The very C-terminus of PRK1/PKN is essential for its activation by RhoA and downstream signaling

PRK1 is a lipid- and Rho GTPase-activated serine/threonine protein kinase implicated in the regulation of receptor trafficking, cytoskeletal dynamics and tumorigenesis. Although Rho binding has been mapped to the HR1 region in the regulatory domain of PRK1, the mechanism involved in the control of PRK1 activation following Rho binding is poorly understood. We now provide the first evidence that the very C-terminus beyond the hydrophobic motif in PRK1 is essential for the activation of this kinase by RhoA. Deletion of the HR1 region did not completely abolish the binding of PRK1-ΔHR1 to GTPγS-RhoA nor the activation of this mutant by GTPγS-RhoA in vitro. In contrast, removing of the last six amino acid residues from the C-terminus of PRK1 or truncating of a single C-terminal residue from PRK1-ΔHR1 completely abrogated the activation of these mutants by RhoA both in vitro and in vivo. The critical dependence of the very C-terminus of PRK1 on the signaling downstream of RhoA was further demonstrated by the failure of the PRK1 mutant lacking its six C-terminal residues to augment lisophosphatidic acid-elicited neurite retraction in neuronal cells. Thus, we show that the HR1 region is necessary but not sufficient in eliciting a full activation of PRK1 upon binding of RhoA. Instead, such activation is controlled by the very C-terminus of PRK1. Our results also suggest that the very C-terminus of PRK1, which is the least conserved among members of the protein kinase C superfamily, is a potential drug target for pharmacological intervention of RhoA-mediated signaling pathways

Changes in bacterial concentration in the liver correlate with that in the hepaticojejunostomy after bile duct reconstruction: implication in the pathogenesis of postoperative cholangitis

Postoperative cholangitis is a frequent and unpredictable complication of unknown etiology following bile duct reconstruction (BDR), particularly for biliary atresia. This study was undertaken to correlate the growth of bacteria in the hepaticojejunostomy with that in the liver after BDR. Quantitative bacterial culture was done on the specimens taken from the liver and from the hepaticojejunostomy at 1 week (group 1, n = 7), 1 month (group 2, n = 7), and 2 months (group 3, n = 7) following BDR with Roux-en-Y hepaticojejunostomy in piglets after 2 weeks of common bile duct ligation. The histological examination of the liver and the hepaticojejunostomy, as well as serial monitoring of hemogram and liver function tests, were performed to correlate the findings with the bacterial concentration of the liver and the hepaticojejunostomy following BDR. The bacterial concentration of the hepaticojejunostomy, expressed as log10 colony-forming units per gram (log10 CFU/g) of the hepaticojejunostomy, showed a progressive decrease from 8.38 ± 1.36 in group 1, 7.07 ± 2.54 in group 2, to 3.56 ± 1.31 in group 3 (p = 0.001). The log10 CFU/g of the liver also showed a progressive decrease from 5.02 ± 1.59 in group 1, 3.16 ± 1.56 in group 2, to 2.19 ± 1.09 in group 3 (p = 0.006). There was a significant positive correlation of the log10 CFU/g of the liver (n = 21) with that of the hepaticojejunostomy (n = 21) following BDR (r = 0.600, p = 0.004). Most of the infectious pathogens isolated from the liver were also isolated from the hepaticojejunostomy. The changes in hemoglobin, bilirubin, albumin, and ammonia significantly correlated with the changes of the bacterial concentration of the liver. The results of the study suggests that hepatic bacterial proliferation after BDR is significantly affected by microbial overgrowth in the bilioenteric anastomosis and is associated with deteriorated liver function and hemogram.

The C-terminus of PRK2/PKNγ is required for optimal activation by RhoA in a GTP-dependent manner

PRK2/PKNγ is a Rho effector and a member of the protein kinase C superfamily of serine/threonine kinases. Here, we explore the structure–function relationship between various motifs in the C-terminal half of PRK2 and its kinase activity and regulation. We report that two threonine residues at conserved phosphoacceptor position in the activation loop and the turn motif are essential for the catalytic activity of PRK2, but the phosphomimetic Asp-978 at hydrophobic motif is dispensable for kinase catalytic  competence. Moreover, the PRK2-Δ958 mutant with the turn motif truncated still interacts with 3-phosphoinositide-dependent kinase-1 (PDK-1). Thus, both the intact hydrophobic motif and the turn motif in PRK2 are dispensable for the binding of PDK-1. We also found that while the last seven amino acid residues at the C-terminus of PRK2 are not required for the activation of the kinase by RhoA in vitro, however, the extreme C-terminal segment is critical for the full activation of PRK2 by RhoA in cells in a GTP-dependent manner. Our data suggest that the extreme C-terminus of PRK2 may represent a potential drug target for effector-specific pharmacological intervention of Rho-medicated biological processes.

Is near to . . . and is . . . distant from : exegetical manoeuvres in Janet Frame’s The Carpathians

This paper argues that Janet Frame’s 1988 novel, The Carpathians, can be read as a series of manoeuvres operating at the frontiers of exegesis and fiction. The overall effect of these manoeuvres is to interrogate the conditions of an exegetical (or literary critical) engagement with Frame’s writings. In particular, The Carpathians drills down into the metaphorics of one of the key notions of literary criticism: critical distance. Critical distance is a catch phrase of exegesis, as well as of literary criticism, because it serves to appropriately position the exegete (like the literary critic) as both near to and distant from the object of study: the literary text. However, Frame’s fictional/Scientific concept of the Gravity Star deconstructs the metaphorics of distance and, by extension, critical distance itself, by suggesting a para-doxical relationship of propinquity and remoteness. The Gravity Star is ‘both relatively close and seven billion light years away.’ Thus, Frame introduces chaos into language and logic, with the dual effect of undermining exegetical activity (which depends on the  metaphorics linked to critical distance) and of creatively multiplying the meanings of The Carpathians. In this way, Frame’s novel replaces conventional exegesis with creative exegesis. My paper also looks at the games Frame plays, in this novel and in Towards Another Summer (2007), with Roland Barthes’s notion of the ‘death of the Author.’ Like critical distance, the Author is a prop for exegesis that certain manoeuvres of writing can undermine, thus allowing the literary text to reproduce itself on an interior plane.

Machine learning approaches for modeling spammer behavior

Spam is commonly known as unsolicited or unwanted email messages in the Internet causing potential threat to Internet Security. Users spend a valuable amount of time deleting spam emails. More importantly, ever increasing spam emails occupy server storage space and consume network bandwidth. Keyword-based spam email filtering strategies will eventually be less successful to model spammer behavior as the spammer constantly changes their tricks to circumvent these filters. The evasive tactics that the spammer uses are patterns and these patterns can be modeled to combat spam. This paper investigates the possibilities of modeling spammer behavioral patterns by well-known classification algorithms such as Naïve Bayesian classifier (Naive Bayes), Decision Tree Induction (DTI) and Support Vector Machines (SVMs). Preliminary experimental results demonstrate a promising detection rate of around 92%, which is considerably an enhancement of performance compared to similar spammer behavior modeling research.

Decoration of nitrogen vacancies by oxygen atoms in boron nitride nanotubes

Decoration of nitrogen vacancies by oxygen atoms has been studied by near-edge X-ray absorption fine structure (NEXAFS) around B K-edge in several boron nitride (BN) structures, including bamboo-like and multi-walled BN nanotubes. Breaking of B-N bonds and formation of nitrogen vacancies under low-energy ion bombardment reduces oxidation resistance of BN structures and promotes an efficient oxygen-healing mechanism, in full agreement with some recent theoretical predictions. The formation of mixed O-B-N and B-O bonds is clearly identified by well-resolved peaks in NEXAFS spectra of excited boron atoms.

Weakest collective rationality and the Nash bargaining solution

We propose a new axiom, weakest collective rationality (WCR) which is weaker than both weak Pareto optimality (WPO) in Nash’s (Econometrica 18:155–162, 1950) original characterization and strong individual rationality (SIR) in Roth’s (Math Oper Res 2:64–65, 1977) characterization of the Nash bargaining solution. We then characterize the Nash solution by symmetry (SYM), scale invariance (SI), independence of irrelevant alternatives (IIA) and our weakest collective rationality (WCR) axiom.

Distributive justice and the Nash bargaining solution

Suppes-Sen dominance or SS-proofness (SSP) is a commonly accepted criterion of impartiality in distributive justice. Mariotti (Review of Economic Studies, 66, 733–741, 1999) characterized the Nash bargaining solution using Nash’s (Econometrica, 18, 155–162, 1950) scale invariance (SI) axiom and SSP. In this article, we introduce equity dominance (E-dominance). Using the intersection of SS-dominance and E-dominance requirements, we obtain a weaker version of SSP (WSSP). In addition, we consider α − SSP, where α measures the degree of minimum acceptable inequity aversion; α − SSP is weaker than weak Pareto optimality (WPO) when α = 1. We then show that it is still possible to characterize the Nash solution using WSSP and SI only or using α -SSP, SI, and individual rationality (IR) only for any a Î [0,1)[01). Using the union of SS-dominance and E-dominance requirements, we obtain a stronger version of SSP (SSSP). It turns out that there is no bargaining solution that satisfies SSSP and SI, but the Egalitarian solution turns out to be the unique solution satisfying SSSP.

Writing as capitulation : the shelter of being-responsible

This paper explores the notion of writing and its relationship to an always-existing responsibility. It asks the question of whether writing might necessarily be a kind of biographical undertaking, and then drawing on Heidegger, it inquires into how writing might provoke an ontological encounter for the writer. Via a close investigation of the definitions and etymologies of the word ‘capitulate’, the paper links the concepts of Derridean violence, Hellerian freedom and (post)modernity, non-infinite temporality and assumptions of a metaphysics of presence to a practice of reading/writing. By taking up the Heideggerian concept of Being’s as ex-istence and porosity, it attempts to argue that post-modernity, in coming to terms with the consequences of freedom, offers the subject the opportunity for an ontological encounter with responsibility, and subsequently how an acknowledgement of this thrownness might function in itself as a kind of shelter, albeit an open one.

Linking identities and viewpoints in home movies based on robust feature matching

The identification of useful structures in home video is difficult because this class of video is distinguished from other video sources by its unrestricted, non edited content and the absence of regulated storyline. In addition, home videos contain a lot of motion and erratic camera movements, with shots of the same character being captured from various angles and viewpoints. In this paper, we present a solution to the challenging problem of clustering shots and faces in home videos, based on the use of SIFT features. SIFT features have been known to be robust for object recognition; however, in dealing with the complexities of home video setting, the matching process needs to be augmented and adapted. This paper describes various techniques that can improve the number of matches returned as well as the correctness of matches. For example, existing methods for verification of matches are inadequate for cases when a small number of matches are returned, a common situation in home videos. We address this by constructing a robust classifier that works on matching sets instead of individual matches, allowing the exploitation of the geometric constraints between matches. Finally, we propose techniques for robustly extracting target clusters from individual feature matches.

Utility-based summarization of home videos

The aim of this work is to devise an effective method for static summarization of home video sequences. Based on the premise that the user watching a summary is interested in people related (how many, who, emotional state) or activity related aspects, we formulate a novel approach to video summarization that works to specifically expose relevant video frames that make the content spotting tasks possible. Unlike existing approaches, which work on low-level features which often produce the summary not appealing to the viewer due to the semantic gap between low-level features and high-level concepts, our approach is driven by various utility functions (identity count, identity recognition, emotion recognition, activity recognition, sense of space) that use the results of face detection, face clustering, shot clustering and within cluster frame alignment. The summarization problem is then treated as the problem of extracting the set of key frames that have the maximum combined utility.