Science.gov

Sample records for express higher levels

  1. Higher-order JWKB expressions for the energy levels and the wavefunction at the origin

    SciTech Connect

    Pasupathy, J.; Singh, V.

    1980-09-01

    An exact quantization condition is derived for the energy levels of a particle in a radial potential assumed finite at the origin. This is used to derive corrections to the semiclassical JWKB quantization condition. The normalization integral of the wavefunction is further related to the energy derivative of wavefunction at origin and use this expression to derive the corrections to the semiclassical JWKB expressions for the wavefunction at origin. An application to upsilon leptonic decay width is also given.

  2. Newly paired zebra finches have higher dopamine levels and immediate early gene Fos expression in dopaminergic neurons.

    PubMed

    Banerjee, Sunayana B; Dias, Brian G; Crews, David; Adkins-Regan, Elizabeth

    2013-12-01

    Most birds are socially monogamous, yet little is known about the neural pathways underlying avian monogamy. Recent studies have implicated dopamine as playing a role in courtship and affiliation in a socially monogamous songbird, the zebra finch (Taeniopygia guttata). In the present study, we sought to understand the specific contribution to pair formation in zebra finches of the mesolimbic dopaminergic pathway that projects from the midbrain ventral tegmental area to the nucleus accumbens. We observed that paired birds had higher levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the ventral medial striatum, where the nucleus accumbens is situated, than unpaired birds. Additionally, we found that the percentage of dopaminergic neurons expressing immediate early gene Fos, a marker of neuronal activity, was higher in the ventral tegmental area of paired birds than in that of unpaired birds. These data are consistent with a role for the mesolimbic dopaminergic pathway in pair formation in zebra finches, suggesting the possibility of a conserved neural mechanism of monogamy in birds and mammals.

  3. 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.

  4. Higher Level Thinking Skills through Drama.

    ERIC Educational Resources Information Center

    Gangi, Jane M.

    1990-01-01

    The use of drama in the classroom provides concrete opportunities to explore such higher-level thinking abilities as synthesis, evaluation, and divergent thinking. Suggested activities for use with upper elementary and secondary students involve pantomime, verbal improvisation, expressing emotions, and developing characters. (JDD)

  5. 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.

  6. A Higher Risk of Acute Rejection of Human Kidney Allografts Can Be Predicted from the Level of CD45RC Expressed by the Recipients’ CD8 T Cells

    PubMed Central

    Ordonez, Laurence; Bernard, Isabelle; Chabod, Marianne; Augusto, Jean-François; Lauwers-Cances, Valerie; Cristini, Christelle; Cuturi, Maria-Cristina; Subra, Jean-François; Saoudi, Abdelhadi

    2013-01-01

    Although transplantation is the common treatment for end-stage renal failure, allograft rejection and marked morbidity from the use of immunosuppressive drugs remain important limitations. A major challenge in the field is to identify easy, reliable and noninvasive biomarkers allowing the prediction of deleterious alloreactive immune responses and the tailoring of immunosuppressive therapy in individuals according to the rejection risk. In this study, we first established that the expression of the RC isoform of the CD45 molecule (CD45RC) on CD4 and CD8 T cells from healthy individuals identifies functionally distinct alloreactive T cell subsets that behave differently in terms of proliferation and cytokine secretion. We then investigated whether the frequency of the recipients CD45RC T cell subsets before transplantation would predict acute graft rejection in a cohort of 89 patients who had undergone their first kidney transplantation. We showed that patients exhibiting more than 54.7% of CD8 CD45RChigh T cells before transplantation had a 6 fold increased risk of acute kidney graft rejection. In contrast, the proportions of CD4 CD45RC T cells were not predictive. Thus, a higher risk of acute rejection of human kidney allografts can be predicted from the level of CD45RC expressed by the recipients’ CD8 T cells. PMID:23894540

  7. 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

  8. 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.

  9. 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".

  10. 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.

  11. Discrete coherent states for higher Landau levels

    NASA Astrophysics Data System (ADS)

    Abreu, L. D.; Balazs, P.; de Gosson, M.; Mouayn, Z.

    2015-12-01

    We consider the quantum dynamics of a charged particle evolving under the action of a constant homogeneous magnetic field, with emphasis on the discrete subgroups of the Heisenberg group (in the Euclidean case) and of the SL(2 , R) group (in the Hyperbolic case). We investigate completeness properties of discrete coherent states associated with higher order Euclidean and hyperbolic Landau levels, partially extending classic results of Perelomov and of Bargmann, Butera, Girardello and Klauder. In the Euclidean case, our results follow from identifying the completeness problem with known results from the theory of Gabor frames. The results for the hyperbolic setting follow by using a combination of methods from coherent states, time-scale analysis and the theory of Fuchsian groups and their associated automorphic forms.

  12. 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.

  13. 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 ).

  14. 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.

  15. 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'.

  16. 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 Central

    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

  17. Influence of HLA-C Expression Level on HIV Control

    PubMed Central

    Apps, Richard; Qi, Ying; Carlson, Jonathan M.; Chen, Haoyan; Gao, Xiaojiang; Thomas, Rasmi; Yuki, Yuko; Del Prete, Greg Q.; Goulder, Philip; Brumme, Zabrina L.; Brumme, Chanson J.; John, Mina; Mallal, Simon; Nelson, George; Bosch, Ronald; Heckerman, David; Stein, Judy L.; Soderberg, Kelly A.; Moody, M. Anthony; Denny, Thomas N.; Zeng, Xue; Fang, Jingyuan; Moffett, Ashley; Lifson, Jeffrey D.; Goedert, James J.; Buchbinder, Susan; Kirk, Gregory D.; Fellay, Jacques; McLaren, Paul; Deeks, Steven G.; Pereyra, Florencia; Walker, Bruce; Michael, Nelson L.; Weintrob, Amy; Wolinsky, Steven; Liao, Wilson; Carrington, Mary

    2013-01-01

    A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn’s disease, suggesting a broader influence of HLA expression levels in human disease. PMID:23559252

  18. 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…

  19. 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 &…

  20. 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.

  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.

  2. A higher-level MRP supertree of placental mammals

    PubMed Central

    Beck, Robin MD; Bininda-Emonds, Olaf RP; Cardillo, Marcel; Liu, Fu-Guo Robert; Purvis, Andy

    2006-01-01

    Background The higher-level phylogeny of placental mammals has long been a phylogenetic Gordian knot, with disagreement about both the precise contents of, and relationships between, the extant orders. A recent MRP supertree that favoured 'outdated' hypotheses (notably, monophyly of both Artiodactyla and Lipotyphla) has been heavily criticised for including low-quality and redundant data. We apply a stringent data selection protocol designed to minimise these problems to a much-expanded data set of morphological, molecular and combined source trees, to produce a supertree that includes every family of extant placental mammals. Results The supertree is well-resolved and supports both polyphyly of Lipotyphla and paraphyly of Artiodactyla with respect to Cetacea. The existence of four 'superorders' – Afrotheria, Xenarthra, Laurasiatheria and Euarchontoglires – is also supported. The topology is highly congruent with recent (molecular) phylogenetic analyses of placental mammals, but is considerably more comprehensive, being the first phylogeny to include all 113 extant families without making a priori assumptions of suprafamilial monophyly. Subsidiary analyses reveal that the data selection protocol played a key role in the major changes relative to a previously published higher-level supertree of placentals. Conclusion The supertree should provide a useful framework for hypothesis testing in phylogenetic comparative biology, and supports the idea that biogeography has played a crucial role in the evolution of placental mammals. Our results demonstrate the importance of minimising poor and redundant data when constructing supertrees. PMID:17101039

  3. Cognition = life: Implications for higher-level cognition.

    PubMed

    Stewart, J

    1995-12-01

    Any global consideration of the theme 'Evolution and Cognition' requires a clear definition of what we mean by the term 'cognition'. In contemporary cognitive science, there are two distinct paradigms with contrasting definitions of cognition. The computational theory of mind is based on the syntaxical manipulation of symbolic representations; this paradigm is objectivist because the postulate of a unique independent reality is necessary as a referential basis for semantic grounding of the symbols. The alternative 'constructivist' paradigm is based on the biological metaphor 'cognition = life' and programmatically follows the evolution of cognition from bacteria to civilized humans; it is non-objectivist. There is a definite tendency to consider that the computational theory is appropriate for 'high-level' human cognition, whereas the constructivist approach is appropriate for 'low-level' cognition. This article argues against such a division of labour, since the issue of objectivism is a watershed which continues to demarcate the computational and constructivist paradigms in their respective approaches to higher-level cognition.

  4. Heterophils isolated from chickens resistant to extra-intestinal Salmonella enteritidis infection express higher levels of pro-inflammatory cytokine mRNA following infection than heterophils from susceptible chickens.

    PubMed Central

    Ferro, Pamela J.; Swaggerty, Christina L.; Kaiser, Pete; Pevzner, Igal Y.; Kogut, Michael H.

    2004-01-01

    Previous studies showed differences in in vitro heterophil function between parental (A > B) broilers and F1 reciprocal crosses (D > C). Our objectives were to (1) determine if in vitro variations translate to differences in resistance to Salmonella enteritidis (SE) and (2) quantitate cytokine mRNA in heterophils from SE-infected chicks. One-day-old chicks were challenged and organs were cultured for SE. Chicks with efficient heterophils (A and D) were less susceptible to SE compared to chicks with inefficient heterophils (B and C). Heterophils were isolated from SE-infected chicks and cytokine mRNA expression was evaluated using quantitative real-time RT-PCR. Pro-inflammatory cytokine mRNA was up-regulated in heterophils from SE-resistant chicks compared to susceptible chicks. This is the first report to quantitate cytokine mRNA in heterophils from SE-infected chicks. These data show a relationship between in vitro heterophil function, increased pro-inflammatory cytokine mRNA expression, and increased resistance to SE in 1-day-old chicks. PMID:15635959

  5. Higher brain BDNF gene expression is associated with slower cognitive decline in older adults

    PubMed Central

    Yu, Lei; Boyle, Patricia A.; Schneider, Julie A.; De Jager, Philip L.; Bennett, David A.

    2016-01-01

    Objectives: We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults. Methods: Five hundred thirty-five older participants underwent annual cognitive assessments and brain autopsy at death. BDNF gene expression was measured in the dorsolateral prefrontal cortex. Linear mixed models were used to examine whether BDNF expression was associated with cognitive decline adjusting for age, sex, and education. An interaction term was added to determine whether this association varied with clinical diagnosis proximate to death (no cognitive impairment, mild cognitive impairment, or dementia). Finally, we examined the extent to which the association of Alzheimer disease (AD) pathology with cognitive decline varied by BDNF expression. Results: Higher brain BDNF expression was associated with slower cognitive decline (p < 0.001); cognitive decline was about 50% slower with the 90th percentile BDNF expression vs 10th. This association was strongest in individuals with dementia. The level of BDNF expression was lower in individuals with pathologic AD (p = 0.006), but was not associated with macroscopic infarcts, Lewy body disease, or hippocampal sclerosis. BDNF expression remained associated with cognitive decline in a model adjusting for age, sex, education, and neuropathologies (p < 0.001). Furthermore, the effect of AD pathology on cognitive decline varied by BDNF expression such that the effect was strongest for high levels of AD pathology (p = 0.015); thus, in individuals with high AD pathology (90th percentile), cognitive decline was about 40% slower with the 90th percentile BDNF expression vs 10th. Conclusions: Higher brain BDNF expression is associated with slower cognitive decline and may also reduce the deleterious effects of AD pathology on cognitive decline. PMID:26819457

  6. Spiking neural networks for higher-level information fusion

    NASA Astrophysics Data System (ADS)

    Bomberger, Neil A.; Waxman, Allen M.; Pait, Felipe M.

    2004-04-01

    This paper presents a novel approach to higher-level (2+) information fusion and knowledge representation using semantic networks composed of coupled spiking neuron nodes. Networks of spiking neurons have been shown to exhibit synchronization, in which sub-assemblies of nodes become phase locked to one another. This phase locking reflects the tendency of biological neural systems to produce synchronized neural assemblies, which have been hypothesized to be involved in feature binding. The approach in this paper embeds spiking neurons in a semantic network, in which a synchronized sub-assembly of nodes represents a hypothesis about a situation. Likewise, multiple synchronized assemblies that are out-of-phase with one another represent multiple hypotheses. The initial network is hand-coded, but additional semantic relationships can be established by associative learning mechanisms. This approach is demonstrated with a simulated scenario involving the tracking of suspected criminal vehicles between meeting places in an urban environment.

  7. A Comparison of Artificial Subtle Expressions with Human-like Expressions on Expressing Confidence Level

    NASA Astrophysics Data System (ADS)

    Komatsu, Takanori; Kobayashi, Kazuki; Yamada, Seiji; Funakoshi, Kotaro; Nakano, Mikio

    Expressing the confidence level of a system's suggestions by using speech sounds is an important cue to users of the system for perceiving how likely it is for the suggestions to be correct. We assume that expressing confidence levels by using human-like expressions would cause users to have a poorer impression of the systems than if artificial subtle expressions (ASEs) were used when the quality of the presented information does not match the expressed confidence level. We confirmed that this assumption was correct by conducting a psychological experiment.

  8. Higher-level crustacean phylogeny: consensus and conflicting hypotheses.

    PubMed

    Jenner, Ronald A

    2010-01-01

    This paper presents an overview of current hypotheses of higher-level crustacean phylogeny in order to assist and help focus further research. It concentrates on hypotheses proposed or debated in the recent literature based on morphological, molecular and combined evidence phylogenetic analyses. It can be concluded that crustacean phylogeny remains essentially unresolved. Conflict is rife, irrespective of whether one compares different morphological studies, molecular studies, or both. Using the number of recently proposed alternative sister group hypotheses for each of the major tetraconatan taxa as a rough estimate of phylogenetic uncertainty, it can be concluded that the phylogenetic position of Malacostraca remains the most problematic, closely followed by Branchiopoda, Cephalocarida, Remipedia, Ostracoda, Branchiura, Copepoda and Hexapoda. Future progress will depend upon a broader taxon sampling in molecular analyses, and the further exploration of new molecular phylogenetic markers. However, the need for continued revision and expansion of morphological datasets remains undiminished given the conspicuous lack of agreement between molecules and morphology for positioning several taxa. In view of the unparalleled morphological diversity of Crustacea, and the likely nesting of Hexapoda somewhere within Crustacea, working out a detailed phylogeny of Tetraconata is a crucial step towards understanding arthropod body plan evolution.

  9. PCOS women show significantly higher homocysteine level, independent to glucose and E2 level

    PubMed Central

    Eskandari, Zahra; Sadrkhanlou, Rajab-Ali; Nejati, Vahid; Tizro, Gholamreza

    2016-01-01

    Background: It is reasonable to think that some biochemical characteristics of follicular fluid (FF) surrounding the oocyte may play a critical role in determining the quality of oocyte and the subsequent potential needed to achieve fertilization and embryo development. Objective: This study was carried out to evaluate the levels of FF homocysteine (Hcy) in IVF candidate polycystic ovary syndrome (PCOS) women and any relationships with FF glucose and estradiol (E2) levels. Materials and Methods: In this case control study which was performed in Dr. Tizro Day Care and IVF Center 70 infertile patients were enrolled in two groups: comprising 35 PCOS and 35 non PCOS women. Long protocol was performed for all patients. FF Hcy, glucose and E2 levels were analyzed at the time of oocyte retrieval. Results: It was observed that FF Hcy level was significantly higher in PCOS patients compared with non PCOSs (p<0.01). Observations demonstrated that in PCOS group, the Hcy level increased independent to E2, glucose levels, BMI and age, while the PCOS group showed significantly higher BMI compared with non-PCOS group (p=0.03). However, no significant differences were revealed between groups for FF glucose and E2 levels. Conclusion: Present data showed that although FF glucose and E2 levels were constant in PCOS and non PCOS patients, but the FF Hcy levels in PCOS were significantly increased (p=0.01). PMID:27679823

  10. 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

  11. 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…

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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…

  17. 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…

  18. 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…

  19. E11, Romans theory and higher level duality relations

    NASA Astrophysics Data System (ADS)

    Tumanov, Alexander G.; West, Peter

    2017-02-01

    From the underlying nonlinear realisation, we compute the complete E11 invariant equations of motion in eleven dimensions, at the linearised level, up to and including level four in the fields. Thus, we include the metric, the three and six forms, the dual graviton and three fields at level four. The fields are linked by a set of duality equations, which are first-order in derivatives and transform into each other under the E11 symmetries. From these duality relations, we deduce second-order equations of motion, including those for the usual supergravity fields. As a result the on-shell degrees of freedom are those of the eleven-dimensional supergravity. We also show that the level four fields provide an eleven-dimensional origin of Romans theory and lead to a novel duality relation.

  20. Decreased expression of Klotho in cardiac atria biopsy samples from patients at higher risk of atherosclerotic cardiovascular disease

    PubMed Central

    Corsetti, Giovanni; Pasini, Evasio; Scarabelli, Tiziano M; Romano, Claudia; Agrawal, Pratik R; Chen-Scarabelli, Carol; Knight, Richard; Saravolatz, Louis; Narula, Jagat; Ferrari-Vivaldi, Mario; Flati, Vincenzo; Assanelli, Deodato; Dioguardi, Francesco S

    2016-01-01

    Background Klotho proteins (α- and β) are membrane-based circulating proteins that regulate cell metabolism, as well as the lifespan modulating activity of Fibroblast Growth Factors (FGFs). Recent data has shown that higher plasma circulating Klotho levels reduce cardiovascular risk, suggesting Klotho has a protective role in cardiovascular diseases. However, although so far it has been identified in various organs, it is unknown whether cardiomyocytes express Klotho and FGFs, and whether high cardiovascular risk could affect cardiac expression of Klotho, FGFs and other molecules. Methods We selected 20 patients with an estimated 10-year high atherosclerotic cardiovascular disease and 10 age-matched control subjects with an estimated 10-year low risk undergone cardiac surgery for reasons other than coronary artery by-pass. In myocardial biopsies, we evaluated by immuno-histochemistry whether Klotho and FGFs were expressed in cardiomyocytes, and whether higher cardiovascular risk influenced the expression of other molecules involved in endoplasmic reticulum stress, oxidative stress, inflammation and fibrosis. Results Only cardiomyocytes of patients with a higher cardiovascular risk showed lower expression of Klotho, but higher expressions of FGFs. Furthermore, higher cardiovascular risk was associated with increased expression of oxidative and endoplasmic reticular stress, inflammation and fibrosis. Conclusions This study showed for the first time that Klotho proteins are expressed in human cardiomyocytes and that cardiac expression of Klotho is down-regulated in higher cardiovascular risk patients, while expression of stress-related molecules were significantly increased. PMID:27781061

  1. Putative transmembrane transporter modulates higher-level aggression in Drosophila.

    PubMed

    Chowdhury, Budhaditya; Chan, Yick-Bun; Kravitz, Edward A

    2017-02-28

    By selection of winners of dyadic fights for 35 generations, we have generated a hyperaggressive Bully line of flies that almost always win fights against the parental wild-type Canton-S stock. Maintenance of the Bully phenotype is temperature dependent during development, with the phenotype lost when flies are reared at 19 °C. No similar effect is seen with the parent line. This difference allowed us to carry out RNA-seq experiments and identify a limited number of genes that are differentially expressed by twofold or greater in the Bullies; one of these was a putative transmembrane transporter, CG13646, which showed consistent and reproducible twofold down-regulation in Bullies. We examined the causal effect of this gene on the phenotype with a mutant line for CG13646, and with an RNAi approach. In all cases, reduction in expression of CG13646 by approximately half led to a hyperaggressive phenotype partially resembling that seen in the Bully flies. This gene is a member of a very interesting family of solute carrier proteins (SLCs), some of which have been suggested as being involved in glutamine/glutamate and GABA cycles of metabolism in excitatory and inhibitory nerve terminals in mammalian systems.

  2. The higher you climb: Dark side personality and job level.

    PubMed

    Gøtzsche-Astrup, Oluf; Jakobsen, Joan; Furnham, Adrian

    2016-12-01

    The purpose of this study was to explore the idea that there are dark side personality differences in the profiles of people at different levels in organizations. This study replicates and extends existing leadership research by focusing on self-defeating behavioral tendencies. A Danish consultancy provided data on 264 adults based on assessment reports. This paper explored linear and quadratic relationships between personality and de facto job level. More senior managers scored high on Cluster B/Moving Against Others scales of Bold, Colorful and Imaginative, and low on Cautious and Dutiful. These Danish data are compared to data from Great Britain and New Zealand which show very similar findings. Practice should take into account that dark side personality traits associated with an assertive, sometimes hostile, interpersonal orientation, predict leadership level up to a point.

  3. 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…

  4. 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…

  5. Interpretant Levels Presented by Higher Education Students about the Seasons

    NASA Astrophysics Data System (ADS)

    Sanzovo, Daniel Trevisan; Laburú, Carlos Eduardo

    2016-12-01

    The aim of this study is to investigate the initial interpretant levels of the seasons of the year presented by students in a physics discipline of undergraduate course of a biological sciences degree at a state university of the south of Brazil. This study is qualitative, it analyzes textual oral representations and images about that astronomical phenomenon. It found that all students showed similar interpretant levels than those without any instruction, focusing their explanation of this concept in the variation of the distance between Earth and the Sun and indeterminate/confused representations. Another important result was the absence of a scientifically correct conception of the subject. The data from this study are in agreement with several studies on the weak training of science teachers in astronomy, and emphasizes the importance of both a re-structuration of the initial training of these future teachers, as well as the continuous teacher training of the working professional ones.

  6. Higher expression of somatic repair genes in long-lived ant queens than workers

    PubMed Central

    Lucas, Eric R.; Privman, Eyal; Keller, Laurent

    2016-01-01

    Understanding why organisms senesce is a fundamental question in biology. One common explanation is that senescence results from an increase in macromolecular damage with age. The tremendous variation in lifespan between genetically identical queen and worker ants, ranging over an order of magnitude, provides a unique system to study how investment into processes of somatic maintenance and macromolecular repair influence lifespan. Here we use RNAseq to compare patterns of expression of genes involved in DNA and protein repair of age-matched queens and workers. There was no difference between queens and workers in 1-day-old individuals, but the level of expression of these genes increased with age and this up-regulation was greater in queens than in workers, resulting in significantly queen-biased expression in 2-month-old individuals in both legs and brains. Overall, these differences are consistent with the hypothesis that higher longevity is associated with increased investment into somatic repair. PMID:27617474

  7. A higher level classification of all living organisms.

    PubMed

    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.

  8. 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

  9. 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

  10. 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

  11. A promoter-level mammalian expression atlas.

    PubMed

    Forrest, Alistair R R; Kawaji, Hideya; Rehli, Michael; Baillie, J Kenneth; de Hoon, Michiel J L; Haberle, Vanja; Lassmann, Timo; Kulakovskiy, Ivan V; Lizio, Marina; Itoh, Masayoshi; Andersson, Robin; Mungall, Christopher J; Meehan, Terrence F; Schmeier, Sebastian; Bertin, Nicolas; Jørgensen, Mette; Dimont, Emmanuel; Arner, Erik; Schmidl, Christian; Schaefer, Ulf; Medvedeva, Yulia A; Plessy, Charles; Vitezic, Morana; Severin, Jessica; Semple, Colin A; Ishizu, Yuri; Young, Robert S; Francescatto, Margherita; Alam, Intikhab; Albanese, Davide; Altschuler, Gabriel M; Arakawa, Takahiro; Archer, John A C; Arner, Peter; Babina, Magda; Rennie, Sarah; Balwierz, Piotr J; Beckhouse, Anthony G; Pradhan-Bhatt, Swati; Blake, Judith A; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Burroughs, A Maxwell; Califano, Andrea; Cannistraci, Carlo V; Carbajo, Daniel; Chen, Yun; Chierici, Marco; Ciani, Yari; Clevers, Hans C; Dalla, Emiliano; Davis, Carrie A; Detmar, Michael; Diehl, Alexander D; Dohi, Taeko; Drabløs, Finn; Edge, Albert S B; Edinger, Matthias; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey; Fang, Hai; Farach-Carson, Mary C; Faulkner, Geoffrey J; Favorov, Alexander V; Fisher, Malcolm E; Frith, Martin C; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furino, Masaaki; Furusawa, Jun-ichi; Geijtenbeek, Teunis B; Gibson, Andrew P; Gingeras, Thomas; Goldowitz, Daniel; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard; Hitchens, Kelly J; Ho Sui, Shannan J; Hofmann, Oliver M; Hoof, Ilka; Hori, Furni; Huminiecki, Lukasz; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R; Jia, Hui; Joshi, Anagha; Jurman, Giuseppe; Kaczkowski, Bogumil; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Kasianov, Artem S; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I; Kawashima, Tsugumi; Kempfle, Judith S; Kenna, Tony J; Kere, Juha; Khachigian, Levon M; Kitamura, Toshio; Klinken, S Peter; Knox, Alan J; Kojima, Miki; Kojima, Soichi; Kondo, Naoto; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T; Laros, Jeroen F J; Lee, Weonju; Lennartsson, Andreas; Li, Kang; Lilje, Berit; Lipovich, Leonard; Mackay-Sim, Alan; Manabe, Ri-ichiroh; Mar, Jessica C; Marchand, Benoit; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison; Mizuno, Yosuke; de Lima Morais, David A; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakachi, Yutaka; Nakahara, Fumio; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Noma, Shohei; Noazaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Ohimiya, Hiroko; Ohno, Hiroshi; Ohshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry A; Pain, Arnab; Passier, Robert; Patrikakis, Margaret; Persson, Helena; Piazza, Silvano; Prendergast, James G D; Rackham, Owen J L; Ramilowski, Jordan A; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Rye, Morten B; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Savvi, Suzana; Saxena, Alka; Schneider, Claudio; Schultes, Erik A; Schulze-Tanzil, Gundula G; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W; Simon, Christophe; Sugiyama, Daisuke; Sugiyama, Takaai; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K; 't Hoen, Peter A C; Tagami, Michihira; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyodo, Hiroo; Toyoda, Tetsuro; Valen, Elvind; van de Wetering, Marc; van den Berg, Linda M; Verado, Roberto; Vijayan, Dipti; Vorontsov, Ilya E; Wasserman, Wyeth W; Watanabe, Shoko; Wells, Christine A; Winteringham, Louise N; Wolvetang, Ernst; Wood, Emily J; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Susan E; Zhang, Peter G; Zhao, Xiaobei; Zucchelli, Silvia; Summers, Kim M; Suzuki, Harukazu; Daub, Carsten O; Kawai, Jun; Heutink, Peter; Hide, Winston; Freeman, Tom C; Lenhard, Boris; Bajic, Vladimir B; Taylor, Martin S; Makeev, Vsevolod J; Sandelin, Albin; Hume, David A; Carninci, Piero; Hayashizaki, Yoshihide

    2014-03-27

    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.

  12. Analysis of baseline gene expression levels from ...

    EPA Pesticide Factsheets

    The use of gene expression profiling to predict chemical mode of action would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies has yielded useful information on baseline fluctuations in gene expression. A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selectiv

  13. Could Low Vitamin D Levels at Birth Mean Higher MS Risk?

    MedlinePlus

    ... gov/news/fullstory_162317.html Could Low Vitamin D Levels at Birth Mean Higher MS Risk? Perhaps, ... HealthDay News) -- Newborns with low levels of vitamin D may have higher odds of developing multiple sclerosis ( ...

  14. 78 FR 72620 - Federal Acquisition Regulation; Higher-Level Contract Quality Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ...(s). Examples of higher-level quality standards include, but are not limited to, ISO 9001, ASQ E... 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...

  15. High VEGFR1/2 expression levels are predictors of poor survival in patients with cervical cancer

    PubMed Central

    Dang, Yun-Zhi; Zhang, Ying; Li, Jian-Ping; Hu, Jing; Li, Wei-Wei; Li, Pei; Wei, Li-Chun; Shi, Mei

    2017-01-01

    Abstract The aim of the study to evaluate the prognostic significance of vascular endothelial growth factor receptor 1 and 2 (VEGFR1/2) expression levels and to correlate these levels with clinicopathological parameters in patients with cervical cancer. Forty-two patients with International Federation of Gynecology and Obstetrics Stage IIB–IVB cervical cancer were analyzed between January 2011 and December 2012. RNA expression levels of VEGFR1/2 were assessed by branched DNA-liquidchip technology and immunohistochemistry. Associations between RNA expression levels, important clinicopathological parameters, and patient survival were statistically evaluated. Higher VEGFR1/2 expression levels were predictive of poor overall survival (P = 0.009 and P = 0.024, respectively). Patients with higher VEGFR1 expression levels were associated with poorer progression-free survival than those with lower VEGFR1 expression levels (P = 0.043). In addition, patients with higher VEGFR1 expression levels were more likely to develop distant metastases than those with lower VEGFR1 expression levels (P = 0.049). Higher VEGFR2 expression levels were associated with larger tumor size (P = 0.037). VEGFR1/2 expression levels were prognostic factors for patients with cervical cancer. Higher VEGFR1/2 expression levels were also predictive of poor overall survival. PMID:28072723

  16. 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

  17. Motor axon synapses on renshaw cells contain higher levels of aspartate than glutamate.

    PubMed

    Richards, Dannette S; Griffith, Ronald W; Romer, Shannon H; Alvarez, Francisco J

    2014-01-01

    Motoneuron synapses on spinal cord interneurons known as Renshaw cells activate nicotinic, AMPA and NMDA receptors consistent with co-release of acetylcholine and excitatory amino acids (EAA). However, whether these synapses express vesicular glutamate transporters (VGLUTs) capable of accumulating glutamate into synaptic vesicles is controversial. An alternative possibility is that these synapses release other EAAs, like aspartate, not dependent on VGLUTs. To clarify the exact EAA concentrated at motor axon synapses we performed a quantitative postembedding colloidal gold immunoelectron analysis for aspartate and glutamate on motor axon synapses (identified by immunoreactivity to the vesicular acetylcholine transporter; VAChT) contacting calbindin-immunoreactive (-IR) Renshaw cell dendrites. The results show that 71% to 80% of motor axon synaptic boutons on Renshaw cells contained aspartate immunolabeling two standard deviations above average neuropil labeling. Moreover, VAChT-IR synapses on Renshaw cells contained, on average, aspartate immunolabeling at 2.5 to 2.8 times above the average neuropil level. In contrast, glutamate enrichment was lower; 21% to 44% of VAChT-IR synapses showed glutamate-IR two standard deviations above average neuropil labeling and average glutamate immunogold density was 1.7 to 2.0 times the neuropil level. The results were not influenced by antibody affinities because glutamate antibodies detected glutamate-enriched brain homogenates more efficiently than aspartate antibodies detecting aspartate-enriched brain homogenates. Furthermore, synaptic boutons with ultrastructural features of Type I excitatory synapses were always labeled by glutamate antibodies at higher density than motor axon synapses. We conclude that motor axon synapses co-express aspartate and glutamate, but aspartate is concentrated at higher levels than glutamate.

  18. Synthetic pillows contain higher levels of cat and dog allergen than feather pillows.

    PubMed

    Custovic, A; Hallam, C; Woodcock, H; Simpson, B; Houghton, N; Simpson, A; Woodcock, A

    2000-05-01

    The use of non-feather pillows has increased over the last few decades. Recently, we found significantly higher levels of dust mite allergens in synthetic pillows than in feather ones. This study investigated the levels of pet allergens in feather and synthetic pillows. Dust samples were collected from 14 pairs of pillows (consisting of one synthetic fibre-filled and one feather-filled). Each pair of pillows had been on the same bed for at least 2 years. The pillows were vacuumed for 1 min on each side through a 355-microm diameter mesh onto a 5-microm vinyl filter, producing a sample of fine dust. Samples were extracted, and cat (Fel d 1) and dog (Can f 1) allergens determined using monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Results were expressed both as total amount of allergen recovered and concentration of allergen per unit weight (ng/g). Total levels of pet allergens were significantly higher in the synthetic pillows (Fel d 1: 6.7-fold difference [95% CI 1.5-29.7], p=0.01; Can f 1: 8-fold difference [95% CI 1.6-39.5], p=0.01). Similarly, when the results were expressed as ng/g, synthetic pillows contained significantly more allergens than feather pillows (Fel d 1: 3.7-fold difference [95% CI 1.3-10.1], p=0.01); Can f 1: 4.4-fold difference [95% CI 1.5-13.2], p=0.01). We have therefore demonstrated that synthetic pillows contain significantly more pet allergens than feather pillows, supporting the view that tightly woven encasements surrounding feather pillows act as a barrier for allergens.

  19. Obese patients have higher circulating protein levels of dipeptidyl peptidase IV.

    PubMed

    Stengel, Andreas; Goebel-Stengel, Miriam; Teuffel, Pauline; Hofmann, Tobias; Buße, Petra; Kobelt, Peter; Rose, Matthias; Klapp, Burghard F

    2014-11-01

    Dipeptidyl peptidase IV (DPPIV) is a protease with broad distribution involved in various homeostatic processes such as immune defense, psychoneuroendocrine functions and nutrition. While DPPIV protein levels were investigated in patients with hyporectic disorders, less is known under conditions of obesity. Therefore, we investigated DPPIV across a broad range of body mass index (BMI). Blood samples from hospitalized patients with normal weight (BMI 18.5-25 kg/m(2)), anorexia nervosa (BMI <17.5 kg/m(2)) and obesity (BMI 30-40, 40-50 and >50 kg/m(2), n = 15/group) were tested cross-sectionally and DPPIV concentration and total enzyme activity and the DPPIV targets, pancreatic polypeptide (PP) and glucagon-like peptide (GLP-1) were measured. DPPIV protein expression was detected in human plasma indicated by a strong band at the expected size of 110 kDa and another major band at 50 kDa, likely representing a fragment comprised of two heavy chains. Obese patients had higher DPPIV protein levels compared to normal weight and anorexics (+50%, p<0.05) resulting in a positive correlation with BMI (r = 0.34, p = 0.004). DPPIV serum activity was similar in all groups (p>0.05), while the concentration/activity ratio was higher in obese patients (p<0.05). Plasma PP levels were highest in anorexic patients (∼ 2-fold increase compared to other groups, p<0.05), whereas GLP-1 did not differ among groups (p<0.05). Taken together, circulating DPPIV protein levels depend on body weight with increased levels in obese resulting in an increased concentration/activity ratio. Since DPPIV deactivates food intake-inhibitory hormones like PP, an increased DPPIV concentration/activity ratio might contribute to reduced food intake-inhibitory signaling under conditions of obesity.

  20. Correlation between liver cancer pain and the HIF-1 and VEGF expression levels

    PubMed Central

    Zhang, Geng; Feng, Gui-Yin; Guo, Yan-Ru; Liang, Dong-Qi; Yuan, Yuan; Wang, Hai-Lun

    2017-01-01

    A possible correlation between liver cancer pain and the hypoxia-inducible factor (HIF)-1 and vascular endothelial growth factor (VEGF) expression levels was examined. From January, 2015 to January, 2016, 30 patients suffering from liver cancer with pain, 30 patients with liver cancer without pain and 30 hepatitis patients with pain were enrolled in the study. Pain level was evaluated by visual analogue scale (VAS), the expression levels of HIF-1 and VEGF mRNA were determined by RT-PCR and the expression levels of HIF-1 and VEGF proteins were examined by ELISA. Before intervention, the VAS in the hepatitis group was significantly higher than that of the liver cancer pain group. However, after intervention the VAS in the two groups was reduced. HIF-1 and VEGF mRNA expression levels in the liver cancer pain group were significantly higher than those in the liver cancer group before and after intervention. The expression levels of HIF-1 and VEGF mRNA in the hepatitis group were the lowest. The expression levels of HIF-1 and VEGF mRNA in the liver cancer pain group considerably increased after intervention. The expression levels of HIF-1 and VEGF mRNA in the other two groups showed no changes before or after intervention. Before and after the intervention, VAS in the liver cancer pain group was positively correlated to the expression levels of HIF-1 and VEGF. Thus, pain occurrence and the pain level in liver cancer patients were correlated with the expression levels of HIF-1 and VEGF. As the regular three-step medicine analgesic ladder is ineffective in these cases, verification of HIF-1 and VEGF expression levels may be considered the new target for pain release. PMID:28123525

  1. GEMS: Gifted Education Module System. Higher Level Thinking in the Junior High.

    ERIC Educational Resources Information Center

    Davis, Hilarie; And Others

    The curriculum, designed for use with gifted students at the junior high level, presents units of instruction which emphasize the higher level thinking skills of analysis, synthesis, and evaluation. An introductory section explains each of the three higher level skills and presents tasks illustrating each one. Four units are presented, complete…

  2. 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

  3. 48 CFR 46.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    .... Examples of higher-level quality standards are ISO 9001, 9002, or 9003; ANSI/ISO/ASQ Q9001-2000; ANSI/ASQC... 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...

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    .... Examples of higher-level quality standards are ISO 9001, 9002, or 9003; ANSI/ISO/ASQ Q9001-2000; ANSI/ASQC... 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...

  5. 48 CFR 46.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... Examples of higher-level quality standards are ISO 9001, 9002, or 9003; ANSI/ISO/ASQ Q9001-2000; ANSI/ASQC... 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...

  6. 48 CFR 46.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    .... Examples of higher-level quality standards are ISO 9001, 9002, or 9003; ANSI/ISO/ASQ Q9001-2000; ANSI/ASQC... 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...

  7. 48 CFR 46.202-4 - Higher-level contract quality requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    .... Examples of higher-level quality standards are ISO 9001, 9002, or 9003; ANSI/ISO/ASQ Q9001-2000; ANSI/ASQC... 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...

  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. TIGIT expression levels on human NK cells correlate with functional heterogeneity among healthy individuals.

    PubMed

    Wang, Feng; Hou, Hongyan; Wu, Shiji; Tang, Qing; Liu, Weiyong; Huang, Min; Yin, Botao; Huang, Jing; Mao, Lie; Lu, Yanfang; Sun, Ziyong

    2015-10-01

    Human NK cells display extensive phenotypic and functional heterogeneity among healthy individuals, but the mechanism responsible for this variation is still largely unknown. Here, we show that a novel immune receptor, T-cell immunoglobulin and ITIM domain (TIGIT), is expressed preferentially on human NK cells but shows wide variation in its expression levels among healthy individuals. We found that the TIGIT expression level is related to the phenotypic and functional heterogeneity of NK cells, and that NK cells from healthy individuals can be divided into three categories according to TIGIT expression. NK cells with low levels of TIGIT expression show higher cytokine secretion capability, degranulation activity, and cytotoxic potential than NK cells with high levels of TIGIT expression. Blockade of the TIGIT pathway significantly increased NK-cell function, particularly in NK cells with high levels of TIGIT expression. We further observed that the TIGIT expression level was inversely correlated with the IFN-γ secretion capability of NK cells in patients with cancers and autoimmune diseases. Importantly, we propose a novel mechanism that links TIGIT expression with NK-cell functional heterogeneity, and this mechanism might partially explain why individuals have different susceptibilities to infection, autoimmune disease, and cancer.

  10. 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…

  11. Sequence determinants of prokaryotic gene expression level under heat stress.

    PubMed

    Xiong, Heng; Yang, Yi; Hu, Xiao-Pan; He, Yi-Ming; Ma, Bin-Guang

    2014-11-01

    Prokaryotic gene expression is environment-dependent and temperature plays an important role in shaping the gene expression profile. Revealing the regulation mechanisms of gene expression pertaining to temperature has attracted tremendous efforts in recent years particularly owning to the yielding of transcriptome and proteome data by high-throughput techniques. However, most of the previous works concentrated on the characterization of the gene expression profile of individual organism and little effort has been made to disclose the commonality among organisms, especially for the gene sequence features. In this report, we collected the transcriptome and proteome data measured under heat stress condition from recently published literature and studied the sequence determinants for the expression level of heat-responsive genes on multiple layers. Our results showed that there indeed exist commonness and consistent patterns of the sequence features among organisms for the differentially expressed genes under heat stress condition. Some features are attributed to the requirement of thermostability while some are dominated by gene function. The revealed sequence determinants of bacterial gene expression level under heat stress complement the knowledge about the regulation factors of prokaryotic gene expression responding to the change of environmental conditions. Furthermore, comparisons to thermophilic adaption have been performed to reveal the similarity and dissimilarity of the sequence determinants for the response to heat stress and for the adaption to high habitat temperature, which elucidates the complex landscape of gene expression related to the same physical factor of temperature.

  12. Analysis of gelsolin expression pattern in developing chicken embryo reveals high GSN expression level in tissues of neural crest origin.

    PubMed

    Mazur, Antonina Joanna; Morosan-Puopolo, Gabriela; Makowiecka, Aleksandra; Malicka-Błaszkiewicz, Maria; Nowak, Dorota; Brand-Saberi, Beate

    2016-01-01

    Gelsolin is one of the most intensively studied actin-binding proteins. However, in the literature comprehensive studies of GSN expression during development have not been performed yet in all model organisms. In zebrafish, gelsolin is a dorsalizing factor that modulates bone morphogenetic proteins signaling pathways, whereas knockout of the gelsolin coding gene, GSN is not lethal in murine model. To study the role of gelsolin in development of higher vertebrates, it is crucial to estimate GSN expression pattern during development. Here, we examined GSN expression in the developing chicken embryo. We applied numerous methods to track GSN expression in developing embryos at mRNA and protein level. We noted a characteristic GSN expression pattern. Although GSN transcripts were present in several cell types starting from early developmental stages, a relatively high GSN expression was observed in eye, brain vesicles, midbrain, neural tube, heart tube, and splanchnic mesoderm. In older embryos, we observed a high GSN expression in the cranial ganglia and dorsal root ganglia. A detailed analysis of 10-day-old chicken embryos revealed high amounts of gelsolin especially within the head region: in the olfactory and optic systems, meninges, nerves, muscles, presumptive pituitary gland, and pericytes, but not oligodendrocytes in the brain. Obtained results suggest that GSN is expressed at high levels in some tissues of ectodermal origin including all neural crest derivatives. Additionally, we describe that silencing of GSN expression in brain vesicles leads to altered morphology of the mesencephalon. This implies gelsolin is crucial for chicken brain development.

  13. 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

  14. Assessing the Need for Higher Levels of Care Among Problem Gambling Outpatients.

    PubMed

    Ledgerwood, David M; Arfken, Cynthia L

    2017-03-02

    Most treatment for gambling disorder is provided on an outpatient basis. Only a small number of jurisdictions in North America provide higher levels of gambling treatment, such as residential or intensive outpatient (IOP) care, despite the potential need for these services. Further, there appear to be few guidelines for determining appropriate level of gambling treatment. The aim of the present study was to assess the appropriateness of higher levels of problem gambling care among clients receiving outpatient treatment. Problem gamblers and their therapists independently completed questionnaires that assessed the need and desire for residential and IOP treatment. About 42% of problem gambling outpatients noted that they would be "probably" or "definitely" willing to attend residential treatment, and about half indicated they would be equally likely to attend IOP. Therapists recommended about a third of their clients as appropriate for higher levels of care. For both client and therapist assessments, there was a significant association between desire or recommendation for level of treatment and severity of gambling and co-occurring problems. Further, therapist recommendations for level of care were significantly associated with client willingness to attend higher levels of treatment. Our data reveal the potential need for higher levels of care for problem gambling, as evaluated by clients and their therapists. Policy implications for the funding of residential and IOP treatment are discussed.

  15. 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

  16. 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.

  17. Map of the Field--Higher Education Research at the State Level. AIR Forum 1982 Paper.

    ERIC Educational Resources Information Center

    Crosson, Patricia H.; Adams, Charles S.

    A map of the field of higher education at the state level is presented that defines theoretical and conceptual frameworks, approaches to analysis, research designs, and methodologies that have been used in the study of the relationships between state governments and institutions of higher education or of state policy structures and processes.…

  18. 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

  19. Gene expression levels in normal human lymphoblasts with variable sensitivities to arsenite: Identification of GGT1 and NFKBIE expression levels as possible biomarkers of susceptibility

    SciTech Connect

    Komissarova, Elena V.; Li Ping; Uddin, Ahmed N.; Chen, Xuyan; Nadas, Arthur; Rossman, Toby G.

    2008-01-15

    Drinking arsenic-contaminated water is associated with increased risk of neoplasias of the skin, lung, bladder and possibly other sites, as well as other diseases. Earlier, we showed that human lymphoblast lines from different normal unexposed donors showed variable sensitivities to the toxic effects of arsenite. In the present study, we used microarray analysis to compare the basal gene expression profiles between two arsenite-resistant (GM02707, GM00893) and two arsenite-sensitive lymphoblast lines (GM00546, GM00607). A number of genes were differentially expressed in arsenite-sensitive and arsenite-resistant cells. Among these, {gamma}-glutamyltranspeptidase 1 (GGT1) and NF{kappa}B inhibitor-epsilon (NFKBIE) showed higher expression levels in arsenite-resistant cells. RT-PCR analysis with gene-specific primers confirmed these results. Reduction of GGT1 expression level in arsenite-resistant lymphoblasts with GGT1-specific siRNA resulted in increased cell sensitivity to arsenite. In conclusion, we have demonstrated for the first time that expression levels of GGT1 and possibly NFKBIE might be useful as biomarkers of genetic susceptibility to arsenite. Expression microarrays can thus be exploited for identifying additional biomarkers of susceptibility to arsenite and to other toxicants.

  20. HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant

    PubMed Central

    Growdon, Whitfield B.; Groeneweg, Jolijn; Byron, Virginia; DiGloria, Celeste; Borger, Darrell R.; Tambouret, Rosemary; Foster, Rosemary; Chenna, Ahmed; Sperinde, Jeff; Winslow, John; Rueda, Bo R.

    2015-01-01

    Background Subsets of high grade endometrial cancer (EnCa) over-express HER2 (ERBB2), yet clinical trials have failed to demonstrate any anti-tumor activity utilizing trastuzumab, an approved platform for HER2 positive breast cancer (BrCa). A truncated p95HER2 variant lacking the trastuzumab binding site may confer resistance. The objective of this investigation was to characterize the expression of the p95HER2 truncated variant in EnCa. Materials and Methods With institutional approval, 86 high grade EnCa tumors were identified with tumor specimens from surgeries performed between 2000-2011. Clinical data were collected and all specimens underwent tumor genotyping, HER2 immunohistochemistry (IHC, HercepTest®), HER2 fluorescent in situ hybridization (FISH), along with total HER2 (H2T) and p95HER2 assessment with VeraTag® testing. Regression models were used to compare a cohort of 86 breast tumors selected for equivalent HER2 protein expression. Results We identified 44 high grade endometrioid and 42 uterine serous carcinomas (USC). IHC identified high HER2 expression (2+ or 3+) in 59% of the tumors. HER2 gene amplification was observed in 16 tumors (12 USC, 4 endometrioid). Both HER2 gene amplification and protein expression correlated with H2T values. High p95HER2 expression above 2.8 RF/mm2 was observed in 53% (n = 54) with significant correlation with H2T levels. When matched to a cohort of 107 breast tumors based on HercepTest HER2 expression, high grade EnCa presented with higher p95 levels (p < 0.001). Conclusions: These data demonstrate that compared to BrCa, high grade EnCa expresses higher levels of p95HER2 possibly providing rationale for the trastuzumab resistance observed in EnCa. PMID:25602714

  1. Expression of JMJD2A in infiltrating duct carcinoma was markedly higher than fibroadenoma, and associated with expression of ARHI, p53 and ER in infiltrating duct carcinoma.

    PubMed

    Li, Bei-Xu; Li, Jia; Luo, Cheng-Liang; Zhang, Ming-Chang; Li, Hui; Li, Li-Liang; Xu, Hong-Fei; Shen, Yi-Wen; Xue, Ai-Min; Zhao, Zi-Qin

    2013-03-01

    Jumonji Domain Containing 2A (JMJD2A) may be a cancer-associated gene involved in human breast cancer. With a view to investigating expression of JMJD2A in human breast cancer and benign lesion tissues as well as relationship between JMJD2A and tumor related proteins, histological and immunohistochemical analysis, Western blot and quantitative real-time PCR in infiltrating duct carcinoma and fibroadenoma for JMJD2A and immunohistochemical analysis and quantitative real-time PCR in infiltrating duct carcinoma for tumor related proteins (ARHI, p53, ER, PR and CerbB-2) were performed. Histological examination validated the clinical diagnosis. The JMJD2A positive rate of infiltrating duct carcinoma was significantly higher than fibroadenoma by immunohistochemical analysis. The mean optical density of JMJD2A in infiltrating duct carcinoma was higher than fibroadenoma by western blot. JMJD2A mRNA level in infiltrating duct carcinoma was higher than fibroadenoma by quantitative real-time PCR. Spearman correlation analysis revealed that the expression of JMJD2A was associated with ARHI, p53 and ER from immunohistochemical results respectively. Pearson correlation analysis revealed that the expression of JMJD2A was associated with ARHI, p53 and ER from quantitative real-time PCR results respectively. Expression of JMJD2A in infiltrating duct carcinoma was higher, and associated with ARHI, p53 and ER. The results may take JMJD2A as a potential diagnostic and therapeutic target in human breast cancer.

  2. 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.

  3. OBJECTIVE TESTS IN SCIENCE FOR THIRD LEVEL N.S.W. HIGHER SCHOOL CERTIFICATE.

    ERIC Educational Resources Information Center

    CULL, R.G.; AND OTHERS

    CONTAINED ARE QUESTIONS AND TESTS TO EVALUATE ACHIEVEMENT IN KNOWLEDGE AND UNDERSTANDING OF THE THIRD LEVEL COURSE IN SCIENCE FOR THE HIGHER SCHOOL CERTIFICATE IN NEW SOUTH WALES, AUSTRALIA. THE QUESTIONS ARE BASED ON THE OFFICIAL SYLLABUS OF THE BOARD OF SENIOR SCHOOL STUDIES. THE QUESTIONS REFLECT THE LEVELS OF UNDERSTANDING AS DEVELOPED BY…

  4. 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…

  5. 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…

  6. Understanding Entry-Level Courses in American Institutions of Higher Education

    ERIC Educational Resources Information Center

    McGaughy, Charis; Hopper-Moore, Greg; Fukuda, Erin; Phillips, Rachel; Rooseboom, Jennifer; Chadwick, Kristine

    2016-01-01

    "Understanding Entry-Level Courses in American Institutions of Higher Education" outlines a study conducted by Educational Policy Improvement Center (EPIC) that empirically identifies the characteristics of work at the college- and career-readiness level in English/language arts, science, and social sciences courses. Using a previously…

  7. Defining maximum levels of higher alcohols in alcoholic beverages and surrogate alcohol products.

    PubMed

    Lachenmeier, Dirk W; Haupt, Simone; Schulz, Katja

    2008-04-01

    Higher alcohols occur naturally in alcoholic beverages as by-products of alcoholic fermentation. Recently, concerns have been raised about the levels of higher alcohols in surrogate alcohol (i.e., illicit or home-produced alcoholic beverages) that might lead to an increased incidence of liver diseases in regions where there is a high consumption of such beverages. In contrast, higher alcohols are generally regarded as important flavour compounds, so that European legislation even demands minimum contents in certain spirits. In the current study we review the scientific literature on the toxicity of higher alcohols and estimate tolerable concentrations in alcoholic beverages. On the assumption that an adult consumes 4 x 25 ml of a drink containing 40% vol alcohol, the maximum tolerable concentrations of 1-propanol, 1-butanol, 2-butanol, isobutanol, isoamyl alcohol and 1-hexanol in such a drink would range between 228 and 3325 g/hl of pure alcohol. A reasonable preliminary guideline level would be 1000 g/hl of pure alcohol for the sum of all higher alcohols. This level is higher than the concentrations usually found in both legal alcoholic beverages and surrogate alcohols, so that we conclude that scientific data are lacking so far to consider higher alcohols as a likely cause for the adverse effects of surrogate alcohol. The limitations of our study include the inadequate toxicological data base leading to uncertainties during the extrapolation of toxicological data between the different alcohols, as well as unknown interactions between the different higher alcohols and ethanol.

  8. 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...

  9. Strategies for psbA gene expression in cyanobacteria, green algae and higher plants: from transcription to PSII repair.

    PubMed

    Mulo, Paula; Sakurai, Isamu; Aro, Eva-Mari

    2012-01-01

    The Photosystem (PS) II of cyanobacteria, green algae and higher plants is prone to light-induced inactivation, the D1 protein being the primary target of such damage. As a consequence, the D1 protein, encoded by the psbA gene, is degraded and re-synthesized in a multistep process called PSII repair cycle. In cyanobacteria, a small gene family codes for the various, functionally distinct D1 isoforms. In these organisms, the regulation of the psbA gene expression occurs mainly at the level of transcription, but the expression is fine-tuned by regulation of translation elongation. In plants and green algae, the D1 protein is encoded by a single psbA gene located in the chloroplast genome. In chloroplasts of Chlamydomonas reinhardtii the psbA gene expression is strongly regulated by mRNA processing, and particularly at the level of translation initiation. In chloroplasts of higher plants, translation elongation is the prevalent mechanism for regulation of the psbA gene expression. The pre-existing pool of psbA transcripts forms translation initiation complexes in plant chloroplasts even in darkness, while the D1 synthesis can be completed only in the light. Replacement of damaged D1 protein requires also the assistance by a number of auxiliary proteins, which are encoded by the nuclear genome in green algae and higher plants. Nevertheless, many of these chaperones are conserved between prokaryotes and eukaryotes. Here, we describe the specific features and fundamental differences of the psbA gene expression and the regeneration of the PSII reaction center protein D1 in cyanobacteria, green algae and higher plants. This article is part of a Special Issue entitled Photosystem II.

  10. 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

  11. DNA Repair Gene Expression Levels as Indicators of Breast Cancer in the Breast Cancer Family Registry

    PubMed Central

    KAPPIL, MAYA A.; LIAO, YUYAN; TERRY, MARY BETH; SANTELLA, REGINA M.

    2017-01-01

    Aim The expression level of DNA repair-related genes and their association with breast cancer status among participants of the New York site of the Breast Cancer Family Registry was investigated. Materials and Methods RNA from mononuclear cells in 194 sister sets (n=475 women) were assayed for ATM, BRCA1, MSH2, MUTYH and XPC gene expression levels and analyzed using generalized estimating equations (GEE). Results Individuals with decreased ATM and MSH2 expression had significantly higher odds for breast cancer compared to individuals with higher levels of expression (odds ratio (OR)=1.1, 95% confidence interval (CI)=1.02, 1.18) and (OR=1.90, 95% CI=1.21, 2.97), respectively. Upon stratifying the GEE model, reductions in ATM and MSH2 expression levels was heightened among women with an extended family history (FH) of breast cancer. Conclusion Reduced expression of ATM and MSH2 compromises DNA repair capacity and, thereby, increases breast cancer prevalence. PMID:27466510

  12. Gene Expression and Regulation of Higher Plants Under Soil Water Stress

    PubMed Central

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

    2009-01-01

    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

  13. Intake of Lutein-Rich Vegetables Is Associated with Higher Levels of Physical Activity.

    PubMed

    Crichton, Georgina; Elias, Merrill; Alkerwi, Ala'a; Buckley, Jonathon

    2015-09-18

    Levels of physical inactivity, a major contributor to burden of disease, are high in many countries. Some preliminary research suggests that circulating lutein concentrations are associated with high levels of physical activity (PA). We aimed to assess whether the intake of lutein-containing foods, including vegetables and eggs, is associated with levels of PA in two studies conducted in different countries. Dietary data and PA data collected from participants in two cross-sectional studies: the Maine-Syracuse Longitudinal Study (MSLS), conducted in Central New York, USA (n = 972), and the Observation of Cardiovascular Risk Factors in Luxembourg Study (ORISCAV-LUX) (n = 1331) were analyzed. Higher intakes of lutein containing foods, including green leafy vegetables, were associated with higher levels of PA in both study sites. Increasing the consumption of lutein-rich foods may have the potential to impact positively on levels of PA. This needs to be further explored in randomized controlled trials.

  14. 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…

  15. 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

  16. 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

  17. Storytelling in the digital world: achieving higher-level learning objectives.

    PubMed

    Schwartz, Melissa R

    2012-01-01

    Nursing students are not passive media consumers but instead live in a technology ecosystem where digital is the language they speak. To prepare the next generation of nurses, educators must incorporate multiple technologies to improve higher-order learning. The author discusses the evolution and use of storytelling as part of the digital world and how digital stories can be aligned with Bloom's Taxonomy so that students achieve higher-level learning objectives.

  18. Higher Grades and Repeated Recurrence of Hepatic Encephalopathy May Be Related to High Serum Manganese Levels.

    PubMed

    Kobtan, Abdelrahman A; El-Kalla, Ferial S; Soliman, Hanan H; Zakaria, Soha S; Goda, Mohamed A

    2016-02-01

    Hepatic encephalopathy is a serious complication of liver failure. Until now, the precise pathophysiologic mechanisms are not fully determined. It has been demonstrated that manganese plays an important role in the pathogenesis of hepatic encephalopathy. Therefore, we studied manganese levels in serum of cirrhotic patients with hepatic encephalopathy in relation to grading and recurrence of hepatic encephalopathy. One hundred persons were enrolled in the study, 80 cirrhotic patients with or without encephalopathy and 20 healthy controls. Hepatic encephalopathy was diagnosed clinically and by laboratory findings. Serum manganese levels were measured in all participants. The grading of hepatic encephalopathy was significantly correlated to the severity of liver dysfunction. The mean serum manganese level was significantly higher in cirrhotic patients than in controls and in cirrhotic patients with encephalopathy than in those without encephalopathy. It was also significantly higher in patients with advanced grading of hepatic encephalopathy. Serum manganese level was positively correlated to number of recurrences of encephalopathy during a 6-month follow-up period. Serum manganese levels were able to predict recurrence of hepatic encephalopathy within 6 months following the episode. Serum manganese levels are positively correlated to the modified Child-Pugh score of cirrhosis as well as grading and number of recurrences of hepatic encephalopathy. Higher manganese levels seem to be related to worsening of the condition, and its measurement may be used as a predictor of repeated recurrences.

  19. 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.

  20. Higher-level Kac-Moody string models and their phenomenological implications

    NASA Astrophysics Data System (ADS)

    Font, Anamaría; Ibáñez, Luis E.; Quevedo, Fernando

    1990-12-01

    We present a systematic approach to string compactifications in which some of the gauge interactions are realized at higher Kac-Moody level. This can be realized in the current constructions of four-dimensional strings including symmetric and asymmetric compactifications. It is shown that there exist higher-level models which can be obtained from exactly marginal deformations of a level-one model, and a simple field theory interpretation is provided in terms of flat scalar field directions in the original level-one model. We then consider the phenomenological possibilities opened to four-dimensional higher-level string models. In particular we show how the levels associated to standard model interactions as well as the massless content of the theory are constrained by unitarity and the renormalization group equations. We also consider the prospects for string GUT models. Mechanisms like "missing partner" in SU(5) or "see-saw" neutrino in SO(10) are only possible for k ⩾ 5. For E 6 at any level only adjoints or fundamentals can be light. A generic feature of the unification models seem to be the existence of relatively light chiral multiplets transforming like (8, 1, 0) + (1, 3, 0) + (1, 1, 0) under SU(3) × SU(2) × U(1). The problems of neutrino masses and proton stability are reconsidered and a possible simultaneous solution involving a discrete gauge symmetry is suggested.

  1. 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

  2. Higher levels of aggression are observed in socially dominant toadfish treated with the selective serotonin reuptake inhibitor, fluoxetine.

    PubMed

    McDonald, M Danielle; Gonzalez, Alexander; Sloman, Katherine A

    2011-01-01

    The following study set out to test the hypothesis that acute treatment with the selective serotonin reuptake inhibitor, fluoxetine, would result in a rise in circulating 5-HT levels and consequently a decrease in territorial aggression in the Gulf toadfish, Opsanus beta. Size-matched pairs of toadfish were implanted intraperitoneally with the same dose of fluoxetine (0, 10 or 25 μg g⁻¹). After a social interaction between a pair of fish, circulating levels of serotonin (5-HT; 5-hydroxytryptamine) and cortisol were measured and relative mRNA expression of the 5-HT(1A) receptor in the toadfish brain was determined using quantitative (real-time) PCR (qPCR). Behavioral endpoints such as the number of aggressive acts and swimming activity were also quantified so that dominant and subordinate fish could be identified. Fluoxetine treatment resulted in an increase in circulating levels of 5-HT, regardless of social status. Circulating cortisol concentrations were unaffected by fluoxetine, but were significantly higher in subordinate individuals when compared to dominant fish. Toadfish brain 5-HT(1A) receptor mRNA expression was not affected by treatment or social status. Lastly and contrary to our predictions, fluoxetine treatment resulted in an increase in the number of aggressive acts made by dominant individuals, with no differences in the level of aggression or swimming activity of subordinate fish. This study is the first to describe elevated aggression in a teleost fish with elevated circulating levels of 5-HT.

  3. 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…

  4. A Tracking Analysis of Compact Students within Level 1 of Their Higher Education Programmes

    ERIC Educational Resources Information Center

    Wakely, Katrina; Saunders, Danny

    2004-01-01

    This article presents a tracking analysis of level 1 undergraduates who entered the University of Glamorgan through the Compact schools initiative. The Compact initiative aims to widen access to higher education by encouraging young people from disadvantaged backgrounds to attend a range of preparatory activities and by offering lower entry…

  5. Exploring the Impact of Higher Level Linguistic Representations on Nonword Repetition Performance

    ERIC Educational Resources Information Center

    van der Lely, Heather K. J.; Gallon, Nichola

    2006-01-01

    Gathercole's (2006) comprehensive and interesting Keynote Article on the nature of the relations between nonword repetition and word learning highlights the complex number of interacting factors that affect this relation through development. In this Commentary we focus on the impact of higher level cognition, particularly linguistic…

  6. 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…

  7. Higher-Level Vocational Education and Training Qualifications: Their Importance in Today's Training Market. Support Document

    ERIC Educational Resources Information Center

    Foster, S.; Bateman, A.; Delaney, B.; Dyson, C.

    2007-01-01

    This document was produced by the authors based on their research for the report "Higher-Level Vocational Education and Training Qualifications: Their Importance in Today's Training Market" [ED499709], and is an added resource for further information. This document contains information regarding: (1) The Australian Qualifications…

  8. 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…

  9. 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…

  10. 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…

  11. 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 three…

  12. 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…

  13. Investigating Student Choices in Performing Higher-Level Comprehension Tasks Using TED

    ERIC Educational Resources Information Center

    Bianchi, Francesca; Marenzi, Ivana

    2016-01-01

    The current paper describes a first experiment in the use of TED talks and open tagging exercises to train higher-level comprehension skills, and of automatic logging of the student's actions to investigate the student choices while performing analytical tasks. The experiment took advantage of an interactive learning platform--LearnWeb--that…

  14. The expression levels of the sirtuins in patients with BCC.

    PubMed

    Temel, Metin; Koç, Mustafa Nihat; Ulutaş, Saffet; Göğebakan, Bülent

    2016-05-01

    Basal cell carcinoma (BCC) is the most common tumor in humans. Reduced expression of sirtuins interferes with DNA repair, which may cause mutations and genomic instability, and eventually leads to tumor development. In the present study, we investigate the expression levels of SIRT genes in non-tumoral and tumor tissues of patients with BCC. A total of 27 patients (16 males, 11 females) with BCC were included in the study; the mean age was 65.40 ± 10.74 years and mean follow-up was 2.5 ± 0.5 years. There were multiple synchronous lesions in six patients, and the remaining 21 patients had a single lesion. Tumor and non-tumoral tissue samples were collected from all patients, and mRNA expression levels of SIRT1-7 (Sirt1.1, Sirt1.2, Sirt2, Sirt3, Sirt4, Sirt5, Sirt6, and Sirt7) were examined by real-time PCR. The results showed that expressions of SIRT1.1, SIRT1.2, SIRT4, SIRT5, SIRT6, and SIRT7 mRNAs were unchanged in tumor tissues of BCC patients compared with non-tumoral tissue samples. Importantly, the expressions of SIRT2 and SIRT3 mRNAs were significantly reduced in tumor tissue samples from BCC patients compared with non-tumoral tissues (P = 0.02 and P = 0.03, respectively). In light of the previous reports that have demonstrated a link between SIRT proteins and cancer, our findings suggest that SIRT2 and SIRT3 may plan important roles in BCC pathogenesis and could be candidate prognostic biomarkers for BCC.

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

    PubMed

    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.

  16. Substrates and inhibitors display different sensitivity to expression level of the dopamine transporter in heterologously expressing cells.

    PubMed

    Chen, Nianhang; Reith, Maarten E A

    2007-04-01

    The use of heterologous expression systems for studying dopamine (DA) transporter (DAT) function has provided important information corroborating and complementing in situ obtained knowledge. Preliminary experiments with human embryonic kidney cells (HEK293) heterologously expressing varying amounts of DAT suggested fluctuations in the potency of cocaine in inhibiting DA uptake and led to the present systematic assessment of the impact of the density of DAT on its function. Transiently expressing intact HEK293 cells, transfected with increasing amounts of DAT cDNA, displayed increasing levels of surface DAT, binding of the cocaine analog [(3)H]2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane ([(3)H]CFT), and uptake of [(3)H]DA, [(3)H]N-methyl-4-phenylpyridinium ([(3)H]MPP(+)), [(3)H]norepinephrine, and [(3)H]serotonin. However, the amount of DAT cDNA and the DAT expression level required to produce 50% of maximal activity was threefold higher for CFT binding than for DA uptake. Increased DAT expression was accompanied by weakened potency in inhibiting [(3)H]DA uptake for cocaine, CFT, benztropine, and its analog JHW025, GBR 12909 and mazindol; their potency in inhibiting [(3)H]CFT binding was unaffected. Inhibition of uptake by the substrates DA, m-tyramine, d-amphetamine, or MPP(+) was also unaffected. Increasing DAT in stably expressing HEK293 cells by stimulation of gene expression with sodium butyrate also decreased the uptake inhibitory potency of a number of the above blockers without affecting the interaction between substrates and DAT. The present results prompt discussion of models explaining how factors regulating DAT expression at the plasma membrane can regulate DAT function and pharmacology.

  17. Effects of porcine oocytes on the expression levels of transcripts encoding glycolytic enzymes in granulosa cells.

    PubMed

    Matsuno, Yuta; Onuma, Asuka; Fujioka, Yoshie A; Emori, Chihiro; Fujii, Wataru; Naito, Kunihiko; Sugiura, Koji

    2016-09-01

    Oocytes play critical roles in regulating the expression of transcripts encoding the glycolytic enzymes phosphofructokinase, platelet (PFKP) and lactate dehydrogenase A (LDHA) in granulosa cells in mice, but whether this is the case in pigs or other mammals has not been adequately investigated. Therefore, the aim of this study was to determine whether porcine oocytes regulate the expression levels of these transcripts in granulosa cells in vitro. Porcine cumulus cells expressed higher levels of PFKP and LDHA transcripts than mural granulosa cells (MGCs). However, co-culturing with oocytes had no significant effect on the isolated cumulus cells. While murine oocytes promoted the expression of both Pfkp and Ldha transcripts by murine MGCs, porcine oocytes promoted the expression of only Pfkp, but not Ldha transcripts by murine MGCs. Neither murine nor porcine oocytes affected PFKP and LDHA expression by porcine MGCs. Moreover, in the presence of porcine follicular fluid, porcine oocytes maintained the expression of PFKP, but not LDHA by porcine cumulus cells. Therefore, porcine oocytes are capable of regulating the expression of PFKP but not LDHA in granulosa cells in coordination with unknown factor(s) present in the follicular fluid.

  18. Plasma homocysteine levels in Taiwanese vegetarians are higher than those of omnivores.

    PubMed

    Hung, Chien-Jung; Huang, Po-Chao; Lu, Shao-Chun; Li, Yi-Hwei; Huang, Hsien-Bin; Lin, Bi-Fong; Chang, Sue-Joan; Chou, Hsu-Fang

    2002-02-01

    Mild hyperhomocysteinemia is an independent risk factor for cardiovascular disease and may result from a deficiency of folate, vitamin B-6 or vitamin B-12. Because vitamin B-12 deficiency is often associated with vegetarianism, this study was designed to examine the effect of Taiwanese vegetarian diets on B-vitamin status and plasma homocysteine levels. Female Buddhist lacto-vegetarians (n = 45; 31-45 y) and matched omnivores (n = 45) recruited in Hualien, Taiwan, were investigated. Taiwanese vegetarians consumed normal amount of folate, but only 21% of Taiwan Recommended Daily Nutrient Allowances (RDNA) values of vitamin B-12. Compared with the omnivores, the vegetarians had significantly higher levels of plasma folate (14.79 +/- 7.70 vs. 11.98 +/- 8.29 nmol/L), but lower levels of vitamin B-12 (207.7 +/- 127.1 vs. 403.5 +/- 138.9 pmol/L). Fasting plasma homocysteine levels were significantly higher in vegetarians than in omnivores (mean: 11.20 +/- 4.27 vs. 8.64 +/- 2.06 micromol/L; median: 10.5 vs. 8.5 micromol/L). Fasting plasma homocysteine was inversely correlated with plasma folate and vitamin B-12 in the vegetarian group. Multiple regression analysis revealed that plasma folate, vitamin B-12 and creatinine were independent determinants of homocysteine variation and contributed to 38.6% of homocysteine variation in the vegetarians. Compared with the omnivores, vegetarians also had significantly lower serum levels of valine, isoleucine, leucine, lysine, alanine and arginine, but higher levels of glycine. In the vegetarian group, fasting plasma homocysteine correlated negatively with serum threonine, lysine, histidine, arginine and cystine, and these amino acids contributed to 38.7% of homocysteine variation. In conclusion, the Buddhist nuns who consumed a lacto-vegetarian diet had mildly elevated fasting plasma homocysteine levels presumably due to lower levels of plasma vitamin B-12.

  19. Protease inhibitor monotherapy is associated with a higher level of monocyte activation, bacterial translocation and inflammation

    PubMed Central

    Torres, Berta; Guardo, Alberto C; Leal, Lorna; Leon, Agathe; Lucero, Constanza; Alvarez-Martinez, Míriam J; Martinez, Miguel J; Vila, Jordi; Martínez-Rebollar, María; González-Cordón, Ana; Gatell, Josep M; Plana, Montserrat; García, Felipe

    2014-01-01

    Introduction Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation. Methods We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed. Results CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16−CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16−CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01). Conclusions Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed. PMID:25280865

  20. Higher levels of brain derived neurotrophic factor but similar nerve growth factor in human milk in women with preeclampsia.

    PubMed

    Dangat, Kamini; Kilari, Anitha; Mehendale, Savita; Lalwani, Sanjay; Joshi, Sadhana

    2013-05-01

    Children born to mothers with preeclampsia have consistently been suggested to be at risk for cognitive and behavioral disorders in later life. Breastfeeding is said to be associated with better neurodevelopment outcomes. Our earlier studies indicated higher levels of docosahexaenoic acid (DHA) in human milk in women with preeclampsia. DHA is known to regulate the expression of neurotrophins and together they play a vital role in neurodevelopment and cognitive performance. The present study examines the levels of maternal plasma and milk neurotrophins [(nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF)] in women with preeclampsia and compares them with normotensive women who served as controls. Singleton pregnant women diagnosed with preeclampsia (n=72) and controls (n=102) were recruited for this study from Bharati Hospital, Pune. Plasma and milk samples were analyzed for NGF and BDNF levels using the Emax Immuno Assay System using promega kits. Maternal plasma NGF and BDNF levels were lower (p<0.01 for both) in women with preeclampsia as compared to the control women. Milk NGF levels were similar while milk BDNF levels were higher (p<0.05) in the preeclampsia group as compared to controls. Plasma NGF levels were positively correlated with milk NGF levels in the control group. Our results indicate the differential regulation of milk NGF and BDNF levels in women with preeclampsia. The present study suggests a role for both NGF and BDNF in human milk for postnatal brain development. Further studies need to examine the associations of DHA and BDNF in human milk with cognition at later ages.

  1. Expression levels of TWIST1 are associated with the clinicopathological stage of B-cell non-Hodgkin lymphoma

    PubMed Central

    JIA, CUNDONG; LIANG, LIPING; YANG, LILI; ZHAO, FENG; BAI, JINGPING

    2014-01-01

    The aim of the present study was to investigate the expression level of TWIST1 in B-cell non-Hodgkin lymphoma (BNHL) and its association with the clinicopathological characteristics of BNHL. Expression levels of TWIST1 were analyzed in patients with BNHL (n=45) and lymphadenosis (n=21) using immunohistochemical staining and western blot analysis. In addition, the mRNA expression levels of TWIST1 in the peripheral blood were detected by fluorescent quantitative polymerase chain reaction. The positive rate of TWIST1 expression in the BNHL tissue was 82.2%, which was significantly higher compared with the lymphadenosis tissue (5%; P<0.05). In addition, the protein expression level of TWIST1 in the BNHL tissue was higher compared with the lymphadenosis tissue. TWIST1 expression was also higher in stage III/IV BNHL tissues than in stage I/II tissues (P<0.05). The tissues were staged following the Ann Arbor system. Furthermore, the mRNA expression level of TWIST1 in the peripheral blood of the BNHL tissue (3.03±0.03) was higher compared with the lymphadenosis tissue, and the mRNA expression level of TWIST1 was higher in stage III/IV (4.41±0.12) tissues than in stage I/II BNHL (2.03±0.08) tissues. In conclusion, TWIST1 expression was higher in the tissue and peripheral blood of patients with BNHL when compared with those with lymphadenosis. Thus, TWIST1 expression was associated with the clinicopathological stage of BNHL. PMID:25289047

  2. 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

  3. Plastid-expressed 5-enolpyruvylshikimate-3-phosphate synthase genes provide high level glyphosate tolerance in tobacco.

    PubMed

    Ye, G N; Hajdukiewicz, P T; Broyles, D; Rodriguez, D; Xu, C W; Nehra, N; Staub, J M

    2001-02-01

    Plastid transformation (transplastomic) technology has several potential advantages for biotechnological applications including the use of unmodified prokaryotic genes for engineering, potential high-level gene expression and gene containment due to maternal inheritance in most crop plants. However, the efficacy of a plastid-encoded trait may change depending on plastid number and tissue type. We report a feasibility study in tobacco plastids to achieve high-level herbicide resistance in both vegetative tissues and reproductive organs. We chose to test glyphosate resistance via over-expression in plastids of tolerant forms of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). Immunological, enzymatic and whole-plant assays were used to prove the efficacy of three different prokaryotic (Achromobacter, Agrobacterium and Bacillus) EPSPS genes. Using the Agrobacterium strain CP4 EPSPS as a model we identified translational control sequences that direct a 10,000-fold range of protein accumulation (to >10% total soluble protein in leaves). Plastid-expressed EPSPS could provide very high levels of glyphosate resistance, although levels of resistance in vegetative and reproductive tissues differed depending on EPSPS accumulation levels, and correlated to the plastid abundance in these tissues. Paradoxically, higher levels of plastid-expressed EPSPS protein accumulation were apparently required for efficacy than from a similar nuclear-encoded gene. Nevertheless, the demonstration of high-level glyphosate tolerance in vegetative and reproductive organs using transplastomic technology provides a necessary step for transfer of this technology to other crop species.

  4. Genes with stable DNA methylation levels show higher evolutionary conservation than genes with fluctuant DNA methylation levels.

    PubMed

    Zhang, Ruijie; Lv, Wenhua; Luan, Meiwei; Zheng, Jiajia; Shi, Miao; Zhu, Hongjie; Li, Jin; Lv, Hongchao; Zhang, Mingming; Shang, Zhenwei; Duan, Lian; Jiang, Yongshuai

    2015-11-24

    Different human genes often exhibit different degrees of stability in their DNA methylation levels between tissues, samples or cell types. This may be related to the evolution of human genome. Thus, we compared the evolutionary conservation between two types of genes: genes with stable DNA methylation levels (SM genes) and genes with fluctuant DNA methylation levels (FM genes). For long-term evolutionary characteristics between species, we compared the percentage of the orthologous genes, evolutionary rate dn/ds and protein sequence identity. We found that the SM genes had greater percentages of the orthologous genes, lower dn/ds, and higher protein sequence identities in all the 21 species. These results indicated that the SM genes were more evolutionarily conserved than the FM genes. For short-term evolutionary characteristics among human populations, we compared the single nucleotide polymorphism (SNP) density, and the linkage disequilibrium (LD) degree in HapMap populations and 1000 genomes project populations. We observed that the SM genes had lower SNP densities, and higher degrees of LD in all the 11 HapMap populations and 13 1000 genomes project populations. These results mean that the SM genes had more stable chromosome genetic structures, and were more conserved than the FM genes.

  5. Does a higher educational level protect against anxiety and depression? The HUNT study.

    PubMed

    Bjelland, Ingvar; Krokstad, Steinar; Mykletun, Arnstein; Dahl, Alv A; Tell, Grethe S; Tambs, K

    2008-03-01

    The relationship of education to the experience of anxiety and depression throughout adult life is unclear. Our knowledge of this relationship is limited and inconclusive. The aim of this study was to examine (1) whether higher educational level protects against anxiety and/or depression, (2) whether this protection accumulates or attenuates with age or time, and (3) whether such a relationship appears to be mediated by other variables. In a sample from the Nord-Trøndelag Health Study 1995--1997 (HUNT 2) (N=50,918) of adults, the cross-sectional associations between educational level and symptom levels of anxiety and depression were examined, stratified by age. The long-term effects of educational level on anxiety/depression were studied in a cohort followed up from HUNT 1 (1984--1986) to HUNT 2 (N=33,774). Low educational levels were significantly associated with both anxiety and depression. The coefficients decreased with increasing age, except for the age group 65-74 years. In the longitudinal analysis, however, the protective effect of education accumulated somewhat with time. The discrepancy between these two analyses may be due to a cohort effect in the cross-sectional analysis. Among the mediators, somatic health exerted the strongest influence, followed by health behaviors and socio-demographic factors. Higher educational level seems to have a protective effect against anxiety and depression, which accumulates throughout life.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Selenoprotein expression is regulated at multiple levels in prostate cells.

    PubMed

    Rebsch, Cheryl M; Penna, Frank J; Copeland, Paul R

    2006-12-01

    Selenium supplementation in a population with low basal blood selenium levels has been reported to decrease the incidence of several cancers including prostate cancer. Based on the clinical findings, it is likely that the antioxidant function of one or more selenoproteins is responsible for the chemopreventive effect, although low molecular weight seleno-compounds have also been posited to selectively induce apoptosis in transformed cells. To address the effects of selenium supplementation on selenoprotein expression in prostate cells, we have undertaken an analysis of antioxidant selenoprotein expression as well as selenium toxicity in non-tumorigenic prostate epithelial cells (RWPE-1) and prostate cancer cells (LNCaP and PC-3). Our results show that two of the glutathione peroxidase family members (GPX1 and GPX4) are highly induced by supplemental selenium in prostate cancer cells but only slightly induced in RWPE-1 cells. In addition, GPX1 levels are dramatically lower in PC-3 cells as compared to RWPE-1 or LNCaP cells. GPX2 protein and mRNA, however, are only detectable in RWPE-1 cells. Of the three selenium compounds tested (sodium selenite, sodium selenate and selenomethionine), only sodium selenite shows toxicity in a physiological range of selenium concentrations. Notably and in contrast to previous studies, RWPE-1 cells were significantly more sensitive to selenite than either of the prostate cancer cell lines. These results demonstrate that selenoproteins and selenium metabolism are regulated at multiple levels in prostate cells.

  11. 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

  12. Arthropod food webs become increasingly lipid-limited at higher trophic levels.

    PubMed

    Wilder, Shawn M; Norris, Michael; Lee, Raymond W; Raubenheimer, David; Simpson, Stephen J

    2013-07-01

    Understanding why food chains are relatively short in length has been an area of research and debate for decades. We tested if progressive changes in the nutritional content of arthropods with trophic position limit the availability of a key nutrient, lipid, for carnivores. Arthropods at higher trophic levels had progressively less lipid and more protein in their bodies compared with arthropods at lower trophic levels. The nutrients present in arthropod bodies were directly related to the nutrients that predators extracted when feeding on those arthropods. As a consequence, nutrient assimilation shifted from lipid-biased to protein-biased as arthropods ascended trophic levels from herbivores to secondary carnivores. Successive changes in the nutritional consequences of predation may ultimately set an upper limit on the number of trophic levels in arthropod communities. Further work is needed to examine the influence of lipid and other nutrients on food web traits in a range of ecosystems.

  13. 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.

  14. 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

  15. B Lymphocyte Stimulator Levels in Systemic Lupus Erythematosus: Higher Circulating Levels in African American Patients and Increased Production after Influenza Vaccination in Patients with Low Baseline Levels

    PubMed Central

    Ritterhouse, Lauren L.; Crowe, Sherry R.; Niewold, Timothy B.; Merrill, Joan T.; Roberts, Virginia C.; Dedeke, Amy B.; Neas, Barbara R.; Thompson, Linda F.; Guthridge, Joel M.; James, Judith A.

    2011-01-01

    Objective Examine the relationship between circulating B lymphocyte stimulator (BLyS) levels and humoral responses to influenza vaccination in systemic lupus erythematosus (SLE) patients, as well as the effect of vaccination on BLyS levels. Clinical and serologic features of SLE that are associated with elevated BLyS levels will also be investigated. Methods Clinical history, disease activity measurements and blood specimens were collected from sixty SLE patients at baseline and after influenza vaccination. Sera were tested for BLyS levels, lupus-associated autoantibodies, serum IFN-α activity, 25-hydroxyvitamin D, and humoral responses to influenza vaccination. Results Thirty percent of SLE patients had elevated BLyS levels, with African American patients having higher BLyS levels than European American patients (p=0.006). Baseline BLyS levels in patients were not correlated with humoral responses to influenza vaccination (p=0.863), and BLyS levels increased post-vaccination only in the subset of patients in the lowest quartile of BLyS levels (p=0.0003). Elevated BLyS levels were associated with increased disease activity as measured by SLEDAI, PGA, and SLAM in European Americans (p=0.035, p=0.016, p=0.018, respectively), but not in African Americans. Elevated BLyS levels were also associated with anti-nRNP (p=0.0003) and decreased 25(OH)D (p=0.018). Serum IFN-α activity was a significant predictor of elevated BLyS in a multivariate analysis (p=0.002). Conclusion African American SLE patients have higher BLyS levels regardless of disease activity. Humoral response to influenza vaccination is not correlated with baseline BLyS levels in SLE patients and only those patients with low baseline BLyS levels demonstrate an increased BLyS response after vaccination. PMID:22127709

  16. 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.

  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.

  18. Interpersonal Violence, PTSD, and Inflammation: Potential Psychogenic Pathways to Higher C-reactive Protein Levels

    PubMed Central

    Heath, Nicole M.; Chesney, Samantha A.; Gerhart, James I.; Goldsmith, Rachel E.; Luborsky, Judith L.; Stevens, Natalie R.; Hobfoll, Steven E.

    2013-01-01

    Interpersonal violence (IPV) is major public health concern with wide-ranging sequelae including depression, posttraumatic stress disorder (PTSD), and possible alterations of immune and inflammation processes. There is a need to identify the psycho-biological pathways through which IPV may translate to altered inflammatory processes since both PTSD and inflammation are associated with serious physical health conditions such as obesity, diabetes, and cardiovascular disease. This study investigated the relationships between IPV, psychological distress, and the inflammatory marker C-reactive protein (CRP), in a sample of 139 urban women who have a high likelihood for having experienced IPV. Participants were recruited from an outpatient gynecology clinic to complete self-report measures about their IPV histories and psychological symptoms, as well as to have their blood sampled using a finger stick. Results indicated that exposure to IPV predicted the presence of probable depression and PTSD diagnoses. Individuals who experience clinical levels of PTSD exhibited higher CRP levels, and this relationship held after adjusting for comorbid depression. Correlational analyses suggested that reexperiencing symptoms may explain the link between PTSD diagnosis and higher levels of CRP. Follow-up path analytic models provided good fit to the overall data, and indicated that the relationship between probable PTSD status and CRP is not explained by higher BMI. Overall, these findings call for increased attention to the role of PTSD in explaining links between trauma and diminished health. PMID:23701836

  19. 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

  20. High level constitutive expression of luciferase reporter by lsd90 promoter in fission yeast.

    PubMed

    Verma, Hemant Kumar; Shukla, Poonam; Alfatah, Md; Khare, Asheesh Kumar; Upadhyay, Udita; Ganesan, Kaliannan; Singh, Jagmohan

    2014-01-01

    Because of a large number of molecular similarities with higher eukaryotes, the fission yeast Schizosaccharomyces pombe has been considered a potentially ideal host for expressing human proteins having therapeutic and pharmaceutical applications. However, efforts in this direction are hampered by lack of a strong promoter. Here, we report the isolation and characterization of a strong, constitutive promoter from S. pombe. A new expression vector was constructed by cloning the putative promoter region of the lsd90 gene (earlier reported to be strongly induced by heat stress) into a previously reported high copy number vector pJH5, which contained an ARS element corresponding to the mat2P flanking region and a truncated URA3m selectable marker. The resulting vector was used to study and compare the level of expression of the luciferase reporter with that achieved with the known vectors containing regulatable promoter nmt1 and the strong constitutive promoter adh1 in S. pombe and the methanol-inducible AOX1 promoter in Pichia pastoris. Following growth in standard media the new vector containing the putative lsd90 promoter provided constitutive expression of luciferase, at a level, which was 19-, 39- and 10-fold higher than that achieved with nmt1, adh1 and AOX1 promoters, respectively. These results indicate a great potential of the new lsd90 promoter-based vector for commercial scale expression of therapeutic proteins in S. pombe.

  1. Expression levels of B7-H3 and TLT-2 in human oral squamous cell carcinoma

    PubMed Central

    ZHANG, SHAN-SHAN; TANG, JING; YU, SHU-YI; MA, LI; WANG, FENG; XIE, SHU-LE; JIN, LONG; YANG, HONG-YU

    2015-01-01

    The aim of the present study was to investigate the role of immune regulatory molecules B7-H3 [also known as cluster of differentiation 276] and triggering receptor expressed on myeloid cell-like transcript-2 (TLT-2) in patients with oral squamous cell carcinoma (OSCC). Human OSCC samples were obtained from 76 patients (female, 32; male, 44; age range, 23–81 years; median age, 50.9 years) that underwent resection for OSCC at Peking University Shenzhen Hospital (Shenzhen, China) between 2007 and 2010. In addition, control oral mucosal samples were obtained from 76 healthy individuals (female, 36; male, 40; age range, 21–62 years; median age, 45.3 years) during wisdom tooth extraction. Protein and gene expression levels of B7-H3 and TLT-2 were determined by immunohistochemical analysis and reverse transcription-polymerase chain reaction (RT-PCR). In the healthy oral mucosa samples, B7-H3 expression was identified to be weak, while the expression of TLT-2 was only detected sporadically in the cell membrane and cytoplasm. By contrast, the two regulatory molecules were widely expressed in the aforementioned localizations in human OSCC specimens upon immunohistochemical examination. Furthermore, quantitative RT-PCR confirmed the presence of significantly higher B7-H3 and TLT-2 expression levels in OSCC specimens compared with the oral mucosa of healthy individuals. The significantly higher expression levels of B7-H3 and TLT-2 in human OSCC specimens may indicate an inhibitory role of these molecules in the antitumoral immune response. To investigate interactions between these two molecules and individual antitumoral immune response in OSCC patients, prospective clinical studies with an adequate sample size are required. PMID:26622626

  2. 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.

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

    PubMed

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

    2016-04-25

    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.

  4. A higher baseline plasma uric acid level is an independent predictor of arterial stiffness

    PubMed Central

    Ding, Xiao-Han; Wang, Xiaona; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei; Ye, Ping

    2017-01-01

    Abstract Hyperuricemia has been demonstrated to be a risk factor for cardiovascular diseases. Though the association between uric acid (UA) and arterial stiffness has been investigated previously in patients with basic diseases, the predictive value of baseline UA level for arterial stiffness has not been conducted. We aimed at identifying the predictive role of UA for arterial stiffness prospectively. A longitudinal follow-up study in a routine health check-up population was performed with an average follow-up of 4.8 years. The demographic information, baseline and follow-up anthropometric parameters, arterial stiffness (pulse-wave velocity, PWV), and biomarker variables including UA have been measured and analyzed. A total of 1447 valid follow-ups were available for the final analysis. Both of the baseline and follow-up UA levels were significantly higher in the arterial stiffness groups than that in the nonarterial stiffness groups (all P values <0.001). The follow-up carotid-femoral PWV [(cf-PWV), r = 0.161, P < 0.001] was strongly correlated with baseline UA. At the follow-up cross-section, cf-PWV was also closely associated with UA (r = 0.101, P < 0.001). Logistic regressions revealed that a higher baseline UA level was an independent predictor of follow-up arterial stiffness assessed by cf-PWV [odds ratio (OR): 1.824; P = 0.046]. A higher baseline level of UA is closely related to arterial stiffness and is an independent predictor of arterial stiffening. PMID:28178136

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. DNA vaccines expressing pneumococcal surface protein A (PspA) elicit protection levels comparable to recombinant protein.

    PubMed

    Ferreira, Daniela M; Miyaji, Eliane N; Oliveira, Maria Leonor S; Darrieux, Michelle; Arêas, Ana Paula M; Ho, Paulo L; Leite, Luciana C C

    2006-04-01

    Pneumococcal surface protein A (PspA) is a promising candidate for the development of cost-effective vaccines against Streptococcus pneumoniae. In the present study, BALB/c mice were immunized with DNA vaccine vectors expressing the N-terminal region of PspA. Animals immunized with a vector expressing secreted PspA developed higher levels of antibody than mice immunized with the vector expressing the antigen in the cytosol. However, both immunogens elicited similar levels of protection against intraperitoneal challenge. Furthermore, immunization with exactly the same fragment in the form of a recombinant protein, with aluminium hydroxide as an adjuvant, elicited even higher antibody levels, but this increased humoral response did not correlate with enhanced protection. These results show that DNA vaccines expressing PspA are able to elicit protection levels comparable to recombinant protein, even though total anti-PspA IgG response is considerably lower.

  10. 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.

  11. 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.

  12. Specific changes in total and mitochondrial proteomes are associated with higher levels of heterosis in maize hybrids.

    PubMed

    Dahal, Diwakar; Mooney, Brian P; Newton, Kathleen J

    2012-10-01

    The phenomenon of hybrid vigor (heterosis) has long been harnessed by plant breeders to improve world food production. However, the changes that are essential for heterotic responses and the mechanisms responsible for heterosis remain undefined. Large increases in biomass and yield in high-heterosis hybrids suggest that alterations in bioenergetic processes may contribute to heterosis. Progeny from crosses between various inbred lines vary in the extent of vigor observed. Field-grown maize F₁ hybrids that consistently exhibited either low or high heterosis across a variety of environments were examined for changes in proteins that may be correlated with increased plant vigor and yield. Unpollinated ears at the time of flowering (ear shoots) were selected for the studies because they are metabolically active, rich in mitochondria, and the sizes of the ears are diagnostic of yield heterosis. Total protein and mitochondrial proteomes were compared among low- and higher-heterosis hybrids. Two-dimensional difference gel electrophoresis was used to identify allelic and/or isoform differences linked to heterosis. Identification of differentially regulated spots by mass spectrometry revealed proteins involved in stress responses as well as primary carbon and protein metabolism. Many of these proteins were identified in multiple spots, but analysis of their abundances by label-free mass spectrometry suggested that most of the expression differences were due to isoform variation rather than overall protein amount. Thus, our proteomics studies suggest that expression of specific alleles and/or post-translational modification of specific proteins correlate with higher levels of heterosis.

  13. 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

  14. Levels of lycopene β-cyclase 1 modulate carotenoid gene expression and accumulation in Daucus carota.

    PubMed

    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.

  15. Higher precision level at individual laying performance tests in noncage housing systems.

    PubMed

    Icken, W; Thurner, S; Heinrich, A; Kaiser, A; Cavero, D; Wendl, G; Fries, R; Schmutz, M; Preisinger, R

    2013-09-01

    With the Weihenstephan funnel nest box, 12 laying hen flocks were tested for their individual laying performance, egg quality, and nesting behavior in a noncage environment. During the whole observation period of 8 yr, a transponder-based data recording system was continuously improved and resulted in a recording accuracy of 97%. At peak production, heritabilities for the number of eggs laid are in some flocks higher than expected. With improved data accuracy, heritability estimates on individual egg weights are more stable. Heritabilities for nesting behavior traits range between a low to moderate level, providing very useful information for laying hen selection to help improve traits that cannot be recorded in cages. Over the years, the benefits of the Weihenstephan funnel nest box for laying hen breeders have grown. This is due to higher data recording accuracies and extended testing capacities, which result in more reliable genetic parameters.

  16. 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

  17. Differential toxicity of cadmium to mustard (Brassica juncia L.) genotypes under higher metal levels.

    PubMed

    Bauddh, Kuldeep; Singh, Rana P

    2011-05-01

    Cadmium application inhibited various growth and biochemical parameters in seedlings of five cultivars of Brassicajuncia L. with different magnitude at lower Cd supply, however, at higher metal applications the variation in Cd toxicity ranged with minor differences. The seedling vigour index (SVI) was inhibited more severely in Gangotri (62.25% over control) and least in Pusa Jai Kisan (8.95%) at 1.0 mM CdCI2. The SVI of all five mustard cultivars, however, severely inhibited (84.29-91.80%) at 5.0 mM Cd. The root and shoot elongation in 7 days old seedlings were inhibited by 32.39-40.38 and 11.83-56.40% respectively at 1.0 mM CdCI2. whereas the varietal differences in root and shoot elongation were 76.71-82.47 and 71.57-78.91 respectively at 5.0 mM CdCI2 The genotypic differences at lower Cd level were more pronounced in shoot elongation than that in the root elongation. The dry weight and moisture content of the seedlings, however, does notshow much varietal differences even at lower Cd level, though the Cd toxicity increased at higher level of Cd application. The metal tolerance index (MTI) and % phytotoxicity of 3 days old seedlings ranged between 43.30-98.37 and 1.63-56.70% respectively at 1.0 mM CdCI2 for different mustard genotypes, whereas at 5.0 mM CdCI2 these factors ranged between 12.26-20.92 and 80.08-87.74% respectively. The varietal differences of MTI and % phytotoxicity was, however, less pronounced at all the metal levels when the seedling attained an age of 7 days. Asimilar trend of genotypic variation was noticed in Cd accumulation in the seedlings at lower and higher levels of Cd supply to the seedlings.Amongst some biochemical parameters e.g. photosynthetic pigments, carbohydrates and proteins in the leaves, the photosynthetic pigments i.e. chlorophylls and carotenoids were decreased more drastically. The carbohydrate content of leaves, however, was the least affected component. Our data indicate that the differential toxicity of cadmium to

  18. Surface L-type Ca2+ channel expression levels are increased in aged hippocampus

    PubMed Central

    Núñez-Santana, Félix Luis; Oh, Myongsoo Matthew; Antion, Marcia Diana; Lee, Amy; Hell, Johannes Wilhelm; Disterhoft, John Francis

    2014-01-01

    Age-related increase in L-type Ca2+ channel (LTCC) expression in hippocampal pyramidal neurons has been hypothesized to underlie the increased Ca2+ influx and subsequent reduced intrinsic neuronal excitability of these neurons that lead to age-related cognitive deficits. Here, using specific antibodies against Cav1.2 and Cav1.3 subunits of LTCCs, we systematically re-examined the expression of these proteins in the hippocampus from young (3 to 4 month old) and aged (30 to 32 month old) F344xBN rats. Western blot analysis of the total expression levels revealed significant reductions in both Cav1.2 and Cav1.3 subunits from all three major hippocampal regions of aged rats. Despite the decreases in total expression levels, surface biotinylation experiments revealed significantly higher proportion of expression on the plasma membrane of Cav1.2 in the CA1 and CA3 regions and of Cav1.3 in the CA3 region from aged rats. Furthermore, the surface biotinylation results were supported by immunohistochemical analysis that revealed significant increases in Cav1.2 immunoreactivity in the CA1 and CA3 regions of aged hippocampal pyramidal neurons. In addition, we found a significant increase in the level of phosphorylated Cav1.2 on the plasma membrane in the dentate gyrus of aged rats. Taken together, our present findings strongly suggest that age-related cognitive deficits cannot be attributed to a global change in L-type channel expression nor to the level of phosphorylation of Cav1.2 on the plasma membrane of hippocampal neurons. Rather, increased expression and density of LTCCs on the plasma membrane may underlie the age-related increase in L-type Ca2+ channel activity in CA1 pyramidal neurons. PMID:24033980

  19. 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.

  20. 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

  1. Low-temperature perception leading to gene expression and cold tolerance in higher plants.

    PubMed

    Knight, Marc R; Knight, Heather

    2012-09-01

    Plant species exhibit a range of tolerances to low temperatures, and these constitute a major determinant of their geographical distribution and use as crops. When tolerance is insufficient, either chilling or freezing injuries result. A variety of mechanisms are employed to evade the ravages of extreme or sub-optimal temperatures. Many of these involve cold-responsive gene expression and require that the drop in temperature is first sensed by the plant. Despite intensive research over the last 100 yr or longer, we still cannot easily answer the question of how plants sense low temperature. Over recent years, genomic and post-genomic approaches have produced a wealth of information relating to the sequence of events leading from cold perception to appropriate and useful responses. However, there are also crucial and significant gaps in the pathways constructed from these data. We describe the literature pertaining to the current understanding of cold perception, signalling and regulation of low-temperature-responsive gene expression in higher plants, raising some of the key questions that still intrigue plant biologists today and that could be targets for future work. Our review focuses on the control of gene expression in the pathways leading from cold perception to chilling and freezing tolerance.

  2. CONSERVED HIGHER ORDER CHROMATIN REGULATES NMDA RECEPTOR GENE EXPRESSION AND COGNITION

    PubMed Central

    Bharadwaj, Rahul; Peter, Cyril J.; Jiang, Yan; Roussos, Panos; Vogel-Ciernia, Annie; Shen, Erica; Mitchell, Amanda; Mao, Wenjie; Whittle, Catheryne; Dincer, Aslihan; Jakovcevski, Mira; Pothula, Venu; Rasmussen, Theodore P.; Giakoumaki, Stella G.; Bitsios, Panos; Sherif, Ajfar; Gardner, Paul D.; Ernst, Patricia; Ghose, Subroto; Sklar, Pamela; Haroutunian, Vahram; Tamminga, Carol; Myers, Richard H.; Futai, Kensuke; Wood, Marcelo A.; Akbarian, Schahram

    2014-01-01

    3-dimensional chromosomal conformations regulate transcription by moving enhancers and regulatory elements into spatial proximity with target genes. Here, we describe activity-regulated long-range loopings bypassing up to 0.5 megabase of linear genome to modulate NMDA glutamate receptor GRIN2B expression in human and mouse prefrontal cortex. Distal intronic and 3’ intergenic loop formations competed with repressor elements to access promoter-proximal sequences, and facilitated expression via a ‘cargo’ of AP-1 and NRF-1 transcription factors and TALE-based transcriptional activators. Neuronal deletion or overexpression of Kmt2a/Mll1 H3K4- and Kmt1e/Setdb1 H3K9-methyltransferase was associated with higher order chromatin changes at distal regulatory Grin2b sequences and impairments in working memory. Genetic polymorphisms and isogenic deletions of loop-bound sequences conferred liability for cognitive performance and decreased GRIN2B expression. Dynamic regulation of chromosomal conformations emerges as a novel layer for transcriptional mechanisms impacting neuronal signaling and cognition. PMID:25467983

  3. 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.

  4. High-level expression and preparation of recombinant human fibrinogen as biopharmaceuticals.

    PubMed

    Hirashima, Masaki; Imamura, Takayuki; Yano, Kentaro; Kawamura, Ryoichi; Meta, Akihiro; Tokieda, Yoshiyuki; Nakashima, Toshihiro

    2016-02-01

    Fibrinogen is a large and complex glycoprotein containing two sets of each of three different chains (α, β and γ). There have been no reports of high-level expression of fibrinogen at commercial levels using mammalian cultured cells such as CHO cells because of the difficulty in highly expressing a protein with such a complex structure. We achieved high-level (1.3 g/l or higher) expression of recombinant human fibrinogen using CHO DG44 cells by optimizing the expression system and culture conditions. We also succeeded in establishing a high-recovery preparation method for recombinant fibrinogen that rarely yields degraded products. To characterize the properties of the recombinant human fibrinogen, we performed SDS-PAGE; western blotting of the α, β and γ chains using specific antibodies and scanning electron microscopy observations of fibrin fibres. We also evaluated the functional equivalence between recombinant fibrinogen and plasma fibrinogen with respect to the release of fibrinopeptides initiated by thrombin and its cross-linking properties. The basic properties of recombinant fibrinogen showed no apparent differences from those of plasma fibrinogen. Here, we report the development of methods for the culture and preparation of recombinant human fibrinogen of satisfactory quality that can be scaled up to the commercial level.

  5. Bio-molecule Surfaces Construction via a Higher-Order Level-Set Method.

    PubMed

    Bajaj, Chandrajit L; Xu, Guo-Liang; Zhang, Qin

    2008-11-01

    We present a general framework for a higher-order spline level-set (HLS) method and apply this to bio-molecule surfaces construction. Starting from a first order energy functional, we obtain a general level set formulation of geometric partial differential equation, and provide an efficient approach to solve this partial differential equation using a C(2) spline basis. We also present a fast cubic spline interpolation algorithm based on convolution and the Z-transform, which exploits the local relationship of interpolatory cubic spline coefficients with respect to given function data values. One example of our HLS method is demonstrated, which is the construction of bio-molecule surfaces (an implicit solvation interface) with their individual atomic coordinates and solvated radii as prerequisite.

  6. Do Sex Offenders Have Higher Levels of Testosterone? Results From a Meta-Analysis.

    PubMed

    Wong, Jennifer S; Gravel, Jason

    2016-03-21

    The purpose of the current study is to review the available scientific evidence on the relationship between testosterone and sexual aggression. A systematic search for all primary studies comparing basal testosterone levels in sex offenders and non-sex offenders was undertaken across 20 electronic databases using an explicit search strategy and inclusion/exclusion criteria. A total of seven studies were identified and 11 effect sizes were computed; effects were pooled using both fixed and random effects meta-analysis models. Although individual study findings present a mix of results wherein sex offenders have higher or lower baseline levels of testosterone than non-sex offenders, pooled results indicate no overall difference between groups. Moderators of the analyses suggest possibly lower rates of testosterone in child molesters than controls; however, results are dependent on study weighting. Limitations, policy implications with respect to chemical castration laws, and future directions for research are discussed.

  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. MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells

    PubMed Central

    Sun, Houfang; Ren, Xiubao; Epling-Burnette, Pearlie K.; Yang, Lili

    2016-01-01

    Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, p<0.001) and observed across all subtypes of MDS using World Health Organization classification (WHO subgroups versus control: RARS, p= 0.009; RCMD, p=0.0002; RAEB1/2, p=0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, p<0.001; Int-2+High, p=0.004). However, unstimulated T-cells from MDS patients (n=20) had significantly higher telomerase activity (p=0.002), higher total hTERT mRNA levels (p=0.001) and hTERT α+β- splice variant expression (p<0.001) compared to controls. Other hTERT splice variants were lower in expression and not significantly different among cases and controls. Telomerase activity was positively correlated with total hTERT levels in MDS (r=0.58, p=0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T-cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression. PMID:27655690

  9. MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells.

    PubMed

    Dong, Wen; Wu, Lei; Sun, Houfang; Ren, Xiubao; Epling-Burnette, Pearlie K; Yang, Lili

    2016-11-01

    Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, p<0.001) and observed across all subtypes of MDS using World Health Organization classification (WHO subgroups versus control: RARS, p= 0.009; RCMD, p=0.0002; RAEB1/2, p=0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, p<0.001; Int-2+High, p=0.004). However, unstimulated T-cells from MDS patients (n=20) had significantly higher telomerase activity (p=0.002), higher total hTERT mRNA levels (p=0.001) and hTERT α+β- splice variant expression (p<0.001) compared to controls. Other hTERT splice variants were lower in expression and not significantly different among cases and controls. Telomerase activity was positively correlated with total hTERT levels in MDS (r=0.58, p=0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T-cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression.

  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. Association between Higher Serum Cortisol Levels and Decreased Insulin Secretion in a General Population

    PubMed Central

    Kamba, Aya; Daimon, Makoto; Murakami, Hiroshi; Otaka, Hideyuki; Matsuki, Kota; Sato, Eri; Tanabe, Jutaro; Takayasu, Shinobu; Matsuhashi, Yuki; Yanagimachi, Miyuki; Terui, Ken; Kageyama, Kazunori; Tokuda, Itoyo; Takahashi, Ippei; Nakaji, Shigeyuki

    2016-01-01

    Glucocorticoids (GCs) are well known to induce insulin resistance. However, the effect of GCs on insulin secretion has not been well characterized under physiological conditions in human. We here evaluated the effect of GCs on insulin secretion/ß-cell function precisely in a physiological condition. A population-based study of 1,071 Japanese individuals enrolled in the 2014 Iwaki study (390 men, 681 women; aged 54.1 ± 15.1 years), those excluded individuals taking medication for diabetes or steroid treatment, were enrolled in the present study. Association between serum cortisol levels and insulin resistance/secretion assessed by homeostasis model assessment using fasting blood glucose and insulin levels (HOMA-R and HOMA-ß, respectively) were examined. Univariate linear regression analyses showed correlation of serum cortisol levels with HOMA-ß (ß = -0.134, p <0.001) but not with HOMA-R (ß = 0.042, p = 0.172). Adjustments for age, gender, and the multiple clinical characteristics correlated with HOMA indices showed similar results (HOMA-ß: ß = -0.062, p = 0.025; HOMA-R: ß = -0.023, p = 0.394). The correlation between serum cortisol levels and HOMA-ß remained significant after adjustment for HOMA- R (ß = -0.057, p = 0.034). When subjects were tertiled based on serum cortisol levels, the highest tertile was at greater risk of decreased insulin secretion (defined as lower one third of HOMA-ß (≤70)) than the lowest tertile, after adjustment for multiple factors including HOMA- R (odds ratio 1.26, 95% confidence interval 1.03–1.54). In conclusion, higher serum cortisol levels are significantly associated with decreased insulin secretion in the physiological cortisol range in a Japanese population. PMID:27861636

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

    PubMed

    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

    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 How genetics affects the brain to produce higher-level dysfunctions in myotonic dystrophy type 1 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 tractbased 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 DM1mainly target the WM, but GM involvement is also crucial in determining the clinical characteristics of DM1.

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

    PubMed Central

    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.

    2016-01-01

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

  14. Higher Circulating Adiponectin Levels Are Associated with Increased Risk of Atrial Fibrillation in Older Adults

    PubMed Central

    Macheret, Fima; Bartz, Traci M.; Djousse, Luc; Ix, Joachim H.; Mukamal, Kenneth J.; Zieman, Susan J.; Siscovick, David S.; Tracy, Russell P.; Heckbert, Susan R.; Psaty, Bruce M.; Kizer, Jorge R.

    2016-01-01

    Background Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner. Methods We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74±5 years). Results During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1–76, the hazard ratio (95% CI) for AF per SD increase in total adiponectin was 1.14 (1.05–1.24), while that for HMW adiponectin was 1.17 (1.08–1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids, and inflammation, did not significantly affect these estimates. Conclusions The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age. PMID:25855796

  15. 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

  16. Deimination level and peptidyl arginine deiminase 2 expression are elevated in astrocytes with increased incubation temperature.

    PubMed

    Enriquez-Algeciras, Mabel; Bhattacharya, Sanjoy K; Serra, Horacio M

    2015-09-01

    Astrocytes respond to environmental cues, including changes in temperatures. Increased deimination, observed in many progressive neurological diseases, is thought to be contributed by astrocytes. We determined the level of deimination and expression of peptidyl arginine deiminase 2 (PAD2) in isolated primary astrocytes in response to changes on either side (31°C and 41°C) of the optimal temperature (37°C). We investigated changes in the astrocytes by using a number of established markers and accounted for cell death with the CellTiter-Blue assay. We found increased expression of glial fibrillary acidic protein, ALDH1L1, and J1-31, resulting from increased incubation temperature and increased expression of TSP1, S100β, and AQP4, resulting from decreased incubation temperature vs. optimal temperature, suggesting activation of different biochemical pathways in astrocytes associated with different incubation temperatures. Mass spectrometric analyses support such trends. The PAD2 level was increased only as a result of increased incubation temperature with a commensurate increased level of deimination. Actin cytoskeleton and iso[4]LGE, a lipid peroxidase modification, also showed an increase with higher incubation temperature. Altogether, these results suggest that temperature, as an environmental cue, activates astrocytes in a different manner on either side of the optimal temperature and that increase in deimination is associated only with the higher temperature side of the spectrum.

  17. Vascular endothelial growth factor receptor 2 gene (KDR) polymorphisms and expression levels in depressive disorder.

    PubMed

    Gałecki, Piotr; Orzechowska, Agata; Berent, Dominika; Talarowska, Monika; Bobińska, Kinga; Gałecka, Elżbieta; Lewiński, Andrzej; Maes, Michael; Szemraj, Janusz

    2013-05-01

    Recent research findings suggest that vascular endothelial growth factor (VEGF) participates in the development of depressive disorder. VEGF is involved in neurogenesis and neuroprotection processes, mediated by vascular endothelial growth factor receptor 2 (VEGFR2). VEGFR2 also plays a role in angiogenesis, a process related to neurogenesis and other biological processes. We examined VEGFR2 (KDR) gene polymorphism, mRNA expression levels, as well as VEGFR2 protein levels in 268 patients diagnosed with a recurrent depressive disorder (rDD) using the ICD-10 criteria, and in 200 healthy controls. Genotyping and gene expression level analysis was performed using polymerase chain reaction (PCR)-based methods. An Enzyme-Linked Immunosorbent Assay (ELISA) was used for measurement of KDR protein levels. Our study found that distribution of KDR polymorphism +1416T/A differs significantly in patients with rDD when compared to healthy subjects, while A allele and AA genotype are risk factors for rDD. KDR mRNA and protein expression are higher in patients with rDD. We also observed a significant association between the -271A/G variant and gene and protein levels. Our study is the first to demonstrate that the KDR gene may serve as a novel genetic marker that could participate in the etiology of rDD. This new pathway may play a role in the inflammatory pathophysiology of depression.

  18. Establishing a STEM Pipeline: Trends in Male and Female Enrollment and Performance in Higher Level Secondary STEM Courses

    ERIC Educational Resources Information Center

    Bergeron, Liz; Gordon, Melissa

    2017-01-01

    The purpose of this study was to understand enrollment and performance differences between male and females in higher level secondary STEM courses. This study analyzes performance and enrollment of 355,688 secondary students in higher level STEM courses. This research also enabled an exploration of country level differences. The enrollment…

  19. Amplification of steroid-mediated SP-B expression by physiological levels of caffeine.

    PubMed

    Fehrholz, Markus; Hütten, Matthias; Kramer, Boris W; Speer, Christian P; Kunzmann, Steffen

    2014-01-01

    Factors positively influencing surfactant homeostasis in general and surfactant protein B (SP-B) expression in particular are considered of clinical importance regarding an improvement of lung function in preterm infants. The objective of this study was to identify effects of physiological levels of caffeine on glucocorticoid-mediated SP-B expression in vitro and in vivo. Levels of SP-B and pepsinogen C were quantified by quantitative real-time RT-PCR or immunoblotting in NCI-H441 cells daily exposed to caffeine and/or dexamethasone (DEX). In vivo, SP-B expression was analyzed in bronchoalveolar lavage (BAL) of preterm sheep exposed to antenatal DEX and/or postnatal caffeine. If DEX and caffeine were continuously present, SP-B mRNA and protein levels were increased for up to 6 days after induction (P < 0.05). Additionally, caffeine enhanced SP-B mRNA expression in DEX-pretreated cells (P < 0.05). Moreover, caffeine amplified DEX-induced pepsinogen C mRNA expression (P < 0.05). After short-term treatment with caffeine in vivo, only slightly higher SP-B levels could be detected in BAL of preterm sheep following antenatal DEX, combined with an increase of arterial oxygen partial pressure (P < 0.01). Our data demonstrated that the continuous presence of caffeine in vitro is able to amplify DEX-mediated SP-B expression. In contrast, short-term improvement of lung function in vivo is likely to be independent of altered SP-B transcription and translation. An impact of caffeine on release of surfactant reservoirs from lamellar bodies could, however, quickly affect SP-B content in BAL, which has to be further investigated. Our findings indicate that caffeine is able to amplify main effects of glucocorticoids that result from changes in surfactant production, maturation, and release.

  20. 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

  1. 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.

  2. 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.

  3. Government and Happiness in 130 Nations: Good Governance Fosters Higher Level and More Equality of Happiness.

    PubMed

    Ott, J C

    2011-05-01

    There are substantial differences in happiness in nations. Average happiness on scale 0-10 ranges in 2006 from 3.24 in Togo to 8.00 in Denmark and the inequality of happiness, as measured by the standard deviation, ranges from 0.85 in Laos to 3.02 in the Dominican Republic. Much of these differences are due to quality of governance and in particular to 'technical' quality. Once a minimum level is reached, rising technical quality boosts average happiness proportionally. Good governance does not only produce a higher level of happiness, but also lowers inequality of happiness among citizens. The relation between good governance and inequality of happiness is not linear, but follows a bell shaped pattern, inequality of happiness being highest in nations where the quality of government is at a medium level. The relation between the size of government and average happiness depends heavily on the quality of government; good-big government adds to happiness but bad-big government does not. Possible explanations of these findings are discussed.

  4. Development of ileal cytokine and immunoglobulin expression levels in response to early feeding in broilers and layers.

    PubMed

    Simon, K; de Vries Reilingh, G; Kemp, B; Lammers, A

    2014-12-01

    Provision of feed in the immediate posthatch period may influence interaction between intestinal microbiota and immune system, and consequently immunological development of the chick. This study addressed ileal immune development in response to early feeding in 2 chicken breeds selected for different production traits: broilers and layers. Chicks of both breeds either received feed and water immediately posthatch or were subjected to a 72-h feed and water delay. Ileal cytokine and immunoglobulin mRNA expression levels were determined at different time points. Effects of early feeding were limited, but breeds differed strikingly regarding cytokine and immunoglobulin expression levels. Cytokine expression levels in broilers were low compared with layers and showed a transient drop in the second to third week of life. In contrast, broilers showed considerably higher expression levels of IgA, IgM, and IgY. These findings indicate that the 2 breeds use different immune strategies, at least on the ileal level.

  5. Levels of aggressiveness are higher among alcohol-related suicides: results from a psychological autopsy study.

    PubMed

    Chachamovich, Eduardo; Ding, Yang; Turecki, Gustavo

    2012-09-01

    Suicide is one of the major causes of deaths worldwide. Several studies have showed that alcohol use disorders (AUD) are associated with suicide ideation, suicide attempts, and suicide completion. The majority of the theoretical conceptualization and the bulk of evidence on suicidal behavior and AUD are based on investigations of nonfatal cases because data on nonfatal suicidal behaviors are more readily available. This study aims to explore demographic, clinical, and behavioral dimensions in a large sample of alcohol-related suicides compared to an age-gender matched sample of non-AUD suicides to identify specific factors associated with AUD suicides. We conducted a psychological autopsy study with 158 pairs of AUD and non-AUD suicides. Findings showed that AUD suicides have lower educational level, more biological children and were more likely to be heavy smokers (OR=3.32). Cases were more likely to have family history of alcohol (OR=1.73) and drug abuse (OR=3.61). Subjects had similar prevalences of depressive disorders, anxiety disorders or psychotic disorders. AUD suicides were more likely to meet criteria for current cocaine abuse/dependence (OR=6.64). With respect to personality disorders, AUD suicides presented higher prevalence of Antisocial Personality Disorder (OR=4.68), and were less likely to meet criteria for Avoidant (OR=0.26) and Obsessive-Compulsive Personality Disorders (OR=0.35). Impulsivity scores were higher in AUD suicides (p=0.18), as well as aggression scores (p<0.001). Results form the conditional logistic regression models showed that cocaine abuse/dependence (OR=4.20) and Antisocial Personality Disorder (OR=6.24) were associated with AUD suicide. After controlling for impulsive-aggressive behaviors, levels of aggression were the only psychopathological feature statistically different between AUD and non-AUD suicides (OR=1.28). In conclusion, higher levels of aggressive behaviors are a specific characteristic of AUD suicides. Apart from

  6. VEGF Polymorphisms Related to Higher Serum Levels of Protein Identify Patients with Hepatocellular Carcinoma

    PubMed Central

    Ferreira, Rafael Fernandes; Pinhel, Marcela Augusta de Souza; da Silva, Renato Ferreira; Fucuta, Patrícia da Silva; Souza, Dorotéia Rossi Silva

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. Major risk factors for hepatocellular carcinoma include chronic liver diseases, carcinogenic agents, and genetic alterations as well as vascular endothelial growth factor (VEGF) involved in angiogenesis process. The aim of this study was to evaluate the association of VEGF-A (C936T and A1154G) with HCC and cirrhosis, in addition to serum levels of VEGF, clinical profile, lifestyle habits, and comorbidities. A total of 346 individuals were studied: 102 with HCC (G1), 117 with cirrhosis (G2), and 127 controls (G3). Polymorphisms were analysed by PCR/RFLP and serum levels of VEGF by ELISA. Alpha error was set at 5%. The wild-type genotype of both polymorphisms prevailed (P > 0.05). In G1, 23% of the patients died, with no relation to genetic profile (P > 0.05). Increased VEGF level was observed in G1 and G3, related to the mutant allele of VEGF-C936T and VEGF-A1154G, respectively, and compared with the wild-type genotype (P = 0.0285; P = 0.0284, resp.) as well as G1 versus G2 and G3 for VEGF-C936T and G1 versus G2 for VEGF-A1154G (P < 0.05 for both). In conclusion, there is a relationship between mutant alleles of VEGF-C936T and VEGF-A1154G polymorphisms and higher VEGF level, making them potential markers for HCC. PMID:27660750

  7. 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

  8. Higher and lower active circulating VWF levels: different facets of von Willebrand disease.

    PubMed

    Casonato, Alessandra; Pontara, Elena; Morpurgo, Margherita; Sartorello, Francesca; De Groot, Philip G; Cattini, Maria G; Daidone, Viviana; De Marco, Luigi

    2015-12-01

    Most circulating von Willebrand factor (VWF) is normally inactive and incapable of binding platelets, but numerous disorders may modify the proportion of active VWF. We explored active VWF levels in patients with von Willebrand disease (VWD) whose VWF had a higher affinity for platelet glycoprotein (GP)Ib, but different susceptibilities to ADAMTS13 and multimer patterns (9 patients lacking large multimers, 10 with a normal pattern); 12 patients with VWF C2362F and R1819_C1948delinsS mutations, which make VWF resistant to ADAMTS13 were also studied. Type 2B patients with abnormal or normal multimers had significantly more active VWF (3·33 ± 1·6 and 3·74 ± 0·74, respectively; normal 0·99 ± 0·23). The type of VWF mutation influenced VWF activation: V1316M was associated with the highest levels in patients with abnormal multimers, and R1341W in those with normal multimers. Pregnancy induced gradually rising active VWF levels and declining platelet counts in one type 2B VWD patient without large multimers. Active VWF levels dropped significantly in patients homozygous for the C2362F mutation or heterozygous for R1819_C1948delinsS mutations (0·2 ± 0·03 and 0·23 ± 0·1, respectively), and less in cases heterozygous for the VWF C2362F mutation (0·55 ± 0·17). We demonstrate that VWF may be more or less activated, with or without any direct involvement of the A1 domain, and regardless of ADAMTS13.

  9. 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.

  10. 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.

  11. Patients with idiopathic recurrent miscarriage show higher levels of DR+ activated T-cells that are less responsive to mitogens.

    PubMed

    Kuon, R J; Schaumann, J; Goeggl, T; Strowitzki, T; Sadeghi, M; Opelz, G; Daniel, V; Toth, B

    2015-11-01

    In 50% of recurrent miscarriages (RM) the cause remains unknown and standardized immunological diagnosis and treatment of idiopathic RM (iRM) is yet not established. In this prospective case-control study, out of 220 RM patients screened, 97 iRM patients were identified and compared to 26 healthy controls without a previous pregnancy or blood transfusion in order to identify deregulated immunological parameters. Blood levels of lymphocyte subpopulations, cytokines and neopterin were determined by FACS, ELISA, and Luminex technique. Lymphocyte function was studied by in-vitro lympocyte proliferation tests. As compared to controls, patients had significantly higher proportions of activated CD3+DR+, CD4+DR+ and CD8+DR+ lymphocytes, elevated levels of neopterin and a lower in-vitro proliferation of lymphocytes (all p<0.05). Within the iRM patients higher proportions of CD3+DR+ T-lymphocytes correlated with higher proportions and absolute numbers of CD4+DR+ and CD8+DR+ T-lymphocytes and lower CD16+CD56+ NK-cells. Further, it was associated with lower absolute numbers of CD19+ B-lymphocytes, CD3+CD25+ T-lymphocytes and CD45+ total lymphocytes (all p<0.05). In addition we found decreased in-vitro lymphocyte proliferation in iRM patients with high CD3+DR+ T-lymphocytes (p<0.05). In summary patients with iRM showed increased activated T-cells that are less responsive to mitogens in-vitro. The inverse relationship of increased DR but decreased CD25 expression on CD3+ T-cells and the decreased in-vitro proliferation characterize an immunological disorder with similarities to T-cell exhaustion in patients with HIV and cancer. These abnormalities potentially contribute to the pathogenesis of iRM and might be a target for future immunomodulatory therapies.

  12. Comparison of microRNA expression levels between initial and recurrent glioblastoma specimens.

    PubMed

    Ilhan-Mutlu, Aysegül; Wöhrer, Adelheid; Berghoff, Anna Sophie; Widhalm, Georg; Marosi, Christine; Wagner, Ludwig; Preusser, Matthias

    2013-05-01

    Glioblastoma is the most frequent primary brain tumour in adults. Recent therapeutic advances increased patient's survival, but tumour recurrence inevitably occurs. The pathobiological mechanisms involved in glioblastoma recurrence are still unclear. MicroRNAs are small RNAs proposed o have important roles for cancer including proliferation, aggressiveness and metastases development. There exist only few data on the involvement of microRNAs in glioblastoma recurrence. We selected the following 7 microRNAs with potential relevance for glioblastoma pathobiology by means of a comprehensive literature search: microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195, microRNA-221 and microRNA-222. We further selected 15 primary glioblastoma patients, of whom formalin fixed and paraffin embedded tissue (FFPE) of the initial and recurrence surgery were available. All patients had received first line treatment consisting of postoperative combined radiochemotherapy with temozolomide (n = 15). Non-neoplastic brain tissue samples from 3 patients with temporal lobe epilepsy served as control. The expression of the microRNAs were analysed by RT-qPCR. These were correlated with each other and with clinical parameters. All microRNAs showed detectable levels of expressions in glioblastoma group, whereas microRNA-10b was not detectable in epilepsy patients. MicroRNAs except microRNA-21 showed significantly higher levels in epilepsy patients when compared to the levels of first resection of glioblastoma. Comparison of microRNA levels between first and second resections revealed no significant change. Cox regression analyses showed no significant association of microRNA expression levels in the tumor tissue with progression free survival times. Expression levels of microRNA-10b, microRNA-21, microRNA-181b, microRNA-181c, microRNA-195, microRNA-221 and microRNA-222 do not differ significantly between initial and recurrent glioblastoma.

  13. Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

    PubMed Central

    Uno, Miyuki; Oba-Shinjo, Sueli Mieko; Camargo, Anamaria Aranha; Moura, Ricardo Pereira; de Aguiar, Paulo Henrique; Cabrera, Hector Navarro; Begnami, Marcos; Rosemberg, Sérgio; Teixeira, Manoel Jacobsen; Marie, Suely Kazue Nagahashi

    2011-01-01

    OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1% of glioblastoma by methylation-specific PCR and 38.8% by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue. PMID:22012047

  14. Increased SNAIL expression and low syndecan levels are associated with high Gleason grade in prostate cancer

    PubMed Central

    POBLETE, CRISTIAN E.; FULLA, JUAN; GALLARDO, MARCELA; MUÑOZ, VALENTINA; CASTELLÓN, ENRIQUE A.; GALLEGOS, IVAN; CONTRERAS, HECTOR R.

    2014-01-01

    Prostate cancer (PC) is a leading male oncologic malignancy wideworld. During malignant transformation, normal epithelial cells undergo genetic and morphological changes known as epithelial-mesenchymal transition (EMT). Several regulatory genes and specific marker proteins are involved in PC EMT. Recently, syndecans have been associated with malignancy grade and Gleason score in PC. Considering that SNAIL is mainly a gene repressor increased in PC and that syndecan promoters have putative binding sites for this repressor, we propose that SNAIL might regulate syndecan expression during PC EMT. The aim of this study was to analyze immunochemically the expression of SNAIL, syndecans 1 and 2 and other EMT markers in a tissue microarray (TMA) of PC samples and PC cell lines. The TMAs included PC samples of different Gleason grade and benign prostatic hyperplasia (BPH) samples, as non-malignant controls. PC3 and LNCaP cell lines were used as models of PC representing different tumorigenic capacities. Semi-quantitative immunohistochemistry was performed on TMAs and fluorescence immunocytochemistry and western blot analysis were conducted on cell cultures. Results show that SNAIL exhibits increased expression in high Gleason specimens compared to low histological grade and BPH samples. Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells. Conversely, syndecan 1, similarly to E-cadherin (a known marker of EMT), shows a decreased expression in high Gleason grades samples and PC3 cells. Interestingly, syndecan 2 shows no changes associated to histological grade. It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1. The mechanism by which SNAIL regulates the expression of syndecan 1 remains to be investigated. PMID:24424718

  15. 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 ∼ 800 ms 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.

  16. Influences of Writing Tasks on Students' Answers to Recall and Higher-Level Test Questions

    NASA Astrophysics Data System (ADS)

    Hand, Brian; Prain, Vaughan; Wallace, Carolyn

    2002-02-01

    This paper reports on two inter-related studies that examined the use of non-traditional writing strategies within secondary school science classrooms. The first study involved Year 10 students who incorporated one letter writing experience into the learning sequence when studying genetics. The second study was with Year 9 students who used both a non-traditional laboratory writing heuristic and letter writing as part of the learning sequence when studying a topic on light. The same teacher was involved in both case studies. A higher-level analogy question was added to the teacher-prepared tests for each study to examine if students who participated in writing-to-learn activities were able to perform significantly better as a group than a group of students who completed traditional teacher directed laboratory activities and note-taking. Results indicate that for the first study there was not a significant difference using t-test analysis, while for the second study involving two writing treatments there was a statistically significant difference using t-test analysis. There was no statistically significant difference in responses between treatment and control groups when answering low level recall questions for either case study. Student interviews indicated awareness by students of the metacognitive value gained by using the non-traditional writing types.

  17. Overgeneral autobiographical memory predicts higher prospective levels of depressive symptoms and intrusions in borderline patients.

    PubMed

    Van den Broeck, Kris; Pieters, Guido; Claes, Laurence; Berens, Ann; Raes, Filip

    2016-11-01

    Overgeneral memory (OGM), the tendency to retrieve categories of events from autobiographical memory instead of single events, is found to be a reliable predictor for future mood disturbances and post-traumatic symptom severity. Patients with borderline personality disorder (BPD) often report co-morbid episodes of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). Therefore, we investigated whether OGM would predict depression severity and (post-traumatic) stress symptoms in BPD patients. At admission (N = 54) and at six-month follow-up (N ≥ 31), BPD patients completed the Structured Clinical Interview for DSM-IV Disorders, the Assessment of DSM-IV Personality Disorders, the Autobiographical Memory Test, the Beck Depression Inventory-2nd edition (BDI-II), and the Impact of Event Scale. OGM at baseline predicted (a) higher levels of depressive symptoms at follow-up and (b) more intrusions related to a stressful event over and above baseline levels of borderline symptoms, depressive symptoms, and intrusions, respectively. No association was found between memory specificity and event-related avoidance at follow-up. Despite previous findings suggesting that OGM in BPD is less robust than in MDD and PTSD, our results suggest that memory specificity in BPD patients may have some relevance for the course of depressive and stress symptomatology in BPD.

  18. Acro-osteolysis is associated with enhanced osteoclastogenesis and higher blood VEGF levels in systemic sclerosis

    PubMed Central

    Park, Jin Kyun; Fava, Andrea; Carrino, John; Del Grande, Filippo; Rosen, Antony; Boin, Francesco

    2015-01-01

    Objective Bone resorption of distal phalanges or acro-osteolysis (AO) can develop in systemic sclerosis (SSc) causing pain and functional limitation. We investigated whether AO may be associated with abnormal osteoclastogenesis in SSc patients and whether hypoxia may be involved in this process. Methods Peripheral blood mononuclear cells (PBMCs) obtained from 26 SSc patients (11 with and 15 without AO) and 14 healthy controls (HC) were cultured in the presence of receptor activator of NF-κB-ligand (RANKL) and macrophage colony-stimulating factor for 9 days. Tartrate resistant acid phosphatase (TRAP)+ multinucleated giant cells (MNGs) containing 3 or more nuclei were counted as osteoclasts (OCs). Plasma levels and effects of vascular endothelial growth factor (VEGF) on OC formation were evaluated. Results SSc patients with AO formed significantly more OCs after 9 days than did subjects without AO (142.4±67.0 vs. 27.2±17.6 MNGs/well, p<0.001) or HC (18.7±27.0 MNGs/well, p <0.001). No significant difference in OC formation was noted between the patients without AO and HC. Plasma levels of VEGF were higher in SSc patients with AO compared to those without (142.4± 69.6 pg/mL vs. 88.1±38.2 pg/mL, p<0.001) or HC (54.2±24.6 pg/mL, p=0.018). Priming with VEGF-A for 24 hours significantly increased OC generation by 5.3±1.9 fold (p=0.03). The radiographic extent of AO was associated with increased OC formation (Spearman rho=0.741, p=0.01). Conclusion Increased OC formation and higher VEGF levels may contribute to AO in SSc patients.Further studies are needed to elucidate whether targeting osteoclastogenesis may provide a specific therapeutic option for SSc-AO. PMID:26361270

  19. 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.

  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. An inducible expression system for high-level expression of recombinant proteins in slow growing mycobacteria.

    PubMed

    Leotta, Lisa; Spratt, Joanne M; Kong, Carlyn U; Triccas, James A

    2015-09-01

    A novel protein expression vector utilising the inducible hspX promoter of Mycobacterium tuberculosis was constructed and evaluated in this study. High-level induction of three mycobacterial antigens, comprising up to 9% of bacterial sonicate, was demonstrated in recombinant Mycobacterium bovis BCG when grown under low-oxygen tension, which serves to enhance hspX promoter activity. Recombinant proteins were efficiently purified from bacterial lysates in a soluble form by virtue of a C-terminal 6-histidine tag. Purification of the immunodominant M. tuberculosis Ag85B antigen using this system resulted in a recombinant protein that stimulated significant IFN-γ release from Ag85B-reactive T cells generated after vaccination of mice with an Ag85B-expressing vaccine. Further, the M. tuberculosis L-alanine dehydrogenase (Ald) protein purified from recombinant BCG displayed strong enzymatic activity in recombinant form. This study demonstrated that high levels of native-like recombinant mycobacterial proteins can be produced in mycobacterial hosts, and this may aid the analysis of mycobacterial protein function and the development of new treatments.

  2. Higher levels of psychological distress are associated with a higher risk of incident diabetes during 18 year follow-up: results from the British household panel survey

    PubMed Central

    2012-01-01

    Background Reviews have shown that depression is a risk factor for the development of type 2 diabetes. However, there is limited evidence for general psychological distress to be associated with incident diabetes. The aim of the present study was to test whether persons who report higher levels of psychological distress are at increased risk to develop type 2 diabetes during 18 years follow up, adjusted for confounders. Methods A prospective analysis using data from 9,514 participants (41 years, SD=14; 44% men) of the British Household Panel Survey. The General Health Questionnaire 12 item version was used to assess general psychological distress, diabetes was measured by means of self-report. Cox proportional hazards regression models were used to calculate the multivariate-adjusted hazard ratio (HR) of incident diabetes during 18 years follow up, comparing participants with low versus high psychological distress at baseline (1991). Results A total of 472 participants developed diabetes 18 year follow up. Those with a high level of psychological distress had a 33% higher hazard of developing diabetes (HR=1.33, 95% CI 1.10–1.61), relative to those with a low level of psychological distress, adjusted for age, sex, education level and household income. After further adjustment for differences in level of energy, health status, health problems and activity level, higher psychological distress was no longer associated with incident diabetes (HR=1.10, 95% CI 0.91-1.34). Conclusions Higher levels of psychological distress are a risk factor for the development of diabetes during an 18 year follow up period. This association may be potentially mediated by low energy level and impaired health status. PMID:23259455

  3. 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…

  4. Potato steroidal glycoalkaloid levels and the expression of key isoprenoid metabolic genes.

    PubMed

    Krits, Pinchas; Fogelman, Edna; Ginzberg, Idit

    2007-12-01

    The potato steroidal glycoalkaloids (SGA) are toxic secondary metabolites, and their total content in tubers should not exceed 20 mg/100 g fresh weight. The two major SGA in cultivated potato (Solanum tuberosum) are alpha-chaconine and alpha-solanine. SGA biosynthetic genes and the genetic factors that control their expression have not yet been determined. In the present study, potato genotypes exhibiting different levels of SGA content showed an association between high SGA levels in their leaves and tubers and high expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase 1 (hmg1) and squalene synthase 1 (pss1), genes of the mevalonic/isoprenoid pathway. Transcripts of other key enzymes of branches of the isoprenoid pathway, vetispiradiene/sesquiterpene synthase (pvs1) and sterol C24-methyltransferase type1 (smt1), were undetectable or exhibited stable expression regardless of SGA content, respectively, suggesting facilitated precursor flow to the SGA biosynthetic branch. The transcript ratio of solanidine glucosyltransferase (sgt2) to solanidine galactosyltransferase (sgt1) was correlated to the documented chaconine-to-solanine ratio in the tested genotypes. Significantly higher expression of hmg1, pss1, smt1, sgt1 and sgt2 was monitored in the tuber phelloderm than in the parenchyma of the tuber's flesh, targeting the former as the main SGA-producing tissue in the tuber, in agreement with the known high SGA content in the layers directly under the tuber skin.

  5. 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…

  6. Focus on the Customer: A New Approach to State-Level Accountability Reporting and Processes for Higher Education.

    ERIC Educational Resources Information Center

    Ruppert, Sandra S.

    This paper outlines the dimensions of a customer-focused system of accountability and describes approaches taken at the state level to respond to the information needs of a broader client base for higher education. Section 1 traces current trends in the development and implementation of state-level accountability policy for higher education. It…

  7. The genetic basis of evolutionary change in gene expression levels

    PubMed Central

    Emerson, J. J.; Li, Wen-Hsiung

    2010-01-01

    The regulation of gene expression is an important determinant of organismal phenotype and evolution. However, the widespread recognition of this fact occurred long after the synthesis of evolution and genetics. Here, we give a brief sketch of thoughts regarding gene regulation in the history of evolution and genetics. We then review the development of genome-wide studies of gene regulatory variation in the context of the location and mode of action of the causative genetic changes. In particular, we review mapping of the genetic basis of expression variation through expression quantitative trait locus studies and measuring the cis/trans component of expression variation in allele-specific expression studies. We conclude by proposing a systematic integration of ideas that combines global mapping studies, cis/trans tests and modern population genetics methodologies, in order to directly estimate the forces acting on regulatory variation within and between species. PMID:20643748

  8. Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression.

    PubMed

    Erez-Roman, Racheli; Pienik, Reut; Futerman, Anthony H

    2010-01-01

    Intervention in the ceramide metabolic pathway is emerging as a novel means to regulate cancer and to modify the activity of chemotherapeutic drugs. We now study mRNA expression levels of the six ceramide synthase (CerS) genes in breast cancer tissue. CerS2 and CerS6 mRNA was significantly elevated in breast cancer tissue compared to paired normal tissue, with approximately half of the individuals showing elevated CerS2 and CerS6 mRNA. A significant correlation was found between CerS2 and CerS6 expression, and between CerS4 and CerS2/CerS6 expression. Moreover, patients that expressed higher CerS2 or 4 mRNA levels tended to show no changes in sphingosine kinase 1 levels, and likewise patients that expressed no change in CerS2 or CerS4 mRNA levels tended to express higher levels of sphingosine kinase 1. Together these results suggest an important role for the CerS genes in breast cancer etiology or diagnosis.

  9. Circulating irisin levels and muscle FNDC5 mRNA expression are independent of IL-15 levels in mice.

    PubMed

    Quinn, LeBris S; Anderson, Barbara G; Conner, Jennifer D; Wolden-Hanson, Tami

    2015-11-01

    Interleukin-15 (IL-15) and irisin are exercise-induced myokines that exert favorable effects on energy expenditure and metabolism. IL-15 can induce PGC-1α expression, which in turn induces expression of irisin and its precursor, FNDC5. Therefore, the present study tested the hypothesis that increases in circulating irisin levels and muscle FNDC5 mRNA expression are dependent on IL-15. Circulating irisin levels and gastrocnemius muscle FNDC5 mRNA expression were examined following acute exercise in control and IL-15-deleted (IL-15 KO) mice, following injection of IL-15 into IL-15 KO mice, and in transgenic mice with elevated circulating IL-15 levels (IL-15 Tg mice). Circulating IL-15 levels and muscle PGC-1α and PPARδ mRNA expressions were determined as positive controls. No effect of IL-15 deletion on post-exercise serum irisin levels or muscle FNDC5 mRNA expression was detected. While serum IL-15 levels and muscle PGC-1α expression were elevated post-exercise in control mice, both serum irisin levels and muscle FNDC5 expression decreased shortly after exercise in both control and IL-15 KO mice. A single injection of recombinant IL-15 into IL-15 KO mice that significantly increased muscle PPARδ and PGC-1α mRNA expressions had no effect on circulating irisin release, but modestly induced muscle FNDC5 expression. Additionally, serum irisin and gastrocnemius muscle FNDC5 expression in IL-15 Tg mice were similar to those of control mice. Muscle FNDC5 mRNA expression and irisin release are not IL-15-dependent in mice.

  10. 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.

  11. Effects of zinc deficiency and zinc supplementation on homocysteine levels and related enzyme expression in rats.

    PubMed

    Jing, Mingyan; Rech, Leslie; Wu, Yinghong; Goltz, Douglas; Taylor, Carla G; House, James D

    2015-04-01

    Methionine synthase (MS) and betaine-homocysteine methyltransferase (BHMT) are both zinc (Zn)-dependent methyltransferases and involved in the methylation of homocysteine. The objective of this study was to investigate the effects of dietary Zn supply on homocysteine levels and expression of the two enzymes in growing rats. Male weanling Sprague-Dawley rats were assigned randomly to four dietary groups (n=8/group) for 3 weeks: Zn deficient (ZD; <1mg Zn/kg); Zn control (ZC; 30mg Zn/kg); Zn supplemented (ZS; 300mg Zn/kg); pair fed (PF; 30mg Zn/kg) to the ZD group. Serum and femur Zn concentrations were 83% and 58% lower in ZD, and 49% and 62% higher in ZS compared to ZC (P<0.001), respectively. The ZD rats had lower feed intake (37%), body weight gains (45%), liver (43%) and kidney (31%) weights than those of ZC (P<0.001), but these parameters in ZD were not significantly different from the PF controls. Serum homocysteine concentrations were 65% higher in ZD compared to PF (P<0.05), and there was no significant difference in serum folate levels between ZD and PF groups. The mRNA expression of liver and kidney MS was 57% and 38% lower in ZD than PF (P<0.001), respectively. Hepatic and renal BHMT mRNA levels were not altered in ZD compared to controls. The aforementioned measurements were not significantly different between ZS and ZC groups, except Zn levels. These results demonstrated that homocysteine homeostasis appeared to be disturbed by Zn deficiency but not Zn supplementation, and elevated serum homocysteine might be due to reduced expression of MS during Zn deficiency.

  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.

  14. Higher Levels of Multiple Paternities Increase Seedling Survival in the Long-Lived Tree Eucalyptus gracilis

    PubMed Central

    Breed, Martin F.; Christmas, Matthew J.; Lowe, Andrew J.

    2014-01-01

    Studying associations between mating system parameters and fitness in natural populations of trees advances our understanding of how local environments affect seed quality, and thereby helps to predict when inbreeding or multiple paternities should impact on fitness. Indeed, for species that demonstrate inbreeding avoidance, multiple paternities (i.e. the number of male parents per half-sib family) should still vary and regulate fitness more than inbreeding – named here as the ‘constrained inbreeding hypothesis’. We test this hypothesis in Eucalyptus gracilis, a predominantly insect-pollinated tree. Fifty-eight open-pollinated progeny arrays were collected from trees in three populations. Progeny were planted in a reciprocal transplant trial. Fitness was measured by family establishment rates. We genotyped all trees and their progeny at eight microsatellite loci. Planting site had a strong effect on fitness, but seed provenance and seed provenance × planting site did not. Populations had comparable mating system parameters and were generally outcrossed, experienced low biparental inbreeding and high levels of multiple paternity. As predicted, seed families that had more multiple paternities also had higher fitness, and no fitness-inbreeding correlations were detected. Demonstrating that fitness was most affected by multiple paternities rather than inbreeding, we provide evidence supporting the constrained inbreeding hypothesis; i.e. that multiple paternity may impact on fitness over and above that of inbreeding, particularly for preferentially outcrossing trees at life stages beyond seed development. PMID:24587373

  15. 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

  16. Multiple-choice exams: an obstacle for higher-level thinking in introductory science classes.

    PubMed

    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.

  17. Dengue patients exhibit higher levels of PrM and E antibodies than their asymptomatic counterparts.

    PubMed

    Yeo, Adeline Syin Lian; Rathakrishnan, Anusyah; Wang, Seok Mui; Ponnampalavanar, Sasheela; Manikam, Rishya; Sathar, Jameela; Kumari Natkunam, Santha; Sekaran, Shamala Devi

    2015-01-01

    Dengue virus infection is a common tropical disease which often occurs without being detected. These asymptomatic cases provide information in relation to the manifestation of immunological aspects. In this study, we developed an ELISA method to compare neutralizing effects of dengue prM and E antibodies between dengue patients and their asymptomatic household members. Recombinant D2 premembrane (prM) was constructed, cloned, and tested for antigenicity. The recombinant protein was purified and tested with controls by using an indirect ELISA method. Positive dengue serum samples with their asymptomatic pair were then carried out onto the developed ELISA. In addition, commercially available recombinant envelope (E) protein was used to develop an ELISA which was tested with the same set of serum samples in the prM ELISA. Asymptomatic individuals showed preexisting heterotypic neutralizing antibodies. The recombinant prM was antigenically reactive in the developed ELISA. Dengue patients had higher prM and E antibodies compared to their household members. Our study highlights the neutralizing antibodies levels with respect to dengue prM and E between dengue patients and asymptomatic individuals.

  18. Higher levels of multiple paternities increase seedling survival in the long-lived tree Eucalyptus gracilis.

    PubMed

    Breed, Martin F; Christmas, Matthew J; Lowe, Andrew J

    2014-01-01

    Studying associations between mating system parameters and fitness in natural populations of trees advances our understanding of how local environments affect seed quality, and thereby helps to predict when inbreeding or multiple paternities should impact on fitness. Indeed, for species that demonstrate inbreeding avoidance, multiple paternities (i.e. the number of male parents per half-sib family) should still vary and regulate fitness more than inbreeding--named here as the 'constrained inbreeding hypothesis'. We test this hypothesis in Eucalyptus gracilis, a predominantly insect-pollinated tree. Fifty-eight open-pollinated progeny arrays were collected from trees in three populations. Progeny were planted in a reciprocal transplant trial. Fitness was measured by family establishment rates. We genotyped all trees and their progeny at eight microsatellite loci. Planting site had a strong effect on fitness, but seed provenance and seed provenance × planting site did not. Populations had comparable mating system parameters and were generally outcrossed, experienced low biparental inbreeding and high levels of multiple paternity. As predicted, seed families that had more multiple paternities also had higher fitness, and no fitness-inbreeding correlations were detected. Demonstrating that fitness was most affected by multiple paternities rather than inbreeding, we provide evidence supporting the constrained inbreeding hypothesis; i.e. that multiple paternity may impact on fitness over and above that of inbreeding, particularly for preferentially outcrossing trees at life stages beyond seed development.

  19. Level of CYP4G19 Expression Is Associated with Pyrethroid Resistance in Blattella germanica.

    PubMed

    Guo, Guang-Zhou; Geng, Yi-Jie; Huang, Da-Na; Xue, Cai-Fang; Zhang, Ren-Li

    2010-01-01

    German cockroaches have become a large problem in the Shenzhen area because of their pesticide resistance, especially to pyrethroid. A pyrethroid called "Jia Chong Qing" to prevent pests for a long time were found to be resistant to "Jia Chong Qing" with resistance index of 3.88 measured using RT-PCR and immunohistochemistry analysis showed that both CYP4G19 mRNA and CYP4G19 protein expression levels in the wild strain were substantially higher than that of a sensitive strain. dsRNA segments derived from the target gene CYP4G19 were prepared using in vitro transcription and were microinjected into abdomens of the wild strain. Two to eight days after injection, the result showed that CYP4G19 mRNA expressions were significantly reduced in the groups injected with dsRNAs.

  20. 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

  1. Changes in endogenous gene transcript and protein levels in maize plants expressing the soybean ferritin transgene

    PubMed Central

    Kanobe, Milly N.; Rodermel, Steven R.; Bailey, Theodore; Scott, M. Paul

    2013-01-01

    Transgenic agricultural crops with increased nutritive value present prospects for contributing to public health. However, their acceptance is poor in many countries due to the perception that genetic modification may cause unintended effects on expression of native genes in the host plant. Here, we tested effects of soybean ferritin transgene (SoyFer1, M64337) on transcript and protein levels of endogenous genes in maize. Results showed that the transgene was successfully introduced and expressed in the maize seed endosperm. mRNA abundance of seven tested iron homeostasis genes and seed storage protein genes differed significantly between seed samples positive and negative for the transgene. The PCR negative samples had higher zein and total protein content compared to the positive samples. However, PCR positive samples had significantly higher concentrations of calcium, magnesium, and iron. We have shown that the soybean ferritin transgene affected the expression of native iron homeostasis genes in the maize plant. These results underscore the importance of taking a holistic approach to the evaluation of transgenic events in target plants, comparing the transgenic plant to the untransformed controls. PMID:23785377

  2. Changes in endogenous gene transcript and protein levels in maize plants expressing the soybean ferritin transgene.

    PubMed

    Kanobe, Milly N; Rodermel, Steven R; Bailey, Theodore; Scott, M Paul

    2013-01-01

    Transgenic agricultural crops with increased nutritive value present prospects for contributing to public health. However, their acceptance is poor in many countries due to the perception that genetic modification may cause unintended effects on expression of native genes in the host plant. Here, we tested effects of soybean ferritin transgene (SoyFer1, M64337) on transcript and protein levels of endogenous genes in maize. Results showed that the transgene was successfully introduced and expressed in the maize seed endosperm. mRNA abundance of seven tested iron homeostasis genes and seed storage protein genes differed significantly between seed samples positive and negative for the transgene. The PCR negative samples had higher zein and total protein content compared to the positive samples. However, PCR positive samples had significantly higher concentrations of calcium, magnesium, and iron. We have shown that the soybean ferritin transgene affected the expression of native iron homeostasis genes in the maize plant. These results underscore the importance of taking a holistic approach to the evaluation of transgenic events in target plants, comparing the transgenic plant to the untransformed controls.

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

    PubMed Central

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

    2016-01-01

    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

  4. The higher level of complexity of K-Ras4B activation at the membrane

    PubMed Central

    Jang, Hyunbum; Banerjee, Avik; Chavan, Tanmay S.; Lu, Shaoyong; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2016-01-01

    Is nucleotide exchange sufficient to activate K-Ras4B? To signal, oncogenic rat sarcoma (Ras) anchors in the membrane and recruits effectors by exposing its effector lobe. With the use of NMR and molecular dynamics (MD) simulations, we observed that in solution, farnesylated guanosine 5′-diphosphate (GDP)-bound K-Ras4B is predominantly autoinhibited by its hypervariable region (HVR), whereas the GTP-bound state favors an activated, HVR-released state. On the anionic membrane, the catalytic domain adopts multiple orientations, including parallel (∼180°) and perpendicular (∼90°) alignments of the allosteric helices, with respect to the membrane surface direction. In the autoinhibited state, the HVR is sandwiched between the effector lobe and the membrane; in the active state, with membrane-anchored farnesyl and unrestrained HVR, the catalytic domain fluctuates reinlessly, exposing its effector-binding site. Dimerization and clustering can reduce the fluctuations. This achieves preorganized, productive conformations. Notably, we also observe HVR-autoinhibited K-Ras4B-GTP states, with GDP-bound-like orientations of the helices. Thus, we propose that the GDP/GTP exchange may not be sufficient for activation; instead, our results suggest that the GDP/GTP exchange, HVR sequestration, farnesyl insertion, and orientation/localization of the catalytic domain at the membrane conjointly determine the active or inactive state of K-Ras4B. Importantly, K-Ras4B-GTP can exist in active and inactive states; on its own, GTP binding may not compel K-Ras4B activation.—Jang, H., Banerjee, A., Chavan, T. S, Lu, S., Zhang, J., Gaponenko, V., Nussinov, R. The higher level of complexity of K-Ras4B activation at the membrane. PMID:26718888

  5. 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

  6. 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

  7. High-level expression of two thermophilic β-mannanases in Yarrowialipolytica.

    PubMed

    YaPing, Wang; Ben, Rao; Ling, Zhang; Lixin, Ma

    2017-02-22

    Two thermophilic β-mannanases (ManA and ManB)were successfully expressed in Yarrowialipolytica using vector pINA1296I. The sequences of manA from Aspergillus niger CBS 513.88 and manB from Bacillus subtilis BCC41051 were optimized based on codon-usage bias in Y.lipolytica and synthesized by overlapping polymerase chain reaction (PCR). We utilized the pINA1296I vector, which allows inserting and expression of multiple copies of an expression cassette, to engineer recombinant strains containing multiple copies of manA or manB. Following verification of target-gene expression by quantitative PCR, fermentation experiments indicated that recombinant protein levels and enzyme activity increased along with increasing manA/manB copy number.After production in a 10 l fermenter, we obtained maximum enzyme activity from strains YLA6 and YLB6 of3024 U/mL and 1024 U/mL, respectively. Additionally, purification and characterization results revealed that the optimum pH and temperature for manA activity were pH∼5 and ∼70 °C, and for manB activity were pH∼7 and 60 °C, respectively. These results indicated that the thermo stabilities of these two enzymes were higher than most other mannanases, making them potentially useful for industrial applications.

  8. 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…

  9. 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…

  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. 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…

  13. 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.

  14. 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…

  15. 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…

  16. 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…

  17. Expression of macrophage migration inhibitory factor (MIF) in bovine oviducts is higher in the postovulatory phase than during the oestrus and luteal phase.

    PubMed

    Nahar, Asrafun; Kadokawa, Hiroya

    2016-07-28

    Whether macrophage migration inhibitory factor (MIF) in the bovine oviduct is important for early embryogenesis has not been well substantiated. The aim of the present study was to test the hypothesis that bovine oviduct expresses higher levels of MIF during the post-ovulation phase. Both ampullary and isthmic samples were collected from Japanese black heifers during oestrus (Day 0; n=5), postovulation (Day 3; n=6) and luteal phase (Days 9-12; n=5). MIF mRNA and protein were extracted from the ampullary and isthmic samples and their levels measured by real-time polymerase chain reaction and western blot analysis respectively. Fluorescent immunohistochemistry was performed on frozen ampullary and isthmic sections using antibodies against MIF. MIF mRNA and protein expression was higher in the postovulatory phase than during oestrus and the luteal phase (P<0.05). Fluorescent immunohistochemistry confirmed that in all phases of the oestrous cycle evaluated, the primary site of MIF expression in the ampulla and isthmus was the tunica mucosa. In conclusion, the bovine ampulla and isthmus have higher MIF expression during the postovulatory phase. Further studies are needed to clarify the role of MIF in bovine oviducts.

  18. High Levels of BCOX1 Expression Are Associated with Poor Prognosis in Patients with Invasive Ductal Carcinomas of the Breast

    PubMed Central

    Liu, Tong; Zhang, Xian-Yu; He, Xiao-Hui; Geng, Jing-Shu; Liu, Yang; Kong, De-Jia; Shi, Qing-Yu; Liu, Feng; Wei, Wei; Pang, Da

    2014-01-01

    This study was to examine the breast cancer-overexpressed gene 1 (BCOX1) expression in invasive ductal carcinomas (IDC) of the breast and its value in the prognosis of the disease. The levels of BCOX1 expression in 491 paired IDC and surrounding non-tumor breast tissues as well as 40 paired fresh specimens were evaluated by tissue microarray, immunohistochemistry and quantitative RT-PCR. The potential associations of high BCOX1 expression with clinicopathological variables and the overall survival of these patients were analyzed. The relative levels of BCOX1 mRNA transcripts in the IDC breast tissues were significantly higher than that in the corresponding non-tumor tissues (P = 0.005). The anti-BCOX1 was predominantly stained in the cytoplasm of breast tissue cells and the levels of BCOX1 expression in the majority of breast cancer tissues were obviously higher than that in the corresponding non-tumor breast tissues. High levels of BCOX1 expression were found in 59.5% (292/491) of breast cancer tissues. The high BCOX1 expression was significantly associated with high histological grade (P = 0.037), positive expression of human epidermal growth factor receptor 2 (HER2, P = 0.031) and triple negative breast cancer (P = 0.027). The high BCOX1 expression in breast cancers was significantly associated with a shorter overall survival of these patients (P = 0.023), particularly in patients with triple negative breast cancer (P = 0.005). Therefore, the high BCOX1 expression may serve as a novel marker of poor prognosis and a potential therapeutic target for patients with IDC of the breast. PMID:24489812

  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.

  20. 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…

  1. Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression.

    PubMed

    Gómez-Sánchez, Rubén; Gegg, Matthew E; Bravo-San Pedro, José M; Niso-Santano, Mireia; Alvarez-Erviti, Lydia; Pizarro-Estrella, Elisa; Gutiérrez-Martín, Yolanda; Alvarez-Barrientos, Alberto; Fuentes, José M; González-Polo, Rosa Ana; Schapira, Anthony H V

    2014-02-01

    Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection.

  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.

  3. Tumor endothelial cells express high pentraxin 3 levels.

    PubMed

    Hida, Kyoko; Maishi, Nako; Kawamoto, Taisuke; Akiyama, Kosuke; Ohga, Noritaka; Hida, Yasuhiro; Yamada, Kenji; Hojo, Takayuki; Kikuchi, Hiroshi; Sato, Masumi; Torii, Chisaho; Shinohara, Nobuo; Shindoh, Masanobu

    2016-12-01

    It has been described that tumor progression has many similarities to inflammation and wound healing in terms of the signaling processes involved. Among biological responses, angiogenesis, which is necessary for tumor progression and metastasis, is a common hallmark; therefore, tumor blood vessels have been considered as important therapeutic targets in anticancer therapy. We focused on pentraxin 3 (PTX3), which is a marker of cancer-related inflammation, but we found no reports on its expression and function in tumor blood vessels. Here we showed that PTX3 is expressed in mouse and human tumor blood vessels based on immunohistochemical analysis. We found that PTX3 is upregulated in primary mouse and human tumor endothelial cells compared to normal endothelial cells. We also showed that PTX3 plays an important role in the proliferation of the tumor endothelial cells. These results suggest that PTX3 is an important target for antiangiogenic therapy.

  4. Steroid hormone receptor gene expression in human breast cancer cells: inverse relationship between oestrogen and glucocorticoid receptor messenger RNA levels.

    PubMed

    Hall, R E; Lee, C S; Alexander, I E; Shine, J; Clarke, C L; Sutherland, R L

    1990-12-15

    The relative expression in human breast cancer cells of messenger ribonucleic acids (mRNA) encoding different steroid hormone receptors is unknown. Accordingly, mRNA levels in total RNA extracted from 13 human breast cancer cell lines were measured by Northern analysis employing complementary DNA probes for the human oestrogen (ER), progesterone (PR), androgen (AR), vitamin D3 (VDR) and glucocorticoid receptors (GR). The 7 ER+ lines expressed a single 6.4 kilobases (kb) ER mRNA. Interestingly, low concentrations of ER mRNA were detected in the ER- cell lines, MDA-MB-330 and BT 20. PR mRNA, predominantly a 13.5 kb species, was expressed in the 6 lines known to be ER+, PR+ by radioligand binding; however, one ER+ cell line, MDA-MB-134, failed to express PR mRNA. A 10.5 kb AR mRNA was expressed at significantly higher levels in ER+ than ER- cell lines. All cell lines expressed a single 4.6 kb mRNA for VDR and a single 7.4 kb mRNA for GR. ER and PR mRNA levels were positively correlated (p = 0.011) and each was positively correlated with androgen receptor (AR) mRNA levels (p less than or equal to 0.009). ER, PR and AR mRNAs were negatively associated with GR levels (p less than or equal to 0.012), while ER and AR mRNA levels were negatively correlated with mRNA for the epidermal growth factor receptor. In contrast, levels of VDR mRNA were unrelated to the concentration of any other steroid receptor mRNA. Our data demonstrate the coordinate expression of ER, PR and AR genes, and an inverse relationship between sex steroid hormone receptor and GR gene expression in human breast cancer cell lines.

  5. 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…

  6. Detection of sugar accumulation and expression levels of correlative key enzymes in winter wheat (Triticum aestivum) at low temperatures.

    PubMed

    Zeng, Yan; Yu, Jing; Cang, Jing; Liu, Lijie; Mu, Yongchao; Wang, Junhong; Zhang, Da

    2011-01-01

    Carbohydrate accumulation is common in frost-resistant plants, and many enzymes participate in this process. The sugar content and expression levels of metabolic enzymes related to sugar biosynthesis in response to drops in temperature were measured in two cultivars of winter wheat (Triticum aestivum) with different cold tolerances. The results indicate that the two cultivars examined, Dongnongdongmai 1 and Jimai 22, accumulated high levels of carbohydrate before November 4 (above 0°C), and that accumulation decreased as temperatures fell. However, this decrease was more modest in Dongnongdongmai 1, which had a higher sugar content. Sucrose and fructose were the main soluble sugars, indicating an important role in freezing tolerance. Gene expression studies revealed that expression of the genes encoding chloroplastic enzymes was significantly upregulated in the tillering nodes. Expression upregulation of TaSS and TaTPT may be helpful for sugar accumulation before November 4.

  7. BCL6 mRNA Expression Level in Invasive Duct Carcinoma not otherwise Specified

    PubMed Central

    Badr, Eman; Masoud, Eman; Eldien, Marwa Serag

    2016-01-01

    Introduction B-Cell Lymphoma 6 (BCL6) has an oncogenic role in tumourigenesis of various malignancies. It represses genes involved in terminal differentiation and plays complementary role with Signal Transducer and Activator of Transcription 3 (STAT3) in triple-negative breast cancer cellular function. Aim To evaluate the expression of BCL6 in cancer breast and determine its correlation with the clinico-pathological features including the molecular subtype of breast carcinoma. Materials and Methods This prospective case control study was carried out on 150 patients, divided into 100 cases of invasive duct carcinoma not otherwise specified and 50 benign breast lesions including fibroadenoma and fibrocystic disease. Fresh tissues were excised, which were then subjected to RNA extraction. The BCL6 mRNA level was assessed using real-time reverse transcription Polymerase Chain Reaction (PCR). Results There was a significant higher levels of BCL6 mRNA in malignant cases compared to benign ones (p<0.001). The level of BCL6 mRNA was higher in cases showing advanced tumor stage (p<0.04), triple negative subtype and associated in situ component (p<0.001) compared to cases with an early stage, luminal or Her 2-neu positive subtypes and those lacking in situ component. Conclusion BCL6 is up-regulated in breast cancer and is associated with poor prognostic features such as advanced stage and triple negative molecular subtype. BCL6 inhibitors might be considered as targeted therapy for breast cancer. PMID:28208987

  8. Production of the R2 subunit of ribonucleotide reductase from herpes simplex virus with prokaryotic and eukaryotic expression systems: higher activity of R2 produced by eukaryotic cells related to higher iron-binding capacity.

    PubMed Central

    Lamarche, N; Matton, G; Massie, B; Fontecave, M; Atta, M; Dumas, F; Gaudreau, P; Langelier, Y

    1996-01-01

    The R2 subunit of ribonucleotide reductase from herpes simplex virus type 2 was overproduced with prokaryotic and eukaryotic expression systems. The recombinant R2 purified by a two-step procedure exhibited a 3-fold higher activity when produced in eukaryotic cells. Precise quantification of the R2 concentration at each step of the purification indicated that the activity was not altered during the purification procedure. Moreover, we have observed that the level of R2 expression, in eukaryotic cells as well as in prokaryotic cells, did not influence R2 activity. Extensive characterization of the recombinant R2 purified from eukaryotic and prokaryotic expression systems has shown that both types of pure R2 preparations were similar in their 76 kDa dimer contents (more than 95%) and in their ability to bind the R1 subunit. However, we have found that the higher activity of R2 produced in eukaryotic cells is more probably related to a higher capability of binding the iron cofactor as well as a 3-fold greater ability to generate the tyrosyl free radical. PMID:8947477

  9. 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

  10. Higher level of NT-proCNP in cerebrospinal fluid of patients with meningitis.

    PubMed

    Tomasiuk, Ryszard; Lipowski, Dariusz; Szlufik, Stanislaw; Peplinska, Krystyna; Mikaszewska-Sokolewicz, Malgorzata

    2016-02-12

    Aminoterminal pro-C type natriuretic peptide (NT-proCNP) as an active form of CNP, has been recently proven to be a potential marker of sepsis and to be linked to inflammatory diseases. So far, there are no studies describing the level of NT-proCNP in meningitis. The purpose of this study was to evaluate the diagnostic value of NT-proCNP in cerebrospinal fluid (CSF) in patients with meningitis and to compare it with the serum level of CRP and procalcitonin (PCT) in this group of patients. The results were compared to serum levels of CRP, PCT and CSF levels of cytosis, protein and lactate. NT-proCNP levels were statistically significant between the control group and the meningitis groups (p=0.02; R=0.3). We also noted a correlation between the level of NT-proCNP in the CSF of all of the study groups (controls and meningitis patients) and the CSF levels of cytosis (p<0.5; R=0.43), protein (p<0.05; R=0.39) and lactate (p<0.05; R=0.34), and also the serum level of CRP (p<0.05; R=0.30), but not serum PCT (p>0.05; R=0.11). These results suggest that NT-proCNP could be a potential marker of meningitis, but it cannot be used to distinguish between the types of meningitis.

  11. Review or True? Using Higher-Level Thinking Questions in Social Studies Instruction

    ERIC Educational Resources Information Center

    Kracl, Carrie L.

    2012-01-01

    Asking surface-level questions is a common practice among educators. Delva Daines's (1986) pilot study indicated that 93 percent of the questions asked during lessons were at the literal level of comprehension and that it was very common for the teachers to restate, rephrase, or answer their own questions before the student had an opportunity to…

  12. 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…

  13. 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 reliable…

  14. 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…

  15. Higher Expression of Proteins in IGF/IR Axes in Colorectal Cancer is Associated with Type 2 Diabetes Mellitus.

    PubMed

    Ding, Jing; Li, Cong; Tang, Jie; Yi, Cheng; Liu, Ji-Yan; Qiu, Meng

    2016-10-01

    Preexisting type 2 diabetes mellitus (preDM) increases occurrence and mortality of colorectal cancer (CRC). Insulin growth factor (IGF)/insulin receptor (IR) axes play an important role in the development of both diabetes and CRC. We aimed to explore the characteristics of proteins expression in IGF/IR axes in CRC tissues with preDM. Two hundred fifty CRC patients in West China hospital were included in analysis. Among them, 125 patients had history of diabetes matched by 125 CRC without diabetes at a 1:1 ratio. Immunohistochemical staining was used to detect the expression of proteins in IGF/IR axis. More positive expression of IGF-1, IGF-1R and IR were found in CRC group with diabetes than in non-diabetes group. No difference was detected in the expression of IR substrate-1, IR substrate-2, IGF-2, IGF binding protein 3, and mammalian target of rapamycin between two groups. Multivariate analysis showed that diabetes history was associated with all of the expression of IGF-1, IGF-1R and IR, and higher T staging and lymph node metastasis were respectively independent factors of IGF-1 and IGF-1R expression in CRC patients. Besides, IGF-1 expression was positively associated with IGF-1R and IR expression in all CRC tissues, and the association of IGF-1 and IR expression seemed to be closer in diabetes group than in non-diabetes group. Higher expression of IGF-1, IGF-1R and IR proteins in CRC was associated with diabetes, suggesting IGF-1/IR signaling may play a special part in development of CRC in patients with diabetes.

  16. 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…

  17. 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.…

  18. Process-Oriented Guided Inquiry Learning Strategy Enhances Students’ Higher Level Thinking Skills in a Pharmaceutical Sciences Course

    PubMed Central

    Verlinden, Nathan; Kruger, Nicholas; Carroll, Ailey; Trumbo, Tiffany

    2015-01-01

    Objective. To determine if the process-oriented guided inquiry learning (POGIL) teaching strategy improves student performance and engages higher-level thinking skills of first-year pharmacy students in an Introduction to Pharmaceutical Sciences course. Design. Overall examination scores and scores on questions categorized as requiring either higher-level or lower-level thinking skills were compared in the same course taught over 3 years using traditional lecture methods vs the POGIL strategy. Student perceptions of the latter teaching strategy were also evaluated. Assessment. Overall mean examination scores increased significantly when POGIL was implemented. Performance on questions requiring higher-level thinking skills was significantly higher, whereas performance on questions requiring lower-level thinking skills was unchanged when the POGIL strategy was used. Student feedback on use of this teaching strategy was positive. Conclusion. The use of the POGIL strategy increased student overall performance on examinations, improved higher-level thinking skills, and provided an interactive class setting. PMID:25741027

  19. 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.

  20. 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,…

  1. 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…

  2. Institutional and Program Level Guidelines for Conflict Management in Higher Education

    ERIC Educational Resources Information Center

    Warters, Bill; Wendy, Smith J.

    2003-01-01

    These guidelines were developed by a national working group seminar hosted by the FIPSE-funded Conflict Management in Higher Education Resource Center. They provide a set of best-practices related to the establishment of conflict-handling services for colleges and universities. Seminar participants were carefully chose to represent faculty,…

  3. Does Higher Education Level the Playing Field? Socio-Economic Differences in Graduate Earnings

    ERIC Educational Resources Information Center

    Crawford, Claire; van der Erve, Laura

    2015-01-01

    Education--and in particular higher education--is often regarded as a route to social mobility. For this to be the case, however, the link between family background and adult outcomes must be broken (or at least reduced) once we take account of an individual's education history. This paper provides new evidence on differences in graduates'…

  4. Higher Level Open Distance Learning in Europe: The Accelerating Pace of Change.

    ERIC Educational Resources Information Center

    D'Azevedo, R. Charters

    1992-01-01

    Europe's socioeconomic climate will undergo rapid change as the single market becomes a reality and technological change accelerates. With companies in some countries now spending more collectively on training than their governments spend on the higher education sector, it is essential to map out a new European strategy for training for the 1990s.…

  5. 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…

  6. Positive attitude toward healthy eating predicts higher diet quality at all cost levels of supermarkets.

    PubMed

    Aggarwal, Anju; Monsivais, Pablo; Cook, Andrea J; Drewnowski, Adam

    2014-02-01

    Shopping at low-cost supermarkets has been associated with higher obesity rates. This study examined whether attitudes toward healthy eating are independently associated with diet quality among shoppers at low-cost, medium-cost, and high-cost supermarkets. Data on socioeconomic status (SES), attitudes toward healthy eating, and supermarket choice were collected using a telephone survey of a representative sample of adult residents of King County, WA. Dietary intake data were based on a food frequency questionnaire. Thirteen supermarket chains were stratified into three categories: low, medium, and high cost, based on a market basket of 100 commonly eaten foods. Diet-quality measures were energy density, mean adequacy ratio, and total servings of fruits and vegetables. The analytical sample consisted of 963 adults. Multivariable regressions with robust standard error examined relations between diet quality, supermarket type, attitudes, and SES. Shopping at higher-cost supermarkets was associated with higher-quality diets. These associations persisted after adjusting for SES, but were eliminated after taking attitudinal measures into account. Supermarket shoppers with positive attitudes toward healthy eating had equally higher-quality diets, even if they shopped at low-, medium-, or high-cost supermarkets, independent of SES and other covariates. These findings imply that shopping at low-cost supermarkets does not prevent consumers from having high-quality diets, as long as they attach importance to good nutrition. Promoting nutrition-education strategies among supermarkets, particularly those catering to low-income groups, can help to improve diet quality.

  7. 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…

  8. 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

  9. Comparison of MMP2 and MMP9 expression levels between primary and metastatic regions of oral squamous cell carcinoma.

    PubMed

    Nishio, Kensuke; Motozawa, Keiko; Omagari, Daisuke; Gojoubori, Takahiro; Ikeda, Takayuki; Asano, Masatake; Gionhaku, Nobuhito

    2016-01-01

    Matrix metalloproteinases (MMPs) and tumor-associated macrophages (TAMs) play important roles in tumor growth. The present study investigated the expression levels of MMP2 and MMP9 in relation to the distribution of TAMs in the primary and metastatic regions of oral squamous cell carcinoma. Twenty-nine cases of oral squamous cell carcinoma (OSCC) with regional lymph node metastasis were selected from available documents in the archives of the Department of Pathology, Nihon University School of Dentistry. Four-micrometer-thick sections were prepared from the primary and metastatic regions. Each section was subjected to immunohistochemical staining using anti-MMP2, anti-MMP9, and anti-CD68 antibodies. The distribution and localization of MMPs and TAMs were compared between primary and metastatic regions. The expression levels of both MMPs were higher in the metastatic regions of lingual and gingival cancers. Statistically significant differences were observed in both T1 and T2 cases. In contrast to the higher expression of MMPs in metastatic regions, a higher number of TAMs were distributed in the primary regions. From these results, MMP expression levels and the numbers of TAMs were expected to have an inverse relationship between the primary and metastatic regions of OSCC. (J Oral Sci 58, 59-65, 2016).

  10. Sources of Signal in 62 Protein-Coding Nuclear Genes for Higher-Level Phylogenetics of Arthropods

    PubMed Central

    Regier, Jerome C.; Zwick, Andreas

    2011-01-01

    Background This study aims to investigate the strength of various sources of phylogenetic information that led to recent seemingly robust conclusions about higher-level arthropod phylogeny and to assess the role of excluding or downweighting synonymous change for arriving at those conclusions. Methodology/Principal Findings The current study analyzes DNA sequences from 68 gene segments of 62 distinct protein-coding nuclear genes for 80 species. Gene segments analyzed individually support numerous nodes recovered in combined-gene analyses, but few of the higher-level nodes of greatest current interest. However, neither is there support for conflicting alternatives to these higher-level nodes. Gene segments with higher rates of nonsynonymous change tend to be more informative overall, but those with lower rates tend to provide stronger support for deeper nodes. Higher-level nodes with bootstrap values in the 80% – 99% range for the complete data matrix are markedly more sensitive to substantial drops in their bootstrap percentages after character subsampling than those with 100% bootstrap, suggesting that these nodes are likely not to have been strongly supported with many fewer data than in the full matrix. Data set partitioning of total data by (mostly) synonymous and (mostly) nonsynonymous change improves overall node support, but the result remains much inferior to analysis of (unpartitioned) nonsynonymous change alone. Clusters of genes with similar nonsynonymous rate properties (e.g., faster vs. slower) show some distinct patterns of node support but few conflicts. Synonymous change is shown to contribute little, if any, phylogenetic signal to the support of higher-level nodes, but it does contribute nonphylogenetic signal, probably through its underlying heterogeneous nucleotide composition. Analysis of seemingly conservative indels does not prove useful. Conclusions Generating a robust molecular higher-level phylogeny of Arthropoda is currently possible

  11. Projected carbon dioxide to increase grass pollen and allergen exposure despite higher ozone levels.

    PubMed

    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.

  12. 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.

  13. Relationship between Legible Handwriting and Level of Success of Third Grade Students in Written Expression

    ERIC Educational Resources Information Center

    Bayat, Seher; Küçükayar, Hasan

    2016-01-01

    This study aims to identify third-grade students' performance levels for written expression and handwriting and to find the relationship between these performances. The study is based on relational screening model. It is carried out with 110 third grade students. Students' levels of success in handwriting and in written expression are evaluated…

  14. 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.

  15. 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…

  16. State-Level Academic Program Review in Higher Education. Report No. 107.

    ERIC Educational Resources Information Center

    Barak, Robert J.; Berdahl, Robert O.

    The state of the art of state-level academic program review is presented. The growth of state agency reviews and three types of state coordinating agencies are discussed. The relation of program review to budget review and planning is outlined, and a description is provided of what programs are reviewed, the criteria for reviewing new programs,…

  17. 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…

  18. 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…

  19. 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…

  20. Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level.

    PubMed

    Price, Edwin R; Rott, Katherine H; Caviedes-Vidal, Enrique; Karasov, William H

    2014-10-01

    Flying vertebrates have been hypothesized to rely heavily on paracellular absorption of nutrients to compensate for having smaller intestines than non-flyers. We tested this hypothesis in an insectivorous bat (Myotis lucifugus) and two insect-eating rodents (Onychomys leucogaster and Peromyscus leucopus). In intact animals, the fractional absorption of orally dosed l-arabinose (Mr 150) was 82% in M. lucifugus, which was more than twice that of the rodents. Absorption of creatinine (Mr 113) was greater than 50% for all species and did not differ between M. lucifugus and the rodents. We also conducted intestinal luminal perfusions on anesthetized animals. Absorption of l-arabinose per nominal surface area in M. lucifugus was nearly double that of the rodents, while absorption of creatinine was not different among species. Using an everted sleeve preparation, we demonstrated that high concentrations of l-arabinose and creatinine did not inhibit their own uptake, validating their use as passive, paracellular probes. Histological measurements indicated that M. lucifugus has more cells, and presumably more tight junctions, per nominal surface area than P. leucopus. This seems unlikely to explain entirely the higher absorption of l-arabinose in M. lucifugus during perfusions, because l-arabinose absorption normalized to the number of enterocytes was still double that of P. leucopus. As an alternative, we investigated tight junction gene expression. M. lucifugus had higher expression of claudin-1 and claudin-15, and lower expression of claudin-2 relative to P. leucopus. Expression of claudin-7 and occludin did not differ among species. Taken together, our results support the hypothesis that bats have evolved higher paracellular nutrient absorption than non-flying animals, and that this phenomenon might be driven by both histological characteristics and differences in tight junction gene expression.

  1. Lipocalin-2 expression and serum levels as early predictors of type 2 diabetes mellitus in obese women.

    PubMed

    Rashad, Nearmeen M; El-Shal, Amal S; Etewa, Rasha L; Wadea, Fady M

    2017-02-01

    Obesity and diabetes are increasing in epidemic proportions globally. Lipocalin-2 (LCN-2) is an inflammatory adipocytokine and obesity-related marker of low-grade inflammation. We aimed to investigate, for first time, the possible role of LCN-2 expression and serum levels in prediction of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) among obese Egyptian women. This study included 188 obese women and 180 controls. Obese women were subdivided into three subgroups according to their fasting blood glucose, normal glucose tolerance (NGT), IGT and T2DM. Circulating LCN-2 expression levels were determined by real time polymerase chain reaction. Serum LCN-2 concentrations were assessed by ELISA. Our findings revealed that LCN-2 expression and serum levels were higher in obese women compared to lean controls. They were higher in IGT and T2DM obese cases than in NGT obese women. Receiver operating characteristic analyses revealed that LCN-2 expression level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.735 and 0.740, respectively). It was an independent predictor of IGT and T2DM among obese women. Serum LCN-2 level was a useful biomarker discriminating IGT from NGT and T2DM from IGT obese women (AUC were 0.705 and 0.728, respectively). It was independent predictor of T2DM without predicting IGT among obese women. The power of combined LCN-2 serum levels and expression in discriminating between IGT from NGT and T2DM from IGT obese women was high (AUC = 0.717 and 0.741, respectively). In conclusion, LCN-2 expression and serum levels could discriminate IGT from NGT and T2DM from IGT obese women and early predicting T2DM among obese women. While, LCN-2 expression level was the independent predictor of IGT in obese women. Combination of both LCN-2 expression and serum levels improved their diagnostic value in early detection of IGT and T2DM among obese women. © 2017 IUBMB Life, 69(2):88-97, 2017.

  2. A Potential VEP Biomarker for Mild Cognitive Impairment: Evidence from Selective Visual Deficit of Higher-Level Dorsal Pathway.

    PubMed

    Yamasaki, Takao; Horie, Shizuka; Ohyagi, Yasumasa; Tanaka, Eri; Nakamura, Norimichi; Goto, Yoshinobu; Kanba, Shigenobu; Kira, Jun-Ichi; Tobimatsu, Shozo

    2016-05-23

    Visual dysfunctions are common in Alzheimer's disease (AD). Our aim was to establish a neurophysiological biomarker for amnestic mild cognitive impairment (aMCI). Visual evoked potentials (VEPs) were recorded in aMCI patients who later developed AD (n = 15) and in healthy older (n = 15) and younger controls (n = 15). Visual stimuli were optimized to separately activate lower and higher levels of the ventral and dorsal streams. We compared VEP parameters across the three groups of participants and conducted a linear correlation analysis between VEPs and data from neuropsychological tests. We then used a receiver operating characteristic (ROC) analysis to discriminate those with aMCI from those who were healthy older adults. The latency and phase of VEPs to lower-level stimuli (chromatic and achromatic gratings) were significantly affected by age but not by cognitive decline. Conversely, VEP latencies for higher-ventral (faces and kanji-words) and dorsal (kana-words and optic flow motion) stimuli were not affected by age, but they were significantly prolonged in aMCI patients. Interestingly, VEPs for higher-dorsal stimuli were related to outcomes of neuropsychological tests. Furthermore, the ROC analysis showed that the highest areas under the curve were obtained for VEP latencies in response to higher-dorsal stimuli. These results suggest aMCI-related functional impairment specific to higher-level visual processing. Further, dysfunction in the higher-level of the dorsal stream could be an early indicator of cognitive decline. Therefore, we conclude that VEPs associated with higher-level dorsal stream activity can be a sensitive biomarker for early detection of aMCI.

  3. The consumption of more vegetables and less meat is associated with higher levels of acculturation among Mongolians in South Korea.

    PubMed

    Tserendejid, Zuunnast; Hwang, Jinah; Lee, Jounghee; Park, Haeryun

    2013-12-01

    Although Mongolian immigrants are a rapidly growing population in South Korea, the 2 countries have distinct diets because of climatic and geographical differences. The Mongolian diet is mostly animal-based with few vegetables and fruits, whereas the Korean diet is largely plant based. The purpose of this study was to examine the association between acculturation and dietary intakes among Mongolians living in South Korea. We hypothesized that higher levels of acculturation would be associated with higher vegetable, fruit, and plant-based food intakes among Mongolian immigrants. A total of 500 Mongolian immigrants participated in this study conducted between December 2010 and May 2011. To measure the acculturation level, we developed an acculturation scale based on the Suinn-Lew Asian self-identity acculturation scale. Dietary intakes were assessed using the 24-hour dietary recall method. Associations between acculturation and dietary intakes were investigated using a general linear model adjusted for demographic characteristics. The participants were grouped into either a low-acculturation group or a high-acculturation group. The high-acculturation group reported significantly higher consumption of vegetables and rice and significantly lower consumption of meat, potatoes, and flour products compared with their low-acculturation counterparts. However, a higher level of acculturation was also significantly related to a higher intake of sodium. These findings could be used to tailor nutrition programs to different acculturation levels.

  4. Expression of neurexin and neuroligin in the enteric nervous system and their down-regulated expression levels in Hirschsprung disease.

    PubMed

    Zhang, Qiangye; Wang, Jian; Li, Aiwu; Liu, Hongzhen; Zhang, Wentong; Cui, Xinhai; Wang, Kelai

    2013-04-01

    To investigate the expression levels of neurexins and neuroligins in the enteric nervous system (ENS) in Hirschsprung Disease (HSCR). Longitudinal muscles with adherent mesenteric plexus were obtained by dissection of the fresh gut wall of mice, guinea pigs, and humans. Double labeling of neurexin I and Hu (a neuron marker), neuroligin 1 and Hu, neurexin I and synaptophysin (a presynaptic marker), and neuroligin 1 and PSD95 (a postsynaptic marker) was performed by immunofluorescence staining. Images were merged to determine the relative localizations of the proteins. Expression levels of neurexin and neuroligin in different segments of the ENS in HSCR were investigated by immunohistochemistry. Neurexin and neuroligin were detected in the mesenteric plexus of mice, guinea pigs, and humans with HSCR. Neurexin was located in the presynapse, whereas neuroligin was located in the postsynapse. Expression levels of neurexin and neuroligin were significant in the ganglionic colonic segment of HSCR, moderate in the transitional segment, and negative in the aganglionic colonic segment. The expressions of neurexin and neuroligin in the transitional segments were significantly down-regulated compared with the levels in the normal segments (P < 0.05). Expression levels of neurexin and neuroligin in ENS are significantly down-regulated in HSCR, which may be involved in the pathogenesis of HSCR.

  5. Expression of FOXO6 is Associated With Oxidative Stress Level and Predicts the Prognosis in Hepatocellular Cancer

    PubMed Central

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

    2016-01-01

    Abstract 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 p

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

    PubMed Central

    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

    2016-01-01

    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 CFTR TAD 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

  7. 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

  8. 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

  9. High expression levels of COX-2 and P300 are associated with unfavorable survival in laryngeal squamous cell carcinoma.

    PubMed

    Chen, Yan-Feng; Luo, Rong-Zhen; Li, Yong; Cui, Bo-Kang; Song, Ming; Yang, An-Kui; Chen, Wen-Kuan

    2013-03-01

    In order to provide a basis for clinical treatment decisions, we explored whether there was a correlation between the expression of COX-2 and P300 and clinical factors in a group of patients with laryngeal squamous cell carcinoma (LSCC). A retrospective analysis of clinicopathological data was conducted in 80 patients with LSCC who presented between January 1997 and December 1998. An immunohistochemistry tissue microarray was conducted of 80 surgically resected LSCC and 20 adjacent normal tissue specimens. Survival analysis and Kaplan-Meier curves were used to compare the effects of clinicopathological factors on survival. The Cox model was applied for multivariate analysis. The expression level of COX-2/P300 in LSCC tissues and adjacent normal tissues were 47.5/50.0 versus 0.0/15.0 %. The expression of COX-2 and P300 was correlated with higher T category, N category, clinical staging, histological grade and recurrence (P < 0.05). P300 expression was correlated with COX-2 expression (P < 0.05). Univariate survival analysis showed that P300, COX-2, N category, clinical staging and recurrence factors were closely correlated with unfavorable survival (P < 0.05). Multivariate analysis showed that COX-2 expression, histological grade and recurrence were independent prognostic factors for LSCC. High expression levels of COX-2 and P300 indicated poor survival outcomes for patients with LSCC.

  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.

  11. Expression of p-AKT characterizes adenoid cystic carcinomas of head and neck with a higher risk for tumor relapses

    PubMed Central

    Völker, Hans-Ullrich; Scheich, Matthias; Berndt, Annette; Haubitz, Imme; Metzger, Alexandra; Müller-Hermelink, Hans-Konrad; Kämmerer, Ulrike; Schmidt, Melanie

    2009-01-01

    Background Adenoid cystic carcinomas are rare tumors with an indolent clinical course, but frequent local relapses. The identification of tumors with a higher relapse risk seems to be interesting. Hence we investigated parameters of glucose metabolism, which were found associated with poor prognosis in other malignancies. Methods Specimen of 29 patients were investigated immunohistochemically with antibodies against p-AKT, TKTL-1 (transketolase-like 1), M2PK (M2 pyruvate kinase), and GLUT-1. Proliferation was investigated by staining with Ki67. The tumors were located at the major or minor salivary glands. Only the typical cribriform subtype was investigated. The initial tumor stage was pT1 or pT2. Results Expression of p-AKT was significantly (P = 0.036) associated with a higher relapse risk in multivariate analysis. Low expression of M2PK was non-significantly (P = 0.065) predictive for a higher risk. TKTL-1 and GLUT-1 were expressed in the majority of cases, albeit not associated with relapse risk. Conclusion Adenoid cystic carcinomas positive for p-AKT show a higher relapse risk. However, other parameters of glucose metabolism investigated here or proliferation (Ki67) were not predictive in this entity. Our findings demonstrate a possible background for therapeutic approaches targeting the inhibition of PI3K/AKT pathway. PMID:19545368

  12. β2-agonist clenbuterol suppresses bacterial phagocytosis of splenic macrophages expressing high levels of macrophage receptor with collagenous structure.

    PubMed

    Shirato, Ken; Sato, Shogo; Sato, Madoka; Hashizume, Yoko; Tachiyashiki, Kaoru; Imaizumi, Kazuhiko

    2013-01-01

    Splenic marginal zone macrophages expressing macrophage receptor with collagenous structure (MARCO) contribute to the clearance of blood-borne pathogens. We determined a splenic adherent cell fraction abundantly containing cells expressing a higher level of MARCO by flow cytometry, and examined the effects of daily administration of an anabolic dose of β2-agonist clenbuterol on the phagocytic capacity of the cells in mice. After 6 weeks of clenbuterol (1.0 mg/kg body weight/d) or vehicle administration to the mice, splenic adherent cells were isolated. These cells were separated into three cell-size subpopulations. Among them, the small-cell subpopulation contained abundantly the cells with markedly higher levels of MARCO and exhibited more intense phagocytic capacity against Escherichia coli, as compared with the other subpopulations. The phagocytic capacity of the small cells was significantly reduced after clenbuterol administration. These results suggest that the utilization of clenbuterol as doping drug impairs bacterial clearance in the spleen.

  13. Plasma concentration, genetic variation, and gene expression levels of matrix metalloproteinase 9 in Iranian patients with coronary artery disease

    PubMed Central

    Mahmoodi, Khalil; Kamali, Koorosh; Karami, Elham; Soltanpour, Mohammad Soleiman

    2017-01-01

    Background: Matrix metalloproteinase 9 (MMP9) -1562C>T (rs3918242) polymorphism has been proposed as a risk factor for coronary artery disease (CAD) with conflicting results. The aim of the present study was to investigate the association of -1562C>T genetic polymorphism, gene expression and circulating levels of MMP9 with CAD risk in an Iranian subpopulation in in Zanjan City. Materials and Methods: This was a retrospective case–control study we investigated retrospectively 100 patients with angiographically verified CAD and 100 matched controls. Genotyping of -1562C>T polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gene expression levels and circulating levels of MMP9 was determined by real-time reverse transcription-PCR and enzyme immunoassay method, respectively. Statistical analysis was done using Student's t-test or Chi-square test by SPSS 16 software. Results: The mean circulating levels of MMP9 were significantly higher in CAD Group than control group (P = 0.002). Mean plasma levels of MMP9 were also significantly higher in triple vessel stenosis patients than double vessel or single vessel stenosis patients (P < 0.001). Moreover, mean plasma levels and gene expression levels of MMP9 were significantly higher in T allele carrier than C allele carrier of MMP9 -1562C>T polymorphism (P = 0.002, P = 0.01, respectively). However, genotype and allele frequencies of MMP9 -1562C>T polymorphism were similar between CAD patients and controls (P > 0.05). Additionally, the -1562C>T polymorphism of MMP9 gene didn't increase the risk of CAD in dominant (P = 0.537) or recessive (P = 0.249) genetic models. Conclusion: Our study demonstrated that circulating levels of MMP9 but not -1562C>T polymorphism of MMP9 gene may be a risk factor for development and severity of CAD in an Iranian subpopulation in Zanjan.

  14. Decreased expression levels of Nurr1 are associated with chronic inflammation in patients with type 2 diabetes.

    PubMed

    Xu, Ying; Huang, Qi; Zhang, Wenfang; Wang, Yaping; Zeng, Qingling; He, Chunyan; Xue, Junli; Chen, Jin; Hu, Xuemei; Xu, Yancheng

    2015-10-01

    Chronic inflammation is associated with insulin resistance, a characteristic of type 2 diabetes (T2D). Nuclear receptor‑related protein 1 (Nurr1) can regulate inflammation, dependent on the nature of individual diseases. However, whether Nurr1 regulates chronic inflammation during the pathogenic process of T2D in humans remains to be fully elucidated. The present study aimed to investigate the potential association between the expression of Nurr1 in peripheral blood mononuclear cells (PBMCs) and inflammation in patients with T2D. The levels of plasma tumor necrosis factor (TNF)α and interleukin (IL)‑6, the relative expression levels of Nurr1, and glycogen synthase kinase (GSK)‑3β phosphorylation in PBMCs from 40 patients with T2D and 40 healthy controls (HC group) were examined, and their potential association with clinical measures were analyzed. The expression levels of Nurr1, induced by high glucose and palmitic acid, were assessed in the PBMCs from the HC group. Compared with the HC group, significantly higher levels of plasma TNFα and IL‑6 were correlated positively with the degree of insulin resistance in the T2D patients. However, significantly lower expression levels of Nurr1 and GSK‑3β phosphorylation in the PBMCs were correlated negatively with the levels of TNFα, IL‑6, fasting insulin and insulin resistance in the T2D patients. Treatment of the PBMCs with high glucose or palmitic acid inhibited the expression of Nurr1 in a dose‑ and time‑dependent manner. Therefore, decreased expression levels of Nurr1 were associated with chronic inflammation and insulin resistance in patients with T2D.

  15. 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…

  16. "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…

  17. 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.

  18. Unconscious fearful priming followed by a psychosocial stress test results in higher cortisol levels.

    PubMed

    Hänsel, Alexander; von Känel, Roland

    2013-10-01

    Human perception of stress includes an automatic pathway that processes subliminal presented stimuli below the threshold of conscious awareness. Subliminal stimuli can therefore activate the physiologic stress system. Unconscious emotional signals were shown to significantly moderate reactions and responses to subsequent stimuli, an effect called 'priming'. We hypothesized that subliminal presentation of a fearful signal during the Stroop task compared with an emotionally neutral one will prime stress reactivity in a subsequently applied psychosocial stress task, thereby yielding a significant increase in salivary cortisol. Half of 36 participants were repeatedly presented either a fearful face or a neutral one. After this, all underwent a psychosocial stress task. The fearful group showed a significant increase in cortisol levels (p = 0.022). This change was not affected by sex, age and body mass index, and it also did not change when taking resting cortisol levels into account. Post-hoc analyses showed that the increase in cortisol in the fearful group started immediately after the psychosocial stress test. Hence, subliminal exposure to a fearful signal in combination with the Stroop and followed by a psychosocial stress test leads to an increase in stress reactivity.

  19. Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects

    PubMed Central

    2012-01-01

    Background The predominant model for regulation of gene expression through DNA methylation is an inverse association in which increased methylation results in decreased gene expression levels. However, recent studies suggest that the relationship between genetic variation, DNA methylation and expression is more complex. Results Systems genetic approaches for examining relationships between gene expression and methylation array data were used to find both negative and positive associations between these levels. A weighted correlation network analysis revealed that i) both transcriptome and methylome are organized in modules, ii) co-expression modules are generally not preserved in the methylation data and vice-versa, and iii) highly significant correlations exist between co-expression and co-methylation modules, suggesting the existence of factors that affect expression and methylation of different modules (i.e., trans effects at the level of modules). We observed that methylation probes associated with expression in cis were more likely to be located outside CpG islands, whereas specificity for CpG island shores was present when methylation, associated with expression, was under local genetic control. A structural equation model based analysis found strong support in particular for a traditional causal model in which gene expression is regulated by genetic variation via DNA methylation instead of gene expression affecting DNA methylation levels. Conclusions Our results provide new insights into the complex mechanisms between genetic markers, epigenetic mechanisms and gene expression. We find strong support for the classical model of genetic variants regulating methylation, which in turn regulates gene expression. Moreover we show that, although the methylation and expression modules differ, they are highly correlated. PMID:23157493

  20. Transcriptome-Level Signatures in Gene Expression and Gene Expression Variability during Bacterial Adaptive Evolution

    PubMed Central

    Erickson, Keesha E.; Otoupal, Peter B.

    2017-01-01

    ABSTRACT Antibiotic-resistant bacteria are an increasingly serious public health concern, as strains emerge that demonstrate resistance to almost all available treatments. One factor that contributes to the crisis is the adaptive ability of bacteria, which exhibit remarkable phenotypic and gene expression heterogeneity in order to gain a survival advantage in damaging environments. This high degree of variability in gene expression across biological populations makes it a challenging task to identify key regulators of bacterial adaptation. Here, we research the regulation of adaptive resistance by investigating transcriptome profiles of Escherichia coli upon adaptation to disparate toxins, including antibiotics and biofuels. We locate potential target genes via conventional gene expression analysis as well as using a new analysis technique examining differential gene expression variability. By investigating trends across the diverse adaptation conditions, we identify a focused set of genes with conserved behavior, including those involved in cell motility, metabolism, membrane structure, and transport, and several genes of unknown function. To validate the biological relevance of the observed changes, we synthetically perturb gene expression using clustered regularly interspaced short palindromic repeat (CRISPR)-dCas9. Manipulation of select genes in combination with antibiotic treatment promotes adaptive resistance as demonstrated by an increased degree of antibiotic tolerance and heterogeneity in MICs. We study the mechanisms by which identified genes influence adaptation and find that select differentially variable genes have the potential to impact metabolic rates, mutation rates, and motility. Overall, this work provides evidence for a complex nongenetic response, encompassing shifts in gene expression and gene expression variability, which underlies adaptive resistance. IMPORTANCE Even initially sensitive bacteria can rapidly thwart antibiotic treatment

  1. Transcriptome-Level Signatures in Gene Expression and Gene Expression Variability during Bacterial Adaptive Evolution.

    PubMed

    Erickson, Keesha E; Otoupal, Peter B; Chatterjee, Anushree

    2017-01-01

    Antibiotic-resistant bacteria are an increasingly serious public health concern, as strains emerge that demonstrate resistance to almost all available treatments. One factor that contributes to the crisis is the adaptive ability of bacteria, which exhibit remarkable phenotypic and gene expression heterogeneity in order to gain a survival advantage in damaging environments. This high degree of variability in gene expression across biological populations makes it a challenging task to identify key regulators of bacterial adaptation. Here, we research the regulation of adaptive resistance by investigating transcriptome profiles of Escherichia coli upon adaptation to disparate toxins, including antibiotics and biofuels. We locate potential target genes via conventional gene expression analysis as well as using a new analysis technique examining differential gene expression variability. By investigating trends across the diverse adaptation conditions, we identify a focused set of genes with conserved behavior, including those involved in cell motility, metabolism, membrane structure, and transport, and several genes of unknown function. To validate the biological relevance of the observed changes, we synthetically perturb gene expression using clustered regularly interspaced short palindromic repeat (CRISPR)-dCas9. Manipulation of select genes in combination with antibiotic treatment promotes adaptive resistance as demonstrated by an increased degree of antibiotic tolerance and heterogeneity in MICs. We study the mechanisms by which identified genes influence adaptation and find that select differentially variable genes have the potential to impact metabolic rates, mutation rates, and motility. Overall, this work provides evidence for a complex nongenetic response, encompassing shifts in gene expression and gene expression variability, which underlies adaptive resistance. IMPORTANCE Even initially sensitive bacteria can rapidly thwart antibiotic treatment through stress

  2. Estimating shifts in diversification rates based on higher-level phylogenies

    PubMed Central

    Smrckova, Jana

    2016-01-01

    Macroevolutionary studies recently shifted from only reconstructing the past state, i.e. the species phylogeny, to also infer the past speciation and extinction dynamics that gave rise to the phylogeny. Methods for estimating diversification dynamics are sensitive towards incomplete species sampling. We introduce a method to estimate time-dependent diversification rates from phylogenies where clades of a particular age are represented by only one sampled species. A popular example of this type of data is phylogenies on the genus- or family-level, i.e. phylogenies where one species per genus or family is included. We conduct a simulation study to validate our method in a maximum-likelihood framework. Further, this method has already been introduced into the Bayesian package MrBayes, which led to new insights into the evolution of Hymenoptera. PMID:27703054

  3. The necessity of rostrolateral prefrontal cortex for higher-level sequential behavior

    PubMed Central

    Desrochers, Theresa M.; Chatham, Christopher H.; Badre, David

    2015-01-01

    Summary Frontal neocortex is thought to support our highest intellectual abilities, including our ability to plan and enact a sequence of tasks toward a desired goal. In everyday life, such task sequences are abstract in that they do not require consistent movement sequences and are often assembled “on the fly”. Yet, remarkably little is known about the necessity of frontal sub-regions for such control. Participants repeatedly completed sequences of simple tasks during fMRI scanning. Rostrolateral prefrontal cortex (RLPFC) activation ramped over sequence position, and reset at the initiation of each new sequence. To establish the necessity and function of RLPFC in this task, participants performed the sequential task while undergoing transcranial magnetic stimulation (TMS) of the RLPFC versus two prefrontal control regions. Across two independent experiments, only RLPFC stimulation increasingly disrupted task performance as each sequence progressed. These data establish RLPFC as necessary for uncertainty resolution during sequence-level control. PMID:26402612

  4. Higher levels of sex chromosome heteromorphism are associated with markedly stronger reproductive isolation.

    PubMed

    Lima, Thiago G

    2014-08-21

    The two 'rules of speciation', Haldane's rule and the large X-effect, describe the genetic basis of postzygotic isolation, and have led to the realization that sex chromosomes play an important role in this process. However, a range of sex determination mechanisms exists in nature, not always involving sex chromosomes. Based on these 'rules of speciation', I test the hypothesis that the presence of sex chromosomes will contribute to a faster evolution of intrinsic postzygotic isolation. I show that taxa that do not have sex chromosomes evolve lower levels of postzygotic isolation than taxa with sex chromosomes, at a similar amount of genetic divergence. Taxa with young homomorphic sex chromosomes show an intermediate pattern compared to taxa with heteromorphic sex chromosomes and taxa without sex chromosomes. These results are consistent with predictions from the two 'rules of speciation', and emphasize the importance of sex chromosomes for the evolution of intrinsic postzygotic isolation.

  5. Performance Analysis of Coherent Optical Communication System for M-QAM Higher Modulation Level

    NASA Astrophysics Data System (ADS)

    Kaur, Amrinder; Dewra, Sanjeev

    2016-12-01

    In this paper, performance of QAM sequence generator in coherent optical communication system is investigated. Results are obtained for different square constellation types such as 4-QAM, 16-QAM, 64-QAM and 256-QAM using Hyperbolic-secant pulse generator. For the distance of 120 km and bit rate of 10 Gbps, it is investigated that 4-QAM provides maximum Q factor of 33.93 and minimum BER of 6e-253, whereas 16-QAM, 64-QAM & 256-QAM provides Q factor of 31.47, 22.85 & 8 and BER of 5e-218, 3e-116 & 2e-16, respectively. Decrement in Quality factor and increase in BER are observed with increment in the M-value of QAM. It is further observed that Eye opening decreases with increment in levels of QAM.

  6. 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...

  7. 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…

  8. 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…

  9. 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…

  10. Reading Comprehension, Working Memory and Higher-Level Language Skills in Children with SLI and/or Dyslexia

    ERIC Educational Resources Information Center

    Wong, Anita M.-Y.; Ho, Connie S.-H.; Au, Terry K.-F.; McBride, Catherine; Ng, Ashley K.-H.; Yip, Lesley P.-W.; Lam, Catherine C.-C.

    2017-01-01

    This study examined (1) whether working memory and higher-level languages skills--inferencing and comprehension monitoring--accounted for individual differences among Chinese children in Chinese reading comprehension, after controlling for age, Chinese word reading and oral language skills, and (2) whether children with specific language…

  11. An Exploration of Higher Level Teaching Assistants' Perceptions of Their Training and Development in the Context of School Workforce Reform

    ERIC Educational Resources Information Center

    Burgess, Hilary; Mayes, Ann Shelton

    2009-01-01

    This paper reports on teaching assistants' perceptions of the Phase 1 Higher Level Teaching Assistant (HLTA) training programme and the match to their changing role in classroom support, and suggests resulting issues for the design and delivery of HLTA training programmes. It explores what impact undertaking the training and gaining HLTA…

  12. 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…

  13. Estimating Genetic and Environmental Influences on Depressive Symptoms in Adolescence: Differing Effects on Higher and Lower Levels of Symptoms

    ERIC Educational Resources Information Center

    Rende, Richard; Slomkowski, Cheryl; Lloyd-Richardson, Elizabeth; Stroud, Laura; Niaura, Raymond

    2006-01-01

    We estimate the relative effect sizes of genetic and environmental influences on both higher and lower levels of depressive symptoms with attention to persistence over a 1-year period in the genetically informative subsample of adolescents participating in the National Longitudinal Study of Adolescent Health (Add Health). Shared environmental…

  14. Mathematics Teachers' Level of Knowledge and Practice on the Implementation of Higher-Order Thinking Skills (HOTS)

    ERIC Educational Resources Information Center

    Abdullah, Abdul Halim; Mokhtar, Mahani; Halim, Noor Dayana Abd; Ali, Dayana Farzeeha; Tahir, Lokman Mohd; Kohar, Umar Haiyat Abdul

    2017-01-01

    This study aims to identify the level of knowledge and practice on the implementation of higher-order thinking skills (HOTS) among mathematics teachers at a secondary school in the district of Terengganu. The study focused on the aspects of curriculum, pedagogy and assessment and compared them with demographic factors of the respondents. It used…

  15. 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…

  16. "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…

  17. 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…

  18. 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…

  19. Evaluating the Use of Synoptic Assessment to Engage and Develop Lower Level Higher Education Students within a Further Education Setting

    ERIC Educational Resources Information Center

    Southall, Jane; Wason, Hilary

    2016-01-01

    Engaging less academically qualified Higher Education students being taught within a Further Education setting, who have weaker study skills and little experience of independent learning, is challenging. Confidence and motivation levels are often low and they feel overwhelmed. Effective assessment design is crucial and needs to capitalise on…

  20. Successful pod infections by Moniliophthora roreri result in differential Theobroma cacao gene expression depending on the clone's level of tolerance.

    PubMed

    Ali, Shahin S; Melnick, Rachel L; Crozier, Jayne; Phillips-Mora, Wilberth; Strem, Mary D; Shao, Jonathan; Zhang, Dapeng; Sicher, Richard; Meinhardt, Lyndel; Bailey, Bryan A

    2014-09-01

    An understanding of the tolerance mechanisms of Theobroma cacao used against Moniliophthora roreri, the causal agent of frosty pod rot, is important for the generation of stable disease-tolerant clones. A comparative view was obtained of transcript populations of infected pods from two susceptible and two tolerant clones using RNA sequence (RNA-Seq) analysis. A total of 3009 transcripts showed differential expression among clones. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis of differentially expressed genes indicated shifts in 152 different metabolic pathways between the tolerant and susceptible clones. Real-time quantitative reverse transcription polymerase chain reaction (real-time qRT-PCR) analyses of 36 genes verified the differential expression. Regression analysis validated a uniform progression in gene expression in association with infection levels and fungal loads in the susceptible clones. Expression patterns observed in the susceptible clones diverged in tolerant clones, with many genes showing higher expression at a low level of infection and fungal load. Principal coordinate analyses of real-time qRT-PCR data separated the gene expression patterns between susceptible and tolerant clones for pods showing malformation. Although some genes were constitutively differentially expressed between clones, most results suggested that defence responses were induced at low fungal load in the tolerant clones. Several elicitor-responsive genes were highly expressed in tolerant clones, suggesting rapid recognition of the pathogen and induction of defence genes. Expression patterns suggested that the jasmonic acid-ethylene- and/or salicylic acid-mediated defence pathways were activated in the tolerant clones, being enhanced by reduced brassinosteroid (BR) biosynthesis and catabolic inactivation of both BR and abscisic acids. Finally, several genes associated with hypersensitive response-like cell death were also induced in tolerant clones.

  1. 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.

  2. Higher Expression of Toll-like Receptors 3, 7, 8, and 9 in Pityriasis Rosea

    PubMed Central

    El-Ela, Mostafa Abou; El-Komy, Mohamed; Hay, Rania Abdel; Hegazy, Rehab; Sharobim, Amin; Rashed, Laila; Amr, Khalda

    2017-01-01

    Background Pityriasis rosea (PR) is a common papulosquamous skin disease in which an infective agent may be implicated. Toll-like receptors (TLRs) play an important role in immune responses and in the pathophysiology of inflammatory skin diseases. Our aim was to determine the possible roles of TLRs 3, 7, 8, and 9 in the pathogenesis of PR. Methods Twenty-four PR patients and 24 healthy individuals (as controls) were included in this case control study. All recruits were subjected to routine laboratory investigations. Biopsies were obtained from one active PR lesion and from healthy skin of controls for the detection of TLR 3, 7, 8, and 9 gene expression using real-time polymerase chain reaction. Results This study included 24 patients (8 females and 16 males) with active PR lesions, with a mean age of 28.62 years. Twenty four healthy age- and sex-matched individuals were included as controls (8 females and 16 males, with a mean age of 30.83 years). The results of the routine laboratory tests revealed no significant differences between both groups. Significantly elevated expression of all studied TLRs were detected in PR patients relative to healthy controls (p < .001). Conclusions TLRs 3, 7, 8, and 9 might be involved in the pathogenesis of PR. PMID:28192646

  3. 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

  4. Hypoxia disrupts the expression levels of circadian rhythm genes in hepatocellular carcinoma.

    PubMed

    Yu, Chao; Yang, Sheng-Li; Fang, Xiefan; Jiang, Jian-Xin; Sun, Cheng-Yi; Huang, Tao

    2015-05-01

    Disturbance in the expression of circadian rhythm genes is a common feature in certain types of cancer, however the mechanisms mediating this disturbance remain to be elucidated. The present study aimed to investigate the effect of hypoxia on the expression of circadian rhythm genes in liver cancer cells and to identify the mechanisms underlying this effect in hepatocellular carcinoma (HCC). The HCC cell line, PLC/PRF/5. was treated with either a vehicle control or CoCl2 at 50, 100 or 200 µΜ for 24 h. Following treatment, the protein expression levels of hypoxia‑inducible factor (HIF)‑1α and HIF‑2α were detected by western blotting and the mRNA expression levels of circadian rhythm genes, including circadian locomotor output cycles kaput (Clock), brain and muscle Arnt‑like 1 (Bmal1), period (Per)1, Per2, Per3, cryptochrome (Cry)1, Cry2 and casein kinase Iε (CKIε), were detected by reverse transcription quantitative polymerase chain reaction (RT‑qPCR). Expression plasmids containing HIF‑1α or HIF‑2α were transfected into the PLC/PRF/5 cells using liposomes and RT‑qPCR was used to determine the effects of the transfections on the expression levels of circadian rhythm genes. Following treatment with CoCl2, the protein expression levels of HIF‑1α and HIF‑2α were upregulated in a CoCl2 concentration‑dependent manner. The mRNA expression levels of Clock, Bmal1 and Cry2 were increased, and the mRNA expression levels of Per1, Per2, Per3, Cry1 and CKIε were decreased following CoCl2 treatment (P<0.05). In the PLC/PRF/5 cells transfected with the plasmid containing HIF‑1α, the mRNA expression levels of Clock, Bmal1 and Cry2 were increased, and the mRNA expression levels of Per1, Per2, Per3, Cry1 and CKIε were decreased. In the PLC/PRF/5 cells transfected with the plasmid containing HIF‑2α, the mRNA expression levels of Clock, Bmal1, Per1, Cry1, Cry2 and CKIε were upregulated, and the mRNA expression levels of Per2 and Per3 were

  5. 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

  6. High-level expression in Corynebacterium glutamicum of nitrile hydratase from Rhodococcus rhodochrous for acrylamide production.

    PubMed

    Kang, Mi-Suk; Han, Sang-Soo; Kim, Mi-Young; Kim, Bu-Youn; Huh, Jong-Pil; Kim, Hak-Sung; Lee, Jin-Ho

    2014-05-01

    The nhhBAG gene of Rhodococcus rhodochrous M33 that encodes nitrile hydratase (NHase), converting acrylonitrile into acrylamide, was cloned and expressed in Corynebacterium glutamicum under the control of an ilvC promoter. The specific enzyme activity in recombinant C. glutamicum cells was about 13.6 μmol/min/mg dry cell weight (DCW). To overexpress the NHase, five types of plasmid variants were constructed by introducing mutations into 80 nucleotides near the translational initiation region (TIR) of nhhB. Of them, pNBM4 with seven mutations showed the highest NHase activity, exhibiting higher expression levels of NhhB and NhhA than wild-type pNBW33, mainly owing to decreased secondary-structure stability and an introduction of a conserved Shine-Dalgarno sequence in the translational initiation region. In a fed-batch culture of recombinant Corynebacterium cells harboring pNBM4, the cell density reached 53.4 g DCW/L within 18 h, and the specific and total enzyme activities were estimated to be 37.3 μmol/min/mg DCW and 1,992 μmol/min/mL, respectively. The use of recombinant Corynebacterium cells for the production of acrylamide from acrylonitrile resulted in a conversion yield of 93 % and a final acrylamide concentration of 42.5 % within 6 h when the total amount of fed acrylonitrile was 456 g.

  7. Leptin Levels Are Higher in Whole Compared to Skim Human Milk, Supporting a Cellular Contribution

    PubMed Central

    Kugananthan, Sambavi; Lai, Ching Tat; Gridneva, Zoya; Mark, Peter J.; Geddes, Donna T.; Kakulas, Foteini

    2016-01-01

    Human milk (HM) contains a plethora of metabolic hormones, including leptin, which is thought to participate in the regulation of the appetite of the developing infant. Leptin in HM is derived from a combination of de novo mammary synthesis and transfer from the maternal serum. Moreover, leptin is partially lipophilic and is also present in HM cells. However, leptin has predominately been measured in skim HM, which contains neither fat nor cells. We optimised an enzyme-linked immunosorbent assay for leptin measurement in both whole and skim HM and compared leptin levels between both HM preparations collected from 61 lactating mothers. Whole HM leptin ranged from 0.2 to 1.47 ng/mL, whilst skim HM leptin ranged from 0.19 to 0.9 ng/mL. Whole HM contained, on average, 0.24 ± 0.01 ng/mL more leptin than skim HM (p < 0.0001, n = 287). No association was found between whole HM leptin and fat content (p = 0.17, n = 287), supporting a cellular contribution to HM leptin. No difference was found between pre- and post-feed samples (whole HM: p = 0.29, skim HM: p = 0.89). These findings highlight the importance of optimising HM leptin measurement and assaying it in whole HM to accurately examine the amount of leptin received by the infant during breastfeeding. PMID:27834797

  8. Personality Measures Link Slower Binocular Rivalry Switch Rates to Higher Levels of Self-Discipline

    PubMed Central

    Antinori, Anna; Smillie, Luke D.; Carter, Olivia L.

    2017-01-01

    In this paper we investigated the relation between personality and the rate of perceptual alternations during binocular rivalry. Studies have demonstrated that slower rivalry alternations are associated with a range of clinical conditions. It is less clear whether rivalry dynamics similarly co-vary with individual differences in psychological traits seen across non-clinical population. We assessed rivalry rates in a non-clinical population (n = 149) and found slower rivalry alternations were positively related r(149) = 0.20, p = 0.01 to industriousness, a trait characterized by a high level of self-discipline using the Big Five Aspect Scales (BFAS). Switch rates were also negatively related r(149) = −0.20, p = 0.01 to cognitive disorganization, a schizotypy trait capturing schizophrenia-like symptoms of disorganization using the Oxford-Liverpool Inventory of feelings and Experiences (O-LIFE). Furthermore, we showed that that these relations with personality were unaffected by the inclusion or exclusion of mixed percept in the response analysis. Together these results are relevant to theoretical models of rivalry investigating individual differences in rivalry temporal dynamics and they may reduce concerns about the impact of task compliance in clinical research using rivalry as a potential diagnostic tool. PMID:28105021

  9. 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.

  10. Leptin Levels Are Higher in Whole Compared to Skim Human Milk, Supporting a Cellular Contribution.

    PubMed

    Kugananthan, Sambavi; Lai, Ching Tat; Gridneva, Zoya; Mark, Peter J; Geddes, Donna T; Kakulas, Foteini

    2016-11-08

    Human milk (HM) contains a plethora of metabolic hormones, including leptin, which is thought to participate in the regulation of the appetite of the developing infant. Leptin in HM is derived from a combination of de novo mammary synthesis and transfer from the maternal serum. Moreover, leptin is partially lipophilic and is also present in HM cells. However, leptin has predominately been measured in skim HM, which contains neither fat nor cells. We optimised an enzyme-linked immunosorbent assay for leptin measurement in both whole and skim HM and compared leptin levels between both HM preparations collected from 61 lactating mothers. Whole HM leptin ranged from 0.2 to 1.47 ng/mL, whilst skim HM leptin ranged from 0.19 to 0.9 ng/mL. Whole HM contained, on average, 0.24 ± 0.01 ng/mL more leptin than skim HM (p < 0.0001, n = 287). No association was found between whole HM leptin and fat content (p = 0.17, n = 287), supporting a cellular contribution to HM leptin. No difference was found between pre- and post-feed samples (whole HM: p = 0.29, skim HM: p = 0.89). These findings highlight the importance of optimising HM leptin measurement and assaying it in whole HM to accurately examine the amount of leptin received by the infant during breastfeeding.

  11. Changing meaning causes coupling changes within higher levels of the cortical hierarchy.

    PubMed

    Schofield, T M; Iverson, P; Kiebel, S J; Stephan, K E; Kilner, J M; Friston, K J; Crinion, J T; Price, C J; Leff, A P

    2009-07-14

    Processing of speech and nonspeech sounds occurs bilaterally within primary auditory cortex and surrounding regions of the superior temporal gyrus; however, the manner in which these regions interact during speech and nonspeech processing is not well understood. Here, we investigate the underlying neuronal architecture of the auditory system with magnetoencephalography and a mismatch paradigm. We used a spoken word as a repeating "standard" and periodically introduced 3 "oddball" stimuli that differed in the frequency spectrum of the word's vowel. The closest deviant was perceived as the same vowel as the standard, whereas the other 2 deviants were perceived as belonging to different vowel categories. The neuronal responses to these vowel stimuli were compared with responses elicited by perceptually matched tone stimuli under the same paradigm. For both speech and tones, deviant stimuli induced coupling changes within the same bilateral temporal lobe system. However, vowel oddball effects increased coupling within the left posterior superior temporal gyrus, whereas perceptually equivalent nonspeech oddball effects increased coupling within the right primary auditory cortex. Thus, we show a dissociation in neuronal interactions, occurring at both different hierarchal levels of the auditory system (superior temporal versus primary auditory cortex) and in different hemispheres (left versus right). This hierarchical specificity depends on whether auditory stimuli are embedded in a perceptual context (i.e., a word). Furthermore, our lateralization results suggest left hemisphere specificity for the processing of phonological stimuli, regardless of their elemental (i.e., spectrotemporal) characteristics.

  12. 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.

  13. Congruence and diversity of butterfly-host plant associations at higher taxonomic levels.

    PubMed

    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.

  14. 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

  15. 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.

  16. Peripheral blood gene expression profiles linked to monoamine metabolite levels in cerebrospinal fluid

    PubMed Central

    Luykx, J J; Olde Loohuis, L M; Neeleman, M; Strengman, E; Bakker, S C; Lentjes, E; Borgdorff, P; van Dongen, E P A; Bruins, P; Kahn, R S; Horvath, S; de Jong, S; Ophoff, R A

    2016-01-01

    The blood–brain barrier separates circulating blood from the central nervous system (CNS). The scope of this barrier is not fully understood which limits our ability to relate biological measurements from peripheral to central phenotypes. For example, it is unknown to what extent gene expression levels in peripheral blood are reflective of CNS metabolism. In this study, we examine links between central monoamine metabolite levels and whole-blood gene expression to better understand the connection between peripheral systems and the CNS. To that end, we correlated the prime monoamine metabolites in cerebrospinal fluid (CSF) with whole-genome gene expression microarray data from blood (N=240 human subjects). We additionally applied gene-enrichment analysis and weighted gene co-expression network analyses (WGCNA) to identify modules of co-expressed genes in blood that may be involved with monoamine metabolite levels in CSF. Transcript levels of two genes were significantly associated with CSF serotonin metabolite levels after Bonferroni correction for multiple testing: THAP7 (P=2.8 × 10−8, β=0.08) and DDX6 (P=2.9 × 10−7, β=0.07). Differentially expressed genes were significantly enriched for genes expressed in the brain tissue (P=6.0 × 10−52). WGCNA revealed significant correlations between serotonin metabolism and hub genes with known functions in serotonin metabolism, for example, HTR2A and COMT. We conclude that gene expression levels in whole blood are associated with monoamine metabolite levels in the human CSF. Our results, including the strong enrichment of brain-expressed genes, illustrate that gene expression profiles in peripheral blood can be relevant for quantitative metabolic phenotypes in the CNS. PMID:27959337

  17. Expression of NKp46 Splice Variants in Nasal Lavage Following Respiratory Viral Infection: Domain 1-Negative Isoforms Predominate and Manifest Higher Activity

    PubMed Central

    Shemer-Avni, Yonat; Kundu, Kiran; Shemesh, Avishai; Brusilovsky, Michael; Yossef, Rami; Meshesha, Mesfin; Solomon-Alemayehu, Semaria; Levin, Shai; Gershoni-Yahalom, Orly; Campbell, Kerry S.; Porgador, Angel

    2017-01-01

    The natural killer (NK) cell activating receptor NKp46/NCR1 plays a critical role in elimination of virus-infected and tumor cells. The NCR1 gene can be transcribed into five different splice variants, but the functional importance and physiological distribution of NKp46 isoforms are not yet fully understood. Here, we shed light on differential expression of NKp46 splice variants in viral respiratory tract infections and their functional difference at the cellular level. NKp46 was the most predominantly expressed natural cytotoxicity receptor in the nasal lavage of patients infected with four respiratory viruses: respiratory syncytia virus, adenovirus, human metapneumovirus, or influenza A. Expression of NKp30 was far lower and NKp44 was absent in all patients. Domain 1-negative NKp46 splice variants (i.e., NKp46 isoform d) were the predominantly expressed isoform in nasal lavage following viral infections. Using our unique anti-NKp46 mAb, D2-9A5, which recognizes the D2 extracellular domain, and a commercial anti-NKp46 mAb, 9E2, which recognizes D1 domain, allowed us to identify a small subset of NKp46 D1-negative splice variant-expressing cells within cultured human primary NK cells. This NKp46 D1-negative subset also showed higher degranulation efficiency in term of CD107a surface expression. NK-92 cell lines expressing NKp46 D1-negative and NKp46 D1-positive splice variants also showed functional differences when interacting with targets. A NKp46 D1-negative isoform-expressing NK-92 cell line showed enhanced degranulation activity. To our knowledge, we provide the first evidence showing the physiological distribution and functional importance of human NKp46 splice variants under pathological conditions. PMID:28261217

  18. 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

  19. Pakistanis living in Oslo have lower serum 1,25-dihydroxyvitamin D levels but higher serum ionized calcium levels compared with ethnic Norwegians. The Oslo Health Study

    PubMed Central

    Holvik, Kristin; Meyer, Haakon E; Søgaard, Anne Johanne; Haug, Egil; Falch, Jan A

    2007-01-01

    Background Persons of Pakistani origin living in Oslo have a much higher prevalence of vitamin D deficiency and secondary hyperparathyroidism but similar bone mineral density compared with ethnic Norwegians. Our objective was to investigate whether Pakistani immigrants living in Oslo have an altered vitamin D metabolism by means of compensatory higher serum levels of 1,25-dihydroxyvitamin D (s-1,25(OH)2D) compared with ethnic Norwegians; and whether serum levels of ionized calcium (s-Ca2+) differ between Pakistanis and Norwegians. Methods In a cross-sectional, population-based study venous serum samples were drawn from 94 Pakistani men and 67 Pakistani women aged 30–60 years, and 290 Norwegian men and 270 Norwegian women aged 45–60 years; in total 721 subjects. Results Pakistanis had lower s-1,25(OH)2D compared with Norwegians (p < 0.001). Age- and gender adjusted mean (95% CI) levels were 93 (86, 99) pmol/l in Pakistanis and 123 (120, 126) pmol/l in Norwegians, p < 0.001. The difference persisted after controlling for body mass index. There was a positive relation between serum 25-hydroxyvitamin D (s-25(OH)D) and s-1,25(OH)2D in both groups. S-Ca2+ was higher in Pakistanis; age-adjusted mean (95% CI) levels were 1.28 (1.27, 1.28) mmol/l in Pakistanis and 1.26 (1.26, 1.26) mmol/l in Norwegians, p < 0.001. In both groups, s-Ca2+ was inversely correlated to serum intact parathyroid hormone levels (s-iPTH). For any s-iPTH, s-Ca2+ was higher in Pakistanis, also when controlling for age. Conclusion Community-dwelling Pakistanis in Oslo with low vitamin D status and secondary hyperparathyroidism have lower s-1,25(OH)2D compared with ethnic Norwegians. However, the Pakistanis have higher s-Ca2+. The cause of the higher s-Ca2+ in Pakistanis in spite of their higher iPTH remains unclear. PMID:17945003

  20. HLA-G expression levels influence the tolerogenic activity of human DC-10

    PubMed Central

    Amodio, Giada; Comi, Michela; Tomasoni, Daniela; Gianolini, Monica Emma; Rizzo, Roberta; LeMaoult, Joël; Roncarolo, Maria-Grazia; Gregori, Silvia

    2015-01-01

    Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule with known immune-modulatory functions. Our group identified a subset of human dendritic cells, named DC-10, that induce adaptive interleukin-10-producing T regulatory type 1 (Tr1) cells via the interleukin-10-dependent HLA-G/ILT4 pathway. In this study we aimed at defining the role of HLA-G in DC-10-mediated Tr1 cell differentiation. We analyzed phenotype, functions, and genetic variations in the 3′ untranslated region of the HLA-G locus of in vitro-differentiated DC-10 from 67 healthy donors. We showed that HLA-G expression on DC-10 is donor-dependent. Functional studies demonstrated that DC-10, independently of HLA-G expression, secrete interleukin-10 and negligible levels of interleukin-12. Interestingly, DC-10 with high HLA-G promote allo-specific anergic T cells that contain a significantly higher frequency of Tr1 cells, defined as interleukin-10-producing (P=0.0121) or CD49b+LAG-3+ (P=0.0031) T cells, compared to DC-10 with low HLA-G. We found that the HLA-G expression on DC-10 is genetically imprinted, being associated with specific variations in the 3′ untranslated region of the gene, and it may be finely tuned by microRNA-mediated post-transcriptional regulation. These data highlight the important role of HLA-G in boosting DC-10 tolerogenic activity and confirm that interleukin-10 production by DC-10 is necessary but not sufficient to promote Tr1 cells at high frequency. These new insights into the role of HLA-G in DC-10-mediated induction of Tr1 cells provide additional information for clinical use in Tr1- or DC-10-based cell therapy approaches. PMID:25661445

  1. HLA-G expression levels influence the tolerogenic activity of human DC-10.

    PubMed

    Amodio, Giada; Comi, Michela; Tomasoni, Daniela; Gianolini, Monica Emma; Rizzo, Roberta; LeMaoult, Joël; Roncarolo, Maria-Grazia; Gregori, Silvia

    2015-04-01

    Human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule with known immune-modulatory functions. Our group identified a subset of human dendritic cells, named DC-10, that induce adaptive interleukin-10-producing T regulatory type 1 (Tr1) cells via the interleukin-10-dependent HLA-G/ILT4 pathway. In this study we aimed at defining the role of HLA-G in DC-10-mediated Tr1 cell differentiation. We analyzed phenotype, functions, and genetic variations in the 3' untranslated region of the HLA-G locus of in vitro-differentiated DC-10 from 67 healthy donors. We showed that HLA-G expression on DC-10 is donor-dependent. Functional studies demonstrated that DC-10, independently of HLA-G expression, secrete interleukin-10 and negligible levels of interleukin-12. Interestingly, DC-10 with high HLA-G promote allo-specific anergic T cells that contain a significantly higher frequency of Tr1 cells, defined as interleukin-10-producing (P=0.0121) or CD49b(+)LAG-3(+) (P=0.0031) T cells, compared to DC-10 with low HLA-G. We found that the HLA-G expression on DC-10 is genetically imprinted, being associated with specific variations in the 3' untranslated region of the gene, and it may be finely tuned by microRNA-mediated post-transcriptional regulation. These data highlight the important role of HLA-G in boosting DC-10 tolerogenic activity and confirm that interleukin-10 production by DC-10 is necessary but not sufficient to promote Tr1 cells at high frequency. These new insights into the role of HLA-G in DC-10-mediated induction of Tr1 cells provide additional information for clinical use in Tr1- or DC-10-based cell therapy approaches.

  2. Bioconcentration of polybrominated diphenyl ethers and organochlorine pesticides in algae is an important contaminant route to higher trophic levels.

    PubMed

    Qiu, Yao-Wen; Zeng, Eddy Y; Qiu, Hanlin; Yu, Kefu; Cai, Shuqun

    2017-02-01

    Persistent organic pollutants (POPs) present in water may be bioconcentrated in phytoplankton and further transferred into higher trophic levels. In the present study, seawater, sediment, phytoplankton and macroalgae (Ulva lactuca L.) samples were collected from two estuarine bays in South China and analyzed for 24 polybrominated diphenyl ethers (PBDEs) and 22 organochlorine pesticides (OCPs). The concentrations of PBDE congeners except BDE-209 were low in both phytoplankton and Ulva. BDE-209 was the predominant congener in phytoplankton and Ulva, accounting for 89.5% and 86.6% of the total average concentrations of PBDEs (48.5 and 4.1ngg(-1)dw), respectively. The average concentrations of DDTs, HCHs and 1-chloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDMU) in phytoplankton were 398, 241 and 11.3ngg(-1)dw, respectively, while those of DDTs and HCHs in Ulva were 8.4 and 33.1ngg(-1)dw. The levels of both PBDEs and OCPs were an order of magnitude higher in phytoplankton than in Ulva, indicating that phytoplankton with larger surface areas have higher uptake efficiency for POPs than Ulva. Bioconcentration factors (BCFs) of DDT and PBDE in phytoplankton from the two bays were in the range of 10(5)-10(6), suggesting that bioconcentration may be one of the key sources of POPs and algae can be an important route for POPs to move toward higher trophic levels.

  3. Word recognition in noise at higher-than-normal levels: Decreases in scores and increases in masking

    NASA Astrophysics Data System (ADS)

    Dubno, Judy R.; Horwitz, Amy R.; Ahlstrom, Jayne B.

    2005-08-01

    Under certain conditions, speech recognition in noise decreases above conversational levels when signal-to-noise ratio is held constant. The current study was undertaken to determine if nonlinear growth of masking and the subsequent reduction in ``effective'' signal-to-noise ratio accounts for this decline. Nine young adults with normal hearing listened to monosyllabic words at three levels in each of three levels of a masker shaped to match the speech spectrum. An additional low-level noise equated audibility by producing equivalent masked thresholds for all subjects. If word recognition was determined entirely by signal-to-noise ratio and was independent of overall speech and masker levels, scores at a given signal-to-noise ratio should remain constant with increasing level. Masked pure-tone thresholds measured in the speech-shaped maskers increased linearly with increasing masker level at lower frequencies but nonlinearly at higher frequencies, consistent with nonlinear growth of upward spread of masking that followed the peaks in the spectrum of the speech-shaped masker. Word recognition declined significantly with increasing level when signal-to-noise ratio was held constant which was attributed to nonlinear growth of masking and reduced ``effective'' signal-to-noise ratio at high speech-shaped masker levels, as indicated by audibility estimates based on the Articulation Index.

  4. Does peer learning or higher levels of e-learning improve learning abilities? A randomized controlled trial.

    PubMed

    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.

  5. 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

  6. 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.

  7. Criteria for high-level expression of a fungal laccase gene in transgenic maize.

    PubMed

    Hood, Elizabeth E; Bailey, Michele R; Beifuss, Katherine; Magallanes-Lundback, Maria; Horn, Michael E; Callaway, Evelyn; Drees, Carol; Delaney, Donna E; Clough, Richard; Howard, John A

    2003-03-01

    Expression of industrial enzymes in transgenic plants offers an alternative system to fungal fermentation for large-scale production. Very high levels of expression are required to make the enzymes cost-effective. We tested several parameters to determine the best method for achieving high levels of expression for a fungal laccase gene. Transgenic maize plants were generated using an Agrobacterium-mediated system. The molecular parameters that induced the highest expression were the maize embryo-preferred globulin 1 promoter and targeting of the protein to the cell wall. Two independent transgenic events that yielded multiple clonal plants were characterized in detail. Independent transgenic events 01 and 03 contained two or one copies of T-DNA, respectively. Plants derived from a single transgenic event varied in expression level, and the variation in expression levels was heritable. Within the seed, expression in these plants was primarily within the embryo, and was associated with seed browning and limited germination. High oil germplasm was used to increase germination, as well as to assist in increasing expression 20-fold in five generations through breeding and selection.

  8. 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...

  9. 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

  10. 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

  11. FMRP Expression Levels in Mouse Central Nervous System Neurons Determine Behavioral Phenotype.

    PubMed

    Arsenault, Jason; Gholizadeh, Shervin; Niibori, Yosuke; Pacey, Laura K; Halder, Sebok K; Koxhioni, Enea; Konno, Ayumu; Hirai, Hirokazu; Hampson, David R

    2016-12-01

    Fragile X mental retardation protein (FMRP) is absent or highly reduced in Fragile X Syndrome, a genetic disorder causing cognitive impairment and autistic behaviors. Previous proof-of-principle studies have demonstrated that restoring FMRP in the brain using viral vectors can improve pathological abnormalities in mouse models of fragile X. However, unlike small molecule drugs where the dose can readily be adjusted during treatment, viral vector-based biological therapeutic drugs present challenges in terms of achieving optimal dosing and expression levels. The objective of this study was to investigate the consequences of expressing varying levels of FMRP selectively in neurons of Fmr1 knockout and wild-type (WT) mice. A wide range of neuronal FMRP transgene levels was achieved in individual mice after intra-cerebroventricular administration of adeno-associated viral vectors coding for FMRP. In all treated knockout mice, prominent FMRP transgene expression was observed in forebrain structures, whereas lower levels were present in more caudal regions of the brain. Reduced levels of the synaptic protein PSD-95, elevated levels of the transcriptional modulator MeCP2, and abnormal motor activity, anxiety, and acoustic startle responses in Fmr1 knockout mice were fully or partially rescued after expression of FMRP at about 35-115% of WT expression, depending on the brain region examined. In the WT mouse, moderate FMRP over-expression of up to about twofold had little or no effect on PSD-95 and MeCP2 levels or on behavioral endophenotypes. In contrast, excessive over-expression in the Fmr1 knockout mouse forebrain (approximately 2.5-6-fold over WT) induced pathological motor hyperactivity and suppressed the startle response relative to WT mice. These results delineate a range of FMRP expression levels in the central nervous system that confer phenotypic improvement in fragile X mice. Collectively, these findings are pertinent to the development of long-term curative

  12. 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.

  13. 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.

  14. 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

  15. KCTD11 expression in medulloblastoma is lower than in adult cerebellum and higher than in neural stem cells.

    PubMed

    Zawlik, Izabela; Zakrzewska, Magdalena; Witusik, Monika; Golanska, Ewa; Kulczycka-Wojdala, Dominika; Szybka, Malgorzata; Piaskowski, Sylwester; Wozniak, Krystyna; Zakrzewski, Krzysztof; Papierz, Wielislaw; Liberski, Pawel P; Rieske, Piotr

    2006-10-01

    Medulloblastoma (MB) is the most common malignant brain tumor of childhood, and the most frequent associated genetic alteration is loss of heterozygosity on chromosome region 7p13. Two genes mapping to this region, KCTD11 (alias REN) and HIC1, have been proposed as involved in MB pathogenesis. We used real-time polymerase chain reaction in 20 tissue samples of primary MB to examine the transcriptional level of the two genes, with reference to two types of controls: adult cerebellum and fetal neural stem cells. A significant reduction of KCTD11 expression relative to adult normal cerebellum was detected in 14 of 20 (70%) of MB samples. Neural stem cells had even lower levels of KCTD11 expression than did MB. HIC1 gene expression was low ( approximately 100 times lower than KCTD11 expression) in MB, and low also in both adult cerebellum and neural stem cells. Hypermethylation of the 5'UTR or the central region of HIC1 (or both) was detected in a significant number of MB samples, as well as in cerebellum and neural stem cells. Our data suggest that KCTD11 may play an important role in MB tumorigenesis, but do not support the role of HIC1 in this tumor development. We argue that recognition of the gene or genes important in MB tumorigenesis depends in part on defining an appropriate control.

  16. 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

  17. 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.

  18. Secondary Data Analytics of Aquaporin Expression Levels in Glioblastoma Stem-Like Cells

    PubMed Central

    Isokpehi, Raphael D; Wollenberg Valero, Katharina C; Graham, Barbara E; Pacurari, Maricica; Sims, Jennifer N; Udensi, Udensi K; Ndebele, Kenneth

    2015-01-01

    Glioblastoma is the most common brain tumor in adults in which recurrence has been attributed to the presence of cancer stem cells in a hypoxic microenvironment. On the basis of tumor formation in vivo and growth type in vitro, two published microarray gene expression profiling studies grouped nine glioblastoma stem-like (GS) cell lines into one of two groups: full (GSf) or restricted (GSr) stem-like phenotypes. Aquaporin-1 (AQP1) and aquaporin-4 (AQP4) are water transport proteins that are highly expressed in primary glial-derived tumors. However, the expression levels of AQP1 and AQP4 have not been previously described in a panel of 92 glioma samples. Therefore, we designed secondary data analytics methods to determine the expression levels of AQP1 and AQP4 in GS cell lines and glioblastoma neurospheres. Our investigation also included a total of 2,566 expression levels from 28 Affymetrix microarray probe sets encoding 13 human aquaporins (AQP0–AQP12); CXCR4 (the receptor for stromal cell derived factor-1 [SDF-1], a potential glioma stem cell therapeutic target]); and PROM1 (gene encoding CD133, the widely used glioma stem cell marker). Interactive visual representation designs for integrating phenotypic features and expression levels revealed that inverse expression levels of AQP1 and AQP4 correlate with distinct phenotypes in a set of cell lines grouped into full and restricted stem-like phenotypes. Discriminant function analysis further revealed that AQP1 and AQP4 expression are better predictors for tumor formation and growth types in glioblastoma stem-like cells than are CXCR4 and PROM1. Future investigations are needed to characterize the molecular mechanisms for inverse expression levels of AQP1 and AQP4 in the glioblastoma stem-like neurospheres. PMID:26279619

  19. Association between sarcopenia and higher-level functional capacity in daily living in community-dwelling elderly subjects in Japan.

    PubMed

    Tanimoto, Yoshimi; Watanabe, Misuzu; Sun, Wei; Sugiura, Yumiko; Tsuda, Yuko; Kimura, Motoshi; Hayashida, Itsushi; Kusabiraki, Toshiyuki; Kono, Koichi

    2012-01-01

    This study aimed to determine the association between sarcopenia, defined by muscle mass, muscle strength, and physical performance, and higher-level functional capacity in community-dwelling Japanese elderly people. Subjects were 1158 elderly, community-dwelling Japanese people aged 65 or older. We used bioelectrical impedance analysis to measure muscle mass, grip strength to measure muscle strength, and usual walking speed to measure physical performance. Sarcopenia was characterized by low muscle mass, plus low muscle strength or low physical performance. Subjects without low muscle mass, low muscle strength, and low physical performance were classified as "normal." Examination of higher-level functional capacity was performed using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). The TMIG-IC is a 13-item questionnaire completed by the subject; it contains five questions on self-maintenance and four questions each on intellectual activity and social role. Sarcopenia was identified in 11.3% and 10.7% of men and women, respectively. The percentage of disability for instrumental activities of daily living (IADL) was 39.0% in men with sarcopenia and 30.6% in women with sarcopenia. After adjustment for age, in men, sarcopenia was significantly associated with IADL disability compared with intermediate and normal subjects. In women, sarcopenia was significantly associated with every subscale of the TMIG-IC disability compared with intermediate and normal subjects. This study revealed that sarcopenia, defined by muscle mass, muscle strength, and physical performance, had a significant association with disability in higher-level functional capacity in elderly Japanese subjects. Interventions to prevent sarcopenia may prevent higher-level functional disability among elderly people.

  20. Histidine tag fusion increases expression levels of active recombinant amelogenin in Escherichia coli.

    PubMed

    Svensson, Johan; Andersson, Christer; Reseland, Janne E; Lyngstadaas, Petter; Bülow, Leif

    2006-07-01

    Amelogenin is a dental enamel matrix protein involved in formation of dental enamel. In this study, we have expressed two different recombinant murine amelogenins in Escherichia coli: the untagged rM179, and the histidine tagged rp(H)M180, identical to rM179 except that it carries the additional N-terminal sequence MRGSHHHHHHGS. The effects of the histidine tag on expression levels, and on growth properties of the amelogenin expressing cells were studied. Purification of a crude protein extract containing rp(H)M180 was also carried out using IMAC and reverse-phase HPLC. The results of this study showed clearly that both growth properties and amelogenin expression levels were improved for E. coli cells expressing the histidine tagged amelogenin rp(H)M180, compared to cells expressing the untagged amelogenin rM179. The positive effect of the histidine tag on amelogenin expression is proposed to be due to the hydrophilic nature of the histidine tag, generating a more hydrophilic amelogenin, which is more compatible with the host cell. Human osteoblasts treated with the purified rp(H)M180 showed increased levels of secreted osteocalcin, compared to untreated cells. This response was similar to cells treated with enamel matrix derivate, mainly composed by amelogenin, suggesting that the recombinant protein is biologically active. Thus, the histidine tag favors expression and purification of biologically active recombinant amelogenin.

  1. Association between higher expression of interleukin-8 (IL-8) and haplotype −353A/−251A/+678T of IL-8 gene with preeclampsia

    PubMed Central

    Sun, Lei; Mao, Dongwei; Cai, Yan; Tan, Wenhua; Hao, Yanlan; Li, Lin; Liu, Wei

    2016-01-01

    Abstract Preeclampsia (PE) is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide. The present study was performed to investigate the role of a CXC chemokine interleukin-8 (IL-8), in the pathogenesis of PE. IL-8 expression levels were assessed in placental and serum samples from 160 pregnant women with PE (N = 68 severe, 92 mild) and 140 healthy donors. Results from enzyme-linked immunosorbent assay showed that the concentration of serum IL-8 in PE patients (180.27 ± 5.81 ng/L) was significantly higher than that in healthy controls (41.57 ± 5.67 ng/L). Patients with severe PE had even higher serum IL-8 levels. Similar messenger RNA and protein expression patterns of IL-8 in placental tissues were confirmed by quantitative real-time polymerase chain reaction and immunohistochemical assay (N = 30 each in the mild PE, severe PE, and control groups). In addition, single nucleotide polymorphisms of IL-8 gene were detected with polymerase chain reaction-restricted fragment length polymorphism/SSP. The frequency of IL-8-251A allele was significantly higher than that in controls (58.4% vs 48.9%, P < 0.05). The occurrence frequency of haplotype −353A/−251A/+678T (AAT) in PE subjects was 27.2% as compared to 21.9% in the control participants (P < 0.05). Our study reveals that IL-8 expression is positively associated with the severity of PE. Presence of haplotype AAT in pregnant women appears to be a risk factor for PE. PMID:28033248

  2. CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception.

    PubMed

    Sciaranghella, Gaia; Wang, Cuiwei; Hu, Haihong; Anastos, Kathryn; Merhi, Zaher; Nowicki, Marek; Stanczyk, Frank Z; Greenblatt, Ruth M; Cohen, Mardge; Golub, Elizabeth T; Watts, D Heather; Alter, Galit; Young, Mary A; Tsibris, Athe M N

    2015-11-01

    Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P < .01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use were associated with increased peripheral T-cell CCR5 expression.

  3. CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception

    PubMed Central

    Sciaranghella, Gaia; Wang, Cuiwei; Hu, Haihong; Anastos, Kathryn; Merhi, Zaher; Nowicki, Marek; Stanczyk, Frank Z.; Greenblatt, Ruth M.; Cohen, Mardge; Golub, Elizabeth T.; Watts, D. Heather; Alter, Galit; Young, Mary A.; Tsibris, Athe M. N.

    2015-01-01

    Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4+ and CD8+ T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P < .01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use were associated with increased peripheral T-cell CCR5 expression. PMID:25895986

  4. High-level expression of a cloned HLA heavy chain gene introduced into mouse cells on a bovine papillomavirus vector.

    PubMed

    DiMaio, D; Corbin, V; Sibley, E; Maniatis, T

    1984-02-01

    A gene encoding the heavy chain of an HLA human histocompatibility antigen was isolated from a library of human DNA by recombination and selection in vivo. After insertion into a bovine papillomavirus (BPV) DNA expression vector, the gene was introduced into cultured mouse cells. Cells transformed with the HLA-BPV plasmids did not appear to contain extrachromosomal viral DNA, whereas BPV recombinants usually replicated as plasmids in transformed cell lines. Large amounts of HLA RNA were produced by the transformed cells, and the rate of synthesis of human heavy chain was several-fold higher than in the JY cell line, a well-characterized human lymphoblastoid cell line which expresses high levels of surface HLA antigen. Substantial amounts of human heavy chain accumulated in the transformed cells, and HLA antigen was present at the cell surface. These observations establish the feasibility of using BPV vectors to study the structure and function of HLA antigens and the expression of cloned HLA genes.

  5. The iron-sensing fur regulator controls expression timing and levels of salmonella pathogenicity island 2 genes in the course of environmental acidification.

    PubMed

    Choi, Eunna; Kim, Hyunkeun; Lee, Hwiseop; Nam, Daesil; Choi, Jeongjoon; Shin, Dongwoo

    2014-06-01

    In order to survive inside macrophages, Salmonella produces a series of proteins encoded by genes within Salmonella pathogenicity island 2 (SPI-2). In the present study, we report that Fur, a central regulator of iron utilization, negatively controls the expression of SPI-2 genes. Time course analysis of SPI-2 expression after the entry of Salmonella into macrophages revealed that SPI-2 genes are induced earlier and at higher levels in the absence of the Fur regulator. It was hypothesized that Fur repressed the SPI-2 expression that was activated during acidification of the phagosome. Indeed, as pH was lowered from pH 7.0 to pH 5.5, the lack of Fur enabled SPI-2 gene expression to be induced at higher pH and to be expressed at higher levels. Fur controlled SPI-2 genes via repression of the SsrB response regulator, a primary activator of SPI-2 expression. Fur repressed ssrB expression both inside macrophages and under acidic conditions, which we ascribe to the direct binding of Fur to the ssrB promoter. Our study suggests that Salmonella could employ iron inside the phagosome to precisely control the timing and levels of SPI-2 expression inside macrophages.

  6. Effects of cell-cycle-dependent expression on random fluctuations in protein levels

    PubMed Central

    Soltani, Mohammad

    2016-01-01

    Expression of many genes varies as a cell transitions through different cell-cycle stages. How coupling between stochastic expression and cell cycle impacts cell-to-cell variability (noise) in the level of protein is not well understood. We analyse a model where a stable protein is synthesized in random bursts, and the frequency with which bursts occur varies within the cell cycle. Formulae quantifying the extent of fluctuations in the protein copy number are derived and decomposed into components arising from the cell cycle and stochastic processes. The latter stochastic component represents contributions from bursty expression and errors incurred during partitioning of molecules between daughter cells. These formulae reveal an interesting trade-off: cell-cycle dependencies that amplify the noise contribution from bursty expression also attenuate the contribution from partitioning errors. We investigate the existence of optimum strategies for coupling expression to the cell cycle that minimize the stochastic component. Intriguingly, results show that a zero production rate throughout the cell cycle, with expression only occurring just before cell division, minimizes noise from bursty expression for a fixed mean protein level. By contrast, the optimal strategy in the case of partitioning errors is to make the protein just after cell division. We provide examples of regulatory proteins that are expressed only towards the end of the cell cycle, and argue that such strategies enhance robustness of cell-cycle decisions to the intrinsic stochasticity of gene expression. PMID:28083102

  7. Effects of cell-cycle-dependent expression on random fluctuations in protein levels.

    PubMed

    Soltani, Mohammad; Singh, Abhyudai

    2016-12-01

    Expression of many genes varies as a cell transitions through different cell-cycle stages. How coupling between stochastic expression and cell cycle impacts cell-to-cell variability (noise) in the level of protein is not well understood. We analyse a model where a stable protein is synthesized in random bursts, and the frequency with which bursts occur varies within the cell cycle. Formulae quantifying the extent of fluctuations in the protein copy number are derived and decomposed into components arising from the cell cycle and stochastic processes. The latter stochastic component represents contributions from bursty expression and errors incurred during partitioning of molecules between daughter cells. These formulae reveal an interesting trade-off: cell-cycle dependencies that amplify the noise contribution from bursty expression also attenuate the contribution from partitioning errors. We investigate the existence of optimum strategies for coupling expression to the cell cycle that minimize the stochastic component. Intriguingly, results show that a zero production rate throughout the cell cycle, with expression only occurring just before cell division, minimizes noise from bursty expression for a fixed mean protein level. By contrast, the optimal strategy in the case of partitioning errors is to make the protein just after cell division. We provide examples of regulatory proteins that are expressed only towards the end of the cell cycle, and argue that such strategies enhance robustness of cell-cycle decisions to the intrinsic stochasticity of gene expression.

  8. Regulatory logic driving stable levels of defective proventriculus expression during terminal photoreceptor specification in flies.

    PubMed

    Yan, Jenny; Anderson, Caitlin; Viets, Kayla; Tran, Sang; Goldberg, Gregory; Small, Stephen; Johnston, Robert J

    2017-03-01

    How differential levels of gene expression are controlled in post-mitotic neurons is poorly understood. In the Drosophila retina, expression of the transcription factor Defective Proventriculus (Dve) at distinct cell type-specific levels is required for terminal differentiation of color- and motion-detecting photoreceptors. Here, we find that the activities of two cis-regulatory enhancers are coordinated to drive dve expression in the fly eye. Three transcription factors act on these enhancers to determine cell-type specificity. Negative autoregulation by Dve maintains expression from each enhancer at distinct homeostatic levels. One enhancer acts as an inducible backup ('dark' shadow enhancer) that is normally repressed but becomes active in the absence of the other enhancer. Thus, two enhancers integrate combinatorial transcription factor input, feedback and redundancy to generate cell type-specific levels of dve expression and stable photoreceptor fate. This regulatory logic may represent a general paradigm for how precise levels of gene expression are established and maintained in post-mitotic neurons.

  9. Regulation of DEK expression by AP-2α and methylation level of DEK promoter in hepatocellular carcinoma.

    PubMed

    Qiao, Ming-Xu; Li, Chun; Zhang, Ai-Qun; Hou, Ling-Ling; Yang, Juan; Hu, Hong-Gang

    2016-10-01

    DEK is overexpressed in multiple invasive tumors. However, the transcriptional regulatory mechanism of DEK remains unclear. In the present study, progressive-type truncation assay indicated that CpG2-2 (-167 bp/+35 bp) was the DEK core promoter, whose methylation inhibited DEK expression. Bisulfite genomic sequencing analysis indicated that the methylation levels of the DEK promoter in normal hepatic cells and tissues were higher than those in hepatocellular carcinoma (HCC) cells. TFSEARCH result revealed transcription factor binding sites in CpG2-2. Among the sites, the AP-2α binding site showed the most significant methylation difference; hence, AP-2α is a key transcription factor that regulates DEK expression. Point or deletion mutation of the AP-2α binding site significantly reduced the promoter activity. Chromatin immunoprecipitation assay demonstrated the binding of AP-2α to the core promoter. Furthermore, knock down of endogenous AP-2α downregulated DEK expression, whereas overexpression of AP-2α upregulated DEK expression. Thus, AP-2α is an important transcription factor of DEK expression, which is correlated with the methylation level of the DEK core promoter in HCC.

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

    PubMed

    Akbas, F; Aydin, Z

    2012-04-03

    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.

  11. Neuromodulation independently determines correlated channel expression and conductance levels in motor neurons of the stomatogastric ganglion.

    PubMed

    Temporal, Simone; Desai, Mohati; Khorkova, Olga; Varghese, Gladis; Dai, Aihua; Schulz, David J; Golowasch, Jorge

    2012-01-01

    Neuronal identity depends on the regulated expression of numerous molecular components, especially ionic channels, which determine the electrical signature of a neuron. Such regulation depends on at least two key factors, activity itself and neuromodulatory input. Neuronal electrical activity can modify the expression of ionic currents in homeostatic or nonhomeostatic fashion. Neuromodulators typically modify activity by regulating the properties or expression levels of subsets of ionic channels. In the stomatogastric system of crustaceans, both types of regulation have been demonstrated. Furthermore, the regulation of the coordinated expression of ionic currents and the channels that carry these currents has been recently reported in diverse neuronal systems, with neuromodulators not only controlling the absolute levels of ionic current expression but also, over long periods of time, appearing to modify their correlated expression. We hypothesize that neuromodulators may regulate the correlated expression of ion channels at multiple levels and in a cell-type-dependent fashion. We report that in two identified neuronal types, three ionic currents are linearly correlated in a pairwise manner, suggesting their coexpression or direct interactions, under normal neuromodulatory conditions. In each cell, some currents remain correlated after neuromodulatory input is removed, whereas the correlations between the other pairs are either lost or altered. Interestingly, in each cell, a different suite of currents change their correlation. At the transcript level we observe distinct alterations in correlations between channel mRNA amounts, including one of the cell types lacking a correlation under normal neuromodulatory conditions and then gaining the correlation when neuromodulators are removed. Synaptic activity does not appear to contribute, with one possible exception, to the correlated expression of either ionic currents or of the transcripts that code for the respective

  12. Krüppel expression levels are maintained through compensatory evolution of shadow enhancers

    PubMed Central

    Wunderlich, Zeba; Bragdon, Meghan D.J.; Vincent, Ben J.; White, Jonathan A.; Estrada, Javier; DePace, Angela H.

    2015-01-01

    Summary Many developmental genes are controlled by shadow enhancers, pairs of enhancers that drive overlapping expression patterns. We hypothesized that compensatory evolution can maintain the total expression of a gene while individual shadow enhancers diverge between species. To test this hypothesis, we analyzed expression driven by orthologous pairs of shadow enhancers from Drosophila melanogaster, Drosophila yakuba, and Drosophila pseudoobscura that control expression of Krüppel, a transcription factor that patterns the anterior-posterior axis of blastoderm embryos. We find that the expression driven by the pair of enhancers is conserved between these three species, but expression levels driven by the individual enhancers are not. Using sequence analysis and experimental perturbation, we show that each shadow enhancer is activated by different transcription factors. These results support the hypothesis that compensatory evolution can occur between shadow enhancers, which has implications for mechanistic and evolutionary studies of gene regulation. PMID:26344774

  13. Krüppel Expression Levels Are Maintained through Compensatory Evolution of Shadow Enhancers.

    PubMed

    Wunderlich, Zeba; Bragdon, Meghan D J; Vincent, Ben J; White, Jonathan A; Estrada, Javier; DePace, Angela H

    2015-09-22

    Many developmental genes are controlled by shadow enhancers—pairs of enhancers that drive overlapping expression patterns. We hypothesized that compensatory evolution can maintain the total expression of a gene, while individual shadow enhancers diverge between species. To test this hypothesis, we analyzed expression driven by orthologous pairs of shadow enhancers from Drosophila melanogaster, Drosophila yakuba, and Drosophila pseudoobscura that control expression of Krüppel, a transcription factor that patterns the anterior-posterior axis of blastoderm embryos. We found that the expression driven by the pair of enhancers is conserved between these three species, but expression levels driven by the individual enhancers are not. Using sequence analysis and experimental perturbation, we show that each shadow enhancer is regulated by different transcription factors. These results support the hypothesis that compensatory evolution can occur between shadow enhancers, which has implications for mechanistic and evolutionary studies of gene regulation.

  14. Role of endogenous cortistatin in the regulation of ghrelin system expression at pancreatic level under normal and obese conditions.

    PubMed

    Chanclón, Belén; Luque, Raúl M; Córdoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; Castaño, Justo P; Gracia-Navarro, Francisco; Martínez-Fuentes, Antonio J

    2013-01-01

    Ghrelin-system components [native ghrelin, In1-ghrelin, Ghrelin-O-acyltransferase enzyme (GOAT) and receptors (GHS-Rs)] are expressed in a wide variety of tissues, including the pancreas, where they exert different biological actions including regulation of neuroendocrine secretions, food intake and pancreatic function. The expression of ghrelin system is regulated by metabolic conditions (fasting/obesity) and is associated with the progression of obesity and insulin resistance. Cortistatin (CORT), a neuropeptide able to activate GHS-R, has emerged as an additional link in gut-brain interplay. Indeed, we recently reported that male CORT deficient mice (cort-/-) are insulin-resistant and present a clear dysregulation in the stomach ghrelin-system. The present work was focused at analyzing the expression pattern of ghrelin-system components at pancreas level in cort-/- mice and their control littermates (cort +/+) under low- or high-fat diet. Our data reveal that all the ghrelin-system components are expressed at the mouse pancreatic level, where, interestingly, In1-ghrelin was expressed at higher levels than native-ghrelin. Thus, GOAT mRNA levels were significantly lower in cort-/- mice compared with controls while native ghrelin, In1-ghrelin and GHS-R transcript levels remained unaltered under normal metabolic conditions. Moreover, under obese condition, a significant increase in pancreatic expression of native-ghrelin, In1-ghrelin and GHS-R was observed in obese cort+/+ but not in cort-/- mice. Interestingly, insulin expression and release was elevated in obese cort+/+, while these changes were not observed in obese cort-/- mice. Altogether, our results indicate that the ghrelin-system expression is clearly regulated in the pancreas of cort+/+ and cort -/- under normal and/or obesity conditions suggesting that this system may play relevant roles in the endocrine pancreas. Most importantly, our data demonstrate, for the first time, that endogenous CORT is essential

  15. A two-level hybrid evolutionary algorithm for modeling one-dimensional dynamic systems by higher-order ODE models.

    PubMed

    Cao, H Q; Kang, L S; Guo, T; Chen, Y P; de Garis, H

    2000-01-01

    This paper presents a new algorithm for modeling one-dimensional (1-D) dynamic systems by higher-order ordinary differential equation (HODE) models instead of the ARMA models as used in traditional time series analysis. A two-level hybrid evolutionary modeling algorithm (THEMA) is used to approach the modeling problem of HODE's for dynamic systems. The main idea of this modeling algorithm is to embed a genetic algorithm (GA) into genetic programming (GP), where GP is employed to optimize the structure of a model (the upper level), while a GA is employed to optimize the parameters of the model (the lower level). In the GA, we use a novel crossover operator based on a nonconvex linear combination of multiple parents which works efficiently and quickly in parameter optimization tasks. Two practical examples of time series are used to demonstrate the THEMA's effectiveness and advantages.

  16. MAP17 and SGLT1 Protein Expression Levels as Prognostic Markers for Cervical Tumor Patient Survival

    PubMed Central

    Perez, Marco; Praena-Fernandez, Juan M.; Felipe-Abrio, Blanca; Lopez-Garcia, Maria A.; Lucena-Cacace, Antonio; Garcia, Angel; Lleonart, Matilde; Roncador, Guiovanna; Marin, Juan J.; Carnero, Amancio

    2013-01-01

    MAP17 is a membrane-associated protein that is overexpressed in human tumors. Because the expression of MAP17 increases reactive oxygen species (ROS) generation through SGLT1 in cancer cells, in the present work, we investigated whether MAP17 and/or SGLT1 might be markers for the activity of treatments involving oxidative stress, such as cisplatin or radiotherapy. First, we confirmed transcriptional alterations in genes involved in the oxidative stress induced by MAP17 expression in HeLa cervical tumor cells and found that Hela cells expressing MAP17 were more sensitive to therapies that induce ROS than were parental cells. Furthermore, MAP17 increased glucose uptake through SGLT receptors. We then analyzed MAP17 and SGLT1 expression levels in cervical tumors treated with cisplatin plus radiotherapy and correlated the expression levels with patient survival. MAP17 and SGLT1 were expressed in approximately 70% and 50% of cervical tumors of different types, respectively, but they were not expressed in adenoma tumors. Furthermore, there was a significant correlation between MAP17 and SGLT1 expression levels. High levels of either MAP17 or SGLT1 correlated with improved patient survival after treatment. However, the patients with high levels of both MAP17 and SGLT1 survived through the end of this study. Therefore, the combination of high MAP17 and SGLT1 levels is a marker for good prognosis in patients with cervical tumors after cisplatin plus radiotherapy treatment. These results also suggest that the use of MAP17 and SGLT1 markers may identify patients who are likely to exhibit a better response to treatments that boost oxidative stress in other cancer types. PMID:23418532

  17. Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein

    PubMed Central

    Torres, Lidiane S.; Okumura, Jéssika V.; Silva, Danilo G. H.; Mimura, Kallyne K. O.; Belini-Júnior, Édis; Oliveira, Renan G.; Lobo, Clarisse L. C.; Oliani, Sonia M.; Bonini-Domingos, Claudia R.

    2016-01-01

    Sickle cell disease (SCD) is an inherited hemolytic anemia whose pathophysiology is driven by polymerization of the hemoglobin S (Hb S), leading to hemolysis and vaso-occlusive events. Inflammation is a fundamental component in these processes and a continuous inflammatory stimulus can lead to tissue damages. Thus, pro-resolving pathways emerge in order to restore the homeostasis. For example there is the annexin A1 (ANXA1), an endogenous anti-inflammatory protein involved in reducing neutrophil-endothelial interactions, accelerating neutrophil apoptosis and stimulating macrophage efferocytosis. We investigated the expression of ANXA1 in plasma of SCD patients and its relation with anemic, hemolytic and inflammatory parameters of the disease. Three SCD genotypes were considered: the homozygous inheritance for Hb S (Hb SS) and the association between Hb S and the hemoglobin variants D-Punjab (Hb SD) and C (Hb SC). ANXA1 and proinflammatory cytokines were quantified by ELISA in plasma of SCD patients and control individuals without hemoglobinopathies. Hematological and biochemical parameters were analyzed by flow cytometry and spectrophotometer. The plasma levels of ANXA1 were about three-fold lesser in SCD patients compared to the control group, and within the SCD genotypes the most elevated levels were found in Hb SS individuals (approximately three-fold higher). Proinflammatory cytokines were higher in SCD groups than in the control individuals. Anemic and hemolytic markers were higher in Hb SS and Hb SD genotypes compared to Hb SC patients. White blood cells and platelets count were higher in Hb SS genotype and were positively correlated to ANXA1 levels. We found that ANXA1 is down-regulated and differentially expressed within the SCD genotypes. Its expression seems to depend on the inflammatory, hemolytic and vaso-occlusive characteristics of the diseased. These data may lead to new biological targets for therapeutic intervention in SCD. PMID:27802331

  18. Abnormal expression levels of sMICA and NKG2D are correlated with poor prognosis in pancreatic cancer

    PubMed Central

    Chen, Jiong; Xu, Hong; Zhu, Xing-Xing

    2016-01-01

    Soluble major histocompatibility complex class I-related chain A molecules (sMICA) and natural-killer group 2 member D (NKG2D) not only correlate with tumorigenesis and progression, but also with tumor invasion and metastasis. In this study, we used immunohistochemistry to investigate the correlation and prognostic significance of the differential expression of sMICA and NKG2D in pancreatic carcinoma and paracarcinoma tissues from 70 patients with pancreatic carcinomas. The results showed that sMICA expression was significantly (P<0.05) higher in tumor tissues (67.1%) than that in adjacent nontumor tissues (31.4%), whereas NKG2D expression was significantly (P<0.001) lower in tumor tissues (32.9%) than that in adjacent nontumor tissues (60.0%). Spearman’s rank correlation test showed a negative correlation between the expression of sMICA and that of NKG2D (r=−0.676, P<0.001). Kaplan–Meier survival analysis showed that a high sMICA expression was significantly correlated with decreased disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001), while a high NKG2D expression was significantly associated with increased DFS (P=0.001) and OS (P=0.001) of the patients. Multivariate analysis showed that a high sMICA expression was an independent predictive factor for poor DFS (P<0.001) and OS (P=0.012); but low NKG2D expression was not an independent prognostic factor for poor DFS (P=0.238) and OS (P=0.574). In conclusion, our findings suggest that the expression levels of sMICA and NKG2D are abnormal and negatively correlated with one another in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for the prognosis of pancreatic carcinoma. PMID:26730197

  19. 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

  20. 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

  1. High-level expression and phosphorylation of phytochrome B modulates flowering time in Arabidopsis.

    PubMed

    Hajdu, Anita; Ádám, Éva; Sheerin, David J; Dobos, Orsolya; Bernula, Péter; Hiltbrunner, Andreas; Kozma-Bognár, László; Nagy, Ferenc

    2015-09-01

    Optimal timing of flowering in higher plants is crucial for successful reproduction and is coordinated by external and internal factors, including light and the circadian clock. In Arabidopsis, light-dependent stabilization of the rhythmically expressed CONSTANS (CO) is required for the activation of FLOWERING LOCUS T (FT), resulting in the initiation of flowering. Phytochrome A and cryptochrome photoreceptors stabilize CO in the evening by attenuating the activity of the CONSTITUTIVE PHOTOMORPHOGENIC 1-SUPPRESSOR OF PHYA-105 1 (COP1-SPA1) ubiquitin ligase complex, which promotes turnover of CO. In contrast, phytochrome B (phyB) facilitates degradation of CO in the morning and delays flowering. Accordingly, flowering is accelerated in phyB mutants. Paradoxically, plants overexpressing phyB also show early flowering, which may arise from an early phase of rhythmic CO expression. Here we demonstrate that overexpression of phyB induces FT transcription at dusk and in the night without affecting the phase or level of CO transcription. This response depends on the light-activated Pfr form of phyB that inhibits the function of the COP1-SPA1 complex by direct interactions. Our data suggest that attenuation of COP1 activity results in the accumulation of CO protein and subsequent induction of FT. We show that phosphorylation of Ser-86 inhibits this function of phyB by accelerating dark reversion and thus depletion of Pfr forms in the night. Our results explain the early flowering phenotype of phyB overexpression and reveal additional features of the molecular machinery by which photoreceptors mediate photoperiodism.

  2. Prostate cancer metastatic to bone has higher expression of the calcium-sensing receptor (CaSR) than primary prostate cancer

    PubMed Central

    Feng, Jie; Xu, Xiaojun; Li, Bo; Brown, Edward; Farris, Alton B.; Sun, Shi-Yong; Yang, Jenny J.

    2015-01-01

    The calcium-sensing receptor (CaSR) is the principal regulator of the secretion of parathyroid hormone and plays key roles in extracellular calcium (Ca2+o) homeostasis. It is also thought to participate in the development of cancer, especially bony metastases of breast and prostate cancer. However, the expression of CaSR has not been systematically analyzed in prostate cancer from patients with or without bony metastases. By comparing human prostate cancer tissue sections in microarrays, we found that the CaSR was expressed in both normal prostate and primary prostate cancer as assessed by immunohistochemistry (IHC). We used two methods to analyze the expression level of CaSR. One was the pathological score read by a pathologist, the other was the positivity% obtained from the Aperio positive pixel count algorithm. Both of the methods gave consistent results. Metastatic prostate cancer tissue obtained from bone had higher CaSR expression than primary prostate cancer (P <0.05). The expression of CaSR in primary prostate cancers of patients with metastases to tissues other than bone was not different from that in primary prostate cancer of patients with or without bony metastases (P >0.05). The expression of CaSR in cancer tissue was not associated with the stage or status of differentiation of the cancer. These results suggest that CaSR may have a role in promoting bony metastasis of prostate cancer, hence raising the possibility of reducing the risk of such metastases with CaSR-based therapeutics. PMID:26065011

  3. A simple and immediate method for simultaneously evaluating expression level and plasmid maintenance in yeast.

    PubMed

    Ishii, Jun; Izawa, Keiko; Matsumura, Shizuka; Wakamura, Kanako; Tanino, Takanori; Tanaka, Tsutomu; Ogino, Chiaki; Fukuda, Hideki; Kondo, Akihiko

    2009-06-01

    To allow the comprehensive assessments of yeast expression systems, a simple and immediate method for simultaneously evaluating the expression level and plasmid maintenance in yeast was demonstrated. This method uses green fluorescent protein (GFP) and flow cytometry (FCM) and is characterized by a dual analysis of the average intensity of GFP fluorescence and the population of GFP-expressing cells. The FCM analysis of GFP fluorescence intensity rapidly quantifies the expression level without complex manipulations, such as the enzymatic reaction of a lacZ reporter assay. Moreover, the single-cell analysis revealed that the proportion of cells expressing GFP in the cell cluster reflects the plasmid retention rate; therefore, the FCM analysis of the GFP-expressing population allows the immediate estimation of the plasmid retention rate without the 2- or 3-day incubation required for colony counting. We show that the FCM analysis with GFP reporter is a suitable method to explore the hopeful expression vector and host strain or establish the several expression systems exhibiting the characteristic properties in yeast.

  4. Gene expression and nucleotide composition are associated with genic methylation level in Oryza sativa

    PubMed Central

    2014-01-01

    Background The methylation of cytosines at CpG dinucleotides, which plays an important role in gene expression regulation, is one of the most studied epigenetic modifications. Thus far, the detection of DNA methylation has been determined mostly by experimental methods, which are not only prone to bench effects and artifacts but are also time-consuming, expensive, and cannot be easily scaled up to many samples. It is therefore useful to develop computational prediction methods for DNA methylation. Our previous studies highlighted the existence of correlations between the GC content of the third codon position (GC3), methylation, and gene expression. We thus designed a model to predict methylation in Oryza sativa based on genomic sequence features and gene expression data. Results We first derive equations to describe the relationship between gene methylation levels, GC3, expression, length, and other gene compositional features. We next assess gene compositional features involving sixmers and their association with methylation levels and other gene level properties. By applying our sixmer-based approach on rice gene expression data we show that it can accurately predict methylation (Pearson’s correlation coefficient r = 0.79) for the majority (79%) of the genes. Matlab code with our model is included. Conclusions Gene expression variation can be used as predictors of gene methylation levels. PMID:24447369

  5. High levels of protein expression using different mammalian CMV promoters in several cell lines.

    PubMed

    Xia, Wei; Bringmann, Peter; McClary, John; Jones, Patrick P; Manzana, Warren; Zhu, Ying; Wang, Soujuan; Liu, Yi; Harvey, Susan; Madlansacay, Mary Rose; McLean, Kirk; Rosser, Mary P; MacRobbie, Jean; Olsen, Catherine L; Cobb, Ronald R

    2006-01-01

    With the recent completion of the human genome sequencing project, scientists are faced with the daunting challenge of deciphering the function of these newly found genes quickly and efficiently. Equally as important is to produce milligram quantities of the therapeutically relevant gene products as quickly as possible. Mammalian expression systems provide many advantages to aid in this task. Mammalian cell lines have the capacity for proper post-translational modifications including proper protein folding and glycosylation. In response to the needs described above, we investigated the protein expression levels driven by the human CMV in the presence or absence of intron A, the mouse and rat CMV promoters with intron A, and the MPSV promoter in plasmid expression vectors. We evaluated the different promoters using an in-house plasmid vector backbone. The protein expression levels of four genes of interest driven by these promoters were evaluated in HEK293EBNA and CHO-K1 cells. Stable and transient transfected cells were utilized. In general, the full-length human CMV, in the presence of intron A, gave the highest levels of protein expression in transient transfections in both cell lines. However, the MPSV promoter resulted in the highest levels of stable protein expression in CHO-K1 cells. Using the CMV driven constitutive promoters in the presence of intron A, we have been able to generate >10 microg/ml of recombinant protein using transient transfections.

  6. TDP-43 aggregation mirrors TDP-43 knockdown, affecting the expression levels of a common set of proteins

    PubMed Central

    Prpar Mihevc, S.; Baralle, Marco; Buratti, Emanuele; Rogelj, Boris

    2016-01-01

    TDP-43 protein plays an important role in regulating transcriptional repression, RNA metabolism, and splicing. Typically it shuttles between the nucleus and the cytoplasm to perform its functions, while abnormal cytoplasmic aggregation of TDP-43 has been associated with neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). For the purpose of this study we selected a set of proteins that were misregulated following silencing of TDP-43 and analysed their expression in a TDP-43-aggregation model cell line HEK293 Flp-in Flag-TDP-43-12x-Q/N F4L. Following TDP-43 sequestration in insoluble aggregates, we observed higher nuclear levels of EIF4A3, and POLDIP3β, whereas nuclear levels of DNMT3A, HNRNPA3, PABPC1 and POLDIP3α dropped, and cytoplasmic levels of RANBP1 dropped. In addition, immunofluorescence signal intensity quantifications showed increased nuclear expression of HNRNPL and YARS, and downregulation of cytoplasmic DPCD. Furthermore, cytoplasmic levels of predominantly nuclear protein ALYREF increased. In conclusion, by identifying a common set of proteins that are differentially expressed in a similar manner in these two different conditions, we show that TDP-43 aggregation has a comparable effect to TDP-43 knockdown. PMID:27665936

  7. Inconformity of CXCL3 Plasma Level and Placenta Expression in Preeclampsia and Its Effect on Trophoblast Viability and Invasion

    PubMed Central

    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

  8. The formation of occlusion-derived virus is affected by the expression level of ODV-E25.

    PubMed

    Chen, Lin; Yang, Rui; Hu, Xiaolong; Xiang, Xingwei; Yu, Shaofang; Wu, Xiaofeng

    2013-05-01

    Odv-e25 is a core gene of baculoviruses and encodes a 25.5 kDa protein located on both budded virus (BV) and occlusion-derived virus (ODV). Our previous study demonstrated that ODV-E25 was required for the formation of intranuclear microvesicles and ODV, and an odv-e25 deletion mutant could be rescued by re-expression of odv-e25 under its native promoter. To investigate the functions of ODV-E25 expression level on ODV formation, the promoter of ie-1 (pIE1), the odv-e25 native promoter, and the polyhedrin promoter (pPH) were used to direct odv-e25 expression. Our results showed that the production of ODV-E25 under its native promoter was higher than that under pIE1 but lower than that under pPH. Viral DNA replication and budded viruses (BVs) production showed that expression of odv-e25 under pIE1 and pPH could not completely repair the defects caused by the deletion of ODV-E25, while expression under its native promoter did. Electron microscopy showed that intranuclear microvesicles were found in all the constructs transfected cells except the odv-e25-null virus. However, mature ODVs only were detected in cells transfected with virus in which odv-e25 was expressed under its native or polyhedrin promoter. These results indicated that the formation occlusion-derived virus was affected by the expression level of ODV-E25.

  9. Expression of heat shock protein 70 is altered by age and diet at the level of transcription.

    PubMed Central

    Heydari, A R; Wu, B; Takahashi, R; Strong, R; Richardson, A

    1993-01-01

    Because heat shock proteins have been shown to play a critical role in protecting cells from hyperthermia and other types of physiological stresses, it was of interest to determine what effect age and caloric restriction have on the ability of cells to regulate the expression of heat shock protein 70 (hsp70), the most prominent and most evolutionarily conserved of the heat shock proteins. Caloric restriction is the only experimental manipulation known to retard aging and increase survival of mammals. The ability of hepatocytes isolated from young/adult (4- to 7-month-old) and old (22- to 28-month-old) male Fischer F344 rats fed ad libitum or a caloric restriction diet (60% of the content of the ad libitum diet) to express hsp70 was determined after a mild heat shock (42.5 degrees C for 30 min). We found that the induction of hsp70 synthesis and mRNA levels by heat shock was 40 to 50% lower in hepatocytes isolated from old rats than in hepatocytes isolated from young rats. Using in situ hybridization, we found that essentially all hepatocytes from the young/adult and old rats expressed hsp70 in response to heat shock; therefore, the age-related decrease in the induction of hsp70 expression was not due to an age-related accumulation of cells that do not respond to heat shock. Measurements of hsp70 mRNA stability and hsp70 transcription demonstrated that the age-related decline in hsp70 expression arose from a decline in hsp70 transcription. Interestingly, the age-related decline in the induction of hsp70 expression was reversed by caloric restriction; e.g., the induction of hsp70 synthesis, mRNA levels, and nuclear transcription were significantly higher in hepatocytes isolated from old rats fed the caloric restricted diet than in hepatocytes isolated from old rats fed ad libitum. The levels of the heat shock transcription factor in nuclear extracts isolated from heat-shocked hepatocytes were measured in a gel shift assay. Binding of the heat shock transcription

  10. Association between Duffy antigen receptor for chemokines expression and levels of inflammation markers in sickle cell anemia patients.

    PubMed

    Nebor, Danitza; Durpes, Marie Claude; Mougenel, Danielle; Mukisi-Mukaza, Martin; Elion, Jacques; Hardy-Dessources, Marie-Dominique; Romana, Marc

    2010-07-01

    Since inflammation plays a prominent role in the pathogenesis of sickle cell anemia (SCA) and Duffy antigen receptor for chemokines (DARC) modulates the function of inflammatory processes, we analyzed the relationship between the erythrocyte DARC phenotype and clinical expression of SCA. DARC locus was genotyped in 212 SS adult patients followed by the sickle cell center of Guadeloupe (French West Indies). After patients' stratification according to RBC DARC expression, the prevalence of renal disease, leg ulcers, priapism and osteonecrosis was compared between patient groups as well as hematological variables and plasma levels of chemokines. Duffy-positive patients exhibited higher counts of white blood cells (9.95+/-2.36 vs 8.88+/-2.32 10(9)/L, p=0.0066), polynuclear neutrophils (5.1+/-1.73 vs 4.51+/-1.71 10(9)/L, p=0.0227), higher plasma levels of IL-8 (4.46+/-1.22 vs 1.47+/-0.5 pg/mL, p=0.0202) and RANTES (27.8+/-4.3 vs 18.1+/-2.3 ng/mL, p=0.04) than Duffy-negative patients. No association was detected between RBC expression of DARC and the studied complications.

  11. Expression of FGF23 is correlated with serum phosphate level in isolated fibrous dysplasia.

    PubMed

    Kobayashi, Keisuke; Imanishi, Yasuo; Koshiyama, Hiroyuki; Miyauchi, Akimitsu; Wakasa, Kenichi; Kawata, Takehisa; Goto, Hitoshi; Ohashi, Hirotsugu; Koyano, Hajime M; Mochizuki, Ryuichi; Miki, Takami; Inaba, Masaaki; Nishizawa, Yoshiki

    2006-04-11

    Fibrous dysplasia (FD) patients sometimes suffer from concomitant hypophosphatemic rickets/osteomalacia, resulting from renal phosphate wasting. It was recently reported that FD tissue in the patients with McCune-Albright syndrome (MAS) expressed fibroblast growth factor-23 (FGF-23), which is now known to be as a pathogenic phosphaturic factor in patients with oncogenic osteomalacia and X-linked hypophosphatemic rickets. Since it remains controversial whether serum phosphate levels are influenced by FGF23 expressions in FD tissue, isolated FD patients without MAS syndrome were examined for the relationship between FGF23 expressions, circulating levels of FGF-23 and phosphate to negate the effects of MAS-associated endocrine abnormalities on serum phosphate. Eighteen paraffin embedded FD tissues and 2 frozen tissues were obtained for the study. Sixteen of 18 isolated FD tissues were successfully analyzed GNAS gene, which exhibited activated mutations observed in MAS. Eight of 16 FD tissues, which exhibited GNAS mutations, revealed positive staining for FGF-23. These evidence indicate that postzygotic activated mutations of GNAS is necessary for the FD tissue formation by mosaic distribution of mutated osteogenic cell lineage, but is not sufficient to elevate FGF23 expression causing generalized osteomalacia with severe renal phosphate wasting. The expression level of FGF23 in isolated FD tissue with hypophosphatemic osteomalacia determined by real-time PCR was abundant close to the levels in OOM tumors. Osteoblasts/osteocytes in woven bone were predominant source of circulating FGF-23 in FD tissues by immunohistochemistry. A negative correlation of the intensity of FGF-23 staining with serum inorganic phosphate levels indicated that the expression of FGF23 in focal FD tissues could be a prominent determinant of serum phosphate levels in isolated FD patient. These data provide novel insights into the regulatory mechanism of serum inorganic phosphate levels in

  12. 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

  13. Age-dependent lower or higher levels of hair mercury in autistic children than in healthy controls.

    PubMed

    Majewska, Maria Dorota; Urbanowicz, Ewa; Rok-Bujko, Paulina; Namyslowska, Irena; Mierzejewski, Paweł

    2010-01-01

    An association between autism and early life exposure to mercury is a hotly debated issue. In this study, 91 autistic Polish children, male and female, 3-4 and 7-9 years old, were compared to 75 age- and sex-matched healthy children with respect to: demographic, perinatal, clinical and developmental measures, parental age, birth order, morphometric measures, vaccination history, and hair mercury content. In demographic and perinatal measures there were no consistent differences between the autistic and control groups. Autistic children had a significantly greater prevalence of adverse reactions after vaccinations and abnormal development than controls. Between 45 and 80% of autistic children experienced developmental regress. Autistic children significantly differed from healthy peers in the concentrations of mercury in hair: younger autistics had lower levels, while older - higher levels than their respective controls. The results suggest that autistic children differ from healthy children in metabolism of mercury, which seems to change with age.

  14. Effects of soybean resistance on variability in life history traits of the higher trophic level parasitoid Meteorus pulchricornis (Hymenoptera: Braconidae).

    PubMed

    Li, X; Li, B; Xing, G; Meng, L

    2017-02-01

    To extrapolate the influence of plant cultivars varying in resistance levels to hosts on parasitoid life history traits, we estimated variation in parasitoid developmental and reproductive performances as a function of resistance in soybean cultivars, which were randomly chosen from a line of resistant genotypes. Our study showed that the parasitoid Meteorus pulchricornis varied widely in offspring survival and lifetime fecundity, but varied slightly in development time and adult body size, in response to the soybean cultivars that varied in resistance to the host Spodoptera litura. Furthermore, the variability in survival and lifetime fecundity was different between attacking the 2nd and the 4th instar host larvae, varying more in survival but less in lifetime fecundity when attacking the 4th than 2nd instar larvae. Our study provides further evidence supporting that plant resistance to herbivorous hosts have variable effects on different life history traits of higher trophic level parasitoids.

  15. An efficient plasmid vector for constitutive high-level expression of foreign genes in Escherichia coli.

    PubMed

    Seo, Jeong-Woo; Hong, Won-kyung; Rairakhwada, Dina; Seo, Pil-Soo; Choi, Min Ho; Song, Ki-Bang; Rhee, Sang-Ki; Kim, Chul Ho

    2009-06-01

    The levansucrase gene (lsrA) from Rahnella aquatilis was strongly expressed in a constitutive manner in Escherichia coli when cloned into a pBluescript KS-based pRL1CP plasmid vector. The native promoter upstream of lsrA and the lacZ promoter cooperatively enhanced the expression of lsrA to a level that was comparable to that of the T7 promoter, which is used in commercial pET expression vector system. A putative rho-independent transcription termination signal downstream of lsrA was crucial for gene expression. This plasmid vector also proved to be applicable for efficient expression of other foreign genes in E. coli.

  16. Higher TNF-α, IGF-1, and Leptin Levels are Found in Tasters than Non-Tasters

    PubMed Central

    Wang, Rui; van Keeken, Nika M. A.; Siddiqui, Sana; Dijksman, Lea M.; Maudsley, Stuart; Derval, Diana; van Dam, P. Sytze; Martin, Bronwen

    2014-01-01

    Taste perception is controlled by taste cells that are present in the tongue that produce and secrete various metabolic hormones. Recent studies have demonstrated that taste receptors in tongue, gut, and pancreas are associated with local hormone secretion. The aim of this study was to determine whether there is a link between taste sensitivity and levels of circulating metabolic hormones in humans and whether taste sensitivity is potentially related to peripheral metabolic regulation. Thirty-one subjects were recruited and separated into tasters and non-tasters based on their phenol thiocarbamide (PTC) bitter taste test results. Fasting plasma and saliva were collected and levels of hormones and cytokines were assayed. We observed significant differences in both hormone levels and hormone-body mass index (BMI) correlation between tasters and non-tasters. Tasters had higher plasma levels of leptin (p = 0.05), tumor necrosis factor-α (TNF-α) (p = 0.04), and insulin-like growth factor 1 (IGF-1) (p = 0.03). There was also a trend toward increased IGF-1 levels in the saliva of tasters (p = 0.06). We found a positive correlation between plasma levels of glucose and BMI (R = 0.4999, p = 0.04) exclusively in non-tasters. In contrast, plasma C-peptide levels were found to be positively correlated to BMI (R = 0.5563, p = 0.03) in tasters. Saliva TNF-α levels were negatively correlated with BMI in tasters (R = −0.5908, p = 0.03). Our findings demonstrate that there are differences in circulating levels of leptin, TNF-α, and IGF-1 between tasters and non-tasters. These findings indicate that in addition to the regulation of food consumption, taste perception also appears to be tightly linked to circulating metabolic hormone levels. People with different taste sensitivity may respond differently to the nutrient stimulation. Further work investigating the link between taste perception and peripheral metabolic control could

  17. 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

  18. Probe-Level Analysis of Expression Microarrays Characterizes Isoform-Specific Degradation during Mouse Oocyte Maturation

    PubMed Central

    Salisbury, Jesse; Hutchison, Keith W.; Wigglesworth, Karen; Eppig, John J.; Graber, Joel H.

    2009-01-01

    Background Gene expression microarrays have provided many insights into changes in gene expression patterns between different tissue types, developmental stages, and disease states. Analyses of these data focused primarily measuring the relative abundance of transcripts of a gene, while treating most or all transcript isoforms as equivalent. Differences in the selection between transcript isoforms can, however, represent critical changes to either the protein product or the posttranscriptional regulation of the transcript. Novel analyses on existing microarray data provide fresh insights and new interpretations into transcriptome-wide changes in expression. Methodology A probe-level analysis of existing gene expression arrays revealed differences in mRNA processing, primarily affecting the 3′-untranslated region. Working with the example of microarrays drawn from a transcriptionally silent period of mouse oocyte development, probe-level analysis (implemented here as rmodel) identified genes whose transcript isoforms have differing stabilities. Comparison of micorarrays measuring cDNA generated from oligo-dT and random primers revealed further differences in the polyadenylation status of some transcripts. Additional analysis provided evidence for sequence-targeted cleavage, including putative targeting sequences, as one mechanism of degradation for several hundred transcripts in the maturing oocyte. Conclusions The capability of probe-level analysis to elicit novel findings from existing expression microarray data was demonstrated. The characterization of differences in stability between transcript isoforms in maturing mouse oocytes provided some mechanistic details of degradation. Similar analysis of existing archives of expression microarray data will likely provide similar discoveries. PMID:19834616

  19. 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.

  20. Tissue Specific Expression Levels of Apoptosis Involved Genes Have Correlations with Codon and Amino Acid Usage

    PubMed Central

    Sadeghi, Iman; Salavaty, Abbas; Nasiri, Habib

    2016-01-01

    Different mechanisms, including transcriptional and post transcriptional processes, regulate tissue specific expression of genes. In this study, we report differences in gene/protein compositional features between apoptosis involved genes selectively expressed in human tissues. We found some correlations between codon/amino acid usage and tissue specific expression level of genes. The findings can be significant for understanding the translational selection on these features. The selection may play an important role in the differentiation of human tissues and can be considered for future studies in diagnosis of some diseases such as cancer. PMID:28154517

  1. 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.

  2. Higher direct bilirubin levels during mid-pregnancy are associated with lower risk of gestational diabetes mellitus.

    PubMed

    Liu, Chaoqun; Zhong, Chunrong; Zhou, Xuezhen; Chen, Renjuan; Wu, Jiangyue; Wang, Weiye; Li, Xiating; Ding, Huisi; Guo, Yanfang; Gao, Qin; Hu, Xingwen; Xiong, Guoping; Yang, Xuefeng; Hao, Liping; Xiao, Mei; Yang, Nianhong

    2017-01-01

    Bilirubin concentrations have been recently reported to be negatively associated with type 2 diabetes mellitus. We examined the association between bilirubin concentrations and gestational diabetes mellitus. In a prospective cohort study, 2969 pregnant women were recruited prior to 16 weeks of gestation and were followed up until delivery. The value of bilirubin was tested and oral glucose tolerance test was conducted to screen gestational diabetes mellitus. The relationship between serum bilirubin concentration and gestational weeks was studied by two-piecewise linear regression. A subsample of 1135 participants with serum bilirubin test during 16-18 weeks gestation was conducted to research the association between serum bilirubin levels and risk of gestational diabetes mellitus by logistic regression. Gestational diabetes mellitus developed in 8.5 % of the participants (223 of 2969). Two-piecewise linear regression analyses demonstrated that the levels of bilirubin decreased with gestational week up to the turning point 23 and after that point, levels of bilirubin were increased slightly. In multiple logistic regression analysis, the relative risk of developing gestational diabetes mellitus was lower in the highest tertile of direct bilirubin than that in the lowest tertile (RR 0.60; 95 % CI, 0.35-0.89). The results suggested that women with higher serum direct bilirubin levels during the second trimester of pregnancy have lower risk for development of gestational diabetes mellitus.

  3. Correlation Analysis Between Expression Levels of Hepatic Growth Hormone Receptor, Janus Kinase 2, Insulin-Like Growth Factor-I Genes and Dwarfism Phenotype in Bama Minipig.

    PubMed

    Yang, Haowen; Jiang, Qinyang; Wu, Dan; Lan, Ganqiu; Fan, Jing; Guo, Yafen; Chen, Baojian; Yang, Xiurong; Jiang, Hesheng

    2015-02-01

    Animal growth and development are complex and sophisticated biological metabolic processes, in which genes plays an important role. In this paper, we employed real-time quantitative PCR (RT-qPCR) to analyze the expression levels of hepatic GHR, JAK2 and IGF-I genes in 1, 30, 180 day of Bama minipig and Landrace with attempt to verify the correlation between the expression of these growth-associated genes and the dwarfism phenotype of Bama minipig. The results showed that the expression levels of these 3 genes in Bama minipigs were down-regulated expressed from 1 day to 30 day, and which was up-regulated expressed in Landrace. The expression levels of the 3 genes on 1, 30, 180 day were prominently higher in Landrace than in Bama minipigs. The significant differences of the 3 genes expression levels on 1 day between this two breeds indicate that different expressions of these genes might occur before birth. It is speculated that the down-regulated expression of the 3 genes may have a close correlation with the dwarfism phenotype of Bama minipig. More investigations in depth of this study is under progress with the help of biochip nanotechnology.

  4. 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…

  5. Decreased incidence of acute graft-versus-host disease by continuous infusion of cyclosporine with a higher target blood level.

    PubMed

    Oshima, Kumi; Kanda, Yoshinobu; Nakasone, Hideki; Arai, Shunya; Nishimoto, Nahoko; Sato, Hiroyuki; Watanabe, Takuro; Hosoya, Noriko; Izutsu, Koji; Asai, Takashi; Hangaishi, Akira; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo

    2008-03-01

    Cyclosporine A (CsA) is the mainstay of pharmacologic prevention of acute graft-versus-host disease (GVHD). We previously reported that continuous infusion of CsA with a target blood level between 250 and 400 ng/ml significantly increased the incidence of acute GVHD compared to twice-daily infusion with a target trough level between 150 and 300 ng/ml. Thus, we raised the target level of CsA continuous infusion to 450-550 ng/ml. We treated 33 patients with the higher target level (CsA500) and compared the efficacy and toxicity with those in the 33 historical control patients (CsA300 group). Other transplantation procedures were not changed. The patients' characteristics were equivalent. The average CsA concentration was adjusted around 500 ng/ml and the actual daily dose was maintained at the initial dose (CsA 3mg/kg/day). Toxicities were equivalently observed among the two groups. The incidence of grades II-IV acute GVHD was significantly lower in the CsA500 group (27 vs. 52%, P = 0.033). The target level of CsA was identified as an independent significant risk factor for grades II-IV acute GVHD (P = 0.039), adjusted for the presence of HLA mismatch. The incidence of chronic GVHD was also decreased in the CsA500 group (47 vs. 73%, P = 0.016). We conclude that the toxicity of the continuous CsA infusion with a target level of 450-550 ng/ml is acceptable and the efficacy to prevent acute GVHD is significant. A larger comparative study is warranted to confirm these findings.

  6. 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.

  7. Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

    SciTech Connect

    Liu, Xia; Liu, Siwen; Bode, Liv; Liu, Chengyu; Zhang, Liang; Wang, Xiao; Li, Dan; Lei, Yang; Peng, Xiaojun; Cheng, Zhongyi; and others

    2015-11-15

    Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection. Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT). Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites. - Highlights: • We used SILAC-based proteomics to analyze the acetylome of BDV infected OL cells. • We quantified 791Kac sites in 473 proteins. • Bioinformatic analysis revealed altered acetylation of metabolic proteins et al. • BDV manipulates the OL acetylome towards higher energy and transporter levels. • BDV infection is associated with enriched phosphate-associated metabolic processes.

  8. Higher Levels of Autoantibodies Targeting Mutated Citrullinated Vimentin in Patients with Psoriatic Arthritis Than in Patients with Psoriasis Vulgaris

    PubMed Central

    Dalmády, Szandra; Kiss, Mária; Képíró, László; Kovács, László; Sonkodi, Gábor; Kemény, Lajos; Gyulai, Rolland

    2013-01-01

    Antibodies against citrullinated proteins/peptides (ACPAs), and especially antibodies targeting mutated citrullinated vimentin (anti-MCVs), are novel biomarkers of rheumatoid arthritis (RA). Whereas ACPAs are specific and sensitive markers for RA, there have hardly been any reports relating to ACPAs in psoriatic arthritis (PsA) or in psoriasis without joint symptoms (PsO). The aim of the present study was to investigate the prevalence of anti-MCVs in PsA and PsO. Serum anti-MCV titers were measured in 46 PsA and 42 PsO patients and in 40 healthy controls by means of a commercial enzyme-linked immunosorbent assay. The potential correlations of the serum autoantibody levels with several clinical and laboratory parameters were examined. The anti-MCV levels in the PsA patients were significantly higher than those in the PsO group. Among the clinical variables, the presence of tender knee joints and nail psoriasis was significantly associated with anti-MCV positivity in the PsA patients. Higher anti-MCV titers in the PsO patients were associated with a more severe disease course and with the early onset of psoriatic skin symptoms. Our results suggest that anti-MCVs can be used as novel markers in the diagnosis of PsA and in a subset of PsO patients. PMID:23573111

  9. A general toolbox for the calculation of higher-order molecular properties using SCF wave functions at the one-, two- and four-component levels of theory

    NASA Astrophysics Data System (ADS)

    Ruud, Kenneth; Bast, Radovan; Gao, Bin; Thorvaldsen, Andreas J.; Ekström, Ulf; Visscher, Lucas

    2012-12-01

    We outline a new approach for the calculation of higher-order molecular properties for self-consistent field (SCF) wave functions (or Kohn-Sham density-functional theory) expressed in time- and perturbation-dependent basis sets. The approach is based on an atomic-orbital-based, open-ended quasienergy derivative formalism, and is applicable for use in linear scaling SCF calculations. In order to enable the calculation of any response property, we have also developed open- ended one- and two-electron integral derivative programs, as well as a program that can calculate derivatives of exchange- correlation functionals to any order using automatic differentiation. These modules have been interfaced to both the Dalton and DIRAC programs. This allows us to calculate molecular properties at the one-, two- and four-component levels of theory using a common theoretical framework and code.

  10. FMRP Expression Levels in Mouse Central Nervous System Neurons Determine Behavioral Phenotype

    PubMed Central

    Arsenault, Jason; Gholizadeh, Shervin; Niibori, Yosuke; Pacey, Laura K.; Halder, Sebok K.; Koxhioni, Enea; Konno, Ayumu; Hirai, Hirokazu; Hampson, David R.

    2016-01-01

    Fragile X mental retardation protein (FMRP) is absent or highly reduced in Fragile X Syndrome, a genetic disorder causing cognitive impairment and autistic behaviors. Previous proof-of-principle studies have demonstrated that restoring FMRP in the brain using viral vectors can improve pathological abnormalities in mouse models of fragile X. However, unlike small molecule drugs where the dose can readily be adjusted during treatment, viral vector–based biological therapeutic drugs present challenges in terms of achieving optimal dosing and expression levels. The objective of this study was to investigate the consequences of expressing varying levels of FMRP selectively in neurons of Fmr1 knockout and wild-type (WT) mice. A wide range of neuronal FMRP transgene levels was achieved in individual mice after intra-cerebroventricular administration of adeno-associated viral vectors coding for FMRP. In all treated knockout mice, prominent FMRP transgene expression was observed in forebrain structures, whereas lower levels were present in more caudal regions of the brain. Reduced levels of the synaptic protein PSD-95, elevated levels of the transcriptional modulator MeCP2, and abnormal motor activity, anxiety, and acoustic startle responses in Fmr1 knockout mice were fully or partially rescued after expression of FMRP at about 35–115% of WT expression, depending on the brain region examined. In the WT mouse, moderate FMRP over-expression of up to about twofold had little or no effect on PSD-95 and MeCP2 levels or on behavioral endophenotypes. In contrast, excessive over-expression in the Fmr1 knockout mouse forebrain (approximately 2.5–6-fold over WT) induced pathological motor hyperactivity and suppressed the startle response relative to WT mice. These results delineate a range of FMRP expression levels in the central nervous system that confer phenotypic improvement in fragile X mice. Collectively, these findings are pertinent to the development of long

  11. A decrease in intact parathyroid hormone (iPTH) levels is associated with higher mortality in prevalent hemodialysis patients

    PubMed Central

    Villa-Bellosta, Ricardo; Rodriguez-Osorio, Laura; Mas, Sebastian; Abadi, Younes; Rubert, Mercedes; de la Piedra, Concepción; Gracia-Iguacel, Carolina; Mahillo, Ignacio; Ortiz, Alberto; Egido, Jesús; González-Parra, Emilio

    2017-01-01

    Background The mortality of dialysis patients is 10- to 100-fold higher than in the general population. Baseline serum PTH levels, and more recently, changes in serum PTH levels (ΔPTH) over time, have been associated to mortality in dialysis patients. Methods We explored the relationship between ΔPTH over 1 year with mortality over the next year in a prospective cohort of 115 prevalent hemodialysis patients from a single center that had median baseline iPTH levels within guideline recommendations. Results Median baseline iPTH levels were 205 (116.5, 400) pg/ml. ΔiPTH between baseline and 1 year was 85.2 ± 57.1 pg/ml. During the second year of follow-up, 27 patients died. ΔiPTH was significantly higher in patients who survived (+157.30 ± 25.82 pg/ml) than in those who died (+39.03 ± 60.95 pg/ml), while baseline iPTH values were not significantly different. The highest mortality (48%) was observed in patients with a decrease in ΔiPTH (ΔiPTH quartile 1, negative ΔiPTH) and the lowest (12%) mortality in quartile 3 ΔiPTH (ΔiPTH increase 101–300 pg/ml). In a logistic regression model, ΔiPTH was associated with mortality with an odds ratio (OR) of 0.998 (95% CI 0.996–0999, p = 0.038). In multivariable analysis, mortality risk was 73% and 88% lower for patients with ΔiPTH 0–100 pg/ml and 101–300 pg/ml, respectively, than for those with a decrease in ΔiPTH. In patients with a decrease in ΔiPTH, the OR for death was 4.131 (1.515–11.27)(p = 0.006). Conclusions In prevalent hemodialysis patients with median baseline iPTH values within the guideline recommended range, a decrease in ΔiPTH was associated with higher mortality. Further studies are required to understand the mechanisms and therapeutic implications of this observation that challenges current clinical practice. PMID:28339474

  12. A comparison of brain gene expression levels in domesticated and wild animals.

    PubMed

    Albert, Frank W; Somel, Mehmet; Carneiro, Miguel; Aximu-Petri, Ayinuer; Halbwax, Michel; Thalmann, Olaf; Blanco-Aguiar, Jose A; Plyusnina, Irina Z; Trut, Lyudmila; Villafuerte, Rafael; Ferrand, Nuno; Kaiser, Sylvia; Jensen, Per; Pääbo, Svante

    2012-09-01

    Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30-75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different.

  13. A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals

    PubMed Central

    Albert, Frank W.; Somel, Mehmet; Carneiro, Miguel; Aximu-Petri, Ayinuer; Halbwax, Michel; Thalmann, Olaf; Blanco-Aguiar, Jose A.; Trut, Lyudmila; Villafuerte, Rafael; Ferrand, Nuno; Kaiser, Sylvia; Jensen, Per; Pääbo, Svante

    2012-01-01

    Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30–75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different. PMID:23028369

  14. Population Level Purifying Selection and Gene Expression Shape Subgenome Evolution in Maize.

    PubMed

    Pophaly, Saurabh D; Tellier, Aurélien

    2015-12-01

    The maize ancestor experienced a recent whole-genome duplication (WGD) followed by gene erosion which generated two subgenomes, the dominant subgenome (maize1) experiencing fewer deletions than maize2. We take advantage of available extensive polymorphism and gene expression data in maize to study purifying selection and gene expression divergence between WGD retained paralog pairs. We first report a strong correlation in nucleotide diversity between duplicate pairs, except for upstream regions. We then show that maize1 genes are under stronger purifying selection than maize2. WGD retained genes have higher gene dosage and biased Gene Ontologies consistent with previous studies. The relative gene expression of paralogs across tissues demonstrates that 98% of duplicate pairs have either subfunctionalized in a tissuewise manner or have diverged consistently in their expression thereby preventing functional complementation. Tissuewise subfunctionalization seems to be a hallmark of transcription factors, whereas consistent repression occurs for macromolecular complexes. We show that dominant gene expression is a strong determinant of the strength of purifying selection, explaining the inferred stronger negative selection on maize1 genes. We propose a novel expression-based classification of duplicates which is more robust to explain observed polymorphism patterns than the subgenome location. Finally, upstream regions of repressed genes exhibit an enrichment in transposable elements which indicates a possible mechanism for expression divergence.

  15. Microfluidic continuum sorting of sub-populations of tumor cells via surface antibody expression levels.

    PubMed

    Jack, Rhonda; Hussain, Khadijah; Rodrigues, Danika; Zeinali, Mina; Azizi, Ebrahim; Wicha, Max; Simeone, Diane M; Nagrath, Sunitha

    2017-03-29

    The extent of inter- and intra-tumor cell heterogeneity observed in patient tumors appears to be directly associated with patient prognosis. Moreover, studies indicate that targeting distinct subpopulations of tumor cells may be more relevant to successfully managing cancer metastasis. The ability to distinguish and characterize unique tumor cell subpopulations within a given sample is thus exigent. Existing platforms separate cells binarily, based on some threshold level of phenotypic characteristics without consideration of the continuum levels of biomarker expression and the associated implications. Herein we describe how specific tumor cell groups have been immunomagnetically enriched according to a continuum of EpCAM surface marker expression levels. Even among a relatively homogenous group of cells such as the PANC-1 cell line, cells could be separated according to their EpCAM levels into low, moderate and high expression. To physiologically assess each subpopulation, a wound healing assay was performed which revealed distinct invasive potentials among each subset. Furthermore, the clinical relevance of the approach was demonstrated by isolating pancreatic cancer CTCs from the same patient sample based on their EpCAM levels. We demonstrate a robust method of isolating CTCs according to their varying protein levels, which enables extensive studies on tumor cell heterogeneity. Interestingly, 5 of 6 samples had CTCs that could be recovered at all three levels of EpCAM expression though the majority of CTCs were recovered as low expression events. Preliminary studies that compare tumor cell subpopulations in this continuum manner can potentially increase our understanding of the dynamic nature of cell heterogeneity and how it relates to patient outcomes. Ultimately further investigation may yield therapeutic targets against virulent cell subpopulations.

  16. Carcinoembryonic antigen expression level as a predictive factor for response to 5-fluorouracil in colorectal cancer.

    PubMed

    Eftekhar, Ebrahim; Naghibalhossaini, Fakhraddin

    2014-01-01

    Carcinoembryonic antigen (CEA) expression has been shown to protect cancer cell lines from apoptosis and anoikis. The aim of this study was to further elucidate the role of CEA expression on resistance to anticancer drugs in human colorectal cancer (CRC). We transfected CEA negative CRC cell line SW742 as well as CHO cells to overexpress CEA and their chemoresistance were assessed by MTT assay. In comparison to the parental cell lines, transfected cells had significantly increased resistance to 5-fluorouracil (5-FU). The results also showed a direct correlation between the amount of cellular CEA protein and 5-FU resistance in CEA expressing cells. We found no significant difference in sensitivity to cisplatin and methotrexate between CEA-transfected cells and their counter parental cells. We also compared the association between CEA expression and chemoresistance of 4 CRC cell lines which differed in the levels of CEA production. The CEA expression levels in monolayer cultures of these cell lines did not correlate with the 5-FU resistance. However, 5-FU treatment resulted in the selection of sub-populations of resistant cells that displayed increased CEA expression levels by increasing drug concentration. We analyzed the effect of 5-FU in a 3D multicellular culture generated from the two CRC cell lines, LS180 and HT29/219. Compared with monolayer culture, CEA production and 5-FU resistance in both cell lines were stimulated by 3D growth. In comparison to the 3D spheroids of parental CHO, we observed a significantly elevated 5-FU resistance in 3D culture of the CEA-expressing CHO transfectants. Our findings suggest that the CEA level may be a suitable biomarker for predicting tumor response to 5-FU-based chemotherapy in CRC.

  17. 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.

  18. Correlation of Cytohistlogical Expression and Serum Level of Ca125 in Ovarian Neoplasm

    PubMed Central

    Das, Chhanda; Mukhopadhyay, Madhumita; Ghosh, Tarun; Saha, Ashis Kumar; Sengupta, Moumita

    2014-01-01

    Context or Background: CA125 is a biomarker that has potential utility across the spectrum: risk assessment, early detection, diagnosis, prognosis, monitoring and therapy. Aims and Objectives: This study was conducted to establish the validity and reliability of correlation of CA125 serum level with immunochemistry expression in imprint cytology and tissues for diagnostic purpose. Materials and Methods: A prospective study was done on 50 cases of clinically and radiologically diagnosed ovarian tumor. Imprint smears were made intraoperatively from fresh samples and stained with M.G.G. stain for air dried smears and Papanicoloau stain for alcohol fixed smears. Stained smear was assessed and compared with subsequent histopathology report. Preoperative blood samples were obtained from all patients and sent for the assay of serum CA125 levels. Analysis of CA125 immunochemistry expression in imprint cytology and tissue was done and correlated with preoperative serum blood CA125 levels. Results: Significant positive correlation was found between elevated serum CA125 levels and cytohistological expression of CA125. Overall sensitivity was 100%, specificity was 86%, positive predictive value was 74% and negative predictive value 100%. Diagnostic accuracy was 90% with high statistical significance (p<0.001). Conclusion: We considered 35 U/mL as the cut-off value when evaluating serum CA125 ovarian cancer. Patients with high serum levels show good cytohistological expression. PMID:24783076

  19. 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

  20. 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.

  1. Formation of higher-order nuclear Rad51 structures is functionally linked to p21 expression and protection from DNA damage-induced apoptosis.

    PubMed

    Raderschall, Elke; Bazarov, Alex; Cao, Jiangping; Lurz, Rudi; Smith, Avril; Mann, Wolfgang; Ropers, Hans-Hilger; Sedivy, John M; Golub, Efim I; Fritz, Eberhard; Haaf, Thomas

    2002-01-01

    After exposure of mammalian cells to DNA damage, the endogenous Rad51 recombination protein is concentrated in multiple discrete foci, which are thought to represent nuclear domains for recombinational DNA repair. Overexpressed Rad51 protein forms foci and higher-order nuclear structures, even in the absence of DNA damage, in cells that do not undergo DNA replication synthesis. This correlates with increased expression of the cyclin-dependent kinase (Cdk) inhibitor p21. Following DNA damage, constitutively Rad51-overexpressing cells show reduced numbers of DNA breaks and chromatid-type chromosome aberrations and a greater resistance to apoptosis. In contrast, Rad51 antisense inhibition reduces p21 protein levels and sensitizes cells to etoposide treatment. Downregulation of p21 inhibits Rad51 foci formation in both normal and Rad51-overexpressing cells. Collectively, our results show that Rad51 expression, Rad51 foci formation and p21 expression are interrelated, suggesting a functional link between mammalian Rad51 protein and p21-mediated cell cycle regulation. This mechanism may contribute to a highly effective recombinational DNA repair in cell cycle-arrested cells and protection against DNA damage-induced apoptosis.

  2. 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

  3. Optimizing heterologous protein production in the periplasm of E. coli by regulating gene expression levels

    PubMed Central

    2013-01-01

    Background In Escherichia coli many heterologous proteins are produced in the periplasm. To direct these proteins to the periplasm, they are equipped with an N-terminal signal sequence so that they can traverse the cytoplasmic membrane via the protein-conducting Sec-translocon. For poorly understood reasons, the production of heterologous secretory proteins is often toxic to the cell thereby limiting yields. To gain insight into the mechanism(s) that underlie this toxicity we produced two secretory heterologous proteins, super folder green fluorescent protein and a single-chain variable antibody fragment, in the Lemo21(DE3) strain. In this strain, the expression intensity of the gene encoding the target protein can be precisely controlled. Results Both SFGFP and the single-chain variable antibody fragment were equipped with a DsbA-derived signal sequence. Producing these proteins following different gene expression levels in Lemo21(DE3) allowed us to identify the optimal expression level for each target gene. Too high gene expression levels resulted in saturation of the Sec-translocon capacity as shown by hampered translocation of endogenous secretory proteins and a protein misfolding/aggregation problem in the cytoplasm. At the optimal gene expression levels, the negative effects of the production of the heterologous secretory proteins were minimized and yields in the periplasm were optimized. Conclusions Saturating the Sec-translocon capacity can be a major bottleneck hampering heterologous protein production in the periplasm. This bottleneck can be alleviated by harmonizing expression levels of the genes encoding the heterologous secretory proteins with the Sec-translocon capacity. Mechanistic insight into the production of proteins in the periplasm is key to optimizing yields in this compartment. PMID:23497240

  4. HER-2 tissue expression correlated with serum levels in breast cancer patients.

    PubMed

    Pribylová, O; Springer, D; Vítková, I; Zima, T; Petruzelka, L

    2007-01-01

    We explored the relationship between circulating HER-2 extracellular domain and tissue HER-2 status in a group of 42 postmenopausal breast cancer patients. All patients were examined before adjuvant chemotherapy or other adjuvant treatment. Serum levels were measured by BAYER Advia Centaur System, Golden, CO (the cut-off level was in our conditions considered at 12 ng/ml). Tissue expression was assayed with the DAKO HercepTest, North America, Inc, Carpinteria, CA. Our findings that serum levels are in consonance with tissue expression could be important in metastatic breast cancer, when it is impossible to get a new tumour sample and establish the actual HER-2 status, which may be different from the primary tumour. Although we know that serum HER-2 concentration cannot be substituted for IHC or FISH, we have observed a statistically significant correlation between serum level concentration and tissue HER-2 status.

  5. Assessment of Interleukin 16 Serum Levels and Skin Expression in Psoriasis Patients in Correlation with Clinical Severity of the Disease

    PubMed Central

    Purzycka-Bohdan, Dorota; Szczerkowska-Dobosz, Aneta; Zablotna, Monika; Wierzbicka, Justyna; Piotrowska, Anna; Zmijewski, Michal A.; Nedoszytko, Boguslaw; Nowicki, Roman

    2016-01-01

    Interleukin 16 (IL-16) has been described as a significant cytokine involved in the recruitment of CD4+ cells during inflammation; however, its potential role in psoriasis has not been defined. Our aim was to investigate the IL-16 serum levels and IL-16 mRNA skin expression in psoriasis patients in correlation with disease severity and mRNA skin expression for CD4. Moreover, the IL-16 skin localization was assessed and the -295 T/C IL-16 polymorphism was analyzed. For this exploratory, observational, and cross-sectional study, 97 unrelated patients with chronic plaque type psoriasis and 104 healthy controls were enrolled. IL-16 serum levels were significantly increased in patients compared with controls (P = 0.000022) and positively correlated with Psoriasis Area and Severity Index (r = 0.34, P = 0.0007), Body Surface Area (r = 0.34, P = 0.01) and were significantly higher in individuals with moderate to severe psoriasis (P = 0.0029). There was no significant correlation between IL-16 serum levels and Dermatology Quality of Life Index and no differences in genotype and allele frequencies for -295 T/C IL-16 polymorphism. The expression of IL-16 (mRNA and protein) was elevated in the margin of psoriatic skin while statistically significant increase in IL-16 immunoreactivity, but not in mRNA level, was observed within plaques. Furthermore, the IL-16 mRNA levels within psoriatic lesions positively correlated with the levels of CD4 mRNA, but not with Psoriasis Area and Severity Index. In conclusion, our data revealed an association between circulating IL-16 and severity of psoriasis which indicates that this cytokine could serve as a potential marker of disease activity. However, further investigations are required. PMID:27788245

  6. Reduced beta 2-microglobulin mRNA levels in transgenic mice expressing a designed hammerhead ribozyme.

    PubMed Central

    Larsson, S; Hotchkiss, G; Andäng, M; Nyholm, T; Inzunza, J; Jansson, I; Ahrlund-Richter, L

    1994-01-01

    We have generated three artificial hammerhead ribozymes, denoted 'Rz-b', 'Rz-c' and 'Rz-d', with different specificities for exon II of the mouse beta-2-microglobulin (beta 2M) mRNA. In this study we tested for ribozyme mediated reduction of beta 2M mRNA in a cell line and in transgenic mice. Transfections of either of the Rz-b, Rz-c or Rz-d plasmids into a mouse cell-line (NIH/3T3) revealed reductions of beta 2M mRNA substrate in each case. Ribozyme expression in individual transfected clones was accompanied with an up to 80% reduction of beta 2M mRNA levels. Rz-c was selected for a transgenic study. Seven Rz-c transgenic founder animals were identified from which three ribozyme expressing families were established and analysed. Expression of the ribozyme transgene was tested for and detected in lung, kidney and spleen. Expression was accompanied with reduction of the beta 2M mRNA levels of heterozygous (Rz+/-) animals compared to non-transgenic litter mates. The effect was most pronounced in lung with more than 90% beta 2M mRNA reduction in individual mice. In summary, expression of our ribozymes in a cell free system, in a cell-line and in transgenic mice were all accompanied with reductions of beta 2M mRNA levels. Images PMID:8036151

  7. Novel Bifidobacterium promoters selected through microarray analysis lead to constitutive high-level gene expression.

    PubMed

    Wang, Yan; Kim, Jin Yong; Park, Myeong Soo; Ji, Geun Eog

    2012-08-01

    For the development of a food-grade expression system for Bifidobacterium, a strong promoter leading to high-level expression of cloned gene is a prerequisite. For this purpose, a promoter screening host-vector system for Bifidobacterium has been established using β-glucosidase from Bifidobacterium lactis as a reporter and Bifidobacterium bifidum BGN4 as a host, which is β-glucosidase negative strain. Seven putative promoters showing constitutive high-level expression were selected through microarray analysis based on the genome sequence of B. bifidum BGN4. They were cloned into upstream of β-glucosidase gene and transformed into Escherichia coli DH5α and B. bifidum BGN4. Promoter activities were analyzed both in E. coli and B. bifidum BGN4 by measuring β-glucosidase activity. β-Glucosidase activities in all of the transformants showed growth-associated characteristics. Among them, P919 was the strongest in B. bifidum BGN4 and showed maximum activity at 18 h, while P895 was the strongest in E. coli DH5α at 7 h. This study shows that novel strong promoters such as P919 can be used for high-level expression of foreign genes in Bifidobacterium and will be useful for the construction of an efficient food-grade expression system.

  8. High-level expression of the Penicillium notatum glucose oxidase gene in Pichia pastoris using codon optimization.

    PubMed

    Gao, Zhaowei; Li, Zhuofu; Zhang, Yuhong; Huang, Huoqing; Li, Mu; Zhou, Liwei; Tang, Yunming; Yao, Bin; Zhang, Wei

    2012-03-01

    The glucose oxidase (GOD) gene from Penicillium notatum was expressed in Pichia pastoris. The 1,815 bp gene, god-w, encodes 604 amino acids. Recombinant GOD-w had optimal activity at 35-40°C and pH 6.2 and was stable, from pH 3 to 7 maintaining >75% maximum activity after incubation at 50°C for 1 h. GOD-w worked as well as commercial GODs to improve bread making. To achieve high-level expression of recombinant GOD in P. pastoris, 272 nucleotides involving 228 residues were mutated, consistent with the codon bias of P. pastoris. The optimized recombinant GOD-m yielded 615 U ml(-1) (2.5 g protein l(-1)) in a 3 l fermentor--410% higher than GOD-w (148 U ml(-1)), and thus is a low-cost alternative for the bread baking industry.

  9. Quercetin promotes neurite growth through enhancing intracellular cAMP level and GAP-43 expression.

    PubMed

    Chen, Ming-Ming; Yin, Zhi-Qi; Zhang, Lu-Yong; Liao, Hong

    2015-09-01

    The present study was designed to investigate the role of quercetin on neurite growth in N1E-115 cells and the underlying mechanisms. Quercetin was evaluated for its effects on cell numbers of neurites, neurite length, intracellular cAMP content, and Gap-43 expression in N1E-115 cells in vitro by use of microscopy, LANCE(tm) cAMP 384 kit, and Western blot analysis, respectively. Our results showed that quercetin could increase the neurite length in a concentration-dependent manner, but had no effect on the numbers of cells. Quercetin significantly increased the expression of cellular cAMP in a time- and concentration-dependent manner. The Gap-43 expression was up-regulated in a time-dependent manner. In conclusion, quercetin could promote neurite growth through increasing the intracellular cAMP level and Gap-43 expression.

  10. 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.

  11. N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells.

    PubMed

    Haug, Jeffrey S; He, Xi C; Grindley, Justin C; Wunderlich, Joshua P; Gaudenz, Karin; Ross, Jason T; Paulson, Ariel; Wagner, Kathryn P; Xie, Yucai; Zhu, Ruihong; Yin, Tong; Perry, John M; Hembree, Mark J; Redenbaugh, Erin P; Radice, Glenn L; Seidel, Christopher; Li, Linheng

    2008-04-10

    Osteoblasts expressing the homophilic adhesion molecule N-cadherin form a hematopoietic stem cell (HSC) niche. Therefore, we examined how N-cadherin expression in HSCs relates to their function. We found that bone marrow (BM) cells highly expressing N-cadherin (N-cadherin(hi)) are not stem cells, being largely devoid of a Lineage(-)Sca1(+)cKit(+) population and unable to reconstitute hematopoietic lineages in irradiated recipient mice. Instead, long-term HSCs form distinct populations expressing N-cadherin at intermediate (N-cadherin(int)) or low (N-cadherin(lo)) levels. The minority N-cadherin(lo) population can robustly reconstitute the hematopoietic system, express genes that may prime them to mobilize, and predominate among HSCs mobilized from BM to spleen. The larger N-cadherin(int) population performs poorly in reconstitution assays when freshly isolated but improves in response to overnight in vitro culture. Their expression profile and lower cell-cycle entry rate suggest N-cadherin(int) cells are being held in reserve. Thus, differential N-cadherin expression reflects functional distinctions between two HSC subpopulations.

  12. 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

  13. Examination of Anxiety Levels and Anger Expression Manners of Undergraduate Table Tennis Players

    ERIC Educational Resources Information Center

    Karademir, Tamer; Türkçapar, Ünal

    2016-01-01

    This research was done for the determination of how their anxiety levels' and anger expressions' get shaped according to some variances. For this reason there were 76 female 125 male totally 201 sportsmen, who participated to the table tennis championship between universities in 2016 and ages differ from 18 to 28, were included the research group.…

  14. 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...

  15. Spontaneously tonic smooth muscle has characteristically higher levels of RhoA/ROK compared with the phasic smooth muscle.

    PubMed

    Patel, Chirag A; Rattan, Satish

    2006-11-01

    The internal anal sphincter (IAS) tone is important for the rectoanal continence. The RhoA/Rho kinase (ROK) pathway has been associated with the agonist-induced sustained contraction of the smooth muscle, but its role in the spontaneously tonic smooth muscle is not known. Present studies compared expression of different components of the RhoA/ROK pathway between the IAS (a truly tonic SM), the rectal smooth muscle (RSM) (a mixture of phasic and tonic), and anococcygeus smooth muscle (ASM) (a purely phasic SM) of rat. RT-PCR and Western blot analyses were performed to determine RhoA, ROCK-II, CPI-17, MYPT1, and myosin light-chain 20 (MLC20). Phosphorylated CPI-17 at threonine-38 residue (p(Thr38)-CPI-17), MYPT1 at threonine-696 residue (p(Thr696)-MYPT1), and MLC20 at threonine-18/serine-19 residues (p(Thr18/Ser19)-MLC20) were also determined in the basal state and after pretreatment with the ROK inhibitor Y 27632. In addition, we compared the effect of Y 27632 on the basal isometric tension and ROK activity in the IAS vs. the RSM. Our data show the highest levels of RhoA, ROCK-II, CPI-17, MLC20, and of phospho-MYPT1, -CPI-17, and -MLC20 in the IAS followed by in the RSM and ASM. Conversely, MYPT1 levels were lowest in the IAS and highest in the ASM. In the IAS, Y 27632 caused a concentration-dependent decrease in the basal tone, levels of phospho-MYPT1, -CPI-17, and -MLC20, and ROK activity. We conclude that RhoA/ROK plays a critical role in the basal tone in the IAS by the inhibition of MLC phosphatase via the phosphorylation of MYPT1 and CPI-17.

  16. 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.

  17. Telaprevir and Ribavirin Interaction: Higher Ribavirin Levels Are Not Only Due to Renal Dysfunction during Triple Therapy

    PubMed Central

    Gutierrez-Valencia, Alicia; Ruiz-Valderas, Rosa; Ben-Marzouk-Hidalgo, Omar J.; Torres-Cornejo, Almudena; Espinosa, Nuria; Castillo-Ferrando, Juan R.; Viciana, Pompeyo

    2015-01-01

    A higher incidence of anemia has been observed during the treatment of hepatitis C virus genotype 1 (HCV-1) infection with pegylated alpha interferon (pegIFN-α), ribavirin, and telaprevir. We assessed the impacts that concomitant administration of telaprevir and changes in the glomerular filtration rate have on ribavirin plasma levels. The minimum concentrations of ribavirin in plasma (ribavirin Cmin) determined during triple therapy including telaprevir were compared with those observed after telaprevir withdrawal and those observed in the same subjects and in a large cohort during a previous course of pegIFN-α plus ribavirin. Intensive pharmacokinetic sampling for ribavirin was performed at steady state during the triple-therapy phase. Ribavirin levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Twenty-seven HCV-1/HIV-coinfected patients were enrolled. The median ribavirin Cmin for triple therapy (4.08 μg/ml; range, 2.14 to 5.56 μg/ml) was higher than that observed after telaprevir withdrawal (1.96 μg/ml; range, 0.41 to 3.45 μg/ml) (P < 0.001) and that observed for 125 HCV-1/HIV-coinfected patients treated only with pegIFN-α plus ribavirin (1.65 μg/ml; range, 0.41 to 5.56 μg/ml) (P < 0.001). The estimated glomerular filtration rate (eGFR) decreased >20% from the baseline value in 11 of 27 patients and became normal after telaprevir removal in almost all cases. There was a negative correlation between eGFR and ribavirin clearance (r2 = 0.257; P = 0.064) but not the ribavirin area under the concentration-time curve from 0 to 12 h (AUC0–12) (r2 = 0.001; P = 0.455). Thus, there is a significant pharmacokinetic interaction between telaprevir and ribavirin that results in very high ribavirin levels, which explains the excess of toxicity observed with this drug combination. A blockade of the proximal tubular transporters might be implicated in both the increase in plasma creatinine and the high ribavirin levels. (This study has

  18. 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.

  19. Is Nasal Polyposis Related to Levels of Serum Vitamin D and Vitamin D Receptor Gene Expression?

    PubMed Central

    Erdag, Omer; Turan, Mahfuz; Ucler, Rıfkı; Berkoz, Mehmet; Garca, Mehmet Fatih; Bozan, Nazım; Kıroglu, Ahmet Faruk; Cankaya, Hakan

    2016-01-01

    Background Nasal polyposis (NP) is the most frequent cause of nasal masses. Despite considerable research on the subject, its etiology has not been fully elucidated, and effective treatment methods have not been developed. Some etiological factors causing low or high expression of genes in genetically predisposed individuals may play a role in the pathogenesis of the disease. The purpose of this study was to assess the relation between levels of vitamin D receptor (VDR) gene expression and serum vitamin D with NP. Material/Methods The study included 46 subjects with NP (NP group) and 40 volunteers (control group). Nasal polyp tissue samples were taken from the NP group and nasal mucosa samples were taken from the control group. Levels of VDR gene expression in the tissue samples were assessed using the real-time polymerase chain reaction (RT-PCR) method. Results Mean serum 25(OH)D levels were 13.38±14.08 ng/ml in the NP group and 10.57±6.44 ng/ml in the control group (p=0.249). VDR gene expression was present in 17.5% of the NP group and 3.3% of the control group, and the difference between the 2 groups was statistically significant (likelihood ratio χ2=3.887; p=0.049). Conclusions This is the first study to assess levels of VDR gene expression in subjects with NP. Our results suggest that VDR gene expression may be associated with the pathogenesis or progression of NP. PMID:27895321

  20. Connexin-deficiency affects expression levels of glial glutamate transporters within the cerebrum.

    PubMed

    Unger, Tina; Bette, Stefanie; Zhang, Jiong; Theis, Martin; Engele, Jürgen

    2012-01-06

    The glial glutamate transporter subtypes, GLT-1/EAAT-2 and GLAST/EAAT-1 clear the bulk of extracellular glutamate and are severely dysregulated in various acute and chronic brain diseases. Despite the previous identification of several extracellular factors modulating glial glutamate transporter expression, our knowledge of the regulatory network controlling glial glutamate transport in health and disease still remains incomplete. In studies with cultured cortical astrocytes, we previously obtained evidence that glial glutamate transporter expression is also affected by gap junctions/connexins. To assess whether gap junctions would likewise control the in vivo expression of glial glutamate transporters, we have now assessed their expression levels in brains of conditional Cx43 knockout mice, total Cx30 knockouts, as well as Cx43/Cx30 double knockouts. We found that either knocking out Cx30, Cx43, or both increases GLT-1/EAAT-2 protein levels in the cerebral cortex to a similar extent. By contrast, GLAST/EAAT-1 protein levels maximally increased in cerebral cortices of Cx30/Cx43 double knockouts, implying that gap junctions differentially affect the expression of GLT-1/EAAT-2 and GLAST/EAAT-1. Quantitative PCR analysis further revealed that increases in glial glutamate transporter expression are brought about by transcriptional and translational/posttranslational processes. Moreover, GLT-1/EAAT-2- and GLAST/EAAT-1 protein levels remained unchanged in the hippocampi of Cx43/Cx30 double knockouts when compared to Cx43fl/fl controls, indicating brain region-specific effects of gap junctions on glial glutamate transport. Since astrocytic gap junction coupling is affected in various forms of brain injuries, our findings point to gap junctions/connexins as important regulators of glial glutamate turnover in the diseased cerebral cortex.

  1. 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.

  2. 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

  3. Expression of tumor necrosis factor-alpha-induced protein 8 in pancreas tissues and its correlation with epithelial growth factor receptor levels.

    PubMed

    Liu, Ke; Qin, Cheng-Kun; Wang, Zhi-Yi; Liu, Su-Xia; Cui, Xian-Ping; Zhang, Dong-Yuan

    2012-01-01

    Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) is a recently identified protein considered to be associated with carcinogenesis. To investigate its expression pattern in pancreatic cancer patients and to analyse its correlation with clinicopathological significance and the expression levels of epithelial growth factor receptor (EGFR), immunohistochemistry was performed to detect the TNFAIP8 and EGFR proteins in pancreatic cancers, pancreatitis tissues, and healthy controls. The results showed stronger staining of TNFAIP8 protein in pancreatic cancer tissues compared with normal pancreas tissue. Furthermore, in 56 patients with pancreatic cancer, the expression levels of TNFAIP8 in patients with low tumor stage was higher than that with high tumor stage, and correlated with tumor staging and lymph node metastasis (P<0.05). Furthermore, TNFAIP8 expression positively correlated with EGFR levels (r=0.671135, P<0.05). These results indicate that TNFAIP8 may play important roles in the progression of pancreatic cancer.

  4. Dynamic changes in the higher-level chromatin organization of specific sequences revealed by in situ hybridization to nuclear halos

    PubMed Central

    1994-01-01

    A novel approach to study the higher level packaging of specific DNA sequences has been developed by coupling high-resolution fluorescence hybridization with biochemical fractionation to remove histones and distend DNA loops to form morphologically reproducible nuclear "halos." Results demonstrate consistent differences in the organization of specific sequences, and further suggest a relationship to functional activity. Pulse-incorporated bromodeoxyuridine representing nascent replicating DNA localized with the base of the chromatin loops in discrete clustered patterns characteristic of intact cells, whereas at increasing chase times, the replicated DNA was consistently found further out on the extended region of the halo. Fluorescence hybridization to unique loci for four transcriptionally inactive sequences produced long strings of signal extending out onto the DNA halo or "loop," whereas four transcriptionally active sequences remained tightly condensed as single spots within the residual nucleus. In contrast, in non-extracted cells, all sequences studied typically remained condensed as single spots of fluorescence signal. Interestingly, two transcriptionally active, tandemly repeated gene clusters exhibited strikingly different packaging by this assay. Analysis of specific genes in single cells during the cell cycle revealed changes in packaging between S-phase and non S-phase cells, and further suggested a dramatic difference in the structural associations in mitotic and interphase chromatin. These results are consistent with and suggestive of a loop domain organization of chromatin packaging involving both stable and transient structural associations, and provide precedent for an approach whereby different biochemical fractionation methods may be used to unravel various aspects of the complex higher-level organization of the genome. PMID:8034736

  5. Soil Microarthropods and Their Relationship to Higher Trophic Levels in the Pedregal de San Angel Ecological Reserve, Mexico

    PubMed Central

    Callejas-Chavero, Alicia; Castaño-Meneses, Gabriela; Razo-González, María; Pérez-Velázquez, Daniela; Palacios-Vargas, José G.; Flores-Martínez, Arturo

    2015-01-01

    Soil fauna is essential for ecosystem dynamics as it is involved in biogeochemical processes, promotes nutrient availability, and affects the animal communities associated with plants. In this study, we examine the possible relationship between the soil microarthropod community on foliage production and quality of the shrub Pittocaulon praecox. We also examine the arthropods associated to its foliage, particularly the size of the main herbivores and of their natural enemies, at two sites with contrasting vegetation cover and productivity. The diversity of soil microarthropods was assessed from soil samples collected monthly under P. praecox individuals over 13 mo. Specimens collected were identified to species or morphospecies. Shrub foliage productivity was evaluated through the amount of litter produced. Resource quality was assessed by the mean content (percentage by weight) of N, C, S, and P of 30 leaves from each shrub. The mean size of herbivores and their natural enemies were determined by measuring 20 adult specimens of each of the most abundant species. We found a higher species richness of soil microarthropods and foliar arthropods in the open site, although the diversity of foliage arthropods was lower in the closed site. Shrubs growing in the closed site tend to produce more, larger, and nutritionally poorer (lower nitrogen content) leaves than open site. Herbivores and their natural enemies were also larger in the closed site. We found a significant positive relationship between the diversity and species richness of foliar arthropods and the nitrogen content of leaves. In general, species richness and diversity of both the foliar and soil fauna, as well as the size of organisms belonging to higher trophic levels, were affected by vegetation cover and primary productivity at each site. These findings highlight the need to simultaneously consider at least four trophic levels (soil organisms, plants, herbivores, and natural enemies) to better understand

  6. Expression of the IRT1 metal transporter is controlled by metals at the levels of transcript and protein accumulation.

    PubMed

    Connolly, Erin L; Fett, Janette P; Guerinot, Mary Lou

    2002-06-01

    Iron, an essential nutrient, is not readily available to plants because of its low solubility. In addition, iron is toxic in excess, catalyzing the formation of hydroxyl radicals that can damage cellular constituents. Consequently, plants must carefully regulate iron uptake so that iron homeostasis is maintained. The Arabidopsis IRT1 gene is the major transporter responsible for high-affinity iron uptake from the soil. Here, we show that the steady state level of IRT1 mRNA was induced within 24 h after transfer of plants to iron-deficient conditions, with protein levels peaking 72 h after transfer. IRT1 mRNA and protein were undetectable 12 h after plants were shifted back to iron-sufficient conditions. Overexpression of IRT1 did not confer dominant gain-of-function enhancement of metal uptake. Analysis of 35S-IRT1 transgenic plants revealed that although IRT1 mRNA was expressed constitutively in these plants, IRT1 protein was present only in the roots when iron is limiting. Under these conditions, plants that overexpressed IRT1 accumulated higher levels of cadmium and zinc than wild-type plants, indicating that IRT1 is responsible for the uptake of these metals and that IRT1 protein levels are indeed increased in these plants. Our results suggest that the expression of IRT1 is controlled by two distinct mechanisms that provide an effective means of regulating metal transport in response to changing environmental conditions.

  7. Engineering the expression level of cytosolic nucleoside diphosphate kinase in transgenic Solanum tuberosum roots alters growth, respiration and carbon metabolism.

    PubMed

    Dorion, Sonia; Clendenning, Audrey; Rivoal, Jean

    2017-03-01

    Nucleoside diphosphate kinase (NDPK) is a ubiquitous enzyme that catalyzes the transfer of the γ-phosphate from a donor nucleoside triphosphate to an acceptor nucleoside diphosphate. In this study we used a targeted metabolomic approach and measurement of physiological parameters to report the effects of the genetic manipulation of cytosolic NDPK (NDPK1) expression on physiology and carbon metabolism in potato (Solanum tuberosum) roots. Sense and antisense NDPK1 constructs were introduced in potato using Agrobacterium rhizogenes to generate a population of root clones displaying a 40-fold difference in NDPK activity. Root growth, O2 uptake, flux of carbon between sucrose and CO2 , levels of reactive oxygen species and some tricarboxylic acid cycle intermediates were positively correlated with levels of NDPK1 expression. In addition, NDPK1 levels positively affected UDP-glucose and cellulose contents. The activation state of ADP-glucose pyrophosphorylase, a key enzyme in starch synthesis, was higher in antisense roots than in roots overexpressing NDPK1. Further analyses demonstrated that ADP-glucose pyrophosphorylase was more oxidized, and therefore less active, in sense clones than antisense clones. Consequently, antisense NDPK1 roots accumulated more starch and the starch to cellulose ratio was negatively affected by the level of NDPK1. These data support the idea that modulation of NDPK1 affects the distribution of carbon between starch and cellulose biosynthetic pathways.

  8. High levels of CC-chemokine expression and downregulated levels of CCR5 during HIV-1/HTLV-1 and HIV-1/HTLV-2 coinfections.

    PubMed

    Oo, Z; Barrios, C S; Castillo, L; Beilke, M A

    2015-05-01

    The human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 are common copathogens among Human Immunodeficiency Virus (HIV)-infected individuals. HTLV-2 may confer a survival benefit among patients with HIV-1/HTLV-2 coinfections, along with lower plasma HIV-1 levels and delayed rates of CD4(+) T-cell decline. These effects have been attributed to the ability of the HTLV-2 viral transactivating Tax2 protein to induce the production of high levels of antiviral CC-chemokines and to downregulate expression of the CCR5 receptor, resulting in impaired entry of HIV-1 into CD4(+) T-cells. This study investigated the innate immunity of coinfected HIV/HTLV individuals by testing the ability of patient PBMCs to produce CC-chemokines in association CCR5 receptor modulation. The cellular proliferative responses of HIV/HTLV coinfected versus HIV monoinfected individuals were also evaluated. Higher levels of MIP-1α, MIP-1β, and RANTES (P < 0.05) were found in HIV-1/HTLV-2 coinfected group compared to HIV-1 monoinfected population. Upregulated levels of RANTES were shown in HIV-1/HTLV-1 after 1 and 3 days of culture (P < 0.05). Lymphocytes from HIV-1/HTLV-2 coinfected individuals showed significant CCR5 downregulation after 1 and 3 days of culture compared to lymphocytes from HIV-1 and uninfected groups (P < 0.05). Lower percentages of CCR5-positive cells were found in HIV-1/HTLV-1 coinfected after 3 days of incubation (P < 0.05). Levels of proliferation were significantly higher in the HIV-1/HTLV-1 group compared to HIV-1 alone (P < 0.05). HTLV-2 and HTLV-1 infections may induce the involvement of innate immunity against HIV-1 via stimulation of CC-chemokines and receptors, potentially modifying CCR5/HIV-1 binding and HIV-1 progression in coinfected individuals.

  9. ClC-7 expression levels critically regulate bone turnover, but not gastric acid secretion.

    PubMed

    Supanchart, C; Wartosch, L; Schlack, C; Kühnisch, J; Felsenberg, D; Fuhrmann, J C; de Vernejoul, M-C; Jentsch, T J; Kornak, U

    2014-01-01

    Mutations in the 2Cl(-)/1H(+)-exchanger ClC-7 impair osteoclast function and cause different types of osteoclast-rich osteopetrosis. However, it is unknown to what extent ClC-7 function has to be reduced to become rate-limiting for bone resorption. In osteoclasts from osteopetrosis patients expression of the mutated ClC-7 protein did not correlate with disease severity and resorption impairment. Therefore, a series of transgenic mice expressing ClC-7 in osteoclasts at different levels was generated. Crossing of these mice with Clcn7(-/-) mutants rescued the osteopetrotic phenotype to variable degrees. One resulting double transgenic line mimicked human autosomal dominant osteopetrosis. The trabecular bone of these mice showed a reduction of osteoblast numbers, osteoid, and osteoblast marker gene expression indicative of reduced osteoblast function. In osteoclasts from these mutants ClC-7 expression levels were 20 to 30% of wildtype levels. These reduced levels not only impaired resorptive activity, but also increased numbers, size and nucleus numbers of osteoclasts differentiated in vitro. Although ClC-7 was expressed in the stomach and PTH levels were high in Clcn7(-/-) mutants loss of ClC-7 did not entail a relevant elevation of gastric pH. In conclusion, we show that in our model a reduction of ClC-7 function by approximately 70% is sufficient to increase bone mass, but does not necessarily enhance bone formation. ClC-7 does not appear to be crucially involved in gastric acid secretion, which explains the absence of an osteopetrorickets phenotype in CLCN7-related osteopetrosis.

  10. Expression of nerve growth factor and neurotrophin-3 mRNAs in hippocampal interneurons: morphological characterization, levels of expression, and colocalization of nerve growth factor and neurotrophin-3.

    PubMed

    Pascual, M; Rocamora, N; Acsády, L; Freund, T F; Soriano, E

    1998-05-25

    We have investigated the distribution and morphology of hippocampal interneurons that express the neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the rat. For this study, we combined in situ hybridization for the detection of NGF and NT-3 mRNAs and immunocytochemistry against the calcium-binding proteins parvalbumin (PARV), calretinin (CALR), and calbindin (CALB). Whereas the majority of PARV+ interneurons expressed NGF mRNA, only subsets of CALR- and CALB-immunoreactive interneurons (23% and 24%, respectively) displayed NGF hybridization. Most CALB/NGF+ cells were located in the stratum oriens/alveus of the CA3-CA1 regions, suggesting that they may include the population of CALB+, hippocamposeptal, nonpyramidal neurons. Most of the nonspiny CALR/NGF+ neurons were located within or in the vicinity of the pyramidal layer and had faint CALR immunostaining and stellate, thin dendrites. Regarding the spiny CALR-immunoreactive cells, we found that most of these neurons in the hilus were NGF+, whereas only 59% of displayed NGF hybridization in the stratum lucidum of the CA3 region. A small subset of PARV- and CALR-immunoreactive cells expressed NT-3 mRNA (16% and 13%, respectively). NT-3 message was not found in the large basket cells of the dentate gyrus, whereas the distribution and morphology of CALR/NT-3+ cells were similar to those of nonspiny CALR/NGF+ cells. In fact, double in situ hybridization analysis confirmed that most NT-3+ neurons also expressed NGF mRNA, indicating coexpression of both neurotrophins in subpopulations of PARV+ and CALR+ neurons. Moreover, the level of NGF mRNA expression was higher in PARV+ neurons than in CALR- and CALB-immunoreactive interneurons, whereas NT-3 message was expressed similarly in PARV+ and CALR+ neurons. The present findings show a differential expression of NGF and NT-3 mRNAs in subsets of hippocampal interneurons and suggest that the expression of these transcripts depends on factors intrinsic to

  11. 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

  12. FOXP3 mRNA expression at 6 months of age is higher in infants who develop atopic dermatitis, but is not affected by giving probiotics from birth.

    PubMed

    Taylor, Angie L; Hale, Jasmine; Hales, Belinda J; Dunstan, Janet A; Thomas, Wayne R; Prescott, Susan L

    2007-02-01

    Factors that influence immune regulation in early life may be implicated in the rise in allergic disease, including reduced microbial burden. The aim of the study was to examine the infant regulatory T-cell function in relation to (a) probiotic supplementation for the first 6 months of life and (b) the subsequent development of an early allergic phenotype. Two hundred and thirty-one allergic, pregnant women were recruited into a randomized, controlled trial. The infants received either a probiotic or placebo daily for the first 6 months of life. One hundred and seventy-eight children completed the study, with blood samples available from 118 (60 placebo; 58 probiotic). CD4(+)CD25(+)CTLA4(+)T-regulatory phenotype and allergen-induced FOXP3 mRNA expression were compared in relation to this intervention as well as according to evidence of early disease (atopic dermatitis). The administration of probiotics was not associated with any significant differences in the proportion of circulating CD4(+)CD25(+)CTLA4(+)cells, or in the resting expression of FOXP3. There were also no relationships between these parameters and patterns of gut colonization, and this probiotic did not reduce the risk of atopic dermatitis. Children who developed atopic dermatitis (n = 36/118) had significantly higher induced FOXP3 expression following stimulation with both house dust mite (HDM) (p = 0.017) and ovalbumin (OVA) allergens (p = 0.021) than those that did not develop atopic dermatitis. Although this relationship was seen in both the probiotic and placebo groups, it was more pronounced in the probiotic group. However, regression analysis demonstrated that higher allergen-induced FOXP3 expression was predicted by the presence of atopic dermatitis (p = 0.018) rather than probiotics supplementation (p = 0.217). The higher levels of allergen-induced FOXP3 in atopic dermatitis suggest activation of these compensatory mechanisms rather than a primary defect in this pathway. Probiotic

  13. Circulating ghrelin level is higher in HNF1A-MODY and GCK-MODY than in polygenic forms of diabetes mellitus.

    PubMed

    Nowak, Natalia; Hohendorff, Jerzy; Solecka, Iwona; Szopa, Magdalena; Skupien, Jan; Kiec-Wilk, Beata; Mlynarski, Wojciech; Malecki, Maciej T

    2015-12-01

    Ghrelin is a hormone that regulates appetite. It is likely to be involved in the pathophysiology of varying forms of diabetes. In animal studies, the ghrelin expression was regulated by the hepatocyte nuclear factor 1 alpha (HNF1A). Mutations of the HNF1A gene cause maturity onset diabetes of the young (MODY). We aimed to assess the circulating ghrelin levels in HNF1A-MODY and in other types of diabetes and to evaluate its association with HNF1A mutation status. Our cohort included 46 diabetic HNF1A gene mutation carriers, 55 type 2 diabetes (T2DM) subjects, 42 type 1 diabetes (T1DM) patients, and 31 glucokinase (GCK) gene mutation carriers with diabetes as well as 51 healthy controls. Plasma ghrelin concentration was measured using the immunoenzymatic assay with polyclonal antibody against the C-terminal fragment of its acylated and desacylated forms. Ghrelin concentrations were 0.75 ± 0.32, 0.70 ± 0.21, 0.50 ± 0.20, and 0.40 ± 0.16 ng/ml in patients with HNF1A-MODY, GCK-MODY, T1DM, and T2DM, respectively. The ghrelin levels were higher in HNF1A-MODY and GCK-MODY than in T1DM and T2DM (p < 0.001 for all comparisons) but lower than in non-diabetic controls (1.02 ± 0.29 ng/ml, p < 0.001 for both comparisons). In the multivariate linear model, the differences between both MODY groups and common diabetes types remained significant. Analysis by a HNF1A mutation type indicated that ghrelin concentration is similar in patients with different types of sequence differences. Plasma ghrelin level is higher in HNF1A-MODY and GCK-MODY than in the common polygenic forms of diabetes.

  14. Development of Saccharomyces cerevisiae producing higher levels of sulfur dioxide and glutathione to improve beer flavor stability.

    PubMed

    Chen, Yefu; Yang, Xu; Zhang, Shijie; Wang, Xiaoqiong; Guo, Changhui; Guo, Xuewu; Xiao, Dongguang

    2012-01-01

    Sulfur compounds, such as sulfite (SO(2)), hydrogen sulfide (H(2)S), and glutathione (GSH), play different roles in beer flavor stability. SO(2) and GSH have antiaging effects which are helpful to improve the flavor stability of beer, whereas H(2)S is undesirable to beer flavor because of its unpleasant aroma. Here, we report the development of Saccharomyces cerevisiae which produces higher levels of SO(2) and GSH but lower level of H(2)S to improve beer flavor stability by nongenetic engineering approaches. After two rounds of UV mutagenesis coupled with specific plate screening methods, one promising mutant named MV16 was obtained. Compared with the original strain, the SO(2) and GSH production of MV16 in fermenting liquor increased by 31% and 30.2%, respectively, while H(2)S content decreased by 74.9%, and the DPPH radical clearance and the resistance staling value of beer fermented by MV16 increased by 24.6% and 33.0%, respectively. The antioxidizability of the mutant was improved significantly. The strategy adopted in our study could be used to obtain S. cerevisiae of improved antiaging properties, and the mutant would be safe for public use.

  15. The Effects of Using Concept Mapping for Improving Advanced Level Biology Students' Lower- and Higher-Order Cognitive Skills

    NASA Astrophysics Data System (ADS)

    Bramwell-Lalor, Sharon; Rainford, Marcia

    2014-03-01

    This paper reports on teachers' use of concept mapping as an alternative assessment strategy in advanced level biology classes and its effects on students' cognitive skills on selected biology concepts. Using a mixed methods approach, the study employed a pre-test/post-test quasi-experimental design involving 156 students and 8 teachers from intact classes. A researcher-constructed Biology Cognitive Skills Test was used to collect the quantitative data. Qualitative data were collected through interviews and students' personal documents. The data showed that the participants utilized concept mapping in various ways and they described positive experiences while being engaged in its use. The main challenge cited by teachers was the limited time available for more consistent use. The results showed that the use of concept mapping in advanced level biology can lead to learning gains that exceed those achieved in classes where mainly traditional methods are used. The students in the concept mapping experimental groups performed significantly better than their peers in the control group on both the lower-order (F(1) = 21.508; p < .001) and higher-order (F(1) = 42.842, p < .001) cognitive items of the biology test. A mean effect size of .56 was calculated representing the contribution of treatment to the students' performance on the test items.

  16. 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.

  17. LDPC Coding for QKD at Higher Photon Flux Levels Based on Spatial Entanglement of Twin beams in PDC

    NASA Astrophysics Data System (ADS)

    Daneshgaran, Fred; Mondin, Marina; Bari, Inam

    2014-04-01

    Twin beams generated by Parametric Down Conversion (PDC) exhibit quantum correlations that has been effectively used as a tool for many applications including calibration of single photon detectors. By now, detection of multi-mode spatial correlations is a mature field and in principle, only depends on the transmission and detection efficiency of the devices and the channel. In [2, 4, 5], the authors utilized their know-how on almost perfect selection of modes of pairwise correlated entangled beams and the optimization of the noise reduction to below the shot-noise level, for absolute calibration of Charge Coupled Device (CCD) cameras. The same basic principle is currently being considered by the same authors for possible use in Quantum Key Distribution (QKD) [3, 1]. The main advantage in such an approach would be the ability to work with much higher photon fluxes than that of a single photon regime that is theoretically required for discrete variable QKD applications (in practice, very weak laser pulses with mean photon count below one are used).The natural setup of quantization of CCD detection area and subsequent measurement of the correlation statistic needed to detect the presence of the eavesdropper Eve, leads to a QKD channel model that is a Discrete Memoryless Channel (DMC) with a number of inputs and outputs that can be more than two (i.e., the channel is a multi-level DMC). This paper investigates the use of Low Density Parity Check (LDPC) codes for information reconciliation on the effective parallel channels associated with the multi-level DMC. The performance of such codes are shown to be close to the theoretical limits.

  18. Higher levels of ethyl paraben and butyl paraben in rat amniotic fluid than in maternal plasma after subcutaneous administration.

    PubMed

    Frederiksen, Hanne; Taxvig, Camilla; Hass, Ulla; Vinggaard, Anne M; Nellemann, Christine

    2008-12-01

    Parabens are a group of antimicrobial preservatives widely used in cosmetics, pharmaceuticals, and in foods. Previous in vitro and in vivo studies have shown weak estrogenic effects of some parabens. Thus, especially, exposure of fetus and infants via the mother is a matter of concern. In order to obtain more knowledge about the distribution of ethyl paraben and butyl paraben in pregnant rats and pups after perinatal exposure, the presented study was designed. The data show response and distribution of ethyl paraben and butyl paraben in maternal rat plasma, pools of amniotic fluids, placenta, whole-body fetuses, and in fetal liver after dosing of dams with 100, 200, and 400 mg/kg body weight (bw)/day from gestational day 7 to 21. After cesarean section of dams, the fluids and tissues were collected, deconjugated, and purified by solid-phase extraction, and ethyl paraben and butyl paraben were analyzed by liquid chromatography-tandem mass spectrometry. Markedly higher levels of ethyl paraben compared to butyl paraben were found in all fluids and tissues. Both ethyl paraben and butyl paraben in maternal plasma, livers, and whole-body tissues from fetus seemed to be saturated after dosing with >or= 100 mg/kg bw/day, while both compounds were excreted into amniotic fluid in a dose-dependent manner. Significant difference was found between the level of ethyl paraben in maternal plasma and amniotic fluid after dosing with 200 mg/kg bw/day as well as between the levels of butyl paraben in maternal plasma and amniotic fluid after dosing with 100, 200, and 400 mg/kg bw/day.

  19. 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.

  20. Constitutively expressed DHAR and MDHAR influence fruit, but not foliar ascorbate levels in tomato.

    PubMed

    Haroldsen, Victor M; Chi-Ham, Cecilia L; Kulkarni, Shashank; Lorence, Argelia; Bennett, Alan B

    2011-10-01

    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 l