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Sample records for 4-fold higher expression

  1. 4-fold photocurrent enhancement in ultrathin nanoplasmonic perovskite solar cells.

    PubMed

    Cai, Boyuan; Peng, Yong; Cheng, Yi-Bing; Gu, Min

    2015-11-30

    Although perovskite materials have been widely investigated for thin-film photovoltaic devices due to the potential for high efficiency, their high toxicity has pressed the development of a solar cell structure of an ultra-thin absorber layer. But insufficient light absorption could be a result of ultra-thin perovskite films. In this paper, we propose a new nanoplasmonic solar cell that integrates metal nanoparticles at its rear/front surfaces of the perovskite layer. Plasmon-enhanced light scattering and near-field enhancement effects from lumpy sliver nanoparticles result in the photocurrent enhancement for a 50 nm thick absorber, which is higher than that for a 300 nm thick flat perovskite solar cell. We also predict the 4-fold photocurrent enhancement in an ultrathin perovskite solar cell with the absorber thickness of 10 nm. Our results pave a new way for ultrathin high-efficiency solar cells with either a lead-based or a lead-free perovskite absorption layer. PMID:26698816

  2. Evaluation of expressions involving higher order derivations

    NASA Technical Reports Server (NTRS)

    Grossman, Robert

    1990-01-01

    The local geometric properties of a nonlinear control system defined by vector fields E(sub 1),..., E(sub M) are determined by the algebraic properties of the iterated Lie brackets of the E(sub j)'s. The problem of rewriting expressions is examined involving the E(sub j)'s in terms of the D(sub mu)'s in such a way as to handle effectively any cancellation occurring due to commuting of the D(sub mu)'s. A data structure is introduced which allows us to organize the computation to take advantage of the symmetries in the expression and reduce the operation count.

  3. Light regulation of gene expression in higher plants

    SciTech Connect

    Tobin, E.M.; Silverthorne, J.

    1985-01-01

    In this review areas of currently active research are considered which have demonstrated that a plant's response to light involves changes in the expression of specific genes at the level of RNA. The regulation of gene expression by phytochrome and the UV-sensitive photoreceptor have been studied most extensively at the molecular level, and this review particularly focuses on such studies in higher plants. Some of the observations made on the differences in gene expression between light-grown and dark-grown plants are also included, although the photoreceptor(s) responsible for the differences may not have been ascertained. In some of these cases, phytochrome involvement has been or may be demonstrated in later studies, while in others the observed differences may be a result of the action of other photoreceptors or of multiple light-affected processes. One such process is the development of chloroplasts, a major developmental step triggered by light in angiosperms. In addition, many of the genes whose expression is changed by light and which have been studied at a molecular level encode chloroplast proteins. 156 references.

  4. Brane brick models, toric Calabi-Yau 4-folds and 2d (0,2) quivers

    NASA Astrophysics Data System (ADS)

    Franco, Sebastián; Lee, Sangmin; Seong, Rak-Kyeong

    2016-02-01

    We introduce brane brick models, a novel type of Type IIA brane configurations consisting of D4-branes ending on an NS5-brane. Brane brick models are T-dual to D1-branes over singular toric Calabi-Yau 4-folds. They fully encode the infinite class of 2 d (generically) {N}=(0,2) gauge theories on the worldvolume of the D1-branes and streamline their connection to the probed geometries. For this purpose, we also introduce new combinatorial procedures for deriving the Calabi-Yau associated to a given gauge theory and vice versa.

  5. Crystalline structures of polymeric hydrocarbon with 3,4-fold helical chains

    NASA Astrophysics Data System (ADS)

    Lian, Chao-Sheng; Li, Han-Dong; Wang, Jian-Tao

    2015-01-01

    Molecular hydrocarbons are well-known to polymerize under pressure to form covalently bonded frameworks. Here we predict by ab initio calculations two distinct three-dimensional hydrocarbon crystalline structures composed of 3-fold and 4-fold helical CH chains in rhombohedral () and tetragonal (I41/a) symmetry, respectively. Both structures with 1:1 stoichiometry are found to be energetically more favorable than solid acetylene and cubane, and even more stable than benzene II solid at high pressure. The calculations on vibrational, electronic, and optical properties reveal that the new chiral hydrocarbons are dynamically stable with large bulk moduli around 200 GPa, and exhibit a transparent insulating behavior with indirect band gaps of 5.9 ~ 6.7 eV and anisotropic adsorption spectra. Such forms of hydrocarbon, once synthesized, would have wide applications in mechanical, optoelectronic, and biological materials.

  6. Crystalline structures of polymeric hydrocarbon with 3,4-fold helical chains

    PubMed Central

    Lian, Chao-Sheng; Li, Han-Dong; Wang, Jian-Tao

    2015-01-01

    Molecular hydrocarbons are well-known to polymerize under pressure to form covalently bonded frameworks. Here we predict by ab initio calculations two distinct three-dimensional hydrocarbon crystalline structures composed of 3-fold and 4-fold helical CH chains in rhombohedral () and tetragonal (I41/a) symmetry, respectively. Both structures with 1:1 stoichiometry are found to be energetically more favorable than solid acetylene and cubane, and even more stable than benzene II solid at high pressure. The calculations on vibrational, electronic, and optical properties reveal that the new chiral hydrocarbons are dynamically stable with large bulk moduli around 200 GPa, and exhibit a transparent insulating behavior with indirect band gaps of 5.9 ~ 6.7 eV and anisotropic adsorption spectra. Such forms of hydrocarbon, once synthesized, would have wide applications in mechanical, optoelectronic, and biological materials. PMID:25579707

  7. Synchrotron radiation circular dichroism spectroscopy study of recombinant T β4 folding

    NASA Astrophysics Data System (ADS)

    Huang, Yung-Chin; Chu, Hsueh-Liang; Chen, Peng-Jen; Chang, Chia-Ching

    Thymosin beta 4 (T β4) is a 43-amino acid small peptide, has been demonstrated that it can promote cardiac repair, wound repair, tissue protection, and involve in the proliferation of blood cell precursor stem cells of bone marrow. Moreover, T β4 has been identified as a multifunction intrinsically disordered protein, which is lacking the stable tertiary structure. Owing to the small size and disordered character, the T β4 protein degrades rapidly and the storage condition is critical. Therefore, it is not easy to reveal its folding mechanism of native T β4. However, recombinant T β4 protein (rT β4), which fused with a 5-kDa peptide in its amino-terminal, is stable and possesses identical function of T β4. Therefore, rT β4 can be used to study its folding mechanism. By using over-critical folding process, stable folding intermediates of rT β4 can be obtained. Structure analysis of folding intermediates by synchrotron radiation circular dichroism (SRCD) and fluorescence spectroscopies indicate that rT β4 is a random coli major protein and its hydrophobic region becomes compact gradually. Moreover, the rT β4 folding is a two state transition. Thermal denaturation analysis indicates that rT β4 lacks stable tertiary structure. These results indicated that rT β4, similar to T β4, is an intrinsically disordered protein. Research is supported by MOST, Taiwan. MOST 103-2112-M-009-011-MY3. Corresponding author: Chia-Ching Chang; ccchang01@faculty.nctu.edu.tw.

  8. Genome-wide expression changes in a higher state of consciousness.

    PubMed

    Ravnik-Glavač, Metka; Hrašovec, Sonja; Bon, Jure; Dreo, Jurij; Dreu, Jurij; Glavač, Damjan

    2012-09-01

    Higher states of consciousness in which the human mind can transcend the boundaries of logic and reason are envisioned as natural to the experience and potential growth of every human being. So far they have been mostly monitored by electrophysiological methods. In this study we were particularly interested in discovering the molecular transcriptional basis of higher states of consciousness. In addition to phenomenological reports of meditators who participated in this study the generated higher states of consciousness were also EEG recorded. We assessed the whole genome gene expression analysis of long-term meditators in four separate trials and detected significant differential gene expression in association with higher states of consciousness. The number of differently expressed genes as well as high proportion of genes themselves differed between meditators. Despite this, gene ontology enrichment analysis found significant biological and molecular processes shared among meditators' higher state of consciousness. PMID:22742996

  9. An inactivated recombinant rabies CVS-11 virus expressing two copies of the glycoprotein elicits a higher level of neutralizing antibodies and provides better protection in mice.

    PubMed

    Xue, Xiang-Hong; Zheng, Xue-Xing; Wang, Hua-Lei; Ma, Jin-Zhu; Li, Ling; Gai, Wei-Wei; Wang, Tie-Cheng; Yang, Song-Tao; Xia, Xian-Zhu

    2014-06-01

    The rabies virus (RABV) G protein is the primary contributor to the pathogenicity and protective immunity of RABV. In this study, we generated a recombinant rCVS-11-G strain containing two copies of the G protein derived from the pathogenic wild-type (wt) CVS-11 strain and based on its infectious clone. Compared with the wtCVS-11 strain, the rCVS-11-G strain possessed a larger virion and 1.4-fold more G protein, but it exhibited a similar growth property to the rCVS-11 strain, including passaging stability in vitro. qPCR results showed that the two G genes were over-expressed in BHK-21 cells infected with the rCVS-11-G strain. However, the rCVS-11-G strain presented an 80 % lower LD50 than the wtCVS-11 strain when intracranially (i.c.) inoculated in adult mice. Adult mice that were either intracranially (i.c.) or intramuscularly (i.m.) inoculated with rCVS-11-G strain developed more acute neurological symptoms and greater mortality than those inoculated with the wtCVS-11 strain. Furthermore, the rCVS-11-G strain was more easily and rapidly taken up by neuroblastoma cells. These data indicated that the rCVS-11-G strain might have increased neurotropism because of the over-expression of the pathogenic G protein. The inactivated rCVS-11-G strain induced significantly higher levels of virus neutralization antibodies and provided better protection from street rabies virus challenge in mice. Therefore, the rCVS-11-G strain may be a promising inactivated vaccine strain due to its better immunogenicity. PMID:24535572

  10. Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics.

    PubMed

    Miksys, Sharon; Rao, Yushu; Hoffmann, Ewa; Mash, Deborah C; Tyndale, Rachel F

    2002-09-01

    Cytochrome P450 (CYP) 2D6 is expressed in liver, brain and other extrahepatic tissues where it metabolizes a range of centrally acting drugs and toxins. As ethanol can induce CYP2D in rat brain, we hypothesized that CYP2D6 expression is higher in brains of human alcoholics. We examined regional and cellular expression of CYP2D6 mRNA and protein by RT-PCR, Southern blotting, slot blotting, immunoblotting and immunocytochemistry. A significant correlation was found between mean mRNA and CYP2D6 protein levels across 13 brain regions. Higher expression was detected in 13 brain regions of alcoholics (n = 8) compared to nonalcoholics (n = 5) (anovap < 0.0001). In hippocampus this was localized in CA1-3 pyramidal cells and dentate gyrus granular neurons. In cerebellum this was localized in Purkinje cells and their dendrites. Both of these brain regions, and these same cell-types, are known to be susceptible to alcohol damage. For one case, a poor metabolizer (CYP2D6*4/*4), there was no detectable CYP2D6 protein, confirming the specificity of the antibody used. These data suggest that in alcoholics elevated brain CYP2D6 expression may contribute to altered sensitivity to centrally acting drugs and to the mediation of neurotoxic and behavioral effects of alcohol. PMID:12354285

  11. Oxytocin enhances attentional bias for neutral and positive expression faces in individuals with higher autistic traits.

    PubMed

    Xu, Lei; Ma, Xiaole; Zhao, Weihua; Luo, Lizhu; Yao, Shuxia; Kendrick, Keith M

    2015-12-01

    There is considerable interest in the potential therapeutic role of the neuropeptide oxytocin in altering attentional bias towards emotional social stimuli in psychiatric disorders. However, it is still unclear whether oxytocin primarily influences attention towards positive or negative valence social stimuli. Here in a double-blind, placebo controlled, between subject design experiment in 60 healthy male subjects we have used the highly sensitive dual-target rapid serial visual presentation (RSVP) paradigm to investigate whether intranasal oxytocin (40IU) treatment alters attentional bias for emotional faces. Results show that oxytocin improved recognition accuracy of neutral and happy expression faces presented in the second target position (T2) during the period of reduced attentional capacity following prior presentation of a first neutral face target (T1), but had no effect on recognition of negative expression faces (angry, fearful, sad). Oxytocin also had no effect on recognition of non-social stimuli (digits) in this task. Recognition accuracy for neutral faces at T2 was negatively associated with autism spectrum quotient (ASQ) scores in the placebo group, and oxytocin's facilitatory effects were restricted to a sub-group of subjects with higher ASQ scores. Our results therefore indicate that oxytocin primarily enhances the allocation of attentional resources towards faces expressing neutral or positive emotion and does not influence that towards negative emotion ones or non-social stimuli. This effect of oxytocin is strongest in healthy individuals with higher autistic trait scores, thereby providing further support for its potential therapeutic use in autism spectrum disorder. PMID:26372768

  12. Olfactory Impact of Higher Alcohols on Red Wine Fruity Ester Aroma Expression in Model Solution.

    PubMed

    Cameleyre, Margaux; Lytra, Georgia; Tempere, Sophie; Barbe, Jean-Christophe

    2015-11-11

    This study focused on the impact of five higher alcohols on the perception of fruity aroma in red wines. Various aromatic reconstitutions were prepared, consisting of 13 ethyl esters and acetates and 5 higher alcohols, all at the average concentrations found in red wine. These aromatic reconstitutions were prepared in several matrices. Sensory analysis revealed the interesting behavior of certain compounds among the five higher alcohols following their individual addition or omission. The "olfactory threshold" of the fruity pool was evaluated in several matrices: dilute alcohol solution, dilute alcohol solution containing 3-methylbutan-1-ol or butan-1-ol individually, and dilute alcohol solution containing the mixture of five higher alcohols, blended together at various concentrations. The presence of 3-methylbutan-1-ol or butan-1-ol alone led to a significant decrease in the "olfactory threshold" of the fruity reconstitution, whereas the mixture of alcohols raised the olfactory threshold. Sensory profiles highlighted changes in the perception of fruity nuances in the presence of the mixture of higher alcohols, with specific perceptive interactions, including a relevant masking effect on fresh- and jammy-fruit notes of the fruity mixture in both dilute alcohol solution and dearomatized red wine matrices. When either 3-methylbutan-1-ol or butan-1-ol was added to the fruity reconstitution in dilute alcohol solution, an enhancement of butyric notes was reported with 3-methylbutan-1-ol and fresh- and jammy-fruit with butan-1-ol. This study, the first to focus on the impact of higher alcohols on fruity aromatic expression, revealed that these compounds participate, both quantitatively and qualitatively, in masking fruity aroma perception in a model fruity wine mixture. PMID:26529563

  13. SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells.

    PubMed

    Barutcu, A Rasim; Lajoie, Bryan R; Fritz, Andrew J; McCord, Rachel P; Nickerson, Jeffrey A; van Wijnen, Andre J; Lian, Jane B; Stein, Janet L; Dekker, Job; Stein, Gary S; Imbalzano, Anthony N

    2016-09-01

    The packaging of DNA into chromatin plays an important role in transcriptional regulation and nuclear processes. Brahma-related gene-1 SMARCA4 (also known as BRG1), the essential ATPase subunit of the mammalian SWI/SNF chromatin remodeling complex, uses the energy from ATP hydrolysis to disrupt nucleosomes at target regions. Although the transcriptional role of SMARCA4 at gene promoters is well-studied, less is known about its role in higher-order genome organization. SMARCA4 knockdown in human mammary epithelial MCF-10A cells resulted in 176 up-regulated genes, including many related to lipid and calcium metabolism, and 1292 down-regulated genes, some of which encode extracellular matrix (ECM) components that can exert mechanical forces and affect nuclear structure. ChIP-seq analysis of SMARCA4 localization and SMARCA4-bound super-enhancers demonstrated extensive binding at intergenic regions. Furthermore, Hi-C analysis showed extensive SMARCA4-mediated alterations in higher-order genome organization at multiple resolutions. First, SMARCA4 knockdown resulted in clustering of intra- and inter-subtelomeric regions, demonstrating a novel role for SMARCA4 in telomere organization. SMARCA4 binding was enriched at topologically associating domain (TAD) boundaries, and SMARCA4 knockdown resulted in weakening of TAD boundary strength. Taken together, these findings provide a dynamic view of SMARCA4-dependent changes in higher-order chromatin organization and gene expression, identifying SMARCA4 as a novel component of chromatin organization. PMID:27435934

  14. Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility

    PubMed Central

    Eidet, Jon R.; Utheim, Tor P.; Ræder, Sten; Lagali, Neil S.; Messelt, Edvard B.; Dartt, Darlene A.

    2016-01-01

    The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjögren’s syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as “daily symptoms of dry mouth the last three months” (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; P<0.001). Patients with xerostomia (60 ± 15 years) were older than those without xerostomia (51 ± 17; P<0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; P<0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 ± 10.0) than those without xerostomia (12.9 ± 8.0; P<0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 ± 0.7) than those without xerostomia (0.7 ± 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients. PMID:27148875

  15. Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility.

    PubMed

    Fostad, Ida G; Eidet, Jon R; Utheim, Tor P; Ræder, Sten; Lagali, Neil S; Messelt, Edvard B; Dartt, Darlene A

    2016-01-01

    The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjögren's syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as "daily symptoms of dry mouth the last three months" (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; P<0.001). Patients with xerostomia (60 ± 15 years) were older than those without xerostomia (51 ± 17; P<0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; P<0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 ± 10.0) than those without xerostomia (12.9 ± 8.0; P<0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 ± 0.7) than those without xerostomia (0.7 ± 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients. PMID:27148875

  16. Gene expression and regulation of higher plants under soil water stress.

    PubMed

    Ni, Fu-Tai; Chu, Li-Ye; Shao, Hong-Bo; Liu, Zeng-Hui

    2009-06-01

    Higher plants not only provide human beings renewable food, building materials and energy, but also play the most important role in keeping a stable environment on earth. Plants differ from animals in many aspects, but the important is that plants are more easily influenced by environment than animals. Plants have a series of fine mechanisms for responding to environmental changes, which has been established during their long-period evolution and artificial domestication. The machinery related to molecular biology is the most important basis. The elucidation of it will extremely and purposefully promote the sustainable utilization of plant resources and make the best use of its current potential under different scales. This molecular mechanism at least includes drought signal recognition (input), signal transduction (many cascade biochemical reactions are involved in this process), signal output, signal responses and phenotype realization, which is a multi-dimension network system and contains many levels of gene expression and regulation. We will focus on the physiological and molecular adaptive machinery of plants under soil water stress and draw a possible blueprint for it. Meanwhile, the issues and perspectives are also discussed. We conclude that biological measures is the basic solution to solving various types of issues in relation to sustainable development and the plant measures is the eventual way. PMID:19949548

  17. Autoregressive Higher-Order Hidden Markov Models: Exploiting Local Chromosomal Dependencies in the Analysis of Tumor Expression Profiles

    PubMed Central

    Seifert, Michael; Abou-El-Ardat, Khalil; Friedrich, Betty; Klink, Barbara; Deutsch, Andreas

    2014-01-01

    Changes in gene expression programs play a central role in cancer. Chromosomal aberrations such as deletions, duplications and translocations of DNA segments can lead to highly significant positive correlations of gene expression levels of neighboring genes. This should be utilized to improve the analysis of tumor expression profiles. Here, we develop a novel model class of autoregressive higher-order Hidden Markov Models (HMMs) that carefully exploit local data-dependent chromosomal dependencies to improve the identification of differentially expressed genes in tumor. Autoregressive higher-order HMMs overcome generally existing limitations of standard first-order HMMs in the modeling of dependencies between genes in close chromosomal proximity by the simultaneous usage of higher-order state-transitions and autoregressive emissions as novel model features. We apply autoregressive higher-order HMMs to the analysis of breast cancer and glioma gene expression data and perform in-depth model evaluation studies. We find that autoregressive higher-order HMMs clearly improve the identification of overexpressed genes with underlying gene copy number duplications in breast cancer in comparison to mixture models, standard first- and higher-order HMMs, and other related methods. The performance benefit is attributed to the simultaneous usage of higher-order state-transitions in combination with autoregressive emissions. This benefit could not be reached by using each of these two features independently. We also find that autoregressive higher-order HMMs are better able to identify differentially expressed genes in tumors independent of the underlying gene copy number status in comparison to the majority of related methods. This is further supported by the identification of well-known and of previously unreported hotspots of differential expression in glioblastomas demonstrating the efficacy of autoregressive higher-order HMMs for the analysis of individual tumor expression

  18. CD34 Over-Expression is Associated With Gliomas’ Higher WHO Grade

    PubMed Central

    Kong, Xiangyi; Guan, Jian; Ma, Wenbin; Li, Yongning; Xing, Bing; Yang, Yi; Wang, Yu; Gao, Jun; Wei, Junji; Yao, Yong; Xu, Zhiqin; Dou, Wanchen; Lian, Wei; Su, Changbao; Ren, Zuyuan; Wang, Renzhi

    2016-01-01

    Abstract CD34 is a transmembrane phosphoglycoprotein that was first identified on hematopoietic stem and progenitor cells. CD34 is known as an optimum marker for microvascular density studies and it is positively stained in pathological and physiologic vessels. The use of CD34 for the prognosis, diagnosis, and treatment of neoplasms has been increasingly discussed. The implications and utilities of CD34 in WHO grades of gliomas and its prognosis have been reported rarely. Also, the WHO grades and prognosis researches remains unclear and controversial. A meta-analysis is the best choice for drawing a convincing conclusion. Several databases were searched. We carefully assess the relevant articles and standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were estimated in terms of the relationship between CD34 expression levels with gliomas’ WHO grades, patients’ ages and gender. We used the Galbraith figure, the I2 test, and Cochran Q test to evaluate the heterogeneity of the included studies. A sensitivity analysis was conducted to assess the pooled results’ stability. A Contour-enhanced funnel plot evaluation was made to assess potential publication bias. Ethics review and approval was not necessary because the meta-analysis did not involve any direct human trials or animal experiments. There were 12 eligible studies, including 684 patients who were considered in the present meta-analysis. All of them were conducted in China. CD34 overexpression in glioma tissues was associated closely, according to the pooled SMD, with higher WHO grade (III + IV) (SMD -1.503, 95% CI -1.685 to -1.321; P = 0.000). There were no significant associations between CD34 and age (SMD -0.223, 95% CI -0.602 to 0.156; P = 0.248) and CD34 and gender (SMD -0.059, 95% CI -0.439, 0.321; P = 0.761). No publication bias was detected according to Contour-enhanced funnel plot. Our results suggested that CD34 overexpression is associated with higher WHO

  19. Low Expressive Vocabulary: Higher Heritability as a Function of More Severe Cases

    ERIC Educational Resources Information Center

    DeThorne, Laura S.; Petrill, Stephen A.; Hayiou-Thomas, Marianna E.; Plomin, Robert

    2005-01-01

    This study of 4,274 pairs of 4-year-old twins from the Twins Early Development Study explored the magnitude of genetic and environmental effects on low expressive vocabulary skill, both as a function of general cognitive ability and as a function of the severity of expressive vocabulary impairment. Assessments were conducted through parent report…

  20. CD105 Over-expression Is Associated with Higher WHO Grades for Gliomas.

    PubMed

    Kong, Xiangyi; Wang, Yu; Liu, Shuai; Xing, Bing; Yang, Yi; Li, Yongning; Ren, Zuyuan; Su, Changbao; Ma, Wenbin; Wang, Renzhi

    2016-07-01

    CD105 is an ancillary receptor of transforming growth factor beta (TGF-β), which has been suggested as a suitable biomarker for cancer-related angiogenesis and neovascularization (Nassiri et al. in Anticancer Res 31:2283-2290, 2011). However, the clinical significance of CD105 in WHO grade was rarely reported and the effects of CD105 signal transduction pathway on gliomas remain controversial and unclear. To get a convincing conclusion, performing a meta-analysis is essential. Relevant literature studies were included via careful evaluation, and standard mean difference (SMD) and hazard ratio (HR) with 95 % confidence intervals (95 % CIs) was calculated. We also made funnel plots to test the heterogeneity. In the present meta-analysis, a total of 11 eligible literatures involving 796 patients were incorporated. They were all conducted in China, revealing that CD105 overexpression in glioma tissues was strongly linked to high WHO grading (III+IV) (SMD -1.785, 95 % CI -2.133, -1.437; p = 0.000). No significant associations between CD105 and age (SMD -0.505, 95 % CI -1.054, 0.043; p = 0. 071), CD105 and gender (SMD 0.101, 95 % CI -0.103, 0.305; p = 0.333), and CD105 and tumor size (SMD -0.433, 95 % CI -1.326, 0.459; p = 0. 341) were detected. Besides, CD105 expression was closely associated with glioma patients' 3-year overall survival (OS; n = 2; HR = 4.357, 95 % CI 1.412, 7.303; p = 0.004). On the basis of Begg's and Egger's test or funnel plot, no publication bias was detected. In a nutshell, this meta-analysis demonstrated that CD105 overexpression correlates to higher WHO grade and poor survival and could be indicated as a helpful prognostic and diagnostic marker, or a useful therapy target. PMID:26884265

  1. Higher expression of SIRT1 induced resistance of esophageal squamous cell carcinoma cells to cisplatin

    PubMed Central

    Shi, Qintong; Wang, Wengong

    2015-01-01

    Background High expression of Sirtuin type 1 (SIRT1) exists in some cancer cells. However, it is still unclear whether SIRT1 affects the sensitivity of esophageal cancer cells to cisplatin. This study was designed to explore the relationship between SIRT1 expression and resistance of esophageal squamous cell carcinoma (ESCC) cells to cisplatin and reveal the underlying mechanism. Methods The tissue samples of 68 ESCC patients were collected from Nanjing Drum Tower Hospital, China. All the patients had undergone cisplatin based combination chemotherapy. The expression of SIRT1and Noxa in tissue samples were analyzed by quantitative real-time reverse PCR (qRT-PCR) and Western blot. Human ESCC cell line (ECa9706 cells) was cultured and a cisplatin-resistant subline (ECa9706-CisR cells) was established by continuous exposure to cisplatin at different concentrations. The expression of SIRT1 and Noxa in both cell lines was analyzed by qRT-PCR and Western blot. siRNA technology was utilized to down-regulate the SIRT1 expression in ECa9706-CisR cells. The influence of SIRT1 silence on sensitivity of ECa9706-CisR cells to cisplatin was confirmed using CCK-8 assay and flow cytometry. Furthermore, the level change of Noxa after SIRT1 silence in ECa9706-CisR cells was determined by qRT-PCR and Western blot. Result SIRT1 and Noxa expression in chemo-resistant patients was significantly increased and decreased respectively, compared with chemo-sensitive patients. SIRT1 expression in ECa9706-CisR cells was significantly increased with a lower Noxa level, compared with normal ECa9706 cells. Cisplatin 5 µM could cause proliferation inhibition, G2/M phase arrest and apoptosis in ECa9706-CisR cells and these effects could be enhanced dramatically by SIRT1 silencing. Moreover, Noxa expression was increased after treated with SIRT1 siRNA. Conclusions Over-expression of SIRT1 may cause resistance of ESCC cells to cisplatin through the mechanism involved with Noxa expression. PMID

  2. Space mutagenesis of genetically engineered bacteria expressing recombinant human interferon α1b and screening of higher yielding strains.

    PubMed

    Wang, Junfeng; Liu, Changting; Liu, Jinyi; Fang, Xiangqun; Xu, Chen; Guo, Yinghua; Chang, De; Su, Longxiang

    2014-03-01

    The aim of this study was to investigate the space mutagenesis of genetically engineered bacteria expressing recombinant human interferon α1b. The genetically engineered bacteria expressing the recombinant interferon α1b were sent into outer space on the Chinese Shenzhou VIII spacecraft. After the 17 day space flight, mutant strains that highly expressed the target gene were identified. After a series of screening of spaceflight-treated bacteria and the quantitative comparison of the mutant strains and original strain, we found five strains that showed a significantly higher production of target proteins, compared with the original strain. Our results support the notion that the outer space environment has unique effects on the mutation breeding of microorganisms, including genetically engineered strains. Mutant strains that highly express the target protein could be obtained through spaceflight-induced mutagenesis. PMID:24096450

  3. The Role of Persuasive Arguments in Changing Affirmative Action Attitudes and Expressed Behavior in Higher Education

    ERIC Educational Resources Information Center

    White, Fiona A.; Charles, Margaret A.; Nelson, Jacqueline K.

    2008-01-01

    The research reported in this article examined the conditions under which persuasive arguments are most effective in changing university students' attitudes and expressed behavior with respect to affirmative action (AA). The conceptual framework was a model that integrated the theory of reasoned action and the elaboration likelihood model of…

  4. Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus.

    PubMed

    Yang, Rui; Kerschner, Jenny L; Gosalia, Nehal; Neems, Daniel; Gorsic, Lidija K; Safi, Alexias; Crawford, Gregory E; Kosak, Steven T; Leir, Shih-Hsing; Harris, Ann

    2016-04-20

    Higher order chromatin structure establishes domains that organize the genome and coordinate gene expression. However, the molecular mechanisms controlling transcription of individual loci within a topological domain (TAD) are not fully understood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene provides a paradigm for investigating these mechanisms.CFTR occupies a TAD bordered by CTCF/cohesin binding sites within which are cell-type-selective cis-regulatory elements for the locus. We showed previously that intronic and extragenic enhancers, when occupied by specific transcription factors, are recruited to the CFTR promoter by a looping mechanism to drive gene expression. Here we use a combination of CRISPR/Cas9 editing of cis-regulatory elements and siRNA-mediated depletion of architectural proteins to determine the relative contribution of structural elements and enhancers to the higher order structure and expression of the CFTR locus. We found the boundaries of the CFTRTAD are conserved among diverse cell types and are dependent on CTCF and cohesin complex. Removal of an upstream CTCF-binding insulator alters the interaction profile, but has little effect on CFTR expression. Within the TAD, intronic enhancers recruit cell-type selective transcription factors and deletion of a pivotal enhancer element dramatically decreases CFTR expression, but has minor effect on its 3D structure. PMID:26673704

  5. Conceptualizing Gender Performance in Higher Education: Exploring Regulation of Identity Expression

    ERIC Educational Resources Information Center

    Fellabaum, Jennifer

    2011-01-01

    While many higher education scholars have considered gender (e.g., Dawson-Threat & Huba, 1996; DeLucia-Waack, Gerrity, Taub, & Baldo, 2001; Jacobs, 1995; Knox, Zusman, & Mcneely, 2004; Lackland & De Lisi, 2001; Massey & Christensen, 1990), most of the literature uses modernistic theories to examine gender roles or gendered differences among…

  6. "A Delicate Balance...": Language as a Tool of Identity Expression for Incarcerated Men Pursuing Higher Education

    ERIC Educational Resources Information Center

    McDowell, Lila

    2014-01-01

    In the course of an initiative to provide higher education to adults in prison, incarcerated men enrolled in an undergraduate degree programme were offered the opportunity to participate in a series of writing workshops. This article examines the products of these workshops, specifically the ways that language chosen by the writers serves as a…

  7. Higher decidual EBI3 and HLA-G mRNA expression in preeclampsia: Cause or consequence of preeclampsia.

    PubMed

    Prins, J R; van der Hoorn, M L P; Keijser, R; Ris-Stalpers, C; van Beelen, E; Afink, G B; Claas, F H J; van der Post, J A M; Scherjon, S A

    2016-01-01

    The maternal immune system must adapt to tolerate the invasion of the allogeneic feto-placental unit. It is generally accepted that improper adaptation causes pregnancy complications like preeclampsia. The Epstein-Barr virus-induced gene 3 (EBI3) protein is a subunit of immune-modulatory cytokines interleukin 27 (IL-27) and IL-35. EBI3 has been reported to associate with HLA-G. In this small pilot study we find higher decidual EBI3 (p<0.05) and HLA-G (p<0.01) mRNA expression in preeclampsia (n=7) compared to normotensive (n=8) pregnancies. Whether the higher EBI3 and HLA-G mRNA expression is a consequence or cause of preeclampsia remains to be answered. Further research to determine the effects on IL-27 and IL-35 is needed. PMID:26472010

  8. The role of persuasive arguments in changing affirmative action attitudes and expressed behavior in higher education.

    PubMed

    White, Fiona A; Charles, Margaret A; Nelson, Jacqueline K

    2008-11-01

    The research reported in this article examined the conditions under which persuasive arguments are most effective in changing university students' attitudes and expressed behavior with respect to affirmative action (AA). The conceptual framework was a model that integrated the theory of reasoned action and the elaboration likelihood model of persuasion. Studies 1 and 2 established effective manipulations of positive?negative AA information, and peripheral?central routes of processing. Study 3 implemented these techniques, and a path analysis was carried out testing the differential effects of valence of information processed via different routes on AA evaluative beliefs, attitudes, intention, and expressed behavior. Results indicated that positive AA messages processed centrally (i.e., for meaning) resulted in significantly more positive evaluative beliefs. Modifications to the original model resulted in a final model with excellent fit to the data that supported the mediating role of intention in the AA attitude?behavior relationship, as predicted by the theory of reasoned action. The findings highlight potential benefits of interventions for improving support for AA policies, provided that positive information is processed at a central, evaluative level. PMID:19025247

  9. The transgenic cloned pig population with integrated and controllable GH expression that has higher feed efficiency and meat production.

    PubMed

    Ju, Huiming; Zhang, Jiaqing; Bai, Lijing; Mu, Yulian; Du, Yutao; Yang, Wenxian; Li, Yong; Sheng, Anzhi; Li, Kui

    2015-01-01

    Sustained expression of the GH gene has been shown to have detrimental effects on the health of animals. In the current study, transgenic founder pigs, with controllable pig growth hormone (pGH) expression, were cloned via the handmade cloning method (HMC), and pGH expression levels were examined at the cellular and organismal levels. The serum pGH levels in 3 founder male pigs were found to be significantly higher after induction with intramuscular injection of doxycycline (DOX) compared to baseline. A daily dose of DOX was administered via feed to these animals for a period of 65 to 155 days. The growth rate, feed efficiency and pGH serum concentration increased in the DOX-induced transgenic group compared with the other groups. 8 numbers of animals were euthanized and the dressing percentage, loin muscle and lean meat percentage were significantly higher in the DOX-induced F1 transgenic group compared with the other groups. In this study a large population of transgenic pigs, with integrated controllable expression of a transgene, was obtained. The transgenic pigs were healthy and normal in terms of reproductive capability. At the same time, feed efficiency was improved, production processes were accelerated and meat yield was increased. PMID:25959098

  10. Chromatin-bound nuclear pore components regulate gene expression in higher eukaryotes

    PubMed Central

    Capelson, Maya; Liang, Yun; Schulte, Roberta; Mair, William; Wagner, Ulrich; Hetzer, Martin W.

    2010-01-01

    Nuclear pore complexes have recently been shown to play roles in gene activation, however their potential involvement in metazoan transcription remains unclear. Here we show that the nucleoporins Sec13, Nup98 and Nup88, as well as a group of FG-repeat nucleoporins, bind to the Drosophila genome at functionally distinct loci that often do not represent NE contact sites. While Nup88 localizes to silent loci, Sec13, Nup98 and a subset of FG-repeat nucleoporins bind to developmentally regulated genes undergoing transcription induction. Strikingly, RNAi-mediated knockdown of intranuclear Sec13 and Nup98 specifically inhibits transcription of their target genes and prevents efficient reactivation of transcription after heat shock, suggesting an essential role of NPC components in regulating complex gene expression programs of multicellular organisms. PMID:20144761

  11. Low Phosphorylated AKT Expression in Laryngeal Cancer: Indications for a Higher Metastatic Risk

    SciTech Connect

    Nijkamp, Monique M.; Span, Paul N.; Stegeman, Hanneke; Grénman, Reidar; Kaanders, Johannes H.A.M.; Bussink, Johan

    2013-10-01

    Purpose: To validate the association of phosphorylated (p)AKT with lymph node metastasis in an independent, homogeneous cohort of patients with larynx cancer. Methods and Materials: Seventy-eight patients with laryngeal cancer were included. Epidermal growth factor receptor, pAKT, vimentin, E-cadherin, hypoxia, and blood vessels were visualized in biopsy material using immunohistochemistry. Positive tumor areas and spatial relationships between markers were assessed by automated image analysis. In 6 laryngeal cancer cell lines, E-cadherin and vimentin messenger RNA was quantified by real-time polymerase chain reaction and by immunohistochemistry before and after treatment with the pAKT inhibitor MK-2206. Results: A significant correlation was found between low pAKT in the primary tumor and positive lymph node status (P=.0005). Tumors with lymph node metastases had an approximately 10-fold lower median pAKT value compared with tumors without lymph node metastases, albeit with large intertumor variations, validating our previous results. After inhibition of pAKT in laryngeal cancer cells with MK-2206, up-regulation of vimentin and a downregulation of E-cadherin occurred, consistent with epithelial–mesenchymal transition. Conclusion: Low pAKT expression in larynx tumors is associated with lymph node metastases. Further, inhibition of pAKT in laryngeal cancer induces epithelial–mesenchymal transition, predisposing for an increased metastatic risk.

  12. Higher efficiency soluble prokaryotic expression, purification, and structural analysis of antimicrobial peptide G13.

    PubMed

    Che, Yuanyuan; Lu, Yinghu; Zha, Xiangdong; Huang, Huoqing; Yang, Peilong; Ma, Lijuan; Xu, Xuejiao

    2016-03-01

    G13 is a 19-residue cationic antimicrobial peptide derived from granulysin. In order to achieve high-level expression of G13 in Escherichia coli cells, and to reduce downstream processing costs, we introduced an Asp-Pro acid labile bond between the His-Patch thioredoxin and G13 and constructed the recombinant plasmid pThiohisA-DP-G13. The plasmid was transformed into E. coli BL21 (DE3). After induction with isopropyl-β-d-thiogalactopyranoside for 5 h, the fusion protein accumulated up to 200 mg/L in soluble form. The fusion protein was released by a high pressure homogenizer, cleaved using 13% acetic acid at 50 °C hydrolysis for 72 h. The recombinant G13 (r-G13) was then successively purified by fractional precipitation with ammonium sulfate and trichloroacetic acid, followed by one-step cation exchange chromatography. The purified r-G13 displayed a single band (about 2.2 kDa) as analyzed by Tris-Tricine buffered SDS-PAGE, and its precise molecular weight was confirmed using tandem mass spectrometry. Analysis of r-G13 by circular dichroism (CD) indicated that r-G13 contained predominantly β-sheet and random coil. Agar plate diffusion assay revealed that the r-G13 exhibited antibacterial activity against both Bacillus subtilis and E. coli. PMID:26581777

  13. Unraveling of the E-helices and Disruption of 4-Fold Pores Are Associated with Iron Mishandling in a Mutant Ferritin Causing Neurodegeneration

    SciTech Connect

    Baraibar, Martin A.; Muhoberac, Barry B.; Garringer, Holly J.; Hurley, Thomas D.; Vidal, Ruben

    2010-03-12

    Mutations in the coding sequence of the ferritin light chain (FTL) gene cause a neurodegenerative disease known as neuroferritinopathy or hereditary ferritinopathy, which is characterized by the presence of intracellular inclusion bodies containing the mutant FTL polypeptide and by abnormal accumulation of iron in the brain. Here, we describe the x-ray crystallographic structure and report functional studies of ferritin homopolymers formed from the mutant FTL polypeptide p.Phe167SerfsX26, which has a C terminus that is altered in amino acid sequence and length. The structure was determined and refined to 2.85 {angstrom} resolution and was very similar to the wild type between residues Ile-5 and Arg-154. However, instead of the E-helices normally present in wild type ferritin, the C-terminal sequences of all 24 mutant subunits showed substantial amounts of disorder, leading to multiple C-terminal polypeptide conformations and a large disruption of the normally tiny 4-fold axis pores. Functional studies underscored the importance of the mutant C-terminal sequence in iron-induced precipitation and revealed iron mishandling by soluble mutant FTL homopolymers in that only wild type incorporated iron when in direct competition in solution with mutant ferritin. Even without competition, the amount of iron incorporation over the first few minutes differed severalfold. Our data suggest that disruption at the 4-fold pores may lead to direct iron mishandling through attenuated iron incorporation by the soluble form of mutant ferritin and that the disordered C-terminal polypeptides may play a major role in iron-induced precipitation and formation of ferritin inclusion bodies in hereditary ferritinopathy.

  14. Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5α expression in PBMC

    PubMed Central

    2014-01-01

    Background At least six host-encoded restriction factors (RFs), APOBEC3G, TRIM5α, tetherin, SAMHD1, schlafen 11, and Mx2 have now been shown to inhibit HIV and/or SIV replication in vitro. To determine their role in vivo in the resistance of macaques to mucosally-acquired SIV, we quantified both pre-exposure (basal) and post-exposure mRNA levels of these RFs, Mx1, and IFNγ in PBMC, lymph nodes, and duodenum of rhesus macaques undergoing weekly low dose rectal exposures to the primary isolate, SIV/DeltaB670. Results Repetitive challenge divided the monkeys into two groups with respect to their susceptibility to infection: highly susceptible (2–3 challenges, 5 monkeys) and poorly susceptible (≥6 challenges, 3 monkeys). Basal RF and Mx1 expression varied among the three tissues examined, with the lowest expression generally detected in duodenal tissues, and the highest observed in PBMC. The one exception was A3G whose basal expression was greatest in lymph nodes. Importantly, significantly higher basal expression of TRIM5α and Mx1 was observed in PBMC of animals more resistant to mucosal infection. Moreover, individual TRIM5α levels were stable throughout a year prior to infection. Post-exposure induction of these genes was also observed after virus appearance in plasma, with elevated levels in PBMC and duodenum transiently occurring 7–10 days post infection. They did not appear to have an effect on control of viremia. Interestingly, minimal to no induction was observed in the resistant animal that became an elite controller. Conclusions These results suggest that constitutively expressed TRIM5α appears to play a greater role in restricting mucosal transmission of SIV than that associated with type I interferon induction following virus entry. Surprisingly, this association was not observed with the other RFs. The higher basal expression of TRIM5α observed in PBMC than in duodenal tissues emphasizes the understated role of the second barrier to systemic

  15. Expression of CD56 is an unfavorable prognostic factor for acute promyelocytic leukemia with higher initial white blood cell counts

    PubMed Central

    Ono, Takaaki; Takeshita, Akihiro; Kishimoto, Yuji; Kiyoi, Hitoshi; Okada, Masaya; Yamauchi, Takahiro; Emi, Nobuhiko; Horikawa, Kentaro; Matsuda, Mitsuhiro; Shinagawa, Katsuji; Monma, Fumihiko; Ohtake, Shigeki; Nakaseko, Chiaki; Takahashi, Masatomo; Kimura, Yukihiko; Iwanaga, Masako; Asou, Norio; Naoe, Tomoki

    2014-01-01

    Expression of CD56 has recently been introduced as one of the adverse prognostic factors in acute promyelocytic leukemia (APL). However, the clinical significance of CD56 antigen in APL has not been well elucidated. We assessed the clinical significance of CD56 antigen in 239 APL patients prospectively treated with all-trans retinoic acid and chemotherapy according to the Japan Adult Leukemia Study Group APL97 protocol. All patients were prospectively treated by the Japan Adult Leukemia Study Group APL97 protocol. The median follow-up period was 8.5 years. Positive CD56 expression was found in 23 APL patients (9.6%). Expression of CD56 was significantly associated with lower platelet count (P = 0.04), severe disseminated intravascular coagulation (P = 0.04), and coexpression of CD2 (P = 0.03), CD7 (P = 0.04), CD34 (P < 0.01) and/or human leukocyte antigen-DR (P < 0.01). Complete remission rate and overall survival were not different between the two groups. However, cumulative incidence of relapse and event-free survival (EFS) showed an inferior trend in CD56+ APL (P = 0.08 and P = 0.08, respectively). Among patients with initial white blood cell counts of 3.0 × 109/L or more, EFS and cumulative incidence of relapse in CD56+ APL were significantly worse (30.8% vs 63.6%, P = 0.008, and 53.8% vs 28.9%, P = 0.03, respectively), and in multivariate analysis, CD56 expression was an unfavorable prognostic factor for EFS (P = 0.04). In conclusion, for APL with higher initial white blood cell counts, CD56 expression should be regarded as an unfavorable prognostic factor. PMID:24206578

  16. Overwintering Is Associated with Reduced Expression of Immune Genes and Higher Susceptibility to Virus Infection in Honey Bees

    PubMed Central

    Steinmann, Nadja; Corona, Miguel; Neumann, Peter; Dainat, Benjamin

    2015-01-01

    The eusocial honey bee, Apis mellifera, has evolved remarkable abilities to survive extreme seasonal differences in temperature and availability of resources by dividing the worker caste into two groups that differ in physiology and lifespan: summer and winter bees. Most of the recent major losses of managed honey bee colonies occur during the winter, suggesting that winter bees may have compromised immune function and higher susceptibility to diseases. We tested this hypothesis by comparing the expression of eight immune genes and naturally occurring infection levels of deformed wing virus (DWV), one of the most widespread viruses in A. mellifera populations, between summer and winter bees. Possible interactions between immune response and physiological activity were tested by measuring the expression of vitellogenin and methyl farnesoate epoxidase, a gene coding for the last enzyme involved in juvenile hormone biosynthesis. Our data show that high DWV loads in winter bees correlate with reduced expression of genes involved in the cellular immune response and physiological activity and high expression of humoral immune genes involved in antibacterial defense compared with summer bees. This expression pattern could reflect evolutionary adaptations to resist bacterial pathogens and economize energy during the winter under a pathogen landscape with reduced risk of pathogenic viral infections. The outbreak of Varroa destructor infestation could have overcome these adaptations by promoting the transmission of viruses. Our results suggest that reduced cellular immune function during the winter may have increased honey bee’s susceptibility to DWV. These results contribute to our understanding of honey bee colony losses in temperate regions. PMID:26121358

  17. Overwintering Is Associated with Reduced Expression of Immune Genes and Higher Susceptibility to Virus Infection in Honey Bees.

    PubMed

    Steinmann, Nadja; Corona, Miguel; Neumann, Peter; Dainat, Benjamin

    2015-01-01

    The eusocial honey bee, Apis mellifera, has evolved remarkable abilities to survive extreme seasonal differences in temperature and availability of resources by dividing the worker caste into two groups that differ in physiology and lifespan: summer and winter bees. Most of the recent major losses of managed honey bee colonies occur during the winter, suggesting that winter bees may have compromised immune function and higher susceptibility to diseases. We tested this hypothesis by comparing the expression of eight immune genes and naturally occurring infection levels of deformed wing virus (DWV), one of the most widespread viruses in A. mellifera populations, between summer and winter bees. Possible interactions between immune response and physiological activity were tested by measuring the expression of vitellogenin and methyl farnesoate epoxidase, a gene coding for the last enzyme involved in juvenile hormone biosynthesis. Our data show that high DWV loads in winter bees correlate with reduced expression of genes involved in the cellular immune response and physiological activity and high expression of humoral immune genes involved in antibacterial defense compared with summer bees. This expression pattern could reflect evolutionary adaptations to resist bacterial pathogens and economize energy during the winter under a pathogen landscape with reduced risk of pathogenic viral infections. The outbreak of Varroa destructor infestation could have overcome these adaptations by promoting the transmission of viruses. Our results suggest that reduced cellular immune function during the winter may have increased honey bee's susceptibility to DWV. These results contribute to our understanding of honey bee colony losses in temperate regions. PMID:26121358

  18. The prelimbic cortex uses higher-order cues to modulate both the acquisition and expression of conditioned fear

    PubMed Central

    Sharpe, Melissa J.; Killcross, Simon

    2015-01-01

    The prelimbic (PL) cortex allows rodents to adapt their responding under changing experimental circumstances. In line with this, the PL cortex has been implicated in strategy set shifting, attentional set shifting, the resolution of response conflict, and the modulation of attention towards predictive stimuli. One interpretation of this research is that the PL cortex is involved in using information garnered from higher-order cues in the environment to modulate how an animal responds to environmental stimuli. However, data supporting this view of PL function in the aversive domain are lacking. In the following experiments, we attempted to answer two questions. Firstly, we wanted to investigate whether the role of the PL cortex in using higher-order cues to influence responding generalizes across appetitive and aversive domains. Secondly, as much of the research has focused on a role for the PL cortex in performance, we wanted to assess whether this region is also involved in the acquisition of hierarchal associations which facilitate an ability to use higher-order cues to modulate responding. In order to answer these questions, we assessed the impact of PL inactivation during both the acquisition and expression of a contextual bi-conditional discrimination. A contextual bi-conditional discrimination involves presenting two stimuli. In one context, one stimulus is paired with shock while the other is presented without shock. In another context, these contingencies are reversed. Thus, animals have to use the present contextual cues to disambiguate the significance of the stimulus and respond appropriately. We found that PL inactivation disrupted both the encoding and expression of these context-dependent associations. This supports a role for the PL cortex in allowing higher-order cues to modulate both learning about, and responding towards, different cues. We discuss these findings in the broader context of functioning in the medial prefrontal cortex (PFC). PMID

  19. The regulation of thermal stress induced apoptosis in corals reveals high similarities in gene expression and function to higher animals

    PubMed Central

    Kvitt, Hagit; Rosenfeld, Hanna; Tchernov, Dan

    2016-01-01

    Recent studies suggest that controlled apoptotic response provides an essential mechanism, enabling corals to respond to global warming and ocean acidification. However, the molecules involved and their functions are still unclear. To better characterize the apoptotic response in basal metazoans, we studied the expression profiles of selected genes that encode for putative pro- and anti-apoptotic mediators in the coral Stylophora pistillata under thermal stress and bleaching conditions. Upon thermal stress, as attested by the elevation of the heat-shock protein gene HSP70’s mRNA levels, the expression of all studied genes, including caspase, Bcl-2, Bax, APAF-1 and BI-1, peaked at 6–24 h of thermal stress (hts) and declined at 72 hts. Adversely, the expression levels of the survivin gene showed a shifted pattern, with elevation at 48–72 hts and a return to basal levels at 168 hts. Overall, we show the quantitative anti-apoptotic traits of the coral Bcl-2 protein, which resemble those of its mammalian counterpart. Altogether, our results highlight the similarities between apoptotic networks operating in simple metazoans and in higher animals and clearly demonstrate the activation of pro-cell survival regulators at early stages of the apoptotic response, contributing to the decline of apoptosis and the acclimation to chronic stress. PMID:27460544

  20. The regulation of thermal stress induced apoptosis in corals reveals high similarities in gene expression and function to higher animals

    NASA Astrophysics Data System (ADS)

    Kvitt, Hagit; Rosenfeld, Hanna; Tchernov, Dan

    2016-07-01

    Recent studies suggest that controlled apoptotic response provides an essential mechanism, enabling corals to respond to global warming and ocean acidification. However, the molecules involved and their functions are still unclear. To better characterize the apoptotic response in basal metazoans, we studied the expression profiles of selected genes that encode for putative pro- and anti-apoptotic mediators in the coral Stylophora pistillata under thermal stress and bleaching conditions. Upon thermal stress, as attested by the elevation of the heat-shock protein gene HSP70’s mRNA levels, the expression of all studied genes, including caspase, Bcl-2, Bax, APAF-1 and BI-1, peaked at 6–24 h of thermal stress (hts) and declined at 72 hts. Adversely, the expression levels of the survivin gene showed a shifted pattern, with elevation at 48–72 hts and a return to basal levels at 168 hts. Overall, we show the quantitative anti-apoptotic traits of the coral Bcl-2 protein, which resemble those of its mammalian counterpart. Altogether, our results highlight the similarities between apoptotic networks operating in simple metazoans and in higher animals and clearly demonstrate the activation of pro-cell survival regulators at early stages of the apoptotic response, contributing to the decline of apoptosis and the acclimation to chronic stress.

  1. The regulation of thermal stress induced apoptosis in corals reveals high similarities in gene expression and function to higher animals.

    PubMed

    Kvitt, Hagit; Rosenfeld, Hanna; Tchernov, Dan

    2016-01-01

    Recent studies suggest that controlled apoptotic response provides an essential mechanism, enabling corals to respond to global warming and ocean acidification. However, the molecules involved and their functions are still unclear. To better characterize the apoptotic response in basal metazoans, we studied the expression profiles of selected genes that encode for putative pro- and anti-apoptotic mediators in the coral Stylophora pistillata under thermal stress and bleaching conditions. Upon thermal stress, as attested by the elevation of the heat-shock protein gene HSP70's mRNA levels, the expression of all studied genes, including caspase, Bcl-2, Bax, APAF-1 and BI-1, peaked at 6-24 h of thermal stress (hts) and declined at 72 hts. Adversely, the expression levels of the survivin gene showed a shifted pattern, with elevation at 48-72 hts and a return to basal levels at 168 hts. Overall, we show the quantitative anti-apoptotic traits of the coral Bcl-2 protein, which resemble those of its mammalian counterpart. Altogether, our results highlight the similarities between apoptotic networks operating in simple metazoans and in higher animals and clearly demonstrate the activation of pro-cell survival regulators at early stages of the apoptotic response, contributing to the decline of apoptosis and the acclimation to chronic stress. PMID:27460544

  2. Increased In Vitro Osteopotential in SHED Associated with Higher IGF2 Expression When Compared with hASCs.

    PubMed

    Fanganiello, Roberto Dalto; Ishiy, Felipe Augusto Andre; Kobayashi, Gerson Shigeru; Alvizi, Lucas; Sunaga, Daniele Yumi; Passos-Bueno, Maria Rita

    2015-08-01

    Mesenchymal stem cell (MSC) osteogenic differentiation potential varies according to factors such as tissue source and cell population heterogeneity. Pre-selection of cell subpopulations harboring higher osteopotential is a promising strategy to achieve a thorough translation of MSC-based therapies to the clinic. Here, we searched for novel molecular markers predictive of osteopotential by comparing MSC populations from two sources harboring different osteogenic potentials. We show that MSCs from human deciduous teeth (SHED) have an intrinsically higher osteogenic potential when compared with MSCs from human adipose tissue (hASCs) under the same in vitro controlled induction system. Transcriptome profiling revealed IGF2 to be one of the top upregulated transcripts before and during early in vitro osteogenic differentiation. Further, exogenous IGF2 supplementation enhanced alkaline phosphatase activity and matrix mineralization, and inhibition of IGF2 lessened these parameters in SHED and hASCs, validating IGF2 as an osteogenic factor in these MSCs. Further, we found IGF2 to be biallelically expressed in SHED, but not in hASCs. We observed a 4 % methylation increase in the imprinting control region within the IGF2-H19 locus in SHED, and this is mainly due to 2 specific CpG sites. Thus, we suggest that IGF2 upregulation in SHED is due to loss of imprinting. This study unravels osteogenic properties in SHED, implying IGF2 as a potential biomarker of MSCs with higher osteopotential, and unveils IGF2 loss-of-imprinting in SHED. PMID:25931278

  3. Recombinant expression and purification of a MAP30-cell penetrating peptide fusion protein with higher anti-tumor bioactivity.

    PubMed

    Lv, Qiang; Yang, Xu-Zhong; Fu, Long-Yun; Lu, Yv-Ting; Lu, Yan-Hua; Zhao, Jian; Wang, Fu-Jun

    2015-07-01

    MAP30 (Momordica Antiviral Protein 30 Kd), a single-stranded type-I ribosome inactivating protein, possesses versatile biological activities including anti-tumor abilities. However, the low efficiency penetrating into tumor cells hampers the tumoricidal effect of MAP30. This paper describes MAP30 fused with a human-derived cell penetrating peptide HBD which overcome the low uptake efficiency by tumor cells and exhibits higher anti-tumor bioactivity. MAP30 gene was cloned from the genomic DNA of Momordica charantia and the recombinant plasmid pET28b-MAP30-HBD was established and transferred into Escherichia coli BL21 (DE3). The recombinant MAP30-HBD protein (rMAP30-HBD) was expressed in a soluble form after being induced by 0.5mM IPTG for 14h at 15°C. The recombinant protein was purified to greater than 95% purity with Ni-NTA affinity chromatography. The rMAP30-HBD protein not only has topological inactivation and protein translation inhibition activity but also showed significant improvements in cytotoxic activity compared to that of the rMAP30 protein without HBD in the tested tumor cell lines, and induced higher apoptosis rates in HeLa cells analyzed by Annexin V-FITC with FACS. This paper demonstrated a new method for improving MAP30 protein anti-tumor activity and might have potential applications in cancer therapy area. PMID:25797209

  4. A porous 4-fold-interpenetrated chiral framework exhibiting vapochromism, single-crystal-to-single-crystal solvent exchange, gas sorption, and a poisoning effect.

    PubMed

    Zeng, Ming-Hua; Tan, Yan-Xi; He, Yan-Ping; Yin, Zheng; Chen, Qing; Kurmoo, Mohamedally

    2013-03-01

    The synthesis and characterization of a 4-fold-interpenetrated pseudodiamond metal-organic framework (MOF), Co(II)(pybz)2·2DMF [pybz = 4-(4-pyridyl)benzoate], are reported. N,N-Dimethylformamide (DMF) of the channels can be removed to give the porous framework, and it can also be exchanged for methanol, ethanol, benzene, and cyclohexane. It is a rare example of a stable MOF based on a single octahedral building unit. The single-crystal structures of Co(II)(pybz)2·2DMF, Co(II)(pybz)2, Co(II)(pybz)2·4MeOH, and Co(II)(pybz)2·2.5EtOH have been successfully determined. In all of them, the framework is marginally modified and contains a highly distorted and strained octahedral node of cobalt with two pyridine nitrogen atoms and two chelate carboxylate groups. In air, the crystals of Co(II)(pybz)2·2DMF readily change color from claret red to light pink. Thermogravimetric analysis and Raman spectroscopy indicate a change in coordination, where the carboxylate becomes monodentate and an additional two water molecules are coordinated to each cobalt atom. In a dry solvent, this transformation does not take place. Tests show that Co(II)(pybz)2 may be a more efficient drying agent than silica gel and anhydrous CuSO4. The desolvated Co(II)(pybz)2 can absorb several gases such as CO2, N2, H2, and CH4 and also vapors of methanol, ethanol, benzene, and cyclohexane. If Co(II)(pybz)2 is exposed to air and followed by reactivation, its sorption capacity is considerably reduced, which we associate with a poisoning effect. Because of the long distance between the cobalt atoms in the structure, the magnetic properties are those of a paramagnet. PMID:23398593

  5. The crystal structure of ferritin from Chlorobium tepidum reveals a new conformation of the 4-fold channel for this protein family.

    PubMed

    Arenas-Salinas, Mauricio; Townsend, Philip D; Brito, Christian; Marquez, Valeria; Marabolli, Vanessa; Gonzalez-Nilo, Fernando; Matias, Cata; Watt, Richard K; López-Castro, Juan D; Domínguez-Vera, José; Pohl, Ehmke; Yévenes, Alejandro

    2014-11-01

    Ferritins are ubiquitous iron-storage proteins found in all kingdoms of life. They share a common architecture made of 24 subunits of five α-helices. The recombinant Chlorobium tepidum ferritin (rCtFtn) is a structurally interesting protein since sequence alignments with other ferritins show that this protein has a significantly extended C-terminus, which possesses 12 histidine residues as well as several aspartate and glutamic acid residues that are potential metal ion binding residues. We show that the macromolecular assembly of rCtFtn exhibits a cage-like hollow shell consisting of 24 monomers that are related by 4-3-2 symmetry; similar to the assembly of other ferritins. In all ferritins of known structure the short fifth α-helix adopts an acute angle with respect to the four-helix bundle. However, the crystal structure of the rCtFtn presented here shows that this helix adopts a new conformation defining a new assembly of the 4-fold channel of rCtFtn. This conformation allows the arrangement of the C-terminal region into the inner cavity of the protein shell. Furthermore, two Fe(III) ions were found in each ferroxidase center of rCtFtn, with an average FeA-FeB distance of 3 Å; corresponding to a diferric μ-oxo/hydroxo species. This is the first ferritin crystal structure with an isolated di-iron center in an iron-storage ferritin. The crystal structure of rCtFtn and the biochemical results presented here, suggests that rCtFtn presents similar biochemical properties reported for other members of this protein family albeit with distinct structural plasticity. PMID:25079050

  6. Untypical connectivity from olfactory sensory neurons expressing OR37 into higher brain centers visualized by genetic tracing.

    PubMed

    Bader, Andrea; Breer, Heinz; Strotmann, Jörg

    2012-05-01

    The OR37 subfamily of odorant receptors(ORs) exists exclusively in mammals. In contrast to ORs in general, they are highly conserved within and across species.These unique features raise the question, whether olfactory information gathered by the OR37 sensory cells is processed in specially designated brain areas. To elucidate the wiring of projection neurons from OR37 glomeruli into higher brain areas, tracing experiments were performed.The application of DiI onto the ventral area of the olfactory bulb, which harbors the OR37 glomeruli, led to the labeling of fibers not only in the typical olfactory cortical regions,but also in the medial amygdala and the hypothalamus. To visualize the projections from a defined OR37 glomerulus more precisely, transgenic mice were studied in which olfactory sensory neurons co-express the receptor subtype OR37C and the transsynaptic tracer wheat germ agglutinin(WGA). WGA became visible not only in the OR37C sensory neurons and the corresponding OR37C glomerulus,but also in cell somata located in the mitral/tufted cell layer adjacent to the OR37C glomerulus, indicating a transfer of WGA onto projection neurons. In the brain, WGA immunoreactivity was not detectable in typical olfactory cortical areas, but instead in distinct areas of the medial amygdala.Detailed mapping revealed that the WGA immunoreactivity was restricted to the posterior-dorsal subnucleus of the medial amygdala. In addition, WGA immunoreactivity was visible in some well-circumscribed areas of the hypothalamus.These results are indicative for a unique connectivity from OR37C sensory cells into higher brain centers. PMID:22294261

  7. Higher expression of monocyte chemoattractant protein 1 and its receptor in brain tissue of intractable epilepsy patients.

    PubMed

    Wang, Chunyan; Yang, Lihua; Zhang, Jiadong; Lin, Zhiguo; Qi, Jiping; Duan, Shurong

    2016-06-01

    We aimed to explore the pathogenesis of monocyte chemoattractant protein-1 (MCP1) and CC chemokine receptor 2 (CCR2) in brain tissue of patients with intractable epilepsy (IE). Hippocampi or temporal lobe tissues were obtained from 40 patients with IE and five patients without IE who had undergone surgical decompression and debridement. The levels of MCP1 and CCR2 were evaluated using immunohistochemistry. Pearson correlation analysis was employed to evaluate the correlation between levels of MCP1 and CCR2 in IE with or without hippocampal sclerosis (HS) and the disease duration, along with age. Higher levels of MCP1 (11.68±4.68% versus 1.72±1.54%) and CCR2 (11.54±4.65% versus 1.52±1.29%; P<0.05) were observed in IE patients compared to controls. Expression levels of MCP1 (R=0.867) and CCR2 (R=0.835) in IE patients with HS were correlated with the disease duration. However, no correlation was found in IE patients without HS. There was also no correlation between levels of MCP1 and CCR2 in IE patients with age, either with HS or without HS. These results suggest that MCP1 and its receptor may play a role in the pathogenesis and progression of IE. PMID:26810469

  8. Chemically Assisted Enucleation Results in Higher G6PD Expression in Early Bovine Female Embryos Obtained by Somatic Cell Nuclear Transfer

    PubMed Central

    Oliveira, Clara Slade; Tetzner, Tatiane Almeida Drummond; de Lima, Marina Ragagnin; de Melo, Danilas Salinet; Niciura, Simone Cristina Méo; Garcia, Joaquim Mansano

    2012-01-01

    Abstract Despite extensive efforts, low efficiency is still an issue in bovine somatic cell nuclear transfer (SCNT). The hypothesis of our study was that the use of cytoplasts produced by chemically assisted enucleation (EN) would improve nuclear reprogramming in nuclear transfer (NT)–derived embryos because it results in lower damage and higher cytoplasm content than conventional EN. For that purpose, we investigated the expression of two X-linked genes: X inactive-specific transcript (XIST) and glucose 6-phosphate dehydrogenase (G6PD). In the first experiment, gene expression was assessed in day-7 female blastocysts from embryonic cell NT (ECNT) groups [conventional, ECNT conv; chemically assisted, ECNT deme (demecolcine)]. Whereas in the ECNT conv group, only one embryo (25%; n=4) expressed XIST transcripts, most embryos showed XIST expression (75%; n=4) in the ECNT deme group. However, no significant differences in transcript abundance of XIST and G6PD were found when comparing the embryos from all groups. In a second experiment using somatic cells as nuclear donors, we evaluated gene expression profiles in female SCNT-derived embryos. No significant differences in relative abundance (RA) of XIST transcripts were observed among the groups. Nonetheless, higher (p<0.05) levels of G6PD were observed in SCNT deme and in vitro–derived groups in comparison to SCNT conv. To know whether higher G6PD expression in embryos derived from SCNT chemically assisted EN indicates higher metabolism in embryos considered of superior quality or if the presence of higher reactive oxygen species (ROS) levels generated by the increased oxygen consumption triggers G6PD activation, the expression of genes related to stress response should be investigated in embryos produced by that technique. PMID:22908977

  9. Microarray Analysis Reveals Higher Gestational Folic Acid Alters Expression of Genes in the Cerebellum of Mice Offspring—A Pilot Study

    PubMed Central

    Barua, Subit; Kuizon, Salomon; Chadman, Kathryn K.; Brown, W. Ted; Junaid, Mohammed A.

    2015-01-01

    Folate is a water-soluble vitamin that is critical for nucleotide synthesis and can modulate methylation of DNA by altering one-carbon metabolism. Previous studies have shown that folate status during pregnancy is associated with various congenital defects including the risk of aberrant neural tube closure. Maternal exposure to a methyl supplemented diet also can alter DNA methylation and gene expression, which may influence the phenotype of offspring. We investigated if higher gestational folic acid (FA) in the diet dysregulates the expression of genes in the cerebellum of offspring in C57BL/6 J mice. One week before gestation and throughout the pregnancy, groups of dams were supplemented with FA either at 2 mg/kg or 20 mg/kg of diet. Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups. Our results revealed that exposure to the higher dose FA diet during gestation dysregulated expression of several genes in the cerebellum of both male and female pups. Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels. These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development. PMID:25629700

  10. Dogs with patent Dirofilaria immitis infection have higher expression of circulating IL-4, IL-10 and iNOS mRNA than those with occult infection.

    PubMed

    Morchón, R; López-Belmonte, J; Bazzocchi, C; Grandi, G; Kramer, L; Simón, F

    2007-01-15

    Dirofilaria immitis is the agent of canine heartworm disease, in which adult worms reside in the pulmonary arteries, producing first stage larvae (microfilariae) that are released into the bloodstream. The present work describes the cytokine and iNOS mRNA expression in the peripheral blood of naturally infected dogs classified as either microfilariemic or amicrofilariemic. Results show that microfilariemic dogs had higher expression of IL-4 and iNOS mRNA than amicrofilariemic dogs. Furthermore, IL-10 mRNA expression was strongly expressed in dogs with circulating microfilariae, compared to only negligible expression in amicrofilariemic dogs. Finally, mf+ status was associated with a predominance in IgG1 production against worm antigens. These results would suggest that circulating mf may stimulate, like in other filarial infections, an immune bias towards unresponsiveness in D. immitis-infected dogs, consenting long-term adult worm survival. PMID:17112598

  11. Directed evolution of G protein-coupled receptors in yeast for higher functional production in eukaryotic expression hosts

    PubMed Central

    Schütz, Marco; Schöppe, Jendrik; Sedlák, Erik; Hillenbrand, Matthias; Nagy-Davidescu, Gabriela; Ehrenmann, Janosch; Klenk, Christoph; Egloff, Pascal; Kummer, Lutz; Plückthun, Andreas

    2016-01-01

    Despite recent successes, many G protein-coupled receptors (GPCRs) remained refractory to detailed molecular studies due to insufficient production yields, even in the most sophisticated eukaryotic expression systems. Here we introduce a robust method employing directed evolution of GPCRs in yeast that allows fast and efficient generation of receptor variants which show strongly increased functional production levels in eukaryotic expression hosts. Shown by evolving three different receptors in this study, the method is widely applicable, even for GPCRs which are very difficult to express. The evolved variants showed up to a 26-fold increase of functional production in insect cells compared to the wild-type receptors. Next to the increased production, the obtained variants exhibited improved biophysical properties, while functional properties remained largely unaffected. Thus, the presented method broadens the portfolio of GPCRs accessible for detailed investigations. Interestingly, the functional production of GPCRs in yeast can be further increased by induced host adaptation. PMID:26911446

  12. Directed evolution of G protein-coupled receptors in yeast for higher functional production in eukaryotic expression hosts.

    PubMed

    Schütz, Marco; Schöppe, Jendrik; Sedlák, Erik; Hillenbrand, Matthias; Nagy-Davidescu, Gabriela; Ehrenmann, Janosch; Klenk, Christoph; Egloff, Pascal; Kummer, Lutz; Plückthun, Andreas

    2016-01-01

    Despite recent successes, many G protein-coupled receptors (GPCRs) remained refractory to detailed molecular studies due to insufficient production yields, even in the most sophisticated eukaryotic expression systems. Here we introduce a robust method employing directed evolution of GPCRs in yeast that allows fast and efficient generation of receptor variants which show strongly increased functional production levels in eukaryotic expression hosts. Shown by evolving three different receptors in this study, the method is widely applicable, even for GPCRs which are very difficult to express. The evolved variants showed up to a 26-fold increase of functional production in insect cells compared to the wild-type receptors. Next to the increased production, the obtained variants exhibited improved biophysical properties, while functional properties remained largely unaffected. Thus, the presented method broadens the portfolio of GPCRs accessible for detailed investigations. Interestingly, the functional production of GPCRs in yeast can be further increased by induced host adaptation. PMID:26911446

  13. Higher gene expression of CYP1A2, 2B1 and 2D2 in the brain of female compared with male rats.

    PubMed

    Nagai, K; Fukuno, S; Suzuki, H; Konishi, H

    2016-06-01

    Cytochrome P450 (CYP) in the brain plays an essential role in the local metabolism of various compounds, including clinically used drugs, toxins, and endogenous substances. In the present study, we compared the expression profiles of mRNAs for several CYP subtypes in the brain between male and female rats. The expression of CYP1A2, CYP2B1, and CYP2D2 in females was significantly higher than that in males. On the other hand, the expression level of the other CYP subtypes examined in the male brain was similar to that in the female brain. These results strongly suggest that marked gender differences exist in the expression profiles of some CYP subtypes in rat brain. PMID:27455552

  14. MEIS1, PREP1, and PBX4 Are Differentially Expressed in Acute Lymphoblastic Leukemia: Association of MEIS1 Expression with Higher Proliferation and Chemotherapy Resistance

    PubMed Central

    2011-01-01

    Background The Three-amino acid-loop-extension (TALE) superfamily of homeodomain-containing transcription factors have been implicated in normal hematopoiesis and in leukemogenesis and are important survival, differentiation, and apoptosis pathway modulators. In this work, we determined the expression levels of TALE genes in leukemic-derived cell lines, in blood samples of patients with Acute lymphoblastic leukemia (ALL), and in the blood samples of healthy donors. Results Here we show increased expression of MEIS1, MEIS2, and PREP1 genes in leukemia-derived cell lines compared with blood normal cells. High levels of MEIS1 and PREP1, and low levels of PBX4 expression were also founded in samples of patients with ALL. Importantly, silencing of MEIS1 decreases the proliferation of leukemia-derived cells but increases their survival after etoposide treatment. Etoposide-induced apoptosis induces down-regulation of MEIS1 expression or PREP1 up-regulation in chemotherapy-resistant cells. Conclusions Our results indicate that up-regulation of MEIS1 is important for sustaining proliferation of leukemic cells and that down-regulation of MEIS1 or up-regulation of PREP1 and PBX genes could be implicated in the modulation of the cellular response to chemotherapeutic-induced apoptosis. PMID:22185299

  15. CD1d expression in renal cell carcinoma is associated with higher relapse rates, poorer cancer-specific and overall survival

    PubMed Central

    Chong, Tsung Wen; Goh, Fera Yiqian; Sim, Mei Yi; Huang, Hong Hong; Thike, Daw Aye Aye; Lim, Weng Khong; Teh, Bin Tean; Tan, Puay Hoon

    2015-01-01

    Aims We hypothesised that CD1d expression in renal cell carcinoma (RCC) may play a role in modifying the host immune response. Our aims were to investigate the expression of CD1d and to correlate this with histopathology and clinical outcomes in a cohort study of patients with RCC. Methods Gene expression and tissue microarray studies on a panel of RCC tissue were performed. Clinicopathological correlation was analysed using χ2/Fisher's exact test. Relapse-free survival, cancer-specific survival and overall survival were calculated for both CD1d high and low expressors. Survival outcomes were estimated with the Kaplan–Meier method and compared using Cox regression analysis. Results Gene expression microarray showed significant expression of CD1d in RCC versus normal renal tissue. By immunohistochemistry, we found that CD1d expression significantly associated with tumour stage/grade, higher relapse rates, poorer cancer-specific and overall survival. Conclusions CD1d expression on RCC correlated with aggressive disease and poorer clinical outcomes. PMID:25477528

  16. Heroin use in Indonesia is associated with higher expression of CCR5 on CD4+ cells and lower ex-vivo production of CCR5 ligands.

    PubMed

    Meijerink, Hinta; Indrati, Agnes R; Soedarmo, Suharyani; Utami, Fitri; de Jong, Cor A J; Alisjahbana, Bachti; van Crevel, Reinout; Wisaksana, Rudi; Van der Ven, Andre J A M

    2015-01-28

    Opioid use may affect HIV infection through altered expression of HIV co-receptors. This was examined in Indonesia among antiretroviral therapy-naive HIV patients, many of whom use drugs. C-C chemokine receptor type 5 (CCR5) expression on CD4+ cells was higher in heroin (P = 0.007), methadone (P = 0.024) and former opioid users (P = 0.003) compared to nonusers, whereas production of RANTES and other CCR5 ligands was similar or lower. This suggests that opioids can affect HIV susceptibility through up-regulation of CCR5 or down-regulation of its ligands. PMID:25834861

  17. Over-expression of VvWRKY1 in grapevines induces expression of jasmonic acid pathway-related genes and confers higher tolerance to the downy mildew.

    PubMed

    Marchive, Chloé; Léon, Céline; Kappel, Christian; Coutos-Thévenot, Pierre; Corio-Costet, Marie-France; Delrot, Serge; Lauvergeat, Virginie

    2013-01-01

    Most WRKY transcription factors activate expression of defence genes in a salicylic acid- and/or jasmonic acid-dependent signalling pathway. We previously identified a WRKY gene, VvWRKY1, which is able to enhance tolerance to fungal pathogens when it is overexpressed in tobacco. The present work analyzes the effects of VvWRKY1 overexpression in grapevine. Microarray analysis showed that genes encoding defence-related proteins were up-regulated in the leaves of transgenic 35S::VvWRKY1 grapevines. Quantitative RT-PCR analysis confirmed that three genes putatively involved in jasmonic acid signalling pathway were overexpressed in the transgenic grapes. The ability of VvWRKY1 to trans-activate the promoters of these genes was demonstrated by transient expression in grape protoplasts. The resistance to the causal agent of downy mildew, Plasmopara viticola, was enhanced in the transgenic plants. These results show that VvWRKY1 can increase resistance of grapevine against the downy mildew through transcriptional reprogramming leading to activation of the jasmonic acid signalling pathway. PMID:23342101

  18. Distinct patterns of expression but similar biochemical properties of protein L-isoaspartyl methyltransferase in higher plants.

    PubMed

    Thapar, N; Kim, A K; Clarke, S

    2001-02-01

    Protein L-isoaspartyl methyltransferase is a widely distributed repair enzyme that initiates the conversion of abnormal L-isoaspartyl residues to their normal L-aspartyl forms. Here we show that this activity is expressed in developing corn (Zea mays) and carrot (Daucus carota var. Danvers Half Long) plants in patterns distinct from those previously seen in winter wheat (Triticum aestivum cv Augusta) and thale cress (Arabidopsis thaliana), whereas the pattern of expression observed in rice (Oryza sativa) is similar to that of winter wheat. Although high levels of activity are found in the seeds of all of these plants, relatively high levels of activity in vegetative tissues are only found in corn and carrot. The activity in leaves was found to decrease with aging, an unexpected finding given the postulated role of this enzyme in repairing age-damaged proteins. In contrast with the situation in wheat and Arabidopsis, we found that osmotic or salt stress could increase the methyltransferase activity in newly germinated seeds (but not in seeds or seedlings), whereas abscisic acid had no effect. We found that the corn, rice, and carrot enzymes have comparable affinity for methyl-accepting substrates and similar optimal temperatures for activity of 45 degrees C to 55 degrees C as the wheat and Arabidopsis enzymes. These experiments suggest that this enzyme may have specific roles in different plant tissues despite a common catalytic function. PMID:11161058

  19. Potential non-B DNA regions in the human genome are associated with higher rates of nucleotide mutation and expression variation

    PubMed Central

    Du, Xiangjun; Gertz, E. Michael; Wojtowicz, Damian; Zhabinskaya, Dina; Levens, David; Benham, Craig J.; Schäffer, Alejandro A.; Przytycka, Teresa M.

    2014-01-01

    While individual non-B DNA structures have been shown to impact gene expression, their broad regulatory role remains elusive. We utilized genomic variants and expression quantitative trait loci (eQTL) data to analyze genome-wide variation propensities of potential non-B DNA regions and their relation to gene expression. Independent of genomic location, these regions were enriched in nucleotide variants. Our results are consistent with previously observed mutagenic properties of these regions and counter a previous study concluding that G-quadruplex regions have a reduced frequency of variants. While such mutagenicity might undermine functionality of these elements, we identified in potential non-B DNA regions a signature of negative selection. Yet, we found a depletion of eQTL-associated variants in potential non-B DNA regions, opposite to what might be expected from their proposed regulatory role. However, we also observed that genes downstream of potential non-B DNA regions showed higher expression variation between individuals. This coupling between mutagenicity and tolerance for expression variability of downstream genes may be a result of evolutionary adaptation, which allows reconciling mutagenicity of non-B DNA structures with their location in functionally important regions and their potential regulatory role. PMID:25336616

  20. Higher expression levels of the HOXA9 gene, closely associated with MLL-PTD and EZH2 mutations, predict inferior outcome in acute myeloid leukemia

    PubMed Central

    Gao, Li; Sun, Junzhong; Liu, Fang; Zhang, Hui; Ma, Yigai

    2016-01-01

    Background Although the biological insight of acute myeloid leukemia (AML) has increased in the past few years, the discovery of novel discriminative biomarkers remains of utmost value for improving outcome predictions. Systematical studies concerning the clinical implications and genetic correlations of HOXA9 aberrations in patients with AML are relatively promising. Materials and methods Here, we investigated mutational status and the mRNA levels of the HOXA9 gene in 258 patients with AML. Furthermore, hematological characteristics, chromosome abnormalities, and genetic mutations associated with AML were analyzed, followed by the assessment of clinical survival. Besides, the expression level and mutational status of MEIS1, a cofactor of HOXA9, were also detected in patients with AML with the aim of a deeper understanding about the homeodomain-containing transcription factors associated with hematological characteristics. Results HOXA9 and MEIS1 mutations were detected in 4.26% and 3.49% AML cases, respectively. No correlations were detected between mutation status and clinical characteristics, cytogenetic and genetic aberrations, and clinical survival. Higher HOXA9 expression levels were correlated with white blood cell count and closely associated with unfavorable karyotype as well as MLL-PTD and EZH2 mutations, whereas, there was an inverse correlation with the French–American–British M3 subtype. Compared with patients with lower HOXA9 expression levels, those with higher HOXA9 expression levels had a lower complete remission rate and inferior survivals in both AML and cytogenetically normal AML. Conclusion HOXA9 expression may serve as a promising biomarker to ameliorate a prognostic model for predicting clinical outcome and consummating individualized treatment in patients with AML. PMID:26929642

  1. Loss of DNase II function in the gonad is associated with a higher expression of antimicrobial genes in Caenorhabditis elegans.

    PubMed

    Yu, Hsiang; Lai, Huey-Jen; Lin, Tai-Wei; Chen, Chang-Shi; Lo, Szecheng J

    2015-08-15

    Three waves of apoptosis shape the development of Caenorhabditis elegans. Although the exact roles of the three DNase II genes (nuc-1, crn-6 and crn-7), which are known to mediate degradation of apoptotic DNA, in the embryonic and larval phases of apoptosis have been characterized, the DNase II acting in the third wave of germ cell apoptosis remains undetermined. In the present study, we performed in vitro and in vivo assays on various mutant nematodes to demonstrate that NUC-1 and CRN-7, but not CRN-6, function in germ cell apoptosis. In addition, in situ DNA-break detection and anti-phosphorylated ERK (extracellular-signal-regulated kinase) staining illustrated the sequential and spatially regulated actions of NUC-1 and CRN-7, at the pachytene zone of the gonad and at the loop respectively. In line with the notion that UV-induced DNA fragment accumulation in the gonad activates innate immunity responses, we also found that loss of NUC-1 and CRN-7 lead to up-regulation of antimicrobial genes (abf-2, spp-1, nlp-29, cnc-2, and lys-7). Our observations suggest that an incomplete digestion of DNA fragments resulting from the absence of NUC-1 or CRN-7 in the gonad could induce the ERK signalling, consequently activating antimicrobial gene expression. Taken together, the results of the present study demonstrate for the first time that nuc-1 and crn-7 play a role in degrading apoptotic DNA in distinct sites of the gonad, and act as negative regulators of innate immunity in C. elegans. PMID:26251453

  2. Sheep primary astrocytes under starvation conditions express higher amount of LC3 II autophagy marker than neurons.

    PubMed

    Mura, Emilio; Lepore, Gianluca; Zedda, Marco; Giua, Stefano; Farina, Vittorio

    2014-03-01

    Autophagy is a general term for the degradation of cytoplasmic components within lysosomes. Recent studies have clearly demonstrated that autophagy has a greater variety of physiological and pathophysiological roles than expected, such as starvation adaptation, intracellular protein and organelle clearance, development, anti-aging, elimination of microorganisms, cell death, tumor suppression and antigen presentation. MAP-LC3 is one of the most common markers  to evaluate autophagic processes. In our study, the autophagic activity in neurons and astrocytes from sheep brain under starving conditions was evaluated. In order to detect LC3 immunoreactivity, confocal analysis by double immunofluorescence was performed together with the cell type markers: GFAP to identify astrocytes, β-III tubulin to identify neurons. The results show that astrocytes are characterized by LC3-positive areas, which increase in a time-dependent manner. In contrast, LC3 immunoreactivity was very weak in neurons. Therefore, it can be assumed that astrocytes show a higher capability than neurons to cope with stress and exhibit a stronger autophagic response. PMID:25181596

  3. Arbuscular mycorrhiza increase artemisinin accumulation in Artemisia annua by higher expression of key biosynthesis genes via enhanced jasmonic acid levels.

    PubMed

    Mandal, Shantanu; Upadhyay, Shivangi; Wajid, Saima; Ram, Mauji; Jain, Dharam Chand; Singh, Ved Pal; Abdin, Malik Zainul; Kapoor, Rupam

    2015-07-01

    It is becoming increasingly evident that the formation of arbuscular mycorrhiza (AM) enhances secondary metabolite production in shoots. Despite mounting evidence, relatively little is known about the underlying mechanisms. This study suggests that increase in artemisinin concentration in Artemisia annua colonized by Rhizophagus intraradices is due to altered trichome density as well as transcriptional patterns that are mediated via enhanced jasmonic acid (JA) levels. Mycorrhizal (M) plants had higher JA levels in leaf tissue that may be due to induction of an allene oxidase synthase gene (AOS), encoding one of the key enzymes for JA production. Non-mycorrhizal (NM) plants were exogenously supplied with a range of methyl jasmonic acid concentrations. When leaves of NM and M plants with similar levels of endogenous JA were compared, these matched closely in terms of shoot trichome density, artemisinin concentration, and transcript profile of artemisinin biosynthesis genes. Mycorrhization increased artemisinin levels by increasing glandular trichome density and transcriptional activation of artemisinin biosynthesis genes. Transcriptional analysis of some rate-limiting enzymes of mevalonate and methyl erythritol phosphate (MEP) pathways revealed that AM increases isoprenoids by induction of the MEP pathway. A decline in artemisinin concentration in shoots of NM and M plants treated with ibuprofen (an inhibitor of JA biosynthesis) further confirmed the implication of JA in the mechanism of artemisinin production. PMID:25366131

  4. Increased Expression of X-Linked Genes in Mammals Is Associated with a Higher Stability of Transcripts and an Increased Ribosome Density

    PubMed Central

    Faucillion, Marie-Line; Larsson, Jan

    2015-01-01

    Mammalian sex chromosomes evolved from the degeneration of one homolog of a pair of ancestral autosomes, the proto-Y. This resulted in a gene dose imbalance that is believed to be restored (partially or fully) through upregulation of gene expression from the single active X-chromosome in both sexes by a dosage compensatory mechanism. We analyzed multiple genome-wide RNA stability data sets and found significantly longer average half-lives for X-chromosome transcripts than for autosomal transcripts in various human cell lines, both male and female, and in mice. Analysis of ribosome profiling data shows that ribosome density is higher on X-chromosome transcripts than on autosomal transcripts in both humans and mice, suggesting that the higher stability is causally linked to a higher translation rate. Our results and observations are in accordance with a dosage compensatory upregulation of expressed X-linked genes. We therefore propose that differential mRNA stability and translation rates of the autosomes and sex chromosomes contribute to an evolutionarily conserved dosage compensation mechanism in mammals. PMID:25786432

  5. Alzheimer patients treated with an AchE inhibitor show higher IL-4 and lower IL-1 beta levels and expression in peripheral blood mononuclear cells.

    PubMed

    Gambi, Francesco; Reale, Marcella; Iarlori, Carla; Salone, Anatolia; Toma, Lucia; Paladini, Carlo; De Luca, Giovanna; Feliciani, Claudio; Salvatore, Mirella; Salerno, Rosa M; Theoharides, Theoharis C; Conti, Pio; Exton, Michael; Gambi, Domenico

    2004-06-01

    The study evaluates the expression and production of cytokines in peripheral blood mononuclear cells of patients with Alzheimer disease treated or not treated with acetylcholinesterase inhibitor, which enhances neuronal transmission. Cytokines associated with brain inflammation such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha have been implicated in the regulation of amyloid peptide protein synthesis. The anti-inflammatory cytokine, IL-4, may suppress the activity of IL-1beta. Patients were assessed for clinical and immunologic features at baseline and after 1 month of treatment with Donepezil, an acetylcholinesterase inhibitor. Peripheral blood mononuclear cells were cultured with and without phytohemagglutinin stimulation. IL-1beta and IL-4 levels were measured by enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used to determine the expression of cytokines in peripheral mononuclear cells. Compared with untreated patients and healthy control subjects, IL-1beta levels and expression decreased in Alzheimer disease patients treated with Donepezil (P < 0.001). In contrast, IL-4 levels and expression were significantly higher in Alzheimer patients treated with the acetylcholinesterase inhibitor. This increment was observed in both unstimulated and phytohemagglutinin-stimulated peripheral blood mononuclear cells. PMID:15118486

  6. Higher Levels of c-Met Expression and Phosphorylation Identify Cell Lines With Increased Sensitivity to AMG-458, a Novel Selective c-Met Inhibitor With Radiosensitizing Effects

    SciTech Connect

    Li Bo; Torossian, Artour; Sun, Yunguang; Du, Ruihong; Dicker, Adam P.; Lu Bo

    2012-11-15

    Purpose: c-Met is overexpressed in some non-small cell lung cancer (NSCLC) cell lines and tissues. Cell lines with higher levels of c-Met expression and phosphorylation depend on this receptor for survival. We studied the effects of AMG-458 on 2 NSCLC cell lines. Methods and Materials: 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium assays assessed the sensitivities of the cells to AMG-458. Clonogenic survival assays illustrated the radiosensitizing effects of AMG-458. Western blot for cleaved caspase 3 measured apoptosis. Immunoblotting for c-Met, phospho-Met (p-Met), Akt/p-Akt, and Erk/p-Erk was performed to observe downstream signaling. Results: AMG-458 enhanced radiosensitivity in H441 but not in A549. H441 showed constitutive phosphorylation of c-Met. A549 expressed low levels of c-Met, which were phosphorylated only in the presence of exogenous hepatocyte growth factor. The combination of radiation therapy and AMG-458 treatment was found to synergistically increase apoptosis in the H441 cell line but not in A549. Radiation therapy, AMG-458, and combination treatment were found to reduce p-Akt and p-Erk levels in H441 but not in A549. H441 became less sensitive to AMG-458 after small interfering RNA knockdown of c-Met; there was no change in A549. After overexpression of c-Met, A549 became more sensitive, while H441 became less sensitive to AMG-458. Conclusions: AMG-458 was more effective in cells that expressed higher levels of c-Met/p-Met, suggesting that higher levels of c-Met and p-Met in NSCLC tissue may classify a subset of tumors that are more sensitive to molecular therapies against this receptor.

  7. Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake

    PubMed Central

    Ranganathan, Perungavur N.; Lu, Yan; Jiang, Lingli; Kim, Changae

    2011-01-01

    Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency. PMID:21768302

  8. Genome-wide transcriptomic analysis reveals correlation between higher WRKY61 expression and reduced symptom severity in Turnip crinkle virus infected Arabidopsis thaliana

    PubMed Central

    Gao, Ruimin; Liu, Peng; Yong, Yuhan; Wong, Sek-Man

    2016-01-01

    Turnip crinkle virus (TCV) is a carmovirus that infects many Arabidopsis ecotypes. Most studies mainly focused on discovery of resistance genes against TCV infection, and there is no Next Generation Sequencing based comparative genome wide transcriptome analysis reported. In this study, RNA-seq based transcriptome analysis revealed that 238 (155 up-regulated and 83 down-regulated) significant differentially expressed genes with at least 15-fold change were determined. Fifteen genes (including upregulated, unchanged and downregulated) were selected for RNA-seq data validation using quantitative real-time PCR, which showed consistencies between these two sets of data. GO enrichment analysis showed that numerous terms such as stress, immunity, defence and chemical stimulus were affected in TCV-infected plants. One putative plant defence related gene named WRKY61 was selected for further investigation. It showed that WRKY61 overexpression plants displayed reduced symptoms and less virus accumulation, as compared to wild type (WT) and WRKY61 deficient lines, suggesting that higher WRKY61 expression level reduced TCV viral accumulation. In conclusion, our transcriptome analysis showed that global gene expression was detected in TCV-infected Arabidopsis thaliana. WRKY61 gene was shown to be negatively correlated with TCV infection and viral symptoms, which may be connected to plant immunity pathways. PMID:27086702

  9. Genome-wide transcriptomic analysis reveals correlation between higher WRKY61 expression and reduced symptom severity in Turnip crinkle virus infected Arabidopsis thaliana.

    PubMed

    Gao, Ruimin; Liu, Peng; Yong, Yuhan; Wong, Sek-Man

    2016-01-01

    Turnip crinkle virus (TCV) is a carmovirus that infects many Arabidopsis ecotypes. Most studies mainly focused on discovery of resistance genes against TCV infection, and there is no Next Generation Sequencing based comparative genome wide transcriptome analysis reported. In this study, RNA-seq based transcriptome analysis revealed that 238 (155 up-regulated and 83 down-regulated) significant differentially expressed genes with at least 15-fold change were determined. Fifteen genes (including upregulated, unchanged and downregulated) were selected for RNA-seq data validation using quantitative real-time PCR, which showed consistencies between these two sets of data. GO enrichment analysis showed that numerous terms such as stress, immunity, defence and chemical stimulus were affected in TCV-infected plants. One putative plant defence related gene named WRKY61 was selected for further investigation. It showed that WRKY61 overexpression plants displayed reduced symptoms and less virus accumulation, as compared to wild type (WT) and WRKY61 deficient lines, suggesting that higher WRKY61 expression level reduced TCV viral accumulation. In conclusion, our transcriptome analysis showed that global gene expression was detected in TCV-infected Arabidopsis thaliana. WRKY61 gene was shown to be negatively correlated with TCV infection and viral symptoms, which may be connected to plant immunity pathways. PMID:27086702

  10. Higher-order Zeeman and spin terms in the electron paramagnetic resonance spin Hamiltonian; their description in irreducible form using Cartesian, tesseral spherical tensor and Stevens' operator expressions.

    PubMed

    McGavin, Dennis G; Tennant, W Craighead

    2009-06-17

    In setting up a spin Hamiltonian (SH) to study high-spin Zeeman and high-spin nuclear and/or electronic interactions in electron paramagnetic resonance (EPR) experiments, it is argued that a maximally reduced SH (MRSH) framed in tesseral combinations of spherical tensor operators is necessary. Then, the SH contains only those terms that are necessary and sufficient to describe the particular spin system. The paper proceeds then to obtain interrelationships between the parameters of the MRSH and those of alternative SHs expressed in Cartesian tensor and Stevens operator-equivalent forms. The examples taken, initially, are those of Cartesian and Stevens' expressions for high-spin Zeeman terms of dimension BS(3) and BS(5). Starting from the well-known decomposition of the general Cartesian tensor of second rank to three irreducible tensors of ranks 0, 1 and 2, the decomposition of Cartesian tensors of ranks 4 and 6 are treated similarly. Next, following a generalization of the tesseral spherical tensor equations, the interrelationships amongst the parameters of the three kinds of expressions, as derived from equivalent SHs, are determined and detailed tables, including all redundancy equations, set out. In each of these cases the lowest symmetry, [Formula: see text] Laue class, is assumed and then examples of relationships for specific higher symmetries derived therefrom. The validity of a spin Hamiltonian containing mixtures of terms from the three expressions is considered in some detail for several specific symmetries, including again the lowest symmetry. Finally, we address the application of some of the relationships derived here to seldom-observed low-symmetry effects in EPR spectra, when high-spin electronic and nuclear interactions are present. PMID:21693947

  11. Express

    Integrated Risk Information System (IRIS)

    Express ; CASRN 101200 - 48 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effect

  12. Multi-tissue analysis of co-expression networks by higher-order generalized singular value decomposition identifies functionally coherent transcriptional modules.

    PubMed

    Xiao, Xiaolin; Moreno-Moral, Aida; Rotival, Maxime; Bottolo, Leonardo; Petretto, Enrico

    2014-01-01

    Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions (e.g., cell-types and disease states). Leveraging these data is especially important for network-based approaches to human disease, for instance to identify coherent transcriptional modules (subnetworks) that can inform functional disease mechanisms and pathological pathways. Yet, genome-scale network analysis across conditions is significantly hampered by the paucity of robust and computationally-efficient methods. Building on the Higher-Order Generalized Singular Value Decomposition, we introduce a new algorithmic approach for efficient, parameter-free and reproducible identification of network-modules simultaneously across multiple conditions. Our method can accommodate weighted (and unweighted) networks of any size and can similarly use co-expression or raw gene expression input data, without hinging upon the definition and stability of the correlation used to assess gene co-expression. In simulation studies, we demonstrated distinctive advantages of our method over existing methods, which was able to recover accurately both common and condition-specific network-modules without entailing ad-hoc input parameters as required by other approaches. We applied our method to genome-scale and multi-tissue transcriptomic datasets from rats (microarray-based) and humans (mRNA-sequencing-based) and identified several common and tissue-specific subnetworks with functional significance, which were not detected by other methods. In humans we recapitulated the crosstalk between cell-cycle progression and cell-extracellular matrix interactions processes in ventricular zones during neocortex expansion and further, we uncovered pathways related to development of later cognitive functions in the cortical plate of the developing brain which were previously unappreciated. Analyses of seven rat tissues identified a multi-tissue subnetwork of co-expressed

  13. Multi-tissue Analysis of Co-expression Networks by Higher-Order Generalized Singular Value Decomposition Identifies Functionally Coherent Transcriptional Modules

    PubMed Central

    Bottolo, Leonardo; Petretto, Enrico

    2014-01-01

    Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions (e.g., cell-types and disease states). Leveraging these data is especially important for network-based approaches to human disease, for instance to identify coherent transcriptional modules (subnetworks) that can inform functional disease mechanisms and pathological pathways. Yet, genome-scale network analysis across conditions is significantly hampered by the paucity of robust and computationally-efficient methods. Building on the Higher-Order Generalized Singular Value Decomposition, we introduce a new algorithmic approach for efficient, parameter-free and reproducible identification of network-modules simultaneously across multiple conditions. Our method can accommodate weighted (and unweighted) networks of any size and can similarly use co-expression or raw gene expression input data, without hinging upon the definition and stability of the correlation used to assess gene co-expression. In simulation studies, we demonstrated distinctive advantages of our method over existing methods, which was able to recover accurately both common and condition-specific network-modules without entailing ad-hoc input parameters as required by other approaches. We applied our method to genome-scale and multi-tissue transcriptomic datasets from rats (microarray-based) and humans (mRNA-sequencing-based) and identified several common and tissue-specific subnetworks with functional significance, which were not detected by other methods. In humans we recapitulated the crosstalk between cell-cycle progression and cell-extracellular matrix interactions processes in ventricular zones during neocortex expansion and further, we uncovered pathways related to development of later cognitive functions in the cortical plate of the developing brain which were previously unappreciated. Analyses of seven rat tissues identified a multi-tissue subnetwork of co-expressed

  14. Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

    PubMed Central

    Bae, Eun Joo; Chen, Bai Hui; Yan, Bing Chun; Shin, Bich Na; Cho, Jeong Hwi; Kim, In Hye; Ahn, Ji Hyeon; Lee, Jae Chul; Tae, Hyun-Jin; Hong, Seongkweon; Kim, Dong Won; Cho, Jun Hwi; Lee, Yun Lyul; Won, Moo-Ho; Park, Joon Ha

    2015-01-01

    The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1–3) between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults. PMID:26199612

  15. Transgenic Eimeria mitis expressing chicken interleukin 2 stimulated higher cellular immune response in chickens compared with the wild-type parasites.

    PubMed

    Li, Zhuoran; Tang, Xinming; Suo, Jingxia; Qin, Mei; Yin, Guangwen; Liu, Xianyong; Suo, Xun

    2015-01-01

    Chicken coccidiosis, caused by Eimeria sp., occurs in almost all poultry farms and causes huge economic losses in the poultry industry. Although this disease could be controlled by vaccination, the reduced feed conservation ratio limits the widespread application of anticoccidial vaccines in broilers because some intermediate and/or low immunogenic Eimeria sp. only elicit partial protection. It is of importance to enhance the immunogenicity of these Eimeria sp. by adjuvants for more effective prevention of coccidiosis. Cytokines have remarkable effects on the immunogenicity of antigens. Interleukin 2 (IL-2), for example, significantly stimulates the activation of CD8+ T cells and other immune cells. In this study, we constructed a transgenic Eimeria mitis line (EmiChIL-2) expressing chicken IL-2 (ChIL-2) to investigate the adjuvant effect of ChIL-2 to enhance the immunogenicity of E. mitis against its infection. Stable transfected EmiChIL-2 population was obtained by pyrimethamine selection and verified by PCR, genome walking, western blotting and indirect immunofluorescence assay. Cellular immune response, E. mitis-specific IFN-γ secretion lymphocytes in the peripheral blood mononuclear cells, stimulated by EmiChIL-2 was analyzed by enzyme-linked immunospot assay (ELISPOT). The results showed that EmiChIL-2 stimulated a higher cellular immune response compared with that of the wild-type parasite infection in chickens. Moreover, after the immunization with EmiChIL-2, elevated cellular immune response as well as reduced oocyst output were observed These results indicated that ChIL-2 expressed by Eimeria sp. functions as adjuvant and IL-2 expressing Eimeria parasites are valuable vaccine strains against coccidiosis. PMID:26082759

  16. Transgenic Eimeria mitis expressing chicken interleukin 2 stimulated higher cellular immune response in chickens compared with the wild-type parasites

    PubMed Central

    Li, Zhuoran; Tang, Xinming; Suo, Jingxia; Qin, Mei; Yin, Guangwen; Liu, Xianyong; Suo, Xun

    2015-01-01

    Chicken coccidiosis, caused by Eimeria sp., occurs in almost all poultry farms and causes huge economic losses in the poultry industry. Although this disease could be controlled by vaccination, the reduced feed conservation ratio limits the widespread application of anticoccidial vaccines in broilers because some intermediate and/or low immunogenic Eimeria sp. only elicit partial protection. It is of importance to enhance the immunogenicity of these Eimeria sp. by adjuvants for more effective prevention of coccidiosis. Cytokines have remarkable effects on the immunogenicity of antigens. Interleukin 2 (IL-2), for example, significantly stimulates the activation of CD8+ T cells and other immune cells. In this study, we constructed a transgenic Eimeria mitis line (EmiChIL-2) expressing chicken IL-2 (ChIL-2) to investigate the adjuvant effect of ChIL-2 to enhance the immunogenicity of E. mitis against its infection. Stable transfected EmiChIL-2 population was obtained by pyrimethamine selection and verified by PCR, genome walking, western blotting and indirect immunofluorescence assay. Cellular immune response, E. mitis-specific IFN-γ secretion lymphocytes in the peripheral blood mononuclear cells, stimulated by EmiChIL-2 was analyzed by enzyme-linked immunospot assay (ELISPOT). The results showed that EmiChIL-2 stimulated a higher cellular immune response compared with that of the wild-type parasite infection in chickens. Moreover, after the immunization with EmiChIL-2, elevated cellular immune response as well as reduced oocyst output were observed These results indicated that ChIL-2 expressed by Eimeria sp. functions as adjuvant and IL-2 expressing Eimeria parasites are valuable vaccine strains against coccidiosis. PMID:26082759

  17. Expression, purification, crystallization and preliminary X-ray analysis of perakine reductase, a new member of the aldo-keto reductase enzyme superfamily from higher plants

    SciTech Connect

    Rosenthal, Cindy; Mueller, Uwe; Panjikar, Santosh; Sun, Lianli; Ruppert, Martin; Zhao, Yu; Stöckigt, Joachim

    2006-12-01

    Perakine reductase, a novel member of the aldo-keto reductase enzyme superfamily of higher plants, is involved in the biosynthesis of monoterpenoid indole alkaloids in the Indian medicinal plant Rauvolfia serpentina. The enzyme has been crystallized in C-centered orthorhombic space group and diffracts to 2.0 Å resolution. Perakine reductase (PR) is a novel member of the aldo-keto reductase enzyme superfamily from higher plants. PR from the plant Rauvolfia serpentina is involved in the biosynthesis of monoterpenoid indole alkaloids by performing NADPH-dependent reduction of perakine, yielding raucaffrinoline. However, PR can also reduce cinnamic aldehyde and some of its derivatives. After heterologous expression of a triple mutant of PR in Escherichia coli, crystals of the purified and methylated enzyme were obtained by the hanging-drop vapour-diffusion technique at 293 K with 100 mM sodium citrate pH 5.6 and 27% PEG 4000 as precipitant. Crystals belong to space group C222{sub 1} and diffract to 2.0 Å, with unit-cell parameters a = 58.9, b = 93.0, c = 143.4 Å.

  18. Influence of nitrogen supply on the production of higher alcohols/esters and expression of flavour-related genes in cachaça fermentation.

    PubMed

    Vidal, Esteban Espinosa; de Billerbeck, Gustavo M; Simões, Diogo Ardaillon; Schuler, Alexandre; François, Jean Marie; de Morais, Marcos Antonio

    2013-05-01

    This study provides the first attempt to analyse the influence of ammonium supplements on sugar-cane juice fermentation and the flavour profile in a cachaça industrial process. The objective was to find a relationship between higher alcohol/ester content and the transcription levels of the main genes involved in production of these compounds under cachaça fermentation. Sugar-cane juice with a low amount of assimilable nitrogen (81 mg N/L), was further supplemented with mid-range or high concentrations of ammonium sulfate. Overall, higher alcohol production was reduced by ammonium supplementation, and this can be correlated with a general downregulation of genes encoding decarboxylases and dehydrogenases of the Ehrlich pathway. The production of acetate esters was enhanced by mid-range ammonium supplementation and the production of acyl esters by high ammonium supplementation. The acyl esters could be correlated with expression of alcohol acyl-transferase EEB1 and the acyl esterase IAH1. PMID:23265543

  19. Expression of a higher plant psbA gene in Synechocystis 6803 yields a functional hybrid photosystem II reaction center complex.

    PubMed Central

    Nixon, P J; Rögner, M; Diner, B A

    1991-01-01

    The psbA gene codes for the D1 polypeptide of the photosystem II reaction center complex and is found in all photosynthetic organisms that carry out oxygenic photosynthesis. Here we describe the construction and characterization of a strain of the cyanobacterium Synechocystis sp PCC 6803 in which the three endogenous psbA genes are replaced by a single psbA gene from the chloroplast genome of the higher plant Poa annua. The resulting chimeric strain, KWPAS, grows photoautotrophically with a doubling time of 26 hours compared with 20 hours for wild-type Synechocystis 6803. The mutant oxidizes water to oxygen at light-saturated rates comparable with wild type, despite differences in 15% of the primary structure of D1 between these species. RNA gel blot analysis indicates the presence in KWPAS of a psbA transcript of approximately 1.25 kilobases, consistent with the chloroplast promoter also acting as a promoter in Synechocystis. By using antibodies specific for the carboxyl-terminal extension of the D1 polypeptide of higher plants, we showed that the D1 polypeptide synthesized by KWPAS is post-translationally modified at the carboxyl terminus, probably through processing. A detailed biophysical analysis of the chimeric photosystem II complex indicated that the rates of forward electron transfer are similar to wild type. The rates of charge recombination between the donor and acceptor sides of the reaction center are, however, accelerated by as much as a factor of nine (QA- to S2) and are the most likely explanation for the lower rate of photoautotrophic growth in the mutant. We conclude that the psbA gene from a higher plant can be expressed in cyanobacteria and its product processed and assembled into a functional chimeric photosystem II reaction center. PMID:1840918

  20. Acute Lymphoid Leukemia Cells with Greater Stem Cell Antigen-1 (Ly6a/Sca-1) Expression Exhibit Higher Levels of Metalloproteinase Activity and Are More Aggressive In Vivo

    PubMed Central

    Hsu, Yu-Chiao; Mildenstein, Kurt; Hunter, Kordell; Tkachenko, Olena; Mullen, Craig A.

    2014-01-01

    Stem cell antigen-1 (Ly6a/Sca-1) is a gene that is expressed in activated lymphocytes, hematopoietic stem cells and stem cells of a variety of tissues in mice. Despite decades of study its functions remain poorly defined. These studies explored the impact of expression of this stem cell associated gene in acute lymphoid leukemia. Higher levels of Ly6a/Sca-1 expression led to more aggressive leukemia growth in vivo and earlier death of hosts. Leukemias expressing higher levels of Ly6a/Sca-1 exhibited higher levels of matrix metalloproteinases. The results suggest the hypothesis that the more aggressive behavior of Ly6a/Sca-1 expressing leukemias is due at least in part to greater capacity to degrade microenvironmental stroma and invade tissues. PMID:24586463

  1. Keratins 17 and 19 expression as prognostic markers in oral squamous cell carcinoma.

    PubMed

    Coelho, B A; Peterle, G T; Santos, M; Agostini, L P; Maia, L L; Stur, E; Silva, C V M; Mendes, S O; Almança, C C J; Freitas, F V; Borçoi, A R; Archanjo, A B; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-01-01

    Five-year survival rates for oral squamous cell carcinoma (OSCC) are 30% and the mortality rate is 50%. Immunohistochemistry panels are used to evaluate proliferation, vascularization, apoptosis, HPV infection, and keratin expression, which are important markers of malignant progression. Keratins are a family of intermediate filaments predominantly expressed in epithelial cells and have an essential role in mechanical support and cytoskeleton formation, which is essential for the structural integrity and stability of the cell. In this study, we analyzed the expressions of keratins 17 and 19 (K17 and K19) by immunohistochemistry in tumoral and non-tumoral tissues from patients with OSCC. The results show that expression of these keratins is higher in tumor tissues compared to non-tumor tissues. Positive K17 expression correlates with lymph node metastasis and multivariate analysis confirmed this relationship, revealing a 6-fold increase in lymph node metastasis when K17 is expressed. We observed a correlation between K17 expression with disease-free survival and disease-specific death in patients who received surgery and radiotherapy. Multivariate analysis revealed that low expression of K17 was an independent marker for early disease relapse and disease-specific death in patients treated with surgery and radiotherapy, with an approximately 4-fold increased risk when compared to high K17 expression. Our results suggest a potential role for K17 and K19 expression profiles as tumor prognostic markers in OSCC patients. PMID:26634475

  2. Macrophages From Irradiated Tumors Express Higher Levels of iNOS, Arginase-I and COX-2, and Promote Tumor Growth

    SciTech Connect

    Tsai, C.-S.; Chen, F.-H.; Wang, C.-C.; Huang, H.-L.; Jung, Shih-Ming; Wu, C.-J.; Lee, C.-C.; McBride, William H.; Chiang, C.-S.; Hong, J.-H. . E-mail: jihong@adm.cgmh.org.tw

    2007-06-01

    Purpose: To investigate the effects of single and fractionated doses of radiation on tumors and tumor-associated macrophages (TAMs), and to elucidate the potential of TAMs to influence tumor growth. Methods and Materials: A murine prostate cell line, TRAMP-C1, was grown in C57Bl/6J mice to 4-mm tumor diameter and irradiated with either 25 Gy in a single dose, or 60 Gy in 15 fractions. The tumors were removed at the indicated times and assessed for a variety of markers related to TAM content, activation status, and function. Results: In tumors receiving a single radiation dose, arginase (Arg-I), and cycloxygenase-2 (COX-2) mRNA expression increased as a small transient wave within 24 h and a larger persistent wave starting after 3 days. Inducible nitric oxide synthase (iNOS) mRNA was elevated only after 3 days and continued to increase up to 3 weeks. After fractionated irradiation, Arg-1 and COX-2 mRNA levels increased within 5 days, whereas iNOS was increased only after 10 fractions of irradiation had been given. Increased levels of Arg-I, COX-2, and, to a lesser extent, iNOS protein were found to associate with TAMs 1-2 weeks after tumor irradiation. Function of TAMs were compared by mixing them with TRAMP-C1 cells and injecting them into mice; TRAMP-C1 cells mixed with TAMs from irradiated tumors appeared earlier and grew significantly faster than those mixed with TAMs from unirradiated tumors or TRAMP-C1 alone. Conclusions: Tumor-associated macrophages in the postirradiated tumor microenvironment express higher levels of Arg-1, COX-2, and iNOS, and promote early tumor growth in vivo.

  3. Differential gene expression between visceral and subcutaneous fat depots.

    PubMed

    Atzmon, G; Yang, X M; Muzumdar, R; Ma, X H; Gabriely, I; Barzilai, N

    2002-01-01

    Abdominal obesity has been linked to the development of insulin resistance and Type 2 diabetes mellitus (DM2). By surgical removal of visceral fat (VF) in a variety of rodent models, we prevented insulin resistance and glucose intolerance, establishing a cause-effect relationship between VF and the metabolic syndrome. To characterize the biological differences between visceral and peripheral fat depots, we obtained perirenal visceral (VF) and subcutaneous (SC) fat from 5 young rats. We extracted mRNA from the fat tissue and performed gene array hybridization using Affymetrix technology with a platform containing 9 000 genes. Out of the 1 660 genes that were expressed in fat tissue, 297 (17.9 %) genes show a two-fold or higher difference in their expression between the two tissues. We present the 20 genes whose expression is higher in VF fat (by 3 - 7 fold) and the 20 genes whose expression is higher in SC fat (by 3 - 150 fold), many of which are predominantly involved in glucose homeostasis, insulin action, and lipid metabolism. We confirmed the findings of gene array expression and quantified the changes in expression in VF of genes involved in insulin resistance (PPARgamma leptin) and its syndrome (angiotensinogen and plasminogen activating inhibitor-1, PAI-1) by real-time PCR (qRT-PCR) technology. Finally, we demonstrated increased expression of resistin in VF by around 12-fold and adiponectin by around 4-fold, peptides that were not part of the gene expression platform. These results indicate that visceral fat and subcutaneous fat are biologically distinct. PMID:12660871

  4. Differential viral levels and immune gene expression in three stocks of Apis mellifera induced by different numbers of Varroa destructor.

    PubMed

    Khongphinitbunjong, Kitiphong; de Guzman, Lilia I; Tarver, Matthew R; Rinderer, Thomas E; Chen, Yanping; Chantawannakul, Panuwan

    2015-01-01

    The viral levels and immune responses of Italian honey bees (IHB), Russian honey bees (RHB) and an outcross of Varroa Sensitive Hygienic bees (POL) deliberately infested with one or two foundress Varroa were compared. We found that the Deformed wing virus (DWV) level in IHB inoculated with one or two foundress Varroa increased to about 10(3) or 10(5) fold the levels of their uninfested brood. In contrast, POL (10(2) or 10(4) fold) and RHB (10(2) or l0(4) fold) supported a lower increase in DWV levels. The feeding of different stages of Varroa nymphs did not increase DWV levels of their pupal hosts. Analyses of their corresponding Varroa mites showed the same trends: two foundress Varroa yielded higher DWV levels than one foundress, and the addition of nymphs did not increase viral levels. Using the same pupae examined for the presence of viruses, 16 out of 24 genes evaluated showed significant differential mRNA expression levels among the three honey bee stocks. However, only four genes (Defensin, Dscam, PPOact and spaetzle), which were expressed at similar levels in uninfested pupae, were altered by the number of feeding foundress Varroa and levels of DWV regardless of stocks. This research provides the first evidence that immune response profiles of different honey bee stocks are induced by Varroa parasitism. PMID:25456452

  5. A field-grown transgenic tomato line expressing higher levels of polyamines reveals legume cover crop mulch-specific perturbations in fruit phenotype at the levels of metabolite profiles, gene expression, and agronomic characteristics

    PubMed Central

    Neelam, Anil; Cassol, Tatiana; Mehta, Roshni A.; Abdul-Baki, Aref A.; Sobolev, Anatoli P.; Goyal, Ravinder K.; Abbott, Judith; Segre, Anna L.; Handa, Avtar K.; Mattoo, Autar K.

    2008-01-01

    Genetic modification of crop plants to introduce desirable traits such as nutritional enhancement, disease and pest resistance, and enhanced crop productivity is increasingly seen as a promising technology for sustainable agriculture and boosting food production in the world. Independently, cultural practices that utilize alternative agriculture strategies including organic cultivation subscribe to sustainable agriculture by limiting chemical usage and reduced tillage. How the two together affect fruit metabolism or plant growth in the field or whether they are compatible has not yet been tested. Fruit-specific yeast S-adenosylmethionine decarboxylase (ySAMdc) line 579HO, and a control line 556AZ were grown in leguminous hairy vetch (Vicia villosa Roth) (HV) mulch and conventional black polyethylene (BP) mulch, and their fruit analysed. Significant genotype×mulch-dependent interactions on fruit phenotype were exemplified by differential profiles of 20 fruit metabolites such as amino acids, sugars, and organic acids. Expression patterns of the ySAMdc transgene, and tomato SAMdc, E8, PEPC, and ICDHc genes were compared between the two lines as a function of growth on either BP or HV mulch. HV mulch significantly stimulated the accumulation of asparagine, glutamate, glutamine, choline, and citrate concomitant with a decrease in glucose in the 556AZ fruits during ripening as compared to BP. It enables a metabolic system in tomato somewhat akin to the one in higher polyamine-accumulating transgenic fruit that have higher phytonutrient content. Finally, synergism was found between HV mulch and transgenic tomato in up-regulating N:C indicator genes PEPC and ICDHc in the fruit. PMID:18469323

  6. A field-grown transgenic tomato line expressing higher levels of polyamines reveals legume cover crop mulch-specific perturbations in fruit phenotype at the levels of metabolite profiles, gene expression, and agronomic characteristics.

    PubMed

    Neelam, Anil; Cassol, Tatiana; Mehta, Roshni A; Abdul-Baki, Aref A; Sobolev, Anatoli P; Goyal, Ravinder K; Abbott, Judith; Segre, Anna L; Handa, Avtar K; Mattoo, Autar K

    2008-01-01

    Genetic modification of crop plants to introduce desirable traits such as nutritional enhancement, disease and pest resistance, and enhanced crop productivity is increasingly seen as a promising technology for sustainable agriculture and boosting food production in the world. Independently, cultural practices that utilize alternative agriculture strategies including organic cultivation subscribe to sustainable agriculture by limiting chemical usage and reduced tillage. How the two together affect fruit metabolism or plant growth in the field or whether they are compatible has not yet been tested. Fruit-specific yeast S-adenosylmethionine decarboxylase (ySAMdc) line 579HO, and a control line 556AZ were grown in leguminous hairy vetch (Vicia villosa Roth) (HV) mulch and conventional black polyethylene (BP) mulch, and their fruit analysed. Significant genotypexmulch-dependent interactions on fruit phenotype were exemplified by differential profiles of 20 fruit metabolites such as amino acids, sugars, and organic acids. Expression patterns of the ySAMdc transgene, and tomato SAMdc, E8, PEPC, and ICDHc genes were compared between the two lines as a function of growth on either BP or HV mulch. HV mulch significantly stimulated the accumulation of asparagine, glutamate, glutamine, choline, and citrate concomitant with a decrease in glucose in the 556AZ fruits during ripening as compared to BP. It enables a metabolic system in tomato somewhat akin to the one in higher polyamine-accumulating transgenic fruit that have higher phytonutrient content. Finally, synergism was found between HV mulch and transgenic tomato in up-regulating N:C indicator genes PEPC and ICDHc in the fruit. PMID:18469323

  7. Minicircle DNA Provides Enhanced and Prolonged Transgene Expression Following Airway Gene Transfer

    PubMed Central

    Munye, Mustafa M.; Tagalakis, Aristides D.; Barnes, Josephine L.; Brown, Rachel E.; McAnulty, Robin J.; Howe, Steven J.; Hart, Stephen L.

    2016-01-01

    Gene therapy for cystic fibrosis using non-viral, plasmid-based formulations has been the subject of intensive research for over two decades but a clinically viable product has yet to materialise in large part due to inefficient transgene expression. Minicircle DNA give enhanced and more persistent transgene expression compared to plasmid DNA in a number of organ systems but has not been assessed in the lung. In this study we compared minicircle DNA with plasmid DNA in transfections of airway epithelial cells. In vitro, luciferase gene expression from minicircles was 5–10-fold higher than with plasmid DNA. In eGFP transfections in vitro both the mean fluorescence intensity and percentage of cells transfected was 2–4-fold higher with minicircle DNA. Administration of equimolar amounts of DNA to mouse lungs resulted in a reduced inflammatory response and more persistent transgene expression, with luciferase activity persisting for 2 weeks from minicircle DNA compared to plasmid formulations. Transfection of equal mass amounts of DNA in mouse lungs resulted in a 6-fold increase in transgene expression in addition to more persistent transgene expression. Our findings have clear implications for gene therapy of airway disorders where plasmid DNA transfections have so far proven inefficient in clinical trials. PMID:26975732

  8. Minicircle DNA Provides Enhanced and Prolonged Transgene Expression Following Airway Gene Transfer.

    PubMed

    Munye, Mustafa M; Tagalakis, Aristides D; Barnes, Josephine L; Brown, Rachel E; McAnulty, Robin J; Howe, Steven J; Hart, Stephen L

    2016-01-01

    Gene therapy for cystic fibrosis using non-viral, plasmid-based formulations has been the subject of intensive research for over two decades but a clinically viable product has yet to materialise in large part due to inefficient transgene expression. Minicircle DNA give enhanced and more persistent transgene expression compared to plasmid DNA in a number of organ systems but has not been assessed in the lung. In this study we compared minicircle DNA with plasmid DNA in transfections of airway epithelial cells. In vitro, luciferase gene expression from minicircles was 5-10-fold higher than with plasmid DNA. In eGFP transfections in vitro both the mean fluorescence intensity and percentage of cells transfected was 2-4-fold higher with minicircle DNA. Administration of equimolar amounts of DNA to mouse lungs resulted in a reduced inflammatory response and more persistent transgene expression, with luciferase activity persisting for 2 weeks from minicircle DNA compared to plasmid formulations. Transfection of equal mass amounts of DNA in mouse lungs resulted in a 6-fold increase in transgene expression in addition to more persistent transgene expression. Our findings have clear implications for gene therapy of airway disorders where plasmid DNA transfections have so far proven inefficient in clinical trials. PMID:26975732

  9. Higher Matrix Stiffness Upregulates Osteopontin Expression in Hepatocellular Carcinoma Cells Mediated by Integrin β1/GSK3β/β-Catenin Signaling Pathway

    PubMed Central

    You, Yang; Zheng, Qiongdan; Dong, Yinying; Wang, Yaohui; Zhang, Lan; Xue, Tongchun; Xie, Xiaoying; Hu, Chao; Wang, Zhiming; Chen, Rongxin; Wang, Yanhong; Cui, Jiefeng; Ren, Zhenggang

    2015-01-01

    Increased stromal stiffness is associated with hepatocellular carcinoma (HCC) development and progression. However, the molecular mechanism by which matrix stiffness stimuli modulate HCC progress is largely unknown. In this study, we explored whether matrix stiffness-mediated effects on osteopontin (OPN) expression occur in HCC cells. We used a previously reported in vitro culture system with tunable matrix stiffness and found that OPN expression was remarkably upregulated in HCC cells with increasing matrix stiffness. Furthermore, the phosphorylation level of GSK3β and the expression of nuclear β-catenin were also elevated, indicating that GSK3β/β-catenin pathway might be involved in OPN regulation. Knock-down analysis of integrin β1 showed that OPN expression and p-GSK3β level were downregulated in HCC cells grown on high stiffness substrate compared with controls. Simultaneously, inhibition of GSK-3β led to accumulation of β-catenin in the cytoplasm and its enhanced nuclear translocation, further triggered the rescue of OPN expression, suggesting that the integrin β1/GSK-3β/β-catenin pathway is specifically activated for matrix stiffness-mediated OPN upregulation in HCC cells. Tissue microarray analysis confirmed that OPN expression was positively correlated with the expression of LOX and COL1. Taken together, high matrix stiffness upregulated OPN expression in HCC cells via the integrin β1/GSK-3β/β-catenin signaling pathway. It highlights a new insight into a pathway involving physical mechanical signal and biochemical signal molecules which contributes to OPN expression in HCC cells. PMID:26280346

  10. Higher Hepatic miR-29 Expression in Undernourished Male Rats During the Postnatal Period Targets the Long-Term Repression of IGF-1.

    PubMed

    Sohi, Gurjeev; Revesz, Andrew; Ramkumar, Julie; Hardy, Daniel B

    2015-09-01

    A nutritional mismatch in postnatal life of low birth weight offspring increases the risk of developing the metabolic syndrome. Moreover, this is associated with decreased hepatic Igf1 expression, leading to impaired growth and metabolism. Previously, we have demonstrated that the timing of nutritional restoration in perinatal life can differentially program hepatic gene expression. Although microRNAs also play an important role in silencing gene expression, to date, the impact of a nutritional mismatch in neonatal life on their long-term expression has not been evaluated. Given the complementarity of miR-29 to the 3' untranslated region of Igf1, we examined how protein restoration in maternal protein restriction rat offspring influences hepatic miR-29 and Igf1 expression in adulthood. Pregnant Wistar rats were designated into 1 of 4 dietary regimes: 20% protein (control), 8% protein during lactation only (LP-Lact), 8% protein during gestation only (LP1) or both (LP2). The steady-state expression of hepatic miR-29 mRNA significantly increased in LP2 offspring at postnatal day 21 and 130, and this was inversely related to hepatic Igf1 mRNA and body weight. Interestingly, this reciprocal association was stronger in LP-Lact offspring at postnatal day 21. Functional relevance of this in vivo relationship was evaluated by transfection of miR-29 mimics in neonatal Clone 9 rat hepatoma cells. Transfection with miR-29 suppressed Igf1 expression by 12 hours. Collectively, these findings implicate that nutritional restoration after weaning (post liver differentiation) in maternal protein restriction rat offspring fails to prevent long-term impaired growth, in part, due to miR-29 suppression of hepatic Igf1 expression. PMID:26151354

  11. Influence of gender on ABCC2 expression in peripheral blood mononuclear cells.

    PubMed

    Sudchada, P; Chareanchim, W; Assawamakin, A; Thaipiya, P; Choochaimongkhol, W; Thiplui, N; Sukmangsa, P

    2015-01-01

    It is known that several factors, including gender, may influence the expression of multidrug resistance associated proteins 2 (MRP2/ABCC2) in the peripheral blood mononuclear cells (PBMCs). This study aims to compare ABCC2 gene expression in PBMCs of healthy males and females. PBMCs were extracted from 48 females and 44 males, and gene expression was measured using real-time quantitative polymerase chain reaction (real-time QPCR). Multiple housekeeping genes (Actin-β, β2-M, GAPDH) were utilized as endogenous controls. The stability of housekeeping genes was verified using the Excel-based Bestkeeper® program. Our results showed that expression level of ABCC2 in PBMCs was 1.2-1.4 fold higher in males compared to that in females, depending on the endogenous control(s) used. However, this difference was not statistically significant. When considering using a single endogenous control gene, GAPDH and Actin-βwere found to be more suitable than β2-M. Moreover, GAPDH + Actin-β, or the combination of all three housekeeping gene as endogenous control(s) showed greater stability than other endogenous control genes for normalization of ABCC2 expression in PBMCs. This study suggests that ABCC2 expression in PBMCs may be, in part, influenced by gender, and that at least two endogenous control genes should be utilized for gene expression normalization. PMID:26681017

  12. Advanced Running Performance by Genetic Predisposition in Male Dummerstorf Marathon Mice (DUhTP) Reveals Higher Sterol Regulatory Element-Binding Protein (SREBP) Related mRNA Expression in the Liver and Higher Serum Levels of Progesterone

    PubMed Central

    Brenmoehl, Julia; Walz, Christina; Ponsuksili, Siriluck; Schwerin, Manfred; Fuellen, Georg; Hoeflich, Andreas

    2016-01-01

    Long-term-selected DUhTP mice represent a non-inbred model for inborn physical high-performance without previous training. Abundance of hepatic mRNA in 70-day male DUhTP and control mice was analyzed using the Affymetrix mouse array 430A 2.0. Differential expression analysis with PLIER corrected data was performed using AltAnalyze. Searching for over-representation in biochemical pathways revealed cholesterol metabolism being most prominently affected in DUhTP compared to unselected control mice. Furthermore, pathway analysis by AltAnalyze plus PathVisio indicated significant induction of glycolysis, fatty acid synthesis and cholesterol biosynthesis in the liver of DUhTP mice versus unselected control mice. In contrast, gluconeogenesis was partially inactivated as judged from the analysis of hepatic mRNA transcript abundance in DUhTP mice. Analysis of mRNA transcripts related to steroid hormone metabolism inferred elevated synthesis of progesterone and reduced levels of sex steroids. Abundance of steroid delta isomerase-5 mRNA (Hsd3b5, FC 4.97) was increased and steroid 17-alpha-monooxygenase mRNA (Cyp17a1, FC -11.6) was massively diminished in the liver of DUhTP mice. Assessment of steroid profiles by LC-MS revealed increased levels of progesterone and decreased levels of sex steroids in serum from DUhTP mice versus controls. Analysis of hepatic mRNA transcript abundance indicates that sterol regulatory element-binding protein-1 (SREBP-1) may play a major role in metabolic pathway activation in the marathon mouse model DUhTP. Thus, results from bioinformatics modeling of hepatic mRNA transcript abundance correlated with direct steroid analysis by mass spectrometry and further indicated functions of SREBP-1 and steroid hormones for endurance performance in DUhTP mice. PMID:26799318

  13. Advanced Running Performance by Genetic Predisposition in Male Dummerstorf Marathon Mice (DUhTP) Reveals Higher Sterol Regulatory Element-Binding Protein (SREBP) Related mRNA Expression in the Liver and Higher Serum Levels of Progesterone.

    PubMed

    Ohde, Daniela; Moeller, Mark; Brenmoehl, Julia; Walz, Christina; Ponsuksili, Siriluck; Schwerin, Manfred; Fuellen, Georg; Hoeflich, Andreas

    2016-01-01

    Long-term-selected DUhTP mice represent a non-inbred model for inborn physical high-performance without previous training. Abundance of hepatic mRNA in 70-day male DUhTP and control mice was analyzed using the Affymetrix mouse array 430A 2.0. Differential expression analysis with PLIER corrected data was performed using AltAnalyze. Searching for over-representation in biochemical pathways revealed cholesterol metabolism being most prominently affected in DUhTP compared to unselected control mice. Furthermore, pathway analysis by AltAnalyze plus PathVisio indicated significant induction of glycolysis, fatty acid synthesis and cholesterol biosynthesis in the liver of DUhTP mice versus unselected control mice. In contrast, gluconeogenesis was partially inactivated as judged from the analysis of hepatic mRNA transcript abundance in DUhTP mice. Analysis of mRNA transcripts related to steroid hormone metabolism inferred elevated synthesis of progesterone and reduced levels of sex steroids. Abundance of steroid delta isomerase-5 mRNA (Hsd3b5, FC 4.97) was increased and steroid 17-alpha-monooxygenase mRNA (Cyp17a1, FC -11.6) was massively diminished in the liver of DUhTP mice. Assessment of steroid profiles by LC-MS revealed increased levels of progesterone and decreased levels of sex steroids in serum from DUhTP mice versus controls. Analysis of hepatic mRNA transcript abundance indicates that sterol regulatory element-binding protein-1 (SREBP-1) may play a major role in metabolic pathway activation in the marathon mouse model DUhTP. Thus, results from bioinformatics modeling of hepatic mRNA transcript abundance correlated with direct steroid analysis by mass spectrometry and further indicated functions of SREBP-1 and steroid hormones for endurance performance in DUhTP mice. PMID:26799318

  14. Characterization and functional expression of a ubiquitously expressed tomato pectin methylesterase.

    PubMed Central

    Gaffe, J; Tiznado, M E; Handa, A K

    1997-01-01

    Pectin methylesterase (PME), a ubiquitous enzyme in plants, de-esterifies the methoxylated pectin in the plant cell wall. We have characterized a PME gene (designated as pmeu1) from tomato (Lycopersicon esculentum) with an expression that is higher in younger root, leaf, and fruit tissues than in older tissues. Hypocotyls and epicotyls show higher accumulation of pmeu1 transcripts compared with cotyledons. pmeu1 represents a single-copy gene in the tomato genome. Comparison of the deduced amino acid sequence of pmeu1 with other PME homologs showed that the N-terminal halves are highly variable, and the C-terminal halves are relatively conserved in plant PMEs. Constitutive expression of a fruit-specific PME antisense gene does not affect the level of pmeu1 transcripts in vegetative tissues but does lower the level of PMEU1 mRNA in developing tomato fruits. These results suggest that there exists developmentally regulated silencing of pmeu1 by a heterologous PME antisense gene. Expression of pmeu1 in tobacco (Nicotiana tabacum) under the control of the cauliflower mosaic virus 35S promoter caused up to a 4-fold increase in PME specific activity that was correlated with the accumulation of PMEU1 mRNA. In vitro transcription-translation analyses show that pmeu1 encodes a 64-kD polypeptide, whereas transgenic tobacco plants expressing pmeu1 accumulate a new 37-kD polypeptide, suggesting extensive posttranslational processing of PMEU1. These results are the first evidence, to our knowledge, of the functional characterization of a PME gene and the extensive modification of the encoded polypeptide. PMID:9276962

  15. Expression and Control of Codon-Optimized Granulocyte Colony-Stimulating Factor in Pichia pastoris.

    PubMed

    Maity, Nitu; Thawani, Ankita; Sharma, Anshul; Gautam, Ashwani; Mishra, Saroj; Sahai, Vikram

    2016-01-01

    Granulocyte colony-stimulating factor (GCSF) has therapeutic applications due to its proven efficacy in different forms of neutropenia and chemotherapy-induced leucopenia. The original 564-bp nucleotide sequence from NCBI was codon optimized and assembled by overlapping PCR method comprising of 16 oligos of 50-nt length with 15 base overhang. The synthetic gene (CO-GCSF) was cloned under glucose utilizing glyceraldehyde 3-phosphate dehydrogenase (GAP) and methanol-utilizing alcohol oxidase (AOX1) promoters and expressed in Pichia pastoris SMD1168 strain. Constitutive expression under GAP resulted in cellular toxicity while AOX1 promoter controlled expression was stable. Variation in the levels of expression was observed among the transformant colonies with transformant #2 secreting up to ∼4 mg/L of GCSF. The molecular mass of the expressed GCSF in P. pastoris was ∼19.0 kDa. Quatitation of the expressed protein was carried out by a highly reproducible gel densitometric method. Effect of several operational and nutritional conditions was studied on GCSF production and the results suggest a general approach for increasing the yield of GCSF several folds (2- to 5-fold) over the standard conditions employed currently. Cultivation of the single-copy integrant in the chemically defined medium in a 5-L fermenter resulted in a volumetric productivity of ∼0.7 mg/L/h at the end of the induction phase, which was about 4-fold higher than attained in the shake flask. PMID:26410223

  16. Extracellular calcium regulates keratinocyte proliferation and HPV 16 E6 RNA expression in vitro.

    PubMed

    Turunen, Aaro; Syrjänen, Stina

    2014-09-01

    Human papillomaviruses (HPV) are known to immortalize oral keratinocytes in vitro, but the underlying mechanisms causing the following resistance to differentiation remain unclear. We investigated the effect of extracellular calcium on the proliferation of HPV16-positive keratinocytes and on the mRNA expression of the viral E6-oncogene. HPV16-positive hypopharyngeal carcinoma cells (UD-SCC-2), spontaneously immortalized- (HMK) and HPV16 E6/E7-immortalized human gingival keratinocytes (IHGK) were grown for 3, 6 and 9 days in Keratinocyte Serum-free Medium with calcium concentrations ranging from 0 mM to 6 mM. Calcium concentrations up to 0.09 mM increased cellular proliferation, which decreased at higher concentrations. A shift of calcium concentration from 0 to 4 mM increased E6 expression in UD-SCC-2 cells 2.4-fold by day 9. Simultaneously, E2 expression increased. The most significant upregulation of E6 and E2 expressions was observed at day 9, grown in high-calcium media and the increase in E6 expression coincided with an increase in involucrin expression, likely indicating cell differentiation. Despite this, HPV-positive cells continued to proliferate even at high-calcium media in contrast to HPV-negative cells. Overexpression of E6 mRNA may be an important feature of HPV16-positive cells to resist the natural calcium gradient in differentiating keratinocytes allowing cell proliferation. PMID:25295350

  17. Effect of Selenium-Enriched Agaricus bisporus (Higher Basidiomycetes) Extracts, Obtained by Pressurized Water Extraction, on the Expression of Cholesterol Homeostasis Related Genes by Low-Density Array.

    PubMed

    Gil-Ramírez, Alicia; Soler-Rivas, Cristina; Rodriguez-Casado, Arantxa; Ruiz-Rodríguez, Alejandro; Reglero, Guillermo; Marín, Francisco Ramón

    2015-01-01

    Culinary-medicinal mushrooms are able to lower blood cholesterol levels in animal models by different mechanisms. They might impair the endogenous cholesterol synthesis and exogenous cholesterol absorption during digestion. Mushroom extracts, obtained using pressurized water extractions (PWE) from Agaricus bisporus basidiomes, supplemented or not supplemented with selenium, were applied to HepG2 cell cultures to study the expression of 19 genes related to cholesterol homeostasis by low-density arrays (LDA). Only the PWE fractions obtained at 25°C showed 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibitory activity. Besides the enzymatic inhibition, PWE extracts may downregulate some of the key genes involved in the cholesterol homeostasis, such as the squalene synthase gene (FDFT1), since its mRNA expression falls by one third of its initial value. In summary, A. bisporus extracts may also modulate biological cholesterol levels by molecular mechanisms further than the enzymatic way previously reported. PMID:25746616

  18. Natural LacI from E. coli yields faster response and higher level of expression than the LVA-tagged LacI.

    PubMed

    Andreassen, Patrick Rosendahl; Fredberg, Sofie; Horan, Mattias; Knudsen, Maria Højberg; Jacobsen, Kirstine; Kjær, Andreas; Krogh, Thøger Jensen; Kronborg, Tina; Mattsson, Nicky Cordua; Schmidt, Sissel Ida; Wille, Heidi; Andersen, Ann

    2014-12-19

    The lac promoter is one of the most commonly used promoters for expression control of recombinant genes in E. coli. In the absence of galactosides, the lac promoter is repressed by its repressor protein LacI. Since the lac promoter is regulated by a repressor, overexpression of LacI is necessary for regulation when the promoter is introduced on a high-copy plasmid. For that purpose, a modified variant of LacI, a LVA-tagged LacI, was submitted to the Registry of Standard Biological Parts and has been used for more than 500 constructs since then. We have found, however, that natural LacI is superior to the LVA-tagged LacI as controller of expression. PMID:25524095

  19. Higher Expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 Chemokines in the Skin Associated with Parasite Density in Canine Visceral Leishmaniasis

    PubMed Central

    Menezes-Souza, Daniel; Guerra-Sá, Renata; Carneiro, Cláudia Martins; Vitoriano-Souza, Juliana; Giunchetti, Rodolfo Cordeiro; Teixeira-Carvalho, Andréa; Silveira-Lemos, Denise; Oliveira, Guilherme Corrêa; Corrêa-Oliveira, Rodrigo; Reis, Alexandre Barbosa

    2012-01-01

    Background The immune response in the skin of dogs infected with Leishmania infantum is poorly understood, and limited studies have described the immunopathological profile with regard to distinct levels of tissue parasitism and the clinical progression of canine visceral leishmaniasis (CVL). Methodology/Principal Findings A detailed analysis of inflammatory cells (neutrophils, eosinophils, mast cells, lymphocytes, and macrophages) as well as the expression of chemokines (CCL2, CCL4, CCL5, CCL13, CCL17, CCL21, CCL24, and CXCL8) was carried out in dermis skin samples from 35 dogs that were naturally infected with L. infantum. The analysis was based on real-time polymerase chain reaction (PCR) in the context of skin parasitism and the clinical status of CVL. We demonstrated increased inflammatory infiltrate composed mainly of mononuclear cells in the skin of animals with severe forms of CVL and high parasite density. Analysis of the inflammatory cell profile of the skin revealed an increase in the number of macrophages and reductions in lymphocytes, eosinophils, and mast cells that correlated with clinical progression of the disease. Additionally, enhanced parasite density was correlated with an increase in macrophages and decreases in eosinophils and mast cells. The chemokine mRNA expression demonstrated that enhanced parasite density was positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression. Conclusions/Significance These findings represent an advance in the knowledge about skin inflammatory infiltrates in CVL and the systemic consequences. Additionally, the findings may contribute to the design of new and more efficient prophylactic tools and immunological therapies against CVL. PMID:22506080

  20. Activation of β-Adrenoceptors by Dobutamine May Induce a Higher Expression of Peroxisome Proliferator-Activated Receptors δ (PPARδ) in Neonatal Rat Cardiomyocytes

    PubMed Central

    Chou, Ming-Ting; Lo, Shih-Hsiang; Cheng, Kai-Chun; Li, Yin-Xiao; Chen, Li-Jen; Cheng, Juei-Tang

    2012-01-01

    Recent evidence showed the role of peroxisome proliferator-activated receptors (PPARs) in cardiac function. Cardiac contraction induced by various agents is critical in restoring the activity of peroxisome proliferator-activated receptors δ (PPARδ) in cardiac myopathy. Because dobutamine is an agent widely used to treat heart failure in emergency setting, this study is aimed to investigate the change of PPARδ in response to dobutamine. Neonatal rat cardiomyocytes were used to examine the effects of dobutamine on PPARδ expression levels and cardiac troponin I (cTnI) phosphorylation via Western blotting analysis. We show that treatment with dobutamine increased PPARδ expression and cTnI phosphorylation in a time- and dose-dependent manner in neonatal rat cardiomyocytes. These increases were blocked by the antagonist of β1-adrenoceptors. Also, the action of dobutamine was related to the increase of calcium ions and diminished by chelating intracellular calcium. Additionally, dobutamine-induced action was reduced by the inhibition of downstream messengers involved in this calcium-related pathway. Moreover, deletion of PPARδ using siRNA generated the reduction of cTnI phosphorylation in cardiomyocytes treated with dobutamine. Thus, we concluded that PPARδ is increased by dobutamine in cardiac cells. PMID:22666095

  1. Differential Expression of Laccase Genes in Pleurotus ostreatus and Biochemical Characterization of Laccase Isozymes Produced in Pichia pastoris

    PubMed Central

    Park, Minsa; Kim, Minseek; Kim, Sinil; Ha, Byeongsuk

    2015-01-01

    In this study, transcriptome analysis of twelve laccase genes in Pleurotus ostreatus revealed that their expression was differentially regulated at different developmental stages. Lacc5 and Lacc12 were specifically expressed in fruiting bodies and primordia, respectively, whereas Lacc6 was expressed at all developmental stages. Lacc1 and Lacc3 were specific to the mycelial stage in solid medium. In order to investigate their biochemical characteristics, these laccases were heterologously expressed in Pichia pastoris using the pPICHOLI-2 expression vector. Expression of the laccases was facilitated by intermittent addition of methanol as an inducer and sole carbon source, in order to reduce the toxic effects associated with high methanol concentration. The highest expression was observed when the recombinant yeast cells were grown for 5 days at 15℃ with intermittent addition of 1% methanol at a 12-hr interval. Investigation of enzyme kinetics using 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) as a substrate revealed that the primordium-specific laccase Lacc12 was 5.4-fold less active than Lacc6 at low substrate concentration with respect to ABTS oxidation activity. The optimal pH and temperature of Lacc12 were 0.5 pH units and 5℃ higher than those of Lacc6. Lacc12 showed maximal activity at pH 3.5 and 50℃, which may reflect the physiological conditions at the primordiation stage. PMID:26539044

  2. Differential Expression of Laccase Genes in Pleurotus ostreatus and Biochemical Characterization of Laccase Isozymes Produced in Pichia pastoris.

    PubMed

    Park, Minsa; Kim, Minseek; Kim, Sinil; Ha, Byeongsuk; Ro, Hyeon-Su

    2015-09-01

    In this study, transcriptome analysis of twelve laccase genes in Pleurotus ostreatus revealed that their expression was differentially regulated at different developmental stages. Lacc5 and Lacc12 were specifically expressed in fruiting bodies and primordia, respectively, whereas Lacc6 was expressed at all developmental stages. Lacc1 and Lacc3 were specific to the mycelial stage in solid medium. In order to investigate their biochemical characteristics, these laccases were heterologously expressed in Pichia pastoris using the pPICHOLI-2 expression vector. Expression of the laccases was facilitated by intermittent addition of methanol as an inducer and sole carbon source, in order to reduce the toxic effects associated with high methanol concentration. The highest expression was observed when the recombinant yeast cells were grown for 5 days at 15℃ with intermittent addition of 1% methanol at a 12-hr interval. Investigation of enzyme kinetics using 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) as a substrate revealed that the primordium-specific laccase Lacc12 was 5.4-fold less active than Lacc6 at low substrate concentration with respect to ABTS oxidation activity. The optimal pH and temperature of Lacc12 were 0.5 pH units and 5℃ higher than those of Lacc6. Lacc12 showed maximal activity at pH 3.5 and 50℃, which may reflect the physiological conditions at the primordiation stage. PMID:26539044

  3. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.; Gregory, Dennis E.

    Decisions made by federal and state courts during 1983 concerning higher education are reported in this chapter. Issues of employment and the treatment of students underlay the bulk of the litigation. Specific topics addressed in these and other cases included federal authority to enforce regulations against age discrimination and to revoke an…

  4. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.

    Litigation in 1987 was very brisk with an increase in the number of higher education cases reviewed. Cases discussed in this chapter are organized under four major topics: (1) intergovernmental relations; (2) employees, involving discrimination claims, tenured and nontenured faculty, collective bargaining and denial of employee benefits; (3)…

  5. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.; Finnegan, Dorothy E.

    The higher education case law in 1988 is extensive. Cases discussed in this chapter are organized under five major topics: (1) intergovernmental relations; (2) employees, involving discrimination claims, tenured and nontenured faculty, collective bargaining, and denial of employee benefits; (3) students, involving admissions, financial aid, First…

  6. Higher Education.

    ERIC Educational Resources Information Center

    Hendrickson, Robert M.

    This eighth chapter of "The Yearbook of School Law, 1986" summarizes and analyzes over 330 state and federal court cases litigated in 1985 in which institutions of higher education were involved. Among the topics examined were relationships between postsecondary institutions and various governmental agencies; discrimination in the employment of…

  7. Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride.

    PubMed

    Yamana, Kazutoshi; Labrie, Fernand; Luu-The, Van

    2010-08-01

    5α-Reductases are crucial enzymes involved in the biosynthesis of dihydrotestosterone, the most potent natural androgen. To date, three types of 5α-reductases, chronologically named types 1, 2 and 3 5α-reductases (SRD5a-1, 2 and 3) have been described. In the present paper, we characterized the activity and compared the mRNA expression levels of SRD5a-3 with those of SRD5a-1 and 2 in various human tissues, and determined its sensitivity to finasteride and dutasteride. We have established HEK-293 cell line that stably expressed SRD5a-3 for studying its activity and the inhibitory effect of finasteride, using [14C]labeled steroids. mRNA expression levels were quantified using real-time PCR in many male and female human tissues including the prostate, adipose tissue, mammary gland, as well as breast and prostate cancer cell lines. Incubation of HEK-SRD5a-3 cells with [14C]4-androstenedione and [14C]testosterone allowed us to show that SRD5a-3 can catalyze very efficiently both substrates 4-androstenedione and testosterone into 5α-androstanedione and dihydrotestosterone, respectively. We observed that the affinity of the enzyme for 4-androstenedione is higher than for testosterone. The activity of SRD5a-3 and SRD5a-2 are similarly sensitive to finasteride, whereas dutasteride is a much more potent inhibitor of SRD5a-3 than SRD5a-2. Tissue distribution analysis shows that SRD5a-3 mRNA expression levels are higher than those of SRD5a-1 and SRD5a-2 in 20 analyzed tissues. In particular, it is highly expressed in the skin, brain, mammary gland and breast cancer cell lines, thus suggesting that SRD5a-3 could play an important role in the production of androgens in these and other peripheral tissues. PMID:25961201

  8. Correlation of Cytochrome P450 Oxidoreductase Expression with the Expression of 10 Isoforms of Cytochrome P450 in Human Liver

    PubMed Central

    Zhang, Hai-Feng; Li, Zhi-Hui; Liu, Jia-Yu; Liu, Ting-Ting; Wang, Ping; Fang, Yan; Zhou, Jun; Cui, Ming-Zhu; Gao, Na; Tian, Xin; Gao, Jie; Wen, Qiang; Jia, Lin-Jing

    2016-01-01

    Human cytochrome P450 oxidoreductase (POR) provides electrons for all microsomal cytochromes P450 (P450s) and plays an indispensable role in drug metabolism catalyzed by this family of enzymes. We evaluated 100 human liver samples and found that POR protein content varied 12.8-fold, from 12.59 to 160.97 pmol/mg, with a median value of 67.99 pmol/mg; POR mRNA expression varied by 26.4-fold. POR activity was less variable with a median value of 56.05 nmol/min per milligram. Cigarette smoking and alcohol consumption clearly influenced POR activity. Liver samples with a 2286822 TT genotype had significantly higher POR mRNA expression than samples with CT genotype. Homozygous carriers of POR2286822C>T, 2286823G>A, and 3823884A>C had significantly lower POR protein levels compared with the corresponding heterozygous carriers. Liver samples from individuals homozygous at 286823G>A, 1135612A>G, and 10954732G>A generally had lower POR activity levels than those from heterozygous or wild-type samples, whereas the common variant POR*28 significantly increased POR activity. There was a strong association between POR and the expression of P450 isoforms at the mRNA and protein level, whereas the relationship at the activity level, as well as the effect of POR protein content on P450 activity, was less pronounced. POR transcription was strongly correlated with both hepatocyte nuclear factor 4 alpha and pregnane X receptor mRNA levels. In conclusion, we have elucidated some potentially important correlations between POR single-nucleotide polymorphisms and POR expression in the Chinese population and have developed a database that correlates POR expression with the expression and activity of 10 P450s important in drug metabolism. PMID:27271371

  9. Correlation of Cytochrome P450 Oxidoreductase Expression with the Expression of 10 Isoforms of Cytochrome P450 in Human Liver.

    PubMed

    Zhang, Hai-Feng; Li, Zhi-Hui; Liu, Jia-Yu; Liu, Ting-Ting; Wang, Ping; Fang, Yan; Zhou, Jun; Cui, Ming-Zhu; Gao, Na; Tian, Xin; Gao, Jie; Wen, Qiang; Jia, Lin-Jing; Qiao, Hai-Ling

    2016-08-01

    Human cytochrome P450 oxidoreductase (POR) provides electrons for all microsomal cytochromes P450 (P450s) and plays an indispensable role in drug metabolism catalyzed by this family of enzymes. We evaluated 100 human liver samples and found that POR protein content varied 12.8-fold, from 12.59 to 160.97 pmol/mg, with a median value of 67.99 pmol/mg; POR mRNA expression varied by 26.4-fold. POR activity was less variable with a median value of 56.05 nmol/min per milligram. Cigarette smoking and alcohol consumption clearly influenced POR activity. Liver samples with a 2286822 TT genotype had significantly higher POR mRNA expression than samples with CT genotype. Homozygous carriers of POR2286822C>T, 2286823G>A, and 3823884A>C had significantly lower POR protein levels compared with the corresponding heterozygous carriers. Liver samples from individuals homozygous at 286823G>A, 1135612A>G, and 10954732G>A generally had lower POR activity levels than those from heterozygous or wild-type samples, whereas the common variant POR*28 significantly increased POR activity. There was a strong association between POR and the expression of P450 isoforms at the mRNA and protein level, whereas the relationship at the activity level, as well as the effect of POR protein content on P450 activity, was less pronounced. POR transcription was strongly correlated with both hepatocyte nuclear factor 4 alpha and pregnane X receptor mRNA levels. In conclusion, we have elucidated some potentially important correlations between POR single-nucleotide polymorphisms and POR expression in the Chinese population and have developed a database that correlates POR expression with the expression and activity of 10 P450s important in drug metabolism. PMID:27271371

  10. Comparison of activity indexes for recognizing enzyme mutants of higher activity with uricase as model

    PubMed Central

    2013-01-01

    Background For screening a library of enzyme mutants, an efficient and cost-effective method for reliable assay of enzyme activity and a decision method for safe recognition of mutants of higher activity are needed. The comparison of activity concentrations of mutants in lysates of transformed Escherichia coli cells against a threshold is unsafe to recognize mutants of higher activity due to variations of both expression levels of mutant proteins and lysis efficiency of transformed cells. Hence, by a spectrophotometric method after verification to measure uricase activity, specific activity calculated from the level of total proteins in a lysate was tested for recognizing a mutant of higher activity. Results During uricase reaction, the intermediate 5-hydroxyisourate interferes with the assay of uric acid absorbance, but the measurement of absorbance at 293 nm in alkaline borate buffer was reliable for measuring uricase initial rates within a reasonable range. The level of total proteins in a lysate was determined by the Bradford assay. Polyacrylamide gel electrophoresis analysis supported different relative abundance of uricase mutant proteins in their lysates; activity concentrations of uricase in such lysates positively correlated with levels of total proteins. Receiver-operation-curve analysis of activity concentration or specific activity yielded area-under-the-curve close to 1.00 for recognizing a mutant with > 200% improvement of activity. For a mutant with just about 80% improvement of activity, receiver-operation-curve analysis of specific activity gave area-under-the-curve close to 1.00 while the analysis of activity concentration gave smaller area-under-the-curve. With the mean plus 1.4-fold of the standard deviation of specific activity of a starting material as the threshold, uricase mutants whose activities were improved by more than 80% were recognized with higher sensitivity and specificity. Conclusion Specific activity calculated from the level of

  11. Comprehensive analysis of Arabidopsis expression level polymorphisms with simple inheritance.

    PubMed

    Plantegenet, Stephanie; Weber, Johann; Goldstein, Darlene R; Zeller, Georg; Nussbaumer, Cindy; Thomas, Jérôme; Weigel, Detlef; Harshman, Keith; Hardtke, Christian S

    2009-01-01

    In Arabidopsis thaliana, gene expression level polymorphisms (ELPs) between natural accessions that exhibit simple, single locus inheritance are promising quantitative trait locus (QTL) candidates to explain phenotypic variability. It is assumed that such ELPs overwhelmingly represent regulatory element polymorphisms. However, comprehensive genome-wide analyses linking expression level, regulatory sequence and gene structure variation are missing, preventing definite verification of this assumption. Here, we analyzed ELPs observed between the Eil-0 and Lc-0 accessions. Compared with non-variable controls, 5' regulatory sequence variation in the corresponding genes is indeed increased. However, approximately 42% of all the ELP genes also carry major transcription unit deletions in one parent as revealed by genome tiling arrays, representing a >4-fold enrichment over controls. Within the subset of ELPs with simple inheritance, this proportion is even higher and deletions are generally more severe. Similar results were obtained from analyses of the Bay-0 and Sha accessions, using alternative technical approaches. Collectively, our results suggest that drastic structural changes are a major cause for ELPs with simple inheritance, corroborating experimentally observed indel preponderance in cloned Arabidopsis QTL. PMID:19225455

  12. High level protein expression in mammalian cells using a safe viral vector: modified vaccinia virus Ankara.

    PubMed

    Hebben, Matthias; Brants, Jan; Birck, Catherine; Samama, Jean-Pierre; Wasylyk, Bohdan; Spehner, Danièle; Pradeau, Karine; Domi, Arban; Moss, Bernard; Schultz, Patrick; Drillien, Robert

    2007-12-01

    Vaccinia virus vectors are attractive tools to direct high level protein synthesis in mammalian cells. In one of the most efficient strategies developed so far, the gene to be expressed is positioned downstream of a bacteriophage T7 promoter within the vaccinia genome and transcribed by the T7 RNA polymerase, also encoded by the vaccinia virus genome. Tight regulation of transcription and efficient translation are ensured by control elements of the Escherichia coli lactose operon and the encephalomyocarditis virus leader sequence, respectively. We have integrated such a stringently controlled expression system, previously used successfully in a standard vaccinia virus backbone, into the modified vaccinia virus Ankara strain (MVA). In this manner, proteins of interest can be produced in mammalian cells under standard laboratory conditions because of the inherent safety of the MVA strain. Using this system for expression of beta-galactosidase, about 15 mg protein could be produced from 10(8) BHK21 cells over a 24-h period, a value 4-fold higher than the amount produced from an identical expression system based on a standard vaccinia virus strain. In another application, we employed the MVA vector to produce human tubulin tyrosine ligase and demonstrate that this protein becomes a major cellular protein upon induction conditions and displays its characteristic enzymatic activity. The MVA vector should prove useful for many other applications in which mammalian cells are required for protein production. PMID:17892951

  13. Differential mRNA expression and glucocorticoid-mediated regulation of TRPM6 and TRPM7 in the heart and kidney throughout murine pregnancy and development.

    PubMed

    Cuffe, James S M; Steane, Sarah; Moritz, Karen M; Paravicini, Tamara M

    2015-01-01

    The transient receptor potential (TRP) channels TRPM6 and TRPM7 are critically involved in maintaining whole body and cellular Mg2+ homeostasis and ensuring the normal function of organs such as the heart and kidney. However, we do not know how the expression of TRPM6 and TPRM7 in these organs changes throughout fetal development and adult life, and whether this expression can be hormonally regulated. This study determined the ontogeny of TRPM6 and TRPM7 mRNA expression from mid-gestation through to adulthood in the mouse. In a second series of experiments, we examined how maternal administration of the glucocorticoids corticosterone and dexamethasone between embryonic days 12.5-15 affected TRPM6 and TRPM7 channel mRNA expression in the mother and fetus. Whilst renal TRPM7 expression was relatively constant throughout development, renal TRPM6 expression was markedly upregulated after birth. In contrast, cardiac TRPM7 expression was 2-4 fold higher in the fetus than in the adult. Surprisingly, TRPM6 expression was detected in the fetal heart (qPCR and in situ hybridization). Glucocorticoid administration during gestation increased fetal cardiac expression of both channels without affecting renal expression. In contrast, in the dam renal TRPM6 and TRPM7 expression was increased by glucocorticoids with no change in the cardiac channel expression. These data suggest that TRPM6 and TRPM7 channels are important in organogenesis, and that elevated maternal glucocorticoid levels can alter the expression of these channels. This suggests that perturbations in hormonal regulatory systems during pregnancy may adversely impact upon normal fetal development, at least in part by altering expression of TRPM channels. PMID:25692682

  14. Expression of prolactin receptors in normal canine mammary tissue, canine mammary adenomas and mammary adenocarcinomas

    PubMed Central

    2012-01-01

    Background Mammary tumors represent the most common neoplastic disease in female dogs. Recently, the promoting role of prolactin (PRL) in the development of human breast carcinoma has been shown. Possible proliferative, anti-apoptotic, migratory and angiogenic effects of PRL on human mammary cancer cells in vitro and in vivo were suggested. The effects of PRL are mediated by its receptor, and alterations in receptor expression are likely to play a role in tumor development. Currently, not much data is available about prolactin receptor (PRLR) expression in canine mammary tumors. To set the basis for investigations on the role of PRL in mammary tumorigenesis in this species, prolactin receptor expression was evaluated by semi-quantitative real time PCR and immunohistochemistry on 10 formalin-fixed, paraffin-embedded samples each of canine non-neoplastic mammary tissue, mammary adenomas and adenocarcinomas. Results The highest PRLR expression levels were found in normal mammary tissue, while adenomas, and to an even higher degree adenocarcinomas, showed a significant decrease in prolactin receptor expression. Compared to normal tissue, PRLR mRNA was reduced 2.4 fold (p = 0.0261) in adenomas and 4.8 fold (p = 0.008) in adenocarcinomas. PRLR mRNA expression was significantly lower in malignant than in benign lesions (p = 0.0165). Immunohistochemistry demonstrated PRLR expression in all three tissue types with signals mostly limited to epithelial cells. Conclusions Malignant transformation of mammary tissue was associated with a decline in prolactin receptor expression. Further studies are warranted to address the functional significance of this finding. PMID:22647582

  15. Overexpression of HER-2 in MDA-MB-435/LCC6 Tumours is Associated with Higher Metabolic Activity and Lower Energy Stress.

    PubMed

    Dragowska, Wieslawa H; Ginj, Mihaela; Kozlowski, Piotr; Yung, Andrew; Ruth, Thomas J; Adam, Michael J; Sossi, Vesna; Bally, Marcel B; Yapp, Donald T T

    2016-01-01

    Overexpresssion of HER-2 in the MDA-MB-435/LCC6 (LCC6(HER-2)) tumour model is associated with significantly increased hypoxia and reduced necrosis compared to isogenic control tumours (LCC6(Vector)); this difference was not related to tumour size or changes in vascular architecture. To further evaluate factors responsible for HER-2-associated changes in the tumour microenvironment, small animal magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure tumour tissue perfusion and metabolism, respectively. The imaging data was further corroborated by analysis of molecular markers pertaining to energy homeostasis, and measurements of hypoxia and glucose consumption. The results showed a strong trend towards higher perfusion rates (~58% greater, p = 0.14), and significantly higher glucose uptake in LCC6(HER-2) (~2-fold greater; p = 0.025), relative to control tumours. The expression of proteins related to energy stress (P-AMPK, P-ACC) and glucose transporters (GLUT1) were lower in LCC6(HER-2) tumours (~2- and ~4-fold, respectively). The in vitro analysis showed that LCC6(HER-2) cells become more hypoxic in 1% oxygen and utilise significantly more glucose in normoxia compared to LCC6(Vector)cells (p < 0.005). Amalgamation of all the data points suggests a novel metabolic adaptation driven by HER-2 overexpression where higher oxygen and glucose metabolic rates produce rich energy supply but also a more hypoxic tumour mass. PMID:26727049

  16. The Role of Hepatocyte Hemojuvelin in the Regulation of Bone Morphogenic Protein-6 and Hepcidin Expression in Vivo*

    PubMed Central

    Zhang, An-Sheng; Gao, Junwei; Koeberl, Dwight D.; Enns, Caroline A.

    2010-01-01

    Both hemojuvelin (HJV) and bone morphogenic protein-6 (BMP6) are essential for hepcidin expression. Hepcidin is the key peptide hormone in iron homeostasis, and is secreted predominantly by hepatocytes. HJV expression is detected in hepatocytes, as well as in skeletal and heart muscle. HJV binds BMP6 and increases hepcidin expression presumably by acting as a BMP co-receptor. We characterized the role of hepatocyte HJV in the regulation of BMP6 and hepcidin expression. In HJV-null (Hjv−/−) mice that have severe iron overload and marked suppression of hepcidin expression, we detected 4-fold higher hepatic BMP6 mRNA than in wild-type counterparts. These results indicate that Hjv−/− mice do not lack BMP6. Furthermore, iron depletion in Hjv−/− mice decreased hepatic BMP6 mRNA. Expression of HJV in hepatocytes of Hjv−/− mice using an AAV2/8 vector, increased hepatic hepcidin mRNA by 65-fold and phosphorylated Smad1/5/8 in the liver by about 2.5-fold. However, no significant change in BMP6 mRNA was detected in either the liver or the small intestine of these animals. Our results revealed a close correlation of hepatic BMP6 mRNA expression with hepatic iron-loading. Together, our data indicate that the regulation of hepatic BMP6 expression by iron is independent of HJV, and that expression of HJV in hepatocytes plays an essential role in hepcidin expression by potentiating the BMP6-mediated signaling. PMID:20363739

  17. The role of hepatocyte hemojuvelin in the regulation of bone morphogenic protein-6 and hepcidin expression in vivo.

    PubMed

    Zhang, An-Sheng; Gao, Junwei; Koeberl, Dwight D; Enns, Caroline A

    2010-05-28

    Both hemojuvelin (HJV) and bone morphogenic protein-6 (BMP6) are essential for hepcidin expression. Hepcidin is the key peptide hormone in iron homeostasis, and is secreted predominantly by hepatocytes. HJV expression is detected in hepatocytes, as well as in skeletal and heart muscle. HJV binds BMP6 and increases hepcidin expression presumably by acting as a BMP co-receptor. We characterized the role of hepatocyte HJV in the regulation of BMP6 and hepcidin expression. In HJV-null (Hjv(-/-)) mice that have severe iron overload and marked suppression of hepcidin expression, we detected 4-fold higher hepatic BMP6 mRNA than in wild-type counterparts. These results indicate that Hjv(-/-) mice do not lack BMP6. Furthermore, iron depletion in Hjv(-/-) mice decreased hepatic BMP6 mRNA. Expression of HJV in hepatocytes of Hjv(-/-) mice using an AAV2/8 vector, increased hepatic hepcidin mRNA by 65-fold and phosphorylated Smad1/5/8 in the liver by about 2.5-fold. However, no significant change in BMP6 mRNA was detected in either the liver or the small intestine of these animals. Our results revealed a close correlation of hepatic BMP6 mRNA expression with hepatic iron-loading. Together, our data indicate that the regulation of hepatic BMP6 expression by iron is independent of HJV, and that expression of HJV in hepatocytes plays an essential role in hepcidin expression by potentiating the BMP6-mediated signaling. PMID:20363739

  18. Expression-Enhanced Fluorescent Proteins Based on Enhanced Green Fluorescent Protein for Super-resolution Microscopy.

    PubMed

    Duwé, Sam; De Zitter, Elke; Gielen, Vincent; Moeyaert, Benjamien; Vandenberg, Wim; Grotjohann, Tim; Clays, Koen; Jakobs, Stefan; Van Meervelt, Luc; Dedecker, Peter

    2015-10-27

    "Smart fluorophores", such as reversibly switchable fluorescent proteins, are crucial for advanced fluorescence imaging. However, only a limited number of such labels is available, and many display reduced biological performance compared to more classical variants. We present the development of robustly photoswitchable variants of enhanced green fluorescent protein (EGFP), named rsGreens, that display up to 30-fold higher fluorescence in E. coli colonies grown at 37 °C and more than 4-fold higher fluorescence when expressed in HEK293T cells compared to their ancestor protein rsEGFP. This enhancement is not due to an intrinsic increase in the fluorescence brightness of the probes, but rather due to enhanced expression levels that allow many more probe molecules to be functional at any given time. We developed rsGreens displaying a range of photoswitching kinetics and show how these can be used for multimodal diffraction-unlimited fluorescence imaging such as pcSOFI and RESOLFT, achieving a spatial resolution of ∼70 nm. By determining the first ever crystal structures of a negative reversibly switchable FP derived from Aequorea victoria in both the "on"- and "off"-conformation we were able to confirm the presence of a cis-trans isomerization and provide further insights into the mechanisms underlying the photochromism. Our work demonstrates that genetically encoded "smart fluorophores" can be readily optimized for biological performance and provides a practical strategy for developing maturation- and stability-enhanced photochromic fluorescent proteins. PMID:26308583

  19. Field resistance to Fusarium oxysporum and Verticillium dahliae in transgenic cotton expressing the plant defensin NaD1

    PubMed Central

    Anderson, Marilyn A.

    2014-01-01

    The plant defensin NaD1, from Nicotiana alata, has potent antifungal activity against a range of filamentous fungi including the two important cotton pathogens, Fusarium oxysporum f. sp. vasinfectum (Fov) and Verticillium dahliae. Transgenic cotton plants expressing NaD1 were produced and plants from three events were selected for further characterization. Homozygous plants were assessed in greenhouse bioassays for resistance to Fov. One line (D1) was selected for field trial testing over three growing seasons in soils naturally infested with Fov and over two seasons in soils naturally infested with V. dahliae. In the field trials with Fov-infested soil, line D1 had 2–3-times the survival rate, a higher tolerance to Fov (higher disease rank), and a 2–4-fold increase in lint yield compared to the non-transgenic Coker control. When transgenic line D1 was planted in V. dahliae-infested soil, plants had a higher tolerance to Verticillium wilt and up to a 2-fold increase in lint yield compared to the non-transgenic Coker control. Line D1 did not exhibit any detrimental agronomic features compared to the parent Coker control when plants were grown in non-diseased soil. This study demonstrated that the expression of NaD1 in transgenic cotton plants can provide substantial resistance to two economically important fungal pathogens. PMID:24502957

  20. Strong seed-specific protein expression from the Vigna radiata storage protein 8SGα promoter in transgenic Arabidopsis seeds.

    PubMed

    Chen, Mo-Xian; Zheng, Shu-Xiao; Yang, Yue-Ning; Xu, Chao; Liu, Jie-Sheng; Yang, Wei-Dong; Chye, Mee-Len; Li, Hong-Ye

    2014-03-20

    Vigna radiata (mung bean) is an important crop plant and is a major protein source in developing countries. Mung bean 8S globulins constitute nearly 90% of total seed storage protein and consist of three subunits designated as 8SGα, 8SGα' and 8SGβ. The 5'-flanking sequences of 8SGα' has been reported to confer high expression in transgenic Arabidopsis seeds. In this study, a 472-bp 5'-flanking sequence of 8SGα was identified by genome walking. Computational analysis subsequently revealed the presence of numerous putative seed-specific cis-elements within. The 8SGα promoter was then fused to the gene encoding β-glucuronidase (GUS) to create a reporter construct for Arabidopsis thaliana transformation. The spatial and temporal expression of 8SGα∷GUS, as investigated using GUS histochemical assays, showed GUS expression exclusively in transgenic Arabidopsis seeds. Quantitative GUS assays revealed that the 8SGα promoter showed 2- to 4-fold higher activity than the Cauliflower Mosaic Virus (CaMV) 35S promoter. This study has identified a seed-specific promoter of high promoter strength, which is potentially useful for directing foreign protein expression in seed bioreactors. PMID:24503210

  1. Engineering production of functional scFv antibody in E. coli by co-expressing the molecule chaperone Skp.

    PubMed

    Wang, Rongzhi; Xiang, Shuangshuang; Feng, Youjun; Srinivas, Swaminath; Zhang, Yonghui; Lin, Mingshen; Wang, Shihua

    2013-01-01

    Single-chain variable fragment (scFv) is a class of engineered antibodies generated by the fusion of the heavy (VH) and light chains (VL) of immunoglobulins through a short polypeptide linker. ScFv play a critical role in therapy and diagnosis of human diseases, and may in fact also be developed into a potential diagnostic and/or therapeutic agent. However, the fact that current scFv antibodies have poor stability, low solubility, and affinity, seriously limits their diagnostic and clinical implication. Here we have developed four different expression vectors, and evaluated their abilities to express a soluble scFv protein. The solubility and binding activity of the purified proteins were determined using both SDS-PAGE and ELISA. Amongst the four purified proteins, the Skp co-expressed scFv showed the highest solubility, and the binding activity to antigen TLH was 3-4 fold higher than the other three purified scFv. In fact, this scFv is specific for TLH and does not cross-react with other TLH-associated proteins and could be used to detect TLH directly in real samples. These results suggest that the pACYC-Duet-skp co-expression vector might be a useful tool for the production of soluble and functional scFv antibody. PMID:24224158

  2. Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma

    PubMed Central

    RODINI, CAMILA OLIVEIRA; XAVIER, FLÁVIA CALÓ AQUINO; PAIVA, KATIÚCIA BATISTA SILVA; DE SOUZA SETÚBAL DESTRO, MARIA FERNANDA; MOYSES, RAQUEL AJUB; MICHALUARTE, PEDRO; CARVALHO, MARCOS BRASILINO; FUKUYAMA, ERICA ERINA; TAJARA, ELOIZA HELENA; OKAMOTO, OSWALDO KEITH; NUNES, FABIO DAUMAS

    2012-01-01

    The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC. PMID:22227861

  3. Homeobox gene expression profile indicates HOXA5 as a candidate prognostic marker in oral squamous cell carcinoma.

    PubMed

    Rodini, Camila Oliveira; Xavier, Flávia Caló Aquino; Paiva, Katiúcia Batista Silva; De Souza Setúbal Destro, Maria Fernanda; Moyses, Raquel Ajub; Michaluarte, Pedro; Carvalho, Marcos Brasilino; Fukuyama, Erica Erina; Tajara, Eloiza Helena; Okamoto, Oswaldo Keith; Nunes, Fabio Daumas

    2012-04-01

    The search for molecular markers to improve diagnosis, individualize treatment and predict behavior of tumors has been the focus of several studies. This study aimed to analyze homeobox gene expression profile in oral squamous cell carcinoma (OSCC) as well as to investigate whether some of these genes are relevant molecular markers of prognosis and/or tumor aggressiveness. Homeobox gene expression levels were assessed by microarrays and qRT-PCR in OSCC tissues and adjacent non-cancerous matched tissues (margin), as well as in OSCC cell lines. Analysis of microarray data revealed the expression of 147 homeobox genes, including one set of six at least 2-fold up-regulated, and another set of 34 at least 2-fold down-regulated homeobox genes in OSCC. After qRT-PCR assays, the three most up-regulated homeobox genes (HOXA5, HOXD10 and HOXD11) revealed higher and statistically significant expression levels in OSCC samples when compared to margins. Patients presenting lower expression of HOXA5 had poorer prognosis compared to those with higher expression (P=0.03). Additionally, the status of HOXA5, HOXD10 and HOXD11 expression levels in OSCC cell lines also showed a significant up-regulation when compared to normal oral keratinocytes. Results confirm the presence of three significantly upregulated (>4-fold) homeobox genes (HOXA5, HOXD10 and HOXD11) in OSCC that may play a significant role in the pathogenesis of these tumors. Moreover, since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC. PMID:22227861

  4. Molecular cloning and differential expression patterns of sigma and omega glutathione S-transferases from Venerupis philippinarum to heavy metals and benzo[a]pyrene exposure

    NASA Astrophysics Data System (ADS)

    Zhang, Linbao; Wu, Huifeng; Liu, Xiaoli; Chen, Leilei; Wang, Qing; Zhao, Jianmin; You, Liping

    2012-05-01

    Glutathione S-transferases (GSTs) are a class of enzymes that facilitate the detoxification of xenobiotics, and also play important roles in antioxidant defense. We identified two glutathione S-transferase isoforms (VpGSTS, sigma GST; VpGSTO, omega GST) from Venerupis philippinarum by RACE approaches. The open reading frames of VpGSTS and VpGSTO were of 612 bp and 729 bp, encoding 203 and 242 amino acids with an estimated molecular mass of 22.88 and 27.94 kDa, respectively. The expression profiles of VpGSTS and VpGSTO responded to heavy metals and benzo[a]pyrene (B[a]P) exposure were investigated by quantitative real-time RT-PCR. The expression of VpGSTS and VpGSTO were both rapidly up-regulated, however, they showed differential expression patterns to different toxicants. Cd displayed stronger induction of VpGSTS expression with an approximately 12-fold increase than that of VpGSTO with a maximum 6.4-fold rise. Cu exposure resulted in similar expression patterns for both VpGSTS and VpGSTO. For B[a]P exposure, the maximum induction of VpGSTO was approximately two times higher than that of VpGSTS. Altogether, these findings implied the involvement of VpGSTS and VpGSTO in host antioxidant responses, and highlighted their potential as a biomarker to Cd and B[a]P exposure.

  5. Quantification of midkine gene expression in Patella caerulea (Mollusca, Gastropoda) exposed to cadmium

    NASA Astrophysics Data System (ADS)

    Stillitano, Francesca; Mugelli, Alessandro; Cerbai, Elisabetta; Vanucci, Silvana

    2007-10-01

    The release of cadmium into many coastal areas represents a threat to ecosystems and human health; cadmium is carcinogenic in mammals and in both marine invertebrates and vertebrates. The use of molluscs to assess the ecologic risk associated with contaminants is strongly recommended on account of their ecological role and on their highly conserved control and regulatory pathways that are often homologous to vertebrate systems. We previously identified a midkine family protein in the limpet Patella caerulea; the midkine is a recently discovered cytokines family with unequivocal informative value on repairing injury and neoplastic processes in mammals. Here we report on midkine ( mdk) and α-tubulin ( α-tub) gene expression patterns in P. caerulea exposed to cadmium. Limpets, collected on two occasions from a breakwater at a marina (Tyrrhenian Sea) were exposed to sublethal cadmium concentrations (0.5 and 1 mg l -1 Cd) over a 10-day exposure period. RNA was extracted from the viscera of unexposed and exposed specimens. Real time TaqMan RT-PCR was performed to measure the relative mdk and α-tub gene expression levels. A remarkable mdk over-expression was observed in all exposed animals with respect to unexposed ones; mdk over-expression was significantly higher in both treatments when compared with un-treatment (mean expression levels: 23- and 38-fold, for 0.5 and 1 mg l -1 Cd treatment, respectively; ANOVA, for both P < 0.01). The study also indicates that the mdk up-regulation was significantly Cd-concentration dependent ( P < 0.05). A significant up-regulation of the constitutive α-tub gene was also observed in 1 mg l -1 Cd-treated animals (mean expression level: 4-fold; ANOVA, P < 0.05). In conclusion, these data provide the first evidence paving the way for the use of the midkine as a promising new biomarker of effect in the environment risk assessment policy.

  6. In utero tobacco exposure epigenetically modifies placental CYP1A1 expression.

    PubMed

    Suter, Melissa; Abramovici, Adi; Showalter, Lori; Hu, Min; Shope, Cynthia Do; Varner, Michael; Aagaard-Tillery, Kjersti

    2010-10-01

    The metabolic pathways used by higher-eukaryotic organisms to deal with potentially carcinogenic xenobiotic compounds from tobacco smoke have been well characterized. Carcinogenic compounds such as polycyclic aromatic hydrocarbons are metabolized sequentially in 2 phases: in phase I, CYP1A1 catalyzes conversion into harmful hydrophilic DNA adducts, whereas in phase II, GSTT1 enables excretion via conjugation into polar electrophiles. In an effort to understand susceptibility to in utero tobacco exposure, we previously characterized known metabolic functional polymorphisms and demonstrated that although deletion of fetal GSTT1 significantly modified birth weight in smokers, no polymorphism fully accounted for fetal growth restriction. Because smoking up-regulates CYP1A1 expression, we hypothesized that nonallelic (epigenetic) dysregulation of placental CYP1A1 expression via alterations in DNA methylation (meCpG) may further modify fetal growth. In the present article, we compared placental expression of multiple CYP family members among gravidae and observed significantly increased CYP1A1 expression among smokers relative to controls (4.4-fold, P < .05). To fully characterize CYP1A1 meCpG status, bisulfite modification and sequencing of the entire proximal 1-kilobase promoter (containing 59 CpG sites) were performed. CpG sites immediately proximal to the 5′-xenobiotic response element transcription factor binding element were significantly hypomethylated among smokers (55.6% vs 45.9% meCpG, P = .027), a finding that uniquely correlated with placental gene expression (r = 0.737, P = .007). Thus, in utero tobacco exposure significantly increases placental CYP1A1 expression in association with differential methylation at a critical xenobiotic response element. PMID:20462615

  7. Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction.

    PubMed

    Alcorn, J; Lu, X; Moscow, J A; McNamara, P J

    2002-11-01

    Transporter-mediated processes in the lactating mammary gland may explain the significant accumulation of certain drugs in breast milk. The purpose of this study was to identify potential candidate drug transport proteins involved in drug accumulation in milk. Quantitative reverse transcription-polymerase chain reaction methods were developed to determine the relative RNA levels of 30 different drug transporter genes. Transporter gene RNA levels in lactating mammary epithelial cells (MEC) purified from pooled fresh breast milk samples were compared with levels in nonlactating MEC, liver, and kidney tissue. Transcripts were detected in lactating MEC for OCT1, OCT3, OCTN1, OCTN2, OATP-A, OATP-B, OATP-D, OATP-E, MRP1, MRP2, MRP5, MDR1, CNT1, CNT3, ENT1, ENT3, NCBT1, PEPT1, and PEPT2. No transcripts were detected for OCT2, OAT1, OAT2, OAT3, OAT4, OATP-C, MRP3, MRP4, CNT2, ENT2, and NCBT2. Lactating MEC demonstrated more than 4-fold higher RNA levels of OCT1, OCTN1, PEPT2, CNT1, CNT3, and ENT3, and more than 4-fold lower RNA levels of MDR1 and OCTN2 relative to nonlactating MEC. Lactating MEC showed significantly higher RNA levels of CNT3 relative to liver and kidney, increased PEPT2 RNA levels relative to liver, and increased OATP-A RNA levels relative to kidney. These data imply CNT3 may play a specialized role in nucleoside accumulation in milk and may identify an important role for PEPT2 and OATP-A transporters at the lactating mammary epithelium. Furthermore, transporters expressed in lactating MEC identify a potential role for these transporters in drug disposition at the mammary gland. PMID:12388627

  8. Elevated expression of orexin receptor 2 (HCRTR2) in benign prostatic hyperplasia is accompanied by lowered serum orexin A concentrations.

    PubMed

    Malendowicz, Witold; Szyszka, Marta; Ziolkowska, Agnieszka; Rucinski, Marcin; Kwias, Zbigniew

    2011-03-01

    In search for the new polypeptides responsible for energy homeostasis which are also involved in regulating the growth and function of the human prostate, we assessed the expression of orexins (OXs) and of orexin receptors (OXRs) in human normal prostate and in benign prostatic hyperplasia (BPH). Conventional RT-PCR revealed the expression of OXR2 in all studied samples obtained either from normal prostates or BPH ones while neither preproorexin (ppOX)nor OXR1 mRNA were detected. In adenomatous prostates, expression levels of OXR2 were 30- to 40-fold higher compared to controls. Western blot analysis demonstrated the presence of OXR2 protein in the studied samples and its expression levels were 4-fold higher in tissue samples from BPH. In normal glands, presence of OXR2-like immunoreactivity was found in the apical parts of epithelial cells as well as in smooth muscle cells of the stroma. Immunostaining for OXR2 was more intense in sections obtained from BPH. Immunohistochemistry did not detect the expression of OXR1-like protein. OXA serum concentrations were lowered in BPH patients (mean ± SE 56±4 ng/ml, n=12; P<0.01) and unaltered in prostate cancer (79±7 ng/ml, n=18) compared to the controls (69±2 ng/ml, n=16). On the contrary, serum OXB levels were similar in all studied groups of patients. We thus have demonstrated the mRNA and protein expression of OXR2, but not of ppOX and OXR1 in both normal and BPH human prostate glands. We also demonstrated notable up-regulation of OXR2 in benign prostatic hyperplasia, an alteration accompanied by lowered serum OXA concentrations. These findings suggest that both OXA and OXR2 may be involved in the pathogenesis and/or maintenance of BPH. PMID:21186399

  9. Synergetic effect of yeast cell-surface expression of cellulase and expansin-like protein on direct ethanol production from cellulose

    PubMed Central

    2013-01-01

    Background Numerous studies have examined the direct fermentation of cellulosic materials by cellulase-expressing yeast; however, ethanol productivity in these systems has not yet reached an industrial level. Certain microorganisms, such as the cellulolytic fungus Trichoderma reesei, produce expansin-like proteins, which have a cellulose-loosening effect that may increase the breakdown of cellulose. Here, to improve the direct conversion of cellulose to ethanol, yeast Saccharomyces cerevisiae co-displaying cellulase and expansin-like protein on the cell surface were constructed and examined for direct ethanol fermentation performance. Results The cellulase and expansin-like protein co-expressing strain showed 246 mU/g-wet cell of phosphoric acid swollen cellulose (PASC) degradation activity, which corresponded to 2.9-fold higher activity than that of a cellulase-expressing strain. This result clearly demonstrated that yeast cell-surface expressed cellulase and expansin-like protein act synergistically to breakdown cellulose. In fermentation experiments examining direct ethanol production from PASC, the cellulase and expansin-like protein co-expressing strain produced 3.4 g/L ethanol after 96 h of fermentation, a concentration that was 1.4-fold higher than that achieved by the cellulase-expressing strain (2.5 g/L). Conclusions The PASC degradation and fermentation ability of an engineered yeast strain was markedly improved by co-expressing cellulase and expansin-like protein on the cell surface. To our knowledge, this is the first report to demonstrate the synergetic effect of co-expressing cellulase and expansin-like protein on a yeast cell surface, which may be a promising strategy for constructing direct ethanol fermenting yeast from cellulose. PMID:23835302

  10. Spanning high-dimensional expression space using ribosome-binding site combinatorics

    PubMed Central

    Zelcbuch, Lior; Antonovsky, Niv; Bar-Even, Arren; Levin-Karp, Ayelet; Barenholz, Uri; Dayagi, Michal; Liebermeister, Wolfram; Flamholz, Avi; Noor, Elad; Amram, Shira; Brandis, Alexander; Bareia, Tasneem; Yofe, Ido; Jubran, Halim; Milo, Ron

    2013-01-01

    Protein levels are a dominant factor shaping natural and synthetic biological systems. Although proper functioning of metabolic pathways relies on precise control of enzyme levels, the experimental ability to balance the levels of many genes in parallel is a major outstanding challenge. Here, we introduce a rapid and modular method to span the expression space of several proteins in parallel. By combinatorially pairing genes with a compact set of ribosome-binding sites, we modulate protein abundance by several orders of magnitude. We demonstrate our strategy by using a synthetic operon containing fluorescent proteins to span a 3D color space. Using the same approach, we modulate a recombinant carotenoid biosynthesis pathway in Escherichia coli to reveal a diversity of phenotypes, each characterized by a distinct carotenoid accumulation profile. In a single combinatorial assembly, we achieve a yield of the industrially valuable compound astaxanthin 4-fold higher than previously reported. The methodology presented here provides an efficient tool for exploring a high-dimensional expression space to locate desirable phenotypes. PMID:23470993

  11. Chaperonin-enhanced Escherichia coli cell-free expression of functional CXCR4.

    PubMed

    Chi, Haixia; Wang, Xiaoqiang; Li, Jiqiang; Ren, Hao; Huang, Fang

    2016-08-10

    G protein-coupled receptors (GPCRs) are important therapeutic targets for a broad spectrum of diseases and disorders. Obtaining milligram quantities of functional receptors through the development of robust production methods are highly demanded to probe GPCR structure and functions. In this study, we analyzed synergies of the bacterial chaperonin GroEL-GroES and cell-free expression for the production of functionally folded C-X-C chemokine GPCR type 4 (CXCR4). The yield of soluble CXCR4 in the presence of detergent Brij-35 reached ∼1.1mg/ml. The chaperonin complex added was found to significantly enhance the productive folding of newly synthesized CXCR4, by increasing both the rate (∼30-fold) and the yield (∼1.3-fold) of folding over its spontaneous behavior. Meanwhile, the structural stability of CXCR4 was also improved with supplied GroEL-GroES, as was the soluble expression of biologically active CXCR4 with a ∼1.4-fold increase. The improved stability together with the higher ligand binding affinity suggests more efficient folding. The essential chaperonin GroEL was shown to be partially effective on its own, but for maximum efficiency both GroEL and its co-chaperonin GroES were necessary. The method reported here should prove generally useful for cell-free production of large amounts of natively folded GPCRs, and even other classes of membrane proteins. PMID:27316829

  12. Age-Related Changes in Hepatic Activity and Expression of Detoxification Enzymes in Male Rats

    PubMed Central

    Vyskočilová, Erika; Szotáková, Barbora; Skálová, Lenka; Bártíková, Hana; Hlaváčová, Jitka

    2013-01-01

    Process of aging is accompanied by changes in the biotransformation of xenobiotics and impairment of normal cellular functions by free radicals. Therefore, this study was designed to determine age-related differences in the activities and/or expressions of selected drug-metabolizing and antioxidant enzymes in young and old rats. Specific activities of 8 drug-metabolizing enzymes and 4 antioxidant enzymes were assessed in hepatic subcellular fractions of 6-week-old and 21-month-old male Wistar rats. Protein expressions of carbonyl reductase 1 (CBR1) and glutathione S-transferase (GST) were determined using immunoblotting. Remarkable age-related decrease in specific activities of CYP2B, CYP3A, and UDP-glucuronosyl transferase was observed, whereas no changes in activities of CYP1A2, flavine monooxygenase, aldo-keto reductase 1C, and antioxidant enzymes with advancing age were found. On the other hand, specific activity of CBR1 and GST was 2.4 folds and 5.6 folds higher in the senescent rats compared with the young ones, respectively. Interindividual variability in CBR1 activity increased significantly with rising age. We suppose that elevated activities of GST and CBR1 may protect senescent rats against xenobiotic as well as eobiotic electrophiles and reactive carbonyls, but they may alter metabolism of drugs, which are CBR1 and especially GSTs substrates. PMID:23971034

  13. Spanning high-dimensional expression space using ribosome-binding site combinatorics.

    PubMed

    Zelcbuch, Lior; Antonovsky, Niv; Bar-Even, Arren; Levin-Karp, Ayelet; Barenholz, Uri; Dayagi, Michal; Liebermeister, Wolfram; Flamholz, Avi; Noor, Elad; Amram, Shira; Brandis, Alexander; Bareia, Tasneem; Yofe, Ido; Jubran, Halim; Milo, Ron

    2013-05-01

    Protein levels are a dominant factor shaping natural and synthetic biological systems. Although proper functioning of metabolic pathways relies on precise control of enzyme levels, the experimental ability to balance the levels of many genes in parallel is a major outstanding challenge. Here, we introduce a rapid and modular method to span the expression space of several proteins in parallel. By combinatorially pairing genes with a compact set of ribosome-binding sites, we modulate protein abundance by several orders of magnitude. We demonstrate our strategy by using a synthetic operon containing fluorescent proteins to span a 3D color space. Using the same approach, we modulate a recombinant carotenoid biosynthesis pathway in Escherichia coli to reveal a diversity of phenotypes, each characterized by a distinct carotenoid accumulation profile. In a single combinatorial assembly, we achieve a yield of the industrially valuable compound astaxanthin 4-fold higher than previously reported. The methodology presented here provides an efficient tool for exploring a high-dimensional expression space to locate desirable phenotypes. PMID:23470993

  14. microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells

    PubMed Central

    Weitzel, R. Patrick; Lesniewski, Mathew L.; Haviernik, Peter; Kadereit, Suzanne; Leahy, Patrick; Greco, Nicholas J.

    2009-01-01

    The reduced expression of nuclear factor of activated T cells-1 (NFAT1) protein in umbilical cord blood (UCB)–derived CD4+ T cells and the corresponding reduction in inflammatory cytokine secretion after stimulation in part underlies their phenotypic differences from adult blood (AB) CD4+ T cells. This muted response may contribute to the lower incidence and severity of high-grade acute graft-versus-host disease (aGVHD) exhibited by UCB grafts. Here we provide evidence that a specific microRNA, miR-184, inhibits NFAT1 protein expression elicited by UCB CD4+ T cells. Endogenous expression of miR-184 in UCB is 58.4-fold higher compared with AB CD4+ T cells, and miR-184 blocks production of NFAT1 protein through its complementary target sequence on the NFATc2 mRNA without transcript degradation. Furthermore, its negative effects on NFAT1 protein and downstream interleukin-2 (IL-2) transcription are reversed through antisense blocking in UCB and can be replicated via exogenous transfection of precursor miR-184 into AB CD4+ T cells. Our findings reveal a previously uncharacterized role for miR-184 in UCB CD4+ T cells and a novel function for microRNA in the early adaptive immune response. PMID:19286996

  15. Swertianlarin, isolated from Swertia mussotii Franch, increases detoxification enzymes and efflux transporters expression in rats.

    PubMed

    Feng, Xin-Chan; Du, Xiaohuang; Chen, Sheng; Yue, Dongmei; Cheng, Ying; Zhang, Liangjun; Gao, Yu; Li, Shaoxue; Chen, Lei; Peng, Zhihong; Yang, Yong; Luo, Weizao; Wang, Rongquan; Chen, Wensheng; Chai, Jin

    2015-01-01

    Swertianlarin, isolated from Swertia mussotii Franch and Enicostemma axillare, has hepatoprotective effects against cholestasis in rat models of hepatotoxicity. However, the underlying molecular mechanism is not clear. We then treated rats with swertianlarin for 7 d and then measured serum liver injury markers, lipids, and bile salts, as well as the expression of bile acid synthesis and detoxification enzymes (e.g. Cyp7a1 and Cyp3a), membrane influx and efflux transporters (e.g. Ntcp and Mrp3), nuclear receptors (e.g. Pxr and Fxr/Shp) and transcriptional factors (e.g. Nrf2 and Hnf3β) in the liver. We found a significant induction of the expression of the basolateral efflux transporters Mrp3 and Mrp4 and canalicular transporter Mdr1 in rats treated with swertianlarin, compared with the controls (1.9-fold and 2.2-fold, P < 0.005, and 3.4-fold, P < 0.05, respectively). The expression of detoxification enzymes Cyp3a, Ugt2b, Sult2a1 and Gsta1 in rats treated with swertianlarin was significantly higher than that in controls (3.7-fold, 2.8-fold, 2.1-fold, and 1.7-fold, respectively, all P < 0.05). Expression of the synthetic enzyme, Cyp8b1, was higher in rats treated with swertianlarin than that in controls (1.8-fold at mRNA level and 3.4-flod at protein level, P < 0.05). Elevated serum levels of the conjugated bile acids, taurocholic acid and taurodeoxycholic acid, and a reduction in levels of serum ALP, unconjugated bile acid αMCA, and TG were observed (all P < 0.05). In conclusion, swertianlarin significantly up-regulates hepatic bile acid detoxification enzymes and efflux transporters in rats, which can increase the water solubility of hydrophobic bile acids and elimination of conjugated bile acids. PMID:25755705

  16. Swertianlarin, isolated from Swertia mussotii Franch, increases detoxification enzymes and efflux transporters expression in rats

    PubMed Central

    Feng, Xin-Chan; Du, Xiaohuang; Chen, Sheng; Yue, Dongmei; Cheng, Ying; Zhang, Liangjun; Gao, Yu; Li, Shaoxue; Chen, Lei; Peng, Zhihong; Yang, Yong; Luo, Weizao; Wang, Rongquan; Chen, Wensheng; Chai, Jin

    2015-01-01

    Swertianlarin, isolated from Swertia mussotii Franch and Enicostemma axillare, has hepatoprotective effects against cholestasis in rat models of hepatotoxicity. However, the underlying molecular mechanism is not clear. We then treated rats with swertianlarin for 7 d and then measured serum liver injury markers, lipids, and bile salts, as well as the expression of bile acid synthesis and detoxification enzymes (e.g. Cyp7a1 and Cyp3a), membrane influx and efflux transporters (e.g. Ntcp and Mrp3), nuclear receptors (e.g. Pxr and Fxr/Shp) and transcriptional factors (e.g. Nrf2 and Hnf3β) in the liver. We found a significant induction of the expression of the basolateral efflux transporters Mrp3 and Mrp4 and canalicular transporter Mdr1 in rats treated with swertianlarin, compared with the controls (1.9-fold and 2.2-fold, P < 0.005, and 3.4-fold, P < 0.05, respectively). The expression of detoxification enzymes Cyp3a, Ugt2b, Sult2a1 and Gsta1 in rats treated with swertianlarin was significantly higher than that in controls (3.7-fold, 2.8-fold, 2.1-fold, and 1.7-fold, respectively, all P < 0.05). Expression of the synthetic enzyme, Cyp8b1, was higher in rats treated with swertianlarin than that in controls (1.8-fold at mRNA level and 3.4-flod at protein level, P < 0.05). Elevated serum levels of the conjugated bile acids, taurocholic acid and taurodeoxycholic acid, and a reduction in levels of serum ALP, unconjugated bile acid αMCA, and TG were observed (all P < 0.05). In conclusion, swertianlarin significantly up-regulates hepatic bile acid detoxification enzymes and efflux transporters in rats, which can increase the water solubility of hydrophobic bile acids and elimination of conjugated bile acids. PMID:25755705

  17. Tissue-specific expression of the human brain natriuretic peptide gene in cardiac myocytes.

    PubMed

    LaPointe, M C; Wu, G; Garami, M; Yang, X P; Gardner, D G

    1996-03-01

    Brain natriuretic peptide (BNP) is a cardiac hormone constitutively expressed in the adult heart. To identify the cis-acting elements involved in regulation of the human BNP gene, we subcloned the full-length promoter (-1818 to +100) and deletions thereof upstream from a luciferase reporter gene and transiently transfected them into primary cultures of neonatal rat atrial and ventricular myocytes and myocardial fibroblasts. Luciferase activity of the full-length construct was higher in ventricular (39064 +/- 8488 relative light units, N=11) and atrial (11225 +/- 1907, N=17) myocytes than myocardial fibroblasts (329 +/- 113, n=5). Maximal promoter activity in ventricular and atrial myocytes was maintained by sequences positioned between -1818 and -1283 relative to the transcription start site. Deletion to -1175 resulted in a decrease, whereas further deletion to -500 effected an increase in reporter activity in both cell types. In ventricular and atrial myocytes, deletion from -500 to -40 reduced luciferase activity 20-fold and 2-fold, respectively, whereas in myocardial fibroblasts, deletion to -40 upregulated the BNP promoter 2-fold. Of note, deleting 16 bp between -127 and -111 reduced luciferase activity 7-fold and 4-fold in ventricular and atrial myocytes, respectively, but had essentially no effect on luciferase activity in fibroblasts. Placement of sequences lying between -127 and -40 upstream from a heterologous thymidine kinase promoter resulted in reporter expression that was 7.4-fold greater than the vector alone in ventricular myocytes, approximately 2-fold greater in atrial myocytes, and equivalent to the vector alone in fibroblasts. For study of activity of the human BNP promoter in adult myocytes, either 408 or 97 bp of 5' flanking sequence coupled to the luciferase reporter gene was injected into the apex of adult male Sprague-Dawley rat hearts. After 7 days, luciferase activity in the injected myocardium was 9.8-fold higher for the longer construct

  18. SOX10 Distinguishes Pilocytic and Pilomyxoid Astrocytomas From Ependymomas but Shows No Differences in Expression Level in Ependymomas From Infants Versus Older Children or Among Molecular Subgroups.

    PubMed

    Kleinschmidt-DeMasters, B K; Donson, Andrew M; Richmond, Abby M; Pekmezci, Melike; Tihan, Tarik; Foreman, Nicholas K

    2016-04-01

    SOX10 is important in nonneoplastic oligodendroglial development, but mRNA transcripts and protein expression are identified in a wider variety of CNS glial neoplasms than oligodendrogliomas. We previously demonstrated high levels of SOX10 mRNA and protein in pilocytic astrocytomas (PAs) but not ependymomas (EPNs). We now extend these studies to investigate subsets of these 2 tumors that affect infants, pilomyxoid astrocytomas (PMAs) and infant (<1 year) ependymomas (iEPNs). By gene expression microarray analysis, we found that iEPNs and all EPNs in older children showed very low SOX10 expression levels, on average 7.1-fold below normal control tissues. EPN groups showed no significant difference in SOX10 expression between iEPN and EPN. PAs/PMAs had 24.1/29.4-fold higher transcript levels, respectively, than those in normal tissues. Using immunohistochemical analysis of adult, pediatric, and infantile EPNs and of PAs/PMAs, we found that EPNs from multiple anatomical locations and both age groups (n = 228) never showed 3+ diffuse nuclear immunostaining for SOX10; the majority were scored at 0 or 1+. Conversely, almost all pediatric and adult PAs and PMAs (n = 47) were scored as 3+. These results suggest that in select settings, SOX10 immunohistochemistry can supplement the diagnosis of PMA and PA and aid in distinguishing them from EPNs. PMID:26945037

  19. An Indel Polymorphism in the MtnA 3' Untranslated Region Is Associated with Gene Expression Variation and Local Adaptation in Drosophila melanogaster

    PubMed Central

    Glaser-Schmitt, Amanda; Duchen, Pablo; Parsch, John

    2016-01-01

    Insertions and deletions (indels) are a major source of genetic variation within species and may result in functional changes to coding or regulatory sequences. In this study we report that an indel polymorphism in the 3’ untranslated region (UTR) of the metallothionein gene MtnA is associated with gene expression variation in natural populations of Drosophila melanogaster. A derived allele of MtnA with a 49-bp deletion in the 3' UTR segregates at high frequency in populations outside of sub-Saharan Africa. The frequency of the deletion increases with latitude across multiple continents and approaches 100% in northern Europe. Flies with the deletion have more than 4-fold higher MtnA expression than flies with the ancestral sequence. Using reporter gene constructs in transgenic flies, we show that the 3' UTR deletion significantly contributes to the observed expression difference. Population genetic analyses uncovered signatures of a selective sweep in the MtnA region within populations from northern Europe. We also find that the 3’ UTR deletion is associated with increased oxidative stress tolerance. These results suggest that the 3' UTR deletion has been a target of selection for its ability to confer increased levels of MtnA expression in northern European populations, likely due to a local adaptive advantage of increased oxidative stress tolerance. PMID:27120580

  20. A unique amyloidogenic apolipoprotein serum amyloid A (apoSAA) isoform expressed by the amyloid resistant CE/J mouse strain exhibits higher affinity for macrophages than apoSAA1 and apoSAA2 expressed by amyloid susceptible CBA/J mice.

    PubMed

    Liang, J; Elliott-Bryant, R; Hajri, T; Sipe, J D; Cathcart, E S

    1998-10-01

    CBA/J and other inbred strains of mice that express the amyloidogenic apolipoprotein serum amyloid A (apoSAA) apoSAA2, together with apoSAA1, are susceptible to amyloid A (AA) amyloidosis, whereas CE/J mice that express a single unique isoform, apoSAACEJ, are resistant. Studies indicate that CBA/JxCE/J hybrid mice that express apoSAA2 in the presence of apoSAACEJ are protected from amyloidogenesis. To define a mechanism by which expression of apoSAACEJ may protect from AA formation in the presence of apoSAA2, binding of recombinant apoSAA (r-apoSAA) isoforms, validated by N-terminal sequencing, to a murine macrophage cell line was investigated. Maximal specific binding occurred after incubation of radiolabeled apoSAA with IC-21 macrophages (1x105 cells/ml) for 30 min at 4 degreesC. The binding of 125I-r-apoSAA1, 125I-r-apoSAA2 and 125I-r-apoSAACEJ was specific and saturable, with an affinity (Kd) of about 2.8, 3.2 and 1.3 nM, respectively, and approximately 2-4x106 sites per cell. Competitive binding experiments indicate apoSAACEJ binds with higher affinity to macrophages than does either apoSAA1 or apoSAA2. We suggest that greater cellular affinity of apoSAACEJ compared to apoSAA2 may contribute to protection from AA amyloid in certain CBA/JxCE/J hybrid mice by interfering with interaction of apoSAA2 by macrophages and hence either membrane associated or intracellular degradation. PMID:9767146

  1. Leucocyte expression of genes implicated in the plasminogen activation cascade is modulated by yoghurt peptides.

    PubMed

    Theodorou, Georgios; Politis, Ioannis

    2016-08-01

    The urokinase-plasminogen activator (u-PA), its receptor (u-PAR) and the inhibitors of u-PA (PAI-1 and PAI-2) provide a multi-molecular system in leucocytes that exerts pleiotropic functions influencing the development of inflammatory and immune responses. The objective of the present study was to examine the ability of water soluble extracts (WSE) obtained from traditional Greek yoghurt made from bovine or ovine milk to modulate the expression of u-PA, u-PAR, PAI-1 and PAI-2 in ovine monocytes and neutrophils. WSE were obtained from 8 commercial traditional type Greek yoghurts made from ovine or bovine milk. WSE upregulated the expression of all 4 u-PA related genes in monocytes but the upregulation was much higher in the PAI-1 (10-fold) than in u-PA and u-PAR (3-4 fold) thus, shifting the system towards inhibition. In line with this observation, WSE reduced total and membrane-bound u-PA activity in monocytes. In neutrophils, WSE caused small (50-60%) but significant (P < 0·05) reductions in expression of u-PAR and PAI-2 but had no effect on expression of u-PA, PAI-1 and on total cell-associated and membrane-bound u-PA activity. WSE from yoghurts made from bovine or ovine milk were essentially equally effective in affecting the u-PA system except for the u-PAR gene in ovine neutrophils that was affected (reduced) by the ovine and not the bovine WSE. In conclusion, peptides present in WSE modulated the expression of u-PA related genes but the effect was much more prominent in monocytes than in neutrophils. PMID:27600972

  2. Kidney ischemic injury genes expressed after donor brain death are predictive for the outcome of kidney transplantation.

    PubMed

    Kamińska, D; Kościelska-Kasprzak, K; Drulis-Fajdasz, D; Hałoń, A; Polak, W; Chudoba, P; Jańczak, D; Mazanowska, O; Patrzałek, D; Klinger, M

    2011-10-01

    The results of deceased donor kidney transplantation largely depend on the extent of organ injury induced by brain death and the transplantation procedure. In this study, we analyzed the preprocurement intragraft expression of 29 genes involved in apoptosis, tissue injury, immune cell migration, and activation. We also assessed their influence on allograft function. Before flushing with cold solution we obtained 50 kidney core biopsies of deceased donor kidneys immediately after organ retrieval. The control group included 18 biopsies obtained from living donors. Gene expression was analyzed with low-density arrays (Taqman). LCN2/lipocalin-2 is considered a biomarker of kidney epithelial ischemic injury with a renoprotective function. HAVCR1/KIM-1 is associated with acute tubular injury. Comparison of deceased donor kidneys to control organs revealed a significantly higher expression of LCN2 (8.0-fold P=.0006) and HAVCR1 (4.7-fold, P<.0001). Their expressions positively correlated with serum creatinine concentrations after 6 months after transplantation: LCN2 (r=.65, P<.0001), HAVCR1 (r=.44, P=.006). Kidneys displaying delayed graft function and/or an acute rejection episode in the first 6 months after showed higher LCN2 expression compared to event-free ones (1.7-fold, P=.027). A significantly higher increase in expression of TLR2 (5.2-fold), Interleukin (IL) 18 (4.6-fold), HMGB1 (4.1-fold), GUSB (2.4-fold), CASP3 (2.0-fold) FAS (1.8-fold), and TP53 (1.6-fold) was observed among deceased donor kidneys compared with the control group. Their expression levels were not related to clinical outcomes: however, they showed significant correlations with one another (r>.6, P<.0001). We also observed a slightly reduced expression of IL10 (0.6-fold, P=.004). Our data suggested that increased LCN2 and HAVCR1 expression observed in the kidneys after donor brain death were hallmarks of the organ injury process. LCN2 expression level in retrieved kidneys can predict kidney

  3. Insights into arsenic multi-operons expression and resistance mechanisms in Rhodopseudomonas palustris CGA009

    PubMed Central

    Zhao, Chungui; Zhang, Yi; Chan, Zhuhua; Chen, Shicheng; Yang, Suping

    2015-01-01

    Arsenic (As) is widespread in the environment and causes numerous health problems. Rhodopseudomonas palustris has been regarded as a good model organism for studying arsenic detoxification since it was first demonstrated to methylate environmental arsenic by conversion to soluble or gaseous methylated species. However, the detailed arsenic resistance mechanisms remain unknown though there are at least three arsenic-resistance operons (ars1, ars2, and ars3) in R. palustris. In this study, we investigated how arsenic multi-operons contributed to arsenic detoxification in R. palustris. The expression of ars2 or ars3 operons increased with increasing environmental arsenite (As(III)) concentrations (up to 1.0 mM) while transcript of ars1 operon was not detected in the middle log-phase (55 h). ars2 operon was actively expressed even at the low concentration of As(III) (0.01 μM), whereas the ars3 operon was expressed at 1.0 μM of As(III), indicating that there was a differential regulation mechanism for the three arsenic operons. Furthermore, ars2 and ars3 operons were maximally transcribed in the early log-phase where ars2 operon was 5.4-fold higher than that of ars3 operon. A low level of ars1 transcript was only detected at 43 h (early log-phase). Arsenic speciation analysis demonstrated that R. palustris could reduce As(V) to As(III). Collectively, strain CGA009 detoxified arsenic by using arsenic reduction and methylating arsenic mechanism, while the latter might occur with the presence of higher concentrations of arsenic. PMID:26441915

  4. Elongation factor 1Bgamma (eEF1Bgamma) expression during the molting cycle and cold acclimation in the crayfish Procambarus clarkii.

    PubMed

    Gillen, Christopher M; Gao, Yongping; Niehaus-Sauter, Margaret M; Wylde, Meredith R; Wheatly, Michele G

    2008-06-01

    Eukaryotic elongation factor 1Bgamma (eEF1Bgamma) is a subunit of elongation factor 1 (EF1), which regulates the recruitment of amino acyl-tRNAs to the ribosome during protein synthesis in eukaryotes. In addition to structural roles within eEF1, eEF1Bgamma has properties which suggest sensory or regulatory activities. We have cloned eEF1Bgamma from axial abdominal muscle of freshwater crayfish, Procambarus clarkii. The predicted amino acid sequence has 66% identity to Locusta migratoria eEF1Bgamma and 65% identity to Artemia salina eEF1Bgamma. We measured eEF1Bgamma expression by real-time PCR, using the relative quantification method with 18s ribosomal RNA as an internal calibrator. eEF1Bgamma expression was lowest in gill, axial abdominal muscle, and hepatopancreas, and was highest in the antennal gland (5.7-fold above hepatopancreas) and cardiac muscle (7.8-fold above hepatopancreas). In axial abdominal muscle, eEF1Bgamma expression was 4.4-fold higher in premolt and 11.9 higher in postmolt compared to intermolt. In contrast, eEF1Bgamma was decreased or unchanged in epithelial tissues during pre- and postmolt. eEF1Bgamma expression in the hepatopancreas was 3.5-fold higher during intermolt compared to premolt and was unchanged in gill and antennal gland. No significant differences in eEF1Bgamma were found after 1 week of acclimation to 4 degrees C. These results show that eEF1Bgamma is regulated at the mRNA level with tissue-specific differences in expression patterns. PMID:18407536

  5. Optimized Expression and Purification for High-Activity Preparations of Algal [FeFe]-Hydrogenase

    SciTech Connect

    Yacoby, I.; Tegler, L. T.; Pochekailov, S.; Zhang, S.; King, P. W.

    2012-04-01

    Recombinant expression and purification of metallo-enzymes, including hydrogenases, at high-yields is challenging due to complex, and enzyme specific, post-translational maturation processes. Low fidelities of maturation result in preparations containing a significant fraction of inactive, apo-protein that are not suitable for biophysical or crystallographic studies. We describe the construction, overexpression and high-yield purification of a fusion protein consisting of the algal [2Fe2S]-ferredoxin PetF (Fd) and [FeFe]-hydrogenase HydA1. The maturation of Fd-HydA1 was optimized through improvements in culture conditions and media components used for expression. We also demonstrated that fusion of Fd to the N-terminus of HydA1, in comparison to the C-terminus, led to increased expression levels that were 4-fold higher. Together, these improvements led to enhanced HydA1 activity and improved yield after purification. The strong binding-affinity of Fd for DEAE allowed for two-step purification by ion exchange and StrepTactin affinity chromatography. In addition, the incorporation of a TEV protease site in the Fd-HydA1 linker allowed for the proteolytic removal of Fd after DEAE step, and purification of HydA1 alone by StrepTactin. In combination, this process resulted in HydA1 purification yields of 5 mg L{sup -1} of culture from E. coli with specific activities of 1000 U (U = 1 {micro}mol hydrogen evolved mg{sup -1} min{sup -1}). The [FeFe]-hydrogenases are highly efficient enzymes and their catalytic sites provide model structures for synthetic efforts to develop robust hydrogen activation catalysts. In order to characterize their structure-function properties in greater detail, and to use hydrogenases for biotechnological applications, reliable methods for rapid, high-yield expression and purification are required.

  6. Expression of corticotropin-releasing factor in inflamed tissue is required for intrinsic peripheral opioid analgesia.

    PubMed Central

    Schafer, M; Mousa, S A; Zhang, Q; Carter, L; Stein, C

    1996-01-01

    Immune cell-derived opioid peptides can activate opioid receptors on peripheral sensory nerves to inhibit inflammatory pain. The intrinsic mechanisms triggering this neuroimmune interaction are unknown. This study investigates the involvement of endogenous corticotropin-releasing factor (CRF) and interleukin-1beta (IL-1). A specific stress paradigm, cold water swim (CWS), produces potent opioid receptor-specific antinociception in inflamed paws of rats. This effect is dose-dependently attenuated by intraplantar but not by intravenous alpha-helical CRF. IL-1 receptor antagonist is ineffective. Similarly, local injection of antiserum against CRF, but not to IL-1, dose-dependently reverses this effect. Intravenous anti-CRF is only inhibitory at 10(4)-fold higher concentrations and intravenous CRF does not produce analgesia. Pretreatment of inflamed paws with an 18-mer 3'-3'-end inverted CRF-antisense oligodeoxynucleotide abolishes CWS-induced antinociception. The same treatment significantly reduces the amount of CRF extracted from inflamed paws and the number of CRF-immunostained cells without affecting gross inflammatory signs. A mismatch oligodeoxynucleotide alters neither the CWS effect nor CRF immunoreactivity. These findings identify locally expressed CRF as the predominant agent to trigger opioid release within inflamed tissue. Endogenous IL-1, circulating CRF or antiinflammatory effects, are not involved. Thus, an intact immune system plays an essential role in pain control, which is important for the understanding of pain in immunosuppressed patients with cancer or AIDS. Images Fig. 4 PMID:8650225

  7. Cell-Free Protein Expression under Macromolecular Crowding Conditions

    PubMed Central

    Ge, Xumeng; Luo, Dan; Xu, Jianfeng

    2011-01-01

    Background Cell-free protein expression (CFPE) comprised of in vitro transcription and translation is currently manipulated in relatively dilute solutions, in which the macromolecular crowding effects present in living cells are largely ignored. This may not only affect the efficiency of protein synthesis in vitro, but also limit our understanding of the functions and interactions of biomolecules involved in this fundamental biological process. Methodology/Principal Findings Using cell-free synthesis of Renilla luciferase in wheat germ extract as a model system, we investigated the CFPE under macromolecular crowding environments emulated with three different crowding agents: PEG-8000, Ficoll-70 and Ficoll-400, which vary in chemical properties and molecular size. We found that transcription was substantially enhanced in the macromolecular crowding solutions; up to 4-fold increase in the mRNA production was detected in the presence of 20% (w/v) of Ficoll-70. In contrast, translation was generally inhibited by the addition of each of the three crowding agents. This might be due to PEG-induced protein precipitation and non-specific binding of translation factors to Ficoll molecules. We further explored a two-stage CFPE in which transcription and translation was carried out under high then low macromolecular crowding conditions, respectively. It produced 2.2-fold higher protein yield than the coupled CFPE control. The macromolecular crowding effects on CFPE were subsequently confirmed by cell-free synthesis of an approximately two-fold larger protein, Firefly luciferase, under macromolecular crowding environments. Conclusions/Significance Three macromolecular crowding agents used in this research had opposite effects on transcription and translation. The results of this study should aid researchers in their choice of macromolecular crowding agents and shows that two-stage CFPE is more efficient than coupled CFPE. PMID:22174874

  8. Blocking the mitogen activated protein kinase-p38 pathway is associated with increase expression of nitric oxide synthase and higher production of nitric oxide by bovine macrophages infected with Mycobacterium avium subsp paratuberculosis.

    PubMed

    Souza, Cleverson D

    2015-03-15

    This study evaluated the role of the mitogen-activated protein kinase (MAPK)-p38 pathway in the nitric oxide synthase (iNOS) expression and nitric oxide (NO) production by bovine monocyte-derived macrophages ingesting Mycobacterium avium subsp. paratuberculosis (MAP) organisms in vitro. Bovine monocyte-derived macrophages were incubated with MAP organisms with or without a specific inhibitor of the MAPKp38 pathway and activation of the MAPKp38, interleukin - (IL) IL-10, IL-12, iNOS mRNA expression and NO production were evaluated. Incubation of macrophages with MAP organisms activates the MAPKp38 pathway at early time points post infection. Chemically inhibition of MAPKp38 before incubation of bovine macrophages with MAP resulted in increased expression of IL-12 mRNA at 2, 6 and 24h, decreased expression of IL-10 mRNA at 2, 6 and 24h and increased expression of iNOS mRNA at 2 and 6h. Nitric oxide was evaluated to indirectly determine the effects of MAPKp38 pathway on the anti-microbial activity of bovine macrophages. Incubation of bovine macrophages with MAP resulted in modest increased production of NO at 4 and 6h post infection. Pretreatment of bovine macrophages with the MAPKp38 inhibitor SB203580 before addition of MAP organisms resulted in increased production of NO at 2, 4, 6 and 24h post infection. This study expanded our knowledge of the importance of the MAPKp38 pathway in limiting an appropriate macrophage response to MAP and suggested how activation of MAPKp38 pathway may be a target of this organism to disrupt earlier antimicrobial mechanisms of macrophages. These findings raises the interesting possibility that the cellular manipulation of MAPKp38 may be useful in designing novel vaccines against MAP. PMID:25700780

  9. Higher Education Exchange, 2014

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2014-01-01

    Research shows that not only does higher education not see the public; when the public, in turn, looks at higher education, it sees mostly malaise, inefficiencies, expense, and unfulfilled promises. Yet, the contributors to this issue of the "Higher Education Exchange" tell of bright spots in higher education where experiments in working…

  10. Higher Education Exchange, 2008

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2008-01-01

    "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies. Contributors to this issue of the "Higher Education Exchange" examine whether institutions of higher learning are doing anything to increase the capacity of citizens to shape their future.…

  11. Higher Education Exchange, 2010

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2010-01-01

    "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies. Contributors to this issue of the "Higher Education Exchange" examine whether institutions of higher learning are doing anything to increase the capacity of citizens to shape their future.…

  12. Higher Education Exchange, 2011

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2011-01-01

    "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies. Contributors to this issue of the "Higher Education Exchange" examine whether institutions of higher learning are doing anything to increase the capacity of citizens to shape their future.…

  13. Higher Education Exchange, 2012

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2012-01-01

    "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies. Contributors to this issue of the "Higher Education Exchange" examine whether institutions of higher learning are doing anything to increase the capacity of citizens to shape their future.…

  14. GENDER DIFFERENCES IN BRAIN SUSCEPTIBILITY TO OXIDATIVE STRESS ARE MEDIATED BY LEVELS OF PARAOXONASE-2 (PON2) EXPRESSION

    PubMed Central

    Giordano, G.; Tait, L.; Furlong, C.E.; Cole, T.B.; Kavanagh, T.J.; Costa, L.G.

    2013-01-01

    Paraoxonase 2 (PON2), a member of a gene family that also includes PON1 and PON3, is expressed in most tissues, including the brain. In mouse brain, PON2 levels are highest in dopaminergic areas (e.g. striatum), and are higher in astrocytes than in neurons. PON2 is primarily located in mitochondria and exerts a potent antioxidant effect, protecting mouse CNS cells against oxidative stress. The aim of this study was to characterize PON2 expression and functions in the brains of male and female mice. Levels of PON2 (protein, mRNA, and lactonase activity) were higher in brain regions and cells of female mice. Astrocytes and neurons from male mice were significantly more sensitive (by 3–4-fold) to oxidative stress-induced toxicity than the same cells from female mice. Glutathione levels did not differ between genders. Importantly, no significant gender differences in susceptibility to the same oxidants were seen in cells from PON2−/− mice. Treatment with estradiol induced a time- and concentration-dependent increase in the levels of PON2 protein and mRNA in male (4.5-fold) and female (1.8-fold) astrocytes, which was dependent on activation of estrogen receptor alpha. In ovariectomized mice, PON2 protein and mRNA were decreased to male levels in brain regions and in liver. Estradiol protected astrocytes from wild-type mice against oxidative stress-induced neurotoxicity, but did not protect cells from PON2−/− mice. These results suggest that PON2 is a novel major intracellular factor that protects CNS cells against oxidative stress, and confers gender-dependent susceptibility to such stress. The lower expression of PON2 in males may have broad ramifications for susceptibility to diseases involving oxidative stress, including neurodegenerative diseases. PMID:23376469

  15. Novel Strategy of Using Methyl Esters as Slow Release Methanol Source during Lipase Expression by mut+ Pichia pastoris X33

    PubMed Central

    Kumari, Arti; Gupta, Rani

    2014-01-01

    One of the major issues with heterologous production of proteins in Pichia pastoris X33 under AOX1 promoter is repeated methanol induction. To obviate repeated methanol induction, methyl esters were used as a slow release source of methanol in lipase expressing mut+ recombinant. Experimental design was based on the strategy that in presence of lipase, methyl esters can be hydrolysed to release their products as methanol and fatty acid. Hence, upon break down of methyl esters by lipase, first methanol will be used as a carbon source and inducer. Then P. pastoris can switch over to fatty acid as a carbon source for multiplication and biomass maintenance till further induction by methyl esters. We validated this strategy using recombinant P. pastoris expressing Lip A, Lip C from Trichosporon asahii and Lip11 from Yarrowia lipolytica. We found that the optimum lipase yield under repeated methanol induction after 120 h was 32866 U/L, 28271 U/L and 21978 U/L for Lip C, Lip A and Lip 11 respectively. In addition, we found that a single dose of methyl ester supported higher production than repeated methanol induction. Among various methyl esters tested, methyl oleate (0.5%) caused 1.2 fold higher yield for LipA and LipC and 1.4 fold for Lip11 after 120 h of induction. Sequential utilization of methanol and oleic acid by P. pastoris was observed and was supported by differential peroxisome proliferation studies by transmission electron microscopy. Our study identifies a novel strategy of using methyl esters as slow release methanol source during lipase expression. PMID:25170843

  16. Novel strategy of using methyl esters as slow release methanol source during lipase expression by mut+ Pichia pastoris X33.

    PubMed

    Kumari, Arti; Gupta, Rani

    2014-01-01

    One of the major issues with heterologous production of proteins in Pichia pastoris X33 under AOX1 promoter is repeated methanol induction. To obviate repeated methanol induction, methyl esters were used as a slow release source of methanol in lipase expressing mut+ recombinant. Experimental design was based on the strategy that in presence of lipase, methyl esters can be hydrolysed to release their products as methanol and fatty acid. Hence, upon break down of methyl esters by lipase, first methanol will be used as a carbon source and inducer. Then P. pastoris can switch over to fatty acid as a carbon source for multiplication and biomass maintenance till further induction by methyl esters. We validated this strategy using recombinant P. pastoris expressing Lip A, Lip C from Trichosporon asahii and Lip11 from Yarrowia lipolytica. We found that the optimum lipase yield under repeated methanol induction after 120 h was 32866 U/L, 28271 U/L and 21978 U/L for Lip C, Lip A and Lip 11 respectively. In addition, we found that a single dose of methyl ester supported higher production than repeated methanol induction. Among various methyl esters tested, methyl oleate (0.5%) caused 1.2 fold higher yield for LipA and LipC and 1.4 fold for Lip11 after 120 h of induction. Sequential utilization of methanol and oleic acid by P. pastoris was observed and was supported by differential peroxisome proliferation studies by transmission electron microscopy. Our study identifies a novel strategy of using methyl esters as slow release methanol source during lipase expression. PMID:25170843

  17. The Influence of Differentially Expressed Tissue-Type Plasminogen Activator in Experimental Autoimmune Encephalomyelitis: Implications for Multiple Sclerosis.

    PubMed

    Dahl, Lisa Cm; Nasa, Zeyad; Chung, JieYu; Niego, Be'eri; Tarlac, Volga; Ho, Heidi; Galle, Adam; Petratos, Steven; Lee, Jae Young; Alderuccio, Frank; Medcalf, Robert L

    2016-01-01

    Tissue type plasminogen activator (t-PA) has been implicated in the development of multiple sclerosis (MS) and in rodent models of experimental autoimmune encephalomyelitis (EAE). We show that levels of t-PA mRNA and activity are increased ~4 fold in the spinal cords of wild-type mice that are mice subjected to EAE. This was also accompanied with a significant increase in the levels of pro-matrix metalloproteinase 9 (pro-MMP-9) and an influx of fibrinogen. We next compared EAE severity in wild-type mice, t-PA-/- mice and T4+ transgenic mice that selectively over-express (~14-fold) mouse t-PA in neurons of the central nervous system. Our results confirm that t-PA deficient mice have an earlier onset and more severe form of EAE. T4+ mice, despite expressing higher levels of endogenous t-PA, manifested a similar rate of onset and neurological severity of EAE. Levels of proMMP-9, and extravasated fibrinogen in spinal cord extracts were increased in mice following EAE onset regardless of the absence or over-expression of t-PA wild-type. Interestingly, MMP-2 levels also increased in spinal cord extracts of T4+ mice following EAE, but not in the other genotypes. Hence, while the absence of t-PA confers a more deleterious form of EAE, neuronal over-expression of t-PA does not overtly protect against this condition with regards to symptom onset or severity of EAE. PMID:27427941

  18. The Influence of Differentially Expressed Tissue-Type Plasminogen Activator in Experimental Autoimmune Encephalomyelitis: Implications for Multiple Sclerosis

    PubMed Central

    Dahl, Lisa CM; Nasa, Zeyad; Chung, JieYu; Niego, Be’eri; Tarlac, Volga; Ho, Heidi; Galle, Adam; Petratos, Steven; Lee, Jae Young; Alderuccio, Frank; Medcalf, Robert L.

    2016-01-01

    Tissue type plasminogen activator (t-PA) has been implicated in the development of multiple sclerosis (MS) and in rodent models of experimental autoimmune encephalomyelitis (EAE). We show that levels of t-PA mRNA and activity are increased ~4 fold in the spinal cords of wild-type mice that are mice subjected to EAE. This was also accompanied with a significant increase in the levels of pro-matrix metalloproteinase 9 (pro-MMP-9) and an influx of fibrinogen. We next compared EAE severity in wild-type mice, t-PA-/- mice and T4+ transgenic mice that selectively over-express (~14-fold) mouse t-PA in neurons of the central nervous system. Our results confirm that t-PA deficient mice have an earlier onset and more severe form of EAE. T4+ mice, despite expressing higher levels of endogenous t-PA, manifested a similar rate of onset and neurological severity of EAE. Levels of proMMP-9, and extravasated fibrinogen in spinal cord extracts were increased in mice following EAE onset regardless of the absence or over-expression of t-PA wild-type. Interestingly, MMP-2 levels also increased in spinal cord extracts of T4+ mice following EAE, but not in the other genotypes. Hence, while the absence of t-PA confers a more deleterious form of EAE, neuronal over-expression of t-PA does not overtly protect against this condition with regards to symptom onset or severity of EAE. PMID:27427941

  19. Dominating expression of negative regulatory factors downmodulates major histocompatibility complex Class-II expression on dendritic cells in chronic hepatitis C infection

    PubMed Central

    Tomer, Shallu; Chawla, Yogesh K; Duseja, Ajay; Arora, Sunil K

    2016-01-01

    AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells (DCs) in chronic hepatitis C (CHC) patients infected with genotype 3 virus. METHODS: This prospective study was conducted on the cohorts of CHC individuals identified as responders or non-responders to antiviral therapy. Myeloid DCs were isolated from the peripheral blood of each subject using CD1c (BDCA1)+ DC isolation Kit. Monocytes from healthy donor were cultured with DC growth factors such as IL-4 and GM-CSF either in the presence or absence of hepatitis C virus (HCV) viral proteins followed by LPS stimulation. Phenotyping was done by flowcytometry and gene expression profiling was evaluated by real-time PCR. RESULTS: Non-responders [sustained virological response (SVR)-ve] to conventional antiviral therapy had significantly higher expression of genes associated with interferon responsive element such as IDO1 and PD-L1 (6-fold) and negative regulators of JAK-STAT pathway such as SOCS (6-fold) as compared to responders (SVR+ve) to antiviral therapy. The down-regulated genes in non-responders included factors involved in antigen processing and presentation mainly belonging to major histocompatibility complex (MHC) Class-II family as HLA-DP, HLA-DQ (2-fold) and superoxide dismutase (2-fold). Cells grown in the presence of HCV viral proteins had genes down-regulated for factors involved in innate response, interferon signaling, DC maturation and co-stimulatory signaling to T-cells, while the genes for cytokine signaling and Toll-like receptors (4-fold) were up-regulated as compared to cells grown in absence of viral proteins. CONCLUSION: Underexpressed MHC class-II genes and upregulated negative regulators in non-responders indicate diminished capacity to present antigen and may constitute mechanism of functionally defective state of DCs. PMID:27298560

  20. Special Higher Education Bibliography.

    ERIC Educational Resources Information Center

    Weinberg, Meyer

    1982-01-01

    Cites works relevant to the higher education of Blacks and minority group members. Lists references alphabetically under the following headings: (1) financial aid on the campus; (2) Chicanos in higher education; and (3) race and equality on California campuses. (GC)

  1. In vivo modification of tyrosine residues in recombinant mussel adhesive protein by tyrosinase co-expression in Escherichia coli

    PubMed Central

    2012-01-01

    Background In nature, mussel adhesive proteins (MAPs) show remarkable adhesive properties, biocompatibility, and biodegradability. Thus, they have been considered promising adhesive biomaterials for various biomedical and industrial applications. However, limited production of natural MAPs has hampered their practical applications. Recombinant production in bacterial cells could be one alternative to obtain useable amounts of MAPs, although additional post-translational modification of tyrosine residues into 3,4-dihydroxyphenyl-alanine (Dopa) and Dopaquinone is required. The superior properties of MAPs are mainly attributed to the introduction of quinone-derived intermolecular cross-links. To solve this problem, we utilized a co-expression strategy of recombinant MAP and tyrosinase in Escherichia coli to successfully modify tyrosine residues in vivo. Results A recombinant hybrid MAP, fp-151, was used as a target for in vivo modification, and a dual vector system of pET and pACYC-Duet provided co-expression of fp-151 and tyrosinase. As a result, fp-151 was over-expressed and mainly obtained from the soluble fraction in the co-expression system. Without tyrosinase co-expression, fp-151 was over-expressed in an insoluble form in inclusion bodies. The modification of tyrosine residues in the soluble-expressed fp-151 was clearly observed from nitroblue tetrazolium staining and liquid-chromatography-mass/mass spectrometry analyses. The purified, in vivo modified, fp-151 from the co-expression system showed approximately 4-fold higher bulk-scale adhesive strength compared to in vitro tyrosinase-treated fp-151. Conclusion Here, we reported a co-expression system to obtain in vivo modified MAP; additional in vitro tyrosinase modification was not needed to obtain adhesive properties and the in vivo modified MAP showed superior adhesive strength compared to in vitro modified protein. It is expected that this co-expression strategy will accelerate the use of functional MAPs in

  2. Spotlight on Higher Education.

    ERIC Educational Resources Information Center

    Klinger, Donna; Iwanowski, Jay

    1997-01-01

    A number of current issues and initiatives in higher education are highlighted, including impending reauthorization of the Higher Education Act, the need for advocacy of higher education in public policy arenas, a University of Florida program combining accountability and institutional autonomy, and institutional compliance with nonresident alien…

  3. Higher Education Exchange, 2007

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2007-01-01

    "Higher Education Exchange" publishes case studies, analyses, news, and ideas about efforts within higher education to develop more democratic societies. Contributors to this issue of the "Higher Education Exchange" discuss the concept of growing public scholars; each contribution incorporates a student component. Articles include: (1) "Foreword"…

  4. The Higher Education Enterprise.

    ERIC Educational Resources Information Center

    Ottinger, Cecilia A.

    1991-01-01

    Higher education not only contributes to the development of the human resources and intellectual betterment of the nation but is also a major economic enterprise. This research brief reviews and highlights data on the size and growth of higher education and illustrates how higher education institutions are preparing the future labor force. It…

  5. Expression of human membrane skeleton protein genes for protein 4.1 and betaIISigma2-spectrin assayed by real-time RT-PCR.

    PubMed

    Taylor-Harris, Pamela M; Felkin, Leanne E; Birks, Emma J; Franklin, Rodney C G; Yacoub, Magdi H; Baines, Anthony J; Barton, Paul J R; Pinder, Jennifer C

    2005-01-01

    The proteins, spectrin and 4.1 confer support and resilience to animal cell membranes, and promote assembly of multimeric, membrane-bound signalling complexes. Protein 4.1 also plays important roles in tumour suppression and the regulation of cell proliferation. To assess relative tissue expression of the four genes encoding human protein 4.1, we measured mRNA levels using quantitative real-time polymerase chain reaction. We compared 4.1 expression with that of a major splice variant of spectrin, betaIISigma2 that has a shortened C-terminus lacking a pleckstrin homology domain. mRNA for 4.1R is four-fold higher in bone marrow than in tissues with the next highest prevalence: cerebellum, lung, testis and thymus. 4.1G mRNA is highly expressed in brain, spinal cord and testis; 4.1N in brain, spinal cord and adrenal gland; 4.1B in testis, brain, spinal cord, and kidney. Thus, 4.1N, 4.1B and 4.1G all show high accumulation in nervous tissues. mRNA for betaIISigma2-spectrin is ubiquitous, but most abundant in cardiac and nervous tissues. Comparative transcript abundance was analysed in heart and brain. betaIISigma2-spectrin was the most abundant transcript in heart with levels 5 fold greater than 4.1G or 4.1N and at least 9 fold greater than 4.1B. In brain, 4.1N was the most abundant transcript, with levels 2.4 fold greater than 4.1B and at least 4 fold greater than 4.1G or betaIISigma2-spectrin. 4.1R abundance was very low in both tissues. Whilst we expected that 4.1 mRNAs would feature highly in muscle and nerve, we note their high abundance in testis, indicating previously unsuspected functions in reproduction. PMID:15809685

  6. The Australopithecus Afarensis (Lucy) of Higher Education.

    ERIC Educational Resources Information Center

    Gamble, John King

    1999-01-01

    Uses a fictitious character and story to express doubts about the use of business and marketing principles in American higher education. Asserts that higher education is profoundly different from other institutions, and that colleges and universities should be shielded from the vagaries of the market. (CAK)

  7. The New Pork Barrel in Higher Education.

    ERIC Educational Resources Information Center

    Tenzer, Morton J.

    1985-01-01

    Higher education must recognize and express its concern about a growing trend for the federal government to award funds for projects but bypass the peer review process, favoring established scholars or elite institutions and undermining the competitive process. Self-restraint within higher education and adequate funding for peer review projects…

  8. [Expression of the human interferon alpha F gene in the obligate methylotroph Methylobacillus flagellatum KT and Pseudomonas putida].

    PubMed

    Chistoserdov, A Iu; Eremashvili, M R; Mashko, S V; Lapidus, A L; Skvortsova, M A

    1987-08-01

    The expression of human leucocyte interferon alpha F gene in plasmid pLM-IFN alpha F-273 is controlled by a hybrid tac (trp-lac) promoter. A structural gene for interferon alpha F is a component of the hybrid operon lacZ'-IFN alpha F-TcR, that contains an E. coli trp-operon intercystronic region. Plasmid pLM IFN alpha F-273--directed interferon synthesis allows to obtain about 10(7) IU/l. This plasmid was cloned in broad-host-range vector plasmid pAYC31. The hybrid bi-repliconed plasmid containing interferon gene as well as its single-repliconed deletion derivatives obtained by the in vivo recombination, were introduced into obligate methylotroph Methylobacillus flagellatum KT and Pseudomonas putida PpG6. Methylotrophic strain and Pseudomonas were able to transcribe the interferon gene from E. coli tac promoter, the yield of interferon being 2-4-fold higher as compared with the one in the initial host. PMID:3119998

  9. Construction of a cellulase hyper-expression system in Trichoderma reesei by promoter and enzyme engineering

    PubMed Central

    2012-01-01

    Background Trichoderma reesei is the preferred organism for producing industrial cellulases. However, a more efficient heterologous expression system for enzymes from different organism is needed to further improve its cellulase mixture. The strong cbh1 promoter of T. reesei is frequently used in heterologous expression, however, the carbon catabolite repressor CREI may reduce its strength by binding to the cbh1 promoter at several binding sites. Another crucial point to enhance the production of heterologous enzymes is the stability of recombinant mRNA and the prevention of protein degradation within the endoplasmic reticulum, especially for the bacteria originated enzymes. In this study, the CREI binding sites within the cbh1 promoter were replaced with the binding sites of transcription activator ACEII and the HAP2/3/5 complex to improve the promoter efficiency. To further improve heterologous expression efficiency of bacterial genes within T. reesei, a flexible polyglycine linker and a rigid α-helix linker were tested in the construction of fusion genes between cbh1 from T. reesei and e1, encoding an endoglucanase from Acidothermus cellulolyticus. Results The modified promoter resulted in an increased expression level of the green fluorescent protein reporter by 5.5-fold in inducing culture medium and 7.4-fold in repressing culture medium. The fusion genes of cbh1 and e1 were successfully expressed in T. reesei under the control of promoter pcbh1m2. The higher enzyme activities and thermostability of the fusion protein with rigid linker indicated that the rigid linker might be more suitable for the heterologous expression system in T. reesei. Compared to the parent strain RC30-8, the FPase and CMCase activities of the secreted enzyme mixture from the corresponding transformant R1 with the rigid linker increased by 39% and 30% at 60°C, respectively, and the reduced sugar concentration in the hydrolysate of pretreated corn stover (PCS) was dramatically

  10. Cloning and Expression of Multiple Cytochrome P450 Genes: Induction by Fipronil in Workers of the Red Imported Fire Ant (Solenopsis invicta Buren).

    PubMed

    Zhang, Baizhong; Zhang, Lei; Cui, Rukun; Zeng, Xinnian; Gao, Xiwu

    2016-01-01

    Both exogenous and endogenous compounds can induce the expression of cytochrome P450 genes. The insect cytochrome P450 genes related to insecticide resistance are likely to be expressed as the "first line of defense" when challenged with insecticides. In this study, four cytochrome P450 genes, SinvCYP6B1, SinvCYP6A1, SinvCYP4C1, and SinvCYP4G15, were firstly isolated from workers of the red imported fire ant (Solenopsis invicta) through rapid amplification of cDNA ends (RACE) and sequenced. The fipronil induction profiles of the four cytochrome P450 genes and the two previously isolated CYP4AB1 and CYP4AB2 were characterized in workers. The results revealed that the expression of SinvCYP6B1, SinvCYP6A1, CYP4AB2, and SinvCYP4G15, increased 1.4-fold and 1.3-fold more than those of acetone control, respectively, after 24 h exposure to fipronil at concentrations of 0.25 μg mL-1 (median lethal dose) and 0.56 μg mL-1 (90% lethal dose), while no significant induction of the expression of CYP4AB1 and SinvCYP4C1 was detected. Among these genes, SinvCYP6B1 was the most significantly induced, and its maximum expression was 3.6-fold higher than that in acetone control. These results might suggest that multiple cytochrome P450 genes are co-up-regulated in workers of the fire ant through induction mechanism when challenged with fipronil. These findings indicated that cytochrome P450 genes play an important role in the detoxification of insecticides and provide a theoretical basis for the mechanisms of insecticide metabolism in the fire ant. PMID:26982576

  11. Cloning and Expression of Multiple Cytochrome P450 Genes: Induction by Fipronil in Workers of the Red Imported Fire Ant (Solenopsis invicta Buren)

    PubMed Central

    Zhang, Baizhong; Zhang, Lei; Cui, Rukun; Zeng, Xinnian; Gao, Xiwu

    2016-01-01

    Both exogenous and endogenous compounds can induce the expression of cytochrome P450 genes. The insect cytochrome P450 genes related to insecticide resistance are likely to be expressed as the “first line of defense” when challenged with insecticides. In this study, four cytochrome P450 genes, SinvCYP6B1, SinvCYP6A1, SinvCYP4C1, and SinvCYP4G15, were firstly isolated from workers of the red imported fire ant (Solenopsis invicta) through rapid amplification of cDNA ends (RACE) and sequenced. The fipronil induction profiles of the four cytochrome P450 genes and the two previously isolated CYP4AB1 and CYP4AB2 were characterized in workers. The results revealed that the expression of SinvCYP6B1, SinvCYP6A1, CYP4AB2, and SinvCYP4G15, increased 1.4-fold and 1.3-fold more than those of acetone control, respectively, after 24 h exposure to fipronil at concentrations of 0.25 μg mL−1 (median lethal dose) and 0.56 μg mL−1 (90% lethal dose), while no significant induction of the expression of CYP4AB1 and SinvCYP4C1 was detected. Among these genes, SinvCYP6B1 was the most significantly induced, and its maximum expression was 3.6-fold higher than that in acetone control. These results might suggest that multiple cytochrome P450 genes are co-up-regulated in workers of the fire ant through induction mechanism when challenged with fipronil. These findings indicated that cytochrome P450 genes play an important role in the detoxification of insecticides and provide a theoretical basis for the mechanisms of insecticide metabolism in the fire ant. PMID:26982576

  12. Molecular Responses to Photooxidative Stress in Pinus sylvestris (L.) (II. Differential Expression of CuZn-Superoxide Dismutases and Glutathione Reductase.

    PubMed Central

    Karpinski, S.; Wingsle, G.; Karpinska, B.; Hallgren, J. E.

    1993-01-01

    The influence of photooxidative stress on genes expressing superoxide dismutase (Sod) and glutathione reductase (Gor) was analyzed in needles of top and side shoots of 3-year-old Pinus sylvestris (L.) seedlings. The study was carried out in the field during spring recovery. From mid-April the top shoots of seedlings protruded above the snow and thus were exposed to sunlight, whereas the side shoots were covered with snow until May 4. Needles were sampled from top and side shoots on five different occasions. At the beginning of May the mRNA levels for cytosolic CuZn-Sod were significantly higher in top-shoot needles than in side-shoot needles. Similar results were obtained for chloroplastic CuZn-Sod mRNA. After May 6 we could not detect any significant differences between top- and side-shoot needles for either CuZn-Sod mRNA level. Transcript accumulation for the chloroplastic CuZn-Sod was up to 4-fold higher than for cytosolic CuZn-Sod in both types of shoots. On June 1 minimum transcript levels were observed for both CuZn-SOD isoforms. Protein activity analysis for CuZn-SOD isozymes did not reveal any significant differences between top- and side-shoot needles during the whole period of measurements. The mRNA level for chloroplastic Gor was similar in both types of shoots. However, the total GR activity was significantly higher in top-shoot needles than in side-shoot needles at the beginning of May. The analysis of mRNA accumulation for chloroplastic CuZn-Sod and Gor indicates that transcript levels were at least 5- to 20-fold higher for CuZn-Sod than for chloroplastic Gor. The differential expressions of Sod and Gor genes are discussed in relation to regulation of the enzymic scavenging system during photooxidative stress conditions. PMID:12232032

  13. Expression of ADP-ribosyltransferase 1 Is Associated with Poor Prognosis of Glioma Patients.

    PubMed

    Li, Zhen; Yan, Xinling; Sun, Yuyan; Yang, Xiaoqing

    2016-01-01

    Glioma has a poor prognosis due to its rapid overgrowth, diffuse invasion, and chemotherapy resistance. The improvements in clinical outcome are still limited and the identification of novel biomarkers involved in the progression of gliomas is still under critical demands. Amino acid ADP-ribosyltransferase 1 (ART1) is an enzyme that catalyzes the mono-ADP-ribosylation, a reversible post-translational modification. For example, the mono-ADP-ribosylation of transcription factors can affect their binding to target gene promoters. However, the functional significance of ART1 in glioma has not been reported. We collected 107 glioma cases from Qianfoshan Hospital and Yidu Central Hospital of Weifang between April 2008 and September 2015 to analyze the prognosis value of ART1 in gliomas. RT-qPCR analysis showed that the expression level of ART1 mRNA in glioma tissues was 4-fold higher than that in normal brain tissues. According to the immunohistochemical staining results, 44 patients (41.1%) were categorized as ART1 positive (≥ 20% of stained glioma cells), while the other 63 patients (58.9%) categorized as ART1 negative (< 20% of stained glioma cells). Moreover, the mean percentage of ART1-positive cells was 43.7%, 53.6% and 64.2% in WHO grade II, III and IV specimens, respectively. Through univariate and multivariate analyses, we identified ART1 as an independent prognostic factor. We also found that ART1 overexpression in U251 glioblastoma cells could significantly decrease the susceptibility to vincristine, one of tubulin-targeted drugs, which is widely used in clinical treatment for glioma. Taken together, we propose that up-regulation of ART1 expression is associated with the aggressiveness of glioma. PMID:27466078

  14. Study and Implementation of the End-to-End Data Pipeline for the Virtis Imaging Spectrometer Onbaord Venus Express: "From Science Operations Planning to Data Archiving and Higher Lever Processing"

    NASA Astrophysics Data System (ADS)

    Cardesín Moinelo, Alejandro

    2010-04-01

    This PhD Thesis describes the activities performed during the Research Program undertaken for two years at the Istituto Nazionale di AstroFisica in Rome, Italy, as active member of the VIRTIS Technical and Scientific Team, and one additional year at the European Space Astronomy Center in Madrid, Spain, as member of the Mars Express Science Ground Segment. This document will show a study of all sections of the Science Ground Segment of the Venus Express mission, from the planning of the scientific operations, to the generation, calibration and archiving of the science data, including the production of valuable high level products. We will present and discuss here the end-to-end diagram of the ground segment from the technical and scientific point of view, in order to describe the overall flow of information: from the original scientific requests of the principal investigator and interdisciplinary teams, up to the spacecraft, and down again for the analysis of the measurements and interpretation of the scientific results. These scientific results drive to new and more elaborated scientific requests, which are used as feedback to the planning cycle, closing the circle. Special attention is given here to describe the implementation and development of the data pipeline for the VIRTIS instrument onboard Venus Express. During the research program, both the raw data generation pipeline and the data calibration pipeline were developed and automated in order to produce the final raw and calibrated data products from the input telemetry of the instrument. The final raw and calibrated products presented in this work are currently being used by the VIRTIS Science team for data analysis and are distributed to the whole scientific community via the Planetary Science Archive. More than 20,000 raw data files and 10,000 calibrated products have already been generated after almost 4 years of mission. In the final part of the Thesis, we will also present some high level data

  15. Reinventing Higher Education

    ERIC Educational Resources Information Center

    Hayes, Dianne

    2012-01-01

    Higher education institutions are in the battle of a lifetime as they are coping with political and economic uncertainties, threats to federal aid, declining state support, higher tuition rates and increased competition from for-profit institutions. Amid all these challenges, these institutions are pressed to keep up with technological demands,…

  16. Higher Education in Arkansas.

    ERIC Educational Resources Information Center

    Arkansas State Dept. of Higher Education, Little Rock.

    This report presents information about higher education in Arkansas. Arkansas is 49th in the United States in the number of citizens over the age of 25 with a baccalaureate or higher degree. Arkansas faces shortages of qualified teachers and nurses in regions of the state at a time when the number of graduates in these professions is declining…

  17. Minorities in Higher Education.

    ERIC Educational Resources Information Center

    Justiz, Manuel J., Ed.; And Others

    This book presents 19 papers on efforts to increase the participation of members of minority groups in higher education. The papers are: (1) "Demographic Trends and the Challenges to American Higher Education" (Manuel Justiz); (2) "Three Realities: Minority Life in the United States--The Struggle for Economic Equity (adapted by Don M. Blandin);…

  18. Reimagining Christian Higher Education

    ERIC Educational Resources Information Center

    Hulme, E. Eileen; Groom, David E., Jr.; Heltzel, Joseph M.

    2016-01-01

    The challenges facing higher education continue to mount. The shifting of the U.S. ethnic and racial demographics, the proliferation of advanced digital technologies and data, and the move from traditional degrees to continuous learning platforms have created an unstable environment to which Christian higher education must adapt in order to remain…

  19. Quality in Higher Education.

    ERIC Educational Resources Information Center

    Ruben, Brent D., Ed.

    This volume contains 21 new and classic papers and readings on quality philosophies and concepts, first, as they have been applied in business and industry but primarily as they relate to and can be applied in higher education. The introduction is titled "The Quality Approach in Higher Education: Context and Concepts for Change" by Brent D. Ruben.…

  20. Higher Education Exchange 2006

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2006-01-01

    Contributors to this issue of the Higher Education Exchange debate the issues around knowledge production, discuss the acquisition of deliberative skills for democracy, and examine how higher education prepares, or does not prepare, students for citizenship roles. Articles include: (1) "Foreword" (Deborah Witte); (2) "Knowledge, Judgment and…

  1. UNIVERSAL HIGHER EDUCATION.

    ERIC Educational Resources Information Center

    MCGRATH, EARL J.

    THIS DOCUMENT IS A REPORT ON A GROUP INQUIRY INTO THE SUBSTANCE AND IMPLICATIONS OF UNIVERSAL HIGHER EDUCATION. ELEVEN CHAPTERS ARE PAPERS PRESENTED AT A CONFERENCE HELD UNDER THE AUSPICES OF THE INSTITUTE OF HIGHER EDUCATION, TEACHERS COLLEGE, COLUMBIA UNIVERSITY, IN PUERTO RICO, NOVEMBER 15-21, 1964, FORECASTING THE FORM AND MISSION OF AMERICAN…

  2. Reinventing Continuing Higher Education

    ERIC Educational Resources Information Center

    Walshok, Mary Lindenstein

    2012-01-01

    Re-inventing continuing higher education is about finding ways to be a more central player in a region's civic, cultural, and economic life as well as in the education of individuals for work and citizenship. Continuing higher education will require data gathering, analytical tools, convening authority, interpretive skills, new models of delivery,…

  3. Gender and Higher Education

    ERIC Educational Resources Information Center

    Bank, Barbara J., Ed.

    2011-01-01

    This comprehensive, encyclopedic review explores gender and its impact on American higher education across historical and cultural contexts. Challenging recent claims that gender inequities in U.S. higher education no longer exist, the contributors--leading experts in the field--reveal the many ways in which gender is embedded in the educational…

  4. Consumerism in Higher Education

    ERIC Educational Resources Information Center

    Green, Mark

    1973-01-01

    In considering consumerism in higher education, the student becomes the consumer,'' the university the corporation,'' and higher education the education industry.'' Other members of the education fraternity become investors, management, workers, direct consumers, and indirect consumers. This article proposes that it behooves the student to…

  5. [Deregulation and Higher Education].

    ERIC Educational Resources Information Center

    Business Officer, 1982

    1982-01-01

    The extent to which the Reagan Administration has achieved its deregulation goals in the area of higher education is addressed in three articles: "Deregulation and Higher Education: The View a Year Later" (Sheldon Elliot Steinbach); "Student Financial Aid Deregulation: Rhetoric or Reality?" (Robin E. Jenkins); and "Administration Reform of Civil…

  6. Higher Education Exchange

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2009-01-01

    This volume begins with an essay by Noelle McAfee, a contributor who is familiar to readers of Higher Education Exchange (HEX). She reiterates Mathews' argument regarding the disconnect between higher education's sense of engagement and the public's sense of engagement, and suggests a way around the epistemological conundrum of "knowledge produced…

  7. Higher Education Exchange, 2009

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2009-01-01

    This volume begins with an essay by Noelle McAfee, a contributor who is familiar to readers of Higher Education Exchange (HEX). She reiterates Kettering's president David Mathews' argument regarding the disconnect between higher education's sense of engagement and the public's sense of engagement, and suggests a way around the epistemological…

  8. Genetic modification of bone-marrow mesenchymal stem cells and hematopoietic cells with human coagulation factor IX-expressing plasmids.

    PubMed

    Sam, Mohammad Reza; Azadbakhsh, Azadeh Sadat; Farokhi, Farrah; Rezazadeh, Kobra; Sam, Sohrab; Zomorodipour, Alireza; Haddad-Mashadrizeh, Aliakbar; Delirezh, Nowruz; Mokarizadeh, Aram

    2016-05-01

    Ex-vivo gene therapy of hemophilias requires suitable bioreactors for secretion of hFIX into the circulation and stem cells hold great potentials in this regard. Viral vectors are widely manipulated and used to transfer hFIX gene into stem cells. However, little attention has been paid to the manipulation of hFIX transgene itself. Concurrently, the efficacy of such a therapeutic approach depends on determination of which vectors give maximal transgene expression. With this in mind, TF-1 (primary hematopoietic lineage) and rat-bone marrow mesenchymal stem cells (BMSCs) were transfected with five hFIX-expressing plasmids containing different combinations of two human β-globin (hBG) introns inside the hFIX-cDNA and Kozak element and hFIX expression was evaluated by different methods. In BMSCs and TF-1 cells, the highest hFIX level was obtained from the intron-less and hBG intron-I,II containing plasmids respectively. The highest hFIX activity was obtained from the cells that carrying the hBG intron-I,II containing plasmids. BMSCs were able to produce higher hFIX by 1.4 to 4.7-fold increase with activity by 2.4 to 4.4-fold increase compared to TF-1 cells transfected with the same constructs. BMSCs and TF-1 cells could be effectively bioengineered without the use of viral vectors and hFIX minigene containing hBG introns could represent a particular interest in stem cell-based gene therapy of hemophilias. PMID:26928674

  9. Recombinant lactobacilli expressing linoleic acid isomerase can modulate the fatty acid composition of host adipose tissue in mice.

    PubMed

    Rosberg-Cody, Eva; Stanton, Catherine; O'Mahony, Liam; Wall, Rebecca; Shanahan, Fergus; Quigley, Eamonn M; Fitzgerald, Gerald F; Ross, R Paul

    2011-02-01

    We have previously demonstrated that oral administration of a metabolically active Bifidobacterium breve strain, with ability to form cis-9, trans-11 conjugated linoleic acid (CLA), resulted in modulation of the fatty acid composition of the host, including significantly elevated concentrations of c9, t11 CLA and omega-3 (n-3) fatty acids in liver and adipose tissue. In this study, we investigated whether a recombinant lactobacillus expressing linoleic acid isomerase (responsible for production of t10, c12 CLA) from Propionibacterium acnes (PAI) could influence the fatty acid composition of different tissues in a mouse model. Linoleic-acid-supplemented diets (2 %, w/w) were fed in combination with either a recombinant t10, c12 CLA-producing Lactobacillus paracasei NFBC 338 (Lb338), or an isogenic (vector-containing) control strain, to BALB/c mice for 8 weeks. A third group of mice received linoleic acid alone (2 %, w/w). Tissue fatty acid composition was assessed by GLC at the end of the trial. Ingestion of the strain expressing linoleic acid isomerase was associated with a 4-fold increase (P<0.001) in t10, c12 CLA in adipose tissues of the mice when compared with mice that received the isogenic non-CLA-producing strain. The livers of the mice that received the recombinant CLA-producing Lb338 also contained a 2.5-fold (albeit not significantly) higher concentration of t10, c12 CLA, compared to the control group. These data demonstrate that a single gene (encoding linoleic acid isomerase) expressed in an intestinal microbe can influence the fatty acid composition of host fat. PMID:21178166

  10. OGG1 mRNA expression and incision activity in rats are higher in foetal tissue than in adult liver tissue while 8-oxo-2'-deoxyguanosine levels are unchanged.

    PubMed

    Riis, Bente; Risom, Lotte; Loft, Steffen; Poulsen, Henrik Enghusen

    2002-09-01

    This study was set up to investigate the relationships between the formation and removal of DNA damage in form of 8-oxodeoxyguanosine (8-oxodG) in neonatal (day 16 of gestation) as compared to adult rats. The hypothesis addressed was whether the rapidly dividing foetal tissue has an enhanced requirement of DNA repair providing protection against potentially mutagenic DNA damages such as 8-oxodG. The activity of the primary 8-oxodG-repair protein OGG1 was measured by a DNA incision assay and the expression of OGG1 mRNA was measured by Real-Time PCR normalised to 18S rRNA. The tissue level of 8-oxodG was measured by HPLC-ECD. We found a 2-3-fold increased incision activity in the foetal control tissue, together with a 3-15-fold increase in mRNA of OGG1 as compared to liver tissue from adult rats. The levels of 8-oxodG in the foetal tissue were unaltered as compared to the adult groups. To increase the levels of 8-oxodG, the rats received an injection (i.p.) of the hepatotoxin 2-nitropropane. The compound induced significant levels of 8-oxodG in male rat livers 5h after the injection and in the foetuses 24h after the injection, while the female rats showed no increase in 8-oxodG. The incision activity was slightly depressed in both male and female liver tissue and in the foetal tissue 5h after the injection, but significantly increased from 5 to 24h after the injection. However, it did not reach levels significantly above the control levels. In conclusion, this study confirms that foetal tissue has increased levels of OGG1 mRNA and correspondingly an enhanced incision activity on an 8-oxodG substrate in a crude tissue extract. PMID:12509275

  11. Spatial Memory Impairment is Associated with Intraneural Amyloid-β Immunoreactivity and Dysfunctional Arc Expression in the Hippocampal-CA3 Region of a Transgenic Mouse Model of Alzheimer's Disease.

    PubMed

    Morin, Jean-Pascal; Cerón-Solano, Giovanni; Velázquez-Campos, Giovanna; Pacheco-López, Gustavo; Bermúdez-Rattoni, Federico; Díaz-Cintra, Sofía

    2016-01-01

    Dysfunction of synaptic communication in cortical and hippocampal networks has been suggested as one of the neuropathological hallmarks of the early stages of Alzheimer's disease (AD). Also, several lines of evidence have linked disrupted levels of activity-regulated cytoskeletal associated protein (Arc), an immediate early gene product that plays a central role in synaptic plasticity, with AD "synaptopathy". The mapping of Arc expression patterns in brain networks has been extensively used as a marker of memory-relevant neuronal activity history. Here we evaluated basal and behavior-induced Arc expression in hippocampal networks of the 3xTg-AD mouse model of AD. The basal percentage of Arc-expressing cells in 10-month-old 3xTg-AD mice was higher than wild type in CA3 (4.88% versus 1.77% , respectively) but similar in CA1 (1.75% versus 2.75% ). Noteworthy, this difference was not observed at 3 months of age. Furthermore, although a Morris water maze test probe induced a steep (∼4-fold) increment in the percentage of Arc+ cells in the CA3 region of the 10-month-old wild-type group, no such increment was observed in age-matched 3xTg-AD, whereas the amount of Arc+ cells in CA1 increased in both groups. Further, we detected that CA3 neurons with amyloid-β were much more likely to express Arc protein under basal conditions. We propose that in 3xTg-AD mice, intraneuronal amyloid-β expression in CA3 could increase unspecific neuronal activation and subsequent Arc protein expression, which might impair further memory-stabilizing processes. PMID:26836189

  12. On higher structures

    NASA Astrophysics Data System (ADS)

    Baas, Nils A.

    2016-08-01

    In this paper, we discuss various philosophical aspects of the hyperstructure concept extending networks and higher categories. By this discussion, we hope to pave the way for applications and further developments of the mathematical theory of hyperstructures.

  13. Forecasting Higher Education's Future.

    ERIC Educational Resources Information Center

    Boyken, Don; Buck, Tina S.; Kollie, Ellen; Przyborowski, Danielle; Rondinelli, Joseph A.; Hunter, Jeff; Hanna, Jeff

    2003-01-01

    Offers predictions on trends in higher education to accommodate changing needs, lower budgets, and increased enrollment. They involve campus construction, security, administration, technology, interior design, athletics, and transportation. (EV)

  14. Marketing Higher Education

    ERIC Educational Resources Information Center

    O'Brian, Edward J.

    1973-01-01

    Describes the 4 basic areas in which institutional marketing can be put to use in higher educational institutions: educational services offered, pricing (tuition), promotion to prospective students, and distribution (extension courses and courses that go to the student). (PG)

  15. Overexpression of glutathione S-transferase A1-1 in ECV 304 cells protects against busulfan mediated G2-arrest and induces tissue factor expression

    PubMed Central

    Ritter, Christoph A; Sperker, Bernhard; Grube, Markus; Dressel, Dana; Kunert-Keil, Christiane; Kroemer, Heyo K

    2002-01-01

    The antineoplastic drug busulfan is frequently used in preconditioning regimens for bone marrow transplantation. Pharmacokinetics vary tremendously between patients due to extensive metabolism in the liver via conjugation to glutathione catalysed by glutathione S-transferase (GST) A1-1. Since elevated busulfan plasma levels have been reported to be a risk factor for developing veno-occlusive disease (VOD), metabolism of busulfan may play a pivotal role in the induction of VOD. Therefore, we developed a cell model to investigate the influence of busulfan metabolism on its biological effects. GSTA1-1 cDNA was transfected into the cell line ECV 304 and protein expression was demonstrated by Western blotting. Enzymatic activity could be detected by formation of tetrahydrothiophene. Additionally, effects of busulfan treatment on cell cycle and expression of tissue factor have been investigated. A busulfan-induced G2-arrest was reduced in GSTA1-1-transfected cells, which consequently displayed a significantly higher activity of cdc2 kinase (24.1±1.5 AU mg−1 protein) after busulfan treatment compared to controls (14.7±2.3 AU mg−1 protein; P<0.01). Elevated basal expression of tissue factor in GSTA1-1-transfected ECV 304 cells could be 4 fold increased by busulfan treatment. These data demonstrate that ECV 304 cells transfected with GSTA1-1 provide a valuable tool to assess busulfan metabolism in vitro. Furthermore, overexpression of GSTA1-1 leads to a partial protection against cell cycle effects of busulfan and affects tissue factor expression. PMID:12429583

  16. Fatty acid transport and activation and the expression patterns of genes involved in fatty acid trafficking.

    PubMed

    Sandoval, Angel; Fraisl, Peter; Arias-Barrau, Elsa; Dirusso, Concetta C; Singer, Diane; Sealls, Whitney; Black, Paul N

    2008-09-15

    These studies defined the expression patterns of genes involved in fatty acid transport, activation and trafficking using quantitative PCR (qPCR) and established the kinetic constants of fatty acid transport in an effort to define whether vectorial acylation represents a common mechanism in different cell types (3T3-L1 fibroblasts and adipocytes, Caco-2 and HepG2 cells and three endothelial cell lines (b-END3, HAEC, and HMEC)). As expected, fatty acid transport protein (FATP)1 and long-chain acyl CoA synthetase (Acsl)1 were the predominant isoforms expressed in adipocytes consistent with their roles in the transport and activation of exogenous fatty acids destined for storage in the form of triglycerides. In cells involved in fatty acid processing including Caco-2 (intestinal-like) and HepG2 (liver-like), FATP2 was the predominant isoform. The patterns of Acsl expression were distinct between these two cell types with Acsl3 and Acsl5 being predominant in Caco-2 cells and Acsl4 in HepG2 cells. In the endothelial lines, FATP1 and FATP4 were the most highly expressed isoforms; the expression patterns for the different Acsl isoforms were highly variable between the different endothelial cell lines. The transport of the fluorescent long-chain fatty acid C(1)-BODIPY-C(12) in 3T3-L1 fibroblasts and 3T3-L1 adipocytes followed typical Michaelis-Menten kinetics; the apparent efficiency (k(cat)/K(T)) of this process increases over 2-fold (2.1 x 10(6)-4.5 x 10(6)s(-1)M(-1)) upon adipocyte differentiation. The V(max) values for fatty acid transport in Caco-2 and HepG2 cells were essentially the same, yet the efficiency was 55% higher in Caco-2 cells (2.3 x 10(6)s(-1)M(-1) versus 1.5 x 10(6)s(-1)M(-1)). The kinetic parameters for fatty acid transport in three endothelial cell types demonstrated they were the least efficient cell types for this process giving V(max) values that were nearly 4-fold lower than those defined form 3T3-L1 adipocytes, Caco-2 cells and HepG2 cells. The

  17. Higher dimensional Hadamard matrices

    NASA Technical Reports Server (NTRS)

    Schlichta, P. J.

    1979-01-01

    The paper defines higher dimensional Hadamard matrices and enumerates on some of the simplest three-, four-, and five-dimensional cases and procedures for generating them. Special emphasis is given to proper matrices that have a dimensional hierarchy of orthogonalities. It is determined that this property lends itself primarily to the application of higher dimensional Hadamard matrices to error-correcting codes. A list of derived statements for n-dimensional Hadamard matrices are given, as well as a definition of Hadamard matrix families, such as minimal, Petrie polygon, antipodal (n-2)-dimensional sections, and double proximity shells.

  18. Higher Spin Holography

    NASA Astrophysics Data System (ADS)

    Chang, Chi-Ming

    This dissertation splits into two distinct halves. The first half is devoted to the study of the holography of higher spin gauge theory in AdS 3. We present a conjecture that the holographic dual of W N minimal model in a 't Hooft-like large N limit is an unusual "semi-local" higher spin gauge theory on AdS3 x 1. At each point on the S1 lives a copy of three-dimensional Vasiliev theory, that contains an infinite tower of higher spin gauge fields coupled to a single massive complex scalar propagating in AdS3. The Vasiliev theories at different points on the S1 are correlated only through the AdS3 boundary conditions on the massive scalars. All but one single tower of higher spin symmetries are broken by the boundary conditions. This conjecture is checked by comparing tree-level two- and three-point functions, and also one-loop partition functions on both side of the duality. The second half focuses on the holography of higher spin gauge theory in AdS 4. We demonstrate that a supersymmetric and parity violating version of Vasiliev's higher spin gauge theory in AdS4 admits boundary conditions that preserve N = 0,1,2,3,4 or 6 supersymmetries. In particular, we argue that the Vasiliev theory with U( M) Chan-Paton and N = 6 boundary condition is holographically dual to the 2+1 dimensional U(N) k x U(M) -k ABJ theory in the limit of large N, k and finite M. In this system all bulk higher spin fields transform in the adjoint of the U(M) gauge group, whose bulk t'Hooft coupling is M/N. Our picture suggests that the supersymmetric Vasiliev theory can be obtained as a limit of type IIA string theory in AdS4 x CP3, and that the non-Abelian Vasiliev theory at strong bulk 't Hooft coupling smoothly turn into a string field theory. The fundamental string is a singlet bound state of Vasiliev's higher spin particles held together by U(M) gauge interactions.

  19. Higher spin cosmology

    NASA Astrophysics Data System (ADS)

    Krishnan, Chethan; Raju, Avinash; Roy, Shubho; Thakur, Somyadip

    2014-02-01

    We construct cosmological solutions of higher spin gravity in 2+1 dimensional de Sitter space. We show that a consistent thermodynamics can be obtained for their horizons by demanding appropriate holonomy conditions. This is equivalent to demanding the integrability of the Euclidean boundary conformal field theory partition function, and it reduces to Gibbons-Hawking thermodynamics in the spin-2 case. By using the prescription of Maldacena, we relate the thermodynamics of these solutions to those of higher spin black holes in AdS3.

  20. Differential placental gene expression in severe preeclampsia.

    PubMed

    Sitras, V; Paulssen, R H; Grønaas, H; Leirvik, J; Hanssen, T A; Vårtun, A; Acharya, G

    2009-05-01

    We investigated the global placental gene expression profile in severe preeclampsia. Twenty-one women were randomly selected from 50 participants with uncomplicated pregnancies to match 21 patients with severe preeclampsia. A 30K Human Genome Survey Microarray v.2.0 (Applied Biosystems) was used to evaluate the gene expression profile. After RNA isolation, five preeclamptic placentas were excluded due to poor RNA quality. The series composed of 37 hybridizations in a one-channel detection system of chemiluminescence emitted by the microarrays. An empirical Bayes analysis was applied to find differentially expressed genes. In preeclamptic placentas 213 genes were significantly (fold-change>or=2 and p4 fold), FLT1 (3 fold) and FLT4 (2 fold) were up-regulated. PDGFD was down-regulated (2 fold). Several differentially expressed genes were associated with Alzheimer disease, angiogenesis, Notch-, TGFbeta- and VEGF-signalling pathways. Sixteen genes best discriminated preeclamptic from normal placentas. Comparison between early- (<34 weeks) and late-onset preeclampsia showed 168 differentially expressed genes with oxidative stress, inflammation, and endothelin signalling pathways mainly involved in early-onset disease. Validation of the microarray results was performed by RT-PCR, quantitative urine hCG measurement and placental histopathologic examination. In summary, placental gene expression is altered in preeclampsia and we provide a comprehensive list of the differentially expressed genes. Placental gene expression is different between early- and late-onset preeclampsia, suggesting differences in pathophysiology. PMID:19249095

  1. Interdisciplinarity in Higher Education.

    ERIC Educational Resources Information Center

    Hanisch, Thor Einar; Vollmann, Wolfgang, Ed.

    The advantages of an interdisciplinary approach to college instruction and research are examined, based in part on a 1983 symposium of the European Centre for Higher Education. Six case studies are also presented. It is noted that interdisciplinarity opens up possibilities of exchange between individual disciplines and encourages the development…

  2. Higher Education's Strange Paradox.

    ERIC Educational Resources Information Center

    Howe, Harold, II

    The university which has had the temerity to change the world has not had the nerve to change itself to live in that world. The result is that the university's grading system, curriculum, teaching methods, and philosophies are in conflict with the world beyond the campus gates, and higher education does not meet the intellectual and social needs…

  3. Entrepreneurship and Higher Education

    ERIC Educational Resources Information Center

    Potter, Jonathan, Ed.

    2008-01-01

    Stimulating innovative and growth-oriented entrepreneurship is a key economic and societal challenge to which universities and colleges have much to contribute. This book examines the role that higher education institutions are currently playing through teaching entrepreneurship and transferring knowledge and innovation to enterprises and…

  4. California's Future: Higher Education

    ERIC Educational Resources Information Center

    Johnson, Hans

    2015-01-01

    California's higher education system is not keeping up with the changing economy. Projections suggest that the state's economy will continue to need more highly educated workers. In 2025, if current trends persist, 41 percent of jobs will require at least a bachelor's degree and 36 percent will require some college education short of a bachelor's…

  5. Corporatizing Higher Education

    ERIC Educational Resources Information Center

    Lerner, Gerda

    2008-01-01

    The process of changing U.S. higher education institutions along a corporate model has been going on for several decades. It consists of changes, some open, some obscured, on various fronts: the erosion of tenure by attrition; the simultaneous increase in the use of contingent faculty; the rise in tuition; the dramatic decrease in federal and…

  6. Marketing in Higher Education.

    ERIC Educational Resources Information Center

    Hockenberger, Susan J.

    Educational institutions must seek new approaches to institutional planning because of such factors as shrinking traditional college age populations, eroding grants, governmental and judicial incursion, the tightening economic belt, and concern over the relevance of education to modern day needs. The concept of marketing higher education is…

  7. Liberty and Higher Education.

    ERIC Educational Resources Information Center

    Thompson, Dennis F.

    1989-01-01

    John Stuart Mill's principle of liberty is discussed with the view that it needs to be revised to guide moral judgments in higher education. Three key elements need to be modified: the action that is constrained; the constraint on the action; and the agent whose action is constrained. (MLW)

  8. Higher Education Staff.

    ERIC Educational Resources Information Center

    Clery, Sue; Lee, John

    1999-01-01

    This report reviews changes in higher education staff by occupation between 1993 and 1997. Specific attention is paid to staffing patterns in states with right to work laws compared to those without it. When a state enacts a right to work law, it can be assumed it is not supportive of public unions. This analysis is based on data from the National…

  9. Curriculum in Higher Education.

    ERIC Educational Resources Information Center

    Rothman, A. I., Ed.

    1981-01-01

    Four articles on higher education curriculum are presented. In "The Articulate Curriculum" an approach to curriculum description is presented that is designed to have minimal ambiguity concerning the intention, content, and processes of the curriculum and that will lead to questioning several discrete factors in the curriculum planning process. It…

  10. Networks for Higher Education.

    ERIC Educational Resources Information Center

    Interuniversity Communications Council (EDUCOM), Princeton, NJ.

    EDUCOM, the Inter University Communications Council, Inc., planned its 1972 spring conference as a forum for presentations, discussions, and informal meetings to review the present state and the future possibilities of computer networks for higher education. Speeches presented were specifically related to: (1) the current status and future plans…

  11. Evaluation in Higher Education

    ERIC Educational Resources Information Center

    Bognar, Branko; Bungic, Maja

    2014-01-01

    One of the means of transforming classroom experience is by conducting action research with students. This paper reports about the action research with university students. It has been carried out within a semester of the course "Methods of Upbringing". Its goal has been to improve evaluation of higher education teaching. Different forms…

  12. Marketing in Higher Education.

    ERIC Educational Resources Information Center

    Dalili, Farid

    The use of marketing activities by educational institutions and the transfer of marketing activities from business to higher education are considered. Market analysis helps colleges and universities determine what programs, scheduling, or services are strong and to which student market the institution should appeal. It is suggested that the…

  13. Understanding Higher Education Costs

    ERIC Educational Resources Information Center

    Middaugh, Michael F.

    2005-01-01

    Public discussion of higher education costs frequently confuses price with expenditure. This article examines factors associated with increases in the sticker price of a college education and the expenditures incurred by institutions in delivering that education. The discussion suggests that while growth in college tuition is real, access to…

  14. Higher Education Exchange, 2013

    ERIC Educational Resources Information Center

    Brown, David W., Ed.; Witte, Deborah, Ed.

    2013-01-01

    The Kettering Foundation's research has been focused on putting the public back into the public's business for more than thirty years. Some questions that have recently been useful to Kettering researchers as the foundation focuses on its work with institutional actors--especially higher education and its relationship with the public--have…

  15. Women in Higher Education.

    ERIC Educational Resources Information Center

    Pifer, Alan

    Women have traditionally been discriminated against in higher education in both the attainment of degrees and in employment after earning degrees. It has been felt that women are not as capable, reliable, or effective as men in administrative and classroom situations. Statistics show that even at the present time women are underemployed and…

  16. Benchmarking for Higher Education.

    ERIC Educational Resources Information Center

    Jackson, Norman, Ed.; Lund, Helen, Ed.

    The chapters in this collection explore the concept of benchmarking as it is being used and developed in higher education (HE). Case studies and reviews show how universities in the United Kingdom are using benchmarking to aid in self-regulation and self-improvement. The chapters are: (1) "Introduction to Benchmarking" (Norman Jackson and Helen…

  17. Online Higher Education Commodity

    ERIC Educational Resources Information Center

    Chau, Paule

    2010-01-01

    This article analyzes the current trend towards online education. It examines some of the reasons for the trend and the ramifications it may have on students, faculty and institutions of higher learning. The success and profitability of online programs and institutions such as the University of Phoenix has helped to make the move towards online…

  18. Women in Higher Education.

    ERIC Educational Resources Information Center

    O'Donnell, Sheryl, Ed.; Shaver, Barbara, Ed.

    1981-01-01

    Articles on women's studies and females in higher education are presented in this publication. A University of North Dakota project that sought to promote the integration of new research and scholarship results into the curriculum is described in "Women's Equity Committee Offers a Model Project," (Leola Furman, Robert Young). Historical…

  19. Creativity in Higher Education

    ERIC Educational Resources Information Center

    Gaspar, Drazena; Mabic, Mirela

    2015-01-01

    The paper presents results of research related to perception of creativity in higher education made by the authors at the University of Mostar from Bosnia and Herzegovina. This research was based on a survey conducted among teachers and students at the University. The authors developed two types of questionnaires, one for teachers and the other…

  20. Black at Higher Education

    ERIC Educational Resources Information Center

    Kadi-Hanifi, Karima

    2013-01-01

    This is an exploratory paper, drawing on the author's experiences as well as those of three other black lecturers in Higher Education (HE). Three interviews were carried out, asking the same five questions around themes of concern to the author. These are about the learning and teaching approaches used by these lecturers; their experiences of…

  1. Higher Education Exchange 1995.

    ERIC Educational Resources Information Center

    Brown, David W., Ed.

    Nine articles discuss the relationship between the higher education community and the public. The articles are: (1) "On a Certain Blindness in Teaching" by Michael S. Roth, who stresses the necessity of political citizenship education for a healthy democracy; (2) "Monocultural Perspectives and Campus Diversity" by Jane Fried, who explores the…

  2. Unraveling Higher Education's Costs.

    ERIC Educational Resources Information Center

    Gordon, Gus; Charles, Maria

    1998-01-01

    The activity-based costing (ABC) method of analyzing institutional costs in higher education involves four procedures: determining the various discrete activities of the organization; calculating the cost of each; determining the cost drivers; tracing cost to the cost objective or consumer of each activity. Few American institutions have used the…

  3. NEXUS: Digitizing Higher Education.

    ERIC Educational Resources Information Center

    Kirk, Camille

    2000-01-01

    Discussion of digital technology in the context of higher education planning considers how these technologies change teaching; the digital divide; the costs of information technology; hard wiring the campus; material consequences of information technology; digitally enabled crimes and misdemeanors; and libraries and scholarly publishing. Concludes…

  4. Valuing Higher Education

    ERIC Educational Resources Information Center

    Pillay, Gerald J.

    2009-01-01

    The question of the value of higher education is today set in the context of an unprecedented banking and financial crisis. In this context of fundamental change and financial realignment, it is important that we as members of the university remake our case for why the university deserves to be considered alongside all those other worthy causes…

  5. Developing Higher Level Thinking

    ERIC Educational Resources Information Center

    Limbach, Barbara; Waugh, Wendy

    2010-01-01

    This paper identifies an interdisciplinary, five-step process, built upon existing theory and best practices in cognitive development, effective learning environments, and outcomes-based assessment. The "Process for the Development of Higher Level Thinking Skills" provides teachers with an easy to implement method of moving toward a more…

  6. Free Higher Education

    ERIC Educational Resources Information Center

    Reed, Jr., Adolph; Szymanski, Sharon

    2004-01-01

    The crisis of affordability in higher education is intensifying. Illustrations of its resonance abound: from the frequent news articles describing and amplifying the crisis and its sources to legislators' and candidates' proposed responses. Republicans' responses tend to be mainly punitive toward institutions; Democrats' proposals are more…

  7. Shell Higher Olefins Process.

    ERIC Educational Resources Information Center

    Lutz, E. F.

    1986-01-01

    Shows how olefin isomerization and the exotic olefin metathesis reaction can be harnessed in industrial processes. Indicates that the Shell Higher Olefins Process makes use of organometallic catalysts to manufacture alpha-olefins and internal carbon-11 through carbon-14 alkenes in a flexible fashion that can be adjusted to market needs. (JN)

  8. Comparative Higher Education.

    ERIC Educational Resources Information Center

    Altbach, Philip G.

    The comparative higher education course offered at the State University of New York at Buffalo is briefly described, and a course schedule is presented, including required and recommended readings for each topic. The course is intended to provide a broad cross-cultural perspective and considers the growth and development of universities in Europe,…

  9. Short Synthetic Terminators for Improved Heterologous Gene Expression in Yeast.

    PubMed

    Curran, Kathleen A; Morse, Nicholas J; Markham, Kelly A; Wagman, Allison M; Gupta, Akash; Alper, Hal S

    2015-07-17

    Terminators play an important role both in completing the transcription process and impacting mRNA half-life. As such, terminators are an important synthetic component considered in applications such as heterologous gene expression and metabolic engineering. Here, we describe a panel of short (35-70 bp) synthetic terminators that can be used for modulating gene expression in yeast. The best of these synthetic terminator resulted in 3.7-fold more fluorescent protein output and 4.4-fold increase in transcript level compared to that with the commonly used CYC1 terminator. These synthetic terminators offer several advantages over native sequences, including an easily synthesized short length, minimal sequence homology to native sequences, and similar or better performance characteristics than those of commonly used longer terminators. Furthermore, the synthetic terminators are highly functional in both Saccharomyces cerevisiae and an alternative yeast, Yarrowia lipolytica, demonstrating that these synthetic designs are transferrable between diverse yeast species. PMID:25686303

  10. Expressiveness in musical emotions.

    PubMed

    Vieillard, Sandrine; Roy, Mathieu; Peretz, Isabelle

    2012-09-01

    This study was designed to investigate how emotion category, characterized by distinct musical structures (happiness, sadness, threat) and expressiveness (mechanical, expressive) may influence overt and covert behavioral judgments and physiological responses in musically trained and untrained listeners. Mechanical and expressive versions of happy, sad and scary excerpts were presented while physiological measures were recorded. Participants rated the intensity of the emotion they felt. In addition, they monitored excerpts for the presence of brief breaths. Results showed that the emotion categories were rated higher in the expressive than in the mechanical versions and that this effect was larger in musicians. Moreover, expressive excerpts were found to increase skin conductance level more than the mechanical ones, independently of their arousal value, and to slow down response times in the breath detection task relative to the mechanical versions, suggesting enhanced capture of attention by expressiveness. Altogether, the results support the key role of the performer's expression in the listener's emotional response to music. PMID:21761216

  11. Control of Expression of the RNases J1 and J2 in Bacillus subtilis

    PubMed Central

    Jamalli, Ailar; Hébert, Agnès; Zig, Léna

    2014-01-01

    In Bacillus subtilis, the dual activity 5′ exo- and endoribonucleases J1 and J2 are important players in mRNA and stable RNA maturation and degradation. Recent work has improved our understanding of their structure and mechanism of action and identified numerous RNA substrates. However, almost nothing is known about the expression of these enzymes. Here, we have identified the transcriptional and translational signals that control the expression of the rnjA (RNase J1) and rnjB (RNase J2) genes. While the rnjB gene is transcribed constitutively from a sigma A promoter, optimal expression of RNase J1 requires cotranscription and cotranslation with the upstream ykzG gene, encoding a protein of unknown function. In the absence of coupled translation, RNase J1 expression is decreased more than 5-fold. Transcription of the ykzG operon initiates at a sigma A promoter with a noncanonical −35 box that is required for optimal transcription. Biosynthesis of RNase J1 is autocontrolled within a small range (1.4-fold) and also slightly stimulated (1.4-fold) in the absence of RNase J2. These controls are weak but might be useful to maintain the overall RNase J level and possibly also equimolar amounts of the two nucleases in the cell that primarily act as a heterodimer in vivo. PMID:24187087

  12. Transgenic mouse model for estrogen-regulated lipoprotein metabolism: studies on apoVLDL-II expression in transgenic mice.

    PubMed

    Zsigmond, E; Nakanishi, M K; Ghiselli, F E; Chan, L

    1995-07-01

    We have produced transgenic mice that express an estrogen-responsive avian apolipoprotein, apoVLDL-II. An apoVLDL-II natural gene construct containing 4.7 kb of 5' flanking and 19 bp of 3' flanking sequences together with the 4 exon/3 intron structural gene was expressed in a liver-specific manner in transgenic mice. A single injection of estrogen caused a 5.9- to 7.5-fold stimulation of apoVLDL-II mRNA in the liver. The transgene mRNA had the same initiation sites of transcription as the native mRNA isolated from laying hen liver, and the same sites were used before and after estrogen treatment. The number of hepatocytes that stain positive for immunoreactive apoVLDL-II increased from < 1% to 40-60% in 24 h after estrogen treatment. Thus, in trangenic mice as in the cockerel, hepatocytes are biochemically heterogeneous and induction of apoVLDL-II synthesis occurs by recruitment of hepatocytes. In the plamsa compartment, compared to controls, transgenic mice have a 3- to 5-fold higher basal total plasma triglyceride which was accounted for by a 5.4-fold high basal VLDL triglyceride. Estrogen treatment results in a approximately 2-fold increase in the VLDL triglycerides over basal levels and 8.5-fold increase over nontransgenic mice, which did not show any change in VLDL in response to estrogen. Transgenic mice with the integrated apoVLDL-II gene provide a useful model for the study of the regulation of lipoprotein metabolism by estrogen. PMID:7595069

  13. Megakaryocytes contribute to the bone marrow-matrix environment by expressing fibronectin, type IV collagen and laminin

    PubMed Central

    Malara, Alessandro; Currao, Manuela; Gruppi, Cristian; Celesti, Giuseppe; Viarengo, Gianluca; Buracchi, Chiara; Laghi, Luigi; Kaplan, David L.; Balduini, Alessandra

    2014-01-01

    Megakaryocytes associate with the bone marrow vasculature where they convert their cytoplasm into proplatelets that protrude through the vascular endothelium into the lumen and release platelets. The extracellular matrix (ECM) microenvironment plays a critical role in regulating these processes. In this work we demonstrate that, among bone marrow ECM components, fibronectin, type IV collagen and laminin are the most abundant around bone marrow sinusoids and constitute a peri-cellular matrix surrounding megakaryocytes. Most importantly, we report, for the first time, that megakaryocytes express components of the basement membrane and that these molecules contribute to the regulation of megakaryocyte development and bone marrow ECM homeostasis both in vitro and in vivo. In vitro, fibronectin induced a three-fold increase in the proliferation rate of mouse hematopoietic stem cells leading to higher megakaryocyte output with respect to cells treated only with thrombopoietin or other matrices. However, megakaryocyte ploidy level in fibronectin-treated cultures was significantly reduced. Stimulation with type IV collagen resulted in a 1.4-fold increase in megakaryocyte output, while all tested matrices supported proplatelet formation to a similar extent in megakaryocytes derived from fetal liver progenitor cells. In vivo, megakaryocyte expression of fibronectin and basement membrane components was up-regulated during bone marrow reconstitution upon 5-fluorouracil induced myelosuppression, while only type IV collagen resulted up-regulated upon induced thrombocytopenia. In conclusion, this work demonstrates that ECM components impact megakaryocyte behavior differently during their differentiation and highlights a new role for megakaryocyte as ECM-producing cells for the establishment of cell niches during bone marrow regeneration. PMID:24357118

  14. Generalized higher gauge theory

    NASA Astrophysics Data System (ADS)

    Ritter, Patricia; Sämann, Christian; Schmidt, Lennart

    2016-04-01

    We study a generalization of higher gauge theory which makes use of generalized geometry and seems to be closely related to double field theory. The local kinematical data of this theory is captured by morphisms of graded manifolds between the canonical exact Courant Lie 2-algebroid T M ⊕ T ∗ M over some manifold M and a semistrict gauge Lie 2-algebra. We discuss generalized curvatures and infinitesimal gauge transformations. Finite gauge transformation as well as global kinematical data are then obtained from principal 2-bundles over 2-spaces. As dynamical principle, we consider first the canonical Chern-Simons action for such a gauge theory. We then show that a previously proposed 3-Lie algebra model for the six-dimensional (2,0) theory is very naturally interpreted as a generalized higher gauge theory.

  15. Higher than Everest

    NASA Astrophysics Data System (ADS)

    Hodge, Paul

    2001-08-01

    Tired of exploring planet Earth? Have you ever imagined what it would be like to explore the Moon? Ever wonder about the topography of Mars? In this unique guidebook all of your extraterrestrial wanderlust can be fulfilled as Paul Hodge takes you on a virtual tour of the most spectacular sites in the Solar System. Hodge includes the latest information about the Solar System into his vivid descriptions of imaginary, challenging expeditions. Imagine: -- Descending into a fabulous canyon on Mars, one that dwarfs the Earth's Grand Canyon; -- Trekking up Venus' precipitous and scorching Mt. Maxwell; -- Journeying through the snows of Saturn's rings and the incredibly high, icy cliff of Miranda, the moon closest to Uranus. A compelling, extensively illustrated introduction to such otherworldly environments, Higher than Everest makes you believe that someday these adventures may actually take place. Paul Hodge is Professor of Astronomy at the University of Washington, Seattle, and Editor-in-Chief of the Astronomical Journal. Higher than Everest is based on a popular undergraduate course on the planets that he has taught for many years. Hodge's research has spanned from interplanetary dust to the extragalactic distance scale and currently includes star-formation and galactic evolution, using the Hubble Space Telescope to investigate nearby galaxies. He has written several books, most recently Meteorite Craters and Impact Structures of the Earth (Cambridge 1994).

  16. Teaching at higher levels

    NASA Astrophysics Data System (ADS)

    1998-11-01

    Undergraduate physics programmes for the 21st century were under discussion at a recent event held in Arlington, USA, open to two or three members of the physics faculties of universities from across the whole country. The conference was organized by the American Association of Physics Teachers with co-sponsorship from the American Institute of Physics, the American Physical Society and Project Kaleidoscope. Among the various aims were to learn about physics departments that have successfully revitalized their undergraduate physics programmes with innovative introductory physics courses and multi-track majors programmes. Engineers and life scientists were to be asked directly how physics programmes can better serve their students, and business leaders would be speaking on how physics departments can help to prepare their students for the diverse careers that they will eventually follow. It was planned to highlight ways that departments could fulfil their responsibilities towards trainee teachers, to identify the resources needed for revitalizing a department's programme, and to develop guidelines and recommendations for a funding programme to support collaborative efforts among physics departments for carrying out the enhancements required. More details about the conference can be found on the AAPT website (see http://www.aapt.org/programs/rupc.html). Meanwhile the UK's Higher Education Funding Council has proposed a two-pronged approach to the promotion of high quality teaching and learning, as well as widening participation in higher education from 1999-2000. A total of £60m should be available to support these initiatives by the year 2001-2002. As part of this scheme the Council will invite bids from institutions to support individual academics in enhancing learning and teaching, as well as in recognition of individual excellence. As with research grants, such awards would enable staff to pursue activities such as the development of teaching materials

  17. Higher-dimensional targeting

    SciTech Connect

    Kostelich, E.J. ); Grebogi, C. Department of Mathematics and Institute for Physical Science and Technology, University of Maryland, College Park, Maryland 20742 ); Ott, E. Department of Electrical Engineering, University of Maryland, College Park, Maryland 20742 ); Yorke, J.A. )

    1993-01-01

    This paper describes a procedure to steer rapidly successive iterates of an initial condition on a chaotic attractor to a small target region about any prespecified point on the attractor using only small controlling perturbations. Such a procedure is called targeting.'' Previous work on targeting for chaotic attractors has been in the context of one- and two-dimensional maps. Here it is shown that targeting can also be done in higher-dimensional cases. The method is demonstrated with a mechanical system described by a four-dimensional mapping whose attractor has two positive Lyapunov exponents and a Lyapunov dimension of 2.8. The target is reached by making very small successive changes in a single control parameter. In one typical case, 35 iterates on average are required to reach a target region of diameter 10[sup [minus]4], as compared to roughly 10[sup 11] iterates without the use of the targeting procedure.

  18. Semistrict higher gauge theory

    NASA Astrophysics Data System (ADS)

    Jurčo, Branislav; Sämann, Christian; Wolf, Martin

    2015-04-01

    We develop semistrict higher gauge theory from first principles. In particular, we describe the differential Deligne cohomology underlying semistrict principal 2-bundles with connective structures. Principal 2-bundles are obtained in terms of weak 2-functors from the Čech groupoid to weak Lie 2-groups. As is demonstrated, some of these Lie 2-groups can be differentiated to semistrict Lie 2-algebras by a method due to Ševera. We further derive the full description of connective structures on semistrict principal 2-bundles including the non-linear gauge transformations. As an application, we use a twistor construction to derive superconformal constraint equations in six dimensions for a non-Abelian tensor multiplet taking values in a semistrict Lie 2-algebra.

  19. Higher dimensional massive bigravity

    NASA Astrophysics Data System (ADS)

    Do, Tuan Q.

    2016-08-01

    We study higher-dimensional scenarios of massive bigravity, which is a very interesting extension of nonlinear massive gravity since its reference metric is assumed to be fully dynamical. In particular, the Einstein field equations along with the following constraint equations for both physical and reference metrics of a five-dimensional massive bigravity will be addressed. Then, we study some well-known cosmological spacetimes such as the Friedmann-Lemaitre-Robertson-Walker, Bianchi type I, and Schwarzschild-Tangherlini metrics for the five-dimensional massive bigravity. As a result, we find that massive graviton terms will serve as effective cosmological constants in both physical and reference sectors if a special scenario, in which reference metrics are chosen to be proportional to physical ones, is considered for all mentioned metrics. Thanks to the constancy property of massive graviton terms, consistent cosmological solutions will be figured out accordingly.

  20. Differential Virulence Gene Expression of Group A Streptococcus Serotype M3 in Response to Co-Culture with Moraxella catarrhalis

    PubMed Central

    Verhaegh, Suzanne J. C.; Flores, Anthony R.; van Belkum, Alex; Musser, James M.; Hays, John P.

    2013-01-01

    Streptococcus pyogenes (group A Streptococcus, GAS) and Moraxella catarrhalis are important colonizers and (opportunistic) pathogens of the human respiratory tract. However, current knowledge regarding colonization and pathogenic potential of these two pathogens is based on work involving single bacterial species, even though the interplay between respiratory bacterial species is increasingly important in niche occupation and the development of disease. Therefore, to further define and understand polymicrobial species interactions, we investigated whether gene expression (and hence virulence potential) of GAS would be affected upon co-culture with M. catarrhalis. For co-culture experiments, GAS and M. catarrhalis were cultured in Todd-Hewitt broth supplemented with 0.2% yeast extract (THY) at 37°C with 5% CO2 aeration. Each strain was grown in triplicate so that triplicate experiments could be performed. Bacterial RNA was isolated, cDNA synthesized, and microarray transcriptome expression analysis performed. We observed significantly increased (≥4-fold) expression for genes playing a role in GAS virulence such as hyaluronan synthase (hasA), streptococcal mitogenic exotoxin Z (smeZ) and IgG endopeptidase (ideS). In contrast, significantly decreased (≥4-fold) expression was observed in genes involved in energy metabolism and in 12 conserved GAS two-component regulatory systems. This study provides the first evidence that M. catarrhalis increases GAS virulence gene expression during co-culture, and again shows the importance of polymicrobial infections in directing bacterial virulence. PMID:23626831

  1. Expression and Functional Significance of HtrA1 Loss in Endometrial Cancer

    PubMed Central

    Mullany, Sally A.; Moslemi-Kebria, Mehdi; Rattan, Ramandeep; Khurana, Ashwani; Clayton, Amy; Ota, Takayo; Mariani, Andrea; Podratz, Karl C.; Chien, Jeremy; Shridhar, Viji

    2010-01-01

    Purpose The purpose of this study was to determine if loss of serine protease HtrA1 in endometrial cancer will promote the invasive potential of EC cell lines. Experimental design Western blot analysis and immunohistochemistry methods were used to determine HtrA1 expression in EC cell lines and primary tumors, respectively. Migration, invasion assays and in vivo xenograft experiment were performed to compare the extent of metastasis between HtrA1 expressing and HtrA-1 knocked down clones. Results Western blot analysis of HtrA1 in 13 EC cell lines revealed complete loss of HtrA1 expression in all 7 papillary serous EC cell lines. Downregulation of HtrA1 in Hec1A and Hec1B cell lines resulted in a 3-4 fold increase in the invasive potential. Exogenous expression of HtrA1 in Ark 1 and Ark 2 cells resulted in 3-4 fold decrease in both invasive and migration potential of these cells. There was an increased rate of metastasis to the lungs associated with HtrA1 downregulation in Hec1B cells compared to control cells with endogenous HtrA1 expression. Enhanced expression of HtrA1 in Ark 2 cells resulted in significantly less tumor nodules metastasizing to the lungs compared to parental or protease deficient (SA mutant) Ark 2 cells. Immunohistochemical (IHC) analysis showed 57% (105/184) of primary EC tumors had low HtrA1 expression. The association of low HtrA1 expression with high-grade endometrioid tumors was statistically significant (p=0.016). Conclusions Collectively, these data indicate loss of HtrA1 may contribute to the aggressiveness and metastatic ability of endometrial tumors. PMID:21098697

  2. Higher prices in Jamaica.

    PubMed

    1982-03-01

    Price increases in the Jamaica CSM program went into effect on August 31, 1981. The program began in 1975. While the need for higher prices has been under discussion for the past 3 years, this is the 1st time the requisite approval from the Jamaica Price Commission has been obtained. The Jamaica National Family Planning Board (JNFPB) reports that the Panther 3-pack (condom) is up US$0.15 to US$0.30. Each Perle package (oral contraceptive) was increased by US$0.20. Single cycle Perle now sells for US$0.50, and 3-pack Perle sells for US$1.10. The 6-year price stagnation experienced by the CSM program resulted in a decreasing operational budget as program costs continued to rise. Marketing costs alone during this period escalated by 100-300%. For example, Panther pop-up display cartons cost the project US 16U each in 1975. By 1979 the same product cost US 49U. Newspaper advertisements have increased from the 1975 cost of US$68.00 to nearly $200.00 per placement. The overall inflation rate in Jamaica during the last 5 years has averaged more than 20% annually. In the face of these rising costs, outlet expansion for Perle has been prevented, wholesaler margins have been unavailable, and new retailer training has been discontinued. It is projected that the new prices will result in an annual increased revenues of US$80,000 which will be used to reinstate these essential marketing activities. The JNFPB is also planning to introduce a Panther 12-pack and Panther strips to the CSM product line. According to Marketing Manager Aston Evans, "We believe the public is now ready for this type of packaging" which is scheduled to be available soon. Panther is presently only available in a 3-pack, but annual sales have been steady. The new 12-pack will be stocked on supermarket shelves to provide higher product visibility and wider distribution. The selling price has been set as US$1.20 and is expected to yield a 25% increase in sales during the 1st year. A complete sales promotion

  3. Texas Higher Education in Transition.

    ERIC Educational Resources Information Center

    Texas Coll. and Univ. System, Austin. Coordinating Board.

    The status of higher education in Texas is examined in this major report of changes in higher education over the past decade. Information on enrollment, cost, financial aid, job opportunities, and facilities in higher education institutions is given for private higher education, professional higher education, community colleges, and state colleges…

  4. Polyesters in higher plants.

    PubMed

    Kolattukudy, P E

    2001-01-01

    Polyesters occur in higher plants as the structural component of the cuticle that covers the aerial parts of plants. This insoluble polymer, called cutin, attached to the epidermal cell walls is composed of interesterified hydroxy and hydroxy epoxy fatty acids. The most common chief monomers are 10,16-dihydroxy C16 acid, 18-hydroxy-9,10 epoxy C18 acid, and 9,10,18-trihydroxy C18 acid. These monomers are produced in the epidermal cells by omega hydroxylation, in-chain hydroxylation, epoxidation catalyzed by P450-type mixed function oxidase, and epoxide hydration. The monomer acyl groups are transferred to hydroxyl groups in the growing polymer at the extracellular location. The other type of polyester found in the plants is suberin, a polymeric material deposited in the cell walls of a layer or two of cells when a plant needs to erect a barrier as a result of physical or biological stress from the environment, or during development. Suberin is composed of aromatic domains derived from cinnamic acid, and aliphatic polyester domains derived from C16 and C18 cellular fatty acids and their elongation products. The polyesters can be hydrolyzed by pancreatic lipase and cutinase, a polyesterase produced by bacteria and fungi. Catalysis by cutinase involves the active serine catalytic triad. The major function of the polyester in plants is as a protective barrier against physical, chemical, and biological factors in the environment, including pathogens. Transcriptional regulation of cutinase gene in fungal pathogens is being elucidated at a molecular level. The polyesters present in agricultural waste may be used to produce high value polymers, and genetic engineering might be used to produce large quantities of such polymers in plants. PMID:11217409

  5. Expression of the c-myb proto-oncogene in bovine vascular smooth muscle cells.

    PubMed

    Brown, K E; Kindy, M S; Sonenshein, G E

    1992-03-01

    Previously we have shown that bovine vascular smooth muscle cells (SMCs) express c-myb mRNA (Reilly, C. F., Kindy, M. S., Brown, K. E., Rosenberg, R. D., and Sonenshein, G. E. (1989) J. Biol. Chem. 264, 6990-6995). Here we have characterized changes in the low level of c-myb mRNA expressed in quiescent serum-deprived subconfluent SMCs upon entry into the cell cycle. After serum stimulation, levels of c-myb mRNA increased 3-4-fold during late G1 and remained at this level during S phase. A 1.5-kilobase partial c-myb cDNA clone, isolated from a bovine SMC library, was partially sequenced and found to be 89 and 85% homologous to the human and murine c-myb genes, respectively. Using bovine and murine c-myb clones, no change in the rate of c-myb gene transcription or mRNA stability was detected during the cell cycle. Thus, the regulation of changes in c-myb mRNA levels in SMCs appears distinct from mechanisms seen in hematopoietic or fibroblastic cells. Vectors containing myb binding sites linked to the thymidine kinase promoter and the chloramphenicol acetyltransferase reporter gene were transiently transfected into SMC cultures. KHK-CAT-dAX, which contains nine concatenated myb binding sites, exhibited 7-fold more activity than the parental dAX-TK-CAT vector in exponentially growing SMCs. The levels of chloramphenicol acetyltransferase activity in exponentially growing cells were approximately 2-fold higher than in cells that had been serum deprived for 24 h and were entering quiescence. Thus SMCs produce a functional c-myb protein that can activate transcription from a heterologous promoter. Furthermore, introduction of antisense c-myb oligonucleotides to quiescent serum-deprived SMC cultures severely inhibited entry of cells into S phase upon serum addition. Thus, expression of the c-myb oncogene plays an important role in cell cycle progression of SMCs. PMID:1537845

  6. CYP1A expression in liver and gills of roach (Rutilus rutilus) after waterborne exposure to two phenanthrene derivatives, 1-methylphenanthrene and 4-methylphenanthrene.

    PubMed

    Wolińska, Lidia; Brzuzan, Paweł; Woźny, Maciej; Luczyński, Michał K; Góra, Maciej

    2013-07-01

    Phenanthrenes (Phs) substituted with alkyl groups are a class of compound present in the environment, and they appear to be toxic to developing fish. The present study aimed to investigate the effect of waterborne exposure to two monomethyl derivatives of phenanthrene, 1-methylphenanthrene (1M-Ph) and 4-methylphenanthrene (4M-Ph), on cytochrome P450 1A (CYP1A) gene expression in fish gills and liver. Juvenile common roaches (Rutilus rutilus) were exposed to water with dimethyl sulfoxide (DMSO) solutions of 1M-Ph, 4M-Ph, benzo[a]pyrene (BaP; positive control), each at a dose of 100 µg/L, or to water with DMSO alone (negative control group) for 2 d and 7 d. Significant CYP1A responses with regard to treatment and exposure duration were noted (2-way analysis of variance [ANOVA]) in gills (p = 0.013 and p = 0.003, respectively) and liver (p < 0.001). The 2 monomethyl Phs did not induce consistent gene expression changes, except for 4-MPh, which elevated the CYP1A messenger ribonucleic acid (mRNA) level in the liver at the end of the treatment (almost 4-fold; p < 0.05; 7 d). As was expected, exposure to BaP resulted in elevation of CYP1A mRNA expression in treated fish compared with the control group. Expressions after 2 d and 7 d were approximately 220- and 180-fold higher in liver and 8- and 6-fold higher in gills respectively. The CYP1A protein levels remained stable in both tissues, with one notable exception in roach liver treated for 2 d with BaP (∼ 6-fold increase; p < 0.05). The different effects of the 1- and 4-methylphenanthrenes on CYP1A gene expression in roach liver suggest a relationship between chemical or 3-D structure of the differentially substituted monomethyl Phs and their biological activity. PMID:23553963

  7. Expression of γ-tocopherol methyltransferase in chloroplasts results in massive proliferation of the inner envelope membrane and decreases susceptibility to salt and metal-induced oxidative stress by reducing reactive oxygen species

    PubMed Central

    Jin, Shuangxia; Daniell, Henry

    2014-01-01

    Summary The γ-tocopherol methyltransferase (γ-TMT) is an important enzyme regulating synthesis of four tocopherols (α, γ, β and δ). In this report, we investigated the role of γ-TMT in regulating abiotic stress within chloroplasts. The At γ-tmt overexpressed via the tobacco chloroplast genome accumulated up to 7.7% of the total leaf protein, resulting in massive proliferation of the inner envelope membrane (IEM, up to 8 layers). Such high level expression of γ-TMT converted most of γ-tocopherol to α-tocopherol in transplastomic seeds (~10 fold higher) in the absence of abiotic stress. When grown in 400 mM NaCl, α-tocopherol content in transplastomic TMT leaves increased up to 8.2-fold and 2.4-fold higher than wild-type leaves. Likewise, under heavy metal stress α-tocopherol content in the TMT leaves increased up to 7.5-fold, twice higher than in the wild-type. Under extreme salt stress, the wild-type accumulated higher starch and total soluble sugars but TMT plants were able to regulate sugar transport. Hydrogen peroxide and superoxide content in wild-type increased up to 3-fold within 48 hours of NaCl stress when compared to TMT plants. The ion leakage from TMT leaves was significantly less than wild-type plants under abiotic stress and with less malondialdehyde, indicating lower lipid peroxidation. Taken together, these studies show that α-tocopherol plays a crucial role in the alleviation of salt and heavy metal stresses by decreasing ROS, lipid peroxidation and ion leakage, in addition to enhancing vitamin E conversion. Increased proliferation of the IEM should facilitate studies on retrograde signaling from chloroplast to the nucleus. PMID:25051898

  8. Expression of γ-tocopherol methyltransferase in chloroplasts results in massive proliferation of the inner envelope membrane and decreases susceptibility to salt and metal-induced oxidative stresses by reducing reactive oxygen species.

    PubMed

    Jin, Shuangxia; Daniell, Henry

    2014-12-01

    The γ-tocopherol methyltransferase (γ-TMT) is an important enzyme regulating synthesis of four tocopherols (α, γ, β and δ). In this report, we investigated the role of γ-TMT in regulating abiotic stress within chloroplasts. The At γ-tmt overexpressed via the tobacco chloroplast genome accumulated up to 7.7% of the total leaf protein, resulting in massive proliferation of the inner envelope membrane (IEM, up to eight layers). Such high-level expression of γ-TMT converted most of γ-tocopherol to α-tocopherol in transplastomic seeds (~10-fold higher) in the absence of abiotic stress. When grown in 400 mm NaCl, α-tocopherol content in transplastomic TMT leaves increased up to 8.2-fold and 2.4-fold higher than wild-type leaves. Likewise, under heavy metal stress, α-tocopherol content in the TMT leaves increased up to 7.5-fold, twice higher than in the wild type. Under extreme salt stress, the wild type accumulated higher starch and total soluble sugars, but TMT plants were able to regulate sugar transport. Hydrogen peroxide and superoxide content in wild type increased up to 3-fold within 48 h of NaCl stress when compared to TMT plants. The ion leakage from TMT leaves was significantly less than wild-type plants under abiotic stress and with less malondialdehyde, indicating lower lipid peroxidation. Taken together, these studies show that α-tocopherol plays a crucial role in the alleviation of salt and heavy metal stresses by decreasing ROS, lipid peroxidation and ion leakage, in addition to enhancing vitamin E conversion. Increased proliferation of the IEM should facilitate studies on retrograde signalling from chloroplast to the nucleus. PMID:25051898

  9. Report on Higher Education Technology.

    ERIC Educational Resources Information Center

    New Jersey State Commission on Higher Education.

    Recognizing the rapid development of telecommunications and networking technologies and their growing importance to higher education and New Jersey's overall economic competitiveness, New Jersey's Plan for Higher Education called for the Commission on Higher Education and the Presidents' Council to appoint a Higher Education Technology Task Force…

  10. Women in Virginia Higher Education.

    ERIC Educational Resources Information Center

    New University Conference, Hampton, VA. Peninsula Chapter.

    This document explores how Virginia higher education perpetuates stereotypic social roles, the evolution of sexually segregated schools, the current evidences of sexual discrimination towards faculty, staff and students, the State Council of Higher Education's 1967 plan for higher education, the status of Virginia higher education under the law…

  11. Higher Education and Social Change

    ERIC Educational Resources Information Center

    Brennan, John

    2008-01-01

    An agenda for future higher education research is proposed which incorporates four interconnected elements: changing social contexts; their implications for higher education; mechanisms of interaction between higher education and society; higher education's impact on society. The role of comparative research in investigating these topics is…

  12. The effect of combination treatment with trenbolone acetate and estradiol-17β on skeletal muscle expression and plasma concentrations of oxytocin in sheep.

    PubMed

    Kongsuwan, K; Knox, M R; Allingham, P G; Pearson, R; Dalrymple, B P

    2012-07-01

    Implantation of trenbolone acetate (TBA) in conjunction with estradiol-17β (E(2)) increases growth, feed conversion efficiency, and carcass leanness in cattle. Our previous study in Brahman steers suggested that the neuropeptide hormone oxytocin (OXT) may be involved in increasing muscle growth after TBA-E(2) treatment. The present study aimed to determine whether OXT mRNA expression in the longissimus muscle (LM) is also up-regulated in TBA-E(2-)implanted wethers as has been found in steers. Real-time quantitative PCR was used to measure the expression of the gene encoding the OXT precursor, three genes with increased expression in the LM muscle of TBA-E(2)-treated steers, MYOD1 (muscle transcription factor), GREB1 (growth regulation by estrogen in breast cancer 1), and WISP2 (Wnt-1 inducible signaling pathway protein 2), and two genes encoding IGF pathway proteins, IGF1, IGFR, in the LM of both untreated and TBA-E(2)-treated wethers. The expression of OXT mRNA in wethers that received the TBA-E(2) treatment was increased ~4.4-fold (P = 0.01). TBA-E(2) treatment also induced a 2.3-fold increase in circulating OXT (P = 0.001). These data, together with the observation that untreated wethers had much higher baseline concentrations of circulating OXT than previously observed in steers, suggest that wethers and steers have quite different OXT hormone systems. TBA-E(2) treatment had no effect on the expression of IGF1, IGFR, and the muscle regulatory gene MYOD1 mRNA levels in wethers (P ≥ 0.15), but there was an increase in the expression of the two growth-related genes, GREB1 (P = 0.001) and WISP2 (P = 0.04). Both genes are common gene targets for both the estrogen and androgen signaling pathways. Consequently, their actions may contribute to the positive interaction between TBA and E(2) on additive improvements on muscle growth. PMID:22503145

  13. Who's Expressing in "Expressive Writing"?

    ERIC Educational Resources Information Center

    Reed, Janine

    In an attempt to understand what expressive writing means to themselves and to their students, teachers should explore and reflect on various questions regarding expressive writing theories and practices. For many, self-expression is the basis of all serious writing and an important stage in any act of learning, so it is essential to uncover the…

  14. Transforming Higher Education: Implications for State Higher Education Finance Policy.

    ERIC Educational Resources Information Center

    Matthews, Dewayne

    1998-01-01

    Examines how information technology is transforming higher education (asynchronous learning, distance education, customized program structure, customized delivery, outcome-based programs, collaboration, and competition) and discusses implications for state higher education finance policy (competition, student costs, collaboration, and…

  15. Amplification of transgene expression in vitro and in vivo using a novel inhibitor of histone deacetylase.

    PubMed

    Yamano, T; Ura, K; Morishita, R; Nakajima, H; Monden, M; Kaneda, Y

    2000-06-01

    Enhancement of transgene expression is an important issue in human gene therapy. Here we describe a novel system for enhancing transgene expression by cointroduction of plasmid DNA with FR901228, a water-soluble histone deacetylase inhibitor. When a luciferase expression vector was cointroduced into cells with FR901228, luciferase gene expression was enhanced 50-fold in the mouse melanoma cell line B16-F1 and 5200-fold in NIH3T3 cells in comparison to cells without the drug. Luciferase gene expression enhancement was dependent on both drug dose and treatment time. Acetylated histones increased in accordance with drug dose, and the activation of gene expression occurred at the transcriptional level. The stimulation of luciferase gene expression by FR901228 was also observed in a B16-F1 clone stably expressing luciferase. Cointroduction of the luciferase plasmid with FR901228 into a B16-F1 tumor mass activated luciferase gene expression 3- to 4-fold. Thus, activation of transgene expression by FR901228 may serve as a new tool for gene therapy. PMID:10933982

  16. Higher Education and Work. Higher Education Policy Series 23.

    ERIC Educational Resources Information Center

    Brennan, John, Ed.; And Others

    The relationship between higher education and the world of work is examined in terms of the changing structures of higher education institutions and the effect of the relationship on curricula. An international perspective is provided on the changing nature of employment and the labor market; the increasing diversification of higher education…

  17. Uptake of exogenous free cholesterol induces upregulation of tissue factor expression in human monocyte-derived macrophages.

    PubMed Central

    Lesnik, P; Rouis, M; Skarlatos, S; Kruth, H S; Chapman, M J

    1992-01-01

    Lipid-laden macrophages present as foam cells may contribute to the hyperthrombotic state of human atherosclerotic lesions by the production of tissue factor (TF). We investigated the effect of exogenous nonlipoprotein cholesterol on the expression of TF by human monocyte-derived macrophages in culture. Nonlipoprotein cholesterol at 50 micrograms/ml increased TF activity 4-fold; TF induction was dose- and time-dependent. Expression of TF activity was positively correlated with the free cholesterol content of monocyte-derived macrophages, was increased upon inhibition of cholesterol esterification, and reflected de novo synthesis of TF protein. TF expression in cholesterol-loaded macrophages remained sensitive to stimulation (approximately 12-fold) by bacterial lipopolysaccharide, indicating that intracellular free cholesterol and lipopolysaccharide act by distinct mechanisms in inducing TF procoagulant activity. Our results suggest that loading human monocyte-derived macrophages with free cholesterol induces upregulation of TF expression, thereby contributing to thrombus formation at sites of plaque rupture. Images PMID:1438222

  18. Symbiotic Expressions

    NASA Astrophysics Data System (ADS)

    Bernecky, Robert; Herhut, Stephan; Scholz, Sven-Bodo

    We introduce symbiotic expressions, a method for algebraic simplification within a compiler, in lieu of an SMT solver, such as Yices or the Omega Calculator. Symbiotic expressions are compiler-generated expressions, temporarily injected into a program's abstract syntax tree (AST). The compiler's normal optimizations interpret and simplify those expressions, making their results available for the compiler to use as a basis for decisions about further optimization of the source program. The expressions are symbiotic, in the sense that both parties benefit: an optimization benefits, by using the compiler itself to simplify expressions that have been attached, lamprey-like, to the AST by the optimization; the program being compiled benefits, from improved run-time in both serial and parallel environments.

  19. Reflections on Higher Education Research.

    ERIC Educational Resources Information Center

    Keller, George; Moore, Kathryn M.

    1989-01-01

    Two senior scholars assess the first four volumes of "Higher Education: A Handbook of Theory and Research," a series on the nature of higher education as a discipline and the state of research in the field. (Author/MSE)

  20. Differential expression and regulation of anti-hypertrophic genes Npr1 and Npr2 during β-adrenergic receptor activation-induced hypertrophic growth in rats.

    PubMed

    Manivasagam, Senthamizharasi; Subramanian, Vimala; Tumala, Anusha; Vellaichamy, Elangovan

    2016-09-15

    We sought to determine the effect of chronic activation of β-adrenergic receptor (β-AR) on the left ventricular (LV) expression profile of Npr1 and Npr2 (coding for NPR-A and NPR-B, respectively) genes, and the functional activity of these receptors in adult Wistar rat hearts. The Npr1 gene expression was markedly reduced (3.5-fold), while the Npr2 gene expression was up regulated (4-fold) in Isoproterenol (ISO)-treated heart as compared with controls. A gradual reduction in NPR-A protein (3-fold), cGMP levels (75%) and a steady increased expression of NPR-B protein (4-fold), were noticed in ISO hearts. Further, in-vitro membranes assay shows that NPR-A dependent guanylyl cyclase (GC) activity was down-regulated (2-fold), whereas NPR-B dependent GC activity was increased (5-fold) in ISO treated hearts. Atenolol treatment normalized the altered expression of Npr1 and Npr2 genes. In conclusion, the chronic β-AR activation differentially regulates Npr1 and Npr2 genes in the heart. Npr1 down regulation is positively associated with the development of left ventricular hypertrophy (LVH) in ISO rats. PMID:27283501

  1. Internationalization of Chinese Higher Education

    ERIC Educational Resources Information Center

    Chen, Linhan; Huang, Danyan

    2013-01-01

    This paper probes into the development of internationalization of higher education in China from ancient times to modern times, including the emergence of international connections in Chinese higher education and the subsequent development of such connections, the further development of internationalization of Chinese higher education, and the…

  2. Higher Education and the Market

    ERIC Educational Resources Information Center

    Brown, Roger

    2008-01-01

    In this paper, the author explores the answers to the following questions: (1) What does the "marketisation" of higher education mean? (2) What are the potential implications for United Kingdom higher education? and (3) How should everyone handle those implications? He also cites the three main reasons why higher education cannot simply be left to…

  3. Higher Education Studies in Japan

    ERIC Educational Resources Information Center

    Kaneko, Motohisa

    2010-01-01

    The rapid development of higher education in the postwar period has given rise to various problems, and higher education studies in Japan have developed in response to them. What have been the major issues, and how did academic research respond to them, in postwar Japan? This article delineates an outline of higher education studies in general,…

  4. Higher Education in the Eighties.

    ERIC Educational Resources Information Center

    McComas, James D.

    Events and conditions over the last 20 years that have altered the course of higher education are briefly noted, and trends in higher education for the early eighties are examined. Among the past influences on higher education that illustrate the wisdom of planning for a realistic period of time, such as five years, are the following: the massive…

  5. History of Higher Education, 1992.

    ERIC Educational Resources Information Center

    History of Higher Education, 1992

    1992-01-01

    This annual compilation offers six articles on the history of higher education. In the first article, "The Historical Matrix of American Higher Education," Roger L. Geiger provides an overview of the history of American higher education. Following it, E. D. Duryea, Jurgen Herbst, and W. Bruce Leslie comment on his hypothesis which identifies eight…

  6. Advancing Diversity in Higher Education

    ERIC Educational Resources Information Center

    Turner, Caroline S.

    2013-01-01

    This special section of the "Journal of Diversity in Higher Education" ("JDHE") on "Advancing Diversity in Higher Education" emerged from the 2012 Association for the Study of Higher Education Council on Ethnic Participation (ASHE-CEP) Pre-Conference Forum. CEP, a standing committee of ASHE, partnered with the…

  7. A Tax for Higher Education

    ERIC Educational Resources Information Center

    Blumenstyk, Goldie

    2012-01-01

    Higher education pays off handsomely for society. Yet on a nationwide basis, states' support for higher education per full-time-equivalent student has fallen to just $6,290, the lowest in 15 years. A dedicated source of funds for higher education is problematic. But what if state and federal lawmakers applied the impeccable logic of the gas tax to…

  8. The Privitization of Higher Education.

    ERIC Educational Resources Information Center

    Tilak, Jandhyala B. G.

    1991-01-01

    Attributes the growth of private education to excess and differentiated demand for higher education. Argues that evidence shows that the higher quality of private education is exaggerated and that private school attendance does not result in higher salaries for graduates. Criticizes private education as not wholly self-financing, elitist, and…

  9. Higher Education and Public Good

    ERIC Educational Resources Information Center

    Marginson, Simon

    2011-01-01

    Policy debate about whether to maintain public subsidies for higher education has stimulated reconsideration of the public mission of higher education institutions, especially those that provide student places conferring private benefits. If the work of higher education institutions is defined simply as the aggregation of private interests, this…

  10. Economic Trends and Higher Education.

    ERIC Educational Resources Information Center

    Ottinger, Cecilia A.

    1992-01-01

    This research brief highlights current and projected economic trends that affect higher education and discusses some of their implications. The brief is organized into three sections: (1) national economic conditions affecting higher education, which presents data on gross national product, inflation, the Higher Education Price Index, the federal…

  11. Exploring Higher Education Business Models ("If Such a Thing Exists")

    ERIC Educational Resources Information Center

    Harney, John O.

    2013-01-01

    The global economic recession has caused students, parents, and policymakers to reevaluate personal and societal investments in higher education--and has prompted the realization that traditional higher ed "business models" may be unsustainable. Predicting a shakeout, most presidents expressed confidence for their own school's ability to…

  12. The Hierarchical Face: Higher Rankings Lead to Less Cooperative Looks

    ERIC Educational Resources Information Center

    Chen, Patricia; Myers, Christopher G.; Kopelman, Shirli; Garcia, Stephen M.

    2012-01-01

    In 3 studies, we tested the hypothesis that the higher ranked an individual's group is, the less cooperative the facial expression of that person is judged to be. Study 1 established this effect among business school deans, with observers rating individuals from higher ranked schools as appearing less cooperative, despite lacking prior knowledge…

  13. Gas Phase Rovibrational Spectroscopy of Dmso, Part II: Towards the Terahertz Observation of 4-FOLD Clusters

    NASA Astrophysics Data System (ADS)

    Cuisset, Arnaud; Martin-Drumel, Marie-Aline; Hindle, Francis; Mouret, Gael; Sadovskii, Dmitrii A.

    2013-06-01

    Benefiting of the exceptional properties of the AILES synchrotron beamline, the gas phase Far-IR spectrum of DMSO has been recorded and resolved. The rovibrational analysis allowed to discover a new rotational behaviour for a polyatomic molecule: the gyroscopic destabilization. In order to explain this phenomenon, we looked for four-fold energy clusters in the high resolution ground state THz spectrum of DMSO recorded with a sub-THz spectrometer based on a frequency multiplication chain. Pure rotational lines in the 5 lowest vibrationnally excited levels have been recorded below 700 GHz. With near 1000 rotational transitions assigned, high quantum numbers have been reached allowing to discover sequence of four-fold clusters in the out of plane bending mode of DMSO and to study the vibrational dependence of an unusual rotational dynamics. J. B. Brubach et al., AIP Conf. Proc., 1214, (81), 2010. A. Cuisset, L. Nanobashvili, I. Smirnova, R. Bocquet, F. Hindle, G. Mouret, O. Pirali, P. Roy, D. Sadovskii,Chem. Phys. Lett., 492,(30),2010 A. Cuisset, O. Pirali, D. Sadovskii,Phys. Rev. Lett., 109,(094101), 2012. G. Mouret, M. Guinet, A. Cuisset, L. Croizet, S. Eliet, R. Bocquet, F. Hindle, IEEE Sensors Journal, 13, 1, 2013.

  14. Emissions from an International Airport Increase Particle Number Concentrations 4-fold at 10 km Downwind

    PubMed Central

    2014-01-01

    We measured the spatial pattern of particle number (PN) concentrations downwind from the Los Angeles International Airport (LAX) with an instrumented vehicle that enabled us to cover larger areas than allowed by traditional stationary measurements. LAX emissions adversely impacted air quality much farther than reported in previous airport studies. We measured at least a 2-fold increase in PN concentrations over unimpacted baseline PN concentrations during most hours of the day in an area of about 60 km2 that extended to 16 km (10 miles) downwind and a 4- to 5-fold increase to 8–10 km (5–6 miles) downwind. Locations of maximum PN concentrations were aligned to eastern, downwind jet trajectories during prevailing westerly winds and to 8 km downwind concentrations exceeded 75 000 particles/cm3, more than the average freeway PN concentration in Los Angeles. During infrequent northerly winds, the impact area remained large but shifted to south of the airport. The freeway length that would cause an impact equivalent to that measured in this study (i.e., PN concentration increases weighted by the area impacted) was estimated to be 280–790 km. The total freeway length in Los Angeles is 1500 km. These results suggest that airport emissions are a major source of PN in Los Angeles that are of the same general magnitude as the entire urban freeway network. They also indicate that the air quality impact areas of major airports may have been seriously underestimated. PMID:24871496

  15. GUT theories from Calabi-Yau 4-folds with SO(10) singularities

    NASA Astrophysics Data System (ADS)

    Tatar, Radu; Walters, William

    2012-12-01

    We consider an SO(10) GUT model from F-theory compactified on an elliptically fibered Calabi-Yau with a D 5 singularity. To obtain the matter curves and the Yukawa couplings, we use a global description to resolve the singularity along the lines of [14]. We identify the vector and spinor matter representations and their Yukawa couplings and we explicitly build the G-fluxes in the global model and check the agreement with the semi-local results. As our bundle is of type SU(2 k), some extra conditions need to be applied to match the fluxes, as observed in [21].

  16. Emissions from an international airport increase particle number concentrations 4-fold at 10 km downwind.

    PubMed

    Hudda, Neelakshi; Gould, Tim; Hartin, Kris; Larson, Timothy V; Fruin, Scott A

    2014-06-17

    We measured the spatial pattern of particle number (PN) concentrations downwind from the Los Angeles International Airport (LAX) with an instrumented vehicle that enabled us to cover larger areas than allowed by traditional stationary measurements. LAX emissions adversely impacted air quality much farther than reported in previous airport studies. We measured at least a 2-fold increase in PN concentrations over unimpacted baseline PN concentrations during most hours of the day in an area of about 60 km(2) that extended to 16 km (10 miles) downwind and a 4- to 5-fold increase to 8-10 km (5-6 miles) downwind. Locations of maximum PN concentrations were aligned to eastern, downwind jet trajectories during prevailing westerly winds and to 8 km downwind concentrations exceeded 75 000 particles/cm(3), more than the average freeway PN concentration in Los Angeles. During infrequent northerly winds, the impact area remained large but shifted to south of the airport. The freeway length that would cause an impact equivalent to that measured in this study (i.e., PN concentration increases weighted by the area impacted) was estimated to be 280-790 km. The total freeway length in Los Angeles is 1500 km. These results suggest that airport emissions are a major source of PN in Los Angeles that are of the same general magnitude as the entire urban freeway network. They also indicate that the air quality impact areas of major airports may have been seriously underestimated. PMID:24871496

  17. Higher: Setting a Higher Bar for Higher Ed. 2013 Annual Report

    ERIC Educational Resources Information Center

    American Council of Trustees and Alumni, 2014

    2014-01-01

    The American Council of Trustees and Alumni (ACTA) is leading the charge to return "higher" to higher education. We are challenging the status quo to restore academic freedom, academic rigor, and real accountability to higher education. And, we are doing so with an ever-widening network of supporters and partners.

  18. Expression of circadian gens in different rat tissues is sensitive marker of in vivo silver nanoparticles action

    NASA Astrophysics Data System (ADS)

    Minchenko, D. O.; Yavorovsky, O. P.; Zinchenko, T. O.; Komisarenko, S. V.; Minchenko, O. H.

    2012-09-01

    day after treatment of rats with silver nanoparticles. It was also shown that expression level of PFKFB4, a key enzyme of glycolysis regulation, gradually reduces in the brain from 1st to 14th day being up to 4 fold less on 14th day after treatment of animals with silver nanoparticles. Thus, the intratracheally instilled silver nanoparticles significantly affect the expression of PER1, PER2, ARNTL, and CLOCK genes which are an important molecular component of circadian clock system. This is because a disruption of the circadian processes leads to a development of various pathologic processes. The results of this study clearly demonstrate that circadian genes could be a sensitive test for detection of silver nanoparticles toxic action and suggest that more caution is needed in biomedical applications of silver nanoparticles as well as higher level of safety in silver nanoparticles production industry.

  19. Oral administration of supplementary biotin differentially influences the fertility rate and oviductal expression of avidin and avidin-related protein-2 in low- and high-fertility broiler line hens.

    PubMed

    Daryabari, H; Akhlaghi, A; Zamiri, M J; Pirsaraei, Z Ansari; Mianji, G Rahimi; Deldar, H; Eghbalian, A N

    2015-02-01

    Probable involvement of avidin and avidin-related protein-2 (AVR2) in sperm viability in the sperm storage tubules of turkeys has been suggested. The high affinity of biotin to avidin and its analogs is also well documented. The present study aimed to determine the effect of oral biotin on reproductive performance and oviductal mRNA expression of avidin and AVR2 in 2 broiler hen lines with different fertility rates. Low-fertility (line B) and high-fertility (line D) hens (n=144) were randomly allotted to receive 0 (T0), 0.30 (T1), or 0.45 (T2) mg/L biotin in drinking water from 30 through 33 wk of age. The reproductive performance of the hens was evaluated using artificial insemination. At the end of the treatment period, 24 hens per line were killed to assay the expression of avidin and AVR2 in the uterovaginal junction. Supplementary biotin increased egg production from 73.5% for T0 to 87.8% for T2. Hens administered with biotin in line B, but not in line D, showed an increase (8.4%) in fertility rate. Hatchability, chick quality, and overall embryonic mortality were not different among the experimental groups. Real-time PCR data showed that both avidin (P=0.0013) and AVR2 (P<0.0001) expressions were influenced by a biotin×line interaction effect, where low-fertility line B hens receiving the high biotin level recorded respectively a 3.9 and 15.3% increase in avidin and AVR2 mRNA expression, although biotin did not affect these traits in line D hens. Control hens in line D had a dramatically higher AVR2 expression record (7.4-fold) compared with the control hens in line B. The correlation coefficients of fertility rate and avidin expression were 0.73 and 0.66 in lines B and D, respectively. However, the correlation of fertility and AVR2 (r=0.65) was significant for line D hens only. Overall, fertility rate and oviductal expression of avidin and AVR2 were dichotomously affected by oral biotin in low- and high-fertility line hens, where only low-fertility birds

  20. Arabidopsis gene expression patterns are altered during spaceflight

    NASA Astrophysics Data System (ADS)

    Paul, Anna-Lisa; Popp, Michael P.; Gurley, William B.; Guy, Charles; Norwood, Kelly L.; Ferl, Robert J.

    The exposure of Arabidopsis thaliana (Arabidopsis) plants to spaceflight environments results in differential gene expression. A 5-day mission on orbiter Columbia in 1999 (STS-93) carried transgenic Arabidopsis plants engineered with a transgene composed of the alcohol dehydrogenase (Adh) gene promoter linked to the β-Glucuronidase (GUS) reporter gene. The plants were used to evaluate the effects of spaceflight on gene expression patterns initially by using the Adh/GUS transgene to address specifically the possibility that spaceflight induces a hypoxic stress response (Paul, A.L., Daugherty, C.J., Bihn, E.A., Chapman, D.K., Norwood, K.L., Ferl, R.J., 2001. Transgene expression patterns indicate that spaceflight affects stress signal perception and transduction in arabidopsis, Plant Physiol. 126, 613-621). As a follow-on to the reporter gene analysis, we report here the evaluation of genome-wide patterns of native gene expression within Arabidopsis shoots utilizing the Agilent DNA array of 21,000 Arabidopsis genes. As a control for the veracity of the array analyses, a selection of genes was further characterized with quantitative Real-Time RT PCR (ABI - Taqman®). Comparison of the patterns of expression for arrays probed with RNA isolated from plants exposed to spaceflight compared to RNA isolated from ground control plants revealed 182 genes that were differentially expressed in response to the spaceflight mission by more than 4-fold, and of those only 50 genes were expressed at levels chosen to support a conservative change call. None of the genes that are hallmarks of hypoxic stress were induced to this level. However, genes related to heat shock were dramatically induced - but in a pattern and under growth conditions that are not easily explained by elevated temperatures. These gene expression data are discussed in light of current models for plant responses to the spaceflight environment and with regard to potential future spaceflight experiment

  1. α-Phellandrene alters expression of genes associated with DNA damage, cell cycle, and apoptosis in murine leukemia WEHI-3 cells.

    PubMed

    Lin, Jen-Jyh; Yu, Chien-Chih; Lu, Kung-Wen; Chang, Shu-Jen; Yu, Fu-Shun; Liao, Ching-Lung; Lin, Jaung-Geng; Chung, Jing-Gung

    2014-08-01

    α-phellandrene (α-PA) is a cyclic monoterpene, present in natural plants such as Schinus molle L. α-PA promotes immune responses in mice in vivo. However, there is no available information on whether α-PA affects gene expression in leukemia cells. The present study determined effects of α-PA on expression levels of genes associated with DNA damage, cell cycle and apoptotic cell death in mouse leukemia WEHI-3 cells. WEHI-3 cells were treated with 10 μM α-PA for 24 h, cells were harvested and total RNA was extracted, and gene expression was analyzed by cDNA microarray. Results indicated that α-PA up-regulated 10 genes 4-fold, 13 by over 3-fold and 175 by over 2-fold; 21 genes were down-regulated by over 4-fold, 26 genes by over 3-fold and expression of 204 genes was altered by at leas 2-fold compared with the untreated control cells. DNA damage-associated genes such as DNA damage-inducer transcript 4 and DNA fragmentation factor were up-regulated by 4-fold and over 2-fold, respectively; cell-cycle check point genes such as cyclin G2 and cyclin-dependent kinases inhibitor 2D and IA (p21) were up-regulated by over 3-fold and over 2-fold, respectively; apoptosis-associated genes such as BCL2/adenovirus EIB interacting protein 3, XIAP-associated factor 1, BCL2 modifying factor, caspase-8 and FADD-like apoptosis regulator were over 2-fold up-regulated. Furthermore, DNA damage-associated gene TATA box binding protein was over 4-fold down-regulated, and D19Ertd652c (DNA segment) over 2-fold down-regulated; cell cycle-associated gene cyclin E2 was over 2-fold down-regulated; apoptosis associated gene growth arrest-specific 5 was over 9-fold down-regulated, Gm5426 (ATP synthase) was over 3-fold down-regulated, and death box polypeptide 33 was over 2-fold down-regulated. Based on these observations, α-PA altered gene expression in WEHI-3 cells in vitro. PMID:25075043

  2. Promoter/leader deletion analysis and plant expression vectors with the figwort mosaic virus (FMV) full length transcript (FLt) promoter containing single or double enhancer domains.

    PubMed

    Maiti, I B; Gowda, S; Kiernan, J; Ghosh, S K; Shepherd, R J

    1997-03-01

    The boundaries required for maximal expression from the promoter/leader region of the full length transcript of figwort mosaic virus (FLt promoter) coupled to reporter genes were defined by 5' and 3' deletion analyses. In transient expression assays using protoplasts of Nicotiana edwardsonii, a 314 bp FLt promoter fragment sequence (-249 to +65 from the transcription start site) was sufficient for strong expression activity. Plant expression vectors developed with modified FLt promoters were tested with GUS or CAT as reporter genes in transgenic plants. The FLt promoter is a strong constitutive promoter, with strength comparable to or greater than that of the CaMV 35S promoter. The FLt promoter with its double enhancer domain linked to GUS or CAT reporter genes provides an average 4-fold greater activity than the FLt promoter with a single enhancer domain (-55 to -249 bp upstream fragment) in tests with transgenic plants and in protoplast transient expression assays. PMID:9090062

  3. Downregulation of expression of mater genes SOX9, FOXA2, and GATA4 in pancreatic cancer cells stimulated with TGFβ1 epithelial-mesenchymal transition.

    PubMed

    Kondratyeva, L G; Sveshnikova, A A; Grankina, E V; Chernov, I P; Kopantseva, M R; Kopantzev, E P; Sverdlov, E D

    2016-07-01

    We show characteristic morphological changes corresponding to epithelial-mesenchymal transition (EMT) program fulfillment in PANC1 cell line stimulated with TGFβ1. Our results support downregulation of E-cadherin protein. We show 5- and 28-fold increase in SNAI1 and SNAI2 expression levels and 25- and 15-fold decrease in CDH1 and KRT8 expression levels, respectively, which confirms the EMT-program fulfillment. We demonstrate downregulation of expression of pancreatic master genes SOX9, FOXA2, and GATA4 (2-, 5-, and 4-fold, respectively) and absence of significant changes in HES1, NR5A2, and GATA6 expression levels in the cells stimulated with TGFβ1. Our results indicate the absence of induction of expression of PTF1A, PDX1, HNF1b, NEUROG3, RPBJL, NKX6.1, and ONECUT1 genes, which are inactive in PANC1 cell line after the EMT stimulated by TGFβ1. PMID:27599506

  4. Alabama Commission on Higher Education. Occasional Papers on Higher Education.

    ERIC Educational Resources Information Center

    Alabama State Commission on Higher Education, Montgomery.

    Two papers on the funding formula of the Alabama Commission for Higher Education are presented. The first paper, by John F. Porter, Jr., "The Origins and Evolutions of the Funding Formula Model Utilized by the Alabama Commission on Higher Education, 1973-82," presents the historical antecedents for the existing formula elements and notes…

  5. Higher Education in the Byelorussian SSR. Monographs on Higher Education.

    ERIC Educational Resources Information Center

    Bondarenko, E. G.; And Others

    Higher education in the Byelorussian Soviet Socialist Republic (BSSR) is described, including the system's history, current conditions, functions, and structure. The particular shape of the Byelorussian higher education is in part due to the fact that it only came into being as a system after the revolution of 1917, meaning that from the beginning…

  6. Compensation in Higher Education. ERIC/Higher Education Research Currents.

    ERIC Educational Resources Information Center

    Trivett, David A.

    Compensation in higher education is an inclusive term, since all the benefits associated with teaching, research, work with people, and work with knowledge might be included. But in terms of purchasing power it appears that compensation for work in higher education has lost ground against inflation. In contrast, wage and salary earners in many…

  7. Higher Education in the USSR. Monographs on Higher Education.

    ERIC Educational Resources Information Center

    Savelyev, A. Y.; And Others

    This monograph describes the system of higher education in the United Soviet Socialist Republics (USSR). The preface points out that despite perestroika, two features of Soviet education persist, a high degree of unity and centralization and a close link between higher education and employers. Chapter 1, "Historical Overview," begins with 4th…

  8. [Epilepsy with higher brain dysfunction].

    PubMed

    Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Kuroda, Takeshi; Fujita, Kazuhisa; Itaya, Kazuhiro; Ishigaki, Seiichiro; Kawamura, Mitsuru

    2013-02-01

    Acquired higher brain dysfunction is for the most part due to cerebral vascular disease, but epilepsy may also be a cause. In this study with five patients, we discuss the advantages of anti-epileptic drugs (AEDs) for persistent higher brain dysfunction. The patients showed chronic amnesia or acute aphasia, with associated symptoms like personality change. All five cases affected automatism or convulsive attack, though only after the emergence of higher brain dysfunction and administration of AEDs. There were underlying diseases like cerebral arteriovenous malformation in four cases, but the other patient had none. Electroencephalogram and single photon emission computed tomography revealed one case of aphasia epilepsy with higher brain dysfunction. These results suggest the potential therapeutic efficacy of AEDs for persistent higher brain dysfunction, and we must differentiate epilepsy with higher brain dysfunction from dementia or cerebral vascular disease. PMID:23399676

  9. Administrative Effectiveness in Higher Education.

    ERIC Educational Resources Information Center

    Whetten, David A.; Cameron, Kim S.

    1985-01-01

    Determinants of organizational and administrative effectiveness in higher education are discussed, and eight administrator characteristics associated with maintaining and enhancing institutional effectiveness are identified. (MSE)

  10. Higher Education, Employability and Competitiveness

    ERIC Educational Resources Information Center

    Pavlin, Samo; Svetlicic, Marjan

    2012-01-01

    This paper studies the relationship between competitiveness and higher education systems in Europe. It explores whether more competitive countries have developed more labour-market-oriented systems of higher education (HE) that thereby give their graduates greater short term employability potential. Based on and a large-scale survey among 45.000…

  11. Higher Education in the USSR.

    ERIC Educational Resources Information Center

    Saveljev, Alexander

    1983-01-01

    The objectives of the Soviet system of higher education and the expansion of the role of higher education are described, emphasizing the development of labor and industry for increased productivity, creativity, and specialization. A trend toward regular continuing education to keep pace with technological advancement is also noted. (MSE)

  12. Women in Higher Education, 1996.

    ERIC Educational Resources Information Center

    Wenniger, Mary Dee, Ed.

    1996-01-01

    This document consists of the issues of a 1996 newsletter on women students, teachers, and administrators in higher education. Each issue includes feature articles, news on higher education, profiles of significant people in the field, and job announcements. The issues' main articles concern: (1) a successful campaign to increase female…

  13. Queering Transformation in Higher Education

    ERIC Educational Resources Information Center

    Msibi, Thabo

    2013-01-01

    Transformation in higher education has tended to focus on race and sex, at the expense of other forms of discrimination. This article addresses the silencing of "queer" issues in higher education. Using queer theory as a framework, and drawing on current literature, popular media reports, two personal critical incidents and a project…

  14. Theorising Quality in Higher Education

    ERIC Educational Resources Information Center

    Morley, Louise

    2004-01-01

    Britain now has the most heavily regulated higher education system in the world and institutions must deliver best educational value. This book explores the political and psychic economy of quality assurance in higher education and interrogates the discourse and practices associated with the audit culture in Britain. Following Acknowledgements and…

  15. History of Higher Education, 1999.

    ERIC Educational Resources Information Center

    Geiger, Roger L., Ed.

    1999-01-01

    The six papers in this annual volume on the history of higher education cover some of the changes that evolved over the years in various U.S. Institutions. The first paper is: "The Articulation of Secondary and Higher Education: Four Historical Models at the University of Georgia" (J. Patrick McCarthy), which discusses the efforts of trustees and…

  16. Higher Education: Open for Business

    ERIC Educational Resources Information Center

    Gilde, Christian, Ed.

    2007-01-01

    This book addresses a problem in higher learning, which is newly recognized in the academic spotlight: the overcommercialization of higher education. The book asks that you, the reader, think about the following: Did you go to a Coke or Pepsi school? Do your children attend a Nike or Adidas school? Is the college in your town a Dell or Gateway…

  17. Higher Education in New York.

    ERIC Educational Resources Information Center

    Lane, Frederick, Ed.

    1983-01-01

    New York State higher education policy and finance are discussed in four articles. In "Higher Education and Public Policy in New York," Frederick S. Lane considers the state's institutions, policymakers and politics, financing of colleges, enrollment patterns, links to economic development, and the changing educational environment. Paul T.…

  18. Women in Higher Education, 1994.

    ERIC Educational Resources Information Center

    Wenninger, Mary Dee, Ed.

    1994-01-01

    This document consists of the 12 monthly issues of a newsletter on women students, teachers, and administrators in higher education, issued in 1994. Each issue includes feature articles, news on higher education, profiles of significant people in the field, and job announcements. The issues' main article topics are: (1) campuses's changing…

  19. Exploring Higher Education Financing Options

    ERIC Educational Resources Information Center

    Nkrumah-Young, Kofi K.; Powell, Philip

    2011-01-01

    Higher education can be financed privately, financed by governments, or shared. Given that the benefits of education accrue to the individual and the state, many governments opt for shared financing. This article examines the underpinnings of different options for financing higher education and develops a model to compare conditions to choices and…

  20. Unexploited Efficiencies in Higher Education

    ERIC Educational Resources Information Center

    Eyring, Henry C.

    2011-01-01

    In "Unexploited Efficiencies in Higher Education," Henry C. Eyring, a junior majoring in Economics at Brigham Young University-Idaho, argues that one way that the U.S. can compete globally in college attainment is to decrease cost-per-graduate. He explains how many stakeholders in higher education stand to benefit from unexploited…

  1. Feminist Research in Higher Education

    ERIC Educational Resources Information Center

    Ropers-Huilman, Rebecca; Winters, Kelly T.

    2011-01-01

    This essay provides an overview of feminist methodology and its potential to enhance the study of higher education. Foregrounding the multiple purposes and research relationships developed through feminist research, the essay urges higher education scholars to engage feminist theories, epistemologies, and methods to inform policy, research, and…

  2. History of Higher Education, 1994.

    ERIC Educational Resources Information Center

    History of Higher Education, 1994

    1994-01-01

    This annual compilation presents four papers which focus on significant developments in higher education in nineteenth-century Europe and the United States. An introduction to the volume by Roger L. Geiger notes commonalities across the four papers and major trends in historical research on institutions of higher education. The first paper, by…

  3. Higher Education, Poverty and Development

    ERIC Educational Resources Information Center

    Tilak, Jandhyala B. G.

    2010-01-01

    There is a presumption among many policy makers that higher education is not necessary for economic growth and development; it is literacy and basic education and at best secondary education that are argued to be important. Estimates of internal rate of return contributed to strengthening of such a presumption. Accordingly, higher education has…

  4. Fact Book on Higher Education

    ERIC Educational Resources Information Center

    Marks, Joseph L.; Diaz, Alicia A.

    2009-01-01

    The "Southern Regional Education Board (SREB) Fact Book on Higher Education" is one of the nation's most comprehensive collections of comparative data on higher education. For decades, state leaders, policy-makers, researchers and journalists have used the "Fact Book" to find useful data quickly--and to learn more about long-term trends and…

  5. Does Higher Education Need Deschooling?

    ERIC Educational Resources Information Center

    Butson, Russell

    2011-01-01

    This paper presents an attempt to overcome the contemporary obsession with "learning" and proposes that current practices in higher education are aligned too closely with the educational theories and practices developed within pre-university compulsory education. The author takes the position that higher education is substantially different from…

  6. The Marketing of Higher Education.

    ERIC Educational Resources Information Center

    Brooker, George; Noble, Michael

    1985-01-01

    Formal college and university marketing programs are challenging to develop and implement because of the complexity of the marketing mix, the perceived inappropriateness of a traditional marketing officer, the number of diverse groups with input, the uniqueness of higher education institutions, and the difficulty in identifying higher education…

  7. Postmodernism in Higher Educational Administration

    ERIC Educational Resources Information Center

    Demaris, Michalyn C.; Kritsonis, William Allan

    2007-01-01

    Postmodernism has many inferences that can be applied to the theory and practice of higher educational administration. Today, in higher education administrators are continuously focused on strategies that will ensure the future of minority educational institutions. As a result postmodernism is an important factor in the future of higher…

  8. History of American Higher Education

    ERIC Educational Resources Information Center

    McCarthy, Margaret Cain

    2011-01-01

    "History of American Higher Education" documents the fascinating evolution of American colleges and universities, touching on the historical events that shaped them, from the colonial era through the early twenty-first century. Throughout history, higher education has played an important role in the transmission of cultural identity from one…

  9. THE ECONOMICS OF HIGHER EDUCATION.

    ERIC Educational Resources Information Center

    CARTTER, ALLAN M.; AND OTHERS

    THIS PUBLICATION CONTAINS PAPERS PRESENTED AT A COLLOQUIUM HELD BY THE COLLEGE SCHOLARSHIP SERVICE IN 1965. THE PAPERS DEAL BROADLY WITH THE QUESTION OF THE MOST EFFECTIVE METHODS OF FINANCING HIGHER EDUCATION, AND WITH THE ROLE AND PROBLEMS OF THE EDUCATIONAL CONSUMER. THE PAPERS DEAL WITH--(1) THE ECONOMICS OF HIGHER EDUCATION, (2) PRICING…

  10. Innovations in Higher Education? Hah!

    ERIC Educational Resources Information Center

    Kirschner, Ann

    2012-01-01

    One can hardly mention higher education today without hearing the word "innovation," or its understudies "change," "reinvention," "transformation." Last summer the National Governors Association opened its meeting with a plenary session on higher education, innovation, and economic growth. But there is nothing funny about the need for innovation…

  11. Strategy Process in Higher Education

    ERIC Educational Resources Information Center

    Kettunen, Juha

    2010-01-01

    Higher education institutions educate those who are the most talented and best able to secure the future for the next generation. This study examines an efficient strategy process in higher education and emphasises the importance of sufficient dialogue during the process. The study describes the strategy process of the Turku University of Applied…

  12. Learning Entrepreneurship in Higher Education

    ERIC Educational Resources Information Center

    Taatila, Vesa P.

    2010-01-01

    Purpose: There is a constant need to produce more entrepreneurial graduates from higher education institutions. This paper aims to present and discuss several successful cases of entrepreneurial learning environments in order to suggest some important aspects that higher education institutions should consider. Design/methodology/approach: The…

  13. The Overselling of Higher Education

    ERIC Educational Resources Information Center

    Leef, George C.

    2006-01-01

    There is not enough substance behind a degree to warrant the ubiquitous belief that a stint in higher education is a "sine qua non" for success in America. While college diplomas may translate into higher-paying jobs for some, high school signifies little in the way of education these days, so jaded employers' estimates of the real value of…

  14. Institutional Change and Higher Education

    ERIC Educational Resources Information Center

    Loomis, Steven; Rodriguez, Jacob

    2009-01-01

    Institutional change includes the supplanting of the old model of production with a new one, the elimination of old markets and the emergence of new ones. As higher education around the world shifts from national markets to an integrated transnational market, and possibly toward a virtual market, Christian higher education, like other market…

  15. The State and Higher Education.

    ERIC Educational Resources Information Center

    Millard, Richard M.

    Although the federal influence on higher education is important, throughout the United States' history the state role in higher education has been a vital and changing one, and not always uniform. In 1976, two-thirds of the institutional revenue coming from government came from the states, making the state issue an important one. One of the most…

  16. Directory of Higher Education, 2001.

    ERIC Educational Resources Information Center

    Illinois State Board of Higher Education, Springfield.

    This directory contains addresses or other contact information for members of the Illinois Board of Higher Education and administrators at Illinois public and private colleges and universities. Mailing addresses are given for members of the state Board of Higher Education and members of the boards of the institutions listed. Telephone numbers are…

  17. Directory of Higher Education, 2000.

    ERIC Educational Resources Information Center

    Illinois State Board of Higher Education, Springfield.

    This directory lists the names, addresses, and telephone numbers of members of higher education organizations in the state of Illinois. Included for the Illinois Board of Higher Education is an organization chart, list of board and staff members, and a list of members of the Illinois Century Network. Board members and administrative officers are…

  18. Effective Communication in Higher Education

    ERIC Educational Resources Information Center

    Howard, Melissa

    2014-01-01

    The intent for this paper is to show that communication within the higher education field is a current problem. By looking first at the different styles, forms, and audiences for communication, the reader will hopefully gain perspective as to why this is such a problem in higher education today. Since the Millennial generation is the newest set of…

  19. Canuck-Do Higher Education.

    ERIC Educational Resources Information Center

    Rosenfeld, Mark

    2003-01-01

    Discusses how, like Australia, Canadian higher education has experienced large-scale cuts in government funding, the deregulation of tuition and general cost shifting to students, inability to accommodate increased student demand, faculty "brain drain" and shortages, and an erosion of public policy toward viewing higher education as a business.…

  20. Higher Education and Social Commitment.

    ERIC Educational Resources Information Center

    Nasution, S.; Virasai, Banphot, Eds.

    The proceedings of the Regional Institute of Higher Education and Development's seminar and the meaning and implications of social commitment in higher education are reported. The welcoming address (S. Nasution) and the opening address (Y. B. Dato' Murad bin Mohd. Noor) welcome the participants and set the tone for the discussions to follow. The…

  1. Strategic Planning for Higher Education.

    ERIC Educational Resources Information Center

    Kotler, Philip; Murphy, Patrick E.

    1981-01-01

    The framework necessary for achieving a strategic planning posture in higher education is outlined. The most important benefit of strategic planning for higher education decision makers is that it forces them to undertake a more market-oriented and systematic approach to long- range planning. (Author/MLW)

  2. The Higher Education Research Archipelago

    ERIC Educational Resources Information Center

    Macfarlane, Bruce

    2012-01-01

    Ever since he stumbled into doing higher education research as a young academic in the 1980s, the author has been trying to understand it as a "field" of study. His career, as a former business lecturer, then an academic developer and now an associate professor for higher education working in an Education Faculty has given him opportunities to see…

  3. A Higher Education Issues Study.

    ERIC Educational Resources Information Center

    Balm, Gerald J.; Blomberg, Robert

    1987-01-01

    As part of a strategic planning effort guiding community socioeconomic development through 2000, the citizens of Rochester, Minnesota, tackled the problem of providing equitable, accessible, and accountable higher education. Studying external factors and developing an internal situation analysis led to a set of higher education issues and…

  4. Disruptive Technologies in Higher Education

    ERIC Educational Resources Information Center

    Flavin, Michael

    2012-01-01

    This paper analyses the role of "disruptive" innovative technologies in higher education. In this country and elsewhere, Higher Education Institutions (HEIs) have invested significant sums in learning technologies, with Virtual Learning Environments (VLEs) being more or less universal, but these technologies have not been universally adopted and…

  5. Higher Education Marketing: A Challenge.

    ERIC Educational Resources Information Center

    Canterbury, Richard

    1999-01-01

    States that similarities between education and other services may not be sufficient to conclude that services marketing methods can be easily transferred to all markets in higher education. Article identifies and discusses why higher education marketing is a particular challenge. Suggests that understanding these challenges can help in making…

  6. Personnel Management in Higher Education.

    ERIC Educational Resources Information Center

    Millett, John D.; And Others

    This document on personnel management in higher education contains three papers that are designed to be used as guidelines for educational administrators. The first two papers, by John D. Millett, discuss the scope and problems of higher education administration and the problems associated with collective bargaining and tenure on college campuses.…

  7. The Cost of Higher Education.

    ERIC Educational Resources Information Center

    Hartle, Terry W.

    1998-01-01

    A discussion of the current cost and financing of higher education looks at how higher education has been treated in federal policy in recent years, its status in public policy in the near future, including some salient uncertainties, and college cost and student debt. Emphasis is given to trends in the cost of professional education. (MSE)

  8. The Economy and Higher Education.

    ERIC Educational Resources Information Center

    Anderson, Richard E.

    1988-01-01

    The macroeconomic trends shaping the United States economy and the effects of those trends on higher education are considered. Warning institutions of higher education about possible problems in the economy will place them in a better position to react if necessary. The economic environment is discussed in terms of productivity (goods and services…

  9. Minority Access to Higher Education

    ERIC Educational Resources Information Center

    Jackson, Nathaniel

    2012-01-01

    Blacks, Hispanics, Native Americans, and Asian Americans are entitled to equal access to all institutions of higher education. Ensuring greater access and participation by minorities in higher education is one of the most practical ways of moving America closer to the ideal of equal opportunity, which is the actualization of the American dream.…

  10. Higher order stationary subspace analysis

    NASA Astrophysics Data System (ADS)

    Panknin, Danny; von Bünau, Paul; Kawanabe, Motoaki; Meinecke, Frank C.; Müller, Klaus-Robert

    2016-03-01

    Non-stationarity in data is an ubiquitous problem in signal processing. The recent stationary subspace analysis procedure (SSA) has enabled to decompose such data into a stationary subspace and a non-stationary part respectively. Algorithmically only weak non- stationarities could be tackled by SSA. The present paper takes the conceptual step generalizing from the use of first and second moments as in SSA to higher order moments, thus defining the proposed higher order stationary subspace analysis procedure (HOSSA). The paper derives the novel procedure and shows simulations. An obvious trade-off between the necessity of estimating higher moments and the accuracy and robustness with which they can be estimated is observed. In an ideal setting of plenty of data where higher moment information is dominating our novel approach can win against standard SSA. However, with limited data, even though higher moments actually dominate the underlying data, still SSA may arrive on par.

  11. Hepatic Aryl Hydrocarbon Receptor Attenuates Fibroblast Growth Factor 21 Expression.

    PubMed

    Girer, Nathaniel G; Murray, Iain A; Omiecinski, Curtis J; Perdew, Gary H

    2016-07-15

    The Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in many physiological processes. Several studies indicate that AHR is also involved in energy homeostasis. Fibroblast growth factor 21 (FGF21) is an important regulator of the fasting and feeding responses. When administered to various genetic and diet-induced mouse models of obesity, FGF21 can attenuate obesity-associated morbidities. Here, we explore the role of AHR in hepatic Fgf21 expression through the use of a conditional, hepatocyte-targeted AHR knock-out mouse model (Cre(Alb)Ahr(Fx/Fx)). Compared with the congenic parental strain (Ahr(Fx/Fx)), non-fasted Cre(Alb)Ahr(Fx/Fx) mice exhibit a 4-fold increase in hepatic Fgf21 expression, as well as elevated expression of the FGF21-target gene Igfbp1 Furthermore, in vivo agonist activation of AHR reduces hepatic Fgf21 expression during a fast. The Fgf21 promoter contains several putative dioxin response elements (DREs). Using EMSA, we demonstrate that the AHR-ARNT heterodimer binds to a specific DRE that overlaps binding sequences for peroxisome proliferator-activated receptor α (PPARα), carbohydrate response element-binding protein (ChREBP), and cAMP response element-binding protein, hepatocyte specific (CREBH). In addition, we reveal that agonist-activated AHR impairs PPARα-, ChREBP-, and CREBH-mediated promoter activity in Hepa-1 cells. Accordingly, agonist treatment in Hepa-1 cells ablates potent ER stress-driven Fgf21 expression, and pre-treatment with AHR antagonist blocks this effect. Finally, we show that pre-treatment of primary human hepatocytes with AHR agonist diminishes PPARα-, glucose-, and ER stress-driven induction of FGF21 expression, indicating the effect is not mouse-specific. Together, our data show that AHR contributes to hepatic energy homeostasis, partly through the regulation of FGF21 expression and signaling. PMID:27226639

  12. Changes in Liver Metabolic Gene Expression from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Peters, C. P.; Wotring, V. E.

    2012-01-01

    Increased exposure to radiation is one physiological stressor associated with spaceflight. While known to alter normal physiological function, how radiation affects metabolism of administered medications is unclear. Crew health could be affected if the actions of medications used in spaceflight deviated from expectations formed during terrestrial medication use. Three different doses of gamma radiation (50 mGy - 6.05 Gy) and a sham were administered to groups of 6 mice each, and after various intervals of recovery time, liver gene expression was measured with RT-qPCR arrays for drug metabolism and DNA repair enzymes. Results indicated approx.65 genes of the 190 tested were significantly affected by at least one of the radiation doses. Many of the affected genes are involved in the metabolism of drugs with hydrophobic or steroid-like structures, maintenance of redox homeostasis and repair of DNA damage. Most affected genes returned to near control expression levels by 7 days post-treatment. With 6 Gy exposure, metallothionein expression was 132-fold more than control at the 4 hr time point, and fell at each later time point (11-fold at 24 hrs, and 8-fold at 7 days). In contrast, Cyp17a1 showed a 4-fold elevation at 4 hrs after exposure and remained constant for 7 days.

  13. IGF and IGF-binding protein expression in the growth plate of normal, dexamethasone-treated and human IGF-II transgenic mice.

    PubMed

    Smink, J J; Koster, J G; Gresnigt, M G; Rooman, R; Koedam, J A; Van Buul-Offers, S C

    2002-10-01

    Glucocorticoid (GC) treatment in childhood can lead to suppression of longitudinal growth as a side effect. The actions of GCs are thought to be mediated in part by impaired action of the insulin-like growth factors (IGF-I and IGF-II) and their binding proteins (IGFBP-1 to -6). We have studied the effects of GCs on IGF and IGFBP expression at the local level of the growth plate, using non-radioactive in situ hybridization. We treated 3-week-old normal mice for 4 weeks with dexamethasone (DXM). We also treated human IGF-II (hIGF-II) transgenic mice in order to investigate whether IGF-II could protect against the growth retarding effect of this GC. DXM treatment resulted in general growth retardation in both mice strains, however, only in normal mice was tibial length decreased. In both normal and hIGF-II trangenic mice, the total width of the growth plate was not affected, whereas the width of the proliferative zone decreased as a result of the DXM treatment. Additionally, only in normal mice, the width of the hypertrophic zone thickened. Only expression of IGF-I, IGF-II and IGFBP-2 could be detected in the growth plates of 7-week-old normal mice. IGFBP-1, -3, -4, -5 and -6 mRNAs were not detected. DXM treatment of normal mice induced a significant 2.4-fold increase in the number of cells expressing IGF-I mRNA, whereas IGF-II and IGFBP-2 mRNA levels were not affected. In hIGF-II transgenic mice, IGF-I mRNA levels were significantly increased, while endogenous IGF-II and IGFBP-2 mRNAs were unaffected, compared to normal animals. DXM treatment of the hIGF-II transgenic mice induced a further increase of IGF-I mRNA expression, to a similar extent as in DXM-treated normal mice. The increase of IGF-I due to DXM treatment in normal mice might be a reaction in order to minimize the GC-induced growth retardation. Another possibility could be that the increase of IGF-I would contribute to the GC-induced growth retardation by accelerating the differentiation of chondrocytes

  14. Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health?

    PubMed Central

    Pekkala, Satu; Wiklund, Petri K; Hulmi, Juha J; Ahtiainen, Juha P; Horttanainen, Mia; Pöllänen, Eija; Mäkelä, Kari A; Kainulainen, Heikki; Häkkinen, Keijo; Nyman, Kai; Alén, Markku; Herzig, Karl-Heinz; Cheng, Sulin

    2013-01-01

    Recently, contradictory findings have been reported concerning the function of irisin and its precursor gene, skeletal muscle FNDC5, in energy homeostasis, and the associated regulatory role of exercise and PGC-1α. We therefore evaluated whether muscle FNDC5 mRNA and serum irisin are exercise responsive and whether PGC-1α expression is associated with FNDC5 expression. The male subjects in the study performed single exercises: (1) 1 h low-intensity aerobic exercise (AE) (middle-aged, n= 17), (2) a heavy-intensity resistance exercise (RE) bout (young n= 10, older n= 11) (27 vs. 62 years), (3) long-term 21 weeks endurance exercise (EE) training alone (twice a week, middle-aged, n= 9), or (4) combined EE and RE training (both twice a week, middle-aged, n= 9). Skeletal muscle mRNA expression was analysed by quantitative PCR and serum irisin by ELISA. No significant changes were observed in skeletal muscle PGC-1α, FNDC5 and serum irisin after AE, EE training or combined EE + RE training. However, a single RE bout increased PGC-1α by 4-fold in young and by 2-fold in older men, while FNDC5 mRNA only increased in young men post-RE, by 1.4-fold. Changes in PGC-1α or serum irisin were not consistently accompanied by changes in FNDC5. In conclusion, for the most part, neither longer-term nor single exercise markedly increases skeletal muscle FNDC5 expression or serum irisin. Therefore their changes in response to exercise are probably random and not consistent excluding the confirmation of any definitive link between exercise and FNDC5 expression and irisin release in humans. Moreover, irisin and FNDC5 were not associated with glucose tolerance and being overweight, or with metabolic disturbances, respectively. Finally, factor(s) other than PGC-1α and transcription may regulate FNDC5 expression. PMID:24000180

  15. Higher Education: A Growth Industry?

    ERIC Educational Resources Information Center

    Bowen, Howard R.

    1974-01-01

    Discusses the implications for the future of higher education by examining data concerning demographic factors, growth projections, supply factors, expansion concerns, health care needs, and manpower supplies. (Author/PG)

  16. Trends in Higher Education Computing.

    ERIC Educational Resources Information Center

    Thomas, Charles R.

    1984-01-01

    Discusses the effects which changes in computer technology are having on the organization, staffing, and budgets at institutions of higher education. Trends in computer hardware, computer software, and in office automation are also discussed. (JN)

  17. Synthesis of higher monocarboxylic acids

    SciTech Connect

    Taikov, B.F.; Novakovskii, E.M.; Zhelkovskaya, V.P.; Shadrova, V.N.; Shcherbik, P.K.

    1981-01-01

    Brown-coal and peat waxes contain higher monocarboxylic acids, alcohols and esters of them as their main components. In view of this, considerable interest is presented by the preparation of individual compounds among those mentioned above, which is particularly important in the study of the composition and development of the optimum variants of the chemical processing of the waxes. In laboratory practice, to obtain higher monocarboxylic acids use is generally made of electrosynthesis according to Kolbe which permits unbranched higher aliphatic acids with given lengths of the hydrocarbon chain to be obtained. The aim of the present work was to synthesize higher monocarboxylic acids: arachidic, behenic, lignoceric, pentacosanoic, erotic, heptacosanoic, montanic, nonacosanoic, melissic, dotriacontanoic and tetratriacontanoic, which are present in waxes. Characteristics of synthesized acids are tabulated. 20 refs.

  18. Differentiation of Higher Education Institutions.

    ERIC Educational Resources Information Center

    Cazenave, P.; Lapointe, S.

    1983-01-01

    Historical and political influences in the trend toward diversification in French universities are traced. Related issues discussed include institutional versus governmental preferences, institutional functions (curriculum, vocational training, research), and implications for the quality and democratization of higher education. (MSE)

  19. Higher Education: Labor Market Linkage.

    ERIC Educational Resources Information Center

    Asayeghn, Desta

    1982-01-01

    Examines the methodology of three case studies investigating the linkage between higher education and the world of work in the Sudan, Zambia, and Tanzania. Summarizes 12 main findings. Suggests the studies remain traditional human resources planning efforts. (NEC)

  20. Academic Incivility in Higher Education

    ERIC Educational Resources Information Center

    Marchand-Stenhoff, Sandra Marie

    2009-01-01

    Professors and researchers have reported an increase in incivility within their classroom and have expressed their frustration, "...that classroom terrorists have hijacked their courses" (Lepper, 2000). Incivility has produced distractions and stresses that interfere with the instructor's ability to teach and students' ability to learn. Situations…

  1. Hypoxia-induced Bcl-2 expression in endothelial cells via p38 MAPK pathway

    SciTech Connect

    Zhang, Cui-Li; Song, Fei; Zhang, Jing; Song, Q.H.

    2010-04-16

    Angiogenesis and apoptosis are reciprocal processes in endothelial cells. Bcl-2, an anti-apoptotic protein, has been found to have angiogenic activities. The purpose of this study was to determine the role of Bcl-2 in hypoxia-induced angiogenesis in endothelial cells and to investigate the underlying mechanisms. Human aortic endothelial cells (HAECs) were exposed to hypoxia followed by reoxygenation. Myocardial ischemia and reperfusion mouse model was used and Bcl-2 expression was assessed. Bcl-2 expression increased in a time-dependent manner in response to hypoxia from 2 to 72 h. Peak expression occurred at 12 h (3- to 4-fold, p < 0.05). p38 inhibitor (SB203580) blocked hypoxia-induced Bcl-2 expression, whereas PKC, ERK1/2 and PI3K inhibitors did not. Knockdown of Bcl-2 resulted in decreased HAECs' proliferation and migration. Over-expression of Bcl-2 increased HAECs' tubule formation, whereas knockdown of Bcl-2 inhibited this process. In this model of myocardial ischemia and reperfusion, Bcl-2 expression was increased and was associated with increased p38 MAPK activation. Our results showed that hypoxia induces Bcl-2 expression in HAECs via p38 MAPK pathway.

  2. Increased fibroblast telomerase expression precedes myofibroblast α-smooth muscle actin expression in idiopathic pulmonary fibrosis

    PubMed Central

    Waisberg, Daniel Reis; Parra, Edwin Roger; Barbas-Filho, João Valente; Fernezlian, Sandra; Capelozzi, Vera Luiza

    2012-01-01

    OBJECTIVE: This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis. METHODS: Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast α-smooth muscle actin expression and the tissue expression of interleukin-4, transforming growth factor-β, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival. RESULTS: Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-β expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast α-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast α-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival. CONCLUSION: Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast α-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be

  3. Higher comorbidity, poor functional status and higher health care utilization in veterans with prevalent total knee arthroplasty or total hip arthroplasty

    PubMed Central

    Sloan, Jeffrey

    2010-01-01

    The objective of this study was to compare comorbidity, functional ability, and health care utilization in veterans with total knee arthroplasty (TKA) or total hip arthroplasty (THA) versus matched control populations. A cohort of veterans using Veterans Affairs (VA) healthcare system reported limitations in six activities of daily living (ADLs; bathing, dressing, eating, walking, transferring, and using the toilet), demographics, and physician-diagnosed comorbidity. VA databases provided healthcare utilization and International Classification of Diseases-9/Common procedure terminology codes for TKA/THA. Patients were classified as: (1) primary TKA; (2) primary THA; (3) combination group (≤1 procedure); and (4) control veteran population (no THA/TKA). Multivariable regression analyses compared the risk or counts of ADL limitation and in-/out-patient visits. After multivariable adjustment, TKA, THA or combination groups had significantly higher prevalence of the following compared to veteran controls: arthritis, diabetes, or heart disease (p<0.0001 each), severe (≥3) ADL limitation (33%, 42%, 42% vs. 24%; p<0.0001), and annual hospitalization rate (24%, 19%, 26% vs. 16%, p<0.0001). Annual outpatient surgery visits were more (2.5, 2.3, 2.3 vs. 2, p=0.01) and risk of any mental health outpatient visit was lower (12%, 11%, 12% vs. 18%, p=0.0039). All ADLs, except eating, were significantly more limited in arthroplasty groups (p= 0.0009). Severe ADL limitation was more prevalent in veterans with arthroplasty than in two age-matched US cohorts: 13.4 times in ≥65 years; and 1.2-, 1.6-, and 4-fold in ≥85, 75–84, and 65–74 years. Poorer function and higher comorbidity and utilization in veterans with TKA/THA suggest that this group is appropriate for interventions targeted at improving function and decreasing utilization. PMID:19517157

  4. Epithelial but not stromal expression of collagen alpha-1(III) is a diagnostic and prognostic indicator of colorectal carcinoma.

    PubMed

    Wang, Xiao-Qing; Tang, Zu-Xiong; Yu, Dong; Cui, Shu-Jian; Jiang, Ying-Hua; Zhang, Qian; Wang, Jie; Yang, Peng-Yuan; Liu, Feng

    2016-02-23

    Colorectal cancer (CRC) is the third most common cancer in males and the second in females worldwide with very poor prognosis. Collagen alpha-1(III) (COL3A1) gene, encoding an extracellular matrix protein, is upregulated in human cancers. Here, we revealed that COL3A1 was increased in CRC by analysis of five Oncomine gene expression datasets (n = 496). Immunohistochemistry analysis of a tissue microarray (n = 90) demonstrated that cancer epithelial but not stromal COL3A1 was significantly upregulated comparing with the normal counterparts. High COL3A1 mRNA and/or protein expression was accompanied with high stage, T stage, Dukes stage, grade and older age, as well as smoking and recurrence status. Upregulated COL3A1 predicted poor overall (p = 0.003) and disease-free (p = 0.025) survival. Increased epithelial but not stromal COL3A1 protein predicted worse outcome (p = 0.03). Older patients (age>65) with high COL3A1 had worse survival than younger (age≤65) with high COL3A1. Plasma COL3A1 was increased in CRC patients (n = 86) by 5.4 fold comparing with healthy individuals, enteritis and polyps patients. Plasma COL3A1 had an area under curve (AUC) of 0.92 and the best sensitivity/specificity of 98.8%/69.1%. While plasma CEA had a poorer prediction power (AUC = 0.791, sensitivity/selectivity = 70.2%/73.0%). Older patients (age≥60) had higher plasma COL3A1 than younger patients. The epithelial COL3A1 protein had an AUC of 0.975 and the best sensitivity/specificity of 95.2%/91.1%. Silencing of COL3A1 suppressed CRC cell proliferation in in vitro MTT assay and in in vivo Zebra fish xenograft model by downregulation of PI3K/AKT and WNT signaling. COL3A1 was a novel diagnosis and prognosis marker of CRC. PMID:26741506

  5. Epithelial but not stromal expression of collagen alpha-1(III) is a diagnostic and prognostic indicator of colorectal carcinoma

    PubMed Central

    Cui, Shu-Jian; Jiang, Ying-Hua; Zhang, Qian; Wang, Jie; Yang, Peng-Yuan; Liu, Feng

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer in males and the second in females worldwide with very poor prognosis. Collagen alpha-1(III) (COL3A1) gene, encoding an extracellular matrix protein, is upregulated in human cancers. Here, we revealed that COL3A1 was increased in CRC by analysis of five Oncomine gene expression datasets (n = 496). Immunohistochemistry analysis of a tissue microarray (n = 90) demonstrated that cancer epithelial but not stromal COL3A1 was significantly upregulated comparing with the normal counterparts. High COL3A1 mRNA and/or protein expression was accompanied with high stage, T stage, Dukes stage, grade and older age, as well as smoking and recurrence status. Upregulated COL3A1 predicted poor overall (p = 0.003) and disease-free (p = 0.025) survival. Increased epithelial but not stromal COL3A1 protein predicted worse outcome (p = 0.03). Older patients (age>65) with high COL3A1 had worse survival than younger (age≤65) with high COL3A1. Plasma COL3A1 was increased in CRC patients (n = 86) by 5.4 fold comparing with healthy individuals, enteritis and polyps patients. Plasma COL3A1 had an area under curve (AUC) of 0.92 and the best sensitivity/specificity of 98.8%/69.1%. While plasma CEA had a poorer prediction power (AUC = 0.791, sensitivity/selectivity = 70.2%/73.0%). Older patients (age≥60) had higher plasma COL3A1 than younger patients. The epithelial COL3A1 protein had an AUC of 0.975 and the best sensitivity/specificity of 95.2%/91.1%. Silencing of COL3A1 suppressed CRC cell proliferation in in vitro MTT assay and in in vivo Zebra fish xenograft model by downregulation of PI3K/AKT and WNT signaling. COL3A1 was a novel diagnosis and prognosis marker of CRC. PMID:26741506

  6. Revitalizing Higher Education. The Stanford Forum for Higher Education Futures.

    ERIC Educational Resources Information Center

    Meyerson, Joel W., Ed.; Massy, William F., Ed.

    This volume contains six essays on higher education which provide lessons and successful techniques for meeting the challenges of the future. The first essay, "Academic Renewal at Michigan" (James Duderstadt), describes the modern research university as a complex corporate conglomerate in danger of diluting its core business. The successful…

  7. Higher Education Accounting Manual. Utah Coordinating Council of Higher Education.

    ERIC Educational Resources Information Center

    Utah State Coordinating Council of Higher Education, Salt Lake City.

    Recognition of a critical need for accurate and detailed information to refine the process of budgeting funds for higher education in Utah led to the preparation of this accounting manual for universities and colleges in the state. The manual presents guidelines for the uniform accounting and reporting of financial and statistical data, and is…

  8. The Hesburgh Papers: Higher Values in Higher Education.

    ERIC Educational Resources Information Center

    Hesburgh, Theodore M.

    In this book the president of Notre Dame University responds to the critics who see the teaching of religion and values as a hindrance to institutions of higher learning, suggesting that no university is truly a university unless it is universal and moves every scholar to look to the total universe. The significance of values in education is…

  9. Black Holes in Higher Dimensions

    NASA Astrophysics Data System (ADS)

    Horowitz, Gary T.

    2012-04-01

    List of contributors; Preface; Part I. Introduction: 1. Black holes in four dimensions Gary Horowitz; Part II. Five Dimensional Kaluza-Klein Theory: 2. The Gregory-Laflamme instability Ruth Gregory; 3. Final state of Gregory-Laflamme instability Luis Lehner and Frans Pretorius; 4. General black holes in Kaluza-Klein theory Gary Horowitz and Toby Wiseman; Part III. Higher Dimensional Solutions: 5. Myers-Perry black holes Rob Myers; 6. Black rings Roberto Emparan and Harvey Reall; Part IV. General Properties: 7. Constraints on the topology of higher dimensional black holes Greg Galloway; 8. Blackfolds Roberto Emparan; 9. Algebraically special solutions in higher dimensions Harvey Reall; 10. Numerical construction of static and stationary black holes Toby Wiseman; Part V. Advanced Topics: 11. Black holes and branes in supergravity Don Marolf; 12. The gauge/gravity duality Juan Maldacena; 13. The fluid/gravity correspondence Veronika Hubeny, Mukund Rangamani and Shiraz Minwalla; 14. Horizons, holography and condensed matter Sean Hartnoll; Index.

  10. Higher transcription levels in ascorbic acid biosynthetic and recycling genes were associated with higher ascorbic acid accumulation in blueberry.

    PubMed

    Liu, Fenghong; Wang, Lei; Gu, Liang; Zhao, Wei; Su, Hongyan; Cheng, Xianhao

    2015-12-01

    In our preliminary study, the ripe fruits of two highbush blueberry (Vaccinium corymbosum L.) cultivars, cv 'Berkeley' and cv 'Bluecrop', were found to contain different levels of ascorbic acid. However, factors responsible for these differences are still unknown. In the present study, ascorbic acid content in fruits was compared with expression profiles of ascorbic acid biosynthetic and recycling genes between 'Bluecrop' and 'Berkeley' cultivars. The results indicated that the l-galactose pathway was the predominant route of ascorbic acid biosynthesis in blueberry fruits. Moreover, higher expression levels of the ascorbic acid biosynthetic genes GME, GGP, and GLDH, as well as the recycling genes MDHAR and DHAR, were associated with higher ascorbic acid content in 'Bluecrop' compared with 'Berkeley', which indicated that a higher efficiency ascorbic acid biosynthesis and regeneration was likely to be responsible for the higher ascorbic acid accumulation in 'Bluecrop'. PMID:26041210

  11. Profile of Pacific Higher Education.

    ERIC Educational Resources Information Center

    Research and Development Cadre, Honolulu, HI.

    Comparative data concerning institutions of higher education in the Pacific Islands are tabulated and summarized to aid in program planning, development, and implementation in that region. The jurisdictions covered are: American Samoa; Palau; the Northern Mariana Islands; Micronesia; Kosrae; Pohnpei; Truk; Yap; Guam; Hawaii; and the Marshall…

  12. Arbitration in American Higher Education.

    ERIC Educational Resources Information Center

    Clark, Bob Thompson, Ed.

    Areas of concern related to grievance arbitration in higher education are examined. Selected arbitration awards, court and National Labor Relation Board rulings, and related literature are reviewed, and probable patterns and trends in arbitration are identified. Potential conflicts between collective bargaining and collegiality (self-governance)…

  13. Electronic Assessment in Higher Education

    ERIC Educational Resources Information Center

    Brink, Roelien; Lautenbach, Geoffrey

    2011-01-01

    Assessment is an important cornerstone of education. A world trend in staying abreast of the latest developments in the field of information and communication technology (ICT) has led to an increased demand for electronic assessment in education circles. The critical need and responsibility for higher education to stay on par with the latest…

  14. Student Loans for Higher Education

    ERIC Educational Resources Information Center

    Simons, Charlene Wear

    2008-01-01

    Student loans are a rapidly growing $85 billion a year industry fueled by the substantial higher economic returns associated with a college education, increased demand from students and their parents, and grant and scholarship funds that have not kept pace with rising school tuition and fees. This report describes federally subsidized and…

  15. Transnational Higher Education in Uzbekistan

    ERIC Educational Resources Information Center

    Sia, E. K.

    2014-01-01

    This paper provides an overview of transnational higher education (THE) in Uzbekistan. It includes a brief account of THE current and future market trends. The data, gathered from a literature search, show that the demand for THE (off-campus) is growing even faster than the demand for international (on-campus) programmes. This paper then provides…

  16. The Opening of Higher Education

    ERIC Educational Resources Information Center

    Matkin, Gary W.

    2012-01-01

    In a 1974 report presented to the Organisation for Economic Co-operation and Development (OECD), Martin Trow laid out a framework for understanding large-scale, worldwide changes in higher education. Trow's essay also pointed to the problems that "arise out of the transition from one phase to another in a broad pattern of development of higher…

  17. Elevating the Higher Education Beat.

    ERIC Educational Resources Information Center

    Harney, John O.

    1998-01-01

    Problems in media coverage of higher education in New England are examined, noting high turnover in journalists covering colleges and universities and journalists' lack of time to visit campuses. What coverage there is appears to be focused heavily on a few prestigious institutions and state colleges where news is easily gathered from bureaucrats…

  18. Refocusing Higher Education Budget Development.

    ERIC Educational Resources Information Center

    Illinois State Board of Higher Education, Springfield.

    This report proposes changes to the current higher education budget development process in Illinois in order to provide more information to institutions and to make the process more inclusive and open. It argues that budget development should be goal-based and accountable, responsive, incentive-based, recognize diversity of institutions, stable…

  19. Higher Ambitions Summit. Rapporteur Report

    ERIC Educational Resources Information Center

    Nash, Ian

    2014-01-01

    The Sutton Trust and Pearson two-day summit on higher ambitions in apprenticeships and vocational education drew more than 120 leaders in education, training and employment, policy makers, academics, and researchers to London. Delegates heard from political leaders stressing the importance they attach to high-quality apprenticeships. Presentations…

  20. Student Influence and Higher Education.

    ERIC Educational Resources Information Center

    Juola, Arvo E.

    Since 1965, student views and feelings have influenced great changes in higher education, sometimes to the detriment of long-term interests in academic institutions and colleges. One conspicuous recent trend is the desire of college students for more influence, impact, or power. Other prevalent attitudes may be characterized as a desire to be…

  1. Catholic Higher Education as Mission

    ERIC Educational Resources Information Center

    Lowery, Daniel

    2012-01-01

    This article uses the work of Anthony J. Gittins to reframe our understanding of Catholic higher education as mission. The broad adoption of this framework would require a common intellectual foundation, the possibility of which is dismissed by many. An accessible ontology is implied, however, in the existential analysis and theology of Karl…

  2. Gender Issues within Higher Education

    ERIC Educational Resources Information Center

    European Students' Union (NJ1), 2008

    2008-01-01

    This handbook functions as a crown on the European Students' Union's work on gender equality over the past two years. Since the establishment of the Gender Equality Committee, a lot of work has been done to improve gender equality in higher education generally, and in student unions more particularly. This handbook gathers the experiences and…

  3. Evaluating Teaching in Higher Education

    ERIC Educational Resources Information Center

    Weinberg, Bruce A.; Hashimoto, Masanori; Fleisher, Belton M.

    2009-01-01

    The authors develop an original measure of learning in higher education, based on grades in subsequent courses. Using this measure of learning, they show that student evaluations are positively related to current grades but unrelated to learning once current grades are controlled. They offer evidence that the weak relationship between learning and…

  4. Class Struggle in Higher Education

    ERIC Educational Resources Information Center

    Clawson, Dan; Leiblum, Mishy

    2008-01-01

    Public higher education has undergone a process similar to that in the national polity: a one-sided struggle by those with power to shape the institution to be more market driven, more focused on what will generate (non-state) revenues, more dominated by top administrators, and less concerned about the working class and people of color. This…

  5. A Balanced Higher Education System

    ERIC Educational Resources Information Center

    Brown, Roger

    2011-01-01

    This article explores what is meant by "a balanced higher education system". It argues that the Clarkian "triangle of coordination" (Clark, 1983) and the more recent model of Martinez and Richardson (2003) should be replaced by one that distinguishes between "self" and "collective" interests in both the academy and the wider society. Such a scheme…

  6. Higher Education's Coming Leadership Crisis

    ERIC Educational Resources Information Center

    Appadurai, Arjun

    2009-01-01

    The full impact of the current recession on American higher education remains uncertain, but drops in applications, faculty autonomy and job security, frozen salaries and hiring processes, and scaling back of new facilities and programs are already being seen. American colleges face tough times ahead for teaching, research, and capital projects…

  7. Digital Resilience in Higher Education

    ERIC Educational Resources Information Center

    Weller, Martin; Anderson, Terry

    2013-01-01

    Higher education institutions face a number of opportunities and challenges as the result of the digital revolution. The institutions perform a number of scholarship functions which can be affected by new technologies, and the desire is to retain these functions where appropriate, whilst the form they take may change. Much of the reaction to…

  8. Student Success in Higher Education

    ERIC Educational Resources Information Center

    American Federation of Teachers (NJ), 2011

    2011-01-01

    Often, campus policies and public debate on student success has been too heavily focused on standardization of curriculum and assessment and on an unacceptably flawed graduation rate formula. The report, "Student Success in Higher Education," brings the voice of front-line faculty and staff into student success policymaking to ensure that ideas…

  9. American Higher Education in Transition

    ERIC Educational Resources Information Center

    Ehrenberg, Ronald G.

    2011-01-01

    American higher education is in transition and if there ever was a "golden age" for faculty, it probably is behind us. The best historical data on the composition of faculty is collected annually by the American Mathematical Society. Between 1967 and 2009, the share of full-time faculty with PhDs remained constant at about 90 percent at doctoral…

  10. Project Management in Higher Education

    ERIC Educational Resources Information Center

    Alpert, Shannon Atkinson

    2011-01-01

    This study identified factors that influenced the use of project management in higher education research projects. Using a qualitative grounded theory approach that included in-depth interviews with assistant professors, the researcher examined how these individuals were using project management processes and tools and factors that enabled,…

  11. History of Higher Education, 1995.

    ERIC Educational Resources Information Center

    Geiger, Robert L., Ed.

    1995-01-01

    This annual compilation presents four papers on different aspects of the history of higher education in Europe and the United States. The first paper is "The Rights of Man and the Rites of Youth: Fraternity and Riot at Eighteenth Century Harvard" by Leon Jackson. This paper argues that the lines of division in the student body at…

  12. History of Higher Education, 1996.

    ERIC Educational Resources Information Center

    Geiger, Robert L., Ed.

    1996-01-01

    The four papers in this annual volume on the history of higher education cover some of the changes that evolved over the years in various U.S. institutions. The first paper is: "The Harvard Tutors: The Beginning of an Academic Profession, 1690-1825" (John D. Burton), which discusses the shift from Harvard's original tutorship model to its modern…

  13. Mobile Learning in Higher Education

    ERIC Educational Resources Information Center

    Fraga, Lucretia M.

    2012-01-01

    This mixed method research study investigated the beliefs of university faculty regarding mobile learning. As well as to determine if providing technology professional development to university faculty supports the increase of mobile learning opportunities in higher education. This study used the Beliefs About Mobile Learning Inventory (BAMLI) to…

  14. Gender Equity in Higher Education

    ERIC Educational Resources Information Center

    Washington Higher Education Coordinating Board, 2006

    2006-01-01

    Title IX of the Education Amendments of 1972 bans discrimination in schools receiving federal financial assistance with regard to both academics and athletics. The law has helped ensure that women have access to both academic and athletic opportunities at most higher education institutions in the United States, dramatically increasing the range…

  15. Higher Education Profiles & Trends 2013

    ERIC Educational Resources Information Center

    Tennessee Higher Education Commission, 2013

    2013-01-01

    The statute [T.C.A. Section 49-7-202(c)(7)] requires the Tennessee Higher Education Commission to prepare a biennial report for the governor and the general assembly, "commenting upon major developments, trends, new policies, budgets and financial considerations which in the judgment of the commission will be useful to the governor and to the…

  16. The Battle for Higher Standards

    ERIC Educational Resources Information Center

    Luna, Tom; Rush, Mike; Gramer, Rod; Stewart, Roger

    2014-01-01

    To remain internationally competitive, states needed clearer, higher, and comparable K-12 learning standards aligned with college and career expectations, and as ambitious as those of the countries that lead the world in education. Idaho's old academic standards were not preparing students for postsecondary education, which contributed to the…

  17. American Higher Education in Decline.

    ERIC Educational Resources Information Center

    Ashworth, Kenneth H.

    The decline in the quality of American higher education over the past several decades and the ramifications of this phenomena are discussed in this book. It is suggested that in responding to modern egalitarianism and the need to attract students, colleges and universities have initiated innovative programs, noncampuses, and nontraditional degrees…

  18. On Education: The Higher Education.

    ERIC Educational Resources Information Center

    West, Thomas G.

    1980-01-01

    Higher education is described as a name for the highest formation of soul and mind, and the highest goal of education is "wisdom." Practical wisdom and theoretical wisdom are seen as exemplified at their peak in the comprehension of the genuine statesman and the genuine philosopher. (MLW)

  19. Higher Education Evaluation in Germany

    ERIC Educational Resources Information Center

    Schmidt, Bernhard; von Hippel, Aiga; Tippelt, Rudolf

    2010-01-01

    Quality assurance in the area of higher education has become a central issue among both politicians and scientists. University evaluations which refer to both research and teaching are an important element of quality assurance. The present contribution starts out by determining the different components of quality at universities according to…

  20. Danger: Work on Higher Levels.

    ERIC Educational Resources Information Center

    Lapointe, Archie E.

    The Assessment Policy Committee of the National Assessment of Educational Progress (NAEP) has directed the NAEP staff to focus the 1985-86 Assessments of Reading, Mathematics, Science, and Computer Competence on the higher-order skills. Each Learning Area Committee worked independently developing three-dimensional models. These defined what could…

  1. Higher Education: Building Connecticut's Workforce

    ERIC Educational Resources Information Center

    DeLisa, Cynthia L.; Placzek, Dana W.

    2004-01-01

    The Connecticut Departments of Labor (DOL) and Higher Education (DHE), working in close collaboration with the University of Connecticut, Connecticut State University, Connecticut Community Colleges and Charter Oak State College, present this comprehensive report on employment outcomes for graduates of the State's public college system. This…

  2. Higher Education and the Law.

    ERIC Educational Resources Information Center

    Edwards, Harry T.; Nordin, Virginia Davis

    The proliferation of laws, regulations, and judicial opinions affecting higher education and the nature of the impact of these laws on the academic community are examined. Designed for use by both students and practitioners, the book employs the "case method" design based on the belief that law cases furnish the best sources for study and review…

  3. Epistemological Development in Higher Education

    ERIC Educational Resources Information Center

    Richardson, John T. E.

    2013-01-01

    Research has been carried out on students' epistemological development in higher education for at least 50 years. Researchers on both sides of the Atlantic have converged on accounts that describe students' epistemological development in terms of a sequence or hierarchy of qualitatively distinct stages or positions. The rich qualitative data…

  4. Social Stratification in Higher Education

    ERIC Educational Resources Information Center

    Grodsky, Eric; Jackson, Erika

    2009-01-01

    Background/Context: Over the past half century, scholars in a variety of fields have contributed to our understanding of the relationship between higher education and social stratification. We review this literature, highlighting complementarities and inconsistencies. Purpose/Objective/Research Question/Focus of Study: We situate our review of the…

  5. Internal Audit in Higher Education.

    ERIC Educational Resources Information Center

    Holmes, Alison, Ed.; Brown, Sally, Ed.

    This book describes a range of examples of internal audit in higher education as part of a process of the exchange of good practice. The book recognizes well-established links with audit theory from other contexts and makes use of theoretical perspectives explored in the financial sector. The chapters are: (1) "Quality Audit Issues" (Sally Brown…

  6. Disability Discrimination in Higher Education.

    ERIC Educational Resources Information Center

    Weber, Mark C.

    2002-01-01

    Reviews developments in 2000 in the law of disability discrimination as it relates to higher education, which falls into five categories: (1) definition of a qualified individual; (2) accommodations, access, undue burden, and fundamental alteration of programs; (3) intentional discrimination, harassment, and retaliation; (4) Eleventh Amendment…

  7. Employment Discrimination in Higher Education.

    ERIC Educational Resources Information Center

    Hustoles, Thomas P.; Griffin, Oren R.

    2000-01-01

    Reviews court decisions related to employment discrimination in higher education. The most significant development was a series of cases affirming that Eleventh Amendment immunity from private money damage claims brought pursuant to various federal employment discrimination statutes applied to state colleges and universities. (SLD)

  8. Disability Discrimination in Higher Education.

    ERIC Educational Resources Information Center

    Weber, Mark C.

    2000-01-01

    Reviews court cases in 1999 related to disability discrimination in higher education focusing on the Americans with Disabilities Act and section 504 of the Rehabilitation Act of 1973. The "Garrett" case regarding Eleventh Amendment immunity is the case most likely to be significant in the development of the law of disability discrimination. (SLD)

  9. Higher Education and European Regionalism.

    ERIC Educational Resources Information Center

    Paterson, Lindsay

    2001-01-01

    Speculates about the relationship between two fundamental social changes occurring in Europe: the development of a mass higher education system and the slow decay of the old states that were inherited from the 19th century, eroded from below by various movements for national and regional autonomy, and eroded from above by the growing power and…

  10. Academic Rewards in Higher Education.

    ERIC Educational Resources Information Center

    Lewis, Darrel R., Ed.; Becker, William E., Jr., Ed.

    A colloquium series in higher education at the University of Minnesota in the fall and winter of 1977-1978 examined the influence of academic reward systems on faculty behavior and academic productivity. These essays are the collective results of their findings and recommendations. Essays include: "Perspectives from Psychology: Financial…

  11. Collective Bargaining in Higher Education.

    ERIC Educational Resources Information Center

    Mannix, Thomas M., Ed.

    The 1975 conference of the National Center for the Study of Collective Bargaining in Higher Education covered a wide range of topics. The proceedings included discussion of such areas as collective bargaining's impact on governance; the U.S. Congress and public employee legislation; federal legislation from a management perspective and from a…

  12. Women in Higher Education, 1997.

    ERIC Educational Resources Information Center

    Wenniger, Mary Dee, Ed.

    1997-01-01

    The 12 issues of this newsletter focus on issues concerned with women students, faculty, and administrators in higher education. Each issue includes feature articles, news items, and profiles of significant people. The issues' main articles address: women in athletics; leadership development for women; the first year in academic administration;…

  13. Faculty Retention in Higher Education

    ERIC Educational Resources Information Center

    Soomro, Tariq Rahim; Ahmad, Reyaz

    2013-01-01

    Criteria for retaining or firing a highly qualified faculty in higher education in many cases are vague and unclear. This situation is neither a comfortable, nor a healthy, both for the faculty and the administration. Stakeholders have enough reason to blame each other in the absence of transparent mechanism. This paper proposes a transparent…

  14. Higher Education in American Society.

    ERIC Educational Resources Information Center

    Altbach, Philip G., Ed.; Berdahl, Robert O., Ed.

    The wide-ranging impact of social, political and economic forces on higher education and their specific consequences for faculty, students, and administrators is addressed within the broad context of autonomy and accountability. The book is organized around several themes. The first section discusses such basic issues as: the historical…

  15. State Budgeting for Higher Education.

    ERIC Educational Resources Information Center

    Glenny, Lyman A.

    1976-01-01

    State government is and is expected to remain the chief source of funding for higher education. At the same time, the state is confronted with serious policy issues relating to support of research, public services, and adult education, to falling enrollments in some public institutions, to the probable closure of some private liberal arts colleges…

  16. Systems Applications in Higher Education.

    ERIC Educational Resources Information Center

    Schure, Alexander

    This paper discusses the application of computers for higher education and describes a philosophy and initial application of an accountability system that can aid in coping with the problems of occupationally related schools. Discussed are: (1) the role of computers in systems application; (2) the need for systems related information: the…

  17. Disability Studies in Higher Education

    ERIC Educational Resources Information Center

    Taylor, Steven J.

    2011-01-01

    As a topic of study, disability is not new at institutions of higher education. Psychological and intellectual disabilities have been of interest in psychiatry and psychology at least since the late 1800s and early 1900s. The post-World War II era, in particular, witnessed the rapid expansion of academic programs in special education, vocational…

  18. Higher Education as Virtual Conversation

    ERIC Educational Resources Information Center

    Robbins-Bell, Sarah

    2008-01-01

    Whether or not it is an accurate portrayal, the old stereotype of higher education is the lecture hall, where students sit passively and take notes from a wise professor whose experience and knowledge can be shared only in the classroom. The professor's role is to dispense information, and the students' role is to receive it. However idealistic…

  19. Supercomplexity in Higher Education Kinesiology

    ERIC Educational Resources Information Center

    Block, Betty A.; Estes, Steve

    2011-01-01

    This article employs Barnett's (2004) specifications of the aspects that describe the times of "supercomplexity." This term characterizes the challenges universities are facing regarding the expanding and competing forces that are affecting higher education, particularly in the West. Outside forces related to globalization, digital technologies,…

  20. Higher Education for Our Time

    ERIC Educational Resources Information Center

    Burnett, Dana D.; Collins, Natalia D.

    2010-01-01

    Public higher education is currently experiencing a decline in financial support from state governments, an acceleration of enrollment growth, and a shift from a transformational to a transactional student relationship. Private institutions are also struggling with increasing operational costs, and decreases in revenue from endowments and…

  1. Fiscal Issues in Higher Education.

    ERIC Educational Resources Information Center

    Rigolot, Carol, Ed.

    Forty colleges and life insurance presidents met to discuss key historical and contemporary factors influencing fiscal management in higher education, including inflation, salaries, diminishing enrollment figures, energy costs, federal regulations and the increasing cost of research. Differences and similarities between business and academia were…

  2. Women in Higher Education Management.

    ERIC Educational Resources Information Center

    Commonwealth Secretariat, London (England).

    This volume contains 11 papers on the under-representation of women in higher education management in Bahrain, Finland, France, India, Indonesia, Malaysia, Nigeria, Peru, the United States and Canada, the South Pacific and the West Indies. All papers were written by women vice-chancellors, presidents and senior managers of universities in those…

  3. Customer Service in Higher Education.

    ERIC Educational Resources Information Center

    Sines, Robert G., Jr.; Duckworth, Eric A.

    1994-01-01

    It is argued that colleges and universities need to understand the importance of customer service in student retention, particularly in a competitive marketplace. Customer service concepts that work in the private sector are seen as useful in higher education, and a model is proposed. (MSE)

  4. Art in American Higher Institutions.

    ERIC Educational Resources Information Center

    Feldman, Edmund Burke, Ed.

    This volume of 11 articles contains a comprehensive statement about the visual arts as they are encountered in post-secondary education. The articles are: (1) "Art and the Liberal Arts: A Trivial, Artificial, Irrelevant Antagonism" by Albert Bush-Brown; (2) "The Arts in Higher Education: A Question of Priorities" by Lawrence Dennis; (3) "Access to…

  5. Today's Higher Education IT Workforce

    ERIC Educational Resources Information Center

    Bichsel, Jacqueline

    2014-01-01

    The professionals making up the current higher education IT workforce have been asked to adjust to a culture of increased IT consumerization, more sourcing options, broader interest in IT's transformative potential, and decreased resources. Disruptions that include the bring-your-own-everything era, cloud computing, new management practices,…

  6. 2011 Higher Education Sustainability Review

    ERIC Educational Resources Information Center

    Wagner, Margo, Ed.

    2012-01-01

    Looking through the lens of AASHE Bulletin stories in 2011, this year's review reveals an increased focus on higher education access, affordability, and success; more green building efforts than ever before; and growing campus-community engagement on food security, among many other achievements. Contributors include James Applegate (Lumina…

  7. Stakeholder Relationships in Higher Education

    ERIC Educational Resources Information Center

    Kettunen, Juha

    2015-01-01

    The purpose of this study is to develop a stakeholder map to describe the most important stakeholders and the process of stakeholder relationships in higher education. According to the perspective of the balanced scorecard, the classification of stakeholders integrates stakeholders into strategic management. Stakeholder maps are essential in…

  8. Simulation Models in Higher Education.

    ERIC Educational Resources Information Center

    Morrisseau, James J.

    1973-01-01

    This paper, adapted from a Society for College and University Planning conference, discusses cost simulation models in higher education. Emphasis is placed on the art of management, mini-models vs. maxi-models, the useful model, the reporting problem, anatomy of failure, information vs. action, and words of caution. (MJM)

  9. Collective Bargaining in Higher Education.

    ERIC Educational Resources Information Center

    Soberman, Daniel A.; And Others

    Papers are presented from a seminar on collective bargaining in higher education sponsored by the Center for Educational Management Studies of the University of Hawaii. The seminar was designed to address the similarities and differences among various countries and to draw on the experiences of Canada and Europe as they may relate to collective…

  10. Rethinking Higher Education Capital Finance.

    ERIC Educational Resources Information Center

    King, George A.

    1988-01-01

    Capital finance in institutions of higher education is analyzed in light of changes in the Tax Reform Act of 1986 affecting the ability of institutions to finance capital projects and the likelihood of changes in the government's view of tax-exempt financing. The options for colleges and universities are analyzed in the following areas: (1)…

  11. Institutionalizing Diversity: Transforming Higher Education

    ERIC Educational Resources Information Center

    McRae-Yates, Velda

    2009-01-01

    This case study examines plausible efforts to institutionalize diversity in a higher education setting so it becomes part of the strategic mission, and permeates the interactions, discussions, and operations. Review of literature, surveys, and in-depth interviews are conducted at a Massachusetts institution to gather information from faculty,…

  12. Sustainability: Higher Education's New Fundamentalism

    ERIC Educational Resources Information Center

    Peterson, Rachelle; Wood, Peter W.

    2015-01-01

    "Sustainability" is a key idea on college campuses in the United States and the rest of the Western world. To the unsuspecting, sustainability is just a new name for environmentalism. This report is the first in-depth critical study of the sustainability movement in higher education. The focus of this study is on how the sustainability…

  13. Expression of TGF-β3 in isolated fibroblasts from foreskin

    PubMed Central

    Mahmoudi Rad, Mahnaz; Mahmoudi Rad, Niki; Mirdamadi, Yasaman

    2015-01-01

    Background: The multifunctional transforming growth factor beta (TGF-β) is a glycoprotein that exists in three isoforms. TGF-β3 expression increases in fetal wound healing and reduces fibronectin and collagen I and III deposition, and also improves the architecture of the neodermis which is a combination of blood vessels and connective tissue during wound healing. Fibroblasts are key cells in the wound healing process. TGF-β3 plays a critical role in scar-free wound healing and fibroblast actions in the wound healing process. The aim of this study was to express the TGF-β3 gene (tgf-b3) in human foreskin fibroblasts (HFF’s). Methods: We obtained HFF’s from a newborn and a primary fibroblast culture was prepared. The cells were transfected with TGF-β3-pCMV6-XL5 plasmid DNA by both lipofection and electroporation. Expression of TGF-β3 was measured by enzyme-linked immunosorbent assay (ELISA). Results: The highest TGF-β3 expression (8.3-fold greater than control) was obtained by lipofection after 72 hours using 3 µl of transfection reagent. Expression was 1.4-fold greater than control by electroporation. Conclusions: In this study, we successfully increased TGF-β3 expression in primary fibroblast cells. In the future, grafting these transfected fibroblasts onto wounds can help the healing process without scarring. PMID:26989741

  14. Gene expression profiling reveals molecularly and clinically distinct subtypes of glioblastoma multiforme

    PubMed Central

    Liang, Yu; Diehn, Maximilian; Watson, Nathan; Bollen, Andrew W.; Aldape, Ken D.; Nicholas, M. Kelly; Lamborn, Kathleen R.; Berger, Mitchel S.; Botstein, David; Brown, Patrick O.; Israel, Mark A.

    2005-01-01

    Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by genetic instability, intratumoral histopathological variability, and unpredictable clinical behavior. We investigated global gene expression in surgical samples of brain tumors. Gene expression profiling revealed large differences between normal brain samples and tumor tissues and between GBMs and lower-grade oligodendroglial tumors. Extensive differences in gene expression were found among GBMs, particularly in genes involved in angiogenesis, immune cell infiltration, and extracellular matrix remodeling. We found that the gene expression patterns in paired specimens from the same GBM invariably were more closely related to each other than to any other tumor, even when the paired specimens had strikingly divergent histologies. Survival analyses revealed a set of ≈70 genes more highly expressed in rapidly progressing tumors that stratified GBMs into two groups that differed by >4-fold in median duration of survival. We further investigated one gene from the group, FABP7, and confirmed its association with survival in two unrelated cohorts totaling 105 patients. Expression of FABP7 enhanced the motility of glioma-derived cells in vitro. Our analyses thus identify and validate a prognostic marker of both biologic and clinical significance and provide a series of putative markers for additional evaluation. PMID:15827123

  15. Enhanced protein expression in the baculovirus/insect cell system using engineered SUMO fusions.

    PubMed

    Liu, Li; Spurrier, Joshua; Butt, Tauseef R; Strickler, James E

    2008-11-01

    Recombinant protein expression in insect cells varies greatly from protein to protein. A fusion tag that is not only a tool for detection and purification, but also enhances expression and/or solubility would greatly facilitate both structure/function studies and therapeutic protein production. We have shown that fusion of SUMO (small ubiquitin-related modifier) to several test proteins leads to enhanced expression levels in Escherichia coli. In eukaryotic expression systems, however, the SUMO tag could be cleaved by endogenous desumoylase. In order to adapt SUMO-fusion technology to these systems, we have developed an alternative SUMO-derived tag, designated SUMOstar, which is not processed by native SUMO proteases. In the present study, we tested the SUMOstar tag in a baculovirus/insect cell system with several proteins, i.e. mouse UBP43, human tryptase beta II, USP4, USP15, and GFP. Our results demonstrate that fusion to SUMOstar enhanced protein expression levels at least 4-fold compared to either the native or His(6)-tagged proteins. We isolated active SUMOstar tagged UBP43, USP4, USP15, and GFP. Tryptase was active following cleavage with a SUMOstar specific protease. The SUMOstar system will make significant impact in difficult-to-express proteins and especially to those proteins that require the native N-terminal residue for function. PMID:18713650

  16. Extremal higher spin black holes

    NASA Astrophysics Data System (ADS)

    Bañados, Máximo; Castro, Alejandra; Faraggi, Alberto; Jottar, Juan I.

    2016-04-01

    The gauge sector of three-dimensional higher spin gravities can be formulated as a Chern-Simons theory. In this context, a higher spin black hole corresponds to a flat connection with suitable holonomy (smoothness) conditions which are consistent with the properties of a generalized thermal ensemble. Building on these ideas, we discuss a definition of black hole extremality which is appropriate to the topological character of 3 d higher spin theories. Our definition can be phrased in terms of the Jordan class of the holonomy around a non-contractible (angular) cycle, and we show that it is compatible with the zero-temperature limit of smooth black hole solutions. While this notion of extremality does not require supersymmetry, we exemplify its consequences in the context of sl(3|2) ⊕ sl(3|2) Chern-Simons theory and show that, as usual, not all extremal solutions preserve supersymmetries. Remarkably, we find in addition that the higher spin setup allows for non-extremal supersymmetric black hole solutions. Furthermore, we discuss our results from the perspective of the holographic duality between sl(3|2) ⊕ sl(3|2) Chern-Simons theory and two-dimensional CFTs with W (3|2) symmetry, the simplest higher spin extension of the N = 2 super-Virasoro algebra. In particular, we compute W (3|2) BPS bounds at the full quantum level, and relate their semiclassical limit to extremal black hole or conical defect solutions in the 3 d bulk. Along the way, we discuss the role of the spectral flow automorphism and provide a conjecture for the form of the semiclassical BPS bounds in general N = 2 two-dimensional CFTs with extended symmetry algebras.

  17. Bisphenol A disrupts gene expression in human placental trophoblast cells.

    PubMed

    Rajakumar, Chandrew; Guan, Haiyan; Langlois, David; Cernea, Maria; Yang, Kaiping

    2015-06-01

    This study examined the effect of bisphenol A (BPA) on human placental gene expression using primary trophoblast cells as an in vitro model system. Trophoblast cells were isolated from human placentas at term, cultured and then exposed to environmentally relevant concentrations of BPA (0.1-2 μg/ml) for up to 24h, after which levels of 11β-HSD2 mRNA, protein and activity were determined by standard radiometric conversion assay, western blotting, and qRT-PCR, respectively. The mRNA levels of several other prominent placental hormones/factors were also assessed by qRT-PCR. BPA dramatically increased levels of 11β-HSD2 activity, protein and mRNA in a time- and concentration-dependent manner (> 4-fold). BPA also augmented aromatase, glucose transporter-1, CRH, and hCG mRNA levels while reducing the level of leptin mRNA. These findings demonstrate that BPA severely disrupts human placental gene expression in vitro, which suggests that exposure to BPA may contribute to altered placental function and consequent pregnancy complications. PMID:25784278

  18. Design and expression of human alpha7 nicotinic acetylcholine receptor extracellular domain mutants with enhanced solubility and ligand-binding properties.

    PubMed

    Zouridakis, Marios; Zisimopoulou, Paraskevi; Eliopoulos, Elias; Poulas, Konstantinos; Tzartos, Socrates J

    2009-02-01

    In order to facilitate structural studies of the extracellular domain (ECD) of human alpha7 nicotinic acetylcholine receptor (nAChR), we designed several mutants, since the wild-type-ECD forms large oligomers and microaggregates, and expressed them in the yeast Pichia pastoris. Mutant design was based on a 3D model of human alpha7-nAChR-ECD, constructed using as templates the X-ray crystal structure of the homologous acetylcholine-binding protein (AChBP) and the electron microscopy structure of the Torpedo alpha-nAChR-ECD. At least one mutant, mut10, carrying six single-point mutations (Phe3Tyr, Val69Thr, Cys116Ser, Ile165Thr, Val177Thr, Phe187Tyr) and the replacement of its Cys-loop with the corresponding and more hydrophilic AChBP Cys-loop, was expressed with a 4-fold higher expression yield (1.2 mg/L) than the wild-type alpha7-ECD, existing exclusively as a soluble oligomeric, probably pentameric, form, at concentrations up to at least 10 mg/mL, as judged by gel filtration and dynamic light scattering. This mutant displayed a significantly improved (125)I-alpha-bungarotoxin-binding affinity (K(d)=24 nM) compared to the wild-type-ECD (K(d)=70 nM), the binding being inhibited by unlabelled alpha-bungarotoxin, d-tubocurarine or nicotine (K(i) of 21.5 nM, 127 microM and 17.5 mM, respectively). Circular dichroism studies of mut10 revealed (a) a similar secondary structure composition ( approximately 5% alpha-helix, approximately 45% beta-sheet) to that of the AChBP, Torpedo alpha-nAChR-ECD, and mouse alpha1-nAChR-ECD, (b) a well-defined tertiary structure and (c) binding of small cholinergic ligands at micromolar concentrations. Furthermore, electron microscopy showed well-assembled, probably pentameric, particles of mut10. Finally, since deglycosylation did not alter its solubility or ligand-binding properties, mut10, in either its glycosylated or deglycosylated form, is a promising alpha7-ECD mutant for structural studies, useful for the rational drug design to

  19. EDITORIAL: Deeper, broader, higher, better?

    NASA Astrophysics Data System (ADS)

    Dobson, Ken

    1998-07-01

    Honorary Editor The standard of educational achievement in England and Wales is frequently criticized, and it seems to be an axiom of government that schools and teachers need to be shaken up, kept on a tight rein, copiously inspected, shamed and blamed as required: in general, subjected to the good old approach of: ' Find out what Johnny is doing and tell him to stop.' About the only exception to this somewhat severe attitude is at A-level, where the standard is simply golden. Often, comparisons are made between the performance of, say, English children and that of their coevals in other countries, with different customs, systems, aims and languages. But there has been a recent comparison of standards at A-level with a non-A-level system of pre-university education, in an English-speaking country that both sends students to English universities and accepts theirs into its own, and is, indeed, represented in the UK government at well above the level expected from its ethnical weighting in the population. This semi-foreign country is Scotland. The conclusions of the study are interesting. Scotland has had its own educational system, with `traditional breadth', and managed to escape much of the centralized authoritarianism that we have been through south of the border. It is interesting to note that, while for the past dozen years or so the trend in A-level Physics entries has been downwards, there has been an increase in the take-up of Scottish `Highers'. Highers is a one-year course. Is its popularity due to its being easier than A-level? Scottish students keen enough to do more can move on to the Certificate of Sixth Year Studies, and will shortly be able to upgrade a Higher Level into an Advanced Higher Level. A comparability study [ Comparability Study of Scottish Qualifications and GCE Advanced Levels: Report on Physics January 1998 (free from SQA)] was carried out by the Scottish Qualifications Authority (SQA) with the aim (amongst others) of helping

  20. Sarcoptes scabiei Mites Modulate Gene Expression in Human Skin Equivalents

    PubMed Central

    Morgan, Marjorie S.; Arlian, Larry G.; Markey, Michael P.

    2013-01-01

    The ectoparasitic mite, Sarcoptes scabiei that burrows in the epidermis of mammalian skin has a long co-evolution with its hosts. Phenotypic studies show that the mites have the ability to modulate cytokine secretion and expression of cell adhesion molecules in cells of the skin and other cells of the innate and adaptive immune systems that may assist the mites to survive in the skin. The purpose of this study was to identify genes in keratinocytes and fibroblasts in human skin equivalents (HSEs) that changed expression in response to the burrowing of live scabies mites. Overall, of the more than 25,800 genes measured, 189 genes were up-regulated >2-fold in response to scabies mite burrowing while 152 genes were down-regulated to the same degree. HSEs differentially expressed large numbers of genes that were related to host protective responses including those involved in immune response, defense response, cytokine activity, taxis, response to other organisms, and cell adhesion. Genes for the expression of interleukin-1α (IL-1α) precursor, IL-1β, granulocyte/macrophage-colony stimulating factor (GM-CSF) precursor, and G-CSF precursor were up-regulated 2.8- to 7.4-fold, paralleling cytokine secretion profiles. A large number of genes involved in epithelium development and keratinization were also differentially expressed in response to live scabies mites. Thus, these skin cells are directly responding as expected in an inflammatory response to products of the mites and the disruption of the skin’s protective barrier caused by burrowing. This suggests that in vivo the interplay among these skin cells and other cell types, including Langerhans cells, dendritic cells, lymphocytes and endothelial cells, is responsible for depressing the host’s protective response allowing these mites to survive in the skin. PMID:23940705

  1. Analysis of the Promoters Involved in Enterocin AS-48 Expression

    PubMed Central

    Cebrián, Rubén; Rodríguez-Ruano, Sonia; Martínez-Bueno, Manuel; Valdivia, Eva; Maqueda, Mercedes; Montalbán-López, Manuel

    2014-01-01

    The enterocin AS-48 is the best characterized antibacterial circular protein in prokaryotes. It is a hydrophobic and cationic bacteriocin, which is ribosomally synthesized by enterococcal cells and post-translationally cyclized by a head-to-tail peptide bond. The production of and immunity towards AS-48 depend upon the coordinated expression of ten genes organized in two operons, as-48ABC (where genes encoding enzymes with processing, secretion, and immunity functions are adjacent to the structural as-48A gene) and as-48C1DD1EFGH. The current study describes the identification of the promoters involved in AS-48 expression. Seven putative promoters have been here amplified, and separately inserted into the promoter-probe vector pTLR1, to create transcriptional fusions with the mCherry gene used as a reporter. The activity of these promoter regions was assessed measuring the expression of the fluorescent mCherry protein using the constitutive pneumococcal promoter PX as a reference. Our results revealed that only three promoters PA, P2(2) and PD1 were recognized in Enterococcus faecalis, Lactococcus lactis and Escherichia coli, in the conditions tested. The maximal fluorescence was obtained with PX in all the strains, followed by the P2(2) promoter, which level of fluorescence was 2-fold compared to PA and 4-fold compared to PD1. Analysis of putative factors influencing the promoter activity in single and double transformants in E. faecalis JH2-2 demonstrated that, in general, a better expression was achieved in presence of pAM401-81. In addition, the P2(2) promoter could be regulated in a negative fashion by genes existing in the native pMB-2 plasmid other than those of the as-48 cluster, while the pH seems to affect differently the as-48 promoter expression. PMID:24594763

  2. Higher Education for Taxpayers. WebMemo. Number 1547

    ERIC Educational Resources Information Center

    Foster, J. D.

    2007-01-01

    In this brief essay, the author reacts to a recent bill from the House Education and Workforce Committee by praising its identification of wasteful spending on higher education programs while expressing unhappiness with its creation of new entitlements and subsidies. In the author's opinion, the savings produced by the spending cut should instead…

  3. Higher dimensional loop quantum cosmology

    NASA Astrophysics Data System (ADS)

    Zhang, Xiangdong

    2016-07-01

    Loop quantum cosmology (LQC) is the symmetric sector of loop quantum gravity. In this paper, we generalize the structure of loop quantum cosmology to the theories with arbitrary spacetime dimensions. The isotropic and homogeneous cosmological model in n+1 dimensions is quantized by the loop quantization method. Interestingly, we find that the underlying quantum theories are divided into two qualitatively different sectors according to spacetime dimensions. The effective Hamiltonian and modified dynamical equations of n+1 dimensional LQC are obtained. Moreover, our results indicate that the classical big bang singularity is resolved in arbitrary spacetime dimensions by a quantum bounce. We also briefly discuss the similarities and differences between the n+1 dimensional model and the 3+1 dimensional one. Our model serves as a first example of higher dimensional loop quantum cosmology and offers the possibility to investigate quantum gravity effects in higher dimensional cosmology.

  4. Neuroticism Delays Detection of Facial Expressions

    PubMed Central

    Sawada, Reiko; Sato, Wataru; Uono, Shota; Kochiyama, Takanori; Kubota, Yasutaka; Yoshimura, Sayaka; Toichi, Motomi

    2016-01-01

    The rapid detection of emotional signals from facial expressions is fundamental for human social interaction. The personality factor of neuroticism modulates the processing of various types of emotional facial expressions; however, its effect on the detection of emotional facial expressions remains unclear. In this study, participants with high- and low-neuroticism scores performed a visual search task to detect normal expressions of anger and happiness, and their anti-expressions within a crowd of neutral expressions. Anti-expressions contained an amount of visual changes equivalent to those found in normal expressions compared to neutral expressions, but they were usually recognized as neutral expressions. Subjective emotional ratings in response to each facial expression stimulus were also obtained. Participants with high-neuroticism showed an overall delay in the detection of target facial expressions compared to participants with low-neuroticism. Additionally, the high-neuroticism group showed higher levels of arousal to facial expressions compared to the low-neuroticism group. These data suggest that neuroticism modulates the detection of emotional facial expressions in healthy participants; high levels of neuroticism delay overall detection of facial expressions and enhance emotional arousal in response to facial expressions. PMID:27073904

  5. Opportunities for IPY Higher Education and Outreach

    NASA Astrophysics Data System (ADS)

    Sparrow, E. B.

    2007-12-01

    A very rich network for higher education and outreach during the fourth International Polar Year (IPY) exists through the University of the Arctic (UArctic, www.uarctic.org), a collaborative consortium of more than ninety institutions e.g. universities, colleges, and other organizations committed to higher education and research in the North, as well as eighteen other projects submitted as Expression of Intents to the IPY Joint Committee formed into an IPY cluster. The coordination office for this UArctic IPY education outreach efforts is located at the University of Alaska Fairbanks (www.uaf.edu and www.alaska.edu/ipy). The education outreach programs reflect a continuum of learning as a lifelong process that targets different audiences and approaches: 1) primary and secondary students through teacher professional development workshops on science teaching and research; 2) undergraduate students via education and research experience; 3) graduate students through integrated education and research; 4) early career scientists/university faculty via professional development; and 5) communities/ general public via continuing education/adult education either through formal or informal ways. Additionally there are organizations such as the Association of Polar Early Career Scientists (APECS) and the Youth Steering Committee (YSC) including a newly formed group on tertiary education to nurture the next generation of polar and non-polar scientists and foster the leadership of the next IPY.

  6. Regulation of cell division in higher plants

    SciTech Connect

    Jacobs, T.W.

    1992-01-01

    Cell division is arguably the most fundamental of all developmental processes. In higher plants, mitotic activity is largely confined to foci of patterned cell divisions called meristems. From these perpetually embryonic tissues arise the plant's essential organs of light capture, support, protection and reproduction. Once an adequate understanding of plant cell mitotic regulation is attained, unprecedented opportunities will ensue for analyzing and genetically controlling diverse aspects of development, including plant architecture, leaf shape, plant height, and root depth. The mitotic cycle in a variety of model eukaryotic systems in under the control of a regulatory network of striking evolutionary conservation. Homologues of the yeast cdc2 gene, its catalytic product, p34, and the cyclin regulatory subunits of the MPF complex have emerged as ubiquitous mitotic regulators. We have cloned cdc2-like and cyclin genes from pea. As in other eukaryotic model systems, p34 of Pisum sativum is a subunit of a high molecular weight complex which binds the fission yeast p13 protein and displays histone H1 kinase activity in vitro. Our primary objective in this study is to gain baseline information about the regulation of this higher plant cell division control complex in non-dividing, differentiated cells as well as in synchronous and asynchronous mitotic cells. We are investigating cdc2 and cyclin expression at the levels of protein abundance, protein phosphorylation and quaternary associations.

  7. Conserved and Divergent Patterns of DNA Methylation in Higher Vertebrates

    PubMed Central

    Jiang, Ning; Wang, Lin; Chen, Jing; Wang, Luwen; Leach, Lindsey; Luo, Zewei

    2014-01-01

    DNA methylation in the genome plays a fundamental role in the regulation of gene expression and is widespread in the genome of eukaryotic species. For example, in higher vertebrates, there is a “global” methylation pattern involving complete methylation of CpG sites genome-wide, except in promoter regions that are typically enriched for CpG dinucleotides, or so called “CpG islands.” Here, we comprehensively examined and compared the distribution of CpG sites within ten model eukaryotic species and linked the observed patterns to the role of DNA methylation in controlling gene transcription. The analysis revealed two distinct but conserved methylation patterns for gene promoters in human and mouse genomes, involving genes with distinct distributions of promoter CpGs and gene expression patterns. Comparative analysis with four other higher vertebrates revealed that the primary regulatory role of the DNA methylation system is highly conserved in higher vertebrates. PMID:25355807

  8. Asymptotic vacua with higher derivatives

    NASA Astrophysics Data System (ADS)

    Cotsakis, Spiros; Kadry, Seifedine; Kolionis, Georgios; Tsokaros, Antonios

    2016-04-01

    We study limits of vacuum, isotropic universes in the full, effective, four-dimensional theory with higher derivatives. We show that all flat vacua as well as general curved ones are globally attracted by the standard, square root scaling solution at early times. Open vacua asymptote to horizon-free, Milne states in both directions while closed universes exhibit more complex logarithmic singularities, starting from initial data sets of a possibly smaller dimension. We also discuss the relation of our results to the asymptotic stability of the passage through the singularity in ekpyrotic and cyclic cosmologies.

  9. Higher dimensional nonlinear massive gravity

    NASA Astrophysics Data System (ADS)

    Do, Tuan Q.

    2016-05-01

    Inspired by a recent ghost-free nonlinear massive gravity in four-dimensional spacetime, we study its higher dimensional scenarios. As a result, we are able to show the constantlike behavior of massive graviton terms for some well-known metrics such as the Friedmann-Lemaitre-Robertson-Walker, Bianchi type I, and Schwarzschild-Tangherlini (anti-) de Sitter metrics in a specific five-dimensional nonlinear massive gravity under an assumption that its fiducial metrics are compatible with physical ones. In addition, some simple cosmological solutions of the five-dimensional massive gravity are figured out consistently.

  10. Global gene expression analysis of chicken caecal response to Campylobacter jejuni.

    PubMed

    Shaughnessy, Ronan G; Meade, Kieran G; McGivney, Beatrice A; Allan, Brenda; O'Farrelly, Cliona

    2011-07-15

    Campylobacter jejuni colonises the caecum of more than 90% of commercial chickens. Even though colonisation is asymptomatic, we hypothesised that it is mediated by activation of several biological pathways. We therefore used chicken-specific 20K oligonucleotide microarrays to examine global gene expression in C. jejuni-challenged birds. Microarray results demonstrate small but significant fold-changes in expression of 270 genes 20 h post-challenge, corresponding to a wide range of biological processes including cell growth, nutrient metabolism and immunological activity. Expression of NOX1 (2.3-fold) and VCAM1 (1.5-fold) were significantly increased in colonised birds (P<0.05), indicating oxidative burst and endothelial cell activation, respectively. Microarray results, supplemented by qRT-PCR analyses demonstrated increased TOPK (1.9-fold), IL17 (3.6-fold), IL21 (2.1-fold), IL7R (4-fold) and CTLA4 (2.5-fold) gene expression (P<0.05), which was suggestive of T cell mediated activity. Combined these results suggest that C. jejuni has nominal effects on global caecal gene expression in the chicken but significant changes detected are suggestive of a protective intestinal T cell response. PMID:21605915

  11. UVB-induced gene expression in the skin of Xiphophorus maculatus Jp 163 B☆

    PubMed Central

    Yang, Kuan; Boswell, Mikki; Walter, Dylan J.; Downs, Kevin P.; Gaston-Pravia, Kimberly; Garcia, Tzintzuni; Shen, Yingjia; Mitchell, David L.; Walter, Ronald B.

    2014-01-01

    Xiphophorus fish and interspecies hybrids represent long-standing models to study the genetics underlying spontaneous and induced tumorigenesis. The recent release of the Xiphophorus maculatus genome sequence will allow global genetic regulation studies of genes involved in the inherited susceptibility to UVB-induced melanoma within select backcross hybrids. As a first step toward this goal, we report results of an RNA-Seq approach to identify genes and pathways showing modulated transcription within the skin of X. maculatus Jp 163 B upon UVB exposure. X. maculatus Jp 163 B were exposed to various doses of UVB followed by RNA-Seq analysis at each dose to investigate overall gene expression in each sample. A total of 357 genes with a minimum expression change of 4-fold (p-adj < 0.05) were identified as responsive to UVB. The molecular genetic response of Xiphophorus skin to UVB exposure permitted assessment of; (1) the basal expression level of each transcript for each skin sample, (2) the changes in expression levels for each gene in the transcriptome upon exposure to increasing doses of UVB, and (3) clusters of genes that exhibit similar patterns of change in expression upon UVB exposure. These data provide a foundation for understanding the molecular genetic response of fish skin to UVB exposure. PMID:24556253

  12. Increased expression of the diabetes gene SOX4 reduces insulin secretion by impaired fusion pore expansion

    PubMed Central

    Collins, Stephan C.; Do, Hyun Woong; Hastoy, Benoit; Hugill, Alison; Adam, Julie; Chibalina, Margarita V.; Galvanovskis, Juris; Godazgar, Mahdieh; Lee, Sheena; Goldsworthy, Michelle; Salehi, Albert; Tarasov, Andrei I.; Rosengren, Anders H.; Cox, Roger; Rorsman, Patrik

    2016-01-01

    The transcription factor Sox4 has been proposed to underlie the increased type-2 diabetes risk linked to an intronic SNP in CDKAL1. In a mouse model expressing a mutant form of Sox4, glucose-induced insulin secretion is reduced by 40% despite normal intracellular Ca2+ signalling and depolarization-evoked exocytosis. This paradox is explained by a 4-fold increase in kiss-and-run exocytosis (as determined by single-granule exocytosis measurements), in which the fusion pore connecting the granule lumen to the exterior only expands to a diameter of 2 nm that does not allow the exit of insulin. Microarray analysis indicated that this correlated with an increased expression of the exocytosis-regulating protein Stxbp6. In a large collection of human islet preparations (n=63), STXBP6 expression and GIIS correlated positively and negatively with SOX4 expression, respectively. Overexpression of SOX4 in the human insulin-secreting cell EndoC-βH2 interfered with granule emptying and inhibited hormone release, the latter effect was reversed by silencing of STXBP6. These data suggest that increased SOX4 expression inhibits insulin secretion and increased diabetes risk by upregulation of STXBP6 and an increase in kiss-and-run exocytosis at the expense of full fusion. We propose that pharmacological interventions promoting fusion pore expansion may be effective in diabetes therapy. PMID:26993066

  13. Forest bound estuaries are higher methane emitters than paddy fields: A case of Godavari estuary, East Coast of India

    NASA Astrophysics Data System (ADS)

    Krupadam, Reddithota J.; Ahuja, Rashmi; Wate, Satish R.; Anjaneyulu, Yerramilli

    In the Godavari estuary, ambient methane concentrations were monitored for a period of 5 years and the data reveals that the estuary sampling stations have shown a high average maximum value of methane 14.8 ppmv while nearby paddy field sampling stations the methane concentration were 3-4 fold lower than the estuary. The acidic nature of the estuary soils (pH 5.8-6.2) along with redox potential -120mV favours high methane emissions. The samples collected from the edge of the estuary have shown 0.12-0.15% of Fe wherein ambient methane concentrations were 4.8-5.6 ppmv. It was observed that the anoxic condition with high available iron in the soil improves anaerobic decomposition of organic matter to produce methane. The litter production from nearby mangrove vegetation in the estuary is approximately 22,000 tons/annum is a causative factor for higher methane emissions. Remote sensing data was used and developed thematic maps for spatial and temporal distribution of methane using geographical information system. The seasonal trend showed high ambient concentration of methane in winter season, which is mainly due to high moisture content, (OHṡ) radical and lower temperature. The results suggest that high organic matter (2.5-4.2%) along with soil conditions in the estuary are influencing for higher methane emissions, while in paddy fields the available organic matter for methanogenesis is limited.

  14. Atlantic cod (Gadus morhua) CC chemokines: Diversity and expression analysis.

    PubMed

    Borza, Tudor; Stone, Cynthia; Rise, Matthew L; Bowman, Sharen; Johnson, Stewart C

    2010-08-01

    Chemokines are a large, diverse group of small cytokines that can be classified into several families, including the CC chemokines that are characterized by two adjacent cysteines near their amino terminus. CC chemokines play a pivotal role in host defense mechanisms by inducing leukocyte chemotaxis under physiological and inflammatory conditions. Analysis of CC chemokines from teleost fishes indicates that the number of CC chemokine genes and their tissue expression patterns vary largely in this group of vertebrates. Here we describe 32 distinct CC chemokine sequences from Atlantic cod (Gadus morhua) identified by analysis of approximately 206,000 ESTs. Phylogenetic analysis of Atlantic cod CC chemokines placed these sequences in seven clusters, most likely resulting from species-specific gene duplications, and two unique sequences; 12 of these CC chemokines, including at least one member of each cluster, were analyzed by QPCR using four immune-related tissues (head kidney, liver, spleen and blood) obtained from unstimulated, polyriboinosinic polyribocytidylic acid (pIC)-stimulated and formalin-killed atypical Aeromonas salmonicida-stimulated individuals. EST abundance and QPCR analysis indicate that the expression of closely related CC chemokines GmSCYA101 and GmSCYA102, GmSCYA108 and GmSCYA109 or GmSCYA122 and GmSCYA124 can be highly tissue-specific despite substantial sequence identity. Stimulation with the viral mimic pIC or formalin-killed atypical A. salmonicida resulted in increased expression of most of the CC chemokines, indicating that they can be regarded as either inducible (inflammatory) or dual-function rather than constitutive (homeostatic). Tissue specificity, and the level of induction, varied broadly; for example, GmSCYA123 was at least 4-fold up-regulated by both inducers in all tissues analyzed, whereas pIC increased the expression of GmSCYA124 in liver over 1500 times. PMID:20381521

  15. NEWS: Higher education looks to the future

    NASA Astrophysics Data System (ADS)

    2000-05-01

    Early this year UK universities and colleges were urged to prepare themselves for the 21st century and to meet the challenges of globalization and the knowledge economy. A major project to harness new technology in the provision of high quality teaching and learning, both in the UK and overseas, along with the introduction of the `Foundation degree' as a new vocationally focused route into higher education were both announced by the government's Education and Employment Secretary. The Higher Education Funding Council for England is to bring forward proposals for a new collaborative virtual venture: a consortium of `e-Universities'. This partnership between universities and the private sector will develop a novel means of distance learning through exploiting the information and communication technologies. Meanwhile, the new two-year Foundation degrees should enable more young people to benefit from higher education by the age of 30, particularly at the intermediate skills level. Courses could be offered in areas ranging from IT and finance to the creative industries, appealing to a wide range of students, and with the opportunity to progress to an honours degree with only a further 1.3 years of extra study. A HEFCE consultation paper setting out the background and objectives for the e-University project was sent to all institutions, inviting them to submit information on relevant current activities to the project's Steering Group. By July it is intended to publish a detailed programme for the e-University, with a full specification by the autumn, along with expressions of interest and a call for tenders. The formulation of the e-University partnership is intended for early in 2001. These activities have coincided with a cautionary announcement from the Association of University Teachers drawing attention to the lack of younger staff being recruited to posts in UK higher education. Almost a third of UK academics are aged over 50, with the figure in the `old

  16. What are Higher Psychological Functions?

    PubMed

    Toomela, Aaro

    2016-03-01

    The concept of Higher Psychological Functions (HPFs) may seem to be well know in psychology today. Yet closer analysis reveals that HPFs are either not defined at all or if defined, then by a set of characteristics not justified theoretically. It is not possible to determine whether HPFs exist or not, unless they are defined. Most commonly the idea of HPFs is related to Vygotsky's theory. According to him, HPFs are: (1) psychological systems, (2) developing from natural processes, (3) mediated by symbols, (4) forms of psychological cooperation, which are (5) internalized in the course of development, (6) products of historical development, (7) conscious and (8) voluntary (9) active forms of adaptation to the environment, (10) dynamically changing in development, and (11) ontogeny of HPFs recapitulates cultural history. In this article these characteristics are discussed together with the relations among them. It is concluded that HPFs are real psychological phenomena. PMID:26403987

  17. Gravitating multidefects from higher dimensions

    SciTech Connect

    Giovannini, Massimo

    2007-03-15

    Warped configurations admitting pairs of gravitating defects are analyzed. After devising a general method for the construction of multidefects, specific examples are presented in the case of higher-dimensional Einstein-Hilbert gravity. The obtained profiles describe diverse physical situations such as (topological) kink-antikink systems, pairs of nontopological solitons, and bound configurations of a kink and of a nontopological soliton. In all the mentioned cases the geometry is always well behaved (all relevant curvature invariants are regular) and tends to five-dimensional anti-de Sitter space-time for large asymptotic values of the bulk coordinate. Particular classes of solutions can be generalized to the framework where the gravity part of the action includes, as a correction, the Euler-Gauss-Bonnet combination. After scrutinizing the structure of the zero modes, the obtained results are compared with conventional gravitating configurations containing a single topological defect.

  18. Grand Unification in Higher Dimensions

    SciTech Connect

    Hall, Lawrence J.; Nomura, Yasunori

    2002-12-10

    We have recently proposed an alternative picture for the physics at the scale of gauge coupling unification, where the unified symmetry is realized in higher dimensions but is broken locally by a symmetry breaking defect. Gauge coupling unification, the quantum numbers of quarks and leptons and the longevity of the proton arise as phenomena of the symmetrical bulk, while the lightness of the Higgs doublets and the masses of the light quarks and leptons probe the symmetry breaking defect. Moreover, the framework is extremely predictive if the effective higher dimensional theory is valid over a large energy interval up to the scale of strong coupling. Precise agreement with experiments is obtained in the simplest theory --- SU(5) in five dimensions with two Higgs multiplets propagating in the bulk. The weak mixing angle is predicted to be sin^2theta_w = 0.2313 \\pm 0.0004, which fits the data with extraordinary accuracy. The compactification scale and the strong coupling scale are determined to be M_c \\simeq 5 x 10^14 GeV and M_s \\simeq 1 x 10^17 GeV, respectively. Proton decay with a lifetime of order 10^{34} years is expected with a variety of final states such as e^+pi^0, and several aspects of flavor, including large neutrino mixing angles, are understood by the geometrical locations of the matter fields. When combined with a particular supersymmetry breaking mechanism, the theory predicts large lepton flavor violating mu -> e and tau -> mu transitions, with all superpartner masses determined by only two free parameters. The predicted value of the bottom quark mass from Yukawa unification agrees well with the data. This paper is mainly a review of the work presented in hep-ph/0103125, hep-ph/0111068 and hep-ph/0205067.

  19. Role of NF-kappaB-dependent caveolin-1 expression in the mechanism of increased endothelial permeability induced by lipopolysaccharide.

    PubMed

    Tiruppathi, Chinnaswamy; Shimizu, Jun; Miyawaki-Shimizu, Kayo; Vogel, Stephen M; Bair, Angela M; Minshall, Richard D; Predescu, Dan; Malik, Asrar B

    2008-02-15

    We investigated the role of NF-kappaB activation by the bacterial product lipopolysaccharide (LPS) in inducing caveolin-1 (Cav-1) expression and its consequence in contributing to the leakiness of the endothelial barrier. We observed that LPS challenge of human lung microvascular endothelial cells induced concentration- and time-dependent increases in expression of Cav-1 mRNA and protein. The NEMO (NF-kappaB essential modifier binding domain)-binding domain peptide (IkB kinase (IKK)-NEMO-binding domain (NBD) peptide), which prevents NF-kappaB activation by inhibiting the interaction of IKKgamma with the IKK complex, blocked LPS-induced Cav-1 mRNA and protein expression. Knockdown of NF-kappaB subunit p65/RelA expression with small interfering RNA also prevented LPS-induced Cav-1 expression. Caveolae open to the apical and basal plasmalemma of endothelial cells increased 2-4-fold within 4 h of LPS exposure. IKK-NBD peptide markedly reduced the LPS-induced increase in the number of caveolae as well as transendothelial albumin permeability. These observations were recapitulated in mouse studies in which IKK-NBD peptide prevented Cav-1 expression and interfered with the increase in lung microvessel permeability induced by LPS. Thus, LPS mediates NF-kappaB-dependent Cav-1 expression that results in increased caveolae number and thereby contributes to the mechanism of increased transendothelial albumin permeability. PMID:18077459

  20. Rescue of splicing-mediated intron loss maximizes expression in lentiviral vectors containing the human ubiquitin C promoter

    PubMed Central

    Cooper, Aaron R.; Lill, Georgia R.; Gschweng, Eric H.; Kohn, Donald B.

    2015-01-01

    Lentiviral vectors almost universally use heterologous internal promoters to express transgenes. One of the most commonly used promoter fragments is a 1.2-kb sequence from the human ubiquitin C (UBC) gene, encompassing the promoter, some enhancers, first exon, first intron and a small part of the second exon of UBC. Because splicing can occur after transcription of the vector genome during vector production, we investigated whether the intron within the UBC promoter fragment is faithfully transmitted to target cells. Genetic analysis revealed that more than 80% of proviral forms lack the intron of the UBC promoter. The human elongation factor 1 alpha (EEF1A1) promoter fragment intron was not lost during lentiviral packaging, and this difference between the UBC and EEF1A1 promoter introns was conferred by promoter exonic sequences. UBC promoter intron loss caused a 4-fold reduction in transgene expression. Movement of the expression cassette to the opposite strand prevented intron loss and restored full expression. This increase in expression was mostly due to non-classical enhancer activity within the intron, and movement of putative intronic enhancer sequences to multiple promoter-proximal sites actually repressed expression. Reversal of the UBC promoter also prevented intron loss and restored full expression in bidirectional lentiviral vectors. PMID:25520191

  1. Funding in Higher Education and Economic Growth in France and the United Kingdom, 1921-2003

    ERIC Educational Resources Information Center

    Carpentier, Vincent

    2006-01-01

    The UK 2004 Higher Education Act generated important debates about the relationships between higher education (HE), economic growth and social progress. The range of positions expressed in relation to the increase of annual tuition fees raises crucial questions about the public and private funding of higher education and its individual and social…

  2. "Second Chance" Routes into Higher Education: Sweden, Norway and Germany Compared

    ERIC Educational Resources Information Center

    Orr, Dominic; Hovdhaugen, Elisabeth

    2014-01-01

    Widening access to higher education is clearly part of the European policy agenda. Higher education ministers in the Bologna countries, as well as the European Commission, have all expressed a wish to make higher education more representative of national populations. This policy objective has been echoed at national level. One approach to widening…

  3. An interval logic for higher-level temporal reasoning

    NASA Technical Reports Server (NTRS)

    Schwartz, R. L.; Melliar-Smith, P. M.; Vogt, F. H.; Plaisted, D. A.

    1983-01-01

    Prior work explored temporal logics, based on classical modal logics, as a framework for specifying and reasoning about concurrent programs, distributed systems, and communications protocols, and reported on efforts using temporal reasoning primitives to express very high level abstract requirements that a program or system is to satisfy. Based on experience with those primitives, this report describes an Interval Logic that is more suitable for expressing such higher level temporal properties. The report provides a formal semantics for the Interval Logic, and several examples of its use. A description of decision procedures for the logic is also included.

  4. [Paradigm shift in higher education].

    PubMed

    Csóka, Mária

    2009-08-30

    The fast changes that took place in the last quarter of the 20th century made the professionals dealing with pedagogy realize that our school system followed the economical changes in terms of training supply and the matter of education very slowly, if at all; let alone the educational methods. We had to realize that the maintaining of this conservative system is not rational, education has become the most important part of the globalisational competition and the key to the 21st century is learning. Accordingly, the spatial and temporal expenditure of education has become a new trend, namely lifelong learning (LLL). The social needs on education have increased, the expectations of economy and employers have changed: knowledge has become the fund of competitiveness. In this process, universities have got an accentuated role: in addition to being the place of undergraduate training they have become the site of postgraduate courses for the increasing graduate adult masses. Therefore, reform processes have started in a number of European countries in the nineties. The Bologna Declaration signed on 19th June 1999 set a common direction for these reforms, with its signatories aiming to establish a standard European Higher Education Area with harmonized and comparable educational systems by 2010. However, the administrative change itself is not enough to reach the goals; a formal innovation has to be followed by a reform of the contents which means reformation of higher education. In recent years, Hungarian colleges and universities have worked out their educational programs that are suitable for the new structure; it is only the new educational programs that started from 1st September 2006. The author determines the most important parts of the reform of the training system of Semmelweis University Faculty of Health Sciences, which are the following: redrawing of the training philosophy and paradigm, the reform of the training structure of macro level (cognition

  5. Higher Education: A Time for Triage?

    NASA Astrophysics Data System (ADS)

    Lagowski, J. J.

    1995-10-01

    Higher education faces unprecedented challenges. The confluence of changing economic and demographic tends; new patterns of federal and state spending; more explicit expectations by students and their families for affordable, accessible education; and heightened scrutiny by those who claim a legitimate interest in higher education is inescapably altering the environment in which this system operates. Higher education will never again be as it was before. Further, many believe that tinkering around the margins is no longer an adequate response to the new demands. Fundamental change is deemed necessary to meet the challenge of this melange of pressures. A number of commentators have observed that political and corporate America have responded to their challenges by instituting a fundamental restructuring of those institutions. The medical community is also in the midst of a similar basic restructuring of the health care delivery system in this country. Now its education's turn. People are questioning the historically expressed mission of higher education. They make the claim that we cost too much, spend carelessly, teach poorly, plan myopically, and when questioned, act defensively. Educational administrators, from department chairs up, are confronted with the task of simultaneously reforming and cutting back. They have no choice. They must establish politically sophisticated priority settings and effect a hard-nosed reallocation of resources in a social environment where competing public needs have equivalent--or stronger--emotional pulls. Triage in a medical context involves confronting an emergency in which the demand for attention far outstrips available assistance by establishing a sequence of care in which one key individual orchestrates the application of harsh priorities which have been designed to maximize the number of survivors. In recent years, the decisions that have been made in some centers of higher education bear a striking similarity. The literature

  6. Skeletal Muscle-Specific Expression of PGC-1α-b, an Exercise-Responsive Isoform, Increases Exercise Capacity and Peak Oxygen Uptake

    PubMed Central

    Tadaishi, Miki; Miura, Shinji; Kai, Yuko; Kano, Yutaka; Oishi, Yuichi; Ezaki, Osamu

    2011-01-01

    Background Maximal oxygen uptake (VO2max) predicts mortality and is associated with endurance performance. Trained subjects have a high VO2max due to a high cardiac output and high metabolic capacity of skeletal muscles. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a nuclear receptor coactivator, promotes mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training increases PGC-1α in skeletal muscle, PGC-1α-mediated changes may contribute to the improvement of exercise capacity and VO2max. There are three isoforms of PGC-1α mRNA. PGC-1α-b protein, whose amino terminus is different from PGC-1α-a protein, is a predominant PGC-1α isoform in response to exercise. We investigated whether alterations of skeletal muscle metabolism by overexpression of PGC-1α-b in skeletal muscle, but not heart, would increase VO2max and exercise capacity. Methodology/Principal Findings Transgenic mice showed overexpression of PGC-1α-b protein in skeletal muscle but not in heart. Overexpression of PGC-1α-b promoted mitochondrial biogenesis 4-fold, increased the expression of fatty acid transporters, enhanced angiogenesis in skeletal muscle 1.4 to 2.7-fold, and promoted exercise capacity (expressed by maximum speed) by 35% and peak oxygen uptake by 20%. Across a broad range of either the absolute exercise intensity, or the same relative exercise intensities, lipid oxidation was always higher in the transgenic mice than wild-type littermates, suggesting that lipid is the predominant fuel source for exercise in the transgenic mice. However, muscle glycogen usage during exercise was absent in the transgenic mice. Conclusions/Significance Increased mitochondrial biogenesis, capillaries, and fatty acid transporters in skeletal muscles may contribute to improved exercise capacity via an increase in fatty acid utilization. Increases in PGC-1α-b protein or function might be a useful strategy

  7. Chromosomal replicons of higher plants

    SciTech Connect

    Van't Hof, J.

    1987-03-16

    This brief discussion of replicons of higher plants offers a glimpse into the properties of chromosomal DNA replication. It gives evidence that the S phase of unrelated plant species is comprised of temporally ordered replicon families that increase in number with genome size. This orderly process, which assures a normal inheritance of genetic material to recipient daughter cells, is maintained at the level of replicon clusters by two mutually exclusive mechanisms, one involving the rate at which single replicons replicate their allotment of DNA, and another by means of the tempo-pause. The same two mechanisms are used by cells to alter the pattern of chromosomal DNA replication just prior to and during normal development. Both mechanisms are genetically determined and produce genetic effects when disturbed of disrupted by additional non-conforming DNAs. Further insight into how these two mechanisms operate requires more molecular information about the nature of replicons and the factors that govern when a replicon family replicates. Plant material is a rich and ideal source for this information just awaiting exploitation. 63 refs.

  8. Higher order turbulence closure models

    NASA Technical Reports Server (NTRS)

    Amano, Ryoichi S.; Chai, John C.; Chen, Jau-Der

    1988-01-01

    Theoretical models are developed and numerical studies conducted on various types of flows including both elliptic and parabolic. The purpose of this study is to find better higher order closure models for the computations of complex flows. This report summarizes three new achievements: (1) completion of the Reynolds-stress closure by developing a new pressure-strain correlation; (2) development of a parabolic code to compute jets and wakes; and, (3) application to a flow through a 180 deg turnaround duct by adopting a boundary fitted coordinate system. In the above mentioned models near-wall models are developed for pressure-strain correlation and third-moment, and incorporated into the transport equations. This addition improved the results considerably and is recommended for future computations. A new parabolic code to solve shear flows without coordinate tranformations is developed and incorporated in this study. This code uses the structure of the finite volume method to solve the governing equations implicitly. The code was validated with the experimental results available in the literature.

  9. Quantization of higher spin fields

    SciTech Connect

    Wagenaar, J. W.; Rijken, T. A

    2009-11-15

    In this article we quantize (massive) higher spin (1{<=}j{<=}2) fields by means of Dirac's constrained Hamilton procedure both in the situation were they are totally free and were they are coupled to (an) auxiliary field(s). A full constraint analysis and quantization is presented by determining and discussing all constraints and Lagrange multipliers and by giving all equal times (anti)commutation relations. Also we construct the relevant propagators. In the free case we obtain the well-known propagators and show that they are not covariant, which is also well known. In the coupled case we do obtain covariant propagators (in the spin-3/2 case this requires b=0) and show that they have a smooth massless limit connecting perfectly to the massless case (with auxiliary fields). We notice that in our system of the spin-3/2 and spin-2 case the massive propagators coupled to conserved currents only have a smooth limit to the pure massless spin-propagator, when there are ghosts in the massive case.

  10. Higher Education Literature Revisited: Citation Patterns Examined

    ERIC Educational Resources Information Center

    Budd, John M.; Magnuson, Lauren

    2010-01-01

    The discourse of the field of higher education is complex, as is its analysis. Citation analysis is means of examining communicative processes. This study investigates citations in the papers of three core journals in higher education, "Research in Higher Education, Review of Higher Education," and "Journal of Higher Education." The results…

  11. Higher Order Thermal Lattice Boltzmann Model

    NASA Astrophysics Data System (ADS)

    Sorathiya, Shahajhan; Ansumali, Santosh

    2013-03-01

    Lattice Boltzmann method (LBM) modelling of thermal flows, compressible and micro flows requires an accurate velocity space discretization. The sub optimality of Gauss-Hermite quadrature in this regard is well known. Most of the thermal LBM in the past have suffered from instability due to lack of proper H-theorem and accuracy. Motivated from these issues, the present work develops along the two works and and imposes an eighth higher order moment to get correct thermal physics. We show that this can be done by adding just 6 more velocities to D3Q27 model and obtain a ``multi-speed on lattice thermal LBM'' with 33 velocities in 3D and calO (u4) and calO (T4) accurate fieq with a consistent H-theorem and inherent numerical stability. Simulations for Rayleigh-Bernard as well as velocity and temperature slip in micro flows matches with analytical results. Lid driven cavity set up for grid convergence is studied. Finally, a novel data structure is developed for HPC. The authors express their gratitude for computational resources and financial support provide by Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, India.

  12. Olfactory receptor patterning in a higher primate.

    PubMed

    Horowitz, Lisa F; Saraiva, Luis R; Kuang, Donghui; Yoon, Kyoung-hye; Buck, Linda B

    2014-09-10

    The mammalian olfactory system detects a plethora of environmental chemicals that are perceived as odors or stimulate instinctive behaviors. Studies using odorant receptor (OR) genes have provided insight into the molecular and organizational strategies underlying olfaction in mice. One important unanswered question, however, is whether these strategies are conserved in primates. To explore this question, we examined the macaque, a higher primate phylogenetically close to humans. Here we report that the organization of sensory inputs in the macaque nose resembles that in mouse in some respects, but not others. As in mouse, neurons with different ORs are interspersed in the macaque nose, and there are spatial zones that differ in their complement of ORs and extend axons to different domains in the olfactory bulb of the brain. However, whereas the mouse has multiple discrete band-like zones, the macaque appears to have only two broad zones. It is unclear whether the organization of OR inputs in a rodent/primate common ancestor degenerated in primates or, alternatively became more sophisticated in rodents. The mouse nose has an additional small family of chemosensory receptors, called trace amine-associated receptors (TAARs), which may detect social cues. Here we find that TAARs are also expressed in the macaque nose, suggesting that TAARs may also play a role in human olfactory perception. We further find that one human TAAR responds to rotten fish, suggesting a possible role as a sentinel to discourage ingestion of food harboring pathogenic microorganisms. PMID:25209267

  13. Olfactory Receptor Patterning in a Higher Primate

    PubMed Central

    Horowitz, Lisa F.; Saraiva, Luis R.; Kuang, Donghui; Yoon, Kyoung-hye

    2014-01-01

    The mammalian olfactory system detects a plethora of environmental chemicals that are perceived as odors or stimulate instinctive behaviors. Studies using odorant receptor (OR) genes have provided insight into the molecular and organizational strategies underlying olfaction in mice. One important unanswered question, however, is whether these strategies are conserved in primates. To explore this question, we examined the macaque, a higher primate phylogenetically close to humans. Here we report that the organization of sensory inputs in the macaque nose resembles that in mouse in some respects, but not others. As in mouse, neurons with different ORs are interspersed in the macaque nose, and there are spatial zones that differ in their complement of ORs and extend axons to different domains in the olfactory bulb of the brain. However, whereas the mouse has multiple discrete band-like zones, the macaque appears to have only two broad zones. It is unclear whether the organization of OR inputs in a rodent/primate common ancestor degenerated in primates or, alternatively became more sophisticated in rodents. The mouse nose has an additional small family of chemosensory receptors, called trace amine-associated receptors (TAARs), which may detect social cues. Here we find that TAARs are also expressed in the macaque nose, suggesting that TAARs may also play a role in human olfactory perception. We further find that one human TAAR responds to rotten fish, suggesting a possible role as a sentinel to discourage ingestion of food harboring pathogenic microorganisms. PMID:25209267

  14. Syntaxin 1A is expressed in airway epithelial cells, where it modulates CFTR Cl– currents

    PubMed Central

    Naren, Anjaparavanda P.; Di, Anke; Cormet-Boyaka, Estelle; Boyaka, Prosper N.; McGhee, Jerry R.; Zhou, Weihong; Akagawa, Kimio; Fujiwara, Tomonori; Thome, Ulrich; Engelhardt, John F.; Nelson, Deborah J.; Kirk, Kevin L.

    2000-01-01

    The CFTR Cl– channel controls salt and water transport across epithelial tissues. Previously, we showed that CFTR-mediated Cl– currents in the Xenopus oocyte expression system are inhibited by syntaxin 1A, a component of the membrane trafficking machinery. This negative modulation of CFTR function can be reversed by soluble syntaxin 1A peptides and by the syntaxin 1A binding protein, Munc-18. In the present study, we determined whether syntaxin 1A is expressed in native epithelial tissues that normally express CFTR and whether it modulates CFTR currents in these tissues. Using immunoblotting and immunofluorescence, we observed syntaxin 1A in native gut and airway epithelial tissues and showed that epithelial cells from these tissues express syntaxin 1A at >10-fold molar excess over CFTR. Syntaxin 1A is seen near the apical cell surfaces of human bronchial airway epithelium. Reagents that disrupt the CFTR-syntaxin 1A interaction, including soluble syntaxin 1A cytosolic domain and recombinant Munc-18, augmented cAMP-dependent CFTR Cl– currents by more than 2- to 4-fold in mouse tracheal epithelial cells and cells derived from human nasal polyps, but these reagents did not affect CaMK II–activated Cl– currents in these cells. PMID:10675364

  15. Cloning and characterization of a gibberellin-induced RNase expressed in barley aleurone cells

    SciTech Connect

    Rogers, S.W.; Rogers, J.C. . Inst. of Biological Chemistry)

    1999-04-01

    The authors cloned a cDNA for a gibberellin-induced ribonuclease (RNase) expressed in barley (Hordeum vulgare) aleurone and the gene for a second barley RNase expressed in leaf tissue. The protein encoded by the cDNA is unique among RNases described to date in that it contains a novel 23-amino acid insert between the C2 and C3 conserved sequences. Expression of the recombinant protein in tobacco (Ncotiana tabacum) suspension-cultured protoplasts gave an active RNase of the expected size, confirming the enzymatic activity of the protein. Analyses of hormone regulation of re-expression of mRNA for the aleurone RNase revealed that, like the pattern for [alpha]-amylase, mRNA levels increased in the presence of gibberellic acid, and its antagonist abscisic acid prevented this effect. Quantitative studies at early times demonstrated that cycloheximide treatment of aleurone layers increased mRNA levels 4-fold, whereas a combination of gibberellin plus cycloheximide treatment was required to increase [alpha]-amylase mRNA levels to the same extent. These results are consistent with loss of repression as an initial effect of gibberellic acid on transcription of those genes, although the regulatory pathways for the two genes may differ.

  16. Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer.

    PubMed

    Rodrigues, P R S; Maia, L L; Santos, M; Peterle, G T; Alves, L U; Takamori, J T; Souza, R P; Barbosa, W M; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

    2015-01-01

    The leptin gene product is released into the blood stream, passes through the blood-brain barrier, and finds the leptin receptor (LEPR) in the central nervous system. This hormone regulates food intake, hematopoiesis, inflammation, immunity, differentiation, and cell proliferation. The LEPR Gln223Arg polymorphism has been reported to alter receptor function and expression, both of which have been related with prognostics in several tumor types. Furthermore, several studies have shown a relationship between the Gln223Arg polymorphism and tumor development, and its role in oral and oropharyngeal squamous cell carcinoma is now well understood. In this study, 315 DNA samples were used for LEPR Gln223Arg genotyping and 87 primary oral and oropharyngeal squamous cell carcinomas were used for immunohistochemical expression analysis, such that a relationship between these and tumor development and prognosis could be established. Homozygous LEPR Arg223 was found to be associated with a 2-fold reduction in oral and oropharyngeal cancer risk. In contrast, the presence of the Arg223 allele in tumors was associated with worse disease-free and disease-specific survival. Low LEPR expression was found to be an independent risk factor, increasing the risk for lymph node metastasis 4-fold. In conclusion, the Gln223Arg polymorphism and LEPR expression might be valuable markers for oral and oropharyngeal cancer, suggesting that LEPR might serve as a potential target for future therapies. PMID:26634459

  17. Directed Evolution of Brain-Derived Neurotrophic Factor for Improved Folding and Expression in Saccharomyces cerevisiae

    PubMed Central

    Burns, Michael L.; Malott, Thomas M.; Metcalf, Kevin J.; Hackel, Benjamin J.; Chan, Jonah R.

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in nervous system function and has therapeutic potential. Microbial production of BDNF has resulted in a low-fidelity protein product, often in the form of large, insoluble aggregates incapable of binding to cognate TrkB or p75 receptors. In this study, employing Saccharomyces cerevisiae display and secretion systems, it was found that BDNF was poorly expressed and partially inactive on the yeast surface and that BDNF was secreted at low levels in the form of disulfide-bonded aggregates. Thus, for the purpose of increasing the compatibility of yeast as an expression host for BDNF, directed-evolution approaches were employed to improve BDNF folding and expression levels. Yeast surface display was combined with two rounds of directed evolution employing random mutagenesis and shuffling to identify BDNF mutants that had 5-fold improvements in expression, 4-fold increases in specific TrkB binding activity, and restored p75 binding activity, both as displayed proteins and as secreted proteins. Secreted BDNF mutants were found largely in the form of soluble homodimers that could stimulate TrkB phosphorylation in transfected PC12 cells. Site-directed mutagenesis studies indicated that a particularly important mutational class involved the introduction of cysteines proximal to the native cysteines that participate in the BDNF cysteine knot architecture. Taken together, these findings show that yeast is now a viable alternative for both the production and the engineering of BDNF. PMID:25015885

  18. Developmentally Regulated Expression of the Nerve Growth Factor Receptor Gene in the Periphery and Brain

    NASA Astrophysics Data System (ADS)

    Buck, C. R.; Martinez, Humberto J.; Black, Ira B.; Chao, Moses V.

    1987-05-01

    Nerve growth factor (NGF) regulates development and maintenance of function of peripheral sympathetic and sensory neurons. A potential role for the trophic factor in brain has been detected only recently. The ability of a cell to respond to NGF is due, in part, to expression of specific receptors on the cell surface. To study tissue-specific expression of the NGF receptor gene, we have used sensitive cRNA probes for detection of NGF receptor mRNA. Our studies indicate that the receptor gene is selectively and specifically expressed in sympathetic (superior cervical) and sensory (dorsal root) ganglia in the periphery, and by the septum-basal forebrain centrally, in the neonatal rat in vivo. Moreover, examination of tissues from neonatal and adult rats reveals a marked reduction in steady-state NGF receptor mRNA levels in sensory ganglia. In contrast, a 2- to 4-fold increase was observed in the basal forebrain and in the sympathetic ganglia over the same time period. Our observations suggest that NGF receptor mRNA expression is developmentally regulated in specific areas of the nervous system in a differential fashion.

  19. The mechanical properties of Drosophila jump muscle expressing wild-type and embryonic Myosin isoforms.

    PubMed

    Eldred, Catherine C; Simeonov, Dimitre R; Koppes, Ryan A; Yang, Chaoxing; Corr, David T; Swank, Douglas M

    2010-04-01

    Transgenic Drosophila are highly useful for structure-function studies of muscle proteins. However, our ability to mechanically analyze transgenically expressed mutant proteins in Drosophila muscles has been limited to the skinned indirect flight muscle preparation. We have developed a new muscle preparation using the Drosophila tergal depressor of the trochanter (TDT or jump) muscle that increases our experimental repertoire to include maximum shortening velocity (V(slack)), force-velocity curves and steady-state power generation; experiments not possible using indirect flight muscle fibers. When transgenically expressing its wild-type myosin isoform (Tr-WT) the TDT is equivalent to a very fast vertebrate muscle. TDT has a V(slack) equal to 6.1 +/- 0.3 ML/s at 15 degrees C, a steep tension-pCa curve, isometric tension of 37 +/- 3 mN/mm(2), and maximum power production at 26% of isometric tension. Transgenically expressing an embryonic myosin isoform in the TDT muscle increased isometric tension 1.4-fold, but decreased V(slack) 50% resulting in no significant difference in maximum power production compared to Tr-WT. Drosophila expressing embryonic myosin jumped <50% as far as Tr-WT that, along with comparisons to frog jump muscle studies, suggests fast muscle shortening velocity is relatively more important than high tension generation for Drosophila jumping. PMID:20371321

  20. Higher Education: A Time for Triage?

    NASA Astrophysics Data System (ADS)

    Lagowski, J. J.

    1995-10-01

    Higher education faces unprecedented challenges. The confluence of changing economic and demographic tends; new patterns of federal and state spending; more explicit expectations by students and their families for affordable, accessible education; and heightened scrutiny by those who claim a legitimate interest in higher education is inescapably altering the environment in which this system operates. Higher education will never again be as it was before. Further, many believe that tinkering around the margins is no longer an adequate response to the new demands. Fundamental change is deemed necessary to meet the challenge of this melange of pressures. A number of commentators have observed that political and corporate America have responded to their challenges by instituting a fundamental restructuring of those institutions. The medical community is also in the midst of a similar basic restructuring of the health care delivery system in this country. Now its education's turn. People are questioning the historically expressed mission of higher education. They make the claim that we cost too much, spend carelessly, teach poorly, plan myopically, and when questioned, act defensively. Educational administrators, from department chairs up, are confronted with the task of simultaneously reforming and cutting back. They have no choice. They must establish politically sophisticated priority settings and effect a hard-nosed reallocation of resources in a social environment where competing public needs have equivalent--or stronger--emotional pulls. Triage in a medical context involves confronting an emergency in which the demand for attention far outstrips available assistance by establishing a sequence of care in which one key individual orchestrates the application of harsh priorities which have been designed to maximize the number of survivors. In recent years, the decisions that have been made in some centers of higher education bear a striking similarity. The literature

  1. Higher-order Genome Organization in Human Disease

    PubMed Central

    Misteli, Tom

    2010-01-01

    Genomes are organized into complex higher-order structures by folding of the DNA into chromatin fibers, chromosome domains, and ultimately chromosomes. The higher-order organization of genomes is functionally important for gene regulation and control of gene expression programs. Defects in how chromatin is globally organized are relevant for physiological and pathological processes. Mutations and transcriptional misregulation of several global genome organizers are linked to human diseases and global alterations in chromatin structure are emerging as key players in maintenance of genome stability, aging, and the formation of cancer translocations. PMID:20591991

  2. Inducible gene expression of the human immunodeficiency virus LTR in a replication-incompetent herpes simplex virus vector.

    PubMed

    Warden, M P; Weir, J P

    1996-12-01

    Although replication-incompetent herpes simplex virus (HSV) vectors have the capability to express foreign genes, successful development of these vectors for gene delivery would require that expression of the foreign gene be regulated. To investigate the feasibility of obtaining inducible expression of a foreign gene in such a vector, a replication-incompetent HSV vector, vd120/LTR beta, was developed that used the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) to express the Escherichia coli lacZ gene. Examination of lacZ expression from the HIV-1 LTR in vd120/LTR beta-infected cells indicated that the LTR was active as a promoter under both replicating and nonreplicating conditions, although expression of lacZ under nonreplicating conditions was approximately 4-fold lower. In addition, the LTR expressed lacZ in a manner distinct from that of well-characterized HSV-1 promoters of each temporal class. The effect of the HIV-1 regulatory protein Tat on expression from the LTR in vd120/LTR beta was examined by infection of two different HeLa-derived cell lines that constitutively expressed Tat, HL2/3, and HLtat. Compared to infection of HeLa cells, lacZ expression from vd120/LTR beta-infected HL2/3 and HLtat cells increased from 4- to 24-fold, depending on the multiplicity of vector infection. Sustained expression of lacZ from the LTR in vd120/LTR beta-infected cells was not observed even in the continuous presence of Tat, although vector could be recovered for up to 5 days after infection. However, the amount of recoverable vector decreased during this time, suggesting that cellular cytotoxicity may account for some of the decrease in Tat-mediated expression from the LTR. PMID:8941330

  3. Widespread ectopic expression of olfactory receptor genes

    PubMed Central

    Feldmesser, Ester; Olender, Tsviya; Khen, Miriam; Yanai, Itai; Ophir, Ron; Lancet, Doron

    2006-01-01

    Background Olfactory receptors (ORs) are the largest gene family in the human genome. Although they are expected to be expressed specifically in olfactory tissues, some ectopic expression has been reported, with special emphasis on sperm and testis. The present study systematically explores the expression patterns of OR genes in a large number of tissues and assesses the potential functional implication of such ectopic expression. Results We analyzed the expression of hundreds of human and mouse OR transcripts, via EST and microarray data, in several dozens of human and mouse tissues. Different tissues had specific, relatively small OR gene subsets which had particularly high expression levels. In testis, average expression was not particularly high, and very few highly expressed genes were found, none corresponding to ORs previously implicated in sperm chemotaxis. Higher expression levels were more common for genes with a non-OR genomic neighbor. Importantly, no correlation in expression levels was detected for human-mouse orthologous pairs. Also, no significant difference in expression levels was seen between intact and pseudogenized ORs, except for the pseudogenes of subfamily 7E which has undergone a human-specific expansion. Conclusion The OR superfamily as a whole, show widespread, locus-dependent and heterogeneous expression, in agreement with a neutral or near neutral evolutionary model for transcription control. These results cannot reject the possibility that small OR subsets might play functional roles in different tissues, however considerable care should be exerted when offering a functional interpretation for ectopic OR expression based only on transcription information. PMID:16716209

  4. Incorporation of partial polyhedrin homology sequences (PPHS) enhances the production of cloned foreign genes in a baculovirus expression system.

    PubMed

    Gong, Zhaohui; Jin, Yongfeng; Zhang, Yaozhou

    2006-03-01

    Baculovirus expression vector systems (BEVSs) have been used extensively for high-level expression of cloned foreign genes. In many instances, the levels of recombinant protein(s) produced in insect cells and larvae are insufficient for experimental purposes. Thus new techniques and methods are needed to increase significantly the protein expression levels in BEVS. In the present paper, we describe the incorporation of a 15 bp element derived from the 5'-end partial sequence of the polyhedrin gene, which contains the non-coding sequence ATAAAT and the coding sequence ATGCCGAAT, into the 5'-end of the CTB (cholera toxin B subunit)-INS (insulin) fusion gene. With the addition of the PPHS (partial polyhedrin homology sequences), two extra amino acids (Pro-Asn) were added to the N-terminus of the mCTB-INS (modified CTB-INS) fusion protein. This new fusion protein was expressed in both insect cells and larvae using BEVSs. We found that the addition of PPHS enhanced 4-fold the expression of CTB-INS in both insect cells and larvae. Further analysis revealed that the additional two amino acids in mCTB-INS did not significantly affect binding affinity for G(M1) ganglioside. Therefore the PPHS can be used as a constitutive element immediately downstream of the polyhedrin promoter to induce significant increases in the expression levels of cloned foreign genes. PMID:16313236

  5. Basal expression of the cystic fibrosis transmembrane conductance regulator gene is dependent on protein kinase A activity.

    PubMed Central

    McDonald, R A; Matthews, R P; Idzerda, R L; McKnight, G S

    1995-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) functions as a Cl- channel that becomes activated after phosphorylation by cAMP-dependent protein kinase (PKA). We demonstrate that PKA also plays a crucial role in maintaining basal expression of the CFTR gene in the human colon carcinoma cell line T84. Inhibition of PKA activity by expression of a dominant-negative regulatory subunit or treatment with the PKA-selective inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89) caused a complete suppression of CFTR gene expression without affecting other constitutively active genes. Basal expression of a 2.2-kb region of the CFTR promoter linked to a luciferase reporter gene (CFTR-luc) exhibited the same dependence on PKA. The ability of cAMP to induce CFTR over basal levels is cell-type specific. In T84 cells, both the endogenous CFTR gene and CFTR-luc exhibited only a modest inducibility (approximately 2-fold), whereas in the human choriocarcinoma cell line JEG-3, CFTR-luc could be induced at least 4-fold. A variant cAMP-response element is present at position -48 to -41 in the CFTR promoter, and mutation of this sequence blocks basal expression. We conclude that cAMP, acting through PKA, is an essential regulator of basal CFTR gene expression and may mediate an induction of CFTR in responsive cell types. Images Fig. 1 Fig. 3 PMID:7543684

  6. Quantifying higher-order correlations in a neuronal pool

    NASA Astrophysics Data System (ADS)

    Montangie, Lisandro; Montani, Fernando

    2015-03-01

    Recent experiments involving a relatively large population of neurons have shown a very significant amount of higher-order correlations. However, little is known of how these affect the integration and firing behavior of a population of neurons beyond the second order statistics. To investigate how higher-order inputs statistics can shape beyond pairwise spike correlations and affect information coding in the brain, we consider a neuronal pool where each neuron fires stochastically. We develop a simple mathematically tractable model that makes it feasible to account for higher-order spike correlations in a neuronal pool with highly interconnected common inputs beyond second order statistics. In our model, correlations between neurons appear from q-Gaussian inputs into threshold neurons. The approach constitutes the natural extension of the Dichotomized Gaussian model, where the inputs to the model are just Gaussian distributed and therefore have no input interactions beyond second order. We obtain an exact analytical expression for the joint distribution of firing, quantifying the degree of higher-order spike correlations, truly emphasizing the functional aspects of higher-order statistics, as we account for beyond second order inputs correlations seen by each neuron within the pool. We determine how higher-order correlations depend on the interaction structure of the input, showing that the joint distribution of firing is skewed as the parameter q increases inducing larger excursions of synchronized spikes. We show how input nonlinearities can shape higher-order correlations and enhance coding performance by neural populations.

  7. Anti-diabetic property of Tinospora cordifolia and its active compound is mediated through the expression of Glut-4 in L6 myotubes.

    PubMed

    Sangeetha, M K; Priya, C D Mohana; Vasanthi, Hannah R

    2013-02-15

    Tinospora cordifolia is a well reported plant possessing numerous medicinal values including anti-diabetic property. Aim of the present study is to study the mechanism of action of Tinospora cordifolia and its active compound in differentiated myocytes, L6 cells. Key marker of diabetes in cells is the insulin dependent glucose transporter-4 (Glut-4) which also responds to exogenous chemicals, and is over expressed up to 5- and 4-fold, by Tinospora cordifolia and palmatine, respectively. Next to Glut-4, the predominant protein influencing glucose metabolism is PPARα and γ whose expressions were also positively modulated. Further, the inhibitors of insulin pathway prevented glucose uptake mediated by Tinospora cordifolia and palmatine which shows that the activity is majorly mediated through insulin pathway. PMID:23290487

  8. Expression of Enzymes that Metabolize Medications

    NASA Technical Reports Server (NTRS)

    Wotring, V. E.; Peters, C. P.

    2011-01-01

    -treatment. Not all recovered completely by the final time point tested: with 6 Gy exposure, metallothionein expression was 132-fold more than control at the 4 hr time point, and fell at each later time point (11-fold at 24 hrs, and 8-fold at 7 days). In contrast, there were other genes whose expression was altered and remained relatively constant through the 7 day period we tested. One examples is Cyp17a1, which showed a 4-fold elevation at 4 hrs after exposure and remained constant for 7 days after the last treatment. Spaceflight samples evaluated with similar methods and comparisons will be made between the radiation-treated groups and the spaceflight samples. CONCLUSION It seems likely that radiation exposure triggers homeostatic mechanisms, which could include alterations of gene expression. Better understanding of these pathways could aid in optimizing medications doses given to crewmembers who require treatment and eventually, to development of new countermeasures to ameliorate or prevent radiation-induced damage to cells and tissues.

  9. The GENOTEND chip: a new tool to analyse gene expression in muscles of beef cattle for beef quality prediction

    PubMed Central

    2012-01-01

    30 Charolais young bulls slaughtered in year 2, and in the 21 Charolais steers slaughtered in year 1, but not in the group of 19 steers slaughtered in year 2 which differ from the reference group by two factors (gender and year). When the first three groups of animals were analysed together, this subset of genes explained a 4-fold higher proportion of the variability in tenderness than muscle biochemical traits. Conclusion This study underlined the relevance of the GENOTEND chip to identify markers of beef quality, mainly by confirming previous results and by detecting other genes of the heat shock family as potential markers of beef quality. However, it was not always possible to extrapolate the relevance of these markers to all animal groups which differ by several factors (such as gender or environmental conditions of production) from the initial population of reference in which these markers were identified. PMID:22894653

  10. Redefining External Stakeholders in Nordic Higher Education

    ERIC Educational Resources Information Center

    Musial, Kazimierz

    2010-01-01

    Present higher education reforms in the Nordic countries diminish the role and influence of the state on the governance of higher education institutions. While still providing a framework for the management of higher education, in general, the state supervises rather than controls higher education institutions (HEIs). The rhetoric of change…

  11. Illinois Higher Education Annual Report, 2003.

    ERIC Educational Resources Information Center

    Kaplan, James L.; LaVista, Daniel J.

    This report presents information about the Illinois Board of Higher Education and the state of higher education in Illinois. The Illinois Board of Higher Education, a 15-member board, is responsible for planning and coordinating the states system of higher education. The Board has statutory responsibilities for master planning, the budget, program…

  12. Master Plan for Texas Higher Education 1990.

    ERIC Educational Resources Information Center

    Texas Higher Education Coordinating Board, Austin.

    This 5-year plan for Texas higher education, designed to present a "road-map" for all participants in Texas higher education to use in their fulfillment of the higher education mission as established by the Texas Charter for Public Higher Education, is organized around six principles established by the charter. Following an overview on Texas…

  13. Quality Assurance in Chinese Higher Education

    ERIC Educational Resources Information Center

    Li, Yuan

    2010-01-01

    Quality assurance has been integrated into the fabric of higher education in China, with the issue of quality in higher education--how to evaluate it and how to enhance it--now taking centre stage in Chinese higher education. In the past decade, the development of quality assurance in Chinese higher education has covered a broad spectrum of…

  14. African Higher Education: An International Reference Handbook.

    ERIC Educational Resources Information Center

    Teferra, Damtew, Ed.; Altbach, Philip G., Ed.

    This book is a comprehensive survey of all aspects and dimensions of higher education in Africa. It includes a historical overview of higher education, descriptions of the higher education systems in each African country, and analyses of current and timely topics in higher education. Part 1, "Themes," contains 13 essays on trends in African higher…

  15. National Protocols for Higher Education Approval Processes

    ERIC Educational Resources Information Center

    Ministerial Council on Education, Employment, Training and Youth Affairs (NJ1), 2007

    2007-01-01

    The National Protocols for Higher Education Approval Processes (the "National Protocols") are a key element of the national quality assurance framework for Australian higher education. They protect the standing of Australian higher education nationally and internationally by assuring students and the community that higher education institutions in…

  16. Characters related to higher starch accumulation in cassava storage roots

    PubMed Central

    Li, You-Zhi; Zhao, Jian-Yu; Wu, San-Min; Fan, Xian-Wei; Luo, Xing-Lu; Chen, Bao-Shan

    2016-01-01

    Cassava (Manihot esculenta) is valued mainly for high content starch in its roots. Our understanding of mechanisms promoting high starch accumulation in the roots is, however, still very limited. Two field-grown cassava cultivars, Huanan 124(H124) with low root starch and Fuxuan 01(F01) with high root starch, were characterised comparatively at four main growth stages. Changes in key sugars in the leaves, stems and roots seemed not to be strongly associated with the final amount of starch accumulated in the roots. However, when compared with H124, F01 exhibited a more compact arrangement of xylem vascular bundles in the leaf axils, much less callose around the phloem sieve plates in the stems, higher starch synthesis-related enzymatic activity but lower amylase activity in the roots, more significantly up-regulated expression of related genes, and a much higher stem flow rate (SFR). In conclusion, higher starch accumulation in the roots results from the concurrent effects of powerful stem transport capacity highlighted by higher SFR, high starch synthesis but low starch degradation in the roots, and high expression of sugar transporter genes in the stems. A model of high starch accumulation in cassava roots was therefore proposed and discussed. PMID:26892156

  17. Characters related to higher starch accumulation in cassava storage roots.

    PubMed

    Li, You-Zhi; Zhao, Jian-Yu; Wu, San-Min; Fan, Xian-Wei; Luo, Xing-Lu; Chen, Bao-Shan

    2016-01-01

    Cassava (Manihot esculenta) is valued mainly for high content starch in its roots. Our understanding of mechanisms promoting high starch accumulation in the roots is, however, still very limited. Two field-grown cassava cultivars, Huanan 124(H124) with low root starch and Fuxuan 01(F01) with high root starch, were characterised comparatively at four main growth stages. Changes in key sugars in the leaves, stems and roots seemed not to be strongly associated with the final amount of starch accumulated in the roots. However, when compared with H124, F01 exhibited a more compact arrangement of xylem vascular bundles in the leaf axils, much less callose around the phloem sieve plates in the stems, higher starch synthesis-related enzymatic activity but lower amylase activity in the roots, more significantly up-regulated expression of related genes, and a much higher stem flow rate (SFR). In conclusion, higher starch accumulation in the roots results from the concurrent effects of powerful stem transport capacity highlighted by higher SFR, high starch synthesis but low starch degradation in the roots, and high expression of sugar transporter genes in the stems. A model of high starch accumulation in cassava roots was therefore proposed and discussed. PMID:26892156

  18. Generation of a two-center overlap integral over Slater orbitals of higher principal quantum numbers

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1992-01-01

    The expressions for two-center overlap integrals between angular s, p, and d Slater orbitals of arbitrary, higher principal quantum number are explicitly listed. The expressions obtained are extremely compact and independent of the coordinate system. It is further shown that the numerical values of the integrals obtained in this way are free from any numerical instability.

  19. An Ecological Fallacy in Higher Education Policy: The Use, Overuse and Misuse of "Low Participation Neighbourhoods"

    ERIC Educational Resources Information Center

    Harrison, Neil; McCaig, Colin

    2015-01-01

    One form of ecological fallacy is found in the dictum that "you are where you live"--otherwise expressed in the idea that you can infer significant information about an individual or their family from the prevailing conditions around their home. One expression of this within higher education in the UK has been the use (and, arguably,…

  20. ACE expression in monocytes is induced by cytokines, phorbol ester and steroid

    SciTech Connect

    Lazarus, D.; Lanzillo, J.; Fanburg, B. )

    1991-03-15

    Angiotensin converting enzyme (ACE) levels are elevated in the serum and peripheral blood monocytes (PBM) of patients with granulomatous diseases. However, the role of ACE in (Mo) physiology and the regulation of the inflammatory response is not well understood. Since Mo can be stimulated to form giant cells using phorbol esters, glucocorticoids or certain inflammatory cytokines, the authors examined production of ACE protein by normal PBM, a Mo-like cell line, THP-1, and a macrophage-like cell line, U937 following stimulation with these agents. Using a sensitive ELISA assay, they found that in U937 cells, expression of ACE protein increased by 3.4 fold with dexamethasone, 3.7. fold with phorbol 12-myristate acetate (PMA), and 5.8 fold with the two agents combined. The cytokines IL-4 and GM-CSF substantially increased ACE expression, by 7.6 and 7.7 fold respectively, with maximal effect at 0.01 U/ml, while IFN-{gamma} and TNF-{alpha} had little effect. Similar results were found with PBM and THP-1 cells. The combination of dexamethasone and PMA also induced homotypic cluster formation in PBM, suggesting a correlation between cell adhesion and ACE production. The authors conclude that ACE expression in monocytes and macrophages is stimulated by low concentration of glucocorticoids and certain inflammatory cytokines. ACE may participate in the initiation and propagation of granulomatous inflammatory processes.

  1. Optimization of sunflower oil expression

    SciTech Connect

    Singh, M.S.; Farsaie, A.; Stewart, L.E.

    1983-12-01

    Models to predict input energy for sunflower oil extraction were developed for four seed types. Input energy was found to be the lowest in case of whole seed at low seed moisture content (up to 7%), whereas, at higher moisture content, coarsely ground seed required the minimum input energy. Maximum net energy was obtained for coarsely ground seed with 8% moisture content, heated to 35/sup 0/C and expressed at 28 MPa for 5.5 minutes.

  2. Disorder of written expression

    MedlinePlus

    Written expression disorder; Dysgraphia; Specific learning disorder with impairment in written expression ... Specific learning disorder with impairment in written expression is as common as other learning disorders, which is about 5 ...

  3. Tumor necrosis factor-alpha induces nuclear factor-kappaB-dependent TRPC1 expression in endothelial cells.

    PubMed

    Paria, Biman C; Malik, Asrar B; Kwiatek, Angela M; Rahman, Arshad; May, Michael J; Ghosh, Sankar; Tiruppathi, Chinnaswamy

    2003-09-26

    We investigated the role of tumor necrosis factor-alpha (TNF-alpha) in activating the store-operated Ca2+ channels in endothelial cells via the expression of transient receptor potential channel (TRPC) isoforms. We observed that TNF-alpha exposure of human umbilical vein endothelial cells resulted in TRPC1 mRNA and protein expression, whereas it had no effect on TRPC3, TRPC4, or TRPC5 expression. The TRPC1 expression was associated with increased Ca2+ influx after intracellular Ca2+ store depletion with either thrombin or thapsigargin. We cloned the 5'-regulatory region of the human TRPC1 (hTRPC1) gene which contained a TATA box and CCAAT sequence close to the transcription initiation site. We also identified four nuclear factor-kappaB (NF-kappaB)-binding sites in the 5'-regulatory region. To address the contribution of NF-kappaB in the mechanism of TRPC1 expression, we determined the effects of TNF-alpha on expression of the reporter luciferase after transfection of hTRPC1 promoter-luciferase (hTRPC1-Pro-Luc) construct in the human dermal microvascular endothelial cell line. Reporter activity increased >4-fold at 4 h after TNF-alpha challenge. TNF-alpha-induced increase in reporter activity was markedly reduced by co-expression of either kinase-defective IKKbeta kinase mutant or non-phosphorylatable IkappaB mutant. Treatment with NEMO-binding domain peptide, which prevents NF-kappaB activation by selectively inhibiting IKKgamma interaction with IKK complex, also blocked the TNF-alpha-induced TRPC1 expression. Thus, TNF-alpha induces TRPC1 expression through an NF-kappaB-dependent pathway in endothelial cells, which can trigger augmented Ca2+ entry following Ca2+ store depletion. The augmented Ca2+ entry secondary to TRPC1 expression may be an important mechanism of endothelial injury induced by TNF-alpha. PMID:12855710

  4. Role of NF-κB-dependent Caveolin-1 Expression in the Mechanism of Increased Endothelial Permeability Induced by Lipopolysaccharide*S

    PubMed Central

    Tiruppathi, Chinnaswamy; Shimizu, Jun; Miyawaki-Shimizu, Kayo; Vogel, Stephen M.; Bair, Angela M.; Minshall, Richard D.; Predescu, Dan; Malik, Asrar B.

    2008-01-01

    We investigated the role of NF-κB activation by the bacterial product lipopolysaccharide (LPS) in inducing caveolin-1 (Cav-1) expression and its consequence in contributing to the leakiness of the endothelial barrier. We observed that LPS challenge of human lung microvascular endothelial cells induced concentration- and time-dependent increases in expression of Cav-1 mRNA and protein. The NEMO (NF-κB essential modifier binding domain)-binding domain peptide (IkB kinase (IKK)-NEMO-binding domain (NBD) peptide), which prevents NF-κB activation by inhibiting the interaction of IKKγ with the IKK complex, blocked LPS-induced Cav-1 mRNA and protein expression. Knockdown of NF-κB subunit p65/RelA expression with small interfering RNA also prevented LPS-induced Cav-1 expression. Caveolae open to the apical and basal plasmalemma of endothelial cells increased 2–4-fold within 4 h of LPS exposure. IKK-NBD peptide markedly reduced the LPS-induced increase in the number of caveolae as well as transendothelial albumin permeability. These observations were recapitulated in mouse studies in which IKK-NBD peptide prevented Cav-1 expression and interfered with the increase in lung microvessel permeability induced by LPS. Thus, LPS mediates NF-κB-dependent Cav-1 expression that results in increased caveolae number and thereby contributes to the mechanism of increased transendothelial albumin permeability. PMID:18077459

  5. Hispanics and Higher Education: Multicultural Myopia.

    ERIC Educational Resources Information Center

    Erlach, David

    2000-01-01

    Hispanic Americans are underrepresented in higher education and in business faculty. Their career development is often hindered by discrimination and they are often channeled into two-year colleges where attrition is higher. (SK)

  6. New Programs Urged for Higher Education

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1975

    1975-01-01

    The Carnegie Council on Policy Studies in Higher Education released a report which calls for three new programs of Federal aid to higher education: tuition equalization grants, national student loan bank, support for large research libraries. (GS)

  7. Reclaiming Our Soul: Democracy and Higher Education.

    ERIC Educational Resources Information Center

    Chickering, Arthur W.

    2003-01-01

    Explores how, as higher education faces new financial realities together with escalating demands for more accountability, a call to reclaim the soul of higher education and with it, the soul of democracy, will require significant institutional and personal transformations. (EV)

  8. Hispanic Higher Education and HSIs. Fact Sheet

    ERIC Educational Resources Information Center

    Hispanic Association of Colleges and Universities, 2012

    2012-01-01

    This paper presents facts about Hispanic higher education. Facts on the following topics are presented: (1) Hispanic demographics; (2) Hispanic academic attainment; (3) Hispanic higher education; and (4) Hispanic-Serving Institutions (HSIs).

  9. Measuring Competencies of Higher Education Graduates

    ERIC Educational Resources Information Center

    Allen, Jim; Ramaekers, Ger; van der Velden, Rolf

    2005-01-01

    This chapter describes a new conceptual model for measuring competencies of higher education graduates. The proposed instrument can become a valuable tool for higher education quality management, policy evaluation, and scientific research. (Contains 1 figure.)

  10. India's Higher Education Challenges

    ERIC Educational Resources Information Center

    Altbach, Philip G.

    2014-01-01

    India, with the world'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's higher education system is characterized by "islands of excellence in a sea of mediocrity." The mainstream…

  11. Colleges and the Governance of Higher Education

    ERIC Educational Resources Information Center

    Parry, Gareth

    2013-01-01

    The governance of higher education in colleges and college sectors that offer other types of education and training is distinctive in four main respects. First, governance structures are frequently separate and different for higher education and for other segments of tertiary education. Second, the size and scope of the higher-level education…

  12. The Changing Nature of China's Higher Education

    ERIC Educational Resources Information Center

    Chen, Linhan

    2013-01-01

    This paper discusses the changing nature of China's higher education by turning to the changes that happened to China's higher education system brought about by implementing different government policies of higher education. The implementation of the policies, the restructuring of universities and independent colleges in 1952, the enrolling of…

  13. Twenty Years of Higher Education in Virginia.

    ERIC Educational Resources Information Center

    Davies, Gordon K.

    This report on Virginia higher education briefly reviews the impact of economic recession, slashed budgets, increased tuition, and increasing politicization upon the state's higher education system, and then looks ahead to issues critical to the higher education's future in the state. The report proposes action in three areas: (1) adequate funding…

  14. When Higher Working Memory Capacity Hinders Insight

    ERIC Educational Resources Information Center

    DeCaro, Marci S.; Van Stockum, Charles A., Jr.; Wieth, Mareike B.

    2016-01-01

    Higher working memory capacity (WMC) improves performance on a range of cognitive and academic tasks. However, a greater ability to control attention sometimes leads individuals with higher WMC to persist in using complex, attention-demanding approaches that are suboptimal for a given task. We examined whether higher WMC would hinder insight…

  15. Reconfiguring the Higher Education Value Chain

    ERIC Educational Resources Information Center

    Pathak, Virendra; Pathak, Kavita

    2010-01-01

    Forces of demand and supply are changing the dynamics of the higher education market. Transformation of institutions of higher learning into competitive enterprise is underway. Higher education institutions are seemingly under intense pressure to create value and focus their efforts and scarce funds on activities that drive up value for their…

  16. Guidelines for Planning in Higher Education.

    ERIC Educational Resources Information Center

    Anderson, Kenneth E.; Acero, Herman D.

    Guidelines for planning in higher education (which might have an application in Colombia) are described. Chapter 1 provides an expanded definition of higher education that includes noncollege channels to lifelong education and embraces all viable postsecondary education. Chapter 2 addresses current problems facing higher education, such as lack of…

  17. Higher order architecture of collections of objects

    NASA Astrophysics Data System (ADS)

    Baas, Nils A.

    2015-01-01

    We show that on an arbitrary collection of objects there is a wide variety of higher order architectures governed by hyperstructures. Higher order gluing, local to global processes, fusion of collections, bridges and higher order types are discussed. We think that these types of architectures may have interesting applications in many areas of science.

  18. Higher Education and Basic Health Needs.

    ERIC Educational Resources Information Center

    Nasution, S.; Virasai, Banphot, Eds.

    The proceedings of the Regional Institute of Higher Education and Development's seminar on higher education's commitment to the basic health needs of society are recorded. The first part of the seminar contains the official opening and several addresses that focus on basic health care in Southeast Asia. Part II, "Contributions of Higher Education…

  19. Character Development Practices in Higher Education Institutions

    ERIC Educational Resources Information Center

    Wesley, Vernon L.

    2010-01-01

    Character Development continues to be the all too unintentional elephant in the room of Higher Education. This project looked at what character development practices are being accomplished and who in higher education is making it happen. No longer satisfied with leaving the task to elementary and secondary education, higher education has begun to…

  20. Measuring Institutional Performance in Higher Education.

    ERIC Educational Resources Information Center

    Meyerson, Joel W., Ed.; Massy, William F., Ed.

    This collection of seven essays from the Stanford Forum for Higher Education Futures focuses on how downsizing, quality management, and reengineering have are affecting higher education. An introductory paper, "Introduction: Change in Higher Education: Its Effect on Institutional Performance," (Joel W. Meyerson and Sandra L. Johnson) notes that…