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Sample records for express higher levels

  1. 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

  2. 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…

  3. 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

  4. 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

  5. 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

  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. 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

  8. 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.

  9. 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…

  10. 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

  11. Higher level twisted Zhu algebras

    SciTech Connect

    Ekeren, Jethro van

    2011-05-15

    The study of twisted representations of graded vertex algebras is important for understanding orbifold models in conformal field theory. In this paper, we consider the general setup of a vertex algebra V, graded by {Gamma}/Z for some subgroup {Gamma} of R containing Z, and with a Hamiltonian operator H having real (but not necessarily integer) eigenvalues. We construct the directed system of twisted level p Zhu algebras Zhu{sub p,{Gamma}}(V), and we prove the following theorems: For each p, there is a bijection between the irreducible Zhu{sub p,{Gamma}}(V)-modules and the irreducible {Gamma}-twisted positive energy V-modules, and V is ({Gamma}, H)-rational if and only if all its Zhu algebras Zhu{sub p,{Gamma}}(V) are finite dimensional and semisimple. The main novelty is the removal of the assumption of integer eigenvalues for H. We provide an explicit description of the level p Zhu algebras of a universal enveloping vertex algebra, in particular of the Virasoro vertex algebra Vir{sup c} and the universal affine Kac-Moody vertex algebra V{sup k}(g) at non-critical level. We also compute the inverse limits of these directed systems of algebras.

  12. 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

  13. 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

  14. 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

  15. Levels of Analysis in Higher Education Research

    ERIC Educational Resources Information Center

    Tight, Malcolm

    2012-01-01

    This article examines the levels of analysis adopted in higher education research, using a database of 567 articles published in 15 leading higher education journals internationally during 2010. Level of analysis is a relatively overlooked issue in this field of research, when compared with methodology, theory and/or topic--to which it is, of…

  16. Web life: Confused at a Higher Level

    NASA Astrophysics Data System (ADS)

    2010-08-01

    This two-person blog owes its name to Enrico Fermi, who supposedly informed a visiting lecturer that although he used to be confused about the lecture topic, "having listened to your lecture, I am still confused. But on a higher level".

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Higher-level simulations of turbulent flows

    NASA Technical Reports Server (NTRS)

    Ferziger, J. H.

    1981-01-01

    The fundamentals of large eddy simulation are considered and the approaches to it are compared. Subgrid scale models and the development of models for the Reynolds-averaged equations are discussed as well as the use of full simulation in testing these models. Numerical methods used in simulating large eddies, the simulation of homogeneous flows, and results from full and large scale eddy simulations of such flows are examined. Free shear flows are considered with emphasis on the mixing layer and wake simulation. Wall-bounded flow (channel flow) and recent work on the boundary layer are also discussed. Applications of large eddy simulation and full simulation in meteorological and environmental contexts are included along with a look at the direction in which work is proceeding and what can be expected from higher-level simulation in the future.

  3. 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.

  4. 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.

  5. NEWS: Help for the higher level

    NASA Astrophysics Data System (ADS)

    2000-03-01

    January 2000 saw the instigation of a network of subject centres to promote high quality learning and teaching practices in universities and colleges throughout the UK. A total of £30m has been committed over five years by the four funding bodies for UK higher education to this Learning and Teaching Support Network (LTSN). The network will consist of 24 subject centres, each hosted by a university or college, plus a Generic Learning and Teaching Centre based in York (as part of the new Institute for Learning and Teaching). The latter centre will give advice on issues that affect higher education as a whole - such as the use of information technology. Among the tasks for the subject centres will be: the collation and promotion of information on good practice; the promotion of computing and IT approaches to teaching, learning and assessment; the provision of opportunities for professional development; and the maintenance of working relationships with professional bodies both in the UK and internationally. The subject centre for the Physical Sciences will be at the University of Hull (contact Dr Tina Overton, tel: 01482 465 453) with Engineering at Loughborough, Materials at Liverpool, Medicine at Newcastle, Mathematics, Statistics and Operational Research at Birmingham. The first annual conference of the Institute for Learning and Teaching in Higher Education is planned for 27 - 29 June at the College of Ripon and York St John. More details of this and the other events organized by the Institute can be obtained from ILT, Genesis 3, Innovation Way, York Science Park, Heslington, York YO10 5DQ (tel: 01904 434222, enquiries@ilt.ac.uk or www.ilt.ac.uk ).

  6. 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

  7. Higher LPA2 and LPA6 mRNA Levels in Hepatocellular Carcinoma Are Associated with Poorer Differentiation, Microvascular Invasion and Earlier Recurrence with Higher Serum Autotaxin Levels.

    PubMed

    Enooku, Kenichiro; Uranbileg, Baasanjav; Ikeda, Hitoshi; Kurano, Makoto; Sato, Masaya; Kudo, Hiroki; Maki, Harufumi; Koike, Kazuhiko; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    Hepatocellular carcinoma (HCC) commonly develops in patients with liver fibrosis; in these patients, the blood levels of lysophosphatidic acid (LPA) and its generating enzyme autotaxin (ATX) increase with the liver fibrosis stage. We aimed to examine the potential relevance of ATX and LPA in HCC. Fifty-eight HCC patients who underwent surgical treatment were consecutively enrolled in the study. Among the LPA receptors in HCC, higher LPA2 mRNA levels correlated with poorer differentiation, and higher LPA6 mRNA levels correlated with microvascular invasion, which suggested a higher malignant potential of HCC with increased LPA2 and LPA6 expression. In patients with primary HCC, neither LPA2 nor LPA6 mRNA levels were associated with recurrence. However, when serum ATX levels were combined for analysis as a surrogate for plasma LPA levels, the cumulative intra-hepatic recurrence rate was higher in patients in whom both serum ATX levels and LPA2 or LPA6 mRNA levels were higher than the median. However, the mRNA level of phosphatidic acid-selective phospholipase A1ɑ, another LPA-generating enzyme, in HCC patients was not associated with pathological findings or recurrence, even in combination with the expression of LPA receptors. Higher LPA2 mRNA levels were associated with poorer differentiation, and higher LPA6 levels were associated with microvascular invasion in HCC; both became a risk factor for recurrence after surgical treatment when combined with increased serum ATX levels. ATX and LPA receptors merit consideration as therapeutic targets of HCC. PMID:27583415

  8. 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

  9. Outcomes from Higher-Level Vocational Education and Training Qualifications

    ERIC Educational Resources Information Center

    Stanwick, John

    2006-01-01

    Where do higher-level vocational education and training (VET) qualifications lead? This study investigates whether they lead to employment at associate professional or higher occupations, or whether they are a pathway to university studies. Findings indicate that there are good employment outcomes for some graduates, although often at below…

  10. Interactive Learning in a Higher Education Level 1 Mechanics Module.

    ERIC Educational Resources Information Center

    Booth, Kathryn M.; James, Brian W.

    2001-01-01

    Encourages Level 1 students (those taking a subject for the first time at the higher education level) to develop a deeper learning approach. Uses a cooperative learning approach to pose conceptual questions for interactive discussions and changes both teaching method and form of examination paper for a Mechanics module. (Contains 17 references.)…

  11. Sexual differences of imprinted genes' expression levels.

    PubMed

    Faisal, Mohammad; Kim, Hana; Kim, Joomyeong

    2014-01-01

    In mammals, genomic imprinting has evolved as a dosage-controlling mechanism for a subset of genes that play critical roles in their unusual reproduction scheme involving viviparity and placentation. As such, many imprinted genes are highly expressed in sex-specific reproductive organs. In the current study, we sought to test whether imprinted genes are differentially expressed between the two sexes. According to the results, the expression levels of the following genes differ between the two sexes of mice: Peg3, Zim1, Igf2, H19 and Zac1. The expression levels of these imprinted genes are usually greater in males than in females. This bias is most obvious in the developing brains of 14.5-dpc embryos, but also detected in the brains of postnatal-stage mice. However, this sexual bias is not obvious in 10.5-dpc embryos, a developmental stage before the sexual differentiation. Thus, the sexual bias observed in the imprinted genes is most likely attributable by gonadal hormones rather than by sex chromosome complement. Overall, the results indicate that several imprinted genes are sexually different in terms of their expression levels, and further suggest that the transcriptional regulation of these imprinted genes may be influenced by unknown mechanisms associated with sexual differentiation. PMID:24125951

  12. Teaching Higher Level Thinking Skills through Computer Courseware.

    ERIC Educational Resources Information Center

    Edwards, Lois

    A rationale is presented for teaching gifted students to gain computer literacy, learn programing, use utility software (e.g., word processing packages), and use interactive educational courseware containing drills, simulations, or educational strategy games to develop higher level and creative thinking skills. Evaluation of courseware for gifted…

  13. Middle Level Technician/Higher Technical & Business Skills. Evaluation Report.

    ERIC Educational Resources Information Center

    European Social Fund, Dublin (Ireland).

    A study examined European Social Fund (ESF)-funded middle-level technician (MLT) and higher technical and business skills (HTBS) courses at Irish technical colleges. Data were obtained from the following: review of relevant literature; review of all program-monitoring documents submitted by Ireland's Department of Education since 1990; interviews…

  14. Seeking a Higher Level of Arts Integration across the Curriculum

    ERIC Educational Resources Information Center

    Sotiropoulou-Zormpala, Marina

    2016-01-01

    To seek a higher level of arts integration across the education curriculum, I investigated designs of teaching through arts activities that would motivate educators to adopt the spirit of "aesthetic teaching." Two different designs were tested, with the second as a continuation of the first. Each ascribes a different educational role to…

  15. Population-level control of gene expression

    NASA Astrophysics Data System (ADS)

    Nevozhay, Dmitry; Adams, Rhys; van Itallie, Elizabeth; Bennett, Matthew; Balazsi, Gabor

    2011-03-01

    Gene expression is the process that translates genetic information into proteins, that determine the way cells live, function and even die. It was demonstrated that cells with identical genomes exposed to the same environment can differ in their protein composition and therefore phenotypes. Protein levels can vary between cells due to the stochastic nature of intracellular biochemical events, indicating that the genotype-phenotype connection is not deterministic at the cellular level. We asked whether genomes could encode isogenic cell populations more reliably than single cells. To address this question, we built two gene circuits to control three cell population-level characteristics: gene expression mean, coefficient of variation and non-genetic memory of previous expression states. Indeed, we found that these population-level characteristics were more predictable than the gene expression of single cells in a well-controlled environment. This research was supported by the NIH Director's New Innovator Award 1DP2 OD006481-01 and Welch Foundation Grant C-1729.

  16. The Role of State Higher Education Governance Structures in State-Level Higher Education Lobbying

    ERIC Educational Resources Information Center

    Burkum, Kurt Richard

    2009-01-01

    Lobbying and lobbyists are integral components of federal and state public policymaking for higher education at the federal and state levels. While the actions and goals of lobbyists appear to be straightforward, the lobbying tactics selected by lobbyists vary for different situations and in different contexts (Browne, 1985; Cook, 1998; Gladieux &…

  17. The timecourse of higher-level face aftereffects.

    PubMed

    Rhodes, Gillian; Jeffery, Linda; Clifford, Colin W G; Leopold, David A

    2007-08-01

    Perceptual aftereffects for simple visual attributes processed early in the cortical hierarchy increase logarithmically with adapting duration and decay exponentially with test duration. This classic timecourse has been reported recently for a face identity aftereffect [Leopold, D. A., Rhodes, G., Müller, K.-M., & Jeffery, L. (2005). The dynamics of visual adaptation to faces. Proceedings of the Royal Society of London, Series B, 272, 897-904], suggesting that the dynamics of visual adaptation may be similar throughout the visual system. An alternative interpretation, however, is that the classic timecourse is a flow-on effect of adaptation of a low-level, retinotopic component of the face identity aftereffect. Here, we examined the timecourse of the higher-level (size-invariant) components of two face aftereffects, the face identity aftereffect and the figural face aftereffect. Both showed the classic pattern of logarithmic build-up and exponential decay. These results indicate that the classic timecourse of face aftereffects is not a flow-on effect of low-level retinotopic adaptation, and support the hypothesis that dynamics of visual adaptation are similar at higher and lower levels of the cortical visual hierarchy. They also reinforce the perceptual nature of face aftereffects, ruling out demand characteristics and other post-perceptual factors as plausible accounts. PMID:17619045

  18. Light gazpachos contain higher phytochemical levels than conventional gazpachos.

    PubMed

    Vallverdú-Queralt, Anna; Medina-Remón, Alexander; Estruch, Ramón; Lamuela-Raventós, Rosa M

    2013-08-01

    Light gazpachos in comparison with conventional alternatives are interesting because of their low percentage of fat and high content of bioactive compounds that are beneficial for human health. An hybrid quadrupole time-of-flight mass spectrometer was used to identify those metabolites that have the greatest impact on the overall metabolic profile in light gazpachos as compared to conventional alternatives. Individual polyphenols were quantified using liquid chromatography-electrospray ionization tandem mass spectrometry. Data obtained revealed that light gazpachos displayed a higher significant phytochemical content than conventionally produced alternatives. The compounds found in significantly higher (p < 0.05) amounts in light versus conventional gazpachos were: caffeoylquinic and dicaffeoylquinic acids, caffeic and caffeic acid hexosides, kaempferol-3-O-rutinoside, ferulic and ferulic acid hexosides, naringenin-7-O-glucoside, naringenin, rutin and quercetin. Light gazpachos may play a crucial role in terms of health benefits (lower fat and higher bioactive compound intake). Higher consumption levels of phenolic compounds, which are greater in light products, along with caloric restriction and physical activity may be helpful in preventing obesity. PMID:23729418

  19. Epstein-Barr Viruses (EBVs) Deficient in EBV-Encoded RNAs Have Higher Levels of Latent Membrane Protein 2 RNA Expression in Lymphoblastoid Cell Lines and Efficiently Establish Persistent Infections in Humanized Mice

    PubMed Central

    Gregorovic, Goran; Boulden, Elizabeth A.; Bosshard, Rachel; Elgueta Karstegl, Claudio; Skalsky, Rebecca; Cullen, Bryan R.; Gujer, Cornelia; Rämer, Patrick; Münz, Christian

    2015-01-01

    Functions of Epstein-Barr virus (EBV)-encoded RNAs (EBERs) were tested in lymphoblastoid cell lines containing EBER mutants of EBV. Binding of EBER1 to ribosomal protein L22 (RPL22) was confirmed. Deletion of EBER1 or EBER2 correlated with increased levels of cytoplasmic EBV LMP2 RNA and with small effects on specific cellular microRNA (miRNA) levels, but protein levels of LMP1 and LMP2A were not affected. Wild-type EBV and EBER deletion EBV had approximately equal abilities to infect immunodeficient mice reconstituted with a human hematopoietic system. PMID:26339045

  20. Epstein-Barr Viruses (EBVs) Deficient in EBV-Encoded RNAs Have Higher Levels of Latent Membrane Protein 2 RNA Expression in Lymphoblastoid Cell Lines and Efficiently Establish Persistent Infections in Humanized Mice.

    PubMed

    Gregorovic, Goran; Boulden, Elizabeth A; Bosshard, Rachel; Elgueta Karstegl, Claudio; Skalsky, Rebecca; Cullen, Bryan R; Gujer, Cornelia; Rämer, Patrick; Münz, Christian; Farrell, Paul J

    2015-11-01

    Functions of Epstein-Barr virus (EBV)-encoded RNAs (EBERs) were tested in lymphoblastoid cell lines containing EBER mutants of EBV. Binding of EBER1 to ribosomal protein L22 (RPL22) was confirmed. Deletion of EBER1 or EBER2 correlated with increased levels of cytoplasmic EBV LMP2 RNA and with small effects on specific cellular microRNA (miRNA) levels, but protein levels of LMP1 and LMP2A were not affected. Wild-type EBV and EBER deletion EBV had approximately equal abilities to infect immunodeficient mice reconstituted with a human hematopoietic system. PMID:26339045

  1. Higher fuel prices are associated with lower air pollution levels.

    PubMed

    Barnett, Adrian G; Knibbs, Luke D

    2014-05-01

    Air pollution is a persistent problem in urban areas, and traffic emissions are a major cause of poor air quality. Policies to curb pollution levels often involve raising the price of using private vehicles, for example, congestion charges. We were interested in whether higher fuel prices were associated with decreased air pollution levels. We examined an association between diesel and petrol prices and four traffic-related pollutants in Brisbane from 2010 to 2013. We used a regression model and examined pollution levels up to 16 days after the price change. Higher diesel prices were associated with statistically significant short-term reductions in carbon monoxide and nitrogen oxides. Changes in petrol prices had no impact on air pollution. Raising diesel taxes in Australia could be justified as a public health measure. As raising taxes is politically unpopular, an alternative political approach would be to remove schemes that put a downward pressure on fuel prices, such as industry subsidies and shopping vouchers that give fuel discounts. PMID:24552771

  2. Serum adropin level and ENHO gene expression in systemic sclerosis.

    PubMed

    Yolbas, Servet; Kara, Murat; Yilmaz, Musa; Aydin, Suleyman; Koca, Suleyman Serdar

    2016-06-01

    Adropin, a secreted protein, is encoded by the energy homeostasis associated (ENHO) gene. It has been implicated in the several physiological and pathological processes such as angiogenesis and apoptosis. Therefore, the aim of present study was to investigate serum adropin levels and ENHO gene expressions in systemic sclerosis (SSc) characterized by vasculopathy, inflammation, and progressive fibrosis of the skin and internal organs. The study includes 27 patients with SSc, 39 patients with Behçet's disease (BD), and 20 healthy controls (HC). Serum adropin levels and ENHO gene expressions by peripheral blood mononuclear cells were analyzed by ELISA method and by real-time PCR, respectively. The serum adropin levels were higher in the SSc and BD groups than in the HC group (p = 0.023 and p < 0.001, respectively). However, there were no significant differences among the groups in terms of ENHO gene expressions (p ANOVA = 0.149). There was no significant difference between the limited and diffuse cutaneous subtypes of SSc in terms of serum adropin level and ENHO gene expression. Moreover, serum adropin level and ENHO gene expression were not associated with the disease activity and severity indexes. ENHO gene expression was correlated with the triglyceride levels in the BD group (r = -0.426, p = 0.027). The augmented serum adropin levels may be expected in the chronic inflammatory disease and seem not to be characteristic of only SSc. However, further studies are needed to explain the precise role of adropin in SSc. PMID:27079850

  3. Higher-level linguistic categories dominate lower-level acoustics in lexical tone processing.

    PubMed

    Zhao, T Christina; Kuhl, Patricia K

    2015-08-01

    Native tonal-language speakers exhibit reduced sensitivity to lexical tone differences within, compared to across, categories (higher-level linguistic category influence). Yet, sensitivity is enhanced among musically trained, non-tonal-language-speaking individuals (lower-level acoustics processing influence). The current study investigated the relative contribution of higher- and lower-level influences when both are present. Seventeen Mandarin musicians completed music pitch and lexical tone discrimination tasks. Similar to English musicians [Zhao and Kuhl (2015). J. Acoust. Soc. Am. 137(3), 1452-1463], Mandarin musicians' overall sensitivity to lexical tone differences was associated with music pitch score, suggesting lower-level contributions. However, the musician's sensitivities to lexical tone pairs along a continuum were similar to Mandarin non-musicians, reflecting dominant higher-level influences. PMID:26328738

  4. Extension of TFTR operations to higher toroidal field levels

    SciTech Connect

    Woolley, R.D.

    1995-12-31

    For the past year, TFTR has sometimes operated at extended toroidal field (TF) levels. The extension to 5.6 Tesla (79 kA) was crucial for TFTR`s November 1994 10.7 MW DT fusion power record. The extension to 6.0 Tesla (85 kA) was commissioned on 9 September 1995. There are several reasons that one could expect the TF coils to survive the higher stresses that develop at higher fields. They were designed to operate at 5.2 Tesla with a vertical field of 0.5 Tesla, whereas the actual vertical field needed for the plasma does not exceed 0.35 Tesla. Their design specification explicitly required they survive some pulses at 6.0 Tesla. TF coil mechanical analysis computer models available during coil design were crude, leading to conservative design. And design analyses also had to consider worst-case misoperations that TFTR`s real time Coil Protection Calculators (CPCs) now positively prevent from occurring.

  5. Calcium regulates caveolin-1 expression at the transcriptional level

    SciTech Connect

    Yang, Xiao-Yan; Huang, Cheng-Cheng; Kan, Qi-Ming; Li, Yan; Liu, Dan; Zhang, Xue-Cheng; Sato, Toshinori; Yamagata, Sadako; Yamagata, Tatsuya

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Caveolin-1 expression is regulated by calcium signaling at the transcriptional level. Black-Right-Pointing-Pointer An inhibitor of or siRNA to L-type calcium channel suppressed caveolin-1 expression. Black-Right-Pointing-Pointer Cyclosporine A or an NFAT inhibitor markedly reduced caveolin-1 expression. Black-Right-Pointing-Pointer Caveolin-1 regulation by calcium signaling is observed in several mouse cell lines. -- Abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca{sup 2+}/calcineurin/NFAT.

  6. A higher-level phylogenetic classification of the Fungi.

    PubMed

    Hibbett, David S; Binder, Manfred; Bischoff, Joseph F; Blackwell, Meredith; Cannon, Paul F; Eriksson, Ove E; Huhndorf, Sabine; James, Timothy; Kirk, Paul M; Lücking, Robert; Thorsten Lumbsch, H; Lutzoni, François; Matheny, P Brandon; McLaughlin, David J; Powell, Martha J; Redhead, Scott; Schoch, Conrad L; Spatafora, Joseph W; Stalpers, Joost A; Vilgalys, Rytas; Aime, M Catherine; Aptroot, André; Bauer, Robert; Begerow, Dominik; Benny, Gerald L; Castlebury, Lisa A; Crous, Pedro W; Dai, Yu-Cheng; Gams, Walter; Geiser, David M; Griffith, Gareth W; Gueidan, Cécile; Hawksworth, David L; Hestmark, Geir; Hosaka, Kentaro; Humber, Richard A; Hyde, Kevin D; Ironside, Joseph E; Kõljalg, Urmas; Kurtzman, Cletus P; Larsson, Karl-Henrik; Lichtwardt, Robert; Longcore, Joyce; Miadlikowska, Jolanta; Miller, Andrew; Moncalvo, Jean-Marc; Mozley-Standridge, Sharon; Oberwinkler, Franz; Parmasto, Erast; Reeb, Valérie; Rogers, Jack D; Roux, Claude; Ryvarden, Leif; Sampaio, José Paulo; Schüssler, Arthur; Sugiyama, Junta; Thorn, R Greg; Tibell, Leif; Untereiner, Wendy A; Walker, Christopher; Wang, Zheng; Weir, Alex; Weiss, Michael; White, Merlin M; Winka, Katarina; Yao, Yi-Jian; Zhang, Ning

    2007-05-01

    A comprehensive phylogenetic classification of the kingdom Fungi is proposed, with reference to recent molecular phylogenetic analyses, and with input from diverse members of the fungal taxonomic community. The classification includes 195 taxa, down to the level of order, of which 16 are described or validated here: Dikarya subkingdom nov.; Chytridiomycota, Neocallimastigomycota phyla nov.; Monoblepharidomycetes, Neocallimastigomycetes class. nov.; Eurotiomycetidae, Lecanoromycetidae, Mycocaliciomycetidae subclass. nov.; Acarosporales, Corticiales, Baeomycetales, Candelariales, Gloeophyllales, Melanosporales, Trechisporales, Umbilicariales ords. nov. The clade containing Ascomycota and Basidiomycota is classified as subkingdom Dikarya, reflecting the putative synapomorphy of dikaryotic hyphae. The most dramatic shifts in the classification relative to previous works concern the groups that have traditionally been included in the Chytridiomycota and Zygomycota. The Chytridiomycota is retained in a restricted sense, with Blastocladiomycota and Neocallimastigomycota representing segregate phyla of flagellated Fungi. Taxa traditionally placed in Zygomycota are distributed among Glomeromycota and several subphyla incertae sedis, including Mucoromycotina, Entomophthoromycotina, Kickxellomycotina, and Zoopagomycotina. Microsporidia are included in the Fungi, but no further subdivision of the group is proposed. Several genera of 'basal' Fungi of uncertain position are not placed in any higher taxa, including Basidiobolus, Caulochytrium, Olpidium, and Rozella. PMID:17572334

  7. Review of Alternative State-Level Higher Education Governance Structures.

    ERIC Educational Resources Information Center

    Oregon Univ. System, Eugene. Office of Academic Affairs.

    As part of the educational planning process, the Oregon State Board of Higher Education requested this review of alternative models for the Oregon University System (OUS). Staff of the Board of Higher Education synthesized existing literature on the variety of U.S. higher education governance structures, including newer models such as the public…

  8. Higher daily physical activity is associated with higher osteocalcin levels in adolescents

    PubMed Central

    Chahla, Saydi E.; Frohnert, Brigitte I.; Thomas, William; Kelly, Aaron S.; Nathan, Brandon M.; Polgreen, Lynda E.

    2015-01-01

    Background Exercise stimulates bone remodeling and improves insulin sensitivity (Si), even without associated weight loss. Osteocalcin (OCN), a bone-derived protein, is associated with improved Si. Purpose We examined how daily physical activity is associated with OCN and Si. Methods Physical activity was measured through questionnaires completed in Minneapolis from 2010 to 2012. A physical activity score (PAQsum) was calculated to quantify physical activity (range 1–5). OCN and bone specific alkaline phosphatase (BAP) were measured by ELISA. Si was measured by the insulin modified frequently sampled IV glucose tolerance test. Results The mean PAQsum value was 2.4 ± 0.8 in 47 participants (12–17.9 years old). PAQsum was positively associated with OCN (p = 0.006). Participants with PAQsum <  2 had significantly lower OCN levels compared to participants with PAQsum >  2 (p < 0.02). Obesity did not modify the association between PAQsum and OCN. There was no statistically significant association between PAQsum and Si or between OCN and Si, even after adjustment for percent body fat. Conclusions OCN is higher in more physically active individuals. More research is needed to clarify the relationship between OCN, physical activity and Si. PMID:26236583

  9. Identifying and Fostering Higher Levels of Geometric Thinking

    ERIC Educational Resources Information Center

    Škrbec, Maja; Cadež, Tatjana Hodnik

    2015-01-01

    Pierre M. Van Hiele created five levels of geometric thinking. We decided to identify the level of geometric thinking in the students in Slovenia, aged 9 to 11 years. The majority of students (60.7%) are at the transition between the zero (visual) level and the first (descriptive) level of geometric thinking. Nearly a third (31.7%) of students is…

  10. Schizophrenia Gene Expression Profile Reverted to Normal Levels by Antipsychotics

    PubMed Central

    Crespo-Facorro, Benedicto; Prieto, Carlos

    2015-01-01

    Background: Despite the widespread use of antipsychotics, little is known of the molecular bases behind the action of antipsychotic drugs. A genome-wide study is needed to characterize the genes that affect the clinical response and their adverse effects. Methods: Here we show the analysis of the blood transcriptome of 22 schizophrenia patients before and after medication with atypical antipsychotics by next-generation sequencing. Results: We found that 17 genes, among the 21 495 genes analyzed, have significantly-altered expression after medication (p-value adjusted [Padj] <0.05). Six genes (ADAMTS2, CD177, CNTNAP3, ENTPD2, RFX2, and UNC45B) out of the 17 are among the 200 genes that we characterized with differential expression in a previous study between antipsychotic-naïve schizophrenia patients and controls (Sainz et al., 2013). This number of schizophrenia-altered expression genes is significantly higher than expected by chance (Chi-test, Padj 1.19E-50), suggesting that at least part of the antipsychotic beneficial effects is exerted by modulating the expression of these genes. Interestingly, all six of these genes were overexpressed in patients and reverted to control levels of expression after treatment. We also found a significant enrichment of genes related to obesity and diabetes, known adverse affects of antipsychotics. Conclusions: These results may facilitate understanding of unknown molecular mechanisms behind schizophrenia symptoms and the molecular mechanisms of antipsychotic drugs. PMID:25522406

  11. System-Level and Strategic Indicators for Monitoring Higher Education in the Twenty-First Century. Studies on Higher Education.

    ERIC Educational Resources Information Center

    Yonezawa, Akiyoshi, Ed.; Kaiser, Frans, Ed.

    Papers in this collection result from the work carried out in the context of an Invitational Roundtable on System-Level Indicators for Higher/Tertiary Education organized by the European Centre for Higher Education (UNESCO-CEPES) and the Research Institute for Higher Education of Hiroshima University, Japan. Section 1, "The Roundtable--An…

  12. Charting the course for nurses' achievement of higher education levels.

    PubMed

    Kovner, Christine T; Brewer, Carol; Katigbak, Carina; Djukic, Maja; Fatehi, Farida

    2012-01-01

    To improve patient outcomes and meet the challenges of the U.S. health care system, the Institute of Medicine recommends higher educational attainment for the nursing workforce. Characteristics of registered nurses (RNs) who pursue additional education are poorly understood, and this information is critical to planning long-term strategies for U.S. nursing education. To identify factors predicting enrollment and completion of an additional degree among those with an associate or bachelor's as their pre-RN licensure degree, we performed logistic regression analysis on data from an ongoing nationally representative panel study following the career trajectories of newly licensed RNs. For associate degree RNs, predictors of obtaining a bachelor's degree are the following: being Black, living in a rural area, nonnursing work experience, higher positive affectivity, higher work motivation, working in the intensive care unit, and working the day shift. For bachelor's RNs, predictors of completing a master's degree are the following: being Black, nonnursing work experience, holding more than one job, working the day shift, working voluntary overtime, lower intent to stay at current employer, and higher work motivation. Mobilizing the nurse workforce toward higher education requires integrated efforts from policy makers, philanthropists, employers, and educators to mitigate the barriers to continuing education. PMID:23158196

  13. Quadrupole mass spectrometer driver with higher signal levels

    NASA Technical Reports Server (NTRS)

    Chutjian, Ara (Inventor); Aalami, Dean (Inventor); Darrach, Murray (Inventor); Orient, Otto (Inventor)

    2003-01-01

    Driving a quadrapole mass spectrometer includes obtaining an air core transformer with a primary and a secondary, matching the secondary to the mass spectrometer, and driving the primary based on first and second voltage levels. Driving of the primary is via an isolating stage that minimizes low level drive signal coupling.

  14. Reaching Higher Ground: Parental Outreach Programs at the Postsecondary Level

    ERIC Educational Resources Information Center

    Torres, Celina; Marquez, Amalia

    2005-01-01

    In this follow-up study to "College Knowledge: What Latino Parents Need to Know and Why They Don't Know It," [see ED469295], the Tomas Rivera Policy Institute examines how postsecondary institutions are mobilizing to address the need for college information among Latino parents. The primary objective of "Reaching Higher Ground" is to profile in…

  15. Assessing Higher Level Learning: Developing Rubrics for Case Analysis

    ERIC Educational Resources Information Center

    Rochford, Linda; Borchert, Patricia S.

    2011-01-01

    Case study analyses allow students to demonstrate proficiency in executing authentic tasks in marketing and management, facilitating faculty evaluation of higher order learning outcomes. Effective and consistent assessment of case analyses depends in large part on the development of sound rubrics. The authors explored the process of rubric…

  16. Higher Level Learning: Universities and Employers Working Together

    ERIC Educational Resources Information Center

    Elliot-Major, Lee

    2006-01-01

    This publication is a timely reminder of the innovative ways in which universities are providing skilled graduates for all sections of the economy. Working with employers is key to this; as the higher education (HE) sector begins to operate in a competitive market, employer-led provision will enable delivery of the skills that the labour market…

  17. Citizen Engagement for Starlight~ Taking it to a higher level

    NASA Astrophysics Data System (ADS)

    Fischer, Audrey Ann

    2015-08-01

    It is clearly evident that the time has come to dramatically increase the level of global citizen engagement for starlight restoration and light pollution abatement.Examining what has worked for other sucessful global campaigns, we'll share a leadership training corp program including a master power point that will be a living document, a truly global collaborative effort by light pollution abatement advocate groups and individuals that will be inclusive and responsive to the needs of current and future leaders... so that they may take activism to the next level... and starlight to the greatest level seen in decades. We can do this if we work together.

  18. HERA-B higher-level triggers: architecture and software

    NASA Astrophysics Data System (ADS)

    Gellrich, Andreas; Medinnis, Mike

    1998-02-01

    HERA-B will be studying CP-violation in the B-system in a high-rate hadronic environment. To accomplish this goal, HERA-B needs a sophisticated data acquisition and trigger system. Except for the first level, all trigger levels are implemented as PC-farms, running the Unix-like operating system, Linux, thus blurring the sharp border between online and offline application software. The hardware architecture and software environments are discussed.

  19. A promoter-level mammalian expression atlas

    PubMed Central

    2015-01-01

    Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly ‘housekeeping’, whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research. PMID:24670764

  20. Higher Level Thinking, Writing, and Democracy among Community College Students

    ERIC Educational Resources Information Center

    Shafer, Gregory

    2013-01-01

    In my work on the college's Committee on Multiculturalism and Ethnic Studies, I found that much of the written work done in our community college was based on lower level cognition, requiring none of the assessment or exploration that is emblematic of critical thought in a democracy. Most of the assignments asked students simply to recite…

  1. Development of Visual Literacy Levels Scale in Higher Education

    ERIC Educational Resources Information Center

    Arslan, Rumiye; Nalinci, Gülbin Zeren

    2014-01-01

    The aim of this study is to develop a scale determining the visual literacy levels of university students. After reviewing the relevant literature a 75 item draft scale was prepared. The scale was applied to 3rd and 4th year students of Education Faculty of Amasya University. Non-functional items have been excluded from the scale as a result of…

  2. Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts.

    PubMed

    Bermejo-Alvarez, P; Rizos, D; Rath, D; Lonergan, P; Gutierrez-Adan, A

    2010-02-23

    Although genetically identical for autosomal Chrs (Chr), male and female preimplantation embryos could display sex-specific transcriptional regulation. To illustrate sex-specific differences at the mRNA level, we compared gene-expression patterns between male and female blastocysts by DNA microarray comparison of nine groups of 60 bovine in vitro-produced blastocysts of each sex. Almost one-third of the transcripts detected showed sexual dimorphism (2,921 transcripts; false-discovery rate, P < 0.05), suggesting that in the absence of hormonal influences, the sex Chrs impose an extensive transcriptional regulation upon autosomal genes. Six genes were analyzed by qPCR in in vivo-derived embryos, which displayed similar sexual dimorphism. Ontology analysis suggested a higher global transcriptional level in females and a more active protein metabolism in males. A gene homolog to an X-linked gene involved in network interactions during spliceosome assembly was found in the Y-Chr. Most of the X-linked-expressed transcripts (88.5%) were up-regulated in females, but most of them (70%) exhibited fold-changes lower than 1.6, suggesting that X-Chr inactivation is partially achieved at the blastocyst stage. Almost half of the transcripts up-regulated in female embryos exhibiting more than 1.6-fold change were present in the X-Chr and eight of them were selected to determine a putative paternal imprinting by gene expression comparison with parthenogenetic embryos. Five (BEX, CAPN6, BEX2, SRPX2, and UBE2A) exhibited a higher expression in females than in parthenotes, suggesting that they are predominantly expressed by the paternal inherited X-Chr and that imprinting may increase the transcriptional skew caused by double X-Chr dosage. PMID:20133684

  3. Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts

    PubMed Central

    Bermejo-Alvarez, P.; Rizos, D.; Rath, D.; Lonergan, P.; Gutierrez-Adan, A.

    2010-01-01

    Although genetically identical for autosomal Chrs (Chr), male and female preimplantation embryos could display sex-specific transcriptional regulation. To illustrate sex-specific differences at the mRNA level, we compared gene-expression patterns between male and female blastocysts by DNA microarray comparison of nine groups of 60 bovine in vitro-produced blastocysts of each sex. Almost one-third of the transcripts detected showed sexual dimorphism (2,921 transcripts; false-discovery rate, P < 0.05), suggesting that in the absence of hormonal influences, the sex Chrs impose an extensive transcriptional regulation upon autosomal genes. Six genes were analyzed by qPCR in in vivo-derived embryos, which displayed similar sexual dimorphism. Ontology analysis suggested a higher global transcriptional level in females and a more active protein metabolism in males. A gene homolog to an X-linked gene involved in network interactions during spliceosome assembly was found in the Y-Chr. Most of the X-linked-expressed transcripts (88.5%) were up-regulated in females, but most of them (70%) exhibited fold-changes lower than 1.6, suggesting that X-Chr inactivation is partially achieved at the blastocyst stage. Almost half of the transcripts up-regulated in female embryos exhibiting more than 1.6-fold change were present in the X-Chr and eight of them were selected to determine a putative paternal imprinting by gene expression comparison with parthenogenetic embryos. Five (BEX, CAPN6, BEX2, SRPX2, and UBE2A) exhibited a higher expression in females than in parthenotes, suggesting that they are predominantly expressed by the paternal inherited X-Chr and that imprinting may increase the transcriptional skew caused by double X-Chr dosage. PMID:20133684

  4. A Higher Level Classification of All Living Organisms

    PubMed Central

    Ruggiero, Michael A.; Gordon, Dennis P.; Orrell, Thomas M.; Bailly, Nicolas; Bourgoin, Thierry; Brusca, Richard C.; Cavalier-Smith, Thomas; Guiry, Michael D.; Kirk, Paul M.

    2015-01-01

    We present a consensus classification of life to embrace the more than 1.6 million species already provided by more than 3,000 taxonomists’ expert opinions in a unified and coherent, hierarchically ranked system known as the Catalogue of Life (CoL). The intent of this collaborative effort is to provide a hierarchical classification serving not only the needs of the CoL’s database providers but also the diverse public-domain user community, most of whom are familiar with the Linnaean conceptual system of ordering taxon relationships. This classification is neither phylogenetic nor evolutionary but instead represents a consensus view that accommodates taxonomic choices and practical compromises among diverse expert opinions, public usages, and conflicting evidence about the boundaries between taxa and the ranks of major taxa, including kingdoms. Certain key issues, some not fully resolved, are addressed in particular. Beyond its immediate use as a management tool for the CoL and ITIS (Integrated Taxonomic Information System), it is immediately valuable as a reference for taxonomic and biodiversity research, as a tool for societal communication, and as a classificatory “backbone” for biodiversity databases, museum collections, libraries, and textbooks. Such a modern comprehensive hierarchy has not previously existed at this level of specificity. PMID:25923521

  5. Change of direction ability test differentiates higher level and lower level soccer referees.

    PubMed

    Yanci, J; Los, Arcos A; Grande, I; Casajús, J A

    2016-06-01

    This report examines the agility and level of acceleration capacity of Spanish soccer referees and investigates the possible differences between field referees of different categories. The speed test consisted of 3 maximum acceleration stretches of 15 metres. The change of direction ability (CODA) test used in this study was a modification of the Modified Agility Test (MAT). The study included a sample of 41 Spanish soccer field referees from the Navarre Committee of Soccer Referees divided into two groups: i) the higher level group (G1, n = 20): 2ndA, 2ndB and 3rd division referees from the Spanish National Soccer League (28.43 ± 1.39 years); and ii) the lower level group (G2, n = 21): Navarre Provincial League soccer referees (29.54 ± 1.87 years). Significant differences were found with respect to the CODA between G1 (5.72 ± 0.13 s) and G2 (6.06 ± 0.30 s), while no differences were encountered between groups in acceleration ability. No significant correlations were obtained in G1 between agility and the capacity to accelerate. Significant correlations were found between sprint and agility times in the G2 and in the total group. The results of this study showed that agility can be used as a discriminating factor for differentiating between national and regional field referees; however, no observable differences were found over the 5 and 15 m sprint tests. PMID:27274111

  6. Change of direction ability test differentiates higher level and lower level soccer referees

    PubMed Central

    Los, Arcos A; Grande, I; Casajús, JA

    2016-01-01

    This report examines the agility and level of acceleration capacity of Spanish soccer referees and investigates the possible differences between field referees of different categories. The speed test consisted of 3 maximum acceleration stretches of 15 metres. The change of direction ability (CODA) test used in this study was a modification of the Modified Agility Test (MAT). The study included a sample of 41 Spanish soccer field referees from the Navarre Committee of Soccer Referees divided into two groups: i) the higher level group (G1, n = 20): 2ndA, 2ndB and 3rd division referees from the Spanish National Soccer League (28.43 ± 1.39 years); and ii) the lower level group (G2, n = 21): Navarre Provincial League soccer referees (29.54 ± 1.87 years). Significant differences were found with respect to the CODA between G1 (5.72 ± 0.13 s) and G2 (6.06 ± 0.30 s), while no differences were encountered between groups in acceleration ability. No significant correlations were obtained in G1 between agility and the capacity to accelerate. Significant correlations were found between sprint and agility times in the G2 and in the total group. The results of this study showed that agility can be used as a discriminating factor for differentiating between national and regional field referees; however, no observable differences were found over the 5 and 15 m sprint tests. PMID:27274111

  7. 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

  8. 48 CFR 46.311 - Higher-level contract quality requirement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Higher-level contract... REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Clauses 46.311 Higher-level contract quality requirement. The contracting officer shall insert the clause at 52.246-11, Higher-Level Contract...

  9. 48 CFR 46.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Higher-level contract... REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Quality Requirements 46.202-4 Higher-level contract quality requirements. (a) Requiring compliance with higher-level quality standards is appropriate...

  10. 48 CFR 46.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Higher-level contract... REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Quality Requirements 46.202-4 Higher-level contract quality requirements. (a) Requiring compliance with higher-level quality standards is appropriate...

  11. 48 CFR 46.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Higher-level contract... REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Quality Requirements 46.202-4 Higher-level contract quality requirements. (a) Requiring compliance with higher-level quality standards is appropriate...

  12. 48 CFR 46.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Higher-level contract... REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Quality Requirements 46.202-4 Higher-level contract quality requirements. (a) Requiring compliance with higher-level quality standards is appropriate...

  13. Lower- and higher-level models of right hemisphere language. A selective survey

    PubMed Central

    Gainotti, Guido

    2016-01-01

    Summary The models advanced to explain right hemisphere (RH) language function can be divided into two main types. According to the older (lower-level) models, RH language reflects the ontogenesis of conceptual and semantic-lexical development; the more recent models, on the other hand, suggest that the RH plays an important role in the use of higher-level language functions, such as metaphors, to convey complex, abstract concepts. The hypothesis that the RH may be preferentially involved in processing the semantic-lexical components of language was advanced by Zaidel in split-brain patients and his model was confirmed by neuropsychological investigations, proving that right brain-damaged patients show selective semantic-lexical disorders. The possible links between lower and higher levels of RH language are discussed, as is the hypothesis that the RH may have privileged access to the figurative aspects of novel metaphorical expressions, whereas conventionalization of metaphorical meaning could be a bilaterally-mediated process involving abstract semantic-lexical codes. PMID:27358218

  14. Lower- and higher-level models of right hemisphere language. A selective survey.

    PubMed

    Gainotti, Guido

    2016-01-01

    The models advanced to explain right hemisphere (RH) language function can be divided into two main types. According to the older (lower-level) models, RH language reflects the ontogenesis of conceptual and semantic-lexical development; the more recent models, on the other hand, suggest that the RH plays an important role in the use of higher-level language functions, such as metaphors, to convey complex, abstract concepts. The hypothesis that the RH may be preferentially involved in processing the semantic-lexical components of language was advanced by Zaidel in splitbrain patients and his model was confirmed by neuropsychological investigations, proving that right brain-damaged patients show selective semanticlexical disorders. The possible links between lower and higher levels of RH language are discussed, as is the hypothesis that the RH may have privileged access to the figurative aspects of novel metaphorical expressions, whereas conventionalization of metaphorical meaning could be a bilaterally-mediated process involving abstract semantic-lexical codes. PMID:27358218

  15. The Two-Level System of Higher Education: Western Traditions and Russian Reality

    ERIC Educational Resources Information Center

    Druzhilov, S. A.

    2011-01-01

    The law on the two-level system of higher education has now gone into effect in Russia: the bachelor's degree will correspond to the first level of higher education, while the master's degree will correspond to the second level. These levels entail separate state educational standards and separate final certification. In the process of adopting…

  16. 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

  17. Aspirations and Career Growth of Mid-Level Administrators in Higher Education.

    ERIC Educational Resources Information Center

    Bogenschutz, Margaret M.; Sagaria, Mary Ann D.

    A study examining the perceptions of career growth and aspirations of mid-level administrators in higher education was undertaken because, though there has been a large recent increase in the number and importance of mid-level administrators in higher education, the structure and nature of higher education organizations seem to constrain…

  18. 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

  19. mef2 activity levels differentially affect gene expression during Drosophila muscle development

    PubMed Central

    Elgar, Stuart J.; Han, Jun; Taylor, Michael V.

    2008-01-01

    Cell differentiation is controlled by key transcription factors, and a major question is how they orchestrate cell-type-specific genetic programs. Muscle differentiation is a well studied paradigm in which the conserved Mef2 transcription factor plays a pivotal role. Recent genomic studies have identified a large number of mef2-regulated target genes with distinct temporal expression profiles during Drosophila myogenesis. However, the question remains as to how a single transcription factor can control such diverse patterns of gene expression. In this study we used a strategy combining genomics and developmental genetics to address this issue in vivo during Drosophila muscle development. We found that groups of mef2-regulated genes respond differently to changes in mef2 activity levels: some require higher levels for their expression than others. Furthermore, this differential requirement correlates with when the gene is first expressed during the muscle differentiation program. Genes that require higher levels are activated later. These results implicate mef2 in the temporal regulation of muscle gene expression, and, consistent with this, we show that changes in mef2 activity levels can alter the start of gene expression in a predictable manner. Together these results indicate that Mef2 is not an all-or-none regulator; rather, its action is more subtle, and levels of its activity are important in the differential expression of muscle genes. This suggests a route by which mef2 can orchestrate the muscle differentiation program and contribute to the stringent regulation of gene expression during myogenesis. PMID:18198273

  20. The Level of Expressed Emotion Scale: A Useful Measure of Expressed Emotion in Adolescents?

    ERIC Educational Resources Information Center

    Nelis, Sharon M.; Rae, Gordon; Liddell, Christine

    2011-01-01

    Research has suggested that self-report measures of expressed emotion (EE) may be employed as a proxy measure of environmental stress in the home. The appropriateness of the Level of Expressed Emotion scale as a measure of perceived expressed emotion was examined in a sample of adolescents. Participants were 239 male and 422 female adolescents…

  1. Babies Fed Rice-Based Cereals Have Higher Arsenic Levels, Study Finds

    MedlinePlus

    ... html Babies Fed Rice-Based Cereals Have Higher Arsenic Levels, Study Finds To avoid potential harm, experts ... rice-based foods may have significantly higher "inorganic" arsenic concentrations in their urine than babies who never ...

  2. Commensurability condition and fractional quantum Hall effect hierarchy in higher Landau levels

    NASA Astrophysics Data System (ADS)

    Jacak, J.; Jacak, L.

    2015-07-01

    The odd structure of the fractional filling hierarchy, which is referred to as the fractional quantum Hall effect, is studied in higher Landau levels using the commensurability condition. The hierarchy of fillings that are derived in this manner is consistent with the experimental observations in the first three Landau levels. The relative poverty of the fractional structure in higher Landau levels compared with the lowest Landau level is explained using commensurability topological arguments. The commensurability criterion for correlated states specific for higher Landau levels (with n ≥ 1), including also the paired states at half fillings of the spinsubbands of these levels, is formulated.

  3. Predictors of Placement in Lower Level versus Higher Level High School Mathematics

    ERIC Educational Resources Information Center

    Archbald, Doug; Farley-Ripple, Elizabeth N.

    2012-01-01

    Educators and researchers have long been interested in determinants of access to honors level and college prep courses in high school. Factors influencing access to upper level mathematics courses are particularly important because of the hierarchical and sequential nature of this subject and because students who finish high school with only lower…

  4. How to achieve high-level expression of microbial enzymes

    PubMed Central

    Liu, Long; Yang, Haiquan; Shin, Hyun-dong; Chen, Rachel R.; Li, Jianghua; Du, Guocheng; Chen, Jian

    2013-01-01

    Microbial enzymes have been used in a large number of fields, such as chemical, agricultural and biopharmaceutical industries. The enzyme production rate and yield are the main factors to consider when choosing the appropriate expression system for the production of recombinant proteins. Recombinant enzymes have been expressed in bacteria (e.g., Escherichia coli, Bacillus and lactic acid bacteria), filamentous fungi (e.g., Aspergillus) and yeasts (e.g., Pichia pastoris). The favorable and very advantageous characteristics of these species have resulted in an increasing number of biotechnological applications. Bacterial hosts (e.g., E. coli) can be used to quickly and easily overexpress recombinant enzymes; however, bacterial systems cannot express very large proteins and proteins that require post-translational modifications. The main bacterial expression hosts, with the exception of lactic acid bacteria and filamentous fungi, can produce several toxins which are not compatible with the expression of recombinant enzymes in food and drugs. However, due to the multiplicity of the physiological impacts arising from high-level expression of genes encoding the enzymes and expression hosts, the goal of overproduction can hardly be achieved, and therefore, the yield of recombinant enzymes is limited. In this review, the recent strategies used for the high-level expression of microbial enzymes in the hosts mentioned above are summarized and the prospects are also discussed. We hope this review will contribute to the development of the enzyme-related research field. PMID:23686280

  5. Gene expression analyses in maize inbreds and hybrids with varying levels of heterosis

    PubMed Central

    Stupar, Robert M; Gardiner, Jack M; Oldre, Aaron G; Haun, William J; Chandler, Vicki L; Springer, Nathan M

    2008-01-01

    Background Heterosis is the superior performance of F1 hybrid progeny relative to the parental phenotypes. Maize exhibits heterosis for a wide range of traits, however the magnitude of heterosis is highly variable depending on the choice of parents and the trait(s) measured. We have used expression profiling to determine whether the level, or types, of non-additive gene expression vary in maize hybrids with different levels of genetic diversity or heterosis. Results We observed that the distributions of better parent heterosis among a series of 25 maize hybrids generally do not exhibit significant correlations between different traits. Expression profiling analyses for six of these hybrids, chosen to represent diversity in genotypes and heterosis responses, revealed a correlation between genetic diversity and transcriptional variation. The majority of differentially expressed genes in each of the six different hybrids exhibited additive expression patterns, and ~25% exhibited statistically significant non-additive expression profiles. Among the non-additive profiles, ~80% exhibited hybrid expression levels between the parental levels, ~20% exhibited hybrid expression levels at the parental levels and ~1% exhibited hybrid levels outside the parental range. Conclusion We have found that maize inbred genetic diversity is correlated with transcriptional variation. However, sampling of seedling tissues indicated that the frequencies of additive and non-additive expression patterns are very similar across a range of hybrid lines. These findings suggest that heterosis is probably not a consequence of higher levels of additive or non-additive expression, but may be related to transcriptional variation between parents. The lack of correlation between better parent heterosis levels for different traits suggests that transcriptional diversity at specific sets of genes may influence heterosis for different traits. PMID:18402703

  6. Sugarcoated isolation: evidence that social avoidance is linked to higher basal glucose levels and higher consumption of glucose

    PubMed Central

    Ein-Dor, Tsachi; Coan, James A.; Reizer, Abira; Gross, Elizabeth B.; Dahan, Dana; Wegener, Meredyth A.; Carel, Rafael; Cloninger, Claude R.; Zohar, Ada H.

    2015-01-01

    Objective: The human brain adjusts its level of effort in coping with various life stressors as a partial function of perceived access to social resources. We examined whether people who avoid social ties maintain a higher fasting basal level of glucose in their bloodstream and consume more sugar-rich food, reflecting strategies to draw more on personal resources when threatened. Methods: In Study 1 (N = 60), we obtained fasting blood glucose and adult attachment orientations data. In Study 2 (N = 285), we collected measures of fasting blood glucose and adult attachment orientations from older adults of mixed gender, using a measure of attachment style different from Study 1. In Study 3 (N = 108), we examined the link between trait-like attachment avoidance, manipulation of an asocial state, and consumption of sugar-rich food. In Study 4 (N = 115), we examined whether manipulating the social network will moderate the effect of attachment avoidance on consumption of sugar-rich food. Results: In Study 1, fasting blood glucose levels corresponded with higher attachment avoidance scores after statistically adjusting for time of assessment and interpersonal anxiety. For Study 2, fasting blood glucose continued to correspond with higher adult attachment avoidance even after statistically adjusting for interpersonal anxiety, stress indices, age, gender, social support and body mass. In Study 3, people high in attachment avoidance consume more sugar-rich food, especially when reminded of asocial tendencies. Study 4 indicated that after facing a stressful task in the presence of others, avoidant people gather more sugar-rich food than more socially oriented people. Conclusion: Results are consistent with the suggestion that socially avoidant individuals upwardly adjust their basal glucose levels and consume more glucose-rich food with the expectation of increased personal effort because of limited access to social resources. Further investigation of this link is warranted

  7. Concepts and Principles for State-Level Higher Education Budgeting. ASHE 1984 Annual Meeting Paper.

    ERIC Educational Resources Information Center

    Jones, Dennis P.

    Basic concepts concerning state-level resource allocation to higher education are discussed. Attention is directed to principles of budgeting regardless of context, the pluralistic nature of higher education, characteristics of higher education production functions, and the typical form of the budget. In addition to the distribution of resources,…

  8. Role of Distance Education in the Expansion of Female Education Higher Level in Pakistan: A Review

    ERIC Educational Resources Information Center

    Malik, Sufiana K.

    2010-01-01

    The present paper investigated the role of distance education in the expansion of educational facilities for females at higher levels of education in Pakistan. The findings of the study report that distance education is playing a vital role in the expansion of female education at higher level as such females who, due to some personal or social…

  9. 48 CFR 246.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... quality requirements. 246.202-4 Section 246.202-4 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Quality Requirements 246.202-4 Higher-level contract quality requirements. (1) Higher-level contract...

  10. 48 CFR 46.311 - Higher-level contract quality requirement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Higher-level contract quality requirement. 46.311 Section 46.311 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Clauses 46.311 Higher-level contract quality requirement. The contracting officer shall...

  11. 48 CFR 46.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Higher-level contract quality requirements. 46.202-4 Section 46.202-4 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Contract Quality Requirements 46.202-4 Higher-level contract quality requirements. (a)...

  12. 78 FR 72620 - Federal Acquisition Regulation; Higher-Level Contract Quality Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ... comment in the Federal Register at 78 FR 28780 on May 16, 2013. 2. FAR Case 2013-002, entitled ``Expanded... RIN 9000-AM65 Federal Acquisition Regulation; Higher-Level Contract Quality Requirements AGENCY... Acquisition Regulation (FAR) to clarify when to use higher-level quality standards in solicitations...

  13. Higher Perceived Stress Scale scores are associated with higher pain intensity and pain interference levels in Older Adults

    PubMed Central

    White, Robert S.; Jiang, Julie; Hall, Charles B.; Katz, Mindy J.; Zimmerman, Molly E.; Sliwinski, Martin; Lipton, Richard B.

    2014-01-01

    Objectives To determine the prevalence of bodily pain measures (pain intensity and pain interference) in elderly people and their relationship with perceived stress scale (PSS) scores. Design Cross-sectional. Setting Community. Participants A representative community sample of 578 subjects aged 70 and older. Measurements The prevalence of pain intensity and pain interference and their relationship with perceived stress scale scores, demographic factors, past medical history, and neuropsychological testing scores were examined. Pain intensity and pain interference were measured by the SF-36 bodily pain questions. Results The study sample of 578 participants has a mean age of 78.8 years and is 63% female. Bivariate analysis for pain measures showed that higher scores on the perceived stress scale, lower neuropsychological test scores, and medical histories were associated with both pain intensity and interference. Logistic regression showed that higher scores on the perceived stress scale were significantly associated with increased odds of having moderate/severe pain intensity and moderate/severe pain interference (with and without the inclusion of for pain intensity in the models). Conclusion Higher PSS scores are associated with higher levels of pain intensity and pain interference. In this cross-sectional analysis, directionality cannot be determined. As both perceived stress and pain are potentially modifiable risk factors for cognitive decline and other poor health outcomes, future research should address temporality and the benefits of treatment. PMID:25516031

  14. 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

  15. Effects of dietary roughage levels on the expression of adipogenic transcription factors in Wagyu steers.

    PubMed

    Yamada, T; Kawakami, S-I; Nakanishi, N

    2009-12-01

    We hypothesized that dietary roughage level would alter the expression levels of adipogenic transcription factors in adipose tissue of Japanese black (Wagyu) steers. Steers were fed whole crop rice silage at three levels: (1) high-roughage feeding group, fed 8kg silage and 5kg concentrate (HR); (2) middle roughage feeding group, fed 5kg silage and 6kg concentrate (MR); and (3) low roughage feeding group, fed 2kg silage and 7kg concentrate (LR) from 22 to 30months of age. In subcutaneous adipose tissue, there were no significant differences in the expression of the adipogenic transcription factors and adipocyte size among feeding groups. In mesenteric adipose tissue, the expression of C/EBPα in the LR and MR groups was significantly higher than that in the HR group. Adipocyte size in the mesenteric adipose tissue of the LR group was significantly larger than that of the HR group. In intermuscular adipose tissue, the expression of C/EBPβ-LAP in the LR group was significantly higher than that in the HR group, and the expression of C/EBPβ-LIP in the LR and MR groups was significantly higher than that in the HR group. Adipocyte size in the intermuscular adipose tissue of the LR and MR groups was significantly smaller than that of the HR group. These results suggest that dietary roughage revel affects the adipose tissue depot-specific differences in C/EBP family expression pattern and adipocyte cellularity in Wagyu steers. PMID:20416623

  16. In plants, expression breadth and expression level distinctly and non-linearly correlate with gene structure

    PubMed Central

    2009-01-01

    Background Compactness of highly/broadly expressed genes in human has been explained as selection for efficiency, regional mutation biases or genomic design. However, highly expressed genes in flowering plants were shown to be less compact than lowly expressed ones. On the other hand, opposite facts have also been documented that pollen-expressed Arabidopsis genes tend to contain shorter introns and highly expressed moss genes are compact. This issue is important because it provides a chance to compare the selectionism and the neutralism views about genome evolution. Furthermore, this issue also helps to understand the fates of introns, from the angle of gene expression. Results In this study, I used expression data covering more tissues and employ new analytical methods to reexamine the correlations between gene expression and gene structure for two flowering plants, Arabidopsis thaliana and Oryza sativa. It is shown that, different aspects of expression pattern correlate with different parts of gene sequences in distinct ways. In detail, expression level is significantly negatively correlated with gene size, especially the size of non-coding regions, whereas expression breadth correlates with non-coding structural parameters positively and with coding region parameters negatively. Furthermore, the relationships between expression level and structural parameters seem to be non-linear, with the extremes of structural parameters possibly scale as power-laws or logrithmic functions of expression levels. Conclusion In plants, highly expressed genes are compact, especially in the non-coding regions. Broadly expressed genes tend to contain longer non-coding sequences, which may be necessary for complex regulations. In combination with previous studies about other plants and about animals, some common scenarios about the correlation between gene expression and gene structure begin to emerge. Based on the functional relationships between extreme values of structural

  17. 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

  18. Affective State Level Recognition in Naturalistic Facial and Vocal Expressions.

    PubMed

    Meng, Hongying; Bianchi-Berthouze, Nadia

    2014-03-01

    Naturalistic affective expressions change at a rate much slower than the typical rate at which video or audio is recorded. This increases the probability that consecutive recorded instants of expressions represent the same affective content. In this paper, we exploit such a relationship to improve the recognition performance of continuous naturalistic affective expressions. Using datasets of naturalistic affective expressions (AVEC 2011 audio and video dataset, PAINFUL video dataset) continuously labeled over time and over different dimensions, we analyze the transitions between levels of those dimensions (e.g., transitions in pain intensity level). We use an information theory approach to show that the transitions occur very slowly and hence suggest modeling them as first-order Markov models. The dimension levels are considered to be the hidden states in the Hidden Markov Model (HMM) framework. Their discrete transition and emission matrices are trained by using the labels provided with the training set. The recognition problem is converted into a best path-finding problem to obtain the best hidden states sequence in HMMs. This is a key difference from previous use of HMMs as classifiers. Modeling of the transitions between dimension levels is integrated in a multistage approach, where the first level performs a mapping between the affective expression features and a soft decision value (e.g., an affective dimension level), and further classification stages are modeled as HMMs that refine that mapping by taking into account the temporal relationships between the output decision labels. The experimental results for each of the unimodal datasets show overall performance to be significantly above that of a standard classification system that does not take into account temporal relationships. In particular, the results on the AVEC 2011 audio dataset outperform all other systems presented at the international competition. PMID:23757552

  19. High-level expression of Proteinase K from Tritirachium album Limber in Pichia pastoris using multi-copy expression strains.

    PubMed

    Yang, Hu; Zhai, Chao; Yu, Xianhong; Li, Zhezhe; Tang, Wei; Liu, Yunyun; Ma, Xiaojian; Zhong, Xing; Li, Guolong; Wu, Di; Ma, Lixin

    2016-06-01

    Proteinase K is widely used in scientific research and industries. This report was aimed to achieve high-level expression of proteinase K using Pichia pastoris GS115 as the host strain. The coding sequence of a variant of proteinase K that has higher activity than the wild type protein was chosen and optimized based on the codon usage preference of P. pastoris. The novel open reading frame was synthesized and a series of multi-copy expression vectors were constructed based on the pHBM905BDM plasmid, allowing for the tandem integration of multiple copies of the target gene into the genome of P. pastoris with a single recombination. These strains were used to study the correlation between the gene copy number and the expression level of proteinase K. The results of quantitative polymerase chain reaction (qPCR) indicated that the tandem expression cassettes were integrated into the host genome stably. Meanwhile, the results of qPCR and enzyme activity assays indicated that the mRNA and protein expression levels of the target gene increased as the gene copy number increased. Moreover, the effect of gene dosage on the expression level of the recombinant protein was more obvious using high-density fermentation. The maximum expression level and enzyme activity of proteinase K, which were obtained from the recombinant yeast strain bearing 5 copies of the target gene after an 84-h induction, were approximately 8.069 mg/mL and 108,295 U/mL, respectively. The recombinant proteinase was purified and characterized. The optimum pH and temperature for the activity of this protease were approximately pH 11 and 55 °C, respectively. PMID:26892536

  20. Predicting Gene Expression Level from Relative Codon Usage Bias: An Application to Escherichia coli Genome

    PubMed Central

    Roymondal, Uttam; Das, Shibsankar; Sahoo, Satyabrata

    2009-01-01

    We present an expression measure of a gene, devised to predict the level of gene expression from relative codon bias (RCB). There are a number of measures currently in use that quantify codon usage in genes. Based on the hypothesis that gene expressivity and codon composition is strongly correlated, RCB has been defined to provide an intuitively meaningful measure of an extent of the codon preference in a gene. We outline a simple approach to assess the strength of RCB (RCBS) in genes as a guide to their likely expression levels and illustrate this with an analysis of Escherichia coli (E. coli) genome. Our efforts to quantitatively predict gene expression levels in E. coli met with a high level of success. Surprisingly, we observe a strong correlation between RCBS and protein length indicating natural selection in favour of the shorter genes to be expressed at higher level. The agreement of our result with high protein abundances, microarray data and radioactive data demonstrates that the genomic expression profile available in our method can be applied in a meaningful way to the study of cell physiology and also for more detailed studies of particular genes of interest. PMID:19131380

  1. NORMAL NASAL GENE EXPRESSION LEVELS USING CDNA ARRAY TECHNOLOGY

    EPA Science Inventory

    Normal Nasal Gene Expression Levels Using cDNA Array Technology.

    The nasal epithelium is a target site for chemically-induced toxicity and carcinogenicity. To detect and analyze genetic events which contribute to nasal tumor development, we first defined the gene expressi...

  2. Impact of STAT/SOCS mRNA Expression Levels after Major Injury

    PubMed Central

    Brumann, M.; Matz, M.; Kusmenkov, T.; Stegmaier, J.; Biberthaler, P.; Kanz, K.-G.; Mutschler, W.; Bogner, V.

    2014-01-01

    Background. Fulminant changes in cytokine receptor signalling might provoke severe pathological alterations after multiple trauma. The aim of this study was to evaluate the posttraumatic imbalance of the innate immune system with a special focus on the STAT/SOCS family. Methods. 20 polytraumatized patients were included. Blood samples were drawn 0 h–72 h after trauma; mRNA expression profiles of IL-10, STAT 3, SOCS 1, and SOCS 3 were quantified by qPCR. Results. IL-10 mRNA expression increased significantly in the early posttraumatic period. STAT 3 mRNA expressions showed a significant maximum at 6 h after trauma. SOCS 1 levels significantly decreased 6 h–72 h after trauma. SOCS 3 levels were significantly higher in nonsurvivors 6 h after trauma. Conclusion. We present a serial, sequential investigation in human neutrophil granulocytes of major trauma patients evaluating mRNA expression profiles of IL-10, STAT 3, SOCS 1, and SOCS 3. Posttraumatically, immune disorder was accompanied by a significant increase of IL-10 and STAT 3 mRNA expression, whereas SOCS 1 mRNA levels decreased after injury. We could demonstrate that death after trauma was associated with higher SOCS 3 mRNA levels already at 6 h after trauma. To support our results, further investigations have to evaluate protein levels of STAT/SOCS family in terms of posttraumatic immune imbalance. PMID:24648661

  3. Babies Fed Rice-Based Cereals Have Higher Arsenic Levels, Study Finds

    MedlinePlus

    ... gov/medlineplus/news/fullstory_158484.html Babies Fed Rice-Based Cereals Have Higher Arsenic Levels, Study Finds ... April 25, 2016 (HealthDay News) -- Parents commonly give rice to their babies as a first food. Now, ...

  4. Evolving entities: towards a unified framework for understanding diversity at the species and higher levels.

    PubMed

    Barraclough, Timothy G

    2010-06-12

    Current approaches to studying the evolution of biodiversity differ in their treatment of species and higher level diversity patterns. Species are regarded as the fundamental evolutionarily significant units of biodiversity, both in theory and in practice, and extensive theory explains how they originate and evolve. However, most species are still delimited using qualitative methods that only relate indirectly to the underlying theory. In contrast, higher level patterns of diversity have been subjected to rigorous quantitative study (using phylogenetics), but theory that adequately explains the observed patterns has been lacking. Most evolutionary analyses of higher level diversity patterns have considered non-equilibrium explanations based on rates of diversification (i.e. exponentially growing clades), rather than equilibrium explanations normally used at the species level and below (i.e. constant population sizes). This paper argues that species level and higher level patterns of diversity can be considered within a common framework, based on equilibrium explanations. It shows how forces normally considered in the context of speciation, namely divergent selection and geographical isolation, can generate evolutionarily significant units of diversity above the level of reproductively isolated species. Prospects for the framework to answer some unresolved questions about higher level diversity patterns are discussed. PMID:20439282

  5. Evolving entities: towards a unified framework for understanding diversity at the species and higher levels

    PubMed Central

    Barraclough, Timothy G.

    2010-01-01

    Current approaches to studying the evolution of biodiversity differ in their treatment of species and higher level diversity patterns. Species are regarded as the fundamental evolutionarily significant units of biodiversity, both in theory and in practice, and extensive theory explains how they originate and evolve. However, most species are still delimited using qualitative methods that only relate indirectly to the underlying theory. In contrast, higher level patterns of diversity have been subjected to rigorous quantitative study (using phylogenetics), but theory that adequately explains the observed patterns has been lacking. Most evolutionary analyses of higher level diversity patterns have considered non-equilibrium explanations based on rates of diversification (i.e. exponentially growing clades), rather than equilibrium explanations normally used at the species level and below (i.e. constant population sizes). This paper argues that species level and higher level patterns of diversity can be considered within a common framework, based on equilibrium explanations. It shows how forces normally considered in the context of speciation, namely divergent selection and geographical isolation, can generate evolutionarily significant units of diversity above the level of reproductively isolated species. Prospects for the framework to answer some unresolved questions about higher level diversity patterns are discussed. PMID:20439282

  6. Promoting Higher Level Thinking in Psychology: Is Active Learning the Answer?

    ERIC Educational Resources Information Center

    Richmond, Aaron S.; Hagan, Lisa Kindelberger

    2011-01-01

    The goal of this study was to investigate which common instructional methods (active vs. direct) best promote higher level thinking in a psychology course. Over a 5-week period, 71 undergraduates were taught psychology using both active learning and direct instruction. Pre- and post-course assessments were coded as either higher or lower level…

  7. An Analysis of the Knowledge Levels of Media Directors Concerning Relevant Copyright Issues in Higher Education.

    ERIC Educational Resources Information Center

    Chase, Mark E.

    This study analyzes the copyright knowledge levels of media directors of selected higher education institutions. A questionnaire was mailed to 466 media professionals at higher educational institutions who were members of the Division of Educational Media Management in the Association for Educational Communications and Technology (AECT). The…

  8. Neuropsychological Characteristics and Their Association with Higher-Level Functional Capacity in Parkinson's Disease

    PubMed Central

    Miura, Kayoko; Matsui, Mie; Takashima, Shutaro; Tanaka, Kortaro

    2015-01-01

    Background/Aims Little is known about the relationship between cognitive functions and higher-level functional capacity (e.g. intellectual activity, social role, and social participation) in Parkinson's disease (PD). The purpose of this study was to clarify neuropsychological characteristics and their association with higher-level functional capacity in PD patients. Methods Participants were 31 PD patients and 23 demographically matched healthy controls. Neuropsychological tests were conducted. One year later, a questionnaire survey evaluated higher-level functional capacity in daily living. Results The PD group scored significantly lower than the control group in all cognitive domains, particularly executive function and processing. Executive function, processing speed, language, and memory were significantly correlated with higher-level functional capacity in PD patients. Stepwise regression showed that only executive function (Trail Making Test-B), together with disease severity (HY stage), predicted the higher-level functional capacity. Conclusion Our findings provide evidence of a relationship between executive function and higher-level functional capacity in patients with PD. PMID:26273243

  9. Protein pheromone expression levels predict and respond to the formation of social dominance networks

    PubMed Central

    Nelson, Adam C.; Cunningham, Christopher B.; Ruff, James S.; Potts, Wayne K.

    2015-01-01

    Communication signals are key regulators of social networks, and are thought to be under selective pressure to honestly reflect social status, including dominance status. The odors of dominants and nondominants differentially influence behavior, and identification of the specific pheromones associated with, and predictive of, dominance status is essential for understanding the mechanisms of network formation and maintenance. In mice, major urinary proteins (MUPs) are excreted in extraordinary large quantities and expression level has been hypothesized to provide an honest signal of dominance status. Here, we evaluate whether MUPs are associated with dominance in wild-derived mice by analyzing expression levels before, during, and after competition for reproductive resources over three days. During competition, dominant males have 24% greater urinary MUP expression than nondominants. The MUP darcin, a pheromone that stimulates female attraction, is predictive of dominance status: dominant males have higher darcin expression before competition. Dominants also have a higher ratio of darcin to other MUPs before and during competition. These differences appear transient, because there are no differences in MUPs or darcin after competition. We also find MUP expression is affected by sire dominance status: socially naive sons of dominant males have lower MUP expression, but this apparent repression is released during competition. A requisite condition for the evolution of communication signals is honesty, and we provide novel insight into pheromones and social networks by showing that MUP and darcin expression is a reliable signal of dominance status, a primary determinant of male fitness in many species. PMID:25867293

  10. [Expression of erythropoietin receptor in leukemia cells and relation of erythropoietin level with leukemic anemia].

    PubMed

    Feng, Mei; Li, Yu-Cui

    2008-12-01

    This study was purposed to investigate the expression of erythropoietin receptor (EPOR) in leukemic cells and the relationship of serum erythropoietin level with anemia in acute leukemia patients, so as to provide a new theoretical basis for the cytokine therapy in acute leukemia with anemia. The EPOR in 30 AL patients was detected by using reverse transcription polymerase chain reaction (RT-PCR), the level of serum erythropoietin was detected by chemiluminescence analysis, the hemoglobin level was assayed by automatic blood counting instrument. The results indicated that EPOR was expressed in 18 out of 30 AL patients, the expression rate of EPOR in AL patients was 60%, however, but the EPOR expression rate in AML was 61.9% (13/21) and 55.6% (5/9) in ALL, the EPOR expression rate was no significant difference between AML and ALL. The EPOR expression rate was significantly lower than that in control group (86.7%) (p<0.05). The relative level of EPOR expression in AML was higher than that in ALL (p<0.05), the average level of EPOR expression in AL was significantly lower than that in control group (p<0.01). The level of sEPO in 30 AL patients was significantly higher than that in control group (p<0.01), and there was negative correlation between the levels of sEPO and Hb (p<0.01). It is concluded that the EPOR is expressed in cells of AL, but the expressive level is low. The EPOR expression rate shows no significant difference between AML and ALL. The mechanism of negative feedback to anemia in acute leukemia is intact. Anemia of acute leukemia is not completely associated with inadequate erythropoietin production and relates to hemopoiesis defect that considered as the main reason. Recombinant human erythropoietin is widely used in treatment of anemia caused by acute leukemia. Whether the treatment with rh-EPO for acute leukemia with anemia will enhance the proliferation of leukemia cells, this problem should be explored further. PMID:19099624

  11. Protein expression analyses at the single cell level.

    PubMed

    Ohno, Masae; Karagiannis, Peter; Taniguchi, Yuichi

    2014-01-01

    The central dogma of molecular biology explains how genetic information is converted into its end product, proteins, which are responsible for the phenotypic state of the cell. Along with the protein type, the phenotypic state depends on the protein copy number. Therefore, quantification of the protein expression in a single cell is critical for quantitative characterization of the phenotypic states. Protein expression is typically a dynamic and stochastic phenomenon that cannot be well described by standard experimental methods. As an alternative, fluorescence imaging is being explored for the study of protein expression, because of its high sensitivity and high throughput. Here we review key recent progresses in fluorescence imaging-based methods and discuss their application to proteome analysis at the single cell level. PMID:25197931

  12. Six Increasingly Higher Levels of Wellness Based on Holistic Principles and Risk Factor Science.

    ERIC Educational Resources Information Center

    Cassel, Russell N.

    1987-01-01

    Describes program for achievement of higher wellness levels based on holistic principles and risk factor science. Levels focus on (1) heart disease risk factors and how to reverse them; (2) unconscious needs at conflict with one's conscious goals; (3) identity status, meaning to love and to be loved; (4) autogenics; and (5) full ego development…

  13. Perceived Effectiveness of Professional Development Programs of Teachers at Higher Education Level

    ERIC Educational Resources Information Center

    Malik, Sufiana Khatoon; Nasim, Uzma; Tabassum, Farkhanda

    2015-01-01

    The major purpose of the study was to assess the perceived effectiveness of professional development programs of teachers at higher educational level. The objectives of the study were: "to assess university level teachers'" opinion about effectiveness of professional development training with reference to quality teaching, to measure…

  14. Text Comprehension in Down Syndrome: The Role of Lower and Higher Level Abilities

    ERIC Educational Resources Information Center

    Levorato, M. Chiara; Roch, Maja; Beltrame, Rossella

    2009-01-01

    The contribution of lower level linguistic abilities (study 1) and a higher level capacity, namely the use of context, (study 2), on text comprehension was studied. Participants were 16 individuals with Down syndrome aged between aged between 8 years 11 months and 16 years 10 months, and 16 children with typical development, aged between 5 years…

  15. Variability among individuals is generated at the gene expression level.

    PubMed

    Peck, Lloyd S; Thorne, Michael A S; Hoffman, Joseph I; Morley, Simon A; Clark, Melody S

    2015-07-01

    Selection acts on individuals, specifically on their differences. To understand adaptation and responses to change therefore requires knowledge of how variation is generated and distributed across traits. Variation occurs on different biological scales, from genetic through physiological to morphological, yet it is unclear which of these carries the most variability. For example, if individual variation is mainly generated by differences in gene expression, variability should decrease progressively from coding genes to morphological traits, whereas if post-translational and epigenetic effects increase variation, the opposite should occur. To test these predictions, we compared levels of variation among individuals in various measures of gene expression, physiology (including activity), and morphology in two abundant and geographically widespread Antarctic molluscs, the clam Laternula elliptica and the limpet Nacella concinna. Direct comparisons among traits as diverse as heat shock protein QPCR assays, whole transcription profiles, respiration rates, burying rate, shell length, and ash-free dry mass were made possible through the novel application of an established metric, the Wentworth Scale. In principle, this approach could be extended to analyses of populations, communities, or even entire ecosystems. We found consistently greater variation in gene expression than morphology, with physiological measures falling in between. This suggests that variability is generated at the gene expression level. These findings have important implications for refining current biological models and predictions of how biodiversity may respond to climate change. PMID:26378322

  16. Diversity of Matriptase Expression Level and Function in Breast Cancer

    PubMed Central

    Welman, Arkadiusz; Sproul, Duncan; Mullen, Peter; Muir, Morwenna; Kinnaird, Andrew R.; Harrison, David J.; Faratian, Dana; Brunton, Valerie G.; Frame, Margaret C.

    2012-01-01

    Overexpression of matriptase has been reported in a variety of human cancers and is sufficient to trigger tumor formation in mice, but the importance of matriptase in breast cancer remains unclear. We analysed matriptase expression in 16 human breast cancer cell lines and in 107 primary breast tumors. The data revealed considerable diversity in the expression level of this protein indicating that the significance of matriptase may vary from case to case. Matriptase protein expression was correlated with HER2 expression and highest expression was seen in HER2-positive cell lines, indicating a potential role in this subgroup. Stable overexpression of matriptase in two breast cancer cell lines had different consequences. In MDA-MB-231 human breast carcinoma cells the only noted consequence of matriptase overexpression was modestly impaired growth in vivo. In contrast, overexpression of matriptase in 4T1 mouse breast carcinoma cells resulted in visible changes in morphology, actin staining and cell to cell contacts. This correlated with downregulation of the cell-cell adhesion molecule E-cadherin. These results suggest that the functions of matriptase in breast cancer are likely to be variable and cell context dependent. PMID:22514623

  17. Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women

    PubMed Central

    Griesbeck, Morgane; Ziegler, Susanne; Laffont, Sophie; Smith, Nikaïa; Chauveau, Lise; Tomezsko, Phillip; Sharei, Armon; Kourjian, Georgio; Porichis, Filippos; Hart, Meghan; Palmer, Christine D.; Sirignano, Michael; Beisel, Claudia; Hildebrandt, Heike; Cénac, Claire; Villani, Alexandra-Chloé; Diefenbach, Thomas J.; Le Gall, Sylvie; Schwartz, Olivier; Herbeuval, Jean-Philippe; Autran, Brigitte; Guéry, Jean-Charles; Chang, J. Judy

    2015-01-01

    Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-α–secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. In mice, genetic ablation of the estrogen receptor 1 (Esr1) gene in the hematopoietic compartment or DC lineage reduced Irf5 mRNA expression in pDCs and IFN-α production. IRF5 mRNA levels furthermore correlated with ESR1 mRNA levels in human pDCs, consistent with IRF5 regulation at the transcriptional level by ESR1. Taken together, these data demonstrate a critical mechanism by which sex differences in basal pDC IRF5 expression lead to higher IFN-α production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation. PMID:26519527

  18. Sex Differences in Plasmacytoid Dendritic Cell Levels of IRF5 Drive Higher IFN-α Production in Women.

    PubMed

    Griesbeck, Morgane; Ziegler, Susanne; Laffont, Sophie; Smith, Nikaïa; Chauveau, Lise; Tomezsko, Phillip; Sharei, Armon; Kourjian, Georgio; Porichis, Filippos; Hart, Meghan; Palmer, Christine D; Sirignano, Michael; Beisel, Claudia; Hildebrandt, Heike; Cénac, Claire; Villani, Alexandra-Chloé; Diefenbach, Thomas J; Le Gall, Sylvie; Schwartz, Olivier; Herbeuval, Jean-Philippe; Autran, Brigitte; Guéry, Jean-Charles; Chang, J Judy; Altfeld, Marcus

    2015-12-01

    Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more IFN-α upon TLR7 stimulation than pDCs from males, yet the mechanisms underlying this difference remain unclear. In this article, we show that basal levels of IFN regulatory factor (IRF) 5 in pDCs were significantly higher in females compared with males and positively correlated with the percentage of IFN-α-secreting pDCs. Delivery of recombinant IRF5 protein into human primary pDCs increased TLR7-mediated IFN-α secretion. In mice, genetic ablation of the estrogen receptor 1 (Esr1) gene in the hematopoietic compartment or DC lineage reduced Irf5 mRNA expression in pDCs and IFN-α production. IRF5 mRNA levels furthermore correlated with ESR1 mRNA levels in human pDCs, consistent with IRF5 regulation at the transcriptional level by ESR1. Taken together, these data demonstrate a critical mechanism by which sex differences in basal pDC IRF5 expression lead to higher IFN-α production upon TLR7 stimulation in females and provide novel targets for the modulation of immune responses and inflammation. PMID:26519527

  19. Prognostic correlation between MTA2 expression level and colorectal cancer

    PubMed Central

    Ding, Weijun; Hu, Wei; Yang, Haihua; Ying, Ting; Tian, Ye

    2015-01-01

    Objectives: Association of MTA2 expression with presence, development, metastasis and prognosis of colorectal cancer (CRC) was investigated. Methods: 90 CRC-related cases with follow-up information were made into tissue microarrays according to the paired principle of cancer tissues and the adjacent tissues. Subsequently, the expression of MAT2 was detected with immunohistochemical analysis and SPSS software was finally utilized to analyze the relationships between experimental data and clinical indicatives. Results: Expression of MTA2 in CRC tissues were notably higher than their adjacent tissues (P < 0.001) and showed significant positive correlation with tumor grade (r2 > 0, P < 0.01). Moreover, survival analysis indicated that MTA2 expression in cancer tissues, serving as an independent correlation factor, was significantly correlated with poor prognosis (P = 0.004). Conclusions: MTA2 is a crucial biomarker that is closely related with prognosis of CRC and also a potential molecular target for evaluating the prognosis and treatment of CRC. PMID:26261611

  20. Translation Levels Control Multi-Spanning Membrane Protein Expression

    PubMed Central

    Brown, Cecilia; Bostrom, Jenny; Fuh, Germaine; Lee, Chingwei V.; Huang, Arthur; Vandlen, Richard L.; Yansura, Daniel G.

    2012-01-01

    Attempts to express eukaryotic multi-spanning membrane proteins at high-levels have been generally unsuccessful. In order to investigate the cause of this limitation and gain insight into the rate limiting processes involved, we have analyzed the effect of translation levels on the expression of several human membrane proteins in Escherichia coli (E. coli). These results demonstrate that excessive translation initiation rates of membrane proteins cause a block in protein synthesis and ultimately prevent the high-level accumulation of these proteins. Moderate translation rates allow coupling of peptide synthesis and membrane targeting, resulting in a significant increase in protein expression and accumulation over time. The current study evaluates four membrane proteins, CD20 (4-transmembrane (TM) helixes), the G-protein coupled receptors (GPCRs, 7-TMs) RA1c and EG-VEGFR1, and Patched 1 (12-TMs), and demonstrates the critical role of translation initiation rates in the targeting, insertion and folding of integral membrane proteins in the E. coli membrane. PMID:22563408

  1. 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

  2. Student's Perceived Level and Teachers' Teaching Strategies of Higher Order Thinking Skills: A Study on Higher Educational Institutions in Thailand

    ERIC Educational Resources Information Center

    Shukla, Divya; Dungsungnoen, Aj Pattaradanai

    2016-01-01

    Higher order thinking skills (HOTS) has portrayed immense industry demand and the major goal of educational institution in imparting education is to inculcate higher order thinking skills. This compiles and mandate the institutions and instructor to develop the higher order thinking skills among students in order to prepare them for effective…

  3. Targeting of a histone acetyltransferase domain to a promoter enhances protein expression levels in mammalian cells.

    PubMed

    Kwaks, T H J; Sewalt, R G A B; van Blokland, R; Siersma, T J; Kasiem, M; Kelder, A; Otte, A P

    2005-01-12

    Silencing of transfected genes in mammalian cells is a fundamental problem that probably involves the (in)accessibility status of chromatin. A potential solution to this problem is to provide a cell with protein factors that make the chromatin of a promoter more open or accessible for transcription. We tested this by targeting such proteins to different promoters. We found that targeting the p300 histone acetyltransferase (HAT) domain to strong viral or cellular promoters is sufficient to result in higher expression levels of a reporter protein. In contrast, targeting the chromatin-remodeling factor Brahma does not result in stable, higher protein expression levels. The long-term effects of the targeted p300HAT domain on protein expression levels are positively reinforced, when also anti-repressor elements are applied to flank the reporter construct. These elements were previously shown to be potent blockers of chromatin-associated repressors. The simultaneous application of the targeted p300HAT domain and anti-repressor elements conveys long-term stability to protein expression. Whereas no copy number dependency is achieved by targeting of the p300HAT domain alone, copy number dependency is improved when anti-repressor elements are included. We conclude that targeting of protein domains such as HAT domains helps to facilitate expression of transfected genes in mammalian cells. However, the simultaneous application of other genomic elements such as the anti-repressor elements prevents silencing more efficiently. PMID:15607223

  4. 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

  5. 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

  6. Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host-parasitoid food chain.

    PubMed

    Sanders, Dirk; Moser, Andrea; Newton, Jason; van Veen, F J Frank

    2016-03-16

    Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host-parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary-secondary-tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ(15)N increased with trophic level, with trophic discrimination factors (Δ(15)N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host-parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems. PMID:26962141

  7. Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host–parasitoid food chain

    PubMed Central

    Moser, Andrea; van Veen, F. J. Frank

    2016-01-01

    Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host–parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary–secondary–tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ15N increased with trophic level, with trophic discrimination factors (Δ15N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host–parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems. PMID:26962141

  8. Using higher-level inquiry to improve spatial ability in an introductory geology course

    NASA Astrophysics Data System (ADS)

    Stevens, Lacey A.

    Visuo-spatial skills, the ability to visually take in information and create a mental image are crucial for success in fields involving science, technology, engineering, and math (STEM) as well as fine arts. Unfortunately, due to a lack of curriculum focused on developing spatial skills, students enrolled in introductory college-level science courses tend to have difficulty with spatially-related activities. One of the best ways to engage students in science activities is through a learning and teaching strategy called inquiry. There are lower levels of inquiry wherein learning and problem-solving are guided by instructions and higher levels of inquiry wherein students have a greater degree of autonomy in learning and creating their own problem-solving strategy. A study involving 112 participants was conducted during the fall semester in 2014 at Bowling Green State University (BGSU) in an 1040 Introductory Geology Lab to determine if a new, high-level, inquiry-based lab would increase participants' spatial skills more than the traditional, low-level inquiry lab. The study also evaluated whether a higher level of inquiry differentially affected low versus high spatial ability participants. Participants were evaluated using a spatial ability assessment, and pre- and post-tests. The results of this study show that for 3-D to 2-D visualization, the higher-level inquiry lab increased participants' spatial ability more than the lower-level inquiry lab. For spatial rotational skills, all participants' spatial ability scores improved, regardless of the level of inquiry to which they were exposed. Low and high spatial ability participants were not differentially affected. This study demonstrates that a lab designed with a higher level of inquiry can increase students' spatial ability more than a lab with a low level of inquiry. A lab with a higher level of inquiry helped all participants, regardless of their initial spatial ability level. These findings show that curriculum

  9. Localizing PRL-2 expression and determining the effects of dietary Mg(2+) on expression levels.

    PubMed

    Gungabeesoon, Jeremy; Tremblay, Michel L; Uetani, Noriko

    2016-07-01

    The phosphatase of regenerating liver (PRL) is a group of protein tyrosine phosphatases that play a key role in cancer progression and metastasis. We previously showed that PRL-2 modulates intracellular Mg(2+) levels and sustains cancer phenotypes by binding to the Mg(2+) transporter CNNM3. However, the physiological functions of PRL-2 in animals remain largely unknown. To better understand which cell types are associated with PRL-2 function, we characterized its expression in mouse tissues using a PRL-2 β-galactosidase reporter mouse model. Our results demonstrated that PRL-2 was ubiquitously expressed, with the highest expression levels observed in the hippocampal pyramidal neurons, ependymal cells, cone and rod photoreceptor cells, endocardium, vascular and bronchial smooth muscle, and collecting ducts in the kidney. On the other hand, PRL-2 expression was undetectable or very low in the parenchymal cells of the liver and pancreas. Our results also indicated that PRL-2 is involved in cell-type-specific Mg(2+) homeostasis and that PRL-2 expression is potentially inversely regulated by dietary Mg(2+) levels. PMID:27015884

  10. 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

  11. 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.

  12. 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

  13. The genetic architecture of gene expression levels in wild baboons

    PubMed Central

    Tung, Jenny; Zhou, Xiang; Alberts, Susan C; Stephens, Matthew; Gilad, Yoav

    2015-01-01

    Primate evolution has been argued to result, in part, from changes in how genes are regulated. However, we still know little about gene regulation in natural primate populations. We conducted an RNA sequencing (RNA-seq)-based study of baboons from an intensively studied wild population. We performed complementary expression quantitative trait locus (eQTL) mapping and allele-specific expression analyses, discovering substantial evidence for, and surprising power to detect, genetic effects on gene expression levels in the baboons. eQTL were most likely to be identified for lineage-specific, rapidly evolving genes; interestingly, genes with eQTL significantly overlapped between baboons and a comparable human eQTL data set. Our results suggest that genes vary in their tolerance of genetic perturbation, and that this property may be conserved across species. Further, they establish the feasibility of eQTL mapping using RNA-seq data alone, and represent an important step towards understanding the genetic architecture of gene expression in primates. DOI: http://dx.doi.org/10.7554/eLife.04729.001 PMID:25714927

  14. The Expression Level of Septin12 Is Critical for Spermiogenesis

    PubMed Central

    Lin, Ying-Hung; Lin, Yung-Ming; Wang, Ya-Yun; Yu, I-Shing; Lin, Yi-Wen; Wang, Yun-Han; Wu, Ching-Ming; Pan, Hsien-An; Chao, Shin-Chih; Yen, Pauline H.; Lin, Shu-Wha; Kuo, Pao-Lin

    2009-01-01

    Septins belong to a family of polymerizing GTP-binding proteins that are required for many cellular functions, such as membrane compartmentalization, vesicular trafficking, mitosis, and cytoskeletal remodeling. One family member, septin12, is expressed specifically in the testis. In this study, we found septin12 expressed in multiple subcellular compartments during terminal differentiation of mouse germ cells. In humans, the testicular tissues of men with either hypospermatogenesis or maturation arrest had lower levels of SEPTIN12 transcripts than normal men. In addition, increased numbers of spermatozoa with abnormal head, neck, and tail morphologies lacked SEPT12 immunostaining signals, as compared with normal spermatozoa. To elucidate the role of septin12, we generated 129 embryonic stem cells containing a septin12 mutant allele with a deletion in the exons that encode the N-terminal GTP-binding domain. Most chimeras derived from the targeted embryonic stem cells were infertile, and the few fertile chimeras only produced offspring with a C57BL/6 background. Semen analysis of the infertile chimeras showed a decreased sperm count, decreased sperm motility, and spermatozoa with defects involving all subcellular compartments. The testicular phenotypes included maturation arrest of germ cells at the spermatid stage, sloughing of round spermatids, and increased apoptosis of germ cells. Electron microscopic examination of spermatozoa showed misshapen nuclei, disorganized mitochondria, and broken acrosomes. Our data indicate that Septin12 expression levels are critical for mammalian spermiogenesis. PMID:19359518

  15. Factors associated with higher levels of depressive symptoms among international university students in the Philippines.

    PubMed

    Lee, Romeo B; Maria, Madelene Sta; Estanislao, Susana; Rodriguez, Cristina

    2013-11-01

    Over the years, the number of international university students has been increasing in the Philippines. Depression tends to be common among this demographic sector, because of the varying challenges and expectations associated with studying abroad. Depression can be prevented if its symptoms, particularly those at higher levels, are identified and addressed early and effectively. This survey examined the social and demographic factors that are significantly associated with higher levels of depressive symptoms. One hundred twenty-six international university students were interviewed using the University Students Depression Inventory. Of the 13 factors analyzed, 3 were found with statistically significant associations with more intense levels of depressive symptoms. These factors were: level of satisfaction with one's financial condition, level of closeness with parents, and level of closeness with peers. In identifying international students with greater risk for depression, characteristics related to their financial condition and primary group relationships can be considered. There is a need to carry out more studies to confirm this initial evidence. The findings can help guide further discourse, research and program to benefit international students with higher levels of depressive symptoms. PMID:24450248

  16. Higher Fibrinogen Levels Predict Progression of Coronary Artery Calcification in Adults with Type 1 Diabetes

    PubMed Central

    Rodrigues, T.C.; Snell-Bergeon, J.K.; Maahs, D.M; Kinney, G.L.; Rewers, M.

    2010-01-01

    Aim To determine whether fibrinogen levels predict independently progression of coronary artery calcification (CAC) in adults with type 1 diabetes. Methods Data from a prospective cohort - the Coronary Artery Calcification in Type 1 Diabetes Study - were evaluated. Fibrinogen levels at baseline were separated into quartiles. CAC was measured twice and averaged at baseline and at follow-up 2.4 ± 0.4 years later. CAC progressors were defined as participants whose square-root transformed CAC volume increased by ≥ 2.53 or development mm of clinical coronary artery disease during the follow-up period. Results Fibrinogen levels were higher in progressors than in non-progressors (276 ± 61 mg/dl versus 259 ± 61 mg/dl, p = 0.0003). CAC progression, adjusted for known cardiovascular risk factors, increased in the highest quartile. Conclusions Higher fibrinogen levels predict CAC progression in type 1 diabetes subjects, independent of standard cardiovascular risk factors. PMID:20079495

  17. 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

  18. The level of cytokines and expression of caspase genes in rheumatoid arthritis.

    PubMed

    Malysheva, I E; Topchieva, L V; Barysheva, O Y; Kurbatova, I V; Vasykova, O A; Vezikova, N N; Marusenko, I M; Nemova, N N

    2016-05-01

    The level of TNFα and IL6 in the blood plasma of patients with rheumatoid arthritis (RA) who received antiinflammatory therapy with methotrexate (MT) was significantly lower than in the patients without MT treatment. The level of caspase 6 and 9 gene transcripts in peripheral blood lymphocytes in patients with rheumatoid arthritic diagnosed for the first time and in patients with MT treatment were not significantly different. At the same time, the level of caspase 3 mRNA expression was significantly higher in the cells of the RA patients with MT therapy compared to the patients without MT therapy. PMID:27417728

  19. Th17 expression and IL-17 levels in laryngeal squamous cell carcinoma patients.

    PubMed

    Li, Fu-Jun; Cai, Zhi-Jian; Yang, Fei; Zhang, Shou-De; Chen, Ming

    2016-05-01

    Conclusion The Th17 cell frequency in peripheral blood and levels of IL-17 showed significant differences between patients with laryngeal squamous cell carcinoma and those with vocal cords polyps. Serum levels of IL-17 were correlated with laryngocarcinoma staging. Objectives To investigate associations among the frequency of Th17 cells, levels of IL-17, and laryngeal squamous cell carcinoma. Method Eighty in-patients with laryngeal squamous cell carcinoma and 114 in-patients with polypus of the vocal cord were enrolled. Th17 cell frequencies in peripheral blood and serum levels of IL-17 were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. The tissue expression levels of IL-17 mRNA transcripts and protein were measured using quantitative RT-PCR or immunohistochemical detection, respectively. Results Th17 cell frequencies in peripheral blood and serum concentrations of IL-17 were significantly higher in patients with laryngocarcinoma compared with those in patients with polyps (p < 0.01 for both Th17 cells and IL-17 levels). Serum concentrations of IL-17 were significantly higher in patients with advanced laryngocarcinoma than in patients with early laryngocarcinoma (p < 0.01). The mRNA and protein levels of IL-17 were significantly higher in laryngocarcinoma tissues than in adjacent normal tissues (p < 0.01 for mRNA levels, p < 0.05 for protein levels). PMID:27052965

  20. The City: A Multidisciplinary Unit Exercising the Higher Level Thinking Skills of Analysis, Synthesis, and Evaluation.

    ERIC Educational Resources Information Center

    Burger, Celia R.

    Designed for use with sixth grade students, this multidisciplinary unit combines independent study of urban areas with activities to develop students' higher level thinking skills. Following suggestions to teachers on strategies for introducing the unit, four options for independent study are described. The first is a study of a topic related to…

  1. Re-Setting the Concentration Levels of Students in Higher Education: An Exploratory Study

    ERIC Educational Resources Information Center

    Burke, Lisa A.; Ray, Ruth

    2008-01-01

    Evidence suggests that college students' concentration levels are limited and hard to maintain. Even though relevant in higher education, scant empirical research exists on interventions to "re-set" their concentration during a college lecture. Using a within-subjects design, four active learning interventions are administered across two…

  2. Systemic Glucose Level Changes with a Carbohydrate-Restricted and Higher Protein Diet Combined with Exercise

    ERIC Educational Resources Information Center

    Bowden, Rodney G.; Lanning, Beth A.; Doyle, Eva I.; Slonaker, Becky; Johnston, Holly M.; Scanes, Georgene

    2007-01-01

    Objective: The authors' purpose in this study was to compare the effects of macronutrient intake on systemic glucose levels in previously sedentary participants who followed 1 of 4 diets that were either higher protein or high carbohydrate, while initiating an exercise program. Participants and Methods: The authors randomly assigned 94 sedentary…

  3. Multiple-Choice Exams: An Obstacle for Higher-Level Thinking in Introductory Science Classes

    ERIC Educational Resources Information Center

    Stanger-Hall, Kathrin F.

    2012-01-01

    Learning science requires higher-level (critical) thinking skills that need to be practiced in science classes. This study tested the effect of exam format on critical-thinking skills. Multiple-choice (MC) testing is common in introductory science courses, and students in these classes tend to associate memorization with MC questions and may not…

  4. Achieving Higher Levels of Success for A.D.H.D. Students Working in Collaborative Groups

    ERIC Educational Resources Information Center

    Simplicio, Joseph S. C.

    2007-01-01

    This article explores a new and innovative strategy for helping students with Attention Deficit Hyperactivity Disorder (A.D.H.D.) achieve higher levels of academic success when working in collaborative groups. Since the research indicates that students with this disorder often have difficulty in maintaining their concentration this strategy is…

  5. Sociological Writing as Higher-Level Thinking: Assignments that Cultivate the Sociological Imagination

    ERIC Educational Resources Information Center

    Massengill, Rebekah Peeples

    2011-01-01

    Educators agree that developing critical thinking skills is a key goal of college education. While the literature on higher-level thinking emphasizes the significance of writing for developing such skills, teachers often receive little guidance about the kinds of writing assignments that can prove most beneficial for helping students to develop…

  6. 48 CFR 52.246-11 - Higher-Level Contract Quality Requirement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Higher-Level Contract Quality Requirement. 52.246-11 Section 52.246-11 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 52.246-11...

  7. 48 CFR 52.246-11 - Higher-Level Contract Quality Requirement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Higher-Level Contract Quality Requirement. 52.246-11 Section 52.246-11 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 52.246-11...

  8. Professional Values and Practice: The Essential Guide for Higher Level Teaching Assistants

    ERIC Educational Resources Information Center

    Watkinson, Anne

    2005-01-01

    This book concentrates on the more theoretical aspects of the Higher Level Teaching Assistant role: professionalism, relationships, statutory frameworks and knowing your limits. It offers guidance and support on fulfilling the standards and succeeding both inside and outside the classroom. The book is divided into the following chapters: (1)…

  9. Spatial Skills as a Predictor of First Grade Girls' Use of Higher Level Arithmetic Strategies

    ERIC Educational Resources Information Center

    Laski, Elida V.; Casey, Beth M.; Yu, Qingyi; Dulaney, Alana; Heyman, Miriam; Dearing, Eric

    2013-01-01

    Girls are more likely than boys to use counting strategies rather than higher-level mental strategies to solve arithmetic problems. Prior research suggests that dependence on counting strategies may have negative implications for girls' later math achievement. We investigated the relation between first-grade girls' verbal and spatial skills and…

  10. Implementing CLT at Higher Secondary Level in Bangladesh: A Review of Change Management

    ERIC Educational Resources Information Center

    Rahman, Md Shidur

    2015-01-01

    CLT (Communicative Language Teaching) was substituted for GTM (Grammar Translation Method) at higher secondary level in Bangladesh in 2001. This replacement of ELT method was a significant change in the English curriculum. This study aimed to determine that the mismanagement of the change is a prime cause of not getting expected CLT outcomes at…

  11. 48 CFR 246.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Higher-level contract quality requirements. 246.202-4 Section 246.202-4 Federal Acquisition Regulations System DEFENSE... requirements, including nongovernment quality system standards adopted to meet DoD needs, are listed in the...

  12. 48 CFR 246.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Higher-level contract quality requirements. 246.202-4 Section 246.202-4 Federal Acquisition Regulations System DEFENSE... requirements, including nongovernment quality system standards adopted to meet DoD needs, are listed in the...

  13. 48 CFR 246.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Higher-level contract quality requirements. 246.202-4 Section 246.202-4 Federal Acquisition Regulations System DEFENSE... requirements, including nongovernment quality system standards adopted to meet DoD needs, are listed in the...

  14. 48 CFR 246.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Higher-level contract quality requirements. 246.202-4 Section 246.202-4 Federal Acquisition Regulations System DEFENSE... requirements, including nongovernment quality system standards adopted to meet DoD needs, are listed in the...

  15. The Influence of Transformational Leadership on the Level of TQM Implementation in the Higher Education Sector

    ERIC Educational Resources Information Center

    Argia, Hassan A. A.; Ismail, Aziah

    2013-01-01

    This current research paper investigates the role of transformational leadership on impacting the level of TQM implementation in the higher education sector. In addition, TQM, as a management philosophy, can be implemented successfully only when incorporated into the prevailing learning organization and adequate understanding of transformational…

  16. Relationship between TLR4 and MCP2 expression levels and habitual abortion.

    PubMed

    Li, X P; Song, L N; Tian, L P; Zhang, Y S

    2016-01-01

    Habitual abortion is associated with the altered expression of multiple genes. This study was carried out to investigate the relationship between expression of Toll-like receptor 4 (TLR4) and monocyte chemotactic protein 2 (MCP2 or CCL8) and habitual abortion. This was done by detecting and comparing their relative expression in peripheral blood and placental villi of patients and healthy fertile women. Based on our previous research, 85 subjects with habitual abortion (study group) and 40 healthy fertile women (control group), who were admitted to our hospital between June 2013 and December 2014, were enrolled in this study. After these subjects signed written informed consent, peripheral blood samples and villous tissues were collected, from which the total RNA was extracted. The expression of TLR4 and MCP2 was detected with quantitative reverse transcription-polymerase chain reaction, using GAPDH as a reference control. The expression of TLR4 and MCP2 in the peripheral blood and villous tissues of the study group was significantly higher than that of the control group (P < 0.05). A positive correlation was also observed between the changes in expression levels of TLR4 and MCP2. In conclusion, TLR4 and MCP2 expression correlated with the occurrence of habitual abortion. Detecting expression changes in TLR4 and MCP2 in the peripheral blood is a feasible method for predicting the occurrence of abortion in women of child-bearing age. PMID:27173235

  17. Carnitine and/or Acetylcarnitine Deficiency as a Cause of Higher Levels of Ammonia

    PubMed Central

    Maldonado, Cecilia; Guevara, Natalia; Queijo, Cecilia; González, Raquel; Fagiolino, Pietro; Vázquez, Marta

    2016-01-01

    Blood carnitine and/or acetylcarnitine deficiencies are postulated in the literature as possible causes of higher ammonia levels. The aim of this study was to investigate if the use of valproic acid, the age of the patients, or certain central nervous system pathologies can cause carnitine and/or acetylcarnitine deficiency leading to increased ammonia levels. Three groups of patients were studied: (A) epileptic under phenytoin monotherapy (n = 31); (B) with bipolar disorder under valproic acid treatment (n = 28); (C) elderly (n = 41). Plasma valproic acid and blood carnitine and acyl carnitine profiles were determined using a validated HPLC and LC-MS/MS method, respectively. Blood ammonia concentration was determined using an enzymatic automated assay. Higher ammonia levels were encountered in patients under valproic acid treatment and in the elderly. This may be due to the lower carnitine and/or acetylcarnitine found in these patients. Patients with controlled seizures had normal carnitine and acetylcarnitine levels. Further studies are necessary in order to conclude if the uncontrolled bipolar disorder could be the cause of higher carnitine and/or acetylcarnitine levels. PMID:26998483

  18. Higher Levels of Psychopathy Predict Poorer Motor Control: Implications for Understanding the Psychopathy Construct

    PubMed Central

    Robinson, Michael D.; Bresin, Konrad

    2014-01-01

    A review of the literature suggests that higher levels of psychopathy may be linked to less effective behavioral control. However, several commentators have urged caution in making statements of this type in the absence of direct evidence. In two studies (total N = 142), moment-to-moment accuracy in a motor control task was examined as a function of dimensional variations in psychopathy in an undergraduate population. As hypothesized, motor control was distinctively worse at higher levels of psychopathy relative to lower levels, both as a function of primary and secondary psychopathy and particularly their shared variance. These novel findings provide support for the idea that motor control systematically varies by psychopathy, in a basic manner, consistent with views of psychopathy emphasizing lesser control. PMID:25419045

  19. Effects of phased joint intervention on Rho/ROCK expression levels in patients with portal hypertension

    PubMed Central

    Shi, Min; Wei, Jue; Meng, Wen-Ying; Wang, Na; Wang, Ting; Wang, Yu-Gang

    2016-01-01

    The current study investigated the effects of phased joint intervention on clinical efficacy and Rho/Rho-associated coil protein kinase (ROCK) expression in patients with portal hypertension complicated by esophageal variceal bleeding (EVB) and hypersplenism. Patients with portal hypertension (n=53) caused by liver cirrhosis complicated by EVB and hypersplenism treated with phased joint intervention were assessed, and portal hemodynamics, blood, liver function, complications, and rebleeding incidence were analyzed. Reverse transcription-quantitative polymerase chain reaction was used to measure Rho, ROCK1 and ROCK2 mRNA expression levels in peripheral blood mononuclear cells prior to and following phased joint intervention, and western blotting was employed to determine the protein expression levels of Rho, ROCK1, ROCK2, phosphorylated (p) myosin phosphatase target subunit 1 (MYPT1) and total-MYPT1. All patients underwent an emergency assessment of hemostasis with a 100% success rate. Varicose veins were alleviated, and portal hemodynamics and liver function improved following intervention. Furthermore, preoperative and postoperative expression levels of Rho, ROCK1 and ROCK2 mRNA were higher compared with the control group. Notably, the mRNA expression levels of Rho, ROCK1 and ROCK2 in the postoperative group were significantly lower when compared with the preoperative group. Protein expression levels of Rho, ROCK1, ROCK2 and pMYPT1 in the postoperative group were lower, as compared with the preoperative group. Concentration levels of transforming growth factor-β1, connective tissue growth factor and platelet-derived growth factor in peripheral blood were significantly reduced following phased joint intervention. Therefore, the present findings demonstrated that phased joint intervention is able to effectively treat EVB and hypersplenism, and improve liver function. The efficacy of phased joint intervention may be associated with its role in the regulation of the

  20. 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

  1. Association of the osteopontin rs1126616 polymorphism and a higher serum osteopontin level with lupus nephritis

    PubMed Central

    SALIMI, SAEEDEH; NOORA, MEHRANGIZ; NABIZADEH, SIMA; REZAEI, MAHNAZ; SHAHRAKI, HOSSAIN; MILAD, MOHAMMADOO-KHORASSANI; NAGHAVI, ANOOSH; FARAJIAN-MASHHADI, FARZANEH; ZAKERI, ZAHRA; SANDOUGHI, MAHNAZ

    2016-01-01

    Osteopontin (OPN) is a chemokine-like glycoprotein that has a prominent role in regulating inflammation and immunity. OPN polymorphisms and elevated OPN levels are associated with systemic lupus erythematosus (SLE) in several populations. The aim of present study was to evaluate the association between the OPN rs1126616 polymorphism and OPN level with SLE susceptibility. A total of 163 SLE patients and 180 age-, gender- and ethnically matched controls were genotyped for the rs1126616 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism method. Serum OPN levels were assayed by the enzyme-linked immunosorbent assay. There was no association between the OPN rs1126616 C/T polymorphism and SLE. The frequency of the OPN rs1126616 CT genotype was significantly higher in SLE patients with nephritis compared to SLE patients without nephritis and controls. Additionally, the frequency of TT genotypes was higher in SLE patients with nephritis compared to controls. The serum OPN levels were significantly higher in SLE patients compared to controls (50.6±22 vs. 35.6±15.8 ng/ml, P<0.001). Increased serum OPN levels were observed in SLE patients with lupus nephritis and joint symptoms. There was no correlation between OPN levels and the OPN rs1126616 polymorphism. The present data suggest that the CT and TT genotypes of the OPN rs1126616 polymorphism could be a risk factor for lupus nephritis. The OPN level is associated with SLE and certain SLE manifestations. However, there was no association between the OPN rs1126616 C/T polymorphism and SLE susceptibility. PMID:26998275

  2. High level expression of kringle 5 fragment of plasminogen in Pichia pastoris.

    PubMed

    Zhou, Yufei; Zheng, Quan; Gao, Jin; Gu, Jun

    2005-02-01

    Angiogensis can be blocked by inhibitors such as endostatin and angiostatin. The kringle 5 fragment of plasminogen also has a potent inhibitory effect on endothelial cell proliferation and leads to the inhibition of angiogenesis. It has promise in anti-angiogenic therapy due to its small size and potent inhibitory effect. Preparation of kringle 5 has been achieved through the proteolysis of native plasminogen and recombinant DNA technology. Bacterially expressed recombinant kringle 5 is mainly insoluble and expressed at low level. The refolding yield is also low. To produce recombinant human kringle 5 in a large quantity, we have genetically modified a strain of Pichia pastoris. On methanol induction, this strain expressed and secreted biologically active, recombinant kringle 5. The expression level of the engineered strain in culture reached more than 300 mgl(-1). Purification was easily achieved by precipitation, hydrophobic and DEAE ion exchange chromatography. The recovery of recombinant kringle 5 was about 50% after purification. Yeast-expressed kringle 5 has a higher activity in anti-endothelial proliferation than bacterially expressed kringle 5. PMID:15717125

  3. Elevated gene expression levels distinguish human from non-human primate brains

    PubMed Central

    Cáceres, Mario; Lachuer, Joel; Zapala, Matthew A.; Redmond, John C.; Kudo, Lili; Geschwind, Daniel H.; Lockhart, David J.; Preuss, Todd M.; Barlow, Carrolee

    2003-01-01

    Little is known about how the human brain differs from that of our closest relatives. To investigate the genetic basis of human specializations in brain organization and cognition, we compared gene expression profiles for the cerebral cortex of humans, chimpanzees, and rhesus macaques by using several independent techniques. We identified 169 genes that exhibited expression differences between human and chimpanzee cortex, and 91 were ascribed to the human lineage by using macaques as an outgroup. Surprisingly, most differences between the brains of humans and non-human primates involved up-regulation, with ≈90% of the genes being more highly expressed in humans. By contrast, in the comparison of human and chimpanzee heart and liver, the numbers of up- and down-regulated genes were nearly identical. Our results indicate that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans and suggests that the human brain is characterized by elevated levels of neuronal activity. PMID:14557539

  4. Levels of Lycopene β-Cyclase 1 Modulate Carotenoid Gene Expression and Accumulation in Daucus carota

    PubMed Central

    Moreno, Juan Camilo; Pizarro, Lorena; Fuentes, Paulina; Handford, Michael; Cifuentes, Victor; Stange, Claudia

    2013-01-01

    Plant carotenoids are synthesized and accumulated in plastids through a highly regulated pathway. Lycopene β-cyclase (LCYB) is a key enzyme involved directly in the synthesis of α-carotene and β-carotene through the cyclization of lycopene. Carotenoids are produced in both carrot (Daucus carota) leaves and reserve roots, and high amounts of α-carotene and β-carotene accumulate in the latter. In some plant models, the presence of different isoforms of carotenogenic genes is associated with an organ-specific function. D. carota harbors two Lcyb genes, of which DcLcyb1 is expressed in leaves and storage roots during carrot development, correlating with an increase in carotenoid levels. In this work, we show that DcLCYB1 is localized in the plastid and that it is a functional enzyme, as demonstrated by heterologous complementation in Escherichia coli and over expression and post transcriptional gene silencing in carrot. Transgenic plants with higher or reduced levels of DcLcyb1 had incremented or reduced levels of chlorophyll, total carotenoids and β-carotene in leaves and in the storage roots, respectively. In addition, changes in the expression of DcLcyb1 are accompanied by a modulation in the expression of key endogenous carotenogenic genes. Our results indicate that DcLcyb1 does not possess an organ specific function and modulate carotenoid gene expression and accumulation in carrot leaves and storage roots. PMID:23555569

  5. Technology and Bloom's Taxonomy: Tools to facilitate higher-level learning in chemistry

    NASA Astrophysics Data System (ADS)

    Morgan, Matthew Earle

    This research project ties together chemistry data acquisition technology, introductory chemistry laboratory experiments. and Bloom's Taxonomy of Educational Objectives into a unified learning model. The goal is to provide faculty and introductory chemistry students with the tools and exercises to experience higher levels of learning, as defined by Bloom's taxonomy. The tools developed as part of this project include data acquisition hardware and software, communications software, and computer simulations that enable higher-level learning situations. A series of five experiments using a discovery-based teaching model are developed as part of the learning model. The experiments bring together the hardware tools, software tools, and learning model to place students in situations that require students to use critical thinking skills and experience higher-level learning. Content-related application problems are also included in the experiments. The experiments are divided into three chemistry units of instruction that build on each other, but can also be used independently. Instructor training is an important part of this project. The successful integration of technology into educational situations cannot be accomplished without the support and understanding of faculty, staff, and teaching assistants. This aspect of the project focuses on shifting teaching and learning paradigms to encourage appropriate technology use and allow technology to become a major aspect of the high-level learning environment. Finally, students were surveyed in an attempt to measure the effectiveness of the learning model. Students were evaluated on chemistry concept retention, as well as their perception of learning. They were also asked how well they enjoyed this form of learning. Along with the tools themselves, this project provides templates that can launch future work in this area. The learning model, data acquisition tools, and experiment writing templates are developed here to provide

  6. Multisensory Stimulation to Improve Low- and Higher-Level Sensory Deficits after Stroke: A Systematic Review.

    PubMed

    Tinga, Angelica Maria; Visser-Meily, Johanna Maria Augusta; van der Smagt, Maarten Jeroen; Van der Stigchel, Stefan; van Ee, Raymond; Nijboer, Tanja Cornelia Wilhelmina

    2016-03-01

    The aim of this systematic review was to integrate and assess evidence for the effectiveness of multisensory stimulation (i.e., stimulating at least two of the following sensory systems: visual, auditory, and somatosensory) as a possible rehabilitation method after stroke. Evidence was considered with a focus on low-level, perceptual (visual, auditory and somatosensory deficits), as well as higher-level, cognitive, sensory deficits. We referred to the electronic databases Scopus and PubMed to search for articles that were published before May 2015. Studies were included which evaluated the effects of multisensory stimulation on patients with low- or higher-level sensory deficits caused by stroke. Twenty-one studies were included in this review and the quality of these studies was assessed (based on eight elements: randomization, inclusion of control patient group, blinding of participants, blinding of researchers, follow-up, group size, reporting effect sizes, and reporting time post-stroke). Twenty of the twenty-one included studies demonstrate beneficial effects on low- and/or higher-level sensory deficits after stroke. Notwithstanding these beneficial effects, the quality of the studies is insufficient for valid conclusion that multisensory stimulation can be successfully applied as an effective intervention. A valuable and necessary next step would be to set up well-designed randomized controlled trials to examine the effectiveness of multisensory stimulation as an intervention for low- and/or higher-level sensory deficits after stroke. Finally, we consider the potential mechanisms of multisensory stimulation for rehabilitation to guide this future research. PMID:26490254

  7. Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease

    PubMed Central

    Ju, Chun-rong; Chen, Miao; Zhang, Jian-heng; Lin, Zhi-ya; Chen, Rong-chang

    2016-01-01

    Objective To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD). Methods The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin. Results The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 ± 2.95) than in those without (13.56 ± 3.09), and much higher than in controls (8.79±2.79), with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05). Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05. Conclusions Plasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD. PMID:26998756

  8. Massively Parallel Interrogation of the Effects of Gene Expression Levels on Fitness.

    PubMed

    Keren, Leeat; Hausser, Jean; Lotan-Pompan, Maya; Vainberg Slutskin, Ilya; Alisar, Hadas; Kaminski, Sivan; Weinberger, Adina; Alon, Uri; Milo, Ron; Segal, Eran

    2016-08-25

    Data of gene expression levels across individuals, cell types, and disease states is expanding, yet our understanding of how expression levels impact phenotype is limited. Here, we present a massively parallel system for assaying the effect of gene expression levels on fitness in Saccharomyces cerevisiae by systematically altering the expression level of ∼100 genes at ∼100 distinct levels spanning a 500-fold range at high resolution. We show that the relationship between expression levels and growth is gene and environment specific and provides information on the function, stoichiometry, and interactions of genes. Wild-type expression levels in some conditions are not optimal for growth, and genes whose fitness is greatly affected by small changes in expression level tend to exhibit lower cell-to-cell variability in expression. Our study addresses a fundamental gap in understanding the functional significance of gene expression regulation and offers a framework for evaluating the phenotypic effects of expression variation. PMID:27545349

  9. Androgen Receptors in a Cichlid Fish, Astatotilapia burtoni: Structure, Localization, and Expression Levels

    PubMed Central

    HARBOTT, LENE K.; BURMEISTER, SABRINA S.; WHITE, RICHARD B.; VAGELL, MIKE; FERNALD, RUSSELL D.

    2009-01-01

    Androgens are an important output of the hypothalamic-pituitary-gonadal (HPG) axis that controls reproduction in all vertebrates. In male teleosts two androgens, testosterone and 11-ketotestosterone, control sexual differentiation and development in juveniles and reproductive behavior in adults. Androgenic signals provide feedback at many levels of the HPG axis, including the hypothalamic neurons that synthesize and release gonadotropin-releasing hormone 1 (GnRH1), but the precise cellular site of androgen action in the brain is not known. Here we describe two androgen receptor subtypes, ARα and ARβ, in the cichlid Astatotilapia burtoni and show that these subtypes are differentially located throughout the adult brain in nuclei known to function in the control of reproduction. ARα was expressed in the ventral part of the ventral telencephalon, the preoptic area (POA) of the hypothalamus and the ventral hypothalamus, whereas ARβ was more widely expressed in the dorsal and ventral telencephalon, the POA, and the ventral and dorsal hypothalamus. We provide the first evidence in any vertebrate that the GnRH1-releasing neurons, which serve as the central control point of the HPG axis, express both subtypes of AR. Using quantitative real-time PCR, we show that A. burtoni AR subtypes have different expression levels in adult tissue, with ARα showing significantly higher expression than ARβ in the pituitary, and ARβ expressed at a higher level than ARα in the anterior and middle brain. These data provide important insight into the role of androgens in regulating the vertebrate reproductive axis. PMID:17614300

  10. Hierarchical Control Using Networks Trained with Higher-Level Forward Models

    PubMed Central

    Wayne, Greg; Abbott, L.F.

    2015-01-01

    We propose and develop a hierarchical approach to network control of complex tasks. In this approach, a low-level controller directs the activity of a “plant,” the system that performs the task. However, the low-level controller may only be able to solve fairly simple problems involving the plant. To accomplish more complex tasks, we introduce a higher-level controller that controls the lower-level controller. We use this system to direct an articulated truck to a specified location through an environment filled with static or moving obstacles. The final system consists of networks that have memorized associations between the sensory data they receive and the commands they issue. These networks are trained on a set of optimal associations that are generated by minimizing cost functions. Cost function minimization requires predicting the consequences of sequences of commands, which is achieved by constructing forward models, including a model of the lower-level controller. The forward models and cost minimization are only used during training, allowing the trained networks to respond rapidly. In general, the hierarchical approach can be extended to larger numbers of levels, dividing complex tasks into more manageable sub-tasks. The optimization procedure and the construction of the forward models and controllers can be performed in similar ways at each level of the hierarchy, which allows the system to be modified to perform other tasks, or to be extended for more complex tasks without retraining lower-levels. PMID:25058706

  11. Enhancing the Schooling Level of the Special Higher Education and Perfecting the Disabled People Higher Education System

    ERIC Educational Resources Information Center

    Wang, Aiguo

    2009-01-01

    It is the urgent problem to quickly develop the graduate education of disabled college students for Chinese special higher education. Through the comparison of the foreign and domestic disabled graduate education actualities, we should constitute the postgraduate cultivation scheme and the education layout which could not only possess Chinese…

  12. Multi-level Expression Design Language: Requirement level (MEDL-R) system evaluation

    NASA Technical Reports Server (NTRS)

    1980-01-01

    An evaluation of the Multi-Level Expression Design Language Requirements Level (MEDL-R) system was conducted to determine whether it would be of use in the Goddard Space Flight Center Code 580 software development environment. The evaluation is based upon a study of the MEDL-R concept of requirement languages, the functions performed by MEDL-R, and the MEDL-R language syntax. Recommendations are made for changes to MEDL-R that would make it useful in the Code 580 environment.

  13. Insect cell transformation vectors that support high level expression and promoter assessment in insect cell culture.

    PubMed

    Shirk, Paul D; Furlong, Richard B

    2016-01-01

    A somatic transformation vector, pDP9, was constructed that provides a simplified means of producing permanently transformed cultured insect cells that support high levels of protein expression of foreign genes. The pDP9 plasmid vector incorporates DNA sequences from the Junonia coenia densovirus that are involved in integration of the densovirus in insect cell chromosomes and a promoter/enhancer system that results in high levels of expression. The plasmid also contains two markers that permit selection of transformed insect cells by antibiotic resistance or by cell-sorting for fluorescent protein expression. Transformation of Bombyx mori Bm5 or Spodoptera frugiperda Sf9 cultured cells with the pDP9 vectors results in the integration of the pDP9 plasmid into genomic DNA of Bm5 and Sf9 cells. pDP9 contains a multiple cloning site (MCS) 3' of the densoviral P9 promoter and insertion of a protein coding sequence within the MCS results in high level expression by pDP9 transformed cells. P9 driven transcription in the pDP9 transformed Sf9 cells produced foreign gene transcript levels that were 30 fold higher than actin 3 driven transgenes and equivalent to hr5IE1 driven transgenes. The pDP9 vector transformation results in the efficient selection of clones for assessment of promoter activity. PMID:26794473

  14. Higher-level fusion for military operations based on abductive inference: proof of principle

    NASA Astrophysics Data System (ADS)

    Pantaleev, Aleksandar V.; Josephson, John

    2006-04-01

    The ability of contemporary military commanders to estimate and understand complicated situations already suffers from information overload, and the situation can only grow worse. We describe a prototype application that uses abductive inferencing to fuse information from multiple sensors to evaluate the evidence for higher-level hypotheses that are close to the levels of abstraction needed for decision making (approximately JDL levels 2 and 3). Abductive inference (abduction, inference to the best explanation) is a pattern of reasoning that occurs naturally in diverse settings such as medical diagnosis, criminal investigations, scientific theory formation, and military intelligence analysis. Because abduction is part of common-sense reasoning, implementations of it can produce reasoning traces that are very human understandable. Automated abductive inferencing can be deployed to augment human reasoning, taking advantage of computation to process large amounts of information, and to bypass limits to human attention and short-term memory. We illustrate the workings of the prototype system by describing an example of its use for small-unit military operations in an urban setting. Knowledge was encoded as it might be captured prior to engagement from a standard military decision making process (MDMP) and analysis of commander's priority intelligence requirements (PIR). The system is able to reasonably estimate the evidence for higher-level hypotheses based on information from multiple sensors. Its inference processes can be examined closely to verify correctness. Decision makers can override conclusions at any level and changes will propagate appropriately.

  15. How does plant chemical diversity contribute to biodiversity at higher trophic levels?

    PubMed

    Schuman, Meredith C; van Dam, Nicole M; Beran, Franziska; Harpole, W Stanley

    2016-04-01

    Plants, perhaps Earth's most accomplished chemists, produce thousands of specialized metabolites having no direct role in cell division or growth. These phytochemicals vary by taxon, with many taxa producing characteristic substance classes; and within taxa, with individual variation in structural variety and production patterns. Observations of corresponding variation in herbivore metabolism, behavior, and diet breadth motivated the development of chemical ecology research. We discuss the importance of plant biodiversity in general and phytochemical diversity in particular for biodiversity and ecological interactions at higher trophic levels. We then provide an overview of the descriptive, molecular and analytical tools which allow modern biologists to investigate phytochemical diversity and its effects on higher trophic levels, from physiological mechanisms to ecological communities. PMID:27436646

  16. Effects of nutritional level of concentrate-based diets on meat quality and expression levels of genes related to meat quality in Hainan black goats.

    PubMed

    Wang, Dingfa; Zhou, Luli; Zhou, Hanlin; Hou, Guanyu; Shi, Liguang; Li, Mao; Huang, Xianzhou; Guan, Song

    2015-02-01

    The present study investigated the effects of the nutritional levels of diets on meat quality and related gene expression in Hainan black goat. Twenty-four goats were divided into six dietary treatments and were fed a concentrate-based diet with two levels of crude protein (CP) (15% or 17%) and three levels of digestive energy (DE) (11.72, 12.55 or 13.39 MJ/kg DM) for 90 days. Goats fed the concentrate-based diet with 17% CP had significantly (P < 0.05) higher average daily gains (ADG) and better feed conversion rates (FCR). The pH 24h value tended to decrease (P < 0.05) with increasing DE levels. The tenderness of Longissimus dorsi muscle (LD) and Semimembranosus muscle (SM) reduced with increasing CP levels (P < 0.05). With increasing DE levels, tenderness was increased (P < 0.05). The heart fatty acid-binding protein (H-FABP) mRNA expression levels in LD and SM increased with increasing DE levels (P < 0.05), but decreased with increasing CP levels (P < 0.05). The calpastatin (CAST) and μ-calpain mRNA expressions levels in LD and SM were affected significantly (P < 0.05) by CP and DE levels in the diet. Therefore, the nutritional levels of diets affect meat quality and expression levels of genes associated with meat quality in Hainan black goats. PMID:25039653

  17. Change in Prostaglandin Expression Levels and Synthesizing Activities in Dry Eye Disease

    PubMed Central

    Shim, Jongwoo; Park, Changhun; Lee, Hyun Soo; Park, Min Soo; Lim, Hyung Taek; Chauhan, Sunil; Dana, Reza; Lee, Hyon; Lee, Hyung Keun

    2013-01-01

    Objective To investigate the expression level of prostaglandins (PGs) and their de novo synthesis in dry eye (DE) disease. Design Cross-sectional case-control study and in vivo mouse experimental study. Participants Forty-six eyes from 23 DE patients and 33 eyes from 17 age- and sex-matched controls were studied. Also, DE-induced murine eyes were compared with control eyes. Methods Patients completed a symptom questionnaire using a 100-mm visual analog scale (VAS). Nanoliquid chromatography tandem mass spectrometry was used for the quantification of PGE2 and PGD2. A DE disease environmental chamber was used to induce DE in mice. One week after induction, enzyme expressions of cyclooxygenase-1, cyclooxygenase-2 (COX-2), PG E synthase (PGES), and PG D synthase (PGDS) in the lacrimal glands, meibomian glands, and corneas were examined using immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Main Outcome Measures The mean PGE2 and PGD2 levels in the tears of DE patients were measured and compared with symptom severity scores. Immunohistochemistry staining patterns and qRT-PCR data of DE mice were quantified. Results The mean PGE2 level in the tears of DE patients (2.72±3.42 ng/ml) was significantly higher than that in the control group (0.88±0.83 ng/ml; P = 0.003). However, the mean PGD2 level in the tears of DE patients (0.11 ±0.22 ng/ml) was significantly lower (0.91 ±3.28 ng/ml; P = 0.028). The mean PGE2-to-PGD2 ratio correlated strongly with VAS scoring (P = 0.008). In DE mice, COX-2 mRNA was significantly higher in ocular surface tissue and lacrimal glands. Furthermore, PGES mRNA was significantly higher in ocular surface tissue, whereas PGDS mRNA was decreased. Immunohistochemistry staining showed elevated COX-2 expression in the lacrimal glands, meibomian glands, corneas, and conjunctivas. Furthermore, PGES expression was found in periductal infiltrated cells of the lacrimal glands and conjunctival epithelium. Also, PGDS

  18. 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

  19. Potential Interactions between the Autonomic Nervous System and Higher Level Functions in Neurological and Neuropsychiatric Conditions

    PubMed Central

    Bassi, Andrea; Bozzali, Marco

    2015-01-01

    The autonomic nervous system (ANS) maintains the internal homeostasis by continuously interacting with other brain structures. Its failure is commonly observed in many neurological and neuropsychiatric disorders, including neurodegenerative and vascular brain diseases, spinal cord injury, and peripheral neuropathies. Despite the different underlying pathophysiological mechanisms, ANS failure associates with various forms of higher level dysfunctions, and may also negatively impact on patients’ clinical outcome. In this review, we will discuss potential relationships between ANS and higher level dysfunctions in a selection of neurological and neuropsychiatric disorders. In particular, we will focus on the effect of a documented fall in blood pressure fulfilling the criteria for orthostatic hypotension and/or autonomic-reflex impairment on cognitive performances. Some evidence supports the hypothesis that cardiovascular autonomic failure may play a negative prognostic role in most neurological disorders. Despite a clear causal relationship between ANS involvement and higher level dysfunctions that is still controversial, this might have implications for neuro-rehabilitation strategies aimed at improving patients’ clinical outcome. PMID:26388831

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

    PubMed

    Rossner, Pavel; Tulupova, Elena; Rossnerova, Andrea; Libalova, Helena; Honkova, Katerina; Gmuender, Hans; Pastorkova, Anna; Svecova, Vlasta; Topinka, Jan; Sram, Radim J

    2015-10-01

    We analyzed the ability of particulate matter (PM) and chemicals adsorbed onto it to induce diverse gene expression profiles in subjects living in two regions of the Czech Republic differing in levels and sources of the air pollution. A total of 312 samples from polluted Ostrava region and 154 control samples from Prague were collected in winter 2009, summer 2009 and winter 2010. The highest concentrations of air pollutants were detected in winter 2010 when the subjects were exposed to: PM of aerodynamic diameter <2.5μm (PM2.5) (70 vs. 44.9μg/m(3)); benzo[a]pyrene (9.02 vs. 2.56ng/m(3)) and benzene (10.2 vs. 5.5μg/m(3)) in Ostrava and Prague, respectively. Global gene expression analysis of total RNA extracted from leukocytes was performed using Illumina Expression BeadChips microarrays. The expression of selected genes was verified by quantitative real-time PCR (qRT-PCR). Gene expression profiles differed by locations and seasons. Despite lower concentrations of air pollutants a higher number of differentially expressed genes and affected KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was found in subjects from Prague. In both locations immune response pathways were affected, in Prague also neurodegenerative diseases-related pathways. Over-representation of the latter pathways was associated with the exposure to PM2.5. The qRT-PCR analysis showed a significant decrease in expression of APEX, ATM, FAS, GSTM1, IL1B and RAD21 in subjects from Ostrava, in a comparison of winter 2010 and summer 2009. In Prague, an increase in gene expression was observed for GADD45A and PTGS2. In conclusion, high concentrations of pollutants in Ostrava were not associated with higher number of differentially expressed genes, affected KEGG pathways and expression levels of selected genes. This observation suggests that chronic exposure to air pollution may result in reduced gene expression response with possible negative health consequences. PMID:26298100

  1. 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

  2. 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

  3. Higher plasma level of STIM1, OPG are correlated with stent restenosis after PCI

    PubMed Central

    Li, Haibin; Jiang, Zhian; Liu, Xiangdong; Yang, Zhihui

    2015-01-01

    Object: Percutaneous Coronary Intervention (PCI) is one of the most effective treatments for Coronary Heart Disease (CHD), but the high rate of In Stent Restenosis (ISR) has plagued clinicians after PCI. We aim to investigate the correlation of plasma Stromal Interaction Molecular 1 (STIM1) and Osteoprotegerin (OPG) level with stent restenosis after PCI. Methods: A total of 100 consecutive patients with Coronary Heart Disease (CHD) received PCI procedure were recruited. Coronary angiography was performed 8 months after their PCI. Then patients were divided into 2 groups: observation group was composed by patients who existing postoperative stenosis after intervention; Control group was composed by patients with no postoperative stenosis. The plasma levels of STIM, OPG in all patients were tested before and after intervention. Pearson correlation and multiple linear regression analysis were performed to analysis the correlation between STIM, OPG level and postoperative stenosis. Results: 35 cases were divided into observation group and other 65 were divided into control group. The plasma levels of STIM, OPG have no statistical difference before their PCI procedure, but we observed higher level of High-sensitivity C-reactive protein (Hs-CRP) existed in observation group. We observed higher level of plasma STIM, OPG in observation group when compared with control group after PCI procedure (P < 0.05). Regression analysis demonstrated that Hs-CRP, STIM1, OPG are independent risk factors for ISR. Conclusion: Elevated levels of plasma STIM1, OPG are independent risk factors for ISR in patients received PCI, which could provide useful information for the restenosis control after PCI. PMID:26885040

  4. 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

  5. Endogenous oxytocin levels are associated with the perception of emotion in dynamic body expressions in schizophrenia.

    PubMed

    Strauss, Gregory P; Keller, William R; Koenig, James I; Sullivan, Sara K; Gold, James M; Buchanan, Robert W

    2015-03-01

    Lower endogenous oxytocin levels have been associated with impaired social cognition in schizophrenia, particularly facial affect identification. Little is known about the relationship between oxytocin and other forms of emotion perception. In the current study, 41 individuals with schizophrenia (SZ) and 22 demographically matched healthy controls (CN) completed a forced-choice affective body expression classification task. Stimuli included dynamic videos of male and female actors portraying 4 discrete emotions: happiness, sadness, anger, and neutral. Plasma oxytocin levels were determined via radioimmunoassay. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ were also less accurate at identifying expressions of happiness and sadness; however, there were no group differences for anger or neutral stimuli. A group×sex interaction was also present, such that female CN were more accurate than male CN, whereas male SZ were more accurate than female SZ. Higher endogenous oxytocin levels were associated with better total recognition in both SZ and CN; this association was specific to females in SZ. Findings indicate that sex plays an important role in identifying emotional expressions in body gestures in SZ, and that individual differences in endogenous oxytocin predict emotion perception accuracy. PMID:25620121

  6. Endogenous Oxytocin Levels Are Associated with the Perception of Emotion in Dynamic Body Expressions in Schizophrenia

    PubMed Central

    Strauss, Gregory P.; Keller, William R.; Koenig, James I.; Sullivan, Sara K.; Gold, James M.; Buchanan, Robert W.

    2015-01-01

    Lower endogenous oxytocin levels have been associated with impaired social cognition in schizophrenia, particularly facial affect identification. Little is known about the relationship between oxytocin and other forms of emotion perception. In the current study, 41 individuals with schizophrenia (SZ) and 22 demographically matched healthy controls (CN) completed a forced-choice affective body expression classification task. Stimuli included dynamic videos of male and female actors portraying 4 discrete emotions: happiness, sadness, anger, and neutral. Plasma oxytocin levels were determined via radioimmunoassay. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ were also less accurate at identifying expressions of happiness and sadness; however, there were no group differences for anger or neutral stimuli. A group x sex interaction was also present, such that female CN were more accurate than male CN, whereas male SZ were more accurate than female SZ. Higher endogenous oxytocin levels were associated with better total recognition in both SZ and CN; this association was specific to females in SZ. Findings indicate that sex plays an important role in identifying emotional expressions in body gestures in SZ, and that individual differences in endogenous oxytocin predict emotion perception accuracy. PMID:25620121

  7. Higher prevalence and levels of Nosema ceranae than Nosema apis infections in Canadian honey bee colonies.

    PubMed

    Emsen, Berna; Guzman-Novoa, Ernesto; Hamiduzzaman, Mollah Md; Eccles, Les; Lacey, Brian; Ruiz-Pérez, Rosario A; Nasr, Medhat

    2016-01-01

    This study was conducted to determine the prevalence and infection levels of the microsporidia fungi Nosema apis and/or Nosema ceranae in honey bee colonies of two Canadian provinces. Three surveys were conducted in the springs of 2008, 2010 and 2012 and PCR identification of Nosema species were performed in samples from 169 and 181 Ontario colonies and from 76 Alberta colonies that tested positive to Nosema spp. Infection levels of positive colonies were determined by microscopy and analyzed by Nosema spp. Results showed that N. ceranae was the dominant species in all three surveys (prevalence range of 41-91 vs. 4-34 % for N. apis), whereas mixed infections were less frequent than single infections (5-25 %). Infection levels of colonies parasitized by N. ceranae were three to five times higher than those of colonies parasitized by N. apis in the three surveys whereas mixed infections showed the highest spore counts. This is the first field study demonstrating significantly higher infection levels in colonies parasitized with either N. ceranae only or with both, N. ceranae and N. apis, than in colonies parasitized with N. apis only. Taken together, these results suggest that N. ceranae may be more virulent and better adapted than N. apis in cold climates such as Canadian environments. PMID:26358102

  8. Serum sTREM-1 level is quite higher in Crimean Congo Hemorrhagic Fever, a viral infection.

    PubMed

    Altay, Fatma Aybala; Elaldi, Nazif; Şentürk, Gönül Çiçek; Altin, Nilgün; Gözel, Mustafa Gökhan; Albayrak, Yurdagül; Şencan, İrfan

    2016-09-01

    Members of triggering receptor expressed on myeloid cells (TREM) family are known as immunmodulators in several infectious or noninfectious inflammatory disorders. The information about their role in viral infections is very limited. To enlighten if there is a relation between soluble TREM-1(sTREM-1) and a viral infection, Crimean Congo Haemorrhagic Fever (CCHF), we investigated the levels of sTREM-1 in the sera of 39 CCHF patients both at admission and at recovery and compared with 40 healthy controls by using microELISA technique. Statistical analysis was made by using Statistical Package for Social Sciences (SPSS) for Windows 20 programme. Value of P < 0.05 was accepted as significant for statistical analyses. Median sTREM-1 level was higher in CCHF group when compared to the control group (1,961 vs. 151.1 pg/ml, respectively; P < 0.001). In CCHF patients, sTREM-1 levels were significantly decreased at recovery compared to initial level measured at hospital admission (1,961 vs. 948 pg/ml, respectively; P = 0.019). ΔsTREM-1 is correlated with ΔCRP, ΔWBC, and ΔPlt. We found that serum levels of sTREM-1 higher than 405.9 pg/ml existed as a cut off point for differentiating CCHF patients and control group with a sensitivity of 94.9% and specifity of 87.5%. It is proved that sTREM-1 is increased and correlates with the clinical and laboratory findings in CCHF, a viral infection characterized by activation of inflammation. This finding may lead new studies to enlighten the pathogenesis of infections developing by activation of inflammatory cascades and high level cytokine releases, especially. J. Med. Virol. 88:1473-1478, 2016. © 2016 Wiley Periodicals, Inc. PMID:26877157

  9. Rabies Virus Vector Transgene Expression Level and Cytotoxicity Improvement Induced by Deletion of Glycoprotein Gene

    PubMed Central

    Ohara, Shinya; Sato, Sho; Oyama, Kei; Tsutsui, Ken-Ichiro; Iijima, Toshio

    2013-01-01

    The glycoprotein (G) of rabies virus (RV) is required for binding to neuronal receptors and for viral entry. G-deleted RV vector is a powerful tool for investigating the organization and function of the neural circuits. It gives the investigator the ability to genetically target initial infection to particular neurons and to control trans-synaptic propagation. In this study we have quantitatively evaluated the effect of G gene deletion on the cytotoxicity and transgene expression level of the RV vector. We compared the characteristics of the propagation-competent RV vector (rHEP5.0-CVSG-mRFP) and the G-deleted RV vector (rHEP5.0-ΔG-mRFP), both of which are based on the attenuated HEP-Flury strain and express monomeric red fluorescent protein (mRFP) as a transgene. rHEP5.0-ΔG-mRFP showed lower cytotoxicity than rHEP5.0-CVSG-mRFP, and within 16 days of infection we found no change in the basic electrophysiological properties of neurons infected with the rHEP5.0-ΔG-mRFP. The mRFP expression level of rHEP5.0-ΔG-mRFP was much higher than that of rHEP5.0-CVSG-mRFP, and 3 days after infection the retrogradely infected neurons were clearly visualized by the expressed fluorescent protein without any staining. This may be due to the low cytotoxicity and/or the presumed change in the polymerase gene (L) expression level of the G-deleted RV vector. Although the mechanisms remains to be clarified, the results of this study indicate that deletion of the G gene greatly improves the usability of the RV vector for studying the organization and function of the neural circuits by decreasing the cytotoxicity and increasing the transgene expression level. PMID:24244660

  10. Splenic Stromal Cells from Aged Mice Produce Higher Levels of IL-6 Compared to Young Mice

    PubMed Central

    Park, Jihyun; Miyakawa, Takuya; Shiokawa, Aya; Nakajima-Adachi, Haruyo; Hachimura, Satoshi

    2014-01-01

    Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly. PMID:24729663

  11. Diabetes is Associated with Higher Trimethylamine N-oxide Plasma Levels.

    PubMed

    Dambrova, M; Latkovskis, G; Kuka, J; Strele, I; Konrade, I; Grinberga, S; Hartmane, D; Pugovics, O; Erglis, A; Liepinsh, E

    2016-04-01

    Recent studies have revealed strong associations between systemic trimethylamine N-oxide (TMAO) levels, atherosclerosis and cardiovascular risk. In addition, plasma L-carnitine levels in patients with high TMAO concentrations predicted an increased risk for cardiovascular disease and incident major adverse cardiac events. The aim of the present study was to investigate the relation between TMAO and L-carnitine plasma levels and diabetes. Blood plasma samples were collected from 12 and 20 weeks old db/db mice and patients undergoing percutaneous coronary intervention. Diabetic compared to non-diabetic db/L mice presented 10-fold higher TMAO, but lower L-carnitine plasma concentrations at 12 weeks of age. After 8 weeks of observation, diabetic db/db mice had significantly increased body weight, insulin resistance and TMAO concentration in comparison to non-diabetic control. In 191 patients undergoing percutaneous coronary intervention the median (interquartile range) plasma concentration of TMAO was 1.8 (1.2-2.6) µmol/L. Analysis of the samples showed a bivariate association of TMAO level with age, total cholesterol and L-carnitine. The multivariate linear regression analysis revealed that, in addition to L-carnitine as the strongest predictor of log transformed TMAO (p<0.001), the parameters of age, diabetes status and body mass index (BMI) were independently associated with increased log transformed TMAO levels (p<0.01).Our data provide evidence that age, diabetes and BMI are associated with higher TMAO levels independently of L-carnitine. These data support the hypothesis of TMAO as a cardiovascular risk marker and warrant further investigation of TMAO for diabetes research applications. PMID:27123785

  12. 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

  13. 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

  14. Relationships between cell cycle regulator gene copy numbers and protein expression levels in Schizosaccharomyces pombe.

    PubMed

    Chino, Ayako; Makanae, Koji; Moriya, Hisao

    2013-01-01

    We previously determined the copy number limits of overexpression for cell division cycle (cdc) regulatory genes in the fission yeast Schizosaccharomyces pombe using the "genetic tug-of-war" (gTOW) method. In this study, we measured the levels of tandem affinity purification (TAP)-tagged target proteins when their copy numbers are increased in gTOW. Twenty analyzed genes showed roughly linear correlations between increased protein levels and gene copy numbers, which suggested a general lack of compensation for gene dosage in S. pombe. Cdc16 and Sid2 protein levels but not their mRNA levels were much lower than that expected by their copy numbers, which suggested the existence of a post-transcriptional down regulation of these genes. The cyclin Cig1 protein level and its mRNA level were much higher than that expected by its copy numbers, which suggested a positive feedback mechanism for its expression. A higher Cdc10 protein level and its mRNA level, probably due to cloning its gene into a plasmid, indicated that Cdc10 regulation was more robust than that previously predicted. PMID:24019917

  15. Effect of temperature on oxidative stress, antioxidant levels and uncoupling protein expression in striped hamsters.

    PubMed

    Zhou, Si-Si; Cao, Li-Li; Xu, Wei-Dong; Cao, Jing; Zhao, Zhi-Jun

    2015-11-01

    According to the rate of living-free radical hypothesis, higher metabolic rates should increase reactive oxygen species (ROS) production. However, the "uncoupling to survive" hypothesis postulates that uncoupling proteins (UCPs) can decrease ROS production by lowering the potential of the inner mitochondrial membrane, in which case the correlation between metabolic rate and ROS levels would be a negative rather than positive. In this study, we examined energy intake, oxidative stress levels, antioxidant activity and the expression of UCPs in brown adipose tissue (BAT), and in the liver, heart, skeletal muscle and brain, of striped hamsters (Cricetulus barabensis) acclimated to either 5 °C or 32.5 °C. The energy intake of hamsters acclimated to 5 °C increased by 70.7%, whereas the energy intake of hamsters acclimated to 32.5 °C decreased by 31.3%, relative to hamsters kept at room temperature (21 °C) (P<0.05). Malonadialdehyde (MDA) levels, total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity in BAT significantly decreased in 5 °C group, but increased in 32.5 °C group, relative to the 21 °C group. Neither ROS levels (i.e. H2O2 levels), nor antioxidants in skeletal muscle, liver, heart or brain tissue, were affected by temperature. UCP1 expression in BAT was significantly up-regulated in 5 °C group, but down-regulated in 32.5 °C group, relative to the 21 °C group. UCP3 expression of skeletal muscle was also up-regulated significantly in hamsters acclimated to 5 °C. These results suggest that the relationship between ROS levels and metabolic rate was negative, rather than positive. UCP1 expression in BAT may have played a role in lowering ROS levels. PMID:26244518

  16. An empirical review: Characteristics of plant microsatellite markers that confer higher levels of genetic variation1

    PubMed Central

    Merritt, Benjamin J.; Culley, Theresa M.; Avanesyan, Alina; Stokes, Richard; Brzyski, Jessica

    2015-01-01

    During microsatellite marker development, researchers must choose from a pool of possible primer pairs to further test in their species of interest. In many cases, the goal is maximizing detectable levels of genetic variation. To guide researchers and determine which markers are associated with higher levels of genetic variation, we conducted a literature review based on 6782 genomic microsatellite markers published from 1997–2012. We examined relationships between heterozygosity (He or Ho) or allele number (A) with the following marker characteristics: repeat type, motif length, motif region, repeat frequency, and microsatellite size. Variation across taxonomic groups was also analyzed. There were significant differences between imperfect and perfect repeat types in A and He. Dinucleotide motifs exhibited significantly higher A, He, and Ho than most other motifs. Repeat frequency and motif region were positively correlated with A, He, and Ho, but correlations with microsatellite size were minimal. Higher taxonomic groups were disproportionately represented in the literature and showed little consistency. In conclusion, researchers should carefully consider marker characteristics so they can be tailored to the desired application. If researchers aim to target high genetic variation, dinucleotide motif lengths with large repeat frequencies may be best. PMID:26312192

  17. Association Between Dental Student-Developed Exam Questions and Learning at Higher Cognitive Levels.

    PubMed

    Gonzalez-Cabezas, Carlos; Anderson, Olivia S; Wright, Mary C; Fontana, Margherita

    2015-11-01

    New dental accreditation standards emphasize that graduates must be competent in the use of critical thinking (a high cognitive-level skill). Despite this new standard, most written assessments in dental school courses are still based on low cognitive-level questions. The aim of this study was to determine if an exercise that allows students to collaboratively write exam questions would help cultivate higher cognitive levels of learning. To evaluate this exercise at one U.S. dental school, the cognitive level (according to Bloom's taxonomy) of multiple-choice exam questions and students' scores across two cohorts in a cariology course were compared. This evaluation took place using a control group in which questions were instructor-generated and an intervention group in which students worked in groups to develop questions. All students in one first-year class participated in the intervention group (n=104); all students in the first-year class two years earlier served as the control group (n=106). Among students in the intervention group, the response rate to a post-intervention survey measuring students' attitudes about the experience was 70% (N=73). The results showed that the students generating their own assessments developed higher cognitive-level exam questions than the instructor-generated assessments. The intervention group (with student-generated assessments) also performed as well or better on tests compared to the control group (with instructor-generated assessments). In the intervention group survey, the vast majority of students agreed that the exercise was helpful for their overall learning experience, but working in teams was said to be the least valuable component of the activity for their learning. This study suggests that student-driven, collaborative assessments can be an important tool for building critical thinking skills in dental classrooms and that it may be worthwhile to expand this type of exercise into other courses. PMID:26522634

  18. The progestin levonorgestrel disrupts gonadotropin expression and sex steroid levels in pubertal roach (Rutilus rutilus).

    PubMed

    Kroupova, H K; Trubiroha, A; Lorenz, C; Contardo-Jara, V; Lutz, I; Grabic, R; Kocour, M; Kloas, W

    2014-09-01

    The aim of the present study was to investigate the effects of the synthetic progestin levonorgestrel (LNG) on the reproductive endocrine system of a teleost fish, the roach (Rutilus rutilus). Pubertal roach were exposed for 28 days in a flow-through system to four concentrations of LNG (3, 31, 312, and 3124 ng/l). Both males and females treated with 3124 ng/l LNG exhibited the upregulated levels of vitellogenin and oestrogen receptor 1 mRNA in the liver. At the same concentration, LNG caused a significant upregulation of the mRNA expression of the gene encoding luteinising hormone β-subunit (lhβ) and the suppression of the mRNA expression of the gene encoding follicle-stimulating hormone β-subunit (fshβ) in the pituitary of both male and female roach. A lower LNG concentration (312 ng/l) suppressed mRNA expression of fshβ in males only. Females treated with 3124 ng/l LNG exhibited significantly lower plasma 11-ketotestosterone (11-KT) and oestradiol (E2) concentrations, whereas their testosterone (T) level was higher compared with the control. Females exposed to 312 ng/l LNG presented significantly lower plasma E2 concentrations. Males exposed to ≥31 ng/l LNG exhibited significantly reduced 11-KT levels. As determined through a histological analysis, the ovaries of females were not affected by LNG exposure, whereas the testes of males exposed to 31 and 312 ng/l LNG exhibited a significantly higher percentage of spermatogonia B compared with the control. The results of the present study demonstrate that LNG disrupts the reproductive system of pubertal roach by affecting the pituitary gonadotropin expression and the sex steroid levels. This disruption was determined to occur in males after exposure to an environmentally relevant concentration (31 ng/l). Moreover, the highest tested concentration of LNG (3124 ng/l) exerted an oestrogenic effect on fish of both sexes. PMID:24893273

  19. Cytomegalovirus DNA in Semen and Blood Is Associated With Higher Levels of Proviral HIV DNA

    PubMed Central

    Gianella, Sara; Anderson, Christy M.; Vargas, Milenka V.; Richman, Douglas D.; Little, Susan J.; Morris, Sheldon R.; Smith, Davey M.

    2013-01-01

    Over three-fourths of human immunodeficiency virus (HIV)–infected men who have sex with men (MSM) have at least one herpesvirus detected in their semen, and cytomegalovirus (CMV) is the most prevalent. The presence of CMV is associated with higher T-cell immune activation and with HIV disease progression in treated and untreated individuals. In this study of 113 antiretroviral (ART)–naive HIV-infected MSM, we found that CMV replication in blood and semen was associated with higher levels of HIV DNA in peripheral blood mononuclear cells. These observations suggest that interventions aimed to reduce CMV replication and, thus, systemic immune activation could decrease the size of the latent HIV reservoir. PMID:23275608

  20. 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

  1. Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)

    PubMed Central

    2013-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD. Methods Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson’s, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies. Results The plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341). No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group of patients and controls showed a statistically significant difference (p < 0.001) for BMI and HOMA_IR, similarly to HDL cholesterol levels (p < 0,006), AST, ALT, γGT, AP and triglycerides levels (p < 0.001). A negative correlation was observed between levels of vitamin B12 and Hcy concentration (p = 0.005). Conclusion Our results indicate that plasma Hcy was higher in NAFLD than controls. The MTHFR C677T and A1298C polymorphisms did not differ significantly between groups, despite the 677TT homozygous frequency was higher in patients (17

  2. Constraints on Tree-Level Higher Order Gravitational Couplings in Superstring Theory

    NASA Astrophysics Data System (ADS)

    Stieberger, Stephan

    2011-03-01

    We consider the scattering amplitudes of five and six gravitons at tree level in superstring theory. Their power series expansions in the Regge slope α' are analyzed through the order α'8 showing some interesting constraints on higher order gravitational couplings in the effective superstring action such as the absence of R5 terms. Furthermore, some transcendentality constraints on the coefficients of the nonvanishing couplings are observed: the absence of zeta values of even weight through the order α'8 like the absence of ζ(2)ζ(3)R6 terms. Our analysis is valid for any superstring background in any space-time dimension, which allows for a conformal field theory description.

  3. Organic foods contain higher levels of certain nutrients, lower levels of pesticides, and may provide health benefits for the consumer.

    PubMed

    Crinnion, Walter J

    2010-04-01

    The multi-billion dollar organic food industry is fueled by consumer perception that organic food is healthier (greater nutritional value and fewer toxic chemicals). Studies of the nutrient content in organic foods vary in results due to differences in the ground cover and maturity of the organic farming operation. Nutrient content also varies from farmer to farmer and year to year. However, reviews of multiple studies show that organic varieties do provide significantly greater levels of vitamin C, iron, magnesium, and phosphorus than non-organic varieties of the same foods. While being higher in these nutrients, they are also significantly lower in nitrates and pesticide residues. In addition, with the exception of wheat, oats, and wine, organic foods typically provide greater levels of a number of important antioxidant phytochemicals (anthocyanins, flavonoids, and carotenoids). Although in vitro studies of organic fruits and vegetables consistently demonstrate that organic foods have greater antioxidant activity, are more potent suppressors of the mutagenic action of toxic compounds, and inhibit the proliferation of certain cancer cell lines, in vivo studies of antioxidant activity in humans have failed to demonstrate additional benefit. Clear health benefits from consuming organic dairy products have been demonstrated in regard to allergic dermatitis. PMID:20359265

  4. 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

  5. Naringin promotes differentiation of bone marrow stem cells into osteoblasts by upregulating the expression levels of microRNA-20a and downregulating the expression levels of PPARγ.

    PubMed

    Fan, Jifeng; Li, Jie; Fan, Qinbo

    2015-09-01

    Naringin is a dihydrotestosterone flavonoid compound that significantly inhibits bone loss, improves bone density, and enhances biomechanical anti‑compression performance. Previous studies have demonstrated that naringin improves the activity levels of osteocalcin (OC) and alkaline phosphatase (ALP) in MC3T3‑E1 osteoblast precursor cells. The present study investigated the effects of naringin on osteoblastic differentiation and inhibition of adipocyte formation in bone marrow stem cells (BMSCs). The levels of osteogenesis were modulated via upregulation of the expression levels of microRNA (miR)‑20a, and downregulation of the expression levels of peroxisome proliferator‑activated receptor γ (PPARγ). The results indicated that naringin significantly enhanced BMSC proliferation in a dose‑dependent manner. In addition, naringin significantly increased the mRNA expression levels of OC, ALP, and collagen type I. Furthermore, naringin decreased the protein expression levels of PPARγ, and increased the expression levels of miR‑20a in the BMSCs. These results suggested that miR‑20a may regulate the expression of PPARγ in BMSCs. To our knowledge, this is the first study to report naringin‑induced osteogenesis via upregulation of the expression levels of miR‑20a, and downregulation of the expression levels of PPARγ. These results indicated the important role of naringin in BMSC differentiation. PMID:26126997

  6. The antioxidant level of Alaska’s wild berries: high, higher and highest

    PubMed Central

    Dinstel, Roxie Rodgers; Cascio, Julie; Koukel, Sonja

    2013-01-01

    Background In the last few years, antioxidants have become the stars of the nutritional world. Antioxidants are important in terms of their ability to protect against oxidative cell damage that can lead to conditions, such as Alzheimer’s disease, cancer and heart disease – conditions also linked with chronic inflammation. The antioxidant and anti-inflammatory effects of Alaska’s wild berries may have the potential to help prevent these diseases. Objective To discover the antioxidant levels of Alaska wild berries and the ways these antioxidant levels translate when preservation methods are applied to the berry. Design This research centred on both the raw berries and products made from the berries. In the first year, a variety of wild berries were tested to discover their oxygen radical absorption capacity (ORAC) in the raw berries. The second level of the research project processed 4 different berries – blueberries, lingonberries, salmonberries, highbush cranberries – into 8 or 9 products made from these berries. The products were tested for both ORAC as well as specific antioxidants. Results The Alaska wild berries collected and tested in the first experiment ranged from 3 to 5 times higher in ORAC value than cultivated berries from the lower 48 states. For instance, cultivated blueberries have an ORAC scale of 30. Alaska wild dwarf blueberries measure 85. This is also higher than lower 48 wild blueberries, which had a score of 61. All of the Alaskan berries tested have a level of antioxidant considered nutritionally valuable, ranging from 19 for watermelon berries to 206 for lingonberries on the ORAC scale. With the processed products made from 4 Alaska wild berries, one of the unexpected outcomes of the research was that the berries continued to have levels of antioxidants considered high, despite the effects of commonly used heat-processing techniques. When berries were dehydrated, per gram ORAC values increased. Conclusion Alaska wild berries have

  7. Higher Alu Methylation Levels in Catch-Up Growth in Twenty-Year-Old Offsprings

    PubMed Central

    Rerkasem, Kittipan; Rattanatanyong, Prakasit; Rerkasem, Amaraporn; Wongthanee, Antika; Rungruengthanakit, Kittipong; Mangklabruks, Ampica; Mutirangura, Apiwat

    2015-01-01

    Alu elements and long interspersed element-1 (LINE-1 or L1) are two major human intersperse repetitive sequences. Lower Alu methylation, but not LINE-1, has been observed in blood cells of people in old age, and in menopausal women having lower bone mass and osteoporosis. Nevertheless, Alu methylation levels also vary among young individuals. Here, we explored phenotypes at birth that are associated with Alu methylation levels in young people. In 2010, 249 twenty-years-old volunteers whose mothers had participated in a study association between birth weight (BW) and nutrition during pregnancy in 1990, were invited to take part in our present study. In this study, the LINE-1 and Alu methylation levels and patterns were measured in peripheral mononuclear cells and correlated with various nutritional parameters during intrauterine and postnatal period of offspring. This included the amount of maternal intake during pregnancy, the mother’s weight gain during pregnancy, birth weight, birth length, and the rate of weight gain in the first year of life. Catch-up growth (CUG) was defined when weight during the first year was >0.67 of the standard score, according to WHO data. No association with LINE-1 methylation was identified. The mean level of Alu methylation in the CUG group was significantly higher than those non-CUG (39.61% and 33.66 % respectively, P < 0.0001). The positive correlation between the history of CUG in the first year and higher Alu methylation indicates the role of Alu methylation, not only in aging cells, but also in the human growth process. Moreover, here is the first study that demonstrated the association between a phenotype during the newborn period and intersperse repetitive sequences methylation during young adulthood. PMID:25807557

  8. Higher blood glucose level associated with body mass index and gut microbiota in elderly people

    PubMed Central

    Sepp, Epp; Kolk, Helgi; Lõivukene, Krista; Mikelsaar, Marika

    2014-01-01

    Background Some dominant bacterial divisions of the intestines have been linked to metabolic diseases such as overweight and diabetes. Objective A pilot study aimed to evaluate the relations between the culturable intestinal bacteria with body mass index (BMI) and some principal cellular and metabolic markers of blood in people older than 65. Design Altogether 38 generally healthy elderly people were recruited: ambulatory (n=19) and orthopedic surgery (n=19). Questionnaires on general health, anthropometric measurements, routine clinical and laboratory data, and quantitative composition of cultivable gut microbiota were performed. Results Blood glucose level was positively correlated with BMI (r=0.402; p=0.014). Higher blood glucose level had negative correlation with relative share of intestinal anaerobic bacteria such as bacteroides (r=−0.434; p=0.0076) and gram-positive anaerobic cocci (r=−0.364; p=0.027). In contrast, the relative share of bifidobacteria (r=0.383; p=0.019) and staphylococci (r=0.433; p=0.008) was positively correlated to blood glucose level. In elderly people, a higher blood glucose concentration was predicted by the reduction of the anaerobes’ proportion (adj. sex, age, and BMI R2=0.192, p=0.028) and that of Bacteroides sp. (adj. R2=0.309, p=0.016). Conclusion A tight interplay between increased BMI, level of blood glucose, and the reduced proportion of cultivable bacteroides is taking place in the gut microbiota of elderly people. PMID:24936169

  9. Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis.

    PubMed

    Pontes, Thaís Brilhante; Chen, Elizabeth Suchi; Gigek, Carolina Oliveira; Calcagno, Danielle Queiroz; Wisnieski, Fernanda; Leal, Mariana Ferreira; Demachki, Samia; Assumpção, Paulo Pimentel; Artigiani, Ricardo; Lourenço, Laércio Gomes; Burbano, Rommel Rodriguez; Arruda Cardoso Smith, Marília

    2014-04-01

    Aberrant methylation has been reported in several neoplasias, including gastric cancer. The methyl-CpG-binding domain (MBD) family proteins have been implicated in the chromatin remodeling process, leading to the modulation of gene expression. To evaluate the role of MBD2 and MBD3 in gastric carcinogenesis and the possible association with clinicopathological characteristics, we assessed the mRNA levels and promoter methylation patterns in gastric tissues. In this study, MBD2 and MBD3 mRNA levels were determined by RT-qPCR in 28 neoplastic and adjacent nonneoplastic and 27 gastritis and non-gastritis samples. The promoter methylation status was determined by bisulfite sequencing, and we found reduced MBD2 and MBD3 levels in the neoplastic samples compared with the other groups. Moreover, a strong correlation between the MBD2 and MBD3 expression levels was observed in each set of paired samples. Our data also showed that the neoplastic tissues exhibited higher MBD2 promoter methylation than the other groups. Interestingly, the non-gastritis group was the only one with positive methylation in the MBD3 promoter region. Furthermore, a weak correlation between gene expression and methylation was observed. Therefore, our data suggest that DNA methylation plays a minor role in the regulation of MBD2 and MBD3 expression, and the presence of methylation at CpGs that interact with transcription factor complexes might also be involved in the modulation of these genes. Moreover, reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis, and thus, further investigations about these genes should be conducted for a better understanding of the role of abnormal methylation involved in this neoplasia. PMID:24338710

  10. Oxidative Damage in Lymphocytes of Copper Smelter Workers Correlated to Higher Levels of Excreted Arsenic

    PubMed Central

    Escobar, Jorge; Varela-Nallar, Lorena; Coddou, Claudio; Nelson, Pablo; Maisey, Kevin; Valdés, Daniel; Aspee, Alexis; Espinosa, Victoria; Rozas, Carlos; Montoya, Margarita; Mandiola, Cristian; Rodríguez, Felipe E.; Acuña-Castillo, Claudio; Escobar, Alejandro; Fernández, Ricardo; Diaz, Hernán; Sandoval, Mario; Imarai, Mónica; Rios, Miguel

    2010-01-01

    Arsenic has been associated with multiple harmful effects at the cellular level. Indirectly these defects could be related to impairment of the integrity of the immune system, in particular in lymphoid population. To characterize the effect of Arsenic on redox status on this population, copper smelter workers and arsenic unexposed donors were recruited for this study. We analyzed urine samples and lymphocyte enriched fractions from donors to determinate arsenic levels and lymphocyte proliferation. Moreover, we studied the presence of oxidative markers MDA, vitamin E and SOD activity in donor plasma. Here we demonstrated that in human beings exposed to high arsenic concentrations, lymphocyte MDA and arsenic urinary levels showed a positive correlation with SOD activity, and a negative correlation with vitamin E serum levels. Strikingly, lymphocytes from the arsenic exposed population respond to a polyclonal stimulator, phytohemaglutinin, with higher rates of thymidine incorporation than lymphocytes of a control population. As well, similar in vitro responses to arsenic were observed using a T cell line. Our results suggest that chronic human exposure to arsenic induces oxidative damage in lymphocytes and could be considered more relevant than evaluation of T cell surveillance. PMID:21253489

  11. Higher-level phylogeny of paraneopteran insects inferred from mitochondrial genome sequences

    PubMed Central

    Li, Hu; Shao, Renfu; Song, Nan; Song, Fan; Jiang, Pei; Li, Zhihong; Cai, Wanzhi

    2015-01-01

    Mitochondrial (mt) genome data have been proven to be informative for animal phylogenetic studies but may also suffer from systematic errors, due to the effects of accelerated substitution rate and compositional heterogeneity. We analyzed the mt genomes of 25 insect species from the four paraneopteran orders, aiming to better understand how accelerated substitution rate and compositional heterogeneity affect the inferences of the higher-level phylogeny of this diverse group of hemimetabolous insects. We found substantial heterogeneity in base composition and contrasting rates in nucleotide substitution among these paraneopteran insects, which complicate the inference of higher-level phylogeny. The phylogenies inferred with concatenated sequences of mt genes using maximum likelihood and Bayesian methods and homogeneous models failed to recover Psocodea and Hemiptera as monophyletic groups but grouped, instead, the taxa that had accelerated substitution rates together, including Sternorrhyncha (a suborder of Hemiptera), Thysanoptera, Phthiraptera and Liposcelididae (a family of Psocoptera). Bayesian inference with nucleotide sequences and heterogeneous models (CAT and CAT + GTR), however, recovered Psocodea, Thysanoptera and Hemiptera each as a monophyletic group. Within Psocodea, Liposcelididae is more closely related to Phthiraptera than to other species of Psocoptera. Furthermore, Thysanoptera was recovered as the sister group to Hemiptera. PMID:25704094

  12. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis

    PubMed Central

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  13. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis.

    PubMed

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  14. Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo

    PubMed Central

    Salin, Karine; Auer, Sonya K.; Rudolf, Agata M.; Anderson, Graeme J.; Cairns, Andrew G.; Mullen, William; Hartley, Richard C.; Selman, Colin; Metcalfe, Neil B.

    2015-01-01

    There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2 in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. PMID:26382073

  15. Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo.

    PubMed

    Salin, Karine; Auer, Sonya K; Rudolf, Agata M; Anderson, Graeme J; Cairns, Andrew G; Mullen, William; Hartley, Richard C; Selman, Colin; Metcalfe, Neil B

    2015-09-01

    There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2 in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. PMID:26382073

  16. Lower prevalence but similar fitness in a parasitic fungus at higher radiation levels near Chernobyl.

    PubMed

    Aguileta, Gabriela; Badouin, Helene; Hood, Michael E; Møller, Anders P; Le Prieur, Stephanie; Snirc, Alodie; Siguenza, Sophie; Mousseau, Timothy A; Shykoff, Jacqui A; Cuomo, Christina A; Giraud, Tatiana

    2016-07-01

    Nuclear disasters at Chernobyl and Fukushima provide examples of effects of acute ionizing radiation on mutations that can affect the fitness and distribution of species. Here, we investigated the prevalence of Microbotryum lychnidis-dioicae, a pollinator-transmitted fungal pathogen of plants causing anther-smut disease in Chernobyl, its viability, fertility and karyotype variation, and the accumulation of nonsynonymous mutations in its genome. We collected diseased flowers of Silene latifolia from locations ranging by more than two orders of magnitude in background radiation, from 0.05 to 21.03 μGy/h. Disease prevalence decreased significantly with increasing radiation level, possibly due to lower pollinator abundance and altered pollinator behaviour. Viability and fertility, measured as the budding rate of haploid sporidia following meiosis from the diploid teliospores, did not vary with increasing radiation levels and neither did karyotype overall structure and level of chromosomal size heterozygosity. We sequenced the genomes of twelve samples from Chernobyl and of four samples collected from uncontaminated areas and analysed alignments of 6068 predicted genes, corresponding to 1.04 × 10(7)  base pairs. We found no dose-dependent differences in substitution rates (neither dN, dS, nor dN/dS). Thus, we found no significant evidence of increased deleterious mutation rates at higher levels of background radiation in this plant pathogen. We even found lower levels of nonsynonymous substitution rates in contaminated areas compared to control regions, suggesting that purifying selection was stronger in contaminated than uncontaminated areas. We briefly discuss the possibilities for a mechanistic basis of radio resistance in this nonmelanized fungus. PMID:27136128

  17. 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

  18. Transgene Expression Levels Determine the Immunogenicity of Transduced Hematopoietic Grafts in Partially Myeloablated Mice

    PubMed Central

    Eixarch, Herena; Gómez, Alba; Kádár, Elisabeth; George, Mónica; Martínez, Nuria; Espejo, Carmen; Pétriz, Jordi; Gimeno, Ramon; Barquinero, Jordi

    2009-01-01

    We investigated whether transgene expression levels influence the immunogenicity of transduced hematopoietic grafts upon transplantation into partially myeloablated mice. To this aim, bone marrow cells (BMCs) transduced with retroviral vectors driving green fluorescent protein (GFP) expression either at high (high-EGFP) or low levels (low-EGFP) were transplanted into congenic recipients conditioned with sublethal doses of total body irradiation (TBI) or busulfan. Virtually all recipients showed evidence of donor engraftment 4 weeks after transplantation. However, as opposed to recipients receiving low-EGFP transduced grafts, the risk of rejecting the EGFP+ cells by 30 days after transplantation was significantly higher in mice conditioned with busulfan and receiving high-EGFP transduced grafts. Anti-EGFP cellular immune responses were demonstrated in high-EGFP-treated mice conditioned with busulfan by interferon-γ (IFN-γ), enzyme-linked immunospot assay (ELISPOT), and cytotoxic T lymphocyte (CTL) assays, in contrast to that observed in mice transplanted with low-EGFP BMC. These results show for the first time that transgene expression levels can be critical for the immunogenicity of gene-modified hematopoietic grafts, especially in immunocompetent or in partially immunosuppressed recipients. These results have profound implications in vector choice and in the design of gene therapy (GT) protocols. PMID:19707185

  19. Bis-(2-ethylhexyl) Phthalate Increases Insulin Expression and Lipid Levels in Drosophila melanogaster.

    PubMed

    Cao, Hao; Wiemerslage, Lyle; Marttila, Petra S K; Williams, Michael J; Schiöth, Helgi B

    2016-09-01

    Bis-(2-ethylhexyl) phthalate (DEHP) is one of the most widely used plasticizers, and human beings are exposed to DEHP via polyvinyl chloride (PVC) materials, medical equipment and even drinking water. While DEHP has been implicated to influence metabolism and endocrine functions, important questions remain about the molecular mechanisms of these effects. We employed the model organism Drosophila melanogaster and examined physiological, molecular and behavioural effects from DEHP-contaminated food. We found that DEHP, at levels comparable to human exposure, made male flies more resistant to starvation and increased lipid levels, while decreasing circulating carbohydrates. Moreover, DEHP-fed male flies had higher expression levels of an insulin-like peptide known to regulate metabolism, as well as the insulin receptor. Our results suggest that long-term DEHP feeding may induce diabetes-like dysfunctions. These findings provide a molecular background of how DEHP may have detrimental effects on metabolic functions. PMID:27009472

  20. CTLA-4 in mesothelioma patients: tissue expression, body fluid levels and possible relevance as a prognostic factor.

    PubMed

    Roncella, Silvio; Laurent, Stefania; Fontana, Vincenzo; Ferro, Paola; Franceschini, Maria Cristiana; Salvi, Sandra; Varesano, Serena; Boccardo, Simona; Vigani, Antonella; Morabito, Anna; Canessa, Pier Aldo; Giannoni, Ugo; Rosenberg, Ilan; Valentino, Alessandro; Fedeli, Franco; Merlo, Domenico Franco; Ceppi, Marcello; Riggio, Salvatore; Romani, Massimo; Saverino, Daniele; Poggi, Alessandro; Pistillo, Maria Pia

    2016-08-01

    CTLA-4 function as a negative regulator of T cell-mediated immune response is well established, whereas much less is known about the immunoregulatory role of its soluble isoform (sCTLA-4). No data are available on CTLA-4 expression and prognostic impact in malignant pleural mesothelioma (MPM). We investigated, by immunohistochemistry, CTLA-4 expression in tumor tissues and, by ELISA, sCTLA-4 levels in sera and matched pleural effusions from 45 MPM patients. Prognostic effect of CTLA-4 expression on overall survival (OS) was assessed through Cox regression and prognostic significance expressed as death rate ratio (HR). We found that 56.0 % of MPM tissues expressed CTLA-4 with variable intensity and percentage of positive cells estimated by the immunoreactive score. sCTLA-4 levels were significantly higher in sera (S-sCTLA-4) than in pleural effusions (PE-sCTLA-4) (geometric mean ratio = 2.70, P value = 0.020). CTLA-4 expression at the tissue level was higher in the epithelioid histological subtype than in the sarcomatoid, whereas at the serum level, it was higher in the sarcomatoid subtype. A homogeneous favorable prognostic effect was found for CTLA-4 overexpression in tissue, serum and pleural effusion. Interestingly, only the PE-sCTLA-4 was found to be a statistically significant positive prognostic factor (HR = 0.37, 95 % CI = 0.18-0.77, P value = 0.007). Indeed, PE-sCTLA-4 correlated with CTLA-4 expression in tissues, whereas this latter expression showed a weak association with OS. To confirm our findings, further experimental evidences obtained from a larger cohort of MPM patients are required. However, our results would indicate a positive correlation of PE-sCTLA-4 levels and OS in MPM patients. PMID:27207606

  1. Higher minor hemoglobin A2 levels in multiple sclerosis patients correlate with lesser disease severity

    PubMed Central

    Ozcan, Muhammed Emin; Ince, Bahri; Karadeli, Hasan Huseyin; Gedikbasi, Asuman; Asil, Talip; Altinoz, Meric A

    2016-01-01

    Objective To define whether minor adult hemoglobin A2 (HbA2, α2δ2) exerts any protective activity in multiple sclerosis (MS). Methods HbA2 levels were measured in 146 MS patients with high performance liquid chromatography and association with MS Severity Scores (MSSS) were determined. HbA2 associations with blood count parameters were also studied using blood counts evaluated on the same day of high performance liquid chromatography sampling. Routine biochemical parameters were also determined to rule out elusively influential factors, such as anemia and thyroid disorders. Results HbA2 levels negatively correlated with MSSS (Spearman correlation, R: −0.186, P=0.025). Exclusion of confounding factors with a generalized linear model revealed an even stronger negative correlation between HbA2 and MSSS (P<0.001). HbA2 positively correlated with red blood cells (RBCs) (R=0.350, P<0.001) and in turn, RBCs negatively correlated with MSSS (R=−0.180, P=0.031). Average HbA2 levels were highest among patients treated with interferon β1a. Conclusion RBC fragility is increased in MS, and recent data suggest that circulating free Hb contributes to neural injury in MS. HbA2 and its oxidative denaturation product hemichrome A2 enhance RBC membrane stability to a greater extent than do major HbA or hemichrome A. Reductions in ischemic cerebrovascular vascular events are reported in β-thalassemia carriers and HbA2 levels are considerably higher in this population. Episodic declines of cerebral blood flow were shown in bipolar disorder, and we have recently shown a protective role of HbA2 against postpartum episodes in females with bipolar disorder. HbA2’s erythroprotective functions may reduce free Hb and long-term neural injury in MS. PMID:27578976

  2. Persistent Smoking after a Diagnosis of Lung Cancer is Associated with Higher Reported Pain Levels

    PubMed Central

    Daniel, Marcella; Keefe, Francis J.; Lyna, Pauline; Peterson, Bercedis; Garst, Jennifer; Kelley, Mike; Bepler, Gerald; Bastian, Lori A.

    2009-01-01

    The purpose of this study is to evaluate the impact of smoking status after a diagnosis of lung cancer on reported pain levels. We conducted a telephone survey of patients with lung cancer identified from four participating sites between September 2004 and July 2006. Patients were asked to rate their usual pain level over the past week on a 0-10 rating scale on which 0 was ‘no pain’ and 10 ‘pain as bad as you can imagine’. We operationally defined persistent smokers as patients who reported continuing to smoke after their lung cancer diagnosis. A logistic regression analyses was used to test the hypothesis that persistent smokers report higher usual pain levels than non-smokers. Overall, 893 patients completed the survey. The majority (76%) was found to have advanced cancer (Stages IIIb and IV). The mean age was 63 (SD=10). Seventeen percent of the patients studied were categorized as persistent smokers. The mean pain score for the study sample was 3.1 (sd=2.7) and 41% reported moderate (4-6) or severe pain (7-10). A greater proportion of persistent smokers reported moderate or severe pain than non-smokers or former smokers (p<.001). Logistic regression analysis revealed that, smoking status was associated with the usual pain even after adjusting for age, perceived health status and other lung cancer symptoms such as dyspnea, fatigue and trouble eating. In conclusion, patients who continue to smoke after a diagnosis of lung cancer report higher levels of usual pain than non-smokers or former smokers. More research is needed to understand the mechanisms that relate nicotine intake to pain and disease progression in late-stage lung cancer. Perspective This article examines the relationship between pain and persistent smoking in patients with lung cancer. Although more research is needed to understand the mechanisms that relate nicotine intake to pain and disease progression, physicians can promote smoking cessation in patients with lung cancer to improve

  3. Leveraging People-Related Maturity Issues for Achieving Higher Maturity and Capability Levels

    NASA Astrophysics Data System (ADS)

    Buglione, Luigi

    During the past 20 years Maturity Models (MM) become a buzzword in the ICT world. Since the initial Crosby's idea in 1979, plenty of models have been created in the Software & Systems Engineering domains, addressing various perspectives. By analyzing the content of the Process Reference Models (PRM) in many of them, it can be noticed that people-related issues have little weight in the appraisals of the capabilities of organizations while in practice they are considered as significant contributors in traditional process and organizational performance appraisals, as stressed instead in well-known Performance Management models such as MBQA, EFQM and BSC. This paper proposes some ways for leveraging people-related maturity issues merging HR practices from several types of maturity models into the organizational Business Process Model (BPM) in order to achieve higher organizational maturity and capability levels.

  4. Constraints on Tree-Level Higher Order Gravitational Couplings in Superstring Theory

    SciTech Connect

    Stieberger, Stephan

    2011-03-18

    We consider the scattering amplitudes of five and six gravitons at tree level in superstring theory. Their power series expansions in the Regge slope {alpha}{sup '} are analyzed through the order {alpha}{sup '8} showing some interesting constraints on higher order gravitational couplings in the effective superstring action such as the absence of R{sup 5} terms. Furthermore, some transcendentality constraints on the coefficients of the nonvanishing couplings are observed: the absence of zeta values of even weight through the order {alpha}{sup '8} like the absence of {zeta}(2){zeta}(3)R{sup 6} terms. Our analysis is valid for any superstring background in any space-time dimension, which allows for a conformal field theory description.

  5. Constraints on tree-level higher order gravitational couplings in superstring theory.

    PubMed

    Stieberger, Stephan

    2011-03-18

    We consider the scattering amplitudes of five and six gravitons at tree level in superstring theory. Their power series expansions in the Regge slope α' are analyzed through the order α'(8) showing some interesting constraints on higher order gravitational couplings in the effective superstring action such as the absence of R(5) terms. Furthermore, some transcendentality constraints on the coefficients of the nonvanishing couplings are observed: the absence of zeta values of even weight through the order α'(8) like the absence of ζ(2)ζ(3)R(6) terms. Our analysis is valid for any superstring background in any space-time dimension, which allows for a conformal field theory description. PMID:21469856

  6. Higher levels of CO2 during late incubation alter the hatch time of chicken embryos.

    PubMed

    Tong, Q; McGonnell, I M; Roulston, N; Bergoug, H; Romanini, C E B; Garain, P; Eterradossi, N; Exadaktylos, V; Bahr, C; Berckmans, D; Demmers, T G M

    2015-01-01

    1. It has been reported that the increasing CO2 tension triggers the embryo to pip the air cell and emerge from the egg. However, the mechanism by which higher CO2 concentrations during the last few days of incubation affect chick physiology and the hatching process is unclear. This study investigated the effect of CO2 concentrations up to 1% during pipping, on the onset and length of the hatch window (HW) and chick quality. 2. Four batches of Ross 308 broiler eggs (600 eggs per batch) were incubated in two small-scale custom-built incubators (Petersime NV). During the final 3 d of incubation, control eggs were exposed to a lower CO2 concentration (0.3%), while the test eggs experienced a higher CO2 concentration programme (peak of 1%). 3. There were no significant differences in blood values, organ weight and body weight. There was also no difference in hatchability between control and test groups. However, a small increase in the chick weight and the percentage of first class chicks was found in the test groups. Furthermore, plasma corticosterone profiles during hatching were altered in embryos exposed to higher CO2; however, they dropped to normal levels at d 21 of incubation. Importantly, the hatching process was delayed and synchronised in the test group, resulting in a narrowed HW which was 2.7 h shorter and 5.3 h later than the control group. 4. These results showed that exposing chicks to 1% CO2 concentration during pipping did not have negative impacts on physiological status of newly hatched chicks. In addition, it may have a significant impact on the physiological mechanisms controlling hatching and have benefits for the health and welfare of chickens by reducing the waiting time after hatching. PMID:25900009

  7. 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

  8. Nursing education in Sweden: development from vocational training to higher level education.

    PubMed

    Kapborg, I

    1998-02-01

    Recent decades have seen several changes within Swedish nursing education. The length of Swedish nursing education was previously 2 years; today, however, it has been adapted to the rules laid down by the European Union, which means that it covers 3 years. Swedish nursing education was raised to university college level as early as 1977; however, it is only in recent years that the education can be said to meet the requirements placed on it. The requirement that the education should be scientifically based entails that the teaching staff should include teachers not only with nursing experience but also with a doctor's degree in nursing. The county councils are the authorities responsible for nursing education with the exception of three university colleges of nursing education which are independent. During the past year, however, seven nursing programmes have gone over to State control, and several more are discussing co-operation. A central evaluation made of Swedish university colleges of nursing education shows that 10 colleges provided education which could not be considered to correspond to the required level of higher education. No university college of nursing education has yet been accorded the right to provide education for the bachelor's degree. The future of the Swedish nurse is uncertain due to a large extent to the reorganization that has taken place within the health services. PMID:9515649

  9. Complimentary lower-level and higher-order systems underpin imitation learning.

    PubMed

    Andrew, Matthew; Bennett, Simon J; Elliott, Digby; Hayes, Spencer J

    2016-04-01

    We examined whether the temporal representation developed during motor training with reduced-frequency knowledge of results (KR; feedback available on every other trial) was transferred to an imitation learning task. To this end, four groups first practised a three-segment motor sequence task with different KR protocols. Two experimental groups received reduced-frequency KR, one group received high-frequency KR (feedback available on every trial), and one received no-KR. Compared to the no-KR group, the groups that received KR learned the temporal goal of the movement sequence, as evidenced by increased accuracy and consistency across training. Next, all groups learned a single-segment movement that had the same temporal goal as the motor sequence task but required the imitation of biological and nonbiological motion kinematics. Kinematic data showed that whilst all groups imitated biological motion kinematics, the two experimental reduced-frequency KR groups were on average ∼800ms more accurate at imitating movement time than the high-frequency KR and no-KR groups. The interplay between learning biological motion kinematics and the transfer of temporal representation indicates imitation involves distinct, but complementary lower-level sensorimotor and higher-level cognitive processing systems. PMID:26897261

  10. Relative expression levels of the HLA class-I proteins in normal and HIV-infected cells 1

    PubMed Central

    Apps, Richard; Meng, Zhaojing; Del Prete, Gregory Q.; Lifson, Jeffrey D.; Zhou, Ming; Carrington, Mary

    2015-01-01

    The expression level of human leukocyte antigens (HLA) is known to influence pathological outcomes: pathogens downregulate HLA to evade host immune responses, host inflammatory reactions upregulate HLA, and differences between people in steady-state expression levels of HLA associate with disease susceptibility. Yet precise quantification of relative expression levels of the various HLA loci is difficult due to the tremendous polymorphism of HLA. We report relative expression levels of HLA-A, HLA-B, HLA-C and HLA-E proteins for the specific haplotype A*02:01, B*44:02, C*05:01, characterized using two independent methods based on flow cytometry and mass spectrometry. Peripheral blood lymphocytes from normal donors showed that HLA-A and HLA-B proteins are expressed at similar levels, which are 13-18 times higher than HLA-C by flow cytometry and 4-5 times higher than HLA-C by mass spectrometry, differences that may reflect variation in the conformation or location of proteins detected. HLA-E was detected at a level 25 times lower than that of HLA-C by mass spectrometry. Primary CD4+ T cells infected with HIV in vitro were also studied since HIV downregulates selective HLA types. HLA-A and -B were reduced on HIV-infected cells by a magnitude that varied between cells in an infected culture. Averaging all infected cells from an individual showed HLA-A to be 1-3 and HLA-B to be 2-5 times higher than HLA-C for different individuals by flow cytometry. These results quantify substantial differences in expression levels of the proteins from different HLA loci, which are very likely physiologically significant on both uninfected and HIV-infected cells. PMID:25754738

  11. HLA-G Level on Monocytoid Dendritic Cells Correlates with Regulatory T Cell Foxp3 Expression in Liver Transplant Tolerance

    PubMed Central

    Castellaneta, Antonino; Mazariegos, George V; Nayyar, Navdeep; Zeevi, Adriana; Thomson, Angus W

    2011-01-01

    Background Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule expressed as membrane-bound and soluble isoforms. Interaction of HLA-G with its receptor, immunoglobulin (Ig)-like transcript (ILT) 4 on dendritic cells (DC) down-regulates their T cell stimulatory ability. Methods We examined expression of HLA-G, ILT4, other immune regulatory molecules (inducible costimulator ligand and glucocorticoid-induced tumor necrosis factor-related receptor ligand), and the activation marker CMRF44 on circulating monocytoid (m) and plasmacytoid (p)DC by monoclonal antibody staining and flow cytometry. Three groups of stable liver transplant recipients,-operationally tolerant (TOL), prospective immunosuppressive drug weaning (PW) and maintenance immunosuppression (MI) were studied, together with healthy controls (HC). Serum HLA-G levels were measured by enzyme-linked immunosorbent assay. Results In TOL patients, mDC but not pDC expressed higher HLA-G than in MI patients or HC. In TOL patients, the incidence of CD4+CD25hiCD127− regulatory T cells (Treg) and the intensity of Treg forkhead box p3 (Foxp3) expression were significantly higher than in the MI group. HLA-G expression on circulating mDC correlated significantly with that of Foxp3 in the TOL group. There was no correlation between immunosuppressive drug (tacrolimus) dose or trough level and HLA-G expression or Treg frequency or Foxp3 expression. The incidence of patients with circulating HLA-G levels >100ng/ml was highest in the TOL group, although statistical significance was not achieved. Conclusions Higher HLA-G expression on circulating mDC in TOL recipients compared with MI or HC, suggests a possible role of HLA-G in immune regulation possibly mediated by enhanced host Treg Foxp3 expression. PMID:21423069

  12. Effect of cadmium on the expression levels of interleukin-1α and interleukin-10 cytokines in human lung cells

    PubMed Central

    ODEWUMI, CAROLINE; LATINWO, LEKAN M.; SINCLAIR, ANDRE; BADISA, VEERA L.D.; ABDULLAH, AHKINYALA; BADISA, RAMESH B.

    2015-01-01

    Cadmium is an environmentally hazardous metal, which causes toxicity in humans. Inhalation of cigarette smoke and industrial fumes containing cadmium are sources of cadmium exposure. It is responsible for the malfunction of various organs, leading to disease particularly in the lungs, liver and kidneys. In the present study, the effect of cadmium chloride (CdCl2) on cell viability, and the expression levels of interleukin (IL)-1α and IL-10 cytokines at various concentrations and incubation durations were assessed in MRC-9 human normal lung and A549 human lung cancer cells to elucidate the mechanism of cadmium toxicity. Cell viability was measured using a crystal violet dye binding assay. The expression levels of the cytokines were measured by cytokine specific enzyme-linked immunosorbent assay kits. The viability assay results revealed higher sensitivity of the A549 lung cancer cells to CdCl2 compared with the normal MRC-9 lung cells. In the normal MRC-9 lung cells, higher expression levels of the cytokines were observed at the lowest CdCl2 concentration at a shorter exposure time compared with the lung cancer cells. Higher levels of the cytokines were observed in the A549 lung cancer cells at all other times and concentrations compared with the MRC-9 cells, indicating higher levels of inflammation. The cytokine levels were reduced at higher CdCl2 concentrations and longer exposure durations, demonstrating the toxic effect of cadmium. The results indicated that CdCl2 affected the expression levels of the cytokines and led to cytotoxicity in human lung cells, and suggested that compounds which reduce inflammation may prevent cadmium toxicity. PMID:26397147

  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. Partners or Adversaries: A Comparative Case Study of Higher-Education Systems and State-Level Accountability

    ERIC Educational Resources Information Center

    Toman, Janelle Krause; Card, Karen Aldred

    2010-01-01

    The accountability focus in higher education historically has been directed at the institutional level. The purpose of this comparative case study, however, was to look at state-level accountability. The research focused on the processes used in Tennessee, Minnesota, and South Dakota. Interviews were conducted with higher education administrators…

  15. Expression Level of Genes Coding for Cell Adhesion Molecules of Cadherin Group in Colorectal Cancer Patients

    PubMed Central

    Lorenc, Zbigniew; Opiłka, Mieszko Norbert; Kruszniewska-Rajs, Celina; Rajs, Antoni; Waniczek, Dariusz; Starzewska, Małgorzata; Lorenc, Justyna; Mazurek, Urszula

    2015-01-01

    Background Colorectal Cancer (CRC) is one of the most frequently diagnosed neoplasms and also one of the main death causes. Cell adhesion molecules are taking part in specific junctions, contributing to tissue integrality. Lower expression of the cadherins may be correlated with poorer differentiation of the CRC, and its more aggressive phenotype. The aim of the study is to designate the cadherin genes potentially useful for the diagnostics, prognostics, and the treatment of CRC. Material/Method Specimens were collected from 28 persons (14 female and 14 male), who were operated for CRC. The molecular analysis was performed using oligonucleotide microarrays, mRNA used was collected from adenocarcinoma, and macroscopically healthy tissue. The results were validated using qRT-PCR technique. Results Agglomerative hierarchical clustering of normalized mRNA levels has shown 4 groups with statistically different gene expression. The control group was divided into 2 groups, the one was appropriate control (C1), the second (C2) had the genetic properties of the CRC, without pathological changes histologically and macroscopically. The other 2 groups were: LSC (Low stage cancer) and HSC (High stage cancer). Consolidated results of the fluorescency of all of the differential genes, designated two coding E-cadherin (CDH1) with the lower expression, and P-cadherin (CDH3) with higher expression in CRC tissue. Conclusions The levels of genes expression are different for several groups of cadherins, and are related with the stage of CRC, therefore could be potentially the useful marker of the stage of the disease, also applicable in treatment and diagnostics of CRC. PMID:26167814

  16. 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

  17. Codon influence on protein expression in E. coli correlates with mRNA levels.

    PubMed

    Boël, Grégory; Letso, Reka; Neely, Helen; Price, W Nicholson; Wong, Kam-Ho; Su, Min; Luff, Jon D; Valecha, Mayank; Everett, John K; Acton, Thomas B; Xiao, Rong; Montelione, Gaetano T; Aalberts, Daniel P; Hunt, John F

    2016-01-21

    Degeneracy in the genetic code, which enables a single protein to be encoded by a multitude of synonymous gene sequences, has an important role in regulating protein expression, but substantial uncertainty exists concerning the details of this phenomenon. Here we analyse the sequence features influencing protein expression levels in 6,348 experiments using bacteriophage T7 polymerase to synthesize messenger RNA in Escherichia coli. Logistic regression yields a new codon-influence metric that correlates only weakly with genomic codon-usage frequency, but strongly with global physiological protein concentrations and also mRNA concentrations and lifetimes in vivo. Overall, the codon content influences protein expression more strongly than mRNA-folding parameters, although the latter dominate in the initial ~16 codons. Genes redesigned based on our analyses are transcribed with unaltered efficiency but translated with higher efficiency in vitro. The less efficiently translated native sequences show greatly reduced mRNA levels in vivo. Our results suggest that codon content modulates a kinetic competition between protein elongation and mRNA degradation that is a central feature of the physiology and also possibly the regulation of translation in E. coli. PMID:26760206

  18. VNN1 Gene Expression Levels and the G-137T Polymorphism Are Associated with HDL-C Levels in Mexican Prepubertal Children

    PubMed Central

    Jacobo-Albavera, Leonor; Aguayo-de la Rosa, Pablo I.; Villarreal-Molina, Teresa; Villamil-Ramírez, Hugo; León-Mimila, Paola; Romero-Hidalgo, Sandra; López-Contreras, Blanca E.; Sánchez-Muñoz, Fausto; Bojalil, Rafael; González-Barrios, Juan Antonio; Aguilar-Salinas, Carlos A.; Canizales-Quinteros, Samuel

    2012-01-01

    Background VNN1 gene expression levels and the G-137T polymorphism have been associated with high density lipoprotein cholesterol (HDL-C) levels in Mexican American adults. We aim to evaluate the contribution of VNN1 gene expression and the G-137T variant to HDL-C levels and other metabolic traits in Mexican prepubertal children. Methodology/Principal Findings VNN1 mRNA expression levels were quantified in peripheral blood leukocytes from 224 unrelated Mexican-Mestizo children aged 6–8 years (107 boys and 117 girls) and were genotyped for the G-137T variant (rs4897612). To account for population stratification, a panel of 10 ancestry informative markers was analyzed. After adjustment for admixture, the TT genotype was significantly associated with lower VNN1 mRNA expression levels (P = 2.9 × 10−5), decreased HDL-C levels (β = −6.19, P = 0.028) and with higher body mass index (BMI) z-score (β = 0.48, P = 0.024) in the total sample. In addition, VNN1 expression showed a positive correlation with HDL-C levels (r = 0.220; P = 0.017) and a negative correlation with BMI z-score (r = −0.225; P = 0.015) only in girls. Conclusion/Significance Our data suggest that VNN1 gene expression and the G-137T variant are associated with HDL-C levels in Mexican children, particularly in prepubertal girls. PMID:23185446

  19. How School Leaders Might Promote Higher Levels of Collective Teacher Efficacy at the Level of School and Team

    ERIC Educational Resources Information Center

    Prelli, Gail E.

    2016-01-01

    Leaders search for effective leadership practices to ensure success. A quantitative study was conducted to determine what behaviors a leader could use to improve collective teacher efficacy at the level of the entire faculty and at the level of grade level teams. This article focuses on using the inverse relationship between transformational…

  20. 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…

  1. GTP Cyclohydrolase I Expression, Protein, and Activity Determine Intracellular Tetrahydrobiopterin Levels, Independent of GTP Cyclohydrolase Feedback Regulatory Protein Expression

    PubMed Central

    Tatham, Amy L.; Crabtree, Mark J.; Warrick, Nicholas; Cai, Shijie; Alp, Nicholas J.; Channon, Keith M.

    2009-01-01

    GTP cyclohydrolase I (GTPCH) is a key enzyme in the synthesis of tetrahydrobiopterin (BH4), a required cofactor for nitricoxide synthases and aromatic amino acid hydroxylases. Alterations of GTPCH activity and BH4 availability play an important role in human disease. GTPCH expression is regulated by inflammatory stimuli, in association with reduced expression of GTP cyclohydrolase feedback regulatory protein (GFRP). However, the relative importance of GTPCH expression versus GTPCH activity and the role of GFRP in relation to BH4 bioavailability remain uncertain. We investigated these relationships in a cell line with tet-regulated GTPCH expression and in the hph-1 mouse model of GTPCH deficiency. Doxycycline exposure resulted in a dose-dependent decrease in GTPCH protein and activity, with a strong correlation between GTPCH expression and BH4 levels (r2 = 0.85, p < 0.0001). These changes in GTPCH and BH4 had no effect on GFRP expression or protein levels. GFRP overexpression and knockdown in tet-GCH cells did not alter GTPCH activity or BH4 levels, and GTPCH-specific knockdown in sEnd.1 endothelial cells had no effect on GFRP protein. In mouse liver we observed a graded reduction of GTPCH expression, protein, and activity, from wild type, heterozygote, to homozygote littermates, with a striking linear correlation between GTPCH expression and BH4 levels (r2 = 0.82, p < 0.0001). Neither GFRP expression nor protein differed between wild type, heterozygote, nor homozygote mice, despite the substantial differences in BH4. We suggest that GTPCH expression is the primary regulator of BH4 levels, and changes in GTPCH or BH4 are not necessarily accompanied by changes in GFRP expression. PMID:19286659

  2. GTP cyclohydrolase I expression, protein, and activity determine intracellular tetrahydrobiopterin levels, independent of GTP cyclohydrolase feedback regulatory protein expression.

    PubMed

    Tatham, Amy L; Crabtree, Mark J; Warrick, Nicholas; Cai, Shijie; Alp, Nicholas J; Channon, Keith M

    2009-05-15

    GTP cyclohydrolase I (GTPCH) is a key enzyme in the synthesis of tetrahydrobiopterin (BH4), a required cofactor for nitricoxide synthases and aromatic amino acid hydroxylases. Alterations of GTPCH activity and BH4 availability play an important role in human disease. GTPCH expression is regulated by inflammatory stimuli, in association with reduced expression of GTP cyclohydrolase feedback regulatory protein (GFRP). However, the relative importance of GTPCH expression versus GTPCH activity and the role of GFRP in relation to BH4 bioavailability remain uncertain. We investigated these relationships in a cell line with tet-regulated GTPCH expression and in the hph-1 mouse model of GTPCH deficiency. Doxycycline exposure resulted in a dose-dependent decrease in GTPCH protein and activity, with a strong correlation between GTPCH expression and BH4 levels (r(2) = 0.85, p < 0.0001). These changes in GTPCH and BH4 had no effect on GFRP expression or protein levels. GFRP overexpression and knockdown in tet-GCH cells did not alter GTPCH activity or BH4 levels, and GTPCH-specific knockdown in sEnd.1 endothelial cells had no effect on GFRP protein. In mouse liver we observed a graded reduction of GTPCH expression, protein, and activity, from wild type, heterozygote, to homozygote littermates, with a striking linear correlation between GTPCH expression and BH4 levels (r(2) = 0.82, p < 0.0001). Neither GFRP expression nor protein differed between wild type, heterozygote, nor homozygote mice, despite the substantial differences in BH4. We suggest that GTPCH expression is the primary regulator of BH4 levels, and changes in GTPCH or BH4 are not necessarily accompanied by changes in GFRP expression. PMID:19286659

  3. Modeling Microbial Dynamics in Aquifers Considering the Interaction Between the Higher Trophic Levels

    NASA Astrophysics Data System (ADS)

    Bajracharya, B. M.; Cirpka, O. A.; Lu, C.

    2014-12-01

    Models of microbial dynamics coupled to solute transport in aquifers typically require the introduction of a bacterial carrying capacity term to prevent excessive microbial growth close to substrate-injection boundaries. The factors controlling this carrying capacity, however, are not fully understood. Most explanations for the occurrence of a carrying capacity discussed are based on the assumption of a bottom-up control of groundwater ecosystems. An alternative explanation is based on top-down control. Our model considers substrate, bacteria and higher trophic levels, such as grazers or bacteriophages. The dissolved substrate is transported with water flow whereas the biomasses of bacteria and grazers are considered essentially immobile. The one-dimensional reactive transport model also accounts for substrate dispersion and a random walk of grazers influenced by the bacteria concentration. The grazers grow on the bacteria, leading to a negative feedback on the bacteria concentration which may limit the turnover of the substrate. A single retentostat model with Monod kinetics of bacterial growth and a second-order grazing shows that the system oscillates but approaches a stable steady state with non-zero concentrations of substrate, bacteria, and grazers. The steady-state concentration of the bacteria biomass is independent of the substrate concentration in the inflow. When coupling several retentostats in a series to mimic a groundwater column, the steady-state bacteria concentrations remain at a constant level over a significant travel distance. The results show that grazing is a possible explanation of the carrying capacity, provided that there is enough substrate to sustain bacteria and grazers.

  4. Do Pediatric Patients Who Receive Care Across Multiple Health Systems Have Higher Levels of Repeat Testing?

    PubMed

    Knighton, Andrew J; Payne, Nathaniel R; Speedie, Stuart

    2016-04-01

    Repetition by clinicians of the same tests for a given patient is common. However, not all repeat tests are necessary for optimal care and can result in unnecessary hardship. Limited evidence suggests that an electronic health record may reduce redundant laboratory testing and imaging by making previous results accessible to physicians. The purpose of this study is to establish a baseline by characterizing repeat testing in a pediatric population and to identify significant risk factors associated with repeated tests, including the impact of using multiple health systems. A population-based retrospective cross-sectional design was used to examine initial and repeat test instances, defined as a second test following an initial test of the same type for the same patient. The study population consisted of 8760 children with 1-25 test claims over a 1-year period. The study setting included all health care service organizations in Minnesota that generated these claims. In all, 17.2% of tests met the definition of repeat test instances, with several risk factors associated with per patient repeat test levels. The incidence of repeat test instances per patient was significantly higher when patients received care from more than 1 health system (adjusted incidence rate ratio 1.4; 95% confidence interval: 1.3-1.5). Repeat test levels are significant in pediatric populations and potentially actionable. Interoperable health information technology may reduce the incidence of repeat test instances in pediatric populations by making prior test results readily accessible. (Population Health Management 2016;19:102-108). PMID:26086359

  5. Gender Differences in Health Literacy Among Korean Adults: Do Women Have a Higher Level of Health Literacy Than Men?

    PubMed

    Lee, Hee Yun; Lee, Jiwoo; Kim, Nam Keol

    2015-09-01

    The role of gender in determining the level of health literacy in Korean adults is unclear. This study aimed to investigate the level of health literacy in Korean adults and identify factors associated with health literacy by gender. This study employed a cross-sectional survey design with a convenient sample of 585 community-dwelling Korean adults age19 years and older. Health literacy was measured by using eight items selected from Chew et al.'s 16-question self-reported health literacy measure. In accordance with Andersen's health behavior model, predisposing, enabling, and need factors were included in the multiple regression model. Women indicated a higher level of health literacy than men in understanding medical forms, directions on medication bottles, and written information offered by health care providers. Additionally, for Korean women, a higher level of health literacy was associated with attaining a higher education level and having a consistent place to receive care. Unmarried men and men who had higher self-rated health reported a higher level of health literacy compared with their counterparts. Lower level of depression and higher monthly income were significantly linked to a higher level of health literacy in both men and women. This study has established the importance of gender differences in health literacy and suggests gender-specific intervention may be warranted to reduce the existing gap in health literacy in both Korean men and women. Future research should replicate this study to confirm whether or not our finding is an international phenomenon. PMID:25122719

  6. 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

  7. Quantifying the Effect of DNA Packaging on Gene Expression Level

    NASA Astrophysics Data System (ADS)

    Kim, Harold

    2010-10-01

    Gene expression, the process by which the genetic code comes alive in the form of proteins, is one of the most important biological processes in living cells, and begins when transcription factors bind to specific DNA sequences in the promoter region upstream of a gene. The relationship between gene expression output and transcription factor input which is termed the gene regulation function is specific to each promoter, and predicting this gene regulation function from the locations of transcription factor binding sites is one of the challenges in biology. In eukaryotic organisms (for example, animals, plants, fungi etc), DNA is highly compacted into nucleosomes, 147-bp segments of DNA tightly wrapped around histone protein core, and therefore, the accessibility of transcription factor binding sites depends on their locations with respect to nucleosomes - sites inside nucleosomes are less accessible than those outside nucleosomes. To understand how transcription factor binding sites contribute to gene expression in a quantitative manner, we obtain gene regulation functions of promoters with various configurations of transcription factor binding sites by using fluorescent protein reporters to measure transcription factor input and gene expression output in single yeast cells. In this talk, I will show that the affinity of a transcription factor binding site inside and outside the nucleosome controls different aspects of the gene regulation function, and explain this finding based on a mass-action kinetic model that includes competition between nucleosomes and transcription factors.

  8. The cohesive metaschema: a higher-level abstraction of the UMLS Semantic Network.

    PubMed

    Perl, Yehoshua; Chen, Zong; Halper, Michael; Geller, James; Zhang, Li; Peng, Yi

    2002-06-01

    The Unified Medical Language System (UMLS) joins together a group of established medical terminologies in a unified knowledge representation framework. Two major resources of the UMLS are its Metathesaurus, containing a large number of concepts, and the Semantic Network (SN), containing semantic types and forming an abstraction of the Metathesaurus. However, the SN itself is large and complex and may still be difficult to view and comprehend. Our structural partitioning technique partitions the SN into structurally uniform sets of semantic types based on the distribution of the relationships within the SN. An enhancement of the structural partition results in cohesive, singly rooted sets of semantic types. Each such set is named after its root which represents the common nature of the group. These sets of semantic types are represented by higher-level components called metasemantic types. A network, called a metaschema, which consists of the meta-semantic types connected by hierarchical and semantic relationships is obtained and provides an abstract view supporting orientation to the SN. The metaschema is utilized to audit the UMLS classifications. We present a set of graphical views of the SN based on the metaschema to help in user orientation to the SN. A study compares the cohesive metaschema to metaschemas derived semantically by UMLS experts. PMID:12669983

  9. Perceptual information for the age level of faces as a higher order invariant of growth.

    PubMed

    Pittenger, J B; Shaw, R E; Mark, L S

    1979-08-01

    Previous work supports the hypothesis that cardioidal strain, a nonlinear topological transformation, offers a plausible mathematical model for the perceived global changes in human craniofacial morphology due to growth. Experiment 1 examined the generality of the effect of this growth transformation on relative age judgments by applying it to profiles of a dog, bird, and monkey. Experiment 2 investigated the abstractness of this transformation by looking at its effect on perceived age level of a Volkswagen "Beetle." In both experiments, cardioidal strain resulted in changes in the perceived age of the nonhuman profiles that were similar to those produced on human faces in earlier work. A second transformation, affine shear, failed to produce as significant an effect on perceived age as cardioidal strain when applied to the same structures. Because cardioidal strain produces changes in structures that do not share an isomorphism of rigid (Euclidian) local features or rigid feature configurations, this transformation seems both sufficiently general and abstract to specify what J.J. Gibson has called a "higher-order invariant of perceptual information. PMID:528953

  10. Multiple-Choice Exams: An Obstacle for Higher-Level Thinking in Introductory Science Classes

    PubMed Central

    Stanger-Hall, Kathrin F.

    2012-01-01

    Learning science requires higher-level (critical) thinking skills that need to be practiced in science classes. This study tested the effect of exam format on critical-thinking skills. Multiple-choice (MC) testing is common in introductory science courses, and students in these classes tend to associate memorization with MC questions and may not see the need to modify their study strategies for critical thinking, because the MC exam format has not changed. To test the effect of exam format, I used two sections of an introductory biology class. One section was assessed with exams in the traditional MC format, the other section was assessed with both MC and constructed-response (CR) questions. The mixed exam format was correlated with significantly more cognitively active study behaviors and a significantly better performance on the cumulative final exam (after accounting for grade point average and gender). There was also less gender-bias in the CR answers. This suggests that the MC-only exam format indeed hinders critical thinking in introductory science classes. Introducing CR questions encouraged students to learn more and to be better critical thinkers and reduced gender bias. However, student resistance increased as students adjusted their perceptions of their own critical-thinking abilities. PMID:22949426

  11. How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1

    PubMed Central

    Serra, Laura; Petrucci, Antonio; Spanò, Barbara; Torso, Mario; Olivito, Giusy; Lispi, Ludovico; Costanzi-Porrini, Sandro; Giulietti, Giovanni; Koch, Giacomo; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

    2015-01-01

    Summary Myotonic dystrophy type 1 (DM1) is a multisystemic disorder dominated by muscular impairment and brain dysfunctions. Although brain damage has previously been demonstrated in DM1, its associations with the genetics and clinical/neuropsychological features of the disease are controversial. This study assessed the differential role of gray matter (GM) and white matter (WM) damage in determining higher-level dysfunctions in DM1. Ten patients with genetically confirmed DM1 and 16 healthy matched controls entered the study. The patients underwent a neuropsychological assessment and quantification of CTG triplet expansion. All the subjects underwent MR scanning at 3T, with studies including T1-weighted volumes and diffusion-weighted images. Voxel-based morphometry and tract-based spatial statistics were used for unbiased quantification of regional GM atrophy and WM integrity. The DM1 patients showed widespread involvement of both tissues. The extent of the damage correlated with CTG triplet expansion and cognition. This study supports the idea that genetic abnormalities in DM1 mainly target the WM, but GM involvement is also crucial in determining the clinical characteristics of DM1. PMID:26214024

  12. Higher Trophic Levels Overwhelm Climate Change Impacts on Terrestrial Ecosystem Functioning

    PubMed Central

    Pelini, Shannon L.; Maran, Audrey M.; Chen, Angus R.; Kaseman, Justine; Crowther, Thomas W.

    2015-01-01

    Forest floor food webs play pivotal roles in carbon cycling, but they are rarely considered in models of carbon fluxes, including soil carbon dioxide emissions (respiration), under climatic warming. The indirect effects of invertebrates on heterotrophic (microbial and invertebrate) respiration through interactions with microbial communities are significant and will be altered by warming. However, the interactive effects of invertebrates and warming on heterotrophic respiration in the field are poorly understood. In this study we combined field and common garden laboratory approaches to examine relationships between warming, forest floor food web structure, and heterotrophic respiration. We found that soil animals can overwhelm the effects of warming (to 5 degrees Celsius above ambient) on heterotrophic respiration. In particular, the presence of higher trophic levels and burrowing detritivores strongly determined heterotrophic respiration rates in temperate forest soils. These effects were, however, context-dependent, with greater effects in a lower-latitude site. Without isolating and including the significant impact of invertebrates, climate models will be incomplete, hindering well-informed policy decisions. PMID:26292214

  13. Higher Trophic Levels Overwhelm Climate Change Impacts on Terrestrial Ecosystem Functioning.

    PubMed

    Pelini, Shannon L; Maran, Audrey M; Chen, Angus R; Kaseman, Justine; Crowther, Thomas W

    2015-01-01

    Forest floor food webs play pivotal roles in carbon cycling, but they are rarely considered in models of carbon fluxes, including soil carbon dioxide emissions (respiration), under climatic warming. The indirect effects of invertebrates on heterotrophic (microbial and invertebrate) respiration through interactions with microbial communities are significant and will be altered by warming. However, the interactive effects of invertebrates and warming on heterotrophic respiration in the field are poorly understood. In this study we combined field and common garden laboratory approaches to examine relationships between warming, forest floor food web structure, and heterotrophic respiration. We found that soil animals can overwhelm the effects of warming (to 5 degrees Celsius above ambient) on heterotrophic respiration. In particular, the presence of higher trophic levels and burrowing detritivores strongly determined heterotrophic respiration rates in temperate forest soils. These effects were, however, context-dependent, with greater effects in a lower-latitude site. Without isolating and including the significant impact of invertebrates, climate models will be incomplete, hindering well-informed policy decisions. PMID:26292214

  14. Fused RSOS lattice models as higher-level nonunitary minimal cosets

    NASA Astrophysics Data System (ADS)

    Tartaglia, Elena; Pearce, Paul A.

    2016-05-01

    We consider the Forrester-Baxter RSOS lattice models with crossing parameter λ = (m‧-m)π/m‧ in Regime III. In the continuum scaling limit, these models are described by the minimal models { M }(m,{m}\\prime ). We conjecture that, for λ < π/n, the n × n fused RSOS models with n≥slant 2 are described by the higher-level coset {({A}1(1))}k\\otimes {({A}1(1))}n/{({A}1(1))}k+n at fractional level k = nM/(M‧-M)-2 with (M,{M}\\prime )=({nm}-(n-1){m}\\prime ,{m}\\prime ). To support this conjecture, we investigate the one-dimensional sums arising from Baxter’s off-critical corner transfer matrices. In unitary cases (m = m‧-1) it is known that, up to leading powers of q, these coincide with the branching functions {b}r,s,{\\ell }{m\\prime -n,{m}\\prime ,n}(q). For general nonunitary cases (m < m‧-1), we identify the ground state one-dimensional RSOS paths and relate them to the quantum numbers (r, s, ℓ) in the various sectors. For n = 1, 2, 3, we obtain the local energy functions H(a, b, c) in a suitable gauge and verify that the associated one-dimensional sums produce finitized forms that converge, as N becomes large, to the fractional level branching functions {b}r,s,{\\ell }M,{M\\prime ,n}(q). Extending the work of Schilling, we also conjecture finitized bosonic branching functions {b}r,s,{\\ell }M,{M\\prime ,n;(N)}(q) for general n and check that these agree with the one-dimensional sums for n = 1, 2, 3 out to system sizes N = 14. Lastly, the finitized Kac characters {χ }r,s,{\\ell }P,{P\\prime ,n;(N)}(q) of the n × n fused logarithmic minimal models { L }{ M }(p,{p}\\prime ) are obtained by taking the logarithmic limit m,{m}\\prime \\to ∞ with m‧/m→p‧/p+.

  15. Sustained high level transgene expression in mammalian cells mediated by the optimized piggyBac transposon system

    PubMed Central

    Chen, Xiang; Cui, Jing; Yan, Zhengjian; Zhang, Hongmei; Chen, Xian; Wang, Ning; Shah, Palak; Deng, Fang; Zhao, Chen; Geng, Nisha; Li, Melissa; Denduluri, Sahitya K.; Haydon, Rex C.; Luu, Hue H.; Reid, Russell R.; He, Tong-Chuan

    2015-01-01

    Sustained, high level transgene expression in mammalian cells, especially stem cells, may be desired in many cases for studying gene functions. Traditionally, stable transgene expression has been accomplished by using retroviral or lentiviral vectors. However, such viral vector-mediated transgene expression is often at low levels and can be reduced over time due to low copy numbers and/or chromatin remodeling repression. The piggyBac transposon has emerged as a promising non-viral vector system for efficient gene transfer into mammalian cells. Despite its inherent advantages over lentiviral and retroviral systems, piggyBac system has not been widely used, at least in part due to the limited availability of piggyBac vectors with manipulation flexibilities. Here, we seek to optimize piggyBac-mediated transgene expression and generate a more efficient, user-friendly piggyBac system. By engineering a panel of versatile piggyBac vectors and constructing recombinant adenoviruses expressing piggyBac transposase (PBase), we demonstrate that adenovirus-mediated PBase expression significantly enhances the integration efficiency and expression level of transgenes in mesenchymal stem cells and osteosarcoma cells, compared to that obtained from co-transfection of the CMV-PBase plasmid. We further determine the drug selection timeline to achieve optimal stable transgene expression. Moreover, we demonstrate that the transgene copy number of piggyBac-mediated integration is approximately 10 times higher than that mediated by retroviral vectors. Using the engineered tandem expression vector, we show that three transgenes can be simultaneously expressed in a single vector with high efficiency. Thus, these results strongly suggest that the optimized piggyBac system is a valuable tool for making stable cell lines with sustained, high transgene expression. PMID:25815368

  16. Effect of High Fat Diets on Body Mass, Oleylethanolamide Plasma Levels and Oxytocin Expression in Growing Rats.

    PubMed

    Sospedra, Isabel; Moral, Raquel; Escrich, Raquel; Solanas, Montserrat; Vela, Elena; Escrich, Eduard

    2015-06-01

    Obesity prevalence in developed countries has promoted the need to identify the mechanisms involved in control of feeding and energy balance. We have tested the hypothesis that different fats present in diet composition may contribute in body weight gain and body indexes by regulation of oxytocin gene (oxt) expression in hypothalamus and Oleylethanolamide (OEA) levels in plasma. Sprague-Dawley rats were fed two high fat diets, based on corn (HCO) and extra virgin olive oil (HOO) and results were compared to a low fat diet (LF). LC-MS/MS analysis showed an increasing trend of OEA plasma levels in HOO group, although no significant differences were found. However, body weight gain of LF and HOO were similar and significantly lower than HCO. HCO rats also had higher Lee index than HOO. Rats fed HOO diet showed higher levels of hypothalamic oxt mRNA expression, which could indicate that oxytocin may be modulated by dietary lipids. PMID:25976631

  17. Insert sequence length determines transfection efficiency and gene expression levels in bicistronic mammalian expression vectors

    PubMed Central

    Payne, Andrew J; Gerdes, Bryan C; Kaja, Simon; Koulen, Peter

    2013-01-01

    Bicistronic expression vectors have been widely used for co-expression studies since the initial discovery of the internal ribosome entry site (IRES) about 25 years ago. IRES sequences allow the 5’ cap-independent initiation of translation of multiple genes on a single messenger RNA strand. Using a commercially available mammalian expression vector containing an IRES sequence with a 3’ green fluorescent protein fluorescent marker, we found that sequence length of the gene of interest expressed 5’ of the IRES site influences both expression of the 3’ fluorescent marker and overall transfection efficiency of the vector construct. Furthermore, we generated a novel construct expressing two distinct fluorescent markers and found that high expression of one gene can lower expression of the other. Observations from this study indicate that caution is warranted in the design of experiments utilizing an IRES system with a short 5’ gene of interest sequence (<300 bp), selection of single cells based on the expression profile of the 3’ optogenetic fluorescent marker, and assumptions made during data analysis. PMID:24380024

  18. Nasal Associated Lymphoid Tissue of the Syrian Golden Hamster Expresses High Levels of PrPC

    PubMed Central

    Clouse, Melissa D.; Shikiya, Ronald A.; Bartz, Jason C.; Kincaid, Anthony E.

    2015-01-01

    The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc) comes into contact with native prion protein (PrPC) and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC) of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer’s patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection. PMID:25642714

  19. The Prominence of Referring Expressions: Message and Lexical Level Effects

    ERIC Educational Resources Information Center

    Lam, Tuan Q.

    2012-01-01

    In conversation, speakers produce some words with greater intensity, longer duration, and higher fundamental frequency (F0) than other words. By making different words in a sentence more prominent than other words, a speaker can change the meaning implied by a sentence. This thesis explores the relationship between processing in the language…

  20. Decisions Made with Less Evidence Involve Higher Levels of Corticosubthalamic Nucleus Theta Band Synchrony.

    PubMed

    Zavala, Baltazar; Tan, Huiling; Little, Simon; Ashkan, Keyoumars; Green, Alexander L; Aziz, Tipu; Foltynie, Thomas; Zrinzo, Ludvic; Zaghloul, Kareem; Brown, Peter

    2016-06-01

    The switch between automatic action selection and more controlled forms of decision-making is a dynamic process thought to involve both cortical and subcortical structures. During sensory conflict, medial pFC oscillations in the theta band (<8 Hz) drive those of the subthalamic nucleus (STN), and this is thought to increase the threshold of evidence needed for one competing response to be selected over another. Here, we were interested in testing whether STN activity is also altered by the rate at which evidence is presented during a congruent dot motion task absent of any explicit sensory conflict. By having a series of randomly moving dots gradually transform to congruent motion at three different rates (slow, medium, fast), we were able to show that a slower rate increased the time it took participants to make a response but did not alter the total amount of evidence that was integrated before the response. Notably, this resulted in a decision being made with a lower amount of instantaneous evidence during the slow and medium trials. Consistent with the idea that medial pFC-STN activity is involved in executing cognitive control, the higher levels of ambiguity during these trials were associated with increased theta band synchrony between the cortex and the STN, with the cortical oscillations Granger-causal to those of the STN. These results further confirm the involvement of the STN in decision-making and suggest that the disruption of this network may underlie some of the unwanted cognitive deficits associated with STN deep brain stimulation. PMID:26845109

  1. The myostatin gene of Mytilus chilensis evidences a high level of polymorphism and ubiquitous transcript expression.

    PubMed

    Núñez-Acuña, Gustavo; Gallardo-Escárate, Cristian

    2014-02-15

    Myostatin (MSTN) is a protein of the Transforming Growth Factor-β (TGF-β) superfamily and plays a crucial role in muscular development for higher vertebrates. However, its biological function in marine invertebrates remains undiscovered. This study characterizes the full-length sequence of the Mytilus chilensis myostatin gene (Mc-MSTN). Furthermore, tissue transcription patterns and putative single nucleotide polymorphisms (SNPs) were also identified. The Mc-MSTN cDNA sequence showed 3528 base pairs (bp), consisting of 161 bp of 5' UTR, 2,110 bp of 3' UTR, and an open reading frame of 1,257 bp encoding for 418 amino acids and with an RXXR proteolytic site and nine cysteine-conserved residues. Gene transcription analysis revealed that the Mc-MSTN has ubiquitous expression among several tissues, with higher expression in the gonads and mantle than in the digestive gland, gills, and hemolymph. Furthermore, high levels of polymorphisms were detected (28 SNPs in 3'-UTR and 9 SNPs in the coding region). Two SNPs were non-synonymous and involved amino acid changes between Glu/Asp and Thr/Ile. Until now, the MSTN gene has been mainly related to muscle growth in marine bivalves. However, the present study suggests a putative biological function not entirely associated to muscle tissue and contributes molecular evidence to the current debate about the function of the MSTN gene in marine invertebrates. PMID:24334117

  2. High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates

    PubMed Central

    Schneider, Anina; Weier, Manuela; Sweep, Fred C. G. J.; Le Roy, Didier; Bernhagen, Jürgen; Calandra, Thierry; Giannoni, Eric

    2016-01-01

    The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis. PMID:26858459

  3. Strategies for achieving high-level expression of genes in Escherichia coli.

    PubMed Central

    Makrides, S C

    1996-01-01

    Progress in our understanding of several biological processes promises to broaden the usefulness of Escherichia coli as a tool for gene expression. There is an expanding choice of tightly regulated prokaryotic promoters suitable for achieving high-level gene expression. New host strains facilitate the formation of disulfide bonds in the reducing environment of the cytoplasm and offer higher protein yields by minimizing proteolytic degradation. Insights into the process of protein translocation across the bacterial membranes may eventually make it possible to achieve robust secretion of specific proteins into the culture medium. Studies involving molecular chaperones have shown that in specific cases, chaperones can be very effective for improved protein folding, solubility, and membrane transport. Negative results derived from such studies are also instructive in formulating different strategies. The remarkable increase in the availability of fusion partners offers a wide range of tools for improved protein folding, solubility, protection from proteases, yield, and secretion into the culture medium, as well as for detection and purification of recombinant proteins. Codon usage is known to present a potential impediment to high-level gene expression in E. coli. Although we still do not understand all the rules governing this phenomenon, it is apparent that "rare" codons, depending on their frequency and context, can have an adverse effect on protein levels. Usually, this problem can be alleviated by modification of the relevant codons or by coexpression of the cognate tRNA genes. Finally, the elucidation of specific determinants of protein degradation, a plethora of protease-deficient host strains, and methods to stabilize proteins afford new strategies to minimize proteolytic susceptibility of recombinant proteins in E. coli. PMID:8840785

  4. High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.

    PubMed

    Roger, Thierry; Schneider, Anina; Weier, Manuela; Sweep, Fred C G J; Le Roy, Didier; Bernhagen, Jürgen; Calandra, Thierry; Giannoni, Eric

    2016-02-23

    The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis. PMID:26858459

  5. Higher Level of Dickkopf-1 is Associated with Low Bone Mineral Density and Higher Prevalence of Vertebral Fractures in Patients with Ankylosing Spondylitis.

    PubMed

    Rossini, Maurizio; Viapiana, Ombretta; Idolazzi, Luca; Ghellere, Francesco; Fracassi, Elena; Troplini, Sonila; Povino, Maria Rosaria; Kunnathully, Vidya; Adami, Silvano; Gatti, Davide

    2016-05-01

    Patients with ankylosing spondylitis (AS) have an increased risk of bone loss and vertebral fractures. In this study, we explored the hypothesis that the excess bone loss and vertebral fractures might be related with the activity of the Wingless signaling pathway, and in particular with the serum levels of its circulating inhibitors, Sclerostin and Dickkopf-1 (DKK1). We recruited 71 patients diagnosed with AS. Lateral radiographs of the total spine were analyzed to detect the presence of vertebral fractures, and bone mineral density (BMD) was assessed in all patients using dual X-ray absorptiometry at lumbar spine and proximal femoral site. Blood samples were obtained and levels of C-reactive protein (CRP), DKK1, and Sclerostin were measured. Blood samples from 71 healthy sex- and age-matched volunteers were collected to be used as controls. Vertebral fractures were detected more commonly among men than in women (29 vs 8 %, respectively). DKK1, but not Sclerostin serum levels, were inversely correlated to lumbar spine Z-score BMD. Patients with one or more prevalent vertebral fractures had significantly higher DKK1 levels, without significant difference in Sclerostin serum levels. A significant positive correlation was found between DKK1 serum levels and CRP (r = 0.240, p = 0.043). The association we found between serum DKK1 levels and BMD values and vertebral fracture prevalence suggests that DKK1 might contribute to the severity of osteoporosis in AS. PMID:26645432

  6. mRNA expression levels of hypoxia-induced and stem cell-associated genes in human glioblastoma.

    PubMed

    Bache, Matthias; Rot, Swetlana; Keßler, Jacqueline; Güttler, Antje; Wichmann, Henri; Greither, Thomas; Wach, Sven; Taubert, Helge; Söling, Ariane; Bilkenroth, Udo; Kappler, Matthias; Vordermark, Dirk

    2015-06-01

    The roles of hypoxia-induced and stem cell-associated genes in the development of malignancy and tumour progression are well known. However, there are a limited number of studies analysing the impact of mRNA expression levels of hypoxia-induced and stem cell-associated genes in the tissues of brain tumours and glioblastoma patients. In this study, tumour tissues from patients with glioblastoma multiforme and tumour adjacent tissues were analysed. We investigated mRNA expression levels of hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), carbonic anhydrase 9 (CA9), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and osteopontin (OPN), and stem cell-associated genes survivin, epidermal growth factor receptor (EGFR), human telomerase reverse transcriptase (hTERT), Nanog and octamer binding transcription factor 4 (OCT4) using quantitative real-time polymerase chain reaction (qRT-PCR). Our data revealed higher mRNA expression levels of hypoxia-induced and stem cell-associated genes in tumour tissue than levels in the tumour adjacent tissues in patients with glioblastoma multiforme. A strong positive correlation between the mRNA expression levels of HIF-2α, CA9, VEGF, GLUT-1 and OPN suggests a specific hypoxia-associated profile of mRNA expression in glioblastoma multiforme. Additionally, the results indicate the role of stem-cell-related genes in tumour hypoxia. Kaplan-Maier analysis revealed that high mRNA expression levels of hypoxia-induced markers showed a trend towards shorter overall survival in glioblastoma patients (P=0.061). Our data suggest that mRNA expression levels of hypoxia-induced genes are important tumour markers in patients with glioblastoma multiforme. PMID:25963717

  7. 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

  8. In the Red? Debt Levels at Higher Education Institutions in China

    ERIC Educational Resources Information Center

    Wu, Daguang; Yu, Kai

    2011-01-01

    Borrowing from banks has become a common practice among Chinese higher education institutions (HEIs), and operating with a heavy debt load has become a characteristic of Chinese higher educational development. Substantial financial commitments acquired by HEIs during their rapid expansion since 1998 are now having serious consequences: numerous…

  9. Global and Local Priorities in Higher Education Policies: A Headache at the National Level?

    ERIC Educational Resources Information Center

    Ahola, Sakari

    2005-01-01

    In November 2001 the Finnish Ministry of Education published a working group report on the internationalisation strategy for higher education, and shortly after another report concentrating on the local dimensions and effects of higher education. In the era of internationalisation and globalisation, local concerns seem to be so great that the…

  10. Implementing English Further/Higher Education Partnerships: The Street Level Perspective

    ERIC Educational Resources Information Center

    Gray, Claire

    2016-01-01

    This paper reports on research into the operation of English further/higher education, with a focus on the role of partnerships in supporting the massification of higher education. The research draws on the bottom-up policy implementation tradition to provide analysis of the effects on partnerships of a quasi-marketised environment. The rationale…

  11. Identifying Higher-Education Level Skill Needs in Labor Markets: The Main Tools Usable for Turkey

    ERIC Educational Resources Information Center

    Alpaydin, Yusuf

    2015-01-01

    There are natural mismatches in the labor market between the demand for higher-educated laborers and the supply of graduates provided by the higher education system in terms of quantity and qualifications. While there are open positions, some graduates still cannot find work. There are various findings indicating that the mismatch between…

  12. Confronting the Neo-Liberal Brute: Reflections of a Higher Education Middle-Level Manager

    ERIC Educational Resources Information Center

    Maistry, S. M.

    2012-01-01

    The higher education scenario in South Africa is fraught with tensions and contradictions. Publicly funded Higher Education Institutions (HEIs) face a particular dilemma. They are expected to fulfill a social mandate which requires a considered response to the needs of the communities in which they are located while simultaneously aspiring for…

  13. Health Behaviors Predict Higher Interleukin-6 levels Among Patients Newly Diagnosed with Head and Neck Squamous Cell Carcinoma

    PubMed Central

    Duffy, Sonia A.; Teknos, Theodoros; Taylor, Jeremy M.G.; Fowler, Karen E.; Islam, Mozaffarul; Wolf, Gregory T.; McLean, Scott; Ghanem, Tamer A.; Terrell, Jeffrey E.

    2013-01-01

    Background Health behaviors have been shown to be associated with recurrence risk and survival rates in cancer patients and are also associated with Interleukin-6 levels, but few epidemiologic studies have investigated the relationship of health behaviors and Interleukin-6 among cancer populations. The purpose of the study is to look at the relationship between five health behaviors: smoking, alcohol problems, body mass index (a marker of nutritional status), physical activity, and sleep and pretreatment Interleukin-6 levels in persons with head and neck cancer. Methods Patients (N=409) were recruited in otolaryngology clinic waiting rooms and invited to complete written surveys. A medical record audit was also conducted. Descriptive statistics and multivariate analyses were conducted to determine which health behaviors were associated with higher Interleukin-6 levels controlling for demographic and clinical variables among newly diagnosed head and neck cancer patients. Results While smoking, alcohol problems, body mass index, physical activity, and sleep were associated with Interleukin-6 levels in bivariate analysis, only smoking (current and former) and decreased sleep were independent predictors of higher Interleukin-6 levels in multivariate regression analysis. Covariates associated with higher Interleukin-6 levels were age and higher tumor stage, while comorbidities were marginally significant. Conclusion Health behaviors, particularly smoking and sleep disturbances, are associated with higher Interleukin-6 levels among head and neck cancer patients. Impact Treating health behavior problems, especially smoking and sleep disturbances, may be beneficial to decreasing Interleukin-6 levels which could have a beneficial effect on overall cancer treatment outcomes. PMID:23300019

  14. Levels of expression of CD19 and CD20 in chronic B cell leukaemias.

    PubMed Central

    Ginaldi, L; De Martinis, M; Matutes, E; Farahat, N; Morilla, R; Catovsky, D

    1998-01-01

    AIMS: To investigate whether the antigen levels of the B cell lineage markers CD19 and CD20 can distinguish between normal and neoplastic B cells or characterise distinct expression patterns among the chronic B cell leukaemias. METHODS: Peripheral blood cells from 70 patients with B cell disorders and 17 healthy donors were analysed by quantitative flow cytometry. Direct immunofluorescence staining was performed with phycoerythrin conjugated CD19 and CD20 monoclonal antibodies. Standard microbeads with different capacities to bind mouse immunoglobulins were used to convert the mean fluorescence intensity (MFI) values into number of antigen molecules/cell, expressed as antibody binding capacity (ABC). RESULTS: CD19 and CD20 ABC values in leukaemic B cells differed from those of normal blood B lymphocytes. The results identified distinct profiles of CD19 and CD20 expression in the various types of B cell leukaemias. In all leukaemias studied except hairy cell leukaemia (HCL), CD19 expression was significantly lower than the mean (SD) value in normal B cells (22 (7) x 10(3) molecules/cell), as follows: chronic lymphocytic leukaemia (CLL), 13 (7) x 10(3); B prolymphocytic leukaemia (B-PLL), 16 (9) x 10(3); splenic lymphoma with villous lymphocytes (SLVL), 15 (11) x 10(3); mantle cell lymphoma (MCL), 10 (7) x 10(3). In HCL there was strong CD19 expression (38 (16) x 10(3)). In contrast, the level of expression of membrane CD20 was higher than the mean (SD) value in normal B cells (94 (16) x 10(3) molecules/cell) in MCL (123 (51) x 10(3)); B-PLL (129 (47) x 10(3)); SLVL (167 (72) x 10(3)); and HCL (312 (110) x 10(3)); while it was significantly lower (65 (11) x 10(3)) in CLL compared with normal B cells and the other B cell leukaemias. CONCLUSIONS: Quantitative determination of CD19 and CD20 may provide useful diagnostic information for the study of B lymphoproliferative disorders. PMID:9708202

  15. Association between ADSL, GARS-AIRS-GART, DGAT1, and DECR1 expression levels and pork meat quality traits.

    PubMed

    Zhang, X D; Zhang, S J; Ding, Y Y; Feng, Y F; Zhu, H Y; Huang, L; Wu, T; Zhou, J; Yin, Z J

    2015-01-01

    In this study, meat quality traits were compared between Chinese lard- and European lean-type pigs. The association between expression of four genes (ADSL, GARS-AIRS-GART, DGAT1, and DECR1) and meat quality traits was also investigated. Meat quality traits were found to differ significantly between pig breeds. Meat color parameter values (a* and b*) and intramuscular fat content in Anqingliubai were significantly higher than those in Landrace (P < 0.01). Meat pH at 1 and 24 h following slaughter was significantly higher in Landrace than in Wei pigs, and meat inosine monophosphate (IMP) content was significantly higher in Landrace than in Wei and Anqingliubai pigs (both P < 0.01). Expression levels of ADSL, GARS-AIRS-GART, and DGAT1 were higher in longissimus lumborum muscle than in heart or liver tissues. ADSL and GARS-AIRS-GART expression levels were correlated with meat IMP content and pH levels. The results of this study will contribute to the understanding of meat quality traits in Chinese lard- and European lean-type pigs. PMID:26600543

  16. Levels of Expression and Immunogenicity of Attenuated Salmonella enterica Serovar Typhimurium Strains Expressing Escherichia coli Mutant Heat-Labile Enterotoxin

    PubMed Central

    Covone, M. Giuseppina; Brocchi, Marcelo; Palla, Emanuela; da Silveira, W. Dias; Rappuoli, Rino; Galeotti, Cesira L.

    1998-01-01

    The effects of heterologous gene dosage as well as Salmonella typhimurium strain variability on immune response toward both the heterologous antigen, the nontoxic mutant of the Escherichia coli heat-labile enterotoxin LTK63, and the carrier Salmonella strain have been analyzed. Effects of a single integration into the host DNA and different-copy-number episomal vectors were compared in S. typhimurium Δcya Δcrp Δasd strains of two different serotypes, UK-1 and SR-11. Expression of the enterotoxin in the different Salmonella isolates in vitro was found to vary considerably and, for the episomal vectors, to correlate with the plasmid copy number. LTK63-specific serum immunoglobulin G (IgG) and mucosal immunoglobulin A (IgA) antibodies were highest in mice immunized with the high-level-expression strain. High anti-LTK63 IgG and IgA titers were found to correspond to higher anti-Salmonella immunity, suggesting that LTK63 exerts an adjuvant effect on response to the carrier. Statistically significant differences in anti-LTK63 immune response were observed between groups of mice immunized with the attenuated Δcya Δcrp UK-1 and SR-11 derivatives producing the antigen at the same rate. These data indicate that the same attenuation in S. typhimurium strains of different genetic backgrounds can influence significantly the immune response toward the heterologous antigen. Moreover, delivery of the LTK63 enterotoxin to the immune system by attenuated S. typhimurium strains is effective only when synthesis of the antigen is very high during the initial phase of invasion, while persistence of the S. typhimurium strain in deep tissues has only marginal influence. PMID:9423862

  17. Does Domain Knowledge Moderate Involvement of Working Memory Capacity in Higher-Level Cognition? A Test of Three Models

    ERIC Educational Resources Information Center

    Hambrick, D.Z.; Oswald, F.L.

    2005-01-01

    Research suggests that both working memory capacity and domain knowledge contribute to individual differences in higher-level cognition. This study evaluated three hypotheses concerning the interplay between these factors. The compensation hypothesis predicts that domain knowledge attenuates the influence of working memory capacity on higher-level…

  18. The Internationalization of Canadian University Research: A Global Higher Education Matrix Analysis of Multi-Level Governance

    ERIC Educational Resources Information Center

    Jones, Glen A.; Oleksiyenko, Anatoly

    2011-01-01

    To date, much of the research on internationalization and globalization of higher education has focused on the institution or higher education system as the unit of analysis. Institution based studies have focused on the analysis of institutional practices and policies designed to further internationalization. System-level studies focus on state…

  19. Baseline corticosterone levels are higher in migrating than sedentary common blackbirds in autumn, but not in spring.

    PubMed

    Eikenaar, Cas; Müller, Florian; Klinner, Thomas; Bairlein, Franz

    2015-12-01

    Corticosterone at baseline levels is thought to be mainly involved in the regulation of uptake, storage and release of energy, processes central to avian migration. Consequently, corticosterone levels are thought to be upregulated during migration, but the temporal pattern of its secretion during migration is not well defined. For example, although it appears that corticosterone levels decrease from flight to stopover, it is unknown if levels at stopover are still elevated and it is largely unclear how these levels compare to non-migratory life-history stages. Furthermore, what role corticosterone plays in crucial migratory processes, such as refueling and departure from stopover, is far from understood. We here determined baseline corticosterone levels in migrating and resident common blackbirds (Turdus merula), sampled simultaneously on Helgoland, a stopover site that also supports a sedentary breeding population. In autumn, migrants had higher corticosterone levels than residents, but in spring levels did not differ between the two groups. Corticosterone levels of migrants were very similar in spring and autumn, whereas in residents levels tended to be higher in spring than autumn. Higher levels in residents in spring than autumn most likely reflect the higher daily workload faced by birds during the pre-breeding than the post-breeding period. Our study thus indicates that, relative to the levels observed in residents in autumn, in spring baseline corticosterone levels were moderately elevated in both migrants and residents and that in autumn levels were moderately elevated in migrants only. Currently, corticosterone's main function at stopover is thought to lie in the regulation of departure. Because most migrant blackbirds stay only one or two days on Helgoland, our results are in line with this idea and suggest that migrating blackbirds up-regulated their corticosterone level in anticipation of an oncoming flight bout. PMID:26163918

  20. 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…

  1. Nonresident Enrollment Demand in Public Higher Education: An Analysis at National, State, and Institutional Levels

    ERIC Educational Resources Information Center

    Zhang, Liang

    2007-01-01

    This article estimates the standard demand equations for nonresident students using national, state, and institutional level data. The national-level analysis reveals a near-unitary price elasticity, but increases in nonresident tuition and fees do not decrease nonresident enrollment. Finally, results from the institutional level of analysis…

  2. Evaluating the Level of Degree Programmes in Higher Education: The Case of Nursing

    ERIC Educational Resources Information Center

    Rexwinkel, Trudy; Haenen, Jacques; Pilot, Albert

    2013-01-01

    The European Quality Assurance system demands that the degree programme level is represented in terms of quantitative outcomes to be valid and reliable. To meet this need the Educational Level Evaluator (ELE) was devised. This conceptually designed procedure with instrumentation aiming to evaluate the level of a degree validly and reliably still…

  3. Mentoring the Organization: Helping Principals Bring Schools to Higher Levels of Effectiveness

    ERIC Educational Resources Information Center

    Kelehear, Zach

    2003-01-01

    Drawing on the work of Frances Fuller's stages of concern, David Hunt's conceptual levels, and Jean Piaget's model of equilibration, a new view of principal leadership is presented. By attending to the preferred learning style of a group, taking into account the level of stress present as a result of initiatives, and listening to the level of…

  4. Level of Aspiration: A Behavioral Expression of Self-Concept.

    ERIC Educational Resources Information Center

    Kay, Richard S.; Felker, Donald W.

    The present study was designed to investigate the role of expectations in self-concept and level of aspiration (LOA) behavior. Specifically, the focus was to investigate self-concept and LOA as covariates and to describe the nature of the relationship if, in fact, one existed. A sample of 80 third and fourth grade students was selected from three…

  5. A Comparative Study of Student Satisfaction Level in Distance Learning and Live Classroom at Higher Education Level

    ERIC Educational Resources Information Center

    Mahmood, Azhar; Mahmood, Sheikh Tariq; Malik, Allah Bakhsh

    2012-01-01

    The technology has embraced the innovative learning methodologies. Distance Learning has taken the place of traditional face-to-face educational environment. The purpose of this study was to compare the level of student satisfaction of graduate distance learning educational psychology course to a traditional classroom educational psychology course…

  6. Antioxidative stress proteins and their gene expression in brown trout (Salmo trutta) from three rivers with different heavy metal levels.

    PubMed

    Hansen, B H; Rømma, S; Garmo, Ø A; Olsvik, P A; Andersen, R A

    2006-07-01

    Three populations of brown trout (Salmo trutta) exposed to different metal levels in their natural environments, were studied with respect to antioxidants metallothionein (MT), superoxide dismutase (SOD) and catalase (CAT) as well as for corresponding mRNA levels. In addition, mRNA levels were studied for glutathione peroxidase (GPx) and glutathione reductase (GR). The Cd/Zn-exposed trout (Naustebekken River) had higher accumulated levels of Cd, Cu and Zn in gills, and higher levels of MT (both protein and mRNA) in liver and kidney as well as in gills compared to the Cu-exposed trout (Rugla River) and trout from an uncontaminated reference river (Stribekken River). Less MT found in the Cu-exposed trout may increase susceptibility to oxidative stress, but no higher levels of antioxidant mRNAs were found in gills of these trouts. The data indicated that chronic exposures of brown trout to Cd, Zn and/or Cu did not involve maintenance of high activities of SOD and CAT enzymes in gills, although SOD mRNA levels were higher in the Cd/Zn-exposed trout. In livers, mRNA levels of SOD, CAT and GPx were higher in the metal-exposed trout, but in the case of GR this was only seen in kidneys of Cd/Zn-exposed trout. However, both metal-exposed groups had higher activities of SOD enzyme in liver compared to the unexposed reference trout, and CAT activity was found to be higher in kidneys of Cu-exposed trout. The Cu-exposed trout did not seem to rely on MT production to avoid Cu toxicity in gills, but rather by keeping the Cu uptake at a low level. A coordinated expression of different stress genes may also be important in chronic metal exposure. It may be concluded that the observed metal effects relies on acclimation rather than on genetic adaptation in the metal exposed populations. PMID:16616685

  7. 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

  8. Was Rumpelstiltskin Robbed? Using Fairy Tales to Promote Higher Level Thinking Skills.

    ERIC Educational Resources Information Center

    Rycik, Mary Taylor; Rycik, James A.

    1990-01-01

    Recommends using fairy tales to help students use higher-order thinking skills. Offers reading activities designed to promote analysis, synthesis, and evaluation while preserving the magic and fun of fairy tales. (MG)

  9. Expression System for High Levels of GAG Lyase Gene Expression and Study of the hepA Upstream Region in Flavobacterium heparinum

    PubMed Central

    Blain, Françoise; Tkalec, A. Lydia; Shao, Zhongqi; Poulin, Catherine; Pedneault, Marc; Gu, Kangfu; Eggimann, Bernhard; Zimmermann, Joe; Su, Hongsheng

    2002-01-01

    A system for high-level expression of heparinase I, heparinase II, heparinase III, chondroitinase AC, and chondroitinase B in Flavobacterium heparinum is described. hepA, along with its regulatory region, as well as hepB, hepC, cslA, and cslB, cloned downstream of the hepA regulatory region, was integrated in the chromosome to yield stable transconjugant strains. The level of heparinase I and II expression from the transconjugant strains was approximately fivefold higher, while heparinase III expression was 10-fold higher than in wild-type F. heparinum grown in heparin-only medium. The chondroitinase AC and B transconjugant strains, grown in heparin-only medium, yielded 20- and 13-fold increases, respectively, in chondroitinase AC and B expression, compared to wild-type F. heparinum grown in chondroitin sulfate A-only medium. The hepA upstream region was also studied using cslA as a reporter gene, and the transcriptional start site was determined to be 26 bp upstream of the start codon in the chondroitinase AC transconjugant strain. The transcriptional start sites were determined for hepA in both the wild-type F. heparinum and heparinase I transconjugant strains and were shown to be the same as in the chondroitinase AC transconjugant strain. The five GAG lyases were purified from these transconjugant strains and shown to be identical to their wild-type counterparts. PMID:12029040

  10. Expression system for high levels of GAG lyase gene expression and study of the hepA upstream region in Flavobacterium heparinum.

    PubMed

    Blain, Françoise; Tkalec, A Lydia; Shao, Zhongqi; Poulin, Catherine; Pedneault, Marc; Gu, Kangfu; Eggimann, Bernhard; Zimmermann, Joe; Su, Hongsheng

    2002-06-01

    A system for high-level expression of heparinase I, heparinase II, heparinase III, chondroitinase AC, and chondroitinase B in Flavobacterium heparinum is described. hepA, along with its regulatory region, as well as hepB, hepC, cslA, and cslB, cloned downstream of the hepA regulatory region, was integrated in the chromosome to yield stable transconjugant strains. The level of heparinase I and II expression from the transconjugant strains was approximately fivefold higher, while heparinase III expression was 10-fold higher than in wild-type F. heparinum grown in heparin-only medium. The chondroitinase AC and B transconjugant strains, grown in heparin-only medium, yielded 20- and 13-fold increases, respectively, in chondroitinase AC and B expression, compared to wild-type F. heparinum grown in chondroitin sulfate A-only medium. The hepA upstream region was also studied using cslA as a reporter gene, and the transcriptional start site was determined to be 26 bp upstream of the start codon in the chondroitinase AC transconjugant strain. The transcriptional start sites were determined for hepA in both the wild-type F. heparinum and heparinase I transconjugant strains and were shown to be the same as in the chondroitinase AC transconjugant strain. The five GAG lyases were purified from these transconjugant strains and shown to be identical to their wild-type counterparts. PMID:12029040

  11. Expression of FOXO6 is Associated With Oxidative Stress Level and Predicts the Prognosis in Hepatocellular Cancer: A Comparative Study.

    PubMed

    Chen, Hai-Yong; Chen, Yao-Min; Wu, Jian; Yang, Fu-Chun; Lv, Zhen; Xu, Xiao-Feng; Zheng, Shu-Sen

    2016-05-01

    The aim of this study was to explore the association of Forkhead box O6 (FOXO6) expression with oxidative stress level and prognosis of hepatocellular cancer (HCC).The case group included tissues of HCC from 128 patients who were hospitalized in Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery of First Affiliated Hospital, School of Medicine, Zhejiang University. The control group included normal liver tissues from 74 patients. RT-PCR and Western blot were used to test expressions of FOXO6, heme oxygenase (HO)-1, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). Dihydroethidium (DHE) was dyed to observe reactive oxygen species (ROS) level. Immunohistochemistry was used to test FOXO6 expression. FOXO6 was silenced in HepG2 cells to detect cell proliferation and apoptosis. The expressions of ROS, HO-1, GPx, SOD, CAT, p27, and cyclin D1 were also detected to further explore the possible mechanism.The expressions of FOXO6, HO-1, GPx, SOD, and CAT in HCC tissue was significantly higher than those in normal and adjacent HCC tissues (P <0.05). The tumor size, TNM stage, Alpha-fetoprotein (AFP) level, the presence or absence of hepatitis B surface antigen (HbsAg), and differentiation degree were related to FOXO6 expression level (all P <0.05). COX analysis showed that high FOXO6 expression, male, positive HBsAg, advanced TNM staging, high expression of AFP, and low degree of differentiation were all risk factors for prognosis in HCC (P <0.05). Compared with the blank group (C group, without transfection) and the negative control (NC) group, the mRNA expressions of ROS, FOXO6, HO-1, SOD, GPx, and CAT were decreased (P <0.05). si-RNA group had significantly decreased proliferation speed during 24 to 72 hours (P <0.05), whereas si-FOXO6 group had remarkably increased G0/G1 staged cells and decreased S-staged cells (P <0.05). The si-FOXO6 group showed notably increased apoptosis rate (P <0.05) and p27

  12. Bisphenol a influences blastocyst implantation via regulating integrin β3 and trophinin expression levels

    PubMed Central

    Pan, Xiaoyan; Wang, Xiyan; Wang, Zhengchao; Wang, Xuenan; Dou, Zhaohua; Li, Zhixin

    2015-01-01

    Objective: This study is to investigate effects of bisphenol A (BPA) on the blastocyst implantation in endometrium. Methods: Pregnant mice were orally administered with BPA. Implantation sites were examined, and serum estrogen level was assayed with ELISA. Protein expression levels were detected with immunohistochemistry and immunofluorescence staining. Results: High doses (400 and 600 mg/kg/day) of BPA remarkably reduced the implantation sites in the pregnant mice. No significant differences were observed in the serum estrogen level across the groups. Moreover, high doses (400 and 600 mg/kg/day) of BPA significantly declined the expression level of endometrial estrogen receptor α (ERα) in the pregnant mice. In addition, high doses (400 and 600 mg/kg/day) of BPA significantly declined the expression levels of integrin β3 and trophinin in the endometrium and blastocysts. Conclusion: BPA declines ERα expression in endometrium, and inhibits adhesion protein expression in endometrium and blastocysts, causing the adhesion failure of blastocyst implantation. PMID:26884915

  13. High-level expression and characterization of a chimeric lipase from Rhizopus oryzae for biodiesel production

    PubMed Central

    2013-01-01

    Background Production of biodiesel from non-edible oils is receiving increasing attention. Tung oil, called “China wood oil” is one kind of promising non-edible biodiesel oil in China. To our knowledge, tung oil has not been used to produce biodiesel by enzymatic method. The enzymatic production of biodiesel has been investigated extensively by using Rhizopus oryzae lipase as catalyst. However, the high cost of R. oryzae lipase remains a barrier for its industrial applications. Through different heterologous expression strategies and fermentation techniques, the highest expression level of the lipase from R. oryzae reached 1334 U/mL in Pichia pastoris, which is still not optimistic for industry applications. Results The prosequence of lipases from Rhizopus sp. is very important for the folding and secretion of an active lipase. A chimeric lipase from R. oryzae was constructed by replacing the prosequence with that from the R. chinensis lipase and expressed in P. pastoris. The maximum activity of the chimera reached 4050 U/mL, which was 11 fold higher than that of the parent. The properties of the chimera were studied. The immobilized chimera was used successfully for biodiesel production from tung oil, which achieved higher FAME yield compared with the free chimeric lipase, non-chimeric lipase and mature lipase. By response surface methodology, three variables, water content, methanol to tung oil molar ratio and enzyme dosage were proved to be crucial parameters for biosynthesis of FAME and the FAME yield reached 91.9±2.5% at the optimized conditions by adding 5.66 wt.% of the initial water based on oil weight, 3.88 of methanol to tung oil molar ratio and 13.24 wt.% of enzyme concentration based on oil weight at 40°C. Conclusions This is the first report on improving the expression level of the lipase from R. oryzae by replacing prosequences. The immobilized chimera was used successfully for biodiesel production from tung oil. Using tung oil as non-edible raw

  14. Understanding the Relative Contributions of Lower-Level Word Processes, Higher-Level Processes, and Working Memory to Reading Comprehension Performance in Proficient Adult Readers

    ERIC Educational Resources Information Center

    Hannon, Brenda

    2012-01-01

    Although a considerable amount of evidence has been amassed regarding the contributions of lower-level word processes, higher-level processes, and working memory to reading comprehension, little is known about the relationships among these sources of individual differences or their relative contributions to reading comprehension performance. This…

  15. Measuring the Quality of Higher Education: Linking Teaching Quality Measures at the Delivery Level to Administrative Measures at the University Level

    ERIC Educational Resources Information Center

    Jones, Sandra

    2003-01-01

    There are a several lenses through which quality in higher education can be viewed. One views quality improvement at the macro or university level, another focuses at the micro or educational-delivery level. One sees quality assessment as an administrative "check-off", the other sees quality as a continuous improvement in educational delivery. One…

  16. A Prototype for the Use of Hypermedia To Foster Higher Level Reasoning in Family and Consumer Education. Final Report.

    ERIC Educational Resources Information Center

    Wisconsin Univ., Madison. Dept of Continuing and Vocational Education.

    This guide outlines a prototype for using hypermedia to help students in secondary-level family and consumer education courses develop higher-level reasoning skills. Chapter 1 examines the nature and potential of hypermedia, with special emphasis on its relevance to family-focused curriculum efforts. The following aspects of designing a local…

  17. Higher Education and Development in South-East Asia. Volume III, Part 1, High-level Manpower for Development.

    ERIC Educational Resources Information Center

    Hunter, Guy

    This document, the first part of the third volume of a study concerned with the role of institutions of higher education in the development of countries in South-East Asia, appraises the high-level manpower needs of the region. The report is divided into two sections: the first includes the major comments on the position of high-level manpower in…

  18. The Relations between Lower and Higher Level Comprehension Skills and Their Role in Prediction of Early Reading Comprehension

    ERIC Educational Resources Information Center

    Silva, Macarena; Cain, Kate

    2015-01-01

    This study of 4- to 6-year-olds had 2 aims: first, to determine how lower level comprehension skills (receptive vocabulary and grammar) and verbal memory support early higher level comprehension skills (inference and literal story comprehension), and second, to establish the predictive power of these skills on subsequent reading comprehension.…

  19. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome

    PubMed Central

    Hurst, Laurence D.; Ghanbarian, Avazeh T.; Forrest, Alistair R. R.; Huminiecki, Lukasz

    2015-01-01

    X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression

  20. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

    PubMed

    Hurst, Laurence D; Ghanbarian, Avazeh T; Forrest, Alistair R R; Huminiecki, Lukasz

    2015-12-01

    X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression

  1. 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…

  2. "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…

  3. Gli2 protein expression level is a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms.

    PubMed

    Sugiyama, Y; Sasajima, J; Mizukami, Y; Koizumi, K; Kawamoto, T; Ono, Y; Karasaki, H; Tanabe, H; Fujiya, M; Kohgo, Y

    2016-06-01

    The hedgehog pathway is known to promote proliferation of pancreatic ductal adenocarcinoma (PDA) and has been shown to restrain tumor progression. To understand how hedgehog causes these effects, we sought to carefully examine protein expression of hedgehog signaling components during different tumor stages. Genetically engineered mice, Pdx1-Cre;LSL-KrasG12D and Pdx1-Cre;LSL-KrasG12D;p53lox/+, were utilized to model distinct phases of tumorigenesis, pancreatic intraepithelial neoplasm (PanIN) and PDA. Human pancreatic specimens of intraductal papillary mucinous neoplasm (IPMN) and PDA were also employed. PanIN and IPMN lesions highly express Sonic Hedgehog, at a level that is slightly higher than that observed in PDA. GLI2 protein is also expressed in both PanIN/IPMN and PDA. Although there was no difference in the nuclear staining, the cytoplasmic GLI2 level in PDA was modest in comparison to that in PanIN/IPMN. Hedgehog interacting protein was strongly expressed in the precursors, whereas the level in PDA was significantly attenuated. There were no differences in expression of Patched1 at early and late stages. Finally, a strong correlation between Sonic Hedgehog and GLI2 staining was found in both human and murine pancreatic tumors. The results indicate that the GLI2 protein level could serve as a feasible marker of ligand-dependent hedgehog activation in pancreatic neoplasms. PMID:27543868

  4. Development Efforts Expanded in Ion Propulsion: Ion Thrusters Developed With Higher Power Levels

    NASA Technical Reports Server (NTRS)

    Patterson, Michael J.; Rawlin, Vincent K.; Sovey, James S.

    2003-01-01

    The NASA Glenn Research Center was the major contributor of 2-kW-class ion thruster technology to the Deep Space 1 mission, which was successfully completed in early 2002. Recently, NASA s Office of Space Science awarded approximately $21 million to Glenn to develop higher power xenon ion propulsion systems for large flagship missions such as outer planet explorers and sample return missions. The project, referred to as NASA's Evolutionary Xenon Thruster (NEXT), is a logical follow-on to the ion propulsion system demonstrated on Deep Space 1. The propulsion system power level for NEXT is expected to be as high as 25 kW, incorporating multiple ion thrusters, each capable of being throttled over a 1- to 6-kW power range. To date, engineering model thrusters have been developed, and performance and plume diagnostics are now being documented. The project team-Glenn, the Jet Propulsion Laboratory, General Dynamics, Boeing Electron Dynamic Devices, the Applied Physics Laboratory, the University of Michigan, and Colorado State University-is in the process of developing hardware for a ground demonstration of the NEXT propulsion system, which comprises a xenon feed system, controllers, multiple thrusters, and power processors. The development program also will include life assessments by tests and analyses, single-string tests of ion thrusters and power systems, and finally, multistring thruster system tests in calendar year 2005. In addition, NASA's Office of Space Science selected Glenn to lead the development of a 25-kW xenon thruster to enable NASA to conduct future missions to the outer planets of Jupiter and beyond, under the High Power Electric Propulsion (HiPEP) program. The development of a 100-kW-class ion propulsion system and power conversion systems are critical components to enable future nuclear-electric propulsion systems. In fiscal year 2003, a team composed of Glenn, the Boeing Company, General Dynamics, the Applied Physics Laboratory, the Naval Research

  5. Object Substitution Masking Induced by Illusory Masks: Evidence for Higher Object-Level Locus of Interference

    ERIC Educational Resources Information Center

    Hirose, Nobuyuki; Osaka, Naoyuki

    2009-01-01

    A briefly presented target can be rendered invisible by a lingering sparse mask that does not even touch it. This form of visual backward masking, called object substitution masking, is thought to occur at the object level of processing. However, it remains unclear whether object-level interference alone produces substitution masking because…

  6. Evaluating the Level of Degree Programmes in Higher Education: Conceptual Design

    ERIC Educational Resources Information Center

    Rexwinkel, Trudy; Haenen, Jacques; Pilot, Albert

    2013-01-01

    Evaluating the level of degree programmes became crucial with the Bologna Agreement in 1999 when European ministers agreed to implement common bachelor's and master's degree programmes and a common system of quality assurance. The European Quality Assurance system demands evaluation of the degree programme level based on valid and…

  7. Gender Disparities in Educational Trajectories in India: Do Females Become More Robust at Higher Levels?

    ERIC Educational Resources Information Center

    Husain, Zakir; Sarkar, Swagata

    2011-01-01

    Studies on educational attainments have tended to focus on attainments at a specific level of education. The change in disparities in attainment over the educational life cycle, however, has been neglected in literature--in India, for instance, the only exceptions are Vaid (2004) and Desai and Kulkarni (2008). This paper uses unit level National…

  8. Phase transitions between lower and higher level management learning in times of crisis: an experimental study based on synergetics.

    PubMed

    Liening, Andreas; Strunk, Guido; Mittelstadt, Ewald

    2013-10-01

    Much has been written about the differences between single- and double-loop learning, or more general between lower level and higher level learning. Especially in times of a fundamental crisis, a transition between lower and higher level learning would be an appropriate reaction to a challenge coming entirely out of the dark. However, so far there is no quantitative method to monitor such a transition. Therefore we introduce theory and methods of synergetics and present results from an experimental study based on the simulation of a crisis within a business simulation game. Hypothesized critical fluctuations - as a marker for so-called phase transitions - have been assessed with permutation entropy. Results show evidence for a phase transition during the crisis, which can be interpreted as a transition between lower and higher level learning. PMID:24011119

  9. Differences in heartbeat awareness among males with higher and lower levels of systolic blood pressure.

    PubMed

    O'Brien, W H; Reid, G J; Jones, K R

    1998-06-01

    Recent empirical findings related to the baroreceptor hypothesis indicate that elevated heart rate, pulse pressure, and blood pressure may dampen exteroception and interoception. We thus predicted that persons with elevated systolic blood pressure would be less able to accurately perceive their heartbeats and profit from feedback training. This study examined the plausibility of this hypothesis by exposing 57 male students (11 with elevated SBP levels and 46 with normotensive SBP levels) to the Whitehead heartbeat perception task with, and without, feedback training. Results indicated that participants with elevated SBP levels were more able to accurately perceive their heartbeats prior to, and after, feedback training. Participants with elevated SBP levels also showed a significant increase in heartbeat perception accuracy when they were provided with feedback training while participants with normotensive blood pressure levels did not show a significant response to feedback training. These findings are interpreted in terms of the ballistic perception model of cardiac awareness. PMID:9641248

  10. 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

  11. Lowering the Cost Barrier to Higher Education for Undocumented Students: A Promising University-Level Intervention

    ERIC Educational Resources Information Center

    Thangasamy, Andrew; Horan, Deborah

    2016-01-01

    Undocumented students, many of Hispanic origin, face among the strictest cost barriers to higher education in the United States. Lack of legal status excludes them from most state and all federal financial aid programs. Furthermore, most states require them to pay out-of-state tuition rates at publicly supported institutions. In a new direction,…

  12. The Validation of Different Kinds of Knowledge at the Higher Education Level

    ERIC Educational Resources Information Center

    Omerzel, Doris Gomezelj; Sirca, Nada Trunk

    2008-01-01

    The creation of a flexible education system, including procedures for the validation of previous education and other forms of knowledge should be one of the objectives of higher education institutions as well as other institutions that are engaged in adult education. To be effective, the system must be developed and implemented in partnership with…

  13. Tensions in Higher Education Leadership: Towards a Multi-Level Model of Leadership Practice

    ERIC Educational Resources Information Center

    Bolden, Richard; Petrov, Georgy; Gosling, Jonathan

    2008-01-01

    UK higher education is undergoing a period of significant change that generates a series of tensions and difficulties for universities and university leaders. This paper explores these tensions through analysis of findings from a study comprising 152 semi-structured face-to-face interviews in 12 UK universities. Building on from theories of…

  14. An Assessment of Anxiety Levels in Dyslexic Students in Higher Education

    ERIC Educational Resources Information Center

    Carroll, Julia M.; Iles, Jane E.

    2006-01-01

    Background: It has long been hypothesized that children with learning disabilities, including dyslexia, may be highly vulnerable to emotional consequences such as anxiety. However, research has centred on school-aged children. Aims: The present study aimed to clarify these findings with dyslexic students in higher education. Samples: Sixteen…

  15. Internal and External Influences on Program-Level Curriculum Development in Higher Education Fashion Merchandising Programs

    ERIC Educational Resources Information Center

    King, Janice E.

    2010-01-01

    In an ever changing global economy, higher education experiences accountability issues in educating the workforce. Graduates require the knowledge and skills necessary to succeed in the global workplace. For graduates to have the opportunity to attain this understanding and expertise, it is critical to identify what influences curriculum…

  16. New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women

    PubMed Central

    2011-01-01

    Background Vaspin and omentin are recently described molecules that belong to the adipokine family and seem to be related to metabolic risk factors. The objectives of this study were twofold: to evaluate vaspin and omentin circulating levels and mRNA expression in subcutaneous and visceral adipose tissues in non-diabetic morbidly obese women; and to assess the relationship of vaspin and omentin with anthropometric and metabolic parameters, and other adipo/cytokines. Design We analysed vaspin and omentin circulating levels in 71 women of European descent (40 morbidly obese [BMI ≥ 40 kg/m2] and 31 lean [BMI ≤ 25]). We assessed vaspin and omentin gene expression in paired samples of visceral and subcutaneous abdominal adipose tissue from 46 women: 40 morbidly obese and 6 lean. We determined serum vaspin and plasma omentin levels with an Enzyme-Linked Immunosorbent Assay and adipose tissue mRNA expression by real time RT-PCR. Results Serum vaspin levels in the morbidly obese were not significantly different from those in controls. They correlated inversely with levels of lipocalin 2 and interleukin 6. Vaspin mRNA expression was significantly higher in the morbidly obese, in both subcutaneous and visceral adipose tissue. Plasma omentin levels were significantly lower in the morbidly obese and they correlated inversely with glucidic metabolism parameters. Omentin circulating levels, then, correlated inversely with the metabolic syndrome (MS). Omentin expression in visceral adipose tissue was significantly lower in morbidly obese women than in controls. Conclusions The present study indicates that vaspin may have a compensatory role in the underlying inflammation of obesity. Decreased omentin circulating levels have a close association with MS in morbidly obese women. PMID:21526992

  17. 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

  18. 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

  19. Morphology, sex steroid level and gene expression analysis in gonadal sex reversal of triploid female (XXX) rainbow trout (Oncorhynchus mykiss).

    PubMed

    Xu, Gefeng; Huang, Tianqing; Jin, Xian; Cui, Cunhe; Li, Depeng; Sun, Cong; Han, Ying; Mu, Zhenbo

    2016-02-01

    In non-mammalian vertebrates, estrogens and expressions of cyp19a1 and foxl2 play critical roles in maintaining ovary differentiation and development, while dmrt1 and sox9 are male-specific genes in testicular differentiation and are highly conserved. In order to deeply understand the morphological change, sex steroids level and molecular mechanism of triploid female gonadal reversal in rainbow trout, we studied the ovary morphology, tendency of estradiol-17β (E2) and testosterone (T) levels and the relative expressions of dmrt1, cyp19a1, sox9 and foxl2 in juvenile and adult fish. Our results demonstrated that the development of triploid female gonads in rainbow trout went through arrested development, oocytes dedifferentiation, ovary reconstruction and sex reversal finally. During early gonadal development (154-334 days post-fertilization), the expressions of foxl2 and cyp19a1 increased linearly, while expressions of dmrt1 and sox9 were extremely suppressed, and E2 level was higher, while T level was lower. During the mid-to-late period of triploid female gonadal development (574-964 days post-fertilization), the expressions of dmrt1 and sox9 remained high and were very close to the quantity of diploid male genes, and T levels were even reaching diploid male plasma concentrations, while expressions of cyp19a1 and foxl2 were decreased, leading to decrease in E2 level. We realized that the development model of rainbow trout triploid female gonads was extremely rare, and the regulatory mechanism was very special. Genes involved in gonadal development and endogenous estrogens are pivotal factors in fish natural sex reversal. PMID:26373423

  20. Exposure to Bisphenol AF disrupts sex hormone levels and vitellogenin expression in zebrafish.

    PubMed

    Yang, Xiaoxi; Liu, Yuchen; Li, Jia; Chen, Minjie; Peng, Di; Liang, Yong; Song, Maoyong; Zhang, Jie; Jiang, Guibin

    2016-03-01

    Bisphenol AF (BPAF) is widely used in food-contact products, electronic devices, and as a cross-linking reagent in fluoroelastomers. There are growing concerns about its toxicity and endocrine-disrupting effects based on its structural similarity with bisphenol A (BPA). The endocrine-disrupting effects of BPAF were studied by exposing 2-month-old zebrafish to 0, 0.05, 0.25, or 1 mg/L BPAF for 28 days and evaluating the effect on growth, histopathology, hormone levels, enzyme activity, and gene expression. The overall fitness was not significantly affected. There were no apparent alterations in the gills and intestine tissues of both sexes after BPAF exposure. However, exposure to 1 mg/L BPAF caused damage to the liver in the male fish, characterized by hepatocellular swelling and vacuolation. There was no obvious effect in the liver of female fish, suggesting that the hepatic toxicity of BPAF is gender dependent. Gonadal examination indicated that exposure to 1 mg/L BPAF caused induction of acellular areas in the testis and retardation of oocyte development in the ovary. BPAF exposure increased free triiodothyronine levels of females in a dose-dependent manner. In males, the testosterone levels decreased in a concentration-dependent manner. In contrast, estradiol levels increased in a concentration-dependent manner and were significantly higher in males exposed to 1 mg/L BPAF compared with the controls. In females, 0.05 and 0.25 mg/L BPAF caused an increase in testosterone levels. Furthermore, the estradiol levels increased in females exposed to 0.05 and 1 mg/L. We observed an upregulation of hepatic vitellogenin in both sexes and significantly higher levels in males exposed to 1 mg/L BPAF and females exposed to 0.25 mg/L BPAF, suggesting that BPAF has an estrogenic activity. Our results indicate that BPAF is an endocrine-disrupting chemical that exerts reproductive toxicity and estrogenic effects on zebrafish. PMID:25213402

  1. Endogenous galectin-3 expression levels modulate immune responses in galectin-3 transgenic mice.

    PubMed

    Chaudhari, Aparna D; Gude, Rajiv P; Kalraiya, Rajiv D; Chiplunkar, Shubhada V

    2015-12-01

    Galectin-3 (Gal-3), a β-galactoside-binding mammalian lectin, is involved in cancer progression and metastasis. However, there is an unmet need to identify the underlying mechanisms of cancer metastasis mediated by endogenous host galectin-3. Galectin-3 is also known to be an important regulator of immune responses. The present study was aimed at analysing how expression of endogenous galectin-3 regulates host immunity and lung metastasis in B16F10 murine melanoma model. Transgenic Gal-3(+/-) (hemizygous) and Gal-3(-/-) (null) mice exhibited decreased levels of Natural Killer (NK) cells and lower NK mediated cytotoxicity against YAC-1 tumor targets, compared to Gal-3(+/+) (wild-type) mice. On stimulation, Gal-3(+/-) and Gal-3(-/-) mice splenocytes showed increased T cell proliferation than Gal-3(+/+) mice. Intracellular calcium flux was found to be lower in activated T cells of Gal-3(-/-) mice as compared to T cells from Gal-3(+/+) and Gal-3(+/-) mice. In Gal-3(-/-) mice, serum Th1, Th2 and Th17 cytokine levels were found to be lowest, exhibiting dysregulation of pro-inflammatory and anti-inflammatory cytokines balance. Marked decrease in serum IFN-γ levels and splenic IFN-γR1 (IFN-γ Receptor 1) expressing T and NK cell percentages were observed in Gal-3(-/-) mice. On recombinant IFN-γ treatment of splenocytes in vitro, Suppressor of Cytokine Signaling (SOCS) 1 and SOCS3 protein expression was higher in Gal-3(-/-) mice compared to that in Gal-3(+/+) and Gal-3(+/-) mice; suggesting possible attenuation of Signal Transducer and Activator of Transcription (STAT) 1 mediated IFN-γ signaling in Gal-3(-/-) mice. The ability of B16F10 melanoma cells to form metastatic colonies in the lungs of Gal-3(+/+) and Gal-3(-/-) mice remained comparable, whereas it was found to be reduced in Gal-3(+/-) mice. Our data indicates that complete absence of endogenous host galectin-3 facilitates lung metastasis of B16F10 cells in mice, which may be contributed by dysregulated immune

  2. Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides

    PubMed Central

    Bach-Mizrachi, H; Underwood, MD; Tin, A; Ellis, SP; Mann, JJ; Arango, V

    2008-01-01

    Deficient levels of serotonin are associated with suicide and depression. Paradoxically, in the dorsal raphe nucleus (DRN) there are more serotonin neurons and more neuronal tryptophan hydroxylase-2 (TPH2) expression postmortem in depressed suicides. In this study, we sought to determine whether greater TPH2 expression in depressed suicides was the result of more TPH2 expression per neuron. In situ hybridization and computer-assisted image analysis were performed on tissue sections throughout the extent of the raphe nuclei at the level of silver grains per neuron to systematically quantify TPH2 neuronal expression. Depressed suicides have 26.5% more TPH2 grain density per neuron in the DRN compared with matched controls (P= 0.04). The difference in grain density is greater at mid- and caudal anatomical levels across the rostrocaudal axis of the DRN. Densitometric analysis of TPH2 expression in the DRN subnuclei showed that higher expression levels were observed at posterior anatomical levels of depressed suicides (121% of control in the caudal subnucleus). Higher TPH2 expression in depressed suicides may explain more TPH2 protein and reflect a homeostatic response to deficient serotonin levels in the brains of depressed suicides. Localized changes in TPH2 expression in specific subnuclei of the DRN suggest that the serotonergic compensatory mechanism in depression and suicide is specifically regulated within the DRN and has implications for regions innervated by this subnucleus. PMID:18180753

  3. 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

  4. Forced chromatin looping raises fetal hemoglobin in adult sickle cells to higher levels than pharmacologic inducers.

    PubMed

    Breda, Laura; Motta, Irene; Lourenco, Silvia; Gemmo, Chiara; Deng, Wulan; Rupon, Jeremy W; Abdulmalik, Osheiza Y; Manwani, Deepa; Blobel, Gerd A; Rivella, Stefano

    2016-08-25

    Overcoming the silencing of the fetal γ-globin gene has been a long-standing goal in the treatment of sickle cell disease (SCD). The major transcriptional enhancer of the β-globin locus, called the locus control region (LCR), dynamically interacts with the developmental stage-appropriate β-type globin genes via chromatin looping, a process requiring the protein Ldb1. In adult erythroid cells, the LCR can be redirected from the adult β- to the fetal γ-globin promoter by tethering Ldb1 to the human γ-globin promoter with custom-designed zinc finger (ZF) proteins (ZF-Ldb1), leading to reactivation of γ-globin gene expression. To compare this approach to pharmacologic reactivation of fetal hemoglobin (HbF), hematopoietic cells from patients with SCD were treated with a lentivirus expressing the ZF-Ldb1 or with chemical HbF inducers. The HbF increase in cells treated with ZF-Ldb1 was more than double that observed with decitabine and pomalidomide; butyrate had an intermediate effect whereas tranylcypromine and hydroxyurea showed relatively low HbF reactivation. ZF-Ldb1 showed comparatively little toxicity, and reduced sickle hemoglobin (HbS) synthesis as well as sickling of SCD erythroid cells under hypoxic conditions. The efficacy and low cytotoxicity of lentiviral-mediated ZF-Ldb1 gene transfer compared with the drug regimens support its therapeutic potential for the treatment of SCD. PMID:27405777

  5. Sea level higher than present 3500 years ago on the northern main Hawaiian Islands

    NASA Astrophysics Data System (ADS)

    Grossman, Eric E.; Fletcher, Charles H., III

    1998-04-01

    New data from an emerged coastal bench and associated fossil beach on Kapapa Island (Oahu), Hawaii, preserve a detailed history of middle to late Holocene sea level. These include 29 new calibrated radiocarbon ages and elevations indicating mean sea level reached a maximum position of 2.00 ± 0.35 m ca. 3500 yr B.P. These results correlate with additional evidence from Hawaii and other Pacific islands and provide constraints on Oahu's long-term uplift rate (0.03 0.07 mm/yr), previously based solely on Pleistocene age shorelines. Our sea-level reconstruction is consistent with geophysical model predictions of Earth's geoid response to the last deglaciation and with observations of increased Antarctic ice volume during the late Holocene.

  6. Projected Carbon Dioxide to Increase Grass Pollen and Allergen Exposure Despite Higher Ozone Levels

    PubMed Central

    Albertine, Jennifer M.; Manning, William J.; DaCosta, Michelle; Stinson, Kristina A.; Muilenberg, Michael L.; Rogers, Christine A.

    2014-01-01

    One expected effect of climate change on human health is increasing allergic and asthmatic symptoms through changes in pollen biology. Allergic diseases have a large impact on human health globally, with 10–30% of the population affected by allergic rhinitis and more than 300 million affected by asthma. Pollen from grass species, which are highly allergenic and occur worldwide, elicits allergic responses in 20% of the general population and 40% of atopic individuals. Here we examine the effects of elevated levels of two greenhouse gases, carbon dioxide (CO2), a growth and reproductive stimulator of plants, and ozone (O3), a repressor, on pollen and allergen production in Timothy grass (Phleum pratense L.). We conducted a fully factorial experiment in which plants were grown at ambient and/or elevated levels of O3 and CO2, to simulate present and projected levels of both gases and their potential interactive effects. We captured and counted pollen from flowers in each treatment and assayed for concentrations of the allergen protein, Phl p 5. We found that elevated levels of CO2 increased the amount of grass pollen produced by ∼50% per flower, regardless of O3 levels. Elevated O3 significantly reduced the Phl p 5 content of the pollen but the net effect of rising pollen numbers with elevated CO2 indicate increased allergen exposure under elevated levels of both greenhouse gases. Using quantitative estimates of increased pollen production and number of flowering plants per treatment, we estimated that airborne grass pollen concentrations will increase in the future up to ∼200%. Due to the widespread existence of grasses and the particular importance of P. pratense in eliciting allergic responses, our findings provide evidence for significant impacts on human health worldwide as a result of future climate change. PMID:25372614

  7. Modeling Coastal Erosion, Passive Inundation, and Dynamic Wave Inundation under Higher Sea Level in Hawaii

    NASA Astrophysics Data System (ADS)

    Anderson, T. R.

    2015-12-01

    Hawaii State legislators recently formed the Interagency Committee on Climate Adaptation to investigate community vulnerability to sea level rise. We developed modeling to provide the committee with assessments of exposure to coastal erosion, wave inundation, and passive flooding based on the IPCC RCP 8.5 model of sea level rise over the 21st Century. We model the exposure to coastal erosion using a hybrid equilibrium profile model (Anderson et al., 2015) that combines historical rates of shoreline change with a Bruun-type model of beach profile translation. Results are mapped in a GIS showing the 80th percentile probability of potential erosion at years 2030, 2050, 2075, and 2100. Wave inundation is modeled using XBeach. We use a 3 m significant wave height to represent a seasonal high swell event. A separate simulation was run for each heightened sea level (corresponding to the years previously mentioned); which accounts for changes in wave dynamics due to the change in water level over the reef platform. We use a bare earth topo/bathy LiDAR DEM derived from data collected during the 2013 JBLTX survey of the Hawaiian Islands. XBeach modeling is done along one-dimensional profiles spaced 20 m apart. From this, we develop a gridded product of water depth and velocity for use in a vulnerability analysis. Passive inundation due to sea level rise, the so-called "bath tub" method, provide estimates of storm drain flooding and groundwater inundation. Our analysis of these three impacts of sea level rise, combined - coastal erosion, wave inundation, and passive flooding - are used with other available data in the FEMA Hazus software to estimate exposure and loss of upland assets.

  8. HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation.

    PubMed

    Petersdorf, Effie W; Gooley, Theodore A; Malkki, Mari; Bacigalupo, Andrea P; Cesbron, Anne; Du Toit, Ernette; Ehninger, Gerhard; Egeland, Torstein; Fischer, Gottfried F; Gervais, Thibaut; Haagenson, Michael D; Horowitz, Mary M; Hsu, Katharine; Jindra, Pavel; Madrigal, Alejandro; Oudshoorn, Machteld; Ringdén, Olle; Schroeder, Marlis L; Spellman, Stephen R; Tiercy, Jean-Marie; Velardi, Andrea; Witt, Campbell S; O'Huigin, Colm; Apps, Richard; Carrington, Mary

    2014-12-18

    Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease. PMID:25323824

  9. HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation

    PubMed Central

    Gooley, Theodore A.; Malkki, Mari; Bacigalupo, Andrea P.; Cesbron, Anne; Du Toit, Ernette; Ehninger, Gerhard; Egeland, Torstein; Fischer, Gottfried F.; Gervais, Thibaut; Haagenson, Michael D.; Horowitz, Mary M.; Hsu, Katharine; Jindra, Pavel; Madrigal, Alejandro; Oudshoorn, Machteld; Ringdén, Olle; Schroeder, Marlis L.; Spellman, Stephen R.; Tiercy, Jean-Marie; Velardi, Andrea; Witt, Campbell S.; O’Huigin, Colm; Apps, Richard; Carrington, Mary

    2014-01-01

    Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient’s only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients’ and donors’ HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient’s mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient’s mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease. PMID:25323824

  10. Identification of Xenologs and Their Characteristic Low Expression Levels in the Cyanobacterium Synechococcus elongatus.

    PubMed

    Álvarez-Canales, Gilberto; Arellano-Álvarez, Guadalupe; González-Domenech, Carmen M; de la Cruz, Fernando; Moya, Andrés; Delaye, Luis

    2015-06-01

    Horizontal gene transfer (HGT) is a central process in prokaryotic evolution. Once a gene is introduced into a genome by HGT, its contribution to the fitness of the recipient cell depends in part on its expression level. Here we show that in Synechococcus elongatus PCC 7942, xenologs derived from non-cyanobacterial sources exhibited lower expression levels than native genes in the genome. In accord with our observation, xenolog codon adaptation indexes also displayed relatively low expression values. These results are in agreement with previous reports that suggested the relative neutrality of most xenologs. However, we also demonstrated that some of the xenologs detected participated in cellular functions, including iron starvation acclimation and nitrate reduction, which corroborate the role of HGT in bacterial adaptation. For example, the expression levels of some of the xenologs detected are known to increase under iron-limiting conditions. We interpreted the overall pattern as an indication that there is a selection pressure against high expression levels of xenologs. However, when a xenolog protein product confers a selective advantage, natural selection can further modulate its expression level to meet the requirements of the recipient cell. In addition, we show that ORFans did not exhibit significantly lower expression levels than native genes in the genome, which suggested an origin other than xenology. PMID:26040248

  11. Improving Student Oral and Written Communication Skills through the Use of Higher Level Thinking.

    ERIC Educational Resources Information Center

    Kovacevich, Karen; Price, Barbara; Ronna, Vicki; Xanos, Pamela

    This study describes a program designed to increase the communication skills of at-risk students. The targeted population consists of kindergarten through third grade students in two elementary schools in a community in central Illinois. The status of family income ranges from low to high levels. Evidence for the existence of inadequate…

  12. The Effects of Higher Education/Military Service on Achievement Levels of Police Academy Cadets.

    ERIC Educational Resources Information Center

    Johnson, Thomas Allen

    This study compared levels of achievement of three groups of Houston (Texas) police academy cadets: those with no military service but with 60 or more college credit hours, those with military service and 0 hours of college credit, and those with military service and 1 to 59 hours of college credit. Prior to 1991, police cadets in Houston were…

  13. Qualifications at Level 5: Progressing in a Career or to Higher Education. Working Paper No 23

    ERIC Educational Resources Information Center

    Grm, Slava Pevec; Bjørnåvold, Jens

    2014-01-01

    This study addresses qualifications at level 5 of the European qualifications framework (EQF) in 15 countries (Belgium (Flanders), the Czech Republic, Denmark, Estonia, Ireland, France, Croatia, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Austria, Portugal, the United Kingdom (EWNI and Scotland) that had linked their national…

  14. Socioeconomic Status, Higher-Level Mathematics Courses, Absenteeism, and Student Mobility as Indicators of Work Readiness

    ERIC Educational Resources Information Center

    Folds, Lea D.; Tanner, C. Kenneth

    2014-01-01

    The purpose of this study was to analyze the relations among socioeconomic status, highest-level mathematics course, absenteeism, student mobility and measures of work readiness of high school seniors in Georgia. Study participants were 476 high school seniors in one Georgia county. The full regression model explained 27.5% of the variance in…

  15. Genome-Wide Tuning of Protein Expression Levels to Rapidly Engineer Microbial Traits.

    PubMed

    Freed, Emily F; Winkler, James D; Weiss, Sophie J; Garst, Andrew D; Mutalik, Vivek K; Arkin, Adam P; Knight, Rob; Gill, Ryan T

    2015-11-20

    The reliable engineering of biological systems requires quantitative mapping of predictable and context-independent expression over a broad range of protein expression levels. However, current techniques for modifying expression levels are cumbersome and are not amenable to high-throughput approaches. Here we present major improvements to current techniques through the design and construction of E. coli genome-wide libraries using synthetic DNA cassettes that can tune expression over a ∼10(4) range. The cassettes also contain molecular barcodes that are optimized for next-generation sequencing, enabling rapid and quantitative tracking of alleles that have the highest fitness advantage. We show these libraries can be used to determine which genes and expression levels confer greater fitness to E. coli under different growth conditions. PMID:26478262

  16. 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.

  17. 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

  18. 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

  19. Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.

    PubMed

    Sowjanya, A Pavani; Rao, Meera; Vedantham, Haripriya; Kalpana, Basany; Poli, Usha Rani; Marks, Morgan A; Sujatha, M

    2016-01-30

    Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer. PMID:26435258

  20. Expression levels of IL-17 and TNF-α in degenerated lumbar intervertebral discs and their correlation

    PubMed Central

    LIU, XIAO-GANG; HOU, HONG-WEI; LIU, YI-LIN

    2016-01-01

    The present study aimed to investigate the expression and roles of interleukin (IL)-17 and tumor necrosis factor (TNF)-α in intervertebral disc degeneration (IDD) and to identify the association between the effects of IL-17 and TNF-α in IDD. This may increase understanding of the pathogenic mechanism underlying IDD, and aid the development of alternative therapies. The experimental group consisted of 40 samples of nucleus pulposus tissue obtained from the intervertebral discs (IVDs) of patients with IDD by surgical intervention, and was further divided into an annulus fibrosus disrupted group, comprising 18 patients in which the external annulus was ruptured, and an annulus fibrosus intact group comprising 22 patients. The control group consisted of 20 samples of nucleus pulposus tissue from the IVDs of patients with traumatic lumbar disc fractures. The mRNA and protein expression levels of IL-17 and TNF-α in the 50 tissue samples were detected by semi-quantitative reverse transcription polymerase chain reaction and immunohistochemical staining, respectively, and the results were statistically analyzed. The IL-17 and TNF-α protein and mRNA expression levels in the annulus fibrosus disrupted and annulus fibrosus intact groups were both higher compared with those in the control group. In addition, the expression levels of IL-17 and TNF-α in the annulus fibrosus disrupted group were significantly higher compared with those in the annulus fibrosus intact group (P<0.01). A positive correlation was identified between the mRNA and protein expression levels of IL-17 and TNF-α in the experimental group (r=0.957, P<0.01). IL-17 and TNF-α may therefore be involved in the progression of human IDD, and may have synergistic effects in the development of IDD. PMID:27284317

  1. Effects of elevated peroxidase levels and corn earworm feeding on gene expression in tomato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tomato gene arrays were used to investigate how high levels of transgenic peroxidase expression and feeding by the corn earworm, Helicoverpa zea, affected expression of defensive and other genes. High peroxidase activity significantly upregulated proteinase inhibitors and a few other defensive gene...

  2. Higher Prevalence of Obesity in Greek Children Living in Rural Areas Despite Increased Levels of Physical Activity

    PubMed Central

    Tambalis, Konstantinos D.; Panagiotakos, Demosthenes B.; Kavouras, Stavros A.; Papoutsakis, Sofia; Sidossis, Labros S.

    2013-01-01

    Aim The purpose of the present study was to evaluate whether levels of physical activity (PA) and sedentary behaviors could explain observed differences in the prevalence of childhood obesity in a sample of Greek children. Methods Epidemiological study. PA and sedentary behaviors were assessed by a self-administrated physical activity checklist. BMI was calculated from measured weight and height. A representative sample of Greek children aged 10 to 12 years attending fifth and sixth grade (N=3,195), living in rural and urban areas were enrolled. Maturation status was not evaluated due to technical reasons. Results Prevalence of obesity was higher among children living in rural areas as compared with urban areas (12.1% vs. 10.7%, p<0.01). Surprisingly, children living in rural areas had higher levels of self reported PA (p<0.001) and met current PA guidelines to a greater extent than their urban counterparts (p<0.05). Furthermore, boys had higher levels of total, light-to-moderate intensity and vigorous intensity PA (VPA), as well as sedentary behaviors, than girls (all p-values <0.05). Stratified analysis by BMI category revealed that normal weight boys and girls had higher levels of total PA and VPA compared with overweight and obese boys from the same type of setting (all p-values<0.05). Conclusions Children living in rural areas have higher levels of PA and more frequently met PA guidelines than their urban counterparts, despite a higher prevalence of obesity. PMID:23724863

  3. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    SciTech Connect

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-06-25

    Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

  4. High-level expression of Bacillus naganoensis pullulanase from recombinant Escherichia coli with auto-induction: effect of lac operator.

    PubMed

    Nie, Yao; Yan, Wei; Xu, Yan; Chen, Wen Bo; Mu, Xiao Qing; Wang, Xinye; Xiao, Rong

    2013-01-01

    Pullulanase plays an important role in specific hydrolysis of branch points in amylopectin and is generally employed as an important enzyme in starch-processing industry. So far, however, the production level of pullulanase is still somewhat low from wide-type strains and even heterologous expression systems. Here the gene encoding Bacillus naganoensis pullulanase was amplified and cloned. For expression of the protein, two recombinant systems, Escherichia coli BL21(DE3)/pET-20b(+)-pul and E. coli BL21(DE3)/pET-22b(+)-pul, were constructed, both bearing T7 promoter and signal peptide sequence, but different in the existance of lac operator and lacI gene encoding lac repressor. Recombinant pullulanase was initially expressed with the activity of up to 14 U/mL by E. coli BL21(DE3)/pET-20b(+)-pul with IPTG induction in LB medium, but its expression level reduced continually with the extension of cryopreservation time and basal expression was observed. However, E. coli BL21(DE3)/pET-22b(+)-pul , involving lac operator downstream of T7 promoter to regulate foreign gene transcription, exhibited pullulanase activity consistently without detected basal expression. By investigating the effect of lac operator, basal expression of foreign protein was found to cause expression instability and negative effect on production of target protein. Thus double-repression strategy was proposed that lac operators in both chromosome and plasmid were bound with lac repressor to repress T7 RNA polymerase synthesis and target protein expression before induction. Consequently, the total activity of pullulanase was remarkably increased to 580 U/mL with auto-induction by lac operator-involved E. coli BL21(DE3)/pET-22b(+)-pul. When adding 0.6% glycine in culture, the extracellular production of pullulanase was significantly improved with the extracellular activity of 502 U/mL, which is a relatively higher level achieved to date for extracellular production of pullulanase. The successful

  5. High-Level Expression of Bacillus naganoensis Pullulanase from Recombinant Escherichia coli with Auto-Induction: Effect of lac Operator

    PubMed Central

    Xu, Yan; Chen, Wen Bo; Mu, Xiao Qing; Wang, Xinye; Xiao, Rong

    2013-01-01

    Pullulanase plays an important role in specific hydrolysis of branch points in amylopectin and is generally employed as an important enzyme in starch-processing industry. So far, however, the production level of pullulanase is still somewhat low from wide-type strains and even heterologous expression systems. Here the gene encoding Bacillus naganoensis pullulanase was amplified and cloned. For expression of the protein, two recombinant systems, Escherichia coli BL21(DE3)/pET-20b(+)-pul and E. coli BL21(DE3)/pET-22b(+)-pul, were constructed, both bearing T7 promoter and signal peptide sequence, but different in the existance of lac operator and lacI gene encoding lac repressor. Recombinant pullulanase was initially expressed with the activity of up to 14 U/mL by E. coli BL21(DE3)/pET-20b(+)-pul with IPTG induction in LB medium, but its expression level reduced continually with the extension of cryopreservation time and basal expression was observed. However, E. coli BL21(DE3)/pET-22b(+)-pul , involving lac operator downstream of T7 promoter to regulate foreign gene transcription, exhibited pullulanase activity consistently without detected basal expression. By investigating the effect of lac operator, basal expression of foreign protein was found to cause expression instability and negative effect on production of target protein. Thus double-repression strategy was proposed that lac operators in both chromosome and plasmid were bound with lac repressor to repress T7 RNA polymerase synthesis and target protein expression before induction. Consequently, the total activity of pullulanase was remarkably increased to 580 U/mL with auto-induction by lac operator-involved E. coli BL21(DE3)/pET-22b(+)-pul. When adding 0.6% glycine in culture, the extracellular production of pullulanase was significantly improved with the extracellular activity of 502 U/mL, which is a relatively higher level achieved to date for extracellular production of pullulanase. The successful

  6. Codon Optimization Significantly Improves the Expression Level of α -Amylase Gene from Bacillus licheniformis in Pichia pastoris.

    PubMed

    Wang, Jian-Rong; Li, Yang-Yuan; Liu, Dan-Ni; Liu, Jing-Shan; Li, Peng; Chen, Li-Zhi; Xu, Shu-De

    2015-01-01

    α-Amylase as an important industrial enzyme has been widely used in starch processing, detergent, and paper industries. To improve expression efficiency of recombinant α-amylase from Bacillus licheniformis (B. licheniformis), the α-amylase gene from B. licheniformis was optimized according to the codon usage of Pichia pastoris (P. pastoris) and expressed in P. pastoris. Totally, the codons encoding 305 amino acids were optimized in which a total of 328 nucleotides were changed and the G+C content was increased from 47.6 to 49.2%. The recombinants were cultured in 96-deep-well microplates and screened by a new plate assay method. Compared with the wild-type gene, the optimized gene is expressed at a significantly higher level in P. pastoris after methanol induction for 168 h in 5- and 50-L bioreactor with the maximum activity of 8100 and 11000 U/mL, which was 2.31- and 2.62-fold higher than that by wild-type gene. The improved expression level makes the enzyme a good candidate for α-amylase production in industrial use. PMID:26171389

  7. High-level expression and characterization of a thermostable xylanase mutant from Trichoderma reesei in Pichia pastoris.

    PubMed

    Li, Yang-yuan; Zhong, Kai-xin; Hu, Ai-hong; Liu, Dan-ni; Chen, Li-zhi; Xu, Shu-de

    2015-04-01

    A gene encoding xylanase 2 mutant from Trichoderma reesei (T2C/T28C, named mxyn2) was cloned into the Pichia pastoris X33 strain using the vector pPICZαA. Recombinant Mxyn2p was functionally expressed in P. pastoris X33 and secreted into the supernatant. Real time qPCR demonstrated that an increase in gene copy number correlated with higher levels of expression. Supernatant from methanol induced cells was concentrated by ultrafiltration with a 10kDa cut off membrane, and purified with ion exchange chromatography using SP Sepharose Fast Flow chromatography. Recombinant Mxyn2p protein had the highest activity at 75°C, while recombinant protein encoded by the "wild type" xylanase gene xyn2, also expressed in Pichia, was 20°C lower. The Mxyn2p enzyme retained more than 70% of its activity after incubation at 80°C for 10min. The effects of the optimal pH and temperature for higher expression levels in P. pastoris were also determined, 6.0 and 22°C, respectively. The maximum xylanase activity of Mxyn2p was 13,000nkat/mg (9.88g/l) in fed-batch cultivation after 168h induction with methanol in a 50l bioreactor. PMID:25434687

  8. Codon Optimization Significantly Improves the Expression Level of α-Amylase Gene from Bacillus licheniformis in Pichia pastoris

    PubMed Central

    Wang, Jian-Rong; Li, Yang-Yuan; Liu, Dan-Ni; Liu, Jing-Shan; Li, Peng; Chen, Li-Zhi; Xu, Shu-De

    2015-01-01

    α-Amylase as an important industrial enzyme has been widely used in starch processing, detergent, and paper industries. To improve expression efficiency of recombinant α-amylase from Bacillus licheniformis (B. licheniformis), the α-amylase gene from B. licheniformis was optimized according to the codon usage of Pichia pastoris (P. pastoris) and expressed in P. pastoris. Totally, the codons encoding 305 amino acids were optimized in which a total of 328 nucleotides were changed and the G+C content was increased from 47.6 to 49.2%. The recombinants were cultured in 96-deep-well microplates and screened by a new plate assay method. Compared with the wild-type gene, the optimized gene is expressed at a significantly higher level in P. pastoris after methanol induction for 168 h in 5- and 50-L bioreactor with the maximum activity of 8100 and 11000 U/mL, which was 2.31- and 2.62-fold higher than that by wild-type gene. The improved expression level makes the enzyme a good candidate for α-amylase production in industrial use. PMID:26171389

  9. Higher levels of central adiposity in healthy premenopausal women with family histories of premenopausal breast cancer.

    PubMed

    Dettenborn, Lucia; James, Gary D; Britton, Julie A; Bovbjerg, Dana H

    2008-01-01

    Research strongly suggests that lower overall adiposity and higher central adiposity are independent risk factors for premenopausal breast cancer in the general population. We aimed to test the possibility that these factors may contribute to familial risk of premenopausal breast cancer. A convenience sample of healthy women, ages 25-49, was recruited to yield three study groups: (1) Women with first-degree family histories of premenopausal breast cancer, operationally defined as being diagnosed prior to age 50 (Group FH < 50, n = 39); (2) Women with first-degree family histories of postmenopausal breast cancer, operationally defined as being diagnosed at age 50 or after (Group FH > or = 50, n = 33); and (3) Women without a history of breast cancer in first-degree relatives (Group FH-, n = 132). Multinomial logistic regression analyses, including possible confounders, waist circumference, and BMI, revealed a lower BMI among FH < 50 compared to either FH- (OR = 0.72; 95% CI = 0.59-0.87), or FH > or = 50 women (OR = 0.75; 95% CI = 0.60-0.95), and higher waist circumferences in FH < 50 compared to either FH- (OR = 1.15; 95% CI = 1.06-1.25), or FH > or = 50 women (OR = 1.16; 95% CI = 1.05-1.28). No group differences were seen for waist skinfold measures. These results support the possibility that differences in patterns of adiposity may contribute to familial risk of premenopausal breast cancer, and suggest the importance of conducting large scale, population-based studies of the link between body size characteristics and familial breast cancer risk. PMID:18161037

  10. Higher levels of serum lycopene are associated with reduced mortality in individuals with metabolic syndrome.

    PubMed

    Han, Guang-Ming; Meza, Jane L; Soliman, Ghada A; Islam, K M Monirul; Watanabe-Galloway, Shinobu

    2016-05-01

    Metabolic syndrome increases the risk of mortality. Increased oxidative stress and inflammation may play an important role in the high mortality of individuals with metabolic syndrome. Previous studies have suggested that lycopene intake might be related to the reduced oxidative stress and decreased inflammation. Using data from the National Health and Nutrition Examination Survey, we examined the hypothesis that lycopene is associated with mortality among individuals with metabolic syndrome. A total of 2499 participants 20 years and older with metabolic syndrome were divided into 3 groups based on their serum concentration of lycopene using the tertile rank method. The National Health and Nutrition Examination Survey from years 2001 to 2006 was linked to the mortality file for mortality follow-up data through December 31, 2011, to determine the mortality rate and hazard ratios (HR) for the 3 serum lycopene concentration groups. The mean survival time was significantly higher in the group with the highest serum lycopene concentration (120.6 months; 95% confidence interval [CI], 118.8-122.3) and the medium group (116.3 months; 95% CI, 115.2-117.4), compared with the group with lowest serum lycopene concentration (107.4 months; 95% CI, 106.5-108.3). After adjusting for possible confounding factors, participants in the highest (HR, 0.61; P = .0113) and in the second highest (HR, 0.67; P = .0497) serum lycopene concentration groups showed significantly lower HRs of mortality when compared with participants in the lower serum lycopene concentration. The data suggest that higher serum lycopene concentration has a significant association with the reduced risk of mortality among individuals with metabolic syndrome. PMID:27101758

  11. High-level expression of HOXB13 is closely associated with tumor angiogenesis and poor prognosis of hepatocellular carcinoma

    PubMed Central

    Zhu, Jian-Yu; Sun, Qi-Kai; Wang, Wei; Jia, Wei-Dong

    2014-01-01

    Homeobox B13 (HOXB13) is generally considered as a crucial regulator of terminal cellular differentiation. More recently, the absent or aberrant expression of HOXB13 has been increasingly implicated in cancer development and metastasis. However, the expression of HOXB13 in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis and prognosis still remain unclear. The aim of the study was to evaluate the expression of HOXB13 in patients with HCC and explore the relationship of HOXB13 expression with clinicopathologic factors, tumor angiogenesis and prognosis. Immunohistochemistry was performed to determine the expression of HOXB13 in HCC and corresponding paracarcinomatous tissues from 72 patients. Vascular endothelial growth factor (VEGF) and CD31 were only examined in tissues of HCC patients mentioned above. The results showed that HOXB13 expression was significantly (P <0.001) higher in HCC (69.4%) than that in surrounding non-tumor tissues (26.4%), positively correlated with tumor VEGF (P <0.001) and microvessel density (MVD) (P = 0.013). Besides, it was associated with tumor capsula (P <0.001), vascular invasion (P <0.001), Edmondson grade (P <0.001), AFP (P = 0.007) and TNM stage (P <0.001). Univariate analysis showed poorer overall survival (OS) rate and disease free survival (DFS) rate in patients expressing higher levels of HOXB13. HOXB13 was also found to be an independent poor prognostic factor of OS and DFS in multivariate analysis. Taken together, our results suggest that increased HOXB13 expression is associated with tumor angiogenesis and progression in HCC and may function as a promising biomarker for unfavorable prognosis of HCC. PMID:25031711

  12. Low-level laser therapy enhances the expression of osteogenic factors during bone repair in rats.

    PubMed

    Tim, Carla Roberta; Pinto, Karina Nogueira Zambone; Rossi, Bruno Rafael Orsini; Fernandes, Kelly; Matsumoto, Mariza Akemi; Parizotto, Nivaldo Antonio; Rennó, Ana Claudia Muniz

    2014-01-01

    The aim of this study was to evaluate the effects of low-level laser therapy (LLLT) on bone formation, immunoexpression of osteogenic factors, and biomechanical properties in a tibial bone defect model in rats. Sixty male Wistar rats were distributed into bone defect control group (CG) and laser irradiated group (LG). Animals were euthanized on days 15, 30, and 45 post-injury. The histological and morphometric analysis showed that the treated animals presented no inflammatory infiltrate and a better tissue organization at 15 and 30 days postsurgery. Also, a higher amount of newly formed bone was observed at 15 days postsurgery. No statistically significant difference was observed in cyclooxygenase-2 immunoexpression among the groups at 15, 30, and 45 days in the immunohistochemical analysis. Considering RUNX-2, the immunoexpression was statistically higher in the LG compared to the CG at 45 days. BMP-9 immunoexpression was significantly higher in the LG in comparison to CG at day 30. However, there was no expressivity for this immunomarker, both in the CG and LG, at the day 45 postsurgery. No statistically significant difference was observed in the receptor activator of nuclear factor kappa-B ligand immunoexpression among the groups in all periods evaluated. No statistically significant difference among the groups was observed in the maximal load in any period of time. Our findings indicate that laser therapy improved bone healing by accelerating the development of newly formed bone and activating the osteogenic factors on tibial defects, but the biomechanical properties in LG were not improved. PMID:23515631

  13. Higher Reported Levels of Depression, Stress, and Anxiety Are Associated with Increased Endorsement of ADHD Symptoms by Postsecondary Students

    ERIC Educational Resources Information Center

    Harrison, Allyson G.; Alexander, Sandra J.; Armstrong, Irene T.

    2013-01-01

    This study examined the extent to which postsecondary students endorse symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) and whether experienced level of stress, depression, or anxiety are associated with higher reporting of ADHD symptoms. Students attending a combined health and counseling service completed the Conners Adult ADHD Rating…

  14. Assessing the Potential for Openness: A Framework for Examining Course-Level OER Implementation in Higher Education

    ERIC Educational Resources Information Center

    Judith, Kate; Bull, David

    2016-01-01

    The implementation of open educational resources (OER) at the course level in higher education poses numerous challenges to education practitioners--ranging from discoverability challenges to the lack of knowledge on how to best localize and utilize OER as courseware. Drawing on case studies of OER initiatives globally, the article discusses…

  15. Levels of Professional Training of Upper-Division Students in Kuzbass Higher Educational Institutions: A Typological Analysis

    ERIC Educational Resources Information Center

    Urban, O. A.

    2008-01-01

    In this article, the data from a sociological survey serve as the basis for an analysis of the levels of professional training of the graduates of higher educational institutions in the Kuzbass region. The object of this survey consisted of upper-division students in daytime enrollment of colleges and universities in Novokuznetsk, which is not…

  16. Music Students' Perception of the Use of Multi-Media Technology at the Graduate Level in Hong Kong Higher Education

    ERIC Educational Resources Information Center

    Ho, Wai-Chung

    2007-01-01

    The core purpose of this paper is to draw together research issues and concrete problems with the use of multimedia technology at the graduate level in higher music education by examining one university's responses to the challenges posed by the use of multimedia technology as a teaching and learning aid for music education. Between June and July…

  17. Workforce Diversity in Higher Education: Career Support Factors Influencing Ascendancy of African American Women to Senior-Level Positions

    ERIC Educational Resources Information Center

    Blackstone, Tondelaya K.

    2011-01-01

    The focus of this study was how knowledge of the barriers to advancement for African American women (AAW) and key career support factors (KCSFs) influence the career advancement of African American women (AAW) to senior-level positions in higher education. The research method for this study consisted of the triangulation of evidence from multiple…

  18. "They Call Me Wonder Woman": The Job Jurisdictions and Work-Related Learning of Higher Level Teaching Assistants

    ERIC Educational Resources Information Center

    Hancock, Roger; Hall, Thelma; Cable, Carrie; Eyres, Ian

    2010-01-01

    This paper reports on an in-depth interview study of the roles, job jurisdictions and associated learning of higher level teaching assistants (HLTAs). This role has the core purpose of covering classes to enable teacher release for planning, preparation and assessment. HLTAs' individual job jurisdictions are described and discussed as are…

  19. Stress Levels in Tenure-Track and Recently Tenured Faculty Members in Selected Institutions of Higher Education in Northeast Tennessee

    ERIC Educational Resources Information Center

    Carr, Amanda R.

    2014-01-01

    The purpose of this quantitative study was to compare the stress, strain, and coping levels between pretenured faculty and recently tenured faculty in institutions of higher education in Northeast Tennessee. Aging faculty population combined with talented people leaving the area is common in rural parts of the United States. There is a need to…

  20. Performance or Enactment? The Role of the Higher Level Teaching Assistant in a Remodelled School Workforce in England

    ERIC Educational Resources Information Center

    Graves, Susan

    2011-01-01

    This article draws on research conducted over two years in the North West of England and is located in the context of workforce remodelling. It examines how the higher level teaching assistant (HLTA) role has developed and is appraised and suggests that the anomalous nature of the role, which often relies on the enactment of observed teacher…

  1. A large-scale, higher-level, molecular phylogenetic study of the insect order Lepidoptera (moths and butterflies)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Higher-level relationships within the Lepidoptera, and particularly within the species-rich subclade Ditrysia, are generally not well understood, although recent studies have yielded progress. 483 taxa spanning 115 of 124 families were sampled for 19 protein-coding nuclear genes. Their aligned nucle...

  2. Study on the Improvement of Vocational and Technical Programs at the Higher Education Level in Taiwan. Based on Students' Perspectives

    ERIC Educational Resources Information Center

    Wu, Mingchang; Tseng, Kuo-hung; Liu, Weite

    2007-01-01

    Technical programs at the higher education level play an important role in the journey of economic development. Technical institutes in Taiwan have been facing challenges while the Taiwan economics rapidly changes in the recent years. Nowadays, the fast revolution of technology and socioeconomic structures just challenges the efficiency and…

  3. Creativity Lost: The Importance of Testing Higher-Level Executive Functions in School-Age Children and Adolescents

    ERIC Educational Resources Information Center

    Delis, Dean C.; Lansing, Amy; Houston, Wes S.; Wetter, Spencer; Han, S. Duke; Jacobson, Mark; Holdnack, James; Kramer, Joel

    2007-01-01

    In school settings, students are typically evaluated using group achievement tests, IQ scales, and college entrance exams that focus more on rote-verbal skills (e.g., vocabulary, mathematical facts) than on higher level executive functions (e.g., abstract thinking, problem solving). However, recent neuropsychological findings suggest that…

  4. Developing a Long-Range Program To Improve Higher-Level Thinking Skills in Hillsborough County Schools.

    ERIC Educational Resources Information Center

    Duval, Eilen; Whitlock, Earl

    1987-01-01

    A project to improve higher level thinking skills of elementary students in Hillsborough County, Florida is reported as a feature article (66p). An introductory overview chapter reviews the literature on teaching thinking skills. Chapter 1 provides background information on the community and the two schools selected for the practicum. The second…

  5. Increasing Higher Level Thinking Skills in Science of Gifted Students in Grades 1-4 through "Hands-On" Activities.

    ERIC Educational Resources Information Center

    Dindial, Myrna J.

    This practicum was designed to increase higher level thinking skills of gifted students in primary school. The project sought to retrain students from recalling science information from the textbook to a more challenging and active form of learning through individual projects and small group and large group activities. Students were given…

  6. Students' Commitment, Engagement and Locus of Control as Predictor of Academic Achievement at Higher Education Level

    ERIC Educational Resources Information Center

    Sarwar, Muhammad; Ashrafi, Ghulam Muhammad

    2014-01-01

    The purpose of this study was to analyze Students' Commitment, Engagement and Locus of Control as predictors of Academic Achievement at Higher Education Level. We used analytical model and conclusive research approach to conduct study and survey method for data collection. We selected 369 students using multistage sampling technique from…

  7. Parental Level of Education: Associations with Psychological Well-Being, Academic Achievement and Reasons for Pursuing Higher Education in Adolescence

    ERIC Educational Resources Information Center

    Schlechter, Melissa; Milevsky, Avidan

    2010-01-01

    The purpose of the current study is to determine the interconnection between parental level of education, psychological well-being, academic achievement and reasons for pursuing higher education in adolescents. Participants included 439 college freshmen from a mid-size state university in the northeastern USA. A survey, including indices of…

  8. Leadership Provided by Non-Academic Middle-Level Managers in the Australian Higher Education Sector: The Enablers

    ERIC Educational Resources Information Center

    Vilkinas, Tricia

    2014-01-01

    This study seeks to identify the leadership behaviours displayed by non-academic middle-level managers in the Australian higher education sector. The study also identifies the importance of these leadership behaviours and the leadership effectiveness of these managers. The integrated competing values framework was used to measure leadership…

  9. Optimality and evolutionary tuning of the expression level of a protein.

    PubMed

    Dekel, Erez; Alon, Uri

    2005-07-28

    Different proteins have different expression levels. It is unclear to what extent these expression levels are optimized to their environment. Evolutionary theories suggest that protein expression levels maximize fitness, but the fitness as a function of protein level has seldom been directly measured. To address this, we studied the lac system of Escherichia coli, which allows the cell to use the sugar lactose for growth. We experimentally measured the growth burden due to production and maintenance of the Lac proteins (cost), as well as the growth advantage (benefit) conferred by the Lac proteins when lactose is present. The fitness function, given by the difference between the benefit and the cost, predicts that for each lactose environment there exists an optimal Lac expression level that maximizes growth rate. We then performed serial dilution evolution experiments at different lactose concentrations. In a few hundred generations, cells evolved to reach the predicted optimal expression levels. Thus, protein expression from the lac operon seems to be a solution of a cost-benefit optimization problem, and can be rapidly tuned by evolution to function optimally in new environments. PMID:16049495

  10. Correlations Between Gene Expression and Mercury Levels in Blood of Boys With and Without Autism

    PubMed Central

    Green, Peter G.; Tian, Yingfang; Hertz-Picciotto, Irva; Pessah, Isaac N.; Hansen, Robin; Yang, Xiaowei; Teng, Jennifer; Gregg, Jeffrey P.; Ashwood, Paul; Van de Water, Judy; Sharp, Frank R.

    2009-01-01

    Gene expression in blood was correlated with mercury levels in blood of 2- to 5-year-old boys with autism (AU) compared to age-matched typically developing (TD) control boys. This was done to address the possibility that the two groups might metabolize toxicants, such as mercury, differently. RNA was isolated from blood and gene expression assessed on whole genome Affymetrix Human U133 expression microarrays. Mercury levels were measured using an inductively coupled plasma mass spectrometer. Analysis of covariance (ANCOVA) was performed and partial correlations between gene expression and mercury levels were calculated, after correcting for age and batch effects. To reduce false positives, only genes shared by the ANCOVA models were analyzed. Of the 26 genes that correlated with mercury levels in both AU and TD boys, 11 were significantly different between the groups (P(Diagnosis*Mercury) ≤ 0.05). The expression of a large number of genes (n = 316) correlated with mercury levels in TD but not in AU boys (P ≤ 0.05), the most represented biological functions being cell death and cell morphology. Expression of 189 genes correlated with mercury levels in AU but not in TD boys (P ≤ 0.05), the most represented biological functions being cell morphology, amino acid metabolism, and antigen presentation. These data and those in our companion study on correlation of gene expression and lead levels show that AU and TD children display different correlations between transcript levels and low levels of mercury and lead. These findings might suggest different genetic transcriptional programs associated with mercury in AU compared to TD children. Electronic supplementary material The online version of this article (doi:10.1007/s12640-009-9137-7) contains supplementary material, which is available to authorized users. PMID:19937285

  11. SAWA: an assistant for higher-level fusion and situation awareness

    NASA Astrophysics Data System (ADS)

    Matheus, Christopher J.; Kokar, Mieczyslaw M.; Baclawski, Kenneth; Letkowski, Jerzy A.; Call, Catherine; Hinman, Michael L.; Salerno, John J.; Boulware, Douglas M.

    2005-03-01

    Situation awareness involves the identification and monitoring of relationships among level-one objects. This problem in general is intractable (i.e., there is a potentially infinite number of relations that could be tracked) and thus requires additional constraints and guidance defined by the user if there is to be any hope of creating practical situation awareness systems. This paper describes a Situation Awareness Assistant (SAWA) that facilitates the development of user-defined domain knowledge in the form of formal ontologies and rule sets and then permits the application of the domain knowledge to the monitoring of relevant relations as they occur in evolving situations. SAWA includes tools for developing ontologies in OWL and rules in SWRL and provides runtime components for collecting event data, storing and querying the data, monitoring relevant relations and viewing the results through a graphical user interface. An application of SAWA to a scenario from the domain of supply logistics is also presented.

  12. High-level expression of the bacterial opd gene in Drosophila melanogaster: improved inducible insecticide resistance.

    PubMed

    Benedict, M Q; Scott, J A; Cockburn, A F

    1994-11-01

    The bacterial parathion hydrolase gene (opd) was expressed in transformed D. melanogaster under the control of an hsp70 promoter. Transformed lines carrying chimaeric genes designed for either cytoplasmic or secretory expression exhibited high- or low-level heat-shock-inducible transient resistance to paraoxon respectively. Greatest levels of resistance occurred approximately 12-16 h after heat shock and well after periods of maximal transcription. Insecticide resistance conferred by the cytoplasmic form of opd is expressed as a semidominant trait. PMID:7704308

  13. Dual transcriptional-translational cascade permits cellular level tuneable expression control

    PubMed Central

    Morra, Rosa; Shankar, Jayendra; Robinson, Christopher J.; Halliwell, Samantha; Butler, Lisa; Upton, Mathew; Hay, Sam; Micklefield, Jason; Dixon, Neil

    2016-01-01

    The ability to induce gene expression in a small molecule dependent manner has led to many applications in target discovery, functional elucidation and bio-production. To date these applications have relied on a limited set of protein-based control mechanisms operating at the level of transcription initiation. The discovery, design and reengineering of riboswitches offer an alternative means by which to control gene expression. Here we report the development and characterization of a novel tunable recombinant expression system, termed RiboTite, which operates at both the transcriptional and translational level. Using standard inducible promoters and orthogonal riboswitches, a multi-layered modular genetic control circuit was developed to control the expression of both bacteriophage T7 RNA polymerase and recombinant gene(s) of interest. The system was benchmarked against a number of commonly used E. coli expression systems, and shows tight basal control, precise analogue tunability of gene expression at the cellular level, dose-dependent regulation of protein production rates over extended growth periods and enhanced cell viability. This novel system expands the number of E. coli expression systems for use in recombinant protein production and represents a major performance enhancement over and above the most widely used expression systems. PMID:26405200

  14. 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

  15. Boric acid increases the expression levels of human anion exchanger genes SLC4A2 and SLC4A3.

    PubMed

    Akbas, F; Aydin, Z

    2012-01-01

    Boron is an important micronutrient in plants and animals. The role of boron in living systems includes coordinated regulation of gene expression, growth and proliferation of higher plants and animals. There are several well-defined genes associated with boron transportation and tolerance in plants and these genes show close homology with human anion exchanger genes. Mutation of these genes also characterizes some genetic disorders. We investigated the toxic effects of boric acid on HEK293 cells and mRNA expression of anion exchanger (SLC4A1, SLC4A2 and SLC4A3) genes. Cytotoxicity of boric acid at different concentrations was tested by using the methylthiazolyldiphenyl-tetrazolium bromide assay. Gene expression profiles were examined using quantitative real-time PCR. In the HEK293 cells, the nontoxic upper concentration of boric acid was 250 μM; more than 500 μM caused cytotoxicity. The 250 μM boric acid concentration increased gene expression level of SLC4A2 up to 8.6-fold and SLC4A3 up to 2.6-fold, after 36-h incubation. There was no significant effect of boric acid on SLC4A1 mRNA expression levels. PMID:22576912

  16. Development of Multigene Expression Signature Maps at the Protein Level from Digitized Immunohistochemistry Slides

    PubMed Central

    Metzger, Gregory J.; Dankbar, Stephen C.; Henriksen, Jonathan; Rizzardi, Anthony E.; Rosener, Nikolaus K.; Schmechel, Stephen C.

    2012-01-01

    Molecular classification of diseases based on multigene expression signatures is increasingly used for diagnosis, prognosis, and prediction of response to therapy. Immunohistochemistry (IHC) is an optimal method for validating expression signatures obtained using high-throughput genomics techniques since IHC allows a pathologist to examine gene expression at the protein level within the context of histologically interpretable tissue sections. Additionally, validated IHC assays may be readily implemented as clinical tests since IHC is performed on routinely processed clinical tissue samples. However, methods have not been available for automated n-gene expression profiling at the protein level using IHC data. We have developed methods to compute expression level maps (signature maps) of multiple genes from IHC data digitized on a commercial whole slide imaging system. Areas of cancer for these expression level maps are defined by a pathologist on adjacent, co-registered H&E slides, allowing assessment of IHC statistics and heterogeneity within the diseased tissue. This novel way of representing multiple IHC assays as signature maps will allow the development of n-gene expression profiling databases in three dimensions throughout virtual whole organ reconstructions. PMID:22438942

  17. OVATION Prime-2013: Extension of auroral precipitation model to higher disturbance levels

    NASA Astrophysics Data System (ADS)

    Newell, P. T.; Liou, K.; Zhang, Y.; Sotirelis, T.; Paxton, L. J.; Mitchell, E. J.

    2014-06-01

    OVATION Prime (OP) is an auroral precipitation model parameterized by solar wind driving. Distinguishing features of the model include an optimized solar wind-magnetosphere coupling function (dΦMP/dt) which predicts auroral power significantly better than Kp or other traditional parameters, the separation of aurora into categories (diffuse aurora, monoenergetic, broadband, and ion), the inclusion of seasonal variations, and separate parameter fits for each magnetic latitude (MLAT) × magnetic local time (MLT) bin, thus permitting each type of aurora and each location to have differing responses to season and solar wind input—as indeed they do. We here introduce OVATION Prime-2013, an upgrade to the 2010 version currently widely available. The most notable advantage of OP-2013 is that it uses UV images from the GUVI instrument on the satellite TIMED for high disturbance levels (dΦMP/dt > 1.2 MWb/s which roughly corresponds to Kp = 5+ or 6-). The range of validity is approximately 0 < dΦMP/dt ≤ 3.0 MWb/s (Kp about 8+). Other upgrades include a reduced susceptibility to salt-and-pepper noise, and smoother interpolation across the postmidnight data gap. The model is tested against an independent data set of hemispheric auroral power from Polar UVI. Over the common range of validity of OP-2010 and OP-2013, the two models predict auroral power essentially identically, primarily because hemispheric power calculations were done in a way to minimize the impact of OP-2010s noise. To quantitatively demonstrate the improvement at high disturbance levels would require multiple very large substorms, which are rare, and insufficiently present in the limited data set of Polar UVI hemispheric power values. Nonetheless, although OP-2010 breaks down in a variety of ways above Kp = 5+ or 6-, OP-2013 continues to show the auroral oval advancing equatorward, at least to 55° MLAT or a bit less, and OP-2013 does not develop spurious large noise patches. We will also discuss the

  18. OVATION Prime -2013: Solar Wind Driven Precipitation Model Extended to Higher Geomagnetic Activity Levels

    NASA Astrophysics Data System (ADS)

    Newell, Patrick; Liou, Kan; Zhang, Yongliang; Sotirelis, Thomas; Paxton, Larry; Mitchell, Elizabeth

    2014-05-01

    OVATION Prime is an auroral precipitation model parameterized by solar wind driving. Distinguishing features of the model include an optimized solar wind-magnetosphere coupling function (dΦMP/dt) which predicts auroral power far better than Kp or other traditional parameters, the separation of aurora into categories (diffuse aurora, monoenergetic, broadband, and ion), the inclusion of seasonal variations, and separate parameter fits for each MLATxMLT bin, thus permitting each type of aurora and each location to have differing responses to season and solar wind input (as indeed they do). We here introduce OVATION Prime-2013, an upgrade to the 2008 version currently widely available. The most notable advantage of OP-2013 is that it uses UV images from the GUVI instrument on the satellite TIMED for high disturbance levels (dΦMP/dt > 12,000 (nT2/3 (km/s)4/3 which roughly corresponds to Kp = 5+ or 6-). The range of validity is thought to be about 0 < dΦMP/dt = 30000 (say Kp = 8 or 8+). Other upgrades include a reduced susceptibility to salt and pepper noise, and smoother interpolation across the postmidnight data gap. We will also provide a comparison of the advantages and disadvantages of other current precipitation models, especially OVATION-SuperMAG, which produces particularly good estimates for total auroral power, at the expense of working best on an historical basis.

  19. A study of improved MHR 50/100 toward a higher level of inherent safety

    SciTech Connect

    Minatsuki, I.; Otani, T.; Shimizu, K.; Oyama, S.; Tsukamoto, H.; Kunitomi, K.

    2012-07-01

    A new concept of the Mitsubishi small-sized High temperature gas-cooled modular Reactors (MHR-50/100) had been developed and published in papers. The study results of the first design concept show that the MHR-50/100 can achieve the inherent safety level set as a design target in case of water ingress during steam generator tube rupture accident. And more specifically, the reactor was shown to remain stable during long-term station black out (SBO) with protection of only passive devices during a depressurization accident and with additional motion of steam dump system during a water ingress accident. Recently greater requirements for safety of future nuclear plants including the MHR-50/100 have been expected. This study has thus made a key design improvement for the MHR-50/100 in order to secure the inherent safety aspect without reliance on active steam dump system in case of a water ingress accident. The innovative technologies listed below have been created and investigated to achieve the improved MHR-50/100 design; (1) Design improvement of steam generator, (2) Heat balance optimization of steam cycle, (3) Control system design of differential pressure between primary helium gas and water/steam, (4) Study on operation procedure during a water ingress accident. (authors)

  20. Pursuit tracking and higher levels of skill development in the human pilot

    NASA Technical Reports Server (NTRS)

    Hess, R. A.

    1981-01-01

    A model of the human pilot is offered for pursuit tracking tasks; the model encompasses an existing model for compensatory tracking. The central hypothesis in the development of this model states that those primary structural elements in the compensatory model responsible for the pilot's equalization capabilities remain intact in the pursuit model. In this latter case, effective low-frequency inversion of the controlled-element dynamics occurs by feeding-forward derived input rate through the equalization dynamics, with low-frequency phase droop minimized. The sharp reduction in low-frequency phase lag beyond that associated with the disappearance of phase droop is seen to accompany relatively low-gain feedback of vehicle output. The results of some recent motion cue research are discussed and interpreted in terms of the compensatory-pursuit display dichotomy. Tracking with input preview is discussed in a qualitative way. In terms of the model, preview is shown to demand no fundamental changes in structure or equalization and to allow the pilot to eliminate the effective time delays that accrue in the inversion of the controlled-element dynamics. Precognitive behavior is discussed, and a model that encompasses all the levels of skill development outlined in the successive organizations of perception theory is finally proposed.

  1. Increased harbor porpoise mortality in the Pacific Northwest, USA: understanding when higher levels may be normal.

    PubMed

    Huggins, Jessica L; Raverty, Stephen A; Norman, Stephanie A; Calambokidis, John; Gaydos, Joseph K; Duffield, Deborah A; Lambourn, Dyanna M; Rice, James M; Hanson, Brad; Wilkinson, Kristin; Jeffries, Steven J; Norberg, Brent; Barre, Lynne

    2015-07-23

    In 2006, a marked increase in harbor porpoise Phocoena phocoena strandings were reported in the Pacific Northwest of the USA, resulting in the declaration of an unusual mortality event (UME) for Washington and Oregon to facilitate investigation into potential causes. The UME was in place during all of 2006 and 2007, and a total of 114 porpoises stranded during this period. Responders examined 95 porpoises; of these, detailed necropsies were conducted on 75 animals. Here we review the findings related to this event and how these compared to the years immediately before and after the UME. Relatively equal numbers among sexes and age classes were represented, and mortalities were attributed to a variety of specific causes, most of which were categorized as trauma or infectious disease. Continued monitoring of strandings during 4 yr following the UME showed no decrease in occurrence. The lack of a single major cause of mortality or evidence of a significant change or event, combined with high levels of strandings over several post-UME years, demonstrated that this was not an actual mortality event but was likely the result of a combination of factors, including: (1) a growing population of harbor porpoises; (2) expansion of harbor porpoises into previously sparsely populated areas in Washington's inland waters; and (3) a more well established stranding network that resulted in better reporting and response. This finding would not have been possible without the integrated response and investigation undertaken by the stranding network. PMID:26203880

  2. Complex interactions in metacommunities, with implications for biodiversity and higher levels of selection

    SciTech Connect

    Wilson, D.S. )

    1992-12-01

    Two common features of biological communities are (a) complex interactions among species, which make community dynamics sensitive to initial conditions, and (b) spatial heterogeneity, which fragments large-scale ecological systems into a mosaic of patches, hereafter termed a metacommunity. This computer simulation study examines the effect of complex interactions on the global and local dynamics od metacommunities. Patches are physically identical and differ only in the initial proportion of species that colonize the patches. The random variation is then magnified by deterministic interactions that cause patches to follow different trajectories based on initial conditions. After a period of interaction, individuals from all patches join a global pool of dispersers that colonize a new generation of patches. Complex interactions can have at least two important effects on metacommunity dynamics. First, the number of species coexisting in the metacommunity can greatly exceed the number of species coexisting in any single patch, despite the fact that the patches are physically identical, the species do not differ in colonization ability, and stochastic effects are absent after the colonization stage. Second, complex interactions provide a new source of variation upon which natural selection can operate at the patch level, providing a mechanism for the evolution of functionally organized communities. 59 refs., 11 figs., 2 tabs.

  3. High-level expression, purification, and characterization of bifunctional ScFv-9R fusion protein.

    PubMed

    Zhang, Xiguang; Xie, Jiasen; Sun, Yan; Xu, Huijing; Du, Tonghua; Liu, Zixuan; Chen, Jinhui; Zheng, Zhong; Liu, Keqiang; Zhang, Jizhou; Kan, Mujie; Li, Xiaokun; Xiao, Yechen

    2014-06-01

    Fibroblast growth factor receptor 3 (FGFR3) is a noted proto-oncogene involved in the pathogenesis of many tumors, so more and more studies focus on the potential use of receptor kinase inhibitor and therapeutic antibodies against FGFR3. In this study, we designed a novel fusion protein containing the single-chain Fv (ScFv) against FGFR3 and 9-arginine, denoted as ScFv-9R. To achieve the high-level production and soluble expression, ScFv and ScFv-9R were fused with small ubiquitin-related modifier (Sumo) by polymerase chain reaction and expressed in Escherichia coli BL21 (DE3). The recombinant bacteria was induced by 0.5 mM isopropyl-β-D-thiogalactopyranoside for 20 h at 20 °C; supernatants of Sumo-ScFv was harvested and purified by DEAE Sepharose FF and Ni-NTA orderly, and supernatants of Sumo-ScFv-9R was harvested and purified by Ni-NTA. After cleaved by the Sumo protease, the recombinant ScFv or ScFv-9R was released from the fusion protein, respectively. The purity of ScFv or ScFV-9R was shown to be higher than 90 %, and their yield reached 3-5 mg per liter of bacterial culture. In vitro data showed that ScFV-9R can attenuate the phosphorylation of FGFR3 and ERK in the absence or presence of FGF9. Gel retardation assay showed that 1 μg of ScFv-9R could efficiently bind to about 4 pmol siRNA. Fluorescent microscope analysis showed that ScFv-9R can efficiently bind and deliver siRNA into RT112 cells. In conclusion, we use Sumo fusion system to acquire high-level production, soluble expression, and bifunctional activity of ScFv-9R in E. coli. Our results also revealed that ScFv-9R, as a novel carrier, may have potential applications in antitumor studies and pharmaceutical development. PMID:24519456

  4. 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

  5. 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

  6. Hepatocyte growth factor stimulates motility, chemotaxis and mitogenesis in ovarian carcinoma cells expressing high levels of c-met.

    PubMed

    Corps, A N; Sowter, H M; Smith, S K

    1997-09-26

    A proportion of ovarian carcinomas markedly overexpress the proto-oncogene c-met, which encodes the receptor for hepatocyte growth factor (HGF). HGF may either stimulate or inhibit the multiplication of its target cells, and may also promote motogenesis and morphogenesis. In this study, we established that the ovarian carcinoma-derived cell-line SK-OV-3 expressed about 20-fold higher levels of c-met protein than are expressed by a second line, CH1. This enabled us to test functional consequences of high-level expression of c-met in ovarian carcinoma cells. The addition of HGF to attached cultures of SK-OV-3 cells caused a change to a motile phenotype, that was evident after 4-6 hr and affected essentially all of the cells by 24 hr. When HGF was placed in the lower compartment of a migration chamber, it induced a 17-fold increase in the migration of SK-OV-3 cells to the lower surface of the filter. Finally, HGF stimulated the incorporation of [3H]-thymidine by cultures of SK-OV-3 cells incubated in medium containing either low (0.2%) or full (10%) FCS. None of these responses were obtained when HGF was added to CH1 cells. We conclude that high levels of c-met expression in ovarian cancer cells may lead to a range of responses to HGF that would promote tumour growth and dissemination. PMID:9334823

  7. Post-harvest light treatment increases expression levels of recombinant proteins in transformed plastids of potato tubers.

    PubMed

    Larraya, Luis M; Fernández-San Millán, Alicia; Ancín, María; Farran, Inmaculada; Veramendi, Jon

    2015-09-01

    Plastid genetic engineering represents an attractive system for the production of foreign proteins in plants. Although high expression levels can be achieved in leaf chloroplasts, the results for non-photosynthetic plastids are generally discouraging. Here, we report the expression of two thioredoxin genes (trx f and trx m) from the potato plastid genome to study transgene expression in amyloplasts. As expected, the highest transgene expression was detected in the leaf (up to 4.2% of TSP). The Trx protein content in the tuber was approximately two to three orders of magnitude lower than in the leaf. However, we demonstrate that a simple post-harvest light treatment of microtubers developed in vitro or soil-grown tubers induces up to 55 times higher accumulation of the recombinant protein in just seven to ten days. After the applied treatment, the Trx f levels in microtubers and soil-grown tubers increased to 0.14% and 0.11% of TSP, respectively. Moreover, tubers stored for eight months maintained the capacity of increasing the foreign protein levels after the light treatment. Post-harvest cold induction (up to five times) at 4°C was also detected in microtubers. We conclude that plastid transformation and post-harvest light treatment could be an interesting approach for the production of foreign proteins in potato. PMID:26121393

  8. Correlation of Notch1/Hes1 Genes Expression Levels in Egyptian Paediatric Patients with Newly Diagnosed and Persistent Primary Immune(Idiopathic) Thrombocytopenic Purpura.

    PubMed

    Gawdat, Rania Mohsen; Hammam, Amira Ahmed; Ezzat, Dina Ahmed

    2016-09-01

    Notch signalling is involved in the development of several autoimmune diseases, one of such diseases is ITP. The aim of this study was to investigate and compare the expression levels of Notch1 receptor and its target Hes1 gene in Egyptian paediatric ITP patients. Real-time quantitative reverse transcriptase polymerase chain reaction was used to analyse the expression levels of Notch1 and Hes1 in 42 children with primary ITP (22 newly diagnosed and 20 persistent) cases. Twenty age and sex matched non-ITP controls were included. The expression levels of Notch1 were higher in newly diagnosed and persistent cases than controls with high statistical significant difference (P value < 0.001, P < 0.001) respectively, similarly as regards the expression levels of HES1 (P value < 0.001, P < 0.007) respectively. A significant positive correlation was found between Notch1 and Hes1 expression levels in newly diagnosed cases (r = 0.587, P value = 0.004). There was an association between levels of both genes in most of ITP patients but Hes1 was markedly elevated than Notch1 in few cases. High expression levels of Notch1/Hes1 indicated the important role of Notch signalling in both newly diagnosed and persistent ITP. High expression levels of Hes1 than Notch1 may shed light on its value as a therapeutic target for future research in ITP. PMID:27429531

  9. High-level intracellular expression of heterologous proteins in Brevibacillus choshinensis SP3 under the control of a xylose inducible promoter

    PubMed Central

    2013-01-01

    Background In past years research has focused on the development of alternative Gram positive bacterial expression systems to produce industrially relevant proteins. Brevibacillus choshinensis is an easy to handle non-sporulating bacterium, lacking extracellular proteases, that has been already shown to provide a high level of recombinant protein expression. One major drawback, limiting the applicability of the Brevibacillus expression system, is the absence of expression vectors based on inducible promoters. Here we used the PxylA inducible promoter, commonly employed in other Bacillae expression systems, in Brevibacillus. Results Using GFP, α-amylase and TcdA-GT as model proteins, high level of intracellular protein expression (up to 250 mg/L for the GFP) was achieved in Brevibacillus, using the pHis1522 vector carrying the B. megaterium xylose-inducible promoter (PxylA). The GFP expression yields were more than 25 fold higher than those reported for B. megaterium carrying the same vector. All the tested proteins show significant increment in their expression levels (2-10 folds) than those obtained using the available plasmids based on the P2 constitutive promoter. Conclusion Combining the components of two different commercially available Gram positive expression systems, such as Brevibacillus (from Takara Bio) and B. megaterium (from Mobitec), we demonstrate that vectors based on the B. megaterium PxylA xylose inducible promoter can be successfully used to induce high level of intracellular expression of heterologous proteins in Brevibacillus. PMID:23374160

  10. OVATION Prime -2013: Solar Wind Driven Precipitation Model Extended to Higher Geomagnetic Activity Levels (Invited)

    NASA Astrophysics Data System (ADS)

    Newell, P. T.; Liou, K.; Zhang, Y.; Paxton, L.; Sotirelis, T.; Mitchell, E. J.

    2013-12-01

    OVATION Prime is an auroral precipitation model parameterized by solar wind driving. Distinguishing features of the model include an optimized solar wind-magnetosphere coupling function (dΦMP/dt) which predicts auroral power far better than Kp or other traditional parameters, the separation of aurora into categories (diffuse aurora, monoenergetic, broadband, and ion), the inclusion of seasonal variations, and separate parameter fits for each MLATxMLT bin, thus permitting each type of aurora and each location to have differing responses to season and solar wind input (as indeed they do). We here introduce OVATION Prime-2013, an upgrade to the 2008 version currently widely available. The most notable advantage of OP-2013 is that it uses UV images from the GUVI instrument on the satellite TIMED for high disturbance levels (dΦMP/dt > 12,000 (nT2/3 (km/s)4/3 which roughly corresponds to Kp = 5+ or 6-). The range of validity is thought to be about 0 < dΦMP/dt = 30000 (say Kp = 8 or 8+). Other upgrades include a reduced susceptibility to salt and pepper noise, and smoother interpolation across the postmidnight data gap. We will also provide a comparison of the advantages and disadvantages of other current precipitation models, especially OVATION-SuperMAG, which produces particularly good estimates for total auroral power, at the expense of working best on an historical basis. OVATION Prime-2013, for high solar wind driving, as TIMED GUVI data takes over from DMSP

  11. Higher levels of neanderthal ancestry in East Asians than in Europeans.

    PubMed

    Wall, Jeffrey D; Yang, Melinda A; Jay, Flora; Kim, Sung K; Durand, Eric Y; Stevison, Laurie S; Gignoux, Christopher; Woerner, August; Hammer, Michael F; Slatkin, Montgomery

    2013-05-01

    Neanderthals were a group of archaic hominins that occupied most of Europe and parts of Western Asia from ∼30,000 to 300,000 years ago (KYA). They coexisted with modern humans during part of this time. Previous genetic analyses that compared a draft sequence of the Neanderthal genome with genomes of several modern humans concluded that Neanderthals made a small (1-4%) contribution to the gene pools of all non-African populations. This observation was consistent with a single episode of admixture from Neanderthals into the ancestors of all non-Africans when the two groups coexisted in the Middle East 50-80 KYA. We examined the relationship between Neanderthals and modern humans in greater detail by applying two complementary methods to the published draft Neanderthal genome and an expanded set of high-coverage modern human genome sequences. We find that, consistent with the recent finding of Meyer et al. (2012), Neanderthals contributed more DNA to modern East Asians than to modern Europeans. Furthermore we find that the Maasai of East Africa have a small but significant fraction of Neanderthal DNA. Because our analysis is of several genomic samples from each modern human population considered, we are able to document the extent of variation in Neanderthal ancestry within and among populations. Our results combined with those previously published show that a more complex model of admixture between Neanderthals and modern humans is necessary to account for the different levels of Neanderthal ancestry among human populations. In particular, at least some Neanderthal-modern human admixture must postdate the separation of the ancestors of modern European and modern East Asian populations. PMID:23410836

  12. Congruence and Diversity of Butterfly-Host Plant Associations at Higher Taxonomic Levels

    PubMed Central

    Ferrer-Paris, José R.; Sánchez-Mercado, Ada; Viloria, Ángel L.; Donaldson, John

    2013-01-01

    We aggregated data on butterfly-host plant associations from existing sources in order to address the following questions: (1) is there a general correlation between host diversity and butterfly species richness?, (2) has the evolution of host plant use followed consistent patterns across butterfly lineages?, (3) what is the common ancestral host plant for all butterfly lineages? The compilation included 44,148 records from 5,152 butterfly species (28.6% of worldwide species of Papilionoidea) and 1,193 genera (66.3%). The overwhelming majority of butterflies use angiosperms as host plants. Fabales is used by most species (1,007 spp.) from all seven butterfly families and most subfamilies, Poales is the second most frequently used order, but is mostly restricted to two species-rich subfamilies: Hesperiinae (56.5% of all Hesperiidae), and Satyrinae (42.6% of all Nymphalidae). We found a significant and strong correlation between host plant diversity and butterfly species richness. A global test for congruence (Parafit test) was sensitive to uncertainty in the butterfly cladogram, and suggests a mixed system with congruent associations between Papilionidae and magnoliids, Hesperiidae and monocots, and the remaining subfamilies with the eudicots (fabids and malvids), but also numerous random associations. The congruent associations are also recovered as the most probable ancestral states in each node using maximum likelihood methods. The shift from basal groups to eudicots appears to be more likely than the other way around, with the only exception being a Satyrine-clade within the Nymphalidae that feed on monocots. Our analysis contributes to the visualization of the complex pattern of interactions at superfamily level and provides a context to discuss the timing of changes in host plant utilization that might have promoted diversification in some butterfly lineages. PMID:23717448

  13. Different levels in orexin concentrations and risk factors associated with higher orexin levels: comparison between detoxified opiate and methamphetamine addicts in 5 Chinese cities.

    PubMed

    Zhang, Haoran; Lian, Zhi; Yan, Shiyan; Bao, Yanping; Liu, Zhimin

    2013-01-01

    This study sought to explore the degree of orexin levels in Chinese opiate and methamphetamine addicts and the differences between them. The cross-sectional study was conducted among detoxified drug addicts from Mandatory Detoxification Center (MDC) in five Chinese cities. Orexin levels were assayed with radioimmunoassay (RIA). Mann-Whitney U test and Kruskal-Wallis test were used to detect differences across groups, and logistic regression was used to explore the association between orexin levels and characteristics of demographic and drug abuse. Between November 2009 and January 2011, 285 opiates addicts, 112 methamphetamine addicts, and 79 healthy controls were enrolled. At drug withdrawal period, both opiate and methamphetamine addicts had lower median orexin levels than controls, and median orexin levels in opiate addicts were higher than those in methamphetamine addicts (all above P < 0.05). Adjusted odds of the above median concentration of orexin were higher for injection than "chasing the dragon" (AOR = 3.1, 95% CI = 1.2-7.9). No significant factors associated with orexin levels of methamphetamine addicts were found. Development of intervention method on orexin system by different administration routes especially for injected opiate addicts at detoxification phase may be significant and was welcome. PMID:24102051

  14. Does peer learning or higher levels of e-learning improve learning abilities? A randomized controlled trial

    PubMed Central

    Worm, Bjarne Skjødt; Jensen, Kenneth

    2013-01-01

    Background and aims The fast development of e-learning and social forums demands us to update our understanding of e-learning and peer learning. We aimed to investigate if higher, pre-defined levels of e-learning or social interaction in web forums improved students’ learning ability. Methods One hundred and twenty Danish medical students were randomized to six groups all with 20 students (eCases level 1, eCases level 2, eCases level 2+, eTextbook level 1, eTextbook level 2, and eTextbook level 2+). All students participated in a pre-test, Group 1 participated in an interactive case-based e-learning program, while Group 2 was presented with textbook material electronically. The 2+ groups were able to discuss the material between themselves in a web forum. The subject was head injury and associated treatment and observation guidelines in the emergency room. Following the e-learning, all students completed a post-test. Pre- and post-tests both consisted of 25 questions randomly chosen from a pool of 50 different questions. Results All students concluded the study with comparable pre-test results. Students at Level 2 (in both groups) improved statistically significant compared to students at level 1 (p>0.05). There was no statistically significant difference between level 2 and level 2+. However, level 2+ was associated with statistically significant greater student's satisfaction than the rest of the students (p>0.05). Conclusions This study applies a new way of comparing different types of e-learning using a pre-defined level division and the possibility of peer learning. Our findings show that higher levels of e-learning does in fact provide better results when compared with the same type of e-learning at lower levels. While social interaction in web forums increase student satisfaction, learning ability does not seem to change. Both findings are relevant when designing new e-learning materials. PMID:24229729

  15. Quantification of phase I / II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate

    PubMed Central

    John, Kaarthik; Ragavan, Narasimhan; Pratt, M. Margaret; Singh, Paras B.; Al-Buheissi, Salah; Matanhelia, Shyam S.; Phillips, David H.; Poirier, Miriam C.; Martin, Francis L.

    2008-01-01

    BACKGROUND Studies of migrant populations suggest that dietary and/or environmental factors play a crucial role in the aetiology of prostatic adenocarcinoma (CaP). The human prostate consists of the peripheral zone (PZ), transition zone (TZ) and central zone (CZ); CaP occurs most often in the PZ. METHODS To investigate the notion that an underlying differential expression of phase I/II genes, and/or the presence of polycyclic aromatic hydrocarbon (PAH)-DNA adducts might explain the elevated PZ susceptibility, we examined prostate tissues (matched tissue sets consisting of PZ and TZ) from men undergoing radical retropubic prostatectomy for CaP (n=26) or cystoprostatectomy (n=1). Quantitative gene expression analysis was employed for cytochrome P450 (CYP) isoforms CYP1A1, CYP1B1 and CYP1A2, as well as N-acetyltransferase 1 and 2 (NAT1 and NAT2) and catechol-O-methyl transferase (COMT). RESULTS CYP1B1, NAT1 and COMT were expressed in all tissue sets; levels of CYP1B1 and NAT1 were consistently higher in the PZ compared to TZ. Immunohistochemistry confirmed the presence of CYP1B1 (nuclear-associated and primarily in basal epithelial cells) and NAT1. Tissue sections from 23 of these aforementioned 27 matched tissue sets were analyzed for PAH-DNA adduct levels using antiserum elicited against DNA modified with r7, t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE). PAH-DNA adduct levels were highest in glandular epithelial cells, but a comparison of PZ and TZ showed no significant differences. CONCLUSION Although expression of activating and/or detoxifying enzymes may be higher in the PZ, PAH-DNA adduct levels appear to be similar in both zones. Therefore, factors other than PAH-DNA adducts may be responsible for promotion of tumour formation in the human prostate. PMID:19143007

  16. Programme alignment in higher-level planning processes: a four-country case-study for Sexual and Reproductive Health.

    PubMed

    Dodd, Rebecca; Huntington, Dale; Hill, Peter

    2009-01-01

    With international development assistance focussed on poverty reduction, national and sector-wide planning processes have become increasingly important in setting agendas. Sector-Wide Approaches (SWAps), Poverty Reduction Strategy Papers (PRSPs), and other higher level planning processes, including Millennium Development Goals (MDGs) reporting, have required new levels of engagement in national and sectoral planning processes. For Sexual and Reproductive Health (SRH), this has had mixed consequences, despite raising the profile of SRH in national planning agendas, and emphasizing the potential of SRH to contribute to the reduction of poverty.Drawing on case-study research from four countries, this paper analyzes alignment of SRH policy with higher-level planning processes. It found that SRH managers are rarely engaged in higher-level planning processes, and while SRH features prominently in the [health] sections of PRSPs, it is not reflected in other sections, and does not necessarily correspond to more resources. Despite these limitations, these planning processes offer synergies that could improve the contribution of SRH to health sector development and poverty reduction. The paper recommends that local donor organizations, including key UN agencies, offer greater support for SRH programme managers in promoting the pro-poor and systems-wide strengths of SRH programmes to planners and policy makers. PMID:19691057

  17. Correlated expression levels of endothelin receptor B and Plexin C1 in melanoma

    PubMed Central

    Kumasaka, Mayuko Y; Yajima, Ichiro; Iida, Machiko; Takahashi, Hiro; Inoue, Yuji; Fukushima, Satoshi; Ihn, Hironobu; Takeda, Kozue; Naito, Yuji; Yoshikawa, Toshikazu; Kato, Masashi

    2015-01-01

    Discussion concerning the effect of endothelin receptor B (Ednrb) on melanoma continues because Ednrb has been reported to have both tumor promoting and suppressive effects for melanoma. In order to examine Ednrb-related signaling in melanomagenesis, DNA microarray analysis for a melanoma from a RFP/RET-transgenic mouse (RET-mouse) and a melanoma from an Ednrb-heterozygously deleted RET-mouse [Ednrb(+/-);RET-mouse], in both of which melanoma spontaneously develops, was performed in this study. We found that the expression level of Plexin C1 (PlxnC1), a suppressor for melanoma, in a melanoma from an Ednrb(+/-);RET-mouse was drastically decreased compared to that in a melanoma from a RET-mouse. Therefore, we further examined the correlation between Ednrb and PlxnC1 expression levels in melanomas. PlxnC1 transcript expression levels in melanomas from Ednrb(+/-);RET-mice were lower than those in melanomas from RET-mice. A strong correlation between Ednrb and PlxnC1 transcript expression levels (R = 0.78, p < 0.01) was also found in melanomas from both RET-mice and Ednrb(+/-);RET-mice. Correspondingly, there was a significant correlation between transcript (R = 0.80; p < 0.01) and protein (R = 0.60; p < 0.01) expression levels of EDNRB and PLXNC1 in human primary melanomas. Together with our results showing that the expression level of PLXNC1 transcript was reduced in EDNRB-depleted human melanoma cells, our results showing positively correlated expression levels of Ednrb/EDNRB and PlxnC1/PLXNC1 in melanoma suggest that PlxnC1/PLXNC1 is involved in the Ednrb/EDNRB-mediated suppressive effect on melanoma. PMID:26045990

  18. Silencing of the HvCKX1 gene decreases the cytokinin oxidase/dehydrogenase level in barley and leads to higher plant productivity.

    PubMed

    Zalewski, Wojciech; Galuszka, Petr; Gasparis, Sebastian; Orczyk, Wacław; Nadolska-Orczyk, Anna

    2010-06-01

    Stable RNA interference-based technology was used to silence the expression of the HvCKX1 gene in barley and the TaCKX1 gene in wheat and triticale. The silencing cassettes containing the fragments of these genes in the sense and antisense orientations were cloned into the pMCG161 binary vector and used for Agrobacterium-based transformation. Out of the five cultivars representing the three studied species, transgenic plants were obtained from one barley cultivar Golden Promise, one wheat cultivar Kontesa, and one triticale cultivar Wanad. Almost 80% of 52 regenerated lines of Golden Promise exhibited significantly decreased cytokinin oxidase/dehydrogenase (CKX) enzyme activity in bulked samples of their T(1) roots. There was a positive correlation between the enzyme activity and the plant productivity, expressed as the yield, the number of seeds per plant, and the 1000 grain weight. Additionally, these traits were associated with a greater root mass. Lower CKX activity led to a higher plant yield and root weight. This higher plant productivity and altered plant architecture were maintained in a population of segregating T(1) plants. The levels of HvCKX1 transcript accumulation were measured in various tissues of Golden Promise and Scarlett non-transgenic barley plants in order to choose the most appropriate plant organs to study the expression and/or silencing of the gene in those transgenic lines. The highest levels of the HvCKX1 transcript were detected in spikes 0 days after pollination (0 DAP), 7 DAP, and 14 DAP, and in the seedling roots. The analysis of HvCKX1 gene expression and CKX enzyme activity and the evaluation of the phenotype were performed in the progeny of seven selected transgenic T(1) lines. The relative expression of HvCKX1 measured in the spikes 0 DAP and 14 DAP, respectively, ranged from 0.52+/-0.04 to 1.15+/-0.26 and from 0.47+/-0.07 to 0.89+/-0.15. The lowest relative values were obtained for the enzyme activity in the spikes at 0 DAP

  19. Interleukins 6 and 15 Levels Are Higher in Subcutaneous Adipose Tissue, but Obesity Is Associated with Their Increased Content in Visceral Fat Depots

    PubMed Central

    Jonas, Marta Izabela; Kurylowicz, Alina; Bartoszewicz, Zbigniew; Lisik, Wojciech; Jonas, Maurycy; Wierzbicki, Zbigniew; Chmura, Andrzej; Pruszczyk, Piotr; Puzianowska-Kuznicka, Monika

    2015-01-01

    Excess adiposity is associated with chronic inflammation, which takes part in the development of obesity-related complications. The aim of this study was to establish whether subcutaneous (SAT) or visceral (VAT) adipose tissue plays a major role in synthesis of pro-inflammatory cytokines. Concentrations of interleukins (IL): 1β, 6, 8 and 15 were measured at the protein level by an ELISA-based method and on the mRNA level by real-time PCR in VAT and SAT samples obtained from 49 obese (BMI > 40 kg/m2) and 16 normal-weight (BMI 20–24.9 kg/m2) controls. IL-6 and IL-15 protein concentrations were higher in SAT than in VAT for both obese (p = 0.003 and p < 0.0001, respectively) and control individuals (p = 0.004 and p = 0.001, respectively), while for IL-1β this was observed only in obese subjects (p = 0.047). What characterized obese individuals was the higher expression of IL-6 and IL-15 at the protein level in VAT compared to normal-weight controls (p = 0.047 and p = 0.016, respectively). Additionally, obese individuals with metabolic syndrome had higher IL-1β levels in VAT than did obese individuals without this syndrome (p = 0.003). In conclusion, concentrations of some pro-inflammatory cytokines were higher in SAT than in VAT, but it was the increased pro-inflammatory activity of VAT that was associated with obesity and metabolic syndrome. PMID:26516848

  20. Effects of discipline-based art education and interdisciplinary art education on artistic development and production, higher-level thinking, and attitudes toward science and social studies

    NASA Astrophysics Data System (ADS)

    Smith, Lisa Lessenberry

    This research was conducted to assess the effectiveness of discipline-based art education (DBAE) and interdisciplinary art (IA) teaching methods on art production, higher level thinking skills, and attitudes toward science and social studies. Two of the sixth-grade classes at a rural West Tennessee school were taught using the DBAE method and two were given the IA treatment. The evaluation of art production was two-fold using an Evaluation of Student Art Projects (Herberholz & Herberholz, 1994) which anonymously measured each group of projects on creativity, expressiveness, organization of elements and principles of art, craftsmanship, and how the artwork related to academic content. The second appraisal of art products involved emergent categorization with reference to Herberholz and Herberholz's (1994) categories of styles and student artistic development. Higher level thinking skills were determined from the Evaluation of Student Essays which measured academic knowledge, composition, and Bloom's higher level thinking stages of analysis, synthesis, and evaluation. Student attitudes toward social studies and science before and after treatment were measured using the Estes Attitude Survey (Estes, Johnstone, & Richards, 1975). T-tests, an analysis of variance (Anova) and data analysis were used to evaluate art production. T-tests were also used to evaluate student essays before and after each treatment. Analysis of data indicated no significant differences between the art products of students in DBAE or IA. There were no significant differences in the attitudes or higher level thinking skills between students undergoing the DBAE or IA treatment. The emergent categorization of art production showed that DBAE produced more overall creativity and originality than IA. The researcher believes that students can benefit from a combination of both methods.

  1. Tumor Vascular Permeability to a Nanoprobe Correlates to Tumor-Specific Expression Levels of Angiogenic Markers

    PubMed Central

    Karathanasis, Efstathios; Chan, Leslie; Karumbaiah, Lohitash; McNeeley, Kathleen; D'Orsi, Carl J.; Annapragada, Ananth V.; Sechopoulos, Ioannis; Bellamkonda, Ravi V.

    2009-01-01

    Background Vascular endothelial growth factor (VEGF) receptor-2 is the major mediator of the mitogenic, angiogenic, and vascular hyperpermeability effects of VEGF on breast tumors. Overexpression of VEGF and VEGF receptor-2 is associated with the degree of pathomorphosis of the tumor tissue and unfavorable prognosis. In this study, we demonstrate that non-invasive quantification of the degree of tumor vascular permeability to a nanoprobe correlates with the VEGF and its receptor levels and tumor growth. Methodology/Principal Findings We designed an imaging nanoprobe and a methodology to detect the intratumoral deposition of a 100 nm-scale nanoprobe using mammography allowing measurement of the tumor vascular permeability in a rat MAT B III breast tumor model. The tumor vascular permeability varied widely among the animals. Notably, the VEGF and VEGF receptor-2 gene expression of the tumors as measured by qRT-PCR displayed a strong correlation to the imaging-based measurements of vascular permeability to the 100 nm-scale nanoprobe. This is in good agreement with the fact that tumors with high angiogenic activity are expected to have more permeable blood vessels resulting in high intratumoral deposition of a nanoscale agent. In addition, we show that higher intratumoral deposition of the nanoprobe as imaged with mammography correlated to a faster tumor growth rate. This data suggest that vascular permeability scales to the tumor growth and that tumor vascular permeability can be a measure of underlying VEGF and VEGF receptor-2 expression in individual tumors. Conclusions/Significance This is the first demonstration, to our knowledge, that quantitative imaging of tumor vascular permeability to a nanoprobe represents a form of a surrogate, functional biomarker of underlying molecular markers of angiogenesis. PMID:19513111

  2. Effect of floral cluster pruning on anthocyanin levels and anthocyanain-related gene expression in 'Houman' grape.

    PubMed

    Zhang, Lei; Xu, Yan-Shuai; Jia, Yue; Wang, Ji-Yuan; Yuan, Yue; Yu, Yang; Tao, Jian-Min

    2016-01-01

    Lateral floral clusters were removed from the main axis of the floral clusters of 'Houman' grape plants, leaving only 3-5-cm-long region of flowers at the end of the central axis. The floral clusters were pruned at 7 days prior to flowering. The effect of the pruning on fruit quality was assessed by determining the composition and levels of anthocyanins in the fruit and anthocyanin-related gene expression. Results indicated that floral cluster pruning significantly improved the quality of the fruit by increasing berry size, fruit weight and the total content of soluble solids. Floral cluster pruning also decreased the level of titratable acidity. Sixteen different anthocyanins were detected in fruit of the pruned clusters, while only 15 were detected in fruit from unpruned clusters. The level of anthocyanins was also significantly higher in fruit of the pruned clusters than in the unpruned clusters. Anthocyanin-related gene expression was also significantly upregulated to a higher level in fruit from pruned floral clusters as compared with unpruned clusters. The upregulation was closely associated with increases in anthocyanin biosynthesis. PMID:27555920

  3. Effect of floral cluster pruning on anthocyanin levels and anthocyanain-related gene expression in ‘Houman’ grape

    PubMed Central

    Zhang, Lei; Xu, Yan-shuai; Jia, Yue; Wang, Ji-yuan; Yuan, Yue; Yu, Yang; Tao, Jian-min

    2016-01-01

    Lateral floral clusters were removed from the main axis of the floral clusters of ‘Houman’ grape plants, leaving only 3–5-cm-long region of flowers at the end of the central axis. The floral clusters were pruned at 7 days prior to flowering. The effect of the pruning on fruit quality was assessed by determining the composition and levels of anthocyanins in the fruit and anthocyanin-related gene expression. Results indicated that floral cluster pruning significantly improved the quality of the fruit by increasing berry size, fruit weight and the total content of soluble solids. Floral cluster pruning also decreased the level of titratable acidity. Sixteen different anthocyanins were detected in fruit of the pruned clusters, while only 15 were detected in fruit from unpruned clusters. The level of anthocyanins was also significantly higher in fruit of the pruned clusters than in the unpruned clusters. Anthocyanin-related gene expression was also significantly upregulated to a higher level in fruit from pruned floral clusters as compared with unpruned clusters. The upregulation was closely associated with increases in anthocyanin biosynthesis. PMID:27555920

  4. Inconformity of CXCL3 plasma level and placenta expression in preeclampsia and its effect on trophoblast viability and invasion.

    PubMed

    Gui, Shunping; Ni, Shanshan; Jia, Jin; Gong, Yunhui; Gao, Linbo; Zhang, Lin; Zhou, Rong

    2014-01-01

    As a member of the chemokine family, CXCL3 was previously known to participate in many pathophysiological events. However, whether CXCL3 stimulates trophoblast invasion as a key process of preeclampsia pathogenesis remains largely unknown. Therefore, the aim of this study was to investigate this hypothesis and determine the effect of CXCL3 on the first trimester trophoblast. Seventy gravidas were included in this study. ELISA was used to detect CXCL3 plasma levels on preeclampsia and normal pregnant groups. CXCL3 protein and mRNA levels were detected via Western blot and real-time quantitative PCR analysis after immunolocalized in human placenta. Moreover, the CXCL3 function in HTR-8/Svneo was analyzed via WST-1 assay, flow cytometry and invasion test. The plasma CXCL3 level in preeclampsia was significantly higher than that in normal pregnancy. CXCL3 expression was observed in the cytoplasm of placental trophoblasts and vascular endothelium in all groups without significant difference between maternal and fetal sides. In addition, placenta CXCL3 expression in severe preeclampsia was significantly lower than those in normal and mild PE groups. Moreover, exogenous CXCL3 can promote the proliferation and invasion of HTR-8/Svneo; however, its effect on apoptosis remains unclear. In summary, a significant abnormality of plasma CXCL3 level and placental CXCL3 expression was discovered in severe preeclampsia; CXCL3 had a function in trophoblast invasion, which indicated its participation in shallow implantation. Therefore CXCL3 might be involved in severe preeclampsia pathogenesis. PMID:25485631

  5. Moving Away from Ones and Zeros, Designing a Ground Data System Based on Higher Levels of Abstraction

    NASA Technical Reports Server (NTRS)

    Tankenson, Michael

    2008-01-01

    Previous JPL ground systems have been designed with the Ground Data System (GDS) engineer in mind. The focus on these systems has been on packaging and delivery of low level information (frames, packets, telemetry values) to the end user. It was not that long ago when project teams would be huddled over a workstation, examining crude displays of telemetry bits organized in various ways, trying to determine the status of a spacecraft. Understanding the data often required additional levels of GDS expertise, or worse, transformation of the raw data into alternative formats followed by ingestion into other tools so that the data became meaningful. The primary focus was often to answer these types of questions: "Why did this particular frame fail Reed-Solomon decode? Why did this packet get marked as invalid? Why am I missing a block of telemetry from my query?" -- which are completely valid questions to ask from a GDS Engineer's point of view, and large families of tools have been designed to help answer these questions. But these are not the questions that most users care about - which are more like: "Why is the battery state of charge trending down? Show me a summary image report for the last traverse to the target. Show me a data accountability summary for the last DSN pass." Answers to these questions, which are what users are looking for, requires a higher level of abstraction and supporting tools than mining through ones and zeros. JPL has created a next generation capability called the Mission Data Processing and Control System (MPCS) which is designed to support this higher level of abstraction by providing customizable views of the ground system combining collections of lower level information into more meaningful ways. Instead of examining frames, packets, and individual telemetry data points -- MPCS is capable of providing comprehensive summary reports, product status, overall flight/ground event status, as well as payload health summaries. Based on these

  6. Vasopressin, but not oxytocin, increases empathic concern among individuals who received higher levels of paternal warmth: a randomized controlled trial

    PubMed Central

    Tabak, Benjamin A.; Meyer, Meghan L.; Castle, Elizabeth; Dutcher, Janine M.; Irwin, Michael R.; Han, Jung H.; Lieberman, Matthew D.; Eisenberger, Naomi I.

    2014-01-01

    Background Empathy improves our ability to communicate in social interactions and motivates prosocial behavior. The neuropeptides arginine vasopressin and oxytocin play key roles in socioemotional processes such as pair bonding and parental care, which suggests that they may be involved in empathic processing. Methods We investigated how vasopressin and oxytocin affect empathic responding in a randomized, double-blind, placebo controlled, between-subjects study design. We also examined the moderating role of parental warmth, as reported in the early family environment, on empathic responding following vasopressin, oxytocin, or placebo administration. Results Among participants who reported higher levels of paternal warmth (but not maternal warmth), vasopressin (vs. placebo and oxytocin) increased ratings of empathic concern after viewing distressing and uplifting videos. No main or interaction effects were found for individuals who received oxytocin. Conclusions Vasopressin has a role in enhancing empathy among individuals who received higher levels of paternal warmth. Trial registration NCT01680718 PMID:25462898

  7. Patients with essential hypertension present higher levels of sE-selectin and sVCAM-1 than normotensive volunteers.

    PubMed

    Palomo, Iván; Marín, Patricio; Alarcón, Marcelo; Gubelin, Gilda; Viñambre, Ximena; Mora, Eduardo; Icaza, Gloria

    2003-11-01

    In essential hypertension (EH) patients, blood pressure can modify serum concentrations of some soluble forms of cell adhesion molecules (CAM), e.g., soluble E-selectin (sE-selectin) and soluble vascular cell adhesion molecule-1 (sVCAM-1). The objective of this study was to compare the serum levels of these CAMs in compensated (CH) and non-compensated (NCH) EH patients. Our findings show that sE-selectin and sVCAM-1 levels are higher in EH patients than normotensive subjects (sVCAM-1: 796+/-52 vs. 605+/-24 ng/mL, p<0.0001, and sE-selectin: 71+/-21 vs. 48+/-14 ng/mL, p<0.0001). Serum concentrations of both CAMs was higher in NCH patients than CH patients. High arterial blood pressure (ABP) may therefore increase the production of cell adhesion molecules, probably through endothelial activation. PMID:14649309

  8. The PXR rs7643645 polymorphism is associated with the risk of higher prostate-specific antigen levels in prostate cancer patients.

    PubMed

    Reyes-Hernández, Octavio D; Vega, Libia; Jiménez-Ríos, Miguel A; Martínez-Cervera, Pedro F; Lugo-García, Juan A; Hernández-Cadena, Leticia; Ostrosky-Wegman, Patricia; Orozco, Lorena; Elizondo, Guillermo

    2014-01-01

    Levels of enzymes that determine testosterone catabolism such as CYP3A4 have been associated with prostate cancer (PCa) risk. Although some studies have related CYP3A4*1B allele, a gene polymorphism that modifies CYP3A4 expression level, with PCa risk, others have failed, suggesting that additional genetic variants may be involved. Expression of CYP3A4 is largely due to the activation of Pregnane X Receptor (PXR). Particularly, rs2472677 and rs7643645 PXR polymorphisms modify CYP3A4 expression levels. To evaluate whether PXR-HNF3β/T (rs2472677), PXR-HNF4/G (rs7643645), and CYP3A4*1B (rs2740574) polymorphisms are associated with PCa a case control-study was performed. The multiple testing analysis showed that the PXR-HNF4/G polymorphism was associated with higher levels of prostate-specific antigen (PSA) in patients with PCa (OR = 3.99, p = 0.03). This association was stronger in patients diagnosed at the age of 65 years or older (OR = 10.8, p = 0.006). Although the CYP3A4*1B/*1B genotype was overrepresented in PCa patients, no differences were observed in the frequency of this and PXR-HNF3β/T alleles between controls and cases. Moreover, no significant association was found between these polymorphisms and PSA, Gleason grade, or tumor lymph node metastasis. PMID:24924803

  9. The PXR rs7643645 Polymorphism Is Associated with the Risk of Higher Prostate-Specific Antigen Levels in Prostate Cancer Patients

    PubMed Central

    Reyes-Hernández, Octavio D.; Vega, Libia; Jiménez-Ríos, Miguel A.; Martínez-Cervera, Pedro F.; Lugo-García, Juan A.; Hernández-Cadena, Leticia; Ostrosky-Wegman, Patricia; Orozco, Lorena; Elizondo, Guillermo

    2014-01-01

    Levels of enzymes that determine testosterone catabolism such as CYP3A4 have been associated with prostate cancer (PCa) risk. Although some studies have related CYP3A4*1B allele, a gene polymorphism that modifies CYP3A4 expression level, with PCa risk, others have failed, suggesting that additional genetic variants may be involved. Expression of CYP3A4 is largely due to the activation of Pregnane X Receptor (PXR). Particularly, rs2472677 and rs7643645 PXR polymorphisms modify CYP3A4 expression levels. To evaluate whether PXR-HNF3β/T (rs2472677), PXR-HNF4/G (rs7643645), and CYP3A4*1B (rs2740574) polymorphisms are associated with PCa a case control-study was performed. The multiple testing analysis showed that the PXR-HNF4/G polymorphism was associated with higher levels of prostate-specific antigen (PSA) in patients with PCa (OR = 3.99, p = 0.03). This association was stronger in patients diagnosed at the age of 65 years or older (OR = 10.8, p = 0.006). Although the CYP3A4*1B/*1B genotype was overrepresented in PCa patients, no differences were observed in the frequency of this and PXR-HNF3β/T alleles between controls and cases. Moreover, no significant association was found between these polymorphisms and PSA, Gleason grade, or tumor lymph node metastasis. PMID:24924803

  10. Significantly Higher Cytokine and Chemokine Levels in Patients with Japanese Spotted Fever than in Those with Tsutsugamushi Disease

    PubMed Central

    Iwasaki, Hiromichi; Ikegaya, Satoshi; Takada, Nobuhiro; Tamaki, Yukiko; Tabara, Kenji; Ueda, Takanori

    2014-01-01

    Tetracyclines are administered to cure Japanese spotted fever (JSF) and tsutsugamushi disease (TD). It is generally said that the clinical course of JSF is worse than that of TD despite antibiotic treatment. The precise mechanism underlying the more severe clinical course of JSF is not fully understood. We therefore examined whether the differential cytokine profile between these two infectious diseases contributes to the difference in clinical severity. The serum concentrations of various cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and gamma interferon [IFN-γ]) and chemokines (IL-8, interferon-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], MIP-1β, and eotaxin) were measured in 32 TD and 21 JSF patients. The results showed that serum levels of TNF-α in the acute phases of TD and JSF were significantly increased, with a higher concentration of TNF-α in patients with JSF (mean, 39.9 pg/ml) than in those with TD (mean, 13.8 pg/ml). Comparatively higher levels of other cytokines and chemokines (IL-6, IFN-γ, IL-8, IP-10, MCP-1, MIP-1α, and MIP-1β) were also observed in the acute phase of JSF. The clinical severity score (3.67 ± 1.71) of JSF patients was higher than that of TD patients (1.47 ± 0.77). Our findings revealed that the cytokine and chemokine levels in the acute phase of JSF were significantly higher than those in the acute phase of TD. The differential cytokine levels may be related to the difference in clinical severity between JSF and TD. PMID:24671792

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

    PubMed

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

    2016-07-01

    Low-normal thyroid function within the euthyroid range may confer higher plasma triglycerides, but relationships with plasma apolipoprotein (apo) E, which plays an important role in the metabolism of triglyceride-rich apoB-containing lipoproteins, are unknown. We determined relationships of plasma apoE with thyroid stimulating hormone (TSH) and free thyroxine (free T4) in euthyroid subjects with and without Type 2 diabetes mellitus (T2DM). TSH, free T4, lipids, and apoE were measured in fasting plasma from 72 T2DM subjects and 82 nondiabetic subjects. The APOE genotype was also determined. Free T4 was slightly higher in T2DM (p=0.030), but TSH levels were not different vs. nondiabetic subjects. The APOE genotype distribution was not different between the groups. None of the participants had the ε2/ε2 genotype. Plasma triglycerides were higher in T2DM (p=0.037). ApoB and apoE levels were not different between the groups. In all subjects combined, multivariable analysis showed that plasma triglycerides (p=0.039), non-high density lipoprotein (non-HDL) cholesterol (p=0.030), and apoE levels (p=0.002) were each independently and positively associated with TSH after adjustment for age, sex, T2DM and the presence of the APOE ε3 allele. Furthermore, the associations of TSH with apoE remained present after adjustment for either triglycerides, non-HDL cholesterol, or apoB (p=0.005 to 0.023). The presence of T2DM did not modify the relationships of TSH with these (apo) lipoprotein variables (p=0.11 to 0.36). In conclusion, low-normal thyroid function, as indicated by higher TSH levels within the euthyroid range, may influence the metabolism of triglyceride-rich lipoproteins by affecting apoE regulation. PMID:26916531

  12. Higher circulating levels of chemokines CXCL10, CCL20 and CCL22 in patients with ischemic heart disease.

    PubMed

    Safa, A; Rashidinejad, H R; Khalili, M; Dabiri, S; Nemati, M; Mohammadi, M M; Jafarzadeh, A

    2016-07-01

    Recruitment of leukocytes is one of the earliest events in the pathogenesis of ischemic heart disease (IHD) and chemokines play an important role in the migration of these cells into the inflammation sites. The aim of this study was to evaluate the CXCL10, CCL20 and CCL22 levels and the single nucleotide polymorphisms (SNPs) rs4508917, rs6749704 and rs4359426 in chemokine genes in patients with IHD to clarify any association. A total of 300 patients with IHD as having acute myocardial infarction (AMI; n=100), stable angina (SA; n=100) or unstable angina (UA; n=100) and 100 healthy subjects as a control group were enrolled to study. Serum samples from all participants were tested for the CXCL10, CCL20 and CCL22 levels by using ELISA. The SNPs were determined by polymerase chain reaction-restriction length polymorphism (PCR-RFLP) method. The mean serum concentrations of CXCL10, CCL20 and CCL22 in AMI patients (395.97±21.20Pg/mL, 108.38±10.31Pg/mL and 1852.58±205.77Pg/mL), SA patients (405.48±27.36Pg/mL, 90.20±7.69Pg/mL and 2322.04±231.23Pg/mL) and UA patients (396.69±22.79Pg/mL, 141.87±18.10Pg/mL and 2754.89±211.70Pg/mL) were significantly higher than in the healthy group (179.38±8.85Pg/mL, 51.92±4.62Pg/mL and 451.82±23.76Pg/mL, respectively; P<0.001). Similarly, the serum levels of CXCL10, CCL20 and CCL22 in total IHD patients (399.38±13.77Pg/mL, 113.49±7.48Pg/mL and 2309.84±126.39Pg/mL, respectively) were also significantly higher as compared with healthy subjects (P<0.001). The serum levels of CCL20 and CCL22 in UA patients were significantly higher than those in SA and AMI patients, respectively (P<0.01 and P<0.003, respectively). The serum levels of CXCL10 and CCL20 in diabetic patients were significantly higher in comparison to non-diabetic patients (P<0.05 and P<0.02, respectively). The serum levels of CCL22 in dyslipidemic- and obese patients were also significantly higher in comparison with non-dyslipidemic- and non-obese patients

  13. 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

  14. The Genomic Landscape of Position Effects on Protein Expression Level and Noise in Yeast.

    PubMed

    Chen, Xiaoshu; Zhang, Jianzhi

    2016-05-25

    Position effect, the influence of the chromosomal location of a gene on its activity, is a fundamental property of the genome. By placing a GFP gene cassette at 482 different locations across all chromosomes in budding yeast, we quantified the position effects on protein expression level and noise at the genomic scale. The position effects are significant, altering the mean protein expression level by up to 15 times and expression noise by up to 20 times. DNA replication timing, 3D chromosomal conformation, and several histone modifications are major covariates of position effects. Essential genes are enriched in genomic regions with inherently low expression noise, supporting the hypothesis that chromosomal clustering of essential genes results from selection against their expressional stochasticity. Position effects exhibit significant interactions with promoters. Together, our results suggest that position effects have shaped the evolution of chromosome organization and should inform future genome engineering efforts. PMID:27185547

  15. 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

  16. A Theoretical Lower Bound for Selection on the Expression Levels of Proteins

    PubMed Central

    Price, Morgan N.; Arkin, Adam P.

    2016-01-01

    We use simple models of the costs and benefits of microbial gene expression to show that changing a protein’s expression away from its optimum by 2-fold should reduce fitness by at least 0.2·P, where P is the fraction the cell’s protein that the gene accounts for. As microbial genes are usually expressed at above 5 parts per million, and effective population sizes are likely to be above 106, this implies that 2-fold changes to gene expression levels are under strong selection, as Ne·s≫1, where Ne is the effective population size and s is the selection coefficient. Thus, most gene duplications should be selected against. On the other hand, we predict that for most genes, small changes in the expression will be effectively neutral. PMID:27289091

  17. A Theoretical Lower Bound for Selection on the Expression Levels of Proteins.

    PubMed

    Price, Morgan N; Arkin, Adam P

    2016-01-01

    We use simple models of the costs and benefits of microbial gene expression to show that changing a protein's expression away from its optimum by 2-fold should reduce fitness by at least [Formula: see text], where P is the fraction the cell's protein that the gene accounts for. As microbial genes are usually expressed at above 5 parts per million, and effective population sizes are likely to be above 10(6), this implies that 2-fold changes to gene expression levels are under strong selection, as [Formula: see text], where Ne is the effective population size and s is the selection coefficient. Thus, most gene duplications should be selected against. On the other hand, we predict that for most genes, small changes in the expression will be effectively neutral. PMID:27289091

  18. Dscam Expression Levels Determine Presynaptic Arbor Sizes in Drosophila Sensory Neurons

    PubMed Central

    Kim, Jung Hwan; Wang, Xin; Coolon, Rosemary; Ye, Bing

    2013-01-01

    SUMMARY Expression of the Down syndrome cell-adhesion molecule (Dscam) is increased in the brains of patients with several neurological disorders. Although Dscam is critically involved in many aspects of neuronal development, little is known about either the mechanism that regulates its expression or the functional consequences of dysregulated Dscam expression. Here, we show that Dscam expression levels serve as an instructive code for the size control of presynaptic arbor. Two convergent pathways, involving dual leucine zipper kinase (DLK) and fragile X mental retardation protein (FMRP), control Dscam expression through protein translation. Defects in this regulation of Dscam translation lead to exuberant presynaptic arbor growth in Drosophila somatosensory neurons. Our findings demonstrate a previously unknown aspect of Dscam function and provide insights into how dysregulated Dscam may contribute to the pathogenesis of neurological disorders. PMID:23764288

  19. The human phenolsulphotransferase polymorphism is determined by the level of expression of the enzyme protein.

    PubMed Central

    Jones, A L; Roberts, R C; Coughtrie, M W

    1993-01-01

    We have examined the expression of platelet phenolsulphotransferase (PST) in 60 individuals. Using an antibody which recognizes both forms of PST present in man (P-PST and M-PST), we determined that the polymorphism of platelet P-PST activity is determined by the level of expression of the enzyme protein. The implications for susceptibility to adverse drug reactions and chemical carcinogenesis are discussed. Images Figure 1 Figure 2 Figure 3 PMID:8257413

  20. Alterations in methylation and expression levels of imprinted genes H19 and Igf2 in the fetuses of diabetic mice.

    PubMed

    Shao, Wei-Juan; Tao, Ling-Yun; Gao, Cheng; Xie, Jian-Yun; Zhao, Ru-Qian

    2008-08-01

    The study aimed to reveal alterations in expression and methylation levels of the growth-related imprinted genes H19 and Igf2 in fetuses of diabetic mice. Diabetes was induced in female mice by intraperitoneal injection of streptozotocin. DNA and total RNA were extracted from fetuses obtained from diabetic and control dams on embryonic day (E) 14. Real-time RT-PCR analysis revealed that the mRNA expression of Igf2 in fetuses from diabetic mice was 0.65-fold of the control counterparts. Bisulfite genomic sequencing demonstrated that the methylation level of the H19-Igf2 imprint control region was 19.1% higher in diabetic fetuses than in those of control dams. In addition, the body weight of pups born to diabetic dams was 26.5% lower than that of the control group. The results indicate that maternal diabetes can affect fetal development by means of altered expression of imprinted genes. The modified genomic DNA methylation status of imprinting genes may account for the change in gene expression. PMID:18724775

  1. An alternative method of enhancing the expression level of heterologous protein in Escherichia coli.

    PubMed

    Yin, Jun; Tian, Hong; Bao, Lichen; Dai, Xin; Gao, Xiangdong; Yao, Wenbing

    2014-12-12

    Though numerous strategy options are available for achieving high expression levels of genes in Escherichia coli, not every gene can be efficiently expressed in this organism. By investigating the relationship between the mRNA secondary structure of translational initiation region (TIR) and gene expression in E.coli, we establish a simple method to design sequences of appropriate TIR (from -35 to +36) that meet a specific expression level as we need. Using this method, overexpression of native human humor necrosis factor α and extracellular domain of Her2/neu protein (aa 23-146) in E. coli were achieved. Differences in expression appeared was mainly related to the efficiency of translation initiation and the stability of mRNA secondary structure, because the intracellular mRNA levels analyzed by real-time RT-PCR were quite similar. Our approach can overcome the steric hindrance of translation startup, and therefore promote translation smoothly to acquire high expression of exogenous protein. PMID:25449272

  2. Stable Plastid Transformation for High-Level Recombinant Protein Expression: Promises and Challenges

    PubMed Central

    Gao, Meili; Li, Yongfei; Xue, Xiaochang; Wang, Xianfeng; Long, Jiangang

    2012-01-01

    Plants are a promising expression system for the production of recombinant proteins. However, low protein productivity remains a major obstacle that limits extensive commercialization of whole plant and plant cell bioproduction platform. Plastid genetic engineering offers several advantages, including high levels of transgenic expression, transgenic containment via maternal inheritance, and multigene expression in a single transformation event. In recent years, the development of optimized expression strategies has given a huge boost to the exploitation of plastids in molecular farming. The driving forces behind the high expression level of plastid bioreactors include codon optimization, promoters and UTRs, genotypic modifications, endogenous enhancer and regulatory elements, posttranslational modification, and proteolysis. Exciting progress of the high expression level has been made with the plastid-based production of two particularly important classes of pharmaceuticals: vaccine antigens, therapeutic proteins, and antibiotics and enzymes. Approaches to overcome and solve the associated challenges of this culture system that include low transformation frequencies, the formation of inclusion bodies, and purification of recombinant proteins will also be discussed. PMID:23093835

  3. Expression of fas protein on CD4+T cells irradiated by low level He-Ne

    NASA Astrophysics Data System (ADS)

    Nie, Fan; Zhu, Jing; Zhang, Hui-Guo

    2005-07-01

    Objective: To investigate the influence on the Expression of Fas protein on CD4+ T cells irradiated by low level He-Ne laser in the cases of psoriasis. Methods:the expression of CD4+ T Fas protein was determined in the casee of psoriasis(n=5) pre and post-low level laser irradiation(30 min、60min and 120min)by flow cytometry as compared withthe control(n=5). Results:In the cases of psoriasis,the expression of CD4+T FAS protein 21.4+/-3.1% was increased significantly than that of control group 16.8+/-2.1% pre-irradiation, p<0.05in the control,there is no difference between pre and post- irradiation,p>0.05in the cases , the expression of CD4+T Fas protein wae positively corelated to the irradiation times, when the energy density arrived to 22.92J/cm2(60 minutes)and 45.84J/cm2(120minutes), the expression of CD4+ T Fas protein was increased significantly as compared with pre-irradiation,p<0.05.Conclusion: The expression of CD4+T Fas protein may be increased by low level He-Ne laser irradiation ,the uncontrolled status of apoptosis could be corrected.

  4. Expression of DNA repair genes in burned skin exposed to low-level red laser.

    PubMed

    Trajano, Eduardo Tavares Lima; Mencalha, Andre Luiz; Monte-Alto-Costa, Andréa; Pôrto, Luís Cristóvão; de Souza da Fonseca, Adenilson

    2014-11-01

    Although red laser lights lie in the region of non-ionizing radiations in the electromagnetic spectrum, there are doubts whether absorption of these radiations causes lesions in the DNA molecule. Our aim was to investigate the expression of the genes involved with base excision and nucleotide excision repair pathways in skin tissue submitted to burn injury and exposed to low-level red laser. Wistar rats were divided as follows: control group-rats burned and not irradiated, laser group-rats burned and irradiated 1 day after injury for five consecutive days, and later laser group-rats injured and treated 4 days after injury for five consecutive days. Irradiation was performed according to a clinical protocol (20 J/cm(2), 100 mW, continuous wave emission mode). The animals were sacrificed on day 10, and scarred tissue samples were withdrawn for total RNA extraction, complementary DNA (cDNA) synthesis, and evaluation of gene expression by quantitative polymerase chain reaction. Low-level red laser exposure (1) reduces the expression of APE1 messenger (mRNA), (2) increases the expression of OGG1 mRNA, (3) reduces the expression of XPC mRNA, and (4) increases the expression of XPA mRNA both in laser and later laser groups. Red laser exposure at therapeutic fluences alters the expression of genes related to base excision and nucleotide excision pathways of DNA repair during wound healing of burned skin. PMID:24930134

  5. High-level expression of Egr-1 and Egr-1–inducible genes in mouse and human atherosclerosis

    PubMed Central

    McCaffrey, Timothy A.; Fu, Chenzhong; Du, Baoheng; Eksinar, Sukru; Kent, K. Craig; Bush, Harry; Kreiger, Karl; Rosengart, Todd; Cybulsky, Myron I.; Silverman, Eric S.; Collins, Tucker

    2000-01-01

    To understand the mRNA transcript profile in the human atherosclerotic lesion, RNA was prepared from the fibrous cap versus adjacent media of 13 patients undergoing carotid endarterectomy. cDNA expression arrays bearing 588 known genes indicated that lesions express unexpectedly high levels of the early growth response gene, Egr-1 (NGFI-A), a zinc-finger transcription factor that modulates a cluster of stress-responsive genes including PDGF and TGF-β. Expression of Egr-1 was an average of 5-fold higher in the lesion than in the adjacent media, a result confirmed by RT-PCR, and many Egr-1–inducible genes were also strongly elevated in the lesion. Time-course analyses revealed that Egr-1 was not induced ex vivo. Immunocytochemistry indicated that Egr-1 was expressed prominently in the smooth muscle–actin positive cells, particularly in areas of macrophage infiltration, and in other cell types, including endothelial cells. Induction of atherosclerosis in LDL receptor-null mice by feeding them a high-fat diet resulted in a progressive increase in Egr-1 expression in the aorta. Thus, induction of Egr-1 by atherogenic factors may be a key step in coordinating the cellular events that result in vascular lesions. PMID:10712437

  6. Interactions between copy number and expression level of genes involved in fluconazole resistance in Candida glabrata

    PubMed Central

    Abbes, Salma; Mary, Charles; Sellami, Hayet; Michel-Nguyen, Annie; Ayadi, Ali; Ranque, Stéphane

    2013-01-01

    Objectives: This study aimed to elucidate the relative involvement of drug resistance gene copy number and overexpression in fluconazole resistance in clinical C. glabrata isolates using a population-based approach. Methods: Fluconazole resistance levels were quantified using the minimal inhibitory concentration (MIC) via Etest method. Both gene expression levels and gene copy number of CgCDR1, CgPDH1, CgERG11, and CgSNQ2 were assessed via quantitative real-time PCR. The influence of the main effects and first-level interactions of both the expression level and copy number of these genes on fluconazole resistance levels were analyzed using a multivariate statistical model. Results: Forty-three C. glabrata isolates were collected from 30 patients during in a hospital survey. In the multivariate analysis, C. glabrata fluconazole MICs were independently increased by CgSNQ2 overexpression (p < 10−4) and the interaction between CgPDH1 gene copy number and CgPDH1 expression level (p = 0.038). In contrast, both CgPDH1 overexpression (p = 0.049) and the interaction between CgSNQ2 and CgERG11 expression (p = 0.003) led to a significant decrease in fluconazole MICs. Conclusion: Fluconazole resistance in C. glabrata involves complex interactions between drug resistance gene expression and/or copy number. The population-based multivariate analysis highlighted the involvement of the CgSNQ2 gene in fluconazole resistance and the complex effect of the other genes such as PDH1 for which overexpression was associated with reduced fluconazole resistance levels, while the interaction between PDH1 overexpression and copy number was associated with increased resistance levels. PMID:24273749

  7. Effects of sexual maturation and feeding level on fatty acid metabolism gene expression in muscle, liver, and visceral adipose tissue of diploid and triploid rainbow trout, Oncorhynchus mykiss.

    PubMed

    Manor, Meghan L; Cleveland, Beth M; Weber, Gregory M; Kenney, P Brett

    2015-01-01

    In many cultured fish species, such as salmonids, gonadal development occurs at the expense of stored energy and nutrients, including lipids. However, mechanisms regulating nutrient repartitioning during sexual maturation are not well understood. This study compared sexually maturing diploid (2N) and sterile triploid (3N) female rainbow trout to investigate effects of sexual maturation on expression of 35 genes involved in fatty acid metabolism, including genes within fatty acid synthesis, β-oxidation, and cofactors of the mTOR and PPAR signaling pathways, in liver, white muscle, and visceral adipose tissue. Diploid fish were fed at different rations (0.25% and 0.50% tank biomass, and satiation) to determine effects of ration on gene expression. Gene expression was affected by ration level only in white muscle; erk and acat2 had higher expression in fish fed higher rations. On the other hand, sexual maturation affected gene expression across all three tissue types. Data indicate 2N fish have higher expression of β-oxidation genes within white muscle and within visceral adipose tissue. These findings support enhanced fatty acid mobilization within these tissues during sexual maturation. Higher expression of fatty acid synthesis genes in 3N female liver is associated with higher expression of mTOR cofactors and pparγ, which reflects continued deposition of lipids in these fish. Furthermore, greater expression of genes involved in β-oxidation pathways across ration levels in 2N females suggests that sexual maturation and the associated maturation-related signals are stronger regulators of lipid metabolism-related genes rather the rations applied in the current study. PMID:25242626

  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. Restored expression levels of TET1 decrease the proliferation and migration of renal carcinoma cells

    PubMed Central

    FAN, MIN; HE, XIAOZHOU; XU, XIANLIN

    2015-01-01

    Renal carcinoma is the most common type of kidney cancer in adults and is responsible for ~90–95% of the cases of kidney cancer. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is a member of the TET family of enzymes, and is expressed at low levels in multiple malignancies. In the present study, a series of experiments were designed and performed to investigate whether the expression of TET1 is clinically correlated with clinical outcomes in renal carcinoma, and to examine the associations between TET1 expression level and the proliferation and migration in renal carcinoma cells. As a result, TET1 was observed to exhibit markedly low expression levels in 54 tumor tissue samples from 54 patients with renal carcinoma. Furthermore, statistical analysis revealed a clinical correlation between low expression levels of TET1 and the prognosis of patients with renal carcinoma. When TET1 was overexpressed in renal carcinoma cells, the viability and invasive abilities of the cells were decreased, and the rate of apoptosis was increased. In conclusion, the results demonstrated that TET1 is involved in tumor inhibition in renal carcinoma by promoting cell apoptosis and inhibiting cell proliferation and invasion, which may be exploited as a novel therapeutic target in the treatment of renal carcinoma. PMID:26165803

  11. Low-level lasers affect uncoupling protein gene expression in skin and skeletal muscle tissues

    NASA Astrophysics Data System (ADS)

    Canuto, K. S.; Sergio, L. P. S.; Paoli, F.; Mencalha, A. L.; Fonseca, A. S.

    2016-03-01

    Wavelength, frequency, power, fluence, and emission mode determine the photophysical, photochemical, and photobiological responses of biological tissues to low-level lasers. Free radicals are involved in these responses acting as second messengers in intracellular signaling processes. Irradiated cells present defenses against these chemical species to avoid unwanted effects, such as uncoupling proteins (UCPs), which are part of protective mechanisms and minimize the effects of free radical generation in mitochondria. In this work UCP2 and UCP3 mRNA gene relative expression in the skin and skeletal muscle tissues of Wistar rats exposed to low-level red and infrared lasers was evaluated. Samples of the skin and skeletal muscle tissue of Wistar rats exposed to low-level red and infrared lasers were withdrawn for total RNA extraction, cDNA synthesis, and the evaluation of gene expression by quantitative polymerase chain reaction. UCP2 and UCP3 mRNA expression was differently altered in skin and skeletal muscle tissues exposed to lasers in a wavelength-dependent effect, with the UCP3 mRNA expression dose-dependent. Alteration on UCP gene expression could be part of the biostimulation effect and is necessary to make cells exposed to red and infrared low-level lasers more resistant or capable of adapting in damaged tissues or diseases.

  12. 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

  13. Higher Fasting Plasma Glucose Levels, within the Normal Range, are Associated with Decreased Processing Speed in High Functioning Young Elderly.

    PubMed

    Raizes, Meytal; Elkana, Odelia; Franko, Motty; Ravona Springer, Ramit; Segev, Shlomo; Beeri, Michal Schnaider

    2015-01-01

    We explored the association of plasma glucose levels within the normal range with processing speed in high functioning young elderly, free of type 2 diabetes mellitus (T2DM). A sample of 41 participants (mean age = 64.7, SD = 10; glucose 94.5 mg/dL, SD = 9.3), were examined with a computerized cognitive battery. Hierarchical linear regression analysis showed that higher plasma glucose levels, albeit within the normal range (<110 mg/dL), were associated with longer reaction times (p <  0.01). These findings suggest that even in the subclinical range and in the absence of T2DM, monitoring plasma glucose levels may have an impact on cognitive function. PMID:26484908

  14. Different 3' end regions strongly influence the level of gene expression in plant cells.

    PubMed Central

    Ingelbrecht, I L; Herman, L M; Dekeyser, R A; Van Montagu, M C; Depicker, A G

    1989-01-01

    We have investigated the functional role of a 3' end region on the expression of a reporter gene in plant cells. In stably transformed plants, expression of the reporter gene without a plant gene 3' end is variable and depends on the fortuitous presence of polyadenylation signals in the downstream sequences. When the reporter gene is flanked by pBR322 DNA, 3'-processing and polyadenylation occurs at (a) cryptic site(s) within these vector sequences. Using a transient gene expression system, we present a deletion analysis of the 3' end of the octopine synthase gene showing that the most proximal polyadenylation signal per se is not sufficient to ensure expression but that a downstream (G)T-rich sequence is also required. Optimal expression of the fusion gene requires more than 98 base pairs and at most 142 base pairs downstream from the most distal polyadenylation site. We analyzed the expression of chimeric genes with 3' end sequences originating from different plant genes. In the transient expression assay, all constructs direct similar neomycin phosphotransferase II activities. However, in stably transformed tissue, the gene constructs displayed characteristic expression levels which varied as much as 60-fold. This result suggests a role for 3' end sequences in post-transcriptional processes such as efficiency of 3'-processing and/or mRNA stability. PMID:2562510

  15. Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues

    PubMed Central

    Azemikhah, Mitra; Ashtiani, Hamidreza Ahmadi; Aghaei, Mahmoud; Rastegar, Hosein

    2015-01-01

    Discoidin domain receptor (DDR) is a new member of the receptor tyrosine kinase family. There are two isoforms of discoidin domain receptor (DDR), DDR1 and DDR2. These receptors play a major role in the adhesion, motility and cell proliferation. Due to the important role of DDR2 in the development of tumor extension, this receptor is pivotal in the field of carcinogenesis. The aim of this study was to investigate the mRNA and protein expression of DDR2, in the malignant, benign prostatic hyperplasia (BPH) and normal tissues of patients with prostate cancer. In this study the gene and protein expression of DDR2 in adjacent normal (n=40), BPH (n=40), and malignant (n=40) prostate tissue were measured using real-time PCR and Western blotting. Then, the correlation of DDR2 gene and protein expression with prognostic factors such as age, tumor grade, tumor stage, lymph node involvement, and serum prostate-specific antigen (PSA) concentration were evaluated. The relative mRNA and protein expression level of DDR2 in malignant and benign prostate tissue was significantly higher than those of adjacent normal tissues (P<0.01). This expression was found to increase approximately 3.5 and 2.1 fold for mRNA and protein levels, respectively. Spearman test indicated a significant correlation between DDR2 mRNA and protein expression with prognostic factors such as tumor grade, stage, lymph node involvement, and serum PSA concentration. However, significant correlation with age was not observed. These findings suggest that DDR2 is a cancer-related gene associated with the aggressive progression of prostate cancer patients. PMID:26600862

  16. Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues.

    PubMed

    Azemikhah, Mitra; Ashtiani, Hamidreza Ahmadi; Aghaei, Mahmoud; Rastegar, Hosein

    2015-01-01

    Discoidin domain receptor (DDR) is a new member of the receptor tyrosine kinase family. There are two isoforms of discoidin domain receptor (DDR), DDR1 and DDR2. These receptors play a major role in the adhesion, motility and cell proliferation. Due to the important role of DDR2 in the development of tumor extension, this receptor is pivotal in the field of carcinogenesis. The aim of this study was to investigate the mRNA and protein expression of DDR2, in the malignant, benign prostatic hyperplasia (BPH) and normal tissues of patients with prostate cancer. In this study the gene and protein expression of DDR2 in adjacent normal (n=40), BPH (n=40), and malignant (n=40) prostate tissue were measured using real-time PCR and Western blotting. Then, the correlation of DDR2 gene and protein expression with prognostic factors such as age, tumor grade, tumor stage, lymph node involvement, and serum prostate-specific antigen (PSA) concentration were evaluated. The relative mRNA and protein expression level of DDR2 in malignant and benign prostate tissue was significantly higher than those of adjacent normal tissues (P<0.01). This expression was found to increase approximately 3.5 and 2.1 fold for mRNA and protein levels, respectively. Spearman test indicated a significant correlation between DDR2 mRNA and protein expression with prognostic factors such as tumor grade, stage, lymph node involvement, and serum PSA concentration. However, significant correlation with age was not observed. These findings suggest that DDR2 is a cancer-related gene associated with the aggressive progression of prostate cancer patients. PMID:26600862

  17. Diagnostic investigations of DKK-1 and PDCD5 expression levels as independent prognostic markers of human chondrosarcoma.

    PubMed

    Zarea, Mojtaba; Mohammadian Bajgiran, Amirhossein; Sedaghati, Farnoush; Hatami, Negin; Taheriazam, Afshin; Yahaghi, Emad; Shakeri, Mohammadreza

    2016-07-01

    In this study, we investigated the expression levels of Dickkopf-1 (DKK-1) and programmed cell death 5 (PDCD5) by using quantitative real-time PCR and immunohistochemistry in patients with chondrosarcoma. The DKK-1 mRNA levels were significantly higher in chondrosarcoma when compared with the corresponding nontumor tissues (mean ± SD: 4.23 ± 1.54; 1.54 ± 0.87; P = 0.001). PDCD5 mRNA levels were remarkably deceased in tumor tissues when compared with corresponding nontumor tissues (mean ± SD: 1.94 ± 0.73; 5.42 ± 1.73; P = 0.001). The high and moderate DKK-1 expressions were observed for 60% of chondrosarcoma samples in comparison with 27.5% of corresponding nontumor tissues (P  =  0.001). Moreover, low expression of PDCD5 was found in 67.5% of the tumor tissues when compared with the nontumor tissues (32.5%; P = 0.002). The results of this study showed that high DKK-1 expression levels were strongly related to MSTS stage (P = 0.011) and the advancement of histological grade (P < 0.001). Furthermore, the PDCD5 expression levels were correlated with histological grade (P < 0.001), MSTS stage (P = 0.016), and distant metastasis (P = 0.001). Kaplan-Meier survival and log-rank survival showed that patients with high DKK-1 levels and low PDCD5 levels were correlated with shorter overall survival (log-rank test P < 0.001). PDCD5 levels, histological grade, and tumor stage were independent predictors of overall survival. In conclusion, DKK-1 and PDCD5 can be independent predictors of overall survival in patients suffering from chondrosarcoma. © 2016 IUBMB Life, 68(7):597-601, 2016. PMID:27255549

  18. Calpain expression in lymphoid cells. Increased mRNA and protein levels after cell activation.

    PubMed

    Deshpande, R V; Goust, J M; Chakrabarti, A K; Barbosa, E; Hogan, E L; Banik, N L

    1995-02-10

    Although calpain is ubiquitously present in human tissues and is thought to play a role in demyelination, its activity is very low in resting normal lymphocytes. To determine the nature of calpain expression at the mRNA and protein levels in human lymphoid cells, we studied human T lymphocytic, B lymphocytic, and monocytic lines as well as peripheral blood mononuclear cells. Stimulation of cells with the phorbol ester phorbol myristate acetate and the calcium ionophore A23187 resulted in increased calpain mRNA and protein expression. Calpain mRNA expression is also increased in human T cells stimulated with anti-CD3. A dissociation between the increases of RNA and protein suggested that calpain could be released from the cells; the subsequent experiments showed its presence in the extracellular environment. 5,6-Dichloro-1b-D-ribofuranosylbenzimidazole, a reversible inhibitor of mRNA synthesis, reduced calpain mRNA levels by 50-67% and protein levels by 72-91%. Its removal resulted in resumption of both calpain mRNA and protein synthesis. Cycloheximide, a translational inhibitor, reduced calpain protein levels by 77-81% and calpain mRNA levels by 96% in activated THP-1 cells. Interferon-gamma induced calpain mRNA and protein in U-937 and THP-1 cells. Dexamethasone increased mRNA expression in THP-1 cells. Our results indicate that activation of lymphoid cells results in de novo synthesis and secretion of calpain. PMID:7852311

  19. 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

  20. TSLP Expression and High Serum TSLP Level Indicate a Poor Prognosis in Gastric Cancer Patients

    PubMed Central

    Watanabe, Joji; Saito, Hiroaki; Miyatani, Kozo; Ikeguchi, Masahide; Umekita, Yoshihisa

    2015-01-01

    Background Thymic stromal lymphopoietin (TSLP) plays an important role in promoting tumor survival, by manipulating the immune response and angiogenesis. However, the clinical significance of TSLP in gastric cancer is unclear. Methods Immunohistochemistry was used to investigate TSLP expression in non-cancerous gastric mucosa and gastric cancer tissue from patients with gastric cancer. Serum TSLP levels were measured using an enzyme-linked immunosorbent assay. Results Tumors with TSLP expression were significantly larger than those without TSLP expression. TSLP expression was observed more frequently in advanced (T2/T3/T4) than in early (T1) gastric cancer and in stage 3/4 than in stage 1/2. Lymph node metastasis, liver metastasis, positive peritoneal lavage cytology, lymphatic invasion, and vascular invasion occurred significantly more often in TSLP-expressing than in non-expressing tumors. The prognosis of patients with TSLP-positive tumors was significantly worse than that of patients with TSLP-negative tumors. Patients with high serum TSLP concentrations also had a significantly worse prognosis than those with low concentrations. Multivariate analysis identified serum TSLP level as an independent prognostic indicator. Conclusion TSLP is closely related to the progression of gastric cancer and may predict survival in these patients. PMID:26538800

  1. Analysis of gene expression patterns and levels in maize hybrids and their parents.

    PubMed

    Nie, H S; Li, S P; Shan, X H; Wu, Y; Su, S Z; Liu, H K; Han, J Y; Yuan, Y P

    2015-01-01

    Heterosis has greatly contributed to conventional plant breeding and is widely used to increase crop plant productivity. However, although some studies have explored the mechanisms of heterosis at the genomic and transcriptome level, these mechanisms still remain unclear. The growth and development of maize seedlings and immature embryos have an important impact on subsequent production. This study investigated differentially expressed genes (DEGs) between parents and reciprocal hybrids in the seedling leaves, roots, and immature embryo 15 days after pollination using amplified fragment length polymorphism (AFLP)-based transcript profiling (cDNA-AFLP). We isolated 180, 170, and 108 genes from the leaves, roots, and immature embryos, respectively, that were differentially expressed between hybrids and parents. Sequencing and functional analysis revealed that 107 transcript-derived fragments in the roots and leaves and 90 in the immature embryos were involved in known functions, whereas many DEGs had roles in plant growth and development, photosynthesis, signal transduction, and seed germination. Quantitative reverse-transcription polymerase chain reaction analysis of relative expression levels between reciprocal hybrids and both parental genotypes of selected genes produced results that were consistent with cDNA-AFLP. We validated the expression patterns of 15 selected genes related to heterosis formation and revealed that most showed non-additive expression in one or both hybrids, including dominant, underdominant, and overdominant expression. This indicates that gene-regulatory interactions among parental alleles play an important role in heterosis during the early developmental stages of maize. PMID:26634505

  2. Higher levels of cardiovascular fitness are associated with better executive function and prefrontal oxygenation in younger and older women

    PubMed Central

    Dupuy, Olivier; Gauthier, Claudine J.; Fraser, Sarah A.; Desjardins-Crèpeau, Laurence; Desjardins, Michèle; Mekary, Said; Lesage, Frederic; Hoge, Rick D.; Pouliot, Philippe; Bherer, Louis

    2015-01-01

    Aim: Many studies have suggested that physical exercise training improves cognition and more selectively executive functions. There is a growing interest to clarify the neurophysiological mechanisms that underlie this effect. The aim of the current study was to evaluate the neurophysiological changes in cerebral oxygenation associated with physical fitness level and executive functions. Method: In this study, 22 younger and 36 older women underwent a maximal graded continuous test (i.e., V˙O2max) in order to classify them into a fitness group (higher vs. lower fit). All participants completed neuropsychological paper and pencil testing and a computerized Stroop task (which contained executive and non-executive conditions) in which the change in prefrontal cortex oxygenation was evaluated with near infrared spectroscopy (NIRS). Results: Our findings revealed a Fitness × Condition interaction (p < 0.05) such that higher fit women scored better on measures of executive functions than lower fit women. In comparison to lower fit women, higher fit women had faster reaction times in the Executive condition of the computerized Stroop task. No significant effect was observed in the non-executive condition of the test and no interactions were found with age. In measures of cerebral oxygenation (ΔHbT and ΔHbO2), we found a main effect of fitness on cerebral oxygenation during the Stroop task such that only high fit women demonstrated a significant increase in the right inferior frontal gyrus. Discussion/Conclusion: Higher fit individuals who demonstrate better cardiorespiratory functions (as measured by V˙O2max) show faster reaction times and greater cerebral oxygenation in the right inferior frontal gyrus than women with lower fitness levels. The lack of interaction with age, suggests that good cardiorespiratory functions can have a positive impact on cognition, regardless of age. PMID:25741267

  3. TRPV1 expression level in isolectin B₄-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity.

    PubMed

    Ono, Kentaro; Ye, Yi; Viet, Chi T; Dang, Dongmin; Schmidt, Brian L

    2015-05-01

    Differential thermal nociception across inbred mouse strains has genetic determinants. Thermal nociception is largely attributed to the heat/capsaicin receptor transient receptor potential vanilloid 1 (TRPV1); however, the contribution of this channel to the genetics of thermal nociception has not been revealed. In this study we compared TRPV1 expression levels and electrophysiological properties in primary sensory neurons and thermal nociceptive behaviors between two (C57BL/6 and BALB/c) inbred mouse strains. Using immunofluorescence and patch-clamp physiology methods, we demonstrated that TRPV1 expression was significantly higher in isolectin B4 (IB4)-positive trigeminal sensory neurons of C57BL/6 relative to BALB/c; the expression in IB4-negative neurons was similar between the strains. Furthermore, using electrophysiological cell classification (current signature method), we showed differences between the two strains in capsaicin sensitivity in IB4-positive neuronal cell types 2 and 13, which were previously reported as skin nociceptors. Otherwise electrophysiological membrane properties of the classified cell types were similar in the two mouse strains. In publicly available nocifensive behavior data and our own behavior data from the using the two mouse strains, C57BL/6 exhibited higher sensitivity to heat stimulation than BALB/c, independent of sex and anatomical location of thermal testing (the tail, hind paw, and whisker pad). The TRPV1-selective antagonist JNJ-17203212 inhibited thermal nociception in both strains; however, removing IB4-positive trigeminal sensory neurons with IB4-conjugated saporin inhibited thermal nociception on the whisker pad in C57BL/6 but not in BALB/c. These results suggest that TRPV1 expression levels in IB4-positive type 2 and 13 neurons contributed to differential thermal nociception in skin of C57BL/6 compared with BALB/c. PMID:25787958

  4. Association between plasma selenium level and NRF2 target genes expression in humans.

    PubMed

    Reszka, Edyta; Wieczorek, Edyta; Jablonska, Ewa; Janasik, Beata; Fendler, Wojciech; Wasowicz, Wojciech

    2015-04-01

    Animal studies in rodent and in vitro studies indicate compensatory role of nuclear factor (erythroid-derived 2)-like (Nrf2) and Nrf2-regulated antioxidant and phase II biotransformation enzymes for the dietary selenium (Se) deficiency or for the loss of selenoproteins. To explore associations between plasma Se level and NRF2-regulated cytoprotective genes expression, an observational study was conducted in a population of 96 healthy non-smoking men living in Central Poland aged 18-83 years with relatively low plasma Se level. NRF2, KEAP2, CAT, EPHX1, GCLC, GCLM, GPX2, GSR, GSTA1, GSTM1, GSTP1, GSTT1, HMOX1, NQO1, PRDX1, SOD1, SOD2, TXNRD1 transcript levels in peripheral blood leukocytes and polymorphism of NRF2-617C/A (rs6721961) in blood genomic DNA were determined by means of quantitative real-time PCR. Mean plasma Se level was found to be 51.10±15.25μg/L (range 23.86-96.18μg/L). NRF2 mRNA level was positively correlated with expression of investigated NRF2-target genes. The multivariate linear regression adjusting for selenium status showed that plasma Se level was significantly inversely associated only with expression of GSTP1 (β-coef.=-0.270, p=0.009), PRDXR1 (β-coef.=-0.245, p=0.017) and SOD2 with an inverse trend toward significance (β-coef.=-0.186, p=0.074), but without an effect of NRF2 gene variants. NRF2 expression was inversely associated with age (r=-0.23, p=0.03) and body mass index (r=-0.29, p<0.001). The findings may suggest a possible link between plasma Se level and cytoprotective response at gene level in humans. PMID:25524402

  5. Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up

    PubMed Central

    Schoindre, Yoland; Jallouli, Moez; Tanguy, Marie-Laure; Ghillani, Pascale; Galicier, Lionel; Aumaître, Olivier; Francès, Camille; Le Guern, Véronique; Lioté, Frédéric; Smail, Amar; Limal, Nicolas; Perard, Laurent; Desmurs-Clavel, Hélène; Thi Huong, Du Le; Asli, Bouchra; Kahn, Jean-Emmanuel; Sailler, Laurent; Ackermann, Félix; Papo, Thomas; Sacré, Karim; Fain, Olivier; Stirnemann, Jérôme; Cacoub, Patrice; Leroux, Gaëlle; Cohen-Bittan, Judith; Hulot, Jean-Sébastien; Lechat, Philippe; Musset, Lucile; Piette, Jean-Charles; Amoura, Zahir; Souberbielle, Jean-Claude; Costedoat-Chalumeau, Nathalie

    2014-01-01

    Objectives Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. Methods Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). Results The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). Conclusions We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate. PMID:25379192

  6. The RNA-binding protein gene, hermes, is expressed at high levels in the developing heart.

    PubMed

    Gerber, W V; Yatskievych, T A; Antin, P B; Correia, K M; Conlon, R A; Krieg, P A

    1999-01-01

    In a screen for novel sequences expressed during embryonic heart development we have isolated a gene which encodes a putative RNA-binding protein. This protein is a member of one of the largest families of RNA-binding proteins, the RRM (RNA Recognition Motif) family. The gene has been named hermes (for HEart, RRM Expressed Sequence). The hermes protein is 197-amino acids long and contains a single RRM domain. In situ hybridization analysis indicates that hermes is expressed at highest levels in the myocardium of the heart and to a lesser extent in the ganglion layer of the retina, the pronephros and epiphysis. Expression of hermes in each of these tissues begins at approximately the time of differentiation and is maintained throughout development. Analysis of the RNA expression of the hermes orthologues from chicken and mouse reveals that, like Xenopus, the most prominent tissue of expression is the developing heart. The sequence and expression pattern of hermes suggests a role in post-transcriptional regulation of heart development. PMID:10096065

  7. Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding.

    PubMed

    Chappell, Paul; Meziane, El Kahina; Harrison, Michael; Magiera, Łukasz; Hermann, Clemens; Mears, Laura; Wrobel, Antony G; Durant, Charlotte; Nielsen, Lise Lotte; Buus, Søren; Ternette, Nicola; Mwangi, William; Butter, Colin; Nair, Venugopal; Ahyee, Trudy; Duggleby, Richard; Madrigal, Alejandro; Roversi, Pietro; Lea, Susan M; Kaufman, Jim

    2015-01-01

    Highly polymorphic major histocompatibility complex (MHC) molecules are at the heart of adaptive immune responses, playing crucial roles in many kinds of disease and in vaccination. We report that breadth of peptide presentation and level of cell surface expression of class I molecules are inversely correlated in both chickens and humans. This relationship correlates with protective responses against infectious pathogens including Marek's disease virus leading to lethal tumours in chickens and human immunodeficiency virus infection progressing to AIDS in humans. We propose that differences in peptide binding repertoire define two groups of MHC class I molecules strategically evolved as generalists and specialists for different modes of pathogen resistance. We suggest that differences in cell surface expression level ensure the development of optimal peripheral T cell responses. The inverse relationship of peptide repertoire and expression is evidently a fundamental property of MHC molecules, with ramifications extending beyond immunology and medicine to evolutionary biology and conservation. PMID:25860507

  8. Gene expression in diplosporous and sexual Eragrostis curvula genotypes with differing ploidy levels.

    PubMed

    Cervigni, Gerardo D L; Paniego, Norma; Pessino, Silvina; Selva, Juan P; Díaz, Marina; Spangenberg, Germán; Echenique, Viviana

    2008-05-01

    The molecular nature of gene expression during the initiation and progress of diplosporous apomixis is still unknown. Moreover, the basis of the close correlation between diplospory and polyploidy is not clarified yet. A comparative expression analysis was performed based on expressed sequence tags (ESTs) sequencing and differential display in an Eragrostis curvula diplosporous tetraploid genotype (T, 4x apo), a sexual diploid derivative obtained from tissue culture (D, 2x sex) and an artificial sexual tetraploid obtained from the diploid seeds after colchicine treatment (C, 4x sex). From a total of 8,884 unigenes sequenced from inflorescence-derived libraries, 112 (1.26%) showed significant differential expression in individuals with different ploidy level and/or variable reproductive mode. Independent comparisons between plants with different reproductive mode (same ploidy) or different ploidy level (same reproductive mode) allowed the identification of genes modulated in response to diplosporous development or polyploidization, respectively. Surprisingly, a group of genes (Group 3) were differentially expressed or silenced only in the 4x sex plant, presenting similar levels of expression in the 4x apo and the 2x sex genotypes. A group of randomly selected differential genes was validated by QR-PCR. Differential display analysis showed that in general the 4x apo and 4x sex expression profiles were more related and different from the 2x sex one, but confirmed the existence of Group 3-type genes, in both inflorescences and leaves. The possible biological significance for the occurrence of this particular group of genes is discussed. In silico mapping onto the rice genome was used to identify candidates mapping to the region syntenic to the diplospory locus. PMID:18311543

  9. Association between the expression levels of tumor necrosis factor-α-induced protein 8 and the prognosis of patients with gastric adenocarcinoma

    PubMed Central

    CHEN, LING; YANG, XIGUI; YANG, XIANGSHAN; FAN, KAIXI; XIAO, PING; ZHANG, JING; WANG, XIUWEN

    2016-01-01

    The present study aimed to investigate the expression levels of tumor necrosis factor-α-induced protein 8 (TNFAIP8) in gastric adenocarcinoma. TNFAIP8 expression levels in gastric adenocarcinoma tissue samples (with and without lymph node metastasis), adjacent normal tissue samples and metastatic lymph node tissue samples were detected by immunohistochemistry. The correlation between TNFAIP8 expression levels and clinicopathological data and gastric adenocarcinoma prognosis was analyzed. The results demonstrated that TNFAIP8 expression in gastric adenocarcinoma tissue samples and metastatic lymph node tissue samples markedly increased at a rate of 47.2% (50/106) and 81.7% (49/60), respectively, as compared with the adjacent normal tissue samples in which no TNGFAIP8 expression was detected (0%). This increase in TNFAIP8 expression was statistically significant. TNFAIP8 expression rates in the primary tumors (60%, 36/60) of patients with lymph node metastasis were significantly higher compared with the primary tumors of patients without lymph node metastasis (30.4%, 14/46). TNFAIP8 expression was associated with an increase in the severity of TNM stage, tumor grade, vascular invasion, lymph node metastasis and serum CA72-4 levels. The overall survival rate of patients with gastric adenocarcinoma and high TNFAIP8 expression was poorer compared with patients with low TNFAIP8 expression, and TNFAIP8 expression was negatively correlated with patient prognosis. The results also demonstrated that TNFAIP8 was an independent prognostic marker in gastric adenocarcinoma (relative risk, 1.736; P=0.029). In conclusion, the results of the present study demonstrated that TNFAIP8 expression was associated with the occurrence, development and metastasis of gastric adenocarcinoma, and negatively correlated with the prognosis of patients with gastric adenocarcinoma. TNFAIP8 may therefore serve as a prognostic factor for gastric adenocarcinoma. PMID:27347043

  10. The Relationship between Multiplication Fact Speed-Recall and Fluency and Higher Level Mathematics Learning with Eighth Grade Middle School Students

    ERIC Educational Resources Information Center

    Curry, Steven James

    2012-01-01

    This quantitative study investigated relationships between higher level mathematics learning and multiplication fact fluency, multiplication fact speed-recall, and reading grade equivalency of eighth grade students in Algebra I and Pre-Algebra. Higher level mathematics learning was indicated by an average score of 80% or higher on first and second…

  11. Correlation between radiation dose and p53 protein expression levels in human lymphocytes.

    PubMed

    Cavalcanti, Mariana B; Fernandes, Thiago S; Silva, Edvane B; Amaral, Ademir

    2015-09-01

    The aim of this research was to evaluate the relationship between p53 protein levels and absorbed doses from in vitro irradiated human lymphocytes. For this, samples of blood from 23 donors were irradiated with 0.5; 1; 2; and 4 Gy from a Cobalt-60 source, and the percentages of lymphocytes expressing p53 were scored using Flow Cytometry. The subjects were divided into 3 groups, in accordance with the p53 levels expressed per radiation dose: low (Group I), high (Group II), and excessive levels (Group III). For all groups, the analyses showed that the p53 expression levels increase with the absorbed dose. Particularly for groups I and II, the correlation between this protein expression and the dose follows the linear-quadratic model, such as for radioinduced chromosomal aberrations. In conclusion, our findings indicate possible applications of this approach in evaluating individual radiosensitivity prior to radiotherapeutical procedures as well as in medical surveillance of occupationally exposed workers. Furthermore, due to the rapidity of flow-cytometric analyses, the methodology here employed would play an important role in emergency responses to a large-scale radiation incident where many people may have been exposed. PMID:26312422

  12. Insect cell transformation vectors that support high level expression and promoter assessment in insect cell culture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A somatic transformation vector, pDP9, was constructed that provides a simplified means of producing permanently transformed cultured insect cells that support high levels of protein expression of foreign genes. The pDP9 plasmid vector incorporates DNA sequences from the Junonia coenia densovirus th...

  13. Elevated interleukin-6 expression levels are associated with intervertebral disc degeneration

    PubMed Central

    DENG, XIAO; ZHAO, FENG; KANG, BAOLIN; ZHANG, XIN

    2016-01-01

    The present study aimed to investigate whether serum interleukin-6 (IL-6) expression levels were associated with the onset and progression of intervertebral disc degeneration (IDD). A comprehensive meta-analysis of the scientific literature from numerous electronic databases was performed, in order to obtain published studies associated with the topic of interest. Relevant case-control studies that had previously assessed a correlation between IL-6 expression levels and IDD were identified using predetermined inclusion and exclusion criteria. The STATA version 12.0 software was used for statistical analysis of the extracted data. A total of 112 studies were initially retrieved, with eight studies meeting the inclusion criteria. These contained a total of 392 subjects, of which 263 were patients with IDD and 129 were healthy controls. A meta-analysis of the eight studies demonstrated that serum IL-6 protein expression levels may be associated with IDD, and this was irrespective of IDD subtype (bulging, protrusion, or sequestration). Notably, serum expression levels of the IL-6 protein were upregulated in intervertebral disc (IVD) protrusion tissue, as compared with normal IVD tissue; thus suggesting that IL-6 may have an important role in the pathophysiological process of IDD. PMID:27073460

  14. High level expression of organophosphorus hydrolase in Pichia pastoris by multicopy ophcM assembly.

    PubMed

    Shen, Wei; Shu, Min; Ma, Lixin; Ni, Hong; Yan, Hong

    2016-03-01

    The residues of organophosphorus pesticides bring serious impact on the environmental safety and people's health. Biodegradation of organophosphorus pesticides is recognized as an ideal method. An organophosphorus hydrolase (OPHCM) from Pseudomonas pseudoalcaligenes was synthesized and expressed in Pichia pastoris. The yield reached approximately 470 mg/l after a 6-d induction in shake flasks. To improve the enzyme production, we describe a novel approach to express OPHCM efficiently with a biobrick assembly method in vitro. Four recombinant plasmids containing 1-4 copies of ophcM-expressing cassettes were constructed and transformed into P. pastoris. Increasing the copy number of ophcM gene enhanced the expression level of OPHCM. The maximum yield and specific activity in P. pastoris harboring two-copy tandem ophcM-expressing cassettes reached 610 mg/l after a 6-d induction in shake flasks and 7.8 g/l in high-density fermentation with specific activity of 13.7 U/mg. The optimum pH and temperature of the recombinant OPHCM activity were 11.0 and 50 °C, respectively. In addition, the enzyme activity of recombinant OPHCM enhanced 57.6% and 30.1% in the presence of 1 mM Cd(2+) and 5% glycerol, respectively. The high expression and good properties of recombinant OPHCM provide an effective solution to solve the pollution of organophosphorus pesticides in the environment. Moreover, the approach for generating multicopy gene expressing vectors here will benefit the study for enhancing the expression level of genes of interest. PMID:26611611

  15. High Levels of MeCP2 Depress MHC Class I Expression in Neuronal Cells

    PubMed Central

    Miralvès, Julie; Magdeleine, Eddy; Kaddoum, Lara; Brun, Hélène; Peries, Sophie; Joly, Etienne

    2007-01-01

    Background The expression of MHC class I genes is repressed in mature neurons. The molecular basis of this regulation is poorly understood, but the genes are particularly rich in CpG islands. MeCP2 is a transcriptional repressor that binds to methylated CpG dinucleotides; mutations in this protein also cause the neurodevelopmental disease called Rett syndrome. Because MHC class I molecules play a role in neuronal connectivity, we hypothesised that MeCP2 might repress MHC class I expression in the CNS and that this might play a role in the pathology of Rett syndrome. Methodology We show here that transiently transfected cells expressing high levels of MeCP2 specifically downregulate cell-surface expression of MHC class I molecules in the neuronal cell line N2A and they prevent the induction of MHC class I expression in response to interferon in these cells, supporting our first hypothesis. Surprisingly, however, overexpression of the mutated forms of MeCP2 that cause Rett syndrome had a similar effect on MHC class I expression as the wild-type protein. Immunohistological analyses of brain slices from MECP2 knockout mice (the MeCP2tm1.1Bird strain) demonstrated a small but reproducible increase in MHC class I when compared to their wild type littermates, but we found no difference in MHC class I expression in primary cultures of mixed glial cells (mainly neurons and astrocytes) from the knockout and wild-type mice. Conclusion These data suggest that high levels of MeCP2, such as those found in mature neurons, may contribute to the repression of MHC expression, but we find no evidence that MeCP2 regulation of MHC class I is important for the pathogenesis of Rett syndrome. PMID:18159237

  16. PAQR3 gene expression and its methylation level in colorectal cancer tissues

    PubMed Central

    Li, Ri-Heng; Zhang, Ai-Min; Li, Shuang; Li, Tian-Yang; Wang, Lian-Jing; Zhang, Hao-Ran; Shi, Jian-Wei; Liu, Xiao-Rui; Chen, Yuan; Chen, Ya-Chao; Wei, Teng-Yao; Gao, Ying; Li, Wei; Tang, Hong-Ying; Tang, Mei-Yu

    2016-01-01

    The aim of the present study was to investigate the PAQR3 gene expression and its methylation level in colorectal cancer tissues, as well as the association with colorectal cancer clinical data. In total, 54 cases of colorectal cancer tissue samples and normal adjacent tissue samples were collected between June, 2013 and July, 2014. RT-PCR and western blot analysis were used to detect the mRNA and protein levels of PAQR3 in colorectal samples, respectively. MSP was used to detect the methylation level of PAQR3 gene in colorectal samples, which was compared with colorectal data. The results showed that a decreased expression level of PAQR3 mRNA in colorectal cancer tissues and the expression reduction rate was 57.4% (31/54). Similarly, the expression level of PAQR3 protein was reduced in cancer tissues, and the reduction rate was 46.3% (25/54), while the protein expression reduction rate in cancer adjacent tissue was 5.6% (3/54), and the difference was statistically significant (P<0.05). Furthermore, the methylation rates of PAQR3 in cancer tissues and cancer adjacent tissues were 33.3% (18/54) and 5.6% (3/54), respectively. In addition, PAQR3 mRNA and protein levels in colorectal cancer tissues were associated with the differentiation degree, lymphatic metastasis and tumor infiltration depth. The methylation level of PAQR3 was associated with age, differentiated degree, lymphatic metastasis and tumor infiltration depth. In conclusion, the expression of PAQR3 mRNA and protein in colorectal cancer was reduced and methylation of PAQR3 occurred. Although the PAQR3 mRNA and protein levels were not associated with gender, age or the location of tumor, there was an association with differentiation degree, lymphatic metastasis and tumor infiltration depth. In addition, the methylation level of PAQR3 was not correlated with gender or tumor location, but was correlated with age, differentiation degree, lymphatic metastasis and tumor infiltration depth. PMID:27588124

  17. Prepartal dietary energy level affects peripartal bovine blood neutrophil metabolic, antioxidant, and inflammatory gene expression.

    PubMed

    Zhou, Z; Bu, D P; Vailati Riboni, M; Khan, M J; Graugnard, D E; Luo, J; Cardoso, F C; Loor, J J

    2015-08-01

    During the dry period, cows can easily overconsume higher-grain diets, a scenario that could impair immune function during the peripartal period. Objectives were to investigate the effects of energy overfeeding on expression profile of genes associated with inflammation, lipid metabolism, and neutrophil function, in 12 multiparous Holstein cows (n=6/dietary group) fed control [CON, 1.34 Mcal/kg of dry matter (DM)] or higher-energy (HE, 1.62 Mcal/kg of DM) diets during the last 45 d of pregnancy. Blood was collected to evaluate 43 genes in polymorphonuclear neutrophil leukocytes (PMNL) isolated at -14, 7, and 14 d relative to parturition. We detected greater expression of inflammatory-related cytokines (IL1B, STAT3, NFKB1) and eicosanoid synthesis (ALOX5AP and PLA2G4A) in HE cows than in CON cows. Around parturition, all cows had a close balance in mRNA expression of the pro-inflammatory IL1B and the anti-inflammatory IL10, with greater expression of both in cows fed HE than CON. The expression of CCL2, LEPR, TLR4, IL6, and LTC4S was undetectable. Cows in the HE group had greater expression of genes involved in PMNL adhesion, motility, migration, and phagocytosis, which was similar to expression of genes related to the pro-inflammatory cytokine. This response suggests that HE cows experienced a chronic state of inflammation. The greater expression of G6PD in HE cows could have been associated with the greater plasma insulin, which would have diverted glucose to other tissues. Cows fed the HE diet also had greater expression of transcription factors involved in metabolism of long-chain fatty acids (PPARD, RXRA), suggesting that immune cells might be predisposed to use endogenous ligands such as nonesterified fatty acids available in the circulation when glucose is in high demand for milk synthesis. The lower overall expression of SLC2A1 postpartum than prepartum supports this suggestion. Targeting interleukin-1β signaling might be of value in terms of controlling

  18. Intercellular Variability in Protein Levels from Stochastic Expression and Noisy Cell Cycle Processes

    PubMed Central

    Soltani, Mohammad; Vargas-Garcia, Cesar A.; Antunes, Duarte; Singh, Abhyudai

    2016-01-01

    Inside individual cells, expression of genes is inherently stochastic and manifests as cell-to-cell variability or noise in protein copy numbers. Since proteins half-lives can be comparable to the cell-cycle length, randomness in cell-division times generates additional intercellular variability in protein levels. Moreover, as many mRNA/protein species are expressed at low-copy numbers, errors incurred in partitioning of molecules between two daughter cells are significant. We derive analytical formulas for the total noise in protein levels when the cell-cycle duration follows a general class of probability distributions. Using a novel hybrid approach the total noise is decomposed into components arising from i) stochastic expression; ii) partitioning errors at the time of cell division and iii) random cell-division events. These formulas reveal that random cell-division times not only generate additional extrinsic noise, but also critically affect the mean protein copy numbers and intrinsic noise components. Counter intuitively, in some parameter regimes, noise in protein levels can decrease as cell-division times become more stochastic. Computations are extended to consider genome duplication, where transcription rate is increased at a random point in the cell cycle. We systematically investigate how the timing of genome duplication influences different protein noise components. Intriguingly, results show that noise contribution from stochastic expression is minimized at an optimal genome-duplication time. Our theoretical results motivate new experimental methods for decomposing protein noise levels from synchronized and asynchronized single-cell expression data. Characterizing the contributions of individual noise mechanisms will lead to precise estimates of gene expression parameters and techniques for altering stochasticity to change phenotype of individual cells. PMID:27536771

  19. Intercellular Variability in Protein Levels from Stochastic Expression and Noisy Cell Cycle Processes.

    PubMed

    Soltani, Mohammad; Vargas-Garcia, Cesar A; Antunes, Duarte; Singh, Abhyudai

    2016-08-01

    Inside individual cells, expression of genes is inherently stochastic and manifests as cell-to-cell variability or noise in protein copy numbers. Since proteins half-lives can be comparable to the cell-cycle length, randomness in cell-division times generates additional intercellular variability in protein levels. Moreover, as many mRNA/protein species are expressed at low-copy numbers, errors incurred in partitioning of molecules between two daughter cells are significant. We derive analytical formulas for the total noise in protein levels when the cell-cycle duration follows a general class of probability distributions. Using a novel hybrid approach the total noise is decomposed into components arising from i) stochastic expression; ii) partitioning errors at the time of cell division and iii) random cell-division events. These formulas reveal that random cell-division times not only generate additional extrinsic noise, but also critically affect the mean protein copy numbers and intrinsic noise components. Counter intuitively, in some parameter regimes, noise in protein levels can decrease as cell-division times become more stochastic. Computations are extended to consider genome duplication, where transcription rate is increased at a random point in the cell cycle. We systematically investigate how the timing of genome duplication influences different protein noise components. Intriguingly, results show that noise contribution from stochastic expression is minimized at an optimal genome-duplication time. Our theoretical results motivate new experimental methods for decomposing protein noise levels from synchronized and asynchronized single-cell expression data. Characterizing the contributions of individual noise mechanisms will lead to precise estimates of gene expression parameters and techniques for altering stochasticity to change phenotype of individual cells. PMID:27536771

  20. Isolation and functional characterization of a cotton ubiquitination-related promoter and 5'UTR that drives high levels of expression in root and flower tissues

    PubMed Central

    2011-01-01

    Background Cotton (Gossypium spp.) is an important crop worldwide that provides raw material to 40% of the textile fiber industry. Important traits have been studied aiming the development of genetically modified crops including resistance to insect and diseases, and tolerance to drought, cold and herbicide. Therefore, the characterization of promoters and regulatory regions is also important to achieve high gene expression and/or a specific expression pattern. Commonly, genes involved in ubiquitination pathways are highly and differentially expressed. In this study, we analyzed the expression of a cotton ubiquitin-conjugating enzyme (E2) family member with no previous characterization. Results Nucleotide analysis revealed high identity with cotton E2 homologues. Multiple alignment showed a premature stop codon, which prevents the encoding of the conserved cysteine residue at the E2 active site, and an intron that is spliced in E2 homologues, but not in GhGDRP85. The GhGDRP85 gene is highly expressed in different organs of cotton plants, and has high transcript levels in roots. Its promoter (uceApro2) and the 5'UTR compose a regulatory region named uceA1.7, and were isolated from cotton and studied in Arabidopsis thaliana. uceA1.7 shows strong expression levels, equaling or surpassing the expression levels of CaMV35S. The uceA1.7 regulatory sequence drives GUS expression 7-fold higher in flowers, 2-fold in roots and at similar levels in leaves and stems. GUS expression levels are decreased 7- to 15-fold when its 5'UTR is absent in uceApro2. Conclusions uceA1.7 is a strong constitutive regulatory sequence composed of a promoter (uceApro2) and its 5'UTR that will be useful in genetic transformation of dicots, having high potential to drive high levels of transgene expression in crops, particularly for traits desirable in flower and root tissues. PMID:22115195

  1. Evaluating the prognostic significance of FBXW7 expression level in human breast cancer by a meta-analysis of transcriptional profiles

    PubMed Central

    Wei, Guangwei; Wang, Yunshan; Zhang, Pengju; Lu, Jing; Mao, Jian-Hua

    2012-01-01

    The tumor suppressor gene FBXW7 is mutated in numerous types of human cancers leading to loss of its function and/or expression. However the clinic significance of FBXW7 alterations remains largely unknown. Here, we carried out a meta-analysis of 10 gene expression microarray studies for a total 1900 patients of breast cancer with clinic information to evaluate the prognostic impact of FBXW7 mRNA expression. The FBXW7 mRNA levels significantly reduced in breast cancer compared to normal tissues. In addition, significant difference in the FBXW7 mRNA levels was found among molecular subtypes (normal-like, luminal A, luminal B, ERBB2 and basal). ERBB2 and basal tumors had significantly lower average FBXW7 mRNA level than normal-like tumors, whereas luminal A and B tumors have the lowest average FBXW7 mRNA level. The patients with higher FBXW7 mRNA level significantly increased disease-free survival, particularly in the group of patients with ER negative and basal subtype tumors. Moreover, higher FBXW7 mRNA level also significantly increased overall survival in the patients with ER negative tumors. But we strikingly found opposite effect of FBXW7 expression on overall survival in different subtypes. The patients with higher FBXW7 mRNA level significantly decreased overall survival in normal-like subtype while the patients with higher FBXW7 mRNA level significantly increased overall survival in ERBB2 and Basal subtype. Taken together, our results suggest that FBXW7 mRNA levels were a prognostic factor for disease-free and overall survival according to ER status and molecular subtypes. PMID:23105958

  2. Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study

    PubMed Central

    Uemoto, Shinji; Yoshida, Kazuhiro; Saiura, Akio; Watanabe, Masayuki; Maehara, Yoshihiko; Oki, Eiji; Ikeda, Yasuharu; Matsuda, Hiroyuki; Yamamoto, Masakazu; Shimada, Mitsuo; Taketomi, Akinobu; Unno, Michiaki; Sugihara, Kenichi; Ogata, Yutaka; Eguchi, Susumu; Kitano, Seigo; Shirouzu, Kazuo; Saiki, Yasumitsu; Takamori, Hiroshi; Mori, Masaki; Hirata, Toshihiko; Wakabayashi, Go; Kokudo, Norihiro

    2015-01-01

    Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman's correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression. PMID:26372896

  3. High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes.

    PubMed Central

    Haber, B A; Chin, S; Chuang, E; Buikhuisen, W; Naji, A; Taub, R

    1995-01-01

    The regenerating liver after partial hepatectomy is one of the few physiologic models of cellular proliferation in the adult animal. During hepatic regeneration, the animal is able to maintain metabolic homeostasis despite the acute loss of two thirds of hepatic tissue. In examining the molecular mechanisms regulating hepatic regeneration, we isolated novel immediate-early genes that are rapidly induced as the remnant liver undergoes the transition from its normal quiescent state into the G1 phase of the cell cycle. One of the most rapidly and highly induced genes which we initially termed RL-1, encodes rat glucose-6-phosphatase (rG6Pase). G6Pase mRNA peaks at 30 min and 36-48 h after hepatectomy correlating with the first and second rounds of cell division. This finding is compatible with studies that showed that G6Pase enzyme activity increases during liver regeneration. However, the increase in G6Pase mRNA is much more dramatic, indicating that it is a more sensitive indicator of this regulation. G6Pase gene expression peaks in the perinatal time period in the liver and remains elevated during the first month of life. The expression of the G6Pase gene is also dramatically elevated in BB diabetic rats, again higher than the enzyme elevation, and its relative induction after partial hepatectomy is blunted in these animals. Insulin treatment of partially hepatectomized diabetic animals downregulates the expression of G6Pase mRNA. Using specific antibodies against G6Pase, we detect a 36-kD G6Pase protein, and its level is elevated in regenerating and diabetic livers. The pattern of G6Pase mRNA expression appears to reflect similar changes in insulin and glucagon levels which accompany diabetes and hepatic proliferation. The elevation of G6Pase expression in these conditions is indicative of its importance as a regulator of glucose homeostasis in normal and abnormal physiologic states. Images PMID:7860767

  4. Cell-cell channels, viruses, and evolution: via infection, parasitism, and symbiosis toward higher levels of biological complexity.

    PubMed

    Baluska, Frantisek

    2009-10-01

    Between prokaryotic cells and eukaryotic cells there is dramatic difference in complexity which represents a problem for the current version of the cell theory, as well as for the current version of evolution theory. In the past few decades, the serial endosymbiotic theory of Lynn Margulis has been confirmed. This results in a radical departure from our understanding of living systems: the eukaryotic cell represents de facto"cells-within-cell." Higher order "cells-within-cell" situations are obvious at the eukaryotic cell level in the form of secondary and tertiary endosymbiosis, or in the male and female gametophytes of higher plants. The next challenge of the current version of the cell theory is represented by the fact that the multicellular fungi and plants are, in fact, supracellular assemblies as their cells are not physically separated from each other. Moreover, there are also examples of alliances and mergings between multicellular organisms. Infection, especially the viral one, but also bacterial and fungal infections, followed by symbiosis, is proposed to act as the major force that drives the biological evolution toward higher complexity. PMID:19845631

  5. Neural mechanisms underlying the higher levels of subjective well-being in extraverts: pleasant bias and unpleasant resistance.

    PubMed

    Yuan, Jiajin; Zhang, Jinfu; Zhou, Xiaolin; Yang, Jiemin; Meng, Xianxin; Zhang, Qinglin; Li, Hong

    2012-03-01

    The present study investigated the neural mechanisms that underlie the higher levels of subjective well-being in extraverts. The impact of extraversion on the human sensitivity to pleasant and unpleasant pictures of diverse emotional intensities was examined. We recorded event-related potentials (ERPs) for highly positive (HP), moderately positive (MP), and neutral stimuli in the pleasant session, and for highly negative (HN), moderately negative (MN), and neutral stimuli in the unpleasant session, while subjects (16 extraverts and 16 ambiverts) performed a standard/deviant categorization task, irrespective of the emotionality of the deviant stimuli. The results showed significant emotion effects for HP and MP stimuli at the P2 and P3 components in extraverts, but not in ambiverts. Despite a pronounced emotion effect for HN stimuli across the P2, N2, and P3 components in both samples, ambiverts displayed a significant emotion effect for MN stimuli at the N2 and P3 components that was absent in extraverts. The posterior cingulate cortices, which connect multiple neural regions that are important in interactions of emotion and extraversion, may mediate the extravert-specific emotion effect for pleasant stimuli. Thus, extraverts are less susceptible to unpleasant stimuli of mild intensity than are ambiverts, while extraverts have an additional enhanced sensitivity to pleasant stimuli, regardless of emotion intensity. Consequently, the decreased threshold for pleasant emotion and the increased threshold for unpleasant emotion might be essential neural mechanisms that underlie the higher levels of subjective well-being in extraverts. PMID:21987094

  6. Oxytocin, but not vasopressin, impairs social cognitive ability among individuals with higher levels of social anxiety: a randomized controlled trial.

    PubMed

    Tabak, Benjamin A; Meyer, Meghan L; Dutcher, Janine M; Castle, Elizabeth; Irwin, Michael R; Lieberman, Matthew D; Eisenberger, Naomi I

    2016-08-01

    Individuals with social anxiety are characterized by a high degree of social sensitivity, which can coincide with impairments in social cognitive functioning (e.g. theory of mind). Oxytocin (OT) and vasopressin (AVP) have been shown to improve social cognition, and OT has been theorized as a potential therapeutic agent for individuals with social anxiety disorder. However, no study has investigated whether these neuropeptides improve social cognitive ability among socially anxious individuals. In a randomized, double-blind, placebo controlled, between-subjects design we investigated whether social anxiety moderated the effects of OT or AVP (vs placebo) on social working memory (i.e. working memory that involves manipulating social information) and non-social working memory. OT vs placebo impaired social working memory accuracy in participants with higher levels of social anxiety. No differences were found for non-social working memory or for AVP vs placebo. Results suggest that OT administration in individuals with higher levels of social anxiety may impair social cognitive functioning. Randomized-controlled trial registration: NCT01680718. PMID:27053769

  7. Decreased blood riboflavin levels are correlated with defective expression of RFT2 gene in gastric cancer

    PubMed Central

    Eli, Maynur; Li, De-Sheng; Zhang, Wei-Wei; Kong, Bing; Du, Chen-Song; Wumar, Maimaitiaili; Mamtimin, Batur; Sheyhidin, Ilyar; Hasim, Ayshamgul

    2012-01-01

    AIM: To investigate the relationship between blood riboflavin levels and riboflavin transporter 2 (RFT2) gene expression in gastric carcinoma (GC) development. METHODS: High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC. Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue. RESULTS: A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane (0.398 ± 0.149 vs 1.479 ± 0.587; P = 0.040). Tumors exhibited low RFT2 protein expression (75%, 16.7%, 8.3% and 0% for no RFT2 staining, weak staining, medium staining and strong staining, respectively), which was significantly lower than that in the normal mucous membrane (10%, 16.7%, 26.7% and 46.7% for no RFT2 staining, weak staining, medium staining and strong staining, respectively; P < 0.05). Tumors with low RFT2 expression were significantly associated with tumor stage and histological grade. Moreover, a significantly decrease in Uyghur patients was observed compared with Han patients. However, other parameters-gender, tumor location and lymph node metastasis-showed no significant relationship with RFT2 expression. Blood riboflavin levels were reverse correlated with development of GC (1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients; P < 0.05). A positive correlation of plasma riboflavin levels with defective expression of RFT2 protein was found in GC patients (χ2 = 2.619; P = 0.019). CONCLUSION: Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC. PMID:22791947

  8. Role of EGFR expression levels in the regulation of integrin function by EGF.

    PubMed

    Vial, Daniel; McKeown-Longo, Paula J

    2016-06-01

    Activation of β1 integrins in dormant tumor cells has been linked to metastatic progression, suggesting that therapies designed to maintain β1 integrins in an inactive state may be useful in the prevention of metastatic disease. Our earlier studies have demonstrated that EGF regulates the activation state of the α5β1 integrin in EGFR overexpressing tumor cells through an ERK/p90RSK signaling pathway. Activation of this pathway by EGF resulted in the filamin A dependent inactivation of the α5β1 integrin receptor for fibronectin. The current study was designed to address the role of EGFR overexpression in the regulation of α5β1 integrin activation state by EGF. Lentiviral knockdown of EGFR coupled with limited dilution cloning was used to develop A431 squamous carcinoma cell lines expressing high, moderate, and low levels of EGFR. Inactivation of α5β1 integrin by EGF was shown to correlate with both the level of EGFR expression and the extent of p90RSK phosphorylation, but not with the level of ERK phosphorylation, suggesting that high levels of EGFR promote α5β1 integrin inactivation through sustained activation of p90RSK. Treatment of cells with EGFR kinase inhibitor resulted in a reactivation of the integrin which could be reversed with the phosphatase inhibitor, menadione. Taken together, these findings indicate that p90RSK may function to maintain dormancy in tumor cells expressing high levels of EGFR. © 2015 Wiley Periodicals, Inc. PMID:26053065

  9. The Expression of c-Myb Correlates with the Levels of Rhabdomyosarcoma-specific Marker Myogenin

    PubMed Central

    Kaspar, Petr; Zikova, Martina; Bartunek, Petr; Sterba, Jaroslav; Strnad, Hynek; Kren, Leos; Sedlacek, Radislav

    2015-01-01

    The transcription factor c-Myb is required for modulation of progenitor cells in several tissues, including skeletal muscle and its upregulation is observed in many human malignancies. Rhabdomyosarcomas (RMS) are a heterogeneous group of mesodermal tumors with features of developing skeletal muscle. Several miRNAs are downregulated in RMS, including miR-150, a negative regulator of c-Myb expression. Using the C2C12 myoblast cell line, a cellular model of skeletal muscle differentiation, we showed that miR-150 controls c-Myb expression mainly at the level of translation. We hypothesized that a similar mechanism of c-Myb regulation operates in RMS tumors. We examined expression of c-Myb by immunohistochemistry and revealed c-Myb positivity in alveolar and embryonal tumors, the two most common subgroups of RMS. Furthermore, we showed direct correlation between c-Myb production and myogenin expression. Interestingly, high myogenin levels indicate poor prognosis in RMS patients. c-Myb could, therefore, contribute to the tumor phenotype by executing its inhibitory role in skeletal muscle differentiation. We also showed that c-Myb protein is abundant in migratory C2C12 myoblasts and its ectopic expression potentiates cell motility. In summary, our results implicate that metastatic properties of some RMS subtypes might be linked to c-Myb function. PMID:26462877

  10. The Expression of c-Myb Correlates with the Levels of Rhabdomyosarcoma-specific Marker Myogenin.

    PubMed

    Kaspar, Petr; Zikova, Martina; Bartunek, Petr; Sterba, Jaroslav; Strnad, Hynek; Kren, Leos; Sedlacek, Radislav

    2015-01-01

    The transcription factor c-Myb is required for modulation of progenitor cells in several tissues, including skeletal muscle and its upregulation is observed in many human malignancies. Rhabdomyosarcomas (RMS) are a heterogeneous group of mesodermal tumors with features of developing skeletal muscle. Several miRNAs are downregulated in RMS, including miR-150, a negative regulator of c-Myb expression. Using the C2C12 myoblast cell line, a cellular model of skeletal muscle differentiation, we showed that miR-150 controls c-Myb expression mainly at the level of translation. We hypothesized that a similar mechanism of c-Myb regulation operates in RMS tumors. We examined expression of c-Myb by immunohistochemistry and revealed c-Myb positivity in alveolar and embryonal tumors, the two most common subgroups of RMS. Furthermore, we showed direct correlation between c-Myb production and myogenin expression. Interestingly, high myogenin levels indicate poor prognosis in RMS patients. c-Myb could, therefore, contribute to the tumor phenotype by executing its inhibitory role in skeletal muscle differentiation. We also showed that c-Myb protein is abundant in migratory C2C12 myoblasts and its ectopic expression potentiates cell motility. In summary, our results implicate that metastatic properties of some RMS subtypes might be linked to c-Myb function. PMID:26462877

  11. Analysis of gene expression levels in individual bacterial cells without image segmentation

    SciTech Connect

    Kwak, In Hae; Son, Minjun; Hagen, Stephen J.

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer We present a method for extracting gene expression data from images of bacterial cells. Black-Right-Pointing-Pointer The method does not employ cell segmentation and does not require high magnification. Black-Right-Pointing-Pointer Fluorescence and phase contrast images of the cells are correlated through the physics of phase contrast. Black-Right-Pointing-Pointer We demonstrate the method by characterizing noisy expression of comX in Streptococcus mutans. -- Abstract: Studies of stochasticity in gene expression typically make use of fluorescent protein reporters, which permit the measurement of expression levels within individual cells by fluorescence microscopy. Analysis of such microscopy images is almost invariably based on a segmentation algorithm, where the image of a cell or cluster is analyzed mathematically to delineate individual cell boundaries. However segmentation can be ineffective for studying bacterial cells or clusters, especially at lower magnification, where outlines of individual cells are poorly resolved. Here we demonstrate an alternative method for analyzing such images without segmentation. The method employs a comparison between the pixel brightness in phase contrast vs fluorescence microscopy images. By fitting the correlation between phase contrast and fluorescence intensity to a physical model, we obtain well-defined estimates for the different levels of gene expression that are present in the cell or cluster. The method reveals the boundaries of the individual cells, even if the source images lack the resolution to show these boundaries clearly.

  12. High-level transgene expression in plant cells: effects of a strong scaffold attachment region from tobacco.

    PubMed Central

    Allen, G C; Hall, G; Michalowski, S; Newman, W; Spiker, S; Weissinger, A K; Thompson, W F

    1996-01-01

    We have previously shown that yeast scaffold attachment regions (SARs) flanking a chimeric beta-glucuronidase (GUS) reporter gene increased per-copy expression levels by 24-fold in tobacco suspension cell lines stably transformed by microprojectile bombardment. In this study, we examined the effect of a DNA fragment originally identified in a tobacco genomic clone by its activity in an in vitro binding assay. The tobacco SAR has much greater scaffold binding affinity than does the yeast SAR, and tobacco cell lines stably transformed with constructs containing the tobacco SAR accumulated greater than fivefold more GUS enzyme activity than did lines transformed with the yeast SAR construct. Relative to the control construct, flanking the GUS gene with plant SARs increased overall expression per transgene copy by almost 140-fold. In transient expression assays, the same construct increased expression only approximately threefold relative to a control without SARs, indicating that the full SAR effect requires integration into chromosomal DNA. GUS activity in individual stable transformants was not simply proportional to transgene copy number, and the SAR effect was maximal in cell lines with fewer than approximately 10 transgene copies per tobacco genome. Lines with significantly higher copy numbers showed greatly greatly reduced expression relative to the low-copy-number lines. Our results indicate that strong SARs flanking a transgene greatly increases expression without eliminating variation between transformants. We propose that SARs dramatically reduce the severity or likelihood of homology-dependent gene silencing in cells with small numbers of transgenes but do not prevent silencing of transgenes present in many copies. PMID:8672887

  13. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment.

    PubMed

    Sustarsic, Elahu G; Junnila, Riia K; Kopchick, John J

    2013-11-01

    Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute's NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data, GH could be a new therapeutic target in melanoma. PMID:24134847

  14. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    PubMed Central

    Sustarsic, Elahu G.; Junnila, Riia K.; Kopchick, John J.

    2013-01-01

    Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data, GH could be a new therapeutic target in melanoma. PMID:24134847

  15. Cleavage efficient 2A peptides for high level monoclonal antibody expression in CHO cells.

    PubMed

    Chng, Jake; Wang, Tianhua; Nian, Rui; Lau, Ally; Hoi, Kong Meng; Ho, Steven C L; Gagnon, Peter; Bi, Xuezhi; Yang, Yuansheng

    2015-01-01

    Linking the heavy chain (HC) and light chain (LC) genes required for monoclonal antibodies (mAb) production on a single cassette using 2A peptides allows control of LC and HC ratio and reduces non-expressing cells. Four 2A peptides derived from the foot-and-mouth disease virus (F2A), equine rhinitis A virus (E2A), porcine teschovirus-1 (P2A) and Thosea asigna virus (T2A), respectively, were compared for expression of 3 biosimilar IgG1 mAbs in Chinese hamster ovary (CHO) cell lines. HC and LC were linked by different 2A peptides both in the absence and presence of GSG linkers. Insertion of a furin recognition site upstream of 2A allowed removal of 2A residues that would otherwise be attached to the HC. Different 2A peptides exhibited different cleavage efficiencies that correlated to the mAb expression level. The relative cleavage efficiency of each 2A peptide remains similar for expression of different IgG1 mAbs in different CHO cells. While complete cleavage was not observed for any of the 2A peptides, GSG linkers did enhance the cleavage efficiency and thus the mAb expression level. T2A with the GSG linker (GT2A) exhibited the highest cleavage efficiency and mAb expression level. Stably amplified CHO DG44 pools generated using GT2A had titers 357, 416 and 600 mg/L for the 3 mAbs in shake flask batch cultures. Incomplete cleavage likely resulted in incorrectly processed mAb species and aggregates, which were removed with a chromatin-directed clarification method and protein A purification. The vector and methods presented provide an easy process beneficial for both mAb development and manufacturing. PMID:25621616

  16. Cleavage efficient 2A peptides for high level monoclonal antibody expression in CHO cells

    PubMed Central

    Chng, Jake; Wang, Tianhua; Nian, Rui; Lau, Ally; Hoi, Kong Meng; Ho, Steven CL; Gagnon, Peter; Bi, Xuezhi; Yang, Yuansheng

    2015-01-01

    Linking the heavy chain (HC) and light chain (LC) genes required for monoclonal antibodies (mAb) production on a single cassette using 2A peptides allows control of LC and HC ratio and reduces non-expressing cells. Four 2A peptides derived from the foot-and-mouth disease virus (F2A), equine rhinitis A virus (E2A), porcine teschovirus-1 (P2A) and Thosea asigna virus (T2A), respectively, were compared for expression of 3 biosimilar IgG1 mAbs in Chinese hamster ovary (CHO) cell lines. HC and LC were linked by different 2A peptides both in the absence and presence of GSG linkers. Insertion of a furin recognition site upstream of 2A allowed removal of 2A residues that would otherwise be attached to the HC. Different 2A peptides exhibited different cleavage efficiencies that correlated to the mAb expression level. The relative cleavage efficiency of each 2A peptide remains similar for expression of different IgG1 mAbs in different CHO cells. While complete cleavage was not observed for any of the 2A peptides, GSG linkers did enhance the cleavage efficiency and thus the mAb expression level. T2A with the GSG linker (GT2A) exhibited the highest cleavage efficiency and mAb expression level. Stably amplified CHO DG44 pools generated using GT2A had titers 357, 416 and 600 mg/L for the 3 mAbs in shake flask batch cultures. Incomplete cleavage likely resulted in incorrectly processed mAb species and aggregates, which were removed with a chromatin-directed clarification method and protein A purification. The vector and methods presented provide an easy process beneficial for both mAb development and manufacturing. PMID:25621616

  17. Population-level expression variability of mitochondrial DNA-encoded genes in humans

    PubMed Central

    Wang, Gang; Yang, Ence; Mandhan, Ishita; Brinkmeyer-Langford, Candice L; Cai, James J

    2014-01-01

    Human mitochondria contain multiple copies of a circular genome made up of double-stranded DNA (mtDNA) that encodes proteins involved in cellular respiration. Transcript abundance of mtDNA-encoded genes varies between human individuals, yet the level of variation in the general population has not been systematically assessed. In the present study, we revisited large-scale RNA sequencing data generated from lymphoblastoid cell lines of HapMap samples of European and African ancestry to estimate transcript abundance and quantify expression variation for mtDNA-encoded genes. In both populations, we detected up to over 100-fold difference in mtDNA gene expression between individuals. The marked variation was not due to differences in mtDNA copy number between individuals, but was shaped by the transcription of hundreds of nuclear genes. Many of these nuclear genes were co-expressed with one another, resulting in a module-enriched co-expression network. Significant correlations in expression between genes of the mtDNA and nuclear genomes were used to identify factors involved with the regulation of mitochondrial functions. In conclusion, we determined the baseline amount of variability in mtDNA gene expression in general human populations and cataloged a complete set of nuclear genes whose expression levels are correlated with those of mtDNA-encoded genes. Our findings will enable the integration of information from both mtDNA and nuclear genetic systems, and facilitate the discovery of novel regulatory pathways involving mitochondrial functions. PMID:24398800

  18. Constitutively expressed DHAR and MDHAR influence fruit, but not foliar ascorbate levels in tomato

    PubMed Central

    Haroldsen, Victor M.; Chi-Ham, Cecilia L.; Kulkarni, Shashank; Lorence, Argelia; Bennett, Alan B.

    2012-01-01

    Vitamin C (l-ascorbate, AsA) is an essential nutrient required in key metabolic functions in humans and must be obtained from the diet, mainly from fruits and vegetables. Given its importance in human health and plant physiology we sought to examine the role of the ascorbate recycling enzymes monodehydroascorbate reductase (MDHAR) and dehydroascorbate reductase (DHAR) in tomato (Solanum lycopersicum), an economically important fruit crop. Cytosolic-targeted tomato genes Mdhar and Dhar were cloned and over-expressed under a constitutive promoter in tomato var. Micro-Tom. Lines with increased protein levels and enzymatic activity were identified and examined. Mature green and red ripe fruit from DHAR over-expressing lines had a 1.6 fold increase in AsA content in plants grown under relatively low light conditions (150 µmol m−2 s−1). Conversely, MDHAR over-expressers had significantly reduced AsA levels in mature green fruits by 0.7 fold. Neither over-expressing line had altered levels of AsA in foliar tissues. These results underscore a complex regulation of the AsA pool size in tomato. PMID:21875809

  19. Genome-level analysis of genetic regulation of liver gene expression networks

    SciTech Connect

    Gatti, Daniel; Maki, Akira; Chesler, Elissa J; Kirova, Roumyana; Kosyk, Oksana; Lu, Lu; Manly, Kenneth; Matthews, Douglas B.; Qu, Yanhua; Williams, Robert; Perkins, Andy; Langston, Michael A; Threadgill, David; Rusyn, Ivan

    2007-01-01

    Liver is the primary site for metabolism of nutrients, drugs and chemical agents. While metabolic pathways are complex and tightly regulated, genetic variation among individuals, reflected in variation in gene expression levels, introduces complexity into research on liver disease. This study aimed to dissect genetic networks that control liver gene expression by combining largescale quantitative mRNA expression analysis with genetic mapping in a reference population of BXD recombinant inbred mouse strains for which extensive SNP, haplotype and phenotypic data is publicly available. We profiled gene expression in livers of naive mice of both sexes from C57BL/6J, DBA/2J, B6D2F1, and 37 BXD strains using Agilent oligonucleotide microarrays. This data was used to map quantitative trait loci (QTLs) responsible for variation in expression of about 19,000 transcripts. We identified polymorphic cis- and trans-acting loci, including several loci that control expression of large numbers of genes in liver, by comparing the physical transcript position with the location of the controlling QTL. The data is available through a public web-based resource (www.genenetwork.org) that allows custom data mining, identification of co-regulated transcripts and correlated phenotypes, cross-tissue and -species comparisons, as well as testing of a broad array of hypotheses.

  20. Tumor redox metabolism correlation with the expression level of red fluorescent protein

    NASA Astrophysics Data System (ADS)

    Sha, Shuang; Wang, Anle; Lin, Qiaoya; Zhang, Zhihong

    2015-03-01

    The redox metabolism is variable and complicated with the progress of tumor development. Whether the tumor redox state will affect the exogenous gene expression or not, are still not clear now . To investigate the relationship between tumor endogenous redox state and the exogenous gene expression level, a far red fluorescent protein fRFP was used to monitor tumor cells proliferation and as an exogenous protein expression in tumors. NADH (nicotinamide adenine dinucleotide) and Fp (flavin protein) are two important coenzymes in the mitochondria respiratory chain, which can be as a standard representation for redox metabolism state. Three tumor subcutaneous models (melanoma, human pancreatic carcinoma and nasopharyngeal carcinoma) were used to observe their redox state and protein expression by our home-made redox scanner. The results showed that the distribution of fRFP fluorescent protein expression in the inner tumor regions are heterogeneous, and the fluorescent intensity of fRFP and the fluorescent intensity of NADH have high correlation. In addition, we also found the linear coefficient in three tumors are different, the value of coefficient is (R2 = 0.966 and R2 = 0.943) in melanoma, (R2 = 0.701 and R2 = 0.942) in human pancreatic carcinoma, and (R2 = 0.994) in nasopharyngeal carcinoma, respectively. From these results, we consider that the exogenous protein expression of fRFP in tumor had some relationship with the tumor redox state of NADH.

  1. Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice

    SciTech Connect

    Hufbauer, M.; Lazic, D.; Akguel, B.; Brandsma, J.L.; Pfister, H.; Weissenborn, S.J.

    2010-08-01

    Human papillomavirus 8 (HPV8) is involved in skin cancer development in epidermodysplasia verruciformis patients. Transgenic mice expressing HPV8 early genes (HPV8-CER) developed papillomas, dysplasias and squamous cell carcinomas. UVA/B-irradiation and mechanical wounding of HPV8-CER mouse skin led to prompt papilloma induction in about 3 weeks. The aim of this study was to analyze the kinetics and level of transgene expression in response to skin irritations. Transgene expression was already enhanced 1 to 2 days after UVA/B-irradiation or tape-stripping and maintained during papilloma development. The enhanced transgene expression could be assigned to UVB and not to UVA. Papilloma development was thus always paralleled by an increased transgene expression irrespective of the type of skin irritation. A knock-down of E6 mRNA by tattooing HPV8-E6-specific siRNA led to a delay and a lower incidence of papilloma development. This indicates that the early increase of viral oncogene expression is crucial for induction of papillomatosis.

  2. 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

  3. Does Prison Crowding Predict Higher Rates of Substance Use Related Parole Violations? A Recurrent Events Multi-Level Survival Analysis

    PubMed Central

    Ruderman, Michael A.; Wilson, Deirdra F.; Reid, Savanna

    2015-01-01

    Objective This administrative data-linkage cohort study examines the association between prison crowding and the rate of post-release parole violations in a random sample of prisoners released with parole conditions in California, for an observation period of two years (January 2003 through December 2004). Background Crowding overextends prison resources needed to adequately protect inmates and provide drug rehabilitation services. Violence and lack of access to treatment are known risk factors for drug use and substance use disorders. These and other psychosocial effects of crowding may lead to higher rates of recidivism in California parolees. Methods Rates of parole violation for parolees exposed to high and medium levels of prison crowding were compared to parolees with low prison crowding exposure. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox model for recurrent events. Our dataset included 13070 parolees in California, combining individual level parolee data with aggregate level crowding data for multilevel analysis. Results Comparing parolees exposed to high crowding with those exposed to low crowding, the effect sizes from greatest to least were absconding violations (HR 3.56 95% CI: 3.05–4.17), drug violations (HR 2.44 95% CI: 2.00–2.98), non-violent violations (HR 2.14 95% CI: 1.73–2.64), violent and serious violations (HR 1.88 95% CI: 1.45–2.43), and technical violations (HR 1.86 95% CI: 1.37–2.53). Conclusions Prison crowding predicted higher rates of parole violations after release from prison. The effect was magnitude-dependent and particularly strong for drug charges. Further research into whether adverse prison experiences, such as crowding, are associated with recidivism and drug use in particular may be warranted. PMID:26492490

  4. RNA-Seq workflow: gene-level exploratory analysis and differential expression

    PubMed Central

    Love, Michael I.; Anders, Simon; Kim, Vladislav; Huber, Wolfgang

    2015-01-01

    Here we walk through an end-to-end gene-level RNA-Seq differential expression workflow using Bioconductor packages. We will start from the FASTQ files, show how these were aligned to the reference genome, and prepare a count matrix which tallies the number of RNA-seq reads/fragments within each gene for each sample. We will perform exploratory data analysis (EDA) for quality assessment and to explore the relationship between samples, perform differential gene expression analysis, and visually explore the results. PMID:26674615

  5. [The expression level of adhesion molecules on neutrophils depending at segmentation of their nuclei].

    PubMed

    Kashutin, S L; Danilov, S I; Vereshchagina, E N; Kluchareva, S V

    2013-11-01

    The article deals with results of detection of expression level of adhesion molecules on neutrophils and segmentation of their nuclei. It is established that in conditions of absence of antigen stimulation neutrophils of circulating pool express molecules of L-selectin in 53.34%, LFA-1 molecules in 65.64%, ICAM-1 in 40.51%, LE4-3 in 58.72% and PECAM-1 in 59.74%. The full readiness to realization of phase of sliding, strong adhesion and immediately transmigration itselfis detected in neutrophils with five segments in nucleus. PMID:24640111

  6. On the relationship between an Asian haplotype on chromosome 6 that reduces androstenone levels in boars and the differential expression of SULT2A1 in the testis

    PubMed Central

    2014-01-01

    Background Androstenone is one of the major compounds responsible for boar taint, a pronounced urine-like odor produced when cooking boar meat. Several studies have identified quantitative trait loci (QTL) for androstenone level on Sus scrofa chromosome (SSC) 6. For one of the candidate genes in the region SULT2A1, a difference in expression levels in the testis has been shown at the protein and RNA level. Results Haplotypes were predicted for the QTL region and their effects were estimated showing that haplotype 1 was consistently related with a lower level, and haplotype 2 with a higher level of androstenone. A recombinant haplotype allowed us to narrow down the QTL region from 3.75 Mbp to 1.94 Mbp. An RNA-seq analysis of the liver and testis revealed six genes that were differentially expressed between homozygotes of haplotypes 1 and 2. Genomic sequences of these differentially expressed genes were checked for variations within potential regulatory regions. We identified one variant located within a CpG island that could affect expression of SULT2A1 gene. An allele-specific expression analysis in the testis did not show differential expression between the alleles of SULT2A1 located on the different haplotypes in heterozygous animals. However a synonymous mutation C166T (SSC6: 49,117,861 bp in Sscrofa 10.2; C/T) was identified within the exon 2 of SULT2A1 for which the haplotype 2 only had the C allele which was higher expressed than the T allele, indicating haplotype-independent allelic-imbalanced expression between the two alleles. A phylogenetic analysis for the 1.94 Mbp region revealed that haplotype 1, associated with low androstenone level, originated from Asia. Conclusions Differential expression could be observed for six genes by RNA-seq analysis. No difference in the ratio of C:T expression of SULT2A1 for the haplotypes was found by the allele-specific expression analysis, however, a difference in expression between the C over T allele was found for a

  7. Expression Levels of LCORL Are Associated with Body Size in Horses

    PubMed Central

    Metzger, Julia; Schrimpf, Rahel; Philipp, Ute; Distl, Ottmar

    2013-01-01

    Body size is an important characteristic for horses of various breeds and essential for the classification of ponies concerning the limit value of 148 cm (58.27 inches) height at the withers. Genome-wide association analyses revealed the highest associated quantitative trait locus for height at the withers on horse chromosome (ECA) 3 upstream of the candidate gene LCORL. Using 214 Hanoverian horses genotyped on the Illumina equine SNP50 BeadChip and 42 different horse breeds across all size ranges, we confirmed the highly associated single nucleotide polymorphism BIEC2-808543 (−log10P = 8.3) and the adjacent gene LCORL as the most promising candidate for body size. We investigated the relative expression levels of LCORL and its two neighbouring genes NCAPG and DCAF16 using quantitative real-time PCR (RT-qPCR). We could demonstrate a significant association of the relative LCORL expression levels with the size of the horses and the BIEC2-808543 genotypes within and across horse breeds. In heterozygous C/T-horses expression levels of LCORL were significantly decreased by 40% and in homozygous C/C-horses by 56% relative to the smaller T/T-horses. Bioinformatic analyses indicated that this SNP T>C mutation is disrupting a putative binding site of the transcription factor TFIID which is important for the transcription process of genes involved in skeletal bone development. Thus, our findings suggest that expression levels of LCORL play a key role for body size within and across horse breeds and regulation of the expression of LCORL is associated with genetic variants of BIEC2-808543. This is the first functional study for a body size regulating polymorph