999 resultados para F-actin networks


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Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

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It has been estimated that infection with the enteric protozoan parasite Entamoeba histolytica kills more than 50,000 people a year. Central to the pathogenesis of this organism is its ability to directly lyse host cells and cause tissue destruction. Amebic lesions show evidence of cell lysis, tissue necrosis, and damage to the extracellular matrix. The specific molecular mechanisms by which these events are initiated, transmitted, and effected are just beginning to be uncovered. In this article we review what is known about host cell adherence and contact-dependent cytolysis. We cover the involvement of the actin cytoskeleton and small GTP-binding proteins of the p21rho-family in the process of cell killing and phagocytosis, and also look at how amebic interactions with molecules of the extracellular matrix contribute to its cytopathic effects.

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As a result of recent investigations, the cytoskeleton can be viewed as a cytoplasmic system of interconnected filaments with three major integrative levels: self-assembling macromolecules, filamentous polymers, e.g., microtubules, intermediate filaments and actin filaments, and supramolecular structures formed by bundles of these filaments or networks resulting from cross-bridges between these major cytoskeletal polymers. The organization of this biological structure appears to be sensitive to fine spatially and temporally dependent regulatory signals. In differentiating neurons, regulation of cytoskeleton organization is particularly relevant, and the microtubule-associated protein (MAP) tau appears to play roles in the extension of large neuritic processes and axons as well as in the stabilization of microtubular polymers along these processes. Within this context, tau is directly involved in defining neuronal polarity as well as in the generation of neuronal growth cones. There is increasing evidence that elements of the extracellular matrix contribute to the control of cytoskeleton organization in differentiating neurons, and that these regulations could be mediated by changes in MAP activity. In this brief review, we discuss the possible roles of tau in mediating the effects of extracellular matrix components on the internal cytoskeletal arrays and its organization in growing neurons.

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Increasing renewable energy utilization is a challenge that is tried to be solved in different ways. One of the most promising options for renewable energy is different biomasses, and the bioenergy field offers numerous emerging business opportunities. The actors in the field have rarely all the needed know-how and resources for exploiting these opportunities, and thus it is reasonable to seize them in cooperation. Networking is not an easy task to carry out, however, and in addition to its advantages for the firms engaged, it sets numerous challenges as well. The development of a network is a result of several steps firms need to take. In order to gain optimal advantage of their networks, firms need to weigh out with whom, why and how they should cooperate. In addition, everything does not depend on the firms themselves, as several factors in the external environment set their own enablers and barriers for cooperation. The formation of a network around a business opportunity is thus a multiphase process. The objective of this thesis is to depict this process via a step-by-step analysis and thus increase understanding on the whole development path from an entrepreneurial opportunity to a successful business network. The empirical evidence has been gathered by discussing the opportunities of animal manure refinement to biogas and forest biomass utilization for heating in Finland. The thesis comprises two parts. The first part provides an overview of the study, and the second part includes five research publications. The results reveal that it is essential to identify and analyze all the steps in the development process of a network, and several frameworks are used in the thesis to analyze these steps. The frameworks combine the views of theory and practical experiences of empirical study, and thus give new multifaceted views for the discussion on SME networking. The results indicate that the ground for cooperation should be investigated adequately by taking account of the preconditions in all the three contexts in which the actors operate: the social context, the region and the institutional environment. In case the project advances to exploitation, the assets and objectives of the actors should be paired off, which sets a need for relationships and sub-networks differing in breadth and depth. Different relationships and networks require different kinds of maintenance and management. Moreover, the actors should have the capability to change the formality or strategy of the relationships if needed. The drivers for these changes come along with the changing environment, which causes changes in the objectives of the actors and this way in the whole network. Bioenergy as the empirical field of the study represents well an industrial field with many emerging opportunities, a motley group of actors, and sensitivity for fast changes.

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We report here for the first time the structure and function of a promoter from a cestode. The ability of DNA fragments respectively encompassing the 935-bp and 524-bp regions upstream from the ATG codon from the EgactI and EgactII actin genes of Echinococcus granulosus to promote transcription was studied in the NIH3T3 mouse cell line. The results of transfection assays showed that both regions have strong promoter activity in these cells. The fragments were tested in both orientations and the 524-bp fragment of EgactII presented a bidirectional promoter activity. Deletion analysis of EgactI and EgactII promoters indicated the presence of regulatory regions containing putative silencer elements. These results indicate that both EgactI and EgactII promoters are functional and that the preliminary functional evaluation of E. granulosus and possibly of other cestode promoters can be performed in heterologous cell lines.

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Cross-sector collaboration and partnerships have become an emerging and desired strategy in addressing huge social and environmental challenges. Despite its popularity, cross-sector collaboration management has proven to be very challenging. Even though cross-sector collaboration and partnership management have been widely studied and discussed in recent years, their effectiveness as well as their ability to create value with respect to the problems they address has remained very challenging. There is little or no evidence of their ability to create value. Regarding all these challenges, this study aims to explore how to manage cross-sector collaborations and partnerships to be able to improve their effectiveness and to create more value for all partners involved in collaboration as well as for customers. The thesis is divided into two parts. The first part comprises an overview of relevant literature (including strategic management, value networks and value creation theories), followed by presenting the results of the whole thesis and the contribution made by the study. The second part consists of six research publications, including both quantitative and qualitative studies. The chosen research strategy is triangulation, as the study includes four types of triangulation: (1) theoretical triangulation, (2) methodological triangulation, (3) data triangulation and (4) researcher triangulation. Two publications represent conceptual development, which are based on secondary data research. One publication is a quantitative study, carried out through a survey. The other three publications represent qualitative studies, based on case studies, where data was collected through interviews and workshops, with participation of managers from all three sectors: public, private and the third (nonprofit). The study consolidates the field of “strategic management of value networks,” which is proposed to be applied in the context of cross-sector collaboration and partnerships, with the aim of increasing their effectiveness and the process of value creation. Furthermore, the study proposes a first definition for the strategic management of value networks. The study also proposes and develops two strategy tools that are recommended to be used for the strategic management of value networks in cross-sector collaboration and partnerships. Taking a step forward, the study implements the strategy tools in practice, aiming to show and to demonstrate how new value can be created by using the developed strategy tools for the strategic management of value networks. This study makes four main contributions. (1) First, it brings a theoretical contribution by providing new insights and consolidating the field of strategic management of value networks, also proposing a first definition for the strategic management of value networks. (2) Second, the study makes a methodical contribution by proposing and developing two strategy tools for value networks of cross-sector collaboration: (a) value network mapping, a method that allows us to assess the current and the potential value network and (b) the Value Network Scorecard, a method of performance measurement and performance prediction in cross-sector collaboration. (3) Third, the study has managerial implications, offering new solutions and empirical evidence on how to increase the effectiveness of cross-sector collaboration and also allow managers to understand how new value can be created in cross-sector partnerships and how to get the full potential of collaboration. (4) And fourth, the study also has practical implications, allowing managers to understand how to use in practice the strategy tools developed in this study, providing discussions on the limitations regarding the proposed tools as well as general limitations involved in the study.

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The aim of the present study was to investigate the expression of alpha-smooth muscle actin (alpha-SM-actin) and proliferating cell nuclear antigen (PCNA) in renal cortex from patients with focal segmental glomerulosclerosis (FSGS) and their correlations with parameters of renal disease progression. We analyzed renal biopsies from 41 patients with idiopathic FSGS and from 14 control individuals. The alpha-SM-actin immunoreaction was evaluated using a score that reflected the changes in the extent and intensity of staining in the glomerular or cortical area. The PCNA reaction was quantified by counting the labeled cells of the glomeruli or renal cortex. The results, reported as median ± percentile (25th; 75th), showed that the alpha-SM-actin scores in the glomeruli and tubulointerstitium from the renal cortex were 2.0 (2.0; 4.0) and 3.0 (3.0; 4.0), respectively, in patients with FSGS, and 0.5 (0.0; 1.0) and 0.0 (0.0; 0.5) in the controls. The number of PCNA-positive cells per glomerulus and graded field of tubulointerstitium from the renal cortex was 0.2 (0.0; 0.4) and 1.1 (0.3; 2.2), respectively, for patients with FSGS, and 0.0 (0.0; 0.5) and 0.0 (0.0; 0.0) for controls. The present data showed an increase of alpha-SM-actin and PCNA expression in glomeruli and renal cortex from FSGS patients. The extent of immunoreaction for alpha-SM-actin in the tubulointerstitial area was correlated with the intensity of proteinuria. However, there was no correlation between the kidney expression of these proteins and the reciprocal of plasma creatinine level or renal fibrosis. These findings suggest that the immunohistochemical alterations may be reversible.

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The Thesis is dedicated to development of an operative tool to support decision making of battery energy storages implementation in distribution networks. The basics of various battery technologies, their perspectives and challenges are represented in the Thesis. Mathematical equations that describe economic effect from battery energy storage installation are offered. The main factors that influence profitability of battery settings have been explored and mathematically defined. Mathematical model and principal trends of battery storage profitability under an impact of the major factors are determined. The meaning of annual net value was introduced to show the difference between savings and required costs. The model gives a clear vision for dependencies between annual net value and main factors. Proposals for optimal network and battery characteristics are suggested.

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In the present study, we modeled a reaching task as a two-link mechanism. The upper arm and forearm motion trajectories during vertical arm movements were estimated from the measured angular accelerations with dual-axis accelerometers. A data set of reaching synergies from able-bodied individuals was used to train a radial basis function artificial neural network with upper arm/forearm tangential angular accelerations. The trained radial basis function artificial neural network for the specific movements predicted forearm motion from new upper arm trajectories with high correlation (mean, 0.9149-0.941). For all other movements, prediction was low (range, 0.0316-0.8302). Results suggest that the proposed algorithm is successful in generalization over similar motions and subjects. Such networks may be used as a high-level controller that could predict forearm kinematics from voluntary movements of the upper arm. This methodology is suitable for restoring the upper limb functions of individuals with motor disabilities of the forearm, but not of the upper arm. The developed control paradigm is applicable to upper-limb orthotic systems employing functional electrical stimulation. The proposed approach is of great significance particularly for humans with spinal cord injuries in a free-living environment. The implication of a measurement system with dual-axis accelerometers, developed for this study, is further seen in the evaluation of movement during the course of rehabilitation. For this purpose, training-related changes in synergies apparent from movement kinematics during rehabilitation would characterize the extent and the course of recovery. As such, a simple system using this methodology is of particular importance for stroke patients. The results underlie the important issue of upper-limb coordination.

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The actions of thyroid hormone (TH) on pancreatic beta cells have not been thoroughly explored, with current knowledge being limited to the modulation of insulin secretion in response to glucose, and beta cell viability by regulation of pro-mitotic and pro-apoptotic factors. Therefore, the effects of TH on proinsulin gene expression are not known. This led us to measure: a) proinsulin mRNA expression, b) proinsulin transcripts and eEF1A protein binding to the actin cytoskeleton, c) actin cytoskeleton arrangement, and d) proinsulin mRNA poly(A) tail length modulation in INS-1E cells cultured in different media containing: i) normal fetal bovine serum - FBS (control); ii) normal FBS plus 1 µM or 10 nM T3, for 12 h, and iii) FBS depleted of TH for 24 h (Tx). A decrease in proinsulin mRNA content and attachment to the cytoskeleton were observed in hypothyroid (Tx) beta cells. The amount of eEF1A protein anchored to the cytoskeleton was also reduced in hypothyroidism, and it is worth mentioning that eEF1A is essential to attach transcripts to the cytoskeleton, which might modulate their stability and rate of translation. Proinsulin poly(A) tail length and cytoskeleton arrangement remained unchanged in hypothyroidism. T3 treatment of control cells for 12 h did not induce any changes in the parameters studied. The data indicate that TH is important for proinsulin mRNA expression and translation, since its total amount and attachment to the cytoskeleton are decreased in hypothyroid beta cells, providing evidence that effects of TH on carbohydrate metabolism also include the control of proinsulin gene expression.

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Liver cirrhosis is one of the most common diseases of Chinese patients. Herein, we report the high expression of a newly identified histone 3 lysine 4 demethylase, retinoblastoma binding protein 2 (RBP2), and its role in liver cirrhosis in humans. The siRNA knockdown of RBP2 expression in hepatic stellate cells (HSCs) reduced levels of α-smooth muscle actin (α-SMA) and vimentin and decreased the proliferation of HSCs; and overexpression of RBP2 increased α-SMA and vimentin levels. Treatment with transforming growth factor β (TGF-β) upregulated the expression of RBP2, α-SMA, and vimentin, and the siRNA knockdown of RBP2 expression attenuated TGF-β-mediated upregulation of α-SMA and vimentin expression and HSC proliferation. Furthermore, RBP2 was highly expressed in cirrhotic rat livers. Therefore, RBP2 may participate in the pathogenesis of liver cirrhosis by regulating the expression of α-SMA and vimentin. RBP2 may be a useful marker for the diagnosis and treatment of liver cirrhosis.

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Recent Storms in Nordic countries were a reason of long power outages in huge territories. After these disasters distribution networks' operators faced with a problem how to provide adequate quality of supply in such situation. The decision of utilization cable lines rather than overhead lines were made, which brings new features to distribution networks. The main idea of this work is a complex analysis of medium voltage distribution networks with long cable lines. High value of cable’s specific capacitance and length of lines determine such problems as: high values of earth fault currents, excessive amount of reactive power flow from distribution to transmission network, possibility of a high voltage level at the receiving end of cable feeders. However the core tasks was to estimate functional ability of the earth fault protection and the possibility to utilize simplified formulas for operating setting calculations in this network. In order to provide justify solution or evaluation of mentioned above problems corresponding calculations were made and in order to analyze behavior of relay protection principles PSCAD model of the examined network have been created. Evaluation of the voltage rise in the end of a cable line have educed absence of a dangerous increase in a voltage level, while excessive value of reactive power can be a reason of final penalty according to the Finish regulations. It was proved and calculated that for this networks compensation of earth fault currents should be implemented. In PSCAD models of the electrical grid with isolated neutral, central compensation and hybrid compensation were created. For the network with hybrid compensation methodology which allows to select number and rated power of distributed arc suppression coils have been offered. Based on the obtained results from experiments it was determined that in order to guarantee selective and reliable operation of the relay protection should be utilized hybrid compensation with connection of high-ohmic resistor. Directional and admittance based relay protection were tested under these conditions and advantageous of the novel protection were revealed. However, for electrical grids with extensive cabling necessity of a complex approach to the relay protection were explained and illustrated. Thus, in order to organize reliable earth fault protection is recommended to utilize both intermittent and conventional relay protection with operational settings calculated by the use of simplified formulas.