WorldWideScience

Sample records for growth depend similarly

  1. Self-similar growth of three-dimensional fault

    International Nuclear Information System (INIS)

    Zhou Huilan.

    1989-04-01

    By using forthright mathematical treatment, this paper expands the two-dimensional Self-Similar model of faulting proposed by Fukao and Furumoto (1985) in three-dimensions, and explains the energy ratio of α of precursor to main shock, magnitude difference ΔΜ between the main shock and its largest aftershock, and b value in magnitude-frequency relationship. The present model gives α 0.08, ΔΜ = 1.21 and b = 1.5, respectively. These results are more consistent with the observations than the two-dimensional model. (author). 3 refs, 2 figs, 2 tabs

  2. Dependence centrality similarity: Measuring the diversity of profession levels of interests

    Science.gov (United States)

    Yan, Deng-Cheng; Li, Ming; Wang, Bing-Hong

    2017-08-01

    To understand the relations between developers and software, we study a collaborative coding platform from the perspective of networks, including follower networks, dependence networks and developer-project bipartite networks. Through the analyzing of degree distribution, PageRank and degree-dependent nearest neighbors' centrality, we find that the degree distributions of all networks have a power-law form except the out-degree distributions of dependence networks. The nearest neighbors' centrality is negatively correlated with degree for developers but fluctuates around the average for projects. In order to measure the diversity of profession levels of interests, a new index called dependence centrality similarity is proposed and the correlation between dependence centrality similarity and degree is investigated. The result shows an obvious negative correlations between dependence centrality similarity and degree.

  3. The compositional similarity of urban forests among the world's cities is scale dependent

    Science.gov (United States)

    Jun Yang; Frank A. La Sorte; Petr Pysek; Pengbo Yan; David Nowak; Joe McBride

    2015-01-01

    Aim We examined species composition of urban forests from local to global scales using occurrence and abundance information to determine how compositional similarity is defined across spatial scales. We predicted that urban forests have become more homogeneous world-wide, which should result in minimal scale dependence that is more pronounced for non-native species,...

  4. Noonan syndrome and Turner syndrome patients respond similarly to 4 years' growth-hormone therapy

    DEFF Research Database (Denmark)

    Lee, Peter A; Ross, Judith L; Pedersen, Birgitte Tønnes

    2015-01-01

    BACKGROUND: Turner syndrome (TS) and Noonan syndrome (NS) are distinct syndromes associated with short stature and other similar phenotypic features. We compared the responses to growth hormone (GH) therapy of TS and NS patients enrolled in the NordiNet® International Outcome Study (IOS) or the A...

  5. Self-similar measures in multi-sector endogenous growth models

    International Nuclear Information System (INIS)

    La Torre, Davide; Marsiglio, Simone; Mendivil, Franklin; Privileggi, Fabio

    2015-01-01

    We analyze two types of stochastic discrete time multi-sector endogenous growth models, namely a basic Uzawa–Lucas (1965, 1988) model and an extended three-sector version as in La Torre and Marsiglio (2010). As in the case of sustained growth the optimal dynamics of the state variables are not stationary, we focus on the dynamics of the capital ratio variables, and we show that, through appropriate log-transformations, they can be converted into affine iterated function systems converging to an invariant distribution supported on some (possibly fractal) compact set. This proves that also the steady state of endogenous growth models—i.e., the stochastic balanced growth path equilibrium—might have a fractal nature. We also provide some sufficient conditions under which the associated self-similar measures turn out to be either singular or absolutely continuous (for the three-sector model we only consider the singularity).

  6. The obesity epidemic and food addiction: clinical similarities to drug dependence.

    Science.gov (United States)

    Fortuna, Jeffrey L

    2012-01-01

    As of 2010 nearly 70% of adult Americans were overweight or obese. Specifically, 35.7% of adult Americans are obese, and this is the highest level of obesity in the recorded history of the United States. A number of environmental factors, most notably the number of fast food outlets, have contributed to the obesity epidemic as well as to the binge prone dynamic. There is evidence that bingeing on sugar-dense, palatable foods increases extracellular dopamine in the striatum and thereby possesses addictive potential. Moreover, elevated blood glucose levels catalyze the absorption of tryptophan through the large neutral amino acid (LNAA) complex and its subsequent conversion into the mood-elevating chemical serotonin. There appear to be several biological and psychological similarities between food addiction and drug dependence including craving and loss of control. Nonetheless there is at least one apparent difference: acute tryptophan depletion does not appear to induce a relapse in recovering drug-dependent individuals, although it may induce dysphoria. In some individuals, palatable foods have palliative properties and can be viewed as a form of self medication. This article will examine environmental factors that have contributed to the obesity epidemic, and will compare the clinical similarities and differences of food addiction and drug dependence.

  7. Structural similarity causes different category-effects depending on task characteristics

    DEFF Research Database (Denmark)

    Gerlach, Christian

    2001-01-01

    are more globally visually similar than artefacts, but that this difference between categories affects performance in different ways depending on task characteristics. Thus, the greater overlap between natural objects may be a disadvantage when the demand on perceptual differentiation is high (as......It has been suggested that category-specific impairments for natural objects may reflect that natural objects are more globally visually similar than artefacts and therefore more difficult to recognize following brain damage [Aphasiology 13 (1992) 169]. This account has been challenged...... by the finding that the 'normal' disadvantage claimed for natural objects may be reversed when items from the categories of natural objects and artefacts are matched for visual complexity, familiarity and name frequency [Neuropsychologia 37 (1999) 1263]. In the experiments reported here it was investigated...

  8. Similarity and Difference in Drug Addiction Process Between Heroin- and Methamphetamine-Dependent Users.

    Science.gov (United States)

    Wang, Ziyun; Li, Wei-Xiu; Zhi-Min, Liu

    2017-03-21

    This study aimed to compare the drug addiction process between Chinese heroin- and methamphetamine (MA)-dependent users via a modified 4-stage addiction model (experimentation, occasional use, regular use, and compulsive use). A descriptive study was conducted among 683 eligible participants. In the statistical analysis, we selected 340 heroin- and 295 MA-dependent users without illicit drug use prior to onset of heroin or MA use. The addiction process of heroin-dependent users was shorter than that of MA-dependent users, with shorter transitions from the onset of drug-use to the first drug craving (19.5 vs. 50.0 days), regular use (30.0 vs. 60.0 days), and compulsive use (50.0 vs. 85.0 days). However, no significant differences in the addiction process were observed in frequency of drug administration, except that heroin users reported more administrations of the drug (20.0 vs. 15.0) before progressing to the stage of compulsive drug use. A larger proportion of regular heroin users progressed to use illicit drugs recklessly than did MA users. Most heroin and MA users reported psychological dependence as their primary motivation for compulsive drug use, but more heroin users selected uncomfortable symptoms upon ceasing drug use as further reason to continue. Our results suggest that typical heroin and MA users may experience a similar four-stage addiction process, but MA users might undergo a longer addiction process (in days). More research is necessary to further explore factors influencing the drug addiction process.

  9. Domestication and growth hormone transgenesis cause similar changes in gene expression in coho salmon (Oncorhynchus kisutch).

    Science.gov (United States)

    Devlin, Robert H; Sakhrani, Dionne; Tymchuk, Wendy E; Rise, Matthew L; Goh, Benjamin

    2009-03-03

    Domestication has been extensively used in agricultural animals to modify phenotypes such as growth rate. More recently, transgenesis of growth factor genes [primarily growth hormone (GH)] has also been explored as a rapid approach to accelerating performance of agricultural species. Growth rates of many fishes respond dramatically to GH gene transgenesis, whereas genetic engineering of domestic mammalian livestock has resulted in relatively modest gains. The most dramatic effects of GH transgenesis in fish have been seen in relatively wild strains that have undergone little or no selection for enhanced growth, whereas genetic modification of livestock necessarily has been performed in highly domesticated strains that already possess very rapid growth. Such fast-growing domesticates may be refractory to further stimulation if the same regulatory pathways are being exploited by both genetic approaches. By directly comparing gene expression in wild-type, domestic, and GH transgenic strains of coho salmon, we have found that domestication and GH transgenesis are modifying similar genetic pathways. Genes in many different physiological pathways show modified expression in domestic and GH transgenic strains relative to wild-type, but effects are strongly correlated. Genes specifically involved in growth regulation (IGF1, GHR, IGF-II, THR) are also concordantly regulated in domestic and transgenic fish, and both strains show elevated levels of circulating IGF1. Muscle expression of GH in nontransgenic strains was found to be elevated in domesticated fish relative to wild type, providing a possible mechanism for growth enhancement. These data have implications for genetic improvement of existing domesticated species and risk assessment and regulation of emerging transgenic strains.

  10. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction.

    Science.gov (United States)

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R; Rattan, Ramandeep

    2015-05-10

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent.

  11. Role of MYC in Anchorage-Dependent Growth

    National Research Council Canada - National Science Library

    Benaud, Christelle

    2000-01-01

    .... We have shown, here using a human mammary epithelial model, that the expression of the early growth control gene, c-Myc, is directly regulated by cell adhesion through a 1 integrin-dependent pathway...

  12. Peroxisomal catalase deficiency modulates yeast lifespan depending on growth conditions

    NARCIS (Netherlands)

    Kawalek, Adam; Lefevre, Sophie D.; Veenhuis, Marten; van der Klei, Ida J.

    We studied the role of peroxisomal catalase in chronological aging of the yeast Hansenula polymorpha in relation to various growth substrates. Catalase-deficient (cat) cells showed a similar chronological life span (CLS) relative to the wild-type control upon growth on carbon and nitrogen sources

  13. Scaling relation between earthquake magnitude and the departure time from P wave similar growth

    Science.gov (United States)

    Noda, Shunta; Ellsworth, William L.

    2016-01-01

    We introduce a new scaling relation between earthquake magnitude (M) and a characteristic of initial P wave displacement. By examining Japanese K-NET data averaged in bins partitioned by Mw and hypocentral distance, we demonstrate that the P wave displacement briefly displays similar growth at the onset of rupture and that the departure time (Tdp), which is defined as the time of departure from similarity of the absolute displacement after applying a band-pass filter, correlates with the final M in a range of 4.5 ≤ Mw ≤ 7. The scaling relation between Mw and Tdp implies that useful information on the final M can be derived while the event is still in progress because Tdp occurs before the completion of rupture. We conclude that the scaling relation is important not only for earthquake early warning but also for the source physics of earthquakes.

  14. Localized Technological Change and Path-Dependent Growth

    OpenAIRE

    Bassanini, A.

    1997-01-01

    In recent years the theory of macroeconomic growth has seen an expanding literature building upon the idea that technological change is localized (technology-specific) to investigate various phenomena such as leapfrogging, take-off, and social mobility. In this paper I explore the relationship between localized technological change and dependence on history of long-run aggregate output growth. The growth model I set forth show that, subject to mild assumptions on the stochastic process repres...

  15. Density-dependent growth in invasive Lionfish (Pterois volitans.

    Directory of Open Access Journals (Sweden)

    Cassandra E Benkwitt

    Full Text Available Direct demographic density dependence is necessary for population regulation and is a central concept in ecology, yet has not been studied in many invasive species, including any invasive marine fish. The red lionfish (Pterois volitans is an invasive predatory marine fish that is undergoing exponential population growth throughout the tropical western Atlantic. Invasive lionfish threaten coral-reef ecosystems, but there is currently no evidence of any natural population control. Therefore, a manipulative field experiment was conducted to test for density dependence in lionfish. Juvenile lionfish densities were adjusted on small reefs and several demographic rates (growth, recruitment, immigration, and loss were measured throughout an 8-week period. Invasive lionfish exhibited direct density dependence in individual growth rates, as lionfish grew slower at higher densities throughout the study. Individual growth in length declined linearly with increasing lionfish density, while growth in mass declined exponentially with increasing density. There was no evidence, however, for density dependence in recruitment, immigration, or loss (mortality plus emigration of invasive lionfish. The observed density-dependent growth rates may have implications for which native species are susceptible to lionfish predation, as the size and type of prey that lionfish consume is directly related to their body size. The absence of density-dependent loss, however, contrasts with many native coral-reef fish species and suggests that for the foreseeable future manual removals may be the only effective local control of this invasion.

  16. Zebra finches have a light-dependent magnetic compass similar to migratory birds.

    Science.gov (United States)

    Pinzon-Rodriguez, Atticus; Muheim, Rachel

    2017-04-01

    Birds have a light-dependent magnetic compass that provides information about the spatial alignment of the geomagnetic field. It is proposed to be located in the avian retina and mediated by a light-induced, radical-pair mechanism involving cryptochromes as sensory receptor molecules. To investigate how the behavioural responses of birds under different light spectra match with cryptochromes as the primary magnetoreceptor, we examined the spectral properties of the magnetic compass in zebra finches. We trained birds to relocate a food reward in a spatial orientation task using magnetic compass cues. The birds were well oriented along the trained magnetic compass axis when trained and tested under low-irradiance 521 nm green light. In the presence of a 1.4 MHz radio-frequency electromagnetic (RF)-field, the birds were disoriented, which supports the involvement of radical-pair reactions in the primary magnetoreception process. Birds trained and tested under 638 nm red light showed a weak tendency to orient ∼45 deg clockwise of the trained magnetic direction. Under low-irradiance 460 nm blue light, they tended to orient along the trained magnetic compass axis, but were disoriented under higher irradiance light. Zebra finches trained and tested under high-irradiance 430 nm indigo light were well oriented along the trained magnetic compass axis, but disoriented in the presence of a RF-field. We conclude that magnetic compass responses of zebra finches are similar to those observed in nocturnally migrating birds and agree with cryptochromes as the primary magnetoreceptor, suggesting that light-dependent, radical-pair-mediated magnetoreception is a common property for all birds, including non-migratory species. © 2017. Published by The Company of Biologists Ltd.

  17. Reynolds-number dependence of turbulence enhancement on collision growth

    Directory of Open Access Journals (Sweden)

    R. Onishi

    2016-10-01

    Full Text Available This study investigates the Reynolds-number dependence of turbulence enhancement on the collision growth of cloud droplets. The Onishi turbulent coagulation kernel proposed in Onishi et al. (2015 is updated by using the direct numerical simulation (DNS results for the Taylor-microscale-based Reynolds number (Reλ up to 1140. The DNS results for particles with a small Stokes number (St show a consistent Reynolds-number dependence of the so-called clustering effect with the locality theory proposed by Onishi et al. (2015. It is confirmed that the present Onishi kernel is more robust for a wider St range and has better agreement with the Reynolds-number dependence shown by the DNS results. The present Onishi kernel is then compared with the Ayala–Wang kernel (Ayala et al., 2008a; Wang et al., 2008. At low and moderate Reynolds numbers, both kernels show similar values except for r2 ∼ r1, for which the Ayala–Wang kernel shows much larger values due to its large turbulence enhancement on collision efficiency. A large difference is observed for the Reynolds-number dependences between the two kernels. The Ayala–Wang kernel increases for the autoconversion region (r1, r2 < 40 µm and for the accretion region (r1 < 40 and r2 > 40 µm; r1 > 40 and r2 < 40 µm as Reλ increases. In contrast, the Onishi kernel decreases for the autoconversion region and increases for the rain–rain self-collection region (r1, r2 > 40 µm. Stochastic collision–coalescence equation (SCE simulations are also conducted to investigate the turbulence enhancement on particle size evolutions. The SCE with the Ayala–Wang kernel (SCE-Ayala and that with the present Onishi kernel (SCE-Onishi are compared with results from the Lagrangian Cloud Simulator (LCS; Onishi et al., 2015, which tracks individual particle motions and size evolutions in homogeneous isotropic turbulence. The SCE-Ayala and SCE-Onishi kernels show consistent

  18. BMP signaling regulates satellite cell-dependent postnatal muscle growth.

    Science.gov (United States)

    Stantzou, Amalia; Schirwis, Elija; Swist, Sandra; Alonso-Martin, Sonia; Polydorou, Ioanna; Zarrouki, Faouzi; Mouisel, Etienne; Beley, Cyriaque; Julien, Anaïs; Le Grand, Fabien; Garcia, Luis; Colnot, Céline; Birchmeier, Carmen; Braun, Thomas; Schuelke, Markus; Relaix, Frédéric; Amthor, Helge

    2017-08-01

    Postnatal growth of skeletal muscle largely depends on the expansion and differentiation of resident stem cells, the so-called satellite cells. Here, we demonstrate that postnatal satellite cells express components of the bone morphogenetic protein (BMP) signaling machinery. Overexpression of noggin in postnatal mice (to antagonize BMP ligands), satellite cell-specific knockout of Alk3 (the gene encoding the BMP transmembrane receptor) or overexpression of inhibitory SMAD6 decreased satellite cell proliferation and accretion during myofiber growth, and ultimately retarded muscle growth. Moreover, reduced BMP signaling diminished the adult satellite cell pool. Abrogation of BMP signaling in satellite cell-derived primary myoblasts strongly diminished cell proliferation and upregulated the expression of cell cycle inhibitors p21 and p57 In conclusion, these results show that BMP signaling defines postnatal muscle development by regulating satellite cell-dependent myofiber growth and the generation of the adult muscle stem cell pool. © 2017. Published by The Company of Biologists Ltd.

  19. Similar temperature dependencies of glycolytic enzymes : An evolutionary adaptation to temperature dynamics?

    NARCIS (Netherlands)

    Cruz, L.A.B.; Hebly, M.; Duong, G.H.; Wahl, S.A.; Pronk, J.T.; Heijnen, J.J.; Daran-Lapujade, P.; Van Gulik, W.M.

    2012-01-01

    Background Temperature strongly affects microbial growth, and many microorganisms have to deal with temperature fluctuations in their natural environment. To understand regulation strategies that underlie microbial temperature responses and adaptation, we studied glycolytic pathway kinetics in

  20. How glitter relates to gold : Similarity-dependent reward prediction errors in the human striatum

    NARCIS (Netherlands)

    Kahnt, T.; Park, S.Q.; Burke, C.; Tobler, P.N.

    2012-01-01

    Optimal choices benefit from previous learning. However, it is not clear how previously learned stimuli influence behavior to novel but similar stimuli. One possibility is to generalize based on the similarity between learned and current stimuli. Here, we use neuroscientific methods and a novel

  1. Density-dependent growth and metamorphosis in the larval bronze ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 28; Issue 4. Density-dependent growth and metamorphosis in the larval bronze frog Rana temporalis is influenced by genetic relatedness of the cohort. S Girish S K Saidapur. Articles Volume 28 Issue 4 June 2003 pp 489-496 ...

  2. Density-dependent growth and metamorphosis in the larval bronze ...

    Indian Academy of Sciences (India)

    Unknown

    [Girish S and Saidapur S K 2002 Density-dependent growth and metamorphosis in the larval bronze frog Rana temporalis is influenced by genetic relatedness of the ... kin interaction during larval development in anurans seems to vary with the ... leaves were cut into small pieces of uniform size before boiling. Ten grams of ...

  3. Similarity transformed coupled cluster response (ST-CCR) theory--a time-dependent similarity transformed equation-of-motion coupled cluster (STEOM-CC) approach.

    Science.gov (United States)

    Landau, Arie

    2013-07-07

    This paper presents a new method for calculating spectroscopic properties in the framework of response theory utilizing a sequence of similarity transformations (STs). The STs are preformed using the coupled cluster (CC) and Fock-space coupled cluster operators. The linear and quadratic response functions of the new similarity transformed CC response (ST-CCR) method are derived. The poles of the linear response yield excitation-energy (EE) expressions identical to the ones in the similarity transformed equation-of-motion coupled cluster (STEOM-CC) approach. ST-CCR and STEOM-CC complement each other, in analogy to the complementarity of CC response (CCR) and equation-of-motion coupled cluster (EOM-CC). ST-CCR/STEOM-CC and CCR/EOM-CC yield size-extensive and size-intensive EEs, respectively. Other electronic-properties, e.g., transition dipole strengths, are also size-extensive within ST-CCR, in contrast to STEOM-CC. Moreover, analysis suggests that in comparison with CCR, the ST-CCR expressions may be confined to a smaller subspace, however, the precise scope of the truncation can only be determined numerically. In addition, reformulation of the time-independent STEOM-CC using the same parameterization as in ST-CCR, as well as an efficient truncation scheme, is presented. The shown convergence of the time-dependent and time-independent expressions displays the completeness of the presented formalism.

  4. Filling Predictable and Unpredictable Gaps, with and without Similarity-Based Interference: Evidence for LIFG Effects of Dependency Processing.

    Science.gov (United States)

    Leiken, Kimberly; McElree, Brian; Pylkkänen, Liina

    2015-01-01

    One of the most replicated findings in neurolinguistic literature on syntax is the increase of hemodynamic activity in the left inferior frontal gyrus (LIFG) in response to object relative (OR) clauses compared to subject relative clauses. However, behavioral studies have shown that ORs are primarily only costly when similarity-based interference is involved and recently, Leiken and Pylkkänen (2014) showed with magnetoencephalography (MEG) that an LIFG increase at an OR gap is also dependent on such interference. However, since ORs always involve a cue indicating an upcoming dependency formation, OR dependencies could be processed already prior to the gap-site and thus show no sheer dependency effects at the gap itself. To investigate the role of gap predictability in LIFG dependency effects, this MEG study compared ORs to verb phrase ellipsis (VPE), which was used as an example of a non-predictable dependency. Additionally, we explored LIFG sensitivity to filler-gap order by including right node raising structures, in which the order of filler and gap is reverse to that of ORs and VPE. Half of the stimuli invoked similarity-based interference and half did not. Our results demonstrate that LIFG effects of dependency can be elicited regardless of whether the dependency is predictable, the stimulus materials evoke similarity-based interference, or the filler precedes the gap. Thus, contrary to our own prior data, the current findings suggest a highly general role for the LIFG in dependency interpretation that is not limited to environments involving similarity-based interference. Additionally, the millisecond time-resolution of MEG allowed for a detailed characterization of the temporal profiles of LIFG dependency effects across our three constructions, revealing that the timing of these effects is somewhat construction-specific.

  5. Filling Predictable and Unpredictable Gaps, with and without Similarity-Based Interference: Evidence for LIFG Effects of Dependency Processing

    Science.gov (United States)

    Leiken, Kimberly; McElree, Brian; Pylkkänen, Liina

    2015-01-01

    One of the most replicated findings in neurolinguistic literature on syntax is the increase of hemodynamic activity in the left inferior frontal gyrus (LIFG) in response to object relative (OR) clauses compared to subject relative clauses. However, behavioral studies have shown that ORs are primarily only costly when similarity-based interference is involved and recently, Leiken and Pylkkänen (2014) showed with magnetoencephalography (MEG) that an LIFG increase at an OR gap is also dependent on such interference. However, since ORs always involve a cue indicating an upcoming dependency formation, OR dependencies could be processed already prior to the gap-site and thus show no sheer dependency effects at the gap itself. To investigate the role of gap predictability in LIFG dependency effects, this MEG study compared ORs to verb phrase ellipsis (VPE), which was used as an example of a non-predictable dependency. Additionally, we explored LIFG sensitivity to filler-gap order by including right node raising structures, in which the order of filler and gap is reverse to that of ORs and VPE. Half of the stimuli invoked similarity-based interference and half did not. Our results demonstrate that LIFG effects of dependency can be elicited regardless of whether the dependency is predictable, the stimulus materials evoke similarity-based interference, or the filler precedes the gap. Thus, contrary to our own prior data, the current findings suggest a highly general role for the LIFG in dependency interpretation that is not limited to environments involving similarity-based interference. Additionally, the millisecond time-resolution of MEG allowed for a detailed characterization of the temporal profiles of LIFG dependency effects across our three constructions, revealing that the timing of these effects is somewhat construction-specific. PMID:26635655

  6. Filling predictable and unpredictable gaps, with and without similarity-based interference: Evidence for LIFG effects of dependency processing

    Directory of Open Access Journals (Sweden)

    Kimberly eLeiken

    2015-11-01

    Full Text Available One of the most replicated findings in neurolinguistic literature on syntax is the increase of hemodynamic activity in the left inferior frontal gyrus (LIFG in response to object relative clauses (ORs compared to subject relative clauses (SRs. However, behavioral studies have shown that ORs are primarily only costly when similarity-based interference is involved and recently, Leiken & Pylkkänen (2014 showed with magnetoencephalography (MEG that an LIFG increase at an OR gap is also dependent on such interference. However, since ORs always involve a cue indicating an upcoming dependency formation, OR dependencies could be processed already prior to the gap-site and thus show no sheer dependency effects at the gap itself. To investigate the role of gap predictability in LIFG dependency effects, this MEG study compared ORs to Verb Phrase Ellipsis (VPE, which was used as an example of a non-predictable dependency. Additionally, we explored LIFG sensitivity to filler-gap order by including Right Node Raising (RNR structures, in which the order of filler and gap is reverse to that of ORs and VPE. Half of the stimuli invoked similarity-based interference and half did not. Our results demonstrate that LIFG effects of dependency can be elicited regardless of whether the dependency is predictable, the stimulus materials evoke similarity-based interference, or the filler precedes the gap. Thus, contrary to our own prior data, the current findings suggest a highly general role for the LIFG in dependency interpretation that is not limited to environments involving similarity-based interference. Additionally, the millisecond time-resolution of MEG allowed for a detailed characterization of the temporal profiles of LIFG dependency effects across our three constructions, revealing that the timing of these effects is somewhat construction-specific.

  7. Resolving nanoparticle growth mechanisms from size- and time-dependent growth rate analysis

    Science.gov (United States)

    Pichelstorfer, Lukas; Stolzenburg, Dominik; Ortega, John; Karl, Thomas; Kokkola, Harri; Laakso, Anton; Lehtinen, Kari E. J.; Smith, James N.; McMurry, Peter H.; Winkler, Paul M.

    2018-01-01

    Atmospheric new particle formation occurs frequently in the global atmosphere and may play a crucial role in climate by affecting cloud properties. The relevance of newly formed nanoparticles depends largely on the dynamics governing their initial formation and growth to sizes where they become important for cloud microphysics. One key to the proper understanding of nanoparticle effects on climate is therefore hidden in the growth mechanisms. In this study we have developed and successfully tested two independent methods based on the aerosol general dynamics equation, allowing detailed retrieval of time- and size-dependent nanoparticle growth rates. Both methods were used to analyze particle formation from two different biogenic precursor vapors in controlled chamber experiments. Our results suggest that growth rates below 10 nm show much more variation than is currently thought and pin down the decisive size range of growth at around 5 nm where in-depth studies of physical and chemical particle properties are needed.

  8. Medium-dependent control of the bacterial growth rate.

    Science.gov (United States)

    Ehrenberg, Måns; Bremer, Hans; Dennis, Patrick P

    2013-04-01

    By combining results from previous studies of nutritional up-shifts we here re-investigate how bacteria adapt to different nutritional environments by adjusting their macromolecular composition for optimal growth. We demonstrate that, in contrast to a commonly held view the macromolecular composition of bacteria does not depend on the growth rate as an independent variable, but on three factors: (i) the genetic background (i.e. the strain used), (ii) the physiological history of the bacteria used for inoculation of a given growth medium, and (iii) the kind of nutrients in the growth medium. These factors determine the ribosome concentration and the average rate of protein synthesis per ribosome, and thus the growth rate. Immediately after a nutritional up-shift, the average number of ribosomes in the bacterial population increases exponentially with time at a rate which eventually is attained as the final post-shift growth rate of all cell components. After a nutritional up-shift from one minimal medium to another minimal medium of higher nutritional quality, ribosome and RNA polymerase syntheses are co-regulated and immediately increase by the same factor equal to the increase in the final growth rate. However, after an up-shift from a minimal medium to a medium containing all 20 amino acids, RNA polymerase and ribosome syntheses are no longer coregulated; a smaller rate of synthesis of RNA polymerase is compensated by a gradual increase in the fraction of free RNA polymerase, possibly due to a gradual saturation of mRNA promoters. We have also analyzed data from a recent publication, in which it was concluded that the macromolecular composition in terms of RNA/protein and RNA/DNA ratios is solely determined by the effector molecule ppGpp. Our analysis indicates that this is true only in special cases and that, in general, medium adaptation also depends on factors other than ppGpp. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  9. Similar age-dependent levothyroxine requirements of schoolchildren with congenital or acquired hypothyroidism.

    Science.gov (United States)

    Perlsteyn, Martin; Deladoëy, Johnny; Van Vliet, Guy

    2016-06-01

    A recent study in children suggested that levothyroxine requirements are higher in congenital than in acquired hypothyroidism but did not match for severity of disease. Here, we studied only children with congenital or acquired hypothyroidism who had an undetectable fT4 at diagnosis. There were eight girls with congenital hypothyroidism due to athyreosis and eight girls with acquired hypothyroidism due to autoimmune thyroid disease. The median levothyroxine dose received at the most recent visit when serum TSH was levothyroxine requirement decreased by 0.5 mcg/kg/day for every 4-year period. When strictly matched for severity of disease, levothyroxine requirements are similar in school-age children with congenital or acquired hypothyroidism and decrease with age. Thus, in congenital hypothyroidism treated early with high-dose levothyroxine, pituitary resistance to thyroxine feedback does not appear to be present at school age. • Pediatric studies unmatched for severity have suggested that levothyroxine requirements are higher in congenital than in acquired hypothyroidism. What is new: • When strictly matched for severity, levothyroxine requirements are similar in children with congenital or acquired hypothyroidism and decrease with age.

  10. Evolution of space dependent growth in the teleost Astyanax mexicanus.

    Directory of Open Access Journals (Sweden)

    Natalya D Gallo

    Full Text Available The relationship between growth rate and environmental space is an unresolved issue in teleosts. While it is known from aquaculture studies that stocking density has a negative relationship to growth, the underlying mechanisms have not been elucidated, primarily because the growth rate of populations rather than individual fish were the subject of all previous studies. Here we investigate this problem in the teleost Astyanax mexicanus, which consists of a sighted surface-dwelling form (surface fish and several blind cave-dwelling (cavefish forms. Surface fish and cavefish are distinguished by living in spatially contrasting environments and therefore are excellent models to study the effects of environmental size on growth. Multiple controlled growth experiments with individual fish raised in confined or unconfined spaces showed that environmental size has a major impact on growth rate in surface fish, a trait we have termed space dependent growth (SDG. In contrast, SDG has regressed to different degrees in the Pachón and Tinaja populations of cavefish. Mating experiments between surface and Pachón cavefish show that SDG is inherited as a dominant trait and is controlled by multiple genetic factors. Despite its regression in blind cavefish, SDG is not affected when sighted surface fish are raised in darkness, indicating that vision is not required to perceive and react to environmental space. Analysis of plasma cortisol levels showed that an elevation above basal levels occurred soon after surface fish were exposed to confined space. This initial cortisol peak was absent in Pachón cavefish, suggesting that the effects of confined space on growth may be mediated partly through a stress response. We conclude that Astyanax reacts to confined spaces by exhibiting SDG, which has a genetic component and shows evolutionary regression during adaptation of cavefish to confined environments.

  11. Lead-dependent infective endocarditis and pocket infection – similarities and differences

    Directory of Open Access Journals (Sweden)

    Anna Polewczyk

    2016-01-01

    Full Text Available Introduction : Infectious complications in patients with implanted pacemakers are divided into infections of the generator pocket (PI and lead-dependent infective endocarditis (LDIE. Aim of the research: Identification of risk factors for developing different types of infections and evaluation of the extent of infectious complications. Material and methods : We compared two groups of patients with infectious complications, who underwent transvenous lead extraction (TLE in the Reference Centre between March 2006 and July 2013. The groups consisted of 414 patients with LDIE and 205 with PI. We analysed risk factors, clinical manifestations, inflammatory markers, microbiology, and echocardiography results. Results : The coexistence of LDIE and PI was observed in 62.1% patients. There were no significant differences in the presence of host-dependent risk factors. Patients with LDIE significantly more frequently had abrasion of leads (35.1.% vs. 21.0%; p = 0.0001 connected with other procedural risk factors: a larger number of the leads (2.2 vs. 2.0; p = 0.004 lead loops (24.6% vs. 13.2%; p = 0.001, and longer time interval from the last procedure prior to TLE (28.7 vs. 22.6 months; p = 0.005. Fever and pulmonary infections, higher level of erythrocyte sedimentation rate, C-reactive protein, procalcitonin, vegetation presence, and higher pulmonary systolic pressure were also revealed in patients with LDIE. Positive blood and leads culture were observed in 34.5% and 46.4% patients with LDIE. Conclusions: The frequent coexistence of LDIE and PI confirms their common pathogenesis, but the phenomenon of abrasion suggests also another mechanism for the development of LDIE. Intensity of clinical syndromes, high inflammatory parameters, echocardiography, and microbiology findings are helpful in assessment of the extensity of the infection.

  12. The conditions of similarity and generalized dependences for calculating convective heat transfer in supercritical pressure coolants

    Science.gov (United States)

    Deev, V. I.; Kharitonov, V. S.; Churkin, A. N.; Baisov, A. M.

    2017-11-01

    In this report the assessment of the results of recent experimental investigations of heat transfer in turbulent flow of supercritical water and modeling fluids (carbon dioxide, Freon) in vertical channels of different geometry (tubes, annular gaps and rod bundles) is presented. The conditions of similarity and the system of criteria, which determine the intensity of heat exchange in the fluids near the critical point, are considered. Due to the small hydraulic diameter of the heat exchange channels in the core of nuclear reactors it is possible to neglect the gravitational forces compared to the acceleration caused by the thermal inertia effects and the forces of viscosity. Based on these ideas two comprehensive criteria were proposed. Their application in the basic equation of heat transfer suggested by the authors earlier for the normal regimes satisfactorily (with an error of 20–25%) describes the features of change of heat transfer coefficient in the deteriorated and mixed regimes of heat transfer. The system of equations suitable for engineering calculation of heat transfer in channels of nuclear reactors cooled with supercritical pressure water was developed.

  13. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction

    OpenAIRE

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T.; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R.; Rattan, Ramandeep

    2015-01-01

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse ...

  14. Thresholds of time dependent intergranular crack growth in a nickel disc alloy Alloy 720Li

    Directory of Open Access Journals (Sweden)

    Li Hangyue

    2014-01-01

    Full Text Available At high temperatures in air, introducing a dwell period at the peak stress of fatigue cycles promotes time dependent intergranular crack growth which can increase crack growth rates by upto a few orders of magnitude from the rates of transgranular fatigue crack growth in superalloys. It is expected that time dependent intergranular crack growth in nickel-based superalloys may not occur below a critical mechanical driving force, ΔKth−IG, analogous to a fatigue threshold (ΔKth and a critical temperature, Tth. In this study, dwell fatigue crack growth tests have been carefully designed and conducted on Alloy 720Li to examine such thresholds. Unlike a fatigue threshold, the threshold stress intensity factor range for intergranular crack growth is observed to be highly sensitive to microstructure, dwell time and test procedure. The near threshold crack growth behaviour is made complex by the interactions between grain boundary oxidation embrittlement and crack tip stress relaxation. In general, lower ΔKth−IG values are associated with finer grain size and/or shorter dwell times. Often a load increasing procedure promotes stress relaxation and tends to lead to higher ΔKth−IG. When there is limited stress relaxation at the crack tip, similar ΔKth−IG values are measured with load increasing and load shedding procedures. They are generally higher than the fatigue threshold (ΔKth despite faster crack growth rates (da/dN in the stable crack growth regime. Time dependent intergranular crack growth cannot be activated below a temperature of 500 ∘C.

  15. TEAD mediates YAP-dependent gene induction and growth control.

    Science.gov (United States)

    Zhao, Bin; Ye, Xin; Yu, Jindan; Li, Li; Li, Weiquan; Li, Siming; Yu, Jianjun; Lin, Jiandie D; Wang, Cun-Yu; Chinnaiyan, Arul M; Lai, Zhi-Chun; Guan, Kun-Liang

    2008-07-15

    The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent gene expression. TEAD is also required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition. CTGF is identified as a direct YAP target gene important for cell growth. Moreover, the functional relationship between YAP and TEAD is conserved in Drosophila Yki (the YAP homolog) and Scalloped (the TEAD homolog). Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP.

  16. Nonlinear response arising from non self-similar crack growth in finite thickness plates

    International Nuclear Information System (INIS)

    Sih, G.C.; Chen, C.

    1982-07-01

    Described in this report is a three-dimensional finite element procedure for finding the stresses in a finite thickness plate with a through crack. The Mode I loading is increased incrementally such that crack growth occurs in segments. The individual crack profiles are assumed to coincide with the locations of minimum strain energy density, (dW/dV)/sub min/. Its shape is found to change during growth. Each successive crack growth increment will increase even though the rising load increment is kept constant. Three different plate thickness to half crack length ratios were analyzed. An average critical crack ligament distance r/sub c/ = 0.172 in (0.437 cm) being independent of crack and specimen size was obtained. This corresponds to an analytically predicted fracture toughness S/sub c/ = r/sub c/ (dW/dV)/sub c/ = 15.489 lb/in (2708.825 N/m) for A533B steel at -10 0 F. Data at low temperature were used in order to confine crack growth within the linear elastic range

  17. Growth pattern and growth dependent mortality of larval and pelagic juvenile North Sea cod Gadus morhua

    DEFF Research Database (Denmark)

    Nielsen, Rune; Munk, Peter

    2004-01-01

    and May 2001), and larval/juvenile growth history from each of the sampling sequences was outlined. Growth rate was estimated by fitting a Laird-Gompertz equation to lengths-at-age, and we found the mean specific growth rate in length at age 20 d was 3.2% d(-1), declining to 1.9% d(-1) at an age of 90 d....... Otolith radius and larval standard length were highly correlated, and otolith growth was used as a measure of larval somatic growth. The larvae were divided into 3 groups dependent on their hatch-date, and for each hatch group, the same period of past growth was compared between fish sampled in April...... and May. A 2-way repeated-measurement ANOVA revealed a significant higher past growth of fish sampled in May in 2 of the 3 hatch-groups, implying a higher mortality of the slow growing larvae. Additionally, otolith size at age differed significantly between the April and May sampling of the oldest larvae...

  18. Ubiquitination-dependent mechanisms regulate synaptic growth and function.

    Science.gov (United States)

    DiAntonio, A; Haghighi, A P; Portman, S L; Lee, J D; Amaranto, A M; Goodman, C S

    2001-07-26

    The covalent attachment of ubiquitin to cellular proteins is a powerful mechanism for controlling protein activity and localization. Ubiquitination is a reversible modification promoted by ubiquitin ligases and antagonized by deubiquitinating proteases. Ubiquitin-dependent mechanisms regulate many important processes including cell-cycle progression, apoptosis and transcriptional regulation. Here we show that ubiquitin-dependent mechanisms regulate synaptic development at the Drosophila neuromuscular junction (NMJ). Neuronal overexpression of the deubiquitinating protease fat facets leads to a profound disruption of synaptic growth control; there is a large increase in the number of synaptic boutons, an elaboration of the synaptic branching pattern, and a disruption of synaptic function. Antagonizing the ubiquitination pathway in neurons by expression of the yeast deubiquitinating protease UBP2 (ref. 5) also produces synaptic overgrowth and dysfunction. Genetic interactions between fat facets and highwire, a negative regulator of synaptic growth that has structural homology to a family of ubiquitin ligases, suggest that synaptic development may be controlled by the balance between positive and negative regulators of ubiquitination.

  19. Dose-response regressions for algal growth and similar continuous endpoints: Calculation of effective concentrations

    DEFF Research Database (Denmark)

    Christensen, Erik R.; Kusk, Kresten Ole; Nyholm, Niels

    2009-01-01

    We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose -responsemodels on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50......% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4...

  20. Gait in ducks (Anas platyrhynchos and chickens (Gallus gallus – similarities in adaptation to high growth rate

    Directory of Open Access Journals (Sweden)

    B. M. Duggan

    2016-08-01

    Full Text Available Genetic selection for increased growth rate and muscle mass in broiler chickens has been accompanied by mobility issues and poor gait. There are concerns that the Pekin duck, which is on a similar selection trajectory (for production traits to the broiler chicken, may encounter gait problems in the future. In order to understand how gait has been altered by selection, the walking ability of divergent lines of high- and low-growth chickens and ducks was objectively measured using a pressure platform, which recorded various components of their gait. In both species, lines which had been selected for large breast muscle mass moved at a slower velocity and with a greater step width than their lighter conspecifics. These high-growth lines also spent more time supported by two feet in order to improve balance when compared with their lighter, low-growth conspecifics. We demonstrate that chicken and duck lines which have been subjected to intense selection for high growth rates and meat yields have adapted their gait in similar ways. A greater understanding of which components of gait have been altered in selected lines with impaired walking ability may lead to more effective breeding strategies to improve gait in poultry.

  1. Unbounded growth patterns of reproducing, competing polymers—similarities to biological evolution

    Science.gov (United States)

    Gregor Worst, Emanuel; Zimmer, Philipp; Wollrab, Eva; Kruse, Karsten; Ott, Albrecht

    2016-10-01

    Since the origin of life the interplay between reproduction, variation, and selection has been driving the emergence of new species. The evolution of the Earth’s biosphere appears to innovate unceasingly instead of coming to a stall. Here, we introduce a model system of linear molecules where new polymers appear by spontaneous ligation. The polymers proliferate following a template-based mechanism. Our combined experimental and theoretical study shows that for sufficiently rapid autocatalysis the reproduction process selects particular lengths—while ever longer polymers emerge. We suggest similarities to biological evolution.

  2. Health-related quality of life in alcohol dependence: Similar cross-cultural impact beyond specific drinking habits.

    Science.gov (United States)

    Luquiens, Amandine; Owens, Lynn; Whalley, Diane; Rahhali, Nora; Laramée, Philippe; Crawford, Rebecca; Llorca, Pierre-Michel; Falissard, Bruno; Aubin, Henri-Jean

    2017-08-14

    This study explores sociocultural differences in alcohol-related impact on quality of life between France and United Kingdom. We included 38 alcohol-dependent patients in France and United Kingdom in 10 focus groups. We used a text-mining approach. Three classes of each corpus regarded identical themes across the countries: (a) core impact on quality of life, (b) drinking habits, (c) sources of help. Core impact was similar between the two countries. Main differences were in drinking habits and referral to sources of help. Despite differences in drinking habits, the domains of life impacted by alcohol were non-country specific.

  3. Chemical dynamics between wells across a time-dependent barrier: Self-similarity in the Lagrangian descriptor and reactive basins

    Science.gov (United States)

    Junginger, Andrej; Duvenbeck, Lennart; Feldmaier, Matthias; Main, Jörg; Wunner, Günter; Hernandez, Rigoberto

    2017-08-01

    In chemical or physical reaction dynamics, it is essential to distinguish precisely between reactants and products for all times. This task is especially demanding in time-dependent or driven systems because therein the dividing surface (DS) between these states often exhibits a nontrivial time-dependence. The so-called transition state (TS) trajectory has been seen to define a DS which is free of recrossings in a large number of one-dimensional reactions across time-dependent barriers and thus, allows one to determine exact reaction rates. A fundamental challenge to applying this method is the construction of the TS trajectory itself. The minimization of Lagrangian descriptors (LDs) provides a general and powerful scheme to obtain that trajectory even when perturbation theory fails. Both approaches encounter possible breakdowns when the overall potential is bounded, admitting the possibility of returns to the barrier long after the trajectories have reached the product or reactant wells. Such global dynamics cannot be captured by perturbation theory. Meanwhile, in the LD-DS approach, it leads to the emergence of additional local minima which make it difficult to extract the optimal branch associated with the desired TS trajectory. In this work, we illustrate this behavior for a time-dependent double-well potential revealing a self-similar structure of the LD, and we demonstrate how the reflections and side-minima can be addressed by an appropriate modification of the LD associated with the direct rate across the barrier.

  4. Physical growth in children with transfusion-dependent thalassemia

    Directory of Open Access Journals (Sweden)

    Harish K Pemde

    2011-02-01

    Full Text Available Harish K Pemde, Jagdish Chandra, Divya Gupta, Varinder Singh, Rajni Sharma, AK DuttaDepartment of Pediatrics, Lady Hardinge Medical College, Kalawati Saran Children's Hospital, New Delhi, IndiaObjective: To describe physical growth and related factors in transfusion-dependent thalassemia patients.Methods: This is a cross-sectional analysis of the records of the patients registered at and being followed up by the Thalassemia Day Care Center (TDCC at Kalawati Saran Children's Hospital, New Delhi, India. Clinical and laboratory parameters were recorded on a spreadsheet for analysis. Clinical parameters included weight, height, sexual maturity ratings, and general and systemic physical examination. Laboratory parameters included pretransfusion hemoglobin (Hb, periodic serum ferritin, and tests for viral markers of human immunodeficiency virus (HIV and hepatitis B and C. Z-scores for weight, height, and body mass index (BMI were calculated using World Health Organization reference data. Statistical analysis was carried out using Microsoft Excel® and Stata® software.Results: Out of 214 patients registered at the TDCC since 2001, 154 were included in this study. The mean age of patients was 9.19 years (range 0.5–20 years. Pretransfusion Hb was well maintained (mean 9.21 g/dL; 95% confidence interval [CI]: 9.06–9.36, but the mean serum ferritin levels were approximately three times (3112 ng/mL the desired value despite the patients being on deferiprone (72% or deferasirox (25%. One-third (33.11% of the patients had short stature, 13% were thin, and 10.82% were very thin (BMI z-score <-3. No patient was overweight or obese. Linear regression coefficient showed that for every 1-year increase in age, the mean ferritin value increased by 186.21 pg/mL (95% CI: 143.31–228.27. Height z-scores had significant correlation with mean ferritin levels, whereas correlation with mean pretransfusion Hb was not significant statistically. Mean ferritin levels

  5. Investigation of function similarities between the sarcoplasmic reticulum and platelet calcium-dependent adenosinetriphosphatases with the inhibitors quercetin and calmidazolium

    International Nuclear Information System (INIS)

    Fischer, T.H.; Campbell, K.P.; White, G.C. II

    1987-01-01

    The platelet and skeletal sarcoplasmic reticulum calcium-dependent adenosinetriphosphatases (Ca 2+ -ATPases) were functionally compared with respect to substrate activation by steady-state kinetic methods using the inhibitors quercetin and calmidazolium. Quercetin inhibited platelet and sarcoplasmic reticulum Ca 2+ -ATPase activities in a dose-dependent manner with IC 50 values of 25 and 10 μM, respectively. Calmidazolium also inhibited platelet and sarcoplasmic reticulum Ca 2+ -ATPase activities, with half-maximal inhibition measured at 5 and 4 μM, respectively. Both inhibitors also affected the [ 45 Ca] calcium transport activity of intact platelet microsomes at concentrations similar to those which reduced Ca 2+ -ATPase activity. These inhibitors were then used to examine substrate ligation by the platelet and sarcoplasmic reticulum calcium pump proteins. For both Ca 2+ -ATPase proteins, quercetin has an affinity for the E-Ca 2 (fully ligated with respect to calcium at the exterior high-affinity calcium binding sites, unligated with respect to ATP) conformational state of the protein that is approximately 10-fold grater than for other conformational states in the hydrolytic cycle. Quercetin can thus be considered a competitive inhibitor of the calcium pump proteins with respect to ATP. In contrast to the effect of quercetin, calmidazolium interacts with the platelet and sarcoplasmic reticulum Ca 2+ -ATPases in an uncompetitive manner. The dissociation constants for this inhibitor for the different conformational states of the calcium pump proteins were similar, indicating that calmidazolium has equal affinity for all of the reaction intermediates probed. These observations indicate that the substrate ligation processes are similar for the two pump proteins. This supports the concept that the hydrolytic cycles of the two proteins are comparable

  6. Effects of hepatocyte growth factor on glutathione synthesis, growth, and apoptosis is cell density-dependent

    International Nuclear Information System (INIS)

    Yang Heping; Magilnick, Nathaniel; Xia Meng; Lu, Shelly C.

    2008-01-01

    Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen that exerts opposing effects depending on cell density. Glutathione (GSH) is the main non-protein thiol in mammalian cells that modulates growth and apoptosis. We previously showed that GSH level is inversely related to cell density of hepatocytes and is positively related to growth. Our current work examined whether HGF can modulate GSH synthesis in a cell density-dependent manner and how GSH in turn influence HGF's effects. We found HGF treatment of H4IIE cells increased cell GSH levels only under subconfluent density. The increase in cell GSH under low density was due to increased transcription of GSH synthetic enzymes. This correlated with increased protein levels and nuclear binding activities of c-Jun, c-Fos, p65, p50, Nrf1 and Nrf2 to the promoter region of these genes. HGF acts as a mitogen in H4IIE cells under low cell density and protects against tumor necrosis factor α (TNFα)-induced apoptosis by limiting JNK activation. However, HGF is pro-apoptotic under high cell density and exacerbates TNFα-induced apoptosis by potentiating JNK activation. The increase in cell GSH under low cell density allows HGF to exert its full mitogenic effect but is not necessary for its anti-apoptotic effect

  7. Using a laboratory-based growth model to estimate mass- and temperature-dependent growth parameters across populations of juvenile Chinook Salmon

    Science.gov (United States)

    Perry, Russell W.; Plumb, John M.; Huntington, Charles

    2015-01-01

    To estimate the parameters that govern mass- and temperature-dependent growth, we conducted a meta-analysis of existing growth data from juvenile Chinook Salmon Oncorhynchus tshawytscha that were fed an ad libitum ration of a pelleted diet. Although the growth of juvenile Chinook Salmon has been well studied, research has focused on a single population, a narrow range of fish sizes, or a narrow range of temperatures. Therefore, we incorporated the Ratkowsky model for temperature-dependent growth into an allometric growth model; this model was then fitted to growth data from 11 data sources representing nine populations of juvenile Chinook Salmon. The model fit the growth data well, explaining 98% of the variation in final mass. The estimated allometric mass exponent (b) was 0.338 (SE = 0.025), similar to estimates reported for other salmonids. This estimate of b will be particularly useful for estimating mass-standardized growth rates of juvenile Chinook Salmon. In addition, the lower thermal limit, optimal temperature, and upper thermal limit for growth were estimated to be 1.8°C (SE = 0.63°C), 19.0°C (SE = 0.27°C), and 24.9°C (SE = 0.02°C), respectively. By taking a meta-analytical approach, we were able to provide a growth model that is applicable across populations of juvenile Chinook Salmon receiving an ad libitum ration of a pelleted diet.

  8. Similar outcome in insulin-dependent and noninsulin-dependent diabetic patients after off-pump coronary artery bypass grafting with multiple skeletonized arterial conduits.

    Science.gov (United States)

    Suzuki, Tomoaki; Asai, Tohru; Nota, Hiromitsu; Kinoshita, Takeshi; Fujino, Susumu; Takashima, Noriyuki

    2015-05-01

    We were interested in whether current multiarterial off-pump coronary artery bypass graft surgery can improve the clinical outcome for insulin-dependent diabetes mellitus patients. Between January 2002 and December 2013, 1,064 consecutive patients underwent isolated off-pump coronary artery bypass surgery at our hospital; 551 of these patients had diabetes. Of these 551 patients, 166 had insulin-dependent diabetes (IDM) and the remaining 385 had noninsulin-dependent diabetes (NIDM). The propensity score was calculated to achieve one-to-two matching sets (IDM 143 versus NIDM 286). Ten patients (3.5%) in the NIDM group and 2 patients (1.4%) in the IDM group died in hospital (p = 0.18). Insulin dependency was not an independent risk factor for any early death or major complications. Follow-up was complete for 96.5% of the patients, with a mean follow-up of 4.6 ± 3.8 years. Overall survival rate at 10 years was 76.3% for the NIDM group and 73.1% for the IDM group (p = 0.79). The rate of 10-year actuarial freedom from major adverse cardiac events was 89.6% in the NIDM group and 86.3% in the IDM group (p = 0.72). Multivariate Cox proportional hazard regression analysis revealed that female sex, congestive heart failure, previous myocardial infarction, lower ejection fraction, and at least one major complication were independent risk factors for combined cardiac events. Insulin dependency did not affect any outcome in the long term. Early and long-term outcomes after off-pump skeletonized multiarterial coronary artery bypass graft surgery were similar among the IDM and NIDM patients. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Determination of Nitrate Reductase Assay Depending on the Microbial Growth

    International Nuclear Information System (INIS)

    El-Kabbany, H.M.

    2012-01-01

    A rapid micro-dilution assay for determination of the antimicrobial susceptibility of different bacterial isolates was developed. This assay is based on the ability of the most of viable organisms to reduce nitrates. The MIC or MBC could be determined by nitrate reductase (NR) only after 30 to 90 min of incubation depending on the behaviour of microbial growth. Bacterial viability is detected by a positive nitrite reduction rather than visible turbidity. The nitrate reduction assay was compared with standard micro-assay using 250 isolates of different taxa against 10 antibiotics belonging to different classes. An excellent agreement of 82.5 % was found between the two methods and only 17.5 % of 1794 trials showed difference in the determined MIC by tow-dilution interval above or below the MIC determined by the turbidimetric method under the same test conditions. However, the nitrate reduction assay was more rapid and sensitive in detecting viable bacteria and so, established an accurate estimate of the minimal inhibitory concentration (MIC) or the minimal bacterial concentration (MBC). The nitrate reduction assay offers the additional advantage that it could be used to determine the MBC without having to subculture the broth. 232 cases of resistance were detected by NR and 4 different media were tested for susceptibility test. The bacterial isolates were exposed to ultra violet (UV) light for different period

  10. Noise-Induced Transitions in a Population Growth Model Based on Size-Dependent Carrying Capacity

    Directory of Open Access Journals (Sweden)

    Neeme Lumi

    2014-01-01

    Full Text Available The stochastic dynamics of a population growth model with size-dependent carrying capacity is considered. The effect of a fluctuating environment on population growth is modeled as a multiplicative dichotomous noise. At intermediate values of population size the deterministic counterpart of the model behaves similarly to the Von Foerster model for human population, but at small and very large values of population size substantial differences occur. In the stochastic case, an exact analytical solution for the stationary probability distribution is found. It is established that variation of noise correlation time can cause noise-induced transitions between three different states of the system characterized by qualitatively different behaviors of the probability distributions of the population size. Also, it is shown that, in some regions of the system parameters, variation of the amplitude of environmental fluctuations can induce single unidirectional abrupt transitions of the mean population size.

  11. Proximity-Dependent Inhibition of Growth of Mannheimia haemolytica by Pasteurella multocida

    Science.gov (United States)

    Bavananthasivam, Jegarubee; Dassanayake, Rohana P.; Kugadas, Abirami; Shanthalingam, Sudarvili; Call, Douglas R.; Knowles, Donald P.

    2012-01-01

    Mannheimia haemolytica, Pasteurella multocida, and Bibersteinia trehalosi have been identified in the lungs of pneumonic bighorn sheep (BHS; Ovis canadensis). Of these pathogens, M. haemolytica has been shown to consistently cause fatal pneumonia in BHS under experimental conditions. However, M. haemolytica has been isolated by culture less frequently than the other bacteria. We hypothesized that the growth of M. haemolytica is inhibited by other bacteria in the lungs of BHS. The objective of this study was to determine whether P. multocida inhibits the growth of M. haemolytica. Although in monoculture both bacteria exhibited similar growth characteristics, in coculture with P. multocida there was a clear inhibition of growth of M. haemolytica. The inhibition was detected at mid-log phase and continued through the stationary phase. When cultured in the same medium, the growth of M. haemolytica was inhibited when both bacteria were separated by a membrane that allowed contact (pore size, 8.0 μm) but not when they were separated by a membrane that limited contact (pore size, 0.4 μm). Lytic bacteriophages or bactericidal compounds could not be detected in the culture supernatant fluid from monocultures of P. multocida or from P. multocida-M. haemolytica cocultures. These results indicate that P. multocida inhibits the growth of M. haemolytica by a contact- or proximity-dependent mechanism. If the inhibition of growth of M. haemolytica by P. multocida occurs in vivo as well, it could explain the inconsistent isolation of M. haemolytica from the lungs of pneumonic BHS. PMID:22798357

  12. Learning of a simple grapho-motor task by young children and adults: similar acquisition but age-dependent retention.

    Science.gov (United States)

    Julius, Mona S; Adi-Japha, Esther

    2015-01-01

    Many new skills are acquired during early childhood. Typical laboratory skill learning tasks are not applicable for developmental studies that involve children younger than 8 years of age. It is not clear whether young children and adults share a basic underlying skill learning mechanism. In the present study, the learning and retention of a simple grapho-motor pattern were studied in three age groups: 5-6, 7-8, and 19-29 years. Each block of the task consists of identical patterns arranged in a spaced writing array. Progression across the block involves on-page movements while producing the pattern, and off-page movements between patterns. The participants practiced the production of the pattern using a digitizing tablet and were tested at 24 h and 2 weeks post-practice. All age groups produced the task blocks more quickly with practice, and the learning rate was inversely related to the initial production time. All groups exhibited additional gains 24 h post-practice that were well-retained 2 weeks later. The accuracy of the participants was maintained throughout the 2-weeks period. These findings suggest that young children and young adults use a similar mechanism when learning the task. Nevertheless, the 6-years-old spent more time off-page during retention testing than when tested at 24 h post-practice, thus supporting the notion that an age advantage may exists in the long-term retention of skills due to planning-dependent aspects.

  13. Another brick in the cell wall: biosynthesis dependent growth model.

    Directory of Open Access Journals (Sweden)

    Adelin Barbacci

    Full Text Available Expansive growth of plant cell is conditioned by the cell wall ability to extend irreversibly. This process is possible if (i a tensile stress is developed in the cell wall due to the coupling effect between turgor pressure and the modulation of its mechanical properties through enzymatic and physicochemical reactions and if (ii new cell wall elements can be synthesized and assembled to the existing wall. In other words, expansive growth is the result of coupling effects between mechanical, thermal and chemical energy. To have a better understanding of this process, models must describe the interplay between physical or mechanical variable with biological events. In this paper we propose a general unified and theoretical framework to model growth in function of energy forms and their coupling. This framework is based on irreversible thermodynamics. It is then applied to model growth of the internodal cell of Chara corallina modulated by changes in pressure and temperature. The results describe accurately cell growth in term of length increment but also in term of cell pectate biosynthesis and incorporation to the expanding wall. Moreover, the classical growth model based on Lockhart's equation such as the one proposed by Ortega, appears as a particular and restrictive case of the more general growth equation developed in this paper.

  14. Another Brick in the Cell Wall: Biosynthesis Dependent Growth Model

    Science.gov (United States)

    Barbacci, Adelin; Lahaye, Marc; Magnenet, Vincent

    2013-01-01

    Expansive growth of plant cell is conditioned by the cell wall ability to extend irreversibly. This process is possible if (i) a tensile stress is developed in the cell wall due to the coupling effect between turgor pressure and the modulation of its mechanical properties through enzymatic and physicochemical reactions and if (ii) new cell wall elements can be synthesized and assembled to the existing wall. In other words, expansive growth is the result of coupling effects between mechanical, thermal and chemical energy. To have a better understanding of this process, models must describe the interplay between physical or mechanical variable with biological events. In this paper we propose a general unified and theoretical framework to model growth in function of energy forms and their coupling. This framework is based on irreversible thermodynamics. It is then applied to model growth of the internodal cell of Chara corallina modulated by changes in pressure and temperature. The results describe accurately cell growth in term of length increment but also in term of cell pectate biosynthesis and incorporation to the expanding wall. Moreover, the classical growth model based on Lockhart's equation such as the one proposed by Ortega, appears as a particular and restrictive case of the more general growth equation developed in this paper. PMID:24066142

  15. Growth activity in human septal cartilage: age-dependent incorporation of labeled sulfate in different anatomic locations

    International Nuclear Information System (INIS)

    Vetter, U.; Pirsig, W.; Heinze, E.

    1983-01-01

    Growth activity in different areas of human septal cartilage was measured by the in vitro incorporation of 35 S-labeled NaSO 4 into chondroitin sulfate. Septal cartilage without perichondrium was obtained during rhinoplasty from 36 patients aged 6 to 35 years. It could be shown that the anterior free end of the septum displays high growth activity in all age groups. The supra-premaxillary area displayed its highest growth activity during prepuberty, showing thereafter a continuous decline during puberty and adulthood. A similar age-dependent pattern in growth activity was found in the caudal prolongation of the septal cartilage. No age-dependent variations could be detected in the posterior area of the septal cartilage

  16. Learning of a simple grapho-motor task by young children and adults: Similar acquisition but age-dependent retention

    Directory of Open Access Journals (Sweden)

    Mona eJulius

    2015-03-01

    Full Text Available Many new skills are acquired during early childhood. Typical laboratory skill learning tasks are not applicable for developmental studies that involve children younger than 8 years of age. It is not clear whether young children and adults share a basic underlying skill learning mechanism. In the present study, the learning and retention of a simple grapho-motor pattern were studied in three age groups: 5-6 years, 7-8 years, and 19-29 years. Each block of the task consists of identical patterns arranged in a spaced writing array. Progression across the block involves on-page movements while producing the pattern, and off-page movements between patterns. The participants practiced the production of the pattern using a digitizing tablet and were tested at 24 hours and two weeks post-practice. All age groups produced the task blocks more quickly with practice, and the learning rate was inversely related to the initial production time across and within the groups. All groups exhibited additional gains 24 hours post-practice that were well retained 2 weeks later. The accuracy of the participants was maintained throughout the two-week period. These findings suggest that young children and young adults use a similar mechanism when learning the task. A separate analysis of the on-page and off-page movement times per block indicated that during retention testing, the 6-year-olds spent more time off-page than when tested at 24 hours post-practice, thus supporting the notion that an age advantage may exists in the long-term retention of skills due to planning-dependent aspects.

  17. Density-dependent growth of the polychaete Diopatra aciculata

    Directory of Open Access Journals (Sweden)

    Milada Safarik

    2006-12-01

    Full Text Available Effects of intraspecific density on growth of the tube-building polychaete Diopatra aciculata (Onuphidae were examined over a three-month period within a marine worm aquaculture facility. Three polychaete densities (500, 1000 and 2000 worms/m2 were represented within triplicate 0.30 m2 boxes containing late juvenile D. aciculata, sandy sediment and recirculating seawater. Daily food ration per worm was held constant across all density levels. Total length, weight and number of segments were recorded for 20 polychaetes randomly removed from each of nine treatment boxes at weeks 1, 7 and 14. Mean daily growth was higher during weeks 1-7 than during weeks 7-14 for all growth variables at each density level. Polychaetes at the highest density level exhibited lower rates of growth and more broken and/or regenerating posterior segments than those at low density. High D. aciculata density was also associated with reduced dissolved oxygen concentrations and high polychaete mortality (20%. At medium polychaete density (1000/m2, D. aciculata exhibited low levels of apparent stress and high biomass return per unit area, both of which are important considerations in the aquaculture rearing of this species. We suggest that further studies focus on age- and size-related factors contributing to density effects on polychaete growth.

  18. Perversities of Extreme Dependence and Unequal Growth in the TAR

    NARCIS (Netherlands)

    A.M. Fischer (Andrew Martín)

    2007-01-01

    textabstractThis first in a series of independent analyses by Andrew Martin Fischer, commissioned by Tibet Watch, a research-based organisation established in London in 2006, examines the rapid growth that has been generated in the Tibetan Autonomous Region (TAR) through the extremely heavy

  19. Perversities of Extreme Dependence and Unequal Growth in the TAR

    NARCIS (Netherlands)

    A.M. Fischer (Andrew Martín)

    2007-01-01

    textabstractThe official Chinese press recently came out with a series of articles reporting the latest statistics on the phenomenally rapid economic growth that has been taking place in the Tibet Autonomous Region (TAR) since the mid-1990s through sheer force of Central Government subsidies.

  20. Role of prey and intraspecific density dependence on the population growth of an avian top predator

    Science.gov (United States)

    Fernandez-de-Simon, Javier; Díaz-Ruiz, Francisco; Cirilli, Francesca; Tortosa, Francisco S.; Villafuerte, Rafael; Ferreras, Pablo

    2014-10-01

    Exploring predator-prey systems in diverse ecosystems increases our knowledge about ecological processes. Predator population growth may be positive when conspecific density is low but predators also need areas with prey availability, associated with competition, which increases the risk of suffering losses but stabilises populations. We studied relationships between European rabbits Oryctolagus cuniculus (prey) and adult eagle owls Bubo bubo (predators) in south-western Europe. We assessed models explaining the predator population growth and stability. We estimated the abundance of rabbits and adult eagle owls during three years in eight localities of central-southern Spain. We explored models including rabbit and adult eagle owl abundance, accounting for yearly variations and including the locality as a random variable. We found that population growth of adult eagle owls was positive in situations with low conspecific abundance and tended to be negative but approaching equilibrium in situations of higher conspecific abundance. Population growth was also positively related to previous summer rabbit density when taking into account eagle owl conspecific abundance, possibly indicating that rabbits may support recruitment. Furthermore, abundance stability of adult eagle owls was positively related to previous winter-spring rabbit density, which could suggest predator population stabilisation through quick territory occupation in high-quality areas. These results exemplify the trade-off between prey availability and abundance of adult predators related to population growth and abundance stability in the eagle owl-rabbit system in south-western Europe. Despite rabbits have greatly declined during the last decades and eagle owls locally specialise on them, eagle owls currently have a favourable conservation status. As eagle owls are the only nocturnal raptor with such dependence on rabbits, this could point out that predators may overcome prey decreases in areas with

  1. Survival and growth of epiphytic ferns depend on resource sharing

    Directory of Open Access Journals (Sweden)

    Hua-Zheng eLu

    2016-03-01

    Full Text Available Locally available resources can be shared within clonal plant systems through physiological integration, thus enhancing their survival and growth. Most epiphytes exhibit clonal growth habit, but few studies have tested effects of physiological integration (resource sharing on survival and growth of epiphytes and whether such effects vary with species. We conducted two experiments, one on individuals (single ramets and another on groups (several ramets within a plot, with severed and intact rhizome treatments (without and with physiological integration on two dominant epiphytic ferns (Polypodiodes subamoena and Lepisorus scolopendrium in a subtropical montane moist forest in Southwest China. Rhizome severing (preventing integration significantly reduced ramet survival in the individual experiment and number of surviving ramets in the group experiment, and it also decreased biomass of both species in both experiments. However, the magnitude of such integration effects did not vary significantly between the two species. We conclude that resource sharing may be a general strategy for clonal epiphytes to adapt to forest canopies where resources are limited and heterogeneously distributed in space and time.

  2. Female promiscuity and maternally dependent offspring growth rates in mammals.

    Science.gov (United States)

    Garratt, Michael; Brooks, Robert C; Lemaître, Jean-François; Gaillard, Jean-Michel

    2014-04-01

    Conflicts between family members are expected to influence the duration and intensity of parental care. In mammals, the majority of this care occurs as resource transfer from mothers to offspring during gestation and lactation. Mating systems can have a strong influence on the severity of familial conflict--where female promiscuity is prevalent, conflict is expected to be higher between family members, causing offspring to demand more resources. If offspring are capable of manipulating their mothers and receive resources in proportion to their demands, resource transfer should increase with elevated promiscuity. We tested this prediction, unexplored across mammals, using a comparative approach. The total durations of gestation and lactation were not related to testes mass, a reliable proxy of female promiscuity across taxa. Offspring growth during gestation, however, and weaning mass, were positively correlated with testes mass, suggesting that offspring gain resources from their mothers at faster rates when familial conflict is greater. During gestation, the relationship between offspring growth and testes mass was also related to placenta morphology, with a stronger relationship between testes mass and growth observed in species with a less invasive placenta. Familial conflict could have a pervasive influence on patterns of parental care in mammals. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  3. Study of the temperature dependence of the uniaxial creep property of similar material of new soft rock

    Science.gov (United States)

    Wang, Y. Y.; Wu, Y.; Fan, X. Y.; Zhang, J. L.; Guo, P.; Li, J. G.

    2017-11-01

    Using the experimental method, the experimental research of creep properties were conducted under different temperature ranging from 10°C to 60°C. The similar material of new soft rock consists of paraffin, which can obtain that the deformation contains the instantaneous elastic deformation and creep deformation through the uniaxial creep experimental results. And thus the increase of temperature has great influence on the creep characteristics of similar soft rock according to the creep curve of similar soft rock at 10°C to 60°C. With the increase of temperature, the slope of the stress-strain curve of similar soft rock is increasing, while the average of the creep modulus is decreasing, which means that the capacity of resist deformation is reduced. Therefore, the creeps law of high-temperature and short-time can be shown the creep phenomenon of low-temperature and long-time, and further shorten the creep experimental cycle.

  4. Similar clinical features among patients with severe adult growth hormone deficiency diagnosed with insulin tolerance test or arginine or glucagon stimulation tests

    DEFF Research Database (Denmark)

    Toogood, Andrew; Brabant, Georg; Maiter, Dominique

    2012-01-01

    To determine whether insulin tolerance tests (ITTs), arginine stimulation tests (ASTs), and glucagon stimulation tests (GST) identify patients who have similar clinical features of growth hormone (GH) deficiency when a diagnostic GH threshold of 3 μg/L is used.......To determine whether insulin tolerance tests (ITTs), arginine stimulation tests (ASTs), and glucagon stimulation tests (GST) identify patients who have similar clinical features of growth hormone (GH) deficiency when a diagnostic GH threshold of 3 μg/L is used....

  5. Carbonate clumped isotope variability in shallow water corals: Temperature dependence and growth-related vital effects

    Science.gov (United States)

    Saenger, Casey; Affek, Hagit P.; Felis, Thomas; Thiagarajan, Nivedita; Lough, Janice M.; Holcomb, Michael

    2012-12-01

    Geochemical variations in shallow water corals provide a valuable archive of paleoclimatic information. However, biological effects can complicate the interpretation of these proxies, forcing their application to rely on empirical calibrations. Carbonate clumped isotope thermometry (Δ47) is a novel paleotemperature proxy based on the temperature dependent "clumping" of 13C-18O bonds. Similar Δ47-temperature relationships in inorganically precipitated calcite and a suite of biogenic carbonates provide evidence that carbonate clumped isotope variability may record absolute temperature without a biological influence. However, large departures from expected values in the winter growth of a hermatypic coral provided early evidence for possible Δ47 vital effects. Here, we present the first systematic survey of Δ47 in shallow water corals. Sub-annual Red Sea Δ47 in two Porites corals shows a temperature dependence similar to inorganic precipitation experiments, but with a systematic offset toward higher Δ47 values that consistently underestimate temperature by ˜8 °C. Additional analyses of Porites, Siderastrea, Astrangia and Caryophyllia corals argue against a number of potential mechanisms as the leading cause for this apparent Δ47 vital effect including: salinity, organic matter contamination, alteration during sampling, the presence or absence of symbionts, and interlaboratory differences in analytical protocols. However, intra- and inter-coral comparisons suggest that the deviation from expected Δ47 increases with calcification rate. Theoretical calculations suggest this apparent link with calcification rate is inconsistent with pH-dependent changes in dissolved inorganic carbon speciation and with kinetic effects associated with CO2 diffusion into the calcifying space. However, the link with calcification rate may be related to fractionation during the hydration/hydroxylation of CO2 within the calcifying space. Although the vital effects we describe will

  6. Temperature dependence of protein solubility-determination, application to crystallization, and growth kinetics studies

    Science.gov (United States)

    Rosenberger, Franz

    1993-01-01

    A scintillation method was developed for determinations of the temperature dependence of the solubility, and of nucleation induction times of proteins, in 50-100 mu(l) volumes of solution. Solubility data for lysozyme and horse serum albumin were obtained for various combinations of pH and precipitant concentrations. These data and the nucleation induction information were used for dynamic crystallization control, that is, for the controlled separation of nucleation and growth stages. Individual lysozyme and horse serum albumin crystals were grown in 15-20 mu(l) solution volumes contained in x-ray capillaries. The morphology and kinetics of the growth and dissolution of lysozyme in aqueous solutions with 2.5 percent NaCl and at pH = 4.5 was studied in situ with a depth resolution of 300 A (4 unit cells) by high resolution optical microscopy and digital image processing. The bulk super- or under saturation, sigma, of the solution inside a closed growth cell was controlled by temperature. The growth habit was bound by (110) and (101) faces that grew through layer spreading, although with different growth rate dependencies on supersaturation/temperature. At sigma less than 10 (obtained at higher temperatures) growth was purely kinetic ally controlled, with impurity effects (macrostep formation and kinetic hindrance) becoming significant for sigma less than 2. At sigma greater than 10 (lower temperatures), anisotropies in the interfacial kinetics were more pronounced, with interfacial kinetics and bulk transport becoming equally important to the growth morphology. Growth rates were growth history dependent. The formation of striations (layers of irregularly incorporated solution) was unambiguously correlated with growth temperature variations. Etching exposed dislocations and various high-index faces whose growth morphologies were studied during return to the steady state growth form. Growth steps were observed to originate from two-dimensional nuclei or from outcrops

  7. Growth rates of rhizosphere microorganisms depend on competitive abilities of plants for nitrogen

    Science.gov (United States)

    Blagodatskaya, Evgenia; Littschwager, Johanna; Lauerer, Marianna; Kuzyakov, Yakov

    2010-05-01

    Rhizosphere - one of the most important ‘hot spots' in soil - is characterized not only by accelerated turnover of microbial biomass and nutrients but also by strong intra- and inter-specific competition. Intra-specific competition occurs between individual plants of the same species, while inter-specific competition can occur both at population level (plant species-specific, microbial species-specific interactions) and at community level (plant - microbial interactions). Such plant - microbial interactions are mainly governed by competition for available N sources, since N is one of the main growth limiting nutrients in natural ecosystems. Functional structure and activity of microbial community in rhizosphere is not uniform and is dependent on quantity and quality of root exudates which are plant specific. It is still unclear how microbial growth and turnover in the rhizosphere are dependent on the features and competitive abilities of plants for N. Depending on C and N availability, acceleration and even retardation of microbial activity and carbon mineralization can be expected in the rhizosphere of plants with high competitive abilities for N. We hypothesized slower microbial growth rates in the rhizosphere of plants with smaller roots, as they usually produce less exudates compared to plants with small shoot-to-root ratio. As the first hypothesis is based solely on C availability, we also expected the greater effect of N availability on microbial growth in rhizosphere of plants with smaller root mass. These hypothesis were tested for two plant species of strawberry: Fragaria vesca L. (native species), and Duchesnea indica (Andrews) Focke (an invasive plant in central Europe) growing in intraspecific and interspecific competition. Microbial biomass and the kinetic parameters of microbial growth in the rhizosphere were estimated by dynamics of CO2 emission from the soil amended with glucose and nutrients. Specific growth rate (µ) of soil microorganisms was

  8. Growth is similar in premature infants fed human milk fortified with a human milk or bovine milk-based fortifier

    Science.gov (United States)

    Preterm infants require fortification of human milk (HM) to provide adequate nutrients for growth. A human milk fortifier (HMF) made from donor human milk has recently been introduced. However, limited data are available comparing the growth outcomes of this product with current fortifiers. We evalu...

  9. Investigation of a growth model incorporating density dependence for the mackerel management plan simulations

    NARCIS (Netherlands)

    Brunel, T.P.A.

    2015-01-01

    This report presents a framework to model density dependent growth for the North East Atlantic mackerel. The model used is the classical von Bertalanffy equation, but modified so that growth is reduced when stock size increases. The model developed was able to reproduce quite closely the trends in

  10. The transcription factor ABI4 Is required for the ascorbic acid-dependent regulation of growth and regulation of jasmonate-dependent defense signaling pathways in Arabidopsis.

    Science.gov (United States)

    Kerchev, Pavel I; Pellny, Till K; Vivancos, Pedro Diaz; Kiddle, Guy; Hedden, Peter; Driscoll, Simon; Vanacker, Hélène; Verrier, Paul; Hancock, Robert D; Foyer, Christine H

    2011-09-01

    Cellular redox homeostasis is a hub for signal integration. Interactions between redox metabolism and the ABSCISIC ACID-INSENSITIVE-4 (ABI4) transcription factor were characterized in the Arabidopsis thaliana vitamin c defective1 (vtc1) and vtc2 mutants, which are defective in ascorbic acid synthesis and show a slow growth phenotype together with enhanced abscisic acid (ABA) levels relative to the wild type (Columbia-0). The 75% decrease in the leaf ascorbate pool in the vtc2 mutants was not sufficient to adversely affect GA metabolism. The transcriptome signatures of the abi4, vtc1, and vtc2 mutants showed significant overlap, with a large number of transcription factors or signaling components similarly repressed or induced. Moreover, lincomycin-dependent changes in LIGHT HARVESTING CHLOROPHYLL A/B BINDING PROTEIN 1.1 expression were comparable in these mutants, suggesting overlapping participation in chloroplast to nucleus signaling. The slow growth phenotype of vtc2 was absent in the abi4 vtc2 double mutant, as was the sugar-insensitive phenotype of the abi4 mutant. Octadecanoid derivative-responsive AP2/ERF-domain transcription factor 47 (ORA47) and AP3 (an ABI5 binding factor) transcripts were enhanced in vtc2 but repressed in abi4 vtc2, suggesting that ABI4 and ascorbate modulate growth and defense gene expression through jasmonate signaling. We conclude that low ascorbate triggers ABA- and jasmonate-dependent signaling pathways that together regulate growth through ABI4. Moreover, cellular redox homeostasis exerts a strong influence on sugar-dependent growth regulation.

  11. A similarity solution of time dependent MHD liquid film flow over stretching sheet with variable physical properties

    Directory of Open Access Journals (Sweden)

    M. Idrees

    2018-03-01

    Full Text Available An analysis is performed for the fluid dynamics incorporating the variation of viscosity and thermal conductivity on an unsteady two-dimensional free surface flow of a viscous incompressible conducting fluid taking into account the effect of a magnetic field. Surface tension quadratically vary with temperature while fluid viscosity and thermal conductivity are assumed to vary as a linear function of temperature. The boundary layer partial differential equations in cartesian coordinates are transformed into a system of nonlinear ordinary differential equations (ODEs by similarity transformation. The developed nonlinear equations are solved analytically by Homotopy Analysis Method (HAM while numerically by using the shooting method. The Effects of natural parameters such as the variable viscosity parameter A, variable thermal conductivity parameter N, Hartmann number Ma, film Thickness, unsteadiness parameter S, Thermocapillary number M and Prandtl number Pr on the velocity and temperature profiles are investigated. The results for the surface skin friction coefficient f″(0, Nusselt number (heat flux -θ′(0 and free surface temperature θ(1 are presented graphically and in tabular form. Keywords: Variable viscosity and thermal conductivity, Thermocapillary number, Magnetic field, Thin film, Unsteady stretching surface

  12. A similarity solution of time dependent MHD liquid film flow over stretching sheet with variable physical properties

    Science.gov (United States)

    Idrees, M.; Rehman, Sajid; Shah, Rehan Ali; Ullah, M.; Abbas, Tariq

    2018-03-01

    An analysis is performed for the fluid dynamics incorporating the variation of viscosity and thermal conductivity on an unsteady two-dimensional free surface flow of a viscous incompressible conducting fluid taking into account the effect of a magnetic field. Surface tension quadratically vary with temperature while fluid viscosity and thermal conductivity are assumed to vary as a linear function of temperature. The boundary layer partial differential equations in cartesian coordinates are transformed into a system of nonlinear ordinary differential equations (ODEs) by similarity transformation. The developed nonlinear equations are solved analytically by Homotopy Analysis Method (HAM) while numerically by using the shooting method. The Effects of natural parameters such as the variable viscosity parameter A, variable thermal conductivity parameter N, Hartmann number Ma, film Thickness, unsteadiness parameter S, Thermocapillary number M and Prandtl number Pr on the velocity and temperature profiles are investigated. The results for the surface skin friction coefficient f″ (0) , Nusselt number (heat flux) -θ‧ (0) and free surface temperature θ (1) are presented graphically and in tabular form.

  13. Antagonistic interactions between the cAMP-dependent protein kinase and Tor signaling pathways modulate cell growth in Saccharomyces cerevisiae.

    Science.gov (United States)

    Ramachandran, Vidhya; Herman, Paul K

    2011-02-01

    Eukaryotic cells integrate information from multiple sources to respond appropriately to changes in the environment. Here, we examined the relationship between two signaling pathways in Saccharomyces cerevisiae that are essential for the coordination of cell growth with nutrient availability. These pathways involve the cAMP-dependent protein kinase (PKA) and Tor proteins, respectively. Although these pathways control a similar set of processes important for growth, it was not clear how their activities were integrated in vivo. The experiments here examined this coordination and, in particular, tested whether the PKA pathway was primarily a downstream effector of the TORC1 signaling complex. Using a number of reporters for the PKA pathway, we found that the inhibition of TORC1 did not result in diminished PKA signaling activity. To the contrary, decreased TORC1 signaling was generally associated with elevated levels of PKA activity. Similarly, TORC1 activity appeared to increase in response to lower levels of PKA signaling. Consistent with these observations, we found that diminished PKA signaling partially suppressed the growth defects associated with decreased TORC1 activity. In all, these data suggested that the PKA and TORC1 pathways were functioning in parallel to promote cell growth and that each pathway might restrain, either directly or indirectly, the activity of the other. The potential significance of this antagonism for the regulation of cell growth and overall fitness is discussed.

  14. B16 melanoma tumor growth is delayed in mice in an age-dependent manner

    Directory of Open Access Journals (Sweden)

    Christina Pettan-Brewer

    2012-08-01

    Full Text Available A major risk factor for cancer is increasing age, which suggests that syngeneic tumor implants in old mice would grow more rapidly. However, various reports have suggested that old mice are not as permissive to implanted tumor cells as young mice. In order to determine and characterize the age-related response to B16 melanoma, we implanted 5×105 tumor cells into 8, 16, 24, and 32-month-old male C57BL/6 (B6 and C57BL/6×BALB/c F1 (CB6 F1 mice subcutaneously in the inguinal and axillary spaces, or intradermally in the lateral flank. Results showed decreased tumor volume with increasing age, which varied according to mouse genetic background and the implanted site. The B6 strain showed robust tumor growth at 8 months of age at the inguinal implantation site, with an average tumor volume of 1341.25 mm3. The 16, 24, and 32-month age groups showed a decrease in tumor growth with tumor volumes of 563.69, 481.02, and 264.55 mm3, respectively (p≤0.001. The axillary implantation site was less permissive in 8-month-old B6 mice with an average tumor volume of 761.52 mm3. The 24- and 32-month age groups showed a similar decrease in tumor growth with tumor volumes of 440 and 178.19 mm3, respectively (p≤0.01. The CB6F1 strain was not as tumor permissive at 8 months of age as B6 mice with average tumor volumes of 446.96 and 426.91 mm3 for the inguinal and axillary sites, respectively. There was a decrease in tumor growth at 24 months of age at both inguinal and axillary sites with an average tumor volume of 271.02 and 249.12 mm3, respectively (p≤0.05. The strain dependence was not apparent in 8-month-old mice injected intradermally with B16 melanoma cells, with average tumor volumes of 736.82 and 842.85 mm3 for B6 and CB6 F1, respectively. However, a strain difference was seen in 32-month-old B6 mice with an average decrease in tumor volume of 250.83 mm3 (p≤0.01. In contrast, tumor growth significantly decreased earlier in CB6 F1 mice with average

  15. Similar biodiversity of ectomycorrhizal fungi in set-aside plantations and ancient old-growth broadleaved forests.

    Science.gov (United States)

    Spake, Rebecca; van der Linde, Sietse; Newton, Adrian C; Suz, Laura M; Bidartondo, Martin I; Doncaster, C Patrick

    2016-02-01

    Setting aside overmature planted forests is currently seen as an option for preserving species associated with old-growth forests, such as those with dispersal limitation. Few data exist, however, on the utility of set-aside plantations for this purpose, or the value of this habitat type for biodiversity relative to old-growth semi-natural ecosystems. Here, we evaluate the contribution of forest type relative to habitat characteristics in determining species richness and composition in seven forest blocks, each containing an ancient old-growth stand (> 1000 yrs) paired with a set-aside even-aged planted stand (ca. 180 yrs). We investigated the functionally important yet relatively neglected ectomycorrhizal fungi (EMF), a group for which the importance of forest age has not been assessed in broadleaved forests. We found that forest type was not an important determinant of EMF species richness or composition, demonstrating that set-aside can be an effective option for conserving ancient EMF communities. Species richness of above-ground EMF fruiting bodies was principally related to the basal area of the stand (a correlate of canopy cover) and tree species diversity, whilst richness of below-ground ectomycorrhizae was driven only by tree diversity. Our results suggest that overmature planted forest stands, particularly those that are mixed-woods with high basal area, are an effective means to connect and expand ecological networks of ancient old-growth forests in historically deforested and fragmented landscapes for ectomycorrhizal fungi.

  16. Do chestnut, northern red, and white oak germinant seedlings respond similarly to light treatments? Growth and biomass

    Science.gov (United States)

    Joanne Rebbeck; Kurt Gottschalk; Amy. Scherzer

    2011-01-01

    Northern red oak (Quercus rubra L.) seedling growth has been extensively studied. White oak (Quercus alba L.) and chestnut oak (Quercus prinus L.), however, are far less investigated despite their importance among upland oak species in eastern North American forests. We characterized white and chestnut oak...

  17. Market Structure, Financial Dependence and Industrial Growth: Evidence from the Banking Industry in Emerging Asian Economies.

    Science.gov (United States)

    Khan, Habib Hussain; Ahmad, Rubi Binit; Gee, Chan Sok

    2016-01-01

    In this study, we examine the role of market structure for growth in financially dependent industries from 10 emerging Asian economies over the period of 1995-2011. Our approach departs from existing studies in that we apply four alternative measures of market structure based on structural and non-structural approaches and compare their outcomes. Results indicate that higher bank concentration may slow down the growth of financially dependent industries. Bank competition on the other hand, allows financially dependent industries to grow faster. These findings are consistent across a number of sensitivity checks such as alternative measures of financial dependence, institutional factors (including property rights, quality of accounting standards and bank ownership), and endogeneity consideration. In sum, our study suggests that financially dependent industries grow more in more competitive/less concentrated banking systems. Therefore, regulatory authorities need to be careful while pursuing a consolidation policy for banking sector in emerging Asian economies.

  18. Market Structure, Financial Dependence and Industrial Growth: Evidence from the Banking Industry in Emerging Asian Economies

    Science.gov (United States)

    Khan, Habib Hussain; Ahmad, Rubi Binit; Gee, Chan Sok

    2016-01-01

    In this study, we examine the role of market structure for growth in financially dependent industries from 10 emerging Asian economies over the period of 1995–2011. Our approach departs from existing studies in that we apply four alternative measures of market structure based on structural and non-structural approaches and compare their outcomes. Results indicate that higher bank concentration may slow down the growth of financially dependent industries. Bank competition on the other hand, allows financially dependent industries to grow faster. These findings are consistent across a number of sensitivity checks such as alternative measures of financial dependence, institutional factors (including property rights, quality of accounting standards and bank ownership), and endogeneity consideration. In sum, our study suggests that financially dependent industries grow more in more competitive/less concentrated banking systems. Therefore, regulatory authorities need to be careful while pursuing a consolidation policy for banking sector in emerging Asian economies. PMID:27490847

  19. Dose dependency of time of onset of radiation-induced growth hormone deficiency

    International Nuclear Information System (INIS)

    Clayton, P.E.; Shalet, S.M.

    1991-01-01

    Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showed that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis

  20. Modeling of scale-dependent bacterial growth by chemical kinetics approach.

    Science.gov (United States)

    Martínez, Haydee; Sánchez, Joaquín; Cruz, José-Manuel; Ayala, Guadalupe; Rivera, Marco; Buhse, Thomas

    2014-01-01

    We applied the so-called chemical kinetics approach to complex bacterial growth patterns that were dependent on the liquid-surface-area-to-volume ratio (SA/V) of the bacterial cultures. The kinetic modeling was based on current experimental knowledge in terms of autocatalytic bacterial growth, its inhibition by the metabolite CO2, and the relief of inhibition through the physical escape of the inhibitor. The model quantitatively reproduces kinetic data of SA/V-dependent bacterial growth and can discriminate between differences in the growth dynamics of enteropathogenic E. coli, E. coli JM83, and Salmonella typhimurium on one hand and Vibrio cholerae on the other hand. Furthermore, the data fitting procedures allowed predictions about the velocities of the involved key processes and the potential behavior in an open-flow bacterial chemostat, revealing an oscillatory approach to the stationary states.

  1. Individualism in plant populations: using stochastic differential equations to model individual neighbourhood-dependent plant growth.

    Science.gov (United States)

    Lv, Qiming; Schneider, Manuel K; Pitchford, Jonathan W

    2008-08-01

    We study individual plant growth and size hierarchy formation in an experimental population of Arabidopsis thaliana, within an integrated analysis that explicitly accounts for size-dependent growth, size- and space-dependent competition, and environmental stochasticity. It is shown that a Gompertz-type stochastic differential equation (SDE) model, involving asymmetric competition kernels and a stochastic term which decreases with the logarithm of plant weight, efficiently describes individual plant growth, competition, and variability in the studied population. The model is evaluated within a Bayesian framework and compared to its deterministic counterpart, and to several simplified stochastic models, using distributional validation. We show that stochasticity is an important determinant of size hierarchy and that SDE models outperform the deterministic model if and only if structural components of competition (asymmetry; size- and space-dependence) are accounted for. Implications of these results are discussed in the context of plant ecology and in more general modelling situations.

  2. Size-dependent standard deviation for growth rates: Empirical results and theoretical modeling

    Science.gov (United States)

    Podobnik, Boris; Horvatic, Davor; Pammolli, Fabio; Wang, Fengzhong; Stanley, H. Eugene; Grosse, I.

    2008-05-01

    We study annual logarithmic growth rates R of various economic variables such as exports, imports, and foreign debt. For each of these variables we find that the distributions of R can be approximated by double exponential (Laplace) distributions in the central parts and power-law distributions in the tails. For each of these variables we further find a power-law dependence of the standard deviation σ(R) on the average size of the economic variable with a scaling exponent surprisingly close to that found for the gross domestic product (GDP) [Phys. Rev. Lett. 81, 3275 (1998)]. By analyzing annual logarithmic growth rates R of wages of 161 different occupations, we find a power-law dependence of the standard deviation σ(R) on the average value of the wages with a scaling exponent β≈0.14 close to those found for the growth of exports, imports, debt, and the growth of the GDP. In contrast to these findings, we observe for payroll data collected from 50 states of the USA that the standard deviation σ(R) of the annual logarithmic growth rate R increases monotonically with the average value of payroll. However, also in this case we observe a power-law dependence of σ(R) on the average payroll with a scaling exponent β≈-0.08 . Based on these observations we propose a stochastic process for multiple cross-correlated variables where for each variable (i) the distribution of logarithmic growth rates decays exponentially in the central part, (ii) the distribution of the logarithmic growth rate decays algebraically in the far tails, and (iii) the standard deviation of the logarithmic growth rate depends algebraically on the average size of the stochastic variable.

  3. Catalyst and its diameter dependent growth kinetics of CVD grown GaN nanowires

    International Nuclear Information System (INIS)

    Samanta, Chandan; Chander, D. Sathish; Ramkumar, J.; Dhamodaran, S.

    2012-01-01

    Graphical abstract: GaN nanowires with controlled diameter and aspect ratio has been grown using a simple CVD technique. The growth kinetics of CVD grown nanowires investigated in detail for different catalysts and their diameters. A critical diameter important to distinguish the growth regimes has been discussed in detail. The results are important which demonstrates the growth of diameter and aspect ratio controlled GaN nanowires and also understand their growth kinetics. Highlights: ► Controlled diameter and aspect ratio of GaN nanowires achieved in simple CVD reactor. ► Nanowire growth kinetics for different catalyst and its diameters were understood. ► Adatoms vapor pressure inside reactor plays a crucial role in growth kinetics. ► Diffusion along nanowire sidewalls dominate for gold and nickel catalysts. ► Gibbs–Thomson effect dominates for palladium catalyst. -- Abstract: GaN nanowires were grown using chemical vapor deposition with controlled aspect ratio. The catalyst and catalyst-diameter dependent growth kinetics is investigated in detail. We first discuss gold catalyst diameter dependent growth kinetics and subsequently compare with nickel and palladium catalyst. For different diameters of gold catalyst there was hardly any variation in the length of the nanowires but for other catalysts with different diameter a strong length variation of the nanowires was observed. We calculated the critical diameter dependence on adatoms pressure inside the reactor and inside the catalytic particle. This gives an increasing trend in critical diameter as per the order gold, nickel and palladium for the current set of experimental conditions. Based on the critical diameter, with gold and nickel catalyst the nanowire growth was understood to be governed by limited surface diffusion of adatoms and by Gibbs–Thomson effect for the palladium catalyst.

  4. Evidence for dose-dependent effects on plant growth by Stenotrophomonas strains from different origins.

    Science.gov (United States)

    Suckstorff, I; Berg, G

    2003-01-01

    To assess the influence of Stenotrophomonas on plants, the interaction of 16 Stenotrophomonas strains from clinical and environmental sources with strawberry plant seedlings was analysed. In vitro, all Stenotrophomonas strains influenced plant growth when applied to seedlings. Whereas most of the Stenotrophomonas strains promoted root growth and hair development, a statistically significantly negative influence on the length of stem was found. Although strains from a clinical origin also showed statistically significant effects on plants, this was generally lower when compared with environmental strains. For three selected strains, a strong dose-dependent effect was observed for all parameters. In vitro, a correlation was found between plant growth promotion and production of a plant growth hormone, indole-3-acetic acid (IAA). Xanthomonas campestris, a phylogenetically very closely related species to Stenotrophomonas, was used as a phytopathogenic control. It too confirmed the reduction of plant growth in this in vitro system. Independent of their origin, Stenotrophomonas strains can produce IAA in vitro and subsequently, influence plant growth. The effect of Stenotrophomonas presence on plants was dose-dependent. The dose-dependent effect of Stenotrophomonas, a bacterium of both biotechnological and medical interest, is of great interest for biocontrol applications of plant-associated strains. This paper is the first report that clearly demonstrates the phytopathogenic capacity of Stenotrophomonas.

  5. Growth and time dependent alignment of KCl crystals in Hemoglobin LB monolayer

    International Nuclear Information System (INIS)

    Mahato, Mrityunjoy; Pal, Prabir; Tah, Bidisha; Kamilya, Tapanendu; Talapatra, G.B.

    2012-01-01

    Nature and organism often use the biomineralization technique to build up various highly regular structures such as bone, teeth, kidney stone etc., and recently this becomes the strategy to design and synthesis of novel biocomposite materials. We report here the controlled crystallization of KCl in Langmuir and Langmuir Blodgett (LB) monolayer of Hemoglobin (Hb) at ambient condition. The nucleation and growth of KCl crystals in Hb monolayer has temporal and KCl concentration dependency. The growth of KCl crystals in LB film of Hb has distinct behavior in the alignment of crystals from linear to fractal like structures depending on growth time. The crystallographic identity of the biomineralized KCl crystal is confirmed from HR-TEM, XRD, and from powder diffraction simulation. Our results substantiated that the template of Langmuir monolayer of proteins plays a crucial role in biomineralization as well as in designing and synthesizing of novel biocomposite materials. Highlights: ► Biomineralization of KCl crystal has been studied in Hemoglobin LB film. ► KCl crystal growth is time and concentration of KCl dependent. ► The alignment of KCl crystal growth is fractal nature with time. ► The unfolding of Hb and evaporation factor has some role in crystallization and fractal growth.

  6. Chirality-Dependent Vapor-Phase Epitaxial Growth and Termination of Single-Wall Carbon Nanotubes

    Science.gov (United States)

    Liu, Bilu; Liu, Jia; Zhou, Chongwu; USC nanolab Team

    2014-03-01

    Chirality-pure single-wall carbon nanotubes are highly desired for both fundamental study and many of their technological applications. Recently, we have shown that chirality-pure short nanotubes can be used as seeds for vapor-phase epitaxial cloning growth, opening up a new route toward chirality-controlled carbon nanotube synthesis. Nevertheless, the yield of vapor-phase epitaxial growth is rather limited at the present stage, due to the lack of mechanistic understanding of the process. Here we report chirality-dependent growth kinetics and termination mechanism for the vapor-phase epitaxial growth of seven single- chirality nanotubes of (9, 1), (6, 5), (8, 3), (7, 6), (10, 2), (6, 6), and (7, 7), covering near zigzag, medium chiral angle, and near armchair semiconductors, as well as armchair metallic nanotubes. Our results reveal that the growth rates of nanotubes increase with their chiral angles while the active lifetimes of the growth hold opposite trend. Consequently, the chirality distribution of a nanotube ensemble is jointly determined by both growth rates and lifetimes. These results correlate nanotube structures and properties with their growth behaviors and deepen our understanding of chirality-controlled growth of nanotubes.

  7. Investment in secreted enzymes during nutrient-limited growth is utility dependent.

    Science.gov (United States)

    Cezairliyan, Brent; Ausubel, Frederick M

    2017-09-12

    Pathogenic bacteria secrete toxins and degradative enzymes that facilitate their growth by liberating nutrients from the environment. To understand bacterial growth under nutrient-limited conditions, we studied resource allocation between cellular and secreted components by the pathogenic bacterium Pseudomonas aeruginosa during growth on a protein substrate that requires extracellular digestion by secreted proteases. We identified a quantitative relationship between the rate of increase of cellular biomass under nutrient-limiting growth conditions and the rate of increase in investment in secreted proteases. Production of secreted proteases is stimulated by secreted signals that convey information about the utility of secreted proteins during nutrient-limited growth. Growth modeling using this relationship recapitulated the observed kinetics of bacterial growth on a protein substrate. The proposed regulatory strategy suggests a rationale for quorum-sensing-dependent stimulation of the production of secreted enzymes whereby investment in secreted enzymes occurs in proportion to the utility they confer. Our model provides a framework that can be applied toward understanding bacterial growth in many environments where growth rate is limited by the availability of nutrients.

  8. Vitamin B12–dependent taurine synthesis regulates growth and bone mass

    Science.gov (United States)

    Roman-Garcia, Pablo; Quiros-Gonzalez, Isabel; Mottram, Lynda; Lieben, Liesbet; Sharan, Kunal; Wangwiwatsin, Arporn; Tubio, Jose; Lewis, Kirsty; Wilkinson, Debbie; Santhanam, Balaji; Sarper, Nazan; Clare, Simon; Vassiliou, George S.; Velagapudi, Vidya R.; Dougan, Gordon; Yadav, Vijay K.

    2014-01-01

    Both maternal and offspring-derived factors contribute to lifelong growth and bone mass accrual, although the specific role of maternal deficiencies in the growth and bone mass of offspring is poorly understood. In the present study, we have shown that vitamin B12 (B12) deficiency in a murine genetic model results in severe postweaning growth retardation and osteoporosis, and the severity and time of onset of this phenotype in the offspring depends on the maternal genotype. Using integrated physiological and metabolomic analysis, we determined that B12 deficiency in the offspring decreases liver taurine production and associates with abrogation of a growth hormone/insulin-like growth factor 1 (GH/IGF1) axis. Taurine increased GH-dependent IGF1 synthesis in the liver, which subsequently enhanced osteoblast function, and in B12-deficient offspring, oral administration of taurine rescued their growth retardation and osteoporosis phenotypes. These results identify B12 as an essential vitamin that positively regulates postweaning growth and bone formation through taurine synthesis and suggests potential therapies to increase bone mass. PMID:24911144

  9. Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway.

    Science.gov (United States)

    Markworth, James F; Cameron-Smith, David

    2013-01-01

    Arachidonic acid (AA) is the metabolic precursor to a diverse range of downstream bioactive lipid mediators. A positive or negative influence of individual eicosanoid species [e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro. C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was amplified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AA-stimulated growth was associated with markedly increased secretion of PGF(2α) and PGE(2); however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway.

  10. Time dependent fracture growth in intact crystalline rock: new laboratory procedures

    International Nuclear Information System (INIS)

    Backers, T.; Stephansson, O.

    2008-01-01

    Short term laboratory tests to determine the strength of rock material are commonly used to assess stability of rock excavations. However, loading the rock below its short term strength may lead to delayed failure due to slow stable fracture growth. This time-dependent phenomenon is called subcritical fracture growth. A fracture mechanics based approach is applied in this study to determine the parameters describing subcritical fracture growth under Mode Ⅰ (tensile) and Mode Ⅱ (in-plane shear) loading in terms of the stress intensity factors of saturated granodiorite from the) Aespoe HRL. A statistical method is applied to data from three-point bending (tension) and Punch-Through Shear with Confining Pressure, PTS/CP, (shear) experiments. One population of each set-up was subjected to rapid loading tests yielding a strength probability distribution. A second population was loaded up to a certain fraction of the statistical percentage for failure and the time-to-failure was determined. From these two populations the subcritical fracture growth parameters were determined successfully. Earlier studies demonstrated subcritical fracture growth under Mode I loading conditions, but this study shows that under a Mode Ⅱ load time-dependent fracture growth exists as well. (authors)

  11. STATUS OF BONE METABOLISM AND LINEAR GROWTH OF INFANTS DEPENDENT ON MOTHER'S CALCIUM PROVISION

    Directory of Open Access Journals (Sweden)

    L.A. Shcheplyagina

    2006-01-01

    Full Text Available The article deals with the analytical findings of the mineral metabolism, bone metabolism and linear growth along with the bone strength of the infants dependent on the mother's calcium and vitamin D provision during pregnancy. The researchers have prospectively examined 160 mother–newborn infant pairs and 87 children for 6–8 months. They confirmed that infant's calcium and vitamin D provision depends on calcium and vitamin d contained in mother's body. Prophylaxis and correction of the calcium and vitamin D deficit in the mother's body will ensure necessary rates of the linear growth, mineral metabolism, and bone remodeling both during antenatal period and within the first 6–8 months, following the birth, increase the bone strength and reduce the frequency of rachitic and rachiticblike changes in the infant skeleton.Key words: newborn infants, infants, calcium provision, bone metabolism, linear growth, bone strength.

  12. Optimal litter size for individual growth of European rabbit pups depends on their thermal environment.

    Science.gov (United States)

    Rödel, H G; Hudson, R; von Holst, D

    2008-04-01

    In altricial mammals and birds, the presence of a large number of litter or brood mates often affects the development of individual offspring by reducing the share of resources provided by the parents. However, sibling presence can also be favourable, conferring thermoregulatory benefits when ambient temperatures are low. Consequently, shifts in the relation between costs and benefits of sibling presence can be expected as a function of the thermal environment. In a study of a European rabbit population (Oryctolagus cuniculus) living in a field enclosure, we investigated the effects of litter size and soil temperature on pup growth over 7 years. Temperatures inside the subterranean nests were positively correlated with soil temperature and with litter size. Soil temperature varied strongly across the breeding season, ranging from 3 to 21 degrees C. Under warmer soil temperature conditions (10-15 degrees C and >15 degrees C), pup growth decreased with increasing litter size, where litters of two pups (smallest litter size considered) showed the highest growth rates. In contrast, under colder soil temperature conditions (growth rates were found in litters of three pups. We also asked if such temperature-dependent differences in the optimal pup growth rates might be explained by differences in maternal characteristics, which might affect lactational performance. We assessed maternal performance using females' postpartum body mass and social rank. However, we did not find consistent differences in maternal characteristics between females giving birth to different-sized litters during different soil temperature conditions, which would have provided an alternative explanation for the observed differences in litter size-dependent pup growth. We conclude that under colder soil temperature conditions, the thermal benefits of a greater number of littermates outweigh the negative consequences of competition for milk, leading to an environment-dependent shift in the optimal

  13. Growth dependence of conjugation explains limited plasmid invasion in biofilms: an individual‐based modelling study

    DEFF Research Database (Denmark)

    Merkey, Brian; Lardon, Laurent; Seoane, Jose Miguel

    2011-01-01

    Plasmid invasion in biofilms is often surprisingly limited in spite of the close contact of cells in a biofilm. We hypothesized that this poor plasmid spread into deeper biofilm layers is caused by a dependence of conjugation on the growth rate (relative to the maximum growth rate) of the donor...... and scan speed) and spatial reach (EPS yield, conjugal pilus length) are more important for successful plasmid invasion than the recipients' growth rate or the probability of segregational loss. While this study identifies one factor that can limit plasmid invasion in biofilms, the new individual....... By extending an individual‐based model of microbial growth and interactions to include the dynamics of plasmid carriage and transfer by individual cells, we were able to conduct in silico tests of this and other hypotheses on the dynamics of conjugal plasmid transfer in biofilms. For a generic model plasmid...

  14. Density Dependence and Growth Rate: Evolutionary Effects on Resistance Development to Bt (Bacillus thuringiensis).

    Science.gov (United States)

    Martinez, Jeannette C; Caprio, Michael A; Friedenberg, Nicholas A

    2018-02-09

    It has long been recognized that pest population dynamics can affect the durability of a pesticide, but dose remains the primary component of insect resistance management (IRM). For transgenic pesticidal traits such as Bt (Bacillus thuringiensis Berliner (Bacillales: Bacillaceae)), dose (measured as the mortality of susceptibles caused by a toxin) is a relatively fixed characteristic and often falls below the standard definition of high dose. Hence, it is important to understand how pest population dynamics modify durability and what targets they present for IRM. We used a deterministic model of a generic arthropod pest to examine how timing and strength of density dependence interacted with population growth rate and Bt mortality to affect time to resistance. As in previous studies, durability typically reached a minimum at intermediate doses. However, high population growth rates could eliminate benefits of high dose. The timing of density dependence had a more subtle effect. If density dependence operated simultaneously with Bt mortality, durability was insensitive to its strengths. However, if density dependence was driven by postselection densities, decreasing its strength could increase durability. The strength of density dependence could affect durability of both single traits and pyramids, but its influence depended on the timing of density dependence and size of the refuge. Our findings suggest the utility of a broader definition of high dose, one that incorporates population-dynamic context. That maximum growth rates and timing and strength of interactions causing density dependent mortality can all affect durability, also highlights the need for ecologically integrated approaches to IRM research. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Growth but not photosynthesis response of a host plant to infection by a holoparasitic plant depends on nitrogen supply.

    Science.gov (United States)

    Shen, Hao; Xu, Shu-Jun; Hong, Lan; Wang, Zhang-Ming; Ye, Wan-Hui

    2013-01-01

    Parasitic plants can adversely influence the growth of their hosts by removing resources and by affecting photosynthesis. Such negative effects depend on resource availability. However, at varied resource levels, to what extent the negative effects on growth are attributed to the effects on photosynthesis has not been well elucidated. Here, we examined the influence of nitrogen supply on the growth and photosynthesis responses of the host plant Mikania micrantha to infection by the holoparasite Cuscuta campestris by focusing on the interaction of nitrogen and infection. Mikania micrantha plants fertilized at 0.2, 1 and 5 mM nitrate were grown with and without C. campestris infection. We observed that the infection significantly reduced M. micrantha growth at each nitrate fertilization and more severely at low than at high nitrate. Such alleviation at high nitrate was largely attributed to a stronger influence of infection on root biomass at low than at high nitrate fertilization. However, although C. campestris altered allometry and inhibited host photosynthesis, the magnitude of the effects was independent of nitrate fertilizations. The infection reduced light saturation point, net photosynthesis at saturating irradiances, apparent quantum yield, CO2 saturated rate of photosynthesis, carboxylation efficiency, the maximum carboxylation rate of Rubisco, and maximum light-saturated rate of electron transport, and increased light compensation point in host leaves similarly across nitrate levels, corresponding to a similar magnitude of negative effects of the parasite on host leaf soluble protein and Rubisco concentrations, photosynthetic nitrogen use efficiency and stomatal conductance across nitrate concentrations. Thus, the more severe inhibition in host growth at low than at high nitrate supplies cannot be attributed to a greater parasite-induced reduction in host photosynthesis, but the result of a higher proportion of host resources transferred to the parasite at

  16. Growth but Not Photosynthesis Response of a Host Plant to Infection by a Holoparasitic Plant Depends on Nitrogen Supply

    Science.gov (United States)

    Shen, Hao; Xu, Shu-Jun; Hong, Lan; Wang, Zhang-Ming; Ye, Wan-Hui

    2013-01-01

    Parasitic plants can adversely influence the growth of their hosts by removing resources and by affecting photosynthesis. Such negative effects depend on resource availability. However, at varied resource levels, to what extent the negative effects on growth are attributed to the effects on photosynthesis has not been well elucidated. Here, we examined the influence of nitrogen supply on the growth and photosynthesis responses of the host plant Mikania micrantha to infection by the holoparasite Cuscuta campestris by focusing on the interaction of nitrogen and infection. Mikania micrantha plants fertilized at 0.2, 1 and 5 mM nitrate were grown with and without C. campestris infection. We observed that the infection significantly reduced M. micrantha growth at each nitrate fertilization and more severely at low than at high nitrate. Such alleviation at high nitrate was largely attributed to a stronger influence of infection on root biomass at low than at high nitrate fertilization. However, although C. campestris altered allometry and inhibited host photosynthesis, the magnitude of the effects was independent of nitrate fertilizations. The infection reduced light saturation point, net photosynthesis at saturating irradiances, apparent quantum yield, CO2 saturated rate of photosynthesis, carboxylation efficiency, the maximum carboxylation rate of Rubisco, and maximum light-saturated rate of electron transport, and increased light compensation point in host leaves similarly across nitrate levels, corresponding to a similar magnitude of negative effects of the parasite on host leaf soluble protein and Rubisco concentrations, photosynthetic nitrogen use efficiency and stomatal conductance across nitrate concentrations. Thus, the more severe inhibition in host growth at low than at high nitrate supplies cannot be attributed to a greater parasite-induced reduction in host photosynthesis, but the result of a higher proportion of host resources transferred to the parasite at

  17. Growth but not photosynthesis response of a host plant to infection by a holoparasitic plant depends on nitrogen supply.

    Directory of Open Access Journals (Sweden)

    Hao Shen

    Full Text Available Parasitic plants can adversely influence the growth of their hosts by removing resources and by affecting photosynthesis. Such negative effects depend on resource availability. However, at varied resource levels, to what extent the negative effects on growth are attributed to the effects on photosynthesis has not been well elucidated. Here, we examined the influence of nitrogen supply on the growth and photosynthesis responses of the host plant Mikania micrantha to infection by the holoparasite Cuscuta campestris by focusing on the interaction of nitrogen and infection. Mikania micrantha plants fertilized at 0.2, 1 and 5 mM nitrate were grown with and without C. campestris infection. We observed that the infection significantly reduced M. micrantha growth at each nitrate fertilization and more severely at low than at high nitrate. Such alleviation at high nitrate was largely attributed to a stronger influence of infection on root biomass at low than at high nitrate fertilization. However, although C. campestris altered allometry and inhibited host photosynthesis, the magnitude of the effects was independent of nitrate fertilizations. The infection reduced light saturation point, net photosynthesis at saturating irradiances, apparent quantum yield, CO2 saturated rate of photosynthesis, carboxylation efficiency, the maximum carboxylation rate of Rubisco, and maximum light-saturated rate of electron transport, and increased light compensation point in host leaves similarly across nitrate levels, corresponding to a similar magnitude of negative effects of the parasite on host leaf soluble protein and Rubisco concentrations, photosynthetic nitrogen use efficiency and stomatal conductance across nitrate concentrations. Thus, the more severe inhibition in host growth at low than at high nitrate supplies cannot be attributed to a greater parasite-induced reduction in host photosynthesis, but the result of a higher proportion of host resources

  18. Sapling growth rates reveal conspecific negative density dependence in a temperate forest.

    Science.gov (United States)

    Ramage, Benjamin S; Johnson, Daniel J; Gonzalez-Akre, Erika; McShea, William J; Anderson-Teixeira, Kristina J; Bourg, Norman A; Clay, Keith

    2017-10-01

    Local tree species diversity is maintained in part by conspecific negative density dependence (CNDD). This pervasive mechanism occurs in a variety of forms and ecosystems, but research to date has been heavily skewed toward tree seedling survival in tropical forests. To evaluate CNDD more broadly, we investigated how sapling growth rates were affected by conspecific adult neighbors in a fully mapped 25.6 ha temperate deciduous forest. We examined growth rates as a function of the local adult tree neighborhood (via spatial autoregressive modeling) and compared the spatial positioning of faster-growing and slower-growing saplings with respect to adult conspecific and heterospecific trees (via bivariate point pattern analysis). In addition, to determine whether CNDD-driven variation in growth rates leaves a corresponding spatial signal, we extended our point pattern analysis to a static, growth-independent comparison of saplings and the next larger size class. We found that negative conspecific effects on sapling growth were most prevalent. Five of the nine species that were sufficiently abundant for analysis exhibited CNDD, while only one species showed evidence of a positive conspecific effect, and one or two species, depending on the analysis, displayed heterospecific effects. There was general agreement between the autoregressive models and the point pattern analyses based on sapling growth rates, but point pattern analyses based on single-point-in-time size classes yielded results that differed markedly from the other two approaches. Our work adds to the growing body of evidence that CNDD is an important force in temperate forests, and demonstrates that this process extends to sapling growth rates. Further, our findings indicate that point pattern analyses based solely on size classes may fail to detect the process of interest (e.g., neighborhood-driven variation in growth rates), in part due to the confounding of tree size and age.

  19. Nanoelectroablation of Murine Tumors Triggers a CD8-Dependent Inhibition of Secondary Tumor Growth.

    Directory of Open Access Journals (Sweden)

    Richard Nuccitelli

    Full Text Available We have used both a rat orthotopic hepatocellular carcinoma model and a mouse allograft tumor model to study liver tumor ablation with nanosecond pulsed electric fields (nsPEF. We confirm that nsPEF treatment triggers apoptosis in rat liver tumor cells as indicated by the appearance of cleaved caspase 3 and 9 within two hours after treatment. Furthermore we provide evidence that nsPEF treatment leads to the translocation of calreticulin (CRT to the cell surface which is considered a damage-associated molecular pattern indicative of immunogenic cell death. We provide direct evidence that nanoelectroablation triggers a CD8-dependent inhibition of secondary tumor growth by comparing the growth rate of secondary orthotopic liver tumors in nsPEF-treated rats with that in nsPEF-treated rats depleted of CD8+ cytotoxic T-cells. The growth of these secondary tumors was severely inhibited as compared to tumor growth in CD8-depleated rats, with their average size only 3% of the primary tumor size after the same one-week growth period. In contrast, when we depleted CD8+ T-cells the second tumor grew more robustly, reaching 54% of the size of the first tumor. In addition, we demonstrate with immunohistochemistry that CD8+ T-cells are highly enriched in the secondary tumors exhibiting slow growth. We also showed that vaccinating mice with nsPEF-treated isogenic tumor cells stimulates an immune response that inhibits the growth of secondary tumors in a CD8+-dependent manner. We conclude that nanoelectroablation triggers the production of CD8+ cytotoxic T-cells resulting in the inhibition of secondary tumor growth.

  20. Galaxies in x-ray selected clusters and groups in Dark Energy Survey Data I: Stellar mass growth of bright central galaxies since Z similar to 1.2

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Miller, C.; McKay, T.; Rooney, P.; Evrard, A. E.; Romer, A. K.; Perfecto, R.; Song, J; Desai, S.; Mohr, J. J.; Vikram, V.

    2016-01-10

    Using the science verification data of the Dark Energy Survey for a new sample of 106 X-ray selected clusters and groups, we study the stellar mass growth of bright central galaxies (BCGs) since redshift z similar to 1.2. Compared with the expectation in a semi-analytical model applied to the Millennium Simulation, the observed BCGs become under-massive/under-luminous with decreasing redshift. We incorporate the uncertainties associated with cluster mass, redshift, and BCG stellar mass measurements into an analysis of a redshift-dependent BCG-cluster mass relation, m(*) proportional to (M-200/1.5 x 10(14)M(circle dot))(0.24 +/- 0.08)(1+z)(-0.19 +/- 0.34), and compare the observed relation to the model prediction. We estimate the average growth rate since z = 1.0 for BCGs hosted by clusters of M-200,M-z = 10(13.8)M(circle dot); at z = 1.0: m(*, BCG) appears to have grown by 0.13 +/- 0.11 dex, in tension at the similar to 2.5 sigma significance level with the 0.40 dex growth rate expected from the semi-analytic model. We show that the build-up of extended intracluster light after z = 1.0 may alleviate this tension in BCG growth rates.

  1. Indoor-biofilter growth and exposure to airborne chemicals drive similar changes in plant root bacterial communities.

    Science.gov (United States)

    Russell, Jacob A; Hu, Yi; Chau, Linh; Pauliushchyk, Margarita; Anastopoulos, Ioannis; Anandan, Shivanthi; Waring, Michael S

    2014-08-01

    Due to the long durations spent inside by many humans, indoor air quality has become a growing concern. Biofiltration has emerged as a potential mechanism to clean indoor air of harmful volatile organic compounds (VOCs), which are typically found at concentrations higher indoors than outdoors. Root-associated microbes are thought to drive the functioning of plant-based biofilters, or biowalls, converting VOCs into biomass, energy, and carbon dioxide, but little is known about the root microbial communities of such artificially grown plants, how or whether they differ from those of plants grown in soil, and whether any changes in composition are driven by VOCs. In this study, we investigated how bacterial communities on biofilter plant roots change over time and in response to VOC exposure. Through 16S rRNA amplicon sequencing, we compared root bacterial communities from soil-grown plants with those from two biowalls, while also comparing communities from roots exposed to clean versus VOC-laden air in a laboratory biofiltration system. The results showed differences in bacterial communities between soil-grown and biowall-grown plants and between bacterial communities from plant roots exposed to clean air and those from VOC-exposed plant roots. Both biowall-grown and VOC-exposed roots harbored enriched levels of bacteria from the genus Hyphomicrobium. Given their known capacities to break down aromatic and halogenated compounds, we hypothesize that these bacteria are important VOC degraders. While different strains of Hyphomicrobium proliferated in the two studied biowalls and our lab experiment, strains were shared across plant species, suggesting that a wide range of ornamental houseplants harbor similar microbes of potential use in living biofilters. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever

    Science.gov (United States)

    1989-01-01

    Clamfication) Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever 𔃼 PERSONAL AjTHOR(S...FELD GROUP SUBGROUP Antibody-Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever . 19...clinically diagnosed as dengue hemorrhagic fever . Antibody-dependent enhancement of virus growth was quantitated by measurement of virus yields in

  3. Similar expression patterns of bestrophin-4 and cGMP dependent Ca2+-activated chloride channel activity in the vasculature

    DEFF Research Database (Denmark)

    Bouzinova, Elena V.; Larsen, Per; Matchkov, Vladimir

    2008-01-01

    PCR, Western blot and immunohistochemistry. Using RT-PCR we identified bestrophin-4 mRNA expression in rat mesenteric small arteries, aorta and renal arteries, while no expression was seen in pulmonary arteries. Using a bestrophin-4 specific antibody (verified by Western blotting of the heterologously...... expressed epitope) Western blot detected a ~65 kDa band in cell lysates from rat mesenteric small arteries and aorta, which was not seen in pulmonary arteries and when preincubated with the immunizing peptide. The distribution of bestrophin-4 mRNA and protein has a pattern similar to the cGMP-dependent Cl...

  4. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ

    Science.gov (United States)

    Garofalo, Robert S.; Orena, Stephen J.; Rafidi, Kristina; Torchia, Anthony J.; Stock, Jeffrey L.; Hildebrandt, Audrey L.; Coskran, Timothy; Black, Shawn C.; Brees, Dominique J.; Wicks, Joan R.; McNeish, John D.; Coleman, Kevin G.

    2003-01-01

    The serine/threonine kinase Akt/PKB plays key roles in the regulation of cell growth, survival, and metabolism. It remains unclear, however, whether the functions of individual Akt/PKB isoforms are distinct. To investigate the function of Akt2/PKBβ, mice lacking this isoform were generated. Both male and female Akt2/PKBβ-null mice exhibit mild growth deficiency and an age-dependent loss of adipose tissue or lipoatrophy, with all observed adipose depots dramatically reduced by 22 weeks of age. Akt2/PKBβ-deficient mice are insulin resistant with elevated plasma triglycerides. In addition, Akt2/PKBβ-deficient mice exhibit fed and fasting hyperglycemia, hyperinsulinemia, glucose intolerance, and impaired muscle glucose uptake. In males, insulin resistance progresses to a severe form of diabetes accompanied by pancreatic β cell failure. In contrast, female Akt2/PKBβ-deficient mice remain mildly hyperglycemic and hyperinsulinemic until at least one year of age. Thus, Akt2/PKBβ-deficient mice exhibit growth deficiency similar to that reported previously for mice lacking Akt1/PKBα, indicating that both Akt2/PKBβ and Akt1/PKBα participate in the regulation of growth. The marked hyperglycemia and loss of pancreatic β cells and adipose tissue in Akt2/PKBβ-deficient mice suggest that Akt2/PKBβ plays critical roles in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass for which other Akt/PKB isoforms are unable to fully compensate. PMID:12843127

  5. H2-dependent attachment kinetics and shape evolution in chemical vapor deposition graphene growth

    Science.gov (United States)

    Meca, Esteban; Shenoy, Vivek B.; Lowengrub, John

    2017-09-01

    Experiments on graphene growth through chemical vapor deposition (CVD) involving methane (CH4) and hydrogen (H2) gases reveal a complex shape evolution and a non-monotonic dependence on the partial pressure of H2 ({{p}{{\\text{H}2}}} ). To explain these intriguing observations, we develop a microkinetic model for the stepwise decomposition of CH4 into mobile radicals and consider two possible mechanisms of attachment to graphene crystals: CH radicals to hydrogen-decorated edges of the crystals and C radicals to bare crystal edges. We derive an effective mass flux and an effective kinetic coefficient, both of which depend on {{p}{{\\text{H}2}}} , and incorporate these into a phase field model. The model reproduces both the non-monotonic dependence on {{p}{{\\text{H}2}}} and the characteristic shapes of graphene crystals observed in experiments. At small {{p}{{\\text{H}2}}} , growth is limited by the kinetics of attachment while at large {{p}{{\\text{H}2}}} growth is limited because the effective mass flux is small. We also derive a simple analytical model that captures the non-monotone behavior, enables the two mechanisms of attachment to be distinguished and provides guidelines for CVD growth of defect-free 2D crystals.

  6. Activity-Dependent Dendritic Spine Shrinkage and Growth Involve Downregulation of Cofilin via Distinct Mechanisms

    Science.gov (United States)

    Calabrese, Barbara; Saffin, Jean-Michel; Halpain, Shelley

    2014-01-01

    A current model posits that cofilin-dependent actin severing negatively impacts dendritic spine volume. Studies suggested that increased cofilin activity underlies activity-dependent spine shrinkage, and that reduced cofilin activity induces activity-dependent spine growth. We suggest instead that both types of structural plasticity correlate with decreased cofilin activity. However, the mechanism of inhibition determines the outcome for spine morphology. RNAi in rat hippocampal cultures demonstrates that cofilin is essential for normal spine maintenance. Cofilin-F-actin binding and filament barbed-end production decrease during the early phase of activity-dependent spine shrinkage; cofilin concentration also decreases. Inhibition of the cathepsin B/L family of proteases prevents both cofilin loss and spine shrinkage. Conversely, during activity-dependent spine growth, LIM kinase stimulates cofilin phosphorylation, which activates phospholipase D-1 to promote actin polymerization. These results implicate novel molecular mechanisms and prompt a revision of the current model for how cofilin functions in activity-dependent structural plasticity. PMID:24740405

  7. Temperature-dependent growth of Geomyces destructans, the fungus that causes bat white-nose syndrome

    Science.gov (United States)

    Verant, Michelle L.; Boyles, Justin G.; Waldrep, William; Wibbelt, Gudrun; Blehert, David S.

    2012-01-01

    White-nose syndrome (WNS) is an emergent disease estimated to have killed over five million North American bats. Caused by the psychrophilic fungus Geomyces destructans, WNS specifically affects bats during hibernation. We describe temperature-dependent growth performance and morphology for six independent isolates of G. destructans from North America and Europe. Thermal performance curves for all isolates displayed an intermediate peak with rapid decline in performance above the peak. Optimal temperatures for growth were between 12.5 and 15.8°C, and the upper critical temperature for growth was between 19.0 and 19.8°C. Growth rates varied across isolates, irrespective of geographic origin, and above 12°C all isolates displayed atypical morphology that may have implications for proliferation of the fungus. This study demonstrates that small variations in temperature, consistent with those inherent of bat hibernacula, affect growth performance and physiology of G. destructans, which may influence temperature-dependent progression and severity of WNS in wild bats.

  8. L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

    Science.gov (United States)

    Cartwright, Stephanie P; Bill, Roslyn M; Hipkiss, Alan R

    2012-01-01

    The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

  9. Dependence of morphometric allometries on the growth kinetics of body parts.

    Science.gov (United States)

    Nijhout, H Frederik

    2011-11-07

    As overall size varies, the sizes of body parts of many animals often appear to be related to each other by a power law, commonly called the allometric equation. Orderly scaling relationships among body parts are widespread in the animal world, but there is no general agreement about how these relationships come about. Presumably they depend on the patterns of growth of body parts, and simple analyses have shown that exponential growth can lead to size relationships that are well-described by the allometric equation. Exponential growth kinetics also allow for a simple biological interpretation of the coefficients of the power relationship. Nevertheless, many tissues do not grow with exponential kinetics, nor do they grow for the same period of time, and the consequences of more realistic growth patterns on the resulting allometric relationships of body parts are not well understood. In this paper I derive a set of allometric equations that assume different kinetics of growth: linear, exponential and sigmoidal. In these derivations I also include differences in development times as a variable, in addition to differences in the growth rates and initial sizes of the two structures whose allometric relationship is compared. I show how these equations can be used to deduce the effect of different causes of variation in absolute size on the resulting allometry. Variation in size can be due to variation in the duration of development, variation in growth rate or variation in initial size. I show that the meaning of the coefficients of the allometric equation depends on exactly how size variation comes about. I show that if two structures are assumed to grow with sigmoidal kinetics (logistic and Gompertz) the resulting allometric equations do not have a simple and intuitive structure and produce graphs that, over a sufficiently large range of sizes, can vary from linear, to sigmoidal to hump-shaped. Over a smaller range of absolute sizes, these sigmoid growth kinetics can

  10. Saccharomyces cerevisiae biofilm tolerance towards systemic antifungals depends on growth phase.

    Science.gov (United States)

    Bojsen, Rasmus; Regenberg, Birgitte; Folkesson, Anders

    2014-12-04

    Biofilm-forming Candida species cause infections that can be difficult to eradicate, possibly because of antifungal drug tolerance mechanisms specific to biofilms. In spite of decades of research, the connection between biofilm and drug tolerance is not fully understood. We used Saccharomyces cerevisiae as a model for drug susceptibility of yeast biofilms. Confocal laser scanning microscopy showed that S. cerevisiae and C. glabrata form similarly structured biofilms and that the viable cell numbers were significantly reduced by treatment of mature biofilms with amphotericin B but not voriconazole, flucytosine, or caspofungin. We showed that metabolic activity in yeast biofilm cells decreased with time, as visualized by FUN-1 staining, and mature, 48-hour biofilms contained cells with slow metabolism and limited growth. Time-kill studies showed that in exponentially growing planktonic cells, voriconazole had limited antifungal activity, flucytosine was fungistatic, caspofungin and amphotericin B were fungicidal. In growth-arrested cells, only amphotericin B had antifungal activity. Confocal microscopy and colony count viability assays revealed that the response of growing biofilms to antifungal drugs was similar to the response of exponentially growing planktonic cells. The response in mature biofilm was similar to that of non-growing planktonic cells. These results confirmed the importance of growth phase on drug efficacy. We showed that in vitro susceptibility to antifungal drugs was independent of biofilm or planktonic growth mode. Instead, drug tolerance was a consequence of growth arrest achievable by both planktonic and biofilm populations. Our results suggest that efficient strategies for treatment of yeast biofilm might be developed by targeting of non-dividing cells.

  11. Rate-Independent Processes with Linear Growth Energies and Time-Dependent Boundary Conditions

    Czech Academy of Sciences Publication Activity Database

    Kružík, Martin; Zimmer, J.

    2012-01-01

    Roč. 5, č. 3 (2012), s. 591-604 ISSN 1937-1632 R&D Projects: GA AV ČR IAA100750802 Grant - others:GA ČR(CZ) GAP201/10/0357 Institutional research plan: CEZ:AV0Z10750506 Keywords : concentrations * oscillations * time-dependent boundary conditions * rate-independent evolution Subject RIV: BA - General Mathematics http://library.utia.cas.cz/separaty/2011/MTR/kruzik-rate-independent processes with linear growth energies and time-dependent boundary conditions.pdf

  12. Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner

    DEFF Research Database (Denmark)

    Hald, Andreas; Eickhardt, Hanne; Maerkedahl, Rasmus Baadsgaard

    2012-01-01

    Rearrangement of the skin during wound healing depends on plasmin and plasminogen, which serve to degrade fibrin depositions in the provisional matrix and thereby facilitate keratinocyte migration. In the current study, we investigated whether plasmin and plasminogen likewise played a role during...... by maintaining patency of the tumor vasculature.-Hald, A., Eickhardt, H., Maerkedahl, R. B., Feldborg, C. W., Egerod, K. L., Engelholm. L. H., Laerum, O. D., Lund, L. R., Rønø, B. Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner....

  13. Hydrogen-enhanced fatigue crack growth in steels and its frequency dependence

    Science.gov (United States)

    Matsunaga, Hisao; Takakuwa, Osamu; Yamabe, Junichiro; Matsuoka, Saburo

    2017-06-01

    In the context of the fatigue life design of components, particularly those destined for use in hydrogen refuelling stations and fuel cell vehicles, it is important to understand the hydrogen-induced, fatigue crack growth (FCG) acceleration in steels. As such, the mechanisms for acceleration and its influencing factors are reviewed and discussed in this paper, with a special focus on the peculiar frequency dependence of the hydrogen-induced FCG acceleration. Further, this frequency dependence is debated by introducing some potentially responsible elements, along with new experimental data obtained by the authors. This article is part of the themed issue 'The challenges of hydrogen and metals'.

  14. Growth Mechanism of Strain-Dependent Morphological Change in PEDOT:PSS Films.

    Science.gov (United States)

    Lee, Yoo-Yong; Choi, Gwang Mook; Lim, Seung-Min; Cho, Ju-Young; Choi, In-Suk; Nam, Ki Tae; Joo, Young-Chang

    2016-04-29

    Understanding the mechanism of the strain-dependent conductivity change in polymers in stretched conditions is important. We observed a strain-induced growth of the conductive regions of PSS films, induced by a coalescence of conductive PEDOT-rich cores. This growth due to coalescence leads to a gradual decrease in the electrical resistivity up to 95%, independent of the thickness of the PSS films. The primary mechanism for the evolution of the PEDOT-rich cores proceeds by the cores growing larger as they consuming relatively smaller cores. This process is caused by a strain-induced local rearrangement of PEDOT segments in the vicinity of PSS shells around the cores and also changes the chemical environment in PEDOT, induced by the electron-withdrawing effects around the PEDOT chains. The strain-induced growth mechanism is beneficial to understanding the phenomenon of polymeric chain rearrangement in mechanical deformation and to modulating the electrical conductivity for practical applications.

  15. Temperature-dependent respiration-growth relations in ancestral maize cultivars

    Science.gov (United States)

    Bruce N. Smith; Jillian L. Walker; Rebekka L. Stone; Angela R. Jones; Lee D. Hansen

    2001-01-01

    Shoots from 4- to 6-day old seedlings of seven ancestral or old cultivars of Zea mays L. were placed in a calorimeter. Dark metabolic heat rate (q) and CO2 production rate (RCO2) were measured at nine temperatures (5, 10, 15, 20, 25, 30, 35, 40, and 45 °C). Temperature dependencies of q and RCO2 were used to model response of both growth and substrate carbon conversion...

  16. Population and prehistory I: Food-dependent population growth in constant environments.

    Science.gov (United States)

    Lee, Charlotte T; Tuljapurkar, Shripad

    2008-06-01

    We present a demographic model that describes the feedbacks between food supply, human mortality and fertility rates, and labor availability in expanding populations, where arable land area is not limiting. This model provides a quantitative framework to describe how environment, technology, and culture interact to influence the fates of preindustrial agricultural populations. We present equilibrium conditions and derive approximations for the equilibrium population growth rate, food availability, and other food-dependent measures of population well-being. We examine how the approximations respond to environmental changes and to human choices, and find that the impact of environmental quality depends upon whether it manifests through agricultural yield or maximum (food-independent) survival rates. Human choices can complement or offset environmental effects: greater labor investments increase both population growth and well-being, and therefore can counteract lower agricultural yield, while fertility control decreases the growth rate but can increase or decrease well-being. Finally we establish equilibrium stability criteria, and argue that the potential for loss of local stability at low population growth rates could have important consequences for populations that suffer significant environmental or demographic shocks.

  17. Random mutagenesis identifies factors involved in formate-dependent growth of the methanogenic archaeon Methanococcus maripaludis.

    Science.gov (United States)

    Sattler, Christian; Wolf, Sandro; Fersch, Julia; Goetz, Stefan; Rother, Michael

    2013-09-01

    Methane is a key intermediate in the carbon cycle and biologically produced by methanogenic archaea. Most methanogens are able to conserve energy by reducing CO2 to methane using molecular hydrogen as electron donor (hydrogenotrophic methanogenesis), but several hydrogenotrophic methanogens can also use formate as electron donor for methanogenesis. Formate dehydrogenase (Fdh) oxidizes formate to CO2 and is involved in funneling reducing equivalents into the methanogenic pathway, but details on other factors relevant for formate-dependent physiology of methanogens are not available. To learn more about the factors involved in formate-dependent growth of Methanococcus maripaludis strain JJ, we used a recently developed system for random in vitro mutagenesis, which is based on a modified insect transposable element to create 2,865 chromosomal transposon mutants and screened them for impaired growth on formate. Of 12 M. maripaludis transposon-induced mutants exhibiting this phenotype, the transposon insertion sites in the chromosome were mapped. Among the genes, apparently affecting formate-dependent growth were those encoding archaeal transcription factor S, a regulator of ion transport, and carbon monoxide dehydrogenase/acetyl-CoA synthase. Interestingly, in seven of the mutants, transposons were localized in a 10.2 kb region where Fdh1, one of two Fdh isoforms in the organism, is encoded. Two transcription start sites within the 10.2 kb region could be mapped, and quantification of transcripts revealed that transposon insertion in this region diminished fdhA1 expression due to polar effects.

  18. Growth-Rate Dependent Regulation of tRNA Level and Charging in Bacillus licheniformis.

    Science.gov (United States)

    Ferro, Iolanda; Liebeton, Klaus; Ignatova, Zoya

    2017-10-13

    Cellular growth crucially depends on protein synthesis and the abundance of translational components. Among them, aminoacyl-tRNAs play a central role in biosynthesis and shape the kinetics of mRNA translation, thus influencing protein production. Here, we used microarray-based approaches to determine the charging levels and tRNA abundance of Bacillus licheniformis. We observed an interesting cross-talk among tRNA expression, charging pattern, and growth rate. For a large subset of tRNAs, we found a co-regulated and augmented expression at high growth rate. Their tRNA aminoacylation level is kept relatively constant through riboswitch-regulated expression of the cognate aminoacyl-tRNA-synthetase (AARS). We show that AARSs with putative riboswitch-controlled expression are those charging tRNAs with amino acids which disfavor cell growth when individually added to the nutrient medium. Our results suggest that the riboswitch-regulated AARS expression in B. licheniformis is a powerful mechanism not only to maintain a constant ratio of aminoacyl-tRNA independent of the growth rate but concomitantly to control the intracellular level of free amino acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Acetylsalicylic acid inhibits the growth of melanoma tumors via SOX2-dependent-PAF-R-independent signaling pathway.

    Science.gov (United States)

    Thyagarajan, Anita; Saylae, Jeremiah; Sahu, Ravi P

    2017-07-25

    Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA. The current studies using stably PAF-R-positive (B16-PAFR) and negative (B16-MSCV) murine melanoma cells and PAF-R-expressing and deficient mice, demonstrate that ASA inhibits the in-vitro and in-vivo growth of highly aggressive B16F10 melanoma via bypassing tumoral or stromal PAF-R signaling. Similar ASA-induced effects in-vitro were seen in human melanoma and nasopharyngeal carcinoma cells positive or negative in PAF-R. Mechanistically, the ASA-induced decrease in cell survival and increase in apoptosis were significantly blocked by prostaglandin F2 alpha (PGF2α) agonists. Importantly, PCR array and qRT-PCR analysis of B16-tumors revealed significant downregulation of sry-related high-mobility-box-2 (SOX2) oncogene by ASA treatment. Interestingly, modulation of SOX2 expression by PGF2α agonists and upregulation by fibroblast growth factor 1 (FGF-1) rescued melanoma cells from ASA-induced decreased survival and increased apoptosis. Moreover, PGF2α-receptor antagonist, AL8810 mimics ASA-induced decreased melanoma cells survival which was significantly blocked by PGF2α and FGF-1. These findings indicate that ASA inhibits the growth of aggressive melanoma via SOX2-dependent-PAF-R-indepedent pathway.

  20. Growth-Dependent Catalase Localization in Exiguobacterium oxidotolerans T-2-2T Reflected by Catalase Activity of Cells

    Science.gov (United States)

    Hanaoka, Yoshiko; Takebe, Fumihiko; Nodasaka, Yoshinobu; Hara, Isao; Matsuyama, Hidetoshi; Yumoto, Isao

    2013-01-01

    A psychrotolerant and H2O2-resistant bacterium, Exiguobacterium oxidotolerans T-2-2T, exhibits extraordinary H2O2 resistance and produces catalase not only intracellularly but also extracellularly. The intracellular and extracellular catalases exhibited the same enzymatic characteristics, that is, they exhibited the temperature-dependent activity characteristic of a cold-adapted enzyme, their heat stabilities were similar to those of mesophilic enzymes and very high catalytic intensity. In addition, catalase gene analysis indicated that the bacterium possessed the sole clade 1 catalase gene corresponding to intracellular catalase. Hence, intracellular catalase is secreted into the extracellular space. In addition to intracellular and extracellular catalases, the inner circumference of the cells showed the localization of catalase in the mid-stationary growth phase, which was observed by immunoelectron microscopy using an antibody against the intracellular catalase of the strain. The cells demonstrated higher catalase activity in the mid-stationary growth phase than in the exponential growth phase. The catalase localized in the inner circumference can be dissociated by treatment with Tween 60. Thus, the localized catalase is not tightly bound to the inner circumference of the cells and may play a role in the oxidative defense of the cells under low metabolic state. PMID:24204687

  1. History-dependent coupled growth of creep damage under variable stress conditions

    Science.gov (United States)

    Kawai, M.

    1998-08-01

    A multiaxial constitutive model is presented for the description of the history-dependent inelastic and damage behavior of polycrystalline metallic materials in the high-temperature range under variable loading conditions. A particular emphasis is placed on a new formulation for the history-dependent material degradation which is based on a coupling between hardening and damage. The total damage is given by the sum of damage components which have different history dependence. The associated continuum damage variables are defined through their evolution equations coupled with hardening parameters involved with a kinematic hardening model. The non-classical coupling between hardening and damage is incorporated into the modified kinematic hardening model which has. been developed for describing the complicated hardening and softening behavior under repeated stress changes. Numerical simulations for different material parameters show that the proposed damage-coupled constitutive model can predict an acceleration as well as a deceleration of creep damage growth due to stress variations.

  2. Density regulation in Northeast Atlantic fish populations: Density dependence is stronger in recruitment than in somatic growth.

    Science.gov (United States)

    Zimmermann, Fabian; Ricard, Daniel; Heino, Mikko

    2018-01-30

    Population regulation is a central concept in ecology, yet in many cases its presence and the underlying mechanisms are difficult to demonstrate. The current paradigm maintains that marine fish populations are predominantly regulated by density-dependent recruitment. While it is known that density-dependent somatic growth can be present too, its general importance remains unknown and most practical applications neglect it. This study aimed to close this gap by for the first time quantifying and comparing density dependence in growth and recruitment over a large set of fish populations. We fitted density-dependent models to time-series data on population size, recruitment and age-specific weight from commercially exploited fish populations in the Northeast Atlantic Ocean and the Baltic Sea. Data were standardized to enable a direct comparison within and among populations, and estimated parameters were used to quantify the impact of density regulation on population biomass. Statistically significant density dependence in recruitment was detected in a large proportion of populations (70%), whereas for density dependence in somatic growth the prevalence of density dependence depended heavily on the method (26% and 69%). Despite age-dependent variability, the density dependence in recruitment was consistently stronger among age groups and between alternative approaches that use weight-at-age or weight increments to assess growth. Estimates of density-dependent reduction in biomass underlined these results: 97% of populations with statistically significant parameters for growth and recruitment showed a larger impact of density-dependent recruitment on population biomass. The results reaffirm the importance of density-dependent recruitment in marine fishes, yet they also show that density dependence in somatic growth is not uncommon. Furthermore, the results are important from an applied perspective because density dependence in somatic growth affects productivity and

  3. A class of vertex-edge-growth small-world network models having scale-free, self-similar and hierarchical characters

    Science.gov (United States)

    Ma, Fei; Su, Jing; Hao, Yongxing; Yao, Bing; Yan, Guanghui

    2018-02-01

    The problem of uncovering the internal operating function of network models is intriguing, demanded and attractive in researches of complex networks. Notice that, in the past two decades, a great number of artificial models are built to try to answer the above mentioned task. Based on the different growth ways, these previous models can be divided into two categories, one type, possessing the preferential attachment, follows a power-law P(k) ∼k-γ, 2 < γ < 3. The other has exponential-scaling feature, P(k) ∼α-k. However, there are no models containing above two kinds of growth ways to be presented, even the study of interconnection between these two growth manners in the same model is lacking. Hence, in this paper, we construct a class of planar and self-similar graphs motivated from a new attachment way, vertex-edge-growth network-operation, more precisely, the couple of both them. We report that this model is sparse, small world and hierarchical. And then, not only is scale-free feature in our model, but also lies the degree parameter γ(≈ 3 . 242) out the typical range. Note that, we suggest that the coexistence of multiple vertex growth ways will have a prominent effect on the power-law parameter γ, and the preferential attachment plays a dominate role on the development of networks over time. At the end of this paper, we obtain an exact analytical expression for the total number of spanning trees of models and also capture spanning trees entropy which we have compared with those of their corresponding component elements.

  4. Stocking density affects the growth performance of broilers in a sex-dependent fashion.

    Science.gov (United States)

    Zuowei, S; Yan, L; Yuan, L; Jiao, H; Song, Z; Guo, Y; Lin, H

    2011-07-01

    The effects of stocking density, sex, and dietary ME concentration on live performance, footpad burns, and leg weakness of broilers were investigated. A total of 876 male and 1,020 female 1-d-old chicks were placed in 24 pens to simulate final stocking density treatments of 26 kg (LSD; 10 males or 12 females/m(2)) and 42 kg (HSD; 16 males or 18 females/m(2)) of BW/m(2) floor space. Two series of experimental diets with a 150 kcal/kg difference in ME concentration (2,800, 2,900, and 3,000 or 2,950, 3,050, and 3,150 kcal of ME/kg) were compared in a 3-phase feeding program. The HSD treatment significantly decreased BW gain and feed conversion ratio (FCR). The HSD chickens consumed less feed by 35 d of age; thereafter, the reverse was true. Male chickens had significantly higher feed intake (FI), BW gain, and FCR compared with females. A significant interaction was found of stocking density and age for FI, BW gain, and FCR. Compared with LSD treatment, HSD broilers had a higher FI and a lower FCR from 36 to 42 d of age. Stocking density, sex, and age had a significant interaction for BW gain and FCR. Female broilers had worse BW gain and FCR when stocked at high density from 36 to 42 d of age. Stocking density had no significant influence on breast, thigh, or abdominal fat yield. Female broilers had significantly higher breast yield and abdominal fat. Male broilers and HSD treatment had high footpad burn and gait scores. A low ME diet increased footpad burn score but had no effect on gait score. The result indicated that stocking density had a more severe effect on the growth of male broilers before 35 d of age. Female broilers need more space than males at similar BW per square meter near marketing age. The incidence and severity of leg weakness are associated with sex, diet, and stocking density. This result suggests that the deteriorated effect of high stocking density is sex and age dependent.

  5. Fitness Impact of Obligate Intranuclear Bacterial Symbionts Depends on Host Growth Phase.

    Science.gov (United States)

    Bella, Chiara; Koehler, Lars; Grosser, Katrin; Berendonk, Thomas U; Petroni, Giulio; Schrallhammer, Martina

    2016-01-01

    According to text book definition, parasites reduce the fitness of their hosts whereas mutualists provide benefits. But biotic and abiotic factors influence symbiotic interactions, thus under certain circumstances parasites can provide benefits and mutualists can harm their host. Here we addressed the question which intrinsic biotic factors shape a symbiosis and are crucial for the outcome of the interaction between the obligate intranuclear bacterium Holospora caryophila ( Alphaproteobacteria; Rickettsiales ) and its unicellular eukaryotic host Paramecium biaurelia (Alveolata; Ciliophora). The virulence of H. caryophila , i.e., the negative fitness effect on host division and cell number, was determined by growth assays of several P. biaurelia strains. The performances of genetically identical lines either infected with H. caryophila or symbiont-free were compared. Following factors were considered as potentially influencing the outcome of the interaction: (1) host strain, (2) parasite strain, and (3) growth phases of the host. All three factors revealed a strong effect on the symbiosis. In presence of H. caryophila , the Paramecium density in the stationary growth phase decreased. Conversely, a positive effect of the bacteria during the exponential phase was observed for several host × parasite combinations resulting in an increased growth rate of infected P. biaurelia . Furthermore, the fitness impact of the tested endosymbionts on different P. biaurelia lines was not only dependent on one of the two involved strains but distinct for the specific combination. Depending on the current host growth phase, the presence of H. caryophila can be harmful or advantageous for P. biaurelia . Thus, under the tested experimental conditions, the symbionts can switch from the provision of benefits to the exploitation of host resources within the same host population and a time-span of less than 6 days.

  6. L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

    Directory of Open Access Journals (Sweden)

    Stephanie P Cartwright

    Full Text Available The dipeptide L-carnosine (β-alanyl-L-histidine has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose, 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol, L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

  7. StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase

    Energy Technology Data Exchange (ETDEWEB)

    Zemla, A; Lang, D; Kostova, T; Andino, R; Zhou, C

    2010-11-29

    Most of the currently used methods for protein function prediction rely on sequence-based comparisons between a query protein and those for which a functional annotation is provided. A serious limitation of sequence similarity-based approaches for identifying residue conservation among proteins is the low confidence in assigning residue-residue correspondences among proteins when the level of sequence identity between the compared proteins is poor. Multiple sequence alignment methods are more satisfactory - still, they cannot provide reliable results at low levels of sequence identity. Our goal in the current work was to develop an algorithm that could overcome these difficulties and facilitate the identification of structurally (and possibly functionally) relevant residue-residue correspondences between compared protein structures. Here we present StralSV, a new algorithm for detecting closely related structure fragments and quantifying residue frequency from tight local structure alignments. We apply StralSV in a study of the RNA-dependent RNA polymerase of poliovirus and demonstrate that the algorithm can be used to determine regions of the protein that are relatively unique or that shared structural similarity with structures that are distantly related. By quantifying residue frequencies among many residue-residue pairs extracted from local alignments, one can infer potential structural or functional importance of specific residues that are determined to be highly conserved or that deviate from a consensus. We further demonstrate that considerable detailed structural and phylogenetic information can be derived from StralSV analyses. StralSV is a new structure-based algorithm for identifying and aligning structure fragments that have similarity to a reference protein. StralSV analysis can be used to quantify residue-residue correspondences and identify residues that may be of particular structural or functional importance, as well as unusual or unexpected

  8. Density dependent growth changes through juvenile and early adult life of North East Atlantic Mackerel (Scomber scombrus)

    DEFF Research Database (Denmark)

    Jansen, Teunis; Burns, F.

    2015-01-01

    . The effect of adult density was minor, but increasing with age. The ontogenetic progression in density dependant regulation of growth appeared to reflect the spatial dynamics (migration patterns) in the feeding season. This is the first time growth patterns quantified in the adult mackerel population have......Density dependence of somatic growth has an important, but overlooked, impact on fisheries management advice. We therefore examined how growth relates to abundance in a case where growth has been observed to vary substantially in recent years, namely North East Atlantic mackerel, one of the most...... widespread and commercially important fish stocks in the North Atlantic. Growth of juvenile and early adult North East Atlantic mackerel was found to be decreasing since the late 1990s. Modelling showed that growth was related to density. Mean growth rate during the first year was tightly correlated...

  9. Minimal sulfur requirement for growth and sulfur-dependent metabolism of the hyperthermophilic archaeon Staphylothermus marinus

    Directory of Open Access Journals (Sweden)

    Xiaolei Hao

    2003-01-01

    Full Text Available Staphylothermus marinus is an anaerobic hyperthermophilic archaeon that uses peptides as carbon and energy sources. Elemental sulfur (S° is obligately required for its growth and is reduced to H2S. The metabolic functions and mechanisms of S° reduction were explored by examining S°-dependent growth and activities of key enzymes present in this organism. All three forms of S° tested—sublimed S°, colloidal S° and polysulfide—were used by S. marinus, and no other sulfur-containing compounds could replace S°. Elemental sulfur did not serve as physical support but appeared to function as an electron acceptor. The minimal S° concentration required for optimal growth was 0.05% (w/v. At this concentration, there appeared to be a metabolic transition from H2 production to S° reduction. Some enzymatic activities related to S°-dependent metabolism, including sulfur reductase, hydrogenase, glutamate dehydrogenase and electron transfer activities, were detected in cell-free extracts of S. marinus. These results indicate that S° plays an essential role in the heterotrophic metabolism of S. marinus. Reducing equivalents generated by the oxidation of amino acids from peptidolysis may be transferred to sulfur reductase and hydrogenase, which then catalyze the production of H2S and H2, respectively.

  10. A wheat SIMILAR TO RCD-ONE gene enhances seedling growth and abiotic stress resistance by modulating redox homeostasis and maintaining genomic integrity.

    Science.gov (United States)

    Liu, Shuantao; Liu, Shuwei; Wang, Mei; Wei, Tiandi; Meng, Chen; Wang, Meng; Xia, Guangmin

    2014-01-01

    Plant growth inhibition is a common response to salinity. Under saline conditions, Shanrong No. 3 (SR3), a bread wheat (Triticum aestivum) introgression line, performs better than its parent wheat variety Jinan 177 (JN177) with respect to both seedling growth and abiotic stress tolerance. Furthermore, the endogenous reactive oxygen species (ROS) was also elevated in SR3 relative to JN177. The SR3 allele of sro1, a gene encoding a poly(ADP ribose) polymerase (PARP) domain protein, was identified to be crucial for both aspects of its superior performance. Unlike RADICAL-INDUCED CELL DEATH1 and other Arabidopsis thaliana SIMILAR TO RCD-ONE (SRO) proteins, sro1 has PARP activity. Both the overexpression of Ta-sro1 in wheat and its heterologous expression in Arabidopsis promote the accumulation of ROS, mainly by enhancing the activity of NADPH oxidase and the expression of NAD(P)H dehydrogenase, in conjunction with the suppression of alternative oxidase expression. Moreover, it promotes the activity of ascorbate-GSH cycle enzymes and GSH peroxidase cycle enzymes, which regulate ROS content and cellular redox homeostasis. sro1 is also found to be involved in the maintenance of genomic integrity. We show here that the wheat SRO has PARP activity; such activity could be manipulated to improve the growth of seedlings exposed to salinity stress by modulating redox homeostasis and maintaining genomic stability.

  11. A Wheat SIMILAR TO RCD-ONE Gene Enhances Seedling Growth and Abiotic Stress Resistance by Modulating Redox Homeostasis and Maintaining Genomic Integrity[C][W

    Science.gov (United States)

    Liu, Shuantao; Liu, Shuwei; Wang, Mei; Wei, Tiandi; Meng, Chen; Wang, Meng; Xia, Guangmin

    2014-01-01

    Plant growth inhibition is a common response to salinity. Under saline conditions, Shanrong No. 3 (SR3), a bread wheat (Triticum aestivum) introgression line, performs better than its parent wheat variety Jinan 177 (JN177) with respect to both seedling growth and abiotic stress tolerance. Furthermore, the endogenous reactive oxygen species (ROS) was also elevated in SR3 relative to JN177. The SR3 allele of sro1, a gene encoding a poly(ADP ribose) polymerase (PARP) domain protein, was identified to be crucial for both aspects of its superior performance. Unlike RADICAL-INDUCED CELL DEATH1 and other Arabidopsis thaliana SIMILAR TO RCD-ONE (SRO) proteins, sro1 has PARP activity. Both the overexpression of Ta-sro1 in wheat and its heterologous expression in Arabidopsis promote the accumulation of ROS, mainly by enhancing the activity of NADPH oxidase and the expression of NAD(P)H dehydrogenase, in conjunction with the suppression of alternative oxidase expression. Moreover, it promotes the activity of ascorbate-GSH cycle enzymes and GSH peroxidase cycle enzymes, which regulate ROS content and cellular redox homeostasis. sro1 is also found to be involved in the maintenance of genomic integrity. We show here that the wheat SRO has PARP activity; such activity could be manipulated to improve the growth of seedlings exposed to salinity stress by modulating redox homeostasis and maintaining genomic stability. PMID:24443520

  12. New parametrization for the scale dependent growth function in general relativity

    International Nuclear Information System (INIS)

    Dent, James B.; Dutta, Sourish; Perivolaropoulos, Leandros

    2009-01-01

    We study the scale-dependent evolution of the growth function δ(a,k) of cosmological perturbations in dark energy models based on general relativity. This scale dependence is more prominent on cosmological scales of 100h -1 Mpc or larger. We derive a new scale-dependent parametrization which generalizes the well-known Newtonian approximation result f 0 (a)≡(dlnδ 0 /dlna)=Ω(a) γ (γ=(6/11) for ΛCDM) which is a good approximation on scales less than 50h -1 Mpc. Our generalized parametrization is of the form f(a)=(f 0 (a)/1+ξ(a,k)), where ξ(a,k)=(3H 0 2 Ω 0m )/(ak 2 ). We demonstrate that this parametrization fits the exact result of a full general relativistic evaluation of the growth function up to horizon scales for both ΛCDM and dynamical dark energy. In contrast, the scale independent parametrization does not provide a good fit on scales beyond 5% of the horizon scale (k≅0.01h -1 Mpc).

  13. Dependence of growth of the phases of multiphase binary systems on the diffusion parameters

    Science.gov (United States)

    Molokhina, L. A.; Rogalin, V. E.; Filin, S. A.; Kaplunov, I. A.

    2017-12-01

    A mathematical model of the diffusion interaction of a binary system with several phases on the equilibrium phase diagram is presented. The theoretical and calculated dependences of the layer thickness of each phase in the multiphase diffusion zone on the isothermal annealing time and the ratio of the diffusion parameters in the neighboring phases with an unlimited supply of both components were constructed. The phase formation and growth in the diffusion zone during "reactive" diffusion corresponds to the equilibrium state diagram for two components, and the order of their appearance in the diffusion zone depends only on the ratio of the diffusion parameters in the phases themselves and on the duration of the incubation periods. The dependence of phase appearance on the incubation periods, annealing time, and difference in the movement rates of the components across the interface boundaries was obtained. An example of the application of the model for processing the experimental data on phase growth in a two-component three-phase system was given.

  14. Saccharomyces cerevisiae biofilm tolerance towards systemic antifungals depends on growth phase

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2014-01-01

    used Saccharomyces cerevisiae as a model for drug susceptibility of yeast biofilms. Confocal laser scanning microscopy showed that S. cerevisiae and C. glabrata form similarly structured biofilms and that the viable cell numbers were significantly reduced by treatment of mature biofilms...... with amphotericin B but not voriconazole, flucytosine, or caspofungin. We showed that metabolic activity in yeast biofilm cells decreased with time, as visualized by FUN-1 staining, and mature, 48-hour biofilms contained cells with slow metabolism and limited growth. Time-kill studies showed that in exponentially...... growing planktonic cells, voriconazole had limited antifungal activity, flucytosine was fungistatic, caspofungin and amphotericin B were fungicidal. In growth-arrested cells, only amphotericin B had antifungal activity. Confocal microscopy and colony count viability assays revealed that the response...

  15. Metabolic efficiency in yeast Saccharomyces cerevisiae in relation to temperature dependent growth and biomass yield.

    Science.gov (United States)

    Zakhartsev, Maksim; Yang, Xuelian; Reuss, Matthias; Pörtner, Hans Otto

    2015-08-01

    Canonized view on temperature effects on growth rate of microorganisms is based on assumption of protein denaturation, which is not confirmed experimentally so far. We develop an alternative concept, which is based on view that limits of thermal tolerance are based on imbalance of cellular energy allocation. Therefore, we investigated growth suppression of yeast Saccharomyces cerevisiae in the supraoptimal temperature range (30-40°C), i.e. above optimal temperature (Topt). The maximal specific growth rate (μmax) of biomass, its concentration and yield on glucose (Yx/glc) were measured across the whole thermal window (5-40°C) of the yeast in batch anaerobic growth on glucose. Specific rate of glucose consumption, specific rate of glucose consumption for maintenance (mglc), true biomass yield on glucose (Yx/glc(true)), fractional conservation of substrate carbon in product and ATP yield on glucose (Yatp/glc) were estimated from the experimental data. There was a negative linear relationship between ATP, ADP and AMP concentrations and specific growth rate at any growth conditions, whilst the energy charge was always high (~0.83). There were two temperature regions where mglc differed 12-fold, which points to the existence of a 'low' (within 5-31°C) and a 'high' (within 33-40°C) metabolic mode regarding maintenance requirements. The rise from the low to high mode occurred at 31-32°C in step-wise manner and it was accompanied with onset of suppression of μmax. High mglc at supraoptimal temperatures indicates a significant reduction of scope for growth, due to high maintenance cost. Analysis of temperature dependencies of product formation efficiency and Yatp/glc revealed that the efficiency of energy metabolism approaches its lower limit at 26-31°C. This limit is reflected in the predetermined combination of Yx/glc(true), elemental biomass composition and degree of reduction of the growth substrate. Approaching the limit implies a reduction of the safety margin

  16. Stochastic population growth in spatially heterogeneous environments: the density-dependent case.

    Science.gov (United States)

    Hening, Alexandru; Nguyen, Dang H; Yin, George

    2018-02-01

    This work is devoted to studying the dynamics of a structured population that is subject to the combined effects of environmental stochasticity, competition for resources, spatio-temporal heterogeneity and dispersal. The population is spread throughout n patches whose population abundances are modeled as the solutions of a system of nonlinear stochastic differential equations living on [Formula: see text]. We prove that r, the stochastic growth rate of the total population in the absence of competition, determines the long-term behaviour of the population. The parameter r can be expressed as the Lyapunov exponent of an associated linearized system of stochastic differential equations. Detailed analysis shows that if [Formula: see text], the population abundances converge polynomially fast to a unique invariant probability measure on [Formula: see text], while when [Formula: see text], the population abundances of the patches converge almost surely to 0 exponentially fast. This generalizes and extends the results of Evans et al. (J Math Biol 66(3):423-476, 2013) and proves one of their conjectures. Compared to recent developments, our model incorporates very general density-dependent growth rates and competition terms. Furthermore, we prove that persistence is robust to small, possibly density dependent, perturbations of the growth rates, dispersal matrix and covariance matrix of the environmental noise. We also show that the stochastic growth rate depends continuously on the coefficients. Our work allows the environmental noise driving our system to be degenerate. This is relevant from a biological point of view since, for example, the environments of the different patches can be perfectly correlated. We show how one can adapt the nondegenerate results to the degenerate setting. As an example we fully analyze the two-patch case, [Formula: see text], and show that the stochastic growth rate is a decreasing function of the dispersion rate. In particular, coupling two

  17. Temperature-dependent templated growth of porphine thin films on the (111) facets of copper and silver

    International Nuclear Information System (INIS)

    Diller, Katharina; Klappenberger, Florian; Allegretti, Francesco; Papageorgiou, Anthoula C.; Fischer, Sybille; Duncan, David A.; Lloyd, Julian A.; Oh, Seung Cheol; Barth, Johannes V.; Maurer, Reinhard J.; Reuter, Karsten

    2014-01-01

    The templated growth of the basic porphyrin unit, free-base porphine (2H-P), is characterized by means of X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) spectroscopy measurements and density functional theory (DFT). The DFT simulations allow the deconvolution of the complex XPS and NEXAFS signatures into contributions originating from five inequivalent carbon atoms, which can be grouped into C–N and C–C bonded species. Polarization-dependent NEXAFS measurements reveal an intriguing organizational behavior: On both Cu(111) and Ag(111), for coverages up to one monolayer, the molecules adsorb undeformed and parallel to the respective metal surface. Upon increasing the coverage, however, the orientation of the molecules in the thin films depends on the growth conditions. Multilayers deposited at low temperatures exhibit a similar average tilting angle (30° relative to the surface plane) on both substrates. Conversely, for multilayers grown at room temperature a markedly different scenario exists. On Cu(111) the film thickness is self-limited to a coverage of approximately two layers, while on Ag(111) multilayers can be grown easily and, in contrast to the bulk 2H-P crystal, the molecules are oriented perpendicular to the surface. This difference in molecular orientation results in a modified line-shape of the C 1s XPS signatures, which depends on the incident photon energy and is explained by comparison with depth-resolved DFT calculations. Simulations of ionization energies for differently stacked molecules show no indication for a packing-induced modification of the multilayer XP spectra, thus indicating that the comparison of single molecule calculations to multilayer data is justified

  18. Glucagon Amyloid-like Fibril Morphology Is Selected via Morphology-Dependent Growth Inhibition

    DEFF Research Database (Denmark)

    Andersen, C.B.; Otzen, D.; Christiansen, Gunna

    2007-01-01

    Protein Structure and Biophysics, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Malov, Denmark, Centre for Insoluble Protein Structures (inSPIN), Department of Life Sciences, Aalborg University, Sohngaardsholmsvej 49, DK-9000 Aalborg, Denmark, and Institute of Medical Microbiology and Immunology...... twisted fibril seeds cannot grow at high concentrations. We conclude that there exists a morphology-dependent mechanism for inhibition of glucagon fibril growth. Light scattering experiments indicate that glucagon is mainly monomeric below 1 mg/mL and increasingly trimeric above this concentration. We...

  19. Ab initio structural modeling of and experimental validation for Chlamydia trachomatis protein CT296 reveal structural similarity to Fe(II) 2-oxoglutarate-dependent enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Kemege, Kyle E.; Hickey, John M.; Lovell, Scott; Battaile, Kevin P.; Zhang, Yang; Hefty, P. Scott (Michigan); (Kansas); (HWMRI)

    2012-02-13

    Chlamydia trachomatis is a medically important pathogen that encodes a relatively high percentage of proteins with unknown function. The three-dimensional structure of a protein can be very informative regarding the protein's functional characteristics; however, determining protein structures experimentally can be very challenging. Computational methods that model protein structures with sufficient accuracy to facilitate functional studies have had notable successes. To evaluate the accuracy and potential impact of computational protein structure modeling of hypothetical proteins encoded by Chlamydia, a successful computational method termed I-TASSER was utilized to model the three-dimensional structure of a hypothetical protein encoded by open reading frame (ORF) CT296. CT296 has been reported to exhibit functional properties of a divalent cation transcription repressor (DcrA), with similarity to the Escherichia coli iron-responsive transcriptional repressor, Fur. Unexpectedly, the I-TASSER model of CT296 exhibited no structural similarity to any DNA-interacting proteins or motifs. To validate the I-TASSER-generated model, the structure of CT296 was solved experimentally using X-ray crystallography. Impressively, the ab initio I-TASSER-generated model closely matched (2.72-{angstrom} C{alpha} root mean square deviation [RMSD]) the high-resolution (1.8-{angstrom}) crystal structure of CT296. Modeled and experimentally determined structures of CT296 share structural characteristics of non-heme Fe(II) 2-oxoglutarate-dependent enzymes, although key enzymatic residues are not conserved, suggesting a unique biochemical process is likely associated with CT296 function. Additionally, functional analyses did not support prior reports that CT296 has properties shared with divalent cation repressors such as Fur.

  20. Function Modelling Of The Market And Assessing The Degree Of Similarity Between Real Properties - Dependent Or Independent Procedures In The Process Of Office Property Valuation

    Directory of Open Access Journals (Sweden)

    Barańska Anna

    2015-09-01

    Full Text Available Referring to the developed and presented in previous publications (e.g. Barańska 2011 two-stage algorithm for real estate valuation, this article addresses the problem of the relationship between the two stages of the algorithm. An essential part of the first stage is the multi-dimensional function modelling of the real estate market. As a result of selecting the model best fitted to the market data, in which the dependent variable is always the price of a real property, a set of market attributes is obtained, which in this model are considered to be price-determining. In the second stage, from the collection of real estate which served as a database in the process of estimating model parameters, the selected objects are those which are most similar to the one subject to valuation and form the basis for predicting the final value of the property being valued. Assessing the degree of similarity between real properties can be carried out based on the full spectrum of real estate attributes that potentially affect their value and which it is possible to gather information about, or only on the basis of those attributes which were considered to be price-determining in function modelling. It can also be performed by various methods. This article has examined the effect of various approaches on the final value of the property obtained using the two-stage prediction. In order fulfill the study aim precisely as possible, the results of each calculation step of the algorithm have been investigated in detail. Each of them points to the independence of the two procedures.

  1. Experience-dependent plasticity and modulation of growth regulatory molecules at central synapses.

    Directory of Open Access Journals (Sweden)

    Simona Foscarin

    Full Text Available Structural remodeling or repair of neural circuits depends on the balance between intrinsic neuronal properties and regulatory cues present in the surrounding microenvironment. These processes are also influenced by experience, but it is still unclear how external stimuli modulate growth-regulatory mechanisms in the central nervous system. We asked whether environmental stimulation promotes neuronal plasticity by modifying the expression of growth-inhibitory molecules, specifically those of the extracellular matrix. We examined the effects of an enriched environment on neuritic remodeling and modulation of perineuronal nets in the deep cerebellar nuclei of adult mice. Perineuronal nets are meshworks of extracellular matrix that enwrap the neuronal perikaryon and restrict plasticity in the adult CNS. We found that exposure to an enriched environment induces significant morphological changes of Purkinje and precerebellar axon terminals in the cerebellar nuclei, accompanied by a conspicuous reduction of perineuronal nets. In the animals reared in an enriched environment, cerebellar nuclear neurons show decreased expression of mRNAs coding for key matrix components (as shown by real time PCR experiments, and enhanced activity of matrix degrading enzymes (matrix metalloproteinases 2 and 9, which was assessed by in situ zymography. Accordingly, we found that in mutant mice lacking a crucial perineuronal net component, cartilage link protein 1, perineuronal nets around cerebellar neurons are disrupted and plasticity of Purkinje cell terminal is enhanced. Moreover, all the effects of environmental stimulation are amplified if the afferent Purkinje axons are endowed with enhanced intrinsic growth capabilities, induced by overexpression of GAP-43. Our observations show that the maintenance and growth-inhibitory function of perineuronal nets are regulated by a dynamic interplay between pre- and postsynaptic neurons. External stimuli act on this interaction

  2. Localization and stretch-dependence of lung elastase activity in development and compensatory growth.

    Science.gov (United States)

    Young, Sarah Marie; Liu, Sheng; Joshi, Rashika; Batie, Matthew R; Kofron, Matthew; Guo, Jinbang; Woods, Jason C; Varisco, Brian Michael

    2015-04-01

    Synthesis and remodeling of the lung matrix is necessary for primary and compensatory lung growth. Because cyclic negative force is applied to developing lung tissue during the respiratory cycle, we hypothesized that stretch is a critical regulator of lung matrix remodeling. By using quantitative image analysis of whole-lung and whole-lobe elastin in situ zymography images, we demonstrated that elastase activity increased twofold during the alveolar stage of postnatal lung morphogenesis in the mouse. Remodeling was restricted to alveolar walls and ducts and was nearly absent in dense elastin band structures. In the mouse pneumonectomy model of compensatory lung growth, elastase activity increased threefold, peaking at 14 days postpneumonectomy and was higher in the accessory lobe compared with other lobes. Remodeling during normal development and during compensatory lung growth was different with increased major airway and pulmonary arterial remodeling during development but not regeneration, and with homogenous remodeling throughout the parenchyma during development, but increased remodeling only in subpleural regions during compensatory lung growth. Left lung wax plombage prevented increased lung elastin during compensatory lung growth. To test whether the adult lung retains an innate capacity to remodel elastin, we developed a confocal microscope-compatible stretching device. In ex vivo adult mouse lung sections, lung elastase activity increased exponentially with strain and in peripheral regions of lung more than in central regions. Our study demonstrates that lung elastase activity is stretch-dependent and supports a model in which externally applied forces influence the composition, structure, and function of the matrix during periods of alveolar septation. Copyright © 2015 the American Physiological Society.

  3. One sample is not enough: Differences and similarities in element concentrations of tree rings in dependence of sampling direction and height along the stem

    Science.gov (United States)

    Scharnweber, Tobias; Hevia Cabal, Andrea; van der Maaten, Ernst; Buras, Allan; Wilmking, Martin

    2015-04-01

    with a Cu X-ray beam on 1.2 mm thick wooden laths with a resolution of 50 µm, averaged within annual ring boundaries and normalized for comparison. First results point to both differences and similarities in count-rates of the analyzed elements along stem radii and stem heights. Namely, clear but non-systematic differences were observed for most elements at high frequency (interannual) resolution, whereas longer term (decadal) trends were rather similar. This holds true for nutrients, non-nutrients as well as their ratios that for example could serve as indicators for changes in soil acidity. To enhance the desired common environmental signal and to average out physiologically controlled differences in element distribution in the xylem, we propose to analyze more than one sample per tree and to develop specific chronology building procedures also in dendrochemical studies. Meeting these initial challenges promises a host of new opportunities in dendrochemistry and all its scientific and practical applications. Padilla, K.L., Anderson, K.A., 2002. Trace element concentration in tree-rings biomonitoring centuries of environmental change. Chemosphere 49, 575-585. Pearson, C.L., Dale, D.S., Brewer, P.W., Kuniholm, P.I., Lipton, J., Manning, S.W., 2009. Dendrochemical analysis of a tree-ring growth anomaly associated with the Late Bronze Age eruption of Thera. J. Archaeol. Sci. 36, 1206-1214. Watmough, S.A., 1999. Monitoring historical changes in soil and atmospheric trace metal levels by dendrochemical analysis. Environ. Pollut. 106, 391-403.

  4. Activation of a calcium-dependent protein kinase involved in the Azospirillum growth promotion in rice.

    Science.gov (United States)

    Ribaudo, Claudia M; Curá, José A; Cantore, María L

    2017-02-01

    Rice seedlings (Oryza sativa) inoculated with the plant growth-promoting rhizobacteria Azospirillum brasilense FT326 showed an enhanced development of the root system 3 days after inoculation. Later on, a remarkable enlargement of shoots was also evident. An increase in the Ca 2+ -dependent histone kinase activity was also detected as a result of inoculation. The biochemical characterization and Western-blot analysis of the kinase strongly supports the hypothesis that it belongs to a member of the rice CDPK family. The fact that the amount of the protein did not change upon inoculation seems to indicate that a posttranslational activation is responsible for the change in the enzymatic activity. An in-gel kinase experiment identified a 46 kDa CDPK like protein kinase as a putative component of the signal transduction pathway triggered by Azospirillum inoculation. To our knowledge, this is the first report on the possible involvement of a Ca 2+ -dependent protein kinase in promotion of rice plants growth by A. brasilense.

  5. APELA promotes tumour growth and cell migration in ovarian cancer in a p53-dependent manner.

    Science.gov (United States)

    Yi, Yuyin; Tsai, Shu-Huei; Cheng, Jung-Chien; Wang, Evan Y; Anglesio, Michael S; Cochrane, Dawn R; Fuller, Megan; Gibb, Ewan A; Wei, Wei; Huntsman, David G; Karsan, Aly; Hoodless, Pamela A

    2017-12-01

    APELA is a small, secreted peptide that can function as a ligand for the G-protein coupled receptor, Apelin Receptor (APLNR, APJ). APELA plays an essential role in endoderm differentiation and cardiac development during embryogenesis. We investigated whether APELA exerts any functions in cancer progression. The Cancer Genome Atlas (TCGA) RNA sequencing datasets, microarray from an OCCC mouse model, and RNA isolated from fresh frozen and FFPE patient tissue were used to assess APELA expression. APELA knockout ovarian clear cell carcinoma (OCCC) cell lines were generated using CRISPR/Cas9. APELA was expressed in various ovarian cancer histotypes and was especially elevated in OCCC. Disruption of APELA expression in OCCC cell lines suppressed cell growth and migration, and altered cell-cycle progression. Moreover, addition of human recombinant APELA peptide to the OCCC cell line OVISE promoted cell growth and migration. Interestingly, OVISE cells do not express APLNR, suggesting that APELA can function through an APLNR-independent pathway. Furthermore, APELA affected cell growth and cell cycle progression in a p53-dependent manner. In addition, APELA knockdown induced p53 expression in cancer cell lines. Our findings uncover a potential oncogenic role for APELA in promoting ovarian tumour progression and provide a possible therapeutic strategy in ovarian cancer by targeting APELA. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Substrate structure dependence of the growth modes of p-quaterphenyl thin films on gold

    International Nuclear Information System (INIS)

    Muellegger, S.; Mitsche, S.; Poelt, P.; Haenel, K.; Birkner, A.; Woell, C.; Winkler, A.

    2005-01-01

    The variably oriented crystallite surfaces of a recrystallized polycrystalline gold sample served as substrates for the investigation of the structure dependence of p-quaterphenyl (4P) thin film growth. The films were prepared in ultrahigh vacuum by organic molecular beam evaporation. Optical microscopy, scanning electron microscopy, combined with laterally resolved electron backscatter diffraction and scanning tunnelling microscopy have been applied to determine the correlation between the substrate surface structure and 4P film morphology. Crystallite surfaces consisting of (110) terraces favour highly anisotropic needle-like 4P growth with the needle orientation normal to the Au directions. Atomic steps on vicinal planes with narrow terraces (< 2 nm) can also induce anisotropy in the 4P thin film growth, in particular elongated 4P islands normal to the step direction. In contrast to that, a nearly isotropic distribution of the needle orientations is observed on Au grains terminated by highly symmetric (111) or (100) crystal planes. Additionally, patches of continuous 4P layers can be found on these surfaces. There is strong evidence that the 4P molecules within the needle-like crystallites are oriented parallel to the Au surface, whereas for the continuous layers the 4P molecules are oriented nearly upright on the surface

  7. Synthesis-condition dependence of carbon nanotube growth by alcohol catalytic chemical vapor deposition method

    Directory of Open Access Journals (Sweden)

    Nobuhito Inami et al

    2007-01-01

    Full Text Available We report the dependence of growth yield of single-walled carbon nanotubes (SWNTs on heat-treatment time and catalyst film thickness by the alcohol catalytic chemical vapor deposition method. Three types of heat-treatment, synthesis of 30 min, synthesis of 30 min after annealing of 30 min, and synthesis of 60 min, were investigated. Thickness of Co catalyst film was varied from 1 to 10 nm. In the case of thinner Co film less than 3 nm, long synthesis time of 60 min is favorable for the effective SWNT growth, because of the small amount of Co catalyst. In the case of thicker Co film more than 3 nm, an amount of grown SWNTs by 30 min synthesis after 30 min annealing and by 60 min synthesis was much higher than that by 30 min synthesis without annealing, showing that total heat-treatment time of 60 min is important for the SWNT growth. Results suggest that the conversion from the thicker film of Co to nano-particle which acts as catalyst takes place during the first 30 min.

  8. EGFR overexpressing cells and tumors are dependent on autophagy for growth and survival

    International Nuclear Information System (INIS)

    Jutten, Barry; Keulers, Tom G.; Schaaf, Marco B.E.; Savelkouls, Kim; Theys, Jan; Span, Paul N.; Vooijs, Marc A.; Bussink, Johan; Rouschop, Kasper M.A.

    2013-01-01

    Background and purpose: The epidermal growth factor receptor (EGFR) is overexpressed, amplified or mutated in various human epithelial tumors, and is associated with tumor aggressiveness and therapy resistance. Autophagy activation provides a survival advantage for cells in the tumor microenvironment. In the current study, we assessed the potential of autophagy inhibition (using chloroquine (CQ)) in treatment of EGFR expressing tumors. Material and methods: Quantitative PCR, immunohistochemistry, clonogenic survival, proliferation assays and in vivo tumor growth were used to assess this potential. Results: We show that EGFR overexpressing xenografts are sensitive to CQ treatment and are sensitized to irradiation by autophagy inhibition. In HNSSC xenografts, a correlation between EGFR and expression of the autophagy marker LC3b is observed, suggesting a role for autophagy in EGFR expressing tumors. This observation was substantiated in cell lines, showing high EGFR expressing cells to be more sensitive to CQ addition as reflected by decreased proliferation and survival. Surprisingly high EGFR expressing cells display a lower autophagic flux. Conclusions: The EGFR high expressing cells and tumors investigated in this study are highly dependent on autophagy for growth and survival. Inhibition of autophagy may therefore provide a novel treatment opportunity for EGFR overexpressing tumors

  9. The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jacques Montagne

    2010-05-01

    Full Text Available S6 kinases (S6Ks act to integrate nutrient and insulin signaling pathways and, as such, function as positive effectors in cell growth and organismal development. However, they also have been shown to play a key role in limiting insulin signaling and in mediating the autophagic response. To identify novel regulators of S6K signaling, we have used a Drosophila-based, sensitized, gain-of-function genetic screen. Unexpectedly, one of the strongest enhancers to emerge from this screen was the nuclear receptor (NR, Drosophila hormone receptor 3 (DHR3, a critical constituent in the coordination of Drosophila metamorphosis. Here we demonstrate that DHR3, through dS6K, also acts to regulate cell-autonomous growth. Moreover, we show that the ligand-binding domain (LBD of DHR3 is essential for mediating this response. Consistent with these findings, we have identified an endogenous DHR3 isoform that lacks the DBD. These results provide the first molecular link between the dS6K pathway, critical in controlling nutrient-dependent growth, and that of DHR3, a major mediator of ecdysone signaling, which, acting together, coordinate metamorphosis.

  10. Hedgehog-dependent proliferation drives modular growth during morphogenesis of a dermal bone

    Science.gov (United States)

    Huycke, Tyler R.; Eames, B. Frank; Kimmel, Charles B.

    2012-01-01

    In the developing skeleton, dermal bone morphogenesis includes the balanced proliferation, recruitment and differentiation of osteoblast precursors, yet how bones acquire unique morphologies is unknown. We show that Hedgehog (Hh) signaling mediates bone shaping during early morphogenesis of the opercle (Op), a well characterized dermal bone of the zebrafish craniofacial skeleton. ihha is specifically expressed in a local population of active osteoblasts along the principal growing edge of the bone. Mutational studies show that Hh signaling by this osteoblast population is both necessary and sufficient for full recruitment of pre-osteoblasts into the signaling population. Loss of ihha function results in locally reduced proliferation of pre-osteoblasts and consequent reductions in recruitment into the osteoblast pool, reduced bone edge length and reduced outgrowth. Conversely, hyperactive Hh signaling in ptch1 mutants causes opposite defects in proliferation and growth. Time-lapse microscopy of early Op morphogenesis using transgenically labeled osteoblasts demonstrates that ihha-dependent bone development is not only region specific, but also begins exactly at the onset of a second phase of morphogenesis, when the early bone begins to reshape into a more complex form. These features strongly support a hypothesis that dermal bone development is modular, with different gene sets functioning at specific times and locations to pattern growth. The Hh-dependent module is not limited to this second phase of bone growth: during later larval development, the Op is fused along the dysmorphic edge to adjacent dermal bones. Hence, patterning within a module may include adjacent regions of functionally related bones and might require that signaling pathways function over an extended period of development. PMID:22627283

  11. Ethylene is differentially regulated during sugar beet germination and affects early root growth in a dose-dependent manner.

    Science.gov (United States)

    Abts, Willem; Van de Poel, Bram; Vandenbussche, Bert; De Proft, Maurice P

    2014-10-01

    By integrating molecular, biochemical, and physiological data, ethylene biosynthesis in sugar beet was shown to be differentially regulated, affecting root elongation in a concentration-dependent manner. There is a close relation between ethylene production and seedling growth of sugar beet (Beta vulgaris L.), yet the exact function of ethylene during this early developmental stage is still unclear. While ethylene is mostly considered to be a root growth inhibitor, we found that external 1-aminocyclopropane-1-carboxylic acid (ACC) regulates root growth in sugar beet in a concentration-dependent manner: low concentrations stimulate root growth while high concentrations inhibit root growth. These results reveal that ethylene action during root elongation is strongly concentration dependent. Furthermore our detailed study of ethylene biosynthesis kinetics revealed a very strict gene regulation pattern of ACC synthase (ACS) and ACC oxidase (ACO), in which ACS is the rate liming step during sugar beet seedling development.

  12. Calcium-dependent protein kinases regulate polarized tip growth in pollen tubes.

    Science.gov (United States)

    Myers, Candace; Romanowsky, Shawn M; Barron, Yoshimi D; Garg, Shilpi; Azuse, Corinn L; Curran, Amy; Davis, Ryan M; Hatton, Jasmine; Harmon, Alice C; Harper, Jeffrey F

    2009-08-01

    Calcium signals are critical for the regulation of polarized growth in many eukaryotic cells, including pollen tubes and neurons. In plants, the regulatory pathways that code and decode Ca(2+) signals are poorly understood. In Arabidopsis thaliana, genetic evidence presented here indicates that pollen tube tip growth involves the redundant activity of two Ca(2+)-dependent protein kinases (CPKs), isoforms CPK17 and -34. Both isoforms appear to target to the plasma membrane, as shown by imaging of CPK17-yellow fluorescent protein (YFP) and CPK34-YFP in growing pollen tubes. Segregation analyses from two independent sets of T-DNA insertion mutants indicate that a double disruption of CPK17 and -34 results in an approximately 350-fold reduction in pollen transmission efficiency. The near sterile phenotype of homozygous double mutants could be rescued through pollen expression of a CPK34-YFP fusion. In contrast, a transgene rescue was blocked by mutations engineered to disrupt the Ca(2+)-activation mechanism of CPK34 (CPK34-YFP-E465A,E500A), providing in vivo evidence linking Ca(2+) activation to a biological function of a CPK. While double mutant pollen tubes displayed normal morphology, relative growth rates for the most rapidly growing tubes were reduced by more than three-fold compared with wild type. In addition, while most mutant tubes appeared to grow far enough to reach ovules, the vast majority (>90%) still failed to locate and fertilize ovules. Together, these results provide genetic evidence that CPKs are essential to pollen fitness, and support a mechanistic model in which CPK17 and -34 transduce Ca(2+) signals to increase the rate of pollen tube tip growth and facilitate a response to tropism cues.

  13. Characteristics of feeding tube dependency with respect to food aversive behaviour and growth.

    Science.gov (United States)

    Wilken, Markus; Bartmann, Peter; Dovey, Terence M; Bagci, Soyhan

    2018-04-01

    The use of feeding tubes in pediatric medical procedures and management has dramatically increased over the last three decades. With this increase, the prevalence of Feeding Tube Dependency (FTD) - a reliance on enteral feeding following medical recovery due to lack of oral intake of nutrition, despite being able to eat- has increased too. It has been suggested, that cases with FTD show avoidant feeding behaviours such as food refusal, gagging or swallowing resistance, but evidence for this hypothesis is scarce. In a German population of 146 cases requesting feeding tube dependency treatment between 2005 and 2008 the frequency of occurrence of avoidant behaviour in FTD cases has been evaluated and was correlated to growth. The study includes children under 50 months of age being tube fed for at least three months. Parents received the Anamnestic Questionnaire for Feeding Disorder and Tube Weaning (AFT), which evaluates nutritional supply, tube feeding, feeding disorder symptoms, medical diagnosis, growth and psychosocial variables. The study group was comprised of 101 children (50 male, 51 female), with a median age of 15 months (IQR: 10-26.5) and a median tube feeding duration of 13 months (IQR: 8-27). The most prevalent medical diagnoses were congenital malformations (n = 51) and prematurity (n = 27). Parents reported daily symptoms of food aversion through all age groups, like food refusal 2 (IQR: 1-3), gagging 1 (IQR: 0-3), vomiting 1 (0.1-2) and total symptoms 6 (5-11). Vomiting was negatively correlated with weight and length percentile and head circumference. Cases with FTD show frequent and persistent food avoidant behaviors, which may be explain the need for specific psychological treatment during transitioning from tube dependency to oral eating. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Biochar effects on soil-resident ligninolytic fungi: in vitro growth response and its pH dependence

    Science.gov (United States)

    Taskin, Eren; Loffredo, Elisabetta

    2016-04-01

    Ligninolytic fungi play an essential role on soil fertility because of their decomposing activity that allows nutrients inside biomasses to be released back into the soil. Their enzymes are able to degrade lignin which is otherwise recalcitrant to microbial and chemical degradation. Biochar (BC) has been recently proposed as a soil amendment that may contribute to climate change mitigation via carbon sequestration in soil. Pyrolysis conditions, feedstock and several other factors affect BC characteristics which in turn may influence BC impact on soil microorganisms and terrestrial ecosystems. However, limited information is available in the literature about BC's impact on ligninolytic fungi. The objective of this in vitro study was to assess the impact of BC and pH change caused by BC addition on three soil-resident ligninolytic fungi, Pleurotus ostreatus, Trametes versicolor and Bjerkandera adusta. The BC sample used in this study was obtained from 100% red spruce pellets pyrolysed at a temperature of 550 °C, and it was added to PDA medium directly as solid BC at the doses of 2 g L-1 (BC-LD) and 10 g L-1 (BC-HD). pH values were determined and the experiments were conducted either adjusting the pH of the controls either without pH adjustment. The fungi were inoculated separately in Petri dishes filled with the various media and the radial mycelial growth was measured at several sampling times. Results obtained showed a fungal growth response clearly dependent on the species and the BC dose. BC-LD stimulated the growth of P. ostreatus and T. versicolor, whereas it inhibited that of B. adusta. BC-HD stimulated the growth of P. ostreatus and inhibited that of T. versicolor and B. adusta. Similar responses were obtained with or without pH adjustment for P. ostreatus and T. versicolor, whereas a pH dependency was found for B. adusta. The effects of these and other pertinent treatments on fungal enzymes of the fungi are currently under investigation.

  15. Local environment and density-dependent feedbacks determine population growth in a forest herb

    DEFF Research Database (Denmark)

    Dahlgren, Johan Petter; Östergård, Hannah; Ehrlén, Johan

    2014-01-01

    Linking spatial variation in environmental factors to variation in demographic rates is essential for a mechanistic understanding of the dynamics of populations. However, we still know relatively little about such links, partly because feedbacks via intraspecific density make them difficult...... shade on survival and growth, while density was negatively correlated with these vital rates. Density was also negatively correlated with average individual size in the study plots, which is consistent with self-thinning. In addition, average plant sizes were larger than predicted by density in plots...... similar to those observed in the field. The results illustrate how the local environment can determine dynamics of populations and that intraspecific density may have to be more carefully considered in studies of plant demography and population viability analyses of threatened species. We conclude...

  16. Scale-dependent portfolio effects explain growth inflation and volatility reduction in landscape demography.

    Science.gov (United States)

    Hui, Cang; Fox, Gordon A; Gurevitch, Jessica

    2017-11-21

    Population demography is central to fundamental ecology and for predicting range shifts, decline of threatened species, and spread of invasive organisms. There is a mismatch between most demographic work, carried out on few populations and at local scales, and the need to predict dynamics at landscape and regional scales. Inspired by concepts from landscape ecology and Markowitz's portfolio theory, we develop a landscape portfolio platform to quantify and predict the behavior of multiple populations, scaling up the expectation and variance of the dynamics of an ensemble of populations. We illustrate this framework using a 35-y time series on gypsy moth populations. We demonstrate the demography accumulation curve in which the collective growth of the ensemble depends on the number of local populations included, highlighting a minimum but adequate number of populations for both regional-scale persistence and cross-scale inference. The attainable set of landscape portfolios further suggests tools for regional population management for both threatened and invasive species.

  17. Cosmological observables, IR growth of fluctuations, and scale-dependent anisotropies

    DEFF Research Database (Denmark)

    B. Giddings, Steven; Sloth, Martin Snoager

    2011-01-01

    We extend semiclassical methods in inflationary cosmology that capture leading IR corrections to correlators. Such large IR effects can be absorbed into a coordinate change when examining sufficiently local observables, but not when comparing observations at large separation in scales, such as seen...... by a late-time observer. The analysis is facilitated by definition of a scale-dependent metric and physical momentum. These assist definition of "IR-safe" observables seen by a post-inflationary observer, which are contrasted to those based on the local geometry of the reheating surface....... For such observables, the observer's horizon provides an effective IR cutoff. IR growth contributes to enhanced statistical inhomogeneities/anisotropies at short scales, observation of which by a present day observer might be sought in 21 cm measurements. Such IR corrections are argued to grow large for a very late...

  18. Photosynthate consumption and carbon turnover in the rhizosphere depending on plant species and growth conditions

    International Nuclear Information System (INIS)

    Sauerbeck, D.R.; Helal, H.M.; Nonnen, S.; Allard, J.-l.

    1982-01-01

    The root tissue which can be isolated from soils represents only part of the total plant carbon incorporation. Between 20 and 40% of the photosynthetic production of plants is expended for root growth and root metabolism. This indicates a striking turnover of energy in the rhizosphere, because relatively litle root-derived organic matter remains there until harvest time. Plant species and variety, soil conditions and temperature were shown to be the most decisive factors governing the assimilate consumption of plant root systems. A special technique is described which enables to study how this extensive turnover affects the surrounding soil depending on its proximity to the roots. Plant-derived carbon can be detected up to 20mm away from the roots. A priming effect has been found on the decomposition of soil organic matter. This explains why, in spite of the rhizo-deposition mentioned, no net-accumulation of carbon in the rhizosphere has been found. (Author) [pt

  19. Cysteine peptidases in the tomato trypanosomatid Phytomonas serpens: influence of growth conditions, similarities with cruzipain and secretion to the extracellular environment.

    Science.gov (United States)

    Elias, Camila G R; Pereira, Fernanda M; Dias, Felipe A; Silva, Thiago L A; Lopes, Angela H C S; d'Avila-Levy, Claudia M; Branquinha, Marta H; Santos, André L S

    2008-12-01

    We have characterized the cysteine peptidase production by Phytomonas serpens, a tomato trypanosomatid. The parasites were cultivated in four distinct media, since growth conditions could modulate the synthesis of bioactive molecules. The proteolytic profile has not changed qualitatively regardless the media, showing two peptidases of 38 and 40kDa; however, few quantitative changes were observed including a drastic reduction (around 70%) on the 40 and 38kDa peptidase activities when parasites were grown in yeast extract and liver infusion trypticase medium, respectively, in comparison with parasites cultured in Warren medium. The time-span of growth did not significantly alter the protein and peptidase expression. The proteolytic activities were blocked by classical cysteine peptidase inhibitors (E-64, leupeptin, and cystatin), being more active at pH 5.0 and showing complete dependence to reducing agents (dithiothreitol and l-cysteine) for full activity. The cysteine peptidases were able to hydrolyze several proteinaceous substrates, including salivary gland proteins from Oncopeltus fasciatus, suggesting broad substrate utilization. By means of agglutination, fluorescence microscopy, flow cytometry and Western blotting analyses we showed that both cysteine peptidases produced by P. serpens share common epitopes with cruzipain, the major cysteine peptidase of Trypanosoma cruzi. Moreover, our data suggest that the 40kDa cysteine peptidase was located at the P. serpens cell surface, attached to membrane domains via a glycosylphosphatidylinositol anchor. The 40kDa peptidase was also detected in the cell-free culture supernatant, in an active form, which suggests secretion of this peptidase to the extracellular environment.

  20. The ATPase and protease domains of yeast mitochondrial Lon : Roles in proteolysis and respiration-dependent growth

    NARCIS (Netherlands)

    van Dijl, JM; Kutejova, E; Suda, K; Perecko, D; Schatz, G; Suzuki, CK

    1998-01-01

    The ATP-dependent Lon protease of Saccharomyces cerevisiae mitochondria is required for selective proteolysis in the matrix, maintenance of mitochondrial DNA, and respiration-dependent growth. Lon may also possess a chaperone-like function that facilitates protein degradation and protein-complex

  1. Effect of Trichoderma on horticultural seedlings' growth promotion depending on inoculum and substrate type.

    Science.gov (United States)

    Marín-Guirao, J I; Rodríguez-Romera, P; Lupión-Rodríguez, B; Camacho-Ferre, F; Tello-Marquina, J C

    2016-10-01

    The biostimulant effect of Trichoderma spp. on horticultural crops are highly variable. Thus, practical use of Trichoderma sp. requires feasible formulated products and suitable substrates. This study evaluates the survival and the growth-promotion effect of a Trichoderma saturnisporum rice formulation compared with a nonformulated conidia suspension (seven treatments in total), on tomato, pepper and cucumber seedlings grown in two substrates: (i) rich in organic matter (OM) and (ii) mineral substrate without OM. The results showed beneficial effects on seedling growth in the OM-rich substrate when T. saturnisporum rice formulation (mainly at maximum concentration) was applied, but the effects were opposite when the mineral substrate without OM was used. The effects were closely linked to the level of inoculum in the substrate, which was greater upon application of the formulated inoculum as opposed to the nonformulated one. The use of rice to prepare the inoculum of T. saturnisporum seems to be promising for seedling growth in the nursery when it is applied in a substrate that is rich in organic matter, but it must be considered that under certain conditions of food shortage, Trichoderma sp. could show pathogenicity to seedlings. This study provides evidence of the complexity inherent in the use of micro-organisms in agriculture, while also confirming that the activity of the biofertilizers based on Trichoderma depends on the type of inoculum and its concentration, as well as the properties of the medium in which the fungi develop. Further studies assessing the effectiveness or possible pathogenicity of Trichoderma in different soils under greenhouse conditions must be addressed. © 2016 The Society for Applied Microbiology.

  2. Biocontrol agents promote growth of potato pathogens, depending on environmental conditions.

    Science.gov (United States)

    Cray, Jonathan A; Connor, Mairéad C; Stevenson, Andrew; Houghton, Jonathan D R; Rangel, Drauzio E N; Cooke, Louise R; Hallsworth, John E

    2016-05-01

    There is a pressing need to understand and optimize biological control so as to avoid over-reliance on the synthetic chemical pesticides that can damage environmental and human health. This study focused on interactions between a novel biocontrol-strain, Bacillus sp. JC12GB43, and potato-pathogenic Phytophthora and Fusarium species. In assays carried out in vitro and on the potato tuber, the bacterium was capable of near-complete inhibition of pathogens. This Bacillus was sufficiently xerotolerant (water activity limit for growth = 0.928) to out-perform Phytophthora infestans (~0.960) and challenge Fusarium coeruleum (~0.847) and Fusarium sambucinum (~0.860) towards the lower limits of their growth windows. Under some conditions, however, strain JC12GB43 stimulated proliferation of the pathogens: for instance, Fusarium coeruleum growth-rate was increased under chaotropic conditions in vitro (132 mM urea) by >100% and on tubers (2-M glycerol) by up to 570%. Culture-based assays involving macromolecule-stabilizing (kosmotropic) compatible solutes provided proof-of-principle that the Bacillus may provide kosmotropic metabolites to the plant pathogen under conditions that destabilize macromolecular systems of the fungal cell. Whilst unprecedented, this finding is consistent with earlier reports that fungi can utilize metabolites derived from bacterial cells. Unless the antimicrobial activities of candidate biocontrol strains are assayed over a full range of field-relevant parameters, biocontrol agents may promote plant pathogen infections and thereby reduce crop yields. These findings indicate that biocontrol activity, therefore, ought to be regarded as a mode-of-behaviour (dependent on prevailing conditions) rather than an inherent property of a bacterial strain. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  3. Basal metabolic state governs AIF-dependent growth support in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Scott, Andrew J.; Wilkinson, Amanda S.; Wilkinson, John C.

    2016-01-01

    Apoptosis-inducing factor (AIF), named for its involvement in cell death pathways, is a mitochondrial protein that regulates metabolic homeostasis. In addition to supporting the survival of healthy cells, AIF also plays a contributory role to the development of cancer through its enzymatic activity, and we have previously shown that AIF preferentially supports advanced-stage prostate cancer cells. Here we further evaluated the role of AIF in tumorigenesis by exploring its function in pancreatic cancer, a disease setting that most often presents at an advanced stage by the time of diagnosis. A bioinformatics approach was first employed to investigate AIF mRNA transcript levels in pancreatic tumor specimens vs. normal tissues. AIF-deficient pancreatic cancer cell lines were then established via lentiviral infection. Immunoblot analysis was used to determine relative protein quantities within cells. Cell viability was measured by flow cytometry; in vitro and Matrigel™ growth/survival using Coulter™ counting and phase contrast microscopy; and glucose consumption in the absence and presence of Matrigel™ using spectrophotometric methods. Archival gene expression data revealed a modest elevation of AIF transcript levels in subsets of pancreatic tumor specimens, suggesting a possible role in disease progression. AIF expression was then suppressed in a panel of five pancreatic cancer cell lines that display diverse metabolic phenotypes. AIF ablation selectively crippled the growth of cells in vitro in a manner that directly correlated with the loss of mitochondrial respiratory chain subunits and altered glucose metabolism, and these effects were exacerbated in the presence of Matrigel™ substrate. This suggests a critical metabolic role for AIF to pancreatic tumorigenesis, while the spectrum of sensitivities to AIF ablation depends on basal cellular metabolic phenotypes. Altogether these data indicate that AIF supports the growth and survival of metabolically defined

  4. Temperature dependences of growth rates and carrying capacities of marine bacteria depart from metabolic theoretical predictions

    KAUST Repository

    Huete-Stauffer, Tamara Megan

    2015-09-11

    Using the metabolic theory of ecology (MTE) framework, we evaluated over a whole annual cycle the monthly responses to temperature of the growth rates (μ) and carrying capacities (K) of heterotrophic bacterioplankton at a temperate coastal site. We used experimental incubations spanning 6oC with bacterial physiological groups identified by flow cytometry according to membrane integrity (live), nucleic acid content (HNA and LNA) and respiratory activity (CTC+). The temperature dependence of μat the exponential phase of growth was summarized by the activation energy (E), which was variable (-0.52 to 0.72 eV) but followed a seasonal pattern, only reaching the hypothesized value for aerobic heterotrophs of 0.65 eV during the spring bloom for the most active bacterial groups (live, HNA, CTC+). K (i.e. maximum experimental abundance) peaked at 4 × 106 cells mL-1 and generally covaried with μbut, contrary to MTE predictions, it did not decrease consistently with temperature. In the case of live cells, the responses of μand K to temperature were positively correlated and related to seasonal changes in substrate availability, indicating that the responses of bacteria to warming are far from homogeneous and poorly explained by MTE at our site. © FEMS 2015.

  5. Vector population growth and condition-dependent movement drive the spread of plant pathogens.

    Science.gov (United States)

    Shaw, Allison K; Peace, Angela; Power, Alison G; Bosque-Pérez, Nilsa A

    2017-08-01

    Plant viruses, often spread by arthropod vectors, impact natural and agricultural ecosystems worldwide. Intuitively, the movement behavior and life history of vectors influence pathogen spread, but the relative contribution of each factor has not been examined. Recent research has highlighted the influence of host infection status on vector behavior and life history. Here, we developed a model to explore how vector traits influence the spread of vector-borne plant viruses. We allowed vector life history (growth rate, carrying capacity) and movement behavior (departure and settlement rates) parameters to be conditional on whether the plant host is infected or healthy and whether the vector is viruliferous (carrying the virus) or not. We ran simulations under a wide range of parameter combinations and quantified the fraction of hosts infected over time. We also ran case studies of the model for Barley yellow dwarf virus, a persistently transmitted virus, and for Potato virus Y, a non-persistently transmitted virus. We quantified the relative importance of each parameter on pathogen spread using Latin hypercube sampling with the statistical partial rank correlation coefficient technique. We found two general types of mechanisms in our model that increased the rate of pathogen spread. First, increasing factors such as vector intrinsic growth rate, carrying capacity, and departure rate from hosts (independent of whether these factors were condition-dependent) led to more vectors moving between hosts, which increased pathogen spread. Second, changing condition-dependent factors such as a vector's preference for settling on a host with a different infection status than itself, and vector tendency to leave a host of the same infection status, led to increased contact between hosts and vectors with different infection statuses, which also increased pathogen spread. Overall, our findings suggest that vector population growth rates had the greatest influence on rates of virus

  6. Climate Effects on Growth, Body Condition, and Survival Depend on the Genetic Characteristics of the Population.

    Science.gov (United States)

    Romero-Diaz, Cristina; Breedveld, Merel C; Fitze, Patrick S

    2017-11-01

    Climatic change is expected to affect individual life histories and population dynamics, potentially increasing vulnerability to extinction. The importance of genetic diversity has been highlighted for adaptation and population persistence. However, whether responses of life-history traits to a given environmental condition depend on the genetic characteristics of a population remains elusive. Here we tested this hypothesis in the lizard Zootoca vivipara by simultaneously manipulating habitat humidity, a major climatic predictor of Zootoca's distribution, and adult male color morph frequency, a trait with genome-wide linkage. Interactive effects of humidity and morph frequency had immediate effects on growth and body condition of juveniles and yearlings, as well as on adult survival, and delayed effects on offspring size. In yearlings, higher humidity led to larger female body size and lower humidity led to higher male compared to female survival. In juveniles and yearlings, some treatment effects were compensated over time. The results show that individual responses to environmental conditions depend on the population's color morph frequency, age class, and sex and that these affect intra- and inter-age class competition. Moreover, humidity affected the competitive environment rather than imposing trait-based selection on specific color morphs. This indicates that species' responses to changing environments (e.g., to climate change) are highly complex and difficult to accurately reconstruct and predict without information on the genetic characteristics and demographic structure of populations.

  7. Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I

    International Nuclear Information System (INIS)

    Drago, J.; Murphy, M.; Carroll, S.M.; Harvey, R.P.; Bartlett, P.F.

    1991-01-01

    Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo

  8. Fern Stomatal Responses to ABA and CO2Depend on Species and Growth Conditions.

    Science.gov (United States)

    Hõrak, Hanna; Kollist, Hannes; Merilo, Ebe

    2017-06-01

    Changing atmospheric CO 2 levels, climate, and air humidity affect plant gas exchange that is controlled by stomata, small pores on plant leaves and stems formed by guard cells. Evolution has shaped the morphology and regulatory mechanisms governing stomatal movements to correspond to the needs of various land plant groups over the past 400 million years. Stomata close in response to the plant hormone abscisic acid (ABA), elevated CO 2 concentration, and reduced air humidity. Whether the active regulatory mechanisms that control stomatal closure in response to these stimuli are present already in mosses, the oldest plant group with stomata, or were acquired more recently in angiosperms remains controversial. It has been suggested that the stomata of the basal vascular plants, such as ferns and lycophytes, close solely hydropassively. On the other hand, active stomatal closure in response to ABA and CO 2 was found in several moss, lycophyte, and fern species. Here, we show that the stomata of two temperate fern species respond to ABA and CO 2 and that an active mechanism of stomatal regulation in response to reduced air humidity is present in some ferns. Importantly, fern stomatal responses depend on growth conditions. The data indicate that the stomatal behavior of ferns is more complex than anticipated before, and active stomatal regulation is present in some ferns and has possibly been lost in others. Further analysis that takes into account fern species, life history, evolutionary age, and growth conditions is required to gain insight into the evolution of land plant stomatal responses. © 2017 American Society of Plant Biologists. All Rights Reserved.

  9. Cryospectrophotometric determination of tumor intravascular oxyhemoglobin saturations: dependence on vascular geometry and tumor growth.

    Science.gov (United States)

    Fenton, B M; Rofstad, E K; Degner, F L; Sutherland, R M

    1988-12-21

    To delineate the complex relationships between overall tumor oxygenation and vascular configuration, intravascular oxyhemoglobin (HbO2) saturation distributions were measured with cryospectrophotometric techniques. Four factors related to vascular morphometry and tumor growth were evaluated: a) vessel diameter, b) distance of vessel from the tumor surface, c) tumor volume, and d) vascular density. To measure intertumor heterogeneity, two murine sarcomas (RIF-1 and KHT) and two human ovarian carcinoma xenografts (OWI and MLS) were utilized. In contrast to skeletal muscle, a preponderance of very low HbO2 saturations was observed for both large and small tumors of all lines. Saturations up to about 90% were also generally present, however, even in very large tumors. Variations in vascular configuration were predominantly tumor-line dependent rather than due to inherent characteristics of the host vasculature, and widely disparate HbO2 distributions were found for alternate lines implanted in identical host mice. Although peripheral saturations remained fairly constant with tumor growth, HbO2 values were markedly lower for vessels nearer the tumor center and further decreased with increasing tumor volume. HbO2 saturations did not change substantially with increasing vascular density (except for KHT tumors), although density did decrease with increasing distance from tumor surface. Combined effects of vessel diameter, tumor volume, and vessel location on HbO2 saturations were complex and varied markedly with both tumor line and vessel class. For specific classes, HbO2 distributions correlated closely with radiobiological hypoxic fractions, i.e., for tumor lines in which hypoxic fraction increased substantially with tumor volume, corresponding HbO2 values decreased, while for lines in which hypoxic fraction remained constant, HbO2 values also were unchanged. Although these trends may also be a function of differing oxygen consumption rates between tumor lines

  10. Is Growth Differentiation Factor 11 a Realistic Therapeutic for Aging-Dependent Muscle Defects?

    Science.gov (United States)

    Harper, Shavonn C; Brack, Andrew; MacDonnell, Scott; Franti, Michael; Olwin, Bradley B; Bailey, Beth A; Rudnicki, Michael A; Houser, Steven R

    2016-04-01

    This "Controversies in Cardiovascular Research" article evaluates the evidence for and against the hypothesis that the circulating blood level of growth differentiation factor 11 (GDF11) decreases in old age and that restoring normal GDF11 levels in old animals rejuvenates their skeletal muscle and reverses pathological cardiac hypertrophy and cardiac dysfunction. Studies supporting the original GDF11 hypothesis in skeletal and cardiac muscle have not been validated by several independent groups. These new studies have either found no effects of restoring normal GDF11 levels on cardiac structure and function or have shown that increasing GDF11 or its closely related family member growth differentiation factor 8 actually impairs skeletal muscle repair in old animals. One possible explanation for what seems to be mutually exclusive findings is that the original reagent used to measure GDF11 levels also detected many other molecules so that age-dependent changes in GDF11 are still not well known. The more important issue is whether increasing blood [GDF11] repairs old skeletal muscle and reverses age-related cardiac pathologies. There are substantial new and existing data showing that GDF8/11 can exacerbate rather than rejuvenate skeletal muscle injury in old animals. There is also new evidence disputing the idea that there is pathological hypertrophy in old C57bl6 mice and that GDF11 therapy can reverse cardiac pathologies. Finally, high [GDF11] causes reductions in body and heart weight in both young and old animals, suggestive of a cachexia effect. Our conclusion is that elevating blood levels of GDF11 in the aged might cause more harm than good. © 2016 American Heart Association, Inc.

  11. The Transcription Factor ABI4 Is Required for the Ascorbic Acid–Dependent Regulation of Growth and Regulation of Jasmonate-Dependent Defense Signaling Pathways in Arabidopsis[C][W

    Science.gov (United States)

    Kerchev, Pavel I.; Pellny, Till K.; Vivancos, Pedro Diaz; Kiddle, Guy; Hedden, Peter; Driscoll, Simon; Vanacker, Hélène; Verrier, Paul; Hancock, Robert D.; Foyer, Christine H.

    2011-01-01

    Cellular redox homeostasis is a hub for signal integration. Interactions between redox metabolism and the ABSCISIC ACID-INSENSITIVE-4 (ABI4) transcription factor were characterized in the Arabidopsis thaliana vitamin c defective1 (vtc1) and vtc2 mutants, which are defective in ascorbic acid synthesis and show a slow growth phenotype together with enhanced abscisic acid (ABA) levels relative to the wild type (Columbia-0). The 75% decrease in the leaf ascorbate pool in the vtc2 mutants was not sufficient to adversely affect GA metabolism. The transcriptome signatures of the abi4, vtc1, and vtc2 mutants showed significant overlap, with a large number of transcription factors or signaling components similarly repressed or induced. Moreover, lincomycin-dependent changes in LIGHT HARVESTING CHLOROPHYLL A/B BINDING PROTEIN 1.1 expression were comparable in these mutants, suggesting overlapping participation in chloroplast to nucleus signaling. The slow growth phenotype of vtc2 was absent in the abi4 vtc2 double mutant, as was the sugar-insensitive phenotype of the abi4 mutant. Octadecanoid derivative-responsive AP2/ERF-domain transcription factor 47 (ORA47) and AP3 (an ABI5 binding factor) transcripts were enhanced in vtc2 but repressed in abi4 vtc2, suggesting that ABI4 and ascorbate modulate growth and defense gene expression through jasmonate signaling. We conclude that low ascorbate triggers ABA- and jasmonate-dependent signaling pathways that together regulate growth through ABI4. Moreover, cellular redox homeostasis exerts a strong influence on sugar-dependent growth regulation. PMID:21926335

  12. Local environment and density-dependent feedbacks determine population growth in a forest herb.

    Science.gov (United States)

    Dahlgren, Johan P; Ostergård, Hannah; Ehrlén, Johan

    2014-12-01

    Linking spatial variation in environmental factors to variation in demographic rates is essential for a mechanistic understanding of the dynamics of populations. However, we still know relatively little about such links, partly because feedbacks via intraspecific density make them difficult to observe in natural populations. We conducted a detailed field study and investigated simultaneous effects of environmental factors and the intraspecific density of individuals on the demography of the herb Lathyrus vernus. In regression models of vital rates we identified effects associated with spring shade on survival and growth, while density was negatively correlated with these vital rates. Density was also negatively correlated with average individual size in the study plots, which is consistent with self-thinning. In addition, average plant sizes were larger than predicted by density in plots that were less shaded by the tree canopy, indicating an environmentally determined carrying capacity. A size-structured integral projection model based on the vital rate regressions revealed that the identified effects of shade and density were strong enough to produce differences in stable population sizes similar to those observed in the field. The results illustrate how the local environment can determine dynamics of populations and that intraspecific density may have to be more carefully considered in studies of plant demography and population viability analyses of threatened species. We conclude that demographic approaches incorporating information about both density and key environmental factors are powerful tools for understanding the processes that interact to determine population dynamics and abundances.

  13. Composition and growth procedure-dependent properties of electrodeposited CuInSe 2 thin films

    Science.gov (United States)

    Babu, S. Moorthy; Ennaoui, A.; Lux-Steiner, M. Ch.

    2005-02-01

    CuInSe 2 thin films were deposited on molybdenum-coated glass substrates by electrodeposition. Deposition was carried out with a variety of electrochemical bath compositions. The quality of the deposits depends very much on the source materials as well as the concentration of the same in the electrolyte. The deposition potential was varied from -0.4 to -0.75 V vs. SCE. The pH of the solution was adjusted to 1.5-2 using diluted sulphuric acid. Chloride salts containing bath yield good surface morphology, but there is always excess of the metallic content in the deposited films. Different growth procedures, like initial metallic layers of copper or indium, layers of copper selenide or indium selenide before the actual deposition of ternary chalcopyrite layers were attempted. Fabrication pathway, morphological and compositional changes due to the different precursor route has been analysed. The quality of the deposits prepared by one-step electrodeposition is better than the deposits with a two-stage process. The deposited films were characterized with XRD, SEM-EDAX, UV-visible spectroscopy and I- V characteristics. The deposited films were annealed in air as well as in nitrogen atmosphere. The influence of annealing temperature, environment and annealing time on the properties of the films are evaluated. Attempts were made to fabricate solar cell structure from the deposited absorber films. The structure of Mo/CuInSe 2/CdS/ZnO/Ni was characterized with surface, optical and electrical studies.

  14. Frank-ter Haar syndrome protein Tks4 regulates epidermal growth factor-dependent cell migration.

    Science.gov (United States)

    Bögel, Gábor; Gujdár, Annamária; Geiszt, Miklós; Lányi, Árpád; Fekete, Anna; Sipeki, Szabolcs; Downward, Julian; Buday, László

    2012-09-07

    Mutations in the SH3PXD2B gene coding for the Tks4 protein are responsible for the autosomal recessive Frank-ter Haar syndrome. Tks4, a substrate of Src tyrosine kinase, is implicated in the regulation of podosome formation. Here, we report a novel role for Tks4 in the EGF signaling pathway. In EGF-treated cells, Tks4 is tyrosine-phosphorylated and associated with the activated EGF receptor. This association is not direct but requires the presence of Src tyrosine kinase. In addition, treatment of cells with LY294002, an inhibitor of PI 3-kinase, or mutations of the PX domain reduces tyrosine phosphorylation and membrane translocation of Tks4. Furthermore, a PX domain mutant (R43W) Tks4 carrying a reported point mutation in a Frank-ter Haar syndrome patient showed aberrant intracellular expression and reduced phosphoinositide binding. Finally, silencing of Tks4 was shown to markedly inhibit HeLa cell migration in a Boyden chamber assay in response to EGF or serum. Our results therefore reveal a new function for Tks4 in the regulation of growth factor-dependent cell migration.

  15. Growth hormone activity in mitochondria depends on GH receptor Box 1 and involves caveolar pathway targeting

    International Nuclear Information System (INIS)

    Perret-Vivancos, Cecile; Abbate, Aude; Ardail, Dominique; Raccurt, Mireille; Usson, Yves; Lobie, Peter E.; Morel, Gerard

    2006-01-01

    Growth hormone (GH) binding to its receptor (GHR) initiates GH-dependent signal transduction and internalization pathways to generate the biological effects. The precise role and way of action of GH on mitochondrial function are not yet fully understood. We show here that GH can stimulate cellular oxygen consumption in CHO cells transfected with cDNA coding for the full-length GHR. By using different GHR cDNA constructs, we succeeded in determining the different parts of the GHR implicated in the mitochondrial response to GH. Polarography and two-photon excitation fluorescence microscopy analysis showed that the Box 1 of the GHR intracellular domain was required for an activation of the mitochondrial respiration in response to a GH exposure. However, confocal laser scanning microscopy demonstrated that cells lacking the GHR Box 1 could efficiently internalize the hormone. We demonstrated that internalization mediated either by clathrin-coated pits or by caveolae was able to regulate GH mitochondrial effect: these two pathways are both essential to obtain the GH stimulatory action on mitochondrial function. Moreover, electron microscopic and biochemical approaches allowed us to identify the caveolar pathway as essential for targeting GH and GHR to mitochondria

  16. Dependence on the growth direction of the strain in AlGaSb alloys

    Energy Technology Data Exchange (ETDEWEB)

    Rojas-Lopez, M; Delgado-Macuil, R; Gayou, V L; Orduna-Diaz, A [CIBA-Tlaxcala, IPN, Tlaxcala, Tlax. (Mexico); Momox-Beristain, E [FC-BUAP, Puebla, Pue. (Mexico); Salazar-Hernandez, B [CIICAp-UAEM, Cuernavaca, Mor. (Mexico); Rodriguez, A G, E-mail: marlonrl@yahoo.com.m [IICO-UASLP, San Luis Potosi, S.L.P. (Mexico)

    2009-05-01

    High resolution x-ray diffraction profiles were obtained from Al{sub x}Ga{sub 1-x}Sb layers grown on (001) and (111) GaSb substrates. The out of plane lattice parameter, was estimated directly from the symmetrical diffractions for (001) and (111) alloys. These results show that all the layers are strained, and those grown on (001) GaSb are slightly more strained than the corresponding layers grown on (111) GaSb. This difference is explained by the dependence of the strain ratio on growth direction. The out of plane lattice parameter as a function of Al content is higher than the corresponding bulk lattice parameter of Al{sub x}Ga{sub 1-x}Sb layers obtained with Vegard's law. Also, the perpendicular and the in-plane lattice parameter expected for pseudomorphic alloys, was estimated from the strain ratios, assuming an elastic deformation and using the EDX alloy composition to interpolate the elastic constants C{sub ij}. This estimation also shows that almost all the layers are fully strained.

  17. Substrate-orientation dependent epitaxial growth of highly ordered diamond nanosheet arrays by chemical vapor deposition.

    Science.gov (United States)

    Wang, Shuguang; Ji, Xixi; Ao, Yu; Yu, Jie

    2018-02-08

    Three-dimensional ordering of two-dimensional nanomaterials has long been a challenge. Simultaneously, diamond nanomaterials are difficult to synthesize due to the harsh synthesizing conditions required. Here, we report substrate-crystal-orientation dependent growth of diamond nanosheets (DNSs) by chemical vapor deposition, which generates different DNS arrays on different substrates. The DNSs are grown by the in-plane epitaxy of the diamond {111} planes. So the arrays are highly ordered and solely determined by the spatial orientation of the {111} planes in the diamond FCC structure. The DNSs grown on the {110}, {111}, {001}, and {113} oriented substrates show inclination angles ranging from 90 to 29.5°. The DNSs with larger inclination angles grow preferentially, forming parallelogram arrays with inclination angles of 90° on the {110} substrates and parallel-line arrays with inclination angles of 80° on the {113} substrates. The density, thickness, size, and morphology of the DNSs have been well controlled. The present understanding and materials are highly promising for many applications such as sensors, catalysis, photonics, thermal management, and electronics.

  18. Time dependent effects of two absorption enhancers on the nasal absorption of growth hormone in rabbits

    DEFF Research Database (Denmark)

    Vermehren, Charlotte; Hansen, H.S.; Thomsen, M.K.

    1996-01-01

    Enhancer-based drug preparations allow absorption of peptid drugs. We investigated the reversibility with time of nasal absorption of human growth hormone (hGH) induced by the absorption enhancers didecanoylhposphatidylcholine (DDPC) and Ó-cyclodextrin (Ó-CD). Rabbits were dosed intranasally...... with enhancer in the absence of hGH at time -3, -1, -0.5 and 0 h. At time zero the same groups of rabbits were dosed with a hGH powder devoid of the enhancers. Values for plasma hGH AUC and Cmax were estimated in order to measure the degree of absorption, and rabbits receiving hGH together with enhancers were...... used as positive references. With an enhancer preparation of 8% DDPC and 30% Ó-CD, the hGH AUC and Cmax values showed a significant time-dependent decrease after enhancer administration. This may indicate recovery of the enhancer-induced mucosal leakiness as well as clearance of the enhancers from...

  19. Time dependent effects of two absorption enhancers on the nasal absorption of growth hormone in rabbits

    DEFF Research Database (Denmark)

    Vermehren, C.; Hansen, Harald S.; Thomsen, M.K.

    1996-01-01

    Enhancer-based drug preparations allow absorption of peptide drugs. We investigated the reversibility with time of nasal absorption of human growth hormone (hGH) induced by the absorption enhancers didecanoylphosphatidylcholine (DDPC) and a-cyclodextrin (a-CD). Rabbits were dosed intranasally...... with enhancer in the absence of hGH at time -3, -1, -0.5 and 0 h. At time zero the same groups of rabbits were dosed with a hGH powder devoid of the enhancers. Values for plasma hGH AUC and C(max) were estimated in order to measure the degree of absorption, and rabbits receiving hGH together with enhancers were...... used as positive references. With an enhancer preparation of 8% DDPC and 30% a-CD, the hGH AUC and C(max) values showed a significant time-dependent decrease after enhancer administration. This may indicate recovery of the enhancer-induced mucosal leakiness as well as clearance of the enhancers from...

  20. Effect of Microstructure on Time Dependent Fatigue Crack Growth Behavior In a P/M Turbine Disk Alloy

    Science.gov (United States)

    Telesman, Ignacy J.; Gabb, T. P.; Bonacuse, P.; Gayda, J.

    2008-01-01

    A study was conducted to determine the processes which govern hold time crack growth behavior in the LSHR disk P/M superalloy. Nineteen different heat treatments of this alloy were evaluated by systematically controlling the cooling rate from the supersolvus solutioning step and applying various single and double step aging treatments. The resulting hold time crack growth rates varied by more than two orders of magnitude. It was shown that the associated stress relaxation behavior for these heat treatments was closely correlated with the crack growth behavior. As stress relaxation increased, the hold time crack growth resistance was also increased. The size of the tertiary gamma' in the general microstructure was found to be the key microstructural variable controlling both the hold time crack growth behavior and stress relaxation. No relationship between the presence of grain boundary M23C6 carbides and hold time crack growth was identified which further brings into question the importance of the grain boundary phases in determining hold time crack growth behavior. The linear elastic fracture mechanics parameter, Kmax, is unable to account for visco-plastic redistribution of the crack tip stress field during hold times and thus is inadequate for correlating time dependent crack growth data. A novel methodology was developed which captures the intrinsic crack driving force and was able to collapse hold time crack growth data onto a single curve.

  1. Growth hormone-dependent phosphorylation of tyrosine 333 and/or 338 of the growth hormone receptor

    DEFF Research Database (Denmark)

    VanderKuur, J A; Wang, X; Zhang, L

    1995-01-01

    Many signaling pathways initiated by ligands that activate receptor tyrosine kinases have been shown to involve the binding of SH2 domain-containing proteins to specific phosphorylated tyrosines in the receptor. Although the receptor for growth hormone (GH) does not contain intrinsic tyrosine...

  2. A PKC-dependent recruitment of MMP-2 controls semaphorin-3A growth-promoting effect in cortical dendrites.

    Directory of Open Access Journals (Sweden)

    Bertrand Gonthier

    Full Text Available There is increasing evidence for a crucial role of proteases and metalloproteinases during axon growth and guidance. In this context, we recently described a functional link between the chemoattractive Sema3C and Matrix metalloproteinase 3 (MMP3. Here, we provide data demonstrating the involvement of MMP-2 to trigger the growth-promoting effect of Sema3A in cortical dendrites. The in situ analysis of MMP-2 expression and activity is consistent with a functional growth assay demonstrating in vitro that the pharmacological inhibition of MMP-2 reduces the growth of cortical dendrites in response to Sema3A. Hence, our results suggest that the selective recruitment and activation of MMP-2 in response to Sema3A requires a PKC alpha dependent mechanism. Altogether, we provide a second set of data supporting MMPs as effectors of the growth-promoting effects of semaphorins, and we identify the potential signalling pathway involved.

  3. Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain.

    Science.gov (United States)

    Lundberg, Elena; Kriström, Berit; Jonsson, Bjorn; Albertsson-Wikland, Kerstin

    2015-12-18

    Responsiveness to GH treatment can be estimated by both growth and ∆IGF-I. The primary aim of the present study was to investigate if mimicking the physiological increase during puberty in GH secretion, by using a higher GH dose could lead to pubertal IGFs in short children with low GH secretion. The secondary aim was to explore the relationship between IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio and gain in height. A multicentre, randomized, clinical trial (TRN88-177) in 104 children (90 boys), who had received GH 33 μg/kg/day during at least 1 prepubertal year. They were followed from GH start to adult height (mean, 7.5 years; range, 4.6-10.7). At onset of puberty, children were randomized into three groups, to receive 67 μg/kg/day (GH(67)) given once (GH(67x1); n = 30) or divided into two daily injection (GH(33x2); n = 36), or to remain on a single 33 μg/kg/day dose (GH(33x1); n = 38). The outcome measures were change and obtained mean on-treatment IGF-I(SDS), IGFBP3(SDS) and IGF-I/IGFBP3 ratio(SDS) during prepuberty and puberty. These variables were assessed in relation to prepubertal, pubertal and total gain in heightSDS. Mean prepubertal increases 1 year after GH start were: 2.1 IGF-I(SDS), 0.6 IGFBP3(SDS) and 1.5 IGF-I/IGFBP3ratio(SDS). A significant positive correlation was found between prepubertal ∆IGFs and both prepubertal and total gain in height(SDS). During puberty changes in IGFs were GH dose-dependent: mean pubertal level of IGF-I(SDS) was higher in GH(67) vs GH(33) (p = 0.031). First year pubertal ∆IGF-I(SDS) was significantly higher in the GH(67)vs GH(33) group (0.5 vs -0.1, respectively, p = 0.007), as well as ∆IGF-I(SDS) to the pubertal mean level (0.2 vs -0.2, p = 0.028). In multivariate analyses, the prepubertal increase in '∆IGF-I(SDS) from GH start' and the 'GH dose-dependent pubertal ∆IGF-I(SDS)' were the most important variables for explaining variation in prepubertal (21 %), pubertal (26 %) and total

  4. Growth factor-induced contraction of human bronchial smooth muscle is Rho-kinase-dependent

    NARCIS (Netherlands)

    Gosens, Reinout; Schaafsma, D.; Grootte Bromhaar, M.M; Vrugt, B.; Zaagsma, Hans; Meurs, Herman; Nelemans, Herman

    2004-01-01

    Growth factors have been implicated in the pathophysiology of asthma. However, the putative effects of these growth factors on human airway smooth muscle tone are still largely unknown. We performed contraction experiments using human bronchial smooth muscle ring preparations. The growth factor

  5. Calorie restriction decreases murine and human pancreatic tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression in an insulin-like growth factor-1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Alison E Harvey

    Full Text Available Calorie restriction (CR prevents obesity and has potent anticancer effects that may be mediated through its ability to reduce serum growth and inflammatory factors, particularly insulin-like growth factor (IGF-1 and protumorigenic cytokines. IGF-1 is a nutrient-responsive growth factor that activates the inflammatory regulator nuclear factor (NF-κB, which is linked to many types of cancers, including pancreatic cancer. We hypothesized that CR would inhibit pancreatic tumor growth through modulation of IGF-1-stimulated NF-κB activation and protumorigenic gene expression. To test this, 30 male C57BL/6 mice were randomized to either a control diet consumed ad libitum or a 30% CR diet administered in daily aliquots for 21 weeks, then were subcutaneously injected with syngeneic mouse pancreatic cancer cells (Panc02 and tumor growth was monitored for 5 weeks. Relative to controls, CR mice weighed less and had decreased serum IGF-1 levels and smaller tumors. Also, CR tumors demonstrated a 70% decrease in the expression of genes encoding the pro-inflammatory factors S100a9 and F4/80, and a 56% decrease in the macrophage chemoattractant, Ccl2. Similar CR effects on tumor growth and NF-κB-related gene expression were observed in a separate study of transplanted MiaPaCa-2 human pancreatic tumor cell growth in nude mice. In vitro analyses in Panc02 cells showed that IGF-1 treatment promoted NF-κB nuclear localization, increased DNA-binding of p65 and transcriptional activation, and increased expression of NF-κB downstream genes. Finally, the IGF-1-induced increase in expression of genes downstream of NF-κB (Ccdn1, Vegf, Birc5, and Ptgs2 was decreased significantly in the context of silenced p65. These findings suggest that the inhibitory effects of CR on Panc02 pancreatic tumor growth are associated with reduced IGF-1-dependent NF-κB activation.

  6. Characterization of Alternaria and Penicillium species from similar substrata based on growth at different temperature, pH and water activity

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Frisvad, Jens Christian

    2002-01-01

    Fifty-eight Alternaria isolates representing 10 species or species-groups and 66 Penicillium isolates representing 18 species were examined for their growth response to the combined effects of water activity, temperature and pH in an extended Central Composite Design. Growth responses were recorded...

  7. The ATPase and protease domains of yeast mitochondrial Lon: Roles in proteolysis and respiration-dependent growth

    OpenAIRE

    van Dijl, Jan Maarten; Kutejová, Eva; Suda, Kitaru; Perečko, Dušan; Schatz, Gottfried; Suzuki, Carolyn K.

    1998-01-01

    The ATP-dependent Lon protease of Saccharomyces cerevisiae mitochondria is required for selective proteolysis in the matrix, maintenance of mitochondrial DNA, and respiration-dependent growth. Lon may also possess a chaperone-like function that facilitates protein degradation and protein-complex assembly. To understand the influence of Lon’s ATPase and protease activities on these functions, we examined several Lon mutants for their ability to complement defects of Lon-deleted yeast cells. We...

  8. Skeletal development in Acropora palmata (Lamarck 1816): a scanning electron microscope (SEM) comparison demonstrating similar mechanisms of skeletal extension in axial versus encrusting growth

    Science.gov (United States)

    Gladfelter, E. H.

    2007-12-01

    Many Acropora palmata colonies consist of an encrusting basal portion and erect branches. Linear growth of the skeleton results in extension along the substrate (encrusting growth), lengthening of branches (axial growth) and thickening of branches and crust (radial growth). Scanning Electron Microscopy is used to compare the mechanisms of skeletal extension between encrusting growth and axial growth. In encrusting growth, the distal margin of the skeleton lacks corallites (which develop about 1 mm from the edge); in contrast, in axial growth, axial corallites along the branch tip form the distal portion of the skeleton. In both locations, the distal margin of the skeleton consists of a lattice-like structure composed of rods that extend from the body of the skeleton and bars that connect these rods. An actively extending skeleton is characterized by sharply pointed rods and partially developed bars. Distal growth of rods (and formation of bars) is effected by the formation of new sclerodermites. Each sclerodermite begins with the deposition of fusiform crystals (that range in length from 1 to 5 μm). These provide a surface for nucleation and growth of spherulitic tufts, clusters of short (<1 μm long) aragonite needles. The needles that are oriented perpendicular to the axis of the skeletal element (rod or bar), and perpendicular to the overlying calicoblastic epithelium, continue extension to appear on the surface of the skeleton as 10-15 μm wide bundles (of needle tips) called fasciculi. However, some crusts that abut competitors for space have a different morphology of skeletal elements (rods and bars). The distal edge of these crusts terminates in blunt coalescing rods, and bars that are fully formed. Absence of fusiform crystals, lack of sharply pointed rods and bars, and full development of sclerodermites characterize a skeletal region that has ceased, perhaps only temporarily, skeletal extension.

  9. Lack of Radiation Dose or Quality Dependence of Epithelial-to-Mesenchymal Transition (EMT) Mediated by Transforming Growth Factor β

    International Nuclear Information System (INIS)

    Andarawewa, Kumari L.; Costes, Sylvain V.; Fernandez-Garcia, Ignacio; Chou, William S.; Ravani, Shraddha A.; Park, Howard; Barcellos-Hoff, Mary Helen

    2011-01-01

    Purpose: Epithelial-to-mesenchymal transition (EMT) is a phenotype that alters cell morphology, disrupts morphogenesis, and increases motility. Our prior studies have shown that the progeny of human mammary epithelial cells (HMECs) irradiated with 2 Gy undergoes transforming growth factor β (TGF-β)-mediated EMT. In this study we determined whether radiation dose or quality affected TGF-β-mediated EMT. Methods and Materials: HMECs were cultured on tissue culture plastic or in Matrigel (BD Biosciences, San Jose, CA) and exposed to low or high linear energy transfer (LET) and TGF-β (400 pg/mL). Image analysis was used to measure membrane-associated E-cadherin, a marker of functional epithelia, or fibronectin, a product of mesenchymal cells, as a function of radiation dose and quality. Results: E-cadherin was reduced in TGF-β-treated cells irradiated with low-LET radiation doses between 0.03 and 2 Gy compared with untreated, unirradiated cells or TGF-β treatment alone. The radiation quality dependence of TGF-β-mediated EMT was determined by use of 1 GeV/amu (gigaelectron volt / atomic mass unit) 56 Fe ion particles at the National Aeronautics and Space Administration's Space Radiation Laboratory. On the basis of the relative biological effectiveness of 2 for 56 Fe ion particles' clonogenic survival, TGF-β-treated HMECs were irradiated with equitoxic 1-Gy 56 Fe ion or 2-Gy 137 Cs radiation in monolayer. Furthermore, TGF-β-treated HMECs irradiated with either high- or low-LET radiation exhibited similar loss of E-cadherin and gain of fibronectin and resulted in similar large, poorly organized colonies when embedded in Matrigel. Moreover, the progeny of HMECs exposed to different fluences of 56 Fe ion underwent TGF-β-mediated EMT even when only one-third of the cells were directly traversed by the particle. Conclusions: Thus TGF-β-mediated EMT, like other non-targeted radiation effects, is neither radiation dose nor quality dependent at the doses examined.

  10. Dependence of photosynthesis and energy dissipation activity upon growth form and light environment during the winter.

    Science.gov (United States)

    Adams, W W; Demmig-Adams, B; Rosenstiel, T N; Ebbert, V

    2001-01-01

    Two very distinctive responses of photosynthesis to winter conditions have been identified. Mesophytic species that continue to exhibit growth during the winter typically exhibit higher maximal rates of photosynthesis during the winter or when grown at lower temperatures compared to individuals examined during the summer or when grown at warmer temperatures. In contrast, sclerophytic evergreen species growing in sun-exposed sites typically exhibit lower maximal rates of photosynthesis in the winter compared to the summer. On the other hand, shaded individuals of those same sclerophytic evergreen species exhibit similar or higher maximal rates of photosynthesis in the winter compared to the summer. Employment of the xanthophyll cycle in photoprotective energy dissipation exhibits similar characteristics in the two groups of plants (mesophytes and shade leaves of sclerophytic evergreens) that exhibit upregulation of photosynthesis during the winter. In both, zeaxanthin + antheraxanthin (Z + A) are retained and PS II remains primed for energy dissipation only on nights with subfreezing temperatures, and this becomes rapidly reversed upon exposure to increased temperatures. In contrast, Z + A are retained and PS II remains primed for energy dissipation over prolonged periods during the winter in sun leaves of sclerophytic evergreen species, and requires days of warming to become fully reversed. The rapid disengagement of this energy dissipation process in the mesophytes and shade sclerophytes apparently permits a rapid return to efficient photosynthesis and increased activity on warmer days during the winter. This may be associated with a decreasing opportunity for photosynthesis in source leaves relative to the demand for photosynthesis in the plant's sinks. In contrast, the sun-exposed sclerophytes - with a relatively high source to sink ratio - maintain PS II in a state primed for high levels of energy dissipation activity throughout much of the winter. Independent

  11. Temperature dependence of the minimum V/III ratio for the growth of In[sub x]Ga[sub 1-x]As

    Energy Technology Data Exchange (ETDEWEB)

    Riechert, H. (Siemens Corporate Research and Development, Muenchen (Germany)); Averbeck, R. (Siemens Corporate Research and Development, Muenchen (Germany)); Bernklau, D. (Siemens Corporate Research and Development, Muenchen (Germany))

    1993-02-01

    We have quantitatively determined the minimum V/III ratios for the growth of In[sub x]Ga[sub 1-x]As(x=0, 0.1, 0.2 and 0.53) on GaAs and InP. Minimum As[sub 4] fluxes were measured for a wide range of growth temperatures using a transition of the surface reconstruction. Their temperature dependence can be fitted very well by the typical curve for thermally activated behavior. We find In[sub x]Ga[sub 1-x]As and GaAs are found to be similar (1.9 and 2.1 eV, respectively) but the rates of As-desorption are much higher for In[sub x]Ga[sub 1-x]As. This may be seen as evidence for a less effective dissociative reaction of As[sub 4] with In than with Ga. (orig.)

  12. Antimicrobial Effect of 15 Medicinal Plant Species and their Dependency on Climatic Conditions of Growth in Different Geographical and Ecological Areas of Fars Province

    Directory of Open Access Journals (Sweden)

    Abbas Abdollahi

    2012-05-01

    Full Text Available Background: The effects of medicinal plants are variable in different conditions. Here, the antimicrobial effect of 15 medicinal plant species and their dependency on the climatic condition of growth in different geographical and ecological areas of Fars Province were studied. Materials and Methods: In This empirical study, the antimicrobial effect of hydro-alcoholic extract of 15 medicinal plant species was examined against standard bacterial strains comparing to conventional therapeutic antibiotics using disk diffusion assay and serial broth dilution. Results: All Extracts were effective against S.aureus ATCC 25923 growth; also Peganum harmala, Myrtus communis, Mentha pulegium, Mentha spp, and Zataria multiflora extracts were observed to have antimicrobial activity against E.coli ATCC 25922. This antimicrobial activity had partially similar results, comparing to conventional antibioticsConclusion: Medicinal plants produce various amounts of antimicrobial substances under the climatic and ecological conditions of each zone, which must be considered in manufacturing herbal medicines.

  13. Nicotine stimulates nerve growth factor in lung fibroblasts through an NFκB-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Cherry Wongtrakool

    Full Text Available Airway hyperresponsiveness (AHR is classically found in asthma, and persistent AHR is associated with poor asthma control. Although airway smooth muscle (ASM cells play a critical pathophysiologic role in AHR, the paracrine contributions of surrounding cells such as fibroblasts to the contractile phenotype of ASM cells have not been examined fully. This study addresses the hypothesis that nicotine promotes a contractile ASM cell phenotype by stimulating fibroblasts to increase nerve growth factor (NGF secretion into the environment.Primary lung fibroblasts isolated from wild type and α7 nicotinic acetylcholine receptor (α7 nAChR deficient mice were treated with nicotine (50 µg/ml in vitro for 72 hours. NGF levels were measured in culture media and in bronchoalveolar lavage (BAL fluid from asthmatic, smoking and non-smoking subjects by ELISA. The role of the NFκB pathway in nicotine-induced NGF expression was investigated by measuring NFκB nuclear translocation, transcriptional activity, chromatin immunoprecipitation assays, and si-p65 NFκB knockdown. The ability of nicotine to stimulate a fibroblast-mediated, contractile ASM cell phenotype was confirmed by examining expression of contractile proteins in ASM cells cultured with fibroblast-conditioned media or BAL fluid.NGF levels were elevated in the bronchoalveolar lavage fluid of nicotine-exposed mice, current smokers, and asthmatic children. Nicotine increased NGF secretion in lung fibroblasts in vitro in a dose-dependent manner and stimulated NFκB nuclear translocation, p65 binding to the NGF promoter, and NFκB transcriptional activity. These responses were attenuated in α7 nAChR deficient fibroblasts and in wild type fibroblasts following NFκB inhibition. Nicotine-treated, fibroblast-conditioned media increased expression of contractile proteins in ASM cells.Nicotine stimulates NGF release by lung fibroblasts through α7 nAChR and NFκB dependent pathways. These novel findings

  14. Kinetic behaviours of aggregate growth driven by time-dependent migration, birth and death

    Science.gov (United States)

    Zhu, Sheng-Qing; Yang, Shun-You; Ke, Jianhong; Lin, Zhenquan

    2008-12-01

    We propose a dynamic growth model to mimic some social phenomena, such as the evolution of cities' population, in which monomer migrations occur between any two aggregates and monomer birth/death can simultaneously occur in each aggregate. Considering the fact that the rate kernels of migration, birth and death processes may change with time, we assume that the migration rate kernel is ijf(t), and the self-birth and death rate kernels are ig1(t) and ig2(t), respectively. Based on the mean-field rate equation, we obtain the exact solution of this model and then discuss semi-quantitatively the scaling behaviour of the aggregate size distribution at large times. The results show that in the long-time limit, (i) if ∫t0g1(t') dt'/∫t0g2(t') dt' >= 1 or exp{∫t0[g2(t') - g1(t')] dt'}/∫t0f(t') dt' → 0, the aggregate size distribution ak(t) can obey a generalized scaling form; (ii) if ∫t0g1(t') dt'/∫t0g2(t') dt' → 0 and exp ∫t0[g2(t') - g1(t') dt'/∫t0f(t') dt' → ∞, ak(t) can take a scale-free form and decay exponentially in size k; (iii) ak(t) will satisfy a modified scaling law in the remaining cases. Moreover, the total mass of aggregates depends strongly on the net birth rate g1(t) - g2(t) and evolves exponentially as exp{∫t0[g1(t') - g2(t')] dt'}, which is in qualitative agreement with the evolution of the total population of a country in real world.

  15. Dependence of the cyanobacterium Prochlorococcus on hydrogen peroxide scavenging microbes for growth at the ocean's surface.

    Directory of Open Access Journals (Sweden)

    J Jeffrey Morris

    2011-02-01

    Full Text Available The phytoplankton community in the oligotrophic open ocean is numerically dominated by the cyanobacterium Prochlorococcus, accounting for approximately half of all photosynthesis. In the illuminated euphotic zone where Prochlorococcus grows, reactive oxygen species are continuously generated via photochemical reactions with dissolved organic matter. However, Prochlorococcus genomes lack catalase and additional protective mechanisms common in other aerobes, and this genus is highly susceptible to oxidative damage from hydrogen peroxide (HOOH. In this study we showed that the extant microbial community plays a vital, previously unrecognized role in cross-protecting Prochlorococcus from oxidative damage in the surface mixed layer of the oligotrophic ocean. Microbes are the primary HOOH sink in marine systems, and in the absence of the microbial community, surface waters in the Atlantic and Pacific Ocean accumulated HOOH to concentrations that were lethal for Prochlorococcus cultures. In laboratory experiments with the marine heterotroph Alteromonas sp., serving as a proxy for the natural community of HOOH-degrading microbes, bacterial depletion of HOOH from the extracellular milieu prevented oxidative damage to the cell envelope and photosystems of co-cultured Prochlorococcus, and facilitated the growth of Prochlorococcus at ecologically-relevant cell concentrations. Curiously, the more recently evolved lineages of Prochlorococcus that exploit the surface mixed layer niche were also the most sensitive to HOOH. The genomic streamlining of these evolved lineages during adaptation to the high-light exposed upper euphotic zone thus appears to be coincident with an acquired dependency on the extant HOOH-consuming community. These results underscore the importance of (indirect biotic interactions in establishing niche boundaries, and highlight the impacts that community-level responses to stress may have in the ecological and evolutionary outcomes for co

  16. Action spectrum for cryptochrome-dependent hypocotyl growth inhibition in Arabidopsis.

    Science.gov (United States)

    Ahmad, Margaret; Grancher, Nicholas; Heil, Mary; Black, Robert C; Giovani, Baldissera; Galland, Paul; Lardemer, Danielle

    2002-06-01

    Cryptochrome blue-light photoreceptors are found in both plants and animals and have been implicated in numerous developmental and circadian signaling pathways. Nevertheless, no action spectrum for a physiological response shown to be entirely under the control of cryptochrome has been reported. In this work, an action spectrum was determined in vivo for a cryptochrome-mediated high-irradiance response, the blue-light-dependent inhibition of hypocotyl elongation in Arabidopsis. Comparison of growth of wild-type, cry1cry2 cryptochrome-deficient double mutants, and cryptochrome-overexpressing seedlings demonstrated that responsivity to monochromatic light sources within the range of 390 to 530 nm results from the activity of cryptochrome with no other photoreceptor having a significant primary role at the fluence range tested. In both green- and norflurazon-treated (chlorophyll-deficient) seedlings, cryptochrome activity is fairly uniform throughout its range of maximal response (390-480 nm), with no sharply defined peak at 450 nm; however, activity at longer wavelengths was disproportionately enhanced in CRY1-overexpressing seedlings as compared with wild type. The action spectrum does not correlate well with the absorption spectra either of purified recombinant cryptochrome photoreceptor or to that of a second class of blue-light photoreceptor, phototropin (PHOT1 and PHOT2). Photoreceptor concentration as determined by western-blot analysis showed a greater stability of CRY2 protein under the monochromatic light conditions used in this study as compared with broad band blue light, suggesting a complex mechanism of photoreceptor activation. The possible role of additional photoreceptors (in particular phytochrome A) in cryptochrome responses is discussed.

  17. Delivery of CdiA nuclease toxins into target cells during contact-dependent growth inhibition.

    Science.gov (United States)

    Webb, Julia S; Nikolakakis, Kiel C; Willett, Julia L E; Aoki, Stephanie K; Hayes, Christopher S; Low, David A

    2013-01-01

    Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiB/CdiA family of two-partner secretion proteins. CDI systems deploy a variety of distinct toxins, which are contained within the polymorphic C-terminal region (CdiA-CT) of CdiA proteins. Several CdiA-CTs are nucleases, suggesting that the toxins are transported into the target cell cytoplasm to interact with their substrates. To analyze CdiA transfer to target bacteria, we used the CDI system of uropathogenic Escherichia coli 536 (UPEC536) as a model. Antibodies recognizing the amino- and carboxyl-termini of CdiA(UPEC536) were used to visualize transfer of CdiA from CDI(UPEC536+) inhibitor cells to target cells using fluorescence microscopy. The results indicate that the entire CdiA(UPEC536) protein is deposited onto the surface of target bacteria. CdiA(UPEC536) transfer to bamA101 mutants is reduced, consistent with low expression of the CDI receptor BamA on these cells. Notably, our results indicate that the C-terminal CdiA-CT toxin region of CdiA(UPEC536) is translocated into target cells, but the N-terminal region remains at the cell surface based on protease sensitivity. These results suggest that the CdiA-CT toxin domain is cleaved from CdiA(UPEC536) prior to translocation. Delivery of a heterologous Dickeya dadantii CdiA-CT toxin, which has DNase activity, was also visualized. Following incubation with CDI(+) inhibitor cells targets became anucleate, showing that the D.dadantii CdiA-CT was delivered intracellularly. Together, these results demonstrate that diverse CDI toxins are efficiently translocated across target cell envelopes.

  18. An Empirical Study on the Nexus of Poverty, GDP Growth, Dependency Ratio and Employment in Developing Countries

    Directory of Open Access Journals (Sweden)

    Sinnathurai Vijayakumar

    2013-06-01

    Full Text Available The paper has scrutinized the nexus among poverty, economic growth, employment and dependency ratio in developing countries. The primary intension behind this study is to find out the association between variables such as poverty, economic growth, agricultural and industrial employment and dependency ratio due to the gap in the existing literature. This study fully relies on cross country data and involves forty one countries which have been selected from Asia,Latin America and Sub-Saharan Africa. For this study, OLS method, correlation and econometric tools have been employed. Two models employed in the analysis are goodness of fit because both p-value and F-statistics in the models are less than 5%. The results bring to light the fact that age dependency ratio has had a tremendous impact on poverty and poverty has had a relatively very high impact on the age dependency ratio. Even though Industrial employment has anegative association with poverty incidence, it does not have a significant impact on poverty. The finding that economic growth, poverty and industrial employment significantly affect the agedependency ratio in model two is practicable and consistent with economic theories. Thus stable economic growth with an increase in labour productivity and labour intensive technology is anactive remedy for solving this problem.

  19. Verbal Short-Term Memory Span in Children: Long-Term Modality Dependent Effects of Intrauterine Growth Restriction

    Science.gov (United States)

    Geva, R.; Eshel, R.; Leitner, Y.; Fattal-Valevski, A.; Harel, S.

    2008-01-01

    Background: Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. Methods: This long-term, prospective design study…

  20. The ATPase and protease domains of yeast mitochondrial Lon: roles in proteolysis and respiration-dependent growth.

    Science.gov (United States)

    van Dijl, J M; Kutejová, E; Suda, K; Perecko, D; Schatz, G; Suzuki, C K

    1998-09-01

    The ATP-dependent Lon protease of Saccharomyces cerevisiae mitochondria is required for selective proteolysis in the matrix, maintenance of mitochondrial DNA, and respiration-dependent growth. Lon may also possess a chaperone-like function that facilitates protein degradation and protein-complex assembly. To understand the influence of Lon's ATPase and protease activities on these functions, we examined several Lon mutants for their ability to complement defects of Lon-deleted yeast cells. We also developed a rapid procedure for purifying yeast Lon to homogeneity to study the enzyme's activities and oligomeric state. A point mutation in either the ATPase or the protease site strongly inhibited the corresponding activity of the pure protein but did not alter the protein's oligomerization; when expressed at normal low levels neither of these mutant enzymes supported respiration-dependent growth of Lon-deleted cells. When the ATPase- or the protease-containing regions of Lon were expressed as separate truncated proteins, neither could support respiration-dependent growth of Lon-deleted cells; however, coexpression of these two separated regions sustained wild-type growth. These results suggest that yeast Lon contains two catalytic domains that can interact with one another even as separate proteins, and that both are essential for the different functions of Lon.

  1. Light-Dependency of Growth and Secondary Metabolite Production in the Captive Zooxanthellate Soft Coral Sinularia flexibilis

    NARCIS (Netherlands)

    Khalesi, M.K.; Beeftink, H.H.; Wijffels, R.H.

    2009-01-01

    The branching zooxanthellate soft coral Sinularia flexibillis releases antimicrobial and toxic compounds with potential pharmaceutical importance. As photosynthesis by the symbiotic algae is vital to the host, the light-dependency of the coral, including its specific growth rate (µ day-1) and the

  2. Growth hormone-dependent phosphorylation of tyrosine 333 and/or 338 of the growth hormone receptor

    DEFF Research Database (Denmark)

    VanderKuur, J A; Wang, X; Zhang, L

    1995-01-01

    and a reduction of GH-dependent phosphorylation of the full-length receptor. Consistent with Tyr333 and/or Tyr338 serving as substrates of JAK2, these substitutions resulted in a loss of tyrosyl phosphorylation of truncated receptor in an in vitro kinase assay using substantially purified GH.GHR.JAK2 complexes...

  3. The neuropeptide schistosomin and haemolymph from parasitized snails induce similar changes in excitability in neuroendocrine cells controlling reproduction and growth in a freshwater snail

    NARCIS (Netherlands)

    Hordijk, P. L.; de Jong-Brink, M.; ter Maat, A.; Pieneman, A. W.; Lodder, J. C.; Kits, K. S.

    1992-01-01

    Infection of the snail Lymnaea stagnalis with the schistosome parasite Trichobilharzia ocellata results in inhibition of reproduction and in giant growth. Parasite-related effects on the neuroendocrine centres that control these processes were studied electrophysiologically. Haemolymph from infected

  4. Characterization of Alternaria and Penicillium species from similar substrata based on growth at different temperature, pH and water activity

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Frisvad, Jens Christian

    2002-01-01

    Fifty-eight Alternaria isolates representing 10 species or species-groups and 66 Penicillium isolates representing 18 species were examined for their growth response to the combined effects of water activity, temperature and pH in an extended Central Composite Design. Growth responses were recorded...... as colony diameter after one and two weeks of growth and analysed using different multivariate statistical analyses. The isolates, when analysed by principal Component Analysis, clustered according to their genus and to some degree to species or species groups and not according to substratum as excepted...... incubated at two different temperatures were enough to get genus segregation and to some extent species segregation. The results also showed that water activity, temperature and pH interact strongly in their effect on growth rates and that the squared products (optima) of water activity, temperature and p...

  5. Cytotoxic T lymphocyte-dependent tumor growth inhibition by a vascular endothelial growth factor–superantigen conjugate

    International Nuclear Information System (INIS)

    Sun, Qingwen; Jiang, Songmin; Han, Baohui; Sun, Tongwen; Li, Zhengnan; Zhao, Lina; Gao, Qiang; Sun, Jialin

    2012-01-01

    Highlights: ► We construct and purify a fusion protein VEGF–SEA. ► VEGF–SEA strongly repressed the growth of murine solid sarcoma 180 (S180) tumors. ► T cells driven by VEGF–SEA were accumulated around tumor cells bearing VEGFR by mice image model. ► VEGF–SEA can serve as a tumor targeting agent and sequester CTLs into the tumor site. ► The induced CTLs could release the cytokines, perforins and granzyme B to kill the tumor cells. -- Abstract: T cells are major lymphocytes in the blood and passengers across the tumor vasculature. If these T cells are retained in the tumor site, a therapeutic potential will be gained by turning them into tumor-reactive cytotoxic T lymphocytes (CTLs). A fusion protein composed of human vascular endothelial growth factor (VEGF) and staphylococcal enterotoxin A (SEA) with a D227A mutation strongly repressed the growth of murine solid sarcoma 180 (S180) tumors (control versus VEGF–SEA treated with 15 μg, mean tumor weight: 1.128 g versus 0.252 g, difference = 0.876 g). CD4 + and CD8 + T cells driven by VEGF–SEA were accumulated around VEGFR expressing tumor cells and the induced CTLs could release the tumoricidal cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Meanwhile, intratumoral CTLs secreted cytolytic pore-forming perforin and granzyme B proteins around tumor cells, leading to the death of tumor cells. The labeled fusion proteins were gradually targeted to the tumor site in an imaging mice model. These results show that VEGF–SEA can serve as a tumor targeting agent and sequester active infiltrating CTLs into the tumor site to kill tumor cells, and could therefore be a potential therapeutical drug for a variety of cancers.

  6. Cytotoxic T lymphocyte-dependent tumor growth inhibition by a vascular endothelial growth factor-superantigen conjugate

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Qingwen [Shanghai Chest Hospital, Shanghai 200433 (China); State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433 (China); Jiang, Songmin [State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433 (China); Han, Baohui [Shanghai Chest Hospital, Shanghai 200433 (China); Sun, Tongwen [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China); Li, Zhengnan; Zhao, Lina; Gao, Qiang [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Sun, Jialin, E-mail: jialin_sun@126.com [Wuhan Junyu Innovation Pharmaceuticals, Inc., Wuhan 430079 (China)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer We construct and purify a fusion protein VEGF-SEA. Black-Right-Pointing-Pointer VEGF-SEA strongly repressed the growth of murine solid sarcoma 180 (S180) tumors. Black-Right-Pointing-Pointer T cells driven by VEGF-SEA were accumulated around tumor cells bearing VEGFR by mice image model. Black-Right-Pointing-Pointer VEGF-SEA can serve as a tumor targeting agent and sequester CTLs into the tumor site. Black-Right-Pointing-Pointer The induced CTLs could release the cytokines, perforins and granzyme B to kill the tumor cells. -- Abstract: T cells are major lymphocytes in the blood and passengers across the tumor vasculature. If these T cells are retained in the tumor site, a therapeutic potential will be gained by turning them into tumor-reactive cytotoxic T lymphocytes (CTLs). A fusion protein composed of human vascular endothelial growth factor (VEGF) and staphylococcal enterotoxin A (SEA) with a D227A mutation strongly repressed the growth of murine solid sarcoma 180 (S180) tumors (control versus VEGF-SEA treated with 15 {mu}g, mean tumor weight: 1.128 g versus 0.252 g, difference = 0.876 g). CD4{sup +} and CD8{sup +} T cells driven by VEGF-SEA were accumulated around VEGFR expressing tumor cells and the induced CTLs could release the tumoricidal cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Meanwhile, intratumoral CTLs secreted cytolytic pore-forming perforin and granzyme B proteins around tumor cells, leading to the death of tumor cells. The labeled fusion proteins were gradually targeted to the tumor site in an imaging mice model. These results show that VEGF-SEA can serve as a tumor targeting agent and sequester active infiltrating CTLs into the tumor site to kill tumor cells, and could therefore be a potential therapeutical drug for a variety of cancers.

  7. The mitogen-activated protein kinase pathway mediates growth arrest or E1A-dependent apoptosis in SKBR3 human breast cancer cells.

    Science.gov (United States)

    Blagosklonny, M V

    1998-11-09

    Previously, we have shown that phorbol ester (PMA) induces p21(WAF1/CIP1)-dependent growth arrest in SKBr3 breast cancer and LNCaP prostate cancer cells. Here, I demonstrate that inhibition of Raf-1 kinase by dominant-negative Raf-1 or pharmacological depletion of Raf-1 prevented PMA-mediated induction of p21(WAF1/CIP1). Similarly, PD98059, a specific inhibitor of MEK, abolished p21(WAF1/CIP1) induction and PMA-induced growth arrest. Like PMA, the H-ras oncogene, another activator of the Raf-1/MEK/MAPK pathway, transactivated p21(WAF1/CIP1) in SKBr3 cells. I further investigated PMA-induced growth arrest following infection of SKBr3 cells with 12S E1A-expressing adenovirus. Although high levels of E1A oncoprotein prevented both PMA-induced p21(WAF1/CIP1) and growth arrest, smaller amounts of E1A abrogated growth arrest without down-regulation of p21(WAF1/CIP1). Therefore, E1A can stimulate proliferation downstream of p21(WAF1/CIP1). Albeit less effective than full activity, either Rb- or p300-binding activity of E1A was sufficient for the abrogation of PMA-mediated growth arrest. E1A-driven proliferation of PMA-treated SKBr3 cells was accompanied by apoptosis. New therapeutic approaches can be envisioned that would utilize stimulation of the Raf-1/MEK/MAPK pathway to inhibit growth of PMA-sensitive cancer cells.

  8. Widespread Dependence of Backup NHEJ on Growth State: Ramifications for the Use of DNA-PK Inhibitors

    International Nuclear Information System (INIS)

    Singh, Satyendra K.; Wu Wenqi; Zhang Lihua; Klammer, Holger; Wang Minli; Iliakis, George

    2011-01-01

    Purpose: The backup pathway of nonhomologous end joining (B-NHEJ) enables cells to process DNA double-strand breaks (DSBs) when the DNA-PK-dependent pathway of NHEJ (D-NHEJ) is compromised. Our previous results show marked reduction in the activity of B-NHEJ when LIG4 -/- mouse embryo fibroblasts (MEFs) cease to grow and enter a plateau phase. The dependence of B-NHEJ on growth state is substantially stronger than that of D-NHEJ and points to regulatory mechanisms or processing determinants that require elucidation. Because the different D-NHEJ mutants show phenotypes distinct in their details, it is necessary to characterize the dependence of their DSB repair capacity on growth state and to explore species-specific responses. Methods and Materials: DSB repair was measured in cells of different genetic background from various species using pulsed-field gel electrophoresis, or the formation of γ-H2AX foci, at different stages of growth. Results: Using pulsed-field gel electrophoresis, we report a marked reduction of B-NHEJ during the plateau phase of growth in KU and XRCC4, mouse or Chinese hamster, mutants. Notably, this reduction is only marginal in DNA-PKcs-deficient cells. However, reduced B-NHEJ is also observed in repair proficient, plateau-phase cells after treatment with DNA-PK inhibitors. The reduction of B-NHEJ activity in the plateau phase of growth does not derive from the reduced expression of participating proteins, is detectable by γ-H2AX foci analysis, and leads to enhanced cell killing. Conclusions: These results further document the marked dependence on growth state of an essential DSB repair pathway and show the general nature of the effect. Molecular characterization of the mechanism underlying this response will help to optimize the administration of DNA repair inhibitors as adjuvants in radiation therapy.

  9. Field dependent transition to the non-linear regime in magnetic hyperthermia experiments: Comparison between maghemite, copper, zinc, nickel and cobalt ferrite nanoparticles of similar sizes

    Directory of Open Access Journals (Sweden)

    E. L. Verde

    2012-09-01

    Full Text Available Further advances in magnetic hyperthermia might be limited by biological constraints, such as using sufficiently low frequencies and low field amplitudes to inhibit harmful eddy currents inside the patient's body. These incite the need to optimize the heating efficiency of the nanoparticles, referred to as the specific absorption rate (SAR. Among the several properties currently under research, one of particular importance is the transition from the linear to the non-linear regime that takes place as the field amplitude is increased, an aspect where the magnetic anisotropy is expected to play a fundamental role. In this paper we investigate the heating properties of cobalt ferrite and maghemite nanoparticles under the influence of a 500 kHz sinusoidal magnetic field with varying amplitude, up to 134 Oe. The particles were characterized by TEM, XRD, FMR and VSM, from which most relevant morphological, structural and magnetic properties were inferred. Both materials have similar size distributions and saturation magnetization, but strikingly different magnetic anisotropies. From magnetic hyperthermia experiments we found that, while at low fields maghemite is the best nanomaterial for hyperthermia applications, above a critical field, close to the transition from the linear to the non-linear regime, cobalt ferrite becomes more efficient. The results were also analyzed with respect to the energy conversion efficiency and compared with dynamic hysteresis simulations. Additional analysis with nickel, zinc and copper-ferrite nanoparticles of similar sizes confirmed the importance of the magnetic anisotropy and the damping factor. Further, the analysis of the characterization parameters suggested core-shell nanostructures, probably due to a surface passivation process during the nanoparticle synthesis. Finally, we discussed the effect of particle-particle interactions and its consequences, in particular regarding discrepancies between estimated

  10. Facet-dependent study of efficient growth of graphene on copper by ...

    Indian Academy of Sciences (India)

    Abstract. The growth of graphene by chemical vapour deposition (CVD) on copper is the most promising scal- able method for high-quality graphene. The use of ethanol, an economic and safe precursor, for the fast growth of graphene on copper by a home-built CVD set-up was analysed. Full coverage of uniform ...

  11. Facet-dependent study of efficient growth of graphene on copper

    Indian Academy of Sciences (India)

    The growth of graphene by chemical vapour deposition (CVD) on copper is the most promising scalable method for high-quality graphene. The use of ethanol, an economic and safe precursor, for the fast growth of graphene on copper by a home-built CVD set-up was analysed. Full coverage of uniform single-layer ...

  12. Facet-dependent study of efficient growth of graphene on copper by ...

    Indian Academy of Sciences (India)

    The growth of graphene by chemical vapour deposition (CVD) on copper is the most promising scalable method for high-quality graphene. The use of ethanol, an economic and safe precursor, for the fast growth of graphene on copper by a home-built CVD set-up was analysed. Full coverage of uniform single-layer ...

  13. Transcription factor control of growth rate dependent genes in Saccharomyces cerevisiae: A three factor design

    DEFF Research Database (Denmark)

    Fazio, Alessandro; Jewett, Michael Christopher; Daran-Lapujade, Pascale

    2008-01-01

    transcription factor target sets, transcription factors that coordinate balanced growth were also identified. Our analysis shows that FhII, Rap1, and Sfp1, regulating protein biosynthesis, have significantly enriched target sets for genes up-regulated with increasing growth rate. Cell cycle regulators...

  14. The Success of Thread-embedding Therapy in Generating Hair Re-growth in Mice Points to Its Possibly Having a Similar Effect in Humans

    Directory of Open Access Journals (Sweden)

    Hyun Jong Shin

    2015-12-01

    Full Text Available Objectives: Recently, thread-embedding therapy (TET has been widely applied in Korean medicine for cosmetic purposes such as reducing skin wrinkles. An inserted thread was reported to have induced continuous stimulation, followed by support for connective tissue regeneration. However, the potential role of TET in hairgrowth has not yet been reported. Methods: We designed this study to evaluate whether TET has a hair-growth-promoting effect. C57 black 6 (C57BL/6 mice were divided into three groups: normal saline-treated, minoxidil-treated, and thread-embedded groups. Normal saline or 5% minoxidil was topically sprayed on the dorsal skin of the mice once a day for 16 days. Medical threads were embedded into the dorsal skin of the mice in a single application. Hair growth activity was evaluated by using dermoscopic and microscopic observations. Sections of the dorsal skin were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU, proliferating cell nuclear antigen (PCNA, fibroblast growth factor-7 (FGF-7, and fibroblast growth factor-5 (FGF-5 were detected by using immunohistochemical staining. A reverse transcription-polymerase chain reaction (RT-PCR analysis was adopted to measure the messenger RNA (mRNA expressions of FGF-7 and FGF-5. Results: TET enhanced anagen development in the hair follicles of C57BL/6 mice. The expressions of BrdU and PCNA, both of which imply active cellular proliferation, were increased by using TET. Moreover, TET increased the expression of FGF-7, an anagen-inducing growth factor, while decreasing the expression of FGF-5, an anagen-cessation growth factor, both at the protein and the mRNA levels. Conclusion: TET enhanced hair re-growth in C57BL/6 mice. TET regulated the expressions of anagen-associated growth factors and activated the proliferation of hair follicular cells in depilated skin lesions. Considering its long-lasting effect, TET may be a good alternative therapeutic for the treatment of

  15. SUV2, which encodes an ATR-related cell cycle checkpoint and putative plant ATRIP, is required for aluminium-dependent root growth inhibition in Arabidopsis.

    Science.gov (United States)

    Sjogren, Caroline A; Larsen, Paul B

    2017-09-01

    A suppressor mutagenesis screen was conducted in order to identify second site mutations that could reverse the extreme hypersensitivity to aluminium (Al) seen for the Arabidopsis mutant, als3-1. From this screen, it was found that a loss-of-function mutation in the previously described SUV2 (SENSITIVE TO UV 2), which encodes a putative plant ATRIP homologue that is a component of the ATR-dependent cell checkpoint response, reversed the als3-1 phenotype. This included prevention of hallmarks associated with als3-1 including Al-dependent terminal differentiation of the root tip and transition to endoreduplication. From this analysis, SUV2 was determined to be required for halting cell cycle progression and triggering loss of the quiescent centre (QC) following exposure to Al. In conjunction with this, SUV2 was found to have a similar role as ATR, ALT2 and SOG1 in Al-dependent stoppage of root growth, all of which are required for promotion of expression of a suite of genes that likely are part of an Al-dependent DNA damage transcriptional response. This work argues that these Al response factors work together to detect Al-dependent damage and subsequently activate a DNA damage response pathway that halts the cell cycle and subsequently promotes QC differentiation and entrance into endocycling. © 2017 John Wiley & Sons Ltd.

  16. Nuclear energy consumption and economic growth in OECD countries: Cross-sectionally dependent heterogeneous panel causality analysis

    International Nuclear Information System (INIS)

    Nazlioglu, Saban; Lebe, Fuat; Kayhan, Selim

    2011-01-01

    The purpose of this study is to determine the direction causality between nuclear energy consumption and economic growth in OECD countries. The empirical model that includes capital and labor force as the control variables is estimated for the panel of fourteen OECD countries during the period 1980-2007. Apart from the previous studies in the nuclear energy consumption and economic growth relationship, this study utilizes the novel panel causality approach, which allows both cross-sectional dependency and heterogeneity across countries. The findings show that there is no causality between nuclear energy consumption and economic growth in eleven out of fourteen cases, supporting the neutrality hypothesis. As a sensitivity analysis, we also conduct Toda-Yamamoto time series causality method and find out that the results from the panel causality analysis are slightly different than those from the time-series causality analysis. Thereby, we can conclude that the choice of statistical tools in analyzing the nature of causality between nuclear energy consumption and economic growth may play a key role for policy implications. - Highlights: → Causality between nuclear energy consumption and economic growth is examined for OECD countries. → Panel causality method, which allows cross-sectional dependency and heterogeneity, is utilized. → The neutrality hypothesis is supported.

  17. Proteome Analysis of Cold Response in Spring and Winter Wheat (Triticum aestivum) Crowns Reveals Similarities in Stress Adaptation and Differences in Regulatory Processes between the Growth Habits

    Czech Academy of Sciences Publication Activity Database

    Kosová, K.; Vítámvás, P.; Planchon, S.; Renaut, J.; Vaňková, Radomíra; Prášil, I.T.

    2013-01-01

    Roč. 12, č. 11 (2013), s. 4830-4845 ISSN 1535-3893 R&D Projects: GA ČR GA522/09/2058 Institutional research plan: CEZ:AV0Z50380511 Keywords : 2D-DIGE analysis * cold stress * spring and winter growth habit Subject RIV: ED - Physiology Impact factor: 5.001, year: 2013

  18. Inhibition of fibroblast growth by Notch1 signaling is mediated by induction of Wnt11-dependent WISP-1.

    Directory of Open Access Journals (Sweden)

    Zhao-Jun Liu

    Full Text Available Fibroblasts are an integral component of stroma and important source of growth factors and extracellular matrix (ECM. They play a prominent role in maintaining tissue homeostasis and in wound healing and tumor growth. Notch signaling regulates biological function in a variety of cells. To elucidate the physiological function of Notch signaling in fibroblasts, we ablated Notch1 in mouse (Notch1(Flox/Flox embryonic fibroblasts (MEFs. Notch1-deficient (Notch1(-/- MEFs displayed faster growth and motility rate compared to Notch1(Flox/Flox MEFs. Such phenotypic changes, however, were reversible by reconstitution of Notch1 activation via overexpression of the intracellular domain of Notch1 (NICD1 in Notch1-deficient MEFs. In contrast, constitutive activation of Notch1 signaling by introducing NICD1 into primary human dermal fibroblasts (FF2441, which caused pan-Notch activation, inhibited cell growth and motility, whereas cellular inhibition was relievable when the Notch activation was countered with dominant-negative mutant of Master-mind like 1 (DN-MAML-1. Functionally, "Notch-activated" stromal fibroblasts could inhibit tumor cell growth/invasion. Moreover, Notch activation induced expression of Wnt-induced secreted proteins-1 (WISP-1/CCN4 in FF2441 cells while deletion of Notch1 in MEFs resulted in an opposite effect. Notably, WISP-1 suppressed fibroblast proliferation, and was responsible for mediating Notch1's inhibitory effect since siRNA-mediated blockade of WISP-1 expression could relieve cell growth inhibition. Notch1-induced WISP-1 expression appeared to be Wnt11-dependent, but Wnt1-independent. Blockade of Wnt11 expression resulted in decreased WISP-1 expression and liberated Notch-induced cell growth inhibition. These findings indicated that inhibition of fibroblast proliferation by Notch pathway activation is mediated, at least in part, through regulating Wnt1-independent, but Wnt11-dependent WISP-1 expression.

  19. Growth and flowering of Helleborus argutifolius (Viviani grown in pots depending on substrate type

    Directory of Open Access Journals (Sweden)

    Monika Henschke

    2014-09-01

    Full Text Available An experiment was conducted on the effect of substrate type on growth of Corsican hellebore (Helleborus argutifolius Viviani. Plants were grown for two years in pots with substrates whose components included Klasmann highmoor peat and Hartmann highmoor peat, mineral soil, expanded clay and perlite at various volumetric ratios. Vegetative growth and flowering were observed in hellebores. It was shown that substrates exhibited a varied effect on plant growth. Corsican hellebore in a substrate with a considerable addition of mineral soil was lower, but more branched, and it did not form inflorescences. An optimal medium for growing H. argutifolius in pots was Hartmann’s de-acidified peat + mineral soil (1:1 v:v. In this medium vegetative growth of plants was extensive, flowering was early and abundant, and long peduncles were produced.

  20. Lanthanide-Dependent Regulation of Methanol Oxidation Systems in Methylobacterium extorquens AM1 and Their Contribution to Methanol Growth.

    Science.gov (United States)

    Vu, Huong N; Subuyuj, Gabriel A; Vijayakumar, Srividhya; Good, Nathan M; Martinez-Gomez, N Cecilia; Skovran, Elizabeth

    2016-04-01

    Methylobacterium extorquens AM1 has two distinct types of methanol dehydrogenase (MeDH) enzymes that catalyze the oxidation of methanol to formaldehyde. MxaFI-MeDH requires pyrroloquinoline quinone (PQQ) and Ca in its active site, while XoxF-MeDH requires PQQ and lanthanides, such as Ce and La. Using MeDH mutant strains to conduct growth analysis and MeDH activity assays, we demonstrate that M. extorquens AM1 has at least one additional lanthanide-dependent methanol oxidation system contributing to methanol growth. Additionally, the abilities of different lanthanides to support growth were tested and strongly suggest that both XoxF and the unknown methanol oxidation system are able to use La, Ce, Pr, Nd, and, to some extent, Sm. Further, growth analysis using increasing La concentrations showed that maximum growth rate and yield were achieved at and above 1 μM La, while concentrations as low as 2.5 nM allowed growth at a reduced rate. Contrary to published data, we show that addition of exogenous lanthanides results in differential expression from the xox1 and mxa promoters, upregulating genes in the xox1 operon and repressing genes in the mxa operon. Using transcriptional reporter fusions, intermediate expression from both the mxa and xox1 promoters was detected when 50 to 100 nM La was added to the growth medium, suggesting that a condition may exist under which M. extorquens AM1 is able to utilize both enzymes simultaneously. Together, these results suggest that M. extorquens AM1 actively senses and responds to lanthanide availability, preferentially utilizing the lanthanide-dependent MeDHs when possible. The biological role of lanthanides is a nascent field of study with tremendous potential to impact many areas in biology. Our studies demonstrate that there is at least one additional lanthanide-dependent methanol oxidation system, distinct from the MxaFI and XoxF MeDHs, that may aid in classifying additional environmental organisms as methylotrophs. Further

  1. Rate-dependent mode I interlaminar crack growth mechanisms in graphite/epoxy and graphite/PEEK

    Science.gov (United States)

    Gillespie, J. W., Jr.; Carlsson, L. A.; Smiley, A. J.

    1987-01-01

    In this paper the mode I fracture behavior of graphite/epoxy and graphite/PEEK composites is examined over four decades of crosshead rates (0.25-250 mm/min). Straight-sided double-cantilever-beam specimens consisting of unidirectional laminates were tested at room temperature. For graphite/epoxy the load-deflection response was linear to fracture, and stable slow crack growth initiating at the highest load level was observed for all rates tested. In contrast, mode I crack growth in the graphite/PEEK material was often unstable and showed stick-slip behavior. Subcritical crack growth occurring prior to the onset of fracture was observed at intermediate displacement rates. A mechanism for the fracture behavior of the graphite/PEEK material (based on viscoelastic, plastic, and microcrack coalescence in the process zone) is proposed and related to the observed rate-dependent phenomena.

  2. The optimal combination of standard metabolic rate and aerobic scope for somatic growth depends on food availability

    OpenAIRE

    Auer, Sonya K.; Salin, Karine; Rudolf, Agata Marta; Anderson, Graeme J.; Metcalfe, Neil B.

    2015-01-01

    Metabolic rates can vary as much as threefold among individuals of the same size and age in a population, but why such variation persists is unclear given that they determine the energetic cost of living. Relationships between standard metabolic rate (SMR), growth and survival can vary with environmental conditions, suggesting that the fitness consequences of a given metabolic phenotype may be context-dependent. Less attention has focused on the link between absolute aerobic scope (AS, the di...

  3. Qualitative Analysis of a Diffusive Ratio-Dependent Holling-Tanner Predator-Prey Model with Smith Growth

    Directory of Open Access Journals (Sweden)

    Zongmin Yue

    2013-01-01

    Full Text Available We investigated the dynamics of a diffusive ratio-dependent Holling-Tanner predator-prey model with Smith growth subject to zero-flux boundary condition. Some qualitative properties, including the dissipation, persistence, and local and global stability of positive constant solution, are discussed. Moreover, we give the refined a priori estimates of positive solutions and derive some results for the existence and nonexistence of nonconstant positive steady state.

  4. Disturbance is required for CO2-dependent promotion of woody plant growth in grasslands

    DEFF Research Database (Denmark)

    Loveys, Beth R.; Egerton, John J. G.; Bruhn, Dan

    2010-01-01

    -top chambers flushed with either ambient or elevated [CO2] from March 2004 to January 2005 (autumn to summer). These seedlings were planted into three treatments (i.e. bare soil, soil covered with straw or soil supporting a sward of live pasture grass) to separate effects of grass on seedling growth into those...... suffered negligible damage. These results reveal the complexity of competitive inhibition of plant growth in which ineffective competition for resources such as soil water enhances the vulnerability of the plant to abiotic stress, in this case frost. Tree seedlings growing in bare soil and straw commenced...... resources or competitive enhancement of environmental stress. Nevertheless, elevated [CO2] could promote invasion of grasslands due to enhancement of woody plant growth in bare soil created by disturbances....

  5. Computer simulation of temperature-dependent growth of fractal and compact domains in diluted Ising models

    DEFF Research Database (Denmark)

    Sørensen, Erik Schwartz; Fogedby, Hans C.; Mouritsen, Ole G.

    1989-01-01

    temperature are studied as functions of temperature, time, and concentration. At zero temperature and high dilution, the growing solid is found to have a fractal morphology and the effective fractal exponent D varies with concentration and ratio of time scales of the two dynamical processes. The mechanism...... responsible for forming the fractal solid is shown to be a buildup of a locally high vacancy concentration in the active growth zone. The growth-probability measure of the fractals is analyzed in terms of multifractality by calculating the f(α) spectrum. It is shown that the basic ideas of relating...... probability measures of static fractal objects to the growth-probability distribution during formation of the fractal apply to the present model. The f(α) spectrum is found to be in the universality class of diffusion-limited aggregation. At finite temperatures, the fractal solid domains become metastable...

  6. Opioid-dependent growth of glial cultures: Suppression of astrocyte DNA synthesis by met-enkephalin

    Energy Technology Data Exchange (ETDEWEB)

    Stiene-Martin, A.; Hauser, K.F. (Univ. of Kentucky, Lexington (USA))

    1990-01-01

    The action of met-enkephalin on the growth of astrocytes in mixed-glial cultures was examined. Primary, mixed-glial cultures were isolated from 1 day-old mouse cerebral hemispheres and continuously treated with either basal growth media, 1 {mu}M met-enkephalin, 1 {mu}M met-enkephalin plus the opioid antagonist naloxone, or naloxone alone. Absolute numbers of neural cells were counted in unstained preparations, while combined ({sup 3}H)-thymidine autoradiography and glial fibrillary acid protein (GFAP) immunocytochemistry was performed to identify specific changes in astrocytes. When compared to control and naloxone treated cultures, met-enkephalin caused a significant decrease in both total cell numbers, and in ({sup 3}H)-thymidine incorporation by GFAP-positive cells with flat morphology. These results indicate that met-enkephalin suppresses astrocyte growth in culture.

  7. Isolate-dependent growth, virulence, and cell wall composition in the human pathogen Aspergillus fumigatus.

    Directory of Open Access Journals (Sweden)

    Nansalmaa Amarsaikhan

    Full Text Available The ubiquitous fungal pathogen Aspergillus fumigatus is a mediator of allergic sensitization and invasive disease in susceptible individuals. The significant genetic and phenotypic variability between and among clinical and environmental isolates are important considerations in host-pathogen studies of A. fumigatus-mediated disease. We observed decreased radial growth, rate of germination, and ability to establish colony growth in a single environmental isolate of A. fumigatus, Af5517, when compared to other clinical and environmental isolates. Af5517 also exhibited increased hyphal diameter and cell wall β-glucan and chitin content, with chitin most significantly increased. Morbidity, mortality, lung fungal burden, and tissue pathology were decreased in neutropenic Af5517-infected mice when compared to the clinical isolate Af293. Our results support previous findings that suggest a correlation between in vitro growth rates and in vivo virulence, and we propose that changes in cell wall composition may contribute to this phenotype.

  8. The semantic similarity ensemble

    Directory of Open Access Journals (Sweden)

    Andrea Ballatore

    2013-12-01

    Full Text Available Computational measures of semantic similarity between geographic terms provide valuable support across geographic information retrieval, data mining, and information integration. To date, a wide variety of approaches to geo-semantic similarity have been devised. A judgment of similarity is not intrinsically right or wrong, but obtains a certain degree of cognitive plausibility, depending on how closely it mimics human behavior. Thus selecting the most appropriate measure for a specific task is a significant challenge. To address this issue, we make an analogy between computational similarity measures and soliciting domain expert opinions, which incorporate a subjective set of beliefs, perceptions, hypotheses, and epistemic biases. Following this analogy, we define the semantic similarity ensemble (SSE as a composition of different similarity measures, acting as a panel of experts having to reach a decision on the semantic similarity of a set of geographic terms. The approach is evaluated in comparison to human judgments, and results indicate that an SSE performs better than the average of its parts. Although the best member tends to outperform the ensemble, all ensembles outperform the average performance of each ensemble's member. Hence, in contexts where the best measure is unknown, the ensemble provides a more cognitively plausible approach.

  9. Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner.

    Science.gov (United States)

    Choi, Yun-Young; Choi, Yuri; Kim, Jisook; Choi, Hyeonhae; Shin, Jiwon; Roh, Jaesook

    2016-01-01

    This study investigated the dose- and time-dependent effects of caffeine consumption throughout puberty in peripubertal rats. A total of 85 male SD rats were randomly divided into four groups: control and caffeine-fed groups with 20, 60, or 120 mg/kg/day through oral gavage for 10, 20, 30, or 40 days. Caffeine decreased body weight gain and food consumption in a dose- and time-dependent manner, accompanied by a reduction in muscle and body fat. In addition, it caused a shortening and lightening of leg bones and spinal column. The total height of the growth plate decreased sharply at 40 days in the controls, but not in the caffeine-fed groups, and the height of hypertrophic zone in the caffeine-fed groups was lower than in the control. Caffeine increased the height of the secondary spongiosa, whereas parameters related to bone formation, such as bone area ratio, thickness and number of trabeculae, and bone perimeter, were significantly reduced. Furthermore, serum levels of IGF-1, estradiol, and testosterone were also reduced by the dose of caffeine exposure. Our results demonstrate that caffeine consumption can dose- and time-dependently inhibit longitudinal bone growth in immature male rats, possibly by blocking the physiologic changes in body composition and hormones relevant to bone growth.

  10. Temperature dependent growth and optical properties of SnO2 ...

    Indian Academy of Sciences (India)

    Administrator

    Keywords. SnO2; nanostructures; growth mechanism; optical properties. 1. Introduction. One-dimensional (1D) oxide nanostructures such as wires, rods, belts, and tubes have become the focus of intensive research owing to their unique applications in mesoscopic physics and fabrication of nanoscaled devices. They not.

  11. Using time-dependent models to investigate body condition and growth rate of the giant gartersnake

    Science.gov (United States)

    Coates, P.S.; Wylie, G.D.; Halstead, B.J.; Casazza, Michael L.

    2009-01-01

    Identifying links between phenotypic attributes and fitness is a primary goal of reproductive ecology. Differences in within-year patterns of body condition between sexes of gartersnakes in relation to reproduction and growth are not fully understood. We conducted an 11-year field study of body condition and growth rate of the giant gartersnake Thamnophis gigas across 13 study areas in the Central Valley of California, USA. We developed a priori mixed effects models of body condition index (BCI), which included covariates of time, sex and snout-vent length and reported the best-approximating models using an information theoretic approach. Also, we developed models of growth rate index (GRI) using covariates of sex and periods based on reproductive behavior. The largest difference in BCI between sexes, as predicted by a non-linear (cubic) time model, occurred during the mating period when female body condition (0.014??0.001 se) was substantially greater than males (-0.027??0.002 se). Males likely allocated energy to search for mates, while females likely stored energy for embryonic development. We also provided evidence that males use more body energy reserves than females during hibernation, perhaps because of different body temperatures between sexes. We found GRI of male snakes was substantially lower during the mating period than during a non-mating period, which indicated that a trade-off existed between searching for mates and growth. These findings contribute to our understanding of snake ecology in a Mediterranean climate. ?? 2009 The Zoological Society of London.

  12. Time-dependent Creep Crack Growth Behavior of Alloy 617 at 800 .deg. C

    International Nuclear Information System (INIS)

    Kim, Woogon; Kim, Minhwan; Kim, Yongwan; Park, Jaeyoung; Ekaputra, I. M. W.

    2014-01-01

    The VHTR components are designed to be used for a 60 year lifetime at a high temperature, the creep crack growth (CCG) behavior as well as creep behavior is very important for the design application due to creep damage during the long service life at elevated temperatures. Alloy 617 is a major candidate material for the IHX component. The design of the component, which will operate well into the creep range, will require a good understanding of creep crack growth deformation. Efforts are now being undertaken in the Generation IV program to provide data needed for the design and licensing of the nuclear plants, and with this goal in mind, to meet the needs of the conceptual designers of the VHTR system, 'Gen-IV Materials Handbook DB' is being established through an international collaboration program of several GIF (Gen-IV Forum) countries. CCG experimental data should be prepared to 'the Gen-IV Materials Handbook DB' website, because the CCG data for Alloy 617 are not available in the ASME design code. In this paper, experimental creep crack growth data were obtained through a series of CCG tests performed under different applied loads at 800 .deg. C. The CCG behavior was characterized in terms of the C * fracture mechanics parameter, and the CCGR equation for Alloy 617 was presented. Experimental CCG data of Alloy 617 were obtained from a series of creep crack growth tests under different applied loads at 800 .deg. C

  13. Growth condition dependence of unintentional oxygen incorporation in epitaxial GaN.

    Science.gov (United States)

    Schubert, Felix; Wirth, Steffen; Zimmermann, Friederike; Heitmann, Johannes; Mikolajick, Thomas; Schmult, Stefan

    2016-01-01

    Growth conditions have a tremendous impact on the unintentional background impurity concentration in gallium nitride (GaN) synthesized by molecular beam epitaxy and its resulting chemical and physical properties. In particular for oxygen identified as the dominant background impurity we demonstrate that under optimized growth stoichiometry the growth temperature is the key parameter to control its incorporation and that an increase by 55 °C leads to an oxygen reduction by one order of magnitude. Quantitatively this reduction and the resulting optical and electrical properties are analyzed by secondary ion mass spectroscopy, photoluminescence, capacitance versus voltage measurements, low temperature magneto-transport and parasitic current paths in lateral transistor test structures based on two-dimensional electron gases. At a growth temperature of 665 °C the residual charge carrier concentration is decreased to below 10 15  cm -3 , resulting in insulating behavior and thus making the material suitable for beyond state-of-the-art device applications.

  14. Synechococcus growth in the ocean may depend on the lysis of heterotrophic bacteria

    Czech Academy of Sciences Publication Activity Database

    Weinbauer, M.G.; Bonilla-Findji, O.; Chan, A.M.; Dolan, J. R.; Short, S.M.; Šimek, Karel; Wilhelm, S. W.; Suttle, C.A.

    2011-01-01

    Roč. 33, č. 10 (2011), s. 1465-1476 ISSN 0142-7873 R&D Projects: GA ČR(CZ) GA206/08/0015 Institutional research plan: CEZ:AV0Z60170517 Keywords : viruses * growth control of cyanobacteria * heterotrophic bacterioplankton Subject RIV: EE - Microbiology, Virology Impact factor: 2.079, year: 2011

  15. Breeding objectives for sheep should be customised depending on variation in pasture growth across years

    NARCIS (Netherlands)

    Rose, I.J.; Mulder, H.A.; Thompson, A.N.; Werf, van der J.H.J.; Arendonk, van J.A.M.

    2015-01-01

    Breeding programmes for livestock require economic weights for traits that reflect the most profitable animal in a given production system, which affect the response in each trait after selection. The profitability of sheep production systems is affected by changes in pasture growth as well as

  16. Endogenous growth of population and income depending on resource and knowledge.

    Science.gov (United States)

    Prskawetz, A; Feichtinger, G; Luptacik, M; Milik, A; Wirl, F; Hof, F; Lutz, W

    1999-01-01

    This study focuses on the dynamic, endogenous, nonlinear interactions between the economy, population growth and the environment. Literature on endogenous growth theory was reviewed and the 3-sector demoeconomic model was provided as the analytical framework for the study of sustainable development through the integration of population growth, resource use and economic growth. The model is described in such a way that the labor force is considered as a free migrating variable among three different kinds of employment: the primary sector, which harvests a renewable resource, the secondary or industrial sector, and the tertiary sector, which is responsible for the accumulation of the stock that represents a public good for all three sectors. Presented in this paper is a nontechnical outline of the model that describes the economic, demographic, and environmental interactions considered. Also given are dynamics, market equilibrium and dynamic feedback rules. Furthermore, numerical analysis of the model quantifying the resulting time paths of the variables involved is included. The dynamics are simply the outcome of the nonlinear interactions of the demographic, economic and environmental modules. Numerical studies have also shown that the system variables move with different velocity. Technology and population can generally be regarded as slow moving variables by comparison with resources.

  17. Effects of Elevated Ambient Temperature on Reproductive Outcomes and Offspring Growth Depend on Exposure Time

    Directory of Open Access Journals (Sweden)

    Huda Yahia Hamid

    2012-01-01

    Full Text Available Reproductive performance has been shown to be greatly affected by changes in environmental factors, such as temperature. However, it is also crucial to identify the particular stage of pregnancy that is most adversely affected by elevated ambient temperature. The aims of this study were to determine the effect on reproductive outcomes of exposure to elevated ambient temperature during different stages of pregnancy and to determine the effect of prenatal heat stress on offspring growth. Sixty pregnant rats were used in this study. The rats were divided equally into four groups as group 1 (control, group 2 (exposed to elevated temperature following implantation, group 3 (exposed to elevated temperature during pre- and periimplantation, and group 4 (exposed to elevated temperature during pre- and periimplantation and following implantation. Groups 3 and 4 had prolonged gestation periods, reduced litter sizes, and male-biased sex ratios. Moreover, the growth patterns of group 3 and 4 pups were adversely affected by prenatal exposure to elevated temperature. The differences between group 1 and group 3 and between group 1 and group 4 were highly significant. However, no significant differences were observed between groups 1 and 2 in the gestation length, sex ratios, and growth patterns. Thus, it can be concluded that exposure to elevated ambient temperature during pre- and periimplantation has stronger adverse effects on reproductive outcomes and offspring growth than postimplantation exposure.

  18. Temperature-dependent sensitivity of growth and photosynthesis of Scenedesmus obliquus, Navicula pelliculosa and two strains of Microcystis aeruginosa to the herbicide atrazine.

    Science.gov (United States)

    Chalifour, Annie; Juneau, Philippe

    2011-05-01

    The temperature-dependent sensitivities of two algal species and two strains of cyanobacteria to the photosynthesis-inhibiting herbicide atrazine were evaluated in order to understand how the interaction between acclimation temperature and herbicide will affect growth and photosynthesis of aquatic microorganisms. The green alga Scenedesmus obliquus, the diatom Navicula pelliculosa and a toxic and non-toxic strain of Microcystis aeruginosa were acclimated to three different temperatures (10, 15 and 25°C) and exposed to five concentrations of the herbicide atrazine (0-0.15μM) for 72h. Growth, photosynthetic yields, energy fluxes within photosystem II and pigment content were then measured as potential responses to each treatment. With the exception of N. pelliculosa, the toxicity of atrazine was higher when microorganisms were acclimated to lower temperatures. N. pelliculosa was not only the most tolerant to atrazine, but also had a similar sensitivity to this herbicide at every temperature. The observed differences in growth sensitivity to atrazine at low temperature are associated with the ability of algae and cyanobacteria to cope with high excitation pressure, by increasing its protective carotenoid content and non-photochemical energy dissipation. Our results demonstrate that future guidelines for the protection of aquatic life should consider water temperature as an important factor influencing the toxicity of atrazine to aquatic microorganisms. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  19. Growth-rate dependency of de novo resveratrol production in chemostat cultures of an engineered Saccharomyces cerevisiae strain.

    Science.gov (United States)

    Vos, Tim; de la Torre Cortés, Pilar; van Gulik, Walter M; Pronk, Jack T; Daran-Lapujade, Pascale

    2015-09-14

    Saccharomyces cerevisiae has become a popular host for production of non-native compounds. The metabolic pathways involved generally require a net input of energy. To maximize the ATP yield on sugar in S. cerevisiae, industrial cultivation is typically performed in aerobic, sugar-limited fed-batch reactors which, due to constraints in oxygen transfer and cooling capacities, have to be operated at low specific growth rates. Because intracellular levels of key metabolites are growth-rate dependent, slow growth can significantly affect biomass-specific productivity. Using an engineered Saccharomyces cerevisiae strain expressing a heterologous pathway for resveratrol production as a model energy-requiring product, the impact of specific growth rate on yeast physiology and productivity was investigated in aerobic, glucose-limited chemostat cultures. Stoichiometric analysis revealed that de novo resveratrol production from glucose requires 13 moles of ATP per mole of produced resveratrol. The biomass-specific production rate of resveratrol showed a strong positive correlation with the specific growth rate. At low growth rates a substantial fraction of the carbon source was invested in cellular maintenance-energy requirements (e.g. 27 % at 0.03 h(-1)). This distribution of resources was unaffected by resveratrol production. Formation of the by-products coumaric, phloretic and cinnamic acid had no detectable effect on maintenance energy requirement and yeast physiology in chemostat. Expression of the heterologous pathway led to marked differences in transcript levels in the resveratrol-producing strain, including increased expression levels of genes involved in pathways for precursor supply (e.g. ARO7 and ARO9 involved in phenylalanine biosynthesis). The observed strong differential expression of many glucose-responsive genes in the resveratrol producer as compared to a congenic reference strain could be explained from higher residual glucose concentrations and higher

  20. Lower glucose-dependent insulinotropic polypeptide (GIP) response but similar glucagon-like peptide 1 (GLP-1), glycaemic, and insulinaemic response to ancient wheat compared to modern wheat depends on processing

    DEFF Research Database (Denmark)

    Bakhøj, S; Flint, A.; Holst, Jens Juul

    2003-01-01

    OBJECTIVE: To test the hypothesis that bread made from the ancient wheat Einkorn (Triticum monococcum) reduces the insulin and glucose responses through modulation of the gastrointestinal responses of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) compared...... whole grain bread elicit a reduced gastrointestinal response of GIP compared to conventional yeast bread. No differences were found in the glycaemic, insulinaemic and GLP-1 responses. Processing of starchy foods such as wheat may be a powerful tool to modify the postprandial GIP response....

  1. Wakefield dependent emittance growth in the SLAC [Stanford Linear Accelerator Center] linac

    International Nuclear Information System (INIS)

    Bane, K.L.F.

    1990-10-01

    In this note we describe the emittance growth we can expect at bunch populations of N = 3,4,5 x 10 10 in the SLC linac. We will discuss briefly the effects of injection jitter, injection drift, and coherent oscillations starting in the middle of the linac. Finally, we will discuss in a more thorough manner the effects of random misalignment errors throughout the linac

  2. Growth phase dependent hydrogen isotopic fractionation in alkenone-producing haptophytes

    Science.gov (United States)

    Wolhowe, M. D.; Prahl, F. G.; Probert, I.; Maldonado, M.

    2009-08-01

    Recent works have investigated use of the hydrogen isotopic composition of C37 alkenones (δDK37s, lipid biomarkers of certain haptophyte microalgae, as an independent paleosalinity proxy. We discuss herein the factors impeding the success of such an application and identify the potential alternative use of δDK37s measurements as a proxy for non-thermal, physiological stress impacts on the U37K' paleotemperature index. Batch-culture experiments with the haptophyte Emiliania huxleyi (CCMP 1742) were conducted to determine the magnitude and variability of the isotopic contrasts between individual C37 alkenones. Further experiments were conducted with Emiliania huxleyi (CCMP 1742) andGephyrocapsa oceanica (PZ3-1) to determine whether, and to what extent, δDK37s varies between the physiological extremes of nutrient-replete exponential growth and nutrient-depleted senescence. Emiliania huxleyi was observed to exhibit an isotopic contrast between di- and tri-unsaturated C37 alkenones (αK37:3-K37:2≈0.97) that is nearly identical to that reported recently by others for environmental samples. Furthermore, this contrast appears to be constant with growth stage. The consistency of the offset across different growth stages suggests that a single, well-defined value for αK37:3-K37:2 may exist and that its use in an isotope mass-balance will allow accurate determination of δD values for individual alkenones without having to rely on time- and labor-intensive chemical separations. The isotopic fractionation between growth medium and C37 alkenones was observed to increase dramatically upon the onset of nutrient-depletion-induced senescence, suggesting that δDK37s may serve as an objective tool for recognizing and potentially correcting, at least semi-quantitatively, for the effects of nutrient stress on U37K' temperature records.

  3. Invasive growth of Saccharomyces cerevisiae depends on environmental triggers: a quantitative model.

    Science.gov (United States)

    Zupan, Jure; Raspor, Peter

    2010-04-01

    In this contribution, the influence of various physicochemical factors on Saccharomyces cerevisiae invasive growth is examined quantitatively. Agar-invasion assays are generally applied for in vitro studies on S. cerevisiae invasiveness, the phenomenon observed as a putative virulence trait in this clinically more and more concerning yeast. However, qualitative agar-invasion assays, used until now, strongly limit the feasibility and interpretation of analyses and therefore needed to be improved. Besides, knowledge in this field concerning the physiology of invasive growth, influenced by stress conditions related to the human alimentary tract and food, is poor and should be expanded. For this purpose, a quantitative agar-invasion assay, presented in our previous work, was applied in this contribution to clarify the significance of the stress factors controlling the adhesion and invasion of the yeast in greater detail. Ten virulent and non-virulent S. cerevisiae strains were assayed at various temperatures, pH values, nutrient starvation, modified atmosphere, and different concentrations of NaCl, CaCl2 and preservatives. With the use of specific parameters, like a relative invasion, eight invasive growth models were hypothesized, which enabled intelligible interpretation of the results. A strong preference for invasive growth (meaning high relative invasion) was observed when the strains were grown on nitrogen- and glucose-depleted media. A significant increase in the invasion of the strains was also determined at temperatures typical for human fever (37-39 degrees C). On the other hand, a strong repressive effect on invasion was found in the presence of salts, anoxia and some preservatives. Copyright 2010 John Wiley & Sons, Ltd.

  4. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells.

    Science.gov (United States)

    Liang, Yayun; Mafuvadze, Benford; Aebi, Johannes D; Hyder, Salman M

    2016-01-01

    Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4'-[6-(allylmethylamino)hexyloxy]-4-bromo-2'-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells. Our

  5. Protective Effect of Metformin Against Walker 256 Tumor Growth is Not Dependent on Metabolism Improvement

    Directory of Open Access Journals (Sweden)

    Claudinéia Conationi da Silva Franco

    2014-11-01

    Full Text Available Background/Aims: The objective of the current work was to test the effect of metformin on the tumor growth in rats with metabolic syndrome. Methods: We obtained pre-diabetic hyperinsulinemic rats by neonatal treatment with monosodium L-glutamate (MSG, which were chronically treated every day, from weaning to 100 day old, with dose of metformin (250 mg/kg body weight. After the end of metformin treatment, the control and MSG rats, treated or untreated with metformin, were grafted with Walker 256 carcinoma cells. Tumor weight was evaluated 14 days after cancer cell inoculation. The blood insulin, glucose levels and glucose-induced insulin secretion were evaluated. Results: Chronic metformin treatment improved the glycemic homeostasis in pre-diabetic MSG-rats, glucose intolerance, tissue insulin resistance, hyperinsulinemia and decreased the fat tissue accretion. Meanwhile, the metformin treatment did not interfere with the glucose insulinotropic effect on isolated pancreatic islets. Chronic treatment with metformin was able to decrease the Walker 256 tumor weight by 37% in control and MSG rats. The data demonstrated that the anticancer effect of metformin is not related to its role in correcting metabolism imbalances, such as hyperinsulinemia. However, in morphological assay to apoptosis, metformin treatment increased programmed cell death. Conclusion: Metformin may have a direct effect on cancer growth, and it may programs the rat organism to attenuate the growth of Walker 256 carcinoma.

  6. Saccharomyces cerevisiae biofilm tolerance towards systemic antifungals depends on growth phase

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2014-01-01

    used Saccharomyces cerevisiae as a model for drug susceptibility of yeast biofilms. Confocal laser scanning microscopy showed that S. cerevisiae and C. glabrata form similarly structured biofilms and that the viable cell numbers were significantly reduced by treatment of mature biofilms...

  7. Intrauterine growth-restricted piglets have similar gastric emptying rates but lower rectal temperatures and altered blood values when compared with normal-weight piglets at birth

    DEFF Research Database (Denmark)

    Williams, Charlotte Amdi; Klarlund, M. V.; Pedersen, Janni Hales

    2016-01-01

    that the gastric emptying rate and blood glucose would be lower in IUGR piglets. We investigated gastric emptying rates in normal and IUGR piglets and blood glucose and rectal temperatures at birth and after 15, 30, 60, and 120 min. In addition, blood parameters relevant for metabolism were studied. Forty...... for poor immunization and glucose absorption in IUGR piglets. It is estimated that IUGR piglets consume less colostrum per kilogram BW than normal-weight piglets within the first 24 h, which could be due to a slower gastric emptying rate and a compromised energy metabolism. Therefore, we hypothesized...... normal and IUGR piglets were similar, but gastric DM residuals tended to be greater in IUGR piglets. Differences were observed in blood values and rectal temperatures, with lower values in IUGR piglets. Therefore, it is likely that factors like hypothermia and possibly reduced metabolic function are more...

  8. Growth and development are similar in VLBW children born appropriate and small for gestational age: an interim report on 97 preschool children.

    Science.gov (United States)

    Ranke, Michael B; Vollmer, Brigitte; Traunecker, Richard; Wollmann, Hartmut A; Goelz, Rangmar R; Seibold-Weiger, Karin; Speer, Christian P; Krägeloh-Mann, Ingeborg

    2007-09-01

    To investigate growth and development in a cohort of children born with very low birth weight (VLBW) treated at a single tertiary neonatal unit. We studied 97 children born between January 1995 and July 1997 with BW development were collected. Small for gestational age (SGA) was defined as weight and/or length at birth <10th percentile; shortness at follow-up was defined as height <10th percentile. Comparison was made between the appropriate for gestational age (AGA) (n = 46) and SGA (n = 51) groups. At follow-up, 23 AGA and 35 SGA children were short, had a smaller head circumference (-1.9 vs -0.8 SDS), were lighter at birth (BW -1.3 vs -0.7 SDS), and had a higher rate of broncho-pulmonary dysplasia (BPD) (28 vs 12); no differences in neonatal characteristics or neurological status were evident. A higher frequency of motor delay occurred in the 'short' group. Short children also had a smaller head circumference (HC) (-1.6 vs -0.7). Short SGA children had a higher frequency of BPD, smaller HC (-2.1 vs -1.0), and a slightly higher proportion of suspicious neurological findings, motor delay, and speech and language delay (n.s.). Preterm VLBW infants, whether AGA or SGA at birth, face the risk of being short at preschool age. Height outcome is probably influenced by postnatal factors. Our data also suggest that short stature is associated with developmental difficulties in this population.

  9. Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel

    Science.gov (United States)

    Uzoh, C C; Holly, J M P; Biernacka, K M; Persad, R A; Bahl, A; Gillatt, D; Perks, C M

    2011-01-01

    Background: The development of androgen independence, chemo-, and radioresistance are critical markers of prostate cancer progression and the predominant reasons for its high mortality. Understanding the resistance to therapy could aid the development of more effective treatments. Aim: The aim of this study is to investigate the effects of insulin-like growth factor-binding protein-2 (IGFBP-2) on prostate cancer cell proliferation and its effects on the response to docetaxel. Methods: DU145 and PC3 cells were treated with IGFBP-2, insulin-like growth factor I (IGF-I) alone or in combination with blockade of the IGF-I receptor or integrin receptors. Cells were also treated with IGFBP-2 short interfering ribonucleic acid with or without a PTEN (phosphatase and tensin homologue deleted on chromosome 10) inhibitor or docetaxel. Tritiated thymidine incorporation was used to measure cell proliferation and Trypan blue cell counting for cell death. Levels of IGFBP-2 mRNA were measured using RT–PCR. Abundance and phosphorylation of proteins were assessed using western immunoblotting. Results: The IGFBP-2 promoted cell growth in both cell lines but with PC3 cells this was in an IGF-dependent manner, whereas with DU145 cells the effect was independent of IGF receptor activation. This IGF-independent effect of IGFBP-2 was mediated by interaction with β-1-containing integrins and a consequent increase in PTEN phosphorylation. We also determined that silencing IGFBP-2 in both cell lines increased the sensitivity of the cells to docetaxel. Conclusion: The IGFBP-2 has a key role in the growth of prostate cancer cells, and silencing IGFBP-2 expression reduced the resistance of these cells to docetaxel. Targeting IGFBP-2 may increase the efficacy of docetaxel. PMID:21487405

  10. Evaluation of wavelength-dependent hair growth effects on low-level laser therapy: an experimental animal study.

    Science.gov (United States)

    Kim, Tae-Hoon; Kim, Nam-Jeong; Youn, Jong-In

    2015-08-01

    In this study, we aimed to investigate the wavelength-dependent effects of hair growth on the shaven backs of Sprague-Dawley rats using laser diodes with wavelengths of 632, 670, 785, and 830 nm. Each wavelength was selected by choosing four peak wavelengths from an action spectrum in the range 580 to 860 nm. The laser treatment was performed on alternating days over a 2-week period. The energy density was set to 1.27 J/cm(2) for the first four treatments and 1.91 J/cm(2) for the last four treatments. At the end of the experiment, both photographic and histological examinations were performed to evaluate the effect of laser wavelength on hair growth. Overall, the results indicated that low-level laser therapy (LLLT) with a 830-nm wavelength resulted in greater stimulation of hair growth than the other wavelengths examined and 785 nm also showed a significant effect on hair growth.

  11. Trade-offs between microbial growth phases lead to frequency-dependent and non-transitive selection.

    Science.gov (United States)

    Manhart, Michael; Adkar, Bharat V; Shakhnovich, Eugene I

    2018-02-14

    Mutations in a microbial population can increase the frequency of a genotype not only by increasing its exponential growth rate, but also by decreasing its lag time or adjusting the yield (resource efficiency). The contribution of multiple life-history traits to selection is a critical question for evolutionary biology as we seek to predict the evolutionary fates of mutations. Here we use a model of microbial growth to show that there are two distinct components of selection corresponding to the growth and lag phases, while the yield modulates their relative importance. The model predicts rich population dynamics when there are trade-offs between phases: multiple strains can coexist or exhibit bistability due to frequency-dependent selection, and strains can engage in rock-paper-scissors interactions due to non-transitive selection. We characterize the environmental conditions and patterns of traits necessary to realize these phenomena, which we show to be readily accessible to experiments. Our results provide a theoretical framework for analysing high-throughput measurements of microbial growth traits, especially interpreting the pleiotropy and correlations between traits across mutants. This work also highlights the need for more comprehensive measurements of selection in simple microbial systems, where the concept of an ordinary fitness landscape breaks down. © 2018 The Author(s).

  12. Arabidopsis cryptochrome 1 is a soluble protein mediating blue light-dependent regulation of plant growth and development

    International Nuclear Information System (INIS)

    Lin ChenTao; Ahmad, M.; Cashmore, A.R.

    1996-01-01

    Cryptochrome 1 (CRY1) is a flavin-type blue type receptor of Arabidopsis thaliana which mediates inhibition of hypocotyl elongation. In the work described in this report it is demonstrated that CRY1 is a soluble protein expressed in both young seedlings grown either in the dark or under light, and in different organs of adult plants. The functional role of CRY1 was further investigated using transgenic Arabidopsis plants overexpressing CRY1. It is demonstrated that overexpression of CRY1 resulted in hypersensitivity to blue, UV-A, and green light for the inhibition of hypocotyl elongation response. Transgenic plants overexpressing CRY1 also exhibited a dwarf phenotype with reduced size in almost every organ. This was in keeping with the previous observation of reciprocal alterations found in hy4 mutant plants and is consistent with a hypothesis that CRY1 mediates a light-dependent process resulting in a general inhibitory effect on plant growth. In addition, transgenic plants overexpressing CRY1 showed increased anthocyanin accumulation in response to blue, UV-A, and green light in a fluence rate-dependent manner. This increase in anthocyanin accumulation in transgenic plants was shown to be concomitant with increased blue light-induction of CHS gene expression. It is concluded that CRY1 is a photoreceptor mediating blue light-dependent regulation of gene expression in addition to its affect on plant growth. (author)

  13. Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.

    Science.gov (United States)

    Takito, Jiro; Kimura, Junko; Kajima, Koji; Uozumi, Nobuyuki; Watanabe, Makoto; Yokosuka, Akihito; Mimaki, Yoshihiro; Nakamura, Masanori; Ohizumi, Yasushi

    2016-07-01

    Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.

  14. The extent to which ATP demand controls the glycolytic flux depends strongly on the organism and conditions for growth

    DEFF Research Database (Denmark)

    Købmann, Brian Jensen; Westerhoff, H.V.; Snoep, J.L.

    2002-01-01

    Using molecular genetics we have introduced uncoupled ATPase activity in two different bacterial species, Escherichia coli and Lactococcus lactis, and determined the elasticities of the growth rate and glycolytic flux towards the intracellular [ATP]/[ADP] ratio. During balanced growth in batch...... cultures of E. coli the ATP demand was found to have almost full control on the glycolytic flux (FCC=0.96) and the flux could be stimulated by 70%. In contrast to this, in L. lactis the control by ATP demand on the glycolytic flux was close to zero. However, when we used non-growing cells of L. lactis...... (which have a low glycolytic flux) the ATP demand had a high flux control and the flux could be stimulated more than two fold. We suggest that the extent to which ATP demand controls the glycolytic flux depends on how much excess capacity of glycolysis is present in the cells....

  15. Climate and site dependence of the annual growth of silver fir (Abies alba Mill.) in the Northern Apennines, Italy

    Energy Technology Data Exchange (ETDEWEB)

    Gambetti, D.; Lo Vecchio, G.; Nanni, T. [Consiglio Nazionale delle Ricerche, Bologna (Italy). FISBAT; Schweingruber, F.H. [Federal Institute for Forest, Snow and Landscape Research, Birmensdorf (Switzerland)

    2000-04-01

    The study is focused on the relationship between ring width formation of the silver fir and the climatic factors. Therefore, material on two sites of the Northern Apennine has been collected at different altitudes, slope and soil characteristics and has been compared tree ring width with meteorological data from a neighbouring station. The results are that the ring growth depends mainly on the winter mean temperature of the current year, the summer precipitation and the mean summer temperature of the preceding year. The influence of winter mean temperature is more pronounced at high altitudes. The mean summer temperature and summer precipitation had a stronger effect on the growth year at lower altitudes and on the following year at higher altitudes.

  16. Dose-dependent effects of extracted microcystins on embryonic development, larval growth and histopathological changes of southern catfish (Silurus meridionalis).

    Science.gov (United States)

    Zhang, Xuezhen; Xie, Ping; Wang, Weimin; Li, Dapeng; Li, Li; Tang, Rong; Lei, Hehua; Shi, Zechao

    2008-03-01

    A laboratory toxic experiment was conducted to examine dose-dependent effects of extracted microcystins (MCs) on embryonic development, larval growth and histopathological changes of southern catfish (Silurus meridionalis). Fertilized eggs were incubated in solutions with four concentrations of MCs (0, 1, 10, 100 microg MC-L Req l(-1)). Higher MCs retarded egg development (2-10h delays) and larval growth, reduced hatching rate (up to 45%), and caused high malformation rate (up to 15%) and hepatocytes damage (characterized by disorganization of cell structure and a loss of adherence between hepatocytes, cellular degeneration with vacuolar hepatocytes and marginal nuclei, even hepatocellular necrosis). A 10 microg MC-L Req l(-1) is close to a high concentration in natural cyanobacterial blooms, suggesting a possible existence of such toxic effects in eutrophic waters.

  17. Growth condition-dependent cell surface proteome analysis of Enterococcus faecium.

    Science.gov (United States)

    Sinnige, Jan C; de Been, Mark; Zhou, Miaomiao; Bonten, Marc J M; Willems, Rob J L; Top, Janetta

    2015-11-01

    The last 30 years Enterococcus faecium has become an important nosocomial pathogen in hospitals worldwide. The aim of this study was to obtain insight in the cell surface proteome of E. faecium when grown in laboratory and clinically relevant conditions. Enterococcus faecium E1162, a clinical blood stream isolate, was grown until mid-log phase in brain heart infusion medium (BHI) with, or without 0.02% bile salts, Tryptic Soy Broth with 1% glucose (TSBg) and urine, and its cell surface was "shaved" using immobilized trypsin. Peptides were identified using MS/MS. Mapping against the translated E1162 whole genome sequence identified 67 proteins that were differentially detected in different conditions. In urine, 14 proteins were significantly more and nine proteins less abundant relative to the other conditions. Growth in BHI-bile and TSBg, revealed four and six proteins, respectively, which were uniquely present in these conditions while two proteins were uniquely present in both conditions. Thus, proteolytic shaving of E. faecium cells identified differentially surface exposed proteins in different growth conditions. These proteins are of special interest as they provide more insight in the adaptive mechanisms and may serve as targets for the development of novel therapeutics against this multi-resistant emerging pathogen. All MS data have been deposited in the ProteomeXchange with identifier PXD002497 (http://proteomecentral.proteomexchange.org/dataset/PXD002497). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Cell cycle-dependent differentiation dynamics balances growth and endocrine differentiation in the pancreas

    DEFF Research Database (Denmark)

    Kim, Yung Hae; Larsen, Hjalte List; Rué, Paul

    2015-01-01

    Organogenesis relies on the spatiotemporal balancing of differentiation and proliferation driven by an expanding pool of progenitor cells. In the mouse pancreas, lineage tracing at the population level has shown that the expanding pancreas progenitors can initially give rise to all endocrine...... differentiation process is consistent with a simple model of cell cycle-dependent stochastic priming of progenitors to endocrine fate. The findings provide insights to define control parameters to optimize the generation of β-cells in vitro....

  19. Role of Erbin in ErbB2-dependent breast tumor growth

    Science.gov (United States)

    Tao, Yanmei; Shen, Chengyong; Luo, Shiwen; Traoré, Wilfried; Marchetto, Sylvie; Santoni, Marie-Josée; Xu, Linlin; Wu, Biao; Shi, Chao; Mei, Jinghong; Bates, Ryan; Liu, Xihui; Zhao, Kai; Xiong, Wen-Cheng; Borg, Jean-Paul; Mei, Lin

    2014-01-01

    ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2), a receptor tyrosine kinase of the ErbB family, is overexpressed in around 25% of breast cancers. In addition to forming a heterodimer with other ErbB receptors in response to ligand stimulation, ErbB2 can be activated in a ligand-independent manner. We report here that Erbin, an ErbB2-interacting protein that was thought to act as an antitumor factor, is specifically expressed in mammary luminal epithelial cells and facilitates ErbB2-dependent proliferation of breast cancer cells and tumorigenesis in MMTV-neu transgenic mice. Disruption of their interaction decreases ErbB2-dependent proliferation, and deletion of the PDZ domain in Erbin hinders ErbB2-dependent tumor development in MMTV-neu mice. Mechanistically, Erbin forms a complex with ErbB2, promotes its interaction with the chaperon protein HSP90, and thus prevents its degradation. Finally, ErbB2 and Erbin expression correlates in human breast tumor tissues. Together, these observations establish Erbin as an ErbB2 regulator for breast tumor formation and progression. PMID:25288731

  20. Does Innovation Performance Depend on Economic Growth?: The Case of a Country in Transition

    Directory of Open Access Journals (Sweden)

    Andrzej H Jasinski

    2011-12-01

    Full Text Available This paper is an attempt to analyze a possible influence of economic growth on innovation performance. Econometric model based on principal component analysis is the research tool. Poland, as a country in transition, is here a case-study. The analysis has confirmed an interesting pattern: in 1989-2007, corporate innovation performance was changing, in principle, in the same direction as macro-economic changes but with a one-to-two-year delay. This is some proof that the innovation activity followed the cyclical development of the national economy. Innovation performance was demand-driven, i.e., pulled by demand resulting from the economy's recovery and high economic growth. So, technological innovation appeared to be highly sensitive to the general economic situation in Poland as a transitional economy. Economic growth seems to be a kind of tag-boat pulling innovation activities in the business sector.Este artículo intenta analizar una posible influencia del crecimiento económico en el desempeño de la innovación. La herramienta de investigación empleada es el modelo econométrico basado en un componente principal de análisis. El estudio de caso es Polonia, una economía en transición. El análisis ha confirmado un patrón interesante: durante el periodo 1989-2007, el desempeño de la innovación cambió, en principio, en la misma dirección que los cambios macroeconómicos pero con un retraso de uno a dos años. Esto muestra de algún modo que la actividad innovadora correspondió al desarrollo cíclico de la economía nacional. El desempeño innovador se orientó por la demanda, es decir, una demanda impulsada por la recuperación económica y el alto crecimiento económico. Por lo tanto, la innovación tecnológica parece ser muy sensible a la situación económica en general de Polonia, como economía en transición. El crecimiento económico parece ser una especie de motor que impulsa las actividades innovadoras del sector de negocios.

  1. Androgen-dependent somatotroph function in a hypogonadal adolescent male: evidence for control of exogenous androgens on growth hormone release

    International Nuclear Information System (INIS)

    Mauras, N.; Blizzard, R.M.; Rogol, A.D.

    1989-01-01

    A 14(10/12)-year-old white male with primary gonadal failure following testicular irradiation for acute lymphocytic leukemia was evaluated for poor growth. He had received 2400 rad of prophylactic cranial irradiation. The growth velocity had decelerated from 7 to 3.2 cm/yr over 3 years. His bone age was 12(0/12) years (by TW2-RUS), and his peak growth hormone (GH) response to provocative stimuli was 1.4 ng/mL. The 24-hour GH secretion was studied by drawing blood every 20 minutes for 24 hours. The resulting GH profile was analyzed by a computerized pulse detection algorithm, CLUSTER. Timed serum GH samples were also obtained after a 1 microgram/kg IV bolus injection of the GH releasing factor (GRH). The studies showed a flat 24-hour profile and a peak GH response to GRH of 3.9 ng/ml. Testosterone enanthate treatment was started, 100 mg IM every 4 weeks. Ten months after the initiation of therapy the calculated growth rate was 8.6 cm/yr. The 24-hour GH study and GRH responses were repeated at the time, showing a remarkably normal 24-hour GH secretory pattern and a peak GH response to GRH of 14.4 ng/mL. Testosterone therapy was discontinued, and 4 months later similar studies were repeated. A marked decrease in the mean 24-hour GH secretion and mean peak height occurred, but with maintenance of the GH pulse frequency. The GH response to GRH was intermediate, with a peak of 8 ng/mL. There was no further growth during those 4 months despite open epiphyses

  2. Radiation-induced p53 protein response in the A549 cell line is culture growth-phase dependent

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, N.F.; Gurule, D.M.; Carpenter, T.R.

    1995-12-01

    One role of the p53 tumor suppressor protein has been recently revealed. Kastan, M.B. reported that p53 protein accumulates in cells exposed to ionizing radiation. The accumulation of p53 protein is in response to DNA damage, most importantly double-strand breaks, that results from exposure to ionizing radiation. The rise in cellular p53 levels is necessary for an arrest in the G{sub 1} phase of the cell cycle to provide additional time for DNA repair. The p53 response has also been demonstrated to enhance PCNA-dependent repair. p53 is thus an important regulator of the cellular response to DNA-damaging radiation. From this data, it can be concluded that the magnitude of the p53 response is not dependent on the phase of culture growth.

  3. Growth and magnetic properties dependence of the Co–Cu/Cu films electrodeposited under high magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Franczak, Agnieszka, E-mail: agnieszka.franczak@mtm.kuleuven.be [Laboratoire d’Ingénierie et Sciences des Matériaux (LISM EA 4695), Université de Reims Champagne-Ardenne, UFR Sciences et Naturelles, Bat. 6, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2 (France); Department of Materials Science (MTM), KU Leuven, Kasteelpark Arenberg 44, 3001 Haverlee (Leuven) (Belgium); Levesque, Alexandra [Laboratoire d’Ingénierie et Sciences des Matériaux (LISM EA 4695), Université de Reims Champagne-Ardenne, UFR Sciences et Naturelles, Bat. 6, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2 (France); Zabinski, Piotr [Laboratory of Physical Chemistry and Electrochemistry, Faculty of Non-Ferrous Metals, AGH University of Science and Technology, al. A. Mickiewicza 30, 30059 Krakow (Poland); Li, Donggang [Key Laboratory of Electromagnetic Processing of Materials (Ministry of Education), Northeastern University, 314 Box, 110004 Shenyang (China); Czapkiewicz, Maciej [Department of Electronics, AGH University of Science and Technology, al. A. Mickiewicza 30, 30059 Krakow (Poland); Kowalik, Remigiusz [Laboratory of Physical Chemistry and Electrochemistry, Faculty of Non-Ferrous Metals, AGH University of Science and Technology, al. A. Mickiewicza 30, 30059 Krakow (Poland); Bohr, Frédéric [Laboratoire d’Ingénierie et Sciences des Matériaux (LISM EA 4695), Université de Reims Champagne-Ardenne, UFR Sciences et Naturelles, Bat. 6, Moulin de la Housse, BP 1039, 51687 Reims Cedex 2 (France); and others

    2015-07-15

    The present work is focused on the investigations of magnetic properties dependence on microstructure of Co–Cu/Cu films electrodeposited under superimposed high magnetic field. The experimental results indicate a strong effect of an external magnetic field on the morphology of deposited films, more precisely on the Co:Cu ratio that determines the film growth. It is shown that the Co–Cu/Cu films electrodeposited without superimposed magnetic field consisted of two clearly visible features: compact film with incorporated granular particles. Under a superimposed external high magnetic field the privilege growth of the particles was induced. As a consequence, development of the well-defined branched structure of Co–Cu/Cu film was observed. In contrary, the phase compositional investigations do not reveal any changes in the phase formation during electrodeposition under magnetic field conditions. Thus, it is assumed that a strong growth of Co–Cu/Cu films in (111) direction under magnetic or non-magnetic electrodeposition conditions is related with the growth of Cu (111) plane and embedded into it some of the Co fcc atoms of same (111) orientation, as well as the Co hcp atoms that grows in the (002) direction. This non-equilibrium growth of Co–Cu/Cu films under magnetic deposition conditions affects strongly the magnetic properties of deposited films, revealing that films obtained under magnetic fields higher than 3 T were no more magnetic materials. - Highlights: • Co–Cu/Cu electrodeposits were obtained at elevated temperature under HMFs. • The effects of HMFs on microstructure and magnetic properties were investigated. • Interesting morphological changes due to HMFs has been observed. • Changes in Co:Cu ratio due to HMFs modified the magnetic properties of deposits.

  4. Interactions between carbon and nitrogen sources depend on RIM15 and determine fermentative or respiratory growth in Saccharomyces cerevisiae.

    Science.gov (United States)

    Olivares-Marin, Ivanna Karina; Madrigal-Perez, Luis Alberto; Canizal-Garcia, Melina; García-Almendárez, Blanca E; González-Hernández, Juan Carlos; Regalado-Gonzalez, Carlos

    2018-03-30

    Nutritional homeostasis is fundamental for alcoholic fermentation in Saccharomyces cerevisiae. Carbon and nitrogen have been related to this metabolic process; nevertheless, little is known about their interactions with the media and the energetic metabolism. Rim15p kinase is a point of convergence among different nutrient-activated signaling pathways; this makes it a target to investigate the relationship between nutritional status and energetic metabolism. To improve the current knowledge of nutrient interactions and their association with RIM15, we validated the doubling time as an indicator of growth phenotype, confirming that this kinetic parameter can be related to the cellular bioenergetic status. This endorses the usefulness of a threshold in doubling time values as an indicator of fermentative (≤ 6.5 h) and respiratory growth (≥ 13.2 h). Using the doubling time as response variable, we find that (i) two second-order interactions between type and concentration of carbon and nitrogen sources significantly affected the growth phenotype of S. cerevisiae; (ii) these metabolic interactions changed when RIM15 was deleted, suggesting a dependence on this gene; (iii) high concentration of ammonium (5% w/v) is toxic for S. cerevisiae cells; (iv) proline prompted fermentative growth phenotype regardless presence or absence of RIM15; (v) RIM15 deletion reverted ammonium toxicity when cells were grown in glucose (10% w/v); and (vi) RIM15 deletion improves fermentative metabolism probably by a partial inhibition of the respiration capacity. This study reveals the existence of synergic and diverse roles of carbon and nitrogen sources that are affected by RIM15, influencing the fermentative and respiratory growth of S. cerevisiae.

  5. Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy.

    Science.gov (United States)

    de Oliveira, Soraya I; Andrade, Luciana N S; Onuchic, Ana C; Nonogaki, Sueli; Fernandes, Patrícia D; Pinheiro, Mônica C; Rohde, Ciro B S; Chammas, Roger; Jancar, Sonia

    2010-05-13

    tumour cells grown in vitro. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R. We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours.

  6. Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy

    International Nuclear Information System (INIS)

    Oliveira, Soraya I de; Andrade, Luciana NS; Onuchic, Ana C; Nonogaki, Sueli; Fernandes, Patrícia D; Pinheiro, Mônica C; Rohde, Ciro BS; Chammas, Roger; Jancar, Sonia

    2010-01-01

    tumour cells grown in vitro. At the tissue level, a few cells (probably macrophages) stained positively with antibodies to PAF-R. We suggest that PAF-R-dependent pathways are activated during experimental tumour growth, modifying the microenvironment and the phenotype of the tumour macrophages in such a way as to favour tumour growth. Combination therapy with a PAF-R antagonist and a chemotherapeutic drug may represent a new and promising strategy for the treatment of some tumours

  7. Growth of intestinal epithelium in organ culture is dependent on EGF signalling

    International Nuclear Information System (INIS)

    Abud, Helen E.; Watson, Nadine; Heath, Joan K.

    2005-01-01

    Differentiation of endoderm into intestinal epithelium is initiated at E13.5 of mouse development when there are significant changes in morphology resulting in the conversion of undifferentiated stratified epithelium into a mature epithelial monolayer. Here we demonstrate that monolayer formation is associated with the selective apoptosis of superficial cells lining the lumen while cell proliferation is progressively restricted to cells adjacent to the basement membrane. We describe an innovative embryonic gut culture system that maintains the three-dimensional architecture of gut and in which these processes are recapitulated in vitro. Explants taken from specific regions of the gut and placed into organ culture develop and express molecular markers (Cdx1, Cdx2 and A33 antigen) in the same spatial and temporal pattern observed in vivo indicating that regional specification is maintained. Inhibition of the epidermal growth factor receptor (EGFR) tyrosine kinase using the specific inhibitor AG1478 significantly reduced the proliferation and survival of cells within the epithelial cell layer of cultured gut explants. This demonstrates an essential role for the EGF signalling pathway during the early stages of intestinal development

  8. Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations

    International Nuclear Information System (INIS)

    Becerikli, Mustafa; Jacobsen, Frank; Rittig, Andrea; Köhne, Wiebke; Nambiar, Sandeep; Mirmohammadsadegh, Alireza; Stricker, Ingo; Tannapfel, Andrea; Wieczorek, Stefan; Epplen, Joerg Thomas; Tilkorn, Daniel; Steinstraesser, Lars

    2013-01-01

    Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies “initial” and “final” passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations. -- Highlights: Increased proliferative potential of late passage STS cells was: • Not associated with epigenetic changes (methylation changes at LINE-1, PTEN). • Not associated with mutation status of KRAS, BRAF. • Dependent on presence/absence of chromosomal aberrations

  9. Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Becerikli, Mustafa; Jacobsen, Frank; Rittig, Andrea; Köhne, Wiebke [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany); Nambiar, Sandeep; Mirmohammadsadegh, Alireza; Stricker, Ingo; Tannapfel, Andrea [Institute of Pathology, Ruhr-University Bochum (Germany); Wieczorek, Stefan; Epplen, Joerg Thomas [Department of Human Genetics, Ruhr-University Bochum (Germany); Tilkorn, Daniel [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany); Steinstraesser, Lars, E-mail: lars.steinstraesser@rub.de [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany)

    2013-07-15

    Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies “initial” and “final” passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations. -- Highlights: Increased proliferative potential of late passage STS cells was: • Not associated with epigenetic changes (methylation changes at LINE-1, PTEN). • Not associated with mutation status of KRAS, BRAF. • Dependent on presence/absence of chromosomal aberrations.

  10. Characterization of ubiquitination dependent dynamics in growth factor receptor signaling by quantitative proteomics

    DEFF Research Database (Denmark)

    Akimov, Vyacheslav; Rigbolt, Kristoffer T G; Nielsen, Mogens M

    2011-01-01

    Protein ubiquitination is a dynamic reversible post-translational modification that plays a key role in the regulation of numerous cellular processes including signal transduction, endocytosis, cell cycle control, DNA repair and gene transcription. The conjugation of the small protein ubiquitin...... investigating ubiquitination on a proteomic scale, mainly due to the inherited complexity and heterogeneity of ubiquitination. We describe here a quantitative proteomics strategy based on the specificity of ubiquitin binding domains (UBDs) and Stable Isotope Labeling by Amino acids in Cell culture (SILAC...... as ubiquitination-dependent events in signaling pathways. In addition to a detailed seven time-point profile of EGFR ubiquitination over 30 minutes of ligand stimulation, our data determined prominent involvement of Lysine-63 ubiquitin branching in EGF signaling. Furthermore, we found two centrosomal proteins, PCM1...

  11. Trophic Relationships between the Parasitic Plant Species Phelipanche ramosa (L.) and Different Hosts Depending on Host Phenological Stage and Host Growth Rate

    Science.gov (United States)

    Moreau, Delphine; Gibot-Leclerc, Stéphanie; Girardin, Annette; Pointurier, Olivia; Reibel, Carole; Strbik, Florence; Fernández-Aparicio, Mónica; Colbach, Nathalie

    2016-01-01

    Phelipanche ramosa (L.) Pomel (branched broomrape) is a holoparasitic plant that reproduces on crops and also on weeds, which contributes to increase the parasite seed bank in fields. This parasite extracts all its nutrients at the host’s expense so that host–parasite trophic relationships are crucial to determine host and parasite growth. This study quantified the intensity with which P. ramosa draws assimilates from its host and analyzed whether it varied with host species, host phenological stage and host growth rate. A greenhouse experiment was conducted on three host species: the crop species Brassica napus (L.) (oilseed rape) and two weed species, Capsella bursa-pastoris (L.) Medik. and Geranium dissectum (L.). Plants were grown with or without P. ramosa and under three light levels to modulate host growth rate. The proportion of host biomass loss due to parasitism by P. ramosa differed between host species (at host fructification, biomass loss ranged from 34 to 84%). B. napus and C. bursa-pastoris displayed a similar response to P. ramosa, probably because they belong to the same botanical family. The sensitivity to P. ramosa in each host species could be related to the precocity of P. ramosa development on them. Host compartments could be ranked as a function of their sensitivity to parasitism, with the reproductive compartment being the most severely affected, followed by stems and roots. The proportion of biomass allocated to leaves was not reduced by parasitism. The proportion of pathosystem biomass allocated to the parasite depended on host species. It generally increased with host stage progression but was constant across light induced-host growth rate, showing that P. ramosa adapts its growth to host biomass production. The rank order of host species in terms of sink strength differed from that in terms of host sensitivity. Finally, for B. napus, the biomass of individual parasite shoots decreased with increasing their number per host plant

  12. Trophic relationships between the parasitic plant species Phelipanche ramosa (L. and different hosts depending on host phenological stage and host growth rate

    Directory of Open Access Journals (Sweden)

    Delphine Moreau

    2016-07-01

    Full Text Available Phelipanche ramosa (L. Pomel (branched broomrape is a holoparasitic plant that reproduces on crops and also on weeds, which contributes to increase the parasite seed bank in fields. This parasite extracts all its nutrients at the host's expense so that host-parasite trophic relationships are crucial to determine host and parasite growth. This study quantified the intensity with which P. ramosa draws assimilates from its host and analyzed whether it varied with host species, host phenological stage and host growth rate. A greenhouse experiment was conducted on three host species: the crop species Brassica napus (L. (oilseed rape and two weed species, Capsella bursa-pastoris (L. Medik. and Geranium dissectum (L.. Plants were grown with or without P. ramosa and under three light levels to modulate host growth rate. The proportion of host biomass loss due to parasitism by P. ramosa differed between host species (at host fructification, biomass loss ranged from 34% to 84%. Brassica napus and C. bursa-pastoris displayed a similar response to P. ramosa, probably because they belong to the same botanical family. The sensitivity to P. ramosa in each host species could be related to the precocity of P. ramosa development on them. Host compartments could be ranked as a function of their sensitivity to parasitism, with the reproductive compartment being the most severely affected, followed by stems and roots. The proportion of biomass allocated to leaves was not reduced by parasitism. The proportion of pathosystem biomass allocated to the parasite depended on host species. It generally increased with host stage progression but was constant across light induced-host growth rate, showing that P. ramosa adapts its growth to host biomass production. The rank order of host species in terms of sink strength differed from that in terms of host sensitivity. Finally, for B. napus, the biomass of individual parasite shoots decreased with increasing their number per

  13. Supersaturation Control using Analytical Crystal Size Distribution Estimator for Temperature Dependent in Nucleation and Crystal Growth Phenomena

    Science.gov (United States)

    Zahari, Zakirah Mohd; Zubaidah Adnan, Siti; Kanthasamy, Ramesh; Saleh, Suriyati; Samad, Noor Asma Fazli Abdul

    2018-03-01

    The specification of the crystal product is usually given in terms of crystal size distribution (CSD). To this end, optimal cooling strategy is necessary to achieve the CSD. The direct design control involving analytical CSD estimator is one of the approaches that can be used to generate the set-point. However, the effects of temperature on the crystal growth rate are neglected in the estimator. Thus, the temperature dependence on the crystal growth rate needs to be considered in order to provide an accurate set-point. The objective of this work is to extend the analytical CSD estimator where Arrhenius expression is employed to cover the effects of temperature on the growth rate. The application of this work is demonstrated through a potassium sulphate crystallisation process. Based on specified target CSD, the extended estimator is capable of generating the required set-point where a proposed controller successfully maintained the operation at the set-point to achieve the target CSD. Comparison with other cooling strategies shows a reduction up to 18.2% of the total number of undesirable crystals generated from secondary nucleation using linear cooling strategy is achieved.

  14. Secretory pathway-dependent localization of the Saccharomyces cerevisiae Rho GTPase-activating protein Rgd1p at growth sites.

    Science.gov (United States)

    Lefèbvre, Fabien; Prouzet-Mauléon, Valérie; Hugues, Michel; Crouzet, Marc; Vieillemard, Aurélie; McCusker, Derek; Thoraval, Didier; Doignon, François

    2012-05-01

    Establishment and maintenance of cell polarity in eukaryotes depends upon the regulation of Rho GTPases. In Saccharomyces cerevisiae, the Rho GTPase activating protein (RhoGAP) Rgd1p stimulates the GTPase activities of Rho3p and Rho4p, which are involved in bud growth and cytokinesis, respectively. Consistent with the distribution of Rho3p and Rho4p, Rgd1p is found mostly in areas of polarized growth during cell cycle progression. Rgd1p was mislocalized in mutants specifically altered for Golgi apparatus-based phosphatidylinositol 4-P [PtdIns(4)P] synthesis and for PtdIns(4,5)P(2) production at the plasma membrane. Analysis of Rgd1p distribution in different membrane-trafficking mutants suggested that Rgd1p was delivered to growth sites via the secretory pathway. Rgd1p may associate with post-Golgi vesicles by binding to PtdIns(4)P and then be transported by secretory vesicles to the plasma membrane. In agreement, we show that Rgd1p coimmunoprecipitated and localized with markers specific to secretory vesicles and cofractionated with a plasma membrane marker. Moreover, in vivo imaging revealed that Rgd1p was transported in an anterograde manner from the mother cell to the daughter cell in a vectoral manner. Our data indicate that secretory vesicles are involved in the delivery of RhoGAP Rgd1p to the bud tip and bud neck.

  15. Temperature dependence of the minimum V/III ratio for the growth of In xGa 1-xAs

    Science.gov (United States)

    Riechert, H.; Averbeck, R.; Bernklau, D.

    1993-02-01

    We have quantitatively determined the minimum V/III ratios for the growth of In xGa 1- xAs ( x = 0, 0.1, 0.2 and 0.53) on GaAs and InP. Minimum As 4 fluxes were measured for a wide range of growth temperatures using a transition of the surface reconstruction. Their temperature dependence can be fitted very well by thetypical curve for thermally activated behavior. We find that the basic reaction kinetics of As 4 with In xGa 1- xAs are the same as with GaAs. The activation energies for As desorption from In xGa 1- xAs and GaAs are found to be similar (1.9 and 2.1 eV, respectively) but the rates of As- In xGa 1- xAs. This may be seen as evidence for a less effective dissociative reaction of As 4 with In than with Ga.

  16. Predicting impacts of future human population growth and development on occupancy rates of forest-dependent birds

    Science.gov (United States)

    Brown, Michelle L.; Donovan, Therese; Schwenk, W. Scott; Theobald, David M.

    2014-01-01

    Forest loss and fragmentation are among the largest threats to forest-dwelling wildlife species today, and projected increases in human population growth are expected to increase these threats in the next century. We combined spatially-explicit growth models with wildlife distribution models to predict the effects of human development on 5 forest-dependent bird species in Vermont, New Hampshire, and Massachusetts, USA. We used single-species occupancy models to derive the probability of occupancy for each species across the study area in the years 2000 and 2050. Over half a million new housing units were predicted to be added to the landscape. The maximum change in housing density was nearly 30 houses per hectare; however, 30% of the towns in the study area were projected to add less than 1 housing unit per hectare. In the face of predicted human growth, the overall occupancy of each species decreased by as much as 38% (ranging from 19% to 38% declines in the worst-case scenario) in the year 2050. These declines were greater outside of protected areas than within protected lands. Ninety-seven percent of towns experienced some decline in species occupancy within their borders, highlighting the value of spatially-explicit models. The mean decrease in occupancy probability within towns ranged from 3% for hairy woodpecker to 8% for ovenbird and hermit thrush. Reductions in occupancy probability occurred on the perimeters of cities and towns where exurban development is predicted to increase in the study area. This spatial approach to wildlife planning provides data to evaluate trade-offs between development scenarios and forest-dependent wildlife species.

  17. Natural resource dependence, human capital accumulation, and economic growth: A combined explanation for the resource curse and the resource blessing

    International Nuclear Information System (INIS)

    Shao, Shuai; Yang, Lili

    2014-01-01

    In existing studies, no consensus has been reached on the relationship between natural resource dependence and human capital accumulation. To narrow the divergence, this paper carries out a normative research to explain the co-existence of the phenomena of the resource curse and the resource blessing based on an organic combination of conceptual and mathematical models. It first establishes a conceptual model to analyse the potential effects of the government's policy preference and natural resource development activities on human capital accumulation and economic growth. Furthermore, it develops an endogenous growth model to normatively illuminate the effects in the conceptual model and to explore the condition for the occurrence of the resource curse. The conceptual model analysis indicates that the rate of return on education investment and government behaviours play the crucial role in promoting the formation of the economic virtuous circle at the micro-level and macro-level, respectively, while resource development activities exert dual impacts on the circle. The main mechanisms in the conceptual model can be validated in the mathematical model. The rise in the subjective discount rate, the elasticity of intertemporal substitution, and resource goods price are adverse to the economic virtuous circle, while high-quality education and the institutional environment giving priority to manufacturing can become the necessary condition and sufficient condition for forming the circle, respectively. The allocation efficiency of production factors plays a decisive role in whether the blessing occurs, whereas sufficient human capital is an essential guarantee for evading the curse. - Highlights: • We conduct normative research combining a conceptual model and a mathematical model. • We discuss the potential impact of resource dependence on human capital and growth. • We explain the co-existence of the resource blessing and resource curse phenomena.

  18. [Age-dependent alteration of insulin and ghrelin expression in pancreatic islets of intrauterine growth-retarded rats].

    Science.gov (United States)

    Wang, Xiu-Min; Liang, Li; Du, Li-Zhong

    2008-05-01

    To evaluate the age-dependent alteration of insulin and ghrelin expression in the pancreatic islets of intrauterine growth-retarded (IUGR) rats during development and to identify the role of ghrelin in insulin resistance induced by IUGR. Neonatal SD rats were divided into normal birth weight group (N group) and intrauterine growth-retarded group (I group). Plasma glucose, ghrelin and serum insulin were analyzed at day 1, 3, 7 and 10 and at week 2, 3, 4,8 and 12 after birth.Entire pancreas samples were collected for determination of ghrelin and insulin mRNA. Immunohistochemical double-staining and confocal microscopy was performed on rat pancreas. Plasma insulin levels of I group were lower than those of N group at day 1, 3 and 7 (P insulin resistance index (HOMA-IR) of I group was higher than that of N group at day 1, 3 and 7 (Pinsulin, HOMA-IR and ghrelin concentrations decreased in an age-dependent manner (F = 4.12 to approximately 125.97, P insulin (+) cells and ghrelin (+) cells in both groups decreased in an age-dependent manner (F = -49.29 to approximately 427.28, PInsulin secretion was negatively correlated with ghrelin contents in both groups (r=-0.895, P=0.000; r=-0.458, P=0.002). Percentage of insulin(+) cells was negatively correlated with the percentage of ghrelin (+) cells in pancreatic islets in both groups (r=-0.810,P=0.000; r=-0.714, P=0.000). The distributions of ghrelin (+) cells in pancreatic islets of I group were different from those of N group. The effects of IUGR on weight, plasma ghrelin levels and insulin secretion of pups rats persist after birth and ghrelin may be involved in the process of insulin resistance in IUGR rats.

  19. Cytosolic phospholipase A2 activation correlates with HER2 overexpression and mediates estrogen-dependent breast cancer cell growth.

    LENUS (Irish Health Repository)

    Caiazza, Francesco

    2010-05-01

    Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) catalyzes the hydrolysis of membrane glycerol-phospholipids to release arachidonic acid as the first step of the eicosanoid signaling pathway. This pathway contributes to proliferation in breast cancer, and numerous studies have demonstrated a crucial role of cyclooxygenase 2 and prostaglandin E(2) release in breast cancer progression. The role of cPLA(2)alpha activation is less clear, and we recently showed that 17beta-estradiol (E2) can rapidly activate cPLA(2)alpha in MCF-7 breast cancer cells. Overexpression or gene amplification of HER2 is found in approximately 30% of breast cancer patients and correlates with a poor clinical outcome and resistance to endocrine therapy. This study reports the first evidence for a correlation between cPLA(2)alpha enzymatic activity and overexpression of the HER2 receptor. The activation of cPLA(2)alpha in response to E2 treatment was biphasic with the first phase dependent on trans-activation through the matrix metalloproteinase-dependent release of heparin-bound epidermal growth factor. EGFR\\/HER2 heterodimerization resulted in downstream signaling through the ERK1\\/2 cascade to promote cPLA(2)alpha phosphorylation at Ser505. There was a correlation between HER2 and cPLA(2)alpha expression in six breast cancer cell lines examined, and inhibition of HER2 activation or expression in the SKBR3 cell line using herceptin or HER2-specific small interfering RNA, respectively, resulted in decreased activation and expression of cPLA(2)alpha. Pharmacological blockade of cPLA(2)alpha using a specific antagonist suppressed the growth of both MCF-7 and SKBR3 cells by reducing E2-induced proliferation and by stimulating cellular apoptosis and necrosis. This study highlights cPLAalpha(2) as a potential target for therapeutic intervention in endocrine-dependent and endocrine-independent breast cancer.

  20. The phosphorylation-dependent regulation of nuclear SREBP1 during mitosis links lipid metabolism and cell growth

    Science.gov (United States)

    Bengoechea-Alonso, Maria Teresa; Ericsson, Johan

    2016-01-01

    ABSTRACT The SREBP transcription factors are major regulators of lipid metabolism. Disturbances in lipid metabolism are at the core of several health issues facing modern society, including cardiovascular disease, obesity and diabetes. In addition, the role of lipid metabolism in cancer cell growth is receiving increased attention. Transcriptionally active SREBP molecules are unstable and rapidly degraded in a phosphorylation-dependent manner by Fbw7, a ubiquitin ligase that targets several cell cycle regulatory proteins for degradation. We have previously demonstrated that active SREBP1 is stabilized during mitosis. We have now delineated the mechanisms involved in the stabilization of SREBP1 in mitotic cells. This process is initiated by the phosphorylation of a specific serine residue in nuclear SREBP1 by the mitotic kinase Cdk1. The phosphorylation of this residue creates a docking site for a separate mitotic kinase, Plk1. Plk1 interacts with nuclear SREBP1 in mitotic cells and phosphorylates a number of residues in the C-terminal domain of the protein, including a threonine residue in close proximity of the Fbw7 docking site in SREBP1. The phosphorylation of these residues by Plk1 blocks the interaction between SREBP1 and Fbw7 and attenuates the Fbw7-dependent degradation of nuclear SREBP1 during cell division. Inactivation of SREBP1 results in a mitotic defect, suggesting that SREBP1 could regulate cell division. We propose that the mitotic phosphorylation and stabilization of nuclear SREBP1 during cell division provides a link between lipid metabolism and cell proliferation. Thus, the current study provides additional support for the emerging hypothesis that SREBP-dependent lipid metabolism may be important for cell growth. PMID:27579997

  1. Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

    Directory of Open Access Journals (Sweden)

    Yao Jorge L

    2008-04-01

    Full Text Available Abstract Background Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive. Methods Flat panel detector-based cone beam computed tomography (FPDCT was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT. Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1 protein expression. Results Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071 and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.. Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients. Conclusion

  2. Discrete cyclic di-GMP-dependent control of bacterial predation versus axenic growth in Bdellovibrio bacteriovorus.

    Directory of Open Access Journals (Sweden)

    Laura Hobley

    2012-02-01

    Full Text Available Bdellovibrio bacteriovorus is a Delta-proteobacterium that oscillates between free-living growth and predation on Gram-negative bacteria including important pathogens of man, animals and plants. After entering the prey periplasm, killing the prey and replicating inside the prey bdelloplast, several motile B. bacteriovorus progeny cells emerge. The B. bacteriovorus HD100 genome encodes numerous proteins predicted to be involved in signalling via the secondary messenger cyclic di-GMP (c-di-GMP, which is known to affect bacterial lifestyle choices. We investigated the role of c-di-GMP signalling in B. bacteriovorus, focussing on the five GGDEF domain proteins that are predicted to function as diguanylyl cyclases initiating c-di-GMP signalling cascades. Inactivation of individual GGDEF domain genes resulted in remarkably distinct phenotypes. Deletion of dgcB (Bd0742 resulted in a predation impaired, obligately axenic mutant, while deletion of dgcC (Bd1434 resulted in the opposite, obligately predatory mutant. Deletion of dgcA (Bd0367 abolished gliding motility, producing bacteria capable of predatory invasion but unable to leave the exhausted prey. Complementation was achieved with wild type dgc genes, but not with GGAAF versions. Deletion of cdgA (Bd3125 substantially slowed predation; this was restored by wild type complementation. Deletion of dgcD (Bd3766 had no observable phenotype. In vitro assays showed that DgcA, DgcB, and DgcC were diguanylyl cyclases. CdgA lacks enzymatic activity but functions as a c-di-GMP receptor apparently in the DgcB pathway. Activity of DgcD was not detected. Deletion of DgcA strongly decreased the extractable c-di-GMP content of axenic Bdellovibrio cells. We show that c-di-GMP signalling pathways are essential for both the free-living and predatory lifestyles of B. bacteriovorus and that obligately predatory dgcC- can be made lacking a propensity to survive without predation of bacterial pathogens and thus possibly

  3. Density-dependent effects on growth, body size, and clutch size in Black Brant

    Science.gov (United States)

    Sedinger, James S.; Lindberg, Mark S.; Person, Brian T.; Eichholz, Michael W.; Herzog, Mark P.; Flint, Paul L.

    1998-01-01

    We documented gosling size in late summer, adult body size, and clutch size of known-age Black Brant (Branta bernicla nigricans) females nesting on the Tutakoke River colony between 1986 and 1995. During this period, the colony increased from 1,100 to >5,000 nesting pairs. Gosling mass at 30 days of age declined from 764 ± SE of 13 g and 723 ± 15 g for males and females, respectively, in the 1986 cohort, to 665 ± 18 g and 579 ± 18 g in the 1994 cohort. Gosling size was directly negatively correlated with number of Black Brant broods. We detected no trend in adult body size for individuals from these cohorts; in fact, adults from the 1992 and 1994 cohorts had the largest overall masses. Clutch size increased with age from 3.4 eggs for 2-year-old females to 4.4 eggs for 5-year-old females. Clutch size declined during the study by 0.20 (3-year-old females) to 0.45 (2-year-old females) eggs. Clutch size did not decline between the 1986 and 1990 cohorts for females that were >5 years old. Our results for clutch size and gosling size are similar to those recorded for Lesser Snow Geese (Chen caerulescens caerulescens). Our failure to detect a trend in adult body size, however, differs from the response of other geese to increasing population density. We interpret this difference in effects of density on adult size between Black Brant and other geese as an indication of stronger selection against the smallest individuals in Black Brant relative to other species of geese.

  4. Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2.

    Science.gov (United States)

    Liu, J; Liu, Z; Gao, L; Chen, L; Zhang, H

    2016-10-01

    The objective of the present study was to investigate the intestinal development of newborn intrauterine growth-restricted (IUGR) piglets subjected to normal nutrient intake (NNI) or restricted nutrient intake (RNI). Newborn normal birth weight (NBW) and IUGR piglets were allotted to NNI or RNI levels for 4 weeks from day 8 postnatal. IUGR piglets receiving NNI had similar growth performance compared with that of NBW piglets. Small intestine length and villous height were greater in IUGR piglets fed the NNI than that of piglets fed the RNI. Lactase activity was increased in piglets fed the NNI compared with piglets fed the RNI. Absorptive function, represented by active glucose transport by the Ussing chamber method and messenger RNA (mRNA) expressions of two main intestinal glucose transporters, Na+-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), were greater in IUGR piglets fed the NNI compared with piglets fed the RNI regimen. The apoptotic process, characterized by caspase-3 activity (a sign of activated apoptotic cells) and mRNA expressions of p53 (pro-apoptotic), bcl-2-like protein 4 (Bax) (pro-apoptotic) and B-cell lymphoma-2 (Bcl-2) (anti-apoptotic), were improved in IUGR piglets fed the NNI regimen. To test the hypothesis that improvements in intestinal development of IUGR piglets fed NNI might be mediated through circulating glucagon-like peptide-2 (GLP-2), GLP-2 was injected subcutaneously to IUGR piglets fed the RNI from day 8 to day 15 postnatal. Although the intestinal development of IUGR piglets fed the RNI regimen was suppressed compared with those fed the NNI regimen, an exogenous injection of GLP-2 was able to bring intestinal development to similar levels as NNI-fed IUGR piglets. Collectively, our results demonstrate that IUGR neonates that have NNI levels could improve intestinal function via the regulation of GLP-2.

  5. Host factor I, Hfq, binds to Escherichia coli ompA mRNA in a growth rate-dependent fashion and regulates its stability

    DEFF Research Database (Denmark)

    Vytvytska, O; Jakobsen, J S; Balcunaite, G

    1998-01-01

    RNA. In hfq mutant cells with a deficient Hfq gene product, the RNA-binding activity is missing, and analysis of the ompA mRNA showed that the growth-rate dependence of degradation is lost. Furthermore, the half-life of the ompA mRNA is prolonged in the mutant cells, irrespective of growth rate. Hfq has...

  6. Brassinolide Increases Potato Root Growth In Vitro in a Dose-Dependent Way and Alleviates Salinity Stress

    Directory of Open Access Journals (Sweden)

    Yueqing Hu

    2016-01-01

    Full Text Available Brassinosteroids (BRs are steroidal phytohormones that regulate various physiological processes, such as root development and stress tolerance. In the present study, we showed that brassinolide (BL affects potato root in vitro growth in a dose-dependent manner. Low BL concentrations (0.1 and 0.01 μg/L promoted root elongation and lateral root development, whereas high BL concentrations (1–100 μg/L inhibited root elongation. There was a significant (P<0.05 positive correlation between root activity and BL concentrations within a range from 0.01 to 100 μg/L, with the peak activity of 8.238 mg TTC·g−1 FW·h−1 at a BL concentration of 100 μg/L. Furthermore, plants treated with 50 μg/L BL showed enhanced salt stress tolerance through in vitro growth. Under this scenario, BL treatment enhanced the proline content and antioxidant enzymes’ (superoxide dismutase, peroxidase, and catalase activity and reduced malondialdehyde content in potato shoots. Application of BL maintain K+ and Na+ homeostasis by improving tissue K+/Na+ ratio. Therefore, we suggested that the effects of BL on root development from stem fragments explants as well as on primary root development are dose-dependent and that BL application alleviates salt stress on potato by improving root activity, root/shoot ratio, and antioxidative capacity in shoots and maintaining K+/Na+ homeostasis in potato shoots and roots.

  7. Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Martowicz Agnieszka

    2012-10-01

    Full Text Available Abstract Background The epithelial cell adhesion molecule (EpCAM has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. Methods For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAMhigh breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3. Moreover, EpCAMlow breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. Results In comparison to non-specific silencing controls (n/s-crtl knockdown of EpCAM (E#2 in EpCAMhigh cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAMlow cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. Conclusions The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer.

  8. Global alterations of the transcriptional landscape during yeast growth and development in the absence of Ume6-dependent chromatin modification.

    Science.gov (United States)

    Lardenois, Aurélie; Becker, Emmanuelle; Walther, Thomas; Law, Michael J; Xie, Bingning; Demougin, Philippe; Strich, Randy; Primig, Michael

    2015-10-01

    Chromatin modification enzymes are important regulators of gene expression and some are evolutionarily conserved from yeast to human. Saccharomyces cerevisiae is a major model organism for genome-wide studies that aim at the identification of target genes under the control of conserved epigenetic regulators. Ume6 interacts with the upstream repressor site 1 (URS1) and represses transcription by recruiting both the conserved histone deacetylase Rpd3 (through the co-repressor Sin3) and the chromatin-remodeling factor Isw2. Cells lacking Ume6 are defective in growth, stress response, and meiotic development. RNA profiling studies and in vivo protein-DNA binding assays identified mRNAs or transcript isoforms that are directly repressed by Ume6 in mitosis. However, a comprehensive understanding of the transcriptional alterations, which underlie the complex ume6Δ mutant phenotype during fermentation, respiration, or sporulation, is lacking. We report the protein-coding transcriptome of a diploid MAT a/α wild-type and ume6/ume6 mutant strains cultured in rich media with glucose or acetate as a carbon source, or sporulation-inducing medium. We distinguished direct from indirect effects on mRNA levels by combining GeneChip data with URS1 motif predictions and published high-throughput in vivo Ume6-DNA binding data. To gain insight into the molecular interactions between successive waves of Ume6-dependent meiotic genes, we integrated expression data with information on protein networks. Our work identifies novel Ume6 repressed genes during growth and development and reveals a strong effect of the carbon source on the derepression pattern of transcripts in growing and developmentally arrested ume6/ume6 mutant cells. Since yeast is a useful model organism for chromatin-mediated effects on gene expression, our results provide a rich source for further genetic and molecular biological work on the regulation of cell growth and cell differentiation in eukaryotes.

  9. Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

    International Nuclear Information System (INIS)

    Martowicz, Agnieszka; Spizzo, Gilbert; Gastl, Guenther; Untergasser, Gerold

    2012-01-01

    The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAM high breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAM low breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAM high cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAM low cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer

  10. Novel Oncogenic Mutations of CBL in Human Acute Myeloid Leukemia That Activate Growth and Survival Pathways Depend on Increased Metabolism*

    Science.gov (United States)

    Fernandes, Margret S.; Reddy, Mamatha M.; Croteau, Nicole J.; Walz, Christoph; Weisbach, Henry; Podar, Klaus; Band, Hamid; Carroll, Martin; Reiter, Andreas; Larson, Richard A.; Salgia, Ravi; Griffin, James D.; Sattler, Martin

    2010-01-01

    Acute myeloid leukemia (AML) is characterized by multiple mutagenic events that affect proliferation, survival, as well as differentiation. Recently, gain-of-function mutations in the α helical structure within the linker sequence of the E3 ubiquitin ligase CBL have been associated with AML. We identified four novel CBL mutations, including a point mutation (Y371H) and a putative splice site mutation in AML specimens. Characterization of these two CBL mutants revealed that coexpression with the receptor tyrosine kinases FLT3 (Fms-like tyrosine kinase 3) or KIT-induced ligand independent growth or ligand hyperresponsiveness, respectively. Growth of cells expressing mutant CBL required expression and kinase activity of FLT3. In addition to the CBL-dependent phosphorylation of FLT3 and CBL itself, transformation was associated with activation of Akt and STAT5 and required functional expression of the small GTPases Rho, Rac, and Cdc42. Furthermore, the mutations led to constitutively elevated intracellular reactive oxygen species levels, which is commonly linked to increased glucose metabolism in cancer cells. Inhibition of hexokinase with 2-deoxyglucose blocked the transforming activity of CBL mutants and reduced activation of signaling mechanisms. Overall, our data demonstrate that mutations of CBL alter cellular biology at multiple levels and require not only the activation of receptor proximal signaling events but also an increase in cellular glucose metabolism. Pathways that are activated by CBL gain-of-function mutations can be efficiently targeted by small molecule drugs. PMID:20622007

  11. SIRT3-dependent GOT2 acetylation status affects the malate–aspartate NADH shuttle activity and pancreatic tumor growth

    Science.gov (United States)

    Yang, Hui; Zhou, Lisha; Shi, Qian; Zhao, Yuzheng; Lin, Huaipeng; Zhang, Mengli; Zhao, Shimin; Yang, Yi; Ling, Zhi-Qiang; Guan, Kun-Liang; Xiong, Yue; Ye, Dan

    2015-01-01

    The malate–aspartate shuttle is indispensable for the net transfer of cytosolic NADH into mitochondria to maintain a high rate of glycolysis and to support rapid tumor cell growth. The malate–aspartate shuttle is operated by two pairs of enzymes that localize to the mitochondria and cytoplasm, glutamate oxaloacetate transaminases (GOT), and malate dehydrogenases (MDH). Here, we show that mitochondrial GOT2 is acetylated and that deacetylation depends on mitochondrial SIRT3. We have identified that acetylation occurs at three lysine residues, K159, K185, and K404 (3K), and enhances the association between GOT2 and MDH2. The GOT2 acetylation at these three residues promotes the net transfer of cytosolic NADH into mitochondria and changes the mitochondrial NADH/NAD+ redox state to support ATP production. Additionally, GOT2 3K acetylation stimulates NADPH production to suppress ROS and to protect cells from oxidative damage. Moreover, GOT2 3K acetylation promotes pancreatic cell proliferation and tumor growth in vivo. Finally, we show that GOT2 K159 acetylation is increased in human pancreatic tumors, which correlates with reduced SIRT3 expression. Our study uncovers a previously unknown mechanism by which GOT2 acetylation stimulates the malate–aspartate NADH shuttle activity and oxidative protection. PMID:25755250

  12. SIRT3-dependent GOT2 acetylation status affects the malate-aspartate NADH shuttle activity and pancreatic tumor growth.

    Science.gov (United States)

    Yang, Hui; Zhou, Lisha; Shi, Qian; Zhao, Yuzheng; Lin, Huaipeng; Zhang, Mengli; Zhao, Shimin; Yang, Yi; Ling, Zhi-Qiang; Guan, Kun-Liang; Xiong, Yue; Ye, Dan

    2015-04-15

    The malate-aspartate shuttle is indispensable for the net transfer of cytosolic NADH into mitochondria to maintain a high rate of glycolysis and to support rapid tumor cell growth. The malate-aspartate shuttle is operated by two pairs of enzymes that localize to the mitochondria and cytoplasm, glutamate oxaloacetate transaminases (GOT), and malate dehydrogenases (MDH). Here, we show that mitochondrial GOT2 is acetylated and that deacetylation depends on mitochondrial SIRT3. We have identified that acetylation occurs at three lysine residues, K159, K185, and K404 (3K), and enhances the association between GOT2 and MDH2. The GOT2 acetylation at these three residues promotes the net transfer of cytosolic NADH into mitochondria and changes the mitochondrial NADH/NAD(+) redox state to support ATP production. Additionally, GOT2 3K acetylation stimulates NADPH production to suppress ROS and to protect cells from oxidative damage. Moreover, GOT2 3K acetylation promotes pancreatic cell proliferation and tumor growth in vivo. Finally, we show that GOT2 K159 acetylation is increased in human pancreatic tumors, which correlates with reduced SIRT3 expression. Our study uncovers a previously unknown mechanism by which GOT2 acetylation stimulates the malate-aspartate NADH shuttle activity and oxidative protection. © 2015 The Authors.

  13. Growth hormone-insulin-like growth factor-I axis in adult insulin-dependent diabetic patients: evidence for central hypersensitivity to growth hormone-releasing hormone and peripheral resistance to growth hormone.

    Science.gov (United States)

    Fainstein Day, P; Fagin, J A; Vaglio, R M; Litwak, L E; Picasso, M F; Gutman, R A

    1998-12-01

    The aim of this study was to assess the GH-IGFI axis, GH receptor availability, as reflected by the levels of GH-BP, and the amount of GH-dependent IGFBP-3 in adult IDDM patients with different degrees of metabolic control. Thus, 10 adult well-controlled IDDMs (HbA1 7.8 +/- 0.4%), 10 adult non-ketotic poorly controlled IDDMs (HbA1 13.3 +/- 7%) and 14 sex- and age-matched healthy controls were subjected to two intravenous GH-RH stimulation tests with 0.1 and 1.0 microg/kg body weight respectively, and a plasma IGF-1 generation test induced by the administration of hGH. Poorly controlled IDDM patients exhibited an exaggerated GH response to 1.0 microg/kg of GH-RH when compared to healthy control subjects. Low fasting plasma IGF-1 levels and a blunted IGF-1 response to exogenously administered hGH were also found in poorly controlled IDDMs when compared to the healthy control group. GH-BP levels were significantly lower in IDDMs than in normal controls, and correlated positively with the IGF-1 generation capacity after hGH. Serum IGFBP-3 levels measured by RIA were similar in IDDM and control groups. Good glycemic control for 5.7 +/- 0.9 months did not correct the above mentioned abnormalities of the GH-IGF-1 axis. Our findings suggest that IDDM is associated with a diminished availability of GH receptors and synthesis of IGF-1. GH might then increase as a compensatory mechanism, further down-regulating liver GH receptors, and thus perpetuating the initial abnormality.

  14. Growth medium-dependent regulation of Myxococcus xanthus fatty acid content is controlled by the esg locus.

    Science.gov (United States)

    Bartholomeusz, G; Zhu, Y; Downard, J

    1998-10-01

    We compared the cellular fatty acid profiles of Myxococcus xanthus cells grown in either a Casitone-based complex medium or a chemically defined medium. The cells grown in the complex medium had a much higher content of the abundant branched-chain fatty acid iso-15:0 and several other branched-chain species. The higher branched-chain fatty acid content of the cells grown in the complex medium was dependent on the esg locus, which encodes the E1alpha and E1beta components of a branched-chain keto acid dehydrogenase (BCKAD) multienzyme complex involved in branched-chain fatty acid biosynthesis. Cells grown in the complex medium were also found to have a higher level of esg transcription and more BCKAD enzyme activity than cells from the chemically defined medium. The level of esg transcription appears to be an important factor in the growth medium-dependent regulation of the M. xanthus branched-chain fatty acid content.

  15. Brassinolide Increases Potato Root GrowthIn Vitroin a Dose-Dependent Way and Alleviates Salinity Stress.

    Science.gov (United States)

    Hu, Yueqing; Xia, Shitou; Su, Yi; Wang, Huiqun; Luo, Weigui; Su, Shengying; Xiao, Langtao

    2016-01-01

    Brassinosteroids (BRs) are steroidal phytohormones that regulate various physiological processes, such as root development and stress tolerance. In the present study, we showed that brassinolide (BL) affects potato root in vitro growth in a dose-dependent manner. Low BL concentrations (0.1 and 0.01  μ g/L) promoted root elongation and lateral root development, whereas high BL concentrations (1-100  μ g/L) inhibited root elongation. There was a significant ( P enzymes' (superoxide dismutase, peroxidase, and catalase) activity and reduced malondialdehyde content in potato shoots. Application of BL maintain K + and Na + homeostasis by improving tissue K + /Na + ratio. Therefore, we suggested that the effects of BL on root development from stem fragments explants as well as on primary root development are dose-dependent and that BL application alleviates salt stress on potato by improving root activity, root/shoot ratio, and antioxidative capacity in shoots and maintaining K + /Na + homeostasis in potato shoots and roots.

  16. Insulin-like Growth Factor-Dependent Proliferation and Survival of Triple-Negative Breast Cancer Cells: Implications for Therapy

    Directory of Open Access Journals (Sweden)

    Zoë Davison

    2011-06-01

    Full Text Available Triple-negative breast cancers have a poor prognosis and are not amenable to endocrine- or HER2-targeted therapies. The prevailing view is that targeting the insulin-like growth factor (IGF signal transduction pathway will not be beneficial for triple-negative breast cancers because their growth is not IGF-responsive. The present study investigates the importance of IGFs in the proliferation and survival of triple-negative breast cancer cells. Estrogen and progesterone receptors, HER2, type I IGF, and insulin receptors were measured by Western transfer analysis. The effects of IGF-1 on proliferation were assessed by DNA quantitation and on cell survival by poly (ADP-ribose polymerase cleavage. The effect of IGF-1 on phosphorylation of the IGF receptors, Akt and mitogen-activated protein kinase, was measured by Western transfer analysis. Seven cell lines were identified as models of triple-negative breast cancer and shown to express IGF receptors at levels similar to those present in estrogen-responsive cell lines known to respond to IGFs. IGF-1 increased the proliferation and cell survival of all triple-negative cell lines. Proliferation was attenuated after reduction of type I IGF receptor expression. Cells that express higher levels of receptor were more sensitive to subnanomolar IGF-1 concentrations, but the magnitude of the effects was not correlated simply with the absolute amount or phosphorylation of the IGF receptors, Akt or mitogen-activated protein kinase. These results show that IGFs stimulate cell proliferation and promote cell survival in triple-negative breast cancer cells and warrant investigation of the IGF signal transduction pathway as a therapeutic target for the treatment of triple-negative breast cancer.

  17. Implications of late-in-life density-dependent growth for fishery size-at-entry leading to maximum sustainable yield

    DEFF Research Database (Denmark)

    van Gemert, Rob; Andersen, Ken Haste

    2018-01-01

    Currently applied fisheries models and stock assessments rely on the assumption that density-dependent regulation only affects processes early in life, as described by stock–recruitment relationships. However, many fish stocks also experience density-dependent processes late in life......, such as density-dependent adult growth. Theoretical studies have found that, for stocks which experience strong late-in-life density dependence, maximum sustainable yield (MSY) is obtained with a small fishery size-at-entry that also targets juveniles. This goes against common fisheries advice, which dictates...... that primarily adults should be fished. This study aims to examine whether the strength of density-dependent growth in actual fish stocks is sufficiently strong to reduce optimal fishery size-at-entry to below size-at-maturity. A size-structured model is fitted to three stocks that have shown indications of late-in-life...

  18. Mycorrhizal symbiosis effects on growth of chalk false-brome (Brachypodium pinnatum) are dependent on the environmental light regime.

    Science.gov (United States)

    Füzy, Anna; Bothe, Hermann; Molnár, Edit; Biró, Borbála

    2014-03-01

    AMF (arbuscular mycorrhizal fungi) colonization of the grass chalk false-brome (Brachypodium pinnatum (L.) P. B.) was studied in selected habitats under spatially different light regimes: (a) shade condition under oak trees, (b) half shade in a shrubby area and (c) full-sun conditions on unshaded grassland. This study assessed the variations in AMF colonization of the grass dependent on the light supply in field habitats. Soil, root and shoot samples were collected four times during the vegetation period (in June, July, September and October). Root colonization, root and shoot biomass as well as soil water content were determined. The highest rate of AMF colonization was detected in June under half-sun and full-sun conditions, where about 50% of the roots were colonized. The average amount of arbuscules was less than 20% in the roots at the three sites, with the highest number of arbuscules in June, under half-sun and full-sun conditions, however, not under the trees. Overall, best mycorrhizal colonization occurred during summer, and its rate decreased in autumn. This tendency inversely correlated with the amount of precipitation, and thus with the water content of soils. The high colonization rate of the examined root samples, and also its seasonal fluctuation, might reflect the importance of the symbiosis where inorganic nutrients and water are the growth-limiting factors. The marginal AMF colonization of chalk false-brome under shade conditions indicates that plants do not use AMF under all stress conditions. When low light limits photosynthesis and thus growth of the plants, they dispense with the colonization of AMF in order to save the expenditure of organic carbon. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. A thermal-electrochemical model that gives spatial-dependent growth of solid electrolyte interphase in a Li-ion battery

    Science.gov (United States)

    Liu, Lin; Park, Jonghyun; Lin, Xianke; Sastry, Ann Marie; Lu, Wei

    2014-12-01

    The formation of a SEI layer and its growth cause internal resistance increase and capacity loss, leading to performance degradation of lithium-ion batteries. In order to comprehensively investigate the effects of SEI growth on battery performance, a one-dimensional thermal-electrochemical model was developed. This model is equipped with a growth mechanism of the SEI layer coupled with thermal evolution, based on the diffusional process of the solvent through the SEI layer and the kinetic process at the interface between the solid and liquid phases. The model is able to reveal the effects of diffusivity, reaction kinetics and temperature on SEI layer growth and cell capacity fade. We show that depending on the SEI thickness, the growth can be kinetics-limited or diffusion-limited. With the layer becoming thicker, its growth rate slows down gradually due to increased diffusion resistance. The SEI layer grows faster during charge than discharge due to the difference in the electron flux through the SEI layer and the temperature change during cycling. Temperature rise due to reaction and joule heating accelerates the SEI layer growth, leading to more capacity loss. Our model can provide insights on position-dependent SEI growth rate and be used to guide the strategic monitoring location.

  20. Proteomic analysis of Clostridium thermocellum core metabolism: relative protein expression profiles and growth phase-dependent changes in protein expression

    Directory of Open Access Journals (Sweden)

    Rydzak Thomas

    2012-09-01

    Full Text Available Abstract Background Clostridium thermocellum produces H2 and ethanol, as well as CO2, acetate, formate, and lactate, directly from cellulosic biomass. It is therefore an attractive model for biofuel production via consolidated bioprocessing. Optimization of end-product yields and titres is crucial for making biofuel production economically feasible. Relative protein expression profiles may provide targets for metabolic engineering, while understanding changes in protein expression and metabolism in response to carbon limitation, pH, and growth phase may aid in reactor optimization. We performed shotgun 2D-HPLC-MS/MS on closed-batch cellobiose-grown exponential phase C. thermocellum cell-free extracts to determine relative protein expression profiles of core metabolic proteins involved carbohydrate utilization, energy conservation, and end-product synthesis. iTRAQ (isobaric tag for relative and absolute quantitation based protein quantitation was used to determine changes in core metabolic proteins in response to growth phase. Results Relative abundance profiles revealed differential levels of putative enzymes capable of catalyzing parallel pathways. The majority of proteins involved in pyruvate catabolism and end-product synthesis were detected with high abundance, with the exception of aldehyde dehydrogenase, ferredoxin-dependent Ech-type [NiFe]-hydrogenase, and RNF-type NADH:ferredoxin oxidoreductase. Using 4-plex 2D-HPLC-MS/MS, 24% of the 144 core metabolism proteins detected demonstrated moderate changes in expression during transition from exponential to stationary phase. Notably, proteins involved in pyruvate synthesis decreased in stationary phase, whereas proteins involved in glycogen metabolism, pyruvate catabolism, and end-product synthesis increased in stationary phase. Several proteins that may directly dictate end-product synthesis patterns, including pyruvate:ferredoxin oxidoreductases, alcohol dehydrogenases, and a putative

  1. The NADP+-dependent glutamate dehydrogenase of the yeast Kluyveromyces marxianus responds to nitrogen repression similarly to Saccharomyces cerevisiae Glutamato desidrogenase dependente de NADP+ da levedura Kluyveromyces marxianus responde à repressão catabólica de maneira similar à Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Marcos Antonio de Morais-Júnior

    2003-12-01

    Full Text Available NADP+-dependent glutamate dehydrogenase (NADP+-Gdh is the first step in ammonia assimilation pathway in Saccharomyces cerevisiae and the knowledge of its regulation is the key for many biotechnological purposes such as single cell protein production. The regulation of NADP+-Gdh activity in Kluyveromyces marxianus cells was evaluated under different ammonia supply in batch cultivations. The results showed that K. marxianus NADP+-Gdh activity is induced over a narrow range of extracellular ammonia supply, being repressed by both high ammonia concentration and the glutamate formed. This activity is not growth-associated and may function mainly to trace low amounts of ammonia after growth cessation. The results demonstrated that NADP+-Gdh may not be the main enzyme for ammonia assimilation in K. marxianus, as it has been postulated for K. lactis, instead is subjected to the same regulatory mechanism described for S. cerevisiae.Glutamato desidrogenase dependente de NADP+ (NADP+-Gdh constitui o primeiro passo enzimático no mecanismo de assimilação de nitrogênio em Saccharomyces cerevisiae e o conhecimento de sua regulação é chave na iniciativa de vários propósitos biotecnológicos, tais como a produção de proteína microbiana. A regulação da atividade NADP+-Gdh em células de Kluyveromyces marxianus foi avaliada a partir de diferentes condições de suprimento de amonia em cultivo em batelada. Os resultados mostraram que a atividade NADP+-Gdh de K. marxianus foi induzida em uma estreita faixa de concentração de amonia no meio, sendo reprimida tanto por altas concentrações deste composto quanto pelo produto glutamato. Esta atividade não está associada ao crescimento celular e deve funcionar principalmente no rastreamento de pequenas quantidades de amonia após a parada do crescimento celular. Isto demonstra que NADP+-Gdh não deve ser a principal enzima de assimilação de amonia em K. marxianus, como tem sido postulado para K

  2. Xenoestrogens modulate vascular endothelial growth factor secretion in breast cancer cells through an estrogen receptor-dependent mechanism.

    Science.gov (United States)

    Buteau-Lozano, Hélène; Velasco, Guillaume; Cristofari, Monique; Balaguer, Patrick; Perrot-Applanat, Martine

    2008-02-01

    Environmental chemicals may affect human health by disrupting endocrine function. Their possible role in the mammary gland and breast tumors is still unknown. Previous studies have demonstrated that vascular endothelial growth factor (VEGF), a key factor in angiogenesis and tumor progression, is an estrogen-regulated gene. We analyzed whether VEGF expression is regulated by different xenoestrogens in several breast cancer cells, MELN (derived from MCF-7) and MELP (derived from MDA-MB-231) and stably expressing estrogen receptor alpha (ERalpha); these cell lines stably express estrogen response element (beta-globin)-luciferase. Genistein, bisphenol A (BPA), 4-(tert-octyl)phenol (OP), dieldrin, and several phthalates, including benzyl butyl phthalate (BBP) and di-ethyl-2-hexyle phthalate (DEHP), were first shown to be estrogenic. These compounds induced a dose-dependent increase of VEGF secretion in MELN and MCF-7 cells; maximal effect was observed at 1-10 microM non-cytotoxic concentrations and was inhibited by the antiestrogen ICI 182 780. VEGF increase was not observed in ERalpha-negative MDA-MB-231 cells. Most substances increased VEGF transcript levels in MELN cells. In contrast, gamma-hexachlorocyclohexane, vinclozolin, and the phthalates (mono-n-butyl ester phthalic acid, di-isononyle phthalate, and di-isodecyle phthalate) were ineffective on both VEGF secretion and estrogenic luciferase induction in these cell lines. Specific kinase inhibitors PD98059, SB203580, or LY294002 suppressed the xenoestrogen-induced VEGF response, suggesting activation of MEK, p38 kinase, and phosphatidylinositol-3-kinase pathways. Our in vitro results show for the first time that genistein and xenoestrogens (BPA, OP, dieldrin, BBP, and DEHP at high concentrations) up-regulate VEGF expression in MELN cells by an ER-dependent mechanism. Since VEGF increases capillary permeability and breast tumor angiogenesis in vivo, the physiological relevance of these findings is discussed.

  3. Dose-dependent functions of fibroblast growth factor 9 regulate the fate of murine XY primordial germ cells†

    Science.gov (United States)

    Ulu, Ferhat; Kim, Sung-Min; Yokoyama, Toshifumi; Yamazaki, Yukiko

    2017-01-01

    Abstract Male differentiation of primordial germ cells (PGCs) is initiated by the inhibition of entry into meiosis and exposure to male-inducing factor(s), which are regulated by somatic elements of the developing gonad. Fibroblast growth factor 9 (FGF9) produced by pre-Sertoli cells is essential for male gonadal differentiation and also contributes to survival and male differentiation of XY PGCs. However, it is not clear how FGF9 regulates PGC fate. Using a PGC culture system, we identified dose-dependent, fate-determining functions of FGF9 in XY PGCs. Treatment with low levels of FGF9 (0.2 ng/ml) increased expression of male-specific Dnmt3L and Nanos2 in XY PGCs. Conversely, treatment with high levels of FGF9 (25 ng/ml) suppressed male-specific gene expression and stimulated proliferation of XY PGCs. Western blotting showed that low FGF9 treatment enhanced p38 MAPK (mitogen-activated protein kinase) phosphorylation in the same cells. In contrast, high FGF9 treatment significantly stimulated the ERK (extracellular signal-regulated kinase)1/2 signaling pathway in XY PGCs. We investigated the relationship between the ERK1/2 signaling pathway stimulated by high FGF9 and regulation of PGC proliferation. An ERK1/2 inhibitor (U0126) suppressed the PGC proliferation that would otherwise be stimulated by high FGF9 treatment, and increased Nanos2 expression in XY PGCs. Conversely, a p38 MAPK inhibitor (SB202190) significantly suppressed Nanos2 expression that would otherwise be stimulated by low FGF9 in XY PGCs. Taken together, our results suggest that stage-specific expression of FGF9 in XY gonads regulates the balance between proliferation and differentiation of XY PGCs in a dose-dependent manner. PMID:28395336

  4. Dose-dependent functions of fibroblast growth factor 9 regulate the fate of murine XY primordial germ cells.

    Science.gov (United States)

    Ulu, Ferhat; Kim, Sung-Min; Yokoyama, Toshifumi; Yamazaki, Yukiko

    2017-01-01

    Male differentiation of primordial germ cells (PGCs) is initiated by the inhibition of entry into meiosis and exposure to male-inducing factor(s), which are regulated by somatic elements of the developing gonad. Fibroblast growth factor 9 (FGF9) produced by pre-Sertoli cells is essential for male gonadal differentiation and also contributes to survival and male differentiation of XY PGCs. However, it is not clear how FGF9 regulates PGC fate. Using a PGC culture system, we identified dose-dependent, fate-determining functions of FGF9 in XY PGCs. Treatment with low levels of FGF9 (0.2 ng/ml) increased expression of male-specific Dnmt3L and Nanos2 in XY PGCs. Conversely, treatment with high levels of FGF9 (25 ng/ml) suppressed male-specific gene expression and stimulated proliferation of XY PGCs. Western blotting showed that low FGF9 treatment enhanced p38 MAPK (mitogen-activated protein kinase) phosphorylation in the same cells. In contrast, high FGF9 treatment significantly stimulated the ERK (extracellular signal-regulated kinase)1/2 signaling pathway in XY PGCs. We investigated the relationship between the ERK1/2 signaling pathway stimulated by high FGF9 and regulation of PGC proliferation. An ERK1/2 inhibitor (U0126) suppressed the PGC proliferation that would otherwise be stimulated by high FGF9 treatment, and increased Nanos2 expression in XY PGCs. Conversely, a p38 MAPK inhibitor (SB202190) significantly suppressed Nanos2 expression that would otherwise be stimulated by low FGF9 in XY PGCs. Taken together, our results suggest that stage-specific expression of FGF9 in XY gonads regulates the balance between proliferation and differentiation of XY PGCs in a dose-dependent manner. © The Author 2016. Published by Oxford University Press on behalf of Society for the Study of Reproduction.

  5. Renewing the Respect for Similarity

    Directory of Open Access Journals (Sweden)

    Shimon eEdelman

    2012-07-01

    Full Text Available In psychology, the concept of similarity has traditionally evoked a mixture of respect, stemmingfrom its ubiquity and intuitive appeal, and concern, due to its dependence on the framing of the problemat hand and on its context. We argue for a renewed focus on similarity as an explanatory concept, bysurveying established results and new developments in the theory and methods of similarity-preservingassociative lookup and dimensionality reduction — critical components of many cognitive functions, aswell as of intelligent data management in computer vision. We focus in particular on the growing familyof algorithms that support associative memory by performing hashing that respects local similarity, andon the uses of similarity in representing structured objects and scenes. Insofar as these similarity-basedideas and methods are useful in cognitive modeling and in AI applications, they should be included inthe core conceptual toolkit of computational neuroscience.

  6. Parathyroid hormone linked to a collagen binding domain promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner.

    Science.gov (United States)

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Seymour, Andrew; Sakon, Joshua; Gensure, Robert

    2014-08-01

    Chemotherapy-induced alopecia is a major source of psychological stress in patients undergoing cancer chemotherapy, and it can influence treatment decisions. Although there is currently no therapy for alopecia, a fusion protein of parathyroid hormone and collagen binding domain (PTH-CBD) has shown promise in animal models. The aim of this study was to determine whether there are dose-dependent effects of PTH-CBD on chemotherapy-induced alopecia in a mouse model. C57BL/6J mice were waxed to synchronize hair follicles; treated on day 7 with vehicle or PTH-CBD (100, 320, and 1000 mcg/kg subcutaneous injection); and treated on day 9 with vehicle or cyclophosphamide (150 mg/kg intraperitoneally). Mice were photographed every 3-4 days and killed on day 63 for histological analysis. Photographs were quantified by gray scale analysis to assess hair content. Mice not receiving chemotherapy showed regrowth of hair 2 weeks after waxing and normal histology after 2 months. Mice receiving chemotherapy alone showed marked hair loss after chemotherapy, which was sustained for 10 days and was followed by rapid regrowth of a normal coat. Histological analysis revealed rapid cycling dystrophic anagen/catagen follicles. Animals receiving chemotherapy and PTH-CBD showed decreased hair loss and more rapid regrowth of hair than that seen with chemotherapy alone (increased hair growth by gray scale analysis, Phair follicles in animals receiving the highest dose of PTH-CBD were in a quiescent phase, similar to that in mice that did not receive chemotherapy. Single-dose subcutaneous administration of PTH-CBD showed dose-dependent effects in minimizing hair loss and speeding up recovery from chemotherapy-induced alopecia.

  7. Host factor I, Hfq, binds to Escherichia coli ompA mRNA in a growth rate-dependent fashion and regulates its stability

    DEFF Research Database (Denmark)

    Vytvytska, O; Jakobsen, J S; Balcunaite, G

    1998-01-01

    ompA was purified and identified as Hfq, a host factor initially recognized for its function in phage Qbeta replication. The ompA RNA-binding activity parallels the amount of Hfq, which is elevated in bacteria cultured at slow growth rate, a condition leading to facilitated degradation of the ompA m...... suggest a regulatory role for Hfq that specifically facilitates the ompA mRNA degradation in a growth rate-dependent manner....

  8. Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.

    Directory of Open Access Journals (Sweden)

    Hanna Björkelund

    Full Text Available The interaction of the epidermal growth factor (EGF with its receptor (EGFR is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of (125I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®.Highly repeatable and precise measurements show that the overall apparent affinity of the (125I-EGF - EGFR interaction is greatly dependent on cell line at normal culturing conditions, ranging from K(D ≈ 200 pM on SKBR3 cells to K(D≈8 nM on A431 cells. The (125I-EGF - EGFR binding curves (irrespective of cell line have strong signs of multiple simultaneous interactions. Furthermore, for the cell lines A431 and SKOV3, gefitinib treatment increases the (125I-EGF - EGFR affinity, in particular when the cells are starved. The (125I-EGF - EGFR interaction on cell line U343 is sensitive to starvation while as on SKBR3 it is insensitive to gefitinib and starvation.The intriguing pattern of the binding characteristics proves that the cellular context is important when deciphering how EGF interacts with EGFR. From a general perspective, care is advisable when generalizing ligand-receptor interaction results across multiple cell-lines.

  9. Phosphorus and Iron Deficiencies Influences Rice Shoot Growth in an Oxygen Dependent Manner: Insight from Upland and Lowland Rice

    Directory of Open Access Journals (Sweden)

    Jenjira Mongon

    2017-03-01

    Full Text Available Rice is the main staple crop for one-third of the world population. To maximize yields, large quantities and constant input of fertilizers containing essential nutrients such as phosphorus (P and iron (Fe are added. Rice can germinate in both aerobic and anaerobic conditions, but the crosstalk between oxygen (O2 and nutrients such as P and Fe on plant growth remains obscure. The aim of this work was to test whether such interactions exist, and, if so, if they are conserved between up- and lowland rice varieties. To do so, we assessed shoot and root biomass as well as inorganic phosphate (Pi accumulation in four rice varieties, including two lowland rice varieties Nipponbare and Suphanburi 1 (SPR1 (adapted to non-aerated condition and two upland rice varieties CMU122 and Sew Mae Jun (SMJ (adapted to aerated condition under various conditions of Pi and/or Fe deficiencies, in aerated and non-areated solution. Under these different experimental conditions, our results revealed that the altered shoot biomass in Nipponbare and SPR1 was O2-dependent but to a lesser extent in CMU122 and SMJ cultivars. In this perspective, discovering the biological significance and molecular basis of these mineral elements and O2 signal interaction is needed to fully appreciate the performance of plants to multiple environmental changes.

  10. Temperature-Dependent Growth Modeling of Environmental and Clinical Legionella pneumophila Multilocus Variable-Number Tandem-Repeat Analysis (MLVA) Genotypes.

    Science.gov (United States)

    Sharaby, Yehonatan; Rodríguez-Martínez, Sarah; Oks, Olga; Pecellin, Marina; Mizrahi, Hila; Peretz, Avi; Brettar, Ingrid; Höfle, Manfred G; Halpern, Malka

    2017-04-15

    Legionella pneumophila causes waterborne infections resulting in severe pneumonia. High-resolution genotyping of L. pneumophila isolates can be achieved by multiple-locus variable-number tandem-repeat analysis (MLVA). Recently, we found that different MLVA genotypes of L. pneumophila dominated different sites in a small drinking-water network, with a genotype-related temperature and abundance regime. The present study focuses on understanding the temperature-dependent growth kinetics of the genotypes that dominated the water network. Our aim was to model mathematically the influence of temperature on the growth kinetics of different environmental and clinical L. pneumophila genotypes and to compare it with the influence of their ecological niches. Environmental strains showed a distinct temperature preference, with significant differences among the growth kinetics of the three studied genotypes (Gt4, Gt6, and Gt15). Gt4 strains exhibited superior growth at lower temperatures (25 and 30°C), while Gt15 strains appeared to be best adapted to relatively higher temperatures (42 and 45°C). The temperature-dependent growth traits of the environmental genotypes were consistent with their distribution and temperature preferences in the water network. Clinical isolates exhibited significantly higher growth rates and reached higher maximal cell densities at 37°C and 42°C than the environmental strains. Further research on the growth preferences of L. pneumophila clinical and environmental genotypes will result in a better understanding of their ecological niches in drinking-water systems as well as in the human body. IMPORTANCE Legionella pneumophila is a waterborne pathogen that threatens humans in developed countries. The bacteria inhabit natural and man-made freshwater environments. Here we demonstrate that different environmental L. pneumophila genotypes have different temperature-dependent growth kinetics. Moreover, Legionella strains that belong to the same species

  11. Kidney function and size in type 1 (insulin-dependent) diabetic patients before and during growth hormone administration for one week

    DEFF Research Database (Denmark)

    Christiansen, JS; Gammelgaard, J; Frandsen, M

    1982-01-01

    Kidney function and size were studied in seven well-controlled male Type 1 (insulin-dependent) diabetic patients before and after administration of highly purified human growth hormone for one week. Glomerular filtration rate, renal plasma flow (steady state infusion technique with urinary...... collections using 125I-iothalamate and 131I-hippuran), kidney size (ultrasonic scanning) and urinary excretion rates of albumin and beta-2-microglobulin were measured. Highly purified growth hormone was injected subcutaneously, 2 IU in the morning and 4 IU in the evening. The growth hormone dosage applied...... induced an elevation in plasma growth hormone concentration from the normal level seen in these very well controlled diabetics to levels within the range previously demonstrated in normally controlled Type 1 diabetic patients. During the week of growth hormone administration, glycaemic control...

  12. Time dependent physiological characterization of yeast oxidative stress response and growth modulation of protein kinase/phosphatase mutants

    DEFF Research Database (Denmark)

    Altintas, Ali; Workman, Christopher

    2013-01-01

    .25, 0.50 and 1.0 mM). Understanding the growth physiology of S. cerevisiae allows us to estimate the link between genotype and stress-response phenotype. Growth physiology parameters, such as growth rate, diauxic shift times, stress-induced stasis times, were measured in fermentative batch cultures...

  13. miRNA-34b as a tumor suppressor in estrogen-dependent growth of breast cancer cells

    Science.gov (United States)

    2011-01-01

    Introduction Estrogen is involved in several physiological and pathological processes through estrogen receptor (ER)-mediated transcriptional gene regulation. miRNAs (miRs), which are noncoding RNA genes, may respond to estrogen and serve as posttranscriptional regulators in tumorigenic progression, especially in breast cancer; however, only limited information about this possibility is available. In the present study, we identified the estrogen-regulated miR-34b and investigated its functional role in breast cancer progression. Methods Estrogen-regulated miRNAs were identified by using a TaqMan low density array. Our in vivo Tet-On system orthotopic model revealed the tumor-suppressive ability of miR-34b. Luciferase reporter assays and chromatin immunoprecipitation assay demonstrated miR-34b were regulated by p53-ER interaction. Results In this study, we identified one such estrogen downregulated miRNA, miR-34b, as an oncosuppressor that targets cyclin D1 and Jagged-1 (JAG1) in an ER+/wild-type p53 breast cancer cell line (MCF-7), as well as in ovarian and endometrial cells, but not in ER-negative or mutant p53 breast cancer cell lines (T47D, MBA-MB-361 and MDA-MB-435). There is a negative association between ERα and miR-34b expression levels in ER+ breast cancer patients. Tet-On induction of miR-34b can cause inhibition of tumor growth and cell proliferation. Also, the overexpression of miR-34b inhibited ER+ breast tumor growth in an orthotopic mammary fat pad xenograft mouse model. Further validation indicated that estrogen's inhibition of miR-34b expression was mediated by interactions between ERα and p53, not by DNA methylation regulation. The xenoestrogens diethylstilbestrol and zeranol also showed similar estrogenic effects by inhibiting miR-34b expression and by restoring the protein levels of the miR-34b targets cyclin D1 and JAG1 in MCF-7 cells. Conclusions These findings reveal that miR-34b is an oncosuppressor miRNA requiring both ER+ and wild-type p

  14. The Burkholderia bcpAIOB genes define unique classes of two-partner secretion and contact dependent growth inhibition systems.

    Science.gov (United States)

    Anderson, Melissa S; Garcia, Erin C; Cotter, Peggy A

    2012-01-01

    Microbes have evolved many strategies to adapt to changes in environmental conditions and population structures, including cooperation and competition. One apparently competitive mechanism is contact dependent growth inhibition (CDI). Identified in Escherichia coli, CDI is mediated by Two-Partner Secretion (TPS) pathway proteins, CdiA and CdiB. Upon cell contact, the toxic C-terminus of the TpsA family member CdiA, called the CdiA-CT, inhibits the growth of CDI(-) bacteria. CDI(+) bacteria are protected from autoinhibition by an immunity protein, CdiI. Bioinformatic analyses indicate that CDI systems are widespread amongst α, β, and γ proteobacteria and that the CdiA-CTs and CdiI proteins are highly variable. CdiI proteins protect against CDI in an allele-specific manner. Here we identify predicted CDI system-encoding loci in species of Burkholderia, Ralstonia and Cupriavidus, named bcpAIOB, that are distinguished from previously-described CDI systems by gene order and the presence of a small ORF, bcpO, located 5' to the gene encoding the TpsB family member. A requirement for bcpO in function of BcpA (the TpsA family member) was demonstrated, indicating that bcpAIOB define a novel class of TPS system. Using fluorescence microscopy and flow cytometry, we show that these genes are expressed in a probabilistic manner during culture of Burkholderia thailandensis in liquid medium. The bcpAIOB genes and extracellular DNA were required for autoaggregation and adherence to an abiotic surface, suggesting that CDI is required for biofilm formation, an activity not previously attributed to CDI. By contrast to what has been observed in E. coli, the B. thailandensis bcpAIOB genes only mediated interbacterial competition on a solid surface. Competition occurred in a defined spatiotemporal manner and was abrogated by allele-specific immunity. Our data indicate that the bcpAIOB genes encode distinct classes of CDI and TPS systems that appear to function in sociomicrobiological

  15. The Burkholderia bcpAIOB genes define unique classes of two-partner secretion and contact dependent growth inhibition systems.

    Directory of Open Access Journals (Sweden)

    Melissa S Anderson

    Full Text Available Microbes have evolved many strategies to adapt to changes in environmental conditions and population structures, including cooperation and competition. One apparently competitive mechanism is contact dependent growth inhibition (CDI. Identified in Escherichia coli, CDI is mediated by Two-Partner Secretion (TPS pathway proteins, CdiA and CdiB. Upon cell contact, the toxic C-terminus of the TpsA family member CdiA, called the CdiA-CT, inhibits the growth of CDI(- bacteria. CDI(+ bacteria are protected from autoinhibition by an immunity protein, CdiI. Bioinformatic analyses indicate that CDI systems are widespread amongst α, β, and γ proteobacteria and that the CdiA-CTs and CdiI proteins are highly variable. CdiI proteins protect against CDI in an allele-specific manner. Here we identify predicted CDI system-encoding loci in species of Burkholderia, Ralstonia and Cupriavidus, named bcpAIOB, that are distinguished from previously-described CDI systems by gene order and the presence of a small ORF, bcpO, located 5' to the gene encoding the TpsB family member. A requirement for bcpO in function of BcpA (the TpsA family member was demonstrated, indicating that bcpAIOB define a novel class of TPS system. Using fluorescence microscopy and flow cytometry, we show that these genes are expressed in a probabilistic manner during culture of Burkholderia thailandensis in liquid medium. The bcpAIOB genes and extracellular DNA were required for autoaggregation and adherence to an abiotic surface, suggesting that CDI is required for biofilm formation, an activity not previously attributed to CDI. By contrast to what has been observed in E. coli, the B. thailandensis bcpAIOB genes only mediated interbacterial competition on a solid surface. Competition occurred in a defined spatiotemporal manner and was abrogated by allele-specific immunity. Our data indicate that the bcpAIOB genes encode distinct classes of CDI and TPS systems that appear to function in

  16. Pollen Tube Growth Regulation by Free Anions Depends on the Interaction between the Anion Channel SLAH3 and Calcium-Dependent Protein Kinases CPK2 and CPK20.

    NARCIS (Netherlands)

    Gutermuth, T.; Lassig, R.; Portes, M.T.; Maierhofer, T.; Romeis, T.; Borst, J.W.; Hedrich, R.; Feijó, J.A.; Konrad, K.R.

    2013-01-01

    Apical growth in pollen tubes (PTs) is associated with the presence of tip-focused ion gradients and fluxes, implying polar localization or regulation of the underlying transporters. The molecular identity and regulation of anion transporters in PTs is unknown. Here we report a negative gradient of

  17. Antagonistic Growth Effects of Mercury and Selenium in Caenorhabditis elegans Are Chemical-Species-Dependent and Do Not Depend on Internal Hg/Se Ratios.

    Science.gov (United States)

    Wyatt, Lauren H; Diringer, Sarah E; Rogers, Laura A; Hsu-Kim, Heileen; Pan, William K; Meyer, Joel N

    2016-03-15

    The relationship between mercury (Hg) and selenium (Se) toxicity is complex, with coexposure reported to reduce, increase, and have no effect on toxicity. Different interactions may be related to chemical compound, but this has not been systematically examined. Our goal was to assess the interactive effects between the two elements on growth in the nematode Caenorhabditis elegans, focusing on inorganic and organic Hg (HgCl2 and MeHgCl) and Se (selenomethionine, sodium selenite, and sodium selenate) compounds. We utilized aqueous Hg/Se dosing molar ratios that were either above, below, or equal to 1 and measured the internal nematode total Hg and Se concentrations for the highest concentrations of each Se compound. Observed interactions were complicated, differed between Se and Hg compounds, and included greater-than-additive, additive, and less-than-additive growth impacts. Biologically significant interactions were only observed when the dosing Se solution concentration was 100-25,000 times greater than the dosing Hg concentration. Mitigation of growth impacts was not predictable on the basis of internal Hg/Se molar ratio; improved growth was observed at some internal Hg/Se molar ratios both above and below 1. These findings suggest that future assessments of the Hg and Se relationship should incorporate chemical compound into the evaluation.

  18. Concentration- and time-dependent response of human gingival fibroblasts to fibroblast growth factor 2 immobilized on titanium dental implants.

    Science.gov (United States)

    Ma, Qianli; Wang, Wei; Chu, Paul K; Mei, Shenglin; Ji, Kun; Jin, Lei; Zhang, Yumei

    2012-01-01

    Titanium (Ti) implants are widely used clinically, but peri-implantitis remains one of the most common and serious complications. Healthy integration between gingival tissue and the implant surface is critical to long-term success in dental implant therapy. The objective of this study was to investigate how different concentrations of immobilized fibroblast growth factor 2 (FGF2) on the titania nanotubular surface influence the response of human gingival fibroblasts (HGFs). Pure Ti metal was anodized at 20 V to form a vertically organized titanium dioxide nanotube array on which three concentrations of FGF2 (250 ng/mL, 500 ng/mL, or 1000 ng/mL) were immobilized by repeated lyophilization. Surface topography was observed and FGF2 elution was detected using enzyme-linked immunosorbent assay. The bioactivity changes of dissolvable immobilized FGF2 were measured by methyl-thiazolyl-tetrazolium assay. Behavior of HGFs was evaluated using adhesion and methyl-thiazolyl-tetrazolium bromide assays. The FGF2 remained for several days on the modified surface on which HGFs were cultured. Over 90% of the dissolvable immobilized FGF2 had been eluted by Day 9, whereas the FGF2 activity was found to diminish gradually from Day 1 to Day 9. The titania nanotubular surface with an optimal preparing concentration (500 ng/mL) of FGF2 immobilization exhibited improved HGF functions such as cellular attachment, proliferation, and extracellular matrix-related gene expression. Moreover, significant bidirectional as well as concentration- and time-dependent bioactivity was observed. Synergism of the FGF2-impregnated titanium dioxide nanotubular surface revealed good gingival-implant integration, indicating that these materials might have promising applications in dentistry and other biomedical devices.

  19. Caspase dependent and independent mechanisms of apoptosis across gestation in a sheep model of placental insufficiency and intrauterine growth restriction.

    Science.gov (United States)

    Monson, Troy; Wright, Tanner; Galan, Henry L; Reynolds, Paul R; Arroyo, Juan A

    2017-05-01

    Increased placental apoptosis is a hallmark of intrauterine growth restricted (IUGR). Several molecules have been shown to be involved in the control of apoptosis during this disease. Our objective was to determine the expression of Bcl2, Bax, phospho XIAP, AIF, caspase 3 and 9, and telomerase activity across gestation in an ovine hyperthermia-induced model of IUGR. Pregnant sheep were placed in hyperthermic (HT) conditions to induce IUGR along with age-matched controls. Placental tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days of gestational age (dGA) to determine the expression of apoptotic molecules during the development of IUGR. Compared to the control placenta, IGUR pregnancies showed: significantly reduced placental Bcl2 in early gestation (55 dGA) with a significant increase observed at mid gestation (95 dGA); decreased placental pXIAP at both mid and near term gestational days (95 and 130 dGA); placental AIF increased only at 55 dGA (early gestation); active caspase 3 increased at both mid and near term gestational days (95 and 130 dGA); caspase 9 only increased at mid gestation (95 dGA) and decreased Telomerase activity near term. Placental apoptosis, mediated in part by the apoptosis related molecule, participates in the development of IUGR. Findings from this study suggest a caspase-independent apoptotic pathway during early gestation and caspase-dependent apoptosis at mid and near term gestation. The data also implicate decreased activation of XIAP as a plausible factor involved in the control of placental apoptosis during IUGR.

  20. Exogenous insulin-like growth factor 2 administration enhances memory consolidation and persistence in a time-dependent manner.

    Science.gov (United States)

    Lee, Younghwan; Lee, Young Woo; Gao, Qingtao; Lee, Younghwa; Lee, Hyung Eun; Ryu, Jong Hoon

    2015-10-05

    Memory consolidation is an important process for the formation of long-term memory. We have previously reported that mature brain-derived neurotrophic factor enhances memory consolidation within 9h after initial learning. Recent studies suggest that insulin-like growth factor 2 (IGF2) significantly enhances memory consolidation and prevents forgetting. Thus, we hypothesized that IGF2 exerts its activity on cognitive performance in a time-dependent manner as observed in our previous study. In the one-trial step-through inhibitory avoidance task, we demonstrate that a bilateral injection of IGF2 into the dorsal hippocampus 6 or 9 h after training significantly enhanced the step-through latencies compared with the vehicle-treated controls in the retention trial, which was conducted 24 h after the acquisition trial. However, 12h post-training, IGF2 injection did not increase the step-through latencies. Intriguingly, in the retention trial at 21 days after the training, hippocampal IGF2 injection 6, 9 or 12 h after the acquisition trial significantly increased the step-through latencies compared with the vehicle-treated controls. IGF2 administration at 9 h and 12 h after the acquisition trial significantly increased discrimination index and exploration time on the novel-located object in the test trial at 24 h and 21 days, respectively, after the acquisition trial in the novel location recognition task. In addition, IGF2-induced an increase in the step-through latencies in the retention trial 24 h or 21 days, respectively, after the initial learning was completely abolished by co-injected anti-IGF2 receptor antibody. These results suggest that IGF2 enhances memory consolidation within 9h after initial learning, and increased IGF2 within the 12 h after the acquisition trial, which represents a delayed consolidation phase, is also critical for memory persistence. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Dependence of critical current properties on growth temperature and doping level of nanorods in PLD-YBa2Cu3Oy films

    International Nuclear Information System (INIS)

    Fujita, N.; Haruta, M.; Ichinose, A.; Maeda, T.; Horii, S.

    2013-01-01

    Highlights: •We fabricated Y123 films with Ba–Nb–O nanorods at various growth temperatures. •Irreversibility lines depended on growth temperature and doping level of Ba–Nb–O. •Nanorod morphology was drastically changed by growth temperature (T s ). •Its T s dependence of the matching field was different from that for Er123 + Ba–Nb–O. -- Abstract: The vortex-Bose-glass-like irreversibility lines (ILs) emerged for 2.5 and 5.0 at.% Ba–Nb–O (BNO)-doped YBa 2 Cu 3 O y films deposited by PLD using Nd:YAG-laser. The ILs strongly depended on growth temperature (T s ) in addition to the doping level of BNO. The vortex glass region was expanded with increasing T s or doping level of BNO. Drastic change of the nanorod morphology from short and bended nanorods to long and linear nanorods with increasing T s was clarified. Moreover, it was found that T s -dependent ILs were quite different from our previous results in BNO-doped ErBa 2 Cu 3 O y films

  2. Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes

    NARCIS (Netherlands)

    Finlay, D.K.; Sinclair, L.V.; Feijoo, C.; Waugh, C.M.; Hagenbeek, T.J.; Spits, H.; Cantrell, D.A.

    2009-01-01

    In normal T cell progenitors, phosphoinositide-dependent kinase l (PDK1)-mediated phosphorylation and activation of protein kinase B (PKB) is essential for the phosphorylation and inactivation of Foxo family transcription factors, and also controls T cell growth and proliferation. The current study

  3. CTX-M-1 β-lactamase expression in Escherichia coli is dependent on cefotaxime concentration, growth phase and gene location

    DEFF Research Database (Denmark)

    Kjeldsen, Thea S. B.; Overgaard, Martin; Nielsen, Søren S.

    2015-01-01

    blaCTX-M-1 mRNA expression and CTX-M-1 protein levels were dependent on cefotaxime concentration, growth phase and gene location. These results provide insight into the expression of cephalosporin resistance in CTX-M-1-producing E. coli, improving our understanding of the relationship between ant...

  4. Growth temperature dependence of flux pinning properties in ErBa2Cu3Oy thin films with nano-rods

    International Nuclear Information System (INIS)

    Haruta, M.; Sueyoshi, T.; Fujiyoshi, T.; Mukaida, M.; Kai, H.; Matsumoto, K.; Mele, P.; Maeda, T.; Horii, S.

    2011-01-01

    Nano-rods were introduced into ErBa 2 Cu 3 O y thin films to improve J c . Pinning properties depended on the growth temperature of the films. Morphology of nano-rods was affected by the growth temperature. The growth temperature is important to achieve high in-field J c 's. Irreversibility lines and distributions of local critical current density (J cl ) based on the percolation transition model were affected by the growth temperature (T s ) in 3.5 wt.%-BaNb 2 O 6 -doped ErBa 2 Cu 3 O y thin films. The vortex-Bose-glass-like state appeared by the introduction of nano-rods, and this vortex state was affected by T s . The shape and width of the J cl distribution strongly depended on T s . These results are probably caused by variations of the density and the growth direction for nano-rods reflecting T s . The growth temperature is an important factor to achieve higher critical current properties under magnetic fields for coated conductors of rare-earth-based cuprates with nano-rods.

  5. Growth temperature dependence of flux pinning properties in ErBa{sub 2}Cu{sub 3}O{sub y} thin films with nano-rods

    Energy Technology Data Exchange (ETDEWEB)

    Haruta, M., E-mail: haruta.masakazu@kochi-tech.ac.jp [Kochi University of Technology, Tosayamada-cho, Kami-shi, Kochi 782-8502 (Japan); Sueyoshi, T.; Fujiyoshi, T. [Kumamoto University, 2-39-1, Kurokami, Kumamoto 860-8555 (Japan); Mukaida, M.; Kai, H. [Kyushu University, 744 Moto-oka, Nishi-ku, Fukuoka 819-0385 (Japan); Matsumoto, K.; Mele, P. [Kyushu Institute of Technology, 1-1 Sensui-cho, Tobata-ku, Kitakyushu 804-8550 (Japan); Maeda, T.; Horii, S. [Kochi University of Technology, Tosayamada-cho, Kami-shi, Kochi 782-8502 (Japan)

    2011-11-15

    Nano-rods were introduced into ErBa{sub 2}Cu{sub 3}O{sub y} thin films to improve J{sub c}. Pinning properties depended on the growth temperature of the films. Morphology of nano-rods was affected by the growth temperature. The growth temperature is important to achieve high in-field J{sub c}'s. Irreversibility lines and distributions of local critical current density (J{sub cl}) based on the percolation transition model were affected by the growth temperature (T{sub s}) in 3.5 wt.%-BaNb{sub 2}O{sub 6}-doped ErBa{sub 2}Cu{sub 3}O{sub y} thin films. The vortex-Bose-glass-like state appeared by the introduction of nano-rods, and this vortex state was affected by T{sub s}. The shape and width of the J{sub cl} distribution strongly depended on T{sub s}. These results are probably caused by variations of the density and the growth direction for nano-rods reflecting T{sub s}. The growth temperature is an important factor to achieve higher critical current properties under magnetic fields for coated conductors of rare-earth-based cuprates with nano-rods.

  6. Family with sequence similarity 83, member B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild-type epidermal growth factor receptor

    Science.gov (United States)

    Yamaura, Takumi; Ezaki, Junji; Okabe, Naoyuki; Takagi, Hironori; Ozaki, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Fukuhara, Mitsuro; Muto, Satoshi; Matsumura, Yuki; Hasegawa, Takeo; Hoshino, Mika; Osugi, Jun; Shio, Yutaka; Waguri, Satoshi; Tamura, Hirosumi; Imai, Jun-Ichi; Ito, Emi; Yanagisawa, Yuka; Honma, Reiko; Watanabe, Shinya; Suzuki, Hiroyuki

    2018-01-01

    Lung adenocarcinoma (ADC) patients with tumors that harbor no targetable driver gene mutation, such as epidermal growth factor receptor (EGFR) gene mutations, have unfavorable prognosis, and thus, novel therapeutic targets are required. Family with sequence similarity 83, member B (FAM83B) is a biomarker for squamous cell lung cancer. FAM83B has also recently been shown to serve an important role in the EGFR signaling pathway. In the present study, the molecular and clinical impact of FAM83B in lung ADC was investigated. Matched tumor and adjacent normal tissue samples were obtained from 216 patients who underwent complete lung resection for primary lung ADC and were examined for FAM83B expression using cDNA microarray analysis. The associations between FAM83B expression and clinicopathological parameters, including patient survival, were examined. FAM83B was highly expressed in tumors from males, smokers and in tumors with wild-type EGFR. Multivariate analyses further confirmed that wild-type EGFR tumors were significantly positively associated with FAM83B expression. In survival analysis, FAM83B expression was associated with poor outcomes in disease-free survival and overall survival, particularly when stratified against tumors with wild-type EGFR. Furthermore, FAM83B knockdown was performed to investigate its phenotypic effect on lung ADC cell lines. Gene silencing by FAM83B RNA interference induced growth suppression in the HLC-1 and H1975 lung ADC cell lines. FAM83B may be involved in lung ADC tumor proliferation and can be a predictor of poor survival. FAM83B is also a potential novel therapeutic target for ADC with wild-type EGFR. PMID:29434849

  7. WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer.

    Science.gov (United States)

    Yoshikawa, Hirohide; Matsubara, Kenichi; Zhou, Xiaoling; Okamura, Shu; Kubo, Takahiko; Murase, Yaeko; Shikauchi, Yuko; Esteller, Manel; Herman, James G; Wei Wang, Xin; Harris, Curtis C

    2007-11-01

    We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line. These results indicate that WNT10B can be deregulated by either overexpression or silencing in cancer. We found that WNT10B up-regulated beta-catenin/Tcf activity. However, WNT10B-overexpressing cells demonstrated a reduced growth rate and anchorage-independent growth that is independent of the beta-catenin/Tcf activation, because mutant beta-catenin-transduced cells did not suppress growth, and dominant-negative hTcf-4 failed to alleviate the growth suppression by WNT10B. Although WNT10B expression alone inhibits cell growth, it acts synergistically with the fibroblast growth factor (FGF) to stimulate cell growth. WNT10B is bifunctional, one function of which is involved in beta-catenin/Tcf activation, and the other function is related to the down-regulation of cell growth through a different mechanism. We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator.

  8. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth

    DEFF Research Database (Denmark)

    Zhao, Jian; Yuan, Xuejun; Frödin, Morten

    2003-01-01

    Phosphorylation of transcription factors by mitogen-activated protein kinase (MAPK) cascades links cell signaling with the control of gene expression. Here we show that growth factors induce rRNA synthesis by activating MAPK-dependent signaling cascades that target the RNA polymerase I......-specific transcription initiation factor TIF-IA. Activation of TIF-IA and ribosomal gene transcription is sensitive to PD98059, indicating that TIF-IA is targeted by MAPK in vivo. Phosphopeptide mapping and mutational analysis reveals two serine residues (S633 and S649) that are phosphorylated by ERK and RSK kinases....... Replacement of S649 by alanine inactivates TIF-IA, inhibits pre-rRNA synthesis, and retards cell growth. The results provide a link between growth factor signaling, ribosome production, and cell growth, and may have a major impact on the mechanism of cell transformation....

  9. TIF-IA-dependent regulation of ribosome synthesis in drosophila muscle is required to maintain systemic insulin signaling and larval growth.

    Science.gov (United States)

    Ghosh, Abhishek; Rideout, Elizabeth J; Grewal, Savraj S

    2014-10-01

    The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis-a limiting step in ribosome biogenesis-via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs) from the brain and increased expression of Imp-L2-a secreted factor that binds and inhibits dILP activity-from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis.

  10. Variation in growth of young and adult size in barnacle geese Branta leucopsis : Evidence for density dependence

    NARCIS (Netherlands)

    Loonen, MJJE; Oosterbeek, K; Drent, RH

    1997-01-01

    A colony of Svalbard Barnacle Geese Branta leucopsis was studied near Ny Alesund, Spitsbergen. Breeding started in 1980 and the colony size followed a sigmoidal curve with little increase in numbers in the period 1992-1995. Over the period 1991-1995 gosling growth declined, mortality during growth

  11. GPR-4 is a predicted G-protein-coupled receptor required for carbon source-dependent asexual growth and development in Neurospora crassa.

    Science.gov (United States)

    Li, Liande; Borkovich, Katherine A

    2006-08-01

    The filamentous fungus Neurospora crassa is able to utilize a wide variety of carbon sources. Here, we examine the involvement of a predicted G-protein-coupled receptor (GPCR), GPR-4, during growth and development in the presence of different carbon sources in N. crassa. Deltagpr-4 mutants have reduced mass accumulation compared to the wild type when cultured on high levels of glycerol, mannitol, or arabinose. The defect is most severe on glycerol and is cell density dependent. The genetic and physical relationship between GPR-4 and the three N. crassa Galpha subunits (GNA-1, GNA-2, and GNA-3) was explored. All three Galpha mutants are defective in mass accumulation when cultured on glycerol. However, the phenotypes of Deltagna-1 and Deltagpr-4 Deltagna-1 mutants are identical, introduction of a constitutively activated gna-1 allele suppresses the defects of the Deltagpr-4 mutation, and the carboxy terminus of GPR-4 interacts most strongly with GNA-1 in the yeast two-hybrid assay. Although steady-state cyclic AMP (cAMP) levels are normal in Deltagpr-4 strains, exogenous cAMP partially remediates the dry mass defects of Deltagpr-4 mutants on glycerol medium and Deltagpr-4 strains lack the transient increase in cAMP levels observed in the wild type after addition of glucose to glycerol-grown liquid cultures. Our results support the hypothesis that GPR-4 is coupled to GNA-1 in a cAMP signaling pathway that regulates the response to carbon source in N. crassa. GPR-4-related GPCRs are present in the genomes of several filamentous ascomycete fungal pathogens, raising the possibility that a similar pathway regulates carbon sensing in these organisms.

  12. Src tyrosine kinase mediates platelet-derived growth factor BB-induced and redox-dependent migration in metanephric mesenchymal cells

    Science.gov (United States)

    Gorin, Yves

    2013-01-01

    The adult kidney is derived from the interaction between the metanephric blastema and the ureteric bud. Platelet-derived growth factor (PDGF) receptor β is essential for the development of the mature glomerular tuft, as mice deficient for this receptor lack mesangial cells. This study investigated the role of Src tyrosine kinase in PDGF-mediated reactive oxygen species (ROS) generation and migration of metanephric mesenchymal cells (MMCs). Cultured embryonic MMCs from wild-type and PDGF receptor-deficient embryos were established. Migration was determined via wound-healing assay. Unlike PDGF AA, PDGF BB-induced greater migration in MMCs with respect to control. This was abrogated by neutralizing an antibody to PDGF BB. Phosphatidylinositol 3-kinase (PI3K) inhibitors suppressed PDGF BB-induced migration. Conversely, mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) inhibitors had no effect. Src inhibitors inhibited PDGF-induced cell migration, PI3K activity, and Akt phosphorylation. Adenoviral dominant negative Src (AD DN Src) abrogated PDGF BB-induced Akt phosphorylation. Hydrogen peroxide stimulated cell migration. PDGF BB-induced wound closure was inhibited by the antioxidants N-acetyl-l-cysteine, tiron, and the flavoprotein inhibitor diphenyleneiodonium. These cells express the NADPH oxidase homolog Nox4. Inhibiting Nox4 with antisense oligonucleotides or small interfering RNA (siRNA) suppressed PDGF-induced wound closure. Inhibition of Src with siRNA reduced PDGF BB-induced ROS generation as assessed by 2′,7′-dichlorodihydrofluorescein diacetate fluorescence. Furthermore, PDGF BB-stimulated ROS generation and migration were similarly suppressed by Ad DN Src. In MMCs, PDGF BB-induced migration is mediated by PI3K and Src in a redox-dependent manner involving Nox4. Src may be upstream to PI3K and Nox4. PMID:24197068

  13. Similarity transformations of MAPs

    Directory of Open Access Journals (Sweden)

    Andersen Allan T.

    1999-01-01

    Full Text Available We introduce the notion of similar Markovian Arrival Processes (MAPs and show that the event stationary point processes related to two similar MAPs are stochastically equivalent. This holds true for the time stationary point processes too. We show that several well known stochastical equivalences as e.g. that between the H 2 renewal process and the Interrupted Poisson Process (IPP can be expressed by the similarity transformations of MAPs. In the appendix the valid region of similarity transformations for two-state MAPs is characterized.

  14. The growth hormone dependent serine protease inhibitor, Spi 2.1 inhibits the des (1-3) insulin-like growth factor-I generating protease.

    Science.gov (United States)

    Maake, C; Yamamoto, H; Murphy, L J

    1997-12-01

    The conversion of insulin-like growth factor-I (IGF-I) to the biologically more active des (1-3) IGF-I variant is catalyzed by a ubiquitous protease. This proteolytic activity is inhibited by human alpha1-antitrypsin and soy-bean trypsin inhibitor and is up-regulated in serum and tissue extracts of hypophysectomized rats. These observations lead us to investigate whether the growth hormone regulated, serine protease inhibitor, Spi 2.1 was able to inhibit the des (1-3) IGF-I generating protease. Dihydrofolate reductase deficient Chinese hamster ovary (CHO(dhfr-ve)) cells were transfected with a rat Spi 2.1 expression vector containing the dhfr and neomycin resistance gene. Stable transfectants were selected using G418 and amplified using methotrexate. Conditioned medium from Spi 2.1 transfected CHO cells potently inhibited proteolytic activity directed against a synthetic hexa-peptide with a sequence identical to the N-terminal of IGF-I. In contrast conditioned medium from wild-type CHO cells had little effect. Based upon these observations we suggest that our previous finding of enhanced des (1-3) IGF-I generating protease activity in growth hormone deficient rats may be, at least partly explained by reduced levels of Spi 2.1. Furthermore, we propose that the regulation of the generation of des (1-3) IGF-I may be an additional potential site of growth hormone regulation of IGF-I action.

  15. The ABA receptor PYL8 promotes lateral root growth by enhancing MYB77-dependent transcription of auxin-responsive genes.

    Science.gov (United States)

    Zhao, Yang; Xing, Lu; Wang, Xingang; Hou, Yueh-Ju; Gao, Jinghui; Wang, Pengcheng; Duan, Cheng-Guo; Zhu, Xiaohong; Zhu, Jian-Kang

    2014-06-03

    The phytohormone abscisic acid (ABA) regulates plant growth, development, and abiotic stress responses. ABA signaling is mediated by a group of receptors known as the PYR1/PYL/RCAR family, which includes the pyrabactin resistance 1-like protein PYL8. Under stress conditions, ABA signaling activates SnRK2 protein kinases to inhibit lateral root growth after emergence from the primary root. However, even in the case of persistent stress, lateral root growth eventually recovers from inhibition. We showed that PYL8 is required for the recovery of lateral root growth, following inhibition by ABA. PYL8 directly interacted with the transcription factors MYB77, MYB44, and MYB73. The interaction of PYL8 and MYB77 increased the binding of MYB77 to its target MBSI motif in the promoters of multiple auxin-responsive genes. Compared to wild-type seedlings, the lateral root growth of pyl8 mutant seedlings and myb77 mutant seedlings was more sensitive to inhibition by ABA. The recovery of lateral root growth was delayed in pyl8 mutant seedlings in the presence of ABA, and the defect was rescued by exposing pyl8 mutant seedlings to the auxin IAA (3-indoleacetic acid). Thus, PYL8 promotes lateral root growth independently of the core ABA-SnRK2 signaling pathway by enhancing the activities of MYB77 and its paralogs, MYB44 and MYB73, to augment auxin signaling. Copyright © 2014, American Association for the Advancement of Science.

  16. Reduction of stem growth and site dependency of leaf injury in Massachusetts black cherries exhibiting ozone symptoms

    International Nuclear Information System (INIS)

    Vollenweider, P.; Woodcock, H.; Kelty, M.J.; Hofer, R.-M.

    2003-01-01

    Ozone symptomatic trees had a reduced stem growth and symptom expression was enhanced on moister and better growing stands. - Leaf ozone symptoms in natural ecosystems are increasingly reported but ozone effects on tree growth and the mediation of site conditions are still little documented. This study tests two hypotheses: (1) leaf injury in black cherry is associated with decline in radial growth, (2) symptoms are more prevalent on mesic sites. On sites supporting black cherry across Massachusetts, tree growth and leaf ozone injury were surveyed in 1996 using a randomized plot network established in the 1960s. Forty-seven percent of 120 trees sampled for ozone symptoms were symptomatic with generally low levels of injury. Over a 31-year period symptomatic trees had 28% lower stem growth rates than asymptomatic trees. Ozone symptom expression was enhanced in well growing stands on moister, cooler and more elevated sites. Ozone appeared to increase environmental stress and had a more pronounced effect on growth in better growing black cherry stands. This complicates management decisions as thinning increases growth and moisture availability

  17. Similarity Measure of Graphs

    Directory of Open Access Journals (Sweden)

    Amine Labriji

    2017-07-01

    Full Text Available The topic of identifying the similarity of graphs was considered as highly recommended research field in the Web semantic, artificial intelligence, the shape recognition and information research. One of the fundamental problems of graph databases is finding similar graphs to a graph query. Existing approaches dealing with this problem are usually based on the nodes and arcs of the two graphs, regardless of parental semantic links. For instance, a common connection is not identified as being part of the similarity of two graphs in cases like two graphs without common concepts, the measure of similarity based on the union of two graphs, or the one based on the notion of maximum common sub-graph (SCM, or the distance of edition of graphs. This leads to an inadequate situation in the context of information research. To overcome this problem, we suggest a new measure of similarity between graphs, based on the similarity measure of Wu and Palmer. We have shown that this new measure satisfies the properties of a measure of similarities and we applied this new measure on examples. The results show that our measure provides a run time with a gain of time compared to existing approaches. In addition, we compared the relevance of the similarity values obtained, it appears that this new graphs measure is advantageous and  offers a contribution to solving the problem mentioned above.

  18. New Similarity Functions

    DEFF Research Database (Denmark)

    Yazdani, Hossein; Ortiz-Arroyo, Daniel; Kwasnicka, Halina

    2016-01-01

    In data science, there are important parameters that affect the accuracy of the algorithms used. Some of these parameters are: the type of data objects, the membership assignments, and distance or similarity functions. This paper discusses similarity functions as fundamental elements in membership...

  19. Similarity after Goodman

    NARCIS (Netherlands)

    Decock, L.B.; Douven, I.

    2011-01-01

    In a famous critique, Goodman dismissed similarity as a slippery and both philosophically and scientifically useless notion. We revisit his critique in the light of important recent work on similarity in psychology and cognitive science. Specifically, we use Tversky's influential set-theoretic

  20. Judgments of brand similarity

    NARCIS (Netherlands)

    Bijmolt, THA; Wedel, M; Pieters, RGM; DeSarbo, WS

    This paper provides empirical insight into the way consumers make pairwise similarity judgments between brands, and how familiarity with the brands, serial position of the pair in a sequence, and the presentation format affect these judgments. Within the similarity judgment process both the

  1. Parallelised online biomass monitoring in shake flasks enables efficient strain and carbon source dependent growth characterisation of Saccharomyces cerevisiae.

    Science.gov (United States)

    Bruder, Stefan; Reifenrath, Mara; Thomik, Thomas; Boles, Eckhard; Herzog, Konrad

    2016-07-25

    Baker's yeast, Saccharomyces cerevisiae, as one of the most often used workhorses in biotechnology has been developed into a huge family of application optimised strains in the last decades. Increasing numbers of strains render their characterisation highly challenging, even with the simple methods of growth-based analytics. Here we present a new sensor system for the automated, non-invasive and parallelisable monitoring of biomass in continuously shaken shake flask cultures, called CGQ ("cell growth quantifier"). The CGQ implements a dynamic approach of backscattered light measurement, allowing for efficient and accurate growth-based strain characterisation, as exemplarily demonstrated for the four most commonly used laboratory and industrial yeast strains, BY4741, W303-1A, CEN.PK2-1C and Ethanol Red. Growth experiments revealed distinct carbon source utilisation differences between the investigated S. cerevisiae strains. Phenomena such as diauxic shifts, morphological changes and oxygen limitations were clearly observable in the growth curves. A strictly monotonic non-linear correlation of OD600 and the CGQ's backscattered light intensities was found, with strain-to-strain as well as growth-phase related differences. The CGQ measurements showed high resolution, sensitivity and smoothness even below an OD600 of 0.2 and were furthermore characterised by low background noise and signal drift in combination with high reproducibility. With the CGQ, shake flask fermentations can be automatically monitored regarding biomass and growth rates with high resolution and parallelisation. This makes the CGQ a valuable tool for growth-based strain characterisation and development. The exceptionally high resolution allows for the identification of distinct metabolic differences and shifts as well as for morphologic changes. Applications that will benefit from that kind of automatized biomass monitoring include, amongst many others, the characterization of deregulated native or

  2. Kisspeptin stimulates growth hormone release by utilizing Neuropeptide Y pathways and is dependent on the presence of ghrelin

    Science.gov (United States)

    Although kisspeptin is the primary stimulator of gonadotropin releasing hormone secretion and therefore the hypothalamic-pituitary gonadal axis, new findings suggest kisspeptin can also regulate additional neuroendocrine processes including release of growth hormone (GH). Central delivery of kisspep...

  3. Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner

    OpenAIRE

    Hirbe, Angela C.; Uluçkan, Özge; Morgan, Elizabeth A.; Eagleton, Mark C.; Prior, Julie L.; Piwnica-Worms, David; Trinkaus, Kathryn; Apicelli, Anthony; Weilbaecher, Katherine

    2007-01-01

    Inhibition of osteoclast (OC) activity has been associated with decreased tumor growth in bone in animal models. Increased recognition of factors that promote osteoclastic bone resorption in cancer patients led us to investigate whether increased OC activation could enhance tumor growth in bone. Granulocyte colony-stimulating factor (G-CSF) is used to treat chemotherapy-induced neutropenia, but is also associated with increased markers of OC activity and decreased bone mineral density (BMD). ...

  4. Dependence of growth inhibiting action of increased planting density on capacity of lettuce plants to synthesize ABA.

    Science.gov (United States)

    Vysotskaya, Lidiya B; Arkhipova, Tatyana N; Kudoyarova, Guzel R; Veselov, Stanislav Yu

    2018-01-01

    Inhibition of lettuce plant growth under increased planting density was accompanied by accumulation of abscisic acid (ABA) in the shoots of competing plants. To check causal relationship between these responses we studied the effect of decreased synthesis of ABA on growth indexes and hormonal balance of lettuce plants under elevated density of their planting (one (single) or three (competing) plants per pot). Herbicide fluridone was used to inhibit ABA synthesis. Preliminary experiments with single plants showed that presence of fluridone in the soil solution at rather low concentration (0.001mg/L) did not affect either chlorophyll content or growth rate of shoots and roots during at least one week. Treatment of competing (grouped) plants with this concentration of fluridone prevented both accumulation of ABA and competition induced growth inhibition. These results confirm important role of this hormone in the growth inhibiting effect of increased planting density. Furthermore, as in the case of ABA, fluridone prevented allocation of indoleacetic acid (IAA) to the shoots of competing plants likely contributing to leveling off the increase in the ratio of leaf area to their mass that is characteristic effect of shading in the dense plant populations. The results suggest involvement of ABA in allocation of IAA in competing plants. Application of fluridone did not influence the concentration of cytokinins in the shoots, whose level was decreased by competition either in fluridone treated or control (untreated with fluridone) plants. Accumulation of ABA in the shoots of competing plants accompanied by inhibition of their growth and the absence of either accumulation of ABA or inhibition of their growth in fluridone treated grouped plants confirms importance of ABA synthesis for growth response to competition. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Elastic–plastic void expansion in near-self-similar shapes

    DEFF Research Database (Denmark)

    Tvergaard, Viggo

    2011-01-01

    For void growth in an elastic–plastic strain hardening material the preferred shape of the void is calculated, dependent on the macroscopic stress state. Axisymmetric cell model analyses are carried out with a very small initial void size relative to the cell dimensions. Large deformations...... of the strain hardening level and of the initial yield strain are studied....... during the growth. Thus, the shapes found give only approximately self-similar growth. The results are compared with self-similar shapes determined previously for nonlinear viscous solids, subject to power law creep. For the time independent elastic–plastic material considered here the effect...

  6. GDNF induces RET-SRC-HER2-dependent growth in trastuzumab-sensitive but SRC-independent growth in resistant breast tumor cells.

    Science.gov (United States)

    Gardaneh, Mossa; Shojaei, Sahar; Kaviani, Ahmad; Behnam, Babak

    2017-04-01

    We investigated the role of glial cell line-derived neurotrophic factor (GDNF) in compensating trastuzumab (TZMB)-induced apoptosis in HER2 + breast cancer (BC) cells using xenograft tumors. We generated BC xenografts in nude mice using samples from three patients selected based on their HER2 status and response to TZMB therapy. TZMB treatment resulted in shrinkage of the HER2 + TZMB-sensitive xenograft tumor but not the HER2 - or HER2 + TZMB-resistant ones. GDNF neutralized TZMB activity and induced growth in all tumors. Three distinct cell lines were derived from these tumors and named, respectively, TZMB-sensitive (TSTC), HER2 - (HNTC), and TZMB-resistant (TRTC). Over 50% of TRTC but 1% of TSTC cells expressed CD44, whereas 84% of TSTC were CD24 + compared to only 1% of TRTC, despite comparable levels of HER2 detected in both. TZMB induced profound morphological changes toward apoptosis in TSTC but not in TRTC or HNTC. However, GDNF significantly compensated TZMB-mediated TSTC cell loss and promoted growth by 37 and 50%, respectively, in TSTC and TRTC. Inhibition of SRC by Saracatinib (SARC) blocked GDNF function and accelerated TZMB-mediated cell death in TSTC, but GDNF continued promoting TRTC growth. These changes paralleled with expression levels of the key molecules involved in growth and apoptosis. Collectively, we found in our xenograft samples that firstly SRC mediates GDNF pro-survival functions by bridging RET-HER2 crosstalk in TZMB-responsive BC tumors. Secondly, SARC-TZMB interactions can synergistically eradicate such tumor cells; and thirdly, GDNF can support antibody resistance by acting independent from SRC in tumors with poor HER2 response to TZMB therapy.

  7. The rhizobacterium Variovorax paradoxus 5C-2, containing ACC deaminase, promotes growth and development of Arabidopsis thaliana via an ethylene-dependent pathway.

    Science.gov (United States)

    Chen, Lin; Dodd, Ian C; Theobald, Julian C; Belimov, Andrey A; Davies, William J

    2013-04-01

    Many plant-growth-promoting rhizobacteria (PGPR) associated with plant roots contain the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase and can metabolize ACC, the immediate precursor of the plant hormone ethylene, thereby decreasing plant ethylene production and increasing plant growth. However, relatively few studies have explicitly linked ethylene emission and/or action to growth promotion in these plant-microbe interactions. This study examined effects of the PGPR Variovorax paradoxus 5C-2 containing ACC deaminase on the growth and development of Arabidopsis thaliana using wild-type (WT) plants and several ethylene-related mutants (etr1-1, ein2-1, and eto1-1). Soil inoculation with V. paradoxus 5C-2 promoted growth (leaf area and shoot biomass) of WT plants and the ethylene-overproducing mutant eto1-1, and also enhanced floral initiation of WT plants by 2.5 days. However, these effects were not seen in ethylene-insensitive mutants (etr1-1 and ein2-1) even though bacterial colonization of the root system was similar. Furthermore, V. paradoxus 5C-2 decreased ACC concentrations of rosette leaves of WT plants by 59% and foliar ethylene emission of both WT plants and eto1-1 mutants by 42 and 37%, respectively. Taken together, these results demonstrate that a fully functional ethylene signal transduction pathway is required for V. paradoxus 5C-2 to stimulate leaf growth and flowering of A. thaliana.

  8. Dose-dependent effect of homoeopathic drug Zinc sulphate on plant growth using Bacopa monnieri as model system

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Gupta

    2014-01-01

    Full Text Available Background: Zinc is one of the essential micronutrients in plants required in very low quantity for plant growth and development. In higher concentration, it is known to to reduce the rate of photosynthesis, So homoeopathic preparations tested to see it role on plan growth. Objective: To analyse the effect of homoeopathic preparation of Zinc sulphate on plants through in-vitro assay using Bacopa monnieri as a model plant system. Materials and Methods: Six homoeopathic potencies (1X to 6X of Zinc sulphate were used on a decimal scale along with the control (MS basal agar medium. The samples were evaluated by adding fixed amount (100 μl in the media as well as by dipping the explants in the test sample overnight. At the completion of the incubation period (14 days the fresh and dry weight, number and length of the roots, number and length of the shoots and the number of leaves were analysed. Results: It was observed that Zinc sulphate showed growth inhibition at potencies from 1X to 5X, whereas at potency 6X, it exhibited growth promotion effect, when compared with the control. Conclusion: Homoeopathic drug (Zinc sulphate exhibited growth promotion at higher potency (6X and growth inhibition at lower potencies (1X to 5X on Bacopa monneiri.

  9. Semantic similarity in biomedical ontologies.

    Directory of Open Access Journals (Sweden)

    Catia Pesquita

    2009-07-01

    Full Text Available In recent years, ontologies have become a mainstream topic in biomedical research. When biological entities are described using a common schema, such as an ontology, they can be compared by means of their annotations. This type of comparison is called semantic similarity, since it assesses the degree of relatedness between two entities by the similarity in meaning of their annotations. The application of semantic similarity to biomedical ontologies is recent; nevertheless, several studies have been published in the last few years describing and evaluating diverse approaches. Semantic similarity has become a valuable tool for validating the results drawn from biomedical studies such as gene clustering, gene expression data analysis, prediction and validation of molecular interactions, and disease gene prioritization. We review semantic similarity measures applied to biomedical ontologies and propose their classification according to the strategies they employ: node-based versus edge-based and pairwise versus groupwise. We also present comparative assessment studies and discuss the implications of their results. We survey the existing implementations of semantic similarity measures, and we describe examples of applications to biomedical research. This will clarify how biomedical researchers can benefit from semantic similarity measures and help them choose the approach most suitable for their studies.Biomedical ontologies are evolving toward increased coverage, formality, and integration, and their use for annotation is increasingly becoming a focus of both effort by biomedical experts and application of automated annotation procedures to create corpora of higher quality and completeness than are currently available. Given that semantic similarity measures are directly dependent on these evolutions, we can expect to see them gaining more relevance and even becoming as essential as sequence similarity is today in biomedical research.

  10. Semantic similarity in biomedical ontologies.

    Science.gov (United States)

    Pesquita, Catia; Faria, Daniel; Falcão, André O; Lord, Phillip; Couto, Francisco M

    2009-07-01

    In recent years, ontologies have become a mainstream topic in biomedical research. When biological entities are described using a common schema, such as an ontology, they can be compared by means of their annotations. This type of comparison is called semantic similarity, since it assesses the degree of relatedness between two entities by the similarity in meaning of their annotations. The application of semantic similarity to biomedical ontologies is recent; nevertheless, several studies have been published in the last few years describing and evaluating diverse approaches. Semantic similarity has become a valuable tool for validating the results drawn from biomedical studies such as gene clustering, gene expression data analysis, prediction and validation of molecular interactions, and disease gene prioritization. We review semantic similarity measures applied to biomedical ontologies and propose their classification according to the strategies they employ: node-based versus edge-based and pairwise versus groupwise. We also present comparative assessment studies and discuss the implications of their results. We survey the existing implementations of semantic similarity measures, and we describe examples of applications to biomedical research. This will clarify how biomedical researchers can benefit from semantic similarity measures and help them choose the approach most suitable for their studies.Biomedical ontologies are evolving toward increased coverage, formality, and integration, and their use for annotation is increasingly becoming a focus of both effort by biomedical experts and application of automated annotation procedures to create corpora of higher quality and completeness than are currently available. Given that semantic similarity measures are directly dependent on these evolutions, we can expect to see them gaining more relevance and even becoming as essential as sequence similarity is today in biomedical research.

  11. Similarity or difference?

    DEFF Research Database (Denmark)

    Villadsen, Anders Ryom

    2013-01-01

    While the organizational structures and strategies of public organizations have attracted substantial research attention among public management scholars, little research has explored how these organizational core dimensions are interconnected and influenced by pressures for similarity. In this p......While the organizational structures and strategies of public organizations have attracted substantial research attention among public management scholars, little research has explored how these organizational core dimensions are interconnected and influenced by pressures for similarity....... In this paper I address this topic by exploring the relation between expenditure strategy isomorphism and structure isomorphism in Danish municipalities. Different literatures suggest that organizations exist in concurrent pressures for being similar to and different from other organizations in their field...... of action. It is theorized that to meet this challenge organizations may substitute increased similarity on one core dimension for increased idiosyncrasy on another, but only after a certain level of isomorphism is reached. Results of quantitative analyses support this theory and show that an inverse U...

  12. The effect of urban growth on landscape-scale restoration for a fire-dependent songbird.

    Science.gov (United States)

    Pickens, Bradley A; Marcus, Jeffrey F; Carpenter, John P; Anderson, Scott; Taillie, Paul J; Collazo, Jaime A

    2017-04-15

    A landscape-scale perspective on restoration ecology has been advocated, but few studies have informed restoration with landscape metrics or addressed broad-scale threats. Threats such as urban growth may affect restoration effectiveness in a landscape context. Here, we studied longleaf pine savanna in the rapidly urbanizing southeastern United States where a habitat-specialist bird, Bachman's sparrow (Peucaea aestivalis), is closely associated with savanna vegetation structure and frequent fire. Our objectives were to construct a species distribution model for Bachman's sparrow, determine the relationship between fire and urbanization, quantify the urban growth effect (2010-2090), identify potential restoration areas, and determine the interaction between restoration potential and urban growth by 2050. Number of patches, patch size, and isolation metrics were used to evaluate scenarios. The species distribution model was 88% accurate and emphasized multiscale canopy cover characteristics, fire, and percent habitat. Fires were less common urban areas, and this fire suppression effect exacerbated urban growth effects. For restoration scenarios, canopy cover reduction by 30% resulted in nearly double the amount of habitat compared to the prescribed fire scenario; canopy cover reduction resulted in larger patch sizes and less patch isolation compared to current conditions. The effect of urban growth on restoration scenarios was unequal. Seventy-four percent of restoration areas from the prescribed fire scenario overlapped with projected urban growth, whereas the canopy cover reduction scenario only overlapped by 9%. We emphasize the benefits of simultaneously considering the effects of urban growth and landscape-scale restoration potential to promote a landscape with greater patch sizes and less isolation. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Rosiglitazone Suppresses the Growth and Invasiveness of SGC-7901 Gastric Cancer Cells and Angiogenesis In Vitro via PPARγ Dependent and Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Qing He

    2008-01-01

    Full Text Available Although thiazolidinediones (TZDs were found to be ligands for peroxisome proliferators-activated receptorγ (PPARγ, the mechanism by which TZDs exert their anticancer effect remains unclear. Furthermore, the effect of TZDs on metastatic and angiogenesis potential of cancer cells is unknown. Our results in this paper show that rosiglitazone inhibited SGC-7901 gastric cancer cells growth, caused G1 cell cycle arrest and induced apoptosis in a dose-dependent manner. The effects of rosiglitazone on SGC-7901 cancer cells were completely reversed by treatment with PPARγ antagonist GW9662. Rosiglitazone inhibited SGC-7901 cell migration, invasiveness, and the expression of MMP-2 in dose-dependent manner via PPARγ-independent manner. Rosiglitazone reduced the VEGF induced angiogenesis of HUVEC in dose-dependent manner through PPARγ-dependent pathway. Moreover, rosiglitazone did not affect the expression of VEGF by SGC-7901 cells. Our results demonstrated that by PPARγ ligand, rosiglitazone inhibited growth and invasiveness of SGC-7901 gastric cancer cells and angiogenesis in vitro via PPARγ-dependent or -independent pathway.

  14. The temperature dependence and environmental enhancement mechanism of fatigue crack growth rates of A 351-CF8A cast stainless steel in LWR environment

    International Nuclear Information System (INIS)

    Cullen, W.H.; Haenninen, H.; Toerroenen, K.; Kemppainen, M.

    1984-01-01

    The fatigue crack growth rates for A 351-CF8A cast stainless steel were determined over a range of temperatures from 93 degC to 338 degC (200 degF to 640 degF). The waveform was 17 mHz sinusoidal and the load ratio was 0.2. The environment was borated and lithiated water with a dissolved oxygen content of approximately 1 ppb. The results show an easily measurable (factors of 2 to 8) increase in crack growth rates due to the environment. However, these rates are well within the known band of results for low-alloy pressure vessel and low-carbon piping steels in LWR environments. An extensive fractographic investigation shows fatigue fracture surfaces consisting of brittle morphology. This fracture morphology is similar to that of stress corrosion cracking of stainless steels, suggesting that there is a distinctive environmental assistance mechanism resulting in the increased crack growth rates. (author)

  15. Developmental stage-dependent influence of environmental factors on growth of rural Sundanese children in West Java, Indonesia.

    Science.gov (United States)

    Sekiyama, Makiko; Roosita, Katrin; Ohtsuka, Ryutaro

    2015-05-01

    This study investigated the growth trajectories and the relative relevance levels of nutrition, disease, and hormonal status at various developmental stages among children in adverse environments to provide population-based empirical evidence for the life history theory. Three years of longitudinal anthropometric data in 1-year intervals were obtained from 418 boys and girls aged 0 to 12 years at recruitment. Following the final measurement, the main survey, which included blood and feces sampling, 3-h interval food consumption recall surveys for energy and nutrient intakes and anthropometry, was performed. Blood and feces were used for detecting, respectively, anemia and hormonal (IGF-I and IGFBP-3) levels as well as intestinal helminthiasis (Ascaris, Trichuris, and hookworm). The major findings of this study are summarized as follows: 1) the growth velocity of the subject children lagged behind international standards during childhood and juvenility but caught up during early adolescence; 2) diseases, both intestinal helminths and anemia, had significant effects on growth in childhood but not at older ages; and 3) hormonal status significantly affected growth in the children, with its highest significance in early adolescence. A larger growth than international standards in early adolescence likely follows programmed hormonal mechanisms after the onset of puberty. The onset of puberty might be associated with adequate amounts of nutrient intake and be mediated by hormonal function, because the IGF-IZ score was significantly correlated with energy and protein intakes at the transitional period from juvenility to adolescence, when puberty occurs. © 2015 Wiley Periodicals, Inc.

  16. Growth Temperature Dependence of Morphology of GaN Single Crystals in the Na-Li-Ca Flux Method

    Science.gov (United States)

    Wu, Xi; Hao, Hangfei; Li, Zhenrong; Fan, Shiji; Xu, Zhuo

    2018-02-01

    In this paper, the effect of growth temperature on the morphology and transparency of the GaN crystals obtained by the Li-Ca-added Na Flux method was studied. Addition of Li-Ca was attempted to control the growth habit and further improve transparency of GaN crystals. The samples with wurtzite structure of GaN were confirmed by the x-ray powder diffraction analysis. GaN single crystal with maximum size of about 6 mm was grown at 750°C. As the growth temperature was increased from 700°C to 850°C, the morphology of the crystals changed from pyramid to prism, and their surfaces became smooth. It was found that high growth temperature was beneficial to obtain a transparent crystal, but the evaporation of sodium would suppress its further growth. The E 2 (high) mode in the Raman spectra was at 568 cm-1, and the full-width at half-maximum values of this peak for the crystals obtained at 700°C, 750°C, 800°C, and 850°C were 7.5 cm-1, 10.3 cm-1, 4.4 cm-1, and 4.0 cm-1, respectively. It indicates that all the crystals are stress free and the transparent crystal grown at high temperature has high structural quality or low impurity concentrations.

  17. Predation risk affects growth and reproduction of an invasive snail and its lethal effect depends on prey size

    Science.gov (United States)

    Guo, Jing; Martín, Pablo R.; Zhang, Chunxia

    2017-01-01

    The behavior of invasive species under predation risk has been studied extensively, but their growth and reproductive responses have rarely been investigated. We conducted experiments with juveniles and adults of the invasive freshwater snail Pomacea canaliculata, and we observed changes in growth and reproduction in response to predation risk from a caged predator (Trachemys scripta elegans). P. canaliculata produced eggs earlier in the presence of predators and injured conspecifics compared with the control group (no risk), although the total number of egg masses laid by per female was exceeded by that of the controls after 15 days. Egg hatching success noticeably decreased under predation risk, and the incubation period was significantly prolonged; however, the oviposition height of the snails was not affected. A lethal effect of predation risk was detected in juvenile snails but not in adults. The growth of juvenile P. canaliculata was inhibited under predation risk, probably due to a reduction in food intake. Adult females exhibited a greater reduction in growth under predation risk than males, which likely resulted in part from the high reproductive investment of females in egg laying. These results indicate that P. canaliculata snails under predation risk face a trade-off between predator avoidance and growth and reproduction, where the lethal effect of predation risk is linked to the size of the prey. PMID:29136660

  18. Predation risk affects growth and reproduction of an invasive snail and its lethal effect depends on prey size.

    Directory of Open Access Journals (Sweden)

    Jing Guo

    Full Text Available The behavior of invasive species under predation risk has been studied extensively, but their growth and reproductive responses have rarely been investigated. We conducted experiments with juveniles and adults of the invasive freshwater snail Pomacea canaliculata, and we observed changes in growth and reproduction in response to predation risk from a caged predator (Trachemys scripta elegans. P. canaliculata produced eggs earlier in the presence of predators and injured conspecifics compared with the control group (no risk, although the total number of egg masses laid by per female was exceeded by that of the controls after 15 days. Egg hatching success noticeably decreased under predation risk, and the incubation period was significantly prolonged; however, the oviposition height of the snails was not affected. A lethal effect of predation risk was detected in juvenile snails but not in adults. The growth of juvenile P. canaliculata was inhibited under predation risk, probably due to a reduction in food intake. Adult females exhibited a greater reduction in growth under predation risk than males, which likely resulted in part from the high reproductive investment of females in egg laying. These results indicate that P. canaliculata snails under predation risk face a trade-off between predator avoidance and growth and reproduction, where the lethal effect of predation risk is linked to the size of the prey.

  19. Cyclin A1 modulates the expression of vascular endothelial growth factor and promotes hormone-dependent growth and angiogenesis of breast cancer.

    Directory of Open Access Journals (Sweden)

    Azharuddin Sajid Syed Khaja

    Full Text Available Alterations in cellular pathways related to both endocrine and vascular endothelial growth factors (VEGF may contribute to breast cancer progression. Inhibition of the elevated levels of these pathways is associated with clinical benefits. However, molecular mechanisms by which endocrine-related pathways and VEGF signalling cooperatively promote breast cancer progression remain poorly understood. In the present study, we show that the A-type cyclin, cyclin A1, known for its important role in the initiation of leukemia and prostate cancer metastasis, is highly expressed in primary breast cancer specimens and metastatic lesions, in contrasting to its barely detectable expression in normal human breast tissues. There is a statistically significant correlation between cyclin A1 and VEGF expression in breast cancer specimens from two patient cohorts (p<0.01. Induction of cyclin A1 overexpression in breast cancer cell line MCF-7 results in an enhanced invasiveness and a concomitant increase in VEGF expression. In addition, there is a formation of protein-protein complexes between cyclin A1 and estrogen receptor ER-α cyclin A1 overexpression increases ER-α expression in MCF-7 and T47D cells. In mouse tumor xenograft models in which mice were implanted with MCF-7 cells that overexpressed cyclin A1 or control vector, cyclin A1 overexpression results in an increase in tumor growth and angiogenesis, which is coincident with an enhanced expression of VEGF, VEGFR1 and ER-α Our findings unravel a novel role for cyclin A1 in growth and progression of breast cancer, and suggest that multiple cellular pathways, including cell cycle regulators, angiogenesis and estrogen receptor signalling, may cooperatively contribute to breast cancer progression.

  20. Maternal transmission of a humanised Igf2r allele results in an Igf2 dependent hypomorphic and non-viable growth phenotype.

    Directory of Open Access Journals (Sweden)

    Jennifer Hughes

    Full Text Available The cation independent mannose 6-phosphate/insulin-like growth factor 2 receptor (IGF2R functions in the transportation and regulation of insulin-like growth factor 2 (IGF2 and mannose 6-phosphate modified proteins. The relative and specific titration of IGF2 by high affinity binding of IGF2R represents a mechanism that supports the parental conflict theory of genomic imprinting. Imprinting of Igf2 (paternal allele expressed and Igf2r (maternal allele expressed arose to regulate the relative supply of both proteins. Experiments in the mouse have established that loss of the maternal allele of Igf2r results in disproportionate growth and peri-natal lethality. In order to systematically investigate the consequences of loss of function and of hypomorphic alleles of Igf2r on growth functions, we introduced a conditional human IGF2R exon 3-48 cDNA into the intron 2 region of murine Igf2r. Here we show that the knock-in construct resulted in over-growth when the humanised Igf2r allele was maternally transmitted, a phenotype that was rescued by either paternal transmission of the humanised allele, expression of a wild-type paternal allele or loss of function of Igf2. We also show that expression of IGF2R protein was reduced to less than 50% overall in tissues previously known to be Igf2 growth dependent. This occurred despite the detection of mouse derived peptides, suggesting that trans-splicing of the knock-in human cDNA with the endogenous maternal mouse Igf2r allele. The phenotype following maternal transmission of the humanised allele resulted in overgrowth of the embryo, heart and placenta with partial peri-natal lethality, suggesting that further generation of hypomorphic Igf2r alleles are likely to be at the borderline of maintaining Igf2 dependent viability.

  1. The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the mouse

    Directory of Open Access Journals (Sweden)

    Bayrak Aykut

    2003-05-01

    Full Text Available Abstract Background Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs. CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs. Method In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. Ovaries were collected from 60-day-old cycling B6D2F1/J mice (n = 16. Results Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. However, p16 staining was stronger (++ in the oocytes of all primordial, and 57.4 ± 3.1% of primary follicles compared to the remaining primary and more advanced follicles (+. Interestingly, primary follicles with weaker (+ oocyte staining for p16 had significantly larger mean follicle diameter compared to the primary and primordial follicles with stronger (++ oocyte staining (55.6 ± 2.1 vs. 32.0 ± 1.0 and 26.5 ± 0.7 μm, respectively, p Conclusions These preliminary findings suggest that the initiation of oocyte growth, which seems to lead follicle growth, is associated with diminished p16 expression in the mouse ovary. Further studies are needed to investigate the factors that regulate the expression of p16 in the oocyte, which might also govern the initiation of primordial follicle growth.

  2. A role for random, humidity-dependent epiphytic growth prior to invasion of wheat by Zymoseptoria tritici.

    Science.gov (United States)

    Fones, Helen N; Eyles, Chris J; Kay, William; Cowper, Josh; Gurr, Sarah J

    2017-09-01

    Zymoseptoria tritici causes Septoria leaf blotch of wheat. The prevailing paradigm of the Z. tritici-wheat interaction assumes fungal ingress through stomata within 24-48h, followed by days of symptomless infection. This is extrapolated from studies testing the mode of fungal ingress under optimal infection conditions. Here, we explicitly assess the timing of entry, using GFP-tagged Z. tritici. We show that early entry is comparatively rare, and extended epiphytic growth possible. We test the hypotheses that our data diverge from earlier studies due to: i. random ingress of Z. tritici into the leaf, with some early entry events; ii. previous reliance upon fungal stains, combined with poor attachment of Z. tritici to the leaf, leading to increased likelihood of observing internal versus external growth, compared to using GFP; iii. use of exceptionally high humidity to promote entry in previous studies. We combine computer simulation of leaf-surface growth with thousands of in planta observations to demonstrate that while spores germinate rapidly on the leaf, over 95% of fungi remain epiphytic, growing randomly over the leaf for ten days or more. We show that epiphytic fungi are easily detached from leaves by rinsing and that humidity promotes epiphytic growth, increasing infection rates. Together, these results explain why epiphytic growth has been dismissed and early ingress assumed. The prolonged epiphytic phase should inform studies of pathogenicity and virulence mutants, disease control strategies, and interpretation of the observed low in planta growth, metabolic quiescence and evasion of plant defences by Zymoseptoria during symptomless infection. Copyright © 2017. Published by Elsevier Inc.

  3. Population effects of growth hormone transgenic coho salmon depend on food availability and genotype by environment interactions.

    Science.gov (United States)

    Devlin, Robert H; D'Andrade, Mark; Uh, Mitchell; Biagi, Carlo A

    2004-06-22

    Environmental risk assessment of genetically modified organisms requires determination of their fitness and invasiveness relative to conspecifics and other ecosystem members. Cultured growth hormone transgenic coho salmon (Oncorhynchus kisutch) have enhanced feeding capacity and growth, which can result in large enhancements in body size (>7-fold) relative to nontransgenic salmon, but in nature, the ability to compete for available food is a key factor determining survival fitness and invasiveness of a genotype. When transgenic and nontransgenic salmon were cohabitated and competed for different levels of food, transgenic salmon consistently outgrew nontransgenic fish and could affect the growth of nontransgenic cohorts except when food availability was high. When food abundance was low, dominant individuals emerged, invariably transgenic, that directed strong agonistic and cannibalistic behavior to cohorts and dominated the acquisition of limited food resources. When food availability was low, all groups containing transgenic salmon experienced population crashes or complete extinctions, whereas groups containing only nontransgenic salmon had good (72.0 +/- 4.3% SE) survival, and their population biomass continued to increase. Thus, effects of growth hormone transgenic salmon on experimental populations were primarily mediated by an interaction between food availability and population structure. These data, while indicative of forces which may act on natural populations, also underscore the importance of genotype by environment interactions in influencing risk assessment data for genetically modified organisms and suggest that, for species such as salmon which are derived from large complex ecosystems, considerable caution is warranted in applying data from individual studies.

  4. Co-variation of bacterial and fungal communities in different sorghum cultivars and growth stages is soil dependent

    NARCIS (Netherlands)

    Schlemper, T.R.; van Veen, J.A.; Kuramae, E.E.

    2017-01-01

    Rhizosphere microbial community composition can be influenced by different biotic and abiotic factors. We investigated the composition and co-variation of rhizosphere bacterial and fungal communities from two sorghum genotypes (BRS330 and SRN-39) in three different plant growth stages (emergence of

  5. Betulinic acid inhibits colon cancer cell and tumor growth and induces proteasome-dependent and -independent downregulation of specificity proteins (Sp) transcription factors

    International Nuclear Information System (INIS)

    Chintharlapalli, Sudhakar; Papineni, Sabitha; Lei, Ping; Pathi, Satya; Safe, Stephen

    2011-01-01

    Betulinic acid (BA) inhibits growth of several cancer cell lines and tumors and the effects of BA have been attributed to its mitochondriotoxicity and inhibition of multiple pro-oncogenic factors. Previous studies show that BA induces proteasome-dependent degradation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 in prostate cancer cells and this study focused on the mechanism of action of BA in colon cancer cells. The effects of BA on colon cancer cell proliferation and apoptosis and tumor growth in vivo were determined using standardized assays. The effects of BA on Sp proteins and Sp-regulated gene products were analyzed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a) and ZBTB10 mRNA expression. BA inhibited growth and induced apoptosis in RKO and SW480 colon cancer cells and inhibited tumor growth in athymic nude mice bearing RKO cells as xenograft. BA also decreased expression of Sp1, Sp3 and Sp4 transcription factors which are overexpressed in colon cancer cells and decreased levels of several Sp-regulated genes including survivin, vascular endothelial growth factor, p65 sub-unit of NFκB, epidermal growth factor receptor, cyclin D1, and pituitary tumor transforming gene-1. The mechanism of action of BA was dependent on cell context, since BA induced proteasome-dependent and proteasome-independent downregulation of Sp1, Sp3 and Sp4 in SW480 and RKO cells, respectively. In RKO cells, the mechanism of BA-induced repression of Sp1, Sp3 and Sp4 was due to induction of reactive oxygen species (ROS), ROS-mediated repression of microRNA-27a, and induction of the Sp repressor gene ZBTB10. These results suggest that the anticancer activity of BA in colon cancer cells is due, in part, to downregulation of Sp1, Sp3 and Sp4 transcription factors; however, the mechanism of this response is cell context-dependent

  6. Incremental Similarity and Turbulence

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole E.; Hedevang, Emil; Schmiegel, Jürgen

    This paper discusses the mathematical representation of an empirically observed phenomenon, referred to as Incremental Similarity. We discuss this feature from the viewpoint of stochastic processes and present a variety of non-trivial examples, including those that are of relevance for turbulence...

  7. Results from the PharmaSat Nanosatellite Mission: Dose Dependence of Growth and Metabolic Parameters for S. cerevisiae Grown in Microgravity and Challenged by Voriconazole

    Science.gov (United States)

    Ricco, Antonio; Parra, Macarena; Niesel, David; Ly, Diana; Kudlicki, Andrzej; McGinnis, Michael; Hines, John

    We report cellular growth and metabolic activity results for Saccharomyces cerevisiae grown aboard PharmaSat, a 5.0-kg autonomous, self-contained biological nanosatellite launched as a secondary payload in May of 2009 and presently in Earth orbit at 450 km. The response of S. cerevisiae to three dose levels bracketing the minimum inhibitory concentration (MIC) of the antifungal voriconazole was monitored in microgravity using 3-color absorbance to measure metabolic activity and turbidity (cell number), which were characterized chiefly by two param-eters: (1) the doubling time and (2) the time delay before the onset of rapid growth. Growth was conducted in forty-eight 100-L microwells containing the yeast—one fluidically separate bank of 12 wells for each voriconazole concentration, plus a control bank. Yeast were main-tained in stasis until the satellite had been deployed, the orbit stabilized, the communications links established, and the growth temperature of 27 ° C stabilized. To re-initiate yeast growth, RPMI growth medium was added. The S. cerevisiae were grown for approximately 12 hr, at which time they were challenged with varying concentrations (0, 0.25xMIC, MIC, 4xMIC) of voriconazole; the optical density and the color change of the redox-based viability indicator alamar blue were recorded as growth proceeded for an additional 84 hr. Results telemetered to the ground reveal a 33 percent longer lag time in microgravity and 60 percent longer dou-bling time than identical ground control experiments. Lag and doubling times are essentially unaffected by voriconazole at 0.125 g/mL in either environment; they lengthen similarly at 0.5 g/mL, voriconazole's MIC. At four times MIC, ground controls show no significant growth nor metabolic activity as tracked by alamar blue; in space, while there was also no measurable cellu-lar growth, remarkably, metabolic activity was clearly present (n = 12 wells). Explanations for the differences in metabolic activity and

  8. pH-dependent phytoavailability and speciation of tungsten (W) in soil affecting growth and N nutrition of soy (Glycine max)

    Science.gov (United States)

    Oburger, Eva; Vergara Cid, Carolina; Preiner, Julian; Hu, Junjian; Hann, Stephan; Wanek, Wolfgang; Richter, Andreas

    2017-04-01

    Tungsten (W) is an economically important transition metal that finds a broad scope of applications ranging from household appliances to high-end technology goods. However, in the past decades, increasing industrial and military use of W-based products (particularly ammunition, as well as drilling, milling and cutting tools) opened new pathways of W into natural systems and raise the need for a better understanding of the behavior of W in the environment. Soils play an important role in controlling the bioavailability of pollutants and their entry into the food web via plant uptake as they serve as filter and buffer systems. However, compared to other trace metals, knowledge about the fate of W in the plant-soil environment is rather sketchy. The chemical alikeness of W and molybdenum (Mo) suggests not only similar, typical anionic behaviour in soil but also a potential negative effect of W on important plant physiological processes that require Mo. We examined how soil pH dependent solubility and W speciation affected biomass production, W and nutrient uptake by soy (Glycine max cv Primus) and the activity of molybdoenzymes involved in N assimilation (nitrate reductase) and symbiotic N2 fixation (nitrogenase). Increased solubility of mainly monomeric W in high pH soils resulted in increased W plant uptake, demonstrating a greater risk of entry of W into the food web in alkaline soils. Symbiotic nitrogen fixation was able to compensate for reduced nitrate reductase activity until W soil solution concentrations became too phytotoxic, indicating a more efficient detoxification/compartmentalization mechanism in nodules than in soy leaves. The increasing presence of polymeric W species observed in low pH soils spiked with high W concentrations resulted in decreased W uptake but simultaneously had an overall negative effect on nutrient assimilation and plant growth, suggesting a greater phytotoxicity of W polymers. Our results demonstrate the importance of soil pH for

  9. Requirement of the N-terminal residues of human cytomegalovirus UL112-113 proteins for viral growth and oriLyt-dependent DNA replication.

    Science.gov (United States)

    Kim, Young-Eui; Park, Mi Young; Kang, Kyeong Jin; Han, Tae Hee; Lee, Chan Hee; Ahn, Jin-Hyun

    2015-08-01

    The UL112-113 region of the human cytomegalovirus (HCMV) genome encodes four phosphoproteins of 34, 43, 50, and 84 kDa that promote viral DNA replication. Co-transfection assays have demonstrated that self-interaction of these proteins via the shared N-termini is necessary for their intranuclear distribution as foci and for the efficient relocation of a viral DNA polymerase processivity factor (UL44) to the viral replication sites. However, the requirement of UL112-113 N-terminal residues for viral growth and DNA replication has not been fully elucidated. Here, we investigated the effect of deletion of the N-terminal regions of UL112-113 proteins on viral growth and oriLyt-dependent DNA replication. A deletion of the entire UL112 region or the region encoding the 25 N-terminal amino-acid residues from the HCMV (Towne strain) bacmid impaired viral growth in bacmid-transfected human fibroblast cells, indicating their requirement for viral growth. In co-immunoprecipitation assays using the genomic gene expressing the four UL112-113 proteins together, the 25 N-terminal amino-acid residues were found to be necessary for stable expression of UL112-113 proteins and their self-interaction. These residues were also required for efficient binding to and relocation of UL44, but not for interaction with IE2, an origin-binding transcription factor. In co-transfection/replication assays, replication of the oriLyt-containing plasmid was promoted by expression of intact UL112-113 proteins, but not by the expression of 25-amino-acid residue-deleted proteins. Our results demonstrate that the 25 N-terminal amino-acid residues of UL112-113 proteins that mediate self-interaction contribute to viral growth by promoting their binding to UL44 and the initiation of oriLyt-dependent DNA replication.

  10. Aphid effects on rhizosphere microorganisms and microfauna depend more on barley growth phase than on soil fertilization

    DEFF Research Database (Denmark)

    Madsen, Mette Vestergård; Strandmark, Lisa Bjørnlund; Christensen, Søren

    2004-01-01

    bacteria and fungal feeding nematodes 1 week before spike emergence. Before spike emergence, aphids reduced belowground respiration in NP treatments. These findings strongly indicate that aphids reduced allocation of photoassimilates to roots and deposition of root exudates in the growth phase of the plant......This paper gives the first reports on aphid effects on rhizosphere organisms as influenced by soil nutrient status and plant development. Barley plants grown in pots fertilized with N but without P (N), with N and P (NP), or not fertilized (0) were sampled in the early growth phase (day 25), 1 week....... Contrary to this, 1 week after spike emergence numbers of bacteria, fungal feeding nematodes and Protozoa were higher in rhizospheres of plants subjected to aphids probably because aphids enhanced root mortality and root decomposition. Protozoa and bacterial feeding nematodes were stimulated at different...

  11. Calcium homeostasis is required for contact-dependent helical and sinusoidal tip growth in Candida albicans hyphae

    OpenAIRE

    Brand, Alexandra; Lee, Keunsook; Veses, Veronica; Gow, Neil A R

    2009-01-01

    Hyphae of the dimorphic fungus, Candida albicans, exhibit directional tip responses when grown in contact with surfaces. On hard surfaces or in liquid media, the trajectory of hyphal growth is typically linear, with tip re-orientation events limited to encounters with topographical features (thigmotropism). In contrast, when grown on semisolid surfaces, the tips of C. albicans hyphae grow in an oscillatory manner to form regular two-dimensional sinusoidal curves and three-dimensional helices....

  12. Similarity and denoising.

    Science.gov (United States)

    Vitányi, Paul M B

    2013-02-13

    We can discover the effective similarity among pairs of finite objects and denoise a finite object using the Kolmogorov complexity of these objects. The drawback is that the Kolmogorov complexity is not computable. If we approximate it, using a good real-world compressor, then it turns out that on natural data the processes give adequate results in practice. The methodology is parameter-free, alignment-free and works on individual data. We illustrate both methods with examples.

  13. The dependence of the growth rate and meat content of young boars on semen parameters and conception rate.

    Science.gov (United States)

    Knecht, D; Jankowska-Mąkosa, A; Duziński, K

    2017-05-01

    Boars have a decisive impact on the progress in pig production, however, there is no recent information about the optimal growth parameters during the rearing period for modern breed later used in artificial insemination (AI) stations. Therefore, the objective of the research was to conduct semen parameter and conception rate analyses on the basis of growth rate and meat content assessments made during the rearing of AI boars of different genotypes. The study was carried out between 2010 and 2014 and included 184 boars in five breed combinations: 46 Polish Large White, 50 Polish Landrace, 27 Pietrain, 36 Duroc×Pietrain and 25 Hampshire×Pietrain. Boars were qualified by daily gains and meat content assessment (between 170 and 210 days of life). A total number of 38 272 ejaculates were examined (semen volume (ml), spermatozoa concentration (×106 ml-1), total number of spermatozoa (×109) and number of insemination doses from one ejaculate (n)). The fertility was determined by the conception rate (%). Semen volume, spermatozoa concentration and conception rate (PMeat content affected semen volume, number of insemination doses and conception rate (Pmeat content helps AI stations to increase the efficiency and economic profitability, and the number of insemination doses to increase by up to 300 doses/boar within a year. The analyses of growth parameters may help increase the efficiency and economic viability of AI stations.

  14. Calcium homeostasis is required for contact-dependent helical and sinusoidal tip growth in Candida albicans hyphae.

    Science.gov (United States)

    Brand, Alexandra; Lee, Keunsook; Veses, Veronica; Gow, Neil A R

    2009-03-01

    Hyphae of the dimorphic fungus, Candida albicans, exhibit directional tip responses when grown in contact with surfaces. On hard surfaces or in liquid media, the trajectory of hyphal growth is typically linear, with tip re-orientation events limited to encounters with topographical features (thigmotropism). In contrast, when grown on semisolid surfaces, the tips of C. albicans hyphae grow in an oscillatory manner to form regular two-dimensional sinusoidal curves and three-dimensional helices. We show that, like thigmotropism, initiation of directional tip oscillation in C. albicans hyphae is severely attenuated when Ca2+ homeostasis is perturbed. Chelation of extracellular Ca2+ or deletion of the Ca2+ transporters that modulate cytosolic [Ca2+] (Mid1, Cch1 or Pmr1) did not affect hyphal length but curve formation was severely reduced in mid1Delta and cch1Delta and abolished in pmr1Delta. Sinusoidal hypha morphology was altered in the mid1Delta, chs3Delta and heterozygous pmr1Delta/PMR1 strains. Treatments that affect cell wall integrity, changes in surface mannosylation or the provision of additional carbon sources had significant but less pronounced effects on oscillatory growth. The induction of two- and three-dimensional sinusoidal growth in wild-type C. albicans hyphae is therefore the consequence of mechanisms that involve Ca2+ influx and signalling rather than gross changes in the cell wall architecture.

  15. Variation in pestivirus growth in testicle primary cell culture is more dependent on the individual cell donor than cattle breed.

    Science.gov (United States)

    Weber, Matheus N; Bauermann, Fernando V; Gómez-Romero, Ninnet; Herring, Andy D; Canal, Cláudio W; Neill, John D; Ridpath, Julia F

    2017-03-01

    The causes of bovine respiratory disease complex (BRDC) are multifactorial and include infection with both viral and bacterial pathogens. Host factors are also involved as different breeds of cattle appear to have different susceptibilities to BRDC. Infection with bovine pestiviruses, including bovine viral diarrhea virus 1 (BVDV1), BVDV2 and 'HoBi'-like viruses, is linked to the development of BRDC. The aim of the present study was to compare the growth of different bovine pestiviruses in primary testicle cell cultures obtained from taurine, indicine and mixed taurine and indicine cattle breeds. Primary cells strains, derived from testicular tissue, were generated from three animals from each breed. Bovine pestivirus strains used were from BVDV-1a, BVDV-1b, BVDV-2a and 'HoBi'-like virus. Growth was compared by determining virus titers after one passage in primary cells. All tests were run in triplicate. Virus titers were determined by endpoint dilution and RT-qPCR. Statistical analysis was performed using one way analysis of variance (ANOVA) followed by the Tukey's Multiple Comparison Test (P˂0.05). Significant differences in virus growth did not correlate with cattle breed. However, significant differences were observed between cells derived from different individuals regardless of breed. Variation in the replication of virus in primary cell strains may reflect a genetic predisposition that favors virus replication.

  16. EphB4 Tyrosine Kinase Stimulation Inhibits Growth of MDA-MB-231 Breast Cancer Cells in a Dose and Time Dependent Manner

    Directory of Open Access Journals (Sweden)

    Farnaz Barneh

    2013-01-01

    Full Text Available Background. EphB4 receptor tyrosine kinase is of diagnostic and therapeutic value due to its overexpression in breast tumors. Dual functions of tumor promotion and suppression have been reported for this receptor based on presence or absence of its ligand. To elucidate such discrepancy, we aimed to determine the effect of time- and dose-dependent stimulation of EphB4 on viability and invasion of breast cancer cells via recombinant ephrinB2-Fc. Methods. Cells were seeded into multiwell plates and were stimulated by various concentrations of preclustered ephrinB2-Fc. Cell viability was measured on days 3 and 6 following treatment using alamar-blue when cells were in different states of confluence. Results. Stimulation of cells with ephrinB2 did not pose any significant effect on cell viability before reaching confluence, while inhibition of cell growth was detected after 6 days when cells were in postconfluent state following a dose-dependent manner. EphrinB2 treatment did not affect tubular formation and invasion on matrigel. Conclusion. This study showed that EphB4 can differentially inhibit cells at post confluent state and that presence of ligand manifests growth-inhibitory properties of EphB4 receptor. It is concluded that growth inhibition has occurred possibly due to long treatment with ligand, a process which leads to receptor downregulation.

  17. Host plant secondary metabolite profiling shows a complex, strain-dependent response of maize to plant growth-promoting rhizobacteria of the genus Azospirillum.

    Science.gov (United States)

    Walker, Vincent; Bertrand, Cédric; Bellvert, Floriant; Moënne-Loccoz, Yvan; Bally, René; Comte, Gilles

    2011-01-01

    Most Azospirillum plant growth-promoting rhizobacteria (PGPR) benefit plant growth through source effects related to free nitrogen fixation and/or phytohormone production, but little is known about their potential effects on plant physiology. These effects were assessed by comparing the early impacts of three Azospirillum inoculant strains on secondary metabolite profiles of two different maize (Zea mays) cultivars. After 10d of growth in nonsterile soil, maize methanolic extracts were analyzed by reverse-phase high-performance liquid chromatography (RP-HPLC) and secondary metabolites identified by liquid chromatography/mass spectrometry (LC/MS) and nuclear magnetic resonance (NMR). Seed inoculation resulted in increased shoot biomass (and also root biomass with one strain) of hybrid PR37Y15 but had no stimulatory effect on hybrid DK315. In parallel, Azospirillum inoculation led to major qualitative and quantitative modifications of the contents of secondary metabolites, especially benzoxazinoids, in the maize plants. These modifications depended on the PGPR strain×plant cultivar combination. Thus, Azospirillum inoculation resulted in early, strain-dependent modifications in the biosynthetic pathways of benzoxazine derivatives in maize in compatible interactions. This is the first study documenting a PGPR effect on plant secondary metabolite profiles, and suggests the establishment of complex interactions between Azospirillum PGPR and maize. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).

  18. Immigration-dependent extensive growth in small island tourism economies : The cases of Aruba and Sint Maarten

    NARCIS (Netherlands)

    Alberts, A.

    Aruba and Sint Maarten are two countries within the Kingdom of the Netherlands, situated in the Caribbean. Both have embarked on a dedicated tourism-driven and highly immigration-dependent development model starting in the 1970s and 1980s, making them typical examples of ‘Small Island Tourist

  19. TEMPERATURE-DEPENDENCE OF CHLOROPHYLL FLUORESCENCE INDUCTION AND PHOTOSYNTHESIS IN TOMATO AS AFFECTED BY TEMPERATURE AND LIGHT CONDITIONS DURING GROWTH

    NARCIS (Netherlands)

    JANSSEN, LHJ; WAMS, HE; VANHASSELT, PR

    The temperature dependence of chlorophyll fluorescence induction and photosynthesis of tomato plants grown at different temperatures and light intensities was studied. Chlorophyll fluorescence induction and photosynthetic activity of leaf discs was determined between 0-degrees and 30-degrees-C. Two

  20. Soil compaction effects on growth and root traits of tobacco depend on light, water regime and mechanical stress

    NARCIS (Netherlands)

    Alameda, D.; Anten, N.P.R.; Villar, R.

    2012-01-01

    Soil compaction can strongly affect plant performance as many other stress factors. In nature, many combinations of different stress factors may be found. We expect that the effects of soil compaction may be different depending of the occurrence of other stress. This has not been fully investigated;

  1. More Similar Than Different

    DEFF Research Database (Denmark)

    Pedersen, Mogens Jin

    2018-01-01

    What role do employee features play into the success of different personnel management practices for serving high performance? Using data from a randomized survey experiment among 5,982 individuals of all ages, this article examines how gender conditions the compliance effects of different...... incentive treatments—each relating to the basic content of distinct types of personnel management practices. The findings show that males and females are more similar than different in terms of the incentive treatments’ effects: Significant average effects are found for three out of five incentive...

  2. Endolysosomal membrane trafficking complexes drive nutrient-dependent TORC1 signaling to control cell growth in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kingsbury, Joanne M; Sen, Neelam D; Maeda, Tatsuya; Heitman, Joseph; Cardenas, Maria E

    2014-04-01

    The rapamycin-sensitive and endomembrane-associated TORC1 pathway controls cell growth in response to nutrients in eukaryotes. Mutations in class C Vps (Vps-C) complexes are synthetically lethal with tor1 mutations and confer rapamycin hypersensitivity in Saccharomyces cerevisiae, suggesting a role for these complexes in TORC1 signaling. Vps-C complexes are required for vesicular trafficking and fusion and comprise four distinct complexes: HOPS and CORVET and their minor intermediaries (i)-CORVET and i-HOPS. We show that at least one Vps-C complex is required to promote TORC1 activity, with the HOPS complex having the greatest input. The vps-c mutants fail to recover from rapamycin-induced growth arrest and show low levels of TORC1 activity. TORC1 promotes cell growth via Sch9, a p70(S6) kinase ortholog. Constitutively active SCH9 or hyperactive TOR1 alleles restored rapamycin recovery and TORC1 activity of vps-c mutants, supporting a role for the Vps-C complexes upstream of TORC1. The EGO GTPase complex Exit from G0 Complex (EGOC) and its homologous Rag-GTPase complex convey amino acid signals to TORC1 in yeast and mammals, respectively. Expression of the activated EGOC GTPase subunits Gtr1(GTP) and Gtr2(GDP) partially suppressed vps-c mutant rapamycin recovery defects, and this suppression was enhanced by increased amino acid concentrations. Moreover, vps-c mutations disrupted EGOC-TORC1 interactions. TORC1 defects were more severe for vps-c mutants than those observed in EGOC mutants. Taken together, our results support a model in which distinct endolysosomal trafficking Vps-C complexes promote rapamycin-sensitive TORC1 activity via multiple inputs, one of which involves maintenance of amino acid homeostasis that is sensed and transmitted to TORC1 via interactions with EGOC.

  3. A Novel NHE1-Centered Signaling Cassette Drives Epidermal Growth Factor Receptor–Dependent Pancreatic Tumor Metastasis and Is a Target for Combination Therapy

    Directory of Open Access Journals (Sweden)

    Rosa Angela Cardone

    2015-02-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal cancers principally because of early invasion and metastasis. The epidermal growth factor receptor (EGFR is essential for PDAC development even in the presence of Kras, but its inhibition with erlotinib gives only a modest clinical response, making the discovery of novel EGFR targets of critical interest. Here, we revealed by mining a human pancreatic gene expression database that the metastasis promoter Na+/H+ exchanger (NHE1 associates with the EGFR in PDAC. In human PDAC cell lines, we confirmed that NHE1 drives both basal and EGF-stimulated three-dimensional growth and early invasion via invadopodial extracellular matrix digestion. EGF promoted the complexing of EGFR with NHE1 via the scaffolding protein Na+/H+ exchanger regulatory factor 1, engaging EGFR in a negative transregulatory loop that controls the extent and duration of EGFR oncogenic signaling and stimulates NHE1. The specificity of NHE1 for growth or invasion depends on the segregation of the transient EGFR/Na+/H+ exchanger regulatory factor 1/NHE1 signaling complex into dimeric subcomplexes in different lipid raftlike membrane domains. This signaling complex was also found in tumors developed in orthotopic mice. Importantly, the specific NHE1 inhibitor cariporide reduced both three-dimensional growth and invasion independently of PDAC subtype and synergistically sensitized these behaviors to low doses of erlotinib.

  4. Highly textured Gd2Zr2O7 films grown on textured Ni-5 at.%W substrates by solution deposition route: Growth, texture evolution, and microstructure dependency

    DEFF Research Database (Denmark)

    Yue, Zhao; Grivel, Jean-Claude; Napari, M.

    2012-01-01

    or crystallization in the thicker films. This work not only demonstrates a route for producing textured Gd2Zr2O7 buffer layers with dense structure directly on technical substrates, but also provides some fundamental understandings related to chemical solution derived films grown on metallic substrates.......Growth, texture evolution and microstructure dependency of solution derived Gd2Zr2O7 films deposited on textured Ni-5 at.%W substrates have been extensively studied. Influence of processing parameters, in particular annealing temperature and dwell time, as well as thickness effect on film texture...... the difference of interfacial energy along two directions in the anisotropic metallic substrate. Growth of Gd2Zr2O7 films displays an ultrafast kinetics under optimized conditions. Independency of sharp epitaxial (004) and polycrystalline (222) orientation is revealed from further synchrotron diffraction studies...

  5. Nucleation and growth of surfactant-passivated CdS and HgS nanoparticles: Time-dependent absorption and luminescence profiles

    Science.gov (United States)

    Mehta, S. K.; Kumar, Sanjay; Chaudhary, Savita; Bhasin, K. K.

    2010-01-01

    In this study, we have monitored the formation of CdS and HgS nanoparticles (NPs) using a precipitation method in the presence of surface-active agents. Three surfactants were tested to analyze the dependence of various parameters such as size, growth rate, photoluminescence (PL) emission and polydispersity of NPs on surfactant structure. Optical absorption spectroscopy was mainly used to estimate the optical bandgap and the size of NPs. The surfactant-induced quenching of PL intensity was found to be consistent with the different tendencies of the surfactants to act as Lewis acids towards these surfaces. The time-evolution of the absorbance suggested that the nucleation and growth rates markedly vary in a first-order fashion w.r.t. Cd2+ and Hg2+ salt concentration in excess of sulfide ions. The differences in the stabilization ability of the surfactants are discussed in reference to their structure-dependent adsorption behavior onto the particles. The comparative aspects of the different properties of CdS and HgS NPs prepared with identical methodology are presented in terms of metal cation-surfactant interactions. Changes in UV-vis and PL spectra during nucleation and growth of NPs were used to establish the possible mechanisms for the adsorption of surfactant molecules on the particle surface to restrict the unlimited growth.In this study, we have monitored the formation of CdS and HgS nanoparticles (NPs) using a precipitation method in the presence of surface-active agents. Three surfactants were tested to analyze the dependence of various parameters such as size, growth rate, photoluminescence (PL) emission and polydispersity of NPs on surfactant structure. Optical absorption spectroscopy was mainly used to estimate the optical bandgap and the size of NPs. The surfactant-induced quenching of PL intensity was found to be consistent with the different tendencies of the surfactants to act as Lewis acids towards these surfaces. The time-evolution of the absorbance

  6. Epigenetic control of hypoxia inducible factor-1α-dependent expression of placental growth factor in hypoxic conditions.

    Science.gov (United States)

    Tudisco, Laura; Della Ragione, Floriana; Tarallo, Valeria; Apicella, Ivana; D'Esposito, Maurizio; Matarazzo, Maria Rosaria; De Falco, Sandro

    2014-04-01

    Hypoxia plays a crucial role in the angiogenic switch, modulating a large set of genes mainly through the activation of hypoxia-inducible factor (HIF) transcriptional complex. Endothelial cells play a central role in new vessels formation and express placental growth factor (PlGF), a member of vascular endothelial growth factor (VEGF) family, mainly involved in pathological angiogenesis. Despite several observations suggest a hypoxia-mediated positive modulation of PlGF, the molecular mechanism governing this regulation has not been fully elucidated. We decided to investigate if epigenetic modifications are involved in hypoxia-induced PlGF expression. We report that PlGF expression was induced in cultured human and mouse endothelial cells exposed to hypoxia (1% O 2), although DNA methylation at the Plgf CpG-island remains unchanged. Remarkably, robust hyperacetylation of histones H3 and H4 was observed in the second intron of Plgf, where hypoxia responsive elements (HREs), never described before, are located. HIF-1α, but not HIF-2α, binds to identified HREs. Noteworthy, only HIF-1α silencing fully inhibited PlGF upregulation. These results formally demonstrate a direct involvement of HIF-1α in the upregulation of PlGF expression in hypoxia through chromatin remodeling of HREs sites. Therefore, PlGF may be considered one of the putative targets of anti-HIF therapeutic applications.

  7. Time of Growth Dependent of ZnO-Nanorods by Self-Assembly Methods and its Structural Properties

    Science.gov (United States)

    Aprilia, A.; Bahtiar, A.; Safriani, L.; Ayunita, C. C.; Afifah, N.; Syakir, N.; Risdiana; Saragi, T.; Hidayat, S.; Fitrilawati; Siregar, R. E.

    2017-05-01

    ZnO-nanorods (ZnO-Nrs) have been successfully prepared on glass substrate using self-assembly method by varying deposition time. Zn acetate dehydrate and 2-methoxyethanol was used as raw material and solvent respectively (for ZnO seed layer preparation), meanwhile Zn nitrate hexahydrate and hexametylenetetramine (HMTA) dissolved in deionized water used as solution growth of ZnO-Nanorods (ZnO-Nrs). In this work, deposition times of ZnO-Nrs were varied by 120 min, 150 min, 180 min and 210 minutes at 100°C of annealing temperature. In order to investigate the physical properties of resulting ZnO, several measurements such as x-ray diffraction (XRD), ultra-violet visible spectroscopy and scanning electron microscopy (SEM) were carried out. Based on ZnO nanorods SEM image with varying time depositions, seems that increasing deposition time the nanorod size decrease but when the time reach 210 min, the average size of nanorods turned back increase. From XRD measurement, the average grain size and lattice constant (c) which is assemble the nanorod structure and lattice constant (c) was determined by Debye-Scherrer formula and Bragg law’s respectively. The growth process of ZnO nanorod by 180 min time deposition was known as an appropriate time to produce ZnO nanorods with high crystal quality due to sharp peak intensity of XRD spectrum.

  8. Oxygen-dependent epitaxial growth of Pt(001) thin films on MgO(001) by magnetron sputtering

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, X.Y., E-mail: qxy2001@swu.edu.cn [School of Physical Science and Technology, Southwest University, Chongqing 400715 (China); Wang, R.X.; Li, G.Q.; Zhang, T.; Li, L.T.; Wei, M.L.; Meng, X.S. [School of Physical Science and Technology, Southwest University, Chongqing 400715 (China); Ji, H. [School of Energy Science and Engineering, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan (China); Zhang, Z.; Chan, C.H.; Dai, J.Y. [Department of Applied Physics, The Hong Kong Polytechnic University, Hong Kong (China)

    2017-06-01

    Highlights: • The optimized oxygen ratio for high-quality epitaxial Pt (001) thin films is 15%. • Platinum oxides is formed after the oxygen ratio is more than 30%. • Epitaxial growth of Pt on MgO(001) is cube to cube with Pt(001)//MgO(001). - Abstract: The roles of oxygen gas in crystal orientation, surface morphology and electrical resistivity of Pt thin films grown on MgO(001) substrate by magnetron sputtering are studied. With a well-controlled oxygen ratio (15% oxygen) during sputtering deposition with Ar-O{sub 2} mixture ambient, (001) epitaxial growth of Pt film on MgO substrate is achieved with an epitaxial orientation relationship of (001)Pt//(001)MgO and [100]Pt//[100]MgO. Microstructural and electrical characterizations reveal that the (001) Pt thin films possess very smooth surface and good conductivity. The formation and subsequent decomposition of platinum oxides in the Pt films grown with more than 30% oxygen result in an increase of surface roughness and electrical resistivity. The high-quality Pt(001) film has large potential for integrated electronic device applications.

  9. Chemoheterotrophic growth of the Cyanobacterium Anabaena sp. strain PCC 7120 dependent on a functional cytochrome c oxidase.

    Science.gov (United States)

    Stebegg, Ronald; Wurzinger, Bernhard; Mikulic, Markus; Schmetterer, Georg

    2012-09-01

    Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium commonly used as a model organism for studying cyanobacterial cell differentiation and nitrogen fixation. For many decades, this cyanobacterium was considered an obligate photo-lithoautotroph. We now discovered that this strain is also capable of mixotrophic, photo-organoheterotrophic, and chemo-organoheterotrophic growth if high concentrations of fructose (at least 50 mM and up to 200 mM) are supplied. Glucose, a substrate used by some facultatively organoheterotrophic cyanobacteria, is not effective in Anabaena sp. PCC 7120. The gtr gene from Synechocystis sp. PCC 6803 encoding a glucose carrier was introduced into Anabaena sp. PCC 7120. Surprisingly, the new strain containing the gtr gene did not grow on glucose but was very sensitive to glucose, with a 5 mM concentration being lethal, whereas the wild-type strain tolerated 200 mM glucose. The Anabaena sp. PCC 7120 strain containing gtr can grow mixotrophically and photo-organoheterotrophically, but not chemo-organoheterotrophically with fructose. Anabaena sp. PCC 7120 contains five respiratory chains ending in five different respiratory terminal oxidases. One of these enzymes is a mitochondrial-type cytochrome c oxidase. As in almost all cyanobacteria, this enzyme is encoded by three adjacent genes called coxBAC1. When this locus was disrupted, the cells lost the capability for chemo-organoheterotrophic growth.

  10. The G Protein-Coupled Estrogen Receptor-1, GPER-1, Promotes Fibrillogenesis via a Shc-Dependent Pathway Resulting in Anchorage-Independent Growth

    Science.gov (United States)

    Magruder, Hilary T.; Quinn, Jeffrey A.; Schwartzbauer, Jean E.; Reichner, Jonathan; Huang, Allan

    2016-01-01

    The G protein-coupled estrogen receptor-1, GPER-1, coordinates fibronectin (FN) matrix assembly and release of heparan-bound epidermal growth factor (HB-EGF). This mechanism of action results in the recruitment of FN-engaged integrin α5β1 to fibrillar adhesions and the formation of integrin α5β1-Shc adaptor protein complexes. Here, we show that GPER-1 stimulation of murine 4 T1 or human SKBR3 breast cancer cells with 17β-estradiol (E2β) promotes the formation of focal adhesions and actin stress fibers and results in increased cellular adhesion and haptotaxis on FN, but not collagen. These actions are also induced by the xenoestrogen, bisphenol A, and the estrogen receptor (ER) antagonist, ICI 182, 780, but not the inactive stereoisomer, 17α-estradiol (E2α). In addition, we show that GPER-1 stimulation of breast cancer cells allows for FN-dependent, anchorage-independent growth and FN fibril formation in “hanging drop” assays, indicating that these GPER-1-mediated actions occur independently of adhesion to solid substrata. Stable expression of Shc mutant Y317F lacking its primary tyrosyl phosphorylation site disrupts E2β-induced focal adhesion and actin stress fiber formation and abolishes E2β-enhanced haptotaxis on FN and anchorage-dependent growth. Collectively, these data demonstrate that E2β action via GPER-1 enhances cellular adhesivity and FN matrix assembly and allows for anchorage-independent growth, cellular events that may allow for cellular survival, and tumor progression. PMID:25096985

  11. Sensitivity of Photosynthetic Gas Exchange and Growth of Lodgepole Pine to Climate Variability Depends on the Age of Pleistocene Glacial Surfaces

    Science.gov (United States)

    Osborn, B.; Chapple, W.; Ewers, B. E.; Williams, D. G.

    2014-12-01

    The interaction between soil conditions and climate variability plays a central role in the ecohydrological functions of montane conifer forests. Although soil moisture availability to trees is largely dependent on climate, the depth and texture of soil exerts a key secondary influence. Multiple Pleistocene glacial events have shaped the landscape of the central Rocky Mountains creating a patchwork of soils differing in age and textural classification. This mosaic of soil conditions impacts hydrological properties, and montane conifer forests potentially respond to climate variability quite differently depending on the age of glacial till and soil development. We hypothesized that the age of glacial till and associated soil textural changes exert strong control on growth and photosynthetic gas exchange of lodgepole pine. We examined physiological and growth responses of lodgepole pine to interannual variation in maximum annual snow water equivalence (SWEmax) of montane snowpack and growing season air temperature (Tair) and vapor pressure deficit (VPD) across a chronosequence of Pleistocene glacial tills ranging in age from 700k to 12k years. Soil textural differences across the glacial tills illustrate the varying degrees of weathering with the most well developed soils with highest clay content on the oldest till surfaces. We show that sensitivity of growth and carbon isotope discrimination, an integrated measure of canopy gas exchange properties, to interannual variation SWEmax , Tair and VPD is greatest on young till surfaces, whereas trees on old glacial tills with well-developed soils are mostly insensitive to these interannual climate fluctuations. Tree-ring widths were most sensitive to changes in SWEmax on young glacial tills (p < 0.01), and less sensitive on the oldest till (p < 0.05). Tair correlates strongly with δ13C values on the oldest and youngest tills sites, but shows no significant relationship on the middle aged glacial till. It is clear that

  12. Time-dependent effect of orchidectomy on vascular nitric oxide and thromboxane A2 release. Functional implications to control cell proliferation through activation of the epidermal growth factor receptor.

    Directory of Open Access Journals (Sweden)

    Marta del Campo

    Full Text Available This study analyzes whether the release of nitric oxide (NO and thromboxane A2 (TXA2 depends on the time lapsed since gonadal function is lost, and their correlation with the proliferation of vascular smooth muscle cells (VSMC mediated by the epidermal growth factor receptor (EGFR. For this purpose, aortic and mesenteric artery segments from control and 6-weeks or 5-months orchidectomized rats were used to measure NO and TXA2 release. The results showed that the basal and acetylcholine (ACh-induced NO release were decreased 6 weeks post-orchidectomy both in aorta and mesenteric artery, but were recovered 5 months thereafter up to levels similar to those found in arteries from control rats. The basal and ACh-induced TXA2 release increased in aorta and mesenteric artery 6 weeks post-orchidectomy, and was maintained at high levels 5 months thereafter. Since we previously observed that orchidectomy, which decreased testosterone level, enlarged the muscular layer of mesenteric arteries, the effect of testosterone on VSMC proliferation was analyzed. The results showed that treatment of cultured VSMC with testosterone downregulated mitogenic signaling pathways initiated by the ligand-dependent activation of the EGFR. In contrast, the EGFR pathways were constitutively active in mesenteric arteries of long-term orchidectomized rats. Thus, the exposure of mesenteric arteries from control rats to epidermal growth factor (EGF induced the activation of EGFR signaling pathways. However, the addition of EGF to arteries from orchidectomized rats failed to induce a further activation of these pathways. In conclusion, this study shows that the release of NO depends on the time lapsed since the gonadal function is lost, while the release of TXA2 is already increased after short periods post-orchidectomy. The alterations in these signaling molecules could contribute to the constitutive activation of the EGFR and its downstream signaling pathways after long period

  13. Age-Dependent Decrease in Serum Transforming Growth Factor (TGF-Beta 1 in Healthy Japanese Individuals; Population Study of Serum TGF-Beta 1 Level in Japanese

    Directory of Open Access Journals (Sweden)

    Yoshihiro Okamoto

    2005-01-01

    Full Text Available Transforming growth factor-beta1 (TGF-β1, a multi-functional cytokine, is involved in regulating a variety of cellular activities and the serum/plasma TGF-β1 level is altered with various diseases. However, most published reports have described adult patients, and so we investigated the clinical significance of serum TGF-β1 level in pediatric patients. The diagnostic application of the measurement of serum TGF-β1 level depends critically on the control value, however, there is no information on the control value of serum TGF-β1 for children.

  14. Adaptive Significance of Quorum Sensing-Dependent Regulation of Rhamnolipids by Integration of Growth Rate in Burkholderia glumae: A Trade-Off between Survival and Efficiency.

    Science.gov (United States)

    Nickzad, Arvin; Déziel, Eric

    2016-01-01

    Quorum sensing (QS) is a cell density-dependent mechanism which enables a population of bacteria to coordinate cooperative behaviors in response to the accumulation of self-produced autoinducer signals in their local environment. An emerging framework is that the adaptive significance of QS in the regulation of production of costly extracellular metabolites ("public goods") is to maintain the homeostasis of cooperation. We investigated this model using the phytopathogenic bacterium Burkholderia glumae, which we have previously demonstrated uses QS to regulate the production of rhamnolipids, extracellular surface-active glycolipids promoting the social behavior called "swarming motility." Using mass spectrometric quantification and chromosomal lux-based gene expression, we made the unexpected finding that when unrestricted nutrient resources are provided, production of rhamnolipids is carried out completely independently of QS regulation. This is a unique observation among known QS-controlled factors in bacteria. On the other hand, under nutrient-limited conditions, QS then becomes the main regulating mechanism, significantly enhancing the specific rhamnolipids yield. Accordingly, decreasing nutrient concentrations amplifies rhamnolipid biosynthesis gene expression, revealing a system where QS-dependent regulation is specifically triggered by the growth rate of the population, rather than by its cell density. Furthermore, a gradual increase in QS signal specific concentration upon decrease of specific growth rate suggests a reduction in quorum threshold, which reflects an increase in cellular demand for production of QS-dependent target gene product at low density populations. Integration of growth rate with QS as a decision-making mechanism for biosynthesis of costly metabolites, such as rhamnolipids, could serve to assess the demand and timing for expanding the carrying capacity of a population through spatial expansion mechanisms, such as swarming motility, thus

  15. Modeling of similar economies

    Directory of Open Access Journals (Sweden)

    Sergey B. Kuznetsov

    2017-06-01

    Full Text Available Objective to obtain dimensionless criteria ndash economic indices characterizing the national economy and not depending on its size. Methods mathematical modeling theory of dimensions processing statistical data. Results basing on differential equations describing the national economy with the account of economical environment resistance two dimensionless criteria are obtained which allow to compare economies regardless of their sizes. With the theory of dimensions we show that the obtained indices are not accidental. We demonstrate the implementation of the obtained dimensionless criteria for the analysis of behavior of certain countriesrsquo economies. Scientific novelty the dimensionless criteria are obtained ndash economic indices which allow to compare economies regardless of their sizes and to analyze the dynamic changes in the economies with time. nbsp Practical significance the obtained results can be used for dynamic and comparative analysis of different countriesrsquo economies regardless of their sizes.

  16. Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage

    DEFF Research Database (Denmark)

    Järås, Marcus; Johnels, Petra; Agerstam, Helena

    2009-01-01

    OBJECTIVE: The P190 and P210 BCR/ABL1 fusion genes are mainly associated with different types of hematologic malignancies, but it is presently unclear whether they are functionally different following expression in primitive human hematopoietic cells. MATERIALS AND METHODS: We investigated...... and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. RESULTS: Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells...... and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under...

  17. Density dependence and phenological mismatch: consequences for growth and survival of sub-arctic nesting Canada Geese

    Science.gov (United States)

    Brook, Rodney W.; Leafloor, James O.; Douglas, David C.; Abraham, Kenneth F.

    2015-01-01

    The extent to which species are plastic in the timing of their reproductive events relative to phenology suggests how change might affect their demography. An ecological mismatch between the timing of hatch for avian species and the peak availability in quality and quantity of forage for rapidly growing offspring might ultimately affect recruitment to the breeding population unless individuals can adjust the timing of breeding to adapt to changing phenology. We evaluated effects of goose density, hatch timing relative to forage plant phenology, and weather indices on annual growth of pre-fledging Canada geese (Branta canadensis) from 1993-2010 at Akimiski Island, Nunavut. We found effects of both density and hatch timing relative to forage plant phenology; the earlier that eggs hatched relative to forage plant phenology, the larger the mean gosling size near fledging. Goslings were smallest in years when hatch was latest relative to forage plant phenology, and when local abundance of breeding adults was highest. We found no evidence for a trend in relative hatch timing, but it was apparent that in early springs, Canada geese tended to hatch later relative to vegetation phenology, suggesting that geese were not always able to adjust the timing of nesting as rapidly as vegetation phenology was advanced. Analyses using forage biomass information revealed a positive relationship between gosling size and per capita biomass availability, suggesting a causal mechanism for the density effect. The effects of weather parameters explained additional variation in mean annual gosling size, although total June and July rainfall had a small additive effect on gosling size. Modelling of annual first year survival probability using mean annual gosling size as an annual covariate revealed a positive relationship, suggesting that reduced gosling growth negatively impacts recruitment.

  18. INSULIN LIKE GROWTH FACTOR 1 POSSIBLE DEPENDENCE IN PATIENTS WITH METABOLIC SYNDROME OF NODULAR PATHOLOGY OF THE THYROID GLAND.

    Science.gov (United States)

    Rekvava, M; Dundua, T; Kobulia, M; Javashvili, L; Giorgadze, E

    2017-09-01

    Metabolic syndrome and nodular pathology of the thyroid gland is a widespread problem nowadays. Recently there has been a notable coincidence between metabolic syndrome and nodular pathology of thyroid gland. Hence, it is interesting to reveal the connection between these two diseases. It is possible that insulin-like growth factor system (IGF), namely IGF 1 is connecting link between metabolic syndrome and nodular pathology of thyroid gland, because IGF1 stimulates growth and proliferation of cells in the body. We have investigated18-82 years of age 71 patients. group 1 n27- subjects with thyroid nodular disease, and metabolic syndrome, group 2 n31- subjects with thyroid nodular disease and without metabolic syndrome. group 3 n13 - subjects with metabolic syndrome and no thyroid pathology. In all groups were assessed thyroid structural data, defined parameters of carbohydrate metabolism, thyroid function and blood concentration of IGF1. In patients with hyperinsulinemia IGF 1 was noted in normal or reduced concentration. In I group IGF1 was normal in 70,4% (n=19), decreased in 29,6% (n=8), In II group was normal in 77,4 % (n=24), decreased in 22,6% (n=7) and in III group was normal in 76,9% (n=10), decreased in 23,1% (n=3). Increase of IGF 1 in patients with thyroid nodular disease patients was not noted. Statistically significant connection between IGF1 and thyroid nodules was not revealed. For the further investigation of this connection we plan to measure IGF1 in the thyroid histological samples in the future studies.

  19. Density dependence and phenological mismatch: consequences for growth and survival of sub-arctic nesting Canada Geese

    Directory of Open Access Journals (Sweden)

    Rodney W. Brook

    2015-06-01

    Full Text Available The extent to which species are plastic in the timing of their reproductive events relative to phenology suggests how climate change might affect their demography. An ecological mismatch between the timing of hatch for avian species and the peak availability in quality and quantity of forage for rapidly growing offspring might ultimately affect recruitment to the breeding population unless individuals can adjust the timing of breeding to adapt to changing phenology. We evaluated effects of goose density, hatch timing relative to forage plant phenology, and weather indices on annual growth of pre-fledging Canada geese (Branta canadensis from 1993-2010 at Akimiski Island, Nunavut. We found effects of both density and hatch timing relative to forage plant phenology; the earlier that eggs hatched relative to forage plant phenology, the larger the mean gosling size near fledging. Goslings were smallest in years when hatch was latest relative to forage plant phenology, and when local abundance of breeding adults was highest. We found no evidence for a trend in relative hatch timing, but it was apparent that in early springs, Canada geese tended to hatch later relative to vegetation phenology, suggesting that geese were not always able to adjust the timing of nesting as rapidly as vegetation phenology was advanced. Analyses using forage biomass information revealed a positive relationship between gosling size and per capita biomass availability, suggesting a causal mechanism for the density effect. The effects of weather parameters explained additional variation in mean annual gosling size, although total June and July rainfall had a small additive effect on gosling size. Modelling of annual first-year survival probability using mean annual gosling size as an annual covariate revealed a positive relationship, suggesting that reduced gosling growth negatively impacts recruitment.

  20. Active browsing using similarity pyramids

    Science.gov (United States)

    Chen, Jau-Yuen; Bouman, Charles A.; Dalton, John C.

    1998-12-01

    In this paper, we describe a new approach to managing large image databases, which we call active browsing. Active browsing integrates relevance feedback into the browsing environment, so that users can modify the database's organization to suit the desired task. Our method is based on a similarity pyramid data structure, which hierarchically organizes the database, so that it can be efficiently browsed. At coarse levels, the similarity pyramid allows users to view the database as large clusters of similar images. Alternatively, users can 'zoom into' finer levels to view individual images. We discuss relevance feedback for the browsing process, and argue that it is fundamentally different from relevance feedback for more traditional search-by-query tasks. We propose two fundamental operations for active browsing: pruning and reorganization. Both of these operations depend on a user-defined relevance set, which represents the image or set of images desired by the user. We present statistical methods for accurately pruning the database, and we propose a new 'worm hole' distance metric for reorganizing the database, so that members of the relevance set are grouped together.

  1. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS

    DEFF Research Database (Denmark)

    Holm, Mette; Dybedahl, I; Holm, Mette

    2014-01-01

    This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a trans......This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks...... after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS...... patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations....

  2. Alterations in serum growth hormone (GH)/GH dependent ternary complex components (IGF-I, IGFBP-3, ALS, IGF-I/IGFBP-3 molar ratio) and the influence of these alterations on growth pattern in female rhythmic gymnasts.

    Science.gov (United States)

    Adiyaman, P; Ocal, G; Berberoğlu, M; Evliyaoğlu, O; Aycan, Z; Cetinkaya, E; Bulca, Y; Ersöz, G; Akar, N

    2004-06-01

    Normal growth in children is regulated to a great extent through the actions of the GH/IGF-I axis, a system consisting of GH and its mediators (ternary complex) that modulate growth in many tissues. The ternary complex (IGF-I/IGFBP-3/ALS) provides an acute regulatory mechanism in which IGF-I may be mobilized from the circulating reservoir of 150 kDa complexes to the tissues. Acute exercise is known to be a stimulus for GH secretion. The beneficial effects of scheduled exercise on body composition are also well established. However, the impact of strenuous exercise on the pubertal development of child athletes is still not well understood. The first goal of this study was to assess the acute effects of high intensity exercise training on GH-dependent ternary complex components in female rhythmic gymnasts compared to age-matched healthy female controls with normal physical activity. The second goal was to explore the influence of these exercise-induced changes on skeletal and pubertal growth in the same group prospectively over a period of 4 years. Seventeen female rhythmic gymnasts, aged 11.4 +/- 0.9 years, who had 10 h per week intense exercise for at least 4 months volunteered to participate in this study. Anthropometric measurement of height (Height SDS for chronological age [HtSDS(CA)], parentally adjusted height, predicted adult height), bone age and weight (BMI) were made using standard techniques in gymnasts and controls (aged 12.5 +/- 3.0 years, n = 12). Gymnasts were followed up to 4 years to observe growth velocity and pubertal progression. In order to determine the acute impact of exercise on levels of GH and GH-dependent ternary complex component (IGF-I, IGFBP-3, ALS, IGF-I/IGFBP-3 molar ratio), blood samples were obtained from gymnasts after a routine 2-h high-intensity training program and then after a 2-day rest period. These results were compared with age-matched controls with no scheduled sports activity. Despite the significant increment in serum

  3. Amino acid transporter genes are essential for FLO11-dependent and FLO11-independent biofilm formation and invasive growth in Saccharomyces cerevisiae.

    Science.gov (United States)

    Torbensen, Rasmus; Møller, Henrik Devitt; Gresham, David; Alizadeh, Sefa; Ochmann, Doreen; Boles, Eckhard; Regenberg, Birgitte

    2012-01-01

    Amino acids can induce yeast cell adhesion but how amino acids are sensed and signal the modulation of the FLO adhesion genes is not clear. We discovered that the budding yeast Saccharomyces cerevisiae CEN.PK evolved invasive growth ability under prolonged nitrogen limitation. Such invasive mutants were used to identify amino acid transporters as regulators of FLO11 and invasive growth. One invasive mutant had elevated levels of FLO11 mRNA and a Q320STOP mutation in the SFL1 gene that encodes a protein kinase A pathway regulated repressor of FLO11. Glutamine-transporter genes DIP5 and GNP1 were essential for FLO11 expression, invasive growth and biofilm formation in this mutant. Invasive growth relied on known regulators of FLO11 and the Ssy1-Ptr3-Ssy5 complex that controls DIP5 and GNP1, suggesting that Dip5 and Gnp1 operates downstream of the Ssy1-Ptr3-Ssy5 complex for regulation of FLO11 expression in a protein kinase A dependent manner. The role of Dip5 and Gnp1 appears to be conserved in the S. cerevisiae strain ∑1278b since the dip5 gnp1 ∑1278b mutant showed no invasive phenotype. Secondly, the amino acid transporter gene GAP1 was found to influence invasive growth through FLO11 as well as other FLO genes. Cells carrying a dominant loss-of-function PTR3(647::CWNKNPLSSIN) allele had increased transcription of the adhesion genes FLO1, 5, 9, 10, 11 and the amino acid transporter gene GAP1. Deletion of GAP1 caused loss of FLO11 expression and invasive growth. However, deletions of FLO11 and genes encoding components of the mitogen-activated protein kinase pathway or the protein kinase A pathway were not sufficient to abolish invasive growth, suggesting involvement of other FLO genes and alternative pathways. Increased intracellular amino acid pools in the PTR3(647::CWNKNPLSSIN)-containing strain opens the possibility that Gap1 regulates the FLO genes through alteration of the amino acid pool sizes.

  4. NVP-BKM120 inhibits colon cancer growth via FoxO3a-dependent PUMA induction.

    Science.gov (United States)

    Yang, Shida; Li, Xin; Guan, Wenchang; Qian, Mingqin; Yao, Zhicheng; Yin, Xiaoxue; Zhao, Hongmei

    2017-10-10

    NVP-BKM120, a potent and highly selective PI3K inhibitor, is currently being investigated in phase I/II clinical trials. The mechanisms of action of NVP-BKM120 in colon cancer cells are unclear. In the present study, we investigated how NVP-BKM120 suppresses colon cancer cells growth and potentiates effects of other chemotherapeutic drugs. We found that NVP-BKM120 treatment enhance PUMA induction irrespective of p53 status through the FoxO3a pathway following AKT inhibition. Furthermore, PUMA is required for NVP-BKM120-induced apoptosis in colon cancer cells. In addition, NVP-BKM120 also synergized with 5-Fluorouracil or regorafenib to induce marked apoptosis via PUMA induction. Deficiency of PUMA suppressed apoptosis and antitumor effect of NVP-BKM120 in xenograft model. These results demonstrate a key role of PUMA in mediating the anticancer effects of NVP-BKM120 and suggest that PUMA could be used as an indicator of NVP-BKM120 sensitivity, and also have important implications for it clinical applications.

  5. Trypanosoma brucei Bloodstream Forms Depend upon Uptake of myo-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth.

    Science.gov (United States)

    González-Salgado, Amaia; Steinmann, Michael; Major, Louise L; Sigel, Erwin; Reymond, Jean-Louis; Smith, Terry K; Bütikofer, Peter

    2015-06-01

    myo-Inositol is a building block for all inositol-containing phospholipids in eukaryotes. It can be synthesized de novo from glucose-6-phosphate in the cytosol and endoplasmic reticulum. Alternatively, it can be taken up from the environment via Na(+)- or H(+)-linked myo-inositol transporters. While Na(+)-coupled myo-inositol transporters are found exclusively in the plasma membrane, H(+)-linked myo-inositol transporters are detected in intracellular organelles. In Trypanosoma brucei, the causative agent of human African sleeping sickness, myo-inositol metabolism is compartmentalized. De novo-synthesized myo-inositol is used for glycosylphosphatidylinositol production in the endoplasmic reticulum, whereas the myo-inositol taken up from the environment is used for bulk phosphatidylinositol synthesis in the Golgi complex. We now provide evidence that the Golgi complex-localized T. brucei H(+)-linked myo-inositol transporter (TbHMIT) is essential in bloodstream-form T. brucei. Downregulation of TbHMIT expression by RNA interference blocked phosphatidylinositol production and inhibited growth of parasites in culture. Characterization of the transporter in a heterologous expression system demonstrated a remarkable selectivity of TbHMIT for myo-inositol. It tolerates only a single modification on the inositol ring, such as the removal of a hydroxyl group or the inversion of stereochemistry at a single hydroxyl group relative to myo-inositol. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. Analysis of bacteria by pyrolysis gas chromatography-differential mobility spectrometry and isolation of chemical components with a dependence on growth temperature.

    Science.gov (United States)

    Prasad, Satendra; Pierce, Karisa M; Schmidt, Hartwig; Rao, Jaya V; Güth, Robert; Bader, Sabine; Synovec, Robert E; Smith, Geoffrey B; Eiceman, Gary A

    2007-10-01

    Pyrolysis gas chromatography-differential mobility spectrometry (py-GC-DMS) analysis of E. coli, P. aeruginosa, S. warneri and M. luteus, grown at temperatures of 23, 30, and 37 degrees C, provided data sets of ion intensity, retention time, and compensation voltage for principal component analysis. Misaligned chromatographic axes were treated using piecewise alignment, the impact on the degree of class separation (DCS) of clusters was minor. The DCS, however, was improved between 21 to 527% by analysis of variance with Fisher ratios to remove chemical components independent of growth temperature. The temperature dependent components comprised 84% of all peaks in the py-GC-DMS analysis of E. coli and were attributed to the pyrolytic decomposition of proteins rather than lipids, as anticipated. Components were also isolated in other bacteria at differing amounts: 41% for M. luteus, 14% for P. aeruginosa, and 4% for S. warneri, and differing patterns suggested characteristic dependence on temperature of growth for these bacteria. These components are anticipated to have masses from 100 to 200 Da by inference from differential mobility spectra.

  7. Growth of ligand-target interaction data in ChEMBL is associated with increasing and activity measurement-dependent compound promiscuity.

    Science.gov (United States)

    Hu, Ye; Bajorath, Jürgen

    2012-10-22

    Compounds with high-confidence target annotations and activity measurements in the original and current release of the ChEMBL database have been compared to better understand how the growth of compound activity data might influence the spectrum of ligand-target interactions and the degree of target promiscuity among active compounds. Compared to the original ChEMBL release, a significant increase in the proportion of target promiscuous compounds was observed in the current version. The presence of these compounds led to large-magnitude changes in compound activity-based target and target family relationships and to a reorganization of major target communities. Surprisingly, however, this strong trend toward increasing target promiscuity was largely caused by growth of compounds with exclusive IC(50) measurements. By contrast, compounds with available equilibrium constants, which were also added in large amounts, did not substantially alter compound-based target relationships and notably contribute to increasing target promiscuity. These findings suggest that apparent compound promiscuity is much dependent on experimental conditions under which activities are determined and that care should be taken when evaluating promiscuity and polypharmacology on the basis of assay-dependent activity measurements.

  8. Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1

    DEFF Research Database (Denmark)

    Petersen, B O; Wagener, C; Marinoni, F

    2000-01-01

    CDC6 is conserved during evolution and is essential and limiting for the initiation of eukaryotic DNA replication. Human CDC6 activity is regulated by periodic transcription and CDK-regulated subcellular localization. Here, we show that, in addition to being absent from nonproliferating cells, CDC6...... is targeted for ubiquitin-mediated proteolysis by the anaphase promoting complex (APC)/cyclosome in G(1). A combination of point mutations in the destruction box and KEN-box motifs in CDC6 stabilizes the protein in G(1) and in quiescent cells. Furthermore, APC, in association with CDH1, ubiquitinates CDC6...... in vitro, and both APC and CDH1 are required and limiting for CDC6 proteolysis in vivo. Although a stable mutant of CDC6 is biologically active, overexpression of this mutant or wild-type CDC6 is not sufficient to induce multiple rounds of DNA replication in the same cell cycle. The APC-CDH1-dependent...

  9. MicroRNA-26a/cyclin-dependent kinase 5 axis controls proliferation, apoptosis and in vivo tumor growth of diffuse large B-cell lymphoma cell lines.

    Science.gov (United States)

    Farina, Floriana Maria; Inguscio, Alessandra; Kunderfranco, Paolo; Cortesi, Alice; Elia, Leonardo; Quintavalle, Manuela

    2017-06-22

    Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. Despite a favorable therapeutic response to first-line chemo-immunotherapy, still 30-40% of patients is refractory, or relapse after this treatment. Thus, alternative strategies must be sought. Previous studies have indicated that cyclin-dependent kinase 5 (CDK5), a serine/threonine protein kinase, is involved in tumor development and progression, and it may represent a potential therapeutic target. However, its role in modulating DLBCL growth and progression remains largely unexplored. In this study, we show that CDK5 and its activator, cyclin-dependent kinase 5 activator 1 (CDK5R1 or p35), are overexpressed in DLBCL cell lines and that signal transducer and activator of transcription 3 (STAT3) phosphorylation and activity is dependent on CDK5 expression in DLBCL. Using public data sets, we also demonstrate that patients with DLBCL show a higher expression of CDK5 compared with healthy individuals. By using loss-of-function approaches, we demonstrate that CDK5's activity regulates proliferation and survival of DLBCL cells. MicroRNAs (miRNAs or miRs) are small noncoding RNAs that negatively regulating gene expression and are involved in cancer initiation and progression. We identify miR-26a as direct regulator of p35 expression and CDK5 activity. We show that miR-26a expression is lower in DLBCL cell lines compared to B lymphocytes and that its ectopic expression leads to a drastic reduction of DLBCL tumor growth in vivo and decreased proliferation, cell-cycle progression, and survival in vitro. Remarkably, concomitant overexpression of a 3'-UTR-truncated form of p35 promoted tumor growth in vivo and cell proliferation, cell-cycle progression, and cell survival in vitro. In conclusion, these results demonstrate an important role for miR-26a and CDK5 together in the survival and growth of DLBCL cells, suggesting the existence of potential novel therapeutic targets for the

  10. The inhibitor of growth protein 5 (ING5 depends on INCA1 as a co-factor for its antiproliferative effects.

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    Full Text Available The proteins of the Inhibitor of Growth (ING family are involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. For ING5, its actual role in growth suppression and the necessary partners are not known. In a yeast-two-hybrid approach with human bone marrow derived cDNA, we identified ING5 as well as several other proteins as interaction partners of Inhibitor of cyclin A1 (INCA1 that we previously characterized as a novel interaction partner of cyclin A1/CDK2. ING5 expression in leukemic AML blasts was severely reduced compared to normal bone marrow. In line, ING5 inhibited bone marrow colony formation upon retroviral transduction. However, Inca1(-/- bone marrow colony formation was not suppressed by ING5. In murine embryonic fibroblast (MEF cells from Inca1(+/+ and Inca1(-/- mice, overexpression of ING5 suppressed cell proliferation only in the presence of INCA1, while ING5 had no effect in Inca1(-/- MEFs. ING5 overexpression induced a delay in S-phase progression, which required INCA1. Finally, ING5 overexpression enhanced Fas-induced apoptosis in Inca1(+/+ MEFs, while Inca1(-/- MEFs were protected from Fas antibody-induced apoptosis. Taken together, these results indicate that ING5 is a growth suppressor with suppressed expression in AML whose functions depend on its interaction with INCA1.

  11. Notch 1 and 3 receptor signaling modulates vascular smooth muscle cell growth, apoptosis, and migration via a CBF-1/RBP-Jk dependent pathway.

    Science.gov (United States)

    Sweeney, Catherine; Morrow, David; Birney, Yvonne A; Coyle, Seamus; Hennessy, Colm; Scheller, Agnieszka; Cummins, Philip M; Walls, Dermot; Redmond, Eileen M; Cahill, Paul A

    2004-09-01

    Vascular smooth muscle cell (SMC) fate decisions (cell growth, migration, and apoptosis) are fundamental features in the pathogenesis of vascular disease. We investigated the role of Notch 1 and 3 receptor signaling in controlling adult SMC fate in vitro by establishing that hairy enhancer of split (hes-1 and -5) and related hrt's (hrt-1, -2, and -3) are direct downstream target genes of Notch 1 and 3 receptors in SMC and identified an essential role for nuclear protein CBF-1/RBP-Jk in their regulation. Constitutive expression of active Notch 1 and 3 receptors (Notch IC) resulted in a significant up-regulation of CBF-1/RBP-Jk-dependent promoter activity and Notch target gene expression concomitant with significant increases in SMC growth while concurrently inhibiting SMC apoptosis and migration. Moreover, inhibition of endogenous Notch mediated CBF-1/RBP-Jk regulated gene expression with a non-DNA binding mutant of CBF-1, a Notch IC deleted of its delta RAM domain and the Epstein-Barr virus encoded RPMS-1, in conjunction with pharmacological inhibitors of Notch IC receptor trafficking (brefeldin A and monensin), resulted in a significant decrease in cell growth while concomitantly increasing SMC apoptosis and migration. These findings suggest that endogenous Notch receptors and downstream target genes control vascular cell fate in vitro. Notch signaling, therefore, represents a novel therapeutic target for disease states in which changes in vascular cell fate occur in vivo.

  12. Methoxychlor and triclosan stimulates ovarian cancer growth by regulating cell cycle- and apoptosis-related genes via an estrogen receptor-dependent pathway.

    Science.gov (United States)

    Kim, Joo-Young; Yi, Bo-Rim; Go, Ryeo-Eun; Hwang, Kyung-A; Nam, Ki-Hoan; Choi, Kyung-Chul

    2014-05-01

    Methoxychlor and triclosan are emergent or suspected endocrine-disrupting chemicals (EDCs). Methoxychlor [MXC; 1,1,1-trichlor-2,2-bis (4-methoxyphenyl) ethane] is an organochlorine pesticide that has been primarily used since dichlorodiphenyltrichloroethane (DDT) was banned. In addition, triclosan (TCS) is used as a common component of soaps, deodorants, toothpastes, and other hygiene products at concentrations up to 0.3%. In the present study, the potential impact of MXC and TCS on ovarian cancer cell growth and underlying mechanism(s) was examined following their treatments in BG-1 ovarian cancer cells. As results, MXC and TCS induced BG-1 cell growth via regulating cyclin D1, p21 and Bax genes related with cell cycle and apoptosis. A methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay confirmed that the proliferation of BG-1 ovarian cancer cells was stimulated by MXC (10(-6), 10(-7), 10(-8), and 10(-9)M) or TCS (10(-6), 10(-7), 10(-8), and 10(-9)M). Treatment of BG-1 cells with MXC or TCS resulted in the upregulation of cyclin D1 and downregulation of p21 and Bax transcriptions. In addition, the protein level of cyclin D1 was increased by MXC or TCS while p21 and Bax protein levels appeared to be reduced in these cells. Furthermore, MXC- or TCS-induced alterations of these genes were reversed in the presence of ICI 182,780 (10(-7)M), suggesting that the changes in these gene expressions may be regulated by an ER-dependent signaling pathway. In conclusion, the results of our investigation indicate that two potential EDCs, MXC and TCS, may stimulate ovarian cancer growth by regulating cell cycle- and apoptosis-related genes via an ER-dependent pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Toxoplasma growth in vitro is dependent on exogenous tyrosine and is independent of AAH2 even in tyrosine-limiting conditions.

    Science.gov (United States)

    Marino, Nicole D; Boothroyd, John C

    2017-05-01

    Toxoplasma gondii is an obligate intracellular parasite capable of infecting virtually all nucleated cell types in almost all warm-blooded animals. Interestingly, Toxoplasma has a relatively full repertoire of amino acid biosynthetic machinery, perhaps reflecting its broad host range and, consequently, its need to adapt to a wide array of amino acid resources. Although Toxoplasma has been shown to be auxotrophic for tryptophan and arginine, it has not previously been determined if Toxoplasma is also auxotrophic for tyrosine. Toxoplasma tachyzoites and bradyzoites were recently found to express an amino acid hydroxylase (AAH2) that is capable of synthesizing tyrosine and dihydroxyphenylalanine (DOPA) from phenylalanine; however, the role of AAH2 in tachyzoite and bradyzoite infection has not yet been identified. To determine if Toxoplasma requires exogenous tyrosine for growth, we performed growth assays on tachyzoites and bradyzoites in nutrient-rich media titrated with varying amounts of tyrosine. We found that Toxoplasma tachyzoites form significantly smaller plaques in tyrosine-limiting media in a dose-dependent manner and that this phenotype is not affected by deletion of TgAAH2. To determine if bradyzoites require exogenous tyrosine for growth, we induced differentiation from tachyzoites in vitro in tyrosine-limiting media and found that replication and vacuole number are all decreased in tyrosine-deficient media. Importantly, culture of confluent human fibroblasts in tyrosine-deficient media does not affect their viability, indicating that, at least in vitro, the need for tyrosine is at the level of Toxoplasma, not the host cell supporting its growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Elevation-dependent variations of tree growth and intrinsic water-use efficiency in Schrenk spruce (Picea schrenkiana in the western Tianshan Mountains, China

    Directory of Open Access Journals (Sweden)

    Guoju eWu

    2015-05-01

    Full Text Available Rising atmospheric CO2 concentration (Ca is expected to accelerate tree growth by enhancing photosynthesis and increasing intrinsic water-use efficiency (iWUE. However, the extent of this effect on long-term iWUE and its interactions with climate remains unclear in trees along an elevation gradient. Therefore, we investigated the variation in the radial growth and iWUE of mature Picea schrenkiana trees located in the upper tree-line (A1: 2700 m a.s.l., middle elevation (A2: 2400 m a.s.l., and lower forest limit (A3: 2200 m a.s.l., in relation to the rising Ca and changing climate in the Wusun Mountains of northwestern China, based on the basal area increment (BAI and tree-ring δ13C chronologies from 1960 to 2010. We used the CRU TS3.22 dataset to analyze the general response of tree growth to interannual variability of regional climate, and found that BAI and δ13C are less sensitive to climate at A1 than at A2 and A3. The temporal trends of iWUE were calculated under three theoretical scenarios, as a baseline for interpreting the observed gas exchange at increasing Ca. We found that iWUE increased by 12¬-32% from A1 to A3 over the last 50 years, and showed an elevation-dependent variation in physiological response. The significant negative relationship between BAI and iWUE at A2 and A3 showed that tree growth has been decreasing despite long-term increases in iWUE. However, BAI remained largely stable throughout the study period despite the strongest iWUE increase (at constant intercellular CO2 concentration (Ci before 1980 at A1. Our results indicate a drought-induced limitation of tree growth response to rising CO2 at lower elevations, and no apparent change in tree growth and diminished iWUE improvement since 1980 in the upper tree-line. This study may contradict the expectation that combined effects of elevated Ca and rising temperatures have increased forest productivity, especially in high-elevation forests.

  15. Vascular endothelial growth factor downregulates apolipoprotein M expression by inhibiting Foxa2 in a Nur77-dependent manner.

    Science.gov (United States)

    Hu, Yan-Wei; Zheng, Lei; Wang, Qian; Zhong, Tian-Yu; Yu, Xia; Bao, Jie; Cao, Nan-Nan; Li, Bo; Si-Tu, Bo

    2012-08-01

    We aimed to investigate whether vascular endothelial growth factor (VEGF) influences apolipoprotein M (ApoM) expression and pre-β-high-density lipoprotin (HDL) formation, and whether forkhead box A2 (Foxa2) and Nur77 are involved in this process. We analyzed the serum VEGF concentrations of 264 adults who underwent a medical checkup and found that VEGF concentration was positively correlated with serum triglyceride, total cholesterol, LDL cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), and ApoB concentrations, but was negatively correlated with serum high-density lipoprotein cholesterol (HDL-C) and ApoM concentrations. We further investigated the effects of VEGF on ApoM expression and pre-β-HDL formation, and the mechanisms responsible, in HepG2 cells and mouse primary hepatocytes. VEGF markedly downregulated ApoM expression and pre-β-HDL formation. At the same time, expression of Foxa2 was also inhibited, whereas expression of Nur77 was increased by treatment with VEGF. Furthermore, small interfering (si) RNA knockdown of Foxa2 made the downregulation of VEGF on ApoM expression and pre-β-HDL formation even more obvious. In addition, siRNA knockdown of Nur77 significantly compensated for the inhibitory effect of VEGF on Foxa2 expression, whereas the Nur77 agonist cytosporone B led to the downregulation of Foxa2 expression more significantly than VEGF. Moreover, overexpression of a Nur77 transgene in C57BL/6 mice resulted in decreased serum ApoM and pre-β-HDL levels, whereas si-Nur77-treated mice displayed upregulated serum ApoM and pre-β-HDL levels. These results provide evidence that VEGF may first downregulate expression of Foxa2 by enhancing Nur77 activity and then decrease expression of ApoM and pre-β-HDL formation. Therefore, our study may be useful in understanding the critical effect of VEGF in the pathogenesis of atherosclerosis.

  16. Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation

    International Nuclear Information System (INIS)

    Yun, Hong Shik; Hong, Eun-Hee; Lee, Su-Jae; Baek, Jeong-Hwa; Lee, Chang-Woo; Yim, Ji-Hye; Um, Hong-Duck; Hwang, Sang-Gu

    2013-01-01

    Highlights: •HRP-3 is a radiation- and anticancer drug-responsive protein in A549 cells. •Depletion of HRP-3 induces apoptosis of radio- and chemoresistant A549 cells. •Depletion of HRP-3 promotes ROS generation via inhibition of the Nrf2/HO-1 pathway. •Depletion of HRP-3 enhances ROS-dependent p53 activation and PUMA expression. -- Abstract: Biomarkers based on functional signaling have the potential to provide greater insight into the pathogenesis of cancer and may offer additional targets for anticancer therapeutics. Here, we identified hepatoma-derived growth factor-related protein-3 (HRP-3) as a radioresistance-related gene and characterized the molecular mechanism by which its encoded protein regulates the radio- and chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3 promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of radio- and chemotherapy. This increase in apoptosis was associated with a substantial generation of reactive oxygen species (ROS) that was attributable to inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS-dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is an essential feature of the A549 cell phenotype and a potential radiotherapy target, extending the range of targets in multimodal therapies against lung cancer

  17. Evidence for density-dependent changes in growth, downstream movement, and size of Chinook salmon subyearlings in a large-river landscape

    Science.gov (United States)

    Connor, William P.; Tiffan, Kenneth F.; Plumb, John M.; Moffit, Christine M.

    2013-01-01

    We studied the growth rate, downstream movement, and size of naturally produced fall Chinook Salmon Oncorhynchus tshawytscha subyearlings (age 0) for 20 years in an 8th-order river landscape with regulated riverine upstream rearing areas and an impounded downstream migration corridor. The population transitioned from low to high abundance in association with U.S. Endangered Species Act and other federally mandated recovery efforts. The mean growth rate of parr in the river did not decline with increasing abundance, but during the period of higher abundance the timing of dispersal from riverine habitat into the reservoir averaged 17 d earlier and the average size at the time of downstream dispersal was smaller by 10 mm and 1.8 g. Changes in apparent abundance, measured by catch per unit effort, largely explained the time of dispersal, measured by median day of capture, in riverine habitat. The growth rate of smolts in the reservoir declined from an average of 0.6 to 0.2 g/d between the abundance periods because the reduction in size at reservoir entry was accompanied by a tendency to migrate rather than linger and by increasing concentrations of smolts in the reservoir. The median date of passage through the reservoir was 14 d earlier on average, and average smolt size was smaller by 38 mm and 22.0 g, in accordance with density-dependent behavioral changes reflected by decreased smolt growth. Unexpectedly, smolts during the high-abundance period had begun to reexpress the migration timing and size phenotypes observed before the river was impounded, when abundance was relatively high. Our findings provide evidence for density-dependent phenotypic change in a large river that was influenced by the expansion of a recovery program. Thus, this study shows that efforts to recover native fishes can have detectable effects in large-river landscapes. The outcome of such phenotypic change, which will be an important area of future research, can only be fully judged by

  18. Transforming growth factor-β1 induces cell cycle arrest by activating atypical cyclin-dependent kinase 5 through up-regulation of Smad3-dependent p35 expression in human MCF10A mammary epithelial cells.

    Science.gov (United States)

    Park, Seong Ji; Yang, Sun Woo; Kim, Byung-Chul

    2016-04-08

    Cyclin-dependent kinases (Cdks) play important roles in control of cell division. Cdk5 is an atypical member of Cdk family with non-cyclin-like regulatory subunit, p35, but its role in cell cycle progression is still unclear. In the present study, we investigated the role of Cdk5/p35 on transforming growth factor-β1 (TGF-β1)-induced cell cycle arrest. In human MCF10A mammary epithelial cells, TGF-β1 induced cell cycle arrest at G1 phase and increased p27KIP1 expression. Interestingly, pretreatment with roscovitine, an inhibitor of Cdk5, or transfection with small interfering (si) RNAs specific to Cdk5 and p35 significantly attenuated the TGF-β1-induced p27KIP1 expression and cell cycle arrest. TGF-β1 increased Cdk5 activity via up-regulation of p35 gene at transcriptional level, and these effects were abolished by transfection with Smad3 siRNA or infection of adenovirus carrying Smad3 mutant at the C-tail (3SA). Chromatin immunoprecipitation assay further revealed that wild type Smad3, but not mutant Smad3 (3SA), binds to the region of the p35 promoter region (-1000--755) in a TGF-β1-dependent manner. These results for the first time demonstrate a role of Cdk5/p35 in the regulation of cell cycle progression modulated by TGF-β1. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

    International Nuclear Information System (INIS)

    Penrose, Harrison; Heller, Sandra; Cable, Chloe; Makboul, Rania; Chadalawada, Gita; Chen, Ying; Crawford, Susan E.; Savkovic, Suzana D.

    2016-01-01

    The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

  20. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6

    Energy Technology Data Exchange (ETDEWEB)

    Penrose, Harrison; Heller, Sandra; Cable, Chloe [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Makboul, Rania [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Pathology Department, Assiut University, Assiut (Egypt); Chadalawada, Gita; Chen, Ying [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States); Crawford, Susan E. [Department of Pathology, Saint Louis University School of Medicine, 1402 South Grand Blvd, Saint Louis, MO 63104 (United States); Savkovic, Suzana D., E-mail: ssavkovi@tulane.edu [Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, 1430 Tulane Ave SL-79, New Orleans, LA 70112 (United States)

    2016-01-15

    The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTOR and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.

  1. Synthetic LPETG-containing peptide incorporation in the Staphylococcus aureus cell-wall in a sortase A- and growth phase-dependent manner.

    Directory of Open Access Journals (Sweden)

    Silvie Hansenová Maňásková

    Full Text Available The majority of Staphylococcus aureus virulence- and colonization-associated surface proteins contain a pentapeptide recognition motif (LPXTG. This motif can be recognized and cleaved by sortase A (SrtA which is a membrane-bound transpeptidase. After cleavage these proteins are covalently incorporated into the peptidoglycan. Therefore, SrtA plays a key role in S. aureus virulence. We aimed to generate a substrate mimicking this SrtA recognition motif for several purposes: to incorporate this substrate into the S. aureus cell-wall in a SrtA-dependent manner, to characterize this incorporation and to determine the effect of substrate incorporation on the incorporation of native SrtA-dependent cell-surface-associated proteins. We synthesized substrate containing the specific LPXTG motif, LPETG. As a negative control we used a scrambled version of this substrate, EGTLP and a S. aureus srtA knockout strain. Both substrates contained a fluorescence label for detection by FACScan and fluorescence microscope. A spreading assay and a competitive Luminex assay were used to determine the effect of substrate treatment on native LPXTG containing proteins deposition in the bacterial cell-wall. We demonstrate a SrtA-dependent covalent incorporation of the LPETG-containing substrate in wild type S. aureus strains and several other Gram-positive bacterial species. LPETG-containing substrate incorporation in S. aureus was growth phase-dependent and peaked at the stationary phase. This incorporation negatively correlated with srtA mRNA expression. Exogenous addition of the artificial substrate did not result in a decreased expression of native SrtA substrates (e.g. clumping factor A/B and protein A nor induced a srtA knockout phenotype.

  2. Hemolytic disease of the fetus and newborn due to anti-Ge3: combined antibody-dependent hemolysis and erythroid precursor cell growth inhibition.

    Science.gov (United States)

    Blackall, Douglas P; Pesek, Gina D; Montgomery, Matthew M; Oza, Krishna K; Arndt, Patricia A; Garratty, George; Shahcheraghi, Ali; Denomme, Gregory A

    2008-10-01

    The Gerbich (Ge) antigens are a collection of high-incidence antigens carried on the red blood cell membrane glycoproteins, glycophorins C and D. Antibodies against these antigens are uncommon, and there have been only rare case reports of hemolytic disease of the fetus and newborn due to anti-Ge. In this case report, we present a neonate with severe anemia and hyperbilirubinemia due to anti-Ge3. Routine and special laboratory studies undertaken in this case suggested two mechanisms for the patient's hemolysis and persistent anemia. Antibody-dependent hemolysis was associated with early-onset hyperbilirubinemia, anemia, and a mild reticulocytosis, and inhibition of erythroid progenitor cell growth was associated with late anemia and normal bilirubin and reticulocyte values. Though rare, anti-Ge3 can be a dangerous antibody in pregnancy. Affected neonates may require intensive initial therapy and close follow-up for at least several weeks after delivery.

  3. Iron oxide magnetic nanoparticles combined with actein suppress non-small-cell lung cancer growth in a p53-dependent manner

    Directory of Open Access Journals (Sweden)

    Wang MS

    2017-10-01

    Full Text Available Ming-Shan Wang,1 Liang Chen,2 Ya-Qiong Xiong,2 Jing Xu,2 Ji-Peng Wang,2 Zi-Li Meng2 1Department of Oncology, Huaiyin Hospital of Huai’an City, Huai’an, China; 2Department of Respiration, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China Abstract: Actein (AT is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida that has been investigated for its antitumor effects. AT treatment leads to apoptosis in various cell types, including breast cancer cells, by regulating different signaling pathways. Iron oxide (Fe3O4 magnetic nanoparticles (MNPs are nanomaterials with biocompatible activity and low toxicity. In the present study, the possible benefits of AT in combination with MNPs on non-small-cell lung cancer (NSCLC were explored in in vitro and in vivo studies. AT-MNP treatment contributed to apoptosis in NSCLC cells, as evidenced by activation of the caspase 3-signaling pathway, which was accompanied by downregulation of the antiapoptotic proteins Bcl2 and BclXL, and upregulation of the proapoptotic signals Bax and Bad. The death receptors of TRAIL were also elevated following AT-MNP treatment in a p53-dependent manner. Furthermore, a mouse xenograft model in vivo revealed that AT-MNP treatment exhibited no toxicity and suppressed NSCLC growth compared to either AT or MNP monotherapies. In conclusion, this study suggests a novel therapy to induce apoptosis in suppressing NSCLC growth in a p53-dependent manner by combining AT with Fe3O4 MNPs. Keywords: actein, Fe3O4 magnetic nanoparticles, NSCLC, apoptosis, p53

  4. Cross-kingdom similarities in microbiome functions

    NARCIS (Netherlands)

    Mendes, R.; Raaijmakers, J.M.

    2015-01-01

    Recent advances in medical research have revealed how humans rely on their microbiome for diverse traits and functions. Similarly, microbiomes of other higher organisms play key roles in disease, health, growth and development of their host. Exploring microbiome functions across kingdoms holds

  5. Ectopic expression of a tomato DREB gene affects several ABA processes and influences plant growth and root architecture in an age-dependent manner.

    Science.gov (United States)

    Upadhyay, Rakesh Kumar; Gupta, Asmita; Soni, Devendra; Garg, Rashmi; Pathre, Uday V; Nath, Pravendra; Sane, Aniruddha P

    2017-07-01

    Regulation of whole plant growth and adaptive responses by abscisic acid is complex, requires multiple regulators and largely unknown in plants other than Arabidopsis. We show that over-expression of the tomato SlDREB3/SlERF.H12 (DEHYDRATION RESPONSE ELEMENT BINDING PROTEIN3/ETHYLENE RESPONSE FACTOR. H12) gene can negatively affect many ABA-governed processes across tissues. Its expression leads to early germination in presence of ABA and in response to mannitol, NaCl and glucose. Its expression delays ABA-mediated leaf senescence and natural senescence leading to an increase in plant life by about 20days. Transgenic SlDREB3 lines show reduced ABA-mediated inhibition of conductance and transpiration and a greater sensitivity to water stress. Reduction in sensitivity to ABA-mediated stomatal closure leads to higher photosynthetic rates in transgenic plants than controls. Consequently, transgenic SlDREB3 plants produce a larger number of capsules and greater number of seeds with the increase in yield ranging from 18 to 35% in different seasons under well-watered conditions. Root growth, but not shoot growth, also undergoes a profound increase of about 50% in transgenic SlDREB3 lines. The increase occurs in an age-dependent manner with the most prominent changes being observed between 1.5 and 2.5 months in several independent experiments in different years. SlDREB3 thus seems to govern several ABA-regulated processes across tissues, partly through control over ABA levels. It may encode a factor that is most likely a component of the central ABA response machinery. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Dependent Classes

    DEFF Research Database (Denmark)

    Gasiunas, Vaidas; Mezini, Mira; Ostermann, Klaus

    2007-01-01

    of dependent classes and a machine-checked type soundness proof in Isabelle/HOL [29], the first of this kind for a language with virtual classes and path-dependent types. [29] T.Nipkow, L.C. Poulson, and M. Wenzel. Isabelle/HOL -- A Proof Assistant for Higher-Order Logic, volume 2283 of LNCS, Springer, 2002......Virtual classes allow nested classes to be refined in subclasses. In this way nested classes can be seen as dependent abstractions of the objects of the enclosing classes. Expressing dependency via nesting, however, has two limitations: Abstractions that depend on more than one object cannot...... be modeled and a class must know all classes that depend on its objects. This paper presents dependent classes, a generalization of virtual classes that expresses similar semantics by parameterization rather than by nesting. This increases expressivity of class variations as well as the flexibility...

  7. Unmixing of spectrally similar minerals

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2009-01-01

    Full Text Available techniques is complicated when considering very similar spectral signatures. Iron-bearing oxide/hydroxide/sulfate minerals have similar spectral signatures. The study focuses on how could estimates of abundances of spectrally similar iron-bearing oxide...

  8. Optical band gap demarcation around 2.15 eV depending on preferred orientation growth in red HgI{sub 2} films

    Energy Technology Data Exchange (ETDEWEB)

    Tyagi, Pankaj, E-mail: pankajtyagicicdu@gmail.com

    2017-04-01

    Thermally evaporated stoichiometric films of red HgI{sub 2} show preferred orientation growth with either (102) or (002) orientation. The as grown films shows a change from one preferred orientation to another depending on their thickness, open-air heat-treatment and in-situ heat treatment of films. The in-situ heat-treatment of thermally evaporated stoichiometric films of red HgI{sub 2} with preferred growth of (102) orientation shows a gradual linear decrease in film thickness with in-situ heat-treatment temperature. On in-situ heat-treatment above 80 °C, it is found that HgI{sub 2} films become thinner than 900 nm, which are otherwise difficult to grow due to high vapor pressure of HgI{sub 2}. For these films the preferred orientation also changed from (102) to (002). The optical band gap (E{sub g}) also found to increase linearly with in-situ heat-treatment temperature. It is interesting to note that in-situ heat-treated films having (002) orientation had higher values of optical band gap than (102) orientation films. On combining these results with those of as grown and open-air heat-treated red HgI{sub 2} films reported in the literature, it is evident that there exists an optical band gap demarcation around 2.15 eV for red HgI{sub 2} thin films depending on their preferred orientation growth. Films with (102) orientation are found to have optical band gap less than 2.15 eV and those with (002) orientation are found to have optical band gap more than 2.15 eV. This is irrespective of the physical mean of obtaining the preferred orientation. The preferred orientation can be achieved by either physical means such as growing films with higher thickness, heat-treating them for short duration in open air or heat-treating them in-situ.

  9. Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo.

    Science.gov (United States)

    Dennler, Sylviane; André, Jocelyne; Alexaki, Ismini; Li, Allen; Magnaldo, Thierry; ten Dijke, Peter; Wang, Xiao-Jing; Verrecchia, Franck; Mauviel, Alain

    2007-07-15

    Hedgehog (Hh) and transforming growth factor-beta (TGF-beta) family members are involved in numerous overlapping processes during embryonic development, hair cycle, and cancer. Herein, we show that TGF-beta induces the expression of the Hh signaling molecules Gli1 and Gli2 in various human cell types, including normal fibroblasts and keratinocytes, as well as various cancer cell lines. Gli2 induction by TGF-beta is rapid, independent from Hh receptor signaling, and requires a functional Smad pathway. Gli1 expression is subsequently activated in a Gli2-dependent manner. In transgenic mice overexpressing TGF-beta1 in the skin, Gli1 and Gli2 expression is also elevated and depends on Smad3. In pancreatic adenocarcinoma cell lines resistant to Hh inhibition, pharmacologic blockade of TGF-beta signaling leads to repression of cell proliferation accompanied with a reduction in Gli2 expression. We thus identify TGF-beta as a potent transcriptional inducer of Gli transcription factors. Targeting the cooperation of Hh and TGF-beta signaling may provide new therapeutic opportunities for cancer treatment.

  10. Mild reductions in cytosolic NADP-dependent isocitrate dehydrogenase activity result in lower amino acid contents and pigmentation without impacting growth.

    Science.gov (United States)

    Sulpice, Ronan; Sienkiewicz-Porzucek, Agata; Osorio, Sonia; Krahnert, Ina; Stitt, Mark; Fernie, Alisdair R; Nunes-Nesi, Adriano

    2010-10-01

    Transgenic tomato (Solanum lycopersicum) plants were generated targeting the cytosolic NADP-dependent isocitrate dehydrogenase gene (SlICDH1) via the RNA interference approach. The resultant transformants displayed a relatively mild reduction in the expression and activity of the target enzyme in the leaves. However, biochemical analyses revealed that the transgenic lines displayed a considerable shift in metabolism, being characterized by decreases in the levels of the TCA cycle intermediates, total amino acids, photosynthetic pigments, starch and NAD(P)H. The plants showed little change in photosynthesis with the exception of a minor decrease in maximum photosynthetic efficiency (F (v)/F (m)), and a small decrease in growth compared to the wild type. These results reveal that even small changes in cytosolic NADP-dependent isocitrate dehydrogenase activity lead to noticeable alterations in the activities of enzymes involved in primary nitrate assimilation and in the synthesis of 2-oxoglutarate derived amino acids. These data are discussed within the context of current models for the role of the various isoforms of isocitrate dehydrogenase within plant amino acid metabolism.

  11. Functional coupling between large-conductance potassium channels and Cav3.2 voltage-dependent calcium channels participates in prostate cancer cell growth

    Directory of Open Access Journals (Sweden)

    Florian Gackière

    2013-07-01

    It is strongly suspected that potassium (K+ channels are involved in various aspects of prostate cancer development, such as cell growth. However, the molecular nature of those K+ channels implicated in prostate cancer cell proliferation and the mechanisms through which they control proliferation are still unknown. This study uses pharmacological, biophysical and molecular approaches to show that the main voltage-dependent K+ current in prostate cancer LNCaP cells is carried by large-conductance BK channels. Indeed, most of the voltage-dependent current was inhibited by inhibitors of BK channels (paxillin and iberiotoxin and by siRNA targeting BK channels. In addition, we reveal that BK channels constitute the main K+ channel family involved in setting the resting membrane potential in LNCaP cells at around −40 mV. This consequently promotes a constitutive calcium entry through T-type Cav3.2 calcium channels. We demonstrate, using single-channel recording, confocal imaging and co-immunoprecipitation approaches, that both channels form macromolecular complexes. Finally, using flow cytometry cell cycle measurements, cell survival assays and Ki67 immunofluorescent staining, we show that both BK and Cav3.2 channels participate in the proliferation of prostate cancer cells.

  12. Quinone-dependent D-lactate dehydrogenase Dld (Cg1027 is essential for growth of Corynebacterium glutamicum on D-lactate

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    Oikawa Tadao

    2010-12-01

    Full Text Available Abstract Background Corynebacterium glutamicum is able to grow with lactate as sole or combined carbon and energy source. Quinone-dependent L-lactate dehydrogenase LldD is known to be essential for utilization of L-lactate by C. glutamicum. D-lactate also serves as sole carbon source for C. glutamicum ATCC 13032. Results Here, the gene cg1027 was shown to encode the quinone-dependent D-lactate dehydrogenase (Dld by enzymatic analysis of the protein purified from recombinant E. coli. The absorption spectrum of purified Dld indicated the presence of FAD as bound cofactor. Inactivation of dld resulted in the loss of the ability to grow with D-lactate, which could be restored by plasmid-borne expression of dld. Heterologous expression of dld from C. glutamicum ATCC 13032 in C. efficiens enabled this species to grow with D-lactate as sole carbon source. Homologs of dld of C. glutamicum ATCC 13032 are not encoded in the sequenced genomes of other corynebacteria and mycobacteria. However, the dld locus of C. glutamicum ATCC 13032 shares 2367 bp of 2372 bp identical nucleotides with the dld locus of Propionibacterium freudenreichii subsp. shermanii, a bacterium used in Swiss-type cheese making. Both loci are flanked by insertion sequences of the same family suggesting a possible event of horizontal gene transfer. Conclusions Cg1067 encodes quinone-dependent D-lactate dehydrogenase Dld of Corynebacterium glutamicum. Dld is essential for growth with D-lactate as sole carbon source. The genomic region of dld likely has been acquired by horizontal gene transfer.

  13. Silibinin Inhibits Platelet-Derived Growth Factor-Driven Cell Proliferation via Downregulation of N-Glycosylation in Human Tenon's Fibroblasts in a Proteasome-Dependent Manner.

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    Yi-Hao Chen

    Full Text Available The objective of this study was to evaluate the effects of silibinin on cell proliferation in platelet-derived growth factor (PDGF-treated human Tenon's fibroblasts (HTFs. The effect of silibinin on cell proliferation in PDGF-treated HTFs was determined by examining the expression of proliferating cell nuclear antigen (PCNA and performing WST-1 assays. Cell cycle progression was evaluated using flow cytometry. The related cyclins and cyclin-dependent kinases (CDKs were also analyzed using western blot. A modified rat trabeculectomy model was established to evaluate the effect of silibinin on cell proliferation in vivo. Western blot analysis was carried out to determine the effect of silibinin on the expression of PDGF receptor and on the downstream signaling pathways regulated by PDGF receptor. PDGF elevated the expression of PCNA in HTFs, and this elevation was inhibited by silibinin. The inhibitory effect of silibinin on cell proliferation was also confirmed via WST-1 assay. PDGF-stimulated cell cycle in HTFs was delayed by silibinin, and the related cyclin D1 and CDK4 were also suppressed by silibinin. In the rat model of trabeculectomy, silibinin reduced the expression of PCNA at the site of blebs in vivo. The effects of silibinin on PDGF-stimulated HTFs were mediated via the downregulation of PDGF receptor-regulated signaling pathways, such as ERKs and STATs, which may be partially caused by the downregulation of N-glycosylation of PDGF receptor beta (PDGFRβ. The effect of silibinin on modulation of N-glycosylation of PDGFRβ was mediated in a proteasome-dependent manner. Silibinin inhibited cell proliferation and delayed cell cycle progression in PDGF-treated HTFs in vitro. PDGF also modulated the process of N-glycosylation of the PDGFRβ in a proteasome-dependent manner. Our findings suggest that silibinin has potential therapeutic applications in glaucoma filtering surgery.

  14. Perception of timbre and rhythm similarity in electronic dance music

    NARCIS (Netherlands)

    Honingh, A.; Panteli, M.; Brockmeier, T.; López Mejía, D.I.; Sadakata, M.

    2015-01-01

    Music similarity is known to be a multi-dimensional concept, depending among others on rhythm similarity and timbre similarity. The present study aims to investigate whether such sub-dimensions of similarity can be assessed independently and how they relate to general similarity. To this end, we

  15. Similar effects of long-term exogenous growth hormone (GH) on bone and muscle parameters: a pQCT study of GH-deficient and small-for-gestational-age (SGA) children.

    Science.gov (United States)

    Schweizer, Roland; Martin, David D; Haase, Martin; Roth, Johannes; Trebar, Branko; Binder, Gerhard; Schwarze, C Philipp; Ranke, Michael B

    2007-11-01

    Treatment with GH in short children has focused on height development. Little is known about the concomitant changes in muscle mass, bone structure and bone strength. Muscle area as well as parameters of bone architecture (bone mineral content, BMC; volumetric cortical density, total bone area, TBA; cortical area, cortical thickness, CT; and marrow area) were measured by means of pQCT (Stratec) at 65% of the proximal length of the forearm. The strength-strain index (SSI) was calculated as an indicator of bone strength. Prepubertal children with GHD (mean values: age; 7.2 years; height SDS=-2.9 SDS; GH dose: 30 microg/kg/d) were followed at 0, 6, 12 (n=74) and 24 (n=55) months. Prepubertal children with SGA (mean values: age: 7.1 years; height SDS=-3.4 SDS; GH dose: 55 mug/kg/d) were followed at 0, 6, 12 (n=47) and 24 (n=35) months. Both groups showed a similar increase in height. At GH start, muscle mass and bone characteristics were lower than normal but similar in SGA vs. GHD. Muscle area (mean values, SDS) increased from -3.0 to -1.5 in SGA and from -2.4 to -1.0 in GHD. Bone geometry changed in a biphasic mode, with an increase in total bone area and lowering of bone mineral content (BMC) during the first 12 months, followed by an increase of BMC and CT thereafter. SSI (mean values, mm(3)) improved from 78 to 114 in GHD and from 62 to 101 in SGA after 24 months on GH. The increment in terms of SDS did not reach significance in SGA. SSI correlated positively with muscle area before and during GH treatment. Bone strength and muscle mass are impaired in prepubertal children with GHD and SGA. Exogenous GH can indirectly improve bone structure and strength by inducing an increase in muscle mass. Our findings support the assumption that, in SGA, there is impaired tissue responsiveness to GH.

  16. Physiological Dose-Response of Coffee (Coffea arabica L. Plants to Glyphosate Depends on Growth Stage Respuesta Fisiológica de Plantas de Café (Coffea arabica L. a Glifosato Depende de la Etapa de Crecimiento

    Directory of Open Access Journals (Sweden)

    Leonardo Bianco de Carvalho

    2012-06-01

    Full Text Available Glyphosate is the main herbicide used in coffee (Coffea arabica L. plantations in Brazil. Problems with herbicide drift commonly occur in orchard fields due to non-adequate spraying conditions. A series of experiments was carried out aiming to evaluate physiological dose-response of C. arabica plants submitted to exposure to simulated glyphosate drift in two distinct plant growth stages. Glyphosate was applied at 0, 180, 360, and 720 g acid equivalent (AE ha-1 directly on coffee plants with 10 and 45 d after transplanting (DAT. Glyphosate doses in a range of 180-360 g AE ha-1 increased photosynthesis, transpiration and stomatal conductance in 10 DAT-plants up to 14 d after application (DAA while, in 45 DAT-plants, an increase was observed only up to 2 DAA, but this pattern was not persistent afterwards so that no difference in gas exchange was observed at 60 DAA in both plants. Macronutrient content was not affected by glyphosate application in both plants. Plant DM accumulation was not affected by glyphosate application at 10 DAT-plants, but an increase in plant growth was observed when glyphosate was applied in a range of 360-720 g AE ha-1 in 45 DAT-plants. Coffea arabica cv. Catuaí Vermelho IAC-144 responded differentially to glyphosate drift depending on plant growth stage, regarding on photosynthesis, transpiration, stomatal conductance, and plant growth, in spite of macronutrient nutrition was not affected.Glifosato es el principal herbicida utilizado en las plantaciones de café (Coffea arabica L. en Brasil. Problemas con la deriva de herbicidas comúnmente ocurren en los campos de cultivo debido a condiciones no adecuadas de pulverización. Una serie de experimentos se llevó a cabo con el objetivo de evaluar la relación dosis-respuesta fisiológica de plantas de C. arabica expuestas a situaciones simuladas de exposición a deriva de glifosato en dos etapas distintas de crecimiento de las plantas. El glifosato se aplicó en dosis de 0

  17. Insulin-like growth factor binding protein 3 has opposing actions on malignant and nonmalignant breast epithelial cells that are each reversible and dependent upon cholesterol-stabilized integrin receptor complexes.

    Science.gov (United States)

    Burrows, C; Holly, J M P; Laurence, N J; Vernon, E G; Carter, J V; Clark, M A; McIntosh, J; McCaig, C; Winters, Z E; Perks, C M

    2006-07-01

    IGF-binding protein (IGFBP)-3 is generally considered to have actions that counterbalance those of IGFs and is therefore being developed as a cancer treatment. In breast tumors, however, high levels are associated with aggressive tumors and poor prognosis. Consistent with this we have demonstrated that although IGFBP-3 and a non-IGF-binding fragment (serine phosphorylation domain peptide) reduced attachment and enhanced apoptosis of Hs578T breast cancer cells cultured on collagen or laminin, it promoted their attachment and survival on fibronectin, which is abundant in the matrix of aggressive tumors. We have now examined the factors that determine whether IGFBP-3 has positive or negative actions on breast epithelial cells. IGFBP-3 also promoted survival of Hs578T cells in the presence of an antibody to the beta1-integrin subunit or when cholesterol-stabilized complexes were disrupted. These actions were blocked by IGF-I or a MAPK inhibitor. Serine phosphorylation domain peptide had similar actions on MCF-7 cells that were again reversed on fibronectin or with disruption of cholesterol-stabilized complexes and blocked by the beta1-integrin antibody. In contrast, IGFBP-3 promoted growth and survival for nonmalignant MCF-10A cells, but these effects were again reversed on fibronectin and blocked by the beta1 antibody or a MAPK inhibitor or by disruption of cholesterol-stabilized complexes. On Hs578T cells, IGFBP-3 bound to caveolin-1 and beta1-integrins, enhancing their aggregation, the recruitment of focal adhesion kinase, and the activation of MAPK. In summary, with three breast epithelial cell lines, IGFBP-3 had positive or negative effects on growth and survival dependent upon the status of cholesterol-stabilized integrin receptor complexes.

  18. Genistein-mediated inhibition of glycosaminoglycan synthesis, which corrects storage in cells of patients suffering from mucopolysaccharidoses, acts by influencing an epidermal growth factor-dependent pathway

    Directory of Open Access Journals (Sweden)

    Barańska Sylwia

    2009-03-01

    Full Text Available Abstract Background Mucopolysaccharidoses (MPS are inherited metabolic disorders caused by mutations leading to dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs. Due to their impaired degradation, GAGs accumulate in cells of patients, which results in dysfunction of tissues and organs. Substrate reduction therapy is one of potential treatment of these diseases. It was demonstrated previously that genistein (4', 5, 7-trihydroxyisoflavone inhibits synthesis and reduces levels of GAGs in cultures of fibroblasts of MPS patients. Recent pilot clinical study indicated that such a therapy may be effective in MPS III (Sanfilippo syndrome. Methods To learn on details of the molecular mechanism of genistein-mediated inhibition of GAG synthesis, efficiency of this process was studied by measuring of incorporation of labeled sulfate, storage of GAGs in lysosomes was estimated by using electron microscopic techniques, and efficiency of phosphorylation of epidermal growth factor (EGF receptor was determined by using an ELISA-based assay with fluorogenic substrates. Results Effects of genistein on inhibition of GAG synthesis and accumulation in fibroblasts from patients suffering from various MPS types were abolished in the presence of an excess of EGF, and were partially reversed by an increased concentration of genistein. No such effects were observed when an excess of 17β-estradiol was used instead of EGF. Moreover, EGF-mediated stimulation of phsophorylation of the EGF receptor was impaired in the presence of genistein in both wild-type and MPS fibroblasts. Conclusion The results presented in this report indicate that the mechanism of genistein-mediated inhibition of GAG synthesis operates through epidermal growth factor (EGF-dependent pathway.

  19. Plasma DCLK1 is a marker of hepatocellular carcinoma (HCC): Targeting DCLK1 prevents HCC tumor xenograft growth via a microRNA-dependent mechanism.

    Science.gov (United States)

    Sureban, Sripathi M; Madhoun, Mohammad F; May, Randal; Qu, Dongfeng; Ali, Naushad; Fazili, Javid; Weygant, Nathaniel; Chandrakesan, Parthasarathy; Ding, Kai; Lightfoot, Stanley A; Houchen, Courtney W

    2015-11-10

    Tumor stem cell marker Doublecortin-like kinase1 (DCLK1) is upregulated in several solid tumors. The role of DCLK1 in hepatocellular carcinoma (HCC) is unclear. We immunostained tissues from human livers with HCC, cirrhosis controls (CC), and non-cirrhosis controls (NCC) for DCLK1. Western blot and ELISA analyses for DCLK1 were performed with stored plasma samples. We observed increased immunoreactive DCLK1 in epithelia and stroma in HCC and CCs compared with NCCs, and observed a marked increase in plasma DCLK1 from patients with HCC compared with CC and NCC. Analysis of the Cancer Genome Atlas' HCC dataset revealed that DCLK1 is overexpressed in HCC tumors relative to adjacent normal tissues. High DCLK1-expressing cells had more epithelial-mesenchymal transition (EMT). Various tumor suppressor miRNAs were also downregulated in HCC tumors. We evaluated the effects of DCLK1 knockdown on Huh7.5-derived tumor xenograft growth. This was associated with growth arrest and a marked downregulation of cMYC, and EMT transcription factors ZEB1, ZEB2, SNAIL, and SLUG via let-7a and miR-200 miRNA-dependent mechanisms. Furthermore, upregulation of miR-143/145, a corresponding decrease in pluripotency factors OCT4, NANOG, KLF4, and LIN28, and a reduction of let-7a, miR-143/145, and miR-200-specific luciferase activity was observed. These findings suggest that the detection of elevated plasma DCLK1 may provide a cost-effective, less invasive tool for confirmation of clinical signs of cirrhosis, and a potential companion diagnostic marker for patients with cirrhosis and HCC. Our results support evaluating DCLK1 as a biomarker for detection and as a therapeutic target for eradicating HCC.

  20. Spirulina lipopolysaccharides inhibit tumor growth in a Toll-like receptor 4-dependent manner by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ.

    Science.gov (United States)

    Okuyama, Hiromi; Tominaga, Akira; Fukuoka, Satoshi; Taguchi, Takahiro; Kusumoto, Yutaka; Ono, Shiro

    2017-02-01

    Th17 cells and the cytokine they produce, interleukin (IL)-17, play an important role in tumor progression in humans and in mice. IL-6 and IL-23 are critical cytokines for the differentiation and propagation of Th17 cells, respectively. Bacterial lipopolysaccharides (LPS) are known to stimulate immune cells to produce such inflammatory cytokines. Contrary to Escherichia coli (E. coli) LPS, LPS from Spirulina has low toxicity and barely induces in vivo production of IL-6 and IL-23 in mice. We examined the antitumor effects of Spirulina LPS compared to E. coli LPS in an MH134 hepatoma model. Administration of Spirulina LPS suppressed tumor growth in C3H/HeN mice, but not in Toll-like receptor 4 (TLR4)-mutant C3H/HeJ mice, by reducing serum levels of IL-17 and IL-23, while increasing interferon (IFN)-γ levels. The antitumor activity and IFN-γ production were mediated by T cells. Moreover, in vitro experiments showed that Spirulina LPS impaired the antigen-presenting function that supports the generation of IL-17-producing cells in a toll-like receptor (TLR)4-dependent manner. Of note, injection of anti-IL-17 antibody in tumor-bearing C3H/HeN mice in the absence of Spirulina LPS markedly suppressed tumor growth and augmented IFN-γ responses. Thus, our results support the notion that IFN-γ and IL-17/IL-23 mutually regulate Th17 and Th1 responses in tumor-bearing hosts, and Spirulina LPS modulates the balance of the IFN-γ-IL-17/IL-23 axis towards IFN-γ production, which leads to tumor inhibition. Furthermore, Spirulina LPS effectively inhibited the spontaneous development of mammary tumors. This study has important implications for the exploitation of TLR-based immunomodulators for cancer immunotherapy.

  1. In vitro exposure to xenoestrogens induces growth hormone transcription and release via estrogen receptor-dependent pathways in rat pituitary GH3 cells.

    Science.gov (United States)

    Dang, Vu Hoang; Nguyen, Thi Hoa; Lee, Geun-Shik; Choi, Kyung-Chul; Jeung, Eui-Bae

    2009-08-01

    In this study, we employed an in vitro model to examine the effects of endocrine disruptors (EDs) in the regulation of growth hormone (GH) gene, an important hormone in growth, development and body composition. The rat pituitary cells, GH3, were treated with alkyl-phenols (APs), i.e., 4-tert-octyl-phenol (OP), p-nonyl-phenol (NP) or bisphenol A (BPA) for 24h in a dose-dependent manner (10(-5), 10(-6) and 10(-7)M) and in a time-dependent fashion (1, 3, 6, 12 and 24h) at a high concentration (10(-5)M). An anti-estrogen, ICI 182,780, was used to examine the potential involvement of estrogen receptor (ER) in the induction of GH by EDs through an ER-mediated pathway. Treatment with OP, NP and BPA induced a significant increase in GH gene expression at high and medium doses at 24h. ED-exposure induced a marked increase in GH gene transcription as early as 6h and peaked at 12h. Co-treatment with ICI 182,780 significantly attenuated ED-induced GH expression in GH3 cells. Interestingly, the level of in vitro GH release was significantly increased at 24h in response to OP, NP or BPA, whereas co-treatment with ICI 182,780 significantly reversed ED-induced GH secretion, indicating that ER may take part in both GH gene transcription and its release in these cells. In addition, the activation of extracellular signal-regulated kinases (ERKs), protein kinases B (Akt) or G protein in response to OP, NP or BPA at 24h was observed in this study. Exposure to these APs resulted in a rapid and significant activation of ERK phosphorylation, reflecting that EDs-induced response may involve both genomic and non-genomic pathways in these cells. Taken together, these results may provide new insight into the mode of ED-induced action in GH gene regulation as well as the biological pathway underlying these molecular events.

  2. Extracellular matrix is modulated in advanced glycation end products milieu via a RAGE receptor dependent pathway boosted by transforming growth factor-β1 RAGE.

    Science.gov (United States)

    Serban, Andreea Iren; Stanca, Loredana; Geicu, Ovidiu Ionut; Munteanu, Maria Cristina; Costache, Marieta; Dinischiotu, Anca

    2015-01-01

    Interstitial fibrosis is induced by imbalances in extracellular matrix homeostasis. Advanced glycation end products (AGEs) can bind and activate the receptor for AGEs (RAGE), which is involved in diabetic nephropathy. We set out to identify the role of AGEs in producing alterations leading to matrix hypertrophy and the pathway through which aminoguanidine, as well as anti-RAGE and anti-transforming growth factor (TGF)-β1 antibody treatments could prevent these modifications. Human embryonic kidney (HEK-293) cells were exposed to glycated bovine serum albumin (AGE-BSA) and co-treated with neutralizing antibodies or aminoguanidine. The effects on the transcriptional and translational levels of RAGE, TGF-β1 and collagen IV were evaluated, while metalloproteinase activity was assessed by gelatin zymography. AGE-BSA (200 μg/mL) upregulated RAGE's expression, while TGF-β1 synthesis and the formation of its bioactive form were increased in a dose-dependent manner by AGEs. AGE-BSA exposure increased both matrix metalloproteinase (MMP) activity and collagen IV synthesis, boosted by TGF-β1 upregulation. Aminoguanidine's effects revealed that small concentrations (10 μmol/L) enhance AGE-BSA effects, by increasing the expression of RAGE and TGF-β1, while higher concentrations (100 μmol/L) contribute to their downregulation. Although AGEs regulate RAGE and TGF-β1 by distinct pathways, RAGE activation leads to a further increase of TGF-β1 levels. MMP-2 activity seems to rely on TGF-β1, while MMP-9 was dependent on RAGE. These factors converge to control collagen IV turnover. Furthermore, although the antibody treatments might appear more efficient than AG in decreasing collagen IV levels, the cells compensate the RAGE and TGF-β1 blockade by increasing the mRNA expression of these proteins. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  3. Inhibition of Plasminogen Activator Inhibitor-1 Attenuates Transforming Growth Factor-β-Dependent Epithelial Mesenchymal Transition and Differentiation of Fibroblasts to Myofibroblasts.

    Directory of Open Access Journals (Sweden)

    Keitaro Omori

    Full Text Available Transforming growth factor-β (TGF-β is central during the pathogenesis of pulmonary fibrosis, in which the plasminogen activator inhibitor-1 (PAI-1 also has an established role. TGF-β is also known to be the strongest inducer of PAI-1. To investigate the link between PAI-1 and TGF-β in fibrotic processes, we evaluated the effect of SK-216, a PAI-1-specific inhibitor, in TGF-β-dependent epithelial-mesenchymal transition (EMT and fibroblast to myofibroblast differentiation. In human alveolar epithelial A549 cells, treatment with TGF-β induced EMT, whereas co-treatment with SK-216 attenuated the occurrence of EMT. The inhibition of TGF-β-induced EMT by SK-216 was also confirmed in the experiment using murine epithelial LA-4 cells. Blocking EMT by SK-216 inhibited TGF-β-induced endogenous production of PAI-1 and TGF-β in A549 cells as well. These effects of SK-216 were not likely mediated by suppressing either Smad or ERK pathways. Using human lung fibroblast MRC-5 cells, we demonstrated that SK-216 inhibited TGF-β-dependent differentiation of fibroblasts to myofibroblasts. We also observed this inhibition by SK-216 in human primary lung fibroblasts. Following these in vitro results, we tested oral administration of SK-216 into mice injected intratracheally with bleomycin. We found that SK-216 reduced the degree of bleomycin-induced pulmonary fibrosis in mice. Although the precise mechanisms underlying the link between TGF-β and PAI-1 regarding fibrotic process were not determined, PAI-1 seems to act as a potent downstream effector on the pro-fibrotic property of TGF-β. In addition, inhibition of PAI-1 activity by a PAI-1 inhibitor exerts an antifibrotic effect even in vivo. These data suggest that targeting PAI-1 as a downstream effector of TGF-β could be a promising therapeutic strategy for pulmonary fibrosis.

  4. Transforming growth factor β-induced superficial zone protein accumulation in the surface zone of articular cartilage is dependent on the cytoskeleton.

    Science.gov (United States)

    McNary, Sean M; Athanasiou, Kyriacos A; Reddi, A Hari

    2014-03-01

    The phenotype of articular chondrocytes is dependent on the cytoskeleton, specifically the actin microfilament architecture. Articular chondrocytes in monolayer culture undergo dedifferentiation and assume a fibroblastic phenotype. This process can be reversed by altering the actin cytoskeleton by treatment with cytochalasin. Whereas dedifferentiation has been studied on chondrocytes isolated from the whole cartilage, the effects of cytoskeletal alteration on specific zones of cells such as superficial zone chondrocytes are not known. Chondrocytes from the superficial zone secrete superficial zone protein (SZP), a lubricating proteoglycan that reduces the coefficient of friction of articular cartilage. A better understanding of this phenomenon may be useful in elucidating chondrocyte dedifferentiation in monolayer and accumulation of the cartilage lubricant SZP, with an eye toward tissue engineering functional articular cartilage. In this investigation, the effects of cytoskeletal modulation on the ability of superficial zone chondrocytes to secrete SZP were examined. Primary superficial zone chondrocytes were cultured in monolayer and treated with a combination of cytoskeleton modifying reagents and transforming growth factor β (TGFβ) 1, a critical regulator of SZP production. Whereas cytochalasin D maintains the articular chondrocyte phenotype, the hallmark of the superficial zone chondrocyte, SZP, was inhibited in the presence of TGFβ1. A decrease in TGFβ1-induced SZP accumulation was also observed when the microtubule cytoskeleton was modified using paclitaxel. These effects of actin and microtubule alteration were confirmed through the application of jasplakinolide and colchicine, respectively. As Rho GTPases regulate actin organization and microtubule polymerization, we hypothesized that the cytoskeleton is critical for TGFβ-induced SZP accumulation. TGFβ-mediated SZP accumulation was inhibited by small molecule inhibitors ML141 (Cdc42), NSC23766 (Rac1

  5. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper

    2009-01-01

    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformatio...

  6. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper

    2009-01-01

    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformations...

  7. Epidermal growth factor induces cyclin D1 in human pancreatic carcinoma: evidence for a cyclin D1-dependent cell cycle progression.

    Science.gov (United States)

    Poch, B; Gansauge, F; Schwarz, A; Seufferlein, T; Schnelldorfer, T; Ramadani, M; Beger, H G; Gansauge, S

    2001-10-01

    We recently showed that cyclin D1 is overexpressed in human pancreatic carcinoma cells, and that this overexpression correlates significantly with a poor prognosis. To assess the interrelations of epidermal growth factor (EGF), EGF receptor (EGFR), and cyclin D1 in human pancreatic carcinoma. In pancreatic carcinoma cell lines (BxPC-3, AsPC-1), cell cycle analysis revealed an increase in cells in the S/G1 phase between 18 and 30 hours after stimulation with 50 ng/mL EGF. Cyclin D1 mRNA increased after 2 hours, corresponding to an increase in cyclin D1 protein, with the maximum level between 7.5 and 10 hours after stimulation, as demonstrated by Western blot analysis. We performed immunohistochemical analysis on 61 adenocarcinoma tissues for the expression of EGF, EGFR, and cyclin D1 and demonstrated an overexpression in the tumor cells in 51%, 54%, and 62.3%, respectively, whereas normal human pancreas stained negative for all of the three factors. Interestingly, EGF and EGFR expression correlated significantly with the cyclin D1 expression in human pancreatic tumor cells (p < 0.001 and p < 0.01, respectively). These results demonstrate that cyclin D1 overexpression in the tumor cells of pancreatic carcinoma tissue is at least partly dependent on the mitogenic effects of EGF signaling through the EGFR.

  8. Transforming growth factor beta-activated kinase 1 (TAK1)-dependent checkpoint in the survival of dendritic cells promotes immune homeostasis and function.

    Science.gov (United States)

    Wang, Yanyan; Huang, Gonghua; Vogel, Peter; Neale, Geoffrey; Reizis, Boris; Chi, Hongbo

    2012-02-07

    Homeostatic control of dendritic cell (DC) survival is crucial for adaptive immunity, but the molecular mechanism is not well defined. Moreover, how DCs influence immune homeostasis under steady state remains unclear. Combining DC-specific and -inducible deletion systems, we report that transforming growth factor beta-activated kinase 1 (TAK1) is an essential regulator of DC survival and immune system homeostasis and function. Deficiency of TAK1 in CD11c(+) cells induced markedly elevated apoptosis, leading to the depletion of DC populations, especially the CD8(+) and CD103(+) DC subsets in lymphoid and nonlymphoid tissues, respectively. TAK1 also contributed to DC development by promoting the generation of DC precursors. Prosurvival signals from Toll-like receptors, CD40 and receptor activator of nuclear factor-κB (RANK) are integrated by TAK1 in DCs, which in turn mediated activation of downstream NF-κB and AKT-Foxo pathways and established a gene-expression program. TAK1 deficiency in DCs caused a myeloid proliferative disorder characterized by expansion of neutrophils and inflammatory monocytes, disrupted T-cell homeostasis, and prevented effective T-cell priming and generation of regulatory T cells. Moreover, TAK1 signaling in DCs was required to prevent myeloid proliferation even in the absence of lymphocytes, indicating a previously unappreciated regulatory mechanism of DC-mediated control of myeloid cell-dependent inflammation. Therefore, TAK1 orchestrates a prosurvival checkpoint in DCs that affects the homeostasis and function of the immune system.

  9. Osteitis fibrosa is mediated by Platelet-Derived Growth Factor-A via a phosphoinositide 3-kinase-dependent signaling pathway in a rat model for chronic hyperparathyroidism.

    Science.gov (United States)

    Lowry, Malcolm B; Lotinun, Sutada; Leontovich, Alexey A; Zhang, Minzhi; Maran, Avudaiappan; Shogren, Kristen L; Palama, Brett K; Marley, Kevin; Iwaniec, Urszula T; Turner, Russell T

    2008-11-01

    Abnormal secretion of PTH by the parathyroid glands contributes to a variety of common skeletal disorders. Prior studies implicate platelet-derived growth factor-A (PDGF-A) as an important mediator of selective PTH actions on bone. The present studies used targeted gene profiling and small-molecule antagonists directed against candidate gene products to elucidate the roles of specific PTH-regulated genes and signaling pathways. A group of 29 genes in rats continuously infused with PTH and cotreated with the PDGF receptor antagonist trapidil were differentially expressed compared with PTH treatment alone. Several of the identified genes were functionally clustered as regulators of fibroblast differentiation and extracellular matrix modeling, including the matrix cross-linking enzyme lysyl oxidase (LOX). Treatment with beta-aminopropionitrile, an irreversible inhibitor of LOX activity, dramatically reduced diffuse mineralization but had no effect on PTH-induced fibrosis. In contrast, the receptor tyrosine kinase inhibitor Gleevec and the phosphoinositide 3-kinase inhibitor wortmannin each reduced bone marrow fibrosis. In summary, the present studies support the hypotheses that PTH-induced bone marrow fibrosis is mediated by PDGF-A via a phosphoinositide 3-kinase-dependent signaling pathway and that increased LOX gene expression plays a key role in abnormal mineralization, a hallmark of chronic hyperparathyroidism.

  10. Turbulence growth and its dependency of wake vortices on excitation frequency by local body-force around two-dimensional hump

    Science.gov (United States)

    Yakeno, Aiko; Abe, Yoshiaki; Nonomura, Taku; Kawai, Soshi; Fujii, Kozo

    2017-11-01

    We investigated details of wake vortex dynamics to cause turbulence increase and early flow-reattachment under excitation forcing by a plasma actuator setting around a 2D hump numerically. The local body-force was homogeneous in the spanwise direction and bursting temporally. That actuation generates two-dimensional roll vortices and other turbulence motions such like three-dimensional rib structure in downstream. These dynamics depended on the excitation frequency. We tried to discuss multi-scaled vortices separately with considering the temporal phaseaveraged statistics of the excitation frequency and others, those are related to roll vortices and others with rib structure between rolls. It was found that the maximum value of non-periodic fluctuation in downstream correlated with flow-reattachment performance more than that of periodic fluctuation of roll vortices. The amplitude becomes large around separation position in early reattachment cases. The spacial growth rates of peak values in the wall-normal direction are same for high frequency cases, K-H instability modes, however not true for low frequency cases. In high frequency cases, amplitude in the early state of separation plays a significant rule to increase it in downstream. Strategic Programs for Innovative Research of the High Performance Computing Initiative (No. hp120296,hp130001,hp140207, hp150219) Grant-in-Aid for Scientific Research(B) (No. 15K21677) by the MEXT.

  11. Combination Therapy with c-Met and Src Inhibitors Induces Caspase-Dependent Apoptosis of Merlin-Deficient Schwann Cells and Suppresses Growth of Schwannoma Cells.

    Science.gov (United States)

    Fuse, Marisa A; Plati, Stephani Klingeman; Burns, Sarah S; Dinh, Christine T; Bracho, Olena; Yan, Denise; Mittal, Rahul; Shen, Rulong; Soulakova, Julia N; Copik, Alicja J; Liu, Xue Zhong; Telischi, Fred F; Chang, Long-Sheng; Franco, Maria Clara; Fernandez-Valle, Cristina

    2017-11-01

    Neurofibromatosis type 2 (NF2) is a nervous system tumor disorder caused by inactivation of the merlin tumor suppressor encoded by the NF2 gene. Bilateral vestibular schwannomas are a diagnostic hallmark of NF2. Mainstream treatment options for NF2-associated tumors have been limited to surgery and radiotherapy; however, off-label uses of targeted molecular therapies are becoming increasingly common. Here, we investigated drugs targeting two kinases activated in NF2-associated schwannomas, c-Met and Src. We demonstrated that merlin-deficient mouse Schwann cells (MD-MSC) treated with the c-Met inhibitor, cabozantinib, or the Src kinase inhibitors, dasatinib and saracatinib, underwent a G 1 cell-cycle arrest. However, when MD-MSCs were treated with a combination of cabozantinib and saracatinib, they exhibited caspase-dependent apoptosis. The combination therapy also significantly reduced growth of MD-MSCs in an orthotopic allograft mouse model by greater than 80% of vehicle. Moreover, human vestibular schwannoma cells with NF2 mutations had a 40% decrease in cell viability when treated with cabozantinib and saracatinib together compared with the vehicle control. This study demonstrates that simultaneous inhibition of c-Met and Src signaling in MD-MSCs triggers apoptosis and reveals vulnerable pathways that could be exploited to develop NF2 therapies. Mol Cancer Ther; 16(11); 2387-98. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. The structure of a contact-dependent growth-inhibition (CDI) immunity protein from Neisseria meningitidis MC58

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Kemin; Johnson, Parker M.; Stols, Lucy; Boubion, Bryan; Eschenfeldt, William; Babnigg, Gyorgy; Hayes, Christopher S.; Joachimiak, Andrezj; Goulding, Celia W.

    2015-05-20

    Contact-dependent growth inhibition (CDI) is an important mechanism of intercellular competition between neighboring Gram-negative bacteria. CDI systems encode large surface-exposed CdiA effector proteins that carry a variety of C-terminal toxin domains (CdiA-CTs). All CDI+bacteria also produce CdiI immunity proteins that specifically bind to the cognate CdiA-CT and neutralize its toxin activity to prevent auto-inhibition. Here, the X-ray crystal structure of a CdiI immunity protein fromNeisseria meningitidisMC58 is presented at 1.45 Å resolution. The CdiI protein has structural homology to the Whirly family of RNA-binding proteins, but appears to lack the characteristic nucleic acid-binding motif of this family. Sequence homology suggests that the cognate CdiA-CT is related to the eukaryotic EndoU family of RNA-processing enzymes. A homology model is presented of the CdiA-CT based on the structure of the XendoU nuclease fromXenopus laevis. Molecular-docking simulations predict that the CdiA-CT toxin active site is occluded upon binding to the CdiI immunity protein. Together, these observations suggest that the immunity protein neutralizes toxin activity by preventing access to RNA substrates.

  13. Platelet-derived growth factor receptors form complexes with neuropilin-1 during megakaryocytic differentiation of thrombopoietin-dependent UT-7/TPO cells.

    Science.gov (United States)

    Ohsaka, Akimichi; Hirota-Komatsu, Satoko; Araki, Marito; Komatsu, Norio

    2015-04-10

    Neuropilin-1 (NRP-1) is involved in angiogenesis, but the role of NRP-1 in megakaryocytopoiesis is not yet fully understood. In this study, we investigated whether thrombopoietin (TPO) regulates the expression of platelet-derived growth factor (PDGF) and its receptors (PDGFRs) on TPO-dependent UT-7/TPO cells and whether PDGFRs and NRP-1 on UT-7/TPO cells form complexes during megakaryocytic differentiation. When UT-7/TPO cells were starved of TPO for 24 h and then stimulated with 5 ng/ml TPO, the expression of PDGF-B, PDGFRα, and PDGFRβ were significantly up-regulated after the addition of TPO. TPO also induced tyrosine phosphorylation of PDGFRα but not PDGFRβ, and promoted the formation of PDGFRαβ heterodimer complexes. Furthermore, megakaryocytic differentiation of UT-7/TPO cells on treatment with phorbol myristate acetate (PMA) was accompanied by a marked up-regulation of PDGFRβ and NRP-1 protein expression, complex formation between PDGFRs and NRP-1, PDGFRαβ heterodimer complexes, and an increase in PDGF-BB-binding activity. Immunocytochemistry confirmed complex formation between PDGFRs and NRP-1 and PDGFRαβ heterodimer complexes in PMA-differentiated UT-7/TPO cells. Our observations suggest that NRP-1 is involved in megakaryocytopoiesis through complex formation with PDGFRs, and that NRP-1-PDGFR-complexes may contribute to effective cellular functions mediated by TPO and PDGF in megakaryocytic cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Ocean acidification impact on growth and the pH dependence of trace elements in skeleton of juvenile corals (Acropora digitifera)

    Science.gov (United States)

    Inoue, M.; Suwa, R.; Iguchi, A.; Suzuki, A.; Sakai, K.; Kawahata, H.

    2010-12-01

    The impact of ocean acidification caused by the increasing global concentration of atmospheric CO2 has been studied in marine calcifiers, including hermatypic corals, in which calcification is expected to decrease significantly. However, the effect of elevated pCO2 on the early developmental stage of the coral life cycle has been little studied, even though corals at this stage seem to be susceptible to stresses including ocean acidification. In this study, we reared polyps of Acropora digitifera, one of the dominant species around the Ryukyu Islands, Japan, in seawater of various pH (6.55, 7.31, 7.64, 7.77, 8.03), controlled by CO2 bubbling. We measured the dry weight of the polyp skeletons after the 40 days experiment to investigate the relationship between the aragonite saturation state and polyp growth. In addition, we measured the Mg/Ca, Sr/Ca, Ba/Ca, and U/Ca ratios of their skeletons to estimate the pH dependence of these ratios. Although skeletons of polyps reared at pH 6.55 dissolved during the experiment after settlement, the other skeletal weight of coral polyps increased with the aragonite saturation state. Then, skeletal weight apparently reached a saturation plateau above pH 7.77, a finding in agreement with previous results for adult corals. Ba/Ca and U/Ca were significantly related to pH, whereas Sr/Ca showed a moderate positive correlation with pH. On the other hand, there was no clear relationship between Mg/Ca and pH. Although both the Ba/Ca and U/Ca ratios showed a strong dependency on pH, coral Ba/Ca is reported to be affected by multiple factors such as terrestrial runoff and upwelling. But, U/Ca ratios have been reported a relatively simple dependency on temperature. Therefore, coral U/Ca may have a potential for pH proxy.

  15. Strand specific RNA-sequencing and membrane lipid profiling reveals growth phase-dependent cold stress response mechanisms in Listeria monocytogenes.

    Directory of Open Access Journals (Sweden)

    Patricia Hingston

    Full Text Available The human pathogen Listeria monocytogenes continues to pose a challenge in the food industry, where it is known to contaminate ready-to-eat foods and grow during refrigerated storage. Increased knowledge of the cold-stress response of this pathogen will enhance the ability to control it in the food-supply-chain. This study utilized strand-specific RNA sequencing and whole cell fatty acid (FA profiling to characterize the bacterium's cold stress response. RNA and FAs were extracted from a cold-tolerant strain at five time points between early lag phase and late stationary-phase, both at 4°C and 20°C. Overall, more genes (1.3× were suppressed than induced at 4°C. Late stationary-phase cells exhibited the greatest number (n = 1,431 and magnitude (>1,000-fold of differentially expressed genes (>2-fold, p<0.05 in response to cold. A core set of 22 genes was upregulated at all growth phases, including nine genes required for branched-chain fatty acid (BCFA synthesis, the osmolyte transporter genes opuCBCD, and the internalin A and D genes. Genes suppressed at 4°C were largely associated with cobalamin (B12 biosynthesis or the production/export of cell wall components. Antisense transcription accounted for up to 1.6% of total mapped reads with higher levels (2.5× observed at 4°C than 20°C. The greatest number of upregulated antisense transcripts at 4°C occurred in early lag phase, however, at both temperatures, antisense expression levels were highest in late stationary-phase cells. Cold-induced FA membrane changes included a 15% increase in the proportion of BCFAs and a 15% transient increase in unsaturated FAs between lag and exponential phase. These increases probably reduced the membrane phase transition temperature until optimal levels of BCFAs could be produced. Collectively, this research provides new information regarding cold-induced membrane composition changes in L. monocytogenes, the growth-phase dependency of its cold

  16. Time-dependent alterations in growth, photosynthetic pigments and enzymatic defense systems of submerged Ceratophyllum demersum during exposure to the cyanobacterial neurotoxin anatoxin-a

    International Nuclear Information System (INIS)

    Ha, Mi-Hee; Pflugmacher, Stephan

    2013-01-01

    Highlights: •We examined time-dependent metabolic changes in C. demersum exposed to anatoxin-a. •Biotransformation and antioxidative defense mechanisms responded positively to anatoxin-a. •Decline in chlorophylls contents was detected in company with irreversible plant growth inhibition during exposure to anatoxin-a. •Anatoxin-a exhibits phytotoxic allelopathy by provoking oxidative stress. •Macrophytes may have interactions with anatoxin-a in aquatic environments. -- Abstract: Recently, aquatic macrophytes have been considered as promising tools for eco-friendly water management with a low running cost. However, only little information is available thus far regarding the metabolic capacity of macrophytes for coping with cyanobacterial toxins (cyanotoxins) in the aquatic environment. Cyanotoxins have become emerging contaminants of great concern due to the high proliferation of cyanobacteria (cyanobacterial bloom) accelerated by eutrophication and climate change. Anatoxin-a, one of the common and major cyanotoxins, is suggested as a high priority water pollutant for regulatory consideration owing to its notoriously rapid mode of action as a neurotoxin. In this study, the time-course metabolic regulation of the submerged macrophyte Ceratophyllum demersum (C. demersum) was investigated during exposure to anatoxin-a at an environmentally relevant concentration (15 μg/L). Biotransformation and antioxidative systems in C. demersum responded positively to anatoxin-a through the promoted synthesis of most of the involved enzymes within 8 h. Maximum enzyme activities were exhibited after 24 or 48 h of exposure to anatoxin-a. However, an apparent decline in enzyme activities was also observed at longer exposure duration (168 and 336 h) in company with high steady-state levels of cell internal H 2 O 2 , which showed its highest level after 48 h. Meanwhile, irreversible inhibitory influence on chlorophyll content (vitality) was noticed, whereas the ratio of

  17. Identification of novel growth phase- and media-dependent small non-coding RNAs in Streptococcus pyogenes M49 using intergenic tiling arrays

    Directory of Open Access Journals (Sweden)

    Patenge Nadja

    2012-10-01

    Full Text Available Abstract Background Small non-coding RNAs (sRNAs have attracted attention as a new class of gene regulators in both eukaryotes and bacteria. Genome-wide screening methods have been successfully applied in Gram-negative bacteria to identify sRNA regulators. Many sRNAs are well characterized, including their target mRNAs and mode of action. In comparison, little is known about sRNAs in Gram-positive pathogens. In this study, we identified novel sRNAs in the exclusively human pathogen Streptococcus pyogenes M49 (Group A Streptococcus, GAS M49, employing a whole genome intergenic tiling array approach. GAS is an important pathogen that causes diseases ranging from mild superficial infections of the skin and mucous membranes of the naso-pharynx, to severe toxic and invasive diseases. Results We identified 55 putative sRNAs in GAS M49 that were expressed during growth. Of these, 42 were novel. Some of the newly-identified sRNAs belonged to one of the common non-coding RNA families described in the Rfam database. Comparison of the results of our screen with the outcome of two recently published bioinformatics tools showed a low level of overlap between putative sRNA genes. Previously, 40 potential sRNAs have been reported to be expressed in a GAS M1T1 serotype, as detected by a whole genome intergenic tiling array approach. Our screen detected 12 putative sRNA genes that were expressed in both strains. Twenty sRNA candidates appeared to be regulated in a medium-dependent fashion, while eight sRNA genes were regulated throughout growth in chemically defined medium. Expression of candidate genes was verified by reverse transcriptase-qPCR. For a subset of sRNAs, the transcriptional start was determined by 5′ rapid amplification of cDNA ends-PCR (RACE-PCR analysis. Conclusions In accord with the results of previous studies, we found little overlap between different screening methods, which underlines the fact that a comprehensive analysis of s

  18. Time-dependent alterations in growth, photosynthetic pigments and enzymatic defense systems of submerged Ceratophyllum demersum during exposure to the cyanobacterial neurotoxin anatoxin-a

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Mi-Hee; Pflugmacher, Stephan, E-mail: stephan.pflugmacher@tu-berlin.de

    2013-08-15

    Highlights: •We examined time-dependent metabolic changes in C. demersum exposed to anatoxin-a. •Biotransformation and antioxidative defense mechanisms responded positively to anatoxin-a. •Decline in chlorophylls contents was detected in company with irreversible plant growth inhibition during exposure to anatoxin-a. •Anatoxin-a exhibits phytotoxic allelopathy by provoking oxidative stress. •Macrophytes may have interactions with anatoxin-a in aquatic environments. -- Abstract: Recently, aquatic macrophytes have been considered as promising tools for eco-friendly water management with a low running cost. However, only little information is available thus far regarding the metabolic capacity of macrophytes for coping with cyanobacterial toxins (cyanotoxins) in the aquatic environment. Cyanotoxins have become emerging contaminants of great concern due to the high proliferation of cyanobacteria (cyanobacterial bloom) accelerated by eutrophication and climate change. Anatoxin-a, one of the common and major cyanotoxins, is suggested as a high priority water pollutant for regulatory consideration owing to its notoriously rapid mode of action as a neurotoxin. In this study, the time-course metabolic regulation of the submerged macrophyte Ceratophyllum demersum (C. demersum) was investigated during exposure to anatoxin-a at an environmentally relevant concentration (15 μg/L). Biotransformation and antioxidative systems in C. demersum responded positively to anatoxin-a through the promoted synthesis of most of the involved enzymes within 8 h. Maximum enzyme activities were exhibited after 24 or 48 h of exposure to anatoxin-a. However, an apparent decline in enzyme activities was also observed at longer exposure duration (168 and 336 h) in company with high steady-state levels of cell internal H{sub 2}O{sub 2}, which showed its highest level after 48 h. Meanwhile, irreversible inhibitory influence on chlorophyll content (vitality) was noticed, whereas the ratio of

  19. Bilateral Trade Flows and Income Distribution Similarity.

    Science.gov (United States)

    Martínez-Zarzoso, Inmaculada; Vollmer, Sebastian

    2016-01-01

    Current models of bilateral trade neglect the effects of income distribution. This paper addresses the issue by accounting for non-homothetic consumer preferences and hence investigating the role of income distribution in the context of the gravity model of trade. A theoretically justified gravity model is estimated for disaggregated trade data (Dollar volume is used as dependent variable) using a sample of 104 exporters and 108 importers for 1980-2003 to achieve two main goals. We define and calculate new measures of income distribution similarity and empirically confirm that greater similarity of income distribution between countries implies more trade. Using distribution-based measures as a proxy for demand similarities in gravity models, we find consistent and robust support for the hypothesis that countries with more similar income-distributions trade more with each other. The hypothesis is also confirmed at disaggregated level for differentiated product categories.

  20. Bilateral Trade Flows and Income Distribution Similarity.

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    Inmaculada Martínez-Zarzoso

    Full Text Available Current models of bilateral trade neglect the effects of income distribution. This paper addresses the issue by accounting for non-homothetic consumer preferences and hence investigating the role of income distribution in the context of the gravity model of trade. A theoretically justified gravity model is estimated for disaggregated trade data (Dollar volume is used as dependent variable using a sample of 104 exporters and 108 importers for 1980-2003 to achieve two main goals. We define and calculate new measures of income distribution similarity and empirically confirm that greater similarity of income distribution between countries implies more trade. Using distribution-based measures as a proxy for demand similarities in gravity models, we find consistent and robust support for the hypothesis that countries with more similar income-distributions trade more with each other. The hypothesis is also confirmed at disaggregated level for differentiated product categories.