Exploring TERRA (TElomeric Repeat-containing RNA) Expression and Regulation During Cell Growth in Saccharomyces cerevisiae

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The inflammatory role of angiogenic growth factors : a neutrophil perspective

De par sa présence dans tous les vaisseaux sanguins, l'endothélium joue un rôle clef dans le processus d’hémostase, tant par sa libération de facteurs anticoagulants que par ses changements protéiques qui permettent à l’organisme de déclencher la réparation tissulaire. La fonction anticoagulante de l’endothélium peut être mise en défaut en cas d’atteinte de son intégrité, entrainant la formation de thrombus, le rejet précoce de greffes ou encore l’induction de l’athérosclérose. L’intégrité de l’endothélium est donc capitale pour la prévention de nombreuses maladies cardiovasculaires. Chez l’adulte, les cellules endothéliales (CE), normalement quiescentes, sont rapidement activées en cas d’hypoxie ou d’inflammation, leur permettant ainsi d’amorcer le processus angiogénique comme suit: Tout d’abord, l’induction de l’hyperperméabilité vasculaire permet l’extravasation des protéines plasmatiques. Ensuite, la dégradation de la lame basale par des métalloprotéases permet aux CE de se détacher, de proliférer, de migrer et de s’organiser pour former l’ébauche du futur vaisseau. La dernière étape consiste en la maturation du vaisseau, c’est-à-dire son recouvrement par des cellules murales, telles que les cellules musculaires lisses et les péricytes. Ces processus sont régulés par de nombreux facteurs angiogéniques tels que les membres de la famille Notch, du vascular endothelial growth factor (VEGF), du fibroblast growth factor (FGF), des angiopoïétines, et des matrix metalloproteases (MMP). L’angiogenèse pathologique, soit une insuffisance ou un excès de vascularisation, est impliquée dans les blessures chroniques, les accidents cardiovasculaires, les pathologies coronariennes artérielles, les pathologies tumorales, l’arthrite rhumatoïde, la rétinopathie diabétique, l’athérosclérose, le psoriasis et l’asthme. Ces pathologies sont souvent issues d’une dérégulation de l’activité endothéliale, fréquemment observée conjointement à l’expression continue de molécules d’adhésion leucocytaires, à l’augmentation de la perméabilité vasculaire, et aux anomalies de la vasoréactivité. L’activation non-contrôlée de l’endothélium entraîne ainsi une inflammation chronique et la formation de structures vasculaires anarchiques. Les premiers leucocytes à répondre à l’appel inflammatoire sont les neutrophiles. Equippées d’une panoplie de produits antibactériens puissants mais aussi nocifs pour les tissus qui les entourent, ces cellules polylobées participent à chaque étape du processus inflammatoire, depuis l’induction de l’hyperperméabilité vasculaire jusqu’à la résolution. En effet, grâce à leurs récepteurs, les neutrophiles détectent et interprètent les signaux biochimiques présents dans la circulation et à la surface de l’endothélium, et libèrent aussi leurs propres médiateurs tels le VEGF, les MMP, et l’interleukine-8 (IL-8), dont les effets sont à la fois paracrines et autocrines. Existent-ils d’autres modulateurs typiques de la fonction endothéliale capables d’influencer le comportement des neutrophiles? En effet, notre laboratoire a démontré que chez l’humain, une stimulation directe aux angiopoïétines incitait les neutrophiles à adhérer aux CE, à migrer, à synthétiser et à relâcher l’IL-8, voire même à vivre plus longtemps. La présence du récepteur des angiopoïétines, Tie2, à la surface des neutrophiles laisse présager que la famille possèderait d’autres fonctions leucocytaires encore non-identifiées. Par ailleurs, dans un modèle classique de l’angiogenèse in vivo (matrigel), nous avons observé que sous l’effet du FGF1 et 2, les ébauches des nouveaux vaisseaux étaient parfois accompagnées d’une infiltration de cellules granulocytaires. Ainsi, en partant de ces observations, l’objectif de nos études (présentées ci-après) était d’approfondir nos connaissances sur la relation entre neutrophiles et facteurs angiogéniques, notamment les FGF et les angiopoïétines. Par tests in vitro, nous avons confirmé que les neutrophiles humains exprimaient plusieurs récepteurs du FGF (FGFR1-4) d’une façon hétérogène, et qu’ils migraient vers un gradient des ligands FGF1 et 2. Par ailleurs, nous nous sommes intéressés aux voies de signalisation inflammatoires activées par les ligands FGF1, FGF2, Ang1 et Ang2. Grâce à une stratégie génique ciblant 84 gènes inflammatoires, nous avons identifié plusieurs cibles d’intérêt touchées par Ang1, dont certains membres de la famille de l’IL-1, alors qu’aucun des gènes testés n’avait changé de façon significative sous l’effet des FGF ou d’Ang2. Suite à des cinétiques approfondies, nous avons démontré qu’Ang1 stimulait la transcription de l’ARN messager de l’IL-1β, et augmentait simultanément la quantité de protéine immature (pro-IL-1β; inactive) et clivée (IL-1β « mature »; active). En parallèle, Ang1 augmentait la sécrétion de l’antagoniste naturel de l’IL-1β, l’IL-1RA, sans pour autant stimuler la relâche de l’IL-1β. A l’instar des endotoxines bactériennes dont les effets liés à l’IL-1 dépendaient de la kinase p38, ceux d’Ang1 découlaient presque entièrement des voies de signalisation du p42/44.

Women Industrial Cooperatives- An Analysis of Its Structure, Performance and Growth in Kannur District

In the present study made an attempt to analyse the structure, performance and growth of women industrial cooperatives in kannur district, Kerala. The study encompasses all women industrial cooperatives registered at the district industries center, kannur and that currently exist. The women industrial cooperatives are classified into two ie; group with network and another group without network. In Kannur there are 54 units working as women industrial cooperatives. One of the main problems the women cooperatives face is the lack of working capital followed marketing problem. The competition between cooperatives and private traders is very high. The variables examined to analyse the performance of women industrial cooperatives in Kannur showed that there exists inter unit differences in almost all the variables. The financial structure structure shows that the short term liquidity of women cooperatives in Kannur favour more the units which have political networks; but the long term financial coverage is seen to be highly geared in this group, not because of a decline is net worth but due to highly proportionate increase in financial liabilities in the form of borrowings. The encouragement given by the government through financial stake and other incentives has been the major factor in the formation and growth of women cooperatives. As a result both productivity and efficiency improves in the cooperatives. In short the present study helped to capture the impact, role and dynamics of networking in general and socio political network in particular in relation to intra and inter unit differences on the structure, growth and performance of women industrial cooperatives societies in Kannur district

Amorphous Oxide Transparent Thin Films: Growth, Characterisation and Application to Thin Film Transistors

This work mainly concentrate to understand the optical and electrical properties of amorphous zinc tin oxide and amorphous zinc indium tin oxide thin films for TFT applications. Amorphous materials are promising in achieving better device performance on temperature sensitive substrates compared to polycrystalline materials. Most of these amorphous oxides are multicomponent and as such there exists the need for an optimized chemical composition. For this we have to make individual targets with required chemical composition to use it in conventional thin film deposition techniques like PLD and sputtering. Instead, if we use separate targets for each of the cationic element and if separately control the power during the simultaneous sputtering process, then we can change the chemical composition by simply adjusting the sputtering power. This is what is done in co-sputtering technique. Eventhough there had some reports about thin film deposition using this technique, there was no reports about the use of this technique in TFT fabrication until very recent time. Hence in this work, co-sputtering has performed as a major technique for thin film deposition and TFT fabrication. PLD were also performed as it is a relatively new technique and allows the use high oxygen pressure during deposition. This helps to control the carrier density in the channel and also favours the smooth film surface. Both these properties are crucial in TFT.Zinc tin oxide material is interesting in the sense that it does not contain costly indium. Eventhough some works were already reported in ZTO based TFTs, there was no systematic study about ZTO thin film's various optoelectronic properties from a TFT manufacturing perspective. Attempts have made to analyse the ZTO films prepared by PLD and co-sputtering. As more type of cations present in the film, chances are high to form an amorphous phase. Zinc indium tin oxide is studied as a multicomponent oxide material suitable for TFT fabrication.

Growth and characterisation of p-type delafossite transparent conducting thin films for heterojunction applications

In the present studies, various copper delafossite materials viz; CuAlO2, CuGaO2, CuFeO2 , CuGa1-xFexO2, CuYO2 and CuCaxY1-xO2 were synthesised by solid state reaction technique. These copper delafossite materials were grown in thin film form by rf magnetron sputtering technique. In general copper delafossites exhibit good optical transparency. The conductivity of the CuYO2 could be improved by Ca doping or by oxygen intercalation by annealing the film in oxygen atmosphere. It has so far been impossible to improve the p-type conductivity of CuGaO2 significantly by doping Mg or Ca on the Ga site. The ptype conductivity is presumed to be due to oxygen doping or Cu Vacancies [6]. Reports in literature show, oxygen intercalation or divalent ion doping on Ga site is not possible for CuGaO2 thin films to improve the p-type conductivity. Sintered powder and crystals of CuFeO2 have been reported as the materials having the highest p-type conductivity [14, 15] among the copper and silver delafossites. However the CuFeO2 films are found to be less transparent in the visible region compared to CuGaO2. Hence in the present work, the solid solution between the CuGaO2 and CuFeO2 was effected by solid state reaction, varying the Fe content. The CuGa1-xFexO2 with Fe content, x=0.5 shows an increase in conductivity by two orders, compared to CuGaO2 but the transparency is only about 50% in the visible region which is less than that of CuGaO2 The synthesis of α−AgGaO2 was carried out by two step process which involves the synthesis of β-AgGaO2 by ion exchange reaction followed by the hydrothermal conversion of the β-AgGaO2 into α-AgGaO2. The trace amount of Ag has been reduced substantially in the two step synthesis compared to the direct hydrothermal synthesis. Thin films of α-AgGaO2 were prepared on silicon and Al2O3 substrates by pulsed laser deposition. These studies indicate the possibility of using this material as p-type material in thin film form for transparent electronics. The room temperature conductivity of α-AgGaO2 was measured as 3.17 x 10-4 Scm-1and the optical band gap was estimated as 4.12 eV. A transparent p-n junction thin film diode on glass substrate was fabricated using p-type α-AgGaO2 and n-ZnO.AgCoO2 thin films with 50% transparency in the visible region were deposited on single crystalline Al2O3 and amorphous silica substrates by RF magnetron sputtering and p type conductivity of AgCoO2 was demonstrated by fabricating transparent p-n junction diode with AgCoO2 as p-side and ZnO: Al as n-side using sputtering. The junction thus obtained was found to be rectifying with a forward to reverse current of about 10 at an applied voltage of 3 V.The present study shows that silver delafossite thin films with p-type conductivity can be used for the fabrication of active devices for transparent electronics applications.

Coherent Stranski-Krastanov growth in 1+1 dimensions with anharmonic interactions: An equilibrium study

The formation of coherently strained three-dimensional (3D) islands on top of the wetting layer in the Stranski-Krastanov mode of growth is considered in a model in 1 + 1 dimensions accounting for the anharmonicity and nonconvexity of the real interatomic forces. It is shown that coherent 3D islands can be expected to form in compressed rather than expanded overlayers beyond a critical lattice misfit. In expanded overlayers the classical Stranski-Krastanov growth is expected to occur because the misfit dislocations can become energetically favored at smaller island sizes. The thermodynamic reason for coherent 3D islanding is incomplete wetting owing to the weaker adhesion of the edge atoms. Monolayer height islands with a critical size appear as necessary precursors of the 3D islands. This explains the experimentally observed narrow size distribution of the 3D islands. The 2D-3D transformation takes place by consecutive rearrangements of mono- to bilayer, bi- to trilayer islands, etc., after the corresponding critical sizes have been exceeded. The rearrangements are initiated by nucleation events, each one needing to overcome a lower energetic barrier than the one before. The model is in good qualitative agreement with available experimental observations.

Seeds of growth? Agricultural productivity and the transitional dynamics of the Ramsey model

A two-sector Ramsey-type model of growth is developed to investigate the relationship between agricultural productivity and economy-wide growth. The framework takes into account the peculiarities of agriculture both in production ( reliance on a fixed natural resource base) and in consumption (life-sustaining role and low income elasticity of food demand). The transitional dynamics of the model establish that when preferences respect Engel's law, the level and growth rate of agricultural productivity influence the speed of capital accumulation. A calibration exercise shows that a small difference in agricultural productivity has drastic implications for the rate and pattern of growth of the economy. Hence, low agricultural productivity can form a bottleneck limiting growth, because high food prices result in a low saving rate.

A comparative evaluation of functions for the analysis of growth in male broilers

Data from six studies with male broilers fed diets covering a wide range of energy and protein were used in the current two analyses. In the first analysis, five models, specifically re-parameterized for analysing energy balance data, were evaluated for their ability to determine metabolizable energy intake at maintenance and efficiency of utilization of metabolizable energy intake for producing gain. In addition to the straight line, two types of functional form were used. They were forms describing (i) diminishing returns behaviour (monomolecular and rectangular hyperbola) and (ii) sigmoidal behaviour with a fixed point of inflection (Gompertz and logistic). These models determined metabolizable energy requirement for maintenance to be in the range 437-573 kJ/kg of body weight/day depending on the model. The values determined for average net energy requirement for body weight gain varied from 7(.)9 to 11(.)2 kJ/g of body weight. These values show good agreement with previous studies. In the second analysis, three types of function were assessed as candidates for describing the relationship between body weight and cumulative metabolizable energy intake. The functions used were: (a) monomolecular (diminishing returns behaviour), (b) Gompertz (smooth sigmoidal behaviour with a fixed point of inflection) and (c) Lopez, France and Richards (diminishing returns and sigmoidal behaviour with a variable point of inflection). The results of this analysis demonstrated that equations capable of mimicking the law of diminishing returns describe accurately the relationship between body weight and cumulative metabolizable energy intake in broilers.

Effect of type and timing of oil supplements to sows during pregnancy on the growth performance and endocrine profile of low and normal birth weight offspring

Eighty-eight multiparous sows were used to evaluate whether type and timing of oil supplementation during gestation influences the incidence of low birth weight (LBW). Sows were allocated (eight per treatment) commercial sow pellets (3 kg/d; control diet) or an experimental diet consisting of control diet plus 10 % extra energy in the form of excess pellets, palm oil, olive oil (OO), sunflower oil (SO) or fish oil; experimental diets were fed during either the first half (G1) or second half (G2) of gestation. Growth performance and endocrine profile of LBW ( < 1·09 kg) and normal birth weight (NBW; 1·46–1·64 kg) offspring were compared. Maternal dietary supplementation altered the distribution curve for piglet birth weight. SOG1 sows had a greater proportion of LBW piglets (P < 0·05), whilst it was reduced in the OOG1 group (P < 0·05). Growth rate of LBW piglets was lower compared with their NBW siblings (P < 0·05) when dietary supplementation was offered in G2 but were similar for G1. At birth, LBW offspring of supplemented animals possessed more fat compared with the control group (P < 0·05); LBW offspring of control animals exhibited a more rapid decline in fat free mass/kg prior to weaning. Plasma metabolites and insulin concentrations were influenced by maternal diet and birth weight. In conclusion, maternal dietary supplementation altered the distribution of piglet birth weights and improved the energy status of LBW piglets. Supplementation with MUFA during G1 reduced the incidence of LBW, whereas PUFA had the reverse effect.

The reaction of flavanols with nitrous acid protects against N-nitrosamine formation and leads to the formation of nitroso derivatives which inhibit cancer cell growth

Studies have suggested that diets rich in polyphenols Such as flavonoids may lead to a reduced risk of gastrointestinal cancers. We demonstrate the ability of monomeric and dimeric flavanols to scavenge reactive nitrogen species derived from nitrous acid. Both epicatechin and dimer B2 (epicatechin dimer) inhibited nitrous acid-induced formation of 3-nitrotyrosine and the formation of the carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and dimeric epicatechin with nitrous acid led to the formation of mono- and di-nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the formation of nitrated products. Although, epicatechin was transferred across the jejunum of the small intestine yielding metabolites, its nitroso form was not absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of, and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3 activation and reductions in Akt phosphorylation, suggesting activation of apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also induced significant toxic effects in Caco-2 cells. The inhibitory effects on cellular proliferation were paralleled by early inhibition of ERK 1/2 phosphorylation and later reductions in cyclin D I levels, indicating modulation of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes in which dietary derived flavanols may exert beneficial effects in the gastrointestinal tract. (c) 2005 Elsevier Inc. All rights reserved.

John Lewis Partnership lessons in logical incrementalism and organic growth: a case study and interview with the Chairman, Mr Charlie Mayfield

Purpose – The purpose of this paper is to demonstrate how strategy is developed and implemented in an organisation with an unusual ownership model. Partnerships are not a prevalent form of ownership but as this case demonstrates they can be extremely effective. Furthermore this case demonstrates how logical incrementalism can be used to implement major strategic decisions. Design/methodology/approach – The paper draws on company documentary evidence and a semi-structured interview with Mr Charlie Mayfield, Chairman of John Lewis Partnership. A chairman has a helicopter view of business whose perspectives are rarely captured by strategy researchers. This case study offers an insight into strategic thinking of a chairman and chief executive of a successful company. Research limitations/implications – The case study and interview offer a unique insight into the rationale behind strategic decisions within a successful partnership that has grown organically in a highly competitive retail market without high gearing. Originality/value – This case study sheds light on strategic moves within partnership. Furthermore, very few case studies offer insight into the thinking of a chief executive who has successfully managed a business in a turbulent environment.

Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative RT-PCR confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher relative fitness compared to wild-type virus, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during positive-stranded RNA virus infection.

Arabinose and protocatechuate catabolism genes are important for growth of Rhizobium leguminosarum biovar viciae in the pea rhizosphere

Background and aims: To form nitrogen-fixing nodules on pea roots, Rhizobium leguminosarum biovar viciae must be competitive in the rhizosphere. Our aim was to identify genes important for rhizosphere fitness. Methods: Signature-tagged mutants were screened using microarrays to identify mutants reduced for growth in pea rhizospheres. Candidate mutants were assessed relative to controls for growth in minimal medium, growth in pea rhizospheres and for infection of peas in mixed inoculants. Mutated genes were identified by DNA sequencing and confirmed by transduction. Results: Of 5508 signature-tagged mutants, microarrays implicated 50 as having decreased rhizosphere fitness. Growth tests identified six mutants with rhizosphere-specific phenotypes. The mutation in one of the genes (araE) was in an arabinose catabolism operon and blocked growth on arabinose. The mutation in another gene (pcaM), encoding a predicted solute binding protein for protocatechuate and hydroxybenzoate uptake, decreased growth on protocatechuate. Both mutants were decreased for nodule infection competitiveness with mixed inoculants, but nodulated peas normally when inoculated alone. Other mutants with similar phenotypes had mutations predicted to affect secondary metabolism. Conclusions: Catabolism of arabinose and protocatechuate in the pea rhizosphere is important for competitiveness of R.l. viciae. Other genes predicted to be involved in secondary metabolism are also important.

Ant larval demand reduces aphid colony growth rates in an ant-aphid interaction

Ants often form mutualistic interactions with aphids, soliciting honeydew in return for protective services. Under certain circumstances, however, ants will prey upon aphids. In addition, in the presence of ants aphids may increase the quantity or quality of honeydew produced, which is costly. Through these mechanisms, ant attendance can reduce aphid colony growth rates. However, it is unknown whether demand from within the ant colony can affect the ant-aphid interaction. In a factorial experiment, we tested whether the presence of larvae in Lasius niger ant colonies affected the growth rate of Aphis fabae colonies. Other explanatory variables tested were the origin of ant colonies (two separate colonies were used) and previous diet (sugar only or sugar and protein). We found that the presence of larvae in the ant colony significantly reduced the growth rate of aphid colonies. Previous diet and colony origin did not affect aphid colony growth rates. Our results suggest that ant colonies balance the flow of two separate resources from aphid colonies- renewable sugars or a protein-rich meal, depending on demand from ant larvae within the nest. Aphid payoffs from the ant-aphid interaction may change on a seasonal basis, as the demand from larvae within the ant colony waxes and wanes.

Matrix metalloproteinases, TIMPs and growth factors regulating ameloblastoma behaviour

Aims: Ameloblastoma is an odontogenic neoplasm with local invasiveness and recurrence. We have previously suggested that growth factors and matrix metalloproteinases (MMPs) influence ameloblastoma invasiveness(1). The aim was to study expression of MMPs, tissue inhibitor of metalloproteinases (TIMPs) and growth factors in ameloblastoma. Methods and results: Thirteen cases of solid/multicystic ameloblastoma were examined. As a control, calcifying cystic odontogenic tumour (CCOT), a non-invasive odontogenic neoplasm with ameloblastomatous epithelium was also studied. Immunohistochemistry detected MMPs, TIMPs and growth factors in ameloblastoma and CCOT. The labelling index (LI) of MMP-9 and TIMP-2 was significantly higher in ameloblastoma compared with CCOT. The LI of epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and epidermal growth factor receptor (EGFR) was also increased in ameloblastoma. This neoplasm showed greater expression of MMPs, TIMPs and growth factors compared with CCOT. We then analysed these molecules in ameloblastoma cells and stroma. Ameloblastoma cells exhibited increased LI of MMP-1, -2 and EGFR. We found a positive correlation between EGF and TIMP-1, and between TGF-alpha and TIMP-2. It is known that signals generated by growth factors are transduced by the ERK pathway. Ameloblastoma stroma exhibited the phosphorylated (activated) form of ERK. Conclusions: These results suggest an interplay involving growth factors MMPs and TIMPs that may contribute to ameloblastoma behaviour. Signals generated by this molecular network would be transduced by ERK 1/2 pathway.