Regulation of vacuolar H+-ATPase activity by the Cdc42 effector Ste20 in Saccharomyces cerevisiae

In the budding yeast Saccharomyces cerevisiae, the Cdc42 effector Ste20 plays a crucial role in the regulation of filamentous growth, a response to nutrient limitation. Using the split-ubiquitin technique, we found that Ste20 forms a complex with Vma13, an important regulatory subunit of vacuolar H(+)-ATPase (V-ATPase). This protein-protein interaction was confirmed by a pulldown assay and coimmunoprecipitation. We also demonstrate that Ste20 associates with vacuolar membranes and that Ste20 stimulates V-ATPase activity in isolated vacuolar membranes. This activation requires Ste20 kinase activity and does not depend on increased assembly of the V1 and V0 sectors of the V-ATPase, which is a major regulatory mechanism. Furthermore, loss of V-ATPase activity leads to a strong increase in invasive growth, possibly because these cells fail to store and mobilize nutrients efficiently in the vacuole in the absence of the vacuolar proton gradient. In contrast to the wild type, which grows in rather small, isolated colonies on solid medium during filamentation, hyperinvasive vma mutants form much bigger aggregates in which a large number of cells are tightly clustered together. Genetic data suggest that Ste20 and the protein kinase A catalytic subunit Tpk2 are both activated in the vma13Δ strain. We propose that during filamentous growth, Ste20 stimulates V-ATPase activity. This would sustain nutrient mobilization from vacuolar stores, which is beneficial for filamentous growth.The project was supported by Deutsche Forschungsgemeinschaft grant HO 2098/3 to T.H. and NIH grant R01 GM50322 to P.M.K

Parallel detrended fluctuation analysis for fast event detection on massive PMU data

("(c) 2015 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.")Phasor measurement units (PMUs) are being rapidly deployed in power grids due to their high sampling rates and synchronized measurements. The devices high data reporting rates present major computational challenges in the requirement to process potentially massive volumes of data, in addition to new issues surrounding data storage. Fast algorithms capable of processing massive volumes of data are now required in the field of power systems. This paper presents a novel parallel detrended fluctuation analysis (PDFA) approach for fast event detection on massive volumes of PMU data, taking advantage of a cluster computing platform. The PDFA algorithm is evaluated using data from installed PMUs on the transmission system of Great Britain from the aspects of speedup, scalability, and accuracy. The speedup of the PDFA in computation is initially analyzed through Amdahl's Law. A revision to the law is then proposed, suggesting enhancements to its capability to analyze the performance gain in computation when parallelizing data intensive applications in a cluster computing environment

Parallel detrended fluctuation analysis for fast event detection on massive PMU data

("(c) 2015 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.")Phasor measurement units (PMUs) are being rapidly deployed in power grids due to their high sampling rates and synchronized measurements. The devices high data reporting rates present major computational challenges in the requirement to process potentially massive volumes of data, in addition to new issues surrounding data storage. Fast algorithms capable of processing massive volumes of data are now required in the field of power systems. This paper presents a novel parallel detrended fluctuation analysis (PDFA) approach for fast event detection on massive volumes of PMU data, taking advantage of a cluster computing platform. The PDFA algorithm is evaluated using data from installed PMUs on the transmission system of Great Britain from the aspects of speedup, scalability, and accuracy. The speedup of the PDFA in computation is initially analyzed through Amdahl's Law. A revision to the law is then proposed, suggesting enhancements to its capability to analyze the performance gain in computation when parallelizing data intensive applications in a cluster computing environment

The New Media and Arab Spring: A Critical Analysis

This study critically examined the new media and the Arab awakening phenomenon with the aim of finding out whether the same pattern of Arab spring could be transferred to other parts of Africa, especially West African countries. The study was therefore built on two theoretical foundations known as emancipatory media theory and the new media theory. Using survey research design, 98 respondents were sampled with questionnaire serving as instruments of data collection. The data generated were analysed and presented in simple frequency distribution tables. The study revealed that though the new media can do more in mobilising the people for action as exemplified in its contribution to the success recorded in the Arab spring, it would be difficult for that kind of new media aided uprising to really replicate itself in West Africa considering the political environment. It was, therefore, recommended that government of nations should make itself present in the new media so as to create an interactive avenue for the people to discuss their plight.Key words: new media, Arab spring and social movemen

Legitimacy Maintenance After a Corporate Social Irresponsibility Scandal: Lessons From The Parmalat Case

From the organizations’ perspective, maintaining legitimacy in such contexts has been considered relatively unproblematic (Patriotta, 2011; Scherer et al., 2013) as it entails following adaptive strategies and conforming substantially (or even merely symbolically) to the dominant institutional logics (Suchman, 1995; Elsbach, 1994; Scherer et al., 2013). 3 Nonetheless, whilst the implementation of a adaptive strategy to maintain the corporation with its main audiences is a necessary phase, it cannot be considered sufficient to assure the maintenance of audience support. Audiences evaluate competitive advantage and other sources of reassurance that supporting the company is worthwhile from a rational perspective. This restoration process may be complemented by the corporations’ power over resource dependent audiences. Independent audience decisions are based on the competitive advantage of firm in each business. When their are untouched, the adaptive strategy leads to audience support and successful business rehabilitation processes with all audiences, even with those that were initially harmed. However, if competitive advantage is feeble independent audiences will not sustain the weak business (or corporation) even if adaptive strategies have been implemented. The presence of an unharmed competitive strategy is crucial to the selection of which parts of an organization (or the organization as a whole) can be reintegrated with all the main audiences of the company after a CSI scandal, including the “harmed” audience. The richness of the empirical setting allows us to highlight that a significant difference between firm characteristics that plays a crucial role in determining the reactions of the main constituent audiences and, consequently, the possibility for maintain the legitimacy. The post-crisis turnaround processes to succeed is the possession of sound source(s) of competitive advantage in one (or more) of the business(es) in which the firms operates

From “Strategic Fit” to Synergy Evaluation in M&A Deals

The aim of this paper is to grasp the processes underlying the genesis and assessment of synergies in M&A deals. We proceed to an in-depth scrutiny of the foundations of synergies using Porter’s model of the value chain. A discernment of the nature of synergies and the mode of their emergence is helpful to clarify to what extent and under which boundary conditions it is appropriate to apply the DCF or the real option techniques for evaluating each type of synergy. Combining both financial tools, the methodology suggested for evaluating the synergies is able to: evaluate projects of M&As, orient the selection of target firms and the definition of the premium of acquisition, and drive the integration processes

Corporate social irresponsibility and stakeholders' support: evidence from a case study

Stakeholders' decisions regarding whether to continue to support a firm after it has been perceived as culpable for socially irresponsible behaviour is "coin of the realm" in selecting which firms (or which parts of a firm) will be able to survive a corporate social irresponsibility (CSI) scandal. Our empirical setting is an embedded polar case of audience support, the Parmalat case, following a severe CSI scandal. The scandal represented a "trigger event" that ignited an active reevaluation of the firm on behalf of its stakeholders. We show that, while the firm's cognitive legitimacy was not harmed by the CSI scandal, two dimensions of legitimacy played a key role in stakeholder evaluations: moral and pragmatic legitimacy. The capacity to manage the interplay between these two dimensions emerged as a key factor underlying stakeholders' support. Finally, we argue that if pragmatic legitimacy is feeble it is unlikely that the firm is able to maintain stakeholders' support. Our study suggests that possessing a sound source of competitive advantage in one (or more) of the businesses in which the firm operates is decisive to maintain the support of independent stakeholders following CSI scandal

Neural crest migration is driven by a few trailblazer cells with a unique molecular signature narrowly confined to the invasive front

Neural crest (NC) cell migration is crucial to the formation of peripheral tissues during vertebrate development. However, how NC cells respond to different microenvironments to maintain persistence of direction and cohesion in multicellular streams remains unclear. To address this, we profiled eight subregions of a typical cranial NC cell migratory stream. Hierarchical clustering showed significant differences in the expression profiles of the lead three subregions compared with newly emerged cells. Multiplexed imaging of mRNA expression using fluorescent hybridization chain reaction (HCR) quantitatively confirmed the expression profiles of lead cells. Computational modeling predicted that a small fraction of lead cells that detect directional information is optimal for successful stream migration. Single-cell profiling then revealed a unique molecular signature that is consistent and stable over time in a subset of lead cells within the most advanced portion of the migratory front, which we term trailblazers. Model simulations that forced a lead cell behavior in the trailing subpopulation predicted cell bunching near the migratory domain entrance. Misexpression of the trailblazer molecular signature by perturbation of two upstream transcription factors agreed with the in silico prediction and showed alterations to NC cell migration distance and stream shape. These data are the first to characterize the molecular diversity within an NC cell migratory stream and offer insights into how molecular patterns are transduced into cell behaviors

Use-dependent block of hKv1.5 channels and the molecular determinant by the natural flavone acacetin

In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 60, abstract no. 100published_or_final_versionThe 16th Medical Resarch Conference (MRC), The University of Hong Kong, Hong Kong, China, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17, suppl. 1, p. 60, abstract no. 10

Reduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian cancer

AMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remains obscure. Here, we provide evidence to show that reduced expression of the AMPK-beta1 subunit during tumor progression is associated with the increased oncogenic capacity of advanced ovarian cancer cells. Immunohistochemical analysis revealed that AMPK-beta1 levels were reduced in advanced-stage (P = 0.008), high-grade (P = 0.013) and metastatic ovarian cancers (P = 0.008). Intriguingly, down-regulation of AMPK-beta1 was progressively reduced from tumor stages 1 to 3 of ovarian cancer. Functionally, enforced expression of AMPK-beta1 inhibited ovarian-cancer-cell proliferation, anchorage-independent cell growth, cell migration and invasion. Conversely, depletion of AMPK-beta1 by siRNA enhanced the oncogenic capacities of ovarian cancer cells, suggesting that the loss of AMPK-beta1 favors the aggressiveness of ovarian cancer. Mechanistically, enforced expression of AMPK-beta1 increased AMPK activity, which, in turn, induced cell-cycle arrest via inhibition of AKT/ERK signaling activity as well as impaired cell migration/invasion through the suppression of JNK signaling in ovarian cancer cells. Taken together, these findings suggest that the reduced expression of AMPK-beta1 confers lower AMPK activity, which enhances the oncogenic capacity of advanced-stage ovarian cancer.published_or_final_versio