Interplay between the alpharetroviral Gag protein and SR proteins SF2 and SC35 in the nucleus

Retroviruses are positive-sense, single-stranded RNA viruses that reverse transcribe their RNA genomes into double-stranded DNA for integration into the host cell chromosome. The integrated provirus is used as a template for the transcription of viral RNA. The full-length viral RNA can be used for the translation of the Gag and Gag-Pol structural proteins or as the genomic RNA (gRNA) for encapsidation into new virions by the Gag protein. The mechanism by which Gag selectively incorporates unspliced gRNA into virus particles is poorly understood. Although Gag was previously thought to localize exclusively to the cytoplasm and plasma membrane where particles are released, we found that the Gag protein of Rous sarcoma virus, an alpharetrovirus, undergoes transient nuclear trafficking. When the nuclear export signal of RSV Gag is mutated (Gag.L219A), the protein accumulates in discrete subnuclear foci reminiscent of nuclear bodies such as splicing speckles, paraspeckles, and PML bodies. In this report, we observed that RSV Gag.L219A foci appeared to be tethered in the nucleus, partially co-localizing with the splicing speckle components SC35 and SF2. Overexpression of SC35 increased the number of Gag.L219A nucleoplasmic foci, suggesting that SC35 may facilitate the formation of Gag foci. We previously reported that RSV Gag nuclear trafficking is required for efficient gRNA packaging. Together with the data presented herein, our findings raise the intriguing hypothesis that RSV Gag may co-opt splicing factors to localize near transcription sites. Because splicing occurs co-transcriptionally, we speculate that this mechanism could allow Gag to associate with unspliced viral RNA shortly after its transcription initiation in the nucleus, before the viral RNA can be spliced or exported from the nucleus as an mRNA template

Empirical Issues and Challenges for Multilevel Governance: The Case of the 2010 Vancouver Olympic Winter Games

How did a large network of over 600 actors successfully organize itself to serve a mega project dominated by three levels of government, even as control rested with a non-profit entity, included other sectors, and the governments involved did not normally work well together? The purpose of this paper is to examine how the three levels of government in Canada established a network to coordinate efforts for hosting the 2010 Vancouver Olympic Winter Games. This case study was built by means of documents and interviews, and supported by participant observations. The network was not found to be dense, but did include a multiplexity of ties (e.g., transactions, communications, collaborations, and coordinating bridges) by actors serving diverse strategic goals and scopes of work. The case was compared to data collected for the 2012 London Olympic Games to draw out key network governance coordination themes. Nine governance themes emerged associated with governance structure, processes, and evaluation: coordination mechanisms; internal engagement, momentum, and motivation; external transparency; formalization; balancing autonomy and interdependence; co-location; readiness exercises; political alignment; and time. The findings provide a framework for examining the governance of multi-level, multi-sectorial networks created to undertake a mega project and indicate how a network’s public and non-profit organizations’ activities and procedures can be influenced, modified, and impacted by the other actors (i.e., other public or non-profit organizations).Comment un vaste réseau de plus de 600 acteurs a-t-il réussi à s’organiser pour soutenir un mégaprojet dominé par trois niveaux de gouvernement, alors même que le contrôle relevait d’une entité sans but lucratif, incluait d’autres secteurs et que les gouvernements concernés ne travaillaient normalement pas bien ensemble ? Cet article a pour objet d’examiner comment les trois ordres de gouvernement au Canada ont établi un réseau pour coordonner les interventions en faveur de la tenue des Jeux olympiques d’hiver de 2010 à Vancouver. Cette étude de cas a été réalisée au moyen de documents et d’entrevues, appuyée de l’observation participante. Le réseau, sans être dense, comprend néanmoins une multiplicité de liens (p. ex. transactions, communications, collaborations et ponts de coordination) entre les acteurs qui servent divers objectifs stratégiques et champs d’activité. Le cas a été comparé aux données recueillies pour les Jeux olympiques de 2012 à Londres afin de dégager les principaux thèmes relatifs à la coordination de la gouvernance en réseau. Neuf thèmes associés à la structure, aux processus et à l’évaluation de la gouvernance sont ressortis : mécanismes de coordination, engagement interne, dynamique et motivation, transparence externe, formalisation, équilibre entre autonomie et interdépendance, regroupement, exercices de préparation, alignement politique et temps. Les résultats fournissent un cadre pour l’examen de la gouvernance des réseaux multiniveaux et multisectoriels créés pour entreprendre un mégaprojet et indiquent comment les activités et les procédures des organismes publics et sans but lucratif d’un réseau peuvent être influencées, modifiées et subir les effets des autres acteurs (c’est-à-dire les autres organismes publics ou sans but lucratif)

Multicenter assessment of quantitative sensory testing (QST) for the detection of neuropathic-like pain responses using the topical capsaicin model

Background: The use of quantitative sensory testing (QST) in multicenter studies has been quite limited, due in part to lack of standardized procedures among centers. Aim: The aim of this study was to assess the application of the capsaicin pain model as a surrogate experimental human model of neuropathic pain in different centers and verify the variation in reports of QST measures across centers. Methods: A multicenter study conducted by the Quebec Pain Research Network in six laboratories allowed the evaluation of nine QST parameters in 60 healthy subjects treated with topical capsaicin to model unilateral pain and allodynia. The same measurements (without capsaicin) were taken in 20 patients with chronic neuropathic pain recruited from an independent pain clinic. Results: Results revealed that six parameters detected a significant difference between the capsaicin-treated and the control skin areas: (1) cold detection threshold (CDT) and (2) cold pain threshold (CPT) are lower on the capsaicin-treated side, indicating a decreased in cold sensitivity; (3) heat pain threshold (HPT) was lower on the capsaicin-treated side in healthy subjects, suggesting an increased heat pain sensitivity; (4) dynamic mechanical allodynia (DMA); (5) mechanical pain after two stimulations (MPS2); and (6) mechanical pain summation after ten stimulations (MPS10), are increased on the capsaicin-treated side, suggesting an increased in mechanical pain (P < 0.002). CDT, CPT and HPT showed comparable effects across all six centers, with CPT and HPT demonstrating the best sensitivity. Data from the patients showed significant difference between affected and unaffected body side but only with CDT. Conclusion: These results provide further support for the application of QST in multicenter studies examining normal and pathological pain responses

Cortical Factor Feedback Model for Cellular Locomotion and Cytofission

Eukaryotic cells can move spontaneously without being guided by external cues. For such spontaneous movements, a variety of different modes have been observed, including the amoeboid-like locomotion with protrusion of multiple pseudopods, the keratocyte-like locomotion with a widely spread lamellipodium, cell division with two daughter cells crawling in opposite directions, and fragmentations of a cell to multiple pieces. Mutagenesis studies have revealed that cells exhibit these modes depending on which genes are deficient, suggesting that seemingly different modes are the manifestation of a common mechanism to regulate cell motion. In this paper, we propose a hypothesis that the positive feedback mechanism working through the inhomogeneous distribution of regulatory proteins underlies this variety of cell locomotion and cytofission. In this hypothesis, a set of regulatory proteins, which we call cortical factors, suppress actin polymerization. These suppressing factors are diluted at the extending front and accumulated at the retracting rear of cell, which establishes a cellular polarity and enhances the cell motility, leading to the further accumulation of cortical factors at the rear. Stochastic simulation of cell movement shows that the positive feedback mechanism of cortical factors stabilizes or destabilizes modes of movement and determines the cell migration pattern. The model predicts that the pattern is selected by changing the rate of formation of the actin-filament network or the threshold to initiate the network formation

On a mission: Achieving distinction as a business school?

This paper investigates what business schools are saying in their mission statements and whether they provide a meaningful basis for strategic choice, distinction and differentiation from a positioning perspective; or whether they are the equivalent of “table stakes” in the MBA game - undifferentiated signals that connote legitimacy. Content analysis is undertaken of the mission statements of the Financial Times 2009 top 100 full-time MBA program offering business schools. The statements are mapped and compared in the aggregate and by quartile. We conclude that the statements are for the most part homogeneous and do not serve as a basis for differentiation. However, although achieving distinction through a mission statement may indeed be difficult, it is by no means impossible, and we suggest approaches that business school deans might adopt in an effort to make their brands stand out

The repeating Fast Radio Burst FRB 121102: Multi-wavelength observations and additional bursts

We report on radio and X-ray observations of the only known repeating Fast Radio Burst (FRB) source, FRB 121102. We have detected six additional radio bursts from this source: five with the Green Bank Telescope at 2 GHz, and one at 1.4 GHz at the Arecibo Observatory for a total of 17 bursts from this source. All have dispersion measures consistent with a single value ($\sim559$ pc cm$^{-3}$) that is three times the predicted maximum Galactic value. The 2-GHz bursts have highly variable spectra like those at 1.4 GHz, indicating that the frequency structure seen across the individual 1.4 and 2-GHz bandpasses is part of a wideband process. X-ray observations of the FRB 121102 field with the Swift and Chandra observatories show at least one possible counterpart; however, the probability of chance superposition is high. A radio imaging observation of the field with the Jansky Very Large Array at 1.6 GHz yields a 5$\sigma$ upper limit of 0.3 mJy on any point-source continuum emission. This upper limit, combined with archival WISE 22-$\mu$m and IPHAS H$\alpha$ surveys, rules out the presence of an intervening Galactic HII region. We update our estimate of the FRB detection rate in the PALFA survey to be 1.1$^{+3.7}_{-1.0} \times 10^4$ FRBs sky$^{-1}$ day$^{-1}$ (95% confidence) for peak flux density at 1.4 GHz above 300 mJy. We find that the intrinsic widths of the 12 FRB 121102 bursts from Arecibo are, on average, significantly longer than the intrinsic widths of the 13 single-component FRBs detected with the Parkes telescope.Comment: 18 pages, 5 figures. Accepted for publication in Ap

Planning and Leveraging Event Portfolios: Towards a Holistic Theory

This conceptual paper seeks to advance the discourse on the leveraging and legacies of events by examining the planning, management, and leveraging of event portfolios. This examination shifts the common focus from analyzing single events towards multiple events and purposes that can enable cross-leveraging among different events in pursuit of attainment and magnification of specific ends. The following frameworks are proposed: (1) event portfolio planning and leveraging, and (2) analyzing events networks and inter-organizational linkages. These frameworks are intended to provide, at this infancy stage of event portfolios research, a solid ground for building theory on the management of different types and scales of events within the context of a portfolio aimed to obtain, optimize and sustain tourism, as well as broader community benefits