof-of-concept that anti-apoE4 mAb 9D11, when introduced into the brain, can counteract the apoE4 effects in vivo. Subsequent experiments, utilizing repeated i.p. injections of mAb 9D11, resulted in the formation of apoE/IgG complexes specifically in apoE4 mice. This was associated with reversal of the cognitive impairments of apoE4 in the Morris water maze and the novel object recognition test as well as with reversal of key apoE4-driven pathologies including the hyperphosphorylated tau and the reduced levels of the apoER2 receptor. These results indicate that anti-apoE4 immunotherapy counteracts the cognitive and brain pathological effects of apoE4, and suggest that such an approach could also benefit human apoE4 carriers.

  14. S-Nitrosylation of ApoE in Alzheimer’s Disease

    PubMed Central

    Abrams, Alexander J.; Farooq, Amjad; Wang, Gaofeng

    2011-01-01

    The mechanism by which apolipoprotein E (ApoE) isoforms functionally influence the risk and progression of late-onset Alzheimer’s disease (LOAD) remains hitherto unknown. Herein, we present evidence that all ApoE isoforms bind to nitric oxide synthase 1 (NOS1) and that such protein-protein interaction results in S-nitrosylation of ApoE2 and ApoE3 but not ApoE4. Our structural analysis at atomic level reveals that S-nitrosylation of ApoE2 and ApoE3 proteins may lead to conformational changes resulting in the loss of binding to low-density lipoprotein (LDL) receptors. Collectively, our data suggest that S-nitrosylation of ApoE proteins may play an important role in regulating lipid metabolism and in the pathogenesis of LOAD. PMID:21443265

  15. Impaired Autophagy in APOE4 Astrocytes.

    PubMed

    Simonovitch, Shira; Schmukler, Eran; Bespalko, Alina; Iram, Tal; Frenkel, Dan; Holtzman, David M; Masliah, Eliezer; Michaelson, Danny M; Pinkas-Kramarski, Ronit

    2016-01-01

    Alzheimer's disease (AD) is the most prevalent form of dementia in elderly. Genetic studies revealed allelic segregation of the apolipoprotein E (ApoE) gene in sporadic AD and in families with higher risk of AD. The mechanisms underlying the pathological effects of ApoE4 are not yet entirely clear. Several studies indicate that autophagy, which plays an important role in degradation pathways of proteins, organelles and protein aggregates, may be impaired in AD. In the present study, we investigated the effects of ApoE4 versus the ApoE3 isoform on the process of autophagy in mouse-derived astrocytes. The results obtained reveal that under several autophagy-inducing conditions, astrocytes expressing ApoE4 exhibit lower autophagic flux compared to astrocytes expressing ApoE3. Using an in situ model, we examined the role of autophagy and the effects thereon of ApoE4 in the elimination of Aβ plaques from isolated brain sections of transgenic 5xFAD mice. This revealed that ApoE4 astrocytes eliminate Aβ plaques less effectively than the corresponding ApoE3 astrocytes. Additional experiments showed that the autophagy inducer, rapamycin, enhances Aβ plaque degradation by ApoE4 astrocytes whereas the autophagy inhibitor, chloroquine, blocks Aβ plaque degradation by ApoE3 astrocytes. Taken together, these findings show that ApoE4 impairs autophagy in astrocyte cultures and that this effect is associated with reduced capacity to clear Aβ plaques. This suggests that impaired autophagy may play a role in mediating the pathological effects of ApoE4 in AD.

  16. Gove's War

    ERIC Educational Resources Information Center

    Yarker, Patrick

    2013-01-01

    Policy pursued by Education Secretary Michael Gove promises to bring about the first national teachers' strike for a generation. This article reviews the nature and effect of Gove's intensification of academisation, and outlines ways in which edu-business is involved.

  17. Deleuze's Children

    ERIC Educational Resources Information Center

    Hickey-Moody, Anna Catherine

    2013-01-01

    Children, the image of the child, and the gendered figures of the girl and the boy are thematics that run through the work of Deleuze and feature prominently in his joint writing with Guattari. However, there are many different children in Deleuze's writings. Various child figures do distinct things in Deleuze's work. In this article, I…

  18. ApoE: In Vitro Studies of a Small Molecule Effector.

    PubMed

    Mondal, Tridib; Wang, Hanliu; DeKoster, Gregory T; Baban, Berevan; Gross, Michael L; Frieden, Carl

    2016-05-10

    Apolipoprotein E4 (apoE4), one of three isoforms of apoE, is the major risk factor for developing late onset Alzheimer's disease. The only differences among these isoforms (apoE2, apoE3, and apoE4) are single amino acid changes. Yet these proteins are functionally very different. One approach to ameliorating the effect of apoE4 with respect to Alzheimer's disease would be to find small molecular weight compounds that affect the behavior of apoE4. Few studies of this approach have been carried out in part because there was no complete structure of any full-length apoE isoform until 2011. Here, we focus on one small molecular weight compound, EZ-482, and explore the effects of its binding to apoE. Using hydrogen-deuterium exchange, we determined that EZ-482 binds to the C-terminal domains of both apoE3 and apoE4. The binding to apoE4, however, is accompanied by a unique N-terminal allosteric effect. Using fluorescence methods, we determined an apparent dissociation constant of approximately 8 μM. Although EZ-482 binds to the C-terminal domain, it blocks heparin binding to the N-terminal domain. The residues of apoE that bind heparin are the same as those involved in apoE binding to LDL and LRP-1 receptors. The methods and the data presented here may serve as a template for future studies using small molecular weight compounds to modulate the behavior of apoE.

  19. ApoE4 induces Aβ42, tau, and neuronal pathology in the hippocampus of young targeted replacement apoE4 mice

    PubMed Central

    2013-01-01

    Background Recent findings suggest that the pathological effects of apoE4, the most prevalent genetic risk factor for Alzheimer’s disease (AD), start many years before the onset of the disease and are already detectable at a young age. In the present study we investigated the extent to which such pathological and cognitive impairments also occur in young apoE4 mice. Results This study revealed that the levels of the presynaptic glutamatergic vesicular transporter, VGlut, in the CA3, CA1, and DG hippocampal subfields were lower in hippocampal neurons of young (4-month-old) apoE4-targeted replacement mice than in those of the apoE3 mice. In contrast, the corresponding inhibitory GABAergic nerve terminals and perikarya were not affected by apoE4. This synaptic effect was associated with hyperphosphorylation of tau in these neurons. In addition, apoE4 increased the accumulation of neuronal Aβ42 and induced mitochondrial changes, both of which were specifically pronounced in CA3 neurons. Spatial navigation behavioral studies revealed that these hippocampal pathological effects of apoE4 are associated with corresponding behavioral impairments. Time-course studies revealed that the effects of apoE4 on tau hyperphosphorylation and the mitochondria were already apparent at the age of 1 month and that the apoE4-driven accumulation of neuronal Aβ and reduced VGlut levels evolve later and are apparent at the age of 2–4 months. Furthermore, the levels of tau phosphorylation decrease in apoE3 mice and increase in apoE4 mice between 1 and 4 months, whereas the levels of Aβ42 decrease in apoE3 mice and are not affected in apoE4 mice over the same time period. Conclusions These findings show that apoE4 stimulates the accumulation of Aβ42 and hyperphosphorylated tau and reduces the levels of VGlut in hippocampal neurons of young apoE4-targeted replacement mice and that these neurochemical effects are associated with cognitive impairments. This model is not associated with

  20. ApoE4 induces synaptic and ERG impairments in the retina of young targeted replacement apoE4 mice.

    PubMed

    Antes, Ran; Ezra-Elia, Raaya; Weinberger, Dov; Solomon, Arie; Ofri, Ron; Michaelson, Daniel M

    2013-01-01

    The vertebrate retina, which is part of the central nervous system, is a window into the brain. The present study investigated the extent to which the retina can be used as a model for studying the pathological effects of apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD). Immunohistochemical studies of retinas from young (4 months old) apoE4-targeted replacement mice and from corresponding mice which express the AD benign apoE3 allele, revealed that the density of the perikarya of the different classes of retinal neurons was not affected by apoE4. In contrast, the synaptic density of the retinal synaptic layers, which was assessed immunohistochemically and by immunoblot experiments, was significantly lower in the apoE4 than in the apoE3 mice. This was associated with reduced levels of the presynaptic vesicular glutamatergic transporter, VGluT1, but not of either the GABAergic vesicular transporter, VGaT, or the cholinergic vesicular transporter, VAChT, suggesting that the glutamatergic nerve terminals are preferentially affected by apoE4. In contrast, the post synaptic scaffold proteins PSD-95 and Gephyrin, which reside in excitatory and inhibitory synapses, respectively, were both elevated, and their ratio was not affected by apoE4. Electroretinogram (ERG) recordings revealed significant attenuation of mixed rod-cone responses in dark-adapted eyes of apoE4 mice. These findings suggest that the reduced ERG response in the apoE4 mice may be related to the observed decrease in the retinal nerve terminals and that the retina could be used as a novel model for non-invasive monitoring of the effects of apoE4 on the CNS.

  1. Effects of simulated heat waves on ApoE-/- mice.

    PubMed

    Wang, Chunling; Zhang, Shuyu; Tian, Ying; Wang, Baojian; Shen, Shuanghe

    2014-02-01

    The effects of simulated heat waves on body weight, body temperature, and biomarkers of cardiac function in ApoE-/- mice were investigated. Heat waves were simulated in a meteorological environment simulation chamber according to data from a heat wave that occurred in July 2001 in Nanjing, China. Eighteen ApoE-/- mice were divided into control group, heat wave group, and heat wave BH4 group. Mice in the heat wave and BH4 groups were exposed to simulated heat waves in the simulation chamber. Mice in BH4 group were treated with gastric lavage with BH4 2 h prior to heat wave exposure. Results showed that the heat waves did not significantly affect body weight or ET-1 levels. However, mice in the heat wave group had significantly higher rectal temperature and NO level and lower SOD activity compared with mice in the control group (p < 0.01), indicating that heat wave had negative effects on cardiac function in ApoE-/- mice. Gastric lavage with BH4 prior to heat wave exposure significantly reduced heat wave-induced increases in rectal temperature and decreases in SOD activity. Additionally, pretreatment with BH4 further increased NO level in plasma. Collectively, these beneficial effects demonstrate that BH4 may potentially mitigate the risk of coronary heart disease in mice under heat wave exposure. These results may be useful when studying the effects of heat waves on humans. PMID:24477215

  2. Effects of simulated heat waves on ApoE-/- mice.

    PubMed

    Wang, Chunling; Zhang, Shuyu; Tian, Ying; Wang, Baojian; Shen, Shuanghe

    2014-02-01

    The effects of simulated heat waves on body weight, body temperature, and biomarkers of cardiac function in ApoE-/- mice were investigated. Heat waves were simulated in a meteorological environment simulation chamber according to data from a heat wave that occurred in July 2001 in Nanjing, China. Eighteen ApoE-/- mice were divided into control group, heat wave group, and heat wave BH4 group. Mice in the heat wave and BH4 groups were exposed to simulated heat waves in the simulation chamber. Mice in BH4 group were treated with gastric lavage with BH4 2 h prior to heat wave exposure. Results showed that the heat waves did not significantly affect body weight or ET-1 levels. However, mice in the heat wave group had significantly higher rectal temperature and NO level and lower SOD activity compared with mice in the control group (p < 0.01), indicating that heat wave had negative effects on cardiac function in ApoE-/- mice. Gastric lavage with BH4 prior to heat wave exposure significantly reduced heat wave-induced increases in rectal temperature and decreases in SOD activity. Additionally, pretreatment with BH4 further increased NO level in plasma. Collectively, these beneficial effects demonstrate that BH4 may potentially mitigate the risk of coronary heart disease in mice under heat wave exposure. These results may be useful when studying the effects of heat waves on humans.

  3. Reversal of ApoE4-Driven Brain Pathology by Vascular Endothelial Growth Factor Treatment.

    PubMed

    Salomon-Zimri, Shiran; Glat, Micaela Johanna; Barhum, Yael; Luz, Ishai; Boehm-Cagan, Anat; Liraz, Ori; Ben-Zur, Tali; Offen, Daniel; Michaelson, Daniel M

    2016-06-30

    Apolipoprotein E4 (ApoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with increased neurodegeneration and vascular impairments. Vascular endothelial growth factor (VEGF), originally described as a key angiogenic factor, has recently been shown to play a crucial role in the nervous system. The objective of this research is to examine the role of VEGF in mediating the apoE4-driven pathologies. We show that hippocampal VEGF levels are lower in apoE4 targeted replacement mice compared to the corresponding apoE3 mice. This effect was accompanied by a specific decrease in both VEGF receptor-2 and HIF1-α. We next set to examine whether upregulation of VEGF can reverse apoE4-driven pathologies, namely the accumulation of hyperphosphorylated tau (AT8) and Aβ42, and reduced levels of the pre-synaptic marker, VGluT1, and of the ApoE receptor, ApoER2. This was first performed utilizing intra-hippocampal injection of VEGF-expressing-lentivirus (LV-VEGF). This revealed that LV-VEGF treatment reversed the apoE4-driven cognitive deficits and synaptic pathologies. The levels of Aβ42 and AT8, however, were increased in apoE3 mice, masking any potential effects of this treatment on the apoE4 mice. Follow-up experiments utilizing VEGF-expressing adeno-associated-virus (AAV-VEGF), which expresses VEGF specifically under the GFAP astrocytic promoter, prevented this effects on apoE3 mice, and reversed the apoE4-related increase in Aβ42 and AT8. Taken together, these results suggest that apoE4-driven pathologies are mediated by a VEGF-dependent pathway, resulting in cognitive impairments and brain pathology. These animal model findings suggest that the VEGF system is a promising target for the treatment of apoE4 carriers in AD.

  4. Altered neurotransmission in the lateral amygdala in aged human apoE4 targeted replacement mice.

    PubMed

    Klein, Rebecca C; Acheson, Shawn K; Mace, Brian E; Sullivan, Patrick M; Moore, Scott D

    2014-09-01

    The human APOE4 allele is associated with an early age of onset and increased risk of Alzheimer's disease (AD). Apolipoprotein E is secreted as part of a high-density lipoprotein-like particle by glial cells in the brain for the primary purpose of transport of lipophilic compounds involved in the maintenance of synapses. Previous studies examining synaptic integrity in the amygdala of human apoE targeted replacement (TR) mice showed a decrease in spontaneous excitatory synaptic activity, dendritic arbor, and spine density associated with apoE4 compared with apoE3 and apoE2 in adult male mice. In the present study, we assessed how APOE genotype affects synaptic integrity of amygdala neurons by comparing electrophysiological and morphometric properties in human apoE3, E4, and E2/4 TR mice at the age of 18-20 months. In contrast to adult mice, we found that aged apoE4 TR mice exhibited the highest level of excitatory synaptic activity compared with other cohorts. Additionally, apoE4 mice had significantly greater spontaneous inhibitory activity than all other cohorts. Taken together, there was a significant interaction between genotypes when comparing inhibition relative to excitation; there was a simple main effect of frequency type with an imbalance toward inhibition in apoE4 mice but not in apoE3 or apoE2/4 mice. These results suggest that apoE isoforms differentially influence synaptic transmission throughout the life span, where aging coupled with apoE4 expression, results in an imbalance in maintaining integrity of synaptic transmission.

  5. CSF Apo-E levels associate with cognitive decline and MRI changes

    PubMed Central

    Toledo, Jon B.; Da, Xiao; Weiner, Michael W.; Wolk, David A.; Xie, Sharon X.; Arnold, Steven E.; Davatzikos, Christos; Shaw, Leslie M.; Trojanowski, John Q.

    2014-01-01

    Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer’s disease (AD) and it is thought to do so by modulating levels of the its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD Neuroimaging Initiative (ADNI) subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and grey matter atrophy rate in total tau/Aβ1–42 ratio and APOE genotype adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance. PMID:24385135

  6. Characterization of the apoLp-III/LPS complex: insight in the mode of binding interaction

    PubMed Central

    Oztug, Merve; Martinon, Daisy; Weers, Paul M.M.

    2012-01-01

    Apolipoproteins are able to associate with lipopolysaccharides (LPS), potentially providing protection against septic shock. To gain insight in the molecular details of this binding interaction, apolipophorin III (apoLp-III) from Galleria mellonella was used as a model. The binding of apoLp-III to LPS was optimal around 37–40 °C, close to the LPS phase transition temperature. ApoLp-III formed complexes with LPS from E. coli (serotype O55:B5) with a diameter of 24 nm, a molecular weight of ~390 kDa, containing four molecules of apoLp-III and 24 molecules of LPS. The LPS-bound form of the protein was substantially more resistant to guanidine-induced denaturation compared to unbound protein. The denaturation profile displayed a multiphase character with a steep drop in secondary structure between 0–1 M guanidine, and a slower decrease above 1 M guanidine HCl. In contrast, apoLp-III bound to detoxified LPS was only slightly more resistant to guanidine HCl induced denaturation compared to unbound protein. Analysis of size-exclusion FPLC elution profiles of mixtures of apoLp-III with LPS or detoxified LPS indicated a much weaker binding interaction with detoxified LPS compared to intact LPS. These results indicate that apoLp-III initially interacts with exposed carbohydrate regions, but that the lipid A region is required for a more stable LPS binding interaction. PMID:22779761

  7. The Effect of a High-Fat Diet on Brain Plasticity, Inflammation and Cognition in Female ApoE4-Knockin and ApoE-Knockout Mice

    PubMed Central

    Janssen, Carola I. F.; Jansen, Diane; Mutsaers, Martina P. C.; Dederen, Pieter J. W. C.; Geenen, Bram; Mulder, Monique T.; Kiliaan, Amanda J.

    2016-01-01

    Apolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against high-fat (HF) diet induced neurodegeneration by its role in the maintenance of the integrity of the blood-brain barrier. The influence of a HF diet on the progression of AD-like cognitive and neuropathological changes was assessed in wild-type (WT), human ApoE4 and ApoE-knockout (ApoE-/-) mice to evaluate the modulatory role of ApoE in this process. From 12 months of age, female WT, ApoE4, and ApoE-/- mice were fed either a standard or a HF diet (19% butter, 0.5% cholate, 1.25% cholesterol) throughout life. At 15 months of age mice performed the Morris water maze, evaluating spatial learning and memory. ApoE-/- showed increased spatial learning compared to WT mice (p = 0.009). HF diet improved spatial learning in WT mice (p = 0.045), but did not affect ApoE4 and ApoE-/- mice. Immunohistochemical analyses of the hippocampus demonstrated increased neuroinflammation (CD68) in the cornu ammonis 1 (CA1) region in ApoE4 (p = 0.001) and in ApoE-/- (p = 0.032) mice on standard diet. HF diet tended to increase CD68 in the CA1 in WT mice (p = 0.052), while it decreased in ApoE4 (p = 0.009), but ApoE-/- remained unaffected. A trend towards increased neurogenesis (DCX) was found in both ApoE4 (p = 0.052) and ApoE-/- mice (p = 0.068). In conclusion, these data suggest that HF intake induces different effects in WT mice compared to ApoE4 and ApoE-/- with respect to markers for cognition and neurodegeneration. We propose that HF intake inhibits the compensatory mechanisms of neuroinflammation and neurogenesis in aged female ApoE4 and ApoE-/- mice. PMID:27171180

  8. The Effect of a High-Fat Diet on Brain Plasticity, Inflammation and Cognition in Female ApoE4-Knockin and ApoE-Knockout Mice.

    PubMed

    Janssen, Carola I F; Jansen, Diane; Mutsaers, Martina P C; Dederen, Pieter J W C; Geenen, Bram; Mulder, Monique T; Kiliaan, Amanda J

    2016-01-01

    Apolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against high-fat (HF) diet induced neurodegeneration by its role in the maintenance of the integrity of the blood-brain barrier. The influence of a HF diet on the progression of AD-like cognitive and neuropathological changes was assessed in wild-type (WT), human ApoE4 and ApoE-knockout (ApoE-/-) mice to evaluate the modulatory role of ApoE in this process. From 12 months of age, female WT, ApoE4, and ApoE-/- mice were fed either a standard or a HF diet (19% butter, 0.5% cholate, 1.25% cholesterol) throughout life. At 15 months of age mice performed the Morris water maze, evaluating spatial learning and memory. ApoE-/- showed increased spatial learning compared to WT mice (p = 0.009). HF diet improved spatial learning in WT mice (p = 0.045), but did not affect ApoE4 and ApoE-/- mice. Immunohistochemical analyses of the hippocampus demonstrated increased neuroinflammation (CD68) in the cornu ammonis 1 (CA1) region in ApoE4 (p = 0.001) and in ApoE-/- (p = 0.032) mice on standard diet. HF diet tended to increase CD68 in the CA1 in WT mice (p = 0.052), while it decreased in ApoE4 (p = 0.009), but ApoE-/- remained unaffected. A trend towards increased neurogenesis (DCX) was found in both ApoE4 (p = 0.052) and ApoE-/- mice (p = 0.068). In conclusion, these data suggest that HF intake induces different effects in WT mice compared to ApoE4 and ApoE-/- with respect to markers for cognition and neurodegeneration. We propose that HF intake inhibits the compensatory mechanisms of neuroinflammation and neurogenesis in aged female ApoE4 and ApoE-/- mice. PMID:27171180

  9. The Effect of a High-Fat Diet on Brain Plasticity, Inflammation and Cognition in Female ApoE4-Knockin and ApoE-Knockout Mice.

    PubMed

    Janssen, Carola I F; Jansen, Diane; Mutsaers, Martina P C; Dederen, Pieter J W C; Geenen, Bram; Mulder, Monique T; Kiliaan, Amanda J

    2016-01-01

    Apolipoprotein E4 (ApoE4), one of three common isoforms of ApoE, is a major risk factor for late-onset Alzheimer disease (AD). ApoE-deficient mice, as well as mice expressing human ApoE4, display impaired learning and memory functions and signs of neurodegeneration. Moreover, ApoE protects against high-fat (HF) diet induced neurodegeneration by its role in the maintenance of the integrity of the blood-brain barrier. The influence of a HF diet on the progression of AD-like cognitive and neuropathological changes was assessed in wild-type (WT), human ApoE4 and ApoE-knockout (ApoE-/-) mice to evaluate the modulatory role of ApoE in this process. From 12 months of age, female WT, ApoE4, and ApoE-/- mice were fed either a standard or a HF diet (19% butter, 0.5% cholate, 1.25% cholesterol) throughout life. At 15 months of age mice performed the Morris water maze, evaluating spatial learning and memory. ApoE-/- showed increased spatial learning compared to WT mice (p = 0.009). HF diet improved spatial learning in WT mice (p = 0.045), but did not affect ApoE4 and ApoE-/- mice. Immunohistochemical analyses of the hippocampus demonstrated increased neuroinflammation (CD68) in the cornu ammonis 1 (CA1) region in ApoE4 (p = 0.001) and in ApoE-/- (p = 0.032) mice on standard diet. HF diet tended to increase CD68 in the CA1 in WT mice (p = 0.052), while it decreased in ApoE4 (p = 0.009), but ApoE-/- remained unaffected. A trend towards increased neurogenesis (DCX) was found in both ApoE4 (p = 0.052) and ApoE-/- mice (p = 0.068). In conclusion, these data suggest that HF intake induces different effects in WT mice compared to ApoE4 and ApoE-/- with respect to markers for cognition and neurodegeneration. We propose that HF intake inhibits the compensatory mechanisms of neuroinflammation and neurogenesis in aged female ApoE4 and ApoE-/- mice.

  10. The effects of the apoE4 genotype on the developing mouse retina.

    PubMed

    Maharshak, Idit; Salomon-Zimri, Shiran; Antes, Ran; Liraz, Ori; Nisgav, Yael; Livnat, Tami; Weinberger, Dov; Colton, Carol A; Solomon, Arieh S; Michaelson, Daniel M

    2016-04-01

    Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. The retina, which is as an extension of the central nervous system (CNS), is a particularly suitable model for studying developmental and functional aspects of the neuronal and vascular systems. This study investigates the apoE4-dependent developmental effects on the retinal vasculature and neuronal systems and on the levels of apoE and the vascular endothelial growth factor (VEGF) in the retina. This was performed utilizing retinas of 4, 7, 12, and of 120-day-old human-apoE4-targeted replacement mice and of corresponding mice that express the AD benign isoform, apoE3. The results obtained revealed retinal vascular pathology in the apoE4 mice, which started on the early post-natal days. This includes transient increase in vascular branching, and vascular buds which are round vascular elements representing sprouting or retracting vessels. These effects peaked and ended during the neonatal period. Examination of the synaptic system utilizing the pre-synaptic marker synaptophysin revealed a significant decrease of retinal synaptic density in the apoE4 mice, which was detectable by post-natal day 12 (P12). These morphological changes are associated with neonatal age-dependent elevation in the apoE levels in both apoE3 and apoE4 retinas which is more profound in the apoE4 mice and a corresponding increase in VEGF levels, which is less profound in the apoE4 mice. Additionally, we observed lower levels of retinal VEGF in the apoE4 mice compared to the apoE3 mice retinas on P12. These results show that apoE4 has a transient vascular effect during retinal development that ends in the neonatal period, which is accompanied by a synaptic effect that begins at the end of the neonatal period. These findings show that the apoE4 genotype can have distinct developmental effects on both the retinal vasculature and on neurons and

  11. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations.

    PubMed

    Williams, Benfeard; Convertino, Marino; Das, Jhuma; Dokholyan, Nikolay V

    2015-10-01

    The increased risk of developing Alzheimer's disease (AD) is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD.

  12. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations

    PubMed Central

    Williams II, Benfeard; Convertino, Marino; Das, Jhuma; Dokholyan, Nikolay V.

    2015-01-01

    The increased risk of developing Alzheimer’s disease (AD) is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD. PMID:26506597

  13. The role of APOE in cerebrovascular dysfunction.

    PubMed

    Tai, Leon M; Thomas, Riya; Marottoli, Felecia M; Koster, Kevin P; Kanekiyo, Takahisa; Morris, Alan W J; Bu, Guojun

    2016-05-01

    The ε4 allele of the apolipoprotein E gene (APOE4) is associated with cognitive decline during aging, is the greatest genetic risk factor for Alzheimer's disease and has links to other neurodegenerative conditions that affect cognition. Increasing evidence indicates that APOE genotypes differentially modulate the function of the cerebrovasculature (CV), with apoE and its receptors expressed by different cell types at the CV interface (astrocytes, pericytes, smooth muscle cells, brain endothelial cells). However, research on the role of apoE in CV dysfunction has not advanced as quickly as other apoE-modulated pathways. This review will assess what aspects of the CV are modulated by APOE genotypes during aging and under disease states, discuss potential mechanisms, and summarize the therapeutic significance of the topic. We propose that APOE4 induces CV dysfunction through direct signaling at the CV, and indirectly via modulation of peripheral and central pathways. Further, that APOE4 predisposes the CV to damage by, and exacerbates the effects of, additional risk factors (such as sex, hypertension, and diabetes). ApoE4-induced detrimental CV changes include reduced cerebral blood flow (CBF), modified neuron-CBF coupling, increased blood-brain barrier leakiness, cerebral amyloid angiopathy, hemorrhages and disrupted transport of nutrients and toxins. The apoE4-induced detrimental changes may be linked to pericyte migration/activation, astrocyte activation, smooth muscle cell damage, basement membrane degradation and alterations in brain endothelial cells. PMID:26884068

  14. apoE3[K146N/R147W] acts as a dominant negative apoE form that prevents remnant clearance and inhibits the biogenesis of HDL.

    PubMed

    Fotakis, Panagiotis; Vezeridis, Alexander; Dafnis, Ioannis; Chroni, Angeliki; Kardassis, Dimitris; Zannis, Vassilis I

    2014-07-01

    The K146N/R147W substitutions in apoE3 were described in patients with a dominant form of type III hyperlipoproteinemia. The effects of these mutations on the in vivo functions of apoE were studied by adenovirus-mediated gene transfer in different mouse models. Expression of the apoE3[K146N/R147W] mutant in apoE-deficient (apoE(-/-)) or apoA-I-deficient (apoA-I(-/-))×apoE(-/-) mice exacerbated the hypercholesterolemia and increased plasma apoE and triglyceride levels. In apoE(-/-) mice, the apoE3[K146N/R147W] mutant displaced apoA-I from the VLDL/LDL/HDL region and caused the accumulation of discoidal apoE-containing HDL. The WT apoE3 cleared the cholesterol of apoE(-/-) mice without induction of hypertriglyceridemia and promoted formation of spherical HDL. A unique property of the truncated apoE3[K146N/R147W]202 mutant, compared with similarly truncated apoE forms, is that it did not correct the hypercholesterolemia. The contribution of LPL and LCAT in the induction of the dyslipidemia was studied. Treatment of apoE(-/-) mice with apoE3[K146N/R147W] and LPL corrected the hypertriglyceridemia, but did not prevent the formation of discoidal HDL. Treatment with LCAT corrected hypertriglyceridemia and generated spherical HDL. The combined data indicate that the K146N/R147W substitutions convert the full-length and the truncated apoE3[K146N/R147W] mutant into a dominant negative ligand that prevents receptor-mediated remnant clearance, exacerbates the dyslipidemia, and inhibits the biogenesis of HDL. PMID:24776540

  15. Attributional Gender Bias: Teachers&apos; Ability and Effort Explanations for Students&apos; Math Performance

    ERIC Educational Resources Information Center

    Espinoza, Penelope; Arêas da Luz Fontes, Ana B.; Arms-Chavez, Clarissa J.

    2014-01-01

    Research is presented on the attributional gender bias: the tendency to generate different attributions (explanations) for female versus male students&apos; performance in math. Whereas boys&apos; successes in math are attributed to ability, girls&apos; successes are attributed to effort; conversely, boys&apos; failures in math are attributed to a…

  16. Children&apos;s Talking and Listening within the Classroom: Teachers&apos; Insights

    ERIC Educational Resources Information Center

    Bosacki, Sandra; Rose-Krasnor, Linda; Coplan, Robert J.

    2014-01-01

    Research suggests that social communication (verbal and non-verbal) plays a key role in students&apos; and teachers&apos; elementary-school experiences. Within the framework of sociocognitive developmental theory, this qualitative study investigates teachers&apos; experiences and perceptions of children&apos;s talking and listening habits within…

  17. Jack Michael&apos;s Motivation

    ERIC Educational Resources Information Center

    Miguel, Caio F.

    2013-01-01

    Among many of Jack Michael&apos;s contributions to the field of behavior analysis is his behavioral account of motivation. This paper focuses on the concept of "motivating operation" (MO) by outlining its development from Skinner&apos;s (1938) notion of "drive." Conceptually, Michael&apos;s term helped us change our focus on…

  18. Pupils&apos; Voice: "My Primary School Teacher&apos;&apos;

    ERIC Educational Resources Information Center

    Alkan, Vesile

    2013-01-01

    This study aims to explore pupils&apos; views on how a teacher should be and the reasons for their decisions. Based on qualitative research design, focus group interviews were done with ten 5th graders from a public primary school in Turkey. These pupils were asked the following questions: "how do you think a teacher should be?" and…

  19. Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.

    PubMed

    Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

    2015-12-01

    Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers.

  20. Mothers&apos; Beliefs about Children&apos;s Learning in Hong Kong and the United States: Implications for Mothers&apos; Child-Based Worth

    ERIC Educational Resources Information Center

    Ng, Florrie Fei-Yin; Pomerantz, Eva M.; Lam, Shui-fong

    2013-01-01

    Chinese and American mothers&apos; beliefs about children&apos;s learning and parents&apos; role in it were examined using notions salient in Chinese culture. Mothers from Hong Kong ("n" = 66) and the United States ("n" = 69) indicated their endorsement of the ideas that children&apos;s learning reflects children&apos;s…

  1. Views and Voices of the Working Class: Aída and Rosario

    ERIC Educational Resources Information Center

    Pao, Maria T.

    2014-01-01

    In 2005, Spanish television audiences saw the debut of the nation&apos;s first spinoff, the sitcom "Aída." The show featured the tribulations of its title character and her working-class family in their struggle to "llegar a fin de mes." It seemed to promise a sensibility enacted in the US series "Roseanne," where…

  2. Knockdown of ApoL1 in Zebrafish Larvae Affects the Glomerular Filtration Barrier and the Expression of Nephrin

    PubMed Central

    Kotb, Ahmed M.; Simon, Ole; Blumenthal, Antje; Vogelgesang, Silke; Dombrowski, Frank; Amann, Kerstin; Zimmermann, Uwe; Endlich, Karlhans; Endlich, Nicole

    2016-01-01

    APOL1, a secreted high-density lipoprotein, is expressed in different human tissues. Genetic variants of APOL1 are described to be associated with the development of end stage renal diseases in African Americans. In human kidney, APOL1 is mainly expressed in podocytes that are responsible for proper blood filtration. Since mice do not express ApoL1, the zebrafish is an ideal model to study the role of ApoL1. Injection of morpholinos against zApoL1 into zebrafish eggs and larvae, respectively, induces severe edema indicating a leakage of the filtration barrier. This was demonstrated in zApoL1 knockdown larvae by intravascular injection of fluorescently-labeled 10- and 500-kDa dextrans and by clearance of the vitamin D-binding protein from the circulation. Immunohistochemistry and RT-PCR revealed the reduction of nephrin, a podocyte-specific protein essential for blood filtration. Coinjection of human nephrin mRNA rescued the zApoL1 knockdown induced phenotype. Reduced APOL1 and nephrin levels were also found in biopsies of patients suffering from end stage renal diseases. Our results demonstrate that zApoL1 is essential for proper blood filtration in the zebrafish glomerulus and that zApoL1 affects the expression of nephrin. PMID:27138898

  3. Knockdown of ApoL1 in Zebrafish Larvae Affects the Glomerular Filtration Barrier and the Expression of Nephrin.

    PubMed

    Kotb, Ahmed M; Simon, Ole; Blumenthal, Antje; Vogelgesang, Silke; Dombrowski, Frank; Amann, Kerstin; Zimmermann, Uwe; Endlich, Karlhans; Endlich, Nicole

    2016-01-01

    APOL1, a secreted high-density lipoprotein, is expressed in different human tissues. Genetic variants of APOL1 are described to be associated with the development of end stage renal diseases in African Americans. In human kidney, APOL1 is mainly expressed in podocytes that are responsible for proper blood filtration. Since mice do not express ApoL1, the zebrafish is an ideal model to study the role of ApoL1. Injection of morpholinos against zApoL1 into zebrafish eggs and larvae, respectively, induces severe edema indicating a leakage of the filtration barrier. This was demonstrated in zApoL1 knockdown larvae by intravascular injection of fluorescently-labeled 10- and 500-kDa dextrans and by clearance of the vitamin D-binding protein from the circulation. Immunohistochemistry and RT-PCR revealed the reduction of nephrin, a podocyte-specific protein essential for blood filtration. Coinjection of human nephrin mRNA rescued the zApoL1 knockdown induced phenotype. Reduced APOL1 and nephrin levels were also found in biopsies of patients suffering from end stage renal diseases. Our results demonstrate that zApoL1 is essential for proper blood filtration in the zebrafish glomerulus and that zApoL1 affects the expression of nephrin. PMID:27138898

  4. Impact of a multi-nutrient diet on cognition, brain metabolism, hemodynamics, and plasticity in apoE4 carrier and apoE knockout mice.

    PubMed

    Jansen, Diane; Zerbi, Valerio; Janssen, Carola I F; van Rooij, Daan; Zinnhardt, Bastian; Dederen, Pieter J; Wright, Alan J; Broersen, Laus M; Lütjohann, Dieter; Heerschap, Arend; Kiliaan, Amanda J

    2014-09-01

    Lipid metabolism and genetic background together strongly influence the development of both cardiovascular and neurodegenerative diseases like Alzheimer's disease (AD). A non-pharmacological way to prevent the genotype-induced occurrence of these pathologies is given by dietary behavior. In the present study, we tested the effects of long-term consumption of a specific multi-nutrient diet in two models for atherosclerosis and vascular risk factors in AD: the apolipoprotein ε4 (apoE4) and the apoE knockout (apoE ko) mice. This specific multi-nutrient diet was developed to support neuronal membrane synthesis and was expected to contribute to the maintenance of vascular health. At 12 months of age, both genotypes showed behavioral changes compared to control mice and we found increased neurogenesis in apoE ko mice. The specific multi-nutrient diet decreased anxiety-related behavior in the open field, influenced sterol composition in serum and brain tissue, and increased the concentration of omega-3 fatty acids in the brain. Furthermore, we found that wild-type and apoE ko mice fed with this multi-nutrient diet showed locally increased cerebral blood volume and decreased hippocampal glutamate levels. Taken together, these data suggest that a specific dietary intervention has beneficial effects on early pathological consequences of hypercholesterolemia and vascular risk factors for AD. PMID:23832599

  5. Impact of a multi-nutrient diet on cognition, brain metabolism, hemodynamics, and plasticity in apoE4 carrier and apoE knockout mice.

    PubMed

    Jansen, Diane; Zerbi, Valerio; Janssen, Carola I F; van Rooij, Daan; Zinnhardt, Bastian; Dederen, Pieter J; Wright, Alan J; Broersen, Laus M; Lütjohann, Dieter; Heerschap, Arend; Kiliaan, Amanda J

    2014-09-01

    Lipid metabolism and genetic background together strongly influence the development of both cardiovascular and neurodegenerative diseases like Alzheimer's disease (AD). A non-pharmacological way to prevent the genotype-induced occurrence of these pathologies is given by dietary behavior. In the present study, we tested the effects of long-term consumption of a specific multi-nutrient diet in two models for atherosclerosis and vascular risk factors in AD: the apolipoprotein ε4 (apoE4) and the apoE knockout (apoE ko) mice. This specific multi-nutrient diet was developed to support neuronal membrane synthesis and was expected to contribute to the maintenance of vascular health. At 12 months of age, both genotypes showed behavioral changes compared to control mice and we found increased neurogenesis in apoE ko mice. The specific multi-nutrient diet decreased anxiety-related behavior in the open field, influenced sterol composition in serum and brain tissue, and increased the concentration of omega-3 fatty acids in the brain. Furthermore, we found that wild-type and apoE ko mice fed with this multi-nutrient diet showed locally increased cerebral blood volume and decreased hippocampal glutamate levels. Taken together, these data suggest that a specific dietary intervention has beneficial effects on early pathological consequences of hypercholesterolemia and vascular risk factors for AD.

  6. ApoE genotypes are associated with age at natural menopause in Chinese females.

    PubMed

    Meng, Fan-Tao; Wang, Yan-Li; Liu, Ji; Zhao, Jun; Liu, Rong-Yu; Zhou, Jiang-Ning

    2012-08-01

    Ages at natural menarche and menopause are influenced by several genetic factors. This study aimed to investigate the possible relationship between the apolipoprotein E (ApoE) genotype and the age at menarche and natural menopause in Chinese females. In the current study, 398 (elderly group, aged 47-80 years) and 825 (young group, aged 15-25 years) Chinese females were enrolled under informed content. Ages at natural menarche and menopause were obtained by questionnaires. ApoE genotypes were identified by restriction fragment length polymorphism analysis. In the elderly group, the number of pregnancies and live births and breastfeeding were associated with the age at menopause (P = 0.008, P = 0.002, and P = 0.023, respectively). One-way ANOVA analysis revealed that the ApoE genotype was significantly associated with age at natural menopause (ANM; P = 0.010). Compared with ApoE ε3/3 carriers, ApoE ε3/4 females showed a 1.8-year delay in ANM (P = 0.002). Single ApoE allele-positive/allele-negative analysis also showed that the age at menopause of ApoE ε4 carriers was delayed compared with those who were not carriers (P = 0.023). In the young group, no statistical difference was found in the age of menarche between the carriers of ApoE ε3/3 and ε3/4. Single ApoE allele-positive/allele-negative analysis showed that the age at menarche in ApoE ε4 carriers was slightly earlier than in those who were not carriers (P = 0.048). Meanwhile, univariate association analysis revealed that the ApoE genotypes were not significantly associated with the age at menarche using age as a covariate in the pooled group (young + elderly) (P = 0.143). We demonstrated that the ApoE genotype is significantly linked to the age at natural menopause.

  7. Measuring Beliefs in Centimeters: Private Knowledge Biases Preschoolers&apos; and Adults&apos; Representation of Others&apos; Beliefs

    ERIC Educational Resources Information Center

    Sommerville, Jessica A.; Bernstein, Daniel M.; Meltzoff, Andrew N.

    2013-01-01

    A novel task, using a continuous spatial layout, was created to investigate the degree to which (in centimeters) 3-year-old children&apos;s ("N" = 63), 5-year-old children&apos;s ("N" = 60), and adults&apos; ("N" = 60) own privileged knowledge of the location of an object biased their representation of a…

  8. ApoE allele frequencies in Italian sporadic and familial Alzheimer's disease.

    PubMed

    Sorbi, S; Nacmias, B; Forleo, P; Latorraca, S; Gobbini, I; Bracco, L; Piacentini, S; Amaducci, L

    1994-08-15

    Recent studies have provided evidence of association of apolipoprotein E (ApoE) epsilon 4 allele and late onset familial and sporadic Alzheimer's disease (AD). Epidemiological studies have established allelic variation at the ApoE locus. We have analyzed the ApoE gene polymorphism in a sample of 446 Italian subjects. Our data confirm a significant association between epsilon 4 allele and sporadic AD. The frequency of epsilon 4 allele in early onset familial AD patients was comparable to control values suggesting that epsilon 4 allele does not represent a risk factor for early onset familial AD (EOFAD). Moreover, we found a not previously reported association between ApoE epsilon 2 allele and sporadic AD and EOFAD. PMID:7824157

  9. Broadening the Scope of PDS Liaisons&apos; Roles in Community Schools

    ERIC Educational Resources Information Center

    Ferrara, JoAnne; Gomez, Diane W.

    2014-01-01

    Professional Development School liaisons are accustomed to developing relationships between their respective universities and partner schools. When the partner school is also a &apos;&apos;full service&apos;&apos; or &apos;'community'&apos; school, the partnership&apos;s dynamics change. This article describes the expanded roles of two…

  10. Why Was Kelvin&apos;s Estimate of the Earth&apos;s Age Wrong?

    ERIC Educational Resources Information Center

    Lovatt, Ian; Syed, M. Qasim

    2014-01-01

    This is a companion to our previous paper in which we give a published example, based primarily on Perry&apos;s work, of a graph of ln "y" versus "t" when "y" is an exponential function of "t". This work led us to the idea that Lord Kelvin&apos;s (William Thomson&apos;s) estimate of the Earth&apos;s age was…

  11. The Impact of Adolescents&apos; Dyslexia on Parents&apos; and Their Own Educational Expectations

    ERIC Educational Resources Information Center

    Rimkute, Laura; Torppa, Minna; Eklund, Kenneth; Nurmi, Jari-Erik; Lyytinen, Heikki

    2014-01-01

    The present study examined the role that adolescents&apos; dyslexia plays in their educational expectations, as well as their parents&apos; expectations concerning their offspring&apos;s future education. To investigate this, 170 adolescents were asked to report their educational expectations on two occasions while they were still attending…

  12. Influence of Mothers&apos; Education on Children&apos;s Maths Achievement in Kenya

    ERIC Educational Resources Information Center

    Abuya, Benta A.; Oketch, Moses; Mutisya, Maurice; Ngware, Moses; Ciera, James

    2013-01-01

    Research shows that fathers&apos; level of education predicts achievement of both boys and girls, with significantly greater effect for boys. Similarly, mothers&apos; level of education predicts the achievement of girls but not boys. This study tests the mother-child education achievement hypothesis, by examining the effect of mothers&apos;…

  13. Critical Pedagogy&apos;s Problem with Changing Teachers&apos; Dispositions towards Critical Teaching

    ERIC Educational Resources Information Center

    Neumann, Jacob W.

    2013-01-01

    Increasing teachers&apos; dispositions towards critical teaching is a fundamental goal for critical pedagogy. Because critical educational change cannot occur without teachers&apos; "buy-in," developing teachers&apos; inclination to implement critical teaching into their classrooms is a prerequisite for any successful critical pedagogy…

  14. Individual Differences in Children&apos;s and Parents&apos; Generic Language

    ERIC Educational Resources Information Center

    Gelman, Susan A.; Ware, Elizabeth A.; Kleinberg, Felicia; Manczak, Erika M.; Stilwell, Sarah M.

    2014-01-01

    Generics ("&apos;Dogs&apos; bark") convey important information about categories and facilitate children&apos;s learning. Two studies with parents and their 2- or 4-year-old children (N = 104 dyads) examined whether individual differences in generic language use are as follows: (a) stable over time, contexts, and domains, and (b) linked…

  15. The association between serum ApoE genetic polymorphism and serum lipid level in hemodialysis patients.

    PubMed

    Zhang, Yong; Zhang, Linlin; Cao, Bo

    2015-02-01

    Growing evidence indicates that apolipoprotein E (ApoE) is one of the most important candidate genes for influencing the development of hemodialysis (HD). This study aims to detect the potential association between serum ApoE genetic polymorphism and serum lipid level in HD. A total of 485 subjects were enrolled in this case-control study. The created restriction site polymerase chain reaction and DNA sequencing methods were used to investigate ApoE c.109G>A genetic polymorphism. Our data suggested that there were significant differences in the distribution of allelic and genotypic frequencies between HD patients and healthy controls. The levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, ApoA-I, ApoB, ApoE, and lipoprotein (a) for genotype AA were different from genotype GG in HD patients and healthy controls. Our findings support that the ApoE c.109G>A genetic polymorphism might influence the development of HD and could be a risk factor for assessing HD.

  16. Japanese Children&apos;s Reactions to Family Photographs: Associations with Mothers&apos; Attachment Status

    ERIC Educational Resources Information Center

    Behrens, Kazuko Y.; Umemura, Tomo

    2013-01-01

    This study examined differences in children&apos;s responses to their family photographs within a sample of Japanese 6-year-olds ("N"?=?44), exploring associations with their mothers&apos; attachment status. The differences in children&apos;s photo reactions were captured by a 5-point continuous scale to rate how engaged children were…

  17. James Baldwin&apos;s "Everybody&apos;s Protest Novel": Educating Our Responses to Racism

    ERIC Educational Resources Information Center

    Frank, Jeff

    2014-01-01

    The aim of this article is to establish--and explore--James Baldwin&apos;s significance for educational theory. Through a close reading of "Everybody&apos;s Protest Novel", I show that Baldwin&apos;s thinking is an important (if unrecognized) precursor to the work of Stanley Cavell and Cora Diamond, and is relevant to a number of…

  18. Calculus Students&apos; and Instructors&apos; Conceptualizations of Slope: A Comparison across Academic Levels

    ERIC Educational Resources Information Center

    Nagle, Courtney; Moore-Russo, Deborah; Viglietti, Janine; Martin, Kristi

    2013-01-01

    This study considers tertiary calculus students&apos; and instructors&apos; conceptualizations of slope. Qualitative techniques were employed to classify responses to 5 items using conceptualizations of slope identified across various research settings. Students&apos; responses suggest that they rely on procedurally based conceptualizations of…

  19. Primary Health Care Providers&apos; Knowledge Gaps on Parkinson&apos;s Disease

    ERIC Educational Resources Information Center

    Thompson, Megan R.; Stone, Ramona F.; Ochs, V. Dan; Litvan, Irene

    2013-01-01

    In order to determine primary health care providers&apos; (PCPs) knowledge gaps on Parkinson&apos;s disease, data were collected before and after a one-hour continuing medical education (CME) lecture on early Parkinson&apos;s disease recognition and treatment from a sample of 104 PCPs participating at an annual meeting. The main outcome measure…

  20. Gene-Environment Interaction of ApoE Genotype and Combat Exposure on PTSD

    PubMed Central

    Lyons, Michael J.; Genderson, Margo; Grant, Michael D.; Logue, Mark; Zink, Tyler; McKenzie, Ruth; Franz, Carol E.; Panizzon, Matthew; Lohr, James B.; Jerskey, Beth; Kremen, William S.

    2015-01-01

    Factors determining who develops PTSD following trauma are not well understood. The €4 allele of the apolipoprotein E (apoE) gene is associated with dementia and unfavorable outcome following brain insult. PTSD is also associated with dementia. Given evidence that psychological trauma adversely affects the brain, we hypothesized that the apoE genotype moderates effects of psychological trauma on PTSD pathogenesis. To investigate the moderation of the relationship between PTSD symptoms and combat exposure, we used 172 participants with combat trauma sustained during the Vietnam War. PTSD symptoms were the dependent variable and number of combat experiences, apoE genotype, and the combat experiences × apoE genotype interaction were predictors. We also examined the outcome of a diagnosis of PTSD (n = 39) versus no PTSD diagnosis (n = 131). The combat × apoE genotype interaction was significant for both PTSD symptoms (P = .014) and PTSD diagnosis (P = .009). ApoE genotype moderates the relationship between combat exposure and PTSD symptoms. Although the pathophysiology of PTSD is not well understood, the €4 allele is related to reduced resilience of the brain to insult. Our results are consistent with the €4 allele influencing the effects of psychological trauma on the brain, thereby affecting the risk of PTSD. PMID:24132908

  1. White Teachers&apos; Racial Identities, Perceptions of Students&apos; Behaviors, and Symptoms of Burnout

    ERIC Educational Resources Information Center

    Chen, Cynthia E.

    2013-01-01

    Educational research has examined factors contributing to teachers&apos; burnout symptoms, including their perceptions of student behaviors (Ingersoll, 2003). Interestingly, teacher and students&apos; races have been differentially related to teachers&apos; perceptions of student behavior (Downey & Pribesh, 2004); this disparity in perceptions…

  2. Teaching Laura Kipnis&apos;s "Love&apos;s Labors" in "Ways of Reading"

    ERIC Educational Resources Information Center

    Fike, Matthew A.

    2013-01-01

    This essay describes a method of teaching a very challenging anthology piece: Laura Kipnis&apos;s "Love&apos;s Labors" (chapter 1 of her 2003 "Against Love: A Polemic"). The method, although designed for a critical thinking course, should also provide resources for those who teach Kipnis&apos;s work in writing courses. Using…

  3. On the Relations between Parents&apos; Ideals and Children&apos;s Autonomy

    ERIC Educational Resources Information Center

    de Ruyter, Doret J.; Schinkel, Anders

    2013-01-01

    In this article Doret J. de Ruyter and Anders Schinkel argue that parents&apos; ideals can enhance children&apos;s autonomy, but that they may also have a detrimental effect on the development of children&apos;s autonomy. After describing the concept of "ideals" and elucidating a systems theoretical conception of autonomy, de Ruyter and…

  4. Does Play Matter to Parents? Taiwanese Parents&apos; Perceptions of Child&apos;s Play

    ERIC Educational Resources Information Center

    Lin, Yen-Chun; Yawkey, Thomas D.

    2013-01-01

    The main purpose of this study was to gain an understanding of Taiwanese parents&apos; perceptions of child&apos;s play. Data were collected via parent questionnaires. To ensure greater variability in parents&apos; backgrounds, kindergartens with families from different social backgrounds were recruited. A total sample of 142 parents with…

  5. Master&apos;s Degree Learners&apos; Use of Theory in Designing Instructional Materials

    ERIC Educational Resources Information Center

    Wojtecki, John A.

    2012-01-01

    Educational institutions offering a master&apos;s degree program in instructional design incorporate instructional design theory into the master&apos;s degree course offerings. The responsibility for the student is to develop coursework. Master&apos;s degree learners will use instructional design theory to develop course materials. This study…

  6. A complete backbone spectral assignment of human apolipoprotein AI on a 38 kDa preβHDL (Lp1-AI) particle

    SciTech Connect

    Ren, Xuefeng; Yang, Yunhuang; Neville, T.; Hoyt, David W.; Sparks, Daniel L.; Wang, Jianjun

    2007-06-12

    Apolipoprotein A-I (apoAI, 243-residues) is the major protein component of the high-density lipoprotein (HDL) that has been a hot subject of interests because of its anti-atherogenic properties. This important property of apoAI is related to its roles in reverse cholesterol transport pathway. Upon lipid-binding, apoAI undergoes conformational changes from lipid-free to several different HDL-associated states (1). These different conformational states regulate HDL formation, maturation and transportation. Two initial conformational states of apoAI are lipid-free apoAI and apoAI/preβHDL that recruit phospholipids and cholesterol to form HDL particles. In particular, lipid-free apoAI specifically binds to phospholipids to form lipid-poor apoAI, including apoAI/preβ-HDL (~37 kDa). As a unique class of lipid poor HDL, both in vitro and in vivo evidence demonstrates that apoAI/preβ-HDLs are the most effective acceptors specifically for free cholesterol in human plasma and serves as the precursor of HDL particles (2). Here we report a complete backbone spectral assignment of human apoAI/preβHDL. Secondary structure prediction using backbone NMR parameters indicates that apoAI/preβHDL displays a two-domain structure: the N-terminal four helix-bundle domain (residues 1-186) and the C-terminal flexible domain (residues 187-243). A structure of apoAI/preβ-HDL is the first lipid-associated structure of apoAI and is critical for us to understand how apoAI recruits cholesterol to initialize HDL formation. BMRB deposit with accession number: 15093.

  7. Teachers&apos; Prestige in Spain: Probing the Public&apos;s and the Teachers&apos; Contrary Views

    ERIC Educational Resources Information Center

    Pérez-Díaz, Víctor; Rodríguez, Juan Carlos

    2014-01-01

    We use the results of a public opinion survey we carried out in 2012 on a sample of the Spanish adult population to offer a plausible explanation of one of the main conundrums of primary and secondary school teachers&apos; prestige, not only in Spain, i.e. that, contrary to public discourse and to teachers&apos; perceptions, this prestige has not…

  8. Abca1 Deficiency Affects Alzheimer's Disease-Like Phenotype in Human ApoE4 But Not in ApoE3-Targeted Replacement Mice

    PubMed Central

    Fitz, Nicholas F.; Cronican, Andrea A.; Saleem, Muzamil; Fauq, Abdul H.; Chapman, Robert; Lefterov, Iliya

    2012-01-01

    ATP-binding cassette transporter A1 (ABCA1) transporter regulates cholesterol efflux and is an essential mediator of high-density lipoprotein (HDL) formation. In amyloid precursor protein (APP) transgenic mice, Abca1 deficiency increased amyloid deposition in the brain paralleled by decreased levels of Apolipoprotein E (ApoE). The APOEε4 allele is the major genetic risk factor of sporadic Alzheimer's disease (AD). Here, we reveal the effect of Abca1 deficiency on phenotype in mice expressing human ApoE3 or ApoE4. We used APP/E3 and APP/E4 mice generated by crossing APP/PS1ΔE9 transgenic mice to human APOE3- and APOE4-targeted replacement mice and examined Abca1 gene dose effect on amyloid deposition and cognition. The results from two behavior tests demonstrate that lack of one copy of Abca1 significantly exacerbates memory deficits in APP/E4/Abca1−/+ but not in APP/E3/Abca1−/+ mice. The data for amyloid plaques and insoluble amyloid-β (Aβ) also show that Abca1 hemizygosity increases Aβ deposition only in APP/E4/Abca1−/+ but not in APP/E3/Abca1−/+ mice. Our in vivo microdialysis assays indicate that Abca1 deficiency significantly decreases Aβ clearance in ApoE4-expressing mice, while the effect of Abca1 on Aβ clearance in ApoE3-expressing mice was insignificant. In addition, we demonstrate that plasma HDL and Aβ42 levels in APP/E4/Abca1−/+ mice are significantly decreased, and there is a negative correlation between plasma HDL and amyloid plaques in brain, suggesting that plasma lipoproteins may be involved in Aβ clearance. Overall, our results prove that the presence of functional Abca1 significantly influences the phenotype of APP mice expressing human ApoE4 and further substantiate therapeutic approaches in AD based on ABCA1–APOE regulatory axis. PMID:22993429

  9. Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

    PubMed

    Jasienska, Grazyna; Ellison, Peter T; Galbarczyk, Andrzej; Jasienski, Michal; Kalemba-Drozdz, Malgorzata; Kapiszewska, Maria; Nenko, Ilona; Thune, Inger; Ziomkiewicz, Anna

    2015-03-22

    The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l(-1)) than women with genotypes without ApoE4 (120.49 pmol l(-1)), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.

  10. Role of leucine zipper motif in apoE3 N-terminal domain lipid binding activity.

    PubMed

    Yamamoto, Taichi; Ryan, Robert O

    2006-09-01

    The N terminal domain of human apolipoprotein E3 (apoE3-NT) functions as a ligand for members of the low-density lipoprotein receptor (LDLR) family. Whereas lipid-free apoE3-NT adopts a stable four-helix bundle conformation, a lipid binding induced conformational change is required for LDLR recognition. To investigate the role of a leucine zipper motif identified in the helix bundle on lipid binding activity, three leucine residues in helix 2 (Leu63, Leu71 and Leu78) were replaced by alanine. Recombinant "leucine to alanine" (LA) apoE3-NT was produced in E. coli, isolated and characterized. Stability studies revealed a transition midpoint of guanidine hydrochloride induced denaturation of 2.7 M and 2.1 M for wild type (WT) and LA apoE3-NT, respectively. Results from fluorescent dye binding assays revealed that, compared to WT apoE3-NT, LA apoE3-NT has an increased content of solvent exposed hydrophobic surfaces. In phospholipid vesicle solubilization assays, LA apoE3-NT was more effective than WT apoE3-NT at inducing a time-dependent decrease in dimyristoylphosphatidylglycerol vesicle light scattering intensity. Likewise, in lipoprotein binding assays, LA apoE3-NT protected human low-density lipoprotein from phospholipase C induced aggregation to a greater extent than WT apoE3-NT. On the other hand, LA apoE3-NT and WT apoE3-NT were equivalent in terms of their ability to bind a soluble LDLR fragment. The results suggest that the leucine zipper motif confers stability to the apoE3-NT helix bundle state and may serve to modulate lipid binding activity of this domain and, thereby, influence the conformational transition associated with manifestation of LDLR binding activity.

  11. Exploring Students&apos; Patterns of Reasoning

    ERIC Educational Resources Information Center

    Matloob Haghanikar, Mojgan

    2012-01-01

    As part of a collaborative study of the science preparation of elementary school teachers, we investigated the quality of students&apos; reasoning and explored the relationship between sophistication of reasoning and the degree to which the courses were considered inquiry oriented. To probe students&apos; reasoning, we developed open-ended written…

  12. Teaching the Writer&apos;s Craft

    ERIC Educational Resources Information Center

    Kittle, Penny

    2014-01-01

    "Writing is a core skill for living, not just for school," writes high school English teacher Penny Kittle. Although it&apos;s important to teach students the conventions of grammar, punctuation, and sentence structure, teachers don&apos;t need to approach this task "like scolds, red pens in hand, stamping out sin, and punishing…

  13. Omani Students&apos; Definitions of Geography

    ERIC Educational Resources Information Center

    Al-Nofli, Mohammed Abdullah

    2014-01-01

    Very few studies have been conducted on students&apos; definitions of geography. The purpose of the present study was to add to the existing literature by exploring Omani students&apos; definitions of geography. Participants were 477 students of grade 6 (ages 11-12) and grade 10 (ages 15-16) in one school district in Oman. They had been taught…

  14. Science Teachers&apos; Analogical Reasoning

    ERIC Educational Resources Information Center

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-01-01

    Analogies can play a relevant role in students&apos; learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students&apos; prior knowledge and the scientific knowledge they desire them to understand, but also know how to…

  15. Workers&apos; Education in Palestine

    ERIC Educational Resources Information Center

    Elayassa, Wajih

    2013-01-01

    Due to the political context and the restrictions placed on general freedoms and trade union activities, workers&apos; education in Palestine remained informal and largely reliant on oral memory until the early 1990s. For decades, it was an integral part of political education. Workers&apos; education only became a stand-alone field after the…

  16. Testing Bernoulli&apos;s Law

    ERIC Educational Resources Information Center

    Ivanov, Dragia; Nikolov, Stefan; Petrova, Hristina

    2014-01-01

    In this paper we present three different methods for testing Bernoulli&apos;s law that are different from the standard "tube with varying cross-section." They are all applicable to high-school level physics education, with varying levels of theoretical and experimental complexity, depending on students&apos; skills, and may even be…

  17. India&apos;s Higher Education Challenges

    ERIC Educational Resources Information Center

    Altbach, Philip G.

    2014-01-01

    India, with the world&apos;s second largest higher education system and a rapidly growing economy as one of the BRIC nations, faces significant challenges in building both capacity and excellence in higher education. India&apos;s higher education system is characterized by "islands of excellence in a sea of mediocrity." The mainstream…

  18. Measuring Master&apos;s Student Engagement

    ERIC Educational Resources Information Center

    O'Dair, Katherine G.

    2012-01-01

    Master&apos;s education is the largest segment of graduate education in the United States yet there is a paucity of research about how master&apos;s students experience their programs. Empirical research on student engagement--defined as the time and effort students devote to activities that are linked to educational outcomes and what institutions…

  19. Gene-Environment Interplay in the Link of Friends&apos; and Nonfriends&apos; Behaviors with Children&apos;s Social Reticence in a Competitive Situation

    ERIC Educational Resources Information Center

    Guimond, Fanny-Alexandra; Brendgen, Mara; Vitaro, Frank; Forget-Dubois, Nadine; Dionne, Ginette; Tremblay, Richard E.; Boivin, Michel

    2014-01-01

    This study used a genetically informed design to assess the effects of friends&apos; and nonfriends&apos; reticent and dominant behaviors on children&apos;s observed social reticence in a competitive situation. Potential gene-environment correlations (rGE) and gene-environment interactions (GxE) in the link between (a) friends&apos; and…

  20. The Influence of Teachers&apos; Conceptions on Their Students&apos; Learning: Children&apos;s Understanding of Sheet Music

    ERIC Educational Resources Information Center

    López-Íñiguez, Guadalupe; Pozo, Juan Ignacio

    2014-01-01

    Background: Despite increasing interest in teachers&apos; and students&apos; conceptions of learning and teaching, and how they influence their practice, there are few studies testing the influence of teachers&apos; conceptions on their students&apos; learning. Aims: This study tests how teaching conception (TC; with a distinction between…

  1. Effect of chronic ethanol on hepatic apolipoprotein (Apo)E glycosylation

    SciTech Connect

    Ghosh, P.; Okoh, C.; Chirtel, S.J.; Liu, Q.H.; Lakshman, M.R. George Washington Univ., Washington, DC )

    1991-03-15

    The authors have previously shown that chronic ethanol feeding significantly inhibits the secretion of ApoE in rats. Since many carbohydrate precursors are essential for the synthesis of mature ApoE before it is secreted, the authors have investigated the effects of chronic ethanol on the incorporation of these precursors into ApoE. Male Wistar rats were divided into groups and were pair-fed with Control and Ethanol liquid diets for a period of 8 weeks. At the end, hepatocytes were isolated from each group and {approximately}400 mg cells were incubated in 8 ml final volume of Krebs bicarbonate buffer, pH 7.4 for 30 min. at 37C with the following labeled precursors individually: (2-{sup 3}H)mannose, (6-{sup 3}H)N-acetyl mannosamine, (4,5-{sup 3}H)galactose, (5,6-{sup 3}H)fucose, and (4,5-{sup 3}H)leucine. The incorporation of each precursor into immunoprecipitable ApoE was measured in cell homogenate, microsome and the Golgi fractions. The results showed that chronic ethanol treatment did not significantly inhibit the incorporation of leucine, fucose and galactose into ApoE at any of the subcellular levels. In contrast, chronic ethanol inhibited the incorporation of: (a) mannose into ApoE by 38% both at whole cell and at microsomal level and (b) N-acetyl mannosamine by 26% at the whole cell level and at the Golgi level. Based on these results, it is concluded that chronic ethanol feeding impairs the mannosylation and sialylation of ApoE in rat liver probably by altering the structure and functions of hepatic microsome and Golgi.

  2. [Influence of genetic and environmental factors on lipid metabolism and cardiovascular risk associated with the apoE gene].

    PubMed

    Moreno, Juan Antonio; López-Miranda, José; Pérez-Jiménez, Francisco

    2006-09-01

    The apolipoprotein E (ApoE) plays an important role in lipid metabolism. This apoprotein presents three major isoforms (apoE2, apoE3 and apoE4) that modulate lipid levels. Carriers of the apoE4 allele have higher total and LDL-cholesterol plasma concentration and a greater coronary risk, particularly for myocardial infarction. Nevertheless, not all the people with this allele develop the disease, which suggests that other genetic or environmental factors are necessary for its total expression. In this review, we will analyze the importance of several polymorphisms in the apoE gene promoter region, as well as various environmental factors, including diet, in the association of this gene with lipid metabolism and cardiovascular risk.

  3. Gene-environment interaction of ApoE genotype and combat exposure on PTSD.

    PubMed

    Lyons, Michael J; Genderson, Margo; Grant, Michael D; Logue, Mark; Zink, Tyler; McKenzie, Ruth; Franz, Carol E; Panizzon, Matthew; Lohr, James B; Jerskey, Beth; Kremen, William S

    2013-10-01

    Factors determining who develops PTSD following trauma are not well understood. The €4 allele of the apolipoprotein E (apoE) gene is associated with dementia and unfavorable outcome following brain insult. PTSD is also associated with dementia. Given evidence that psychological trauma adversely affects the brain, we hypothesized that the apoE genotype moderates effects of psychological trauma on PTSD pathogenesis. To investigate the moderation of the relationship between PTSD symptoms and combat exposure, we used 172 participants with combat trauma sustained during the Vietnam War. PTSD symptoms were the dependent variable and number of combat experiences, apoE genotype, and the combat experiences × apoE genotype interaction were predictors. We also examined the outcome of a diagnosis of PTSD (n = 39) versus no PTSD diagnosis (n = 131). The combat × apoE genotype interaction was significant for both PTSD symptoms (P = .014) and PTSD diagnosis (P = .009). ApoE genotype moderates the relationship between combat exposure and PTSD symptoms. Although the pathophysiology of PTSD is not well understood, the €4 allele is related to reduced resilience of the brain to insult. Our results are consistent with the €4 allele influencing the effects of psychological trauma on the brain, thereby affecting the risk of PTSD. PMID:24132908

  4. Aβ immunotherapy for Alzheimer's disease: effects on apoE and cerebral vasculopathy.

    PubMed

    Sakai, Kenji; Boche, Delphine; Carare, Roxana; Johnston, David; Holmes, Clive; Love, Seth; Nicoll, James A R

    2014-12-01

    Aβ immunotherapy for Alzheimer's disease (AD) results in the removal of Aβ plaques and increased cerebral amyloid angiopathy (CAA). In current clinical trials, amyloid-related imaging abnormalities (ARIAs), putatively due to exacerbation of CAA, are concerning side effects. We aimed to assess the role of the Aβ transporter apolipoprotein E (apoE) in the exacerbation of CAA and development of CAA-associated vasculopathy after Aβ immunotherapy. 12 Aβ42-immunized AD (iAD; AN1792, Elan Pharmaceuticals) cases were compared with 28 unimmunized AD (cAD) cases. Immunohistochemistry was quantified for Aβ42, apoE, apoE E4 and smooth muscle actin, and CAA-associated vasculopathy was analyzed. Aβ immunotherapy was associated with redistribution of apoE from cortical plaques to cerebral vessel walls, mirroring the altered distribution of Aβ42. Concentric vessel wall splitting was increased threefold in leptomeningeal vessels after immunotherapy (cAD 6.3 vs iAD 20.6 %, P < 0.001), but smooth muscle cell abnormalities did not differ. The findings suggest that apoE is involved in the removal of plaques and transport of Aβ to the cerebral vasculature induced by Aβ immunotherapy. Immunotherapy was not associated with CAA-related vascular smooth muscle damage, but was accompanied by increased splitting of the vessel wall, perhaps reflecting enhanced deposition and subsequent removal of Aβ. ARIA occurring in some current trials of Aβ immunotherapy may reflect an extreme form of these vascular changes.

  5. Proteomic analysis of changes in protein expression in liver mitochondria in apoE knockout mice.

    PubMed

    Suski, Maciej; Olszanecki, Rafał; Madej, Józef; Totoń-Żurańska, Justyna; Niepsuj, Anna; Jawień, Jacek; Bujak-Giżycka, Beata; Okoń, Krzysztof; Korbut, Ryszard

    2011-05-16

    The involvement of both apolipoprotein E (apoE) and mitochondria in lipid metabolism is widely recognized, however there is surprisingly scarce data about the putative mitochondrial action(s) of this protein. The aim of the study was to screen the alterations in liver mitochondrial proteome caused by apoE deficiency. We applied 2DE-LC-MS/MS methodology to investigate the changes in liver mitochondrial protein expression in 6-months old apoE(-/-) mice as compared to C57BL/6J controls. ApoE(-/-), but not C57BL/6J mice developed visible atherosclerotic changes in aorta and mild, diffuse steatosis of the liver. Collectively, 18 differentially expressed proteins were identified in mitochondria, related to apoptosis, antioxidant and detoxifying mechanisms of mitochondria, as well as lipid metabolism and transport. In conclusion, differential proteomic approach revealed several lines of proteomic evidence that mitochondrial function in the liver of apoE(-/-) mice could be altered as a result of overlapping of pathological and compensatory changes in expression of proteins.

  6. Bringing the ZPD into the Equation: Capturing L2 Development during Computerized Dynamic Assessment (C-DA)

    ERIC Educational Resources Information Center

    Poehner, Matthew E.; Lantolf, James P.

    2013-01-01

    Dynamic Assessment (DA) derives from Vygotsky&apos;s (1987) insight that the use of mediation, attuned to learner needs, enables learners to perform beyond their current level of functioning, thereby providing insights into emerging capabilities. The instructional quality of mediation means that this process simultaneously creates possibilities…

  7. Exercise, but not antioxidants, reversed ApoE4-associated motor impairments in adult GFAP-ApoE mice.

    PubMed

    Chaudhari, Kiran; Wong, Jessica M; Vann, Philip H; Sumien, Nathalie

    2016-05-15

    Motor dysfunction has been found to be predictive of cognitive dysfunction in Alzheimer's disease and to occur earlier than cognitive impairments. While apolipoprotein (Apo) E4 has been associated with cognitive impairments, it remains unclear whether it also increases risk for motor dysfunction. Exercise and antioxidants are often recommended to reduce cognitive declines, however it is unclear whether they can successfully improve motor impairments. This study was designed to determine the extent of the impact of apolipoprotein genotype on motor function, and whether interventions such as exercise and antioxidant intake can improve motor function. This study is the first to identify the nature of the interaction between antioxidant intake and exercise using a mouse model expressing either the human ApoE3 or ApoE4 isoforms under glial fibrillary acid protein promoter (GFAP-ApoE3 and GFAP-ApoE4 mice). The mice were fed either a control diet or the control diet supplemented with vitamins E and C (1.12 IU/g diet α-tocopheryl acetate and 1.65mg/g ascorbic acid). Each genotype/diet group was further divided into a sedentary group or a group that followed a 6 days a week exercise regimen. After 8 weeks on their respective treatment, the mice were administered a battery of motor tests to measure reflexes, strength, coordination and balance. GFAP-ApoE4 mice exhibited impaired motor learning and diminished strength compared to the GFAP-ApoE3 mice. Exercise alone was more efficient at improving motor function and reversing ApoE4-associated impairments than antioxidants alone, even though improvements were rather subtle. Contrarily to expected outcomes, combination of antioxidants and exercise did not yield further improvements of motor function. Interestingly, antioxidants antagonized the beneficial effects of exercise on strength. These data suggest that environmental and genetic factors influence the outcome of interventions on motor function and should be investigated

  8. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation.

    PubMed

    Huang, Zhi H; Reardon, Catherine A; Getz, Godfrey S; Maeda, Nobuyo; Mazzone, Theodore

    2015-02-01

    apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state.

  9. Effect of fenofibrate and atorvastatin on VLDL apoE metabolism in men with the metabolic syndrome

    PubMed Central

    Ooi, Esther M. M.; Ng, Theodore W. K.; Watts, Gerald F.; Chan, Dick C.; Barrett, P. Hugh R.

    2012-01-01

    We examined the effects of fenofibrate and atorvastatin on very low density lipoprotein (VLDL) apolipoprotein (apo)E metabolism in the metabolic syndrome (MetS). We studied 11 MetS men in a randomized, double-blind, crossover trial. VLDL-apoE kinetics were examined using stable isotope methods and compartmental modeling. Compared with placebo, fenofibrate (200 mg/day) and atorvastatin (40 mg/day) decreased plasma apoE concentrations (P < 0.05). Fenofibrate decreased VLDL-apoE concentration and production rate (PR) and increased VLDL-apoE fractional catabolic rate (FCR) compared with placebo (P < 0.05). Compared with placebo, atorvastatin decreased VLDL-apoE concentration and increased VLDL-apoE FCR (P < 0.05). Fenofibrate and atorvastatin had comparable effects on VLDL-apoE concentration. The increase in VLDL-apoE FCR with fenofibrate was 22% less than that with atorvastatin (P < 0.01). With fenofibrate, the change in VLDL-apoE concentration was positively correlated with change in VLDL-apoB concentration, and negatively correlated with change in VLDL-apoB FCR. In MetS, fenofibrate and atorvastatin decreased plasma apoE concentrations. Fenofibrate decreased VLDL-apoE concentration by lowering VLDL-apoE production and increasing VLDL-apoE catabolism. By contrast, atorvastatin decreased VLDL-apoE concentration chiefly by increasing VLDL-apoE catabolism. Our study provides new insights into the mechanisms of action of two different lipid-lowering therapies on VLDL-apoE metabolism in MetS. PMID:22930812

  10. ApoE2 Exaggerates PTSD-Related Behavioral, Cognitive, and Neuroendocrine Alterations.

    PubMed

    Johnson, Lance A; Zuloaga, Damian G; Bidiman, Erin; Marzulla, Tessa; Weber, Sydney; Wahbeh, Helane; Raber, Jacob

    2015-09-01

    Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer's disease (AD). Although possession of E2 is protective in the context of AD, E2 appears to confer an increased incidence and severity of posttraumatic stress disorder (PTSD). However, the biological processes underlying this link remain unclear. In this study, we began to elucidate these associations by examining the effects of apoE on PTSD severity in combat veterans, and on PTSD-like behavior in mice with human apoE. In a group of 92 veterans with PTSD, we observed significantly higher Clinician-Administered PTSD Scale and PTSD Checklist scores in E2+ individuals, as well as alterations in salivary cortisol levels. Furthermore, we measured behavioral and biological outcomes in mice expressing human apoE after a single stressful event as well as following a period of chronic variable stress, a model of combat-related trauma. Mice with E2 showed impairments in fear extinction, and behavioral, cognitive, and neuroendocrine alterations following trauma. To the best of our knowledge, these data constitute the first translational demonstration of PTSD severity in men and PTSD-like symptoms in mice with E2, and point to apoE as a novel biomarker of susceptibility, and potential therapeutic target, for PTSD.

  11. Infants&apos; Discrimination of Female Singing Voices

    ERIC Educational Resources Information Center

    Costa-Giomi, Eugenia; Davila, Yvonne

    2014-01-01

    There&apos;s extensive research on infant&apos;s discrimination of speaking voices but few studies have focused on infant&apos;s discrimination of singing voices. Most investigations on infants&apos; perception of timbre in music have been based on instrumental sounds. We completed an experiment with 7-and 13-month-olds (n = 16 and n = 17…

  12. Average Passenger Occupancy (APO) in Your Community.

    ERIC Educational Resources Information Center

    Stenstrup, Al

    1995-01-01

    Provides details of an activity in which students in grades 4-10 determine the Average Passenger Occupancy (APO) in their community and develop, administer, and analyze a survey to determine attitudes toward carpooling. (DDR)

  13. Effect of Diet and Age on Arterial Stiffening Due to Atherosclerosis in ApoE(-/-) Mice.

    PubMed

    Cilla, M; Pérez, M M; Peña, E; Martínez, M A

    2016-07-01

    This work analyzes the progressive stiffening of the aorta due to atherosclerosis development of both ApoE(-/-) and C57BL/6J mice fed on a Western (n = 5) and a normal (n = 5) chow diet for the ApoE(-/-) group and on a normal chow diet (n = 5) for the C57BL/6J group. Sets of 5 animals from the three groups were killed after 10, 20, 30 and 40 weeks on their respective diets (corresponding to 17, 27, 37 and 47 weeks of age). Mechanical properties (inflation test and axial residual stress measurements) and histological properties were compared for both strains, ApoE(-/-) on the hyper-lipidic diet and both ApoE(-/-) and C57BL/6J on the normal diet, after the same period and after different periods of diet. The results indicated that the aorta stiffness in the ApoE(-/-) and C57BL/6J mice under normal diet remained approximately constant irrespective of their age. However, the arterial stiffness in the ApoE(-/-) on the hyper-lipidic diet increased over time. Statistical differences were found between the group after 10 weeks and the groups after 30 and 40 weeks of a hyper-lipidic diet. Comparing the hyper-lipidic and normal diet mice, statistical differences were also found between both diets in all cases after 40 weeks of diet, frequently after 30 weeks, and in some cases after 20 weeks. The early stages of lesion corresponded to the first 2 weeks of diet. Advanced lesions were found at 30 weeks and, finally, the aorta was completely damaged after 40 weeks of diet. In conclusion, we found substantial changes in the mechanical properties of the aorta walls of the ApoE(-/-) mice fed with the hyper-lipidic diet compared to the normal chow diet groups for both the ApoE(-/-) and C57BL/6J groups. These findings could serve as a reference for the study of changes in the arterial wall properties in cases of atherosclerosis.

  14. Applications of Dweck&apos;s Model of Implicit Theories to Teachers&apos; Self-Efficacy and Emotional Experiences

    ERIC Educational Resources Information Center

    Williams, Alexis Ymon

    2012-01-01

    The current study explored Dweck&apos;s (1999; Dweck & Leggett, 1988) model of implicit theories in the context of teaching in order to establish its usefulness for describing teachers&apos; beliefs about students&apos; ability and social behavior. Further it sought to explain the connections between teachers&apos; implicit beliefs and their…

  15. The Role of Student-Teacher Ratio in Parents&apos; Perceptions of Schools&apos; Engagement Efforts

    ERIC Educational Resources Information Center

    Rodriguez, Raymond J.; Elbaum, Batya

    2014-01-01

    Research suggests a positive relationship between schools&apos; efforts to engage parents and parents&apos; involvement in their child&apos;s education. The authors investigated school socioeconomic status, school size, grade level, and student-teacher ratio as predictors of schools&apos; efforts to engage parents of students receiving special…

  16. How Do Teachers&apos; Beliefs Predict Children&apos;s Interest in Math from Kindergarten to Sixth Grade?

    ERIC Educational Resources Information Center

    Upadyaya, Katja; Eccles, Jacquelynne S.

    2014-01-01

    The present study investigated to what extent teachers&apos; beliefs about children&apos;s achievement contribute to the development of children&apos;s math interest. In addition, the extent to which other possible predictors, such as performance in math, gender, and race/ethnicity would contribute to the development of children&apos;s math…

  17. The Problem of Character Education and Kohlberg&apos;s Moral Education: Critique from Dewey&apos;s Moral Deliberation

    ERIC Educational Resources Information Center

    Liu, Xiangdong

    2014-01-01

    In this article, the author examines Dewey&apos;s moral deliberation. Liu argues that Dewey&apos;s work will enrich both character education and Kohlberg&apos;s moral education. Liu focuses on character education and on Kohlberg&apos;s moral education because these are the two dominant approaches. Character education seeks to cultivate good…

  18. Parents&apos; Views of the National Autistic Society&apos;s EarlyBird Plus Programme

    ERIC Educational Resources Information Center

    Cutress, Anna L.; Muncer, Steven J.

    2014-01-01

    Parent training interventions are recommended for parents soon after their child&apos;s autism spectrum condition diagnosis with the aim of improving parents&apos; psychological well-being and coping, as well as the child&apos;s behaviour. This report explores parents&apos; views of the EarlyBird Plus Programme through data collected routinely in…

  19. Modified apolipoprotein (apo) A-I by artificial sweetener causes severe premature cellular senescence and atherosclerosis with impairment of functional and structural properties of apoA-I in lipid-free and lipid-bound state.

    PubMed

    Jang, Wookju; Jeoung, Nam Ho; Cho, Kyung-Hyun

    2011-05-01

    Long-term consumption of artificial sweeteners (AS) has been the recent focus of safety concerns. However, the potential risk of the AS in cardiovascular disease and lipoprotein metabolism has not been investigated sufficiently. We compared the influence of AS (aspartame, acesulfame K, and saccharin) and fructose in terms of functional and structural correlations of apolipoprotein (apo) A-I and high-density lipoproteins (HDL), which have atheroprotective effects. Long-term treatment of apoA-I with the sweetener at physiological concentration (3 mM for 168 h) resulted in loss of antioxidant and phospholipid binding activities with modification of secondary structure. The AS treated apoA-I exhibited proteolytic cleavage to produce 26 kDa-fragment. They showed pro-atherogenic properties in acetylated LDL phagocytosis of macrophages. Each sweetener alone or sweetener-treated apoA-I caused accelerated senescence in human dermal fibroblasts. These results suggest that long-term consumption of AS might accelerate atherosclerosis and senescence via impairment of function and structure of apoA-I and HDL.

  20. Family history and apoE genotype interaction in Alzheimer`s disease (AD)

    SciTech Connect

    Jarvik, G.P.; Kukull, W.A.; Goddards, K.

    1994-09-01

    The apoE {epsilon}4 allele is associated with increased risk and decreased age of onset of AD. The {epsilon}4 allele may have opposing effects. We determined that family history of a parent or sib with memory problems (famhx+) modified the effect of apoE genotype in a population-based, case (n=165, 72 famhx+)-control (n=233, 73 famhx+) sample. Logistic regression analyses detected a significant apoE genotype (E) by family history (F) by age (A) interaction (ExFxA, p=0.003) and ExF interaction (p=0.0001) in the prediction of AD. ExFxA remained significant when only {epsilon}4+ genotypes were included (p<0.01). ExFxSex (p=0.04) and ExF (p<0.0001) were significant when only {epsilon}4- genotypes were included. Similary, multiple regression detected significant ExF interaction in the prediction of age of AD onset for {epsilon}4+ genotypes (p=0.04) or {epsilon}4- genotypes (p=0.04). Sex did not interact in the prediction of age of onset. Famhx+ increased risk of AD differentially and reduced age of onset except in {epsilon}2+ genotypes. Family history modifies the apoE genotype influence on risk and onset age of AD, suggesting that non-apoE genetic effects interact with apoE in AD. It is most predictive of risk in those with the {epsilon}2{epsilon}3 genotype. Variation in risk and onset among both {epsilon}4+ and {epsilon}4- genotypes demonstrate that {epsilon}2 and {epsilon}3 mediate {epsilon}4 allele effects in AD.

  1. Higher Plasma ApoE Levels are Associated with Low-Normal Thyroid Function: Studies in Diabetic and Nondiabetic Subjects.

    PubMed

    van Tienhoven-Wind, L J N; Dallinga-Thie, G M; Dullaart, R P F

    2016-07-01

    Low-normal thyroid function within the euthyroid range may confer higher plasma triglycerides, but relationships with plasma apolipoprotein (apo) E, which plays an important role in the metabolism of triglyceride-rich apoB-containing lipoproteins, are unknown. We determined relationships of plasma apoE with thyroid stimulating hormone (TSH) and free thyroxine (free T4) in euthyroid subjects with and without Type 2 diabetes mellitus (T2DM). TSH, free T4, lipids, and apoE were measured in fasting plasma from 72 T2DM subjects and 82 nondiabetic subjects. The APOE genotype was also determined. Free T4 was slightly higher in T2DM (p=0.030), but TSH levels were not different vs. nondiabetic subjects. The APOE genotype distribution was not different between the groups. None of the participants had the ε2/ε2 genotype. Plasma triglycerides were higher in T2DM (p=0.037). ApoB and apoE levels were not different between the groups. In all subjects combined, multivariable analysis showed that plasma triglycerides (p=0.039), non-high density lipoprotein (non-HDL) cholesterol (p=0.030), and apoE levels (p=0.002) were each independently and positively associated with TSH after adjustment for age, sex, T2DM and the presence of the APOE ε3 allele. Furthermore, the associations of TSH with apoE remained present after adjustment for either triglycerides, non-HDL cholesterol, or apoB (p=0.005 to 0.023). The presence of T2DM did not modify the relationships of TSH with these (apo) lipoprotein variables (p=0.11 to 0.36). In conclusion, low-normal thyroid function, as indicated by higher TSH levels within the euthyroid range, may influence the metabolism of triglyceride-rich lipoproteins by affecting apoE regulation.

  2. PKR Inhibition Rescues Memory Deficit and ATF4 Overexpression in ApoE ε4 Human Replacement Mice.

    PubMed

    Segev, Yifat; Barrera, Iliana; Ounallah-Saad, Hadile; Wibrand, Karin; Sporild, Ida; Livne, Adva; Rosenberg, Tali; David, Orit; Mints, Meshi; Bramham, Clive R; Rosenblum, Kobi

    2015-09-23

    Sporadic Alzheimer's disease (AD) is an incurable neurodegenerative disease with clear pathological hallmarks, brain dysfunction, and unknown etiology. Here, we tested the hypothesis that there is a link between genetic risk factors for AD, cellular metabolic stress, and transcription/translation regulation. In addition, we aimed at reversing the memory impairment observed in a mouse model of sporadic AD. We have previously demonstrated that the most prevalent genetic risk factor for AD, the ApoE4 allele, is correlated with increased phosphorylation of the translation factor eIF2α. In the present study, we tested the possible involvement of additional members of the eIF2α pathway and identified increased mRNA expression of negative transcription factor ATF4 (aka CREB2) both in human and a mouse model expressing the human ApoE4 allele. Furthermore, injection of a PKR inhibitor rescued memory impairment and attenuated ATF4 mRNA increased expression in the ApoE4 mice. The results propose a new mechanism by which ApoE4 affects brain function and further suggest that inhibition of PKR is a way to restore ATF4 overexpression and memory impairment in early stages of sporadic AD. Significance statement: ATF4 mRNA relative quantities are elevated in ApoE4 allele carriers compared with noncarrier controls. This is true also for the ApoE ε4 human replacement mice. ApoE4 mice injected with PKR inhibitor (PKRi) demonstrate a significant reduction in ATF4 expression levels 3 h after one injection of PKRi. Treatment of ApoE4 human replacement mice with the PKRi before learning rescues the memory impairment of the ApoE4 AD model mice. We think that these results propose a new mechanism by which ApoE4 affects brain function and suggest that inhibition of PKR is a way to restore memory impairment in early stages of sporadic AD.

  3. High serum apolipoprotein E determines hypertriglyceridemic dyslipidemias, coronary disease and apoA-I dysfunctionality.

    PubMed

    Onat, Altan; Can, Günay; Ornek, Ender; Ayhan, Erkan; Erginel-Ünaltuna, Nihan; Murat, Sani N

    2013-01-01

    The relevance of serum apolipoprotein E (apoE) levels to two hypertriglyceridemic dyslipidemias has not been clarified. We explored, in a cross-sectional (and short-term prospective) evaluation, the independent relationship of serum apoE to the atherogenic dyslipidemia, hypertriglyceridemia with elevated apoB (HtgB) and to apoA-I dysfunctionality, previously shown in Turkish adults to be independent of apoE genotype. Serum apoE concentrations were measured by immunonephelometry in 1,127 middle-aged adults. In multivariable regression analysis, apoE concentrations showed log-linear associations with apoB and apoA-I levels, waist circumference, independent of C-reactive protein (CRP), homeostatic model assessment (HOMA) index and other confounders. The likelihood of atherogenic dyslipidemia and of HtgB roughly tripled per 1-SD increment in apoE concentrations, additively to apoE genotype, HOMA, apoA-I, CRP concentrations and waist circumference; yet apoA-I, protective against atherogenic dyslipidemia, appeared to promote HtgB, a finding consistent with apoA-I dysfunctionality in this setting. Each 1-SD increment in the apoE level was moreover, associated in both genders with MetS (at OR 1.5), after adjustment for sex, age, apoB, apoA-I and CRP, or for apoE genotypes. Circulating apoE predicted in both genders age-adjusted prevalent and incident coronary heart disease (CHD), independent of apoE genotype and CRP (OR 1.32 [95 % CI 1.11; 1.58]). To conclude, in a general population prone to MetS, elevated apoE concentrations are strongly linked to HtgB and atherogenic dyslipidemia, irrespective of apoE genotype, are associated with MetS and CHD. Excess apoE reflects pro-inflammatory state and likely autoimmune activation.

  4. Apo J and Apo D: Complementary or Antagonistic Roles in Alzheimer's Disease?

    PubMed

    Del Valle, Eva; Navarro, Ana; Martínez-Pinilla, Eva; Torices, Silvia; Tolivia, Jorge

    2016-05-17

    Apolipoprotein D (Apo D) and Apolipoprotein J (Apo J) are among the only nine apolipoproteins synthesized in the nervous system. Apart from development, these apolipoproteins are implicated in the normal aging process as well as in different neuropathologies as Alzheimer's disease (AD), where a neuroprotective role has been postulated. Different authors have proposed that Apo D and Apo J could be biomarkers for AD but as far as we know, there are no studies about the relationship between them as well as their expression pattern along the progression of the disease. In this paper, using double immunohistochemistry techniques, we have demonstrated that Apo D is mainly located in glial cells while Apo J expression preferentially occurs in neurons; both proteins are also present in AD diffuse and mature senile plaques but without signal overlap. In addition, we have observed that Apo J and Apo D immunostaining shows a positive correlation with the progression of the disease and the Braak's stages. These results suggest complementary and cell-dependent neuroprotective roles for each apolipoprotein during AD progress. PMID:27197790

  5. Students&apos; Perceptions of Their Science Teachers&apos; Pedagogical Content Knowledge

    ERIC Educational Resources Information Center

    Halim, Lilia; Abdullah, Sharifah Intan Sharina Syed; Meerah, T. Subahan Mohd

    2014-01-01

    Pedagogical content knowledge (PCK) is a type of teacher knowledge to be developed by a teacher. PCK is said to contribute to effective teaching. Most studies investigated the development of PCK and its influence on students&apos; learning from the teachers&apos; perspectives. Only a limited number of studies have investigated the components of…

  6. An Exploration of Mothers&apos; Attitudes towards Their Daughters&apos; Menarche

    ERIC Educational Resources Information Center

    Bennett, Clare; Harden, Jane

    2014-01-01

    Menarche is a significant milestone for young women, representing an important juncture between girlhood and maturation. The limited literature that exists suggests that a mother&apos;s reaction to her daughter&apos;s first periods can shape her experiences and perceptions of menstruation which, in turn, may impact on her self-image and,…

  7. Effects of Teachers&apos; Instructional Development on Students&apos; Study Approaches in Higher Education

    ERIC Educational Resources Information Center

    Stes, Ann; De Maeyer, Sven; Gijbels, David; Van Petegem, Peter

    2013-01-01

    Evidence regarding the impact of teachers&apos; instructional development on student learning in higher education is scarce. In this study the authors investigate the impact of an instructional development programme for beginning university teachers on students&apos; approach to studying. They also explore whether this impact is dependent on class…

  8. Extension&apos;s Role in Developing a Farmers&apos; Market

    ERIC Educational Resources Information Center

    Civittolo, David

    2012-01-01

    Interest in access to local food is increasing. Communities of all types and sizes have volunteers interested in creating farmers&apos; markets. Extension can play an important role in the development of farmers&apos; markets because it is ideally suited to organize and coordinate these volunteer energies. By helping community volunteers focus…

  9. Boys&apos; Music? School Context and Middle-School Boys&apos; Musical Choices

    ERIC Educational Resources Information Center

    Bennetts, Kathleen Scott

    2013-01-01

    This article focusses primarily on the findings relating to the musical participation of boys in one Melbourne school. As part of a project that investigated boys&apos; attitudes and participation at fifty-one schools, several contextual features were identified that set "Balton Boys" High School&apos; apart from other participating…

  10. Chilean Adolescents&apos; and Parents&apos; Views on Autonomy Development

    ERIC Educational Resources Information Center

    Martínez, M. Loreto; Pérez, J. Carola; Cumsille, Patricio

    2014-01-01

    This study aims to understand Chilean parents&apos; and adolescents&apos; conceptions of autonomy and whether they hold different expectations for autonomous behaviors by generation and socioeconomic level. A qualitative approach to data collection was used through separate focus groups of parents and adolescents from different socioeconomic…

  11. ApoE Genotype and Alzheimer's Disease in Adults with Down Syndrome: Meta-Analysis.

    ERIC Educational Resources Information Center

    Prashner, V. P.; Chowdhury, T. A.; Rowe, B. R.; Bain, S. C.

    1997-01-01

    ApoE gene polymorphism was examined in 100 adults with Down syndrome with and without dementia (Alzheimer's disease) and 346 control subjects. Additionally, a meta analysis of studies (total N=480 subjects) was performed. Results indicated a similar incidence of the gene across groups but subjects with the allele tended to an earlier onset of…

  12. Malaysian Primary Pre-Service Teachers&apos; Perceptions of Students&apos; Disruptive Behaviour

    ERIC Educational Resources Information Center

    Zakaria, Norzila; Reupert, Andrea; Sharma, Umesh

    2013-01-01

    The purpose of this paper was to investigate Malaysian primary pre-service teachers&apos; perceptions of students&apos; disruptive behaviour and their self-reported strategies to prevent and to manage such behaviours. Results indicate that Malaysian pre-service teachers understand disruptive behaviours to be those that disrupt the learning and…

  13. Parents&apos; and Teachers&apos; Perceptions of Standards-Based and Traditional Report Cards

    ERIC Educational Resources Information Center

    Swan, Gerry M.; Guskey, Thomas R.; Jung, Lee Ann

    2014-01-01

    The purpose of this study was to determine parents&apos; and teachers&apos; perceptions of standards-based and traditional report cards. Participants included 115 parents/guardians of students from a single, midsize school district that had implemented a standards-based report card. During the first two marking periods, all parents/guardians…

  14. The Relationship between Teacher&apos;s Autonomy Support and Students&apos; Autonomy and Vitality

    ERIC Educational Resources Information Center

    Núñez, Juan L.; Fernández, Celia; León, Jaime; Grijalvo, Fernando

    2015-01-01

    What makes a student feel vital and energetic? Using the self-determination framework, we analyzed how the behavior and feelings of students depend on social factors such as the teachers&apos; attitudes. The goal of the study was to test an integrated sequence over a semester in which teacher&apos;s autonomy support acts as a predictor of…

  15. Mapping of ApoE4 related white matter damage using diffusion MRI

    NASA Astrophysics Data System (ADS)

    Tsao, Sinchai; Gajawelli, Niharika; Hwang, Darryl H.; Kriger, Stephen; Law, Meng; Chui, Helena; Weiner, Michael; Lepore, Natasha

    2014-04-01

    ApoliopoproteinE Ɛ4 (ApoE-Ɛ4) polymorphism is the most well known genetic risk factor for developing Alzheimers Disease. The exact mechanism through which ApoE 4 increases AD risk is not fully known, but may be related to decreased clearance and increased oligomerization of Aβ. By making measurements of white matter integrity via diffusion MR and correlating the metrics in a voxel-based statistical analysis with ApoE-Ɛ4 genotype (whilst controlling for vascular risk factor, gender, cognitive status and age) we are able to identify changes in white matter associated with carrying an ApoE Ɛ4 allele. We found potentially significant regions (Puncorrected < 0:05) near the hippocampus and the posterior cingulum that were independent of voxels that correlated with age or clinical dementia rating (CDR) status suggesting that ApoE may affect cognitive decline via a pathway in dependent of normal aging and acute insults that can be measured by CDR and Framingham Coronary Risk Score (FCRS).

  16. Initiating Teachers&apos; Action Research: Empowering Teachers&apos; Voices

    ERIC Educational Resources Information Center

    Bognar, Branko

    2013-01-01

    The role of a teacher as an action researcher in Croatia is still insufficiently appreciated and promoted in initial teachers&apos; training, school students learning and in the employed teachers&apos; professional post-qualification development. In this country, teachers are most frequently perceived as mediators or technicians whose task is to…

  17. Examining the Relationship between Teachers&apos; Instructional Practices and Students&apos; Mathematics Achievement

    ERIC Educational Resources Information Center

    Firmender, Janine M.; Gavin, M. Katherine; McCoach, D. Betsy

    2014-01-01

    The purpose of this study was to determine whether relationships existed between teachers&apos; implementation of two specific discourse-related instructional practices and students&apos; mathematics achievement in geometry and measurement as part of a research study on the effectiveness of an advanced mathematics curriculum for kindergarten and…

  18. Teachers&apos; Perceptions Regarding School Principals&apos; Coaching Skills

    ERIC Educational Resources Information Center

    Yirci, Ramazan; Özdemir, Tuncay Yavuz; Kartal, Seçil Eda; Kocabas, Ibrahim

    2014-01-01

    The purpose of this study was to find out teachers&apos; perceptions about school principals&apos; coaching skills. The study was carried out within qualitative research methods. The study group included 76 teachers in Elazig and 73 teachers in Kahramanmaras provinces of Turkey. All the data were processed using Nvivo 9 software. The results…

  19. Teacher Educators&apos; Professional Development: Towards a Typology of Teacher Educators&apos; Researcherly Disposition

    ERIC Educational Resources Information Center

    Tack, Hanne; Vanderlinde, Ruben

    2014-01-01

    Since the beginning of the twenty-first century, the need for teacher educators&apos;--or those who teach the teachers--professional development became increasingly recognised in both policy and research literature. In this respect, a growing body of publications highly stress the teacher educators&apos; task of engaging in research and becoming a…

  20. Parallels in Preschoolers&apos; and Adults&apos; Judgments about Ownership Rights and Bodily Rights

    ERIC Educational Resources Information Center

    Van de Vondervoort, Julia W.; Friedman, Ori

    2015-01-01

    Understanding ownership rights is necessary for socially appropriate behavior. We provide evidence that preschoolers&apos; and adults&apos; judgments of ownership rights are related to their judgments of bodily rights. Four-year-olds (n = 70) and adults (n = 89) evaluated the acceptability of harmless actions targeting owned property and body…

  1. "Entre Familia": Immigrant Parents&apos; Strategies for Involvement in Children&apos;s Schooling

    ERIC Educational Resources Information Center

    Poza, Luis; Brooks, Maneka Deanna; Valdés, Guadalupe

    2014-01-01

    Teachers and administrators in schools with large, working-class Latino populations often complain of parents&apos; indifference or lack of involvement in children&apos;s schooling because of their low visibility at school events and relatively little face-to-face communication with teachers and school administration. In a series of…

  2. Reelin and apoE actions on signal transduction, synaptic function and memory formation.

    PubMed

    Rogers, Justin T; Weeber, Edwin J

    2008-08-01

    Low-density-lipoprotein receptors (LDLRs) are an evolutionarily ancient surface protein family with the ability to activate a diversity of extracellular signals across the cellular membrane in the adult central nervous system (CNS). Their intimate roles in modulating synaptic plasticity and their necessity in hippocampal-dependent learning and memory have only recently come to light. Two known LDLR ligands, specifically apolipoprotein E (apoE) and reelin, have been the most widely investigated in this regard. Most of our understanding of synaptic plasticity comes from investigation of both pre- and postsynaptic alterations. Therefore, it is interesting to note that neurons and glia that do not contribute to the synaptic junction in question can secrete signaling molecules that affect synaptic plasticity. Notably, reelin and apoE have been shown to modulate hippocampal long-term potentiation in general, and affect NMDA receptor and AMPA receptor regulation specifically. Furthermore, these receptors and signaling molecules have significant roles in neuronal degenerative diseases such as Alzheimer's disease. The recent production of recombinant proteins, knockout and transgenic mice for receptors and ligands and the development of human ApoE targeted replacement mice have significantly expanded our understanding of the roles LDLRs and their ligands have in certain disease states and the accompanying initiation of specific signaling pathways. This review describes the role LDLRs, apoE and reelin have in the regulation of hippocampal synaptic plasticity.

  3. Who&apos;s Really Struggling?: Middle School Teachers&apos; Perceptions of Struggling Readers

    ERIC Educational Resources Information Center

    Moreau, Leah K.

    2014-01-01

    This study explored middle school teachers&apos; perceptions of struggling readers, including influences such as: understandings of components and factors relating to reading difficulties; views of struggling readers&apos; behaviours and affect; classroom implications of their difficulties; and feelings of both competency and responsibility in the…

  4. Addressing K-5 Students&apos; and Preservice Elementary Teachers&apos; Conceptions of Seasonal Change

    ERIC Educational Resources Information Center

    Starakis, Ioannis; Halkia, Krystallia

    2014-01-01

    In this paper, primary school students&apos; and pre-service teachers&apos; ideas of seasonal change are investigated. The research was carried out in nine primary schools in Athens and in the Primary Education Department of the University of Athens. Written reports were used for gathering data while students also had the opportunity to support…

  5. A Class Act? Lecturers&apos; Views on Undergraduates&apos; Employability

    ERIC Educational Resources Information Center

    Morrison, Andrew

    2014-01-01

    This article details the findings of a study into lecturers&apos; perceptions of undergraduate employability. The investigation employed interviews with the staff on a BA (Hons) in Education Studies course at a post-1992 university. The aim was to examine staff beliefs regarding their students&apos; potential employability in the business and…

  6. Apo J and Apo D: Complementary or Antagonistic Roles in Alzheimer's Disease?

    PubMed

    Del Valle, Eva; Navarro, Ana; Martínez-Pinilla, Eva; Torices, Silvia; Tolivia, Jorge

    2016-05-17

    Apolipoprotein D (Apo D) and Apolipoprotein J (Apo J) are among the only nine apolipoproteins synthesized in the nervous system. Apart from development, these apolipoproteins are implicated in the normal aging process as well as in different neuropathologies as Alzheimer's disease (AD), where a neuroprotective role has been postulated. Different authors have proposed that Apo D and Apo J could be biomarkers for AD but as far as we know, there are no studies about the relationship between them as well as their expression pattern along the progression of the disease. In this paper, using double immunohistochemistry techniques, we have demonstrated that Apo D is mainly located in glial cells while Apo J expression preferentially occurs in neurons; both proteins are also present in AD diffuse and mature senile plaques but without signal overlap. In addition, we have observed that Apo J and Apo D immunostaining shows a positive correlation with the progression of the disease and the Braak's stages. These results suggest complementary and cell-dependent neuroprotective roles for each apolipoprotein during AD progress.

  7. The SAPO Campus Recommender System: A Study about Students&apos; and Teachers&apos; Opinions

    ERIC Educational Resources Information Center

    Pedro, Luís; Santos, Carlos; Almeida, Sara Filipa; Ramos, Fernando; Moreira, António; Almeida, Margarida; Antunes, Maria João

    2014-01-01

    This paper aims to assess the relevance and usefulness of the SAPO Campus recommender system, through the analysis of students&apos; and teachers&apos; opinions. Recommender systems, assuming a "technology-driven" approach, have been designed with the primary goal of predicting user interests based on the implicit analysis of their…

  8. Teachers&apos; Perceptions Based on Tenure Status and Gender about Principals&apos; Supervision

    ERIC Educational Resources Information Center

    Range, Bret G.; Finch, Kim; Young, Suzanne; Hvidston, David J.

    2014-01-01

    This descriptive study assessed teachers&apos; attitudes about their formative supervision and the observational ability of principals through the constructs of teacher tenure status and gender. In sum, 255 teachers responded to an online survey indicating teachers&apos; desired feedback focused on classroom climate, student engagement, and…

  9. Oxidative Stress Impairs Learning and Memory in apoE Knockout Mice

    PubMed Central

    Evola, Marianne; Hall, Allyson; Wall, Trevor; Young, Alice; Grammas, Paula

    2010-01-01

    Cardiovascular risk factors, such as oxidative stress and elevated lipids, are linked to the development of cognitive impairment. A mediator common to both stressors is the apolipoprotein E (apoE). The objectives of this study are to determine the effects of apoE deficiency and diet-induced systemic oxidative stress in mice on vascular expression of inflammatory proteins and on cognitive function. Mice are placed on a diet enriched in homocysteine for fifteen weeks and then assessed for spatial learning using an eight-arm radial maze and for inflammatory protein expression by immunohistochemistry. Our results show that diet-induced oxidative stress does not affect cognitive function in normal mice. In contrast, apoE−/− mice on the homocysteine diet show significantly impaired (p < 0. 001) maze performance. ApoE−/− mice also have high cholesterol levels. There is no expression of inflammatory proteins IL-6 and IL-8 in the vasculature of control mice on normal or homocysteine diet and little in apoE−/− mice on normal diet. In contrast, apoE−/− mice on homocysteine diet show pronounced vascular reactivity to IL-6 and IL-8 antibodies. These data show that systemic oxidative stress correlates with expression of inflammatory proteins in the cerebral vasculature and impaired cognitive function. These results are consistent with the hypothesis that an oxidative-inflammatory cycle in the cerebral vasculature could have deleterious consequences for cognition. PMID:20457176

  10. Let&apos;s Burn Them All: A Librarian&apos;s View

    ERIC Educational Resources Information Center

    Werner, Roye

    2014-01-01

    In this rejoinder to "Let&apos;s Burn Them All," a librarian supports the author&apos;s case for eliminating textbooks in the teaching of management and organizational behavior. A move away from textbooks would free libraries from worrying about whether and to what extent to provide expensive textbook access to students, a long-standing…

  11. Relations among Teachers&apos; Emotion Socialization Beliefs and Practices and Preschoolers&apos; Emotional Competence

    ERIC Educational Resources Information Center

    Morris, Carol A. S.; Denham, Susanne A.; Bassett, Hideko H.; Curby, Timothy W.

    2013-01-01

    Research Findings: Utilizing a 3-part model of emotion socialization that included modeling, contingent responding, and teaching, this study examined the associations between 44 teachers&apos; self-reported and observed emotion socialization practices and 326 preschoolers&apos; emotion knowledge and observed emotional behavior. Multilevel analyses…

  12. Apo A-I inhibits foam cell formation in apo E–deficient mice after monocyte adherence to endothelium

    PubMed Central

    Dansky, Hayes M.; Charlton, Sherri A.; Barlow, Courtenay B.; Tamminen, Minna; Smith, Jonathan D.; Frank, Joy S.; Breslow, Jan L.

    1999-01-01

    We have previously shown that expression of the human apo A-I transgene on the apo E–deficient background increases HDL cholesterol and greatly diminishes fatty streak lesion formation. To examine the mechanism, prelesional events in atherosclerotic plaque development were examined in 6- to 8-week-old apo E–deficient and apo E–deficient/human apo A-I transgenic mice. A quantitative assessment of subendothelial lipid deposition by freeze-fracture and deep-etch electron microscopy indicated that elevated apo A-I did not affect the distribution or amount of aortic arch subendothelial lipid deposits. Immunohistochemical staining for VCAM-1 demonstrated similar expression on endothelial cells at prelesional aortic branch sites from both apo E–deficient and apo E–deficient/human apo A-I transgenic mice. Transmission electron microscopy revealed monocytes bound to the aortic arch in mice of both genotypes, and immunohistochemical staining demonstrated that the area occupied by bound mononuclear cells was unchanged. Serum paraoxonase and aryl esterase activity did not differ between apo E–deficient and apo E–deficient/human apo A-I transgenic mice. These data suggest that increases in apo A-I and HDL cholesterol inhibit foam cell formation in apo E–deficient/human apo A-I transgenic mice at a stage following lipid deposition, endothelial activation, and monocyte adherence, without increases in HDL-associated paraoxonase. PMID:10393696

  13. A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice

    PubMed Central

    Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Haast, Roy; Lütjohann, Dieter; Broersen, Laus M.; Heerschap, Arend

    2016-01-01

    APOE ε4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10–12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16–18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging. PMID:27034849

  14. A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice.

    PubMed

    Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Haast, Roy; Lütjohann, Dieter; Broersen, Laus M; Heerschap, Arend; Kiliaan, Amanda J

    2016-01-01

    APOE ε4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10-12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16-18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging. PMID:27034849

  15. A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice.

    PubMed

    Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Haast, Roy; Lütjohann, Dieter; Broersen, Laus M; Heerschap, Arend; Kiliaan, Amanda J

    2016-01-01

    APOE ε4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10-12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16-18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging.

  16. Chronic Internal Exposure to Low Dose 137Cs Induces Positive Impact on the Stability of Atherosclerotic Plaques by Reducing Inflammation in ApoE-/- Mice.

    PubMed

    Le Gallic, Clélia; Phalente, Yohann; Manens, Line; Dublineau, Isabelle; Benderitter, Marc; Gueguen, Yann; Lehoux, Stephanie; Ebrahimian, Teni G

    2015-01-01

    After Chernobyl and Fukushima Daï Chi, two major nuclear accidents, large amounts of radionuclides were released in the environment, mostly caesium 137 (137Cs). Populations living in contaminated territories are chronically exposed to radionuclides by ingestion of contaminated food. However, questions still remain regarding the effects of low dose ionizing radiation exposure on the development and progression of cardiovascular diseases. We therefore investigated the effects of a chronic internal exposure to 137Cs on atherosclerosis in predisposed ApoE-/- mice. Mice were exposed daily to 0, 4, 20 or 100 kBq/l 137Cs in drinking water, corresponding to range of concentrations found in contaminated territories, for 6 or 9 months. We evaluated plaque size and phenotype, inflammatory profile, and oxidative stress status in different experimental groups. Results did not show any differences in atherosclerosis progression between mice exposed to 137Cs and unexposed controls. However, 137Cs exposed mice developed more stable plaques with decreased macrophage content, associated with reduced aortic expression of pro-inflammatory factors (CRP, TNFα, MCP-1, IFNγ) and adhesion molecules (ICAM-1, VCAM-1 and E-selectin). Lesions of mice exposed to 137Cs were also characterized by enhanced collagen and smooth muscle cell content, concurrent with reduced matrix metalloproteinase MMP8 and MMP13 expression. These results suggest that low dose chronic exposure of 137Cs in ApoE-/- mice enhances atherosclerotic lesion stability by inhibiting pro-inflammatory cytokine and MMP production, resulting in collagen-rich plaques with greater smooth muscle cell and less macrophage content. PMID:26046630

  17. Chronic Internal Exposure to Low Dose 137Cs Induces Positive Impact on the Stability of Atherosclerotic Plaques by Reducing Inflammation in ApoE-/- Mice

    PubMed Central

    Le Gallic, Clélia; Phalente, Yohann; Manens, Line; Dublineau, Isabelle; Benderitter, Marc; Gueguen, Yann; Lehoux, Stephanie; Ebrahimian, Teni G.

    2015-01-01

    After Chernobyl and Fukushima Daï Chi, two major nuclear accidents, large amounts of radionuclides were released in the environment, mostly caesium 137 (137Cs). Populations living in contaminated territories are chronically exposed to radionuclides by ingestion of contaminated food. However, questions still remain regarding the effects of low dose ionizing radiation exposure on the development and progression of cardiovascular diseases. We therefore investigated the effects of a chronic internal exposure to 137Cs on atherosclerosis in predisposed ApoE-/- mice. Mice were exposed daily to 0, 4, 20 or 100 kBq/l 137Cs in drinking water, corresponding to range of concentrations found in contaminated territories, for 6 or 9 months. We evaluated plaque size and phenotype, inflammatory profile, and oxidative stress status in different experimental groups. Results did not show any differences in atherosclerosis progression between mice exposed to 137Cs and unexposed controls. However, 137Cs exposed mice developed more stable plaques with decreased macrophage content, associated with reduced aortic expression of pro-inflammatory factors (CRP, TNFα, MCP-1, IFNγ) and adhesion molecules (ICAM-1, VCAM-1 and E-selectin). Lesions of mice exposed to 137Cs were also characterized by enhanced collagen and smooth muscle cell content, concurrent with reduced matrix metalloproteinase MMP8 and MMP13 expression. These results suggest that low dose chronic exposure of 137Cs in ApoE-/- mice enhances atherosclerotic lesion stability by inhibiting pro-inflammatory cytokine and MMP production, resulting in collagen-rich plaques with greater smooth muscle cell and less macrophage content. PMID:26046630

  18. "It&apos;s Not Them, It&apos;s Me": Competing Discourses in One Aspiring Teacher&apos;s Talk

    ERIC Educational Resources Information Center

    Gomez, Mary Louise; Carlson, James R.; Foubert, Jennifer; Powell, Shameka N.

    2014-01-01

    In this paper, we deploy M.M. Bakhtin&apos;s notions about how language works to understand aspiring teachers&apos; struggles about the intersecting roles race, class, gender, language background, and sexual orientation play in students&apos; school lives and learning. Through life-history interviews and document analysis, we investigated the…

  19. STEM High School Administrators&apos;, Teachers&apos;, and Students&apos; Perceptions of Curricular and Instructional Strategies and Practices

    ERIC Educational Resources Information Center

    Bruce-Davis, Micah N.; Gubbins, E. Jean; Gilson, Cindy M.; Villanueva, Merzili; Foreman, Jennifer L.; Rubenstein, Lisa DaVia

    2014-01-01

    The present qualitative study was conducted in response to federal initiatives aimed at increasing the number of science, technology, engineering, and mathematics (STEM) schools in the United States; and to better understand STEM high school administrators&apos;, teachers&apos;, and students&apos; perceptions of the characteristics of the…

  20. The Impact of Teachers&apos; and Supervisors&apos; Involvement on Students&apos; Skill and Affective Development in Service-Learning

    ERIC Educational Resources Information Center

    Leemen, Lee

    2013-01-01

    The study reported an assessment of a university-wide curriculum-based service learning program and, based on the assessment data, analyzed the impact of teachers&apos; and supervisors&apos; involvement on students&apos; skill and affective learning outcomes. The study (n=750) showed that in general the students agreed that their participation in…

  1. Fathers&apos; and Mothers&apos; Home Literacy Involvement and Children&apos;s Cognitive and Social Emotional Development: Implications for Family Literacy Programs

    ERIC Educational Resources Information Center

    Baker, Claire E.

    2013-01-01

    The relations between fathers&apos; and mothers&apos; home literacy involvement at 24 months and children&apos;s cognitive and social emotional development in preschool were examined using a large sample of African American and Caucasian families ("N" = 5190) from the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B). Hierarchical…

  2. Living with Letters: An Exploration of Parents&apos;/Caregivers&apos; Perceptions of Shared Learning Activities, Socially Constructed Meaning, and Preschoolers&apos; Literacy Development

    ERIC Educational Resources Information Center

    Janaszak, Jaclyn

    2013-01-01

    The researcher&apos;s purpose in this descriptive case study, drawn from a suburban school population of pre-kindergarten children and their parents/caregivers was: (a) to explore parents&apos;/caregivers&apos; perceptions of the concept of emergent literacy and how their children develop the ability to read and write; (b) to document the ways in…

  3. Longitudinal Links between Fathers&apos; and Mothers&apos; Harsh Verbal Discipline and Adolescents&apos; Conduct Problems and Depressive Symptoms

    ERIC Educational Resources Information Center

    Wang, Ming-Te; Kenny, Sarah

    2014-01-01

    This study used cross-lagged modeling to examine reciprocal relations between maternal and paternal harsh verbal discipline and adolescents&apos; conduct problems and depressive symptoms. Data were from a sample of 976 two-parent families and their children (51% males; 54% European American, 40% African American). Mothers&apos; and fathers&apos;…

  4. Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2.

    PubMed

    Vandal, Milène; Alata, Wael; Tremblay, Cyntia; Rioux-Perreault, Christine; Salem, Norman; Calon, Frédéric; Plourde, Mélanie

    2014-05-01

    Benefits on cognition from docosahexaenoic acid (DHA, 22 : 6 n-3) intake are absent in humans carrying apolipoprotein E ε4 allele (APOE4), the most important genetic risk factor for Alzheimer's disease (AD). To test the hypothesis that carrying APOE4 impairs DHA distribution, we evaluated plasma and brain fatty acid profiles and uptake of [(14) C]-DHA using in situ cerebral perfusion through the blood-brain barrier in 4- and 13-month-old male and female APOE-targeted replacement mice (APOE2, APOE3, and APOE4), fed with a DHA-depleted diet. Cortical and plasma DHA were 9% lower and 34% higher in APOE4 compared to APOE2 mice, respectively. Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. A significant relationship was established between DHA and apoE concentrations in the cortex of mice (r(2) = 0.21) and AD patients (r(2) = 0.32). Altogether, our results suggest that lower brain uptake of DHA in APOE4 than in APOE2 mice may limit the accumulation of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of AD. Using human APOE2, 3, and 4 isoform-specific transgenic mice, we found a lower brain uptake of docosahexaenoic acid (DHA) in APOE4 than in APOE2 mice that may limit the biodistribution of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of Alzheimer's disease (AD). PMID:24345162

  5. Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2.

    PubMed

    Vandal, Milène; Alata, Wael; Tremblay, Cyntia; Rioux-Perreault, Christine; Salem, Norman; Calon, Frédéric; Plourde, Mélanie

    2014-05-01

    Benefits on cognition from docosahexaenoic acid (DHA, 22 : 6 n-3) intake are absent in humans carrying apolipoprotein E ε4 allele (APOE4), the most important genetic risk factor for Alzheimer's disease (AD). To test the hypothesis that carrying APOE4 impairs DHA distribution, we evaluated plasma and brain fatty acid profiles and uptake of [(14) C]-DHA using in situ cerebral perfusion through the blood-brain barrier in 4- and 13-month-old male and female APOE-targeted replacement mice (APOE2, APOE3, and APOE4), fed with a DHA-depleted diet. Cortical and plasma DHA were 9% lower and 34% higher in APOE4 compared to APOE2 mice, respectively. Brain uptake of [(14) C]-DHA was 24% lower in APOE4 versus APOE2 mice. A significant relationship was established between DHA and apoE concentrations in the cortex of mice (r(2) = 0.21) and AD patients (r(2) = 0.32). Altogether, our results suggest that lower brain uptake of DHA in APOE4 than in APOE2 mice may limit the accumulation of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of AD. Using human APOE2, 3, and 4 isoform-specific transgenic mice, we found a lower brain uptake of docosahexaenoic acid (DHA) in APOE4 than in APOE2 mice that may limit the biodistribution of DHA in cerebral tissues. These data provide a mechanistic explanation for the lack of benefit of DHA in APOE4 carriers on cognitive function and the risk of Alzheimer's disease (AD).

  6. APOE related hippocampal shape alteration in geriatric depression.

    PubMed

    Qiu, Anqi; Taylor, Warren D; Zhao, Zheen; MacFall, James R; Miller, Michael I; Key, Cynthia R; Payne, Martha E; Steffens, David C; Krishnan, K Ranga R

    2009-02-01

    Late-onset depression often precedes the onset of dementia associated with the hippocampal degeneration. Using large deformation diffeomorphic metric mapping (LDDMM), we evaluated apolipoprotein E epsilon-4 allele (apoE E4) effects on hippocampal volume and shape in 38 depressed patients without the apoE E4, 14 depressed patients with one apoE E4, and 31 healthy comparison subjects without the apoE E4. The hippocampal volumes were manually assessed. We applied a diffeomorphic template generation procedure for creating the hippocampal templates based on a subset of the population. The LDDMM mappings were used to generate the hippocampal shape of each subject and characterize the surface deformation of each hippocampus relative to the template. Such deformation was modeled as random field characterized by the Laplace-Beltrami basis functions in the template coordinates. Linear regression was used to examine group differences in the hippocampal volume and shape. We found that there were significant hippocampal shape alternations in both depressed groups while the groups of depressed patients and the group of healthy subjects did not differ in the hippocampal volume. The depressed patients with one apoE E4 show more pronounced shape inward-compression in the anterior CA1 than the depressed patients without the apoE E4 when compared with the healthy controls without the apoE E4. Thus, hippocampal shape abnormalities in late-onset depressed patients with one apoE E4 may indicate future conversion of this group to AD at higher risk than depressed patients without the apoE E4. PMID:19010425

  7. Cathepsin K Deficiency Prevents the Aggravated Vascular Remodeling Response to Flow Cessation in ApoE-/- Mice

    PubMed Central

    Lutgens, Suzanne P. M.; Wijnands, Erwin; Johnson, Jason; Schurgers, Leon J.; Liu, Cong-Lin; Daemen, Mat J. A. P.; Cleutjens, Kitty B. J. M.; Shi, Guo-Ping; Biessen, Erik A. L.; Heeneman, Sylvia

    2016-01-01

    Cathepsin K (catK) is a potent lysosomal cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in apoE-/- and wild type (wt) background. Ligation-induced hyperplasia is considerably aggravated in apoE-/- versus wt mice. CatK protein expression was significantly increased in neointimal lesions of apoE-/- compared with wt mice, suggesting a role for catK in intimal hyperplasia under hyperlipidemic conditions. Surprisingly, CatK deficiency completely blunted the augmented hyperplastic response to flow cessation in apoE-/-, whereas vascular remodeling in wt mice was unaffected. As catK deficiency did neither alter lesion collagen content and elastic laminae fragmentation in vivo, we focused on effects of catK on (systemic) inflammatory responses. CatK deficiency significantly reduced circulating CD3 T-cell numbers, but increased the regulatory T cell subset in apoE-/- but not wt mice. Moreover, catK deficiency changed CD11b+Ly6G-Ly6C high monocyte distribution in apoE-/- but not wt mice and tended to favour macrophage M2a polarization. In conclusion, catK deficiency almost completely blunted the increased vascular remodeling response of apoE-/- mice to flow cessation, possibly by correcting hyperlipidemia-associated pro-inflammatory effects on the peripheral immune response. PMID:27636705

  8. Influence of the APOE genotype on hepatic stress response: Studies in APOE targeted replacement mice and human liver cells.

    PubMed

    Dose, Janina; Nebel, Almut; Piegholdt, Stefanie; Rimbach, Gerald; Huebbe, Patricia

    2016-07-01

    Apolipoprotein E (APOE) is a multifunctional plasma protein mainly acting in lipid metabolism. Human APOE is polymorphic with three major isoforms (APOE2, APOE3 and APOE4). Up to 75% of the body's APOE is produced by the liver. There is increasing evidence from studies in brain-derived cells that APOE4 affects mitochondrial function and biogenesis as well as stress and inflammatory responses - processes, whose disturbances are considered hallmarks of the ageing process. However, although the liver is the main production site of APOE, knowledge about the impact of the APOE genotype on hepatic stress response-related processes is rather limited. Therefore, we studied biomarkers of oxidative status (glutathione levels, 3-nitrotyrosine adducts, protein carbonyl concentration), ER stress (XBP1(S), BiP, DDIT3), proteasome activity, mitochondrial function (respiratory complexes, ATP levels and mitochondrial membrane potential as well as biomarkers of mitochondrial biogenesis, fission and fusion), autophagy (LC3, LAMP2A), apoptosis (BCL2, BAX, CYCS) and DNA damage in the liver of APOE targeted replacement (TR) mice and in Huh7 hepatocytes overexpressing the APOE3 and the APOE4 isoform, respectively. APOE4 mice exhibited a lower chymotrypsin-like and a higher trypsin-like proteasome activity. Levels of protein carbonyls were moderately higher in liver tissue of APOE4 vs. APOE3 mice. Other biomarkers of oxidative stress were similar between the two genotypes. Under basal conditions, the stress-response pathways investigated appeared largely unaffected by the APOE genotype. However, upon stress induction, APOE4 expressing cells showed lower levels of adenosine triphosphate (ATP) and lower mRNA levels of the ATP-generating complex V of the mitochondrial respiratory chain. Overall, our findings provide evidence for a rather low influence of the APOE genotype on the hepatic stress response processes investigated in this study. PMID:27130033

  9. Effects of different isoforms of apoE on aggregation of the α-synuclein protein implicated in Parkinson's disease.

    PubMed

    Emamzadeh, Fatemeh Nouri; Aojula, Harmesh; McHugh, Patrick C; Allsop, David

    2016-04-01

    Parkinson's disease is a progressive brain disorder due to the degeneration of dopaminergic neurons in the substantia nigra. The accumulation of aggregated forms of α-synuclein protein into Lewy bodies is one of the characteristic features of this disease although the pathological role of any such protein deposits in causing neurodegeneration remains elusive. Here, the effects of different apolipoprotein E isoforms (apoE2, apoE3, apoE4) on the aggregation of α-synuclein in vitro were examined using thioflavin T assays and also an immunoassay to detect the formation of multimeric forms. Our results revealed that the aggregation of α-synuclein is influenced by apoE concentration. At low concentrations of apoE (<15nM), all of the isoforms were able to increase the aggregation of α-synuclein (50μM), with apoE4 showing the greatest stimulatory effect. This is in contrast to a higher concentration (>15nM) of these isoforms, where a decrease in the aggregation of α-synuclein was noted. The data show that exceptionally low levels of apoE may seed α-syn aggregation, which could potentially lead to the pathogenesis of α-synuclein-induced neurodegeneration. On the other hand, higher levels of apoE could potentially lower the degree of α-synuclein aggregation and confer protection. The differential effects noted with apoE4 could explain why this particular isoform results in an earlier age of onset for Parkinson's disease.

  10. Effect of plasma lipids and APOE genotype on cognitive decline.

    PubMed

    Yasuno, Fumihiko; Asada, Takashi

    2013-03-01

    A central tenet of brain aging is that "what is good for the heart is good for the brain." We examined the combined effect of plasma lipids and APOE genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein, triglyceride, total cholesterol, and apolipoprotein E (apoE) were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids and cognitive function in APOE4 carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma apoE levels in both E4- and E4+, and HDL level in E4-. Our findings suggest that an interaction between apoE and HDL is facilitated by APOE4, and is possibly linked with an enhancement of neuroplasticity and with resultant protective effects on cognitive function in later life. Preservation of higher plasma apoE and HDL from early life is proposed as a possible strategy for maintaining cognitive function in later life, especially for APOE4-positive individuals.

  11. Analysis of apoB and apoC-II gene polymorphism in random sample and CHD patients from Moscow

    SciTech Connect

    Pogoda, T.V.; Nikonova, A.; Perova, N.V.

    1994-09-01

    We have analyzed the allele frequency distributions of the 3{prime} apoB gene minisatellite and apoC-II gene microsatellite in random sample of coronary heart disease (CHD) patients. For this purpose we used the PCR technique followed by high-resolution PAGE. It was revealed that the apoB allele, harboring 30 repeats (apoB 30), as well as the apoC-II allele harboring 30 repeats (apoC-II 30), were less frequent in patients at the same time as the frequency of the apoB 32 and apoC-II 17 alleles was greater in patients. The greater frequency of apoB alleles which were larger in size than apoB 46 (defined as `long` - L) was observed in patients with high apoB levels (>160mg dl). The analysis of apoB genotype distribution showed that in a random sample the most common genotype was apoB 34,36 (a combination of the most frequent alleles in the random sample). In patients with high apoB levels, it was twice less frequent, and the most common genotype was apoB 36,L (43% versus 12% in the random sample). Analysis of data on a lipid spectrum of subjects from the random sample with different apoB and apoC-II 17 alleles were associated with atherogenic shifts in the lipid profile, at the same time as apoB 30 and apoC-II 30 alleles - with an apparently favorable lipid profile. The increment of the disease-related risk was observed for subjects with a combination of apoB 32 allele or apoB 36,L genotype with the apoC-11 17 allele. Alternatively, combination of these apoB variants with the apoC-II 30 allele resulted in decreased related risk. In conclusion, simultaneous analysis of two candidate gene variants demonstrated interaction in their influence on the lipid spectrum.

  12. A Study on Teachers&apos;, Students&apos; and Their Parents&apos; Views on the FATIH Project

    ERIC Educational Resources Information Center

    Sahin, Semsettin; Aktürk, Ahmet Oguz; Çelik, Ismail

    2013-01-01

    This study investigated the views of teachers, students and their parents on the FATIH (Movement of Enhancing Opportunities and Improving Technology) Project, which was put into service by the Ministry of National Education in cooperation with the Ministry of Transportation in Turkey in November 2010 for the purpose of increasing students&apos;…

  13. "It&apos;s All Shiny and There&apos;s No Pollution": "Barbapapa&apos;s Ark," Environmental Influences

    ERIC Educational Resources Information Center

    Lowe, Virginia

    2013-01-01

    The environmental picture book "Barbapapa&apos;s Ark" was published in 1974. I was keeping a parent-observer record of my two children at the time. The book had a strong influence on them from ages three to six, moving them to query pollution and hunting, in book and environment, and as adults, becoming committed activists for the…

  14. Exploring Primary School CLIL Perceptions in Catalonia: Students&apos;, Teachers&apos; and Parents&apos; Opinions and Expectations

    ERIC Educational Resources Information Center

    Pladevall-Ballester, Elisabet

    2015-01-01

    Analysing participants&apos; perceptions of a Content and Language Integrated Learning (CLIL) experience is essential in order to provide a clear picture of whether CLIL is effectively implemented. This becomes extremely relevant in primary school contexts, where the way the different groups involved in an educational experience feel tends to be…

  15. Responses to Children&apos;s Sadness: Mothers&apos; and Fathers&apos; Unique Contributions and Perceptions

    ERIC Educational Resources Information Center

    Cassano, Michael C.; Zeman, Janice L.; Sanders, Wesley M.

    2014-01-01

    Parental socialization of children&apos;s sadness was examined through self-report, spouse report, and a parent-child sadness discussion task. A total of 79 two-parent, predominantly White, middle-class families participated with one child in grades 2-5 (44 sons; M = 9 years, 8 months). Analyses revealed that mothers and fathers respond…

  16. Primary School Students&apos; Parents&apos; Level of Involvement into Their Children&apos;s Education

    ERIC Educational Resources Information Center

    Sad, Suleyman Nihat; Gurbuzturk, Oguz

    2013-01-01

    The aim of this study was to investigate the extent to which parents of elementary students (1st to 5th) participate in their children&apos;s education with regard to some variables. The study was designed based on descriptive survey model and comparative and correlational associative models. The sample of the research comprised 1252 parents whose…

  17. Lung inflammation and genotoxicity following pulmonary exposure to nanoparticles in ApoE-/- mice

    PubMed Central

    Jacobsen, Nicklas Raun; Møller, Peter; Jensen, Keld Alstrup; Vogel, Ulla; Ladefoged, Ole; Loft, Steffen; Wallin, Håkan

    2009-01-01

    Background The toxic and inflammatory potential of 5 different types of nanoparticles were studied in a sensitive model for pulmonary effects in apolipoprotein E knockout mice (ApoE-/-). We studied the effects instillation or inhalation Printex 90 of carbon black (CB) and compared CB instillation in ApoE-/- and C57 mice. Three and 24 h after pulmonary exposure, inflammation was assessed by mRNA levels of cytokines in lung tissue, cell composition, genotoxicity, protein and lactate dehydrogenase activity in broncho-alveolar lavage (BAL) fluid. Results Firstly, we found that intratracheal instillation of CB caused far more pulmonary toxicity in ApoE-/- mice than in C57 mice. Secondly, we showed that instillation of CB was more toxic than inhalation of a presumed similar dose with respect to inflammation in the lungs of ApoE-/- mice. Thirdly, we compared effects of instillation in ApoE-/- mice of three carbonaceous particles; CB, fullerenes C60 (C60) and single walled carbon nanotubes (SWCNT) as well as gold particles and quantum dots (QDs). Characterization of the instillation media revealed that all particles were delivered as agglomerates and aggregates. Significant increases in Il-6, Mip-2 and Mcp-1 mRNA were detected in lung tissue, 3 h and 24 h following instillation of SWCNT, CB and QDs. DNA damage in BAL cells, the fraction of neutrophils in BAL cells and protein in BAL fluid increased statistically significantly. Gold and C60 particles caused much weaker inflammatory responses. Conclusion Our data suggest that ApoE-/- model is sensitive for evaluating particle induced inflammation. Overall QDs had greatest effects followed by CB and SWCNT with C60 and gold being least inflammatory and DNA-damaging. However the gold was used at a much lower mass dose than the other particles. The strong effects of QDs were likely due to Cd release. The surface area of the instilled dose correlated well the inflammatory response for low toxicity particles. PMID:19138394

  18. Jacques Ranciere&apos;s Lesson on the Lesson

    ERIC Educational Resources Information Center

    Chambers, Samuel A.

    2013-01-01

    This article examines the significance of Jacques Ranciere&apos;s work on pedagogy, and argues that to make sense of Ranciere&apos;s "lesson on the lesson" one must do more but also less than merely explicate Ranciere&apos;s texts. It steadfastly refuses to draw out the lessons of Ranciere&apos;s writings in the manner of a series of…

  19. Teacher Educators&apos; Digital Competence

    ERIC Educational Resources Information Center

    Krumsvik, Rune Johan

    2014-01-01

    This position paper focuses on how the new national curriculum for school and the new general plan for teacher education in Norway change the underlying premises for teaching and learning in today&apos;s teacher education. This has become particularly pressing as a result of the new educational reform "Knowledge Promotion" in schools,…

  20. Students&apos; Differentiated Translation Processes

    ERIC Educational Resources Information Center

    Bossé, Michael J.; Adu-Gyamfi, Kwaku; Chandler, Kayla

    2014-01-01

    Understanding how students translate between mathematical representations is of both practical and theoretical importance. This study examined students&apos; processes in their generation of symbolic and graphic representations of given polynomial functions. The purpose was to investigate how students perform these translations. The result of the…

  1. Find Your School&apos;s Analemma

    ERIC Educational Resources Information Center

    Lough, Tom; Vanover, Courtney

    2014-01-01

    On any given sunny day, Courtney Vanover&apos;s third graders were like alarm clocks, making sure everyone in the room knew when 9:30 was approaching. Why? Because they were participating in a yearlong science project to answer the question, "Where is the tip of the shadow of the school flagpole each morning at 9:30?" Although they did…

  2. Site for Today&apos;s Teachers

    ERIC Educational Resources Information Center

    Brulles, Dina; Brown, Karen L.

    2013-01-01

    This article describes one school district department&apos;s efforts to train and support teachers in providing effective curriculum, instruction, and assessment methods to their students. This large, K-12 district embraces the spectrum of low to high SES schools, a large number of gifted students from diverse populations, and a variety of gifted…

  3. Dewey or Don&apos;t We?

    ERIC Educational Resources Information Center

    Pendergrass, Devona J.

    2013-01-01

    "Dewey or don&apos;t we?" is the question that hundreds, if not thousands, of school librarians across the country are currently asking themselves. Do they throw out what is old but trusted for new organizational systems, or do they continue using the Dewey Decimal Classification (DDC) system and make changes and adjustments to the…

  4. "Math for America" Isn&apos;t

    ERIC Educational Resources Information Center

    Wolfmeyer, Mark

    2014-01-01

    Aspects of the Math for America organization&apos;s actions, aims and affiliations are analyzed for their effects on urban schools and society at large. These aspects are argued as evidence to consider MfA as an agent working against democratic practice and in favor of furthering profit and its resultant inequitable resource distribution. The…

  5. Quirks of Stirling&apos;s Approximation

    ERIC Educational Resources Information Center

    Macrae, Roderick M.; Allgeier, Benjamin M.

    2013-01-01

    Stirling&apos;s approximation to ln "n"! is typically introduced to physical chemistry students as a step in the derivation of the statistical expression for the entropy. However, naive application of this approximation leads to incorrect conclusions. In this article, the problem is first illustrated using a familiar "toy…

  6. Kentucky&apos;s Urban Extension Focus

    ERIC Educational Resources Information Center

    Young, Jeffery; Vavrina, Charles

    2014-01-01

    Defining the success of Urban Extension units is sometimes challenging. For those Extension agents, specialists, administrators, and others who have worked to bring solid, research-based programming to urban communities, it is no surprise that working in these communities brings its own unique and sometimes difficult challenges. Kentucky&apos;s…

  7. In Memory of Garth Boomer: "May He Not &apos;Rust Unburnished&apos; but &apos;Shine in Use&apos;"

    ERIC Educational Resources Information Center

    Brock, Paul

    2013-01-01

    This article is based on the authors&apos; own experience of Garth Boomer as a splendid friend, a superb colleague, and an inspirational leader. In September 2005 the author was invited to deliver the Garth Boomer Memorial Lecture at the Biennial International Conference of the Australian Curriculum Studies Association (ACSA). This article is…

  8. My Brother&apos;s Keeper

    ERIC Educational Resources Information Center

    Obama, Barack

    2014-01-01

    In a White House address, the president announced an initiative to reclaim young boys and men of color. The "My Brother&apos;s Keeper" initiative partners with businesses, foundations, and nonprofits to address disparities in education, justice, and employment. President Obama was introduced by Christian, one of a group of students from…

  9. Text Complexity: Primary Teachers&apos; Views

    ERIC Educational Resources Information Center

    Fitzgerald, Jill; Hiebert, Elfrieda H.; Bowen, Kimberly; Relyea-Kim, E. Jackie; Kung, Melody; Elmore, Jeff

    2015-01-01

    The research question was, "What text characteristics do primary teachers think are most important for early grades text complexity?" Teachers from across the United States accomplished a two-part task. First, to stimulate teachers&apos; thinking about important text characteristics, primary teachers completed an online paired-text…

  10. Ontario&apos;s Student Voice Initiative

    ERIC Educational Resources Information Center

    Courtney, Jean

    2014-01-01

    This article describes in some detail aspects of the Student Voice initiative funded and championed by Ontario&apos;s Ministry of Education since 2008. The project enables thousands of students to make their voices heard in meaningful ways and to participate in student-led research. Some students from grades 7 to 12 become members of the Student…

  11. Students&apos; Perceptions of Plagiarism

    ERIC Educational Resources Information Center

    Fish, Reva; Hura, Gerri

    2013-01-01

    While plagiarism by college students is a serious problem that must be addressed, students generally overestimate the frequency of plagiarism at their schools and blame students they do not know for the majority of incidents. This study looked at students&apos; estimations of the frequency of plagiarism at a large urban college and explored how…

  12. America&apos;s Descent into Madness

    ERIC Educational Resources Information Center

    Giroux, Henry A.

    2014-01-01

    This article describes America&apos;s descent into madness under the regime of neoliberalism that has emerged in the United States since the late 1970s. In part, this is due to the emergence of a public pedagogy produced by the corporate-owned media that now saturates Americans with a market-driven value system that undermines those formative…

  13. Clustering Teachers&apos; Motivations for Teaching

    ERIC Educational Resources Information Center

    Visser-Wijnveen, Gerda J.; Stes, Ann; Van Petegem, Peter

    2014-01-01

    The motivation to teach is a powerful, yet neglected, force in teaching at institutes of higher education. A better understanding of academics&apos; motivations for teaching is necessary. The aim of this mixed-method study was to identify groups with distinctively different motivations for teaching. Six clusters were identified: expertise, duty,…

  14. The Apo Riboswitch as a Molecular Hydra

    PubMed Central

    Wedekind, Joseph E.

    2010-01-01

    Summary Riboswitches ‘sense’ metabolites but knowledge is sparse for structures without bound ligand. Stoddard et al. (2010) determined an apo riboswitch structure ‘closed’ to metabolite binding. Further SAXS, biochemical and computational analyses support ensemble behavior with interconverting open and closed conformations. PMID:20637410

  15. Students&apos; Images of Mathematics

    ERIC Educational Resources Information Center

    Martin, Lee; Gourley-Delaney, Pamela

    2014-01-01

    Students&apos; judgments about "what counts" as mathematics in and out of school have important consequences for problem solving and transfer, yet our understanding of the source and nature of these judgments remains incomplete. Thirty-five sixth grade students participated in a study focused on what activities students judge as…

  16. Gutenberg&apos;s Effects on Universities

    ERIC Educational Resources Information Center

    Moodie, Gavin

    2014-01-01

    This article considers the effects on universities of Gutenberg&apos;s invention of printing. It considers four major effects: the gradual displacement of Latin as the language of scholarship with vernacular languages, the expansion and eventual opening of libraries, major changes to curriculum, and major changes to pedagogy including lectures.…

  17. Students&apos; Ratings of Teacher Practices

    ERIC Educational Resources Information Center

    Stevens, T.; Harris, G.; Liu, X.; Aguirre-Munoz, Z.

    2013-01-01

    In this paper, we explore a novel approach for assessing the impact of a professional development programme on classroom practice of in-service middle school mathematics teachers. The particular focus of this study is the assessment of the impact on teachers&apos; employment of strategies used in the classroom to foster the mathematical habits of…

  18. Inquiry on Teachers&apos; Emotion

    ERIC Educational Resources Information Center

    Schutz, Paul A.

    2014-01-01

    Teaching, like other caring professions, is emotional. These emotions tend to emerge as teachers&apos; goals, standards, and beliefs transact with other classroom stakeholders during everyday school activities. As such, for teachers, the classroom context involves both the extreme happiness and joy from a lesson that goes as planned to the intense…

  19. Mathematics Teachers&apos; Criteria of Dimension

    ERIC Educational Resources Information Center

    Ural, Alattin

    2014-01-01

    The aim of the study is to determine mathematics teachers&apos; decisions about dimensions of the geometric figures, criteria of dimension and consistency of decision-criteria. The research is a qualitative research and the model applied in the study is descriptive method on the basis of general scanning model. 15 mathematics teachers attended the…

  20. Flip Your Students&apos; Learning

    ERIC Educational Resources Information Center

    Sams, Aaron; Bergmann, Jonathan

    2013-01-01

    Flipped learning is not about how to use videos in lessons. It&apos;s about how to best use in-class time with students. That insight is causing educators in classrooms from kindergarten to college to reevaluate how they teach. Flipped learning helps teachers move away from direct instruction as their primary teaching tool toward a more…

  1. What&apos;s in a Symbol?

    ERIC Educational Resources Information Center

    Leadstone, Stuart

    2013-01-01

    This "Science Note" explores the new adaptation of Newton&apos;s Second Law of Motion, "F = ma." In older physics and applied mathematics textbooks this expression appears as "P = mf." The author examines why "f" is now favored over "a" and why practitioners write "P = mf" rather than…

  2. Physical Education Teachers&apos; Organizational Commitment

    ERIC Educational Resources Information Center

    Demir, Hayri

    2013-01-01

    The aim of this study was to determine physical education teachers&apos; organizational commitment levels. The sample consisted of 204 physical education teachers working in the city center of Konya in the 2011 to 2012 academic year. The respondents were randomly selected in this research. Data collected for this research by using the Scale for…

  3. MFA Writers&apos; Relationships with Writing

    ERIC Educational Resources Information Center

    Olthouse, Jill M.

    2013-01-01

    Through a qualitative research design, I explored how eight talented masters in fine arts (MFA) writers related to their craft. The phenomenon "relationship with writing" includes writers&apos; goals, values, identity, and emotions as these relate to writing. I found that that these MFA writers experience compatibilities and conflicts…

  4. ApoE4 expression accelerates hippocampus-dependent cognitive deficits by enhancing Aβ impairment of insulin signaling in an Alzheimer’s disease mouse model

    PubMed Central

    Chan, Elizabeth S.; Shetty, Mahesh Shivarama; Sajikumar, Sreedharan; Chen, Christopher; Soong, Tuck Wah; Wong, Boon-Seng

    2016-01-01

    The apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for Alzheimer’s disease (AD). The AD brain was shown to be insulin resistant at end stage, but the interplay between insulin signaling, ApoE4 and Aβ across time, and their involvement in memory decline is unclear. To investigate insulin response in the ageing mouse hippocampus, we crossed the human ApoE-targeted replacement mice with the mutant human amyloid precursor protein (APP) mice (ApoExAPP). While hippocampal Aβ levels were comparable between ApoE3xAPP and ApoE4xAPP mice at 26 weeks, insulin response was impaired in the ApoE4xAPP hippocampus. Insulin treatment was only able to stimulate insulin signaling and increased AMPA-GluR1 phosphorylation in forskolin pre-treated hippocampal slices from ApoE3xAPP mice. In ApoE4xAPP mice, insulin dysfunction was also associated with poorer spatial memory performance. Using dissociated hippocampal neuron in vitro, we showed that insulin response in ApoE3 and ApoE4 neurons increased AMPA receptor-mediated miniature excitatory postsynaptic current (mEPSC) amplitudes and GluR1-subunit insertion. Pre-treatment of ApoE3 neurons with Aβ42 did not affect insulin-mediated GluR1 subunit insertion. However, impaired insulin sensitivity observed only in the presence of ApoE4 and Aβ42, attenuated GluR1-subunit insertion. Taken together, our results suggest that ApoE4 enhances Aβ inhibition of insulin-stimulated AMPA receptor function, which accelerates memory impairment in ApoE4xAPP mice. PMID:27189808

  5. ApoE4 expression accelerates hippocampus-dependent cognitive deficits by enhancing Aβ impairment of insulin signaling in an Alzheimer's disease mouse model.

    PubMed

    Chan, Elizabeth S; Shetty, Mahesh Shivarama; Sajikumar, Sreedharan; Chen, Christopher; Soong, Tuck Wah; Wong, Boon-Seng

    2016-05-18

    The apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for Alzheimer's disease (AD). The AD brain was shown to be insulin resistant at end stage, but the interplay between insulin signaling, ApoE4 and Aβ across time, and their involvement in memory decline is unclear. To investigate insulin response in the ageing mouse hippocampus, we crossed the human ApoE-targeted replacement mice with the mutant human amyloid precursor protein (APP) mice (ApoExAPP). While hippocampal Aβ levels were comparable between ApoE3xAPP and ApoE4xAPP mice at 26 weeks, insulin response was impaired in the ApoE4xAPP hippocampus. Insulin treatment was only able to stimulate insulin signaling and increased AMPA-GluR1 phosphorylation in forskolin pre-treated hippocampal slices from ApoE3xAPP mice. In ApoE4xAPP mice, insulin dysfunction was also associated with poorer spatial memory performance. Using dissociated hippocampal neuron in vitro, we showed that insulin response in ApoE3 and ApoE4 neurons increased AMPA receptor-mediated miniature excitatory postsynaptic current (mEPSC) amplitudes and GluR1-subunit insertion. Pre-treatment of ApoE3 neurons with Aβ42 did not affect insulin-mediated GluR1 subunit insertion. However, impaired insulin sensitivity observed only in the presence of ApoE4 and Aβ42, attenuated GluR1-subunit insertion. Taken together, our results suggest that ApoE4 enhances Aβ inhibition of insulin-stimulated AMPA receptor function, which accelerates memory impairment in ApoE4xAPP mice.

  6. Studying the role of ApoE in Alzheimer's disease pathogenesis using a systems biology model.

    PubMed

    Kyrtsos, Christina Rose; Baras, John S

    2013-10-01

    Alzheimer's disease (AD) is the most common form of dementia. Even with its well-known symptoms of memory loss and well-characterized pathology of beta amyloid (Aβ) plaques and neurofibrillary tangles, the disease pathogenesis and initiating factors are still not well understood. To tackle this problem, a systems biology model has been developed and used to study the varying effects of variations in the ApoE allele present, as well as the effects of short term and periodic inflammation at low to moderate levels. Simulations showed a late onset peak of Aβ in the ApoE4 case that lead to localized neuron loss which could be ameliorated in part by application of short-term pro-inflammatory mediators. The model that has been developed herein represents one of the first attempts to model AD from a systems approach to study physiologically relevant parameters that may prove useful to physicians in the future. PMID:24131052

  7. Interpreting Students&apos; Writings: Misconception or Misrepresentation?

    ERIC Educational Resources Information Center

    Seah, Lay Hoon

    2013-01-01

    This article demonstrates one particular difficulty of interpreting students&apos; use of language in science classrooms: determining whether a student&apos;s writing indicates a misconception or a misrepresentation. Students&apos; written assignments from a case study are used to illustrate instances where multiple interpretations are possible.…

  8. Asperger&apos;s in the Holmes Family

    ERIC Educational Resources Information Center

    Altschuler, Eric L.

    2013-01-01

    I show that Mycroft Holmes (Sherlock Holmes&apos; brother) is a formally described case of Asperger&apos;s syndrome a half century before Asperger&apos;s description of the syndrome. Further, given the genetic similarity and links between the brothers stated by Sherlock, this also cinches the same diagnosis for Sherlock.

  9. Interrogating Meanings of Work in Children&apos;s Literature

    ERIC Educational Resources Information Center

    Wieland, Stacey M. B.; Bauer, Janell C.

    2015-01-01

    In this article, Wieland and Bauer discuss a teaching activity that helps students understand how meanings of work (MOW) are socially constructed through commonplace texts: children&apos;s books. The activity helps students consider how children&apos;s books shape future workers&apos; understandings of what work is, what kinds of work are most…

  10. Learning about Other People&apos;s Families

    ERIC Educational Resources Information Center

    Goldstein, Tara

    2014-01-01

    While the call for teacher education students to learn about their students&apos; family and community lives remains urgent and compelling, educating teachers about the Other is tricky business. In this article I discuss the use of two performed ethnographies, "Harriet&apos;s House" and "Ana&apos;s Shadow," to provide…

  11. Mencius&apos; Educational Philosophy and Its Contemporary Relevance

    ERIC Educational Resources Information Center

    Huang, Chun-chieh

    2014-01-01

    This article argues that Mencius&apos; education is "holistic education" that aims at igniting the "silent revolution" from within one&apos;s inner mind-heart to be unfolded in society, state, and the world. Mencius&apos; educational philosophy is based on his theory of human nature and his theory of self-cultivation. Mencius…

  12. Gaps in Alzheimer&apos;s Knowledge among College Students

    ERIC Educational Resources Information Center

    Eshbaugh, Elaine M.

    2014-01-01

    Despite the prevalence of the disease, it appears that there may be a need for increased education for formal and family caregivers of those with Alzheimer&apos;s disease and related dementias. Today&apos;s college students will be asked to fill both of these roles in the future. This study examined the level of knowledge of Alzheimer&apos;s…

  13. Principals&apos; Concerns Regarding the Implementation of Change

    ERIC Educational Resources Information Center

    Dozier Pelfrey, Theresa

    2012-01-01

    The purpose of this study was to investigate the Stages of Concern (SoC) that school principals have toward change and then report participants&apos; behavior relevant to their Level of Use (LoU) of an innovation. An understanding of principals&apos; concerns regarding change suggested a variety of factors that impede educational leaders&apos;…

  14. Revitalizing Ernst Mach&apos;s Popular Scientific Lectures

    ERIC Educational Resources Information Center

    Euler, Manfred

    2007-01-01

    Compared to Ernst Mach&apos;s influence on the conceptual development of physics, his efforts to popularize science and his reflections on science literacy are known to a much lesser degree. The approach and the impact of Mach&apos;s popular scientific lectures are discussed in view of today&apos;s problems of understanding science. The key issues…

  15. Feedback Dialogues That Stimulate Students&apos; Reflective Thinking

    ERIC Educational Resources Information Center

    Van der Schaaf, Marieke; Baartman, Liesbeth; Prins, Frans; Oosterbaan, Anne; Schaap, Harmen

    2013-01-01

    How can feedback dialogues stimulate students&apos; reflective thinking? This study aims to investigate: (1) the effects of feedback dialogues between teachers and students on students&apos; perceptions of teacher feedback and (2) the relation between features of feedback dialogues and students&apos; thinking activities as part of reflective…

  16. The Not-so-Random Drunkard&apos;s Walk

    ERIC Educational Resources Information Center

    Ehrhardt, George

    2013-01-01

    This dataset contains the results of a quasi-experiment, testing Karl Pearson&apos;s "drunkard&apos;s walk" analogy for an abstract random walk. Inspired by the alternate hypothesis that drunkards stumble to the side of their dominant hand, it includes data on intoxicated test subjects walking a 10&apos; line. Variables include: the…

  17. Using Computational Simulations to Confront Students&apos; Mental Models

    ERIC Educational Resources Information Center

    Rodrigues, R.; Carvalho, P. Simeão

    2014-01-01

    In this paper we show an example of how to use a computational simulation to obtain visual feedback for students&apos; mental models, and compare their predictions with the simulated system&apos;s behaviour. Additionally, we use the computational simulation to incrementally modify the students&apos; mental models in order to accommodate new data,…

  18. Chemistry Teachers&apos; Knowledge and Application of Models

    ERIC Educational Resources Information Center

    Wang, Zuhao; Chi, Shaohui; Hu, Kaiyan; Chen, Wenting

    2014-01-01

    Teachers&apos; knowledge and application of model play an important role in students&apos; development of modeling ability and scientific literacy. In this study, we investigated Chinese chemistry teachers&apos; knowledge and application of models. Data were collected through test questionnaire and analyzed quantitatively and qualitatively. The…

  19. Connecting to Special Collections of Children&apos;s Literature

    ERIC Educational Resources Information Center

    Brodie, Carolyn S.

    2013-01-01

    The Kent State University School of Library and Information Science serves as the home for two children&apos;s literature special collections. The Reinberger Children&apos;s Library Center is located on the third floor of Kent State&apos;s University Library and includes the Marantz Picturebook Collection for the Study of Picturebook Art. The…

  20. Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice

    PubMed Central

    Zhao, Yang; Dai, Xiao-yan; Zhou, Zhou; Zhao, Ge-xin; Wang, Xian; Xu, Ming-jiang

    2016-01-01

    Aim: Recent evidence suggests that the essential amino acid leucine may be involved in systemic cholesterol metabolism. In this study, we investigated the effects of leucine supplementation on the development of atherosclerosis in apoE null mice. Methods: ApoE null mice were fed with chow supplemented with leucine (1.5% w/v) in drinking water for 8 week. Aortic atherosclerotic lesions were examined using Oil Red O staining. Plasma lipoprotein-cholesterol levels were measured with fast protein liquid chromatography. Hepatic gene expression was detected using real-time PCR and Western blot analyses. Results: Leucine supplementation resulted in 57.6% reduction of aortic atherosclerotic lesion area in apoE null mice, accompanied by 41.2% decrease of serum LDL-C levels and 40.2% increase of serum HDL-C levels. The body weight, food intake and blood glucose level were not affected by leucine supplementation. Furthermore, leucine supplementation increased the expression of Abcg5 and Abcg8 (that were involved in hepatic cholesterol efflux) by 1.28- and 0.86-fold, respectively, and significantly increased their protein levels. Leucine supplementation also increased the expression of Srebf1, Scd1 and Pgc1b (that were involved in hepatic triglyceride metabolism) by 3.73-, 1.35- and 1.71-fold, respectively. Consequently, leucine supplementation resulted in 51.77% reduction of liver cholesterol content and 2.2-fold increase of liver triglyceride content. Additionally, leucine supplementation did not affect the serum levels of IL-6, IFN-γ, TNF-α, IL-10 and IL-12, but markedly decreased the serum level of MCP-1. Conclusion: Leucine supplementation effectively attenuates atherosclerosis in apoE null mice by improving the plasma lipid profile and reducing systemic inflammation. PMID:26687933

  1. Effects of the ApoE epsilon4 allele on olfactory function in Down syndrome.

    PubMed

    Sliger, Melissa; Lander, Timothy; Murphy, Claire

    2004-08-01

    The present study investigated the effects of the apolipoprotein E (ApoE) epsilon4 allele, a risk factor for Alzheimer's disease (AD), on olfactory function in Down syndrome (DS). Brain areas critical to olfactory processing, particularly the entorhinal cortex, show the earliest neuropathological changes in AD. Functionally, odor identification has been shown to be impaired in AD and in persons with the epsilon4 allele. DS is also a risk factor for AD. Thus, we hypothesized greater impairment in epsilon4 positive DS participants. Olfactory function was assessed with the San Diego Odor Identification Test in 34 participants with DS and 34 normal controls. Genomic DNA was prepared from blood samples to obtain ApoE status for the DS participants. Results indicate (1) that participants with DS had significant deficits in olfactory functioning; and (2) that among DS participants, those with an epsilon4 allele had poorer odor identification than those without an epsilon4 allele. The results support the hypothesis that individuals with DS who have an additional genetic risk factor for AD, the ApoE epsilon4 allele, exhibit greater deficits in odor identification. Areas of the brain involved in odor identification may be particularly affected in individuals with DS who carry the epsilon4 allele.

  2. Henrique da Rocha Lima*

    PubMed Central

    Bernardes Filho, Fred; Avelleira, João Carlos Regazzi

    2015-01-01

    Brazilian physician and researcher Henrique da Rocha Lima was born in 1879 in the city of Rio de Janeiro, where he studied medicine and obtained the degree of M.D. in 1901. He specialized in Clinical Medicine in Germany and was the ambassador in European countries of the scientific medicine that emerged from the Oswaldo Cruz Institute in the early twentieth century. Rocha Lima has discovered the causative agent of typhus and had a major contribution to the studies of yellow fever, Chagas disease, Carrión’s disease and histoplasmosis. His genius, his research and his discoveries projected his name, and, with it, the image of Brazil in the international scientific scene. PMID:26131867

  3. The locus for apolipoprotein E (apoE) is close to the Lutheran (Lu) blood group locus on chromosome 19.

    PubMed

    Gedde-Dahl, T; Olaisen, B; Teisberg, P; Wilhelmy, M C; Mevåg, B; Helland, R

    1984-01-01

    Linkage has been described between the loci for apolipoprotein E (apoE) and the complement C3 (C3) on chromosome 19. C3 is known to belong to a linkage group with gene order C3-Se-Lu. The present study revealed linkage between Se and apoE with peak lod score +3.3 at recombination fraction 0.08 in males and +1.36 at 0.22 in females, and linkage between apoE and Lu with lod score +4.52 at zero recombination in sexes combined. The C3-apoE linkage gives lod score +4.00 at theta = 0.18 in males, but +0.04 at theta = 0.45 in females. Triple heterozygote families confirm that apoE is on the Se side and on the Lu side of C3. Allelic association between apoE and Lu has not been ruled out. Combining our data with published data on C3-Se and Se-Lu, this segment of chromosome 19 has an average age sex ratio of female/male recombination of 2.3.

  4. Teachers&apos; Uses of a Learning Trajectory to Support Attention to Students&apos; Mathematical Thinking

    ERIC Educational Resources Information Center

    Edgington, Cynthia Page

    2012-01-01

    Teachers&apos; ability to elicit and build on students&apos; mathematical thinking during instruction is critical in order to support students&apos; mathematical growth. An emerging hypothesis in the field is that the construct of a "learning trajectory" (LT) has the potential to support teachers in making sense of and using student…

  5. Developing Intercultural Understanding for Study Abroad: Students&apos; and Teachers&apos; Perspectives on Pre-Departure Intercultural Learning

    ERIC Educational Resources Information Center

    Holmes, P.; Bavieri, L.; Ganassin, S.

    2015-01-01

    This study reports on students&apos; and teachers&apos; perspectives on a programme designed to develop Erasmus students&apos; intercultural understanding prior to going abroad. We aimed to understand how students and their teachers perceived pre-departure materials in promoting their awareness of key concepts related to interculturality (e.g.,…

  6. The Correlation of Students&apos; Views on Constructivist Teaching Environment and Teachers&apos; Student Control Ideologies

    ERIC Educational Resources Information Center

    Beyhan, Omer

    2013-01-01

    The purpose of this study is to examine the correlation between elementary teachers&apos; student control ideology and students&apos; views on constructivist learning environment. In this study, the correlation between the views of teachers working in elementary schools on student control ideology and students&apos; views on constructivist…

  7. The Role of a Model&apos;s Age for Young Children&apos;s Imitation: A Research Review

    ERIC Educational Resources Information Center

    Zmyj, Norbert; Seehagen, Sabine

    2013-01-01

    The influence of a model&apos;s age on young children&apos;s behaviour has been a subject of considerable debate among developmental theorists. Despite the recent surge of interest, controversy remains about the nature of peer influence in early life. This article reviews studies that investigated the influence of a model&apos;s age on young…

  8. The Intergenerational Congruence of Mothers&apos; and Preschoolers&apos; Narrative Affective Content and Narrative Coherence

    ERIC Educational Resources Information Center

    Sher-Censor, Efrat; Grey, Izabela; Yates, Tuppett M.

    2013-01-01

    Intergenerational congruence of mothers&apos; and preschoolers&apos; narratives about the mother-child relationship was examined in a sample of 198 Hispanic (59.1%), Black (19.2%), and White (21.7%) mothers and their preschool child. Mothers&apos; narratives were obtained with the Five Minute Speech Sample and were coded for negative and positive…

  9. The Relationship between Elementary School Teachers&apos; Perceptions of Principals&apos; Leadership Effectiveness and Teacher Burnout

    ERIC Educational Resources Information Center

    Owens, Sallye Applewhite

    2013-01-01

    Burnout, an ever-present concern in the teaching profession, is arguably related to principals&apos; leadership effectiveness. The purpose of this study was to investigate relationships between elementary school teachers&apos; levels of burnout and their perceptions of their principals&apos; leadership effectiveness. Data were gathered using the…

  10. "Yes, Master&apos;s": A Graduate Degree&apos;s Moment in the Age of Higher Education Innovation

    ERIC Educational Resources Information Center

    Gallagher, Sean

    2014-01-01

    Over the past decade, enrollment in professional master&apos;s degree programs has grown substantially, and this category has outpaced the overall recent flattening of college enrollment. Today, 5 million more U.S. adults hold a master&apos;s degree compared with a decade ago, and in some circles the master&apos;s is being referred to as "the…

  11. Parents&apos; Emotion-Related Beliefs, Behaviours, and Skills Predict Children&apos;s Recognition of Emotion

    ERIC Educational Resources Information Center

    Castro, Vanessa L.; Halberstadt, Amy G.; Lozada, Fantasy T.; Craig, Ashley B.

    2015-01-01

    Children who are able to recognize others&apos; emotions are successful in a variety of socioemotional domains, yet we know little about how school-aged children&apos;s abilities develop, particularly in the family context. We hypothesized that children develop emotion recognition skill as a function of parents&apos; own emotion-related beliefs,…

  12. Teachers&apos; Behavior and Pupils&apos; Achievement Motivation as Determinants of Intended Helping Behavior in Physical Education

    ERIC Educational Resources Information Center

    Kokkonen, Juha A.; Kokkonen, Marja T.; Telama, Risto K.; Liukkonen, Jarmo O.

    2013-01-01

    The present two-wave longitudinal study examined the extent to which physical education (PE) teachers&apos; democratic and socially supportive behavior, pupils&apos; goal orientations, and the perceived motivational climate in PE explained differences in pupils&apos; intended helping behavior by gender in PE classes. The results of 105 boys and…

  13. Teacher Characteristics Associated with Mathematics Teachers&apos; Beliefs and Awareness of Their Students&apos; Mathematical Dispositions

    ERIC Educational Resources Information Center

    Clark, Lawrence M.; DePiper, Jill Neumayer; Frank, Toya Jones; Nishio, Masako; Campbell, Patricia F.; Smith, Toni M.; Griffin, Matthew J.; Rust, Amber H.; Conant, Darcy L.; Choi, Youyoung

    2014-01-01

    This study investigates relationships between teacher characteristics and teachers&apos; beliefs about mathematics teaching and learning and the extent to which teachers claim awareness of their students&apos; mathematical dispositions. Regression analyses revealed statistically significant relationships between teachers&apos; beliefs and…

  14. The Impact of Teachers&apos; Characteristics and Self-Reported Practices on Students&apos; Algebra Achievement

    ERIC Educational Resources Information Center

    Cope, Liza M.

    2013-01-01

    This study examined the impact of teachers&apos; characteristics and self-reported practices on students&apos; Algebra achievement while controlling for students&apos; characteristics. This study is based on the secondary analysis of data collected from a nationally representative sample of 9 th grade students and their mathematics teachers during…

  15. Linkage analysis of plasma ApoE in three ethnic groups: multiple genes with context-dependent effects.

    PubMed

    Klos, K L E; Kardia, S L R; Hixson, J E; Turner, S T; Hanis, C; Boerwinkle, E; Sing, C F

    2005-03-01

    We performed variance component-based linkage analysis in four samples (two of non-Hispanic European-Americans from Rochester, MN; African-Americans from Jackson, MS; and Mexican-Americans from Starr County, TX) to identify chromosomal regions containing genes influencing plasma apolipoprotein E (apoE) levels. The APOE gene region on chromosome (chr) 19 was identified with a LOD > or = 2.00 in both samples from Rochester and the sample from Jackson. Adjustment of apoE levels for differences among means of genotypes defined by the APOE epsilon2/3/4 alleles reduced evidence of linkage, indicating that the APOE gene was responsible for the majority of the linkage signal. In stratified linkage analyses, there was a LOD of 1.70 in the Starr County sibships with average total cholesterol (TC) above the median level for all sibships in that population. Adjustment for APOE genotype did not remove this LOD score, suggesting a second gene in this region may influence apoE variation. Evidence of linkage (LOD= 3.32) on chr 17 was observed in the Starr County sibships with average TC below the median. Inter-individual variation in plasma apoE level may be influenced by variations in the structural gene, and at least one other gene whose effects differ among populations and are dependent on the influence of unmeasured genetic and environmental factors indexed by correlated measures of lipid metabolism. PMID:15720297

  16. Mothers&apos; Beliefs about Risk and Risk-Taking in Children&apos;s Outdoor Play

    ERIC Educational Resources Information Center

    Little, Helen

    2015-01-01

    Changes to social and environmental contexts impact on children&apos;s opportunities for and the nature of outdoor play in many ways. A number of studies over the past decade have noted a trend towards over-protective parenting practices that restrict children&apos;s activities and limit children&apos;s independent mobility and engagement with…

  17. Using Video Analysis to Support Prospective K-8 Teachers&apos; Noticing of Students&apos; Multiple Mathematical Knowledge Bases

    ERIC Educational Resources Information Center

    Roth McDuffie, Amy; Foote, Mary Q.; Bolson, Catherine; Turner, Erin E.; Aguirre, Julia M.; Bartell, Tonya Gau; Drake, Corey; Land, Tonia

    2014-01-01

    As part of a larger research project aimed at transforming preK-8 mathematics teacher preparation, the purpose of this study was to examine the extent to which prospective teachers notice children&apos;s competencies related to children&apos;s mathematical thinking, and children&apos;s community, cultural, and linguistic funds of knowledge or what…

  18. Epigenetic signature and enhancer activity of the human APOE gene.

    PubMed

    Yu, Chang-En; Cudaback, Eiron; Foraker, Jessica; Thomson, Zachary; Leong, Lesley; Lutz, Franziska; Gill, James Anthony; Saxton, Aleen; Kraemer, Brian; Navas, Patrick; Keene, C Dirk; Montine, Thomas; Bekris, Lynn M

    2013-12-15

    The human apolipoprotein E (APOE) gene plays an important role in lipid metabolism. It has three common genetic variants, alleles ε2/ε3/ε4, which translate into three protein isoforms of apoE2, E3 and E4. These isoforms can differentially influence total serum cholesterol levels; therefore, APOE has been linked with cardiovascular disease. Additionally, its ε4 allele is strongly associated with the risk of Alzheimer's disease (AD), whereas the ε2 allele appears to have a modest protective effect for AD. Despite decades of research having illuminated multiple functional differences among the three apoE isoforms, the precise mechanisms through which different APOE alleles modify diseases risk remain incompletely understood. In this study, we examined the genomic structure of APOE in search for properties that may contribute novel biological consequences to the risk of disease. We identify one such element in the ε2/ε3/ε4 allele-carrying 3'-exon of APOE. We show that this exon is imbedded in a well-defined CpG island (CGI) that is highly methylated in the human postmortem brain. We demonstrate that this APOE CGI exhibits transcriptional enhancer/silencer activity. We provide evidence that this APOE CGI differentially modulates expression of genes at the APOE locus in a cell type-, DNA methylation- and ε2/ε3/ε4 allele-specific manner. These findings implicate a novel functional role for a 3'-exon CGI and support a modified mechanism of action for APOE in disease risk, involving not only the protein isoforms but also an epigenetically regulated transcriptional program at the APOE locus driven by the APOE CGI.

  19. Epigenetic signature and enhancer activity of the human APOE gene

    PubMed Central

    Yu, Chang-En; Cudaback, Eiron; Foraker, Jessica; Thomson, Zachary; Leong, Lesley; Lutz, Franziska; Gill, James Anthony; Saxton, Aleen; Kraemer, Brian; Navas, Patrick; Keene, C. Dirk; Montine, Thomas; Bekris, Lynn M.

    2013-01-01

    The human apolipoprotein E (APOE) gene plays an important role in lipid metabolism. It has three common genetic variants, alleles ɛ2/ɛ3/ɛ4, which translate into three protein isoforms of apoE2, E3 and E4. These isoforms can differentially influence total serum cholesterol levels; therefore, APOE has been linked with cardiovascular disease. Additionally, its ɛ4 allele is strongly associated with the risk of Alzheimer's disease (AD), whereas the ɛ2 allele appears to have a modest protective effect for AD. Despite decades of research having illuminated multiple functional differences among the three apoE isoforms, the precise mechanisms through which different APOE alleles modify diseases risk remain incompletely understood. In this study, we examined the genomic structure of APOE in search for properties that may contribute novel biological consequences to the risk of disease. We identify one such element in the ɛ2/ɛ3/ɛ4 allele-carrying 3′-exon of APOE. We show that this exon is imbedded in a well-defined CpG island (CGI) that is highly methylated in the human postmortem brain. We demonstrate that this APOE CGI exhibits transcriptional enhancer/silencer activity. We provide evidence that this APOE CGI differentially modulates expression of genes at the APOE locus in a cell type-, DNA methylation- and ɛ2/ɛ3/ɛ4 allele-specific manner. These findings implicate a novel functional role for a 3′-exon CGI and support a modified mechanism of action for APOE in disease risk, involving not only the protein isoforms but also an epigenetically regulated transcriptional program at the APOE locus driven by the APOE CGI. PMID:23892237

  20. Effects of Simulated Heat Waves with Strong Sudden Cooling Weather on ApoE Knockout Mice.

    PubMed

    Zhang, Shuyu; Kuang, Zhengzhong; Zhang, Xiakun

    2015-05-26

    This study analyzes the mechanism of influence of heat waves with strong sudden cooling on cardiovascular diseases (CVD) in ApoE-/- mice. The process of heat waves with strong sudden cooling was simulated with a TEM1880 meteorological-environment simulation chamber according to the data obtained at 5 a.m. of 19 June 2006 to 11 p.m. of 22 June 2006. Forty-eight ApoE-/- mice were divided into six blocks based on their weight. Two mice from each block were randomly assigned to control, heat wave, temperature drop, and rewarming temperature groups. The experimental groups were transferred into the climate simulator chamber for exposure to the simulated heat wave process with strong sudden temperature drop. After 55, 59, and 75 h of exposure, the experimental groups were successively removed from the chamber to monitor physiological indicators. Blood samples were collected by decollation, and the hearts were harvested in all groups. The levels of heat stress factors (HSP60, SOD, TNF, sICAM-1, HIF-1α), cold stress factors (NE, EPI), vasoconstrictor factors (ANGII, ET-1, NO), and four items of blood lipid (TC, TG, HDL-C, and LDL-C) were measured in each ApoE-/- mouse. Results showed that the heat waves increased the levels of heat stress factors except SOD decreased, and decreased the levels of vasoconstrictor factors and blood lipid factors except TC increased. The strong sudden temperature drop in the heat wave process increased the levels of cold stress factors, vasoconstrictor factors and four blood lipid items (except the level of HDL-C which decreased) and decreased the levels of heat stress factors (except the level of SOD which increased). The analysis showed that heat waves could enhance atherosclerosis of ApoE-/- mice. The strong sudden temperature drop during the heat wave process increased the plasma concentrations of NE and ANGII, which indicates SNS activation, and resulted in increased blood pressure. NE and ANGII are vasoconstrictors involved in systemic

  1. High-Fat Diet Changes Hippocampal Apolipoprotein E (ApoE) in a Genotype- and Carbohydrate-Dependent Manner in Mice.

    PubMed

    Lane-Donovan, Courtney; Herz, Joachim

    2016-01-01

    Alzheimer's disease is a currently incurable neurodegenerative disease affecting millions of individuals worldwide. Risk factors for Alzheimer's disease include genetic risk factors, such as possession of ε4 allele of apolipoprotein E (ApoE4) over the risk-neutral ApoE3 allele, and lifestyle risk factors, such as diet and exercise. The intersection of these two sources of disease risk is not well understood. We investigated the impact of diet on ApoE levels by feeding wildtype, ApoE3, and ApoE4 targeted replacement (TR) mice with chow, high-fat, or ketogenic (high-fat, very-low-carbohydrate) diets. We found that high-fat diet affected both plasma and hippocampal levels of ApoE in an isoform-dependent manner, with high-fat diet causing a surprising reduction of hippocampal ApoE levels in ApoE3 TR mice. Conversely, the ketogenic diet had no effect on hippocampal ApoE. Our findings suggest that the use of dietary interventions to slow the progression AD should take ApoE genotype into consideration.

  2. Doing Good? Interpreting Teachers&apos; Given and Felt Responsibilities for Pupils&apos; Well-Being in an Age of Measurement

    ERIC Educational Resources Information Center

    Edling, Silvia; Frelin, Anneli

    2013-01-01

    The purpose of this study is to theoretically discuss a specific aspect of teachers&apos; responsibilities: their responsibility for pupils&apos; or children&apos;s well-being. We ask two interrelated questions: firstly, how might (Swedish) teachers&apos; sense of responsibilities for their pupils&apos; well-being be understood in relation to…

  3. A Logistic Regression Analysis of Turkey&apos;s 15-Year-Olds&apos; Scoring above the OECD Average on the PISA&apos;09 Reading Assessment

    ERIC Educational Resources Information Center

    Kasapoglu, Koray

    2014-01-01

    This study aims to investigate which factors are associated with Turkey&apos;s 15-year-olds&apos; scoring above the OECD average (493) on the PISA&apos;09 reading assessment. Collected from a total of 4,996 15-year-old students from Turkey, data were analyzed by logistic regression analysis in order to model the data of students who were split…

  4. APOE genotype alters glial activation and loss of synaptic markers in mice.

    PubMed

    Zhu, Yuangui; Nwabuisi-Heath, Evelyn; Dumanis, Sonya B; Tai, Leon M; Yu, Chunjiang; Rebeck, G William; LaDu, Mary Jo

    2012-04-01

    The ε4 allele of the Apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), and affects clinical outcomes of chronic and acute brain damages. The mechanisms by which apoE affect diverse diseases and disorders may involve modulation of the glial response to various types of brain damage. We examined glial activation in a mouse model where each of the human APOE alleles are expressed under the endogenous mouse APOE promoter, as well as in APOE knock-out mice. APOE4 mice displayed increased glial activation in response to intracerebroventricular lipopolysaccharide (LPS) compared to APOE2 and APOE3 mice by several measures. There were higher levels of microglia/macrophage, astrocytes, and invading T-cells after LPS injection in APOE4 mice. APOE4 mice also displayed greater and more prolonged increases of cytokines (IL-1β, IL-6, TNF-α) than APOE2 and APOE3 mice. We found that APOE4 mice had greater synaptic protein loss after LPS injection, as measured by three markers: PSD-95, drebin, and synaptophysin. In all assays, APOE knock-out mice responded similar to APOE4 mice, suggesting that the apoE4 protein may lack anti-inflammatory characteristics of apoE2 and apoE3. Together, these findings demonstrate that APOE4 predisposes to inflammation, which could contribute to its association with Alzheimer's disease and other disorders.

  5. The Mayors&apos; Charter Schools

    ERIC Educational Resources Information Center

    Magee, Michael

    2014-01-01

    In 2007, the case could be made that Rhode Island had, dollar for dollar, the worst-performing public education system in the United States. Despite per-pupil expenditures ranking in the top 10 nationally, the state&apos;s 8th graders fared no better than 40th in reading and 33rd in math on the National Assessment of Educational Progress (NAEP).…

  6. A Nontoxic Barlow&apos;s Wheel

    ERIC Educational Resources Information Center

    Daffron, John A.; Greenslade, Thomas B., Jr.

    2015-01-01

    Barlow&apos;s wheel has been a favorite demonstration since its invention by Peter Barlow (1776-1862) in 1822. In the form shown in Fig. 1, it represents the first electric motor. The interaction between the electric current passing from the axle of the wheel to the rim and the magnetic field produced by the U-magnet produces a torque that turns…

  7. The Effects of Aerobic Exercise on Plasma Adiponectin Level and Adiponectin-related Protein Expression in Myocardial Tissue of ApoE(-/-) Mice.

    PubMed

    Zhu, Xiao-Juan; Chen, Li-Hui; Li, Jiang-Hua

    2015-12-01

    Numerous reports have confirmed the effect of ApoE knockout in the induction of cardiovascular diseases and the protective effect of adiponectin against the progression of cardiovascular diseases. The aim of this study was to reveal the roles of adiponectin signaling in the progression of cardiovascular diseases induced by ApoE knockout and to analyze the healthy effects of aerobic exercise on ApoE knockout mice (ApoE(-/-) mice) through observing the changes of adiponectin signaling caused by ApoE knockout and aerobic exercise. A twelve-week aerobic exercise program was carried out on the male ApoE(-/-) mice and the C57BL / 6J mice (C57 mice) of the same strain. Results show that the body weights, blood lipid level, plasma adiponectin level and adiponectin-related proteins in myocardial tissue were all significantly changed by ApoE knockout. A twelve-week aerobic exercise program exerted only minimal effects on the body weights, blood lipid levels, and plasma adiponectin levels of ApoE(-/-) mice, but increased the expressions of four adiponectin-related proteins, AdipoR1, PPARα, AMPK and P-AMPK, in the myocardial tissue of the ApoE(-/-) mice. In summary, adiponectin signaling may play an import role in the progression of cardiovascular diseases induced by ApoE knockout, and the beneficial health effects of aerobic exercise on ApoE(-/-) mice may be mainly from the increased adiponectin-related protein expression in myocardial tissue. Key pointsA twelve-week aerobic exercise program exerted only limited effects on the body weights and the plasma adiponectin levels of both the normal mice and the ApoE(-/-) mice but did effectively regulate the blood lipid levels of the normal mice (but not the ApoE(-/-) mice).After 12 weeks of aerobic exercise, expression of the adiponectin-related proteins in the myocardial tissue of the ApoE(-/-) and normal mice was increased, but the increased amplitudes of these proteins in the ApoE(-/-) mice were much larger in the ApoE

  8. Impact of apoE deficiency during synaptic remodeling in the mouse olfactory bulb

    PubMed Central

    Nwosu, Ikemefuna; Gairhe, Salina; Struble, Robert G.; Nathan, Britto P.

    2008-01-01

    In this study we examined the role of apoE on the rate of synaptic recovery in the olfactory bulb (OB) following olfactory epithelium (OE) lesioning in mice. We used both immunoblotting and immunohistochemical techniques to compare the density of OB synaptophysin (Syn, a synaptic marker) in apoE-gene deficient/knockout (KO) mice and wild-type (WT) mice following OE lesion. We found that the whole bulb concentrations of Syn, measured by immunoblotting, declined sharply following injury in both WT and KO mice during the degenerative phase (3–7 days). After this initial decline, the Syn concentration gradually increased to normal levels by 56 days in WT mice. In contrast, Syn concentration in KO mice did not recover by day 56 when Syn density in WT was essentially normal. Glomerular Syn density, measured by immunohistochemistry, found a lower density in KO mice at all time points post lesion. This lower concentration of whole bulb Syn parallels the slower recovery of glomerular area in KO mice. The data indicate that apoE deficiency in KO mice is associated with a delayed recovery of the glomerular area and a slower recovery in Syn concentration in the OB. PMID:18621483

  9. Targeting mitochondrial 18 kDa translocator protein (TSPO) regulates macrophage cholesterol efflux and lipid phenotype.

    PubMed

    Taylor, Janice M W; Allen, Anne-Marie; Graham, Annette

    2014-11-01

    The aim of the present study was to establish mitochondrial cholesterol trafficking 18 kDa translocator protein (TSPO) as a potential therapeutic target, capable of increasing macrophage cholesterol efflux to (apo)lipoprotein acceptors. Expression and activity of TSPO in human (THP-1) macrophages were manipulated genetically and by the use of selective TSPO ligands. Cellular responses were analysed by quantitative PCR (Q-PCR), immunoblotting and radiolabelling, including [3H]cholesterol efflux to (apo)lipoprotein A-I (apoA-I), high-density lipoprotein (HDL) and human serum. Induction of macrophage cholesterol deposition by acetylated low-density lipoprotein (AcLDL) increased expression of TSPO mRNA and protein, reflecting findings in human carotid atherosclerosis. Transient overexpression of TSPO enhanced efflux (E%) of [3H]cholesterol to apoA-I, HDL and human serum compared with empty vector (EV) controls, whereas gene knockdown of TSPO achieved the converse. Ligation of TSPO (using PK11195, FGIN-1-27 and flunitrazepam) triggered increases in [3H]cholesterol efflux, an effect that was amplified in TSPO-overexpressing macrophages. Overexpression of TSPO induced the expression of genes [PPARA (peroxisome-proliferator-activated receptor α), NR1H3 (nuclear receptor 1H3/liver X receptor α), ABCA1 (ATP-binding cassette A1), ABCG4 (ATP-binding cassette G4) and APOE (apolipoprotein E)] and proteins (ABCA1 and PPARα) involved in cholesterol efflux, reduced macrophage neutral lipid mass and lipogenesis and limited cholesterol esterification following exposure to AcLDL. Thus, targeting TSPO reduces macrophage lipid content and prevents macrophage foam cell formation, via enhanced cholesterol efflux to (apo)lipoprotein acceptors.

  10. HDL/ApoA-1 infusion and ApoA-1 gene therapy in atherosclerosis

    PubMed Central

    Chyu, Kuang-Yuh; Shah, Prediman K.

    2015-01-01

    The HDL hypothesis stating that simply raising HDL cholesterol (HDL-C) may produce cardiovascular benefits has been questioned recently based on several randomized clinical trials using CETP inhibitors or niacin to raise HDL-C levels. However, extensive pre-clinical data support the vascular protective effects of administration of exogenous ApoA-1 containing preβ-HDL like particles. Several small proof-of-concept clinical trials using such HDL/ApoA-1 infusion therapy have shown encouraging results but definitive proof of efficacy must await large scale clinical trials. In addition to HDL infusion therapy an alternative way to exploit beneficial cardiovascular effects of HDL/ApoA-1 is to use gene transfer. Preclinical studies have shown evidence of benefit using this approach; however clinical validation is yet lacking. This review summarizes our current knowledge of the aforementioned strategies. PMID:26388776

  11. MR histology of advanced atherosclerotic lesions of ApoE- knockout mice

    NASA Astrophysics Data System (ADS)

    Naumova, A.; Yarnykh, V.; Ferguson, M.; Rosenfeld, M.; Yuan, C.

    2016-02-01

    The purposes of this study were to examine the feasibility of determining the composition of advanced atherosclerotic plaques in fixed ApoE-knockout mice and to develop a time-efficient microimaging protocol for MR histological imaging on mice. Five formalin-fixed transgenic ApoE-knockout mice were imaged at the 9.4T Bruker BioSpec MR scanner using 3D spoiled gradient-echo sequence with an isotropic field of view of 24 mm3; TR 20.8 ms; TE 2.6 ms; flip angle 20°, resulted voxel size 47 × 63 × 94 pm3. MRI examination has shown that advanced atherosclerotic lesions of aorta, innominate and carotid arteries in ApoE-knockout mice are characterized by high calcification and presence of the large fibrofatty nodules. MRI quantification of atherosclerotic lesion components corresponded to histological assessment of plaque composition with a correlation coefficient of 0.98.

  12. Readin&apos;, Writin&apos;, Ready for Testin&apos;? Adaptive Assessment in Elective and Standardized-Tested Social Studies Course Contexts

    ERIC Educational Resources Information Center

    Meuwissen, Kevin W.

    2013-01-01

    This is an instrumental case study of 1 novice and 1 experienced secondary social studies teachers&apos; concurrent assessment practices within tightly structured, standardized-tested curricula and flexible elective curricula. It is anchored by 2 questions: (1) How did the teachers&apos; assessment stances and practices manifest across the 2…

  13. Examining Educators&apos; and Employers&apos; Perceptions on Career and Technical Education Graduates&apos; Employability Skills for the Labor Market in Jordan

    ERIC Educational Resources Information Center

    Al-Alawneh, Muhammad Khaled

    2009-01-01

    Preparing skilled and knowledgeable workforce that fits the labor market requires continued collaboration between education and work. Studying educators&apos; and employers&apos; perspectives on technical and non-technical skills may result in improving the quality of the graduates to compete on the level of the local as well as the global labor…

  14. What&apos;s a Degree Got to Do with It? The Civic Engagement of Associate&apos;s and Bachelor&apos;s Degree Holders

    ERIC Educational Resources Information Center

    Newell, Mallory Angeli

    2014-01-01

    This study explored the civic engagement of adults holding an associate&apos;s degree compared to those holding a bachelor&apos;s degree. Most prior research has focused on individuals who hold 4-year degrees; the present study, however, sought to understand differences between holders of 2-year degrees and 4-year degrees. Descriptive statistics…

  15. Pre-Service Teachers&apos; Views of Children&apos;s and Adults&apos; Play in Japan, Taiwan, and the USA

    ERIC Educational Resources Information Center

    Izumi-Taylor, Satomi; Ito, Yoko; Lin, Chia Hui; Lee, Yu-Yuan

    2014-01-01

    Teachers&apos; perspectives of play differ widely because of social and cultural influences that can be seen in their values and beliefs about play in different countries. In a global community, sharing educators&apos; knowledge of play and their perspectives of how to educate children through the use of play would be appropriate and complementary…

  16. "I Mean, the Queen&apos;s Fierce and the King&apos;s Not": Gendered Embodiment in Children&apos;s Drawings

    ERIC Educational Resources Information Center

    Wright, Susan

    2014-01-01

    Gender differences in children&apos;s artwork have been the subject of study for over 100 years. The focus of early research was quite narrow, honing in on issues such as children&apos;s gendered subject preferences, or their ability to render spatial relationships or include detail in their artwork. This has led to some stereotypical conclusions…

  17. A Quantitative Study of Head Start Children&apos;s Strengths, Families&apos; Perspectives, and Teachers&apos; Ratings in the Transition to Kindergarten

    ERIC Educational Resources Information Center

    Robinson, Chanele D.; Diamond, Karen E.

    2014-01-01

    This study examined the association between preschool children&apos;s social-interpersonal skills and their transition to school in the beginning months of kindergarten. One hundred and thirty-three preschool children participated in this study. During the spring of the pre-kindergarten year, children&apos;s social-interpersonal skills were…

  18. The Effect of Children&apos;s Rights Training on Primary School Students&apos; Utilisation and Knowledge Level about Children&apos;s Rights

    ERIC Educational Resources Information Center

    Ozmen, Suna Kaymak; Ocal, Tugba; Ozmen, Ahmet

    2014-01-01

    Recently, children&apos;s rights issue has taken attention. In this study, main purpose was to investigate the utilisation and knowledge level of 4th and 5th grade primary school students after children&apos;s rights training. The participants of this survey study were selected randomly from 10 schools. Results indicated that students had the…

  19. How the Group Investigation Model and the Six-Mirror Model Changed Teachers&apos; Roles and Teachers&apos; and Students&apos; Attitudes towards Diversity

    ERIC Educational Resources Information Center

    Damini, Marialuisa

    2014-01-01

    This paper is based on research that demonstrates the positive effects of the cooperative learning model Group Investigation (GI) and the Six-Mirror model on teacher effectiveness in organizing and scaffolding CL activities, and changing students&apos; and teachers&apos; views of diversity. We explain how the connection between the two models…

  20. Mothers&apos; Early Depressive Symptoms Predict Children&apos;s Low Social Competence in First Grade: Mediation by Children&apos;s Social Cognition

    ERIC Educational Resources Information Center

    Wang, Yiji; Dix, Theodore

    2015-01-01

    Background: This study examined whether social-cognitive processes in children mediate relations between mothers&apos; depressive symptoms across the first 3 years and children&apos;s first-grade social competence. Three maladaptive cognitions were examined: self-perceived social inadequacy, hostile attribution, and aggressive response generation.…

  1. The Little Emperor: Chinese Parents&apos; Assessment of Their Own, Their Partner&apos;s and Their Only Child&apos;s Intelligence

    ERIC Educational Resources Information Center

    Furnham, Adrian; Wu, Chun

    2014-01-01

    This study set out to examine whether Chinese parents, more than people from other nations, over-estimate the intelligence of their son (little emperor) compared to their daughter. In this study, 155 pairs of married couples from mainland China estimated their own, their partner&apos;s and their only child&apos;s overall intelligence and 13…

  2. The Complexity of Thomas Jefferson. A Response to "&apos;The Diffusion of Light&apos;: Jefferson&apos;s Philosophy of Education"

    ERIC Educational Resources Information Center

    Carpenter, James

    2014-01-01

    This response argues that Jefferson&apos;s educational philosophy must be considered in a proper historical context. Holowchak accurately demonstrates both Jefferson&apos;s obsession with education and the political philosophy on which his educational beliefs are built. However, the effort to apply modern democratic and meritocratic attributes to…

  3. A population study of apoE genotype at the age of 85: relation to dementia, cerebrovascular disease, and mortality

    PubMed Central

    Skoog, I.; Hesse, C.; Aevarsson, O.; Landahl, S.; Wahlstrom, J.; Fredman, P.; Blennow, K.

    1998-01-01

    OBJECTIVES—To study the association of apoE genotypes with dementia and cerebrovascular disorders in a population based sample of 85year old people.
METHODS—A representative sample of 85 year old people (303 non-demented, 109 demented) were given a neuropsychiatric and a medical examination and head CT. The apoE isoforms were determined. Dementia was diagnosed according to DSM-III-R.
RESULTS—At the age of 85, carriers of the apoE ε4 allele had an increased odds ratio (OR) for dementia (1.9; p<0.01) and its subtypes Alzheimer's disease (1.9; p<0.05) and vascular dementia (2.0; p<0.05). Among those categorised as having vascular dementia, the apoE ε4 allele was associated with mixed Alzheimer's disease-multi-infarct dementia (OR 6.5; p<0.05), but not with pure multi-infarct dementia (OR 1.5; NS). Only carriers of the apoE ε4 allele who also had ischaemic white matter lesions on CT of the head had an increased OR for dementia (OR 6.1; p=0.00003), and its main subtypes Alzheimer's disease (OR 6.8; p=0.002) and vascular dementia (OR 5.6; p=0.0007), whereas carriers of the apoE ε4 allele without white matter lesions had an OR for dementia of 1.0 (OR for Alzheimer's disease 1.8; NS and for vascular dementia 0.6; NS) and non-carriers of the apoE ε4 allele with white matter lesions had an OR for dementia of 2.2; NS (OR for Alzheimer's disease 2.7; NS and for vascular dementia 1.6; NS). The apoE allele variants were not related to mortality or incidence of dementia between the ages of 85 and 88. The ε2 allele was related to a higher prevalence of stroke or transient ischaemic attack at the age of 85 (OR 2.1; p<0.05) and a higher incidence of multi-infarct dementia during the follow up (OR 2.9; p<0.05).
CONCLUSIONS—Neither the apoE ε4 allele nor white matter lesions are sufficient risk factors by themselves for dementia at very old ages, whereas possession of both these entities increases the risk for Alzheimer's disease and vascular dementia

  4. Rate of atherosclerosis progression in ApoE-/- mice long after discontinuation of cola beverage drinking.

    PubMed

    Otero-Losada, Matilde; Cao, Gabriel; Mc Loughlin, Santiago; Rodríguez-Granillo, Gastón; Ottaviano, Graciela; Milei, José

    2014-01-01

    This study was conducted in order to evaluate the effect of cola beverages drinking on atherosclerosisand test the hypothesis whether cola beverages consumption at early life stages might affect the development and progression of atherosclerosis later in life. ApoE-/- C57BL/6J mice (8 week-old) were randomized in 3 groups (n = 20 each) according to free accessto water (W), sucrose sweetened carbonated cola drink(C) or aspartame-acesulfame K sweetened carbonated 'light' cola drink (L)for the next 8 weeks. Drinking treatment was ended by switching C and L groups to drinking water. Four mice per group and time were sequentially euthanized: before treatment (8 weeks-old), at the end of treatment (16 weeks-old) and after treatment discontinuation (20 weeks-old, 24 weeks-old, 30 week-old mice). Aortic roots and livers were harvested, processed for histology and serial cross-sections were stained. Aortic plaque area was analyzed and plaque/media-ratio was calculated. Early consumption of cola drinks accelerated atherosclerotic plaque progression favoring the interaction between macrophages and myofibroblasts, without the participation of either T lymphocytes or proliferative activity. Plaque/media-ratio varied according to drink treatment (F2,54 = 3.433, p<0.04) and mice age (F4,54 = 5.009, p<0.03) and was higher in C and L groups compared with age-matched W group (p<0.05 at 16 weeks and 20 weeks, p<0.01 at 24 weeks and 30 weeks). Natural evolution of atherosclerosis in ApoE-/- mice (W group) evidenced atherosclerosis acceleration in parallel with a rapid increase in liver inflammation around the 20 weeks of age. Cola drinking within the 8-16 weeks of age accelerated atherosclerosis progression in ApoE-/- mice favoring aortic plaque enlargement (inward remodeling) over media thinning all over the study time. Data suggest that cola drinking at early life stages may predispose to atherosclerosis progression later in life in ApoE-/- mice.

  5. Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE

    PubMed Central

    Bekris, L.M.; Lutz, F.; Yu, C.E.

    2011-01-01

    Genetic variation within the apolipoprotein E gene (APOE) locus is associated with late-onset Alzheimer's disease risk and quantitative traits as well as apoE expression in multiple tissues. The aim of this investigation was to explore the influence of APOE locus cis-regulatory element enhancer region genetic variation on regional gene promoter activity. Luciferase reporter constructs containing haplotypes of APOE locus gene promoters; APOE, APOC1, and TOMM40, and regional putative enhancers; TOMM40 IVS2-4, TOMM40 IVS6 poly-T, as well as previously described enhancers; ME1, or BCR, were evaluated for their effects on luciferase activity in 3 human cell lines. Results of this investigation demonstrate that in SHSY5Y cells, the APOE promoter is significantly influenced by the TOMM40 IVS2-4 and ME1 and the TOMM40 promoter is significantly influenced by the TOMM40 IVS6 poly-T, ME1 and BCR. In HepG2 cells, theTOMM40 promoter is significantly influenced by all four enhancers, whereas the APOE promoter is not influenced by any of the enhancers. The main novel finding of this investigation was that multiple APOE locus cis-elements influence both APOE and TOMM40 promoter activity according to haplotype and cell type suggesting that a complex transcriptional regulatory structure modulates regional expression. PMID:22089642

  6. Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis.

    PubMed

    Pencheva, Nora; Tran, Hien; Buss, Colin; Huh, Doowon; Drobnjak, Marija; Busam, Klaus; Tavazoie, Sohail F

    2012-11-21

    Through in vivo selection of human cancer cell populations, we uncover a convergent and cooperative miRNA network that drives melanoma metastasis. We identify miR-1908, miR-199a-5p, and miR-199a-3p as endogenous promoters of metastatic invasion, angiogenesis, and colonization in melanoma. These miRNAs convergently target apolipoprotein E (ApoE) and the heat shock factor DNAJA4. Cancer-secreted ApoE suppresses invasion and metastatic endothelial recruitment (MER) by engaging melanoma cell LRP1 and endothelial cell LRP8 receptors, respectively, while DNAJA4 promotes ApoE expression. Expression levels of these miRNAs and ApoE correlate with human metastatic progression outcomes. Treatment of cells with locked nucleic acids (LNAs) targeting these miRNAs inhibits metastasis to multiple organs, and therapeutic delivery of these LNAs strongly suppresses melanoma metastasis. We thus identify miRNAs with dual cell-intrinsic/cell-extrinsic roles in cancer, reveal convergent cooperativity in a metastatic miRNA network, identify ApoE as an anti-angiogenic and metastasis-suppressive factor, and uncover multiple prognostic miRNAs with synergistic combinatorial therapeutic potential in melanoma.

  7. Convergent multi-miRNA Targeting of ApoE Drives LRP1/LRP8-Dependent Melanoma Metastasis and Angiogenesis

    PubMed Central

    Pencheva, Nora; Tran, Hien; Buss, Colin; Huh, Doowon; Drobnjak, Marija; Busam, Klaus; Tavazoie, Sohail F.

    2013-01-01

    SUMMARY Through in-vivo selection of human cancer cell populations, we uncover a convergent and cooperative miRNA network that drives melanoma metastasis. We identify miR-1908, miR-199a-5p, and miR-199a-3p as endogenous promoters of metastatic invasion, angiogenesis, and colonization in melanoma. These miRNAs convergently target Apolipoprotein E (ApoE) and the heat-shock factor DNAJA4. Cancer-secreted ApoE suppresses invasion and metastatic endothelial recruitment (MER) by engaging melanoma-cell LRP1 and endothelial-cell LRP8 receptors, respectively–while DNAJA4 promotes ApoE expression. Expression levels of these miRNAs and ApoE correlate with human metastatic progression outcomes. Treatment of cells with locked nucleic acids (LNAs) targeting these miRNAs inhibits metastasis to multiple organs, while therapeutic delivery of these LNAs strongly suppresses melanoma metastasis. We thus identify miRNAs with dual cell-intrinsic/cell-extrinsic roles in cancer, reveal convergent cooperativity in a metastatic miRNA network, identify ApoE as an anti-angiogenic and metastasis-suppressive factor, and uncover multiple prognostic miRNAs with synergistic combinatorial therapeutic potential in melanoma. PMID:23142051

  8. Label-free detection of ApoE4-mediated β-amyloid aggregation on single nanoparticle uncovering Alzheimer's disease.

    PubMed

    Kang, Min Kyung; Lee, Jeewon; Nguyen, Anh H; Sim, Sang Jun

    2015-10-15

    Beta amyloid (Aβ) deposition is a pathological milestone of Alzheimer's disease (AD). This is facilitated by an isoform of Apolipoprotein E4 (ApoE4), which is a dominant risk factor for AD. However, current in vitro Aβ aggregation assays were performed in extreme conditions not linked to physiological conditions, to understand the mechanism of Aβ induced neurotoxicity. Here, we present a simple method for the ApoE4-mediated Aβ aggregation at physiological conditions using single gold nanoparticle based on localized surface plasmon resonance (LSPR). It can be directly observed by dark-field microscope or even by the naked eye. Following LSPR principles, we used ApoE4 inducing Aβ42 self-assemblies on gold nanoparticles (AuNPs) surface via their surface charge interaction. Using physiologically mimic cerebrospinal fluid, we determined a detection limit of 1.5 pM for Aβ42 corresponding to the ~2.9 nm LSPR-peak shift under ApoE4. Interestingly, the result also shows that ApoE4 induces the aggregation of Aβ42 more specifically and rapidly than that of Aβ40. This is the first biomimetic platform for real-time detection of Aβ aggregation, mimicking biological conditions, which can be used to investigate AD directly.

  9. Uncleaved ApoM Signal Peptide Is Required for Formation of Large ApoM/Sphingosine 1-Phosphate (S1P)-enriched HDL Particles*

    PubMed Central

    Liu, Mingxia; Allegood, Jeremy; Zhu, Xuewei; Seo, Jeongmin; Gebre, Abraham K.; Boudyguina, Elena; Cheng, Dongmei; Chuang, Chia-Chi; Shelness, Gregory S.; Spiegel, Sarah; Parks, John S.

    2015-01-01

    Apolipoprotein M (apoM), a plasma sphingosine 1-phosphate (S1P) carrier, associates with plasma HDL via its uncleaved signal peptide. Hepatocyte-specific apoM overexpression in mice stimulates formation of both larger nascent HDL in hepatocytes and larger mature apoM/S1P-enriched HDL particles in plasma by enhancing hepatic S1P synthesis and secretion. Mutagenesis of apoM glutamine 22 to alanine (apoMQ22A) introduces a functional signal peptidase cleavage site. Expression of apoMQ22A in ABCA1-expressing HEK293 cells resulted in the formation of smaller nascent HDL particles compared with wild type apoM (apoMWT). When apoMQ22A was expressed in vivo, using recombinant adenoviruses, smaller plasma HDL particles and decreased plasma S1P and apoM were observed relative to expression of apoMWT. Hepatocytes isolated from both apoMWT- and apoMQ22A-expressing mice displayed an equivalent increase in cellular levels of S1P, relative to LacZ controls; however, relative to apoMWT, apoMQ22A hepatocytes displayed more rapid apoM and S1P secretion but minimal apoMQ22A bound to nascent lipoproteins. Pharmacologic inhibition of ceramide synthesis increased cellular sphingosine and S1P but not medium S1P in both apoMWT and apoMQ22A hepatocytes. We conclude that apoM secretion is rate-limiting for hepatocyte S1P secretion and that its uncleaved signal peptide delays apoM trafficking out of the cell, promoting formation of larger nascent apoM- and S1P-enriched HDL particles that are probably precursors of larger apoM/S1P-enriched plasma HDL. PMID:25627684

  10. APOE polymorphisms influence longitudinal lipid trends preceding intracerebral hemorrhage

    PubMed Central

    Phuah, Chia-Ling; Raffeld, Miriam R.; Ayres, Alison M.; Gurol, M. Edip; Viswanathan, Anand; Greenberg, Steven M.; Biffi, Alessandro; Rosand, Jonathan

    2016-01-01

    Objective: We sought to determine whether APOE genotype influences a previously observed decline in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels preceding primary intracerebral hemorrhage (ICH), as a potential demonstration of nonamyloid mechanisms of APOE in ICH risk. Methods: We performed a single-center retrospective longitudinal analysis using patients with known APOE genotype drawn from an ongoing cohort study of ICH. Serum lipid measurements for TC, triglycerides (TGs), LDL, and high-density lipoprotein (HDL) collected within 2 years before and after index ICH were extracted from electronic medical records. Piecewise linear mixed-effects models were used to compare APOE allele–specific effects on temporal serum lipid trends in ICH. Demographics, medical history, medications, and health maintenance data were included as fixed effects. Inter- and intraindividual variations in lipid levels were modeled as random effects. Results: A total of 124 ICH cases were analyzed. APOE ε4 carriers had greater rates of decline in serum TC and LDL within 6 months preceding ICH (TC: −7.30 mg/dL/mo, p = 0.0035; LDL: −8.44 mg/dL/mo, p = 0.0001). Conversely, serum TC and LDL levels in APOE ε2 carriers were unchanged within the same time period. APOE genotype had no associations with serum HDL or TG trends. Conclusions: APOE allele status predicts serum TC and LDL changes preceding acute ICH. Our results have implications for ongoing efforts in dissecting the role of dyslipidemia in cerebrovascular disease risk. APOE genotype–specific influence on lipid trends provides a clue for one mechanism by which APOE may influence risk of ICH. Further characterization of the metabolic roles of APOE is needed to improve the understanding of APOE biology in cerebrovascular disease risk. PMID:27433544

  11. Full-length apolipoprotein E protects against the neurotoxicity of an apoE-related peptide

    PubMed Central

    Crutcher, K.A.; Lilley, H.N.; Anthony, S. R.; Zhou, W.; Narayanaswami, V.

    2009-01-01

    Apolipoprotein E was found to protect against the neurotoxic effects of a dimeric peptide derived from the receptor-binding region of this protein (residues 141–149). Both apoE3 and apoE4 conferred protection but the major N-terminal fragment of each isoform did not. Nor was significant protection provided by bovine serum albumin or apoA-I. Full-length apoE3 and apoE4 also inhibited the uptake of a fluorescent-labeled derivative of the peptide, suggesting that the mechanism of inhibition might involve competition for cell surface receptors/proteoglycans that mediate endocytosis and/or signaling pathways. These results might bear on the question of the role of apoE in neuronal degeneration, such as occurs in Alzheimer’s disease where apoE4 confers a significantly greater risk of pathology. PMID:19836363

  12. Different Functional and Structural Characteristics between ApoA-I and ApoA-4 in Lipid-Free and Reconstituted HDL State: ApoA-4 Showed Less Anti-Atherogenic Activity

    PubMed Central

    Yoo, Jeong-Ah; Lee, Eun-Young; Park, Ji Yoon; Lee, Seung-Taek; Ham, Sihyun; Cho, Kyung-Hyun

    2015-01-01

    Apolipoprotein A-I and A-IV are protein constituents of high-density lipoproteins although their functional difference in lipoprotein metabolism is still unclear. To compare anti-atherogenic properties between apoA-I and apoA-4, we characterized both proteins in lipid-free and lipid-bound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and 67 Å on native gel electrophoresis, while apoA-I showed scattered band pattern less than 71 Å. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around 101 Å and 113 Å, while apoA-I-rHDL showed almost single band around 98 Å size. Lipid-free apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid-free state, BS3-crosslinking revealed that apoA-4 showed less multimerization tendency upto dimer, while apoA-I showed pentamerization. In rHDL state (95:1), apoA-4 was existed as dimer as like as apoA-I. With higher phospholipid content (255:1), five apoA-I and three apoA-4 were required to the bigger rHDL formation. Regardless of particle size, apoA-I-rHDL showed superior LCAT activation ability than apoA-4-rHDL. Uptake of acetylated LDL was inhibited by apoA-I in both lipid-free and lipid-bound state, while apoA-4 inhibited it only lipid-free state. ApoA-4 showed less anti-atherogenic activity with more sensitivity to glycation. In conclusion, apoA-4 showed inferior physiological functions in lipid-bound state, compared with those of apoA-I, to induce more pro-atherosclerotic properties. PMID:25997739

  13. Different Functional and Structural Characteristics between ApoA-I and ApoA-4 in Lipid-Free and Reconstituted HDL State: ApoA-4 Showed Less Anti-Atherogenic Activity.

    PubMed

    Yoo, Jeong-Ah; Lee, Eun-Young; Park, Ji Yoon; Lee, Seung-Taek; Ham, Sihyun; Cho, Kyung-Hyun

    2015-06-01

    Apolipoprotein A-I and A-IV are protein constituents of high-density lipoproteins although their functional difference in lipoprotein metabolism is still unclear. To compare anti-atherogenic properties between apoA-I and apoA-4, we characterized both proteins in lipid-free and lipid-bound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and 67 Å on native gel electrophoresis, while apoA-I showed scattered band pattern less than 71 Å. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around 101 Å and 113 Å, while apoA-I-rHDL showed almost single band around 98 Å size. Lipid-free apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid-free state, BS3-crosslinking revealed that apoA-4 showed less multimerization tendency upto dimer, while apoA-I showed pentamerization. In rHDL state (95:1), apoA-4 was existed as dimer as like as apoA-I. With higher phospholipid content (255:1), five apoA-I and three apoA-4 were required to the bigger rHDL formation. Regardless of particle size, apoA-I-rHDL showed superior LCAT activation ability than apoA-4-rHDL. Uptake of acetylated LDL was inhibited by apoA-I in both lipid-free and lipid-bound state, while apoA-4 inhibited it only lipid-free state. ApoA-4 showed less anti-atherogenic activity with more sensitivity to glycation. In conclusion, apoA-4 showed inferior physiological functions in lipid-bound state, compared with those of apoA-I, to induce more pro-atherosclerotic properties. PMID:25997739

  14. Mississippi Public High School Counselors&apos; and Principals&apos; Perceptions of the Subject Area Testing Program (SATP2) and Its Impact on Counselors&apos; Job Performance

    ERIC Educational Resources Information Center

    Edwards, Aretha Hargrove

    2012-01-01

    The purpose of this study was to examine Mississippi Delta area public high school counselors&apos; and principals&apos; perception of the impact of SATP2 testing on counselors&apos; services to students in order to determine whether or not testing responsibilities have an adverse effect on counselors&apos; delivery of services to students. This…

  15. "Your Lunch Pail Is Silly!" Children&apos;s and Teachers&apos; Views on Teasing

    ERIC Educational Resources Information Center

    Harwood, Debra; Copfer, Sarah

    2015-01-01

    What is childhood like today? Is it a world fraught with endless joy, fun, and games, or are children experiencing a much different reality? A child&apos;s social interactions can be a source of great enjoyment and are essential to early development. Conversely, young children routinely experience tension, ambiguity, and conflict as they navigate…

  16. Students&apos; Perceptions of Teachers: Implications for Classroom Practices for Supporting Students&apos; Success

    ERIC Educational Resources Information Center

    Guess, Pamela; Bowling, Sara

    2014-01-01

    Positive psychology represents a conceptual framework that emphasizes the need to capitalize on individuals&apos; strengths in order to facilitate optimal functioning. As applied to the educational setting, these concepts have primarily been investigated via teaching life skills to students that encourage overall wellness. School-based strategies…

  17. Principals&apos; Perceptions of Novice School Counselors&apos; Induction: An Afterthought

    ERIC Educational Resources Information Center

    Bickmore, Dana L.; Curry, Jennifer R.

    2013-01-01

    Principals have a clear impact on the transition of teachers into their initial work setting (Allensworth, Ponisciak, Mazzeo, 2009; S. T. Bickmore & D. L. Bickmore, 2010; Scherff, 2008). School administrators&apos; influence on teacher induction is both organizational and relational as they develop structures and practices that support…

  18. Indian Mothers&apos; Perceptions of Their Roles in Their Daughters&apos; University Course Choices

    ERIC Educational Resources Information Center

    Khambhaita, Priya

    2014-01-01

    This paper presents new findings on the experiences of Indian mothers in the roles they play in their daughters&apos; higher education (HE) subject choices. Whilst there are existing studies on White British mothers and parents more generally in terms of parental involvement in education, and a growing number of papers presenting results on…

  19. Students&apos; and Teachers&apos; Perceptions of Using Video Games to Enhance Science Instruction

    ERIC Educational Resources Information Center

    Marino, Matthew T.; Israel, Maya; Beecher, Constance C.; Basham, James D.

    2013-01-01

    Science education video game research points toward promising, but inconclusive results in both student learning outcomes and attitudes. However, student-level variables other than gender have been largely absent from this research. This study examined how students&apos; reading ability level and disability status are related to their video…

  20. Towards the modelling of ageing and atherosclerosis effects in ApoE(-/-) mice aortic tissue.

    PubMed

    Waffenschmidt, Tobias; Cilla, Myriam; Sáez, Pablo; Pérez, Marta M; Martínez, Miguel A; Menzel, Andreas; Peña, Estefanía

    2016-08-16

    The goal of this work consists in a quantitative analysis and constitutive modelling of ageing processes associated to plaque formation in mice arteries. Reliable information on the characteristic evolution of pressure-stretch curves due to the ageing effects is extracted from previous inflation test experiments. Furthermore, characteristic age-dependent material parameters are identified on the basis of a continuum-mechanics-based parameter optimisation technique. The results indicate that the aorta-stiffness of the healthy control mice remains basically constant irrespective of the diet-time and age. In contrast, significant differences exist within the material response and in consequence within the material parameters between the ApoE(-/-) and the control mice as well as for the different locations over the aorta which is underlined by our experimental observations. With regard to the temporal evolution of the material parameters, we observe that the material parameters for the ApoE(-/-) mice aortas exhibit a saturation-type increase with respect to age. PMID:26924660

  1. Participants&apos; Experiences in Hellinger&apos;s Family Constellation Work: A Grounded Theory Study

    ERIC Educational Resources Information Center

    Georgiadou, Sofia

    2012-01-01

    As a recently introduced to the U.S. model of intergenerational systemic therapy from Germany, Bert Hellinger&apos;s Family Constellation Work (FCW) has very limited research support. Hellinger himself has authored a number of publications referencing hundreds of cases, where he implemented his method to approach a broad array of physical,…

  2. Understanding Teachers&apos; Perceptions of Student Support Systems in Relation to Teachers&apos; Stress

    ERIC Educational Resources Information Center

    Ball, Annahita; Anderson-Butcher, Dawn

    2014-01-01

    Expanded school mental health (ESMH) programs are critical for addressing children&apos;s social and emotional development in schools. As broad, multisystem approaches, ESMH programs rely on teachers for effective and sustainable primary, secondary, and tertiary school mental health service delivery. In light of the increasing mental health needs…

  3. Administrators&apos; Views on Teacher Evaluation: Examining Ontario&apos;s Teacher Performance Appraisal

    ERIC Educational Resources Information Center

    Maharaj, Sachin

    2014-01-01

    This study examines the views of administrators (i.e., principals and vice-principals) in Ontario, Canada, with regard to the province&apos;s Teacher Performance Appraisal process. A total of 178 responses were collected from a survey that examined five areas: 1) preparation and training; 2) classroom observations; 3) preparing the formal…

  4. But I&apos;m Married: Understanding Relationship Status and College Students&apos; Sexual Behaviors

    ERIC Educational Resources Information Center

    Oswalt, Sara B.; Wyatt, Tammy J.

    2014-01-01

    Sexual health programs on college campuses are often directed toward single individuals with a focus on sexual risk. Using a sample of college students, this study examines how relationship status relates to sexual behaviors and may be a factor for sexual risk. Based on the study&apos;s results, expansion of sexual health programming on college…

  5. Exploring a National Book-Gifting Scheme: Parents&apos; and Children&apos;s Reactions

    ERIC Educational Resources Information Center

    Wray, David; Medwell, Jane

    2015-01-01

    Several early learning programmes have targeted children&apos;s reading, particularly their relationships with books. One, Bookstart, provided free books to babies attending their eighth-month health check at local clinics. Study of this programme suggested that it led to an improvement in language performance upon school entry. Booktime continues…

  6. ApoE polymorphisms and diarrheal outcomes in Brazilian shanty town children

    PubMed Central

    Oriá, R.B.; Patrick, P.D.; Oriá, M.O.B.; Lorntz, B.; Thompson, M.R.; Azevedo, O.G.R.; Lobo, R.N.B.; Pinkerton, R.F.; Guerrant, R.L.; Lima, A.A.M.

    2011-01-01

    A series of studies have shown that the heavy burdens of diarrheal diseases in the first 2 formative years of life in children living in urban shanty towns have negative effects on physical and cognitive development lasting into later childhood. We have shown that APOE4 is relatively common in shanty town children living in Brazil (13.4%) and suggest that APOE4 has a protective role in cognitive development as well as weight-for-height in children with heavy burdens of diarrhea in early childhood (64/123; 52%), despite being a marker for cognitive decline with Alzheimer’s and cardiovascular diseases later in life. APOE2 frequency was higher among children with heaviest diarrhea burdens during the first 2 years of life, as detected by PCR using the restriction fragment length polymorphism method, raising the possibility that ApoE-cholesterol balance might be critical for growth and cognitive development under the stress of heavy diarrhea burdens and when an enriched fat diet is insufficient. These findings provide a potential explanation for the survival advantage in evolution of genes, which might raise cholesterol levels during heavy stress of diarrhea burdens and malnutrition early in life. PMID:20401432

  7. Time&apos;s Up: Applying Teacher Management Skills to Solving Philadelphia&apos;s Problems

    ERIC Educational Resources Information Center

    Lax, Zach

    2013-01-01

    Teachers are natural problem solvers, and they should be using this quality to their advantage when it comes to solving the systemic issues that plague Philadelphia&apos;s education system. Many of the articles in this issue have already gone into great detail about what is happening in Philadelphia. Torch Lytle has provided a summary of the…

  8. Updating Understandings of "Teaching": Taking Account of Learners&apos; and Teachers&apos; Beliefs

    ERIC Educational Resources Information Center

    Maclellan, Effie

    2015-01-01

    The paper reviews recent psycho-educational literature to identify features of teacher thinking which enable learners to acquire meaningful knowledge. The review establishes that one powerful mechanism to improve teaching in higher education turns on exploiting adults&apos; epistemic beliefs: beliefs about the nature and the acquisition of…

  9. Investigating Elementary Teachers&apos; Thinking about and Learning to Notice Students&apos; Science Ideas

    ERIC Educational Resources Information Center

    Luna, Melissa Jo

    2013-01-01

    Children naturally use observations and everyday thinking to construct explanations as to why phenomena happen in the world. Science instruction can benefit by starting with these ideas to help children build coherent scientific understandings of how the physical world works. To do so, science teaching must involve attending to students&apos;…

  10. Towards the modelling of ageing and atherosclerosis effects in ApoE(-/-) mice aortic tissue.

    PubMed

    Waffenschmidt, Tobias; Cilla, Myriam; Sáez, Pablo; Pérez, Marta M; Martínez, Miguel A; Menzel, Andreas; Peña, Estefanía

    2016-08-16

    The goal of this work consists in a quantitative analysis and constitutive modelling of ageing processes associated to plaque formation in mice arteries. Reliable information on the characteristic evolution of pressure-stretch curves due to the ageing effects is extracted from previous inflation test experiments. Furthermore, characteristic age-dependent material parameters are identified on the basis of a continuum-mechanics-based parameter optimisation technique. The results indicate that the aorta-stiffness of the healthy control mice remains basically constant irrespective of the diet-time and age. In contrast, significant differences exist within the material response and in consequence within the material parameters between the ApoE(-/-) and the control mice as well as for the different locations over the aorta which is underlined by our experimental observations. With regard to the temporal evolution of the material parameters, we observe that the material parameters for the ApoE(-/-) mice aortas exhibit a saturation-type increase with respect to age.

  11. Using an APOS Framework to Understand Teachers&apos; Responses to Questions on the Normal Distribution

    ERIC Educational Resources Information Center

    Bansilal, Sarah

    2014-01-01

    This study is an exploration of teachers&apos; engagement with concepts embedded in the normal distribution. The participants were a group of 290 in-service teachers enrolled in a teacher development program. The research instrument was an assessment task that can be described as an "unknown percentage" problem, which required the…

  12. Researching Teachers&apos; and Parents&apos; Perceptions of Dialogue

    ERIC Educational Resources Information Center

    Tveit, Anne Dorthe

    2014-01-01

    While there has been a great deal of research done on parent involvement and the challenges of conducting effective dialogue in parent-teacher meetings, less attention has been paid to how teachers and parents themselves perceive dialogue. The purpose of the present article is to study whether deliberative principles are vital to teachers&apos;…

  13. Students&apos; Perception of Live Lectures&apos; Inherent Disadvantages

    ERIC Educational Resources Information Center

    Petrovic, Juraj; Pale, Predrag

    2015-01-01

    This paper aims to provide insight into various properties of live lectures from the perspective of sophomore engineering students. In an anonymous online survey conducted at the Faculty of Electrical Engineering and Computing, University of Zagreb, we investigated students&apos; opinions regarding lecture attendance, inherent disadvantages of…

  14. A School&apos;s Organizational Structure and Students&apos; Mathematics Achievements

    ERIC Educational Resources Information Center

    Teaching Children Mathematics, 2010

    2010-01-01

    How a school is organized--or, more specifically, the extent to which teachers work together and treat one another as professionals--can influence elementary school students&apos; mathematics achievement. So suggest the authors of a recent study on the impact of school organization on longitudinal student achievement (Moller, Stephanie, Roslyn A.…

  15. Vocational Education Approach: New TEL Settings--New Prospects for Teachers&apos; Instructional Activities?

    ERIC Educational Resources Information Center

    Hämäläinen, Raija; De Wever, Bram

    2013-01-01

    This study focuses on vocational education teachers&apos; instructional activities in a new technology-enhanced learning (TEL) setting. A content analysis is applied to investigate teachers&apos; and students&apos; interactions in a 3D game context. The findings illustrate that when teachers&apos; and students&apos; interactions are mediated by a…

  16. Human apolipoprotein E4 modulates the expression of Pin1, Sirtuin 1, and Presenilin 1 in brain regions of targeted replacement apoE mice.

    PubMed

    Lattanzio, F; Carboni, L; Carretta, D; Rimondini, R; Candeletti, S; Romualdi, P

    2014-01-01

    The apolipoprotein E4 (apoE4) allele is consistently associated with increased risk for Alzheimer's disease (AD). We investigated the molecular mechanism of this susceptibility by analyzing the levels of genes involved in AD pathogenesis in transgenic mice expressing human apoE3 or apoE4 isoforms. mRNA and protein levels of Pin1, Sirtuin 1 (Sirt1), Presenilin 1 (PS1), and pro-Brain-derived Neurotrophic Factor (BDNF) were analyzed in brain regions affected by neuropathological changes in AD. Pin1 mRNA was significantly higher in the hippocampus of apoE4 mice than in apoE3 controls, whereas lower expression was detected in the entorhinal and parietal cortices. Reduced Pin1 levels may increase neurofibrillary degeneration and amyloidogenic processes, while compensatory mechanisms may take place in the hippocampus to balance spatial memory deficits. Sirt1 levels were significantly reduced in the frontal cortex of apoE4 mice. Sirt1 reduction may hinder its protective role against the formation of plaques and tangles and diminish its anti-inflammatory actions. Sirt1 decrease may also play a role in apoE4-associated memory impairments. Moreover, in apoE4 mice PS1 mRNA levels were lower in the frontal cortex. Lower PS1 expression may hamper γ-secretase function, thus affecting amyloid precursor protein processing. Pro-BDNF mRNA levels did not differ between apoE3 and apoE4 mice in any region analyzed. This study showed dysregulated expression of Pin1, Sirt1, and PS1 genes in different cerebral areas of apoE4 mice, suggesting that these changes may play a role in the mechanism of AD vulnerability.

  17. Daidzein Augments Cholesterol Homeostasis via ApoE to Promote Functional Recovery in Chronic Stroke

    PubMed Central

    Kim, Eunhee; Woo, Moon-Sook; Qin, Luye; Ma, Thong; Beltran, Cesar D.; Bao, Yi; Bailey, Jason A.; Corbett, Dale; Ratan, Rajiv R.; Lahiri, Debomoy K.

    2015-01-01

    Stroke is the world's leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, is a clinically approved agent that has a neuroprotective effect in vitro, and it promotes axon growth in an animal model of optic nerve crush. The current study investigates the efficacy of daidzein on neuroprotection and functional recovery in a clinically relevant mouse model of stroke recovery. In light of the fact that cholesterols are essential lipid substrates in injury-induced synaptic remodeling, we found that daidzein enhanced the cholesterol homeostasis genetic program, including Lxr and downstream transporters, Apoe, Abca1, and Abcg1 genes in vitro. Daidzein also elevated the cholesterol homeostasis genes in the poststroke brain with Apoe, the highest expressing transporter, but did not affect infarct volume or hemispheric swelling. Despite the absence of neuroprotection, daidzein improved motor/gait function in chronic stroke and elevated synaptophysin expression. However, the daidzein-enhanced functional benefits and synaptophysin expression were abolished in Apoe-knock-out mice, suggesting the importance of daidzein-induced ApoE upregulation in fostering stroke recovery. Dissociation between daidzein-induced functional benefits and the absence of neuroprotection further suggest the presence of nonoverlapping mechanisms underlying recovery processes versus acute pathology. With its known safety in humans, early and chronic use of daidzein aimed at augmenting ApoE may serve as a novel, translatable strategy to promote functional recovery in stroke patients without adverse acute effect. SIGNIFICANCE STATEMENT There have been recurring translational failures in treatment strategies for stroke. One underlying issue is the disparity in outcome analysis between animal and clinical studies. The former mainly depends on acute infarct size, whereas long

  18. Lipoprotein clearance mechanisms in LDL receptor-deficient "Apo-B48-only" and "Apo-B100-only" mice.

    PubMed Central

    Véniant, M M; Zlot, C H; Walzem, R L; Pierotti, V; Driscoll, R; Dichek, D; Herz, J; Young, S G

    1998-01-01

    The role of the low density lipoprotein receptor (LDLR) in the clearance of apo-B48-containing lipoproteins and the role of the LDLR-related protein (LRP) in the removal of apo-B100-containing lipoproteins have not been clearly defined. To address these issues, we characterized LDLR-deficient mice homozygous for an "apo-B48-only" allele, an "apo-B100-only" allele, or a wild-type apo-B allele (Ldlr-/- Apob48/48, Ldlr-/-Apob100/100, and Ldlr-/-Apob+/+, respectively). The plasma apo-B48 and LDL cholesterol levels were higher in Ldlr-/-Apob48/48 mice than in Apob48/48 mice, indicating that the LDL receptor plays a significant role in the removal of apo-B48-containing lipoproteins. To examine the role of the LRP in the clearance of apo-B100-containing lipoproteins, we blocked hepatic LRP function in Ldlr-/-Apob100/100 mice by adenoviral-mediated expression of the receptor-associated protein (RAP). RAP expression did not change apo-B100 levels in Ldlr-/-Apob100/100 mice. In contrast, RAP expression caused a striking increase in plasma apo-B48 levels in Apob48/48 and Ldlr-/-Apob48/48 mice. These data imply that LRP is important for the clearance of apo-B48-containing lipoproteins but plays no significant role in the clearance of apo-B100-containing lipoproteins. PMID:9788969

  19. Teachers&apos; Spatial Anxiety Relates to 1st-and 2nd-Graders&apos; Spatial Learning

    ERIC Educational Resources Information Center

    Gunderson, Elizabeth A.; Ramirez, Gerardo; Beilock, Sian L.; Levine, Susan C.

    2013-01-01

    Teachers&apos; anxiety about an academic domain, such as math, can impact students&apos; learning in that domain. We asked whether this relation held in the domain of spatial skill, given the importance of spatial skill for success in math and science and its malleability at a young age. We measured 1st-and 2nd-grade teachers&apos; spatial anxiety…

  20. Altered small-world anatomical networks in Apolipoprotein-E4 (ApoE4) carriers using MRI.

    PubMed

    Goryawala, Mohammed; Zhou, Qi; Duara, Ranjan; Loewenstein, David; Cabrerizo, Mercedes; Barker, Warren; Adjouadi, Malek

    2014-01-01

    Apolipoprotein E (ApoE) gene and primarily its allele e4 have been identified as a risk factor for Alzheimer's disease (AD). The prevalence of the gene in 25-30% in the population makes it essential to estimate its role in neuroregulation and its impact on distributed brain networks. In this study, we provide computational neuroanatomy based interpretation of large-scale and small-world cortical networks in cognitive normal (CN) subjects with differing Apolipoprotein-E4 (ApoE4) gene expression. We estimated large-scale anatomical networks from cortical thickness measurements derived from magnetic resonance imaging in 147 CN subjects explored in relation to ApoE4 genotype (e4+ carriers (n=41) versus e4- non-carriers (n=106)). Brain networks were constructed by thresholding cortical thickness correlation matrices of 68 bilateral regions of the brain analyzed using well-established graph theoretical approaches. Compared to ApoE4 non-carriers, carriers showed increased interregional correlation coefficients in regions like precentral, superior frontal and inferior temporal regions. Interestingly most of the altered connections were intra-hemispheric limited primarily to the right hemisphere. Furthermore, ApoE4 carriers demonstrated abnormal small-world architecture in the cortical networks with increased clustering coefficient and path lengths as compared to non-carrier, suggesting a less optimal topological organization. Additionally non-carriers demonstrated higher betweenness in regions such as middle temporal, para-hippocampal gyrus, posterior cingulate and insula of the default mode network (DMN), also seen in subjects with AD and mild cognitive impairment (MCI). The results suggest that the complex morphological cortical connectivity patterns are altered in ApoE4 carriers as compared to non-carriers, providing evidence for disruption of integrity in large-scale anatomical brain networks.

  1. Teaching the Repeated Prisoner&apos;s Dilemma with a Non-Computerised Adaptation of Axelrod&apos;s Tournament

    ERIC Educational Resources Information Center

    Dennis, Catherine

    2015-01-01

    Darwin&apos;s theory of evolution is explicitly competitive, yet co-operation between individuals is a common phenomenon. The Prisoner&apos;s Dilemma model is central to the teaching of the evolution of co-operation. The best-known explorations of the Prisoner&apos;s Dilemma are the tournaments run by Robert Axelrod in the 1980s. Aimed at students…

  2. ApoE deficiency promotes colon inflammation and enhances the inflammatory potential of oxidized-LDL and TNF-α in primary colon epithelial cells

    PubMed Central

    El-Bahrawy, Ali H.; Tarhuni, Abdelmetalab; Kim, Hogyoung; Subramaniam, Venkat; Benslimane, Ilyes; Elmajeed, Zakaria Y. Abd; Okpechi, Samuel C.; Ghonim, Mohamed A.; Hemeida, Ramadan A.M.; Abo-yousef, Amira M.; El-Sherbiny, Gamal A.; Abdel-Raheem, Ihab T.; Kim, Jong; Naura, Amarjit S.; Boulares, A. Hamid

    2016-01-01

    Although deficiency in Apolipoprotein E (ApoE) is linked to many diseases, its effect on colon homoeostasis remains unknown. ApoE appears to control inflammation by regulating nuclear factor-κB (NF-κB). The present study was designed to examine whether ApoE deficiency affects factors of colon integrity in vivo and given the likelihood that ApoE deficiency increases oxidized lipids and TNF-α, the present study also examined whether such deficiency enhances the inflammatory potential of oxidized-LDL (oxLDL) and TNF-α in colon epithelial cells (CECs), in vitro. Here we show that ApoE deficiency is associated with chronic inflammation systemically and in colonic tissues as assessed by TNF-α levels. Increased colon TNF-α mRNA coincided with a substantial increase in cyclooxygenase (COX)-2. ApoE deficiency enhanced the potential of oxLDL and TNF-α to induce COX-2 expression as well as several other inflammatory factors in primary CECs. Interestingly, oxLDL enhanced TGF-β expression only in ApoE−/−, but not in wild-type, epithelial cells. ApoE deficiency appears to promote COX-2 expression enhancement through a mechanism that involves persistent NF-κB nuclear localization and PI3 and p38 MAP kinases but independently of Src. In mice, ApoE deficiency promoted a moderate increase in crypt length, which was associated with opposing effects of an increase in cell proliferation and apoptosis at the bottom and top of the crypt respectively. Our results support the notion that ApoE plays a central role in colon homoeostasis and that ApoE deficiency may constitute a risk factor for colon pathologies. PMID:27538678

  3. An Analysis of Information Technology Managers&apos; and Executives&apos; Security Concerns on Willingness to Adopt Cloud Computing Solutions

    ERIC Educational Resources Information Center

    Tanque, Marcus M.

    2012-01-01

    The research conducted in this study inquires about Information Technology (IT) managers&apos; and executives&apos; attitudes, beliefs, and knowledge on Cloud Computing (CC) security. The study evaluated how these factors affect IT managers&apos; and executives&apos; willingness to adopt CC solutions in their organizations. Confidentiality,…

  4. European-American and African-American Mothers&apos; Emotion Socialization Practices Relate Differently to Their Children&apos;s Academic and Social-Emotional Competence

    ERIC Educational Resources Information Center

    Nelson, Jackie A.; Leerkes, Esther M.; Perry, Nicole B.; O'Brien, Marion; Calkins, Susan D.; Marcovitch, Stuart

    2013-01-01

    The current study examines whether the relation between mothers&apos; responses to their children&apos;s negative emotions and teachers&apos; reports of children&apos;s academic performance and social-emotional competence are similar or different for European-American and African-American families. Two hundred mothers (137 European-American, 63…

  5. Maurice Gee&apos;s Brilliant Borrowings of Maurice Gee and Significant Others: Realism and Postmodernism in Gee&apos;s Books for Children and Adults

    ERIC Educational Resources Information Center

    van Rij, Vivien

    2013-01-01

    This paper examines the work of one of New Zealand&apos;s most acclaimed writers, Maurice Gee, and the use of his children&apos;s fiction as an experimental ground for postmodernist techniques further developed in his writing for adults. In particular, it considers Gee&apos;s borrowings of his own and others&apos; non-fictional and fictional…

  6. The Backpack Food Program&apos;s Effects on U.S. Elementary Students&apos; Hunger and On-Task Behavior

    ERIC Educational Resources Information Center

    Ecker, Meghan E.; Sifers, Sarah K.

    2013-01-01

    Purpose/Objectives: The purpose of this study was to evaluate the BackPack Food Program&apos;s effectiveness in combating students&apos; hunger over the weekends and school breaks, as well as analyze the program&apos;s effects on students&apos; on-task behavior in the classroom. Additionally, this study examined program satisfaction from students,…

  7. Improving EFL Learners&apos; Reading Levels through Extensive Reading

    ERIC Educational Resources Information Center

    Mermelstein, Aaron David

    2014-01-01

    Today there is an increasing amount of research promoting the effectiveness of extensive reading (ER) towards increasing learners&apos; vocabulary, comprehension, reading speed, and motivation towards reading. However, little has been done to measure the effects of ER on learners&apos; reading levels. This quantitative study examined the effects…

  8. Examining the Factors Contributing to Students&apos; Life Satisfaction

    ERIC Educational Resources Information Center

    Dogan, Ugur; Celik, Eyup

    2014-01-01

    In this study, the authors examined the relationship between students&apos; life satisfaction, school engagement, and confidence in the classroom. An analysis was performed of how students&apos; life satisfaction differs according to their housing, school type, and classroom level. The multidimensional student satisfaction scale, confidence scale…

  9. Guattari&apos;s Ecosophy and Implications for Pedagogy

    ERIC Educational Resources Information Center

    Greenhalgh-Spencer, Heather

    2014-01-01

    Guattari&apos;s ecosophy has implications for many types of pedagogy practiced in the school. While Guattari never explicitly advocated the educational use of ecosophy, I explore in this article how it can be used as a lens to "read" pedagogy in nuanced ways, highlighting oppressive premises and practices. I first discuss Guattari&apos;s…

  10. University Students&apos; Understanding of Electromagnetic Induction

    ERIC Educational Resources Information Center

    Guisasola, Jenaro; Almudi, Jose M.; Zuza, Kristina

    2013-01-01

    This study examined engineering and physical science students&apos; understanding of the electromagnetic induction (EMI) phenomena. It is assumed that significant knowledge of the EMI theory is a basic prerequisite when students have to think about electromagnetic phenomena. To analyse students&apos; conceptions, we have taken into account the…

  11. Tapping Technology&apos;s Potential to Motivate Readers

    ERIC Educational Resources Information Center

    Conradi, Kristin

    2014-01-01

    Technology isn&apos;t inherently motivational to students, but teachers can employ a variety of strategies that can harness technology to promote student engagement. In so doing, teachers can focus on students&apos; self-concept as well as their attitudes as particularly important levers of motivating students to engage in reading.

  12. Professional Learning Communities: Teachers&apos; Perceptions and Student Achievement

    ERIC Educational Resources Information Center

    Peters, Erica

    2013-01-01

    Professional Learning Communities (PLC&apos;s) are designed to help schools improve student achievement; all decisions are based on the needs of students. PLC&apos;s are an effective way to receive professional development (PD), allow for collaboration with fellow teachers, and offer timely intervention to all students. In a district known for PLC…

  13. Small Talk: Children&apos;s Everyday "Molecule" Ideas

    ERIC Educational Resources Information Center

    Jakab, Cheryl

    2013-01-01

    This paper reports on 6-11-year-old children&apos;s "sayings and doings" (Harré 2002) as they explore molecule artefacts in dialectical-interactive teaching interviews (Fleer, "Cultural Studies of Science Education" 3:781-786, 2008; Hedegaard et al. 2008). This sociocultural study was designed to explore children&apos;s…

  14. Main Factors of Teachers&apos; Professional Well-Being

    ERIC Educational Resources Information Center

    Yildirim, Kamil

    2014-01-01

    The purpose of the study was to reveal the main factors of teachers&apos; professional well being. Theoretically constructed model was tested on large scale data belong to 72.190 teachers working at lower secondary level. Theoretical model included teachers&apos; individual, professional and organizational characteristics. Professional well-being…

  15. Philosophical Remarks on Nelson Mandela&apos;s Education Legacy

    ERIC Educational Resources Information Center

    Waghid, Yusef

    2014-01-01

    In this article, I reflect on Nelson Mandela&apos;s (Madiba, the clan name of Mandela) education legacy. I argue that Madiba&apos;s education legacy is constituted by three interrelated aspects: firstly, an education for non-violence guided by deliberation, compassion and reconciliation; secondly, education as responsibility towards the Other; and…

  16. College Students&apos; Beliefs about Supporting a Grieving Peer

    ERIC Educational Resources Information Center

    Tedrick Parikh, Sara J.; Servaty-Seib, Heather L.

    2013-01-01

    The present study used I. Ajzen&apos;s (1991) Theory of Planned Behavior (TBP) to explore college students&apos; beliefs about listening supportively to a grieving friend. Responses to open-ended questions suggested that students ("N" = 23) perceived both benefits and risks, connected with listening supportively, for the grieving friend…

  17. Finnish Secondary School Students&apos; Interreligious Sensitivity

    ERIC Educational Resources Information Center

    Holm, Kristiina; Nokelainen, Petri; Tirri, Kirsi

    2014-01-01

    The aim of this study was to assess the self-evaluations of Finnish secondary school students&apos; (N?=?549) interreligious sensitivity. The data were collected from 12-16-year-old young people with a 15-item Interreligious Sensitivity Scale Questionnaire (IRRSSQ). The IRRSSQ is based on Abu-Nimer&apos;s Developmental Model of Interreligious…

  18. Climate Change in the Preservice Teacher&apos;s Mind

    ERIC Educational Resources Information Center

    Lambert, Julie L.; Bleicher, Robert E.

    2013-01-01

    Given the recent media attention on the public&apos;s shift in opinion toward being more skeptical about climate change, 154 preservice teachers&apos; participated in an intervention in an elementary science methods course. Findings indicated that students developed a deeper level of concern about climate change. Their perceptions on the evidence…

  19. Estonian Preschool Teachers&apos; Views on Learning in Preschool

    ERIC Educational Resources Information Center

    Ugaste, Aino; Tuul, Maire; Niglas, Katrin; Neudorf, Evelyn

    2014-01-01

    As in many Western countries, children&apos;s learning in the curriculum of Estonian Early Childhood Education is seen as a lifelong process, wherein the teacher is primarily a guide to children&apos;s active learning. Thus, a child-centred approach to learning is valued in the national curriculum, but our interest was whether this approach is…

  20. Student Teachers&apos; Conceptions of Teaching Biology

    ERIC Educational Resources Information Center

    Subramaniam, Karthigeyan

    2014-01-01

    The purpose of this qualitative study was to investigate prospective biology teachers&apos; conceptions of teaching biology and identify how these conceptions revealed their strategies for helping their future students&apos; learning of biology. The study utilized drawings, narratives and interviews to investigate the nature of the prospective…

  1. Infants&apos; Preferential Attention to Sung and Spoken Stimuli

    ERIC Educational Resources Information Center

    Costa-Giomi, Eugenia; Ilari, Beatriz

    2014-01-01

    Caregivers and early childhood teachers all over the world use singing and speech to elicit and maintain infants&apos; attention. Research comparing infants&apos; preferential attention to music and speech is inconclusive regarding their responses to these two types of auditory stimuli, with one study showing a music bias and another one…

  2. Modern Analogue of Ohm&apos;s Historical Experiment

    ERIC Educational Resources Information Center

    Mayer, V. V.; Varaksina, E. I.

    2014-01-01

    Students receive a more complete conception of scientific cognition methods if they reproduce fundamentally important historical investigations on their own. Ohm&apos;s investigation realized in 1826 is one of these. This paper presents a simple and accessible experimental unit, in which Ohm&apos;s ideas are implemented with the help of modern…

  3. Children&apos;s Eye Movements in Reading: A Commentary

    ERIC Educational Resources Information Center

    Rayner, Keith; Ardoin, Scott P.; Binder, Katherine S.

    2013-01-01

    are discussed. Specifically, the following topics are addressed: (1) basic methodological issues, (2) prior research findings on children&apos;s reading, (3) research that is missing in the literature regarding children&apos;s eye movements during reading, (4) applied…

  4. Understanding Gauss&apos;s Law Using Spreadsheets

    ERIC Educational Resources Information Center

    Baird, William H.

    2013-01-01

    Some of the results from the electrostatics portion of introductory physics are particularly difficult for students to understand and/or believe. For students who have yet to take vector calculus, Gauss&apos;s law is far from obvious and may seem more difficult than Coulomb&apos;s. When these same students are told that the minimum potential…

  5. Teachers&apos; Experiences of Science Curriculum Reform

    ERIC Educational Resources Information Center

    Ryder, Jim; Banner, Indira; Homer, Matt

    2014-01-01

    We report on a three-year study of teachers&apos; experiences of a major reform of the science National Curriculum for 14- to 16-year-olds in England. Teachers&apos; responses to this curriculum reform were guided by: "personal" aims and biography; "internal" features of their workplace such as departmental collegiality; and…

  6. Exploring Preschool Children&apos;s Science Content Knowledge

    ERIC Educational Resources Information Center

    Guo, Ying; Piasta, Shayne B.; Bowles, Ryan P.

    2015-01-01

    Research Findings: The purpose of this study was to describe children&apos;s science content knowledge and examine the early predictors of science content knowledge in a sample of 194 typically developing preschool children. Children&apos;s science content knowledge was assessed in the fall (Time 1) and spring (Time 2) of the preschool year.…

  7. NOAA&apos;s Education Program: Review and Critique

    ERIC Educational Resources Information Center

    Farrington, John W., Ed.; Feder, Michael A., Ed.

    2010-01-01

    There is a national need to educate the public about the ocean, coastal resources, atmosphere and climate. The National Oceanic and Atmospheric Administration (NOAA), the agency responsible for understanding and predicting changes in the Earth&apos;s environment and conserving and managing coastal and marine resources to meet the nation&apos;s…

  8. Meet AAPT&apos;s New President, Steve Iona

    ERIC Educational Resources Information Center

    Willis, Courtney

    2014-01-01

    I first met Steve Iona 40 years ago at a Denver Area Physics Teachers meeting. Steve had recently completed bachelor&apos;s and master&apos;s degrees in mathematics from the University of Chicago. Being a Colorado native, he was interested in returning to Colorado to teach. Steve had some rather high-powered recommendations, including one from a…

  9. Principals&apos; Leadership Styles and Student Achievement

    ERIC Educational Resources Information Center

    Harnish, David Alan

    2012-01-01

    Many schools struggle to meet No Child Left Behind&apos;s stringent adequate yearly progress standards, although the benchmark has stimulated national creativity and reform. The purpose of this study was to explore teacher perceptions of principals&apos; leadership styles, curriculum reform, and student achievement to ascertain possible factors to…

  10. Undergraduate Women&apos;s Persistence in the Sciences

    ERIC Educational Resources Information Center

    George-Jackson, Casey E.

    2014-01-01

    This study uses longitudinal data of undergraduate students from five public land-grant universities to better understand undergraduate students&apos; persistence in and switching of majors, with particular attention given to women&apos;s participation in science, technology, engineering, and mathematics (STEM) fields. Specifically, the study…

  11. Trends in Exiting Physics Master&apos;s. Focus On

    ERIC Educational Resources Information Center

    Mulvey, Patrick J.; Nicholson, Starr

    2014-01-01

    A physics master&apos;s degree provides the recipient with a variety of career options. Some master&apos;s recipients will continue their education at the graduate level in physics or another field, where others enter the workforce pursuing a wide range of employment opportunities. This "Focus On" provides an in-depth analysis of physics…

  12. Symbolic Notations and Students&apos; Achievements in Algebra

    ERIC Educational Resources Information Center

    Peter, Ebiendele E.; Olaoye, Adetunji A.

    2013-01-01

    This study focuses on symbolic notations and its impact on students&apos; achievement in Algebra. The main reason for this study rests on the observation from personal and professional experiences on students&apos; increasing hatred for Algebra. One hundred and fifty (150) Senior Secondary School Students (SSS) from Ojo Local Education District,…

  13. CTE&apos;s Role in Urban Education

    ERIC Educational Resources Information Center

    Hyslop, Alisha; Imperatore, Catherine

    2013-01-01

    Education in the United States is facing a crisis of completion and performance, both at the secondary and postsecondary levels, with high dropout rates and a significant number of students ill-prepared for further education and careers. These problems are even more acute in America&apos;s urban schools. Today&apos;s CTE is on the cutting edge of…

  14. Children&apos;s Creativity in Day Care

    ERIC Educational Resources Information Center

    Reunamo, Jyrki; Lee, Hui-Chun; Wang, Li-Chen; Ruokonen, Inkeri; Nikkola, Teemu; Malmstrom, Sanna

    2014-01-01

    In this research, children&apos;s creativity in pretend play and the conditions for creativity during high involvement are studied from four points of view: as a zone for proximal development, as a skill, as a personal orientation and as a culturally shared environment creation. The theoretical model is influenced by Vygotsky&apos;s ideas of…

  15. Analysis of Students&apos; Arguments on Evolutionary Theory

    ERIC Educational Resources Information Center

    Basel, Nicolai; Harms, Ute; Prechtl, Helmut

    2013-01-01

    A qualitative exploratory study was conducted to reveal students&apos; argumentation skills in the context of the topic of evolution. Transcripts from problem-centred interviews on secondary students&apos; beliefs about evolutionary processes of adaptation were analysed using a content analysis approach. For this purpose two categorical systems…

  16. Deaf Students&apos; Metacognitive Awareness during Language Comprehension

    ERIC Educational Resources Information Center

    Morrison, Carolyn; Marschark, Marc; Sarchet, Thomastine; Convertino, Carol M.; Borgna, Georgianna; Dirmyer, Richard

    2013-01-01

    This study explored deaf and hearing university students&apos; metacognitive awareness with regard to comprehension difficulties during reading and classroom instruction. Utilising the Reading Awareness Inventory (Milholic, V. 1994. "An inventory to pique students&apos; metacognitive awareness of reading strategies." "Journal of…

  17. Vocational Education for China&apos;s Ethnic Minorities

    ERIC Educational Resources Information Center

    Qian, Minhui

    2013-01-01

    This article analyzes the current status and problems of vocational education for China&apos;s ethnic minorities. It concludes that these problems have both universal areas in common with China&apos;s overall education situation and individual characteristics; they also have both extrinsic and intrinsic qualities. The universal areas include the…

  18. Reflections on Jonathan Boston&apos;s Paper

    ERIC Educational Resources Information Center

    Devine, Nesta

    2014-01-01

    In this article, Nesta Devine responds to Jonathan Boston&apos;s article "Child Poverty in New Zealand: Why It Matters and How It Can Be Reduced" ("Educational Philosophy and Theory," v46 n9 p995-999, 2014). Devine wishes to consider Boston&apos;s position from two angles: one is to rehearse the point that these statistics are…

  19. Primary School Teacher Candidates&apos; Geometric Habits of Mind

    ERIC Educational Resources Information Center

    Köse, Nilu¨fer Y.; Tanisli, Dilek

    2014-01-01

    Geometric habits of mind are productive ways of thinking that support learning and using geometric concepts. Identifying primary school teacher candidates&apos; geometric habits of mind is important as they affect the development of their future students&apos; geometric thinking. Therefore, this study attempts to determine primary school…

  20. Student Disengagement: It&apos;s Deeper than You Think

    ERIC Educational Resources Information Center

    Washor, Elliot; Mojkowski, Charles

    2014-01-01

    American schools are failing to meet the expectations of a wide swath of students, many of them in low-income and rural communities. What&apos;s needed is a new pact putting their expectations at its center. The article is based on the authors&apos; book: "Leaving to Learn: How Out-of-School Learning Increases Student Engagement and Reduces…

  1. Storymakers: Hopa Mountain&apos;s Early Literacy Program

    ERIC Educational Resources Information Center

    Templin, Patricia A.

    2013-01-01

    Hopa Mountain&apos;s StoryMakers program is an innovative, research-based program for donating high quality young children&apos;s books to parents. Hopa Mountain is a nonprofit organization based in Bozeman, Montana. Hopa Mountain works with groups of rural and tribal citizen leaders who form StoryMakers Community Teams to talk one-on-one with…

  2. Students&apos; Stories of Studying Abroad: Reflections upon Return

    ERIC Educational Resources Information Center

    Costello, Jane

    2015-01-01

    Study abroad brings an enriching experience to students&apos; academic and personal lives. This narrative essay relays two students&apos; experiences with study abroad sojourns and touches upon their technology use during their study abroad as recounted in semi-structured interviews. Details of their cultural experiences and reflections thereof as…

  3. Pre-Reading Power: One Classroom&apos;s Experience

    ERIC Educational Resources Information Center

    Thomas, Angela Falter; Vannatta Reinhart, Rachel

    2014-01-01

    Because of the Common Core State Standards there is a renewed emphasis on the importance of visual literacies in today&apos;s classrooms. Students need prior knowledge before approaching these types of texts. This article describes the results of one 6th-grade language arts class&apos;s engagement in pre-reading prior to viewing a theatrical…

  4. Upper Secondary School Pupils&apos; Attitudes towards Natural Science

    ERIC Educational Resources Information Center

    Akarsu, Bayram; Kariper, Afsin

    2013-01-01

    Students&apos; attitudes towards natural science constitute an important area in science education as fewer students are interested in natural science and they do not choose corresponding science disciplines in postsecondary education. The current study reports preliminary results of a survey on high school students&apos; interests and attitudes…

  5. Building Motherhood in the Young Mothers&apos; Group

    ERIC Educational Resources Information Center

    Simonic, Barbara; Poljanec, Andreja

    2014-01-01

    The primary relationship undermines how a newborn will develop. The first three years of a child&apos;s life in particular are fundamental for the development of the child&apos;s brain. This is when the "social brain" develops and grows in response to the spontaneous relationships experienced within the environment and when an…

  6. Modality and Children&apos;s Scope Understanding

    ERIC Educational Resources Information Center

    Liu, Chin-Ting Jimbo; Lee, Hsiu-Fen Hélène

    2014-01-01

    This study intends to shed light on the inconclusive argument pertaining to children&apos;s acquisition of logical form (LF) operation. Specifically, we examined children&apos;s interpretations of sentences with the ambiguous modal verb "yinggai" "should," like "Xiaohua yinggai shangchuang shuijiao le", whose meanings…

  7. Investigating Students&apos; Usage and Acceptance of Electronic Books

    ERIC Educational Resources Information Center

    Sieche, Susan; Krey, Birte; Bastiaens, Theo

    2013-01-01

    The purpose of this study is to investigate students&apos; usage and acceptance of electronic books. Factors correlating with students&apos; attitude towards e-books were examined using the Technology Acceptance Model (Davis, Bagozzi, & Warshaw 1989). A questionnaire was administered online for students at University of Hagen. Results indicate…

  8. An Exploration of Design Students&apos; Inspiration Process

    ERIC Educational Resources Information Center

    Dazkir, Sibel S.; Mower, Jennifer M.; Reddy-Best, Kelly L.; Pedersen, Elaine L.

    2013-01-01

    Our purpose was to explore how different sources of inspiration influenced two groups of students&apos; inspiration process and their attitudes toward their design projects. Assigned sources of inspiration and instructor&apos;s assistance in the search for inspiration varied for two groups of students completing a small culture inspired product…

  9. Teachers&apos; Beliefs about Using a Professional Development Plan

    ERIC Educational Resources Information Center

    Janssen, Sandra; Kreijns, Karel; Bastiaens, Theo J.; Stijnen, Sjef; Vermeulen, Marjan

    2013-01-01

    Professional development plans (PDPs) have recently been introduced in Dutch schools to support teachers&apos; professional development. However, teachers&apos; beliefs regarding the use of PDPs have not been systematically researched, whereas research on the use of PDPs indicates that the implementation is not always successful and depends on how…

  10. Enquiring into Primary Teachers&apos; Geographical Knowledge

    ERIC Educational Resources Information Center

    Catling, Simon; Morley, Emma

    2013-01-01

    Subject knowledge is an important component of primary teachers&apos; repertoire, though it has not been studied widely beyond their understandings of aspects of science and mathematics. Evaluations of the quality of teachers&apos; geographical knowledge for teaching primary geography indicate a disparity between high quality teachers and less…

  11. Teachers&apos; Role in Curriculum Design in Portuguese Schools

    ERIC Educational Resources Information Center

    Mouraz, Ana; Leite, Carlinda; Fernandes, Preciosa

    2013-01-01

    Teachers&apos; role in curriculum design is a broad question that inspires political educational reforms among European countries, a trend that even extends to higher education politics. The perspective on teachers&apos; role in curriculum, both at the level of the policies and of the practices, shapes recent educational reforms in Portugal. These…

  12. Supervisor&apos;s Interactive Model of Organizational Relationships

    ERIC Educational Resources Information Center

    O'Reilly, Frances L.; Matt, John; McCaw, William P.

    2014-01-01

    The Supervisor&apos;s Interactive Model of Organizational Relationships (SIMOR) integrates two models addressed in the leadership literature and then highlights the importance of relationships. The Supervisor&apos;s Interactive Model of Organizational Relationships combines the modified Hersey and Blanchard model of situational leadership, the…

  13. Students&apos; Opinions on Facebook Supported Blended Learning Environment

    ERIC Educational Resources Information Center

    Erdem, Mukaddes; Kibar, Pinar Nuhoglu

    2014-01-01

    The first purpose of this study was to determine students&apos; opinions on blended learning and its implementation. The other purpose was to explore the students&apos; opinions on Facebook integration into blended learning environment. The participants of this study were 40 undergraduate students in their fourth semester of the program.…

  14. Educators&apos; Social and Emotional Skills Vital to Learning

    ERIC Educational Resources Information Center

    Jones, Stephanie M.; Bouffard, Suzanne M.; Weissbourd, Richard

    2013-01-01

    Teachers&apos; social and emotional competencies are very important to their overall effectiveness, but such skills are frequently overlooked. Social and emotional competencies like managing emotions and stress are needed more today than ever before. More practices and policies to support and foster educators&apos; social and emotional…

  15. Children&apos;s Perception of Dialect Variation

    ERIC Educational Resources Information Center

    Wagner, Laura; Clopper, Cynthia G.; Pate, John K.

    2014-01-01

    A speaker&apos;s regional dialect is a rich source of information about that person. Two studies examined five- to six-year-old children&apos;s perception of regional dialect: Can they perceive differences among dialects? Have they made meaningful social connections to specific dialects? Experiment 1 asked children to categorize speakers into…

  16. Stats Don&apos;t Tell the Whole Story

    ERIC Educational Resources Information Center

    Beitler, Alan; Bushong, Delores

    2013-01-01

    This article describes the Wakefield Cohort program at Wakefield High School, located in Arlington, Virginia, which has a thirteen-year history of success in supporting minority male students. While data show the program&apos;s effectiveness, former students&apos; stories are more powerful; therefore, this article presents the stories of two…

  17. University Students&apos; Attitudes toward Physical Education Teaching

    ERIC Educational Resources Information Center

    Li, Fengjuan; Chen, Junjun; Baker, Miles

    2014-01-01

    While there have been many studies into students&apos; attitudes toward Physical Education at the school level, far fewer studies have been conducted at the university level, especially in China. This study explored 949 students&apos; attitudes toward their university Physical Education experiences in four Chinese universities. An intercorrelated…

  18. A Study of Science Teachers&apos; Homework Practices

    ERIC Educational Resources Information Center

    Tas, Yasemin; Sungur-Vural, Semra; Öztekin, Ceren

    2014-01-01

    This study investigates Turkish middle school science teachers&apos; homework practices, the value teachers attach to homework and teachers&apos; communication with parents about homework. One hundred and sixty-eight teachers completed surveys. Teachers reported to assign homework frequently: 93.4 per cent of the teachers reported that they assign…

  19. Coaching Discourse: Supporting Teachers&apos; Professional Learning

    ERIC Educational Resources Information Center

    Heineke, Sally F.

    2013-01-01

    Although coaching is used in many schools to facilitate teachers&apos; professional learning, few studies look closely at coaching discourse. Exploring how coaching facilitates teachers&apos; professional development, this study used tape-recorded coaching sessions and individual post-interviews to examine the one-on-one coaching interactions of 4…

  20. School Life and Adolescents&apos; Self-Esteem Trajectories

    ERIC Educational Resources Information Center

    Morin, Alexandre J. S.; Maïano, Christophe; Marsh, Herbert W.; Nagengast, Benjamin; Janosz, Michel

    2013-01-01

    This study investigates heterogeneity in adolescents&apos; trajectories of global self-esteem (GSE) and the relations between these trajectories and facets of the interpersonal, organizational, and instructional components of students&apos; school life. Methodologically, this study illustrates the use of growth mixture analyses, and how to obtain…

  1. University Students&apos; Perspective on Blended Learning

    ERIC Educational Resources Information Center

    Waha, Barbara; Davis, Kate

    2014-01-01

    This research project explored students&apos; perspective of the appropriate mix of online and face-to-face activities in a master&apos;s programme in library and information science at an Australian university. Identifying aspects that students evaluate as supportive, challenging and efficient in their learning is important for the design of an…

  2. Negative Integer Understanding: Characterizing First Graders&apos; Mental Models

    ERIC Educational Resources Information Center

    Bofferding, Laura

    2014-01-01

    This article presents results of a research study. Sixty-one first graders&apos; responses to interview questions about negative integer values and order and directed magnitudes were examined to characterize the students&apos; mental models. The models reveal that initially, students overrelied on various combinations of whole-number principles as…

  3. Adolescents&apos; Use of Academic Language in Historical Writing

    ERIC Educational Resources Information Center

    Shen, Ting

    2011-01-01

    Despite its importance of academic language, research on academic language is often limited to academic vocabulary and focused on the English language learners. Informed by systemic functional linguistics, this study examined adolescents&apos; use of academic language and the relationships between its use and students&apos; reading ability and…

  4. Responding to Students&apos; Learning Preferences in Chemistry

    ERIC Educational Resources Information Center

    Lewthwaite, Brian; Wiebe, Rick

    2014-01-01

    This paper reports on a teacher&apos;s and his students&apos; responsiveness to a new tetrahedral-oriented (Mahaffy in "J Chem Educ" 83(1):49-55, 2006) curriculum requiring more discursive classroom practices in the teaching of chemistry. In this instrumental case study, we identify the intentions of this learner-centered curriculum and…

  5. Exploring Preservice Teachers&apos; Emerging Understandings of Disciplinary Literacy

    ERIC Educational Resources Information Center

    Masuda, Avis M.

    2014-01-01

    This qualitative inquiry examined 14 secondary preservice teachers&apos; emerging understandings of disciplinary literacy. Data included preservice teachers&apos; written reflections and annotated lesson plans, which were analyzed for understanding of discipline-specific habits of thinking, texts, reading and writing demands of academic texts,…

  6. Turkish Primary Students&apos; Perceptions of Geography

    ERIC Educational Resources Information Center

    Senyurt, Secil

    2014-01-01

    This study provides an in-depth investigation of Turkish primary school students&apos; perceptions of geography. Gender differences in students&apos; perceptions of geography were investigated, including definitions of geography and its field of study. The findings showed that "landforms," "our geographical regions/Turkey,"…

  7. Should We Bother Improving Students&apos; Attendance at Seminars?

    ERIC Educational Resources Information Center

    Gbadamosi, Gbolahan

    2015-01-01

    This study uses action research intervention to improve students&apos; attendance at seminars. Specifically, the study asks the question: will students&apos; attendance improve if they drive their own learning by running their own seminars? Records of lecture and seminar attendance at a module and comparative ones were used. Focus group interviews…

  8. Mediating Multilingual Children&apos;s Language Resources

    ERIC Educational Resources Information Center

    Potts, D.; Moran, M. J.

    2013-01-01

    The everyday reality of children&apos;s multilingualism is a significant resource for expanding students&apos; perspectives on the world, but many questions remain regarding the negotiation of these resources in mainstream classrooms. Drawing on research from a long-term Canadian study of multiliterate pedagogies, this paper explores mediation of…

  9. Describing Elementary Teachers&apos; Operative Systems: A Case Study

    ERIC Educational Resources Information Center

    Dotger, Sharon; McQuitty, Vicki

    2014-01-01

    This case study introduces the notion of an operative system to describe elementary teachers&apos; knowledge and practice. Drawing from complex systems theory, the operative system is defined as the network of knowledge and practices that constituted teachers&apos; work within a lesson study cycle. Data were gathered throughout a lesson study…

  10. Teachers&apos; Work, Food Policies, and Gender in Argentina

    ERIC Educational Resources Information Center

    Robert, Sarah A.; McEntarfer, Heather Killelea

    2014-01-01

    Few studies explore teachers&apos; involvement in school feeding, questioning gendered implications within a feminine and feminized profession. Ethnographic data from one public high school in Metropolitan Buenos Aires suggest that teachers&apos; efforts to address student hunger added new work roles: food advocates/activists, food managers, and…

  11. Students&apos; Conceptions as Dynamically Emergent Structures

    ERIC Educational Resources Information Center

    Brown, David E.

    2014-01-01

    There is wide consensus that learning in science must be considered a process of conceptual change rather than simply information accrual. There are three perspectives on students&apos; conceptions and conceptual change in science that have significant presence in the science education literature: students&apos; ideas as misconceptions, as…

  12. Investigating Young Children&apos;s Learning of Mass Measurement

    ERIC Educational Resources Information Center

    Cheeseman, Jill; McDonough, Andrea; Ferguson, Sarah

    2014-01-01

    This paper reports results of a design experiment regarding young children&apos;s concepts of mass measurement. The research built on an earlier study in which a framework of "growth points" in early mathematics learning and a related, task-based, one-to-one interview to assess children&apos;s understanding of the measurement of mass…

  13. Adolescent Boys&apos; Science Aspirations: Masculinity, Capital, and Power

    ERIC Educational Resources Information Center

    Archer, Louise; DeWitt, Jennifer; Willis, Beatrice

    2014-01-01

    There is widespread international concern about post-16 participation rates in science, with women&apos;s under-representation constituting a particular issue. This paper contributes to these debates through a novel, critical examination of the role of masculinity within boys&apos; negotiations of science aspirations. Drawing on a UK longitudinal…

  14. Leonardo da Vinci and the Downburst.

    NASA Astrophysics Data System (ADS)

    Gedzelman, Stanley David

    1990-05-01

    Evidence from the drawings, experiments, and writings of Leonardo da Vinci are presented to demonstrate that da Vinci recognized and, possibly, discovered the downburst and understood its associated airflow. Other early references to vortex flows resembling downbursts are mentioned.

  15. Perceptual Study of School Principals&apos; Working Knowledge of Special Education and Schools&apos; Level of Educational Services

    ERIC Educational Resources Information Center

    Franklin, Christine

    2012-01-01

    The purpose of this quantitative research study was to determine the relationship between the schools principal&apos;s working knowledge of special education laws, diagnosis procedures, and instructional best practices a relates to the level of educational services within a school&apos;s special education department. To examine this relationship,…

  16. High School English Teachers&apos; and Students&apos; Perceptions, Attitudes and Actual Practices of Continuous Assessment

    ERIC Educational Resources Information Center

    Yigzaw, Abiy

    2013-01-01

    This study examined high school teachers&apos; and students&apos; perceptions, attitudes and actual practices of continuous assessment. The participants of the study were 41 teachers and 808 students in Injabara General and Preparatory, Tilili General Secondary, Mengesha Jembere General Secondary, and Dangila Preparatory schools in West Gojjam,…

  17. Meek and Mild: American Children&apos;s Bibles&apos; Stories of Jesus as a Boy

    ERIC Educational Resources Information Center

    Dalton, Russell W.

    2014-01-01

    The four canonical gospels provide readers with few details of the life of Jesus as a boy. Many authors of children&apos;s bibles in America, however, have been happy to fill in some of the details. This article suggests that these retellings regularly create or adapt stories of Jesus&apos; childhood to teach children virtues that serve to affirm…

  18. Examining the Effects of Math Teachers&apos; Circles on Aspects of Teachers&apos; Mathematical Knowledge for Teaching

    ERIC Educational Resources Information Center

    White, Diana; Donaldson, Brianna; Hodge, Angie; Ruff, Adam

    2013-01-01

    Math Teachers&apos; Circles have been spreading since their emergence in 2006. These professional development programs, aimed primarily at middle-level mathematics teachers (grades 5-9), focus on developing teachers&apos; mathematical problem solving skills, in line with the Common Core State Standards-Standards of Mathematical Practice. Yet, to…

  19. The Effect of Analogy-Based Teaching on Students&apos; Achievement and Students&apos; Views about Analogies

    ERIC Educational Resources Information Center

    Genc, Murat

    2013-01-01

    The purpose of this study is to determine the effect of the analogy-based teaching on students&apos; achievement and students&apos; views about analogies. In this research, Solomon group design which is one of the experimental designs, was implemented. The sample of the research consists of 108 students in four 6th grade classes in Turkey. The…

  20. The Relationship Between Teachers&apos; Mathematical Content and Pedagogical Knowledge, Teachers&apos; Perceptions, and Student Achievement

    ERIC Educational Resources Information Center

    Campbell, Patricia F.; Nishio, Masako; Smith, Toni M.; Clark, Lawrence M.; Conant, Darcy L.; Rust, Amber H.; DePiper, Jill Neumayer; Frank, Toya Jones; Griffin, Matthew J.; Choi, Youyoung

    2014-01-01

    This study of early-career teachers identified a significant relationship between upper-elementary teachers&apos; mathematical content knowledge and their students&apos; mathematics achievement, after controlling for student- and teacher-level characteristics. Findings provide evidence of the relevance of teacher knowledge and perceptions for…

  1. Teachers&apos; and Students&apos; Perceptions of Interactive Whiteboards in the English as a Foreign Language Classroom

    ERIC Educational Resources Information Center

    Öz, Hüseyin

    2014-01-01

    This article reports on the findings of a study conducted to investigate teachers&apos; and students&apos; perceptions of interactive whiteboards (IWBs) in the English as a foreign language (EFL) classroom and to find out differences of perceptions according to some variables such as gender, level of English proficiency, hours of weekly IWB use,…

  2. The Effect of School Counselors&apos; Domain Specialization on Seniors&apos; Milestone Completion and College Access Planning

    ERIC Educational Resources Information Center

    Bond, Nancy J.

    2013-01-01

    The purpose of this study was to determine the effect of senior high school counselors&apos; domain specializations--academic, advanced education, career, and personal/social--from two urban high schools, on alphabetically assigned graduating seniors&apos; with low, mid-range, and high Grade Point Averages documented college and career readiness…

  3. Schools&apos; Openness to Change According to Teachers&apos; Views: A Sample of Turkey/Kocaeli

    ERIC Educational Resources Information Center

    Konakli, Tugba

    2014-01-01

    The purpose of this research is to examine teachers&apos; views about schools&apos; openness to change The sample of the research consists of 397 teachers working in 18 elementary and 12 secondary schools in the central district of Kocaeli. Faculty Change Orientation Scale -FCOS which was developed by Smith & Hoy (2007) was used for the study.…

  4. Productive Resources in Students&apos; Ideas about Energy: An Alternative Analysis of Watts&apos; Original Interview Transcripts

    ERIC Educational Resources Information Center

    Harrer, Benedikt W.; Flood, Virginia J.; Wittmann, Michael C.

    2013-01-01

    For over 30 years, researchers have investigated students&apos; ideas about energy with the intent of reforming instructional practice. In this pursuit, Watts contributed an influential study with his 1983 paper "Some alternative views of energy" ["Phys. Educ." 18, 213 (1983)]. Watts&apos; "alternative frameworks"…

  5. Children&apos;s and Adults&apos; Automatic Processing of Proportion in a Stroop-Like Task

    ERIC Educational Resources Information Center

    Yang, Ying; Hu, Qingfen; Wu, Di; Yang, Shuqi

    2015-01-01

    This current study examined human children&apos;s and adults&apos; automatic processing of proportion using a Stroop-like paradigm. Preschool children and university students compared the areas of two sectors that varied not only in absolute areas but also in the proportions they occupied in their original rounds. A congruity effect was found in…

  6. Science Research Group Leader&apos;s Power and Members&apos; Compliance and Satisfaction with Supervision

    ERIC Educational Resources Information Center

    Meng, Yi; He, Jia; Luo, Changkun

    2014-01-01

    This study investigated the correlations between science research group members&apos; perceptions of power bases used by their group (lab, team) leader (coercive, reward, legitimate, expert and referent) and the effect of those perceptions on group members&apos; attitudinal compliance, behavioral compliance, and satisfaction with supervision.…

  7. How Much Are Harry Potter&apos;s Glasses Worth? Children&apos;s Monetary Evaluation of Authentic Objects

    ERIC Educational Resources Information Center

    Gelman, Susan A.; Frazier, Brandy N.; Noles, Nicholaus S.; Manczak, Erika M.; Stilwell, Sarah M.

    2015-01-01

    Adults attach special value to objects that link to notable people or events--authentic objects. We examined children&apos;s monetary evaluation of authentic objects, focusing on four kinds: celebrity possessions (e.g., Harry Potter&apos;s glasses), original creations (e.g., the very first teddy bear), personal possessions (e.g., your…

  8. The Relationships between Teachers&apos; Perceptions of Principal Leadership and Teachers&apos; Perceptions of School Climate

    ERIC Educational Resources Information Center

    Pulleyn, Janet L.

    2012-01-01

    This research considered relationships among teachers&apos; perceptions of principal leadership and teachers&apos; perceptions of school climate by using the Leadership Practices Inventory (LPI) survey and the Organizational Climate Description Questionnaire (Revised) for Middle Schools (OCDQ-RM) survey. Teachers from six middle schools in the…

  9. Valid Inferences of Teachers&apos; Judgements of Pupils&apos; Reading Literacy: Does Formal Teacher Competence Matter?

    ERIC Educational Resources Information Center

    Johansson, Stefan; Strietholt, Rolf; Rosén, Monica; Myrberg, Eva

    2014-01-01

    The primary aim of this study was to investigate whether and, if so, how formal teacher competence relates to the relationship between pupil reading achievement and teachers judgements&apos; of pupils&apos; reading achievement. The data come from the Swedish participation in the Progress in International Reading Literacy Study (PIRLS) 2001 in…

  10. Family Background, Students&apos; Academic Self-Efficacy, and Students&apos; Career and Life Success Expectations

    ERIC Educational Resources Information Center

    Kim, Mihyeon

    2014-01-01

    This study examined the relationship of family background on students&apos; academic self-efficacy and the impact of students&apos; self-efficacy on their career and life success expectations. The study used the national dataset of the Educational Longitudinal Study of 2002 (ELS: 2002), funded by the U.S. Department of Education. Based on a path…

  11. Teachers&apos; Professional Beliefs about Their Roles and the Pupils&apos; Roles in the School

    ERIC Educational Resources Information Center

    Ahonen, Elsi; Pyhältö, Kirsi; Pietarinen, Janne; Soini, Tiina

    2014-01-01

    In recent decades, many educational reforms have been implemented that aim to effect a change in teachers&apos; and pupils&apos; roles by promoting meaningful learning. Yet, little is known about how teachers perceive these roles as a part of their professional belief system. In this study, 68 Finnish comprehensive school teachers were…

  12. Students&apos; Instructional Dissent and Relationships with Faculty Members&apos; Burnout, Commitment, Satisfaction, and Efficacy

    ERIC Educational Resources Information Center

    Frisby, Brandi N.; Goodboy, Alan K.; Buckner, Marjorie M.

    2015-01-01

    Extending research on instructional dissent beyond student reports, this study examined the potential for students&apos; expressed dissent to have deleterious effects on faculty members. Instructors (N = 113) completed surveys about students&apos; instructional dissent regarding their classes and reported their own burnout, commitment,…

  13. Teachers&apos; Perceptions of Students&apos; Mathematics Proficiency May Exacerbate Early Gender Gaps in Achievement

    ERIC Educational Resources Information Center

    Robinson-Cimpian, Joseph P.; Lubienski, Sarah Theule; Ganley, Colleen M.; Copur-Gencturk, Yasemin

    2014-01-01

    A recent wave of research suggests that teachers overrate the performance of girls relative to boys and hold more positive attitudes toward girls&apos; mathematics abilities. However, these prior estimates of teachers&apos; supposed female bias are potentially misleading because these estimates (and teachers themselves) confound achievement with…

  14. Feedback Consistencies and Inconsistencies: Eight Mentors&apos; Observations on One Preservice Teacher&apos;s Lesson

    ERIC Educational Resources Information Center

    Hudson, Peter

    2014-01-01

    Mentors play a key role in developing preservice teachers for their chosen careers, and providing feedback appears as a significant relational interaction between the mentor and mentee that assists in guiding the mentee&apos;s practices. But what are mentors&apos; perspectives on providing feedback to their mentees? In this case study, eight…

  15. "Two for Flinching": Children&apos;s and Adolescents&apos; Narrative Accounts of Harming Their Friends and Siblings

    ERIC Educational Resources Information Center

    Recchia, Holly; Wainryb, Cecilia; Pasupathi, Monisha

    2013-01-01

    This study investigated differences in children&apos;s and adolescents&apos; experiences of harming their siblings and friends. Participants ("N" = 101; 7-, 11-, and 16-year-olds) provided accounts of events when they hurt a younger sibling and a friend. Harm against friends was described as unusual, unforeseeable, and circumstantial. By…

  16. Campus Leadership&apos;s Influence in Implementing a Community College&apos;s Sustainability Goals: A Case Study

    ERIC Educational Resources Information Center

    Larson, Barbara A.

    2012-01-01

    The case study documented one large, multicampus community college&apos;s progress in implementing sustainability goals outlined in the American College and University Presidents&apos; Climate Commitment (ACUPCC). The case study examined the role of branch-campus presidents and the college president in institutionalizing sustainability. Responses…

  17. Where Did I Come From? US Parents&apos; and Preschool Children&apos;s Participation in Sexual Socialisation

    ERIC Educational Resources Information Center

    Martin, Karin A.; Torres, Jennifer M. C.

    2014-01-01

    This paper applies a sociology of childhood approach to the study of the sexual socialisation of young children in the USA. It examines both children&apos;s and parents&apos; active participation in this dynamic and collaborative process through conversations between 49 parents and their 54 preschool children that were audio-recorded while they…

  18. Let&apos;s Peel the Onion Together: An Application of Schein&apos;s Model of Organizational Culture

    ERIC Educational Resources Information Center

    Yilmaz, Gamze

    2014-01-01

    One of the challenges for undergraduate students is to comprehend abstract and theoretical concepts in communication classes. Given today&apos;s college students&apos; expectations for in-class interaction (Rocca, 2010), it is important that instructors integrate hands-on activities in their lesson plans while teaching theoretical concepts.…

  19. The Ed.D. in Educational Leadership and Administration: The Students&apos; and Alumni&apos;s Experiences

    ERIC Educational Resources Information Center

    Vera, Edith B.

    2012-01-01

    The doctoral experience unfolds many complexities and challenges for students, faculty, and institutions that contribute toward degree completion. The purpose of this study is to investigate the students&apos; and alumni&apos;s experiences afforded by the Ed.D. in Educational Leadership and Administration at the University of Texas at El Paso…

  20. Do Students&apos; Topic Interest and Tutors&apos; Instructional Style Matter in Problem-Based Learning?

    ERIC Educational Resources Information Center

    Wijnia, Lisette; Loyens, Sofie M. M.; Derous, Eva; Schmidt, Henk G.

    2014-01-01

    Two studies investigated the importance of initial topic interest (i.e., expectation of interest) and tutors&apos; autonomy-supportive or controlling instructional styles for students&apos; motivation and performance in problem-based learning (PBL). In Study 1 (N = 93, a lab experiment), each student participated in a simulated group discussion in…

  1. "Invisible" Bilingualism--"Invisible" Language Ideologies: Greek Teachers&apos; Attitudes Towards Immigrant Pupils&apos; Heritage Languages

    ERIC Educational Resources Information Center

    Gkaintartzi, Anastasia; Kiliari, Angeliki; Tsokalidou, Roula

    2015-01-01

    This paper presents data from two studies--a nationwide quantitative research and an ethnographic study--on Greek schoolteachers&apos; attitudes towards immigrant pupils&apos; bilingualism. The quantitative data come from a large-scale questionnaire survey, which aimed at the investigation of the needs and requirements for the implementation of a…

  2. Exploring Asperger&apos;s Syndrome, Schlossberg&apos;s Transition Theory and Federally Mandated Transition Planning: Seeking Improvements

    ERIC Educational Resources Information Center

    Spencer, Tracy Lynne Wright Lyons

    2013-01-01

    Federally mandated transition planning has done little to improve the postsecondary outcomes of people with Asperger&apos;s syndrome. Current high school transition planning for students with Asperger&apos;s attempts to address some of these areas through family involvement, community inclusion, and the active participation of the student in…

  3. School, Activism and Politics at the Movies: Educator Reactions to the Film "Waiting for &apos;Superman&apos;"

    ERIC Educational Resources Information Center

    Wessel Powell, Christy

    2014-01-01

    Context: The documentary film about U.S. education reform, "Waiting for &apos;Superman&apos;," was met with acclaim and controversy when released to theaters in 2010, and again when launching its grassroots "host a screening" campaign in 2011. The campaign ran concurrent with 2011 state legislative sessions, during which…

  4. Effortful Control Moderates Bidirectional Effects between Children&apos;s Externalizing Behavior and Their Mothers&apos; Depressive Symptoms

    ERIC Educational Resources Information Center

    Choe, Daniel E.; Olson, Sheryl L.; Sameroff, Arnold J.

    2014-01-01

    This study examined bidirectional associations between mothers&apos; depressive symptoms and children&apos;s externalizing behavior and whether they were moderated by preschool-age effortful control and gender. Mothers and teachers reported on 224 primarily White, middle-class children at ages 3, 5, and 10. Effortful control was assessed via…

  5. Children&apos;s Understandings of Characters&apos; Beliefs in Persuasive Arguments: Links with Gender and Theory of Mind

    ERIC Educational Resources Information Center

    Kolodziejczyk, Anna M.; Bosacki, Sandra L.

    2015-01-01

    This study investigated the role of gender plays in the relation between children&apos;s theory of mind (ToM) and persuasion. We explored children&apos;s use of the belief information of the characters involved within a persuasive situation. In two studies, children (four- to eight-year-olds) performed a comic strip task that described a…

  6. Teachers&apos; Implementation of the Coaching Role: Do Teachers&apos; Ownership, Sensemaking, and Agency Make a Difference?

    ERIC Educational Resources Information Center

    Ketelaar, Evelien; Beijaard, Douwe; Brok, Perry J.; Boshuizen, Henny P.

    2013-01-01

    The aim of this study was to explore whether teachers&apos; positioning towards an innovation is related to their implementation of it. Positioning was reflected in terms of teachers&apos; ownership, sensemaking, and agency. The innovation that was of central focus in this study pertained to the changing role of teachers towards a more coaching…

  7. What Will I Like Best When I&apos;m All Grown Up? Preschoolers&apos; Understanding of Future Preferences

    ERIC Educational Resources Information Center

    Bélanger, Michèle J.; Atance, Cristina M.; Varghese, Anisha L.; Nguyen, Victoria; Vendetti, Corrie

    2014-01-01

    Three experiments investigated 3-, 4-, and 5-year-olds&apos; (N = 240) understanding that their future or "grown-up" preferences may differ from their current ones (self-future condition). This understanding was compared to children&apos;s understanding of the preferences of a grown-up (adult-now condition) or the grown-up preferences of…

  8. Differences between Students&apos; and Teachers&apos; Perceptions of Education: Profiles to Describe Congruence and Friction

    ERIC Educational Resources Information Center

    Könings, Karen D.; Seidel, Tina; Brand-Gruwel, Saskia; Merriënboer, Jeroen J. G.

    2014-01-01

    Teachers and students have their own perceptions of education. Congruent perceptions contribute to optimal teaching-learning processes and help achieving best learning outcomes. This study investigated patterns in differences between students&apos; and teachers&apos; perceptions of their learning environment. Student profiles were identified…

  9. Chinese Students&apos; Perceptions of Their Creativity and Their Perceptions of Western Students&apos; Creativity

    ERIC Educational Resources Information Center

    Wang, Bingxin; Greenwood, Kenneth Mark

    2013-01-01

    This paper applies the Four C Model of Creativity ("Big-C, little-c, mini-c and Pro-c") to determine Chinese students&apos; perceptions of their own creativity and their perceptions of Western students&apos; creativity. By surveying 100 Chinese students and interviewing 10 of them, this paper discovered that Chinese students generally…

  10. Using Productive Disposition to Differentiate between Students&apos; Level of Precision When Critiquing a Peer&apos;s Work

    ERIC Educational Resources Information Center

    Gilbert, Melissa C.

    2014-01-01

    This study examined the productive disposition of pre-algebra students who demonstrated similar knowledge of the focal content but varied in other academic behaviors expected in the Common Core State Standards for Mathematics (CCSSM). Specifically, the study considered students&apos; attention to precision when critiquing a peer&apos;s work. The…

  11. Parents&apos; and Child Health Professionals&apos; Attitudes towards Dietary Interventions for Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Winburn, Elizabeth; Charlton, Jenna; McConachie, Helen; McColl, Elaine; Parr, Jeremy; O'Hare, Anne; Baird, Gillian; Gringras, Paul; Wilson, David C.; Adamson, Ashley; Adams, Sandra; Le Couteur, Ann

    2014-01-01

    Parents of children with autism spectrum disorders (ASD) use a wide range of interventions including poorly evidenced dietary interventions. To investigate parents&apos; and professionals&apos; experience of dietary interventions and attitudes towards a proposed trial to evaluate the gluten free casein free diet (GFCFD). Survey of UK parents of…

  12. Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB binding

    PubMed Central

    Lazaris, Andreas; Hwang, Kristy S.; Goukasian, Naira; Ramirez, Leslie M.; Eastman, Jennifer; Blanken, Anna E.; Teng, Edmond; Gylys, Karen; Cole, Greg; Saykin, Andrew J.; Shaw, Leslie M.; Trojanowski, John Q.; Jagust, William J.; Weiner, Michael W.

    2015-01-01

    Objective: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. Methods: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [11C]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. Results: Low plasma apoE was significantly associated with high PiB SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. Conclusions: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction. PMID:27066559

  13. Attending to Others&apos; Posts in Asynchronous Discussions: Learners&apos; Online "Listening" and Its Relationship to Speaking

    ERIC Educational Resources Information Center

    Wise, Alyssa Friend; Hausknecht, Simone Nicole; Zhao, Yuting

    2014-01-01

    Theoretical models of collaborative learning through online discussions presuppose that students generally attend to others&apos; posts. However, a succession of studies over the last decade has shown this assumption to be unwarranted. Instead, research indicates that learners attend to others&apos; posts in diverse and particular ways--an…

  14. The Power of Children&apos;s Dialogue Taiwanese Students&apos; Peer-Led Literature Discussion

    ERIC Educational Resources Information Center

    Chang, Chia-Chun

    2011-01-01

    This study built on previous research in the area of peer-led literature discussion. Even though there are numerous studies investigating this type of literacy activity, little is known about Taiwanese elementary students&apos; participation in peer-led literature discussion. This study explored a group of six Taiwanese fourth graders&apos;…

  15. Assessing Teachers&apos; Judgements of Students&apos; Academic Motivation and Emotions across Two Rating Methods

    ERIC Educational Resources Information Center

    Zhu, Mingjing; Urhahne, Detlef

    2014-01-01

    The present study examines the accuracy of teachers&apos; judgements about students&apos; motivation and emotions in English learning with two different rating methods. A sample of 480 sixth-grade Chinese students reported their academic self-concept, learning effort, enjoyment, and test anxiety via a questionnaire and were rated on these…

  16. A Survey Study to Investigate Educators&apos; Perceptions of Superintendents&apos; Leadership Practices and School District Performance

    ERIC Educational Resources Information Center

    Hoggard-Williams, Carolyn L.

    2012-01-01

    An organization&apos;s success centers on its leadership. Critical in the field of education, Houston (2001) proclaimed it best when he declared that superintendents have an opportunity to profoundly affect children&apos;s lives (Lashway, 2002b). Increasingly, empirical studies being conducted on leadership in education highlight the relationship…

  17. Can&apos;t Get No (Dis)satisfaction: The "Statecraft" Simulation&apos;s Effect on Student Decision Making

    ERIC Educational Resources Information Center

    Raymond, Chad

    2014-01-01

    Simulations are often employed as content-teaching tools in political science, but their effect on students&apos; reasoning skills is rarely assessed. This article explores what effect the "Statecraft" simulation might have on undergraduate students&apos; perceptions of their decision making. Decisions are often evaluated on the basis of…

  18. Do Adult ESL Learners&apos; and Their Teachers&apos; Goals for Improving Grammar in Writing Correspond?

    ERIC Educational Resources Information Center

    Zhou, Ally A.; Busch, Michael; Cumming, Alister

    2014-01-01

    Recent research has identified certain goals of adult second language (L2) learners and their teachers for writing instruction in English as a second language (ESL), yet questions remain as to whether students&apos; and teachers&apos; goals correspond in ways that achieve instructional objectives and facilitate L2 development. The present study…

  19. Low-Income Central American Immigrant Mothers&apos; Goals and Their Children&apos;s Classroom Competencies in Preschool

    ERIC Educational Resources Information Center

    Denmark, Nicole Marie; Harden, Brenda Jones; Gonzalez, Maritza

    2014-01-01

    Research Findings: Unlike other Latino groups, there is little information about the early socialization of children from Central American (CA) immigrant families. This study examined CA immigrant mothers&apos; short-term goals and the implications of these goals for children&apos;s behavior in preschool. A total of 47 low-income mothers described…

  20. Beyond Judgment Bias: How Students&apos; Ethnicity and Academic Profile Consistency Influence Teachers&apos; Tracking Judgments

    ERIC Educational Resources Information Center

    Glock, Sabine; Krolak-Schwerdt, Sabine; Klapproth, Florian; Böhmer, Matthias

    2013-01-01

    Research on school tracking has provided evidence that students with immigrant backgrounds are overrepresented in the lower school tracks. As teachers are the main decision makers when it comes to tracking, we investigated whether teachers&apos; tracking judgments are biased by the immigrant backgrounds of the students and how teachers&apos;…

  1. Revisiting Gordon&apos;s Teacher Effectiveness Training: An Intervention Study on Teachers&apos; Social and Emotional Learning

    ERIC Educational Resources Information Center

    Talvio, Markus; Lonka, Kirsti; Komulainen, Erkki; Kuusela, Marjo; Lintunen, Taru

    2013-01-01

    Introduction: This study explored the development of teachers&apos; social and emotional learning (SEL) skills by using "Teacher Effectiveness Training (TET)" (Gordon Training International) as an intervention with two groups of teachers. Further Gordon&apos;s model was approached from the perspective of modern educational psychology.…

  2. Voices from the Gambia: Parents&apos; Perspectives on Their Involvement in Their Children&apos;s Education

    ERIC Educational Resources Information Center

    Colley, Binta M.

    2014-01-01

    Research indicates the positive effects parental involvement can have in reinforcing learners&apos; beliefs about their ability to succeed. In this article, the author explores the nature of parental involvement in children&apos;s education in the Republic of the Gambia. The Gambian example reemphasizes the value of parent-school partnerships as a…

  3. Priorities for Developmental Areas in Early Childhood Education: A Comparison of Parents&apos; and Teachers&apos; Priorities

    ERIC Educational Resources Information Center

    Sackes, Mesut

    2013-01-01

    The purpose of this study was to examine parents&apos; and early childhood teachers&apos; perceptions of the priorities for developmental areas targeted in the Turkish Early Childhood Education Curriculum for children aged 36-72 months. The sample of this study consisted of 1600 parents and 158 early childhood teachers. The study utilized a survey…

  4. Investigating Elementary Principals&apos; Science Beliefs and Knowledge and Its Relationship to Students&apos; Science Outcomes

    ERIC Educational Resources Information Center

    Khan, Uzma Zafar

    2012-01-01

    The aim of this quantitative study was to investigate elementary principals&apos; beliefs about reformed science teaching and learning, science subject matter knowledge, and how these factors relate to fourth grade students&apos; superior science outcomes. Online survey methodology was used for data collection and included a demographic…

  5. Teachers&apos; Autonomy in Today&apos;s Educational Climate: Current Perceptions from an Acceptable Instrument

    ERIC Educational Resources Information Center

    Strong, Luman E. G.; Yoshida, Roland K.

    2014-01-01

    This research evaluated the psychometric properties of Friedman&apos;s (1999) Teacher Work-Autonomy Scale (TWA) to determine whether it was an acceptable instrument to measure U.S. teacher autonomy in the present educational context. A second purpose was to ascertain the current status of teachers&apos; perceptions of their autonomy from a sample…

  6. Relationships among Teachers&apos; Self-Efficacy and Students&apos; Motivation, Atmosphere, and Satisfaction in Physical Education

    ERIC Educational Resources Information Center

    Pan, Yi-Hsiang

    2014-01-01

    The purpose of this study was to confirm the relationships among teachers&apos; self-efficacy, and students&apos; learning motivation, learning atmosphere, and learning satisfaction in senior high school physical education (PE). A sample of 462 PE teachers and 2681 students was drawn using stratified random sampling and cluster sampling from high…

  7. Girls&apos; and Boys&apos; Mathematics Achievement, Affect, and Experiences: Findings from ECLS-K

    ERIC Educational Resources Information Center

    Lubienski, Sarah T.; Robinson, Joseph P.; Crane, Corinna C.; Ganley, Colleen M.

    2013-01-01

    Amid debates about the continued salience of gender in mathematics, this report summarizes an IES-funded investigation of gender-related patterns in the Early Childhood Longitudinal Study-Kindergarten Class of 1998-99 (ECLS-K). Girls&apos; and boys&apos; mathematics achievement, confidence, and interest were examined, along with experiences at…

  8. Electron flux through apo-and holoferritin

    NASA Astrophysics Data System (ADS)

    Axford, Danny N.; Davis, Jason J.

    2007-04-01

    Conductive probe atomic force microscopy (CP-AFM) has been used to investigate electronic transport through the protein ferritin in both its holo and apo forms. The presence of the iron oxide core has a notable effect on both conductance and the molecular response to probe-induced compression. This response can also be contrasted with that of the much smaller metalloprotein cytochrome c, across which electron transport can be simulated by a single non-resonant tunnel barrier model. Tapping mode AFM imaging, in different compressional regimes, reveals both the mineral core of holoferritin and significant collapse of the hollow protein cavity of apoferritin. These topographic findings correlate well with CP-AFM conductance data and facilitate a clearer description of electron transport across these molecules.

  9. ApoB-100, ApoE and CYP7A1 gene polymorphisms in Mexican patients with cholesterol gallstone disease

    PubMed Central

    Jaime, Sánchez-Cuén; Maribel, Aguilar-Medina; Eliakym, Arámbula-Meraz; José, Romero-Navarro; Julio, Granados; Laura, Sicairos-Medina; Rosalío, Ramos-Payán

    2010-01-01

    AIM: To determine the possible association of the ApoB-100 (XbaI), ApoE (HhaI) and CYP7A1 (BsaI) gene polymorphisms, with the development of cholesterol gallstone disease (GD) in a Mexican population. METHODS: The polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by ethnicity, age and sex: patients with GD (n = 101) and stone-free control subjects (n = 101). RESULTS: Allelic frequencies in patients and controls were: 34.16% vs 41.58% (P = 0.124) for X+ of ApoB-100; 4.46% vs 5.94% (P = 0.501) for E2, 85.64% vs 78.22% (P = 0.052) for E3, 9.90% vs 15.84% (P = 0.075) for E4 of ApoE; and 25.74% vs 27.72% (P = 0.653) for C of CYP7A1. Differences in genotypic frequencies between the studied groups were not significant (P < 0.05). CONCLUSION: These results demonstrated that no association exists between the studied polymorphisms and cholelithiasis in this high prevalent population. PMID:20872969

  10. Agonistic antibody to angiotensin II type 1 receptor accelerates atherosclerosis in ApoE-/- mice

    PubMed Central

    Li, Weijuan; Chen, Yaoqi; Li, Songhai; Guo, Xiaopeng; Zhou, Wenping; Zeng, Qiutang; Liao, Yuhua; Wei, Yumiao

    2014-01-01

    This study aimed to investigate the effects of agonistic antibody to angiotensin II type 1 receptor (AT1-AA) on atherosclerosis in male ApoE-/- mice which were employed to establish the animal models of AT1-AA in two ways. In the first group, mice were injected subcutaneously with conjugated AT1 peptide at multiple sites; in the second group, mice were infused with AT1-AA prepared from rabbits that were treated with AT1 peptide intraperitoneally. Mice in each group were further randomly divided into five subgroups and treated with AT1 peptide/AT1-AA, AT1 peptide/AT1-AA plus valsartan, AT1 peptide/AT1-AA plus fenofibrate, AT1 peptide/ AT1-AA plus pyrrolidine dithiocarbamate (PDTC) and control vehicle, respectively. Antibodies were detected in mice (except for mice in control group). Aortic atherosclerotic lesions were assessed by oil red O staining, while plasma CRP, TNF-α, nuclear factor-kappa B (NF-κB) and H2O2 were determined by ELISA. CCR2 (the receptor of MCP-1), macrophages, and smooth muscle cells were detected by immunohistochemistry. P47phox, MCP-1 and eNOS were detected by RT-PCR, while P47phox, NF-κB and MCP-1 were detected by Western blot assay. The aortic atherosclerotic lesions were significantly increased in AT1 peptide/AT1-AA treated mice, along with simultaneous increases in inflammatory parameters. However, mice treated with valsartan, fenofibrate or PDTC showed alleviated progression of atherosclerosis and reductions in inflammatory parameters. Thus, AT1-AA may accelerate aortic atherosclerosis in ApoE-/- mice, which is mediated, at least in part, by the inflammatory reaction involving nicotinamide-adenine dinucleotide phosphate oxidase, reactive oxygen species, and NF-κB. In addition, valsartan, fenofibrate and PDTC may inhibit the AT1-AA induced atherosclerosis. PMID:25628779

  11. Early changes in vascular reactivity in response to 56Fe irradiation in ApoE-/- mice

    NASA Astrophysics Data System (ADS)

    White, C. Roger; Yu, Tao; Gupta, Kiran; Babitz, Stephen K.; Black, Leland L.; Kabarowski, Janusz H.; Kucik, Dennis F.

    2015-03-01

    Epidemiological studies have established that radiation from a number of terrestrial sources increases the risk of atherosclerosis. The accelerated heavy ions in the galacto-cosmic radiation (GCR) that astronauts will encounter on in space, however, interact very differently with tissues than most types of terrestrial radiation, so the health consequences of exposure on deep-space missions are not clear. We demonstrated earlier that 56Fe, an important component of cosmic radiation, accelerates atherosclerotic plaque development. In the present study, we examined an earlier, pro-atherogenic event that might be predictive of later atherosclerotic disease. Decreased endothelium-dependent vasodilation is a prominent manifestation of vascular dysfunction that is thought to predispose humans to the development of structural vascular changes that precede the development of atherosclerotic plaques. To test the effect of heavy-ion radiation on endothelium-dependent vasodilation, we used the same ApoE-/- mouse model in which we previously demonstrated the pro-atherogenic effect of 56Fe on plaque development. Ten week old male ApoE mice (an age at which there is little atherosclerotic plaque in the descending aorta) were exposed to 2.6 Gy 56Fe. The mice were then fed a normal diet and housed under standard conditions. At 4-5 weeks post-irradiation, aortic rings were isolated and endothelial-dependent relaxation was measured. Relaxation in response to acetylcholine was significantly impaired in irradiated mice compared to age-matched, un-irradiated mice. This decrease in vascular reactivity following 56Fe irradiation occurred eight weeks prior to the development of statistically significant exacerbation of aortic plaque formation and may contribute to the formation of later atherosclerotic lesions.

  12. ApoE Receptor 2 mediates trophoblast dysfunction and pregnancy complications induced by antiphospholipid antibodies in mice

    PubMed Central

    Ulrich, Victoria; Gelber, Shari E.; Vukelic, Milena; Sacharidou, Anastasia; Herz, Joachim; Urbanus, Rolf T.; de Groot, Philip G.; Natale, David R.; Harihara, Anirudha; Redecha, Patricia; Abrahams, Vikki M.; Shaul, Philip W.

    2015-01-01

    Objective Pregnancies in women with the antiphospholipid syndrome (APS) are frequently complicated by fetal loss and intrauterine growth restriction (IUGR). How circulating antiphospholipid antibodies (aPL) cause pregnancy complications in APS is poorly understood. We sought to determine if the LDL receptor family member apoE receptor 2 (apoER2) mediates trophoblast dysfunction and pregnancy complications induced by aPL. Methods Placental and trophoblast apoER2 expression was evaluated by immunohistochemistry and immunoblotting. Normal human IgG (NHIgG) and aPL were purified from healthy individuals and APS patients, respectively. The role of apoER2 in aPL-induced changes in trophoblast proliferation, migration and kinase activation was assessed using RNA interference in HTR-8/SVneo cells. The participation of apoER2 in aPL-induced pregnancy loss and IUGR was evaluated in pregnant apoER2+/+ and apoER2−/− mice injected with aPL or NHIgG. Results We found that apoER2 is abundant in human and mouse placental trophoblasts, and in multiple trophoblast-derived cell lines including HTR-8/SVneo cells. ApoER2 and its interaction with the cell surface protein β2-glycoprotein I were required for aPL-induced inhibition of cultured trophoblast proliferation and migration. In parallel, aPL antagonism of Akt kinase activation by EGF in trophoblasts was mediated by apoER2. Furthermore, in a murine passive transfer model of pregnancy complications of APS, apoER2−/− mice were protected from both aPL-induced fetal loss and aPL-induced IUGR. Conclusion ApoER2 plays a major role in the attenuation of trophoblast function by aPL, and the receptor mediates aPL-induced pregnancy complications in vivo in mice. ApoER2-directed interventions can now potentially be developed to combat the pregnancy complications associated with APS. PMID:26474194

  13. CX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production

    PubMed Central

    Arnold, Ludovic; Perrin, Hélène; de Chanville, Camille Baudesson; Saclier, Marielle; Hermand, Patricia; Poupel, Lucie; Guyon, Elodie; Licata, Fabrice; Carpentier, Wassila; Vilar, José; Mounier, Rémi; Chazaud, Bénédicte; Benhabiles, Nora; Boissonnas, Alexandre; Combadiere, Béhazine; Combadiere, Christophe

    2015-01-01

    Muscle injury triggers inflammation in which infiltrating mononuclear phagocytes are crucial for tissue regeneration. The interaction of the CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axis that guides phagocyte infiltration is incompletely understood. Here, we show that CX3CR1 deficiency promotes muscle repair and rescues Ccl2−/− mice from impaired muscle regeneration as a result of altered macrophage function, not infiltration. Transcriptomic analysis of muscle mononuclear phagocytes reveals that Apolipoprotein E (ApoE) is upregulated in mice with efficient regeneration. ApoE treatment enhances phagocytosis by mononuclear phagocytes in vitro, and restores phagocytic activity and muscle regeneration in Ccl2−/− mice. Because CX3CR1 deficiency may compensate for defective CCL2-dependant monocyte recruitment by modulating ApoE-dependent macrophage phagocytic activity, targeting CX3CR1 expressed by macrophages might be a powerful therapeutic approach to improve muscle regeneration. PMID:26632270

  14. CX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production.

    PubMed

    Arnold, Ludovic; Perrin, Hélène; de Chanville, Camille Baudesson; Saclier, Marielle; Hermand, Patricia; Poupel, Lucie; Guyon, Elodie; Licata, Fabrice; Carpentier, Wassila; Vilar, José; Mounier, Rémi; Chazaud, Bénédicte; Benhabiles, Nora; Boissonnas, Alexandre; Combadiere, Béhazine; Combadiere, Christophe

    2015-01-01

    Muscle injury triggers inflammation in which infiltrating mononuclear phagocytes are crucial for tissue regeneration. The interaction of the CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axis that guides phagocyte infiltration is incompletely understood. Here, we show that CX3CR1 deficiency promotes muscle repair and rescues Ccl2(-/-) mice from impaired muscle regeneration as a result of altered macrophage function, not infiltration. Transcriptomic analysis of muscle mononuclear phagocytes reveals that Apolipoprotein E (ApoE) is upregulated in mice with efficient regeneration. ApoE treatment enhances phagocytosis by mononuclear phagocytes in vitro, and restores phagocytic activity and muscle regeneration in Ccl2(-/-) mice. Because CX3CR1 deficiency may compensate for defective CCL2-dependant monocyte recruitment by modulating ApoE-dependent macrophage phagocytic activity, targeting CX3CR1 expressed by macrophages might be a powerful therapeutic approach to improve muscle regeneration. PMID:26632270

  15. Effects of Simulated Heat Waves with Strong Sudden Cooling Weather on ApoE Knockout Mice

    PubMed Central

    Zhang, Shuyu; Kuang, Zhengzhong; Zhang, Xiakun

    2015-01-01

    This study analyzes the mechanism of influence of heat waves with strong sudden cooling on cardiovascular diseases (CVD) in ApoE−/− mice. The process of heat waves with strong sudden cooling was simulated with a TEM1880 meteorological-environment simulation chamber according to the data obtained at 5 a.m. of 19 June 2006 to 11 p.m. of 22 June 2006. Forty-eight ApoE−/− mice were divided into six blocks based on their weight. Two mice from each block were randomly assigned to control, heat wave, temperature drop, and rewarming temperature groups. The experimental groups were transferred into the climate simulator chamber for exposure to the simulated heat wave process with strong sudden temperature drop. After 55, 59, and 75 h of exposure, the experimental groups were successively removed from the chamber to monitor physiological indicators. Blood samples were collected by decollation, and the hearts were harvested in all groups. The levels of heat stress factors (HSP60, SOD, TNF, sICAM-1, HIF-1α), cold stress factors (NE, EPI), vasoconstrictor factors (ANGII, ET-1, NO), and four items of blood lipid (TC, TG, HDL-C, and LDL-C) were measured in each ApoE−/− mouse. Results showed that the heat waves increased the levels of heat stress factors except SOD decreased, and decreased the levels of vasoconstrictor factors and blood lipid factors except TC increased. The strong sudden temperature drop in the heat wave process increased the levels of cold stress factors, vasoconstrictor factors and four blood lipid items (except the level of HDL-C which decreased) and decreased the levels of heat stress factors (except the level of SOD which increased). The analysis showed that heat waves could enhance atherosclerosis of ApoE−/− mice. The strong sudden temperature drop during the heat wave process increased the plasma concentrations of NE and ANGII, which indicates SNS activation, and resulted in increased blood pressure. NE and ANGII are vasoconstrictors

  16. Adopting Frank Warren&apos;s PostSecret Art Project to Illustrate the Role of Secrets in Interpersonal Communication

    ERIC Educational Resources Information Center

    Paxman, Christina G.

    2013-01-01

    The exploration of secrets summons the adage that &apos;&apos;what someone doesn&apos;t know won&apos;t hurt them.&apos;&apos; While this phrase implies that keeping secrets can be advantageous, it also foreshadows another consideration: secrets have the propensity to hurt others (Caughlin, Scott, Miller, & Hefner, 2009). Despite this, the act…

  17. APOE genotype influences functional status among elderly without dementia

    SciTech Connect

    Albert, S.M.; Jacobs, D.M.; Stern, Y.

    1995-12-18

    The presence of apolipoprotein-{epsilon}4 (APOE-{epsilon}4) significantly increases the risk of Alzheimer`s disease (AD). The association between APOE-{epsilon}4 status and functional abilities was explored further in a multicultural sample of community-dwelling, nondemented elders. The sample was limited to cognitively-intact, community-dwelling elders, who were free of stroke or other neurologic disability. In 218 elders who met research criteria, the presence of APOE-{epsilon}4 was associated with poorer functional status, apart from the effects of neuropsychological performance, gender, age, and education (OR = 2.5, 95% CI: 1.3, 4.9). In 158 subjects without an APOE-{epsilon}4 allele, 50% reported no functional limitation; in the 60 subjects with an {epsilon}4 allele, only 28% reported no functional limitation (P < .01). The relationship was not explained by the distribution of co-morbidities. The association between poorer function and the presence of an APOE-{epsilon}4 allele was evident in each ethnic group. In path analyses, the presence of an APOE-{epsilon}4 allele was associated with decreased functional ability in non-demented elders not simply through an association with poorer cognitive status, but also independently. These results suggest that the APOE-{epsilon}4 genotype is associated with functional deficit in people with normal neuropsychological profiles. 29 refs., 1 fig., 3 tabs.

  18. The APOE Gene is Differentially Methylated in Alzheimer's Disease.

    PubMed

    Foraker, Jessica; Millard, Steven P; Leong, Lesley; Thomson, Zachary; Chen, Sunny; Keene, C Dirk; Bekris, Lynn M; Yu, Chang-En

    2015-01-01

    The ɛ4 allele of the human apolipoprotein E gene (APOE) is a well-proven genetic risk factor for the late onset form of Alzheimer's disease (AD). However, the biological mechanisms through which the ɛ4 allele contributes to disease pathophysiology are incompletely understood. The three common alleles of APOE, ɛ2, ɛ3 and ɛ4, are defined by two single nucleotide polymorphisms (SNPs) that reside in the coding region of exon 4, which overlaps with a well-defined CpG island (CGI). Both SNPs change not only the protein codon but also the quantity of CpG dinucleotides, primary sites for DNA methylation. Thus, we hypothesize that the presence of an ɛ4 allele changes the DNA methylation landscape of the APOE CGI and that such epigenetic alteration contributes to AD susceptibility. To explore the relationship between APOE genotype, AD risk, and DNA methylation of the APOE CGI, we applied bisulfite pyrosequencing and evaluated methylation profiles of postmortem brain from 15 AD and 10 control subjects. We observed a tissue-specific decrease in DNA methylation with AD and identified two AD-specific differentially methylated regions (DMRs), which were also associated with APOE genotype. We further demonstrated that one DMR was completely un-methylated in a sub-population of genomes, possibly due to a subset of brain cells carrying deviated APOE methylation profiles. These data suggest that the APOE CGI is differentially methylated in AD brain in a tissue- and APOE-genotype-specific manner. Such epigenetic alteration might contribute to neural cell dysfunction in AD brain. PMID:26402071

  19. The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

    PubMed

    Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

    2015-08-01

    Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity.

  20. Apolipoprotein C-I is an APOE genotype-dependent suppressor of glial activation

    PubMed Central

    2012-01-01

    Background Inheritance of the human ϵ4 allele of the apolipoprotein (apo) E gene (APOE) significantly increases the risk of developing Alzheimer’s disease (AD), in addition to adversely influencing clinical outcomes of other neurologic diseases. While apoE isoforms differentially interact with amyloid β (Aβ), a pleiotropic neurotoxin key to AD etiology, more recent work has focused on immune regulation in AD pathogenesis and on the mechanisms of innate immunomodulatory effects associated with inheritance of different APOE alleles. APOE genotype modulates expression of proximal genes including APOC1, which encodes a small apolipoprotein that is associated with Aβ plaques. Here we tested the hypothesis that APOE-genotype dependent innate immunomodulation may be mediated in part by apoC-I. Methods ApoC-I concentration in cerebrospinal fluid from control subjects of differing APOE genotypes was quantified by ELISA. Real-time PCR and ELISA were used to analyze apoC-I mRNA and protein expression, respectively, in liver, serum, cerebral cortex, and cultured primary astrocytes derived from mice with targeted replacement of murine APOE for human APOE ϵ3 or ϵ4. ApoC-I direct modulation of innate immune activity was investigated in cultured murine primary microglia and astrocytes, as well as human differentiated macrophages, using specific toll-like receptor agonists LPS and PIC as well as Aβ. Results ApoC-I levels varied with APOE genotype in humans and in APOE targeted replacement mice, with ϵ4 carriers showing significantly less apoC-I in both species. ApoC-I potently reduced pro-inflammatory cytokine secretion from primary murine microglia and astrocytes, and human macrophages, stimulated with LPS, PIC, or Aβ. Conclusions ApoC-I is immunosuppressive. Our results illuminate a novel potential mechanism for APOE genotype risk for AD; one in which patients with an ϵ4 allele have decreased expression of apoC-I resulting in increased innate immune activity. PMID

  1. ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT.

    PubMed

    Duka, Adelina; Fotakis, Panagiotis; Georgiadou, Dimitra; Kateifides, Andreas; Tzavlaki, Kalliopi; von Eckardstein, Leonard; Stratikos, Efstratios; Kardassis, Dimitris; Zannis, Vassilis I

    2013-01-01

    The objective of this study was to establish the role of apoA-IV, ABCA1, and LCAT in the biogenesis of apoA-IV-containing HDL (HDL-A-IV) using different mouse models. Adenovirus-mediated gene transfer of apoA-IV in apoA-I(-/-) mice did not change plasma lipid levels. ApoA-IV floated in the HDL2/HDL3 region, promoted the formation of spherical HDL particles as determined by electron microscopy, and generated mostly α- and a few pre-β-like HDL subpopulations. Gene transfer of apoA-IV in apoA-I(-/-) × apoE(-/-) mice increased plasma cholesterol and triglyceride levels, and 80% of the protein was distributed in the VLDL/IDL/LDL region. This treatment likewise generated α- and pre-β-like HDL subpopulations. Spherical and α-migrating HDL particles were not detectable following gene transfer of apoA-IV in ABCA1(-/-) or LCAT(-/-) mice. Coexpression of apoA-IV and LCAT in apoA-I(-/-) mice restored the formation of HDL-A-IV. Lipid-free apoA-IV and reconstituted HDL-A-IV promoted ABCA1 and scavenger receptor BI (SR-BI)-mediated cholesterol efflux, respectively, as efficiently as apoA-I and apoE. Our findings are consistent with a novel function of apoA-IV in the biogenesis of discrete HDL-A-IV particles with the participation of ABCA1 and LCAT, and may explain previously reported anti-inflammatory and atheroprotective properties of apoA-IV. PMID:23132909

  2. Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE(-/-) mice.

    PubMed

    Kumar, Saran; Chen, Mo; Li, Yan; Wong, Fiona H S; Thiam, Chung Wee; Hossain, Md Zakir; Poh, Kian Keong; Hirohata, Satoshi; Ogawa, Hiroko; Angeli, Véronique; Ge, Ruowen

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease characterized by formation of lipid-rich plaques on the inner walls of arteries. ADAMTS4 (a disintegrin-like and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase that regulates versican turnover in the arterial wall and atherosclerotic plaques. Recent reports indicated elevated ADAMTS4 level in human atherosclerotic plaques and in the plasma of acute coronary syndrome patients. Nevertheless, whether increased ADAMTS4 is a consequence of atherosclerosis or ADAMTS4 has a causal role in atherogenesis remains unknown. In this work, we investigated the role of ADAMTS4 in diet induced atherosclerosis using apolipoprotein E deficient (ApoE(-/-)) and Adamts4 knockout mice. We show that ADAMTS4 expression increases in plaques as atherosclerosis progresses in ApoE(-/-) mice. ApoE(-/-)Adamts4(-/-) double knockout mice presented a significant reduction in plaque burden at 18 weeks of age. Loss of ADAMTS4 lead to a more stable plaque phenotype with a significantly reduced plaque vulnerability index characterized by reduced lipid content and macrophages accompanied with a significant increase in smooth muscle cells, collagen deposition and fibrotic cap thickness. The reduced atherosclerosis is accompanied by an altered plasma inflammatory cytokine profile. These results demonstrate for the first time that ADAMTS4 contributes to diet induced atherosclerosis in ApoE(-/-) mice. PMID:27491335

  3. ApoE variant p.V236E is associated with markedly reduced risk of Alzheimer’s disease

    PubMed Central

    2014-01-01

    Recent genome-wide association studies (GWAS) of late-onset Alzheimer’s disease (LOAD) have identified single nucleotide polymorphisms (SNPs) which show significant association at the well-known APOE locus and at nineteen additional loci. Among the functional, disease-associated variants at these loci, missense variants are particularly important because they can be readily investigated in model systems to search for novel therapeutic targets. It is now possible to perform a low-cost search for these “actionable” variants by genotyping the missense variants at known LOAD loci already cataloged on the Exome Variant Server (EVS). In this proof-of-principle study designed to explore the efficacy of this approach, we analyzed three rare EVS variants in APOE, p.L28P, p.R145C and p.V236E, in our case control series of 9114 subjects. p.R145C proved to be too rare to analyze effectively. The minor allele of p.L28P, which was in complete linkage disequilibrium (D’ = 1) with the far more common APOE ϵ4 allele, showed no association with LOAD (P = 0.75) independent of the APOE ϵ4 allele. p.V236E was significantly associated with a marked reduction in risk of LOAD (P = 7.5×10−05; OR = 0.10, 0.03 to 0.45). The minor allele of p.V236E, which was in complete linkage disequilibrium (D’ = 1) with the common APOE ϵ3 allele, identifies a novel LOAD-associated haplotype (APOE ϵ3b) which is associated with decreased risk of LOAD independent of the more abundant APOE ϵ2, ϵ3 and ϵ4 haplotypes. Follow-up studies will be important to confirm the significance of this association and to better define its odds ratio. The ApoE p.V236E substitution is the first disease-associated change located in the lipid-binding, C-terminal domain of the protein. Thus our study (i) identifies a novel APOE missense variant which may profitably be studied to better understand how ApoE function may be modified to reduce risk of LOAD and (ii) indicates that analysis of protein

  4. Specialist Young Musicians&apos; Role Models: Whom Do They Admire and Why?

    ERIC Educational Resources Information Center

    Ivaldi, Antonia

    2013-01-01

    Previous research into adolescents&apos; musical role models has shown that young people are more likely to identify a celebrity figure due to their image and perceived fame, than because of their musical ability. The current research is a development of Ivaldi and O&apos;Neill&apos;s (Adolescents&apos; musical role models: Whom do they admire and…

  5. Both Odor Identification and ApoE-ε4 Contribute to Normative Cognitive Aging

    PubMed Central

    Finkel, Deborah; Reynolds, Chandra A.; Larsson, Maria; Gatz, Margaret; Pedersen, Nancy L.

    2013-01-01

    Research indicates that apoliprotein E (ApoE) plays a role in the development of Alzheimer’s disease (AD) and possibly in the cognitive decline associated with normative aging. More recently, researchers have shown that ApoE is expressed in olfactory brain structures, and a relationship among ApoE, AD, and olfactory function has been proposed. In the current analyses, we investigated the contribution of ApoE and odor identification in decline trajectories associated with normative cognitive aging in various domains, using longitudinal data on cognitive performance available from the Swedish Adoption/Twin Study of Aging. Data on both ApoE status and olfactory functioning were available from 455 individuals ranging in age from 50 to 88 years at the first measurement occasion. Odor identification was measured via a mailed survey. Cognitive performance was assessed in up to 5 waves of in-person testing covering a period of 16 years. Latent growth curve analyses incorporating odor identification and ApoE status indicated a main effect of odor identification on the performance level in three cognitive domains: verbal, memory, and speed. A main effect of ApoE on rates of decline after age 65 was found for verbal, spatial, and speed factors. The consistency of results across cognitive domains provides support for theories that posit central nervous system-wide origins of the olfaction-cognition-ApoE relationship; however, olfactory errors and APOE ε4 show unique and differential effects on cognitive trajectory features. PMID:21517181

  6. Let&apos;s Connect: Using Adobe Connect to Foster Group Collaboration in the Online Classroom

    ERIC Educational Resources Information Center

    Kaufmann, Renee; Frisby, Brandi N.

    2013-01-01

    The need for students to become connected in the classroom parallels the need for students to become socially integrated into the college community. Because technological tools are always changing, the opportunity for all students on- and off-campus to &apos;'meet'&apos; face-to-face and build relationships within the classroom are…

  7. Secondary Pre-Service Teachers&apos; Perceptions of an Ideal Classroom Environment

    ERIC Educational Resources Information Center

    Bartelheim, Frederick J.; Conn, Daniel R.

    2014-01-01

    The classroom environment can impact students&apos; motivation and engagement, and can influence students&apos; academic learning. In some cases, pre-service teachers&apos; influence on the classroom environment may not always be conducive for student learning. This exploratory study investigated pre-service teachers&apos; perceptions of an ideal…

  8. Associations between Chinese EFL Graduate Students&apos; Beliefs and Language Learning Strategies

    ERIC Educational Resources Information Center

    Tang, Mailing; Tian, Jianrong

    2015-01-01

    This study, using Horwitz&apos;s Beliefs about Language Learning Inventory and Oxford&apos;s Strategy Inventory for Language Learning, investigated learners&apos; beliefs about language learning and their choice of strategy categories among 546 graduate students in China. The correlation between learners&apos; beliefs and their strategy categories…

  9. Teachers&apos; Organizational Commitment: Examining the Mediating Effects of Distributed Leadership

    ERIC Educational Resources Information Center

    Devos, Geert; Tuytens, Melissa; Hulpia, Hester

    2014-01-01

    This study examines the relation between principals&apos; leadership and teachers&apos; organizational commitment, mediated by distributed leadership. Data were collected from 1,495 teachers in 46 secondary schools. Structural equation modeling indicated that the effect of principals&apos; leadership on teachers&apos; organizational commitment is…

  10. MBA Students&apos; Workplace Writing: Implications for Business Writing Pedagogy and Workplace Practice

    ERIC Educational Resources Information Center

    Lentz, Paula

    2013-01-01

    Employers frequently complain about the state of their employees&apos; writing skills. Much of the current research on this subject explores workplace writing skills from the employer&apos;s perspective. However, this article examines workplace writing from the employees&apos; perspective. Specifically, it analyzes MBA students&apos; responses to…

  11. Multiple Perspectives on Elementary Teachers&apos; Science Identities: A Case Study

    ERIC Educational Resources Information Center

    Madden, Lauren; Wiebe, Eric

    2015-01-01

    This narrative case study examined the relationship between teacher identity and elementary science teaching. Teacher identity was described using a modification of Gee&apos;s framework incorporating three perspectives: the teachers&apos; self-described identity, the researchers&apos; view of teacher identity, and the students&apos; views of…

  12. Extract from an Interview of Sean O&apos;Connor: 8 September 1986

    ERIC Educational Resources Information Center

    Mulcahy, D. G.; O'Sullivan, Denis

    2014-01-01

    The educational community appreciates the editors of "Irish Educational Studies" for making the Interview with Sean O&apos;Connor, in Dublin, Ireland available to a wider audience in 2014. The interview was originally in Sean O&apos;Connor&apos;s home in Dublin on 8 September 1986. By that time, O&apos;Connor had retired as Secretary of…

  13. Jack Mezirow&apos;s Conceptualisation of Adult Transformative Learning: A Review

    ERIC Educational Resources Information Center

    Calleja, Colin

    2014-01-01

    This paper traces the evolution of Jack Mezirow&apos;s transformative learning theory and its conceptualisation. It discusses the three major influences, namely Thomas Khun&apos;s philosophical conception of paradigm, Freire&apos;s conception of conscientisation and consciousness growth, and Habermas&apos; domains of learning and the discussion of…

  14. Cambodian Early Adolescents&apos; Academic Achievement: The Role of Social Capital

    ERIC Educational Resources Information Center

    Eng, Sothy

    2013-01-01

    This study examined the associations of parents&apos; cultural beliefs and attitudes with respect to fate, traditional gender roles, aspirations, and involvement in children&apos;s academic achievement in Cambodia. Based on Coleman&apos;s social capital theory, a good parent-child relationship enables children&apos;s school success because…

  15. Preschoolers&apos; Emotion Expression and Regulation: Relations with School Adjustment

    ERIC Educational Resources Information Center

    Herndon, Kristina J.; Bailey, Craig S.; Shewark, Elizabeth A.; Denham, Susanne A.; Bassett, Hideko H.

    2013-01-01

    Children&apos;s expression and regulation of emotions are building blocks of their experiences in classrooms. Thus, the authors&apos; primary goal was to investigate whether preschoolers&apos; expression or ability to regulate emotions were associated with teachers&apos; ratings of school adjustment. A secondary goal was to investigate how boys…

  16. An Examination of the Relative Age Effect in Developmental Girls&apos; Hockey in Ontario

    ERIC Educational Resources Information Center

    Smith, Kristy L.; Weir, Patricia L.

    2013-01-01

    The relative age effect (RAE) suggests that athletes may be provided with greater opportunities for success depending on the position of their birthdate in a sport&apos;s selection year. While the effect has been well established in men&apos;s sports, less is known about women&apos;s sports. This study examined the RAE in developmental girls&apos;…

  17. Thirty Points about Motivation from Skinner&apos;s Book "Verbal Behavior"

    ERIC Educational Resources Information Center

    Sundberg, Mark L.

    2013-01-01

    Skinner discussed the topic of motivation in every chapter of the book "Verbal Behavior" (1957), usually with his preferred terminology of &apos;&apos;deprivation, satiation, and aversive stimulation.&apos;&apos; In the current paper, direct quotations are used to systematically take the reader through 30 separate points made by Skinner…

  18. Behavioral testing affects the phenotypic expression of APOE ε3 and APOE ε4 in targeted replacement mice and reduces the differences between them.

    PubMed

    Salomon-Zimri, Shiran; Liraz, Ori; Michaelson, Daniel M

    2015-06-01

    Apolipoprotein E4 (APOE ε4) is the most prevalent genetic risk factor for Alzheimer's disease (AD). Targeted replacement mice that express either APOE ε4 or its AD benign isoform, APOE ε3, are used extensively in behavioral, biochemical, and physiological studies directed at assessing the phenotypic effects of APOE ε4 and at unraveling the mechanisms underlying them. Such experiments often involve pursuing biochemical and behavioral measurements on the same cohort of mice. In view of the possible cross-talk interactions between brain parameters and cognitive performance, we presently investigated the extent to which the phenotypic expression of APOE ε4 and APOE ε4 in targeted replacement mice is affected by behavioral testing. This was performed using young, naïve APOE ε4 and APOE ε3 mice in which the levels of distinct brain parameters are affected by the APOE genotype (e.g., elevated levels of amyloid beta [Aβ] and hyperphosphorylated tau and reduced levels of vesicular glutamate transporter (VGLUT) in hippocampal neurons of APOE ε4 mice). These mice were exposed to a fear-conditioning paradigm, and the resulting effects on the brain parameters were examined. The results obtained revealed that the levels of Aβ, hyperphosphorylated tau, VGluT, and doublecortin of the APOE ε4 and APOE ε3 mice were markedly affected following the exposure of APOE ε4 and APOE ε3 mice to the fear-conditioning paradigm such that the isoform-specific effects of APOE ε4 on these parameters were greatly diminished. The finding that behavioral testing affects the APOE ε3 and APOE ε4 phenotypes and masks the differences between them has important theoretical and practical implications and suggests that the assessment of brain and behavioral parameters should be performed using different cohorts. PMID:27239500

  19. Comparison of anti-endotoxin activity of apoE and apoA mimetic derivatives of a model amphipathic peptide 18A.

    PubMed

    Sharifov, Oleg F; Nayyar, Gaurav; Ternovoy, Vladimir V; Palgunachari, Mayakonda N; Garber, David W; Anantharamaiah, Gm; Gupta, Himanshu

    2014-11-01

    Endotoxemia is a major cause of chronic inflammation, and is an important pathogenic factor in the development of metabolic syndrome and atherosclerosis. Human apolipoprotein E (apoE) and apoA-I are protein components of high-density lipoprotein, which have strong anti-endotoxin activity. Here, we compared anti-endotoxin activity of Ac-hE18A-NH2 and 4F peptides, modified from model amphipathic helical 18A peptide, to mimic, respectively, apoE and apoA-I properties. Ac-hE18A-NH2, stronger than 4F, inhibited endotoxin activity and disaggregated Escherichia coli 055:B5 (wild smooth serotype). Ac-hE18A-NH2 and 4F inhibited endotoxin activity of E. coli 026:B6 (rough-like serotype) to a similar degree. This suggests that Ac-hE18A-NH2 as a dual-domain molecule might interact with both the lipid A and headgroup of smooth LPS, whereas 4F binds lipid A. In C57BL/6 mice, Ac-hE18A-NH2 was superior to 4F in inhibiting the inflammatory responses mediated by E. coli 055:B5, but not E. coli 026:B6. However, in THP-1 cells, isolated human primary leukocytes, and whole human blood, Ac-hE18A-NH2 reduced responses more strongly than 4F to both E. coli serotypes either when peptides were pre-incubated or co-incubated with LPS, indicating that Ac-hE18A-NH2 also has strong anti-inflammatory effects independent of endotoxin-neutralizing properties. In conclusion, Ac-hE18A-NH2 is more effective than 4F in inhibiting LPS-mediated inflammation, which opens prospective clinical applications for Ac-hE18A-NH2.

  20. Metabolism of Apolipoprotein A-II Containing Triglyceride Rich ApoB Lipoproteins in Humans

    PubMed Central

    Desai, Nirav K.; Ooi, Esther M.; Mitchell, Paul D.; Furtado, Jeremy; Sacks, Frank M.

    2015-01-01

    Objective To characterize human triglyceride-rich lipoproteins (TRL) with and without apoA-II and to study their metabolism in vivo. Methods Plasma from 11 participants on a controlled diet given a bolus infusion of [D5]L-phenylalanine to label apoB was combined into four pools and applied to anti-apoA-II immunoaffinity columns. Fractions with and without apoA-II were separated into VLDL and IDL by ultracentrifugation; lipids and apolipoproteins were measured. For kinetic measurements, apoB was isolated and hydrolyzed to the constituent amino acids. Tracer enrichment was measured by GCMS. Metabolic rates were determined by SAAM-II. Results VLDL and IDL with apoA-II comprised 7% and 9% of total VLDL and IDL apoB respectively. VLDL with apoA-II was enriched in apoC-III, apoE, and cholesterol compared to VLDL without apoA-II. Mean apoB FCR of VLDL with apoA-II was significantly lower than for VLDL without apoA-II (2.80±0.96 pools/day v.s. 5.09±1.69 pools/day, P=0.009). A higher percentage of VLDL with apoA-II was converted to IDL than was cleared from circulation, compared to VLDL without apoA-II (96±8% vs. 45±22%; P=0.007). The rate constants for conversion of VLDL to IDL were similar for VLDL with and without apoA-II. Thus, a very low rate constant for clearance accounted for the lower FCR of VLDL with apoA-II. Conclusion VLDL with apoA-II represents a small pool of VLDL particles that has a slow FCR and is predominantly converted to IDL rather than cleared from the circulation. PMID:26071654

  1. Do Mothers and Fathers Perceive Their Child&apos;s Academic Potential in a Similar Way?

    ERIC Educational Resources Information Center

    Rautiainen, Riitta; Räty, Hannu; Kasanen, Kati

    2014-01-01

    The mothers and fathers (n?=?43) of third- and sixth-grade children were asked to assess their child&apos;s academic potential in comparison with the child&apos;s earlier competence and with that of her/his peers. In the interpersonal domain, the mothers&apos; and fathers&apos; perceptions of their child&apos;s academic potential were related to…

  2. Serum Levels of ApoA1 and ApoA2 Are Associated with Cognitive Status in Older Men.

    PubMed

    Ma, Cheng; Li, Jin; Bao, Zhijun; Ruan, Qingwei; Yu, Zhuowei

    2015-01-01

    Background. Advancing age, chronic inflammation, oxidative damage, and disorders of lipid metabolism are positively linked to the late-life cognitive impairment. Serum biomarkers may be associated with the cognitive status in older men. Methods. 440 old male subjects with different cognitive functions were recruited to investigate probable serum markers. Pearson Chi-Squared test, univariate analysis, and multivariate logistic regression analysis were performed to evaluate biomarkers which may be associated with cognitive status. Results. Levels of fundus atherosclerosis (AS) (P < 0.001), age (P < 0.001), serum biomarkers peroxidase (POD) (P = 0.026) and interleukin-6 (IL-6) (P = 0.001), serum levels of high-density lipoprotein cholesterol (HDL-C) (P < 0.001), apolipoprotein A2 (ApoA2) (P = 0.001), and ApoC2 (P = 0.005) showed significant differences. Compared to group 3, ApoA1 in group 1 (OR = 1.30, 95% CI 1.01-1.67) and group 2 (OR = 1.47, 95% CI 1.11-1.94) were higher, while ApoA2 were lower (group 1: OR = 0.43, 95% CI 0.18-1.02; group 2: OR = 0.21, 95% CI 0.08-0.54) after adjusting for control variables. Conclusion. The results demonstrated that age, AS levels, POD, IL-6, HDL-C, ApoA2, and ApoC2 were significantly related to cognitive status. Moreover, ApoA1 and ApoA2 were independently associated with cognitive impairment and late-life dementia. PMID:26682220

  3. Family Context, Mexican-Origin Adolescent Mothers&apos; Parenting Knowledge, and Children&apos;s Subsequent Developmental Outcomes

    ERIC Educational Resources Information Center

    Jahromi, Laudan B.; Guimond, Amy B.; Umaña-Taylor, Adriana J.; Updegraff, Kimberly A.; Toomey, Russell B.

    2014-01-01

    This study examined parenting knowledge among Mexican-origin adolescent mothers (N = 191; M[subscript age] = 16.26 years), family contextual factors associated with adolescents&apos; parenting knowledge, and toddlers&apos; (M[subscript age] = 2.01 years) subsequent developmental outcomes. Data came from home interviews and direct child…

  4. Is Cass&apos;s Model of Homosexual Identity Formation Relevant to Today&apos;s Society?

    ERIC Educational Resources Information Center

    Kenneady, Donna Ann; Oswalt, Sara B.

    2014-01-01

    Cass&apos;s Homosexual Identity Formation Model (1979) is one of the most well-known and well-referenced models of identity development for gay males and lesbians. This article provides a review of Cass&apos;s six steps of the model, as well as research support for and critiques of the model. As the model was developed more than 30 years ago, the…

  5. Inflammatory Stress Sensitizes the Liver to Atorvastatin-Induced Injury in ApoE-/- Mice

    PubMed Central

    Wu, Wei; Zhao, Lei; Yang, Ping; Zhou, Wei; Li, Beibei; Moorhead, John F.; Varghese, Zac; Ruan, Xiong Z.; Chen, Yaxi

    2016-01-01

    Statins, which are revolutionized cholesterol-lowing agents, have been reported to have unfavorable effects on the liver. Inflammatory stress is a susceptibility factor for drug-induced liver injury. This study investigated whether inflammatory stress sensitized the liver to statin-induced toxicity in mice and explored the underlying mechanisms. We used casein injection in ApoE-/- mice to induce inflammatory stress. Half of the mice were orally administered atorvastatin (10mg/kg/d) for 8 weeks. The results showed that casein injection increased the levels of serum pro-inflammatory cytokines (IL-6 and TNFα). Atorvastatin treatment increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in casein injection mice. Moreover, atorvastatin treatment exacerbated hepatic steatosis, inflammation and fibrosis, as well as increased hepatic reactive oxygen species (ROS) and malondialdehyde in casein injection mice. However, above changes were not observed in atorvastatin treated alone mice. The protein expression of liver nuclear factor erythroid 2-related factor 2 (Nrf2) and the mRNA expressions of Nrf2 target genes were increased, together with the enhancement of activities of hepatic catalase and superoxide dismutase in atorvastatin treated alone mice, but these antioxidant responses were lost in mice treated with atorvastatin under inflammatory stress. This study demonstrates that atorvastatin exacerbates the liver injury under inflammatory stress, which may be associated with the loss of adaptive antioxidant response mediated by Nrf2. PMID:27428373

  6. Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/- mice and cultured endothelial cells.

    PubMed

    Cao, Yi; Jacobsen, Nicklas Raun; Danielsen, Pernille Høgh; Lenz, Anke G; Stoeger, Tobias; Loft, Steffen; Wallin, Håkan; Roursgaard, Martin; Mikkelsen, Lone; Møller, Peter

    2014-03-01

    Accumulating evidences indicate that pulmonary exposure to carbon nanotubes (CNTs) is associated with increased risk of lung diseases, whereas the effect on the vascular system is less studied. We investigated vascular effects of 2 types of multiwalled CNTs (MWCNTs) in apolipoprotein E(-/-) mice, wild-type mice, and cultured cells. The ApoE(-/-) mice had accelerated plaque progression in aorta after 5 intracheal instillations of MWCNT (25.6 μg/mouse weekly for 5 weeks). The exposure was associated with pulmonary inflammation, lipid peroxidation, and increased expression of inflammatory, oxidative stress, DNA repair, and vascular activation response genes. The level of oxidatively damaged DNA in lung tissue was unaltered, probably due to increased DNA repair capacities. Despite upregulation of inflammatory genes in the liver, effects on systemic cytokines and lipid peroxidation were minimal. The exposure to MWCNTs in cultured human endothelial cells increased the expression of cell adhesion molecules (ICAM1 and VCAM1). In cocultures, there was increased adhesion of monocytes to endothelial cells after exposure to MWCNT. The exposure to both types of MWCNT was also associated with increased lipid accumulation in monocytic-derived foam cells, which was dependent on concomitant oxidative stress because the antioxidant N-acetylcysteine inhibited the lipid accumulation. Collectively, our results indicate that exposure to MWCNT is associated with accelerated progression of atherosclerosis, which could be related to both increased adherence of monocytes onto the endothelium and oxidative stress-mediated transformation of monocytes to foam cells.

  7. Inflammatory Stress Sensitizes the Liver to Atorvastatin-Induced Injury in ApoE-/- Mice.

    PubMed

    Wu, Wei; Zhao, Lei; Yang, Ping; Zhou, Wei; Li, Beibei; Moorhead, John F; Varghese, Zac; Ruan, Xiong Z; Chen, Yaxi

    2016-01-01

    Statins, which are revolutionized cholesterol-lowing agents, have been reported to have unfavorable effects on the liver. Inflammatory stress is a susceptibility factor for drug-induced liver injury. This study investigated whether inflammatory stress sensitized the liver to statin-induced toxicity in mice and explored the underlying mechanisms. We used casein injection in ApoE-/- mice to induce inflammatory stress. Half of the mice were orally administered atorvastatin (10mg/kg/d) for 8 weeks. The results showed that casein injection increased the levels of serum pro-inflammatory cytokines (IL-6 and TNFα). Atorvastatin treatment increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in casein injection mice. Moreover, atorvastatin treatment exacerbated hepatic steatosis, inflammation and fibrosis, as well as increased hepatic reactive oxygen species (ROS) and malondialdehyde in casein injection mice. However, above changes were not observed in atorvastatin treated alone mice. The protein expression of liver nuclear factor erythroid 2-related factor 2 (Nrf2) and the mRNA expressions of Nrf2 target genes were increased, together with the enhancement of activities of hepatic catalase and superoxide dismutase in atorvastatin treated alone mice, but these antioxidant responses were lost in mice treated with atorvastatin under inflammatory stress. This study demonstrates that atorvastatin exacerbates the liver injury under inflammatory stress, which may be associated with the loss of adaptive antioxidant response mediated by Nrf2. PMID:27428373

  8. Cellular source-specific effects of apolipoprotein (apo) E4 on dendrite arborization and dendritic spine development.

    PubMed

    Jain, Sachi; Yoon, Seo Yeon; Leung, Laura; Knoferle, Johanna; Huang, Yadong

    2013-01-01

    Apolipoprotein (apo) E4 is the leading genetic risk factor for Alzheimer's disease (AD), and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin (learning) and mushroom (memory) spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase (NSE)-apoE4 and apoE4-knockin (KI) mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein (GFAP)-apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4.

  9. Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia

    PubMed Central

    Toledo, Alvaro; Monzón, Javier D.; Coleman, James L.; Garcia-Monco, Juan C.; Benach, Jorge L.

    2015-01-01

    The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease. PMID:25870274

  10. Hypercholesterolemia and ApoE deficiency result in severe infection with Lyme disease and relapsing-fever Borrelia.

    PubMed

    Toledo, Alvaro; Monzón, Javier D; Coleman, James L; Garcia-Monco, Juan C; Benach, Jorge L

    2015-04-28

    The Lyme disease (Borrelia burgdorferi) and relapsing-fever (Borrelia hispanica) agents have distinct infection courses, but both require cholesterol for growth. They acquire cholesterol from the environment and process it to form cholesterol glycolipids that are incorporated onto their membranes. To determine whether higher levels of serum cholesterol could enhance the organ burdens of B. burgdorferi and the spirochetemia of B. hispanica in laboratory mice, apolipoprotein E (apoE)-deficient and low-density lipoprotein receptor (LDLR)-deficient mice that produce large amounts of serum cholesterol were infected with both spirochetes. Both apoE- and LDLR-deficient mice infected with B. burgdorferi had an increased number of spirochetes in the joints and inflamed ankles compared with the infected wild-type (WT) mice, suggesting that mutations in cholesterol transport that result in high serum cholesterol levels can affect the pathogenicity of B. burgdorferi. In contrast, elevated serum cholesterol did not lead to an increase in the spirochetemia of B. hispanica. In the LDLR-deficient mice, the course of infection was indistinguishable from the WT mice. However, infection of apoE-deficient mice with B. hispanica resulted in a longer spirochetemia and increased mortality. Together, these results argue for the apoE deficiency, and not hypercholesterolemia, as the cause for the increased severity with B. hispanica. Serum hyperlipidemias are common human diseases that could be a risk factor for increased severity in Lyme disease.

  11. The use of dipolar couplings for determining the solution structure of rat apo-S100B(betabeta).

    PubMed Central

    Drohat, A. C.; Tjandra, N.; Baldisseri, D. M.; Weber, D. J.

    1999-01-01

    The relative orientations of adjacent structural elements without many well-defined NOE contacts between them are typically poorly defined in NMR structures. For apo-S100B(betabeta) and the structurally homologous protein calcyclin, the solution structures determined by conventional NMR exhibited considerable differences and made it impossible to draw unambiguous conclusions regarding the Ca2+-induced conformational change required for target protein binding. The structure of rat apo-S100B(betabeta) was recalculated using a large number of constraints derived from dipolar couplings that were measured in a dilute liquid crystalline phase. The dipolar couplings orient bond vectors relative to a single-axis system, and thereby remove much of the uncertainty in NOE-based structures. The structure of apo-S100B(betabeta) indicates a minimal change in the first, pseudo-EF-hand Ca2+ binding site, but a large reorientation of helix 3 in the second, classical EF-hand upon Ca2+ binding. PMID:10211826

  12. The elevation of apoB in hypercholesterolemic patients is primarily attributed to the relative increase of apoB/Lp-PLA₂.

    PubMed

    Tellis, Constantinos C; Moutzouri, Eliza; Elisaf, Moses; Wolfert, Robert L; Tselepis, Alexandros D

    2013-12-01

    Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a risk factor of cardiovascular disease. Plasma Lp-PLA₂ is mainly associated with apolipoprotein (apo)B-containing lipoproteins, primarily with low density lipoproteins (LDLs). Importantly, only a proportion of circulating lipoproteins contain Lp-PLA₂. We determined the plasma levels of Lp-PLA₂-bound apoB (apoB/Lp-PLA₂) in patients with primary hypercholesterolemia. The effect of simvastatin therapy was also addressed. The plasma apoB/Lp-PLA₂ concentration in 50 normolipidemic controls and 53 patients with primary hypercholesterolemia at baseline and at 3 months posttreatment with simvastatin (40 mg/day) was determined by an enzyme-linked immunosorbent assay. The concentration of the apoB-containing lipoproteins that do not bind Lp-PLA₂ [apoB/Lp-PLA₂⁻] was calculated by subtracting the apoB/Lp-PLA₂ from total apoB. The apoB/Lp-PLA₂ levels were 3.6-fold higher, while apoB/Lp-PLA₂⁻ were 1.3-fold higher in patients compared with controls. After 3 months of simvastatin treatment apoB/Lp-PLA₂ and apoB/Lp-PLA₂⁻ levels were reduced by 52% and 33%, respectively. The elevation in apoB-containing lipoproteins in hypercholesterolemic patients is mainly attributed to the relative increase in the proatherogenic apoB/Lp-PLA₂, while simvastatin reduces these particles to a higher extent compared with apoB/Lp-PLA₂⁻. Considering that Lp-PLA₂ is proatherogenic, the predominance of apoB/Lp-PLA₂ particles in hypercholesterolemic patients may contribute to their higher atherogenicity and incidence of cardiovascular disease.

  13. Longitudinal Relations among Parents&apos; Reactions to Children&apos;s Negative Emotions, Effortful Control, and Math Achievement in Early Elementary School

    ERIC Educational Resources Information Center

    Swanson, Jodi; Valiente, Carlos; Lemery-Chalfant, Kathryn; Bradley, Robert H.; Eggum-Wilkens, Natalie D.

    2014-01-01

    Panel mediation models and fixed-effects models were used to explore longitudinal relations among parents&apos; reactions to children&apos;s displays of negative emotions, children&apos;s effortful control (EC), and children&apos;s math achievement (N = 291; M age in fall of kindergarten = 5.66 years, SD = 0.39 year) across kindergarten through…

  14. The Effects of a Master&apos;s Program on Teachers&apos; Science Instruction: Results from Classroom Observations, Teacher Reports, and Student Surveys

    ERIC Educational Resources Information Center

    Copur-Gencturk, Yasemin; Hug, Barbara; Lubienski, Sarah Theule

    2014-01-01

    This study examines the impact of a new master&apos;s degree program on the instructional practices of K-8 in-service teachers. This 2.5-year master&apos;s program was designed to deepen in-service teachers&apos; knowledge in science and mathematics and promote greater use of reform-oriented instruction. Teachers&apos; instructional practices were…

  15. A Womb with a Political View: Barbara Park&apos;s "MA! There&apos;s Nothing to Do Here!" Prenatal Parenting, and the Battle over Personhood

    ERIC Educational Resources Information Center

    Abate, Michelle Ann

    2013-01-01

    This essay makes the case that Barbara Park&apos;s picture book "MA! There&apos;s Nothing to Do Here!: A Word from Your Baby-in-Waiting" (2008) adds another equal-parts absurdist and alarming item to the ever-growing responsibilities of expecting mothers: ensuring that their fetus is entertained. The messages that Park&apos;s narrative…

  16. Mapping Low-Income African American Parents&apos; Roles in Their Children&apos;s Education in a Changing Political Economy

    ERIC Educational Resources Information Center

    Greene, Stuart

    2013-01-01

    Background: Much discussion and debate has surrounded the role that low-income minority parents can play in their children&apos;s education. Research focusing on parents&apos; roles has stressed parents&apos; sense of self-efficacy, cultural background, socio-economic factors, and the context of school to explain not only what motivates parents to…

  17. The Role of Collaborative Learning on Training and Development Practices within the Australian Men&apos;s Shed Movement: A Study of Five Men&apos;s Sheds

    ERIC Educational Resources Information Center

    Cavanagh, Jillian; Southcombe, Amie; Bartram, Tim

    2014-01-01

    This study examines the role and impact of collaborative learning on training and development practices in Australian Men&apos;s Sheds. We use a case study approach, underpinned by Peters and Armstrong&apos;s theoretical framework of collaborative learning in adult education, to investigate five Men&apos;s Sheds. Semi-structured interviews were…

  18. Constraints on Conceptual Change: How Elementary Teachers&apos; Attitudes and Understanding of Conceptual Change Relate to Changes in Students&apos; Conceptions

    ERIC Educational Resources Information Center

    Fulmer, Gavin W.

    2013-01-01

    Like their students, teachers may hold a variety of naïve conceptions that have been hypothesized to limit their ability to support students&apos; learning. This study examines whether changes in elementary students&apos; conceptions are related to their teachers&apos; content knowledge, attitudes, and understanding of conceptual change. The study…

  19. Is Montgomery County&apos;s Housing Policy One Answer to Baltimore&apos;s Education Achievement Gap? The Abell Report. Volume 24, No.3

    ERIC Educational Resources Information Center

    Schwartz, Heather L.

    2011-01-01

    In 1966, the Coleman Report firmly established the link between a family&apos;s socioeconomic status and a child&apos;s educational outcomes. Known as the "income achievement gap," the disparity between the achievement of poor and rich children has become entrenched in our nation&apos;s educational landscape: with few exceptions, schools…

  20. Pre-Service Teachers&apos; and Teacher-Educators&apos; Experiences and Attitudes toward Using Social Networking Sites for Collaborative Learning

    ERIC Educational Resources Information Center

    Soomro, Kamal Ahmed; Kale, Ugur; Zai, Sajid Yousuf

    2014-01-01

    Extensive use of social networking sites by students and teachers makes educators and researchers to think whether they can be incorporated in instructional process to facilitate students&apos; learning. This survey-based study records and examines Pakistani pre-service teachers&apos; and teacher-educators&apos; current uses of Facebook, and their…

  1. Transition to Early Childhood Education: Parents&apos; Use of Coping Strategies in Dealing with Children&apos;s Adjustment Difficulties in Hong Kong

    ERIC Educational Resources Information Center

    Lam, Mei Seung

    2014-01-01

    The transition from home to early childhood education can be stressful for both children and parents. How parents cope with this potentially stressful event affects both the children&apos;s adaptation and the parents&apos; lives during the preschooler stage of the family lifecycle. This paper examines how parents respond to their children&apos;s…

  2. Gender Norms, Poverty and Armed Conflict in Côte D&apos;Ivoire: Engaging Men in Women&apos;s Social and Economic Empowerment Programming

    ERIC Educational Resources Information Center

    Falb, K. L.; Annan, J.; King, E.; Hopkins, J.; Kpebo, D.; Gupta, J.

    2014-01-01

    Engaging men is a critical component in efforts to reduce intimate partner violence (IPV). Little is known regarding men&apos;s perspectives of approaches that challenge inequitable gender norms, particularly in settings impacted by armed conflict. This article describes men&apos;s experiences with a women&apos;s empowerment program and highlights…

  3. When Stories Don&apos;t Make Sense: Alternative Ways to Assess Young Children&apos;s Narratives in Social Contexts

    ERIC Educational Resources Information Center

    Kim, MinJeong; Covino, Katharine

    2015-01-01

    Assessing children&apos;s narratives through the lens of intertexual process makes visible children&apos;s funds of knowledge. The authors describe two interrelated alternative assessments that teachers can use to make sense of young children&apos;s narratives in classroom settings. Implications for promoting an intertextually-rich environment…

  4. Do Mothers&apos; and Fathers&apos; Authoritative and Authoritarian Parenting Interact? An Exploration on Schooling Aspects with a Singapore Adolescent Sample

    ERIC Educational Resources Information Center

    Sim, Tick N.; Chin, Jeffery E. H.

    2014-01-01

    Our study sought mainly to examine interactions between mothers&apos; and fathers&apos; authoritative and authoritarian parenting. A total of 284 adolescents (mean age 13.5) from 2 Singapore schools contributed self-report data on their parents&apos; parenting and various schooling aspects. Prior to testing for interactions, adolescents with two…

  5. "I Don&apos;t Think I Could, You Know, Just Teach without Any Emotion": Exploring the Nature and Origin of University Teachers&apos; Emotions

    ERIC Educational Resources Information Center

    Hagenauer, Gerda; Volet, Simone

    2014-01-01

    This article addresses the issue of university teachers&apos; emotions generated through teaching and interacting with students. While research on school teachers&apos; emotions is on the increase, interest in the significance of university teachers&apos; emotions is still limited. In light of the growing attention given to the quality of…

  6. Influence of apoE content on receptor binding of large, bouyant LDL in subjects with different LDL subclass phenotypes.

    PubMed

    Barbagallo, C M; Levine, G A; Blanche, P J; Ishida, B Y; Krauss, R M

    1998-03-01

    We investigated the influence of apolipoprotein (apo) E-containing particles on LDL receptor binding of large, buoyant LDL subfractions (LDL I) from subjects with predominantly large (phenotype A) and small (phenotype B) LDL particles. Direct binding by human fibroblast LDL receptors was tested at 4 degrees C before and after removal of apoE-containing particles by immunoaffinity chromatography. The binding affinity of total LDL I in phenotype B was greater than that in phenotype A (Kd of 1.83+/-0.3 and 3.43+/-0.9 nmol/L, respectively, P<.05). LDL I from phenotype B subjects had a higher apoE to apoB molar ratio than did that from phenotype A (0.16+/-0.04 versus 0.06+/-0.02, P<.05). Nondenaturing gradient gel electrophoresis of apoE-containing LDL I isolated by immunoaffinity chromatography revealed a substantially larger peak particle diameter than in apoE-free LDL I, and comparison of LDL I composition before and after immunoaffinity chromatography suggested an increase in triglyceride content of apoE-containing particles. After removal of these particles, there was a greater than twofold reduction in LDL receptor affinity of phenotype B LDL (Kd of 1.83+/-0.3 to 3.76+/-0.6, P<.01), whereas in phenotype A no change was observed (Kd of 3.43+/-0.9 to 3.57+/-0.4, respectively). The receptor affinity of apoE-free LDL I from phenotype A and B subjects did not differ. These findings confirm that large, buoyant LDL particles from phenotype B subjects have a higher LDL receptor affinity than does LDL I from phenotype A subjects and suggest that this difference is due to an increased content of large, triglyceride-enriched, apoE-containing lipoproteins. It is possible that the accumulation of these particles reflects abnormalities in the metabolism of remnant lipoproteins that contribute to atherosclerosis risk in phenotype B subjects.

  7. Does the geographical gradient of ApoE4 allele exist in China? A systemic comparison among multiple Chinese populations.

    PubMed

    Hu, Peng; Qin, Yuan Han; Jing, Cheng Xue; Lu, Ling; Hu, Bo; Du, Peng Fei

    2011-01-01

    The allelic frequencies of apolipoprotein E (apoE) vary substantially around the world. There is a conspicuous south-to-north gradient of e4 frequencies in Europe, with the proportion of e4 carriers from only 10-15% in the south to 40-50% in the north. The mechanism may be related to the possibility that e4 carriers are less likely to develop vitamin D deficiency. In addition, Asian populations traditionally have lower e4 frequency than Europeans, which may be attributed in part to the scarce or irregular food supplies in Western world in the recent past. However, whether these geographical distribution gradients exist in China is yet unknown. ApoE genotypes of 200 children from Nanning City were determined by PCR-restriction fragment length polymorphism (RFLP) analysis. Allele frequency data of 18 other populations were collected from published sources and correlated with latitude and longitude information from different geographic resources. In our subjects, the frequencies of apoE genotypes were E3/E3: 73.0%, E3/E2: 15.0%, E4/E3: 5.0%, E4/E4: 5.0%, and E4/E2: 2.0%; the frequencies of apoE alleles were e2: 8.5%, e3: 83.0%, and e4: 8.5%, respectively. The total sample consisted of 3,679 individuals from 19 Chinese populations; the allelic frequencies were e2: 7.6%, e3: 85.5%, and e4: 6.9%, respectively; the proportion of e4 carriers was from 4.9% in Kunming to 17.5% in Harbin. Systemic comparison among multiple Chinese populations revealed that positive correlation existed between the e4 allele frequency distribution and latitude north (r=0.586, P=0.008), but no correlation of the e4 allele frequency distribution with longitude east was found (r=-0.018, P=0.942). We conclude that there is a south-to-north, but not an east-to-west gradient for the apoE4 allele in China.

  8. "I Will Be &apos;Fighting&apos; Even More for Pupils with SEN": SENCOs&apos; Role Predictions in the Changing English Policy Context

    ERIC Educational Resources Information Center

    Pearson, Sue; Mitchell, Rafael; Rapti, Maria

    2015-01-01

    The Coalition Government&apos;s "Green Paper" (DfE 2011) proposes a systemic overhaul of services for pupils with special educational needs in England, with increased parental choice of provision and "sharper accountability" (p. 67) in schools. Deadlines for various stages of this reform have not been met, and its final nature…

  9. Ke Ha&apos;a La Puna i Ka Makani: Pele and Hi&apos;iaka Mo&apos;olelo and the Possibilities for Hawaiian Literary Analysis

    ERIC Educational Resources Information Center

    ho'omanawanui, ku'ualoha

    2013-01-01

    In 2003, the University of Hawai&apos;i sponsored a symposium titled "Indigenizing the University." This symposium featured indigenous scholars such as Linda Tuhiwai Smith, Graham Smith, and Taiaiake Alfred, who addressed how indigenous political theory and methods of research were necessary to support indigenous research and how changes…

  10. "Doesn&apos;t Everyone Want That? It&apos;s Just a Given": Swedish Emerging Adults&apos; Expectations on Future Parenthood and Work/Family Priorities

    ERIC Educational Resources Information Center

    Frisén, Ann; Carlsson, Johanna; Wängqvist, Maria

    2014-01-01

    This study investigated Swedish emerging adults&apos; expectations on future parenthood through interviews with 124 Swedish emerging adults who were not yet parents. Thematic analysis showed that most participants were sure they wanted to become parents, but not right now. First, they wanted a stable financial situation, a romantic relationship,…

  11. "I Don&apos;t Think I&apos;ve Ever Had Discussions about Reading": A Case Study of FE Literacy Teachers&apos; Conceptualisations of Literacy

    ERIC Educational Resources Information Center

    Kendall, Alex; McGrath, Karen

    2014-01-01

    Research on reading in the lifelong-learning sector has tended to focus on the attitudes, habits and practices of the recipients of further education (FE), or the practices of literacy within the cultural and contextual environments of the subjects and spaces of further education. Although teachers&apos; conceptualisations of literacy are often…

  12. "Everything&apos;s Upside Down. We&apos;ll Call It Upside Down Valley!": Siblings&apos; Creative Play Themes, Object Use, and Language during Pretend Play

    ERIC Educational Resources Information Center

    Howe, Nina; Abuhatoum, Shireen; Chang-Kredl, Sandra

    2014-01-01

    Research Findings: Pretend play is an important context that supports young children&apos;s developing social-cognitive and creative abilities. The play behaviors of 70 sibling dyads in early and middle childhood were examined for the following indices of creativity in play: (a) play themes (set-up/organization, expected, creative), (b) object use…

  13. The School&apos;s Role in Youths&apos; Political Efficacy: Can School Provide a Compensatory Boost to Students&apos; Political Efficacy?

    ERIC Educational Resources Information Center

    Sohl, Sofia; Arensmeier, Cecilia

    2015-01-01

    In the democracies of today, school often have a dual role to play. Not only should they give students the knowledge they need to enter the labour market, they should also teach young people about democracy, and develop students&apos; capacity to exercise their citizenship. A third task for schools is to enhance political equality in society by…

  14. Representin&apos; and Disrespectin&apos;: African-American Wind Band Students&apos; Meanings of a Composition-Based Secondary Music Curriculum and Classroom Power Structures

    ERIC Educational Resources Information Center

    Hoffman, Adria Rachel; Carter, Bruce Allen

    2013-01-01

    Although cultural diversity is important to the social context of classrooms, few researchers have explored school music experiences from the perspective of students of colour. Possibly of greater concern is the absence of research examining African-American students&apos; educational experiences in early secondary education, during which time the…

  15. "If They&apos;re the Customer, I&apos;m the Meat in the Sandwich": An Exploration of Tertiary Teachers&apos; Metaphorical Constructions of Teaching

    ERIC Educational Resources Information Center

    Emerson, Lisa; Mansvelt, Juliana

    2014-01-01

    Metaphors are a primary influence on the way we perceive and construct our world; they are also a way of revealing beliefs and attitudes that might otherwise be difficult to identify. Furthermore, metaphor has been found to be an effective way of shifting people&apos;s beliefs, attitudes and behaviour. This paper details the findings of a pilot…

  16. Response to John Merrifield&apos;s Comment, "Can We Reasonably Assess &apos;Productivity of Market-Based Educational Reforms&apos;?"

    ERIC Educational Resources Information Center

    Egalite, Anna J.

    2013-01-01

    John Merrifield (in this issue) raises three important observations regarding this review of the literature on the competition effects of school vouchers. The first is an acknowledgment of the limited nature of current school choice markets in the United States. Merrifield&apos;s second observation is that the potential responses to competition…

  17. "You Don&apos;t Need to Be Mean. We&apos;re Friends, Right?": Young Korean-American Children&apos;s Conflicts and References to Friendship

    ERIC Educational Resources Information Center

    Kim, Jinhee

    2014-01-01

    In the eyes of adults, conflicts between children are often treated as problematic social interactions that should be prevented. This study describes how young Korean-American children&apos;s conflict negotiation was a central part of their peer culture at a Korean heritage language school in the United States. Eleven young Korean-American…

  18. Effect of repeated apoA-IMilano/POPC infusion on lipids, (apo)lipoproteins, and serum cholesterol efflux capacity in cynomolgus monkeys.

    PubMed

    Kempen, Herman J; Gomaraschi, Monica; Bellibas, S Eralp; Plassmann, Stephanie; Zerler, Brad; Collins, Heidi L; Adelman, Steven J; Calabresi, Laura; Wijngaard, Peter L J

    2013-09-01

    MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitored. After 7 or 20 infusions, free cholesterol (FC) and phospholipids (PL) were strongly increased, and HDL-cholesterol (HDL-C), apoA-I, and apoA-II were strongly decreased. We then measured short-term effects on apoA-IM, lipids, and (apo)lipoproteins after the first or the last infusion. After the first infusion, PL and FC went up in the HDL region and also in the LDL and VLDL regions. ApoE shifted from HDL to LDL and VLDL regions, while ApoA-IM remained located in the HDL region. On day 41, ApoE levels were 8-fold higher than on day 1, and FC, PL, and apoE resided mostly in LDL and VLDL regions. Drug infusion quickly decreased the endogenous cholesterol esterification rate. ABCA1-mediated cholesterol efflux on day 41 was markedly increased, whereas scavenger receptor type B1 (SRB1) and ABCG1-mediated effluxes were only weakly increased. Strong increase of FC is due to sustained stimulation of ABCA1-mediated efflux, and drop in HDL and formation of large apoE-rich particles are due to lack of LCAT activation. PMID:23828780

  19. Effect of repeated apoA-IMilano/POPC infusion on lipids, (apo)lipoproteins, and serum cholesterol efflux capacity in cynomolgus monkeys[S

    PubMed Central

    Kempen, Herman J.; Gomaraschi, Monica; Bellibas, S. Eralp; Plassmann, Stephanie; Zerler, Brad; Collins, Heidi L.; Adelman, Steven J.; Calabresi, Laura; Wijngaard, Peter L. J.

    2013-01-01

    MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitored. After 7 or 20 infusions, free cholesterol (FC) and phospholipids (PL) were strongly increased, and HDL-cholesterol (HDL-C), apoA-I, and apoA-II were strongly decreased. We then measured short-term effects on apoA-IM, lipids, and (apo)lipoproteins after the first or the last infusion. After the first infusion, PL and FC went up in the HDL region and also in the LDL and VLDL regions. ApoE shifted from HDL to LDL and VLDL regions, while ApoA-IM remained located in the HDL region. On day 41, ApoE levels were 8-fold higher than on day 1, and FC, PL, and apoE resided mostly in LDL and VLDL regions. Drug infusion quickly decreased the endogenous cholesterol esterification rate. ABCA1-mediated cholesterol efflux on day 41 was markedly increased, whereas scavenger receptor type B1 (SRB1) and ABCG1-mediated effluxes were only weakly increased. Strong increase of FC is due to sustained stimulation of ABCA1-mediated efflux, and drop in HDL and formation of large apoE-rich particles are due to lack of LCAT activation. PMID:23828780

  20. Apo-dystrophin-1 and apo-dystrophin-2, products of the Duchenne muscular dystrophy locus: expression during mouse embryogenesis and in cultured cell lines.

    PubMed

    Schofield, J N; Blake, D J; Simmons, C; Morris, G E; Tinsley, J M; Davies, K E; Edwards, Y H

    1994-08-01

    Two promoters in the distal half of the Duchenne Muscular Dystrophy gene drive transcription of mRNAs which have novel first exons and encode the shortened forms of dystrophin, apo-dystrophin-1 (Dp71) and apo-dystrophin-2 (Dp116). Apo-dystrophin-1 has a G + C rich promoter and is expressed in a wide range of cell types, whilst apo-dystrophin-2 is confined to peripheral nerve and brain. We have isolated and sequenced the unique 5' exon of rat apo-dystrophin-2 mRNA. Conceptual translation of this sequence indicates that apo-dystrophin-2 contains a unique 23 amino acid terminal peptide. Using specific probes derived from sequences at the 5' ends of apo-dystrophin-1 and apo-dystrophin-2 we have determined the expression of these two mRNAs during mouse embryonic development by RNA in situ hybridization. In contrast to full-length dystrophin, neither of these short dystrophin transcripts appear before organogenesis is well established. Apo-dystrophin-1 mRNA is detected in midline cells of the ventral neural tube and later, in the ependymal cells lining the ventricles of the brain. These results suggest that apo-dystrophin-1 mRNA is associated with glial cells in the CNS. Apo-dystrophin-1 transcripts are also abundant in the teeth primordia throughout their development. In contrast apo-dystrophin-2 mRNA is largely undetectable during development, although transcripts are seen in the newborn brain. Western blots of late human fetal tissue extracts confirm that apo-dystrophin-2 is most abundant in brain and analysis of RNA and protein in cultured cell lines reveal expression of apo-dystrophin-1 and apo-dystrophin-2 in glioma cells.

  1. APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease.

    PubMed

    Yang, Yue; Cudaback, Eiron; Jorstad, Nikolas L; Hemingway, Jake F; Hagan, Catherine E; Melief, Erica J; Li, Xianwu; Yoo, Tom; Khademi, Shawn B; Montine, Kathleen S; Montine, Thomas J; Keene, C Dirk

    2013-09-01

    Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein-expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT-recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT-recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.

  2. A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice.

    PubMed

    Jahagirdar, Ravi; Zhang, Haiyan; Azhar, Salman; Tobin, Jennifer; Attwell, Sarah; Yu, Raymond; Wu, Jin; McLure, Kevin G; Hansen, Henrik C; Wagner, Gregory S; Young, Peter R; Srivastava, Rai Ajit K; Wong, Norman C W; Johansson, Jan

    2014-09-01

    Despite the benefit of statins in reducing cardiovascular risk, a sizable proportion of patients still remain at risk. Since HDL reduces CVD risk through a process that involves formation of pre-beta particles that facilitates the removal of cholesterol from the lipid-laden macrophages in the arteries, inducing pre-beta particles, may reduce the risk of CVD. A novel BET bromodomain antagonist, RVX-208, was reported to raise apoA-I and increase preβ-HDL particles in non-human primates and humans. In the present study, we investigated the effect of RVX-208 on aortic lesion formation in hyperlipidemic apoE(-/-) mice. Oral treatments of apoE(-/-) mice with 150 mg/kg b.i.d RVX-208 for 12 weeks significantly reduced aortic lesion formation, accompanied by 2-fold increases in the levels of circulating HDL-C, and ∼50% decreases in LDL-C, although no significant changes in plasma apoA-I were observed. Circulating adhesion molecules as well as cytokines also showed significant reduction. Haptoglobin, a proinflammatory protein, known to bind with HDL/apoA-I, decreased >2.5-fold in the RVX-208 treated group. With a therapeutic dosing regimen in which mice were fed Western diet for 10 weeks to develop lesions followed by switching to a low fat diet and concurrent treatment with RVX-208 for 14 weeks, RVX-208 similarly reduced lesion formation by 39% in the whole aorta without significant changes in the plasma lipid parameters. RVX-208 significantly reduced the proinflammatory cytokines IP-10, MIP1(®) and MDC. These results show that the antiatherogenic activity of BET inhibitor, RVX-208, occurs via a combination of lipid changes and anti-inflammatory activities.

  3. VNN1 promotes atherosclerosis progression in apoE-/- mice fed a high-fat/high-cholesterol diet.

    PubMed

    Hu, Yan-Wei; Wu, Shao-Guo; Zhao, Jing-Jing; Ma, Xin; Lu, Jing-Bo; Xiu, Jian-Cheng; Zhang, Yuan; Huang, Chuan; Qiu, Yu-Rong; Sha, Yan-Hua; Gao, Ji-Juan; Wang, Yan-Chao; Li, Shu-Fen; Zhao, Jia-Yi; Zheng, Lei; Wang, Qian

    2016-08-01

    Accumulated evidence shows that vanin-1 (VNN1) plays a key part in glucose metabolism. We explored the effect of VNN1 on cholesterol metabolism, inflammation, apoptosis in vitro, and progression of atherosclerotic plaques in apoE(-/-) mice. Oxidized LDL (Ox-LDL) significantly induced VNN1 expression through an ERK1/2/cyclooxygenase-2/PPARα signaling pathway. VNN1 significantly increased cellular cholesterol content and decreased apoAI and HDL-cholesterol (HDL-C)-mediated efflux by 25.16% and 23.13%, respectively, in THP-1 macrophage-derived foam cells (P < 0.05). In addition, VNN1 attenuated Ox-LDL-induced apoptosis through upregulation of expression of p53 by 59.15% and downregulation of expression of B-cell lymphoma-2 127.13% in THP-1 macrophage (P < 0.05). In vivo, apoE(-/-) mice were divided randomly into two groups and transduced with lentivirus (LV)-Mock or LV-VNN1 for 12 weeks. VNN1-treated mice showed increased liver lipid content and plasma levels of TG (124.48%), LDL-cholesterol (119.64%), TNF-α (148.74%), interleukin (IL)-1β (131.81%), and IL-6 (156.51%), whereas plasma levels of HDL-C (25.75%) were decreased significantly (P < 0.05). Consistent with these data, development of atherosclerotic lesions was increased significantly upon infection of apoE(-/-) mice with LV-VNN1. These observations suggest that VNN1 may be a promising therapeutic candidate against atherosclerosis. PMID:27281478

  4. The APOE Genotype in Idiopathic Normal Pressure Hydrocephalus

    PubMed Central

    Yang, Yi; Mehlig, Kirsten; Rosengren, Annika; Torén, Kjell; Zetterberg, Henrik; Wikkelsö, Carsten

    2016-01-01

    Introduction Amyloid plaque has been reported in brain biopsies from patients with idiopathic normal-pressure hydrocephalus (iNPH) and proposed as a significant feature of the pathophysiology. Presence of the apolipoprotein E ε4 (APOE ε4) allele is associated with increased risk of Alzheimer’s disease (AD). Aims To compare the distribution of APOE genotype in iNPH patients with an age-matched population-based control group and with Alzheimer’s disease (AD) patients. Methods APOE genotype frequencies were determined in 77 iNPH patients (50 men and 27 women, mean age 71.7 years) diagnosed with iNPH, a sample of 691 AD patients and 638 age-matched population controls (299 men and 339 women) from the INTERGENE cohort. Results The APOE distribution did not differ significantly between the iNPH patients and the control population. The per e4-allele odds-ratio (OR) of iNPH was given by OR = 0.90, 95% confidence interval (CI) = (0.50, 1.60) that was considerably smaller than the per-allele OR of AD, OR = 5.34 (4.10, 7.00). Conclusion The results suggest that the APOE-related risk of AD in patients with iNPH is not higher than in the general population. PMID:27441602

  5. Metabolic disturbances and worsening of atherosclerotic lesions in ApoE-/- mice after cola beverages drinking

    PubMed Central

    2013-01-01

    Background Atherosclerosis is a major health burden. Metabolic disorders had been associated with large consumption of soft drinks. The rising incidence of atherosclerosis and metabolic alterations warrants the study of long-term soft drink consumption’ effects on metabolism and atherosclerosis in genetic deficiency of apolipoprotein E which typically develops spontaneous atherosclerosis and metabolic alterations. Methods ApoE-/- mice were randomized in 3 groups accordingly with free access to: water (W), regular cola (C) or light cola (L). After 8 weeks, 50% of the animals in each group were euthanized (Treatment: W8, C8, L8). The remaining mice (all groups) drank water for 8 weeks and were euthanized (Washout: W16, C16, L16). Body weight and food and drink consumption were periodically measured. Blood was collected (biochemistry). At autopsy, transverse aortic sinus sections were serially cut and stained (histomorphometry); livers and kidneys were processed (microscopy). MANOVA (identification of variance factors) was followed by ANOVA and LSD tests (within-factor differences between levels). Conventionally a p< 0.05 was considered significant. Results Treatment increased drinking volumes (vs W8: 4 fold C8, p<0.0001; +47% L8, p<0.02). Only C reduced eating amounts (–54%, p<0.05 vs W8). I). Compared with W8: C8 developed hyperglycemia (+43%, p<0.03) and increased non-HDL cholesterol (+54%, p<0.05); L8 showed decreased glycemia (–15%, p<0.05 vs W8) and increased creatinine (2.5 fold, p<0.04), urea (+74, p<0.03) and aspartate-aminotransferase (2.8 fold, p<0.05). Hypercreatininemia was observed in L16 (2.7 fold vs W16, p<0.05). Hypertriglyceridemia (+91%, p<0.008) and hyperuremia (+68%, p<0.03) developed over time of study (age). II). Treatment caused plaque area increase (vs W8: 28% C8, p<0.02 and 50% L8, p<0.01; vs W16: 43% C16, p<0.05 and 68% L16, p<0.02) and stenosis (vs W8: 38% C8, p<0.04 and 57% L8, p<0.01; vs W16: 71% C16, p<0.01 and 46% L16, p<0

  6. Poor maternal nutrition programmes a pro-atherosclerotic phenotype in ApoE-/- mice.

    PubMed

    Blackmore, Heather L; Piekarz, Ana V; Fernandez-Twinn, Denise S; Mercer, John R; Figg, Nichola; Bennett, Martin; Ozanne, Susan E

    2012-08-01

    Numerous animal studies have consistently shown that early life exposure to LP (low-protein) diet programmes risk factors for CVD (cardiovascular disease) such as dyslipidaemia, high BP (blood pressure) and cardiac dysfunction in the offspring. However, studies on the effect of maternal under-nutrition on offspring development of atherosclerosis are scarce. Applying our LP model to the ApoE(-/-) atherosclerosis-prone mouse model, we investigated the development of atherosclerotic lesions in the aortic root of 6-month-old offspring. In addition, markers of plaque progression including SMA (smooth muscle actin) and Mac3 (macrophage marker 3) were studied. Pregnant dams were fed on a control (20% protein) or on an isocaloric LP diet (8% protein) throughout pregnancy and lactation. After weaning, male offspring were maintained on 20% normal laboratory chow. At 6 months of age, LP offspring showed a significantly greater plaque area (P<0.05) with increased cholesterol clefts and significantly higher indices of DNA damage compared with controls (P<0.05). The expression of HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase) (P<0.05) and LDL (low-density lipoprotein) receptor in the liver of LP offspring were increased. Furthermore, LP offspring had higher LDL-cholesterol levels (P<0.05) and a trend towards elevated insulin. There were no differences in other lipid measurements and fasting glucose between groups. These observations suggest that early exposure to an LP diet accelerates the development and increases the progression of atherosclerotic lesions in young adult offspring. Future studies are needed to elucidate the specific mechanisms linking in utero exposure to a diet low in protein to the development of atherosclerosis.

  7. Exposure to diesel exhaust upregulates COX-2 expression in ApoE knockout mice

    PubMed Central

    Bai, Ni; Tranfield, Erin M.; Kavanagh, Terrance J.; Kaufman, Joel D.; Rosenfeld, Michael E.; van Eeden, Stephan F.

    2015-01-01

    Introduction We have shown that diesel exhaust (DE) inhalation caused progression of atherosclerosis; however, the mechanisms are not fully understood. We hypothesize that exposure to DE upregulates cyclooxygenase (COX) expression and activity, which could play a role in DE-induced atherosclerosis. Methods ApoE knockout mice (30-week old) fed with regular chow were exposed to DE (at 200 μg/m3 of particulate matter) or filtered air (control) for 7 weeks (6 h/day, 5 days/week). The protein and mRNA expression of COX-1 and COX-2 were evaluated by immunohistochemistry analysis and quantitative real-time PCR, respectively. To examine COX activity, thoracic aortae were mounted in a wire myograph, and phenylephrine (PE)-stimulated vasoconstriction was measured with and without the presence of COX antagonists (indomethacin). COX-2 activity was further assessed by urine 2,3-dinor-6-keto PGF1α level, a major metabolite of prostacyclin I2 (PGI2). Results Immunohistochemistry analysis demonstrates that DE exposure enhanced COX-2 expression in both thoracic aorta (p < 0.01) and aortic root (p < 0.03), with no modification of COX-1 expression. The increased COX-2 expression was positively correlated with smooth muscle cell content in aortic lesions (R2 = 0.4081, p < 0.008). The fractional changes of maximal vasoconstriction in the presence of indomethacin was attenuated by 3-fold after DE exposure (p < 0.02). Urine 2,3-dinor-6-keto PGF1α level was 15-fold higher in DE group than the control (p < 0.007). The mRNA expression of COX-2 (p < 0.006) and PGI synthase (p < 0.02), but not COX-1, was significantly augmented after DE exposure. Conclusion We show that DE inhalation enhanced COX-2 expression, which is also associated with phenotypic changes of aortic lesion. PMID:22746401

  8. Effects of Tomato and Soy Germ on Lipid Bioaccumulation and Atherosclerosis in ApoE-/- Mice.

    PubMed

    Smith, Brendon W; Miller, Rita J; Wilund, Kenneth R; O'Brien, William D; Erdman, John W

    2015-08-01

    Dietary patterns with cardiovascular benefits have been recommended, but the relative contributions of individual foods and food components, alone or in combination, remain undefined. Male ApoE(-/-) mice were fed either a purified AIN-93G control diet, a Western diet (WD), or a WD with 10% tomato powder (TP), 2% soy germ (SG), or the combination, for 4 wk (n = 10 per group). Plasma total cholesterol and triglycerides were measured with enzymatic colorimetric kits, and serum amyloid A (SAA) was measured by ELISA. Liver lipids were extracted with chloroform:methanol, and triglycerides, free and esterified cholesterol measured with enzymatic colorimetric kits. Expression of Cyp27a1, Cyp7a1, Abcg5, and Abcg8 in the liver was determined by quantitative polymerase chain reaction. Sections of the aortic root and aorta were cut and stained with hematoxylin and eosin (H&E) to assess extent of atherosclerotic lesions. WD-fed animals had greater liver and adipose weights, plasma cholesterol and SAA, hepatic lipids, and atherosclerosis than AIN-93G animals. TP and SG did not decrease atherosclerosis as measured by H&E-stained sections of the aortic root, aortic arch, and descending aorta. The TP diets further increased plasma cholesterol, but also led to increased expression of the Abcg5/8 transporters involved in cholesterol efflux. Addition of SG alone to the WD attenuated WD-induced increases in plasma cholesterol, liver lipids, and gonadal adipose weight. The results of this study do not support the use of either TP or SG for reduction of atherosclerosis, but suggest some beneficial effects of SG on lipid metabolism in this model of cardiovascular disease. PMID:26173004

  9. Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice

    SciTech Connect

    Srivastava, Sanjay; Vladykovskaya, Elena N.; Haberzettl, Petra; Sithu, Srinivas D.; D'Souza, Stanley E.; States, J. Christopher

    2009-11-15

    Exposure to arsenic-contaminated water has been shown to be associated with cardiovascular disease, especially atherosclerosis. We examined the effect of arsenic exposure on atherosclerotic lesion formation, lesion composition and nature in ApoE-/- mice. Early post-natal exposure (3-week-old mice exposed to 49 ppm arsenic as NaAsO{sub 2} in drinking water for 7 weeks) increased the atherosclerotic lesion formation by 3- to 5-fold in the aortic valve and the aortic arch, without affecting plasma cholesterol. Exposure to arsenic for 13 weeks (3-week-old mice exposed to 1, 4.9 and 49 ppm arsenic as NaAsO{sub 2} in drinking water) increased the lesion formation and macrophage accumulation in a dose-dependent manner. Temporal studies showed that continuous arsenic exposure significantly exacerbated the lesion formation throughout the aortic tree at 16 and 36 weeks of age. Withdrawal of arsenic for 12 weeks after an initial exposure for 21 weeks (to 3-week-old mice) significantly decreased lesion formation as compared with mice continuously exposed to arsenic. Similarly, adult exposure to 49 ppm arsenic for 24 weeks, starting at 12 weeks of age increased lesion formation by 2- to 3.6-fold in the aortic valve, the aortic arch and the abdominal aorta. Lesions of arsenic-exposed mice displayed a 1.8-fold increase in macrophage accumulation whereas smooth muscle cell and T-lymphocyte contents were not changed. Expression of pro-inflammatory chemokine MCP-1 and cytokine IL-6 and markers of oxidative stress, protein-HNE and protein-MDA adducts were markedly increased in lesions of arsenic-exposed mice. Plasma concentrations of MCP-1, IL-6 and MDA were also significantly elevated in arsenic-exposed mice. These data suggest that arsenic exposure increases oxidative stress, inflammation and atherosclerotic lesion formation.

  10. Oral rapamycin inhibits growth of atherosclerotic plaque in apoE knock-out mice

    SciTech Connect

    Waksman, Ron; Pakala, Rajbabu; Burnett, Mary S.; Gulick, Cindy P.; Leborgne, Laurent; Fournadjiev, Jana; Wolfram, Roswitha; Hellinga, David

    2003-03-01

    Introduction: Inflammatory and immunological responses of vascular cells are known to play significant roles in atherosclerotic plaque development. Rapamycin with antiinflammatory, immunosuppressive and antiproliferative properties has been shown to reduce neointima formation when coated on stents. This study is designed to test the potential of oral rapamycin to inhibit atherosclerotic plaque development. Methods: Eight-week-old apoE knock-out mice were fed with 0.25% cholesterol supplemented diet (control diet), control diet containing 50 {mu}g/kg rapamycin (low-dose rapamycin) or 100 {mu}g/kg rapamycin (high-dose rapamycin) for 4 or 8 weeks. Subsets of mice from each group (n=10) were weighed and euthanized. Whole blood rapamycin levels were determined using HPLC-MS/MS, and histological analyses of atherosclerotic lesions in the aortic root were performed. Results: Mice fed with high-dose rapamycin did not gain weight (18.5{+-}1.5 vs. 20.6{+-}0.9 g, P=.01). Blood levels of rapamycin 117{+-}7 pg/ml were detected in the blood of mice fed with high-dose rapamycin for 8 weeks. The plaque area in mice fed with high dose oral rapamycin is significantly less as compared to control (0.168{+-}0.008 vs. 0.326{+-}0.013 mm{sup 2}, P=.001 at 4 weeks; 0.234{+-}0.013 vs. 0.447{+-}0.011 mm{sup 2}, P=.001 at 8 weeks). Lumen area was inversely proportional to the plaque area. Conclusions: The results indicate that oral rapamycin is effective in attenuating the progression of atherosclerotic plaque in the mice.

  11. Binding and repressive activities of apolipoprotein E3 and E4 isoforms on the human ApoD promoter.

    PubMed

    Levros, Louis-Charles; Labrie, Marilyne; Charfi, Cyndia; Rassart, Eric

    2013-12-01

    Apolipoprotein D (ApoD) gene expression is increased in several neurological disorders such as Alzheimer's disease (AD) and multiple sclerosis. We previously showed that transgenic mice that overexpress human ApoD show a better resistance against paraquat or OC43 coronavirus-induced neurodegeneration. Here, we identified several nuclear factors from the cortex of control and OC43-infected mice which bind a fragment of the proximal ApoD promoter in vitro. Of interest, we detected apolipoprotein E (ApoE). Human ApoE consists of three isoforms (E2, E3, and E4) with the E4 and E2 alleles representing a greater and a lower risk for developping AD, respectively. Our results show that ApoE is located in the nucleus and on the ApoD promoter in human hepatic and glioblastoma cells lines. Furthermore, overexpression of ApoE3 and ApoE4 isoforms but not ApoE2 significantly inhibited the ApoD promoter activity in U87 cells (E3/E3 genotype) cultured under normal or different stress conditions while ApoE knock-down by siRNA had a converse effect. Consistent with these results, we also demonstrated by ChIP assay that E3 and E4 isoforms, but not E2, bind the ApoD promoter. Moreover, using the Allen Brain Atlas in situ hybridization database, we observed an inverse correlation between ApoD and ApoE mRNA expression during development and in several regions of the mouse brain, notably in the cortex, hippocampus, plexus choroid, and cerebellum. This negative correlation was also observed for cortex layers IV-VI based on a new Transcriptomic Atlas of the Mouse Neocortical Layers. These findings reveal a new function for ApoE by regulating ApoD gene expression.

  12. C-terminal-truncated apolipoprotein (apo) E4 inefficiently clears amyloid-β (Aβ) and acts in concert with Aβ to elicit neuronal and behavioral deficits in mice

    PubMed Central

    Bien-Ly, Nga; Andrews-Zwilling, Yaisa; Xu, Qin; Bernardo, Aubrey; Wang, Charles; Huang, Yadong

    2011-01-01

    Apolipoprotein (apo) E4 is the major known genetic risk factor for Alzheimer's disease (AD). We have shown in vitro and in vivo that apoE4 preferentially undergoes aberrant cleavage in neurons, yielding neurotoxic C-terminal-truncated fragments. To study the effect of these fragments on amyloid-β (Aβ) clearance/deposition and their potential synergy with Aβ in eliciting neuronal and behavioral deficits, we cross-bred transgenic mice expressing apoE3, apoE4, or apoE4(Δ272–299) with mice expressing human amyloid protein precursor (APP) harboring familial AD mutations (hAPPFAD). At 6–8 mo of age, hAPPFAD mice expressing apoE3 or apoE4 had lower levels of hippocampal Aβ (94% and 89%, respectively) and less Aβ deposition (89% and 87%) than hAPPFAD mice without apoE, whereas hAPPFAD mice expressing mouse apoE had higher Aβ levels. Thus, human apoE stimulates Aβ clearance, but mouse apoE does not. Expression of apoE4(Δ272–299) reduced total Aβ levels by only 63% and Aβ deposition by 46% compared with hAPPFAD mice without apoE. Unlike apoE3 and apoE4, the C-terminal-truncated apoE4 bound poorly with Aβ peptides, leading to decreased Aβ clearance and increased Aβ deposition. Despite their lower levels of Aβ and Aβ deposition, hAPPFAD/apoE4(Δ272–299) mice accumulated pathogenic Aβ oligomers and displayed neuronal and behavioral deficits similar to or more severe than those in hAPPFAD mice. Thus, the C-terminal-truncated apoE4 fragment inefficiently clears Aβ peptides and acts in concert with low levels of Aβ to elicit neuronal and behavioral deficits in mice. PMID:21368138

  13. Tanshinone IIA attenuates atherosclerosis in ApoE(-/-) mice through down-regulation of scavenger receptor expression.

    PubMed

    Tang, Fu-Tian; Cao, Yuan; Wang, Tie-Qiao; Wang, Li-Jing; Guo, Jiao; Zhou, Xiao-Shi; Xu, Suo-Wen; Liu, Wei-Hua; Liu, Pei-Qing; Huang, He-Qing

    2011-01-10

    This study is designed to investigate the protection of tanshinone IIA (TSIIA) against atherosclerosis in apolipoprotein E deficient (ApoE(-/-)) mice and to explore the mechanisms by focusing on the expressions of scavenger receptors, scavenger receptor-A (SR-A) and CD36. The in vivo study demonstrated that TSIIA (10-90mg/kg) inhibited the atherosclerotic lesions, down-regulated the CD68 protein expression in lesion and decreased the contents of cholesterol in aortas of ApoE(-/-) mice. In addition, TSIIA reduced the serum levels of oxidized LDL (oxLDL) and down-regulated the mRNA expression of CD36, SR-A and peroxisome proliferator-activated receptor gamma (PPARγ) in aortas. The in vitro study showed that TSIIA (0.1-10μM) decreased cholesterol level and DiI-oxLDL uptake in mouse peritoneal macrophages treated with oxLDL (50μg/ml). In addition, TSIIA down-regulated the mRNA and protein expression of CD36 but not that of SR-A in oxLDL treated macrophages. TSIIA also down-regulated the mRNA expression of PPARγ in oxLDL treated macrophages. Furthermore, TSIIA reduced the mRNA expression of CD36 in macrophages treated with PPARγ agonist 15d-PGJ(2) (2μM) or troglitazone (50μM), whereas both 15d-PGJ(2) (0.5-1.5μM) and troglitazone (5-20μM) dose-dependently abolished the down-regulation of CD36 expression by TSIIA in oxLDL treated macrophages. These results suggest that TSIIA attenuates the atherosclerotic lesion in ApoE(-/-) mice, which might be attributed to the properties of both anti-oxidation and down-regulation of scavenger receptors. Furthermore, antagonism of PPARγ might be involved in the down-regulation of CD36 by TSIIA.

  14. Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

    SciTech Connect

    Foss, Catherine A.; Bedja, Djahida; Mease, Ronnie C.; Wang, Haofan; Kass, David A.; Chatterjee, Subroto; Pomper, Martin G.

    2015-05-22

    Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis. Methods and results: We previously developed a low-molecular-weight imaging agent, [{sup 125}I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals. Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved. - Highlights: • [{sup 125}I]iodoDPA SPECT detects atherosclerotic plaques in ApoE -/- mice with high contrast. • Plaques are detected in ApoE -/- mice regardless of diet with iodoDPA. • iodoDPA has very low uptake in healthy tissue including healthy TSPO + tissues at 24 h.

  15. 56Fe accelerates development of atherosclerosis in apoE -/-mice

    NASA Astrophysics Data System (ADS)

    Kucik, Dennis; Yu, Tao; Parks, Brian; Yu, Shaohua; Srivastava, Roshni; Gupta, Kiran; Wu, Xing; Khaled, Saman; Chang, Polly; Kabarowski, Janusz

    Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. For example, for women with early breast cancer, the benefit of radiotherapy can be nearly offset by the increased risk of mortality from cardiovascular disease. Head and neck cancer patients who undergo radiation treatment are at significantly elevated risk of stroke, even in a relatively young patient population that would not normally be at risk for atheroscle-rosis. Similarly, atomic bomb survivors had an increased incidence of mortality from coronary artery disease and stroke. Even radiation technologists working before 1950 (when occupational exposure was higher) had increased mortality due to circulatory diseases. Although much is known about the cardiovascular consequences these exposures to X-raus and gamma radiation, the response to the type of radiation likely to be encountered in prolonged space flight has not been determined. A key component of this cosmic radiation is 56Fe, which is particularly damaging to tissues. Using collimated beams, we selectively irradiated aortic arches and carotids (only) of the well-established apoE -/-atherosclerosis mouse model to test directly whether 56Fe exposure is a cardiovascular risk factor. Mice were sacrificed at 13 weeks post-irradiation and dissected, and aortas were divided into areas that had been targeted by the ion beam and those that were not. The area that was covered by plaques was then quantified. Plaque area at 13 weeks post-irradiation was significantly greater in targeted areas of mice that had received 5 Gy of 56Fe as compared to age-and sex-matched un-irradiated controls. In the carotid arteries and aortic roots, significantly greater atherosclerosis was apparent for a 2Gy exposure as well (the lowest dose tested). This demonstrates that even a single exposure to heavy ion radiation is capable of triggering events that culminate in cardiovascular disease, even long after the exposure has

  16. Virtual observatory publishing with DaCHS

    NASA Astrophysics Data System (ADS)

    Demleitner, M.; Neves, M. C.; Rothmaier, F.; Wambsganss, J.

    2014-11-01

    The Data Center Helper Suite DaCHS is an integrated publication package for building VO and Web services, supporting the entire workflow from ingestion to data mapping to service definition. It implements all major data discovery, data access, and registry protocols defined by the VO. DaCHS in this sense works as glue between data produced by the data providers and the standard protocols and formats defined by the VO. This paper discusses central elements of the design of the package and gives two case studies of how VO protocols are implemented using DaCHS' concepts.

  17. The crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia

    PubMed Central

    Sacks, Frank M.

    2015-01-01

    Purpose of review To describe the roles of apolipoprotein C-III (apoC-III) and apoE in VLDL and LDL metabolism Recent findings ApoC-III can block clearance from the circulation of apolipoprotein B (apoB) lipoproteins, whereas apoE mediates their clearance. Normolipidemia is sustained by hepatic secretion of VLDL and IDL subspecies that contain both apoE and apoC-III (VLDL E+C-III+). Most of this VLDL E+C-III+ is speedily lipolyzed, reduced in apoC-III content, and cleared from the circulation as apoE containing dense VLDL, IDL, and light LDL. In contrast, in hypertriglyceridemia, most VLDL is secreted with apoC-III but without apoE, and so it is not cleared until it loses apoC-III during lipolysis to dense LDL. In normolipidemia, the liver also secretes IDL and large and medium-size LDL, whereas in hypertriglyceridemia, the liver secretes more dense LDL with and without apoC-III. These pathways establish the hypertriglyceridemic phenotype and link it metabolically to dense LDL. Dietary carbohydrate compared with unsaturated fat suppresses metabolic pathways mediated by apoE that are qualitatively similar to those suppressed in hypertriglyceridemia. Summary The opposing actions of apoC-III and apoE on subspecies of VLDL and LDL, and the direct secretion of LDL in several sizes, establish much of the basic structure of human apoB lipoprotein metabolism in normal and hypertriglyceridemic humans. PMID:25551803

  18. Direct evidence of a role for Nox2 in superoxide production, reduced nitric oxide bioavailability, and early atherosclerotic plaque formation in ApoE-/- mice.

    PubMed

    Judkins, Courtney P; Diep, Henry; Broughton, Brad R S; Mast, Anja E; Hooker, Elizabeth U; Miller, Alyson A; Selemidis, Stavros; Dusting, Gregory J; Sobey, Christopher G; Drummond, Grant R

    2010-01-01

    The Nox family NADPH oxidases are reactive oxygen species (ROS)-generating enzymes that are strongly implicated in atherogenesis. However, no studies have examined which Nox isoform(s) are involved. Here we investigated the role of the Nox2-containing NADPH oxidase in atherogenesis in apolipoprotein E-null (ApoE(-/-)) mice. Wild-type (C57Bl6/J), ApoE(-/-), and Nox2(-/y)/ApoE(-/-) mice were maintained on a high-fat (21%) diet from 5 wk of age until they were 12 or 19 wk old. Mice were euthanized and their aortas removed for measurement of Nox2 expression (Western blot analysis and immunohistochemistry), ROS production (L012-enhanced chemiluminescence), nitric oxide (NO) bioavailability (contractions to N(omega)-nitro-L-arginine), and atherosclerotic plaque development along the aorta and in the aortic sinus. Nox2 expression was upregulated in the aortic endothelium of ApoE(-/-) mice before the appearance of lesions, and this was associated with elevated ROS levels. Within developing plaques, macrophages were also a prominent source of Nox2. The absence of Nox2 in Nox2(-/y)/ApoE(-/-) double-knockout mice had minimal effects on plasma lipids or lesion development in the aortic sinus in animals up to 19 wk of age. However, an en face examination of the aorta from the arch to the iliac bifurcation revealed a 50% reduction in lesion area in Nox2(-/y)/ApoE(-/-) versus ApoE(-/-) mice, and this was associated with a marked decrease in aortic ROS production and an increased NO bioavailability. In conclusion, this is the first demonstration of a role for Nox2-NADPH oxidase in vascular ROS production, reduced NO bioavailability, and early lesion development in ApoE(-/-) mice, highlighting this Nox isoform as a potential target for future therapies for atherosclerosis. PMID:19837950

  19. Amyloid-β Pathology and APOE Genotype Modulate Retinoid X Receptor Agonist Activity in Vivo*

    PubMed Central

    Tai, Leon M.; Koster, Kevin P.; Luo, Jia; Lee, Sue H.; Wang, Yue-ting; Collins, Nicole C.; Ben Aissa, Manel; Thatcher, Gregory R. J.; LaDu, Mary Jo

    2014-01-01

    Previous data demonstrate that bexarotene (Bex), retinoid X receptor (RXR) agonist, reduces soluble and insoluble amyloid-β (Aβ) in Alzheimer disease (AD)-transgenic mice either by increasing the levels of mouse apolipoprotein E (apoE) or increasing ABCA1/ABCG1-induced apoE lipoprotein association/lipidation. However, although the mechanism of action of RXR agonists remains unclear, a major concern for their use is human (h)-APOE4, the greatest AD genetic risk factor. If APOE4 imparts a toxic gain-of-function, then increasing apoE4 may increase soluble Aβ, likely the proximal AD neurotoxin. If the APOE4 loss-of-function is lipidation of apoE4, then induction of ABCA1/ABCG1 may be beneficial. In novel EFAD-Tg mice (overexpressing h-Aβ42 with h-APOE), levels of soluble Aβ (Aβ42 and oligomeric Aβ) are highest in E4FAD hippocampus (HP) > E3FAD-HP > E4FAD cortex (CX) > E3FAD-CX, whereas levels of lipoprotein-associated/lipidated apoE have the opposite pattern (6 months). In E4FAD-HP, short-term RXR agonist treatment (Bex or LG100268; 5.75–6 months) increased ABCA1, apoE4 lipoprotein-association/lipidation, and apoE4/Aβ complex, decreased soluble Aβ, and increased PSD95. In addition, hydrogel delivery, which mimics low sustained release, was equally effective as gavage for Bex and LG100268. RXR agonists induced no beneficial effects in the E4FAD-HP in a prevention protocol (5–6 months) and actually increased soluble Aβ levels in E3FAD-CX and E4FAD-CX with the short-term protocol, possibly the result of systemic hepatomegaly. Thus, RXR agonists address the loss-of-function associated with APOE4 and exacerbated by Aβ pathology, i.e. low levels of apoE4 lipoprotein association/lipidation. Further studies are vital to address whether RXR agonists are an APOE4-specific AD therapeutic and the systemic side effects that limit translational application. PMID:25217640

  20. High stability of apo-cytochrome c' from thermophilic Hydrogenophilus thermoluteolus.

    PubMed

    Fujii, Sotaro; Masanari, Misa; Yamanaka, Masaru; Wakai, Satoshi; Sambongi, Yoshihiro

    2014-01-01

    Apo-cytochomes c without heme are usually unstructured. Here we showed that apo-form of thermophilic Hydrogenophilus thermoluteolus cytochrome c' (PHCP) was a monomeric protein with high helix content. Apo-PHCP was thermally stable, possibly due to the hydrophobic residues and ion pairs. PHCP is the first example of a structured apo-cytochrome c', which will expand our view of hemoprotein structure formation.