Role and Function of c-Jun Protein Complex in Cancer Cell Behavior

Transcription factors play a crucial role in the regulation of cell behavior by modulating gene expression profiles. Previous studies have described a dual role for the AP-1 family transcription factor c-Jun in the regulation of cellular fate. In various cell types weak and transient activations of c-Jun N-terminal kinase (JNK) and c-Jun appear to contribute to proliferation and survival, whereas strong and prolonged activation of JNK and c-Jun result in apoptosis. These opposite roles played by c-Jun are cell type specific and the molecular mechanisms defining these antonymous c-Jun-mediated responses remain incompletely understood. c-Jun activity in transformed cells is regulated by signalling cascades downstream of oncoproteins such as Ras and Raf. In addition, the pro-proliferative role and the survival promoting function for c-Jun has been described in various cancer models. Furthermore, c-Jun was described to be overexpressed in different cancer types. However, the molecular mechanisms by which c-Jun exerts these oncogenic functions are not all clearly established. Therefore it is of primary interest to further identify molecular mechanisms and functions for c-Jun in cancer. Regulation of gene expression is tightly dependent on accurate protein-protein interactions. Therefore, co-factors for c-Jun may define the functions for c-Jun in cancer. Identification of protein-protein interactions promoting cancer may provide novel possibilities for cancer treatment. In this study, we show that DNA topoisomerase I (TopoI) is a transcriptional co-factor for c-Jun. Moreover, c-Jun and TopoI together promote expression of epidermal growth factor receptor (EGFR) in cancer cells. We also show that the clinically used TopoI inhibitor topotecan reduces EGFR expression. Importantly, the effect of TopoI on EGFR transcription was shown to depend on c-Jun as Jun-/- cells or cells treated with JNK inhibitor SP600125 are resistant to topotecan treatment both in regulation of EGFR expression and cell proliferation. Moreover, c-Jun regulates the nucleolar localization and the function of the ribonucleic acid (RNA) helicase DDX21, a previously identified member of c-Jun protein complex. In addition, c-Jun stimulates rRNA processing by supporting DDX21 rRNA binding. Finally, this study characterizes a DDX21 dependent expression of cyclin dependent kinase (Cdk) 6, a correlation of DDX21 expression with prostate cancer progression and a substrate binding dependency of DDX21 nucleolar localization in prostate cancer cells. Taken together, the results of this study validate the c-Jun-TopoI interaction and precise the c-Jun-DDX21 interaction. Moreover, these results show the importance for protein-protein interaction in the regulation of their cellular functions in cancer cell behavior. Finally, the results presented here disclose new exciting therapeutic opportunities for cancer treatment.

Improving the effectiveness of supply chain development work – an expert role perspective

This study focuses to the intersection of three sets of activities in a company: expert work, development work and supply chain management, SCM. Experts and expert work represent a set of individuals whose efficiency and impact this study is intended to improve, while development work defines the set of organizational activities to focus on. SCM as an expertise area acts as the platform on which this study is built. The study has two aims. Firstly, it aims to derive a model helping an SCM expert to increase the effectiveness of expert work in development tasks by understanding the encountered organizational situations and processes better, reflecting his/her past and future actions to organizational processes and selecting and adjusting the processes and contents of his/her work accordingly. Secondly, it aims to develop applicable approaches and methods to understand, evaluate and manage the organizational processes and situations in development work. The integrative model on approaches and methods to improve the effectiveness of development processes is split to two aggregate dimensions: technical performance of the developed solution and consumption of resources of the development process. Six potential approaches and methods aiming at helping in the management of organizational dimensions are presented in enclosed publications. The approaches focus on three subtasks of development work: decision making, implementation and change, and knowledge accumulation. The approaches and methods have been tested in case studies representing typical development processes in the area of supply chain management. As a result, four suggestions are presented. Firstly, SCM experts are advised to consider the SCM development work to be consisting of development processes. Secondly, inside these processes they should identify and evaluate the risk of difficult decision-making related to organizational factors. Thirdly, they are prompted for an active role in implementation and change, supporting the implementation through whole process. Finally, the development should be seen in a holistic view, taking into account the stage of knowledge and organizational issues related to it, and adopt a knowledge development strategy.

The Social Politics of Fatherhood in Spain and France: a Comparative Analysis of Parental Leave and Shared Residence

The Social Politics of Fatherhood in Spain and France: A Comparative Analysis of Parental Leave and Shared Residence The article provides a comparative analysis of policy developments on leaves for fathers and joint custody in Spain and France in the last decade. These two types of measures have been selected because they are both widely recognised as main instruments to promote new fathering styles and consequently more gender equality in the European Union. While the rhetoric of choice has been developed in both countries in relation to maternal employment and childcare, with better results in France than in Spain, it remains to be seen to what extent choice will also be extended to fathers. Keywords: Fatherhood. Family. Comparative social policy. Parental leave. Joint custody.

Role of PheE15 gate in ligand entry and nitric oxide detoxification function of Mycobacterium tuberculosis truncated hemoglobin N

The truncated hemoglobin N, HbN, of Mycobacterium tuberculosis is endowed with a potent nitric oxide dioxygenase (NOD) activity that allows it to relieve nitrosative stress and enhance in vivo survival of its host. Despite its small size, the protein matrix of HbN hosts a two-branched tunnel, consisting of orthogonal short and long channels, that connects the heme active site to the protein surface. A novel dual-path mechanism has been suggested to drive migration of O(2) and NO to the distal heme cavity. While oxygen migrates mainly by the short path, a ligand-induced conformational change regulates opening of the long tunnel branch for NO, via a phenylalanine (PheE15) residue that acts as a gate. Site-directed mutagenesis and molecular simulations have been used to examine the gating role played by PheE15 in modulating the NOD function of HbN. Mutants carrying replacement of PheE15 with alanine, isoleucine, tyrosine and tryptophan have similar O(2)/CO association kinetics, but display significant reduction in their NOD function. Molecular simulations substantiated that mutation at the PheE15 gate confers significant changes in the long tunnel, and therefore may affect the migration of ligands. These results support the pivotal role of PheE15 gate in modulating the diffusion of NO via the long tunnel branch in the oxygenated protein, and hence the NOD function of HbN.

The state of research and development in Australia: implications for future development

The scale of research and development (R&D), and other technological activities, and the way in which the available resources are managed and organized at the enterprise and national level contribute to the rate of technological change in a country. A well organized national innovation system can be a powerful engine of progress, whereas a lack of interaction between institutions results in the slowing down of technological change, thereby diminishing its contribution to economic growth and welfare. The research object of this thesis is Australia’s national innovation system and the state of R&D in Australia. In order to establish an overall picture of the situation and to be able to make recommendations for future development, the general level of R&D activity and the main performers and funders of R&D within the system are analyzed. The framework policies supporting R&D and prevalent dynamics between different actors and sectors are of specific interest of the research. The findings reveal that the Australian culture is not a culture of research and innovation and that the main challenge is building a coherent system with strong domestic and international linkages.

The stability of right- and left-handed alpha-helices as a function of monomer chirality

Poly-L-alanine forms stable right-handed alpha-helices, whereas Poly-D-alanine is stable as left-handed alpha helices.

Nitrous oxide emissions from an intermittent aeration activated sludge system of an urban wastewater treatment plant

This study investigated the emission of N2O during the sequential aerated (60-min) and non-aerated (30-min) stages of an intermittent aeration cycle in an activated sludge wastewater treatment plant (WWTP). N2O emission occurred during both stages; however, emission was much higher during aeration. Air stripping is the major factor controlling transfer of N2O from the sewage to the atmosphere. The N2O emissions exclusively from the aeration tank represented 0.10% of the influent total nitrogen load and the per capita emission factor was almost 3 times higher than that suggested by the IPCC for inventories of N2O emission from WWTPs.

Intraspecific variability of Holostylis reniformis: concentration of lignans, as determined by maceration and supercritical fluid extraction (SFE-CO2), as a function of plant provenance and plant parts

Maceration and supercritical fluid extraction were used to prepare extracts from parts of plants (Holostylis reniformis) collected in two different regions of Brazil. ¹H NMR, HPLC-DAD-ESI/MS, HPLC-DAD, GC-MS, and chemometric techniques were used to analyse lignans in the extracts and showed that yields of SFE-CO2 were less than or equal to those of hexane maceration extracts. These analyses, in conjunction with the concentrations of aliphatic hydrocarbons, fatty acids and their methyl and ethyl derivatives in the extracts, also allowed the chemical composition of parts and provenance of the plant to be differentiated.

The role of petals in development of grey mould in strawberries

Studies were conducted in annual crops of strawberry (Fragaria x ananassa) (cv. Elsanta to assess the relative importance of petals as an inoculum source of grey mould, caused by Botrytis cinerea and to identify during which period of flower and fruit development the presence of petals has a significant effect on development of grey mould on fruits. In 1998, the incidence of B. cinerea on flower parts was assessed, and the symptoms of grey mould on fruits were characterised with regards to their starting point. The incidence of B. cinerea on petals was 65-85% of those flowers that harboured B. cinerea. The starting point of symptoms was located underneath the sepals in 65-85% of fruits with grey mould, and petals were present at this site in about 50% of the cases. In 1999, four field experiments were conducted to assess the effect of petal removal at different stages of flower and fruit development on incidence of grey mould. The incidence of grey mould on fruits with petals retained till harvest was circa 55% more than on fruits where petals were removed or had dropped naturally by the end of flowering, regardless of planting date or inoculum level of B. cinerea. The incidence of grey mould was hardly different between treatments where petals were removed at young flower stage, old flower stage, or green fruit stage. It is concluded that petals are an effective and stable source of inoculum for fruit infection by B. cinerea. Considering the high probability that retention of petals during fruit expansion and ripening results in fruit infection, the elimination of petals as an inoculum source appears worthwhile even when the incidence of petal retention on fruits is relatively low.

Electrometric studies on uranyl molybdates as a function of pH

The formation and composition of uranyl molybdates obtained by the interaction of uranyl acetate and sodium molybdate at specific pH levels 7.6, 5.5 and 4.1 have been studied by employing electrometric techniques involving pH and conductometric titrations. The results provide cogent evidence for the formation of three uranyl molybdates having the molecular formulae UO2O.MoO3, 3UO2O.7MoO3 and 2UO2O.8MoO3 in the vicinity of pH 5.7, 4.6 and 3.8, respectively. Analytical investigations of the compounds have also been carried out which substantiate the results of electrometric study.

Electrometric investigations on the formation of cerium(III) tungstates as a function of PH

The course of reaction between cerium(III) nitrate and different sodium tungstates (Na2WO4, Na10W12O41 and Na6W12O39) has been followed by means of pH and conductometric titrations between the reactants at different pH levels, in aqueous and alcoholic media, with each of the reagents alternatively used as titrant. The electrometric experiments provide definite evidence of the formation of normal-Ce2O3.3WO3 and para- 5Ce2O3.36WO3 tungstates of cerium in the vicinity of pH 6.2 and 5.3. The formation of normal tungstate is almost quantitative and the pH titrations offer a simple means for determination of cerium(III) or tungstate solutions at suitable concentrations and pH range.

Electrometric studies on formation of cerium vanadates as a function of pH

The precise nature of the reaction between nitric acid and sodium ortho-vanadate solutions has been studied by means of electrometric techniques involving potentiometric and conductometric titrations. The well defined inflections and breaks in the titration curves confirm the existence of the anions, pyro-V2O7(4-), meta-VO3- and poly-H2V10O28(4-) corresponding to the ratios of VO4(3-):H+ as 1:1, 1:2 and 1:2.6 in the neighborhood of pH 10.5, 7.4 and 3.6, respectively. The interaction of cerium(III) nitrate with sodium vanadate solutions, at specific pH levels 12.4, 10.5, 7.4 and 3.6 was also studied by potentiometric and conductometric titrations between the reactants. The end-points obtained from the sharp inflections in the titration curves provide definite evidence for the formation and precipitation of cerium ortho-Ce2O3.V2O5, pyro-2Ce2O3.3V2O5 and meta-Ce2O3.3V2O5 vanadates in the neighborhood of pH 7.4, 6.2 and 4.8, respectively. Analytical investigations on the precipitates formed confirm the results of the electrometric study.

Seeder-fertilizer machine: energetic demand as a function of vegetal covering handling and manure deposition shank depth in no-tillage system

The purpose of this work was evaluating the energetic demand of a seeder-fertilizer machine as a function of the type and handling of vegetal covering culture and of the fertilizer deposition shank depth. A Valtra BM100 tractor was used implemented to pull a high precision seeder-fertilizer machine with four ranks of seeding, spaced 0.9 m for maize culture. Experiment was conducted with design in randomized blocks in factorial plots, in the Laboratory of Machines and Agricultural Mechanization experimental area (LAMMA) of UNESP-Jaboticabal, using two covering cultures (black-mucuna and crotalaria), three handlings of this covering, two mechanical (straw crusher and roller knife) and one chemical (pulverization of herbicide), performed 120 days after seeding of covering cultures and three depths of fertilizer deposition shank, completing 18 treatments, with four repetitions, totaling 72 observations. Parameters of displacement speed, gliding, force on traction bar, peak force, power on pulling bar and fuel consumption were evaluated. It was possible to conclude that force on traction bar was less for depths of 0.11 and 0.14 m of fertilizer plough shank, the same occurring for peak force, power on traction bar and volumetric consumption. The specific consumption was lower at a depth of 0.17 m of fertilizer plough shank. Covering cultures and their handlings did not interfere in the performance of machines under inquiry.

Fuel consumption of a tractor in function of wear, of ballasting and tire inflation pressure

When using appropriate inflation pressures and load capacity (ballast), it may obtain a higher yield and prolongation of the life of the tire, besides it may minimize the problems of loss of traction, increased slippage and fuel consumption. This study aimed to evaluate the fuel consumption of a tractor operating with new and worn tires in three conditions of ballasting and three inflation pressures, when driving on compacted soil with vegetation cover. The experiment was conducted at the experimental unit from the Department of Animal Science, Federal University of Lavras, state of Minas Gerais, Brazil, in an agricultural soil compacted by cattle trampling and with vegetation cover. It was used a tractor 4x2 with front wheel assist, of a 65.62 kW engine power. The tires were of R1 type, diagonal (front: 12.4 to 24; and rear: 18.4 to 30), the average height of the clutches of the new tires were 0.3 and 0.35 m for front and rear tires, respectively, and for the worn tires were 0.018 and 0.0045 m, for the front and the rear tires, respectively. The results showed advantages for the tractor equipped with new tires.